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Biomedical subjects

D Schwartz

Publications and source records attributed to D Schwartz.

At least 199 records · Page 11Linked to original sources

Erythropoietin therapy obviates the need for recurrent transfusions in a patient with severe hemolysis due to prosthetic valves.

Erythropoietin has been proved extremely effective in ameliorating the anemia of chronic renal failure and is currently under intensive investigation. We describe a patient with severe anemia and secondary hemochromatosis due to prosthetic valves, who has been successfully treated with erythropoietin. During 12 months' follow-up, an acceptable hemoglobin level was maintained without any need for blood transfusions; in addition, there was evidence indicating regression of hemochromatosis. This patient illustrates that erythropoietin therapy might prove beneficial for similar cases.

Anemia, Hemolytic↗

Energy demands for walking in dysvascular amputees as related to the level of amputation.

Cardiac function and oxygen consumption were measured in 25 patients who underwent amputation for peripheral vascular disease (PVD), and in five similarly aged control patients with PVD. Five patients at each of the midfoot, Syme's, below-, through-, and above-knee amputation levels and the five controls were measured at rest, normal walking speed, and maximum walking speed on a treadmill. At normal walking speed, all of the patients functioned at approximately 80% of their cardiac capacity. Normal walking speed and cadence decreased and oxygen consumption per meter walked increased with more proximal amputation. The ratio of cardiac function and oxygen consumption at normal walking speed as compared with at rest increased with more proximal amputation, and the capacity to increase walking speed and oxygen consumption lessened. Our results suggest that peripheral vascular insufficiency amputees function at a level approaching their maximum functional capacity. At more proximal amputation levels, the capacity to walk short or long distances is greatly impaired.

Amputation, Surgical↗

Immune-haemolytic anaemia (IHA) after solid organ transplantation due to rhesus antibodies of donor origin: report of 5 cases.

During a 3-year period we observed 5 patients who developed IHA after transplantation of solid organs (4 kidneys, 1 liver) due to irregular anti-erythrocyte antibodies of donor origin (4 times anti-D, once anti-D+C). The onset of acute haemolysis was usually within 2-3 weeks after transplantation; however, 1 patient developed acute haemolysis as late as day 116 after renal transplantation. The course of the clinical and serological signs (DAT positive, 'auto'-antibodies in serum and eluate) was typical and self-limited in all cases, the function of the transplanted organ was usually not affected. All patients could be managed by transfusion of antibody-compatible blood. The administration of azathioprine (1 case) did not seem to have any beneficial effect. The causative antibodies could be demonstrated retrospectively in the serum of 1 donor. Another donor had no detectable irregular anti-erythrocyte antibodies at the time of transplantation, suggesting a secondary immune response of transplanted lymphatic tissue in this case. Both recipients of a kidney from this donor developed IHA. Serum samples of the 2 other donors were not available for investigation. We suggest that a sensitive screening for irregular anti-erythrocyte antibodies in the donor's serum should be performed before any transplantation of solid organs. If such antibodies are found, organs should only be used after irradiation. However, as our experiences show, this cannot prevent IHA in each case. Once haemolysis develops, the correct serological diagnosis and the transfusion of antibody-compatible red blood cells are most important.

Anemia, Hemolytic, Autoimmune↗

Case report: acute renal failure, thrombocytopenia and nonhemolytic icterus probably caused by mefenamic acid (Parkemed)-dependent antibodies.

A 65-year-old, previously healthy man developed acute renal failure, severe thrombocytopenia and hepatic icterus after a small dose of mefenamic acid (Parkemed). Drug-dependent antibodies reacting against platelets could be identified as the most probable cause for this acute and rapidly reversible disorder. A concomitant hemolytic reaction was not observed and accordingly no drug-dependent red cell antibodies could be demonstrated. The drug-specific antibodies were found only during the acute phase using the platelet immunofluorescence test and a solid-phase immunoassay but not with the monoclonal antibody specific immobilization of platelet antigens assay. After discontinuation of the drug the patient steadily improved and fully recovered until day 22 after admission and drug removal. The clinical course strongly suggests that drug-dependent antibodies against mefenamic acid and/or its metabolites reacting by immune complex mechanism were responsible not only for the thrombocytopenia but also for the renal and hepatic failure.

Acute Kidney Injury↗

A cascade model for restenosis. A special case of atherosclerosis progression.

