Search PubMed⌕ Search

Biomedical subjects

R L Clark

Publications and source records attributed to R L Clark.

At least 91 records · Page 5Linked to original sources
PubMed1986

Association between adverse maternal and embryo-fetal effects in norfloxacin-treated and food-deprived rabbits.

Norfloxacin is a new antibiotic which caused embryo-fetal toxicity in association with maternotoxicity when given orally to rabbits at 100 mg/kg/day. The intestinal flora of rabbits is unusually sensitive to many antibiotics and it was suspected that the maternotoxicity and embryo-fetal toxicity caused by oral norfloxacin were secondary to an effect on the intestinal flora. To test this idea, a teratologic study was conducted in which rabbits were dosed on Days 6 to 18 of gestation with norfloxacin given orally at 100 mg/kg/day or subcutaneously at 20 mg/kg/day. The oral treatment caused decreased food consumption (to less than 15 g/day in some animals), body weight loss, an increased resorption rate, and decreased fetal weight. Among the females in the orally dosed group, there was a significant correlation (p less than or equal to 0.005) between the effects on maternal body weight and the resorption rate. The subcutaneous treatment caused little intestinal exposure (biliary excretion = only 2-4% of dose) and no maternotoxicity or embryo-fetal toxicity, even though blood levels of drug were at least as high as those in the oral group. Since the maternotoxicity and embryo-fetal toxicity were specific to the oral route and not correlated with the level of systemic exposure, the maternotoxicity may have been secondary to an effect on the intestinal flora and the embryo-fetal toxicity may have been secondary to the maternotoxicity. The decreased food consumption observed in the oral group may have contributed to the embryo-fetal toxicity since, in a separate study, it was found that lowering the amount of food provided to rabbits on Days 6 to 18 of gestation from 150 g/day to 50 or 15 g/day also caused adverse maternal and fetal effects including, at 15 g/day, fetal malformations.

Animals↗
PubMed1986

Arthropathic properties of cell wall polymers from normal flora bacteria.

Peptidoglycan-polysaccharide (PG-PS) fragments were purified from cell walls of group D streptococci (Streptococcus faecium, strains ATCC 9790 and F-24) with a protocol which minimizes autolytic activity and tested for ability to induce arthritis in rats. PG-PS fragments from cell walls of other normal flora bacteria (Peptostreptococcus productus, and Propionibacterium acnes), group A streptococci, and pseudomurein-PS fragments from cell walls of Methanobacterium formicicum, were similarly purified and tested. Upon intraarticular injection into rat ankles, all PG-PS polymers induced acute inflammation; pseudomurein-PS fragments were approximately five times less active than the PG-PS preparations. After intraperitoneal injection, P. acnes PG-PS induced a minimal acute arthritis, Peptostreptococcus productus PG-PS induced a moderately severe acute joint inflammation followed by a mild chronic arthritis, and both group A and group D streptococcal PG-PS induced severe acute arthritis which evolved into chronic, erosive joint disease; pseudomurein-PS fragments were without effect, consistent with a crucial role for the PG moiety of PG-PS. Chronic arthritis induced by group D streptococcal PG-PS subsided after 60 days, whereas that induced by group A streptococcal PG-PS was still active after 128 days. The arthropathic properties of this modest number of common normal flora bacteria suggest that different PG-PS structures derived from the normal flora have the potential to induce a wide range of responses, from transient acute to chronic erosive joint disease.

Amino Acids↗
PubMed1985

Health expenditures and elderly adults.

The purpose of the study was to examine how health expenditures vary among elderly households and how expenditure patterns across other commodity groups are influenced by various factors, including higher medical expenditures. Household expenditure data for five different age groups of elderly households included in the 1972-1973 Consumer Expenditure Survey were used in the analysis. Multiple regression procedures were used to estimate a complete set of budget share equations with and without health expenditures as an independent variable. Results indicate readjustments in expenditure patterns resulting from higher direct medical payments are likely to lead to significant reductions in food, housing, transportation, and taxes under current policy. This could have important long-run implications for elderly adults as well as for the entire economy. The research also indicated the importance of controlling for age differences when studying expenditure patterns of elderly adults.

