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Biomedical subjects

R Schwartz

Publications and source records attributed to R Schwartz.

At least 145 records · Page 8Linked to original sources

In vitro antifungal activities and in vivo efficacies of 1,3-beta-D-glucan synthesis inhibitors L-671,329, L-646,991, tetrahydroechinocandin B, and L-687,781, a papulacandin.

The in vivo anti-Candida activities of 1,3-beta-D-glucan synthesis inhibitors L-671,329, L-646,991 (cilofungin), L-687,901 (tetrahydroechinocandin B), and L-687,781 (a papulacandin analog) were evaluated by utilizing a murine model of disseminated candidiasis that has enhanced susceptibility to Candida albicans but increased sensitivity for discriminating antifungal efficacy. DBA/2 mice were challenged intravenously with 1 x 10(4) to 5 x 10(4) CFU of C. albicans MY1055 per mouse. Compounds were administered intraperitoneally at concentrations ranging from 1.25 to 10 mg/kg of body weight twice daily for 4 days. At 6 h and 1, 2, 3, 4, 7, and 9 days after challenge, five mice per group were sacrificed and their kidneys were homogenized and plated for enumeration of Candida organisms (CFU per gram). Progressiveness of response trends and no-statistical-significance-of-trend doses were derived to rank compound efficacy. 1,3-beta-D-Glucan synthesis 50% inhibitory concentrations were determined by using a C. albicans (MY1208) membrane glucan assay. Candida and Cryptococcus neoformans MICs and minimal fungicidal concentrations were determined by broth microdilution. L-671,329, L-646,991, L-687,901, and L-687,781 showed similar 1,3-beta-D-glucan activities, with 50% inhibitory concentrations of 0.64, 1.30, 0.85, and 0.16 micrograms/ml, respectively. Data from in vitro antifungal susceptibility studies showed that L-671,329, L-646,991, and L-687,901 had similar MICs ranging from 0.5 to 1.0 micrograms/ml, while L-687,781 showed slightly higher MICs of 1.0 to 2.0 micrograms/ml for C. albicans MY1055. Lipopeptide compounds were ineffective against C. neoformans strains. Results from in vivo experiments comparing significant trend and progressiveness in response analyses indicated that L-671,329 and L-646,991 were equipotent but slightly less active than L-687-901, while L-687,781 was ineffective at 10 mg/kg. Fungicidal activities of L-671,329, L-646,991, and L-687,901 were observed in vivo, with significant reduction in Candida CFU per gram of kidneys compared with those in sham-treated mice at doses of > or = 2.5 mg/kg evident as early as 1 day after challenge.

Animals↗

Persistence of impaired insulin secretion in infant rhesus monkeys that had been hyperinsulinemic in utero.

Chronic in utero hyperinsulinemia in the fetal rhesus monkey produces a number of changes in the fetus that are similar to those found in the human infant of the diabetic mother, including macrosomia, selective organomegaly, and altered insulin secretion during the neonatal period. The chronically hyperinsulinemic fetal rhesus model has been used to test the hypothesis that the effects of chronic hyperinsulinemia persist beyond the neonatal period into later life and may, in part, be responsible for the increased prevalence of impaired glucose tolerance or diabetes found in the human infant of the diabetic mother. We report that infant rhesus monkeys that had plasma insulin concentrations of approximately 10 times basal levels (2176 +/- 808 pmol compared to 172 +/- 101 pmol) exhibited reduced insulin secretion during the first 5 months of life. The integrated incremental change in plasma insulin and immunoreactive C-peptide (IRCP) concentration was significantly reduced by approximately 50% in response to i.v. glucose, arginine, and tolbutamide when given at 3, 4, and 5 months of age. The response to glucagon at 2 months of age was equivocal with a significantly reduced insulin response but without the corresponding IRCP reduction. There was no difference between groups in insulin sensitivity as measured at 6 months of age by an i.v. insulin tolerance test. The glucagon and glucose tolerance tests were repeated annually in both groups until the animals were 3 yr of age with no differences in insulin or IRCP secretion being observed. We conclude that chronic in utero euglycemic hyperinsulinemia results in impaired insulin secretion that persists beyond the neonatal period.

