Kidney Damage Alternative Medicine
Glomerulonephritis, an immunologic disease of the kidneys, affects the glomerulus, a cluster of capillaries that is the filter in the functioning unit of the kidney, the nephron. Inflammation, initiated by immune complexes, injures the glomerulus. Often the disease is acute, but it may be completely undetected until signs of kidney failure appear. This silent disease may prove fatal.
SBP is a bacterial infection of a pre-existing pathophysiological accumulation of peritoneal fluid, a pathophysiological consequence of portal hypertension that develops almost exclusively in patients with chronic liver disease. On the other hand, CAPD represents infection of an artificial dialysis solution that is repetitively infused into and drained from the peritoneal cavity of patients with chronic renal failure in an attempt to dialyze out abnormally retained metabolic products that are normally excreted in the urine. In both disorders bacteria may infect the peritoneal cavity causing abdominal pain, fever, and other signs of peritoneal inflammation. Although both disorders represent bacterial infections of intraperitoneal fluids and the peritoneum, one occurs spontaneously whereas the other usually appears to represent iatrogenic contamination of a synthetic ascitic fluid. The ascitic fluids in these two syndromes are quite different. in the dialysis fluid. Furthermore, the...
Diseases of the kidneys are among the most important causes of death and disability in many countries throughout the world. For example, in 2004, more than 20 million adults in the United States were estimated to have chronic kidney disease. Severe kidney diseases can be divided into two main categories (1) acute renal failure, in which the kidneys abruptly stop working entirely or almost entirely but may eventually recover nearly normal function, and (2) chronic renal failure, in which there is progressive loss of function of more and more nephrons that gradually decreases overall kidney function. Within these two general categories, there are many specific kidney diseases that can affect the kidney blood vessels, glomeruli, tubules, renal interstitium, and parts of the urinary tract outside the kidney, including the ureters and bladder. In this chapter, we discuss specific physiologic abnormalities that occur in a few of the more important types of kidney diseases.
Sleep disturbances are common in renal failure, particularly in the elderly. Around 80 of patients complain of difficulty in initiating sleep (page 183) and it is also common for excessive daytime sleepiness to be a problem 14 . Polysomnography shows a reduction in total sleep time with increased sleep fragmentation and duration of stages 1 and 2 NREM sleep, and with reduction of stages 3 and 4 NREM sleep and REM sleep. A 'subclinical' uraemic encephalopathy, and anti-hypertensive and antidepressant drugs may contribute to daytime sleepiness. Anxiety and depression from the stress of the illness and its treatment are common. Bone pain associated with dialysis may lead to insomnia. Dialysis also increases cytokine production, alters body temperature control and influences mela-tonin secretion. In addition to these problems renal failure is associated with the following.
The causes of acute renal failure can be divided into three main categories 1. Acute renal failure resulting from decreased blood supply to the kidneys this condition is often referred to as prerenal acute renal failure to reflect the fact that the abnormality occurs in a system before the kidneys. This can be a consequence of heart failure with reduced cardiac output and low blood pressure or conditions associated with diminished blood volume and low blood pressure, such as severe hemorrhage. 2. Intrarenal acute renal failure resulting from abnormalities within the kidney itself, including those that affect the blood vessels, glomeruli, or tubules. 3. Postrenal acute renal failure, resulting from obstruction of the urinary collecting system Prerenal Acute Renal Failure Caused by Decreased Blood Flow to the Kidney As long as renal blood flow does not fall below about 20 to 25 per cent of normal, acute renal failure can usually be reversed if the cause of the ischemia is corrected...
ELITE recruited 722 patients and followed them in for 48 weeks. At its conclusion, ELITE investigators determined that kidney function was equally preserved by the two medications. However, the investigators discovered that 17 deaths occurred in the losartan group and 32 deaths in the captopril group (p 0.035). This finding received the principle emphasis in the discussion section of the manuscript. Although the need to repeat the trial was mentioned in the abstract, the balance of the discussion focused on the reduced mortality rate of losartan. According to the authors, This study demonstrated that losartan reduced mortality compared with captopril whether the apparent mortality advantage for losartan over captopril holds true for other ACE inhibitors requires further study. Others even went so far as to attempt to explain the mechanism for the reduction in sudden death observed in ELITE 1 5, 6 .
A number of prosthetic devices have been associated with the occurrence of SBP and have almost certainly contributed pathogenetically to the development of SBP. These devices include (a) ventriculoperitoneal shunts created to decrease the intracranial pressure in patients with hydrocephalus, (b) indwelling intraperitoneal catheters used during chronic ambulatory peritoneal dialysis (CAPD), (c) peritoneovenous shunts in patients with portal hypertension and ascites, and (d) intra-uterine contraceptive devices.
Published case series of severe CAP emphasise that the ICU treatment of this group of patients involves the support of multiple failing organ systems. Most patients die of the complications of multiorgan failure rather than from respiratory failure alone. In the BTS severe CAP study 32 developed acute renal failure and 55 septic shock 25 developed central nervous system problems including vascular events and convulsions.8
It is now established that HTLV-1 is associated with ATL, HTLV-l-associated myelopathy or tropical spastic paraparesis (HAM TSP) and uveitis. Other diseases such as chronic lung disease, monoclonal gammopathy, chronic renal failure, strongyloidiasis and nonspecific dermato-mycosis are also suggested to associate with the viral infection however, further systematic studies are required to establish the exact relationships. Here, only ATL is described.
Capillary isoelectric focusing (CIEF) provides the highest possible separation efficiency for the separation of proteins. Using a gel-free approach, it is possible to couple CIEF online to ESI-MS, offering a powerful tool for the analysis of very complex samples. The limitations for the coupling of CIEF to MS are the volatility of the ampholytes and the transfer of the very narrowly focused zones into the MS without peak broadening. The combination of the cathodic with gravimetric mobilization appears to be the most suitable manner to deal with the peak broadening issue 14,15 . To reduce the influence of the ampholyte on the ionization efficiency of the ESI, a dialysis interface prior to the ESI has been developed 16 . Furthermore, the
High blood pressure (hypertension) is dangerous. If blood pressure is high, the heart has to work harder to pump the same amount of blood, which puts a great stress on the cardiovascular system. Patients with high blood pressure are more prone to heart attacks, heart failure, kidney failure, and strokes. Fortunately, blood pressure can be controlled with appropriate medications and lifestyle modifications, greatly reducing the risk of complications.
The brown rat (R. norvegicus) does not demonstrate clinical symptoms following intraperitoneal inoculation with R. akari but may develop a low-level persistent infection that can be detected by passage of rat tissue suspensions into naive guinea pigs (59). White laboratory rats infected by intraperitoneal inoculation develop fever and mild periorchitis (59,145). Histopathologic changes in the peritoneum include proliferation of connective tissue, infiltration with polymorphonuclear leukocytes, and hypervascularization of viscera. Similar changes occur in the tunica vaginalis, and myocarditis and nephritis are occasionally observed (145). Cotton rats (S. hispidus) are highly susceptible to intraperitoneal infection with R. akari. After
Also investigated was the question of whether the differentially expressed tran-scriptional patterns in PBMCs of patients with RCC were similar to PBMC tran-scriptional responses observed in non-RCC end-stage renal failure. The differentially expressed genes in RCC PBMCs were compared with genes differentially expressed between PBMCs from patients with non-RCC end-stage renal failure (n 9 individuals) and PBMCs from normal volunteers (n 4 individuals). Of these, 9 transcripts differentially expressed in PBMCs from patients with renal failure were also disease-associated transcripts in RCC PBMCs. Thus, the marker gene list from PBMCs of patients with RCC contains a smaller subset of markers commonly involved in immune responses measured ex vivo (activated CD4+ T-cell profiles) and in responses of circulating leukocytes to renal dysfunction (PBMCs from patients with non-RCC renal failure) observed in vivo.