Age Factors↗
PubMed1985

The effects of diltiazem and captopril on glycerol-induced acute renal failure in the rat. Functional, pathologic, and microangiographic studies.

To evaluate the effects of pharmacologic vasodilatation on glycerol-induced acute renal failure, we studied untreated animals and those given Captopril and Diltiazem at periods ranging from 30 minutes to four weeks after the onset of acute renal failure. At each time frame, comparative coded assessments of renal function, histology, and microangiography were performed. Diltiazem, a calcium channel blocker, significantly reduced the severity of the renal failure, decreased the extent of tubular cell necrosis, and was associated with a more rapid histologic and functional recovery. Captopril, an angiotensin converting enzyme inhibitor, did not influence renal function or pathology throughout the four-week observation period. Microangiography revealed marked differences among the experimental groups. Most notably, there was better visualization of the microvasculature in Diltiazem-treated kidneys at one and two weeks. However, at four weeks, all groups showed similar, severe microangiographic abnormalities. Diltiazem offers significant protection against glycerol-induced acute renal failure in rats. Its mechanism of action in this context remains unknown. Renal function and pathology do not correlate well with microangiographic perfusion patterns in this model of acute renal failure.

Acute Kidney Injury↗
PubMed1985

Salpingitis isthmica nodosa: radiologic and clinical correlates.

Salpingitis isthmica nodosa (SIN) is thought to be an inflammatory condition of the fallopian tubes and is strongly associated with infertility and an increased risk of ectopic pregnancy. The diagnosis is best made radiographically at hysterosalpingography (HSG), where the characteristic finding consists of multiple nodular diverticular spaces in close approximation to the true tubal lumen. We reviewed 1,194 HSGs performed over a five year period and identified 45 patients who had SIN (4%). There was a high rate of primary infertility (37.5%) and ectopic pregnancy (9.4%). Of 70 involved tubes, 62 (89%) had evidence of associated inflammation on historic, radiologic, surgical, or histologic grounds. We conclude that SIN is a disorder most likely acquired during the fertile years, and that the lesion is either a direct consequence of infection or that--once present--it predisposes the patient to subsequent infections.

Adult↗
PubMed1985

Insulin-resistant Na+ pump activity in adipocytes from obese humans.

Basal and maximally insulin-stimulated Na+-pump activity was measured in adipocytes from subjects with normal glucose tolerance over a range of body mass indexes (BMI). In a comparison of 13 lean (BMI less than 25) vs. 15 extremely obese (BMI greater than 40) subjects basal activities per unit surface area were similar, but the maximally insulin-stimulated activity was significantly reduced in the extremely obese group [9.2 +/- 0.6 vs. 12.1 +/- 1.0 (min X dam2)-1, P less than 0.05]. The mean percent insulin stimulation of the Na+ pump above basal activity was 48 +/- 7% for the lean compared with 14 +/- 2% for the extremely obese group (P less than 0.001). A similar relationship was observed in these subjects for glucose transport where basal activities per unit surface area again were similar but the maximally insulin-stimulated transport was reduced in the extremely obese subjects (2.2 +/- 0.3 vs 5.1 +/- 0.6 attol/um2 X s, P less than 0.001). These results indicate that alterations in Na+-pump activity may be a manifestation of the insulin-resistant state that could contribute to the development of obesity via decreased cellular thermogenesis.

Adipose Tissue↗
PubMed1985

Renal medullary lymphatics: microradiographic, light, and electron microscopic studies in pigs.

Although renal cortical lymphatics have been extensively studied, the existence of renal medullary lymphatics has not been well documented. We studied renal microlymphatics in pig kidneys by retrograde ureteral injection of barium-sulfate-gelatin-saline mixture. Lymphatics filled as a result of forniceal rupture and interstitial extravasation. Microradiographs were correlated with histology and electron microscopy. We traced renal microlymphatic vessels from the arcuate level not only into the cortex but also into the pyramidal region, and therefore concluded that medullary lymphatics existed.

Animals↗
PubMed1984

Diflunisal-induced maternal anemia as a cause of teratogenicity in rabbits.

