Biomedical subjects
Publications and source records attributed to G Fuller.
An innovative concept in the education of military family practice residents using civilian nursing homes has been introduced. The authors describe the process of nursing home selection in detail, outlining the criteria for institutional and patient selection. The curriculum is discussed and some administrative pitfalls are presented.
A case of prostate cancer in which the parotid gland was the sole site of metastatic disease is presented. Special immunohistochemical stains of the excisional biopsy allowed for rapid, accurate diagnosis and appropriately directed successful therapy.
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Two mouse monoclonal IgG2b antibodies that differ in their CH2 domains have been compared for their blood mean residence times (MRTs) in normal female Rhesus monkeys. A biosynthetically incorporated radiolabel (S-35 methionine) was used to follow blood elimination of the antibodies and urinary excretion. Results indicate that the blood (plasma) MRTs for the Ar13.4 and the ArM16.1 antibodies were remarkably similar in normal Rhesus monkeys. This observation varies greatly from those obtained with these same antibodies in separate studies in normal Balb/c mice. In Balb/c mice, the ArM16.1 antibody was found to be removed from the blood six times faster than the Ar13.4. The CONSAM program was used to fit a multiexponential function to the plasma data obtained from mice and monkeys. The sum of exponentials was then used to calculate the MRT values. These results demonstrate that mouse monoclonal antibody pharmacokinetics significantly differ between normal primates and mice. Presumably the Rhesus monkey better reflects the clinical behavior and pharmacokinetics of mouse monoclonal antibodies than do rodents. Therefore, the use of normal primates for the preclinical evaluation of monoclonal antibodies for in vivo use is suggested.
The serum gonadotropin response to castration was assessed in 8 foetal, 2 neonatal, 30 juvenile, and 2 adult rhesus monkeys (M. mulatta). In the 30 castrated juvenile monkeys and 8 sham-operated controls, concentrations of oestrone, oestradiol, androstenedione, dihydrotestosterone, testosterone and 17OH-progesterone were measured in 10 ml serum pools before, one month after, and one year after the surgical procedure. Castration during foetal life (83-137 days gestation) was followed within 48-72 h by a significant rise in serum FSH levels in males, but had no effect on the already high levels in females. Similarly, castration of males during the first post-natal month raised serum FSH and LH into the adult castrate range; however, after 3 months of age serum gonadotropin levels again declined to the normal juvenile range in spite of the open feedback loop. Orchiectomy of prepubertal juvenile monkeys (age 3 month-2 8/12 years) had no immediate effect on serum gonadotropins, but was followed by a delayed rise in FSH (at age 2 3/12-4 3/12 years) and LH (at age 2 7/12-4 4/12 years) to adult castrate levels. Orchiectomy of older prepubertal (by serum testosterone) or adult males resulted within a few days in a progressive and sustained rise in serum FSH and a more gradual rise in LH. Prepubertal gonadotropin regulation appeared to be sexually dimorphic, since ovariectomy in juvenile females (age 3 months-1 5/12 years) was followed by generally elevated, if somewhat erratic, serum FSH values, with a secondary rise in both FSH and LH levels at 2-2 1/12 years. In both sexes, prepubertal castration caused a significant and sustained decline in serum concentrations of oestradiol; castrated males also showed a decline in serum testosterone levels. Although prepubertal castration also caused in both sexes a slight decline in serum oestrone, and ovariectomy a decline in serum androstenedione and dihydrotestosterone, these effects were not sustained one year later, and values were not significantly different from sham-operated controls. Taken together, these data lend support to a model of primate sexual maturation in which the primary regulator of gonadotropin secretion in both sexes during the prolonged juvenile phase is central inhibition of the hypothalamic GnRH regulator. However, during foetal and neonatal life, and again following the onset of puberty, the major modulator of gonadotropin secretion becomes sex steroid-mediated feedback inhibition.
We investigated an outbreak of nosocomial pneumonia due to gentamicin, methicillin-resistant Staphylococcus aureus (GMRSA). We compared the predisposing factors for pneumonia due to GMRSA to those for pneumonia due to gentamicin, methicillin-sensitive Staphylococcus aureus (GMSSA). Seventeen of 29 patients with staphylococcal pneumonia were infected with GMRSA. Risk factors and associated diseases which selected for infection with GMRSA as opposed to GMSSA included prior antibiotic therapy for a prolonged period of time (p = 0.0001), number of risk factors per patient (p = 0.0001), days hospitalized prior to diagnosis of pneumonia (p = 0.002) and number of associated diseases per patient (p = 0.002). Despite the epidemiologic differences between GMSSA and GMRSA pneumonia, there were no differences in the clinical presentation, course of illness, complications, response to appropriate therapy or outcome between the two groups. Survival was adversely affected by age only among the GMSSA patients (p = 0.02) and by the number of associated diseases (p = 0.005).