BACKGROUND: Restenosis presently limits the long-term success of percutaneous transluminal coronary angioplasty (PTCA) and allied treatments of atheroma. Current views of the pathophysiology of restenosis fail to explain certain important clinical features: Thrombosis, often invoked as a cause of smooth muscle proliferation, wanes before intimal thickening peaks. Prolonged antithrombotic therapy does not eliminate restenosis after PTCA. Furthermore, only a minority of angioplastied lesions develop clinically significant restenosis. METHODS AND RESULTS: We propose a cytokine-growth factor cascade mechanism of restenosis pathobiology that could explain these features of human restenosis. According to this model, PTCA would produce acute local thrombosis and/or mechanical injury that triggers cytokine/growth factor gene expression by resident macrophages and smooth muscle cells. This early acute generation of cytokines could evoke a secondary growth factor and cytokine response that might establish a positive, self-stimulatory autocrine and paracrine feedback loop that would serve to amplify and sustain the proliferative response. This multistage schema would account for the lag between injury and restenosis and the failure of chronic antithrombotic therapy to prevent this process. Human atheromata contain variable numbers of macrophages. The macrophage content of a particular lesion could determine in part propensity to develop restenosis after angioplasty, explaining why all lesions do not develop this process. CONCLUSIONS: Several experimental observations support this novel mechanistic model. Leukocytes and smooth muscle cells express genes for cytokines and growth factors, and products of coagulation and thrombosis can activate mononuclear phagocytes. Cytokines and growth factors often augment their own gene expression and induce one another, providing a potential intralesional amplification loop. Experimental atheroma and advanced human atherosclerotic lesions do not express high levels of growth-stimulatory cytokines such as interleukin-1 or tumor necrosis factor in the basal state but exhibit inducible expression in response to an injurious stimulus. Thus, cascades of autocrine or paracrine mediators whose expression is triggered by vascular injury might contribute to deranged smooth muscle behavior during restenosis.

Angioplasty, Balloon, Coronary↗

Sclerochoroidal calcification.

We studied 19 patients with sclerochoroidal calcification. The findings were bilateral in 16 patients and unilateral in the remaining three patients. The lesions, which were usually multifocal, had two characteristic appearances, plaque-like and tumorlike. Eleven patients had relatively flat, irregularly shaped, plaque-like, yellow-white lesions located between the arcades and the equator. Eight patients had more elevated tumorlike lesions, ranging up to 6 mm in height. All showed patterns on echography consistent with calcification. The calcification was often documented in both the choroid and sclera; sometimes it appeared only in the choroid, but never only in the sclera. Calcium metabolism appeared to be normal in all but two of the nine patients in whom it was investigated. Idiopathic sclerochoroidal calcification has a characteristic echographic and ophthalmoscopic appearance and may be more common than has been realized.

Aged↗

Many variable region genes are utilized in the antibody response of BALB/c mice to the influenza virus A/PR/8/34 hemagglutinin.

We have examined how many different H chain variable (VH) and kappa-chain variable (Vk) germ-line genes are used in the antibody response to the influenza virus A/PR/8/34 hemagglutinin (PR8 HA), and have assessed how the expression of individual VH and/or Vk genes contributes to the generation of specificity for the HA. A panel of 51 hybridoma antibodies that recognize two antigenic regions on the HA were compared for the sequence of their Ig H and L chain V regions. The hybridomas were obtained from 28 individual BALB/c mice that had been immunized with PR8 under a variety of primary and secondary response immunization protocols. The degree and pattern of sequence similarity suggests that 29 different VH genes drawn from seven different VH gene families, and 25 different Vk genes drawn from 12 different Vk gene families were used in this panel. Based on current estimates of the total numbers of VH and Vk genes in the mouse, this suggests that between 2.5 and 10% of the entire VH and Vk germ-line repertoires were used by these hybridomas. Despite this extensive diversity, some V genes were repetitively identified among these hybridomas, and were most often expressed in the context of specific VH/Vk combinations. Because antibodies that used identical VH/Vk combinations also usually displayed similar reactivity patterns with a panel of mutant viruses, this indicates that VH/Vk pairing can be important in establishing the specificity of antibodies for the HA.

Amino Acid Sequence↗

[Sedural toxicity].

