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Biomedical subjects

E A Friedman

Publications and source records attributed to E A Friedman.

At least 163 records · Page 9Linked to original sources

Renal failure in diabetes: a substantive problem in provision of health care.

Approximately 5.8 million people in the United States have been diagnosed by a physician as being diabetic, and an additional 4 to 5 million people have undiagnosed diabetes. Although the incidence of diabetes appears to be declining from a peak of 300 per 100,000 population in 1973, to 230 per 100,000 in 1981, its prevalence continues to rise, due to a 19 percent decline since 1970 in deaths caused by diabetes. In 1982, 34, 583 deaths were attributed to diabetes, resulting in diabetes being ranked as the seventh leading underlying cause of death. Medical and surgical complications of diabetes due to macro- and microvascular disease result in 5,800 new cases of blindness, 4,500 perinatal deaths, 40,000 lower extremity amputations and 3,000 deaths due to diabetic coma (ketotic and hyperosmolar) and at least 4,000 new cases of end-stage renal disease. Hyperglycemia is a major if not sole determinant of diabetic glomerulopathy. The exact mechanism underlying diabetic vasculopathy is under intensive study. Experiments in the induced-diabetic rat and dog suggest that small vessel injury may--under defined circumstances--be associated with the polyol (sorbitol) pathway of glucose metabolism, myoinositol deficiency, capillary hypertension, plasma hyperviscosity, stiff erythrocytes, elevated circulating thromboxane, and platelet-derived growth factor(s). As yet, no single hypothesis fits these seemingly disparate pieces together into a unified formulation of the genesis of diabetic complications. Clinical experience sustains the contention that a functioning kidney transplant proffers the uremic diabetic younger than age 60 a higher probability for survival with good rehabilitation than does either peritoneal dialysis or maintenance hemodialysis. Diabetics treated by kidney transplantation require more than the routine preoperative and postoperative attention afforded to nondiabetic ESRD patients. During initial nephrologic evaluation, concurrent extrarenal vascular disease--especially ophthalmic, cardiovascular, cerebrovascular and in the extremities, often demands immediate attention. Inventory of co-morbid risk factors pre-transplant facilitates their management post-transplant, thereby improving chances for rehabilitation. Consultations with an ophthalmologist and podiatrist familiar with management of the uremic diabetic should be obtained prior to transplant surgery. When performed as a component of pre-transplant evaluation, coronary angiography permits identification and correction, in many patients, of potentially fatal coronary artery disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus, Type 1↗

Heterogeneous responses of human colon carcinomas to hexamethylene bisacetamide.

Primary cultures of resected human colon carcinoma were used to study differentiation agents directly on the biologically relevant cancer cells rather than on highly selected established cell lines. To achieve primary cultures which remained viable and replicating for several days, carcinomas were partly digested to epithelial organoids, which were selectively plated with high efficiency on collagen I-bovine serum albumin films in specially formulated serum-free medium. A monoclonal antibody, 29-15, was identified which binds to a cell surface epitope expressed on 16 of 21 invasive colon carcinomas of the Dukes' B2, C, or D histopathology classes, but not expressed on any of 11 noninvasive benign tumors (adenomas) at identical antibody titer. Noncytotoxic concentrations of the differentiation agent, hexamethylene bisacetamide (HMBA), induced the loss of the 29-15 epitope from HT29 colon carcinoma cells. HMBA also induced HT29 cells to lose the capacity for anchorage-independent growth with a similar dose-response curve and time course to the loss of 29-15 epitope. Twelve primary cultured human colon carcinomas exhibited differential responses when exposed to 1 to 7 mM HMBA for 7 days. Four moderately to well-differentiated carcinomas lost expression of the 29-15 epitope at each HMBA concentration. The tumor growth fraction was decreased in each tumor, with a mean decrease of 76% at 5 mM HMBA. A dose-dependent induction of nonproliferating tumor colonies, lacking [3H]thymidine labeling, occurred in three of the four carcinomas. In six other tumors, including those at less differentiated stages, HMBA induced the opposite effect: a two- to threefold increase in the tumor growth fraction at the optimal value of 5 mM HMBA, an increase in mean colony size, and no loss of the 29-15 malignancy epitope. No effects were observed in the two other carcinomas tested. Thus HMBA was able to induce growth arrest and loss of the malignancy epitope 29-15 in those carcinomas already at an advanced stage of differentiation, and to exert a growth stimulating effect on those carcinomas apparently at more immature stages.