It has been observed that certain compounds appear as frequent hitters in HTS regardless of the biological target, especially when screened at higher than 10 J.M concentration. Figure 5 shows examples of promiscuous HTS hits (McGovern et al., 2002 McGovern et al., 2003 McGovern and Shoichet, 2003). These spurious hits have low potency at 1-10 J.M, noncompetitive and reversible inhibition, flat SAR and poor selectivity. The potency increases with incubation time, but decreases with higher enzyme concentration, temperature, ionic strength and with the addition of urea or BSA. The inhibition is not reversible in a dialysis experiment, suggesting formation of aggregates (Feng et al., 2005).
In 1972 the National Heart and Lung Institute (NHLI) task force estimated an incidence of 75 cases of ARDS per 100 000 population per year.27 Several subsequent studies have estimated a much lower annual incidence of 1.5-13.5 cases per 100 000 population (table 5.5).28-32 There are several reasons why the number of cases may have been overestimated. The task force predated the widespread acceptance of the definition of ARDS and used a broad definition of lung injury that included conditions such as renal failure and volume overload. In addition, the population at risk was not clearly
One specific situation in which patients seem to be particularly vulnerable to TBP is the case of patients under therapy with chronic ambulatory peritoneal dialysis for renal disease (61). The reasons for this are not known, but there are many pertinent contributing factors. First, of course, is that patients on dialysis have chronic renal failure, which per se is accompanied by a type of immunoincompetence (62). This abnormality renders the patients susceptible to a variety of infections. Second, the peritoneal fluid of patients with CAPD, which is a diluted, synthetic peritoneal fluid, is a weak imitation of cirrhotic ascitic fluid that is deficient in many of the antibacterial defenses present in ' 'normal'' ascitic fluid, including a reduced number of fixed and motile phagocytic leukocytes, and almost certainly a deficiency of both specific and nonspecific oncogenic substances and a decreased protein concentration. These factors are characterized by a relative low concentration of...
Chronic ambulatory dialytic peritonitis, is an SBP-like syndrome, that is largely caused by skin contaminating bacteria such as Staphylococcus aureus and Staphylococcus enteriditis, which appears to be caused by contamination of the synthetic dialysis solutions by nonenteric bacteria.
Bacterivores are thought to prefer larger bacteria (Sherr et al., 1992) however, grazing is reported to invigorate populations, leading to faster rates of growth and concomitant increases in bacterial size (Han and Hofle, 1998). Experiments that compared bacterial sizes in seawater passed through 0.45 mm filters to remove the bacterivores, followed by incubation in dialysis bags, resulted in populations having the same size distribution by flow cytometry and failed to show the anticipated grazing effect (Button and Robertson, unpublished). Moreover, while significant changes in bacterial size are often reported with depth, cell sizes by flow cytometry are relatively constant from the surface to several thousand meters where minimal grazing is expected.
The inclusion of context-specific as well as generic aspects of methodological quality may sometimes be desirable. For example, Marx and Marx10 included two questions on the nature of the endpoints, reflecting particular problems encountered in their review of prognosis of idiopathic membranous nephropathy, where many studies used ill-defined surrogate endpoints.
The patient with cirrhosis and bleeding esophageal varices suffers from a debilitating disease with many remote manifestations. These patients often die of hepatic failure, renal failure, or sepsis rather than exsanguination. Accordingly, supportive care is critical to survival. The first order of priority is fluid resuscitation, initially with crystalloid and then, as soon as possible, with packed red blood cells and fresh frozen plasma. The combination of thrombocytopenia (from hypersplenism) and severe hemorrhage may warrant the administration of platelet infusions. Care should be taken to avoid the infusion of too much salt-containing fluid because of avid sodium retention and resultant ascites, edema, and dilutional hyponatremia. The restoration of blood volume should be monitored by hourly urine output through a Foley catheter and by measurement of central venous pressure.
Preeclampsia comprises three conditions that trigger one another in a domino effect water retention, high blood pressure, and protein in your urine (called proteinuria), which can lead to (or be symptomatic of) kidney damage. If you have only one or two of these symptoms, you don't have preeclampsia. All three of the symptoms must be present to be diagnosed with preeclampsia.
Participation of MCT1 in the efflux of metals from the brain to blood was suggested (87). When unbound extracellular aluminum was measured by microdialysis in the jugular vein as well as in the right and left frontal cortices of rats, the steady state brain-to-blood ratio (A p braln) was less than 1, suggesting the presence of a process other than diffusion for transfer across the BBB. After alkalinizing dialysis via a brain microdialysis probe (to pH 10.2), the Kp,braln value increased from 0.35 to 0.80. The addition to the brain dialysate of a proton ionophore, p-(trifluoromethoxy)phenylhydrazone, increased the Kp,braln value from 0.21 to 0.61. These increased Kp,braln values suggest that a proton-dependent process is removing aluminum from brain extracellular fluid. Addition of mersalyl acid, which inhibits MCT1 but not MCT2, to the brain dialysate increased the Kp,braln value from 0.19 to 0.87 (87). Since the monocarboxylate transporters are the only known proton-dependent...
As mentioned, the first clinical report of use of a liver support system utilizing isolated hepatocytes is that of Matsumura, who converted a dialyzer to an artificial liver by adding a cryopreserved rabbit liver cell suspension to the dialysis chamber.11 In addition, he replaced the usual cuprophane membrane with a cellulose membrane permeable to middle range molecules, but not proteins. A 45-year-old man in hepatic failure due to unresectable cholangiocarcinoma underwent hemodialysis for 5 hours. Total serum bilirubin was reduced from 25.0 mg dl to 16.8 mg dl after the first treatment. Three days later, after a second 4 1 2 hour treatment, the total bilirubin level decreased from 18.0 mg dl to 8.0 mg dl. There was no evidence that the device affected the course of liver failure and outcome in this patient and there was no follow-up report on use of this system in a larger number of patients.
Over the past five years since the introduction of the Edmonton Protocol, extensive progress has continued, and notably there are now more patients transplanted with islets since the year 2000 than the total number in the preceding 30 years. This expanded experience has not only confirmed the initial Edmonton findings, but has highlighted important limitations that must be overcome if islet transplantation is to be more broadly applied as a potential cure for diabetes. The results of islet after kidney transplants appear to match the success of islet alone transplants under sirolimus-based immunosuppression. The Milan group has recently shown that long-term islet graft function (with persistent C-peptide secretion) can not only prolong the half-life of a kidney transplant, but is associated with a reduced incidence of diabetic vascular complications leading to significantly enhanced patient survival.35
There are two presentations the adult muscular form, in which prolonged exercise induces weakness and myoglobinuria, and a severe infantile form, in which nonketotic hypoglycemic coma without dicarboxylicaciduria, seizures, hepatomegaly, cardiomegaly, and cardiac arrhythmia are accompanied by low plasma and tissue levels of carnitine with increase in long-chain acylcarnitines. The classic adult form is autosomal recessive and usually affects males between 15 and 30 years of age. The serum creatine kinase value is normal between episodes, carnitine levels are usually normal in plasma and tissues, and long-term muscle weakness is rare, although lipid storage may be seen on muscle biopsy. The differential diagnosis includes other carnitine cycle disorders. Management involves supportive treatment of the renal failure and measures to remove the myoglobin from kidney and avoidance of triggering factors-prolonged exercise, exposure to cold, infections, and fasting. Presentation in the...
Another antiobesity drug, sibutramine, was approved for use in 2001. Sibutramine is meant for people whose body mass index (BMI) registers at 27 or higher. But if you're on thyroid hormone, as well as medications for depression, seizures, glaucoma, osteoporosis, gallbladder disease, liver disease, heart disease or stroke prevention, kidney disease, migraines, or Parkinson's disease, you should discuss whether sibutramine is appropriate.
As indicated, the development of SBP may follow a worsening of the clinical condition of the patient. The clinical data in 213 episodes of SBP are shown in Table 10.3 More than 50 of cirrhotic patients with SBP exhibit hepatic encephalopathy, renal failure, gastrointestinal bleeding, ileus, or septic shock.