Phenazopyridine (Sedural) is widely used in the treatment of dysuria. It is considered a benign drug and most physicians are unaware of its potential toxicity. A 24-year-old woman who developed methemoglobinemia, acute renal failure and hemolytic anemia following a single 1 g dose of the drug is presented.

Acute Kidney Injury↗

Anaesthesia and the child with HIV infection.

The frequency of AIDS in the paediatric population is growing rapidly and is expected to get worse. The anaesthetist will participate in the care of these children in the operating room and the intensive care unit with increasing frequency and must therefore have an understanding of the many manifestations of this syndrome. Children become infected with HIV by transplacental transmission from mother to fetus in over 80% of cases. Early diagnosis in infants can be very difficult. Clinical manifestations of HIV infection in children result from damage to almost every organ system. Considerations for the anaesthetist include: the effects of medications, cardiovascular dysfunction, pulmonary disease, altered metabolism, equipment preparation, choice of anaesthetic, modes of viral transmission and psycho-social issues.

Anesthesia↗

Renal toxicity of enalapril in very elderly patients with progressive, severe congestive heart failure.

We evaluated the safety of enalapril administration in 20 very old (76 +/- 7 years) patients with rapidly progressive congestive heart failure (deteriorating from New York Heart Association class 2 to class 4 on admission). They were all given increasing doses of enalapril regardless of concomitant diuretic therapy and state of hydration. Renal function deteriorated in four patients (group A) and remained unchanged in 16 (group B). The mean pretreatment serum creatinine level in group A was significantly higher than that in group B (2.4 vs 1.3 mg/dl, p less than 0.001). No patient with a serum creatinine level less than 1.9 mg/dl on admission had further impairment of renal function. Groups A and B did not differ by age, concomitant diseases (including hypertension and diabetes mellitus), or medications (including diuretics) or by in-hospital serum electrolyte concentrations and blood pressure. Renal damage was noted during the initial four days of the study and was reversible following discontinuation of enalapril. Our data suggest that enalapril can be safely administered to very old patients with rapidly progressive congestive heart failure provided that the initial serum creatinine level is below 1.9 mg/dl. In patients with a higher serum creatinine level, careful monitoring and prompt discontinuation of enalapril administration can prevent irreversible renal damage.

Age Factors↗

Hypothalamic serotonin in treatments for feeding disorders and depression as studied by brain microdialysis.

Microdialysis was used to measure changes in extracellular serotonin in the hypothalamus of rats while they engaged in feeding behavior or received drug treatments used to treat feeding disorders and affective disorders in humans. Hypothalamic serotonin increased significantly relative to controls in response to (1) intraperitoneal tryptophan after food deprivation, (2) the smell of food and eating a meal, (3) a conditioned taste aversion, (4) d-fenfluramine and fluoxetine, and (5) an amphetamine challenge test after chronic low doses of lithium. In some cases, increases correlated with nonspecific behavioral arousal were seen in the hippocampus. The results suggest that diet, drug, and behavioral therapies, alone or combined, can be used to preferentially modify hypothalamic serotonin in the control of behavioral, emotional, and endocrine problems.

Animals↗

A set of closely related antibodies dominates the primary antibody response to the antigenic site CB of the A/PR/8/34 influenza virus hemagglutinin.

Approximately 50% of the primary antibody response of BALB/c mice to the A/PR/8/34 influenza virus hemagglutinin is directed to the Cb site, one of the four major antigenic regions of the molecule. To determine the structural basis of the anti-Cb site response, we have examined the paratypic and genetic diversity exhibited by a panel of 24 primary and 4 secondary response mAb specific for this antigenic region. Reactivity pattern analysis demonstrated 20 distinct fine specificities among these antibodies, and V region gene sequence analysis showed that they are encoded by 17 different VH gene segments from 6 VH gene families and 14 different VK gene segments from 6 VK gene groups. Despite this overall diversity, many of the antibodies can be placed in a limited number of sets based on the shared expression of VH and/or VK genes. One set contains antibodies encoded by a single gene of the VK4/5 group in combination with one of two closely related genes from the J558 VH family. This set accounts for half of the Cb site-specific primary response hybridomas, indicating that the representation of the various anti-Cb site B cell specificities during the primary response to A/PR/8/34 influenza virus is not uniform. The preferential participation of B cells expressing this VH/VK combination is largely responsible for the dominance of anti-Cb site antibodies in the primary anti-hemagglutinin response.

Amino Acid Sequence↗