Animals↗

Impaired insulin secretion after intravenous glucose in neonatal rhesus monkeys that had been chronically hyperinsulinemic in utero.

Chronic hyperinsulinemia in the fetal rhesus monkey results in fetal macrosomia without change in fetal plasma glucose concentration. After 18 days of hyperinsulinemia, fetuses were delivered by cesarean section, at which time experimental animals had significantly (P less than 0.05) elevated umbilical artery plasma insulin concentrations of 2039 +/- 854 pM compared with 129 +/- 72 pM. Plasma immunoreactive C peptide (IRCP) was significantly reduced to 39 +/- 17 pM compared with 286 +/- 134 pM. Eight hours after the insulin-delivering pumps were removed, plasma glucose, insulin, and IRCP were the same in both the experimental and control groups. At this time, 0.5 g glucose/kg was given intravenously and insulin and IRCP secretion was measured over a 1-hr period. The secretion, as assessed by integrating the incremental response of both insulin and IRCP, was significantly (P less than 0.05) lower by 80% in the experimental animals compared with the controls. Our data show that experimentally produced in utero euglycemic hyperinsulinemia in the fetal rhesus monkey produces a defect in the glucose-mediated insulin secretory mechanism that is detectable in the neonatal period even when hyperinsulinemia is no longer present. This study provides more support for the concept that fuel/hormone-mediated fetal teratogenesis may explain some of the fetopathy of the infant of the diabetic mother.

Animals↗

Marginal adaptation of castings made with dual-arch and custom trays.

This study compared the marginal fit of castings made with custom acrylic trays and metal or plastic dualarch impression trays. Standard clinical and laboratory procedures were used to make 36 gold castings for a metal tipodont die. Mean marginal openings were between 25 and 28 microns in all test groups.

Analysis of Variance↗

Teicoplanin in the treatment of bone and joint infections. Teicoplanin Bone and Joint Cooperative Study Group, USA.

Teicoplanin is a new glycopeptide antibiotic with activity against Gram-positive bacteria, including methicillin-resistant organisms. Teicoplanin is administered once daily, either intravenously or intramuscularly. Teicoplanin was given once daily, intravenously or intramuscularly, in the treatment of hospitalized or ambulatory patients with Gram-positive bone or joint infections. A total of 90/98 patients were evaluated for efficacy; 41 had acute osteomyelitis, 41 had chronic osteomyelitis, and 8 had septic arthritis. At the end of therapy, 37 acute osteomyelitis patients were cured/improved with a 90% cure rate at 6-month follow-up; 2 relapsed and 1 failed. At the end of therapy 30 chronic osteomyelitis patients were cured/improved with an 88% cure rate at 6-month follow-up; 2 relapsed and 1 failed. 100% of the septic arthritis patients were cured at the end of therapy and at 1-month follow-up. The most common bacterial isolates cultured from bone were S. aureus (39 isolates), S. epidermidis (11 isolates), other coagulase-negative staphylococci (20 isolates), enterococci (6 isolates), and other streptococcal species (20 isolates). The most common bacterial isolates cultured from joint fluid were S. aureus (6 isolates) and S. epidermidis (2 isolates). All patients tolerated the intramuscular or intravenous routes of administration well. Adverse reactions were mild and most cases did not require discontinuation of therapy. The majority of therapy was administered on an outpatient basis. Teicoplanin was safe, effective, convenient and relatively well tolerated in patients with acute or chronic osteomyelitis or septic arthritis.

Acute Disease↗

Effect of temporary cements on the bond strength of a resin cement.

This study evaluated the effect of temporary cements with or without eugenol on the bond strength of a dual-cure resin cement to dentin. Etched, silanated Dicor buttons were bonded to dentin surfaces after pretreatment with the cements. The buttons were sheared in an Instron testing machine. The results showed that shear bond strength is not affected by the temporary cements, if the dentin is cleaned with pumice and treated with Prisma Universal Bond 3 dentin bonding system.

Analysis of Variance↗

Phase I clinical and pharmacokinetic trial of flavone acetic acid.