Diflunisal [5-(2,4-difluorophenyl)-salicylic acid] is a new analgesic antiinflammatory drug that, when administered orally to rabbits at 40 and 60 mg/kg/day, caused terata, most commonly axial skeletal defects. These same dosage levels also caused a severe maternal hemolytic anemia following a dramatic decrease in erythrocyte ATP levels. The teratogenicity, anemia, and depletion of ATP were unique to the rabbit among species examined. To test the possible causality between the teratogenic effects and anemia induced by diflunisal, a single dose of 180 mg/kg diflunisal was administered to rabbits on gestation day 5. This treatment produced an anemia that persisted through gestation day 15 in addition to causing the characteristic axial skeletal defects. Since diflunisal was cleared from maternal blood before gestation day 9, the critical day for induction of similar axial skeletal defects by hypoxia, the skeletal malformations probably resulted from maternal hypoxia secondary to anemia and not from a direct and specific effect of the drug on the embryo. In addition, we observed that the diflunisal level in the embryo was less than 5% of the peak maternal blood level probably as a result of high plasma protein binding of diflunisal in the maternal blood (greater than 98%). This relatively low placental transfer may explain the lack of diflunisal teratogenicity in rats and mice compared to aspirin which crosses the placenta more readily. These studies demonstrate that a species that exhibits unusually severe drug-specific maternotoxicity is probably an unsuitable model for the prediction of the teratogenic potential of that drug in humans.

Abnormalities, Drug-Induced↗
PubMed1984

Efficacy of the excretory urogram in the staging of gynecologic malignancies.

It is common for patients suspected of having a gynecologic malignancy to be referred for excretory urography as part of their preoperative staging evaluation. This study investigates the efficacy of this practice using prospective and experimental retrospective interpretations of 88 urograms obtained for this clinical indication. The results indicate that excretory urography reliably depicts the ureters in most cases. However, the urogram is quite insensitive (sensitivity, 7%-33% among the interpretation settings) in demonstrating the extension of malignancy; specificity for this purpose was 79%-97%. The excretory urogram is useful for locating the position of the ureters and demonstrating the presence of obstruction or unsuspected urinary tract abnormalities. Nonetheless, this information also may be obtained by computed tomography, which can more accurately assess the primary mass and indicate the presence of malignant extension.

Adult↗
PubMed1984

Neonatal 'brain damage'-an analysis of 250 claims.

Advances in perinatal care have resulted in decreased neonatal mortality. Increasingly, damage in survivors has been attributed to alleged negligence. We analyzed the 250 claims (1957 to 1982) from one major insurance company for factors to characterize high-risk pregnancies and then to distinguish preventable from nonpreventable causes within the group. Using predetermined criteria, 77 (31%) were classified preventable, 105 (42%) nonpreventable and 68 (27%) indeterminate. Preventable actions could be attributed to family members as well as health care providers. Twenty risk factors were significantly increased in the study group compared with those in a general population and included maternal, gestational, delivery and postdelivery risks. Furthermore, 13 of 25 factors differed significantly between preventable and nonpreventable cases. Those with significantly higher prevalence in preventable cases included prolonged gestation, the use of mid or high forceps, cesarean sections, meconium staining, low one- and five-minute Apgar scores, birth weight exceeding 4.5 kg (10 lb), poor tone, seizures and transfers to neonatal intensive care units. Increased in prevalence in the nonpreventable cases were congenital infections and malformations and the late onset of neurologic abnormalities. These findings suggest preventive measures to reduce unwarranted litigation and certain cases of neonatal brain damage.

Birth Injuries↗
PubMed1983

Studies of enzyme polymorphism in the Kamuela population of Drosophila mercatorum. III. Effects of variation at the alpha GPD locus and subflight stress on the energy charge and glycolytic intermediate concentrations.

We have employed a "level crossing" strategy to study the primary effects of an enzyme polymorphism in Drosophila mercatorum. This strategy consists of following genetic differences across intervening phenotypes to possible fitness effects. In this paper, we report the steady state concentrations of the glycolytic intermediates and the adenylates (intervening phenotypes) in two genotypes (alpha GPD-F, alpha GPD-S) at two stress levels (rest, subflight). We did not detect a genotype or a genotype by stress interaction effect on glycolytic intermediate or adenylate concentrations despite the ability of the experimental design to detect a 20 to 50% difference from the mean of a control. The flux of glycolysis is adequate to maintain the energy charge in both strains under the stress levels considered. If there is a fitness difference between these alpha GPD variants, it is unlikely to be a result of modifications of glycolysis. Subflight stress, however, resulted in an increase in metabolic flux. The observed pattern of intermediate concentration differences is consistent with the modulation of glycolysis by the ratio of the ATP and AMP concentrations acting on phosphofructokinase activity.