Acetamides↗

New chemotherapeutic drug sensitivity assay for colon carcinomas in monolayer culture.

Ten previously untreated colon carcinomas were tested for chemotherapeutic drug sensitivity in primary monolayer culture. Colon carcinomas were partly digested to groups of epithelial cells which plated with a mean efficiency of 42 +/- 9% (SE) on a collagen I-bovine serum albumin substrate in serum-free medium, producing patches of tightly adherent epithelial cells. The cultured cells were judged epithelial by the presence of cytokeratins, an epithelial cell surface epitope, junctional complexes, and brush borders. Each carcinoma was plated in 40 to 60 Petri dishes (35 mm), yielding a mean of 28 +/- 8 (SE) colonies per dish (6832 +/- 1952 cells). Drugs tested in duplicate plates were mitomycin C, cisplatin, streptozotocin, and 5-fluorouracil at 0.1, 1, 10, and 100 micrograms/ml, and at 0.1, 1, and 2x the peak tolerated drug concentration in serum. Twenty-four h after plating, any nonadherent cells were removed, and the adherent tumor cells were continuously exposed to the drugs for 3 days. Each drug induced colony lysis in a dose-dependent manner in responsive tumors. Drug-resistant, cycling cells were identified by [3H]thymidine incorporation in colonies which were not lysed by drug treatment. Each of the ten carcinomas exhibited inherent resistance to one or more chemotherapy drugs within the concentration ranges clinically achievable.

Antineoplastic Agents↗

Renal syndromes in the acquired immunodeficiency syndrome (AIDS): lessons learned from analysis over 5 years.

Renal syndromes associated with the Acquired immunodeficiency syndrome include: potentially reversible acute renal failure, AIDS associated nephropathy which leads to end stage renal disease, and AIDS developing in patients who are being treated by maintenance hemodialysis. The longitudinal study of 95 patients with AIDS and various forms of renal syndrome at two urban institutions indicates that both acute and chronic renal failure is increasing yearly. While some patients with acute renal failure recover renal function and survive for prolonged period, the mortality of dialyzed patients with irreversible renal failure continues to be unsatisfactory. There is a great need for collecting data from high risk areas to analyze the results of maintenance dialysis therapy in patients with AIDS, to assess the economic impact of uremia therapy, and for long-term planning of available resources.

Acquired Immunodeficiency Syndrome↗

Tumor-promoter-enhanced destruction of noninvasive human benign colon tumor cells by cocultivated carcinoma cells.

Colon carcinoma cells are first found as microscopic foci within benign tumors or adenomas. The carcinoma must invade the adenoma which protrudes into the colon lumen before it can infiltrate the bowel wall. A quantitative model for this process has been developed in tissue culture in which human colon carcinoma cells destroy cocultivated adenoma colonies. 43 adenoma colonies were assayed by cocultivation with carcinoma cells. Constitutive secretion of the urokinase form of plasminogen activator by carcinoma cells apparently plays some role in adenoma destruction as inhibition of this protease by the competitive inhibitor benzamidine reversibly inhibited adenoma destruction (p less than 0.01). Elevation of plasminogen activator secretion by addition of the tumor promoter 12-tetradecanoylphorbol-13-acetate significantly enhanced the destruction of colonies cultured from tubular adenomas with only mild dysplasia (p less than 0.025) and from villous, villotubular and tubular adenomas with moderate to severe dysplasia (p less than 0.0005).

Adenoma↗

Ultrasonographic diagnosis of incompetent cervix. A case report.

The ultrasonographic findings of an incompetent cervix, the protrusion of the lower pole of the fetal membranes through the dilated internal os, may precede physical changes in the cervix. The symptoms at that time may be nonspecific. As this case report indicates, we believe that action--either close observation, conservative treatment or surgical intervention--should follow the detection of this condition.

Adult↗

Risk factors for Erb-Duchenne palsy.

The risk factors associated with the occurrence of Erb-Duchenne palsy were examined. Of 22 palsies, 18 were noted among 32,088 nondiabetic gravidas (0.56 per 1000) compared with four among 380 diabetic gravidas (10.5 per 1000), a statistically significant difference. One in six infants of diabetic gravidas who sustained shoulder dystocia experienced an Erb-Duchenne palsy. The incidence of precipitate second-stage labors was high (31.8%) among those infants who experienced the neurologic complication. This labor abnormality is not preventable and may contribute, in many ways, to the neurologic complication. Although recently graduated (less than four years' postresidency training) obstetricians, especially if placed in a high-volume practice, were more likely to experience this adverse outcome than more experienced physicians, even the most senior clinicians delivered infants who were affected.