After nephrectomy, preservation of the residual kidney function is essential. Participation in contact sports, especially football, is not advised. Kidney guards are often recommended, although there is no data regarding their efficacy in injury prevention. More likely, the appliance serves to remind the individual of vulnerability. Although urinary tract infection should be treated aggressively in all patients, this is especially important in those with a single kidney or with renal dysfunction. To rule out obstruction,
A more serious complication is rhabdomyolysis, a rare complication of cytarabine and other drugs, including cyclophosphamide, 5-azacytidine, interferon-A, and interleukin-2 73 . It is thought that the ability of cytarabine to trigger the release of cyto-chrome-c from the mitochondria could lead to uncoupling of the oxidative phosphorylation with subsequent depletion of ATP reserves at the skeletal muscle, resulting in rhabdomyolysis. Whatever the cause, the syndrome is complicated by acute renal failure often requiring hemodialysis 73 .
BIPOTENTIAL OVAL CELL LINES DERIVED FROM ADULT MICE The TgN737 gene was identified by a transgene-induced insertional mutation in the mouse (Moyer et al., 1994). In humans, mutation in the gene causes liver abnormalities and a syndrome similar to autosomal recessive polycystic kidney disease (Yoder et al., 1995). The TgN737Rpw mouse develops biliary hyperplasia, associated with proliferation of cells that morphologically and immunologically resemble oval cells, which then give rise to ductular structures (Richards et al., 1996). This model is particularly interesting in that it induces oval cell proliferation without damaging the parenchyma.
Establishing a diagnosis of Q fever endocarditis is not very difficult. Patients without fever, or with sporadic or low-grade fever, are often misdiagnosed. Q fever should be systematically suspected in a patient with valvular abnormalities, presenting with evocative clinical signs (fever, hepatitis, tiredness, clubbed fingers, weight loss, renal failure), or laboratory findings (elevated ESR, elevated liver enzymes, thrombocytopenia). A Q- fever serology must be carried out in such patients, and the diagnosis can be assessed using modified Duke's criteria (26).
Certain medication may affect renal clearance even in patients with normal kidney function. Tubular secretion is affected by the administered amount of 99mTc-EC. The single dose should not exceed 0.7 mg of EC (use kit for three patients), since secretion may be delayed in cases of impaired renal function, a saturation effect may be observed. Higher doses (entire kit content) should be avoided since the diagnostic value of the renal examination may be biased. 99mTc-EC complex does not contribute to hepatobiliary activity thus, 99mTc-EC is especially suited for the examination of renal function in patients with kidney transplants.
Despite the high profile of type 1 diabetes and the implementation of new genetic screening programs for families and newborns to identify high-risk individuals, the incidence of type 1 diabetes is increasing worldwide. Type 1 diabetes is an especially insidious disease with clinical symptoms usually not being detected until after the patient's own immune system has destroyed 90 of the total insulin-producing P-cells of the endocrine pancreas (Eisenbarth, 1986 Harris, 1999). Although routine insulin injections can provide diabetic patients with their daily insulin requirements, blood glucose excursions are common, resulting in hyperglycemic episodes. Hyperglycemia represents the major health problem for the diabetic patient, especially long term. When inadequately controlled, chronic hyperglycemia can lead to microvascular complications (e.g., retinopathy and blindness, nephropathy and renal failure, neuropathy, foot ulcers, and amputation), and macrovascular complications (e.g.,...
The largest clinical experience with clipped vascular constructs is with vascular access for hemodialysis. Papalois reported one of the largest series enrolling 50 patients in which the VCS was used to create A-V fistula 23 . The anastomotic time was approximately 5 min. In 3 cases it was necessary to apply one extra clip to stop minor anastomotic bleeding. After a follow-up of 2 months to 1 year, all fistulas were in use for dialysis.
Patients with vasculitis may present with isolated pulmonary haemorrhage, but usually there is also systemic involvement. Most patients with Wegener's granulomatosis have granulomatous lesions in the upper respiratory tract which result in chronic sinusitis, epistaxis, chronic otitis media, and deafness. Involvement of the trachea can present with life threatening stridor. Granulomas are also found in many sites outside the respiratory system including the kidney, central nervous system, prostate, parotid and orbit.3 Patients with microscopic polyangiitis and Wegener's granulomatosis also present with systemic symptoms secondary to the small vessel vasculitis. Urine abnormalities include microscopic haema-turia and proteinuria, with red cell casts on microscopy. The serum creatinine may initially be in the normal range, but acute renal failure tends to develop quite rapidly. Renal and respiratory involvement both have a significant effect on mortality.3 24 25 Other organs in which...
Preoperative support with mechanical ventilation, inotropes, prostaglandin and sometimes peritoneal dialysis improves the preoperative condition enough to enable surgery to take place. Transfusion may precipitate pulmonary oedema, and hypotension may further reduce myocardial oxygenation and cause ventricular dysrhythmias or even cardiac arrest.
The consultation document set out a number of scenarios where cloning technology could be applied to make a copy of another human being, envisaging single or multiple copies of a living or a dead fetus, baby, child, or adult. These included parents who might wish to replace an aborted fetus, dead baby, or child killed in an accident produce a sibling to be a compatible tissue or organ donor for a child dying from, say, leukemia or kidney failure or an individual attempting to cheat death by using cloning technology. Mention was also made of the possibility of selecting characteristics in offspring or to assist human reproduction in the case of infertile couples or lesbian couples. Views were sought on the acceptability of cloning in all, or any, of these circumstances.
Pancreatic transplantation has been used to correct insulin deficiency in patients with type 1 diabetes, and is performed most often in conjunction with renal transplantation in patients with diabetic nephropathy (55). Solid-organ transplantation for type 1 diabetes is limited to patients with life-threatening disease however, because of the risks associated with invasive surgical procedures and toxicity of immunosuppressive therapies, it is necessary to induce and maintain allograft tolerance (55). Nevertheless, in a review of more than 2000 pancreas transplants performed in the United States, functional survival of transplanted pancreas was observed in greater than 70 of patients 1 year after transplant, although this rate declined to 66 at 2 years, and 59 at 3 years (55). and identical twin donor organs (66). Whereas patients receiving reduced immunosuppressive therapy following HLA-matched sibling and identical twin organs showed recurrent autoimmunity toward transplanted islet p...
Other uncontrolled studies have reported beneficial effects of combination therapy in patients with co-morbid conditions. Administration of intramuscular T and sildenafil was found to be efficacious in renal transplant patients and in patients on renal dialysis 173 . Oral T has been reported to reverse ED associated with type 2 diabetes in patients failing on sildenafil therapy alone 71 . In conclusion, T combination therapy with PDE5i may improve the response to PDEi in patients with ED and hypogonadism.
These are present in up to 70 of those on dialysis, both peritoneal and haemodialysis. The cause is probably multifactorial, but includes iron deficiency due to dietary restriction and blood loss, changes in dopamine and possibly opioid availability in the brain, and a peripheral neuropathy due to the renal failure. The frequency of periodic limb movements has been shown to predict mortality in renal failure, but periodic limb movements and the restless legs syndrome improve with renal transplantation. They also respond to conventional drug treatment for restless legs and periodic limb movements in sleep, including dopaminergic agents and gabapentin.
Thrombotic thrombocytopenic purpura is characterized clinically by fever, renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. Transient focal neurological signs and a more diffuse encephalopathy are common, but occasionally, persistent neurological deficits due to occlusion of medium-sized arteries or brain hemorrhages occur.y Plasma exchange can be an effective treatment.
Diuretics such as frusemide (often given i.v.), are widely used in heart failure treatment in the perioperative period (Singh et al., 1992) to optimize fluid balance, and are crucial in the face ofpotentially impaired renal function. Continuous infusions of frusemide produces a smoother control of fluid and electrolyte shifts than intermittent i.v. bolus administration (Klinge, 2001). If tolerance to frusemide develops, concomitant use of thiazide diuretics such as chlorthiazide or metolazone, which act synergistically with loop diuretics, may improve diuresis. Care must be taken in all patients receiving diuretics to maintain circulating volume and normal electrolyte concentrations, including potassium, calcium and magnesium.
