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Biomedical subjects

S Anderson

Publications and source records attributed to S Anderson.

At least 505 records · Page 28Linked to original sources
PubMed1985

Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass.

Micropuncture and morphologic studies were performed in four groups of male Munich-Wistar rats after removal of the right kidney and segmental infarction of two-thirds of the left kidney. Groups 1 and 3 received no specific therapy. Groups 2 and 4 were treated with the angiotensin I converting enzyme inhibitor, enalapril, 50 mg/liter of which was put in their drinking water. All rats were fed standard chow. Groups 1 and 2 underwent micropuncture study 4 wk after renal ablation. Untreated group 1 rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR) due to high average values for the mean glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In group 2 rats, treatment with enalapril prevented systemic hypertension and maintained the mean glomerular transcapillary hydraulic pressure gradient at near-normal levels without significantly compromising SNGFR and the glomerular capillary plasma flow rate, as compared with untreated group 1 rats. Groups 3 and 4 were studied 8 wk after renal ablation. Untreated group 3 rats demonstrated persistent systemic hypertension, progressive proteinuria, and glomerular structural lesions, including mesangial expansion and segmental sclerosis. In group 4 rats, treatment with enalapril maintained systemic blood pressure at normal levels over the 8-wk period and significantly limited the development of proteinuria and glomerular lesions. These studies suggest that control of glomerular hypertension effectively limits glomerular injury in rats with renal ablation, and further support the view that glomerular hemodynamic changes mediate progressive renal injury when nephron number is reduced.

Animals↗
PubMed1985

Relief of morning stiffness: a comparative study of naproxen and ibuprofen.

Morning stiffness in 75 patients with mild to moderate rheumatoid arthritis was treated with 1600 mg ibuprofen 4-times daily or 750 mg naproxen twice daily after a placebo-induced flare of this symptom. With the final daily dose of each drug administered at bedtime, both drugs significantly reduced the duration and severity of morning stiffness compared to baseline values but, on average, duration of morning stiffness tended to be shorter for naproxen patients than for ibuprofen patients. No corresponding between-drug difference was found for severity of morning stiffness.

Adolescent↗
PubMed1985

The behaviour in vitro of epidermal cells from normal and pupoid foetus mutant mouse embryos.

Pupoid foetus (pf/pf) is a recessive lethal mutation of the mouse causing epidermal hypertrophy and disorganization of peripheral sensory nerves and mesoderm. The comparative behaviour of epidermal cells from normal and pupoid foetus mutant mouse embryos was studied in vitro. Epidermal explants from the snout region of 12.5- to 13-day embryos were grown in culture for periods of up to 2 weeks. Cultures from both phenotypes were filmed using time-lapse cinemicrography for up to 3 days following explantation. Paths of individual cells were traced as they migrated from the explant, and their rate of locomotion and directional persistence were calculated. Differences in these parameters between the two phenotypes were tested statistically. The overall morphology of the cultures, and the tendency of the cells to detach from the periphery of the cell mass were also compared. The results show that, between 25 and 60 h after explantation, epidermal cells from pupoid foetus embryos move consistently more slowly than normal cells, and follow a more erratic path. This situation is reversed, however, between 16 and 25 h. This suggests that the pf mutation causes an alteration in epidermal cells that affects their locomotion, and which is maintained for a minimum of 3 days in the absence of other influencing factors.

Animals↗
PubMed1985

Phase I evaluation of a synthetic mutant of beta-interferon.