While there are homeostatic mechanisms to protect the brain against wide fluctuations in the availability of essential nutrients, food deprivation is known to influence brain neurochemistry. Given the growing problem of infant undernutrition and the fact that the developing nervous system appears to be especially vulnerable to this type of insult, numerous studies have been conducted to define the relationship between nutritional factors and cellular growth and maturation in the brain. The data suggest that the development of both neural and nonneural elements are significantly affected by undernutrition. This includes processes and substances important for neurotransmission such as transmitter synthesis, degradation and receptor sites. Because many neuropsychiatric conditions can be traced to dysfunctions in synaptic neurochemistry, it is possible that some of the central nervous system abnormalities which result from childhood undernutrition may be a consequence of a modification in synaptic biochemistry. The present report reviews data relating to this issue with the aim of assessing its relevance to developmental neurobiology.
The effect of early undernutrition and dietary rehabilitation on [3H]gamma-aminobutyric acid ([3H]GABA) binding in rat brain cerebral cortex and hippocampus was examined. Undernourished animals were obtained by exposing their mothers to a protein-deficient diet during both gestation and lactation. Saturation analysis of [3H]GABA binding in the cerebral cortex and hippocampus revealed high- and low-affinity components in the undernourished group, whereas control animals possessed only a low-affinity site. The concentration of low-affinity binding sites was greater in the undernourished animals. Rehabilitation of undernourished animals completely abolished the binding site differences. Treatment of brain membranes with Triton X-100 yielded two binding components in both the undernourished and control animals, although the concentration of lower affinity sites was still greater in the undernourished group. Neither the efficacy nor the potency of GABA to activate benzodiazepine binding in cerebral cortex was modified by undernutrition. These data suggest that early undernourishment modifies the characteristics of [3H]GABA binding, perhaps by reducing the brain content of endogenous inhibitors of the higher affinity binding site. The lack of effect on GABA-activated benzodiazepine binding suggests the possibility that neither the high- nor the low-affinity GABA binding sites are coupled to this receptor component.
A significant increase in the activity of prolyl hydroxylase, in the relative collagen synthesis and in the hydroxyproline content was observed in the liver of rats treated for five weeks with CCl4 when compared to control liver. Five weeks after the suspension of the treatment, the activity of prolyl hydroxylase and the relative collagen synthesis returned to normal, but the hydroxyproline content of the liver of the CCl4-treated animals remained significantly higher than that of the controls. These findings suggest that an impairment in the mechanisms responsible for the resorption of the scar tissue could account for the accumulation of collagen within the parenchyma in liver fibrosis.
Collagen synthesis was increased in aortas, mesenteric arteries, cerebral microvessels, pial artery, basilar artery and decreased in the heart of rats made hypertensive with deoxycorticosterone acetate-salt or the spontaneously hypertensive animal. The markers of collagen biosynthesis that were elevated were prolyl hydroxylase, prolyl hydroxylase-related antigen, total collagen content and the incorporation of labelled proline into total protein and into collagen. The antihypertensive drugs reserpine and chlorthiazide could both prevent the increase or reduce the increase in collagen synthesis.
Fertility in a rhesus monkey breeding colony was significantly increased by caging females with males immediately after detection of the preovulatory luteinizing hormone (LH) surge. LH was measured in daily serum samples by a rapid (24-hr) radioimmunoassay which used iodinated ovine LK as tracer and an antiserum to human LH.
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In a survey of California almonds, aflatoxin was found in 14% of 74 samples of unsorted, in-shell almonds as received by the processor in 1972, but it occurred at very low levels (below 20 parts per billion (ppb)) in 90% of the contaminated samples. The overall proportion of individual nuts contaminated was especially low and is estimated with 95% probability to have been in the range of 1 nut/55,300 nuts to 1 nut/14,700 nuts. Aflatoxin contamination is not restriced to any particular section of the almond-growing region of California. Commercial sorting procedures are effective in removing most aflatoxin-contaminated nutmeats, since none of 26 samples of processed, whole nutmeats contained aflatoxin. In contrast, 13 of 27 samples of diced almonds were contaminated, but nine of these 13 samples contained less than 20 ppb. Only one of 25 samples of sliced nutmeats contained aflatoxin (4 ppb). Thus, aflatoxin incidence in almonds varies greatly with the category of finished product. The apparent high incidence in diced nutmeats is probably due mostly to the more uniform distribution of aflatoxin occurring in this product (because of its small particle size) than that occurring in the other products. Sample size requirements for monitoring aflatoxin in almonds are discussed.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.