Flavone acetic acid is a synthetic benzopyrone derivative with an unknown mechanism of action. Thirty-eight patients (30 men and 8 women) were treated once a week for 4 weeks every 5 weeks with doses of flavone acetic acid ranging from 0.33 to 12.5 g/m2. At doses less than or equal to 3.9 g/m2, the drug was administered intravenously over 1 hour; at doses greater than or equal to 5.28 g/m2, the infusion period was lengthened to 6 hours. Treatment of all patients included hydration before and after treatment and alkalization to maintain urine pH at greater than or equal to 6.5. A dose-limiting toxic effect was hypotension at 10 g/m2. Pharmacokinetic studies revealed linear behavior in the eight patients studied, beginning at 3.9 g/m2. Peak plasma levels ranged from 125 to 630 micrograms/mL, with a mean terminal half-life of 22.4 hours. Immunologic monitoring was performed in three patients at 10 g/m2. A transient increase in CD16- and/or Leu-19-positive cells was noted in all three patients. In one patient, this increase correlated with a 10-fold increase in K562 cell killing. There were no objective tumor responses seen in this trial. The recommended phase II dose on this schedule is 8 g/m2. Further studies to elucidate the drug's mechanism of action and to define its immunologic properties are recommended.

Adult↗

Fish oil ingestion in smokers and nonsmokers enhances peroxidation of plasma lipoproteins.

The effect of fish oil ingestion (10 g MaxEPA/day) on the susceptibility of plasma lipoproteins to peroxidation was examined in 20 smokers (study A and B) and 22 nonsmokers (study C). The subjects were examined at the onset of each study (baseline values), divided into control and experimental groups and reexamined 4 weeks later. Smokers were examined 40 h after abstention from smoking (0 time) and 90 min after acute smoking (4-6 cigarettes). The parameters studied were TBARS, which provide an indication of peroxidative injury, and metabolism of conditioned LDL by macrophages as a biological indicator. These parameters were significantly higher (P less than 0.05-0.001) when the 90 min values of smokers were compared to time 0. After 4 weeks of fish oil ingestion, a significant rise above baseline values (33-50%) in plasma and LDL TBARS was found in smokers examined at time 0 and after acute smoking. Peroxidative modification of LDL isolated from smokers fed fish oil resulted in significantly higher TBARS (34-41%) and its metabolism by macrophages was higher (65-139%) compared to baseline values. In nonsmokers, the baseline values of the above parameters were lower than in smokers. Ingestion of fish oil resulted in a significant rise in TBARS in plasma (33%), LDL (137%), conditioned LDL (36-40%) and metabolism of conditioned LDL (70%) by macrophages. In 6 nonsmokers and 4 smokers, 400 mg of vitamin E/day were given with the fish oil. In the nonsmokers, vitamin E counteracted the effect of fish oil more effectively than in the smokers. In the light of the present results, indiscriminate recommendation of fish oil supplementation to the population at large should be cautioned.

Animals↗

Alcohol and drug use in teenagers with diabetes mellitus.

Alcohol and drug use in adolescents with diabetes mellitus was assessed by an anonymous self-administered questionnaire with verification by urine drug screening. Approximately 50% of these adolescents report having tried alcohol and 25% report ongoing use. Almost 25% have tried drugs of abuse and 5% report ongoing use. One of 97 consecutive urine specimens was positive for marijuana. In general, the frequency of alcohol and drug use was less than expected based on other studies of different clinical groups of patients in the same age range. Patients with diabetes who reported drug use or who reported they live in an environment of substance abuse had poorer diabetes control than patients who did not.

Adolescent↗

Prenatal records: a national survey of content.

The uses of prenatal records extend well beyond management of patient care. They are also vehicles for communication, quality assurance, financial compensation, and legal documentation. To serve each of these functions, records should be systematic and detailed. This nationwide study was conducted to assess the extent to which prenatal records in current use include sufficient detail to serve these functions. A random sample of 2746 physicians who listed obstetrics and gynecology, obstetrics, or maternal-fetal medicine as a primary or secondary specialty in the American Medical Association file were contacted by mail and were requested to submit a blank copy of their prenatal records. The records of 969 respondents were examined for the presence or absence of 53 items that corresponded to the five functions identified above. The items of interest were present in 1% to 98% of the records. More than 90% included items of traditional medical-obstetric significance. The percentages of records with items of more contemporary relevance (e.g., cigarette smoking, risk-assessment checklists, psychological stress) were found in lower percentages of the records. Stratified and logistic regression analyses revealed that the most systematic and detailed records were commercially available, were used by physicians in hospital and government program-based practices, and were used by physicians who had completed medical school less than or equal to 15 years before the survey. The findings suggest that physicians who do not use commercially available forms or those who are in private or health maintenance organization practice or have been practicing for more than 15 years should reconsider their prenatal records in light of the functions they will serve in the 1990s and beyond.