SBP still die during hospitalization because of the initial infectious process, the underlying liver disease, or both (12-15,18,32-38). The impact of the development of SBP in patients on the liver transplant waiting list has recently been analyzed. In a preliminary study published in abstract form (39), 6 of patients with chronic liver disease developed SBP while awaiting transplantation, which averaged five months. More important, 62 of these patients died before receiving a liver transplant, whereas the mortality rate of patients who did not develop SBP while awaiting transplantation was only 16 . On the other hand, renal and liver function can deteriorate significantly as a consequence of SBP, and such derangements may persist after the resolution of SBP (8,14,40). Renal impairment may be related to the administration of nephrotoxic antimicrobial agents, such as aminoglycoside antibiotic agents, or to the deletereous effects of the inflammatory response itself (41-44). The...
Surgical transplantation of a vascularized whole pancreas or even half a pancreas can give excellent long-term results,8 with cure of diabetes in many cases. Most patients have suffered from diabetic renal failure and often it has been possible to transplant a kidney and a pancreas from the same donor. Powerful lifelong immunosuppression is necessary, but this would be standard treatment for the kidney graft. The operation is a major surgical procedure with the special danger of leakage of pancreatic digestive enzymes, but results are improving steadily. Unfortunately, the incidence of diabetes is far in excess of the availability of donor pancreata.
Cisplatin is a highly effective chemotherapy drug. Unfortunately, it can be associated with kidney toxicity, resulting in severe and often irreversible renal failure. Several recent studies have investigated the ability of Spirulina to protect rats from cisplatin-induced nephrotoxicity. In one of these studies S. fusiformis was given orally at doses of 500, 1000, or 1500 mg kg body weight from 2 days before until 3 days after the injection of cisplatin.18 Administration of this alga was associated with marked amelioration of the cisplatin-induced changes in kidney morphology and significant, dose-dependent reduction of markers of renal dysfunction, such as serum creatinine and blood urea nitrogen. In addition, Spirulina reduced lipid peroxidation in the kidney and partially reversed the cisplatin-induced decrease in the levels of reduced glutathione and the activity of the antioxidant enzymes SOD and catalase.
Indicating that such cells could account for the high-level expression of immune accessory molecules on B cells of patients with active disease. An increased serum level of soluble CD154 was also reported in SLE and RA in correlation with the relevant autoantibodies and with disease activity. Anti-CD154 antibody therapy prevents autoantibody production and renal immune complex deposition in lupus nephritis, indicating that disruption of this pathway could be a beneficial treatment in SLE (49). Clinical trials are under way (50).
Historically, most candidates have end-stage diabetic nephropathy and receive simultaneous kidney and pancreas (SPK) grafts. Ever-increasing waiting times for pancreatic grafts, however, have persuaded many patients who have available living donors to choose to undergo living donor kidney transplantation and to proceed with listing for pancreatic transplantation if the kidney functions well for at least 6 months (this approach is termed pancreas after kidney PAK ). Given the significant morbidity Figure 10-1 Implantation of a pancreaticoduodenal graft into the right iliac fossa. Our usual technique is to perform a side-to-side duodenojejunostomy to an adjacent loop of small intestine. Other surgeons use a Roux-en-Y duodenojejunostomy. Most transplant surgeons have abandoned the duodenocystostomy anastomosis because of complications related to exit of the pancreatic exocrine Juice through the bladder. If kidney transplantation is also performed, the kidney is implanted into the left...
Another vasoconstrictor, endothelin, is a peptide that can be released by damaged vascular endothelial cells of the kidneys as well as by other tissues. The physiologic role of this autacoid is not completely understood. However, endothelin may contribute to hemostasis (minimizing blood loss) when a blood vessel is severed, which damages the endothelium and releases this powerful vasoconstrictor. Plasma endothelin levels also are increased in certain disease states associated with vascular injury, such as toxemia of pregnancy, acute renal failure, and chronic uremia, and may contribute to renal vasoconstriction and decreased GFR in some of these pathophysiologic conditions.
Secondary complications of unilateral trunkal edema, such as unilateral jaundice, may occur when the accumulated fluid is ascitic in origin (56). This phenomenon occurs because ascitic fluid is high in albumin concentration and because bilirubin binds to albumin. Subcutaneous dissections of ascitic fluid in which the albumin concentrations is high, tend to be brightly jaundiced if the serum bilirubin concentrations are elevated whereas collections of edema fluid in patients with heart disease or nephrosis, in which the albumin concentrations are low, do not. Edema associated with burns or allergic reactions have a high albumin concentration and appear jaundiced. Indeed, this is the basis of the histamine wheal test for jaundice, in which wheals induced by subcutaneous injections of histamine appear jaundiced whereas the surrounding tissue does not. Eosinophilic peritonitis of unknown cause may be associated with chronic ambulatory peritoneal dialysis (60), and may be rapidly corrected...
Effect of Arterial Pressure on Urine Output The Pressure Natriuresis and Pressure Diuresis Mechanisms
Even small increases in arterial pressure often cause marked increases in urinary excretion of sodium and water, phenomena that are referred to as pressure natriuresis and pressure diuresis. Because of the autoregulatory mechanisms described in Chapter 26, increasing the arterial pressure between the limits of 75 and 160 mm Hg usually has only a small effect on renal blood flow and GFR. The slight increase in GFR that does occur contributes in part to the effect of increased arterial pressure on urine output. When GFR autoregulation is impaired, as often occurs in kidney disease, increases in arterial pressure cause much larger increases in GFR.
Although there is a need for more accurate prediction of the absorbed doses, treatment with all mIn-, 90Y- or Lu-labelled SS analogs has been associated with considerable symptomatic improvement with limited side effects that are mainly related to kidney function.50 (See also Chapter 7).
About 100 A.D., Rufus of Ephesus noted hardened kidneys in patients who produced little urine, suffered no pain, and sometimes developed dropsy This description could certainly be chronic glomerulonephritis. Around 1000 A.D., Avicenna, an Arab who authored perhaps the most famous medical text ever, mentioned patients with chronic nephritis. Gulielmus de Sal-iceto's treatise, written in the mid-thirteenth century but not published until 1476, discusses dropsy, scanty urine, and hardened kidneys. This is chronic kidney disease - very likely glomerulonephritis.
Mannitol infusions have up to an 80 response rate and have been shown to increase survival in FHF patients without renal failure.23,28 Serum osmolality should be measured frequently and maintained at 300-320 mOsm. Mannitol should be withheld if osmolality is 320 mOsm or higher, if renal failure occurs or if oliguria and rising serum osmolality develop simultaneously. Repeated administration of mannitol may reverse the osmotic gradient. Thus, mannitol should be discontinued if the ICP does not respond after the first few boluses.
ESS is a leftover term from the days when T4 levels were measured using tests that sometimes failed to provide an accurate picture of the free T4 levels. When patients were severely ill, such as in a coma in the intensive care unit or on a ventilator in the burn unit, various body factors were released that made some thyroid tests look strange. In these people, the free T4 by equilibrium dialysis test showed that the thyroid hormone levels were usually normal. Unless you're ill enough to be in an intensive care unit or on a ventilator, absolutely none of this applies, and it does not account for any TSH test abnormalities or any other thyroid test abnormalities.
The renal-pressure natriuresis mechanism is impaired, and the kidneys will not excrete adequate amounts of salt and water unless the arterial pressure is high or unless kidney function is somehow improved. In other words, if the mean arterial pressure in the essential hypertensive person is 150 mm Hg, acute reduction of the mean arterial pressure artificially to the normal value of Experimental studies in obese animals and obese patients suggest that impaired renal-pressure natri-uresis in obesity hypertension is caused mainly by increased renal tubular reabsorption of salt and water due to increased sympathetic nerve activity and increased levels of angiotensin II and aldosterone. However, if hypertension is not effectively treated, there may also be vascular damage in the kidneys that can reduce the glomerular filtration rate and increase the severity of the hypertension. Eventually uncontrolled hypertension associated with obesity can lead to severe vascular injury and complete...