A synthetic mutant of beta-interferon, produced by recombinant DNA technology, was prepared with serine substituted for the naturally occurring cysteine at amino acid 17. This molecule, after purification to homogeneity, was evaluated in 23 patients with cancer for tolerated doses, safety, and pharmacokinetics. Each patient was begun on twice weekly administration, one dose i.m., then an identical dose i.v. Doses, escalated weekly, were tolerated by 9 of 12 patients at 100 X 10(6) units i.m., 11 of 14 patients at 100 X 10(6) units i.v., and 8 of 10 patients receiving i.v. doses of 200 X 10(6) units. Fever (greater than or equal to 38.9 degrees C), the commonest cause for ceasing dose escalation, occurred in 11 of 13 patients who developed limiting i.v. toxicity and 6 of 11 who developed limiting i.m. toxicity. Patients who did not have progressive cancer after completion of dose escalation received five consecutive daily doses at their maximum tolerated single dose by each route, i.m. and i.v. These two 5-day treatments were given without difficulty. All patients treated with 300 X 10(6) units or less, i.m. (n = 13) or i.v. (n = 10), were able to receive five daily doses without limiting toxicity. Peak serum titers occurred immediately after i.v. administration and declined in an exponential manner thereafter. Despite absence of measurable titers in serum after i.m. injection, fever and significant (P less than 0.05) depression of WBC and platelet counts, serum calcium, and serum cholesterol occurred (prestudy to maximum tolerated dose). An immunoglobulin antibody to beta-interferon, detected by enzyme-linked immunoabsorbent assay, developed in 17 of 23 patients. Neutralizing activity (titer 10(2] was found in only 1 of 23 patients. No immune-mediated sequelae (symptomatic or renal) were identified. Further Phase I and II trials with this molecule will determine whether it will prove to have a better therapeutic index or different spectrum of therapeutic activity from alpha-interferon or gamma-interferon.

Adult↗
PubMed1985

Variations in the [3H]thymidine labeling of S-phase cells in solid mouse tumors.

To determine whether all tumor S-phase cells incorporate [3H]thymidine, we labeled the cells in three mouse tumors (MCa-11, colon-26, and colon-51) in vivo for 1/2 h with [3H]thymidine (10 microCi/g of body weight). Cells from the tumors, as well as control cells from the bone marrows of the tumor-bearing mice, were then placed onto slides and Feulgen stained. The positions of these Feulgen-stained cells were mapped with a computerized scanning stage, and their nuclear DNA content and nuclear areas were determined by absorption cytophotometry. Next, the slides were processed for autoradiography and exposed for 32 or 64 days to obtain plateau labeling. The cells were then relocated, and the areas of the autoradiographic grains over each nucleus were measured. We found that 99% of the S-phase bone marrow cells were labeled. The 5-mm tumors, however, showed a wide range of S-phase labeling, with 94, 89, and 85% of the MCa-11, colon-51, and colon-26 S-phase cells, respectively, being labeled. The same mice bearing both 5- and 20-mm MCa-11 tumors, however, showed 95 and 57% labeling of the S-phase cells in the small and large tumors, respectively. These results show that the [3H]thymidine labeling of S-phase cells varies greatly for experimental mouse tumors of different size and type, and they suggest that "labeling index" and flow cytometric DNA measurements may not give valid estimates of the actual proportions of cycling S-phase cells in such tumors.

Animals↗
PubMed1984

Short-term and long-term survival in patients with alcoholic hepatitis treated with oxandrolone and prednisolone.

A cooperative study was conducted to determine the efficacy of 30 days of treatment with either a glucocorticosteroid (prednisolone) or an anabolic steroid (oxandrolone) in moderate or severe alcoholic hepatitis. One hundred thirty-two patients with moderate disease and 131 with severe disease were randomly assigned to one of three treatments: prednisolone, oxandrolone, or placebo. During the 30 days, mortality in the groups receiving steroid therapy was not significantly different from mortality in the placebo group. Thirteen per cent of the moderately ill patients and 29 per cent of the severely ill patients died. Although neither steroid improved short-term survival, oxandrolone therapy was associated with a beneficial effect on long-term survival. This was especially true in patients with moderate disease: among those who survived for one or two months after the start of treatment the conditional six-month death rate was 3.5 per cent after oxandrolone and 19 to 20 per cent after placebo (P = 0.02). No consistent long-term effect was associated with prednisolone therapy.

Clinical Trials as Topic↗
PubMed1984

Lactate provocation of panic attacks. I. Clinical and behavioral findings.

To assess the pharmacologic and phenomenologic comparability of lactate-induced and naturally occurring panic attacks, patients meeting DSM-III criteria for panic disorder or agoraphobia with panic attacks were infused with 0.5M racemic sodium lactate before and after successful drug treatment. Lactate-induced and naturally occurring panic attacks were symptomatically similar. Following treatment, the patients' response to lactate did not differ from that of normal controls, whereas the pretreatment panic rate was much higher. These data suggest that lactate acts, by as yet unidentified mechanisms, to trigger the same panic attacks as occur spontaneously in vulnerable persons.