Communication↗

Role of circulation in maintaining Na+ and K+ concentration in pelvic patch in Rana catesbeiana.

Skin samples from the pelvic, pectoral, and back areas of frogs were taken from control (C) animals and from dehydrated animals under three conditions: dehydrated and not exposed to a bathing medium (D), dehydrated live and ventral surface exposed to a bathing medium (DL), and dehydrated with heart stopped and ventral surface exposed to a bathing medium (DHS). The skin concentration of Na+ and K+ of the pelvic patch in the absence of circulation was significantly reduced [DHS 286 +/- 22 microM/mg dry wt (n = 6)] compared with control [C 392 +/- 21 microM/mg dry wt (n = 8)]. However, the pelvic skin concentration was maintained in a frog with an intact circulation [DL 381 +/- 26 microM/mg dry wt (n = 7)] even in the presence of a high pelvic water flow [684 +/- 105 cm3.cm-2.s-1.10(-7) (n = 13)]. The water uptake in the pectoral region [231 +/- 54 cm3.cm-2.s-1.10(-7) (n = 13)] was not high enough to predict a dilution, and none was found. The concentrations were 354 +/- 21 (n = 8), 359 +/- 22 (n = 7), 353 +/- 26 (n = 7), and 373 +/- 45 microM/mg dry wt (n = 6) for C, D, DL, and DHS, respectively. Examination of the Na+ and K+ concentrations separately in the pelvic skin shows that the lower salt content in DHS frogs is mainly due to a loss of Na+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cognitive orientation and genital infections in young women.

The purpose was to explore the psychological determinants of common genital infections in young women. The study was done in the framework of the cognitive orientation theory which assumes that cognition guides behavior and provides predictions of behaviors and psychophysiological phenomena. We expected that beliefs of four types (about self, norms, goals, and general) would predict the occurrence and/or frequency of 17 gynecological symptoms (e.g., itching, swelling, different vaginal discharges, abscesses). The subjects were 195 female volunteers, undergraduates, about 23 years old, without gross gynecological disorders, mostly (87.7%) unmarried, mostly (83.6%) having had intercourse. They were administered anonymously questionnaires about demographic variables, frequency and treatment of gynecological symptoms and 3 urological ones (for control), and about cognitive orientation that referred to pretested themes (e.g., assertiveness, hypochondriasis). Stepwise discriminant and regression analyses showed that the belief types enabled predicting the occurrence and frequency of all symptoms, with a mean 34.5% improvement over the 50% chance level, accounting for 45.7-67.2% of the variance. Also the urological symptoms were predicted although at a lower level. Discussion focuses on the specificity of cognitive-motivational determinants and their role in producing conditions favoring physical pathology.

Adult↗

Neonatal hypoglycemia. Back to basics in diagnosis and treatment.

Hypoglycemia continues to be found in infants of diabetic mothers, although the significance of the observation remains to be defined in terms of long-term neuro-development and behavior. Most follow-up studies no longer identify CNS problems. The criterion, i.e., the level of blood glucose at which the diagnosis should be made, has evolved and drifted toward the adult level. No single criterion can be used dependably to make this clinical and chemical diagnosis.

Animals↗

Symptom correlates among adolescents showing Posttraumatic Stress Disorder versus Conduct Disorder.

21 adolescents with a primary diagnosis of Posttraumatic Stress Disorder, 24 Conduct Disordered, and 23 control adolescents were compared on measures of depression, anxiety, behavior problems, and fears. Analyses showed that posttraumatic adolescents showed associated symptoms of depression and state-anxiety, Conduct Disordered adolescents showed depressive trends, and both groups were evaluated by their teachers as showing significant behavior problems.

Adolescent↗