Further Studies on Bacterial Nutrition: The Utilization of Proteid and Non-Proteid Nitrogen.
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Biomedical subjects
Publications and source records attributed to N Berman.
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CONTEXT: EGb 761 is a particular extract of Ginkgo biloba used in Europe to alleviate symptoms associated with numerous cognitive disorders. Its use in dementias is based on positive results from only a few controlled clinical trials, most of which did not include standard assessments of cognition and behavior. OBJECTIVE: To assess the efficacy and safety of EGb in Alzheimer disease and multi-infarct dementia. DESIGN: A 52-week, randomized double-blind, placebo-controlled, parallel-group, multicenter study. PATIENTS: Mildly to severely demented outpatients with Alzheimer disease or multi-infarct dementia, without other significant medical conditions. INTERVENTION: Patients assigned randomly to treatment with EGb (120 mg/d) or placebo. Safety, compliance, and drug dispensation were monitored every 3 months with complete outcome evaluation at 12, 26, and 52 weeks. PRIMARY OUTCOME MEASURES: Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI), and Clinical Global Impression of Change (CGIC). RESULTS: From 309 patients included in an intent-to-treat analysis, 202 provided evaluable data for the 52-week end point analysis. In the intent-to-treat analysis, the EGbgroup had an ADAS-Cog score 1.4 points better than the placebo group (P=.04) and a GERRI score 0.14 points better than the placebo group (P=.004). The same patterns were observed with the evaluable data set in which 27% of patients treated with EGb achieved at least a 4-point improvement on the ADAS-Cog, compared with 14% taking placebo (P=.005); on the GERRI, 37% were considered improved with EGb, compared with 23% taking placebo (P=.003). No difference was seen in the CGIC. Regarding the safety profile of EGb, no significant differences compared with placebo were observed in the number of patients reporting adverse events or in the incidence and severity of these events. CONCLUSIONS: EGb was safe and appears capable of stabilizing and, in a substantial number of cases, improving the cognitive performance and the social functioning of demented patients for 6 months to 1 year. Although modest, the changes induced by EGb were objectively measured by the ADAS-Cog and were of sufficient magnitude to be recognized by the caregivers in the GERRI.
Four polycythemic young adults with inoperable cyanotic congenital heart disease were treated for 12 weeks with 20 mg/kg/day of pentoxifylline in an attempt to increase pulmonary blood flow by improving red blood cell demorability and decreasing whole blood viscosity. Treatment caused a rise in mean arterial oxygen saturation from 75-82%, a fall in the mean oxygen extraction coefficient from 47-40%, and a fall in mean oxygen consumption from 186-169 ml/min/m2. Pentoxifylline decreased whole blood, but not plasma, viscosity at all hematocrits over a range of shear rates. Two patients had significant bleeding episodes during treatment.
In this paper from the Collaborative Depression Study (CDS)--Biological, a set of data analyses are presented which indicate that depressed states and perhaps depressed mood are associated with a greater activation of the adrenomedullary system than the sympathetic nervous system [as measured by norepinephrine (NE) and normetanephrine excretion]. For the most part this finding of predominant activation of the adrenomedullary system is seen in unipolar and not bipolar patients.
Animal and clinical studies suggest that lead exposure disrupts the hypothalamic-pituitary axis. To define more precisely the toxic action of lead on the hypothalamic-pituitary unit, a series of in vivo and in vitro experiments were performed. The first experiment was designed to determine whether lead exposure exerts an inhibitory effect on GnRH secretion as reflected by an enhanced inhibition of luteinizing hormone (LH) secretion in response to the tyrosine hydroxylase inhibitor methyl-p-tyrosine (AMPT). In the control animals, the AMPT dose had no significant effect on LH secretion, whereas LH fell significantly in the lead-treated animals. In experiments designed to evaluate the effects of lead exposure on the pattern of pulsatile release of gonadotropins castrated control and lead-dosed animals were cannulated, and serial blood sampling was performed. Baseline LH and follicle-stimulating hormone values were not statistically different between the control and lead-treated group. There were no significant differences noted in pulsatile patterns when the data were analyzed as groups. Pituitary cells harvested from lead-treated animals released significantly more LH that did the control animals. These data are consistent with the hypothesis that the signals between the hypothalamus and pituitary gland are disrupted by lead exposure in the intact animal. However, the lead-exposed castrated rat's hypothalamic-pituitary unit is able to adapt to the toxic effects of lead.
We report an unusual finding of ostial stenosis of an anomalous left main coronary artery originating from the pulmonary artery in a symptom-free adolescent girl. Transesophageal echocardiography with Doppler color imaging correctly identified all of the salient features of this anomaly including proximal stenoses of the right and left coronary arteries. These findings were subsequently confirmed at cardiac catheterization.