This type of acidosis results from a defect in renal secretion of H+ or in reabsorption of HCO3-, or both. These disorders are generally of two types (1) impairment of renal tubular HCO3- reabsorption, causing loss of HCO3- in the urine, or (2) inability of the renal tubular H+ secretory mechanism to establish a normal acidic urine, causing the excretion of an alkaline urine. In these cases, inadequate amounts of titratable acid and NH4+ are excreted, so that there is net accumulation of acid in the body fluids. Some causes of renal tubular acidosis include chronic renal failure, insufficient aldosterone secretion (Addison's disease), and several hereditary and acquired disorders that impair tubular function, such as Fanconi's syndrome. Chronic Renal Failure. When kidney function declines markedly, there is a buildup of the anions of weak acids in the body fluids that are not being excreted by the kidneys. In addition, the decreased glomerular filtration rate...
Another pair of pharmaceutical products was introduced in 1963. Indomethacin counteracts gouty attacks, and it gradually superseded phenylbutazone. Allopurinol lowers uric acid like probenecid but by a different mechanism. Like probenecid, allopurinol lacks value against gouty attack, but it is effective during renal failure and is convenient.
The most common porphyria with cutaneous manifestations is symptomatic porphyria or porphyria cutanea tarda (PCT). Patients with this disorder usually are older than 40 years, drink heavily, and are unaware that they are sensitive to sunlight. Diabetes mellitus is found in 25 of cases of PCT 90 or more have hepatic siderosis. Nearly all untreated patients with PCT show abnormal bromsulfophthalien retention. PCT is relatively uncommon in women who are not taking estrogens. A PCT-like illness has been observed in patients undergoing hemodialysis for chronic renal failure. PCT also has been linked to several toxins ( e.g., hexachlorobenzene and dioxin). Hepatitis C infection has been implicated as a possible etiologic agent in some patients and may be related to some of the associated liver disease. HIV-positive patients have an increased incidence of PCT associated with hepatitis C infection.
A latent mushroom preparation can be activated when the ionic strength of the buffer is decreased, for instance through dialysis (Fig. 12.5). Decrease of ionic strength stabilises intra-molecular ionic interactions, which may, therefore, be postulated to play a role in this activation process. Other factors that In addition, the pH in the micro-environment of PPO determines the activity of PPO. A decrease of the pH from 6.5 to 4.5, via dialysis, considerably activates latent mushroom PPO, measured against a non-dialysed control (Fig. 12.6). Kenten (1957) and Ichishima et al. (1984) described a similar activation for resp. broad bean and Aspergillus-tyrosinase. The latter also postulated the attachment of a protease to the latent PPO at low pH (see below for proteolytic activation of PPO).
Another variable that might be significant to assess the androgen status in old age is plasma levels of SHBG. Its levels increase even with healthy aging, possibly due to a decrease in growth hormone (GH) production and an increase of the ratio of free estra-diol over FT 75 . Vermeulen and co-workers could demonstrate that the FT value calculated by TT SHBG (according to a second-degree equation following the mass action law) as determined by immunoassay appears to be a rapid, simple, and reliable indicator of BT and FT, comparable to FT values obtained by equilibrium dialysis 165 . An easy-to-use free calculator of calculated FT and BT can be found on www.issam.ch. So, determination of values of T and SHBG might provide a reasonable index of the androgen status in an aging person. BT is also a rather reliable index, but it should be mentioned that direct FT assays using a T analog do not yield a reliable estimate of FT 165 . What is a low T level
Habituation takes place also in the central nervous system of mammals. By monitoring in vivo the release of dopamine in different brain areas of rats using the micro-dialysis technique, it has been found that dopamine in the nucleus accumbens shell is also involved in the habituation phenomenon. Thus in rats, after a feeding of an unusual palatable food, such as Fonzies or chocolate, extracellular dopamine increases in the nucleus accumbens shell, but a second meal of the same food given after either 2 hours, 1 day, or 3 days fails to activate dopaminergic transmission. In addition, the delayed increase after an aversive gustatory stimulus (like quinine solutions) underwent habitua-tion after a single trial. Recovery of responsiveness and of habituation takes place 5 days after the last exposure to the stimulus. In contrast, exposure to Fonzies or chocolate or quinine increases the extracellular dopamine in the pre-frontal cortex, and a second exposure after 2 hours is able again to...
Transfer the aqueous phase to a Centricon 30 microconcentrator and concentrate by spin dialysis to yield a final volume of 25 50 pL. 5. Make the volume up to 2 mL with 1 mM EDTA and repeat the spin dialysis step until the residual volume of the mixture is approx 25 pL. This step is repeated with another 2 mL of 1 mM EDTA.
The structure and function of the GU tract can be assessed by a variety of techniques. Simple screening methodologies include the history, with particular attention to urinary incontinence, urine volumes and urine character (bloody or foamy), as well as, the urinalysis. Creatinine clearance is a simple, cost-effective screen of kidney function. Structural abnormalities can be investigated by several tests, including ultrasound, IVP, CT scan and MRI. Retrograde studies may be useful for structural and functional evaluation of the bladder and ureters. Cystoscopy may be necessary to evaluate hematuria in the long-term survivor. In patients with late-onset hemorrhagic cystitis, cystoscopy may be useful to assess the degree of mucosal damage and to evaluate the etiology of the hematuria. Patients with late-onset hemor-
Normal or increased parathyroid function (renal failure, vitamin D deficiency) Protein-binding and anion-chelation of ionized ealeium Medications (anticalcemic and antineoplastic agents) Multifactorial (gram negative sepsis) Epidemiology and Risk Factors. Except in neonates and patients with RF, hypocalcemia is relatively rare. The most likely cause of hypocalcemia among patients presenting to an emergency room is hypomagnesemia.y Risk factors include past thyroidectomy, neck trauma, a family history of hypocalcemia, malabsorption syndromes, antiepileptic drug usage, severe liver or kidney disease (decreased 1-alpha-hydroxylation of vitamin D), and pancreatitis. The incidence of postsurgical hypoparathyroidism (usually thyroidectomy) varies with the expertise of the surgeon. y The decrease in total serum Ca during pregnancy reflects dilutional hypoalbuminemia and, for that reason, the ionized Ca concentration is unchanged. y
Johnston TD and Katz SM Special considerations in the transplant patient requiring other surgery Surg Clin North Am
Bartolomeo, R.S., Calabrese, P.R., and Taubin, H.L. Spontaneous perforation of the colon A potential complication of chronic renal failure. Am. J. Dig. Dis., 22 656, 1977. 37. Scheff, R.T., Zuckerman, G., Harter, H., et al. Diverticular disease in patients with chronic renal failure Because of polycystic kidney disease. Ann. Intern. Med., 92 2G2, 198G. 38. Dominguez Fernandez, E., Albrecht, K.H., Heemann, U., et al. Prevalence of diverticulosis and incidence of bowel perforation after kidney transplantation in patients with polycystic kidney disease. Transplant. Int., 11 28, 1998. 41. Soravia, C., Baldi, A., Kartheuser, A., et al. Acute colonic complications after kidney transplantation. Acta Chir. Belg., 95 157, 1995.
The roots of S. miltiorrhiza were proved to inhibit cellular cholesterol biosynthesis (Sun and Cai, 1989) and to have vasodilatory, hypotensive, and anticoagulant properties. They are beneficial to patients with chronic renal failure (Chung et al., 1986 Yokozawa et al., 1990). However, use of the decoction of S. Miltiorrhizae in hypertension is questionable because it induces both vasodilatation and vaso-constriction what depends on the dosage and the target vessel (Lei and Chiou, 1986a Lei and Chiou, 1986b). S. Miltiorrhiza dilated coronary vessels both at lower (3 mg ml) or higher (10 mg ml) concentrations, however, it contracted renal, femoral and mesenteric arteries at higher concentration (10.0 mg ml) only. excretion of uremic toxins such as urea and creatinine. In the eighties, magnesium lithospermate B (structure 21), a tetramer of caffeic acid, was isolated from Salviae miltiorrhizae radix and was proved to be responsible for most of the above mentioned effects that facilitate...