Dystocia↗

The types of renal disease in the acquired immunodeficiency syndrome.

Between January 1982 and December 1986, among the 750 patients with the acquired immunodeficiency syndrome (AIDS) who were treated at two adjacent hospitals in New York City, 78 (10.4 percent) needed evaluation for renal disorders. Reversible acute renal failure due to nephrotoxic injury, ischemic injury, or both was present in 23 patients (30 percent) (Group I). The remaining 55 (70 percent) had massive proteinuria, azotemia, or both (AIDS-associated nephropathy; Group II), and irreversible uremia developed in 43. In an additional 18 patients, all of whom had a history of intravenous narcotic drug use, AIDS was diagnosed after the initiation of maintenance hemodialysis for chronic renal failure (Group III). Survival for more than six months after the onset of chronic uremia occurred in only two subjects in Group II; all patients in Group III died within three months of the diagnosis of AIDS. Death in the patients in Groups II and III followed a syndrome of "failure to thrive" characterized by inanition unresponsive to intensive nutritional support and hemodialysis. In contrast, 8 of 17 patients with acute renal failure (Group I) and a serum creatinine concentration above 6 mg per deciliter regained renal function (serum creatinine level, less than 2.0 mg per deciliter). Four of the seven lived for 10 to 24 months, whereas the other four died of sepsis within a month. Our observations suggest that maintenance hemodialysis is not effective in prolonging life either in patients with AIDS-associated nephropathy and uremia or in patients with end-stage renal failure in whom AIDS develops during the course of maintenance dialysis. Hemodialysis may be useful in the management of potentially reversible acute renal failure in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Tissue culture model of adenoma invasion.

Colon carcinoma cells cocultured with adenoma cells were examined under various experimental conditions. Carcinoma cells were shown to have a selective advantage over adenoma cells. This advantage is enhanced by exposure to a tumor promoter.

Adenoma↗

The normal parturient's admission temperature.

The relationship between oral temperature taken at the time of admission and the duration of elapsed labor was evaluated. Onset of labor data revealed a diurnal distribution with an apogee at midnight to 2 AM and a nadir at 11 AM to noon. Temperature data ranged from 94.3 degrees to 99.7 degrees F (34.6 degrees to 37.6 degrees C). The mean temperature of 97.8 degrees +/- 0.8 degrees F (36.6 degrees +/- 0.44 degrees C) is significantly lower (p less than 0.001) than the clinical reference temperature of 98.6 degrees F (37.0 degrees C). A likely explanation is the coincidental admission time (early to late morning) and the nadir of the diurnal variation in temperature. Linear regression fitted to the data (after deletion of six hypothermic outliers) yielded the relationship: temperature = 97.8 degrees F + 0.0115 X duration of elapsed labor (temperature = 36.6 degrees C + 0.0064 X duration of elapsed labor) for which the correlation coefficient is not statistically significant.

Body Temperature↗

Variations of susceptibility to alloxan induced diabetes in the rabbit.

The variations of susceptibility to alloxan induced Diabetes in a total of seventeen rabbits was described. Our study was designed to explore dosage schedules which might improve rabbit responsiveness to and survival after alloxan treatment. A wide range of response to intravenously administered alloxan was observed. Permanent diabetes (blood glucose 350 mg/dl) was found in three rabbits after a single injection (60 mg/kg in one, 100 mg/kg in two). This effect has persisted for eight months. By contrast, two other rabbits injected with a single dose of alloxan (60 mg/kg) developed only transient hyperglycemia. Similarly, four other rabbits either did not respond or had an incomplete response after receiving a total dose of 120 mg/kg. These data suggest that there is extreme variability in individual rabbits susceptibility to the diabetogenic affects of alloxan.

Alloxan↗

Granular juxtaglomerular cell hyperplasia caused by cyclosporine.

Histologic study of kidneys from rabbits given cyclosporine (CsA) revealed a marked hyperplasia of granular cells in the juxtaglomerular (JG) apparatus, but without a significant increase in the total cell number of JG cells. The increase in granular JG cells as compared with the control group was 204% and 406% for 30 mg/kg alternate days and 30 mg/kg daily groups, respectively. The increases for the lower-dosage groups were much smaller, although the increases were statistically significant for all but the 10 mg/kg alternate-days group. Other studies suggest that sympathomimetic activity of CsA may be the mechanism involved in granular JG cell hyperplasia.

Animals↗