Adult↗
PubMed1984

A new statistical procedure for testing equivalence in two-group comparative bioavailability trials.

The clinical problem of testing for equivalence in comparative bioavailability trials is restated in terms of the proper statistical hypotheses. A simple t-test procedure for these hypotheses has been developed that is more powerful than the methods based on usual (shortest) and symmetric confidence intervals. In this note, this new procedure is explained and an example is given, including the method for sample size determination.

Analysis of Variance↗
PubMed1984

Protein-calorie malnutrition associated with alcoholic hepatitis. Veterans Administration Cooperative Study Group on Alcoholic Hepatitis.

Three hundred sixty-three alcoholic patients with alcoholic hepatitis were studied in six Veterans Administration medical centers. By history, alcohol consumption was 227.9 g per day, with a mean duration of 23.8 years. Cirrhosis accompanied the alcoholic hepatitis in 58.7 percent of the patients who underwent biopsy or autopsy. Complete nutritional assessment was performed in 284 patients, and observed nutritional changes were classified into those associated with marasmus or those characterizing kwashiorkor. A smaller comparison group of 21 alcoholic patients matched for age and alcohol consumption but without clinically evident liver disease was also studied in an identical manner. None of the patients with liver disease was completely free from malnutrition, whereas 62 percent of the alcoholic patients without liver disease showed abnormalities. In patients with alcoholic hepatitis, some findings associated with marasmus were seen in 86 percent, and some features of kwashiorkor were observed in 100 percent. When present together, the complete picture of kwashiorkor and marasmus correlated closely with the clinical severity of the liver disease (p less than 0.005). The nearly constant association of either complete or partial kwashiorkor or marasmus suggests that the separation of these two entities is artificial in alcoholic patients with liver disease. Although, experimentally, malnutrition may not be essential for the development of alcoholic hepatitis, clinically, it appears to precede the development of the liver injury, which suggests an interaction. Recognition is important so that appropriate nutritional therapy can be provided.

Adult↗
PubMed1984

Hypoglycemic therapy in patients diagnosed to have diabetes at 30 years of age or older.

Treatment patterns were investigated for a population of diabetic persons diagnosed at 30 years of age or older who received primary medical care in an eleven county area in southern Wisconsin. Of the 6074 patients who met the diagnostic criteria for diabetes, 51% received their primary care from internists, 35% from general practitioners, and 14% from family practitioners. Insulin usage was more frequent in patients with a longer duration of diabetes, younger age at diagnosis and poor recent glucose control. Prescription of oral medications increased with increasing current age and age at diagnosis. A greater proportion of the patients of internists than those of general practitioners were treated with insulin. Oral hypoglycemic agents were prescribed more frequently for patients of general practitioners than for patients of internists. These differences remained after controlling for duration, age at diagnosis, and status of recent glucose control. Therefore, practitioner type is associated with treatment prescribed for diabetic patients diagnosed after 30 years of age.

Administration, Oral↗
PubMed1984

Decreases in serum high-density-lipoprotein cholesterol and total cholesterol resulting from naturally produced and recombinant DNA-derived leukocyte interferons.

A three-phase study was conducted to examine the effect of leukocyte interferon administration on serum high-density-lipoprotein (HDL) cholesterol and total cholesterol levels. In the initial phase, human leukocyte interferon decreased HDL cholesterol (P less than 0.05) and total cholesterol (P less than 0.05) levels in patients with breast carcinoma. Decreases began with initiation of the interferon administration, were sustained throughout the period of treatment, and increased toward pretreatment values with discontinuation of interferon. In the second phase of the study, in neither of two comparison groups of women receiving cytotoxic chemotherapy, excluding interferon, did any similar decrease in HDL cholesterol occur. In a third comparison group of women being treated for metastatic breast carcinoma, a predicted and significant (P less than 0.01) drop in HDL cholesterol level without a concomitant lowering of total cholesterol level occurred immediately following the initiation of androgen therapy. To confirm that the observed cholesterol level decreases were associated with interferon rather than a contaminant thereof, analyses were also carried out on samples from a study utilizing interferon rather than a contaminant thereof, analyses were also carried out on samples from a study utilizing interferon produced by recombinant DNA techniques and purified to homogeneity. A similar decrease in HDL cholesterol (P less than 0.05) and total cholesterol (P less than 0.01) was observed. A definite relationship therefore appears to exist between the administration of human leukocyte interferon and decreased plasma levels of HDL cholesterol and total cholesterol.