The urge to move or unpleasant sensations are worse in the evening or night than during the day, or may only occur in the evening or night. When symptoms are very severe, the worsening at night may not be as noticeable but must have been previously present. Likewise, RLS after drug-induced augmentation (Chapter 26) and RLS associated with renal failure may not have overt nocturnal worsening. It has been noted that RLS is worse in the evening night, and that RLS is worse on lying and sitting during either day or night (14). The nighttime worsening of symptoms with the daytime amelioration seems to occur independently of sleep deprivation or fatigue (15). In two studies, researchers have been able to separate the circadian effects from the impact of both recumbence and rest on symptoms of RLS (16). This confirms that RLS has a true circadian pattern and does not occur in the evening night just because people are less physically active at night. This often results in sleep deprivation,...
Under certain conditions bacteria may enter the peritoneal cavity by traversing the intact intestinal wall. Schweinburg et al demonstrated that in dogs uC-labeled E. coli passed from the bowel into the peritoneal cavity after the introduction of hypertonic solutions into the peritoneum (6). A similar mechanism may explain the enteric bacterial peritonitis which frequently complicates patients undergoing peritoneal dialysis. tion, specific disorders of the GI tract, such as intestinal or biliary obstruction or portal hypertension, may all give rise to BT. Clearly, bacteria may leave the intestinal lumen by passing between the tight junctions of mucosal cells or via transcellular passage directly through intact mucosal cells. BT of different degrees of severity may result in different degrees of bacterial escape to the mesenteric lymph nodes, to portal venous blood, to liver tissue and to the systemic blood. The entry of bacteria, predominantly Staphylococcus aureus, Staphylococcus...
Neonates These babies are often very sick because the coarctation is usually severe and the anastomotic circulation may be minimal at this stage. Clinical diagnosis is confirmed by echocardiography, which will also pick up any other cardiac pathology. The left ventricle may be hypertrophied with poor function and patchy ischaemic necrosis pulmonary oedema and renal failure are common. Prostaglandin infusion to maintain patency of the ductus arteriosus is necessary,
S. pneumoniae is the most common causative organism of community-acquired bacterial meningitis in the adult. Pneumonia and acute and chronic otitis media are important antecedent events. Chronic disease, specifically alcoholism, sickle cell anemia, diabetes, renal failure, cirrhosis, splenectomy, hypogammaglobulinemia, and organ transplantation are predisposing conditions for pneumococcal bacteremia and meningitis. The pneumococci are a common cause of recurrent meningitis in patients with head trauma and cerebrospinal fluid (CSF) rhinorrhea. In the older adult (50 years of age and older), S. pneumoniae is likely to cause meningitis in association with pneumonia or otitis media, and gram-negative bacilli are the likely organisms to cause meningitis in association with chronic lung disease, sinusitis, a neurosurgical procedure, or a
Calcineurin inhibitors have numerous unwanted side effects, including nephrotoxicity, diabetes, hypertension, impaired lipid metabolism, and hirsuitism. Even when drug levels are kept low, significant side effects may develop. This is particularly true in the diabetic patient population where renal function may already be impaired. The incidence of chronic renal failure in nonrenal transplant recipients is an astonishing 16.5 .42 Similarly, the Edmonton group has reported that patients with underlying impaired renal function can experience accelerated nephrotoxicities even when low doses of tacrolimus are used.33 This underscores the appealing and essential nature of a calcineurin inhibitor-free immunosuppressive regimen, particularly for islet transplantation. Nonimmune toxicities are also observed with sirolimus in islet recipients. These include mouth ulceration, peripheral edema, dyslipidemia, weight loss, leukopenia, ovarian cysts and anemia. While not directly nephro-toxic...
Are needed to achieve high protein concentrations. Osmotic pressure dependent microdialysis (SaulandDon, 1984 Ceschini etal., 1996 Zhang and Hjerten, 1997), dialysis against a hygroscopic material such as Sephadex or polyethylene glycols (Middaugh and Volkin, 1992), solvent evaporation by vacuum or nitrogen flow (Rothstein, 1994), and precipitation by salts or solvents are among the procedures used. Selective protein precipitation with an inert agent such as polyethylene glycol 8000 provides a measure of the thermodynamic activity of the protein in equilibrium with PEG precipitates, and extrapolation of the logarithmic plot of the amount of soluble protein versus PEG concentration to zero PEGyields an estimate of the aqueous solubility of proteins in a quick and simple way (Middaugh et al., 1997). Though these micromethods have the advantage of requiring small amounts of protein, they may not be scalable or may lead to protein destabilization or phase changes that could give...
ALF is defined as a dramatic clinical syndrome in which a previously normal liver fails within days or weeks. Three subgroups of ALF can be distinguished, hyperacute, acute, and subacute liver failure. Despite the frequent occurrence of cerebral edema and renal failure in patients with hyperacute liver failure, prognosis without transplantation is relatively good. Survival rates in patients with acute and subacute liver failure, however, are at best 15 (20,21). The etiology of ALF shows marked worldwide variation in underdeveloped countries viral causes predominate, whereas drug-induced hepatotoxicity and seronegative hepatitis predominate in most countries of the Western world (22). To this day, the management of these varying clinical scenarios is essentially supportive. It aims to identify and remove the insult that led to destruction of the liver, whereas preventing associated complications, such as acute renal and respiratory failure, bleeding diatheses, severe sepsis, cerebral...
In fact, SBP frequently determines the occurrence of other complications of cirrhosis, such as gastrointestinal hemorrhage, hepatic encephalopathy, renal failure, and the hepatorenal syndrome (9-12). It has been observed that bacterial infections increase the risk of rebleeding during the early days of hospitalization in cirrhotic patients with gastrointestinal bleeding (13,14). On the other hand, 32-44 of patients show hepatic encephalopathy at the time of the diagnosis of SBP (9,10,12). Finally, the development of renal dysfunction occurs in one-third of patients with SBP and has been demonstrated to be the most important independent predictive factor of mortality during hospitalization in patients with SBP (10,15).
The presentation of the decubitus ulcer, in most cases, is a clearly defined wound associated with limited tissue necrosis in proximity to a boney prominence. Occasionally, the decubitus ulcer development may become complicated by the formation of extensive areas of infection and necrosis (often limb- or life-threatening) that lay outside of the original zones of soft-tissue pressure injury. Two particular examples of this situation are observed when an infected decubitus ulcer leads to the development of necrotizing faciitis and necrotizing cel-lulitis. In most of these cases, we observe these complex infectious wounds developing in patients with compromised immune response (immunosuppressive therapy, acquired immunodeficiency syndrome, renal failure, diabetes) or as complications of absent protective sensation (e.g., spinal cord injury, diabetic neuropathy, paralysis) where the decubitus development and deterioration have gone unchecked. While these situations do not appreciably...
Protide synthesis is altered with albumin level reduction, alteration of coagulation factors and a fall in immunoglobulins. The effects of obstruction extend to detoxification activity of the liver with decreased excretion of the substances metabolised in the liver. The systemic effects of biliary obstruction are evident with regard to cardiovascular activity, renal function, and the coagulation process. Jaundiced patients are more susceptible to developing postoperative shock consequent to depression of left ventricular activity and decreased peripheral vascular resistance as well as plasmatic volume. Renal function is impaired by hyperbilirubinemia, due to the reduction of renal perfusion related to cardiac pump impairment and to renal causes themselves, as natriuretic effects of bile salts and direct parenchymal toxicity of endotoxaemia renal failure in jaundice patients has a mortality that can reach 70 1 . Deprivation of bile at the intestinal level interferes with vitamin K...
After this famous transplant, however, Barnard was often on the leading edge of organ transplantation. Even before the heart transplant, he performed the first kidney transplantation in Africa and, later on, the third heart-lung transplantation in the world. He also performed the world's first heterotopic transplant (sometimes called the piggy-back transplant ), an operation during which a donor heart is placed next to the patient's heart and the two work in parallel. This operation, which is still used today, was developed for circumstances when the donor heart was either questionable or too small.