OBJECTIVE: Transient hypothyroxinemia in premature newborns has been linked with poor neonatal outcomes. We designed this study to evaluate the effects of early thyroxine (T4) administration in the premature infant. STUDY DESIGN: A total of 49 newborns less than 32 weeks' gestation, were randomized in a double-blind, placebo-controlled trial. Within the first 48 hours of life, T4 (10 or 20 micrograms/kg; intravenous or through nasogastric tube, respectively) was administered for a total of 21 days. Chronic lung disease, the primary outcome variable, was defined by oxygen dependency at 28 days of life. RESULTS: The incidence of chronic lung disease, death, grade III or IV intraventricular hemorrhage, periventricular leukomalacia, and sepsis was not different in the placebo and treated groups. CONCLUSION: Early T4 supplementation in preterm newborns less than 32 weeks' gestation does not decrease the incidence of chronic lung disease or other complications of prematurity.
We have used a combined genetic and pharmacological approach to define the time course of the requirement for protein kinase A (PKA) and protein synthesis in long-term memory for contextual fear conditioning in mice. The time course of amnesia in transgenic mice that express R(AB) and have genetically reduced PKA activity in the hippocampus parallels that observed both in mice treated with inhibitors of PKA and mice treated with inhibitors of protein synthesis. This PKA- and protein synthesis-dependent memory develops between 1 hr and 3 hr after training. By injecting the protein synthesis inhibitor anisomycin or the PKA inhibitor Rp-cAMPs at various times after training, we find that depending on the nature of training, contextual memory has either one or two brief consolidation periods requiring synthesis of new proteins, and each of these also requires PKA. Weak training shows two time periods of sensitivity to inhibitors of protein synthesis and PKA, whereas stronger training exhibits only one. These studies underscore the parallel dependence of long-term contextual memory on protein synthesis and PKA and suggest that different training protocols may recruit a common signaling pathway in distinct ways.
Observations that serum follicle-stimulating hormone (FSH) levels begin to rise after initial suppression during chronic gonadotropin-releasing hormone (GnRH) agonist treatment of men with prostate cancer had led to speculation that FSH escape might in part account for the failure of GnRH agonist analogs to completely suppress spermatogenesis in normal eugonadal men. However, previous studies in healthy young men failed to report FSH escape during GnRH agonist treatment for up to 16 weeks. We considered the possibility that this may have been due to the insensitivity of the FSH assays. Accordingly, using highly sensitive and specific two-site directed fluorometric assays and a sustained-release GnRH agonist formulation, we reexamined the issue of whether serum FSH levels rise after initial suppression during chronic GnRH agonist treatment. Two groups of healthy normal men, 19-50 years of age, received 7.5 mg of a long-acting GnRH agonist microcapsule formulation (Lupron Depot; TAP Pharmaceutical Company, North Chicago, Illinois) on days 1 and 30. In addition, the subjects received either 4 or 8 mg/day testosterone replacement by means of a testosterone microcapsule injected intramuscularly on day 1. Serum luteinizing hormone (LH) and FSH levels were measured by sensitive and specific two-site directed fluorometric assays on multiple occasions during the 3-week control period and the 9-week treatment period. Serum LH levels declined to a nadir between 2 and 4 weeks and stayed suppressed throughout the remainder of the treatment period in both the 4- and 8-mg testosterone groups.(ABSTRACT TRUNCATED AT 250 WORDS)
This study examined the pharmacokinetics (the time course and pattern of testosterone release) and pharmacodynamics (effects on accessory sex organ weights, and serum LH and FSH levels) of a biodegradable testosterone microsphere formulation in the male rat. Two hundred seventy-five 55-day-old, sexually mature male rats underwent surgical orchiectomy or sham surgery and were divided into five groups as follows, to receive placebo or testosterone microsphere systems designed to release 25, 75, or 225 micrograms/day testosterone: group I: intact age-matched controls, sham operated, placebo microspheres; group II: surgically orchiectomized, placebo microspheres; group III: surgically orchiectomized, 25 micrograms/day testosterone microspheres; group IV: surgically orchiectomized, 75 micrograms/day testosterone microspheres; and group V: surgically orchiectomized, 225 micrograms/day testosterone microspheres. Serum testosterone levels were fairly uniform from day 2 to 85 without any significant trend. After day 100, serum testosterone levels gradually fell into the castrate range by day 196. There was a dose-dependent increase in serum testosterone levels in groups III, IV, and V over those seen in group II (castrated rats, placebo treated). Prostate and seminal vesicle weights were significantly lower in castrated animals treated with placebo or the 25-micrograms/day testosterone microsphere system (group III). Mean prostate and seminal vesicle weights in groups IV and V were not significantly different from those in intact controls (group I) in the first 85 days. After day 85-100, seminal vesicle and prostate weights declined gradually in groups III, IV, and V, approaching castrate range by day 196.(ABSTRACT TRUNCATED AT 250 WORDS)