Animals↗
PubMed1983

Impact of therapy for differentiated carcinoma of the thyroid: an analysis of 706 cases.

A retrospective analysis of clinical and pathological data was conducted on 706 patients (514 females and 192 males) treated for differentiated thyroid carcinoma at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston from 1951 to 1975 and followed to 1981. The histological diagnoses were mixed papillary/follicular carcinoma (66.7%), papillary carcinoma (14.6%), follicular carcinoma (15.3%), or Hurthle cell carcinoma (3.4%). Patients diagnosed before the age of 40 yr lived significantly longer than those diagnosed over the age of 40 yr, and females lived longer than males. According to survival analyses and disease-free intervals, the order of increasing aggressiveness of the tumors was papillary, mixed, follicular, and Hurthle cell. Total thyroidectomy was associated with longer disease-free intervals and fewer recurrences. The 136 patients who received ablative 131I after surgery had fewer recurrences than a matched group who did not, but the disease-free interval and survival rate showed no significant difference. Further classification showed that patients with follicular and mixed tumors, and those who underwent total thyroidectomy benefited from 131I. There were 78 deaths attributed to thyroid cancer in the whole group. Approximately two thirds occurred in the first 10 yr after diagnosis. In conclusion, total thyroidectomy is recommended, when feasible, for differentiated thyroid cancer, followed by ablative 131I therapy, at least for follicular and mixed varieties.

Adenocarcinoma↗
PubMed1983

Renal arcuate veins: new microangiographic observations.

Standard references state that arcuate veins at the corticomedullary junction form continuous arcades. Because some preliminary anatomic observations seemed to disagree with this traditional teaching, the arcuate veins were systematically studied in normal human kidneys. Microangiographic studies indicate that, unlike the occasional anastomoses that exist between proximal interlobar and segmental veins, arcuate venous communications in humans are extremely rare. Arcuate veins, like the corresponding arteries, should be considered "end vessels."

Adult↗
PubMed1983

Serotonin regulation of palatal cell motility and metabolism.

Serotonin has been previously shown to stimulate palate reorientation. To elucidate the mechanism by which the neurotransmitter may be regulating palate morphogenesis, the effects of serotonin on cell motility and various metabolic reactions have been measured in vitro. To monitor cell motility, a chemotactic system was employed in which cultured palate mesenchymal cells in a modified Boyden chamber migrate toward the chemoattractant(s) in N-18 neuroblastoma conditioned medium. Serotonin stimulated cell motility and 10(-5) M was optimal with nearly 100% stimulation achieved. With N-18 conditioned medium diluted 1:100, serotonin stimulated cell motility 4.9-fold. Serotonin itself was not chemotactic but modulated cell movement in the presence of the chemoattractant. Protein carboxyl methylation was stimulated by serotonin about 100% at concentrations ranging from 3 X 10(-7) M to 3 X 10(-6) M in different experiments. The net stimulation may have been elicited by an indirect effect since serotonin also inhibited demethylation of protein methyl esters. Serotonin was shown to inhibit cyclic AMP in cultured palate cells: 10(-5) M agonist depressed levels to 19% of control in 3 h. Further, prostaglandin E1, which stimulated cyclic AMP levels, markedly inhibited cell motility in the chemotactic assay. Thus there is an inverse relationship between cyclic AMP levels and cell motility in fetal palate cells. Finally it was observed that serotonin stimulated cyclic GMP levels; 10(-5) M serotonin optimally stimulated cyclic GMP with a spike of stimulation (6.1-fold) within 30 sec. In summary, serotonin in palate cells stimulates both protein carboxyl methylation and cyclic GMP. Modulation of these reactions could be regulating cell motility and/or protein secretion, which in turn could function in palate reorientation.

Animals↗