To summarize, the mechanism for forming a dilute urine is to continue reabsorbing solutes from the distal segments of the tubular system while failing to reab-sorb water. In healthy kidneys, fluid leaving the ascending loop of Henle and early distal tubule is always dilute, regardless of the level of ADH. In the absence of ADH, the urine is further diluted in the late distal tubule and collecting ducts, and a large volume of dilute urine is excreted.
Renal failure * Rifampicin, isoniazid and pyrazinamide are safe and can be given in normal dosages. Patients with severe renal failure should receive pyridoxine with isoniazid to prevent peripheral neuropathy. * The safest regimen to give to patients in renal failure is 2HRZ 4HR.
Fluid management in FHF patients requires maintenance of a balance to avoid fluid overload as well as dehydration, as multiorgan failure develops. Central pressure monitoring, cardiac performance and peripheral resistance are determined using a pulmonary artery catheter. Renal failure can occur in the face of pulmonary edema and peripheral vascular collapse strict monitoring of fluid balance is therefore required. Furthermore, cerebral edema and intracranial hypertension require careful fluid administration to avoid expansion of the intravascular space and exacerbation of cerebral edema. One should take into account hidden fluid administration, including fluid used as a vehicle for administering intravenous medications, fluid given to maintain catheter patency, insensible losses and third spacing. Measured fluid balance should be verified twice daily by body weight determinations to ensure accuracy of the replacement estimates. Fluid replacement strategies should anticipate changes in...
Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College 1 Xian Nong Tan Street
The genus Salvia has a variety of more than one hundred species distributed in several regions in China. Thirty of them are used as traditional and folk medicines (Huang 1991). The dried root of Salvia miltiorrhiza, called Danshen, is one of the most well known traditional Chinese medicines among these species. It has the effect of promoting blood circulation and removing stasis, and is widely used for the treat ment of coronary heart diseases, cerebrovascular diseases, hepatitis, hepatocirrhosis, chronic renal failure, dysmenorrhea and neurasthenic insomnia. The chemical constituents of S. miltiorrhiza have been studied for more than fifty years. But the studies have mainly been focused on the lipophylic diterpenoid quinones. According to traditional Chinese medicinal prescriptions it is used as a decoction. Since the seventies injections of Danshen have been used for the treatment of angina pectoris, myocardial infarction and various types of hepatitis. So there should still be...
Male Wistar rats, 200-250g, 6 in each group, were anaesthetised with chloral hydrate (400mg kg). A guide cannula was inserted into the hippocampus CA2 region using standard stereotaxic techniques (A P -4.3 mm M L 4.0 mm D V -3.0 mm) of Paxinos and Watson11. The dialysis experiments commenced 48h post operation. The probe was connected to a micro-infusion pump (Infusion syringe pump 22, Harvard apparatus) and continuously perfused at l min with Ringer solution containing 145 mM NaCl 4 mM KCl 1.3 mM CaCl2 buffered to pH 7.2 with phosphate buffer.
Lanza and his associates set out not only to grow kidneys in culture but also to show the value of therapeutic cloning as applied to organ transplants. For example, a patient suffering from kidney failure currently has two options kidney dialysis, which is costly and cumbersome, or a kidney transplant. Most kidney transplants are allografts therefore the patient has to take immunosuppressants for the remainder of his or her life. Moreover (as shown in the table on page 61), even with immunosuppressants, the long-term patient prognosis is not good. Therapeutic cloning offers a third alternative Clone the patient, allow the
Splicing reactions have very specific buffer requirements, in particular the optimal concentration ranges for monovalent and divalent cations are narrow and depend on the pre-mRNA substrate used. After most purification steps, it is necessary to alter the ionic composition of the fractions prior to assay. It is seldom possible simply to dilute a fraction to lower its salt concentration, unless it is highly active to begin with. Dialysis is usually employed. When dealing with multiple fractions, it is convenient to dialyse small aliquots of each fraction in a multiple dialysis apparatus (BRL, Pierce, Spectrum). If fractions need to be concentrated, this can be done by ultrafiltration in centrifugal units (Amicon) or by precipitating the protein with 80-90 ammonium sulphate. (c) Gel filtration chromatography is a useful method but a drawback is that it causes significant dilution of the purified fractions and this is often accompanied by loss of activity (see Section 4.1.1). Gel...
May be detected by soft tissue radiographs, computerized tomography (CT) scan, or magnetic resonance imaging however, none of these radiographic procedures are more specific or sensitive than physical examination revealing crepitus in soft tissue.5 However, radiographic procedures are particularly helpful to demonstrate gas in deeper tissue such as the uterus. Rapidly-developing signs of systemic toxicity include tachycardia, low-grade fever, and diaphoresis, followed by shock and multiorgan failure. In one study shock was present in 50 of patients presenting and of those who developed shock at some point in their hospitalization, 40 died, compared with 20 in the group as a whole.6 Bacteremia occurs in 15 of patients and may be associated with brisk hemolysis. One patient has been described wth a decrease in the hematocrit from 37 to 0 over a 24-h period.7 Subsequently, despite transfusion with 10 units of packed red blood cells over a 4-h period, the hematocrit never exceeded 7.2 .7...
For the purposes of epidemiological studies, the definition of severe CAP as CAP needing ICU admission is adequate. In practical management terms, however, a more detailed method of assessment is needed. Severe CAP is almost always a multiorgan disease and patients with severe CAP at presentation will either already have, or will be rapidly developing, multiple organ failure. It is important that respiratory and other front line physicians appreciate this aspect of the disease. Apparent stability on high flow oxygen can rapidly change to respiratory, circulatory, and renal failure. Progressive loss of tissue oxygenation needs to be anticipated, recognised quickly, and rapid action taken to prevent its progression to established organ failure.
Although the early survival of allogeneic transplants has increased dramatically in recent years, the incidence of chronic rejection has not decreased appreciably (20). Chronic rejection occurs in all types of solid-organ transplants. In heart transplants, it is characterized by progressive coronary artery disease (21,22) in lung transplants, as bronchiolitis obliterans (5,23). Liver allografts appear to be less affected by chronic rejection, but when it does occur, biliary epithelium is lost leading to hyperbilirubinemia and graft failure (24). Chronic allograft nephropathy is the general term used to describe a slow deterioration of renal allograft function that is characterized histologically by interstitial fibrosis, tubular atrophy, widespread arterial intimal fibrosis, and global glomerulosclerosis (25,26). In many respects, the tissue damage seen during chronic rejection mirrors the pathophysiologic processes seen in other non-transplant-associated disorders (5,26).
Although donor selection increases the risk of allogeneic HSCT in patients with recent-onset type 1 diabetes, the balance of risk versus benefit to HSCT still may be shifted in favor of HSCT. Identification of patients with increased risk for developing severe complications would increase the perceived benefit of allogeneic HSCT for instance, specific genetic polymorphisms are associated with increased risk of proliferative retinopathy (48), nephropathy (49), and coronary heart disease (50). Furthermore, demonstration of islet regeneration and consequent resumption of full metabolic control after allogeneic HSCT would favor allogeneic HSCT. Although differentiation of donor hematopoietic stem cells into pancreatic islets is unlikely, allogeneic HSCT in mice led to homing and engraftment of donor bone marrow-derived endothelial cells in the exocrine pancreas (51). Increased angiogenesis may promote autologous islet regeneration, particularly if therapy with growth factors known to...
At the early stage of hypovolemia, perfusion of the brain is maintained by decreased perfusion of other organs. Reduced perfusion of the kidneys results in reduction in the glomeru-lar filtration rate, oliguria, and increased blood urea concentration (41). This prerenal azotemia can be corrected by administration of fluids that restore the blood volume and renal blood flow. Without treatment of the underlying disease, microvascular endothelial injury continues. If the patient's condition progresses to the development of hypotensive shock, severe renal ischemia may cause acute tubular necrosis and anuric acute renal failure.