Aged↗
PubMed1984

Effect of src infection on long-term marrow cultures: increased self-renewal of hemopoietic progenitor cells without leukemia.

Long-term marrow cultures prepared from mice have been infected with a molecular recombinant of Rous sarcoma virus and murine amphitropic leukemia virus. This resulted in introduction of the src gene into the cultured cells and expression of its protein kinase function. The infected cultures displayed an altered balance in the accumulation of cells in different compartments of granulocyte differentiation. There was a dramatic increase in the stem cell (CFU-S) compartment and the committed progenitor cell (GM-CFC) compartment and a decrease in mature granulocytes. The altered balance appears to be caused by intrinsic alterations in the CFU-S and GM-CFC themselves, which increase their "self-renewal" capacity at the expense of cell differentiation. Remarkably, unlike its effects in other systems, src did not produce a neoplastic transformation of the hemopoietic cells.

Animals↗
PubMed1984

The haematopoietic response to burning: studies in an animal model.

Changes in haematopoiesis which occur in humans after burning injury may have important effects on morbidity and mortality. Because of the heterogeneity of burn patients we studied the regulation of blood cell formation which occurs in an animal using an established mouse model. Mice received a 20 per cent third degree scald injury on the back. Serial studies of a variety of haematopoietic parameters including stem cell, bone marrow and peripheral blood findings were done post burn. Although anaemia occurred frequently after injury red blood cell survival studies and examination of the stool for occult blood showed that neither haemolysis nor blood loss were primary causes of the anaemia. Bone marrow erythroid stem cells fell markedly post burn and this was associated with the development of a substance in serum capable of inhibiting red cell colony formation but not white cell colony formation of normal marrow cells. Reticulocytosis occurred but was mild and the anaemia was primarily of the aregenerative type. Partial compensation for the depressed marrow erythropoiesis occurred in the spleen with an increase in erythroid colony-forming cells and erythroblasts. Marked granulocytosis occurred in the peripheral blood and bone marrow. There was an increase in splenic granulocytic stem cells post burn. Megakaryocytosis was striking in the bone marrow and spleen and there was an increase in peripheral blood platelet count. Evidence of immune stimulation included an increase in the size of the spleen and an increase in peripheral blood and splenic lymphocytes. Correlations of many of these findings suggested that the events were not occurring at random but that the changes in haematopoiesis were linked together. We speculate that the anaemia was the result of the increase in granulopoietic and thrombopoietic effort seen post burn.

Anemia↗
PubMed1984

Bumetanide and furosemide in heart failure.

We assessed the handling of and response to oral bumetanide (1.0 and 2.0 mg) and to furosemide (40 and 80 mg) in 20 patients with stable, compensated congestive heart failure (CHF), comparing the two drugs and, in addition, examining differences from normal subjects. Bumetanide and furosemide were similar in time course of absorption, but patients with CHF had considerably prolonged absorption compared to normal subjects causing attainment of lower peak concentrations of drug. In both CHF and normal subjects, more bumetanide than furosemide was absorbed. The elimination half-life of furosemide was approximately twice that of bumetanide, and both were about two times longer than respective values in normal subjects. "Dose"-response curves were shifted downward from normal with both drugs. In patients with CHF, overall response did not differ between bumetanide and furosemide. The two drugs exhibit subtle differences, the clinical importance of which appears to be negligible from this study. Importantly, however, both drugs showed delayed absorption causing attainment of peak urinary excretion rates of diuretic two- to threefold lower than in normal subjects. This effect along with the abnormal responsivity of the tubule may contribute to the "resistance" to oral doses of diuretics observed clinically even though no quantitative malabsorption of drug occurs.

Absorption↗