The strategy of both HTLV viruses in the absence of intravenous drug usage and rapid movements of peoples was very close to the gentle pathogen persuasion. Both viruses persist with little damage to their host by replicating very slowly while being passed vertically or between adults as an STD. Being poorly transmitted from cell to cell and individual to individual favors the gentle character, but another feature is that they have mechanisms to cause the T-cells to replicate. In AIDS, depletion of T-cells in long-term HIV infection occurs, but this does not occur in HTLV. This allows more opportunities for the virus to be transmitted between humans. These viruses are poorly transmissible and transmission from male to female is rare and the transmission from female to male is very slow (at least for HTLV-I). Though it is passed presumably in the same three ways that HIV is passed to the neonate i.e., in utero, perinatally by blood-to-blood transfer, and (predominately) postnatally via...
Regarding the ODN-based strategy as gene therapy, one of the major concerns is nonspecific effects, particularly those of phosphorothioate-substituted ODNs. This concern is not only related to the antisense and decoy strategies, but also to all ODN-mediated therapy. Non-sequence-specific inhibition may operate through blockade of cell surface receptor activity or interference with other proteins.29 At the same time, ODNs containing GC dinucleotides may bring about immune activation.30 In addition, sequence-specific binding of nontranscriptional factor proteins to ODNs reportedly results in nonspecific effects of ODN-based gene therapy.31 Moreover, Burgess et al. reported that the antiproliferative activity of c-myb and c-myc antisense ODNs in VSMC is caused by a non-antisense mechanism.32 To overcome these issues, careful controlled experiments must be performed to eliminate the potential nonspecific effects of ODN-mediated therapy. For gene therapy using an ODN-based strategy, the...
Type 1 diabetes is characterized by insulin deficiency secondary to progressive T-cell-mediated destruction of insulin-producing pancreatic p cells within the islets of Langerhans. Clinical therapy is supportive blood glucose is controlled by insulin injections, diet, and exercise. Nevertheless, homeostatic maintenance of blood glucose through shifting physiologic conditions is clearly unrealistic, and long-term complications of chronic hyperglycemia, including retinopathy, peripheral neuropathy, stroke, cardiovascular disease, and nephropathy, frequently develop. Although tight glycemic control delays the development of chronic complications (16), the incidence of acute, life-threatening episodes of hypoglycemia is more than three times higher with this treatment (17).
Inhibitors of ACE also constitute a fundamental therapeutic strategy in cardiovascular disease i.e., in heart failure, hypertension, as well as in diabetic and nondiabetic nephropathy. However, the response to these inhibitors varies and the role of the so-called insertion deletion (I D) polymorphism of the ACE gene (32), denoting the presence (I) or absence (D) of a 287-bp element in intron 16 on chromosome 17, has been evaluated with relation to pharmacogenetics. Whereas the presence of the D allele has been linked to higher ACE activity (33) as well as increased mortality in heart failure (34), it has been found that the ACE DD genotype appears to favor a beneficial effect not only of ACE inhibitors, but also in response to P-adrenoceptor blockers (35).
The efficacy of cefotaxime in patients with SBP has been evaluated in different studies (17-19). The first investigation consisted in a randomized controlled trial comparing cefotaxime (2 g every 4 h in patients without renal failure) versus the combination of ampicillin plus tobramycin in a large series of cirrhotic patients with SBP or other severe bacterial infections (17) (Table 11.2). Cefotaxime was more effective in achieving the resolution of SBP than ampicillin plus tobramycin, and, whereas no patient treated with cefotaxime developed nephrotoxicity or superinfections, these two complications occurred in more than 10 of the patients treated with ampicillin plus tobramycin. Following this study, cefotaxime has been considered to be the antibiotic of choice in the empiric treatment of SBP in cirrhotic patients.
In small percentages of Wilms' tumors, specific constitutional syndromes have been identified. Of particular note are the WAGR (Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome, which is found in about 1 of patients with Wilms' tumor, and the Denys-Drash syndrome (DDS) (Wilms' tumor, genitourinary anomalies, early onset renal failure, and predisposition to germ cell tumors), which is reported in a similarly small percentage (3 ) of patients with Wilms' tumor (Drash et al., 1970 Pendergrass, 1976). For both WAGR syndrome and DDS, germline mutations of chromosome 11p13 have been identified. In addition, demonstration of somatic mutations in chromosome 11p13 of some 40 of patients with Wilms' tumor who lacked germline mutations and or LOH at 11p have further implicated this sequence in tumorigenesis (Koufos et al., 1984 Orkin et al.,1984 Kaneko et al., 1991). While it is thought that these mutant proteins behave as dominant negatives, the remaining...
Several polysaccharide fractions isolated from S. platensis have showed a broad-spectrum antiviral activity, characterized by a strong inhibition in vitro of human viruses such as HCMV, HSV-1, HHV-6 and HIV-1. The ongoing biochemical analysis of these preparations (intracellular and extracellular polysaccharides) indicates the presence of spirulan-like substances, in addition to a small group of other uncharac-terized polysaccharides and possibly protein components. The highest inhibition was observed with the extracellular fractions, which presented a therapeutic index of209.2 for HCMV. The extracellular fraction was isolated from culture supernatant by centri-fugation of culture broth, liophylization and dialysis against deionized and ultrapure water. Apparently, this is the first description of antiviral activity of substances isolated from the extracellular fraction of Spirulina.19
Hebb's visionary notion in 1949 of reverberating cell assemblies was an important beginning point for a neurodynamic emphasis. Neurodynamics is thus a relatively new discipline, addressing how brain activation changes over time. The neurodynamic perspective is complementary to traditional perspectives that emphasize structures, connectivities, and neuromodulators in that it seeks to understand the time-dependent changes that occur in neuronal populations (neural network models, by comparison, do not reference time). The behavior of these time-sensitive populations are typically measured by EEG, single unit recordings (inso far as these indirectly imply population behaviors), or magnetoencephalography (MEG) and also in dynamic neurochemical measures, such as in vivo dialysis. Neurodynamics attempts to correlate these signatures from various measurement modalities with behavioral and subjective measurements, focusing on the challenge of modeling context-dependent and sequential...
When comparing men and women, several factors have been examined to determine the outcome after surgery. These include age the presence of risk factors like diabetes, hypertension, and renal failure body size as it relates to the size of the blood vessels (especially the coronary arteries) and race (Caucasian or non-Caucasian). Contributing Factors When undergoing CABG, women are more likely than men to be diabetic or hypertensive or to have pre-existing kidney failure or be experiencing congestive heart failure. They are also statistically more likely to have advanced symptoms of coronary artery disease like severe angina,
The primary use of MRA of the circle of Willis is to evaluate the presence of an unruptured aneurysm that came to medical attention due to the incidental discovery of this lesion by MRI. The use of MRA as a screening test to identify congenital berry aneurysms before rupture in groups at risk (e.g., adult polycystic kidney disease, family history of an aneurysm) would also be desirable. Several studies have shown the sensitivity of MRA to detect congenital aneurysms 5 mm or greater is approximately 90 percent.y , y Figure 23-16 shows an aneurysm detected with MRA. Aneurysms smaller than 5 mm do rupture, although the incidence is reduced. MRA is considered an accurate noninvasive screening test for patients at risk for aneurysms. DSA is required for preoperative planning.
Many commercially available polymers contain impurities which exhibit adverse biological activities and thus may contribute to failure of an allo- or xenograftic implant. These impurities are of several kinds, including monomers, catalysts, and initiators, which are present in synthetically derived polymers. They can usually be removed via dialysis due to their small molecular size. Pyrogens represent the second kind of impurities. They belong to a group of natural compounds of certain gram-negative bacteria (cell wall) and cause fever or sometimes even death when injected intravenously. Chemically, they are represented by a variety of complex lipopolysaccharides with highly hydrophobic character.57 The third group, mitogens, is a rather less defined class of organic compounds which activate many cell types (including lymphocytes, fibroblasts). Their action leads to cell proliferation and to subsequent production of cytokines involved in inflammatory reactions and implant rejection,...
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