Use of the transgluteal route for percutaneous abscess drainage in acute diverticulitis to facilitate delayed surgical repair.
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Biomedical subjects
Publications and source records attributed to B L Murphy.
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The atypical neuroleptic, clozapine, has been shown to have encouraging, but mixed, effects on prefrontal cortical (PFC) cognitive deficits in schizophrenia, a stress-exacerbated disorder involving dopamine (DA) dysregulation. The current study examined the effects of acute clozapine pretreatment on the spatial working memory deficits induced by the pharmacological stressor, FG7142, in monkeys. Previous research has shown that FG7142 impairs spatial working memory in rats and monkeys through excessive DA receptor stimulation in the PFC (Murphy et al. 1996). Lower clozapine doses (1-3 mg/kg p.o.) reversed the FG7142-induced spatial working memory deficits, whereas doses in the clinical range (e.g., 6 mg/kg, p.o.) did not improve cognitive function in most animals. Clozapine alone produced a dose-related impairment in delayed response performance. These results from nonhuman primates suggest that the clozapine doses commonly used to treat schizophrenia may not be optimal for treating the PFC cognitive deficits associated with this illness.
This study aims to evaluate the ability of quantitative computed tomography (QCT) bone mineral density (BMD) measurement of vertebral bodies to predict risk of hip fracture. We also examine the predictive value of the radiographic Singh index and its relationship to the vertebral BMD. The vertebral BMD (using a QCT protocol) and radiographic Singh index were evaluated in 86 white females who had sustained a hip fracture after minor trauma. 86 age-matched female controls were also studied. All patients were post-menopausal, the age range was 52-95 years. BMD values were found to be low in both the study group and controls; there was no statistically significant difference between the groups. A low Singh index did not correlate with hip fracture, nor did it correlate with low vertebral BMD measurement. We conclude that vertebral BMD and radiographic Singh index are not reliable predictors of hip fracture in the elderly female.
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The anxiogenic benzodiazepine inverse agonist FG7142 increases dopamine turnover in rodent prefrontal cortex but not in other dopamine terminal field areas. FG7142-induced increases in prefrontal cortical dopamine receptor stimulation impair prefrontal-dependent, but not nonprefrontal-dependent, cognitive tasks in rats and monkeys. The degree of impairment correlates with levels of prefrontal cortical dopamine turnover in rats and can be blocked in rats and monkeys with dopamine receptor antagonists, suggesting that increased dopamine turnover is directly related to the cognitive deficits. The current study examined nondopaminergic drug effects on FG7142-perturbed biochemistry and cognition. Both the noradrenergic alpha-2 agonist clonidine and the glycine/NMDA antagonist (+)HA966 prevented the FG7142-induced increase in dopamine turnover in rodent prefrontal cortex. Infusion of (+)HA966 into the ventral tegmental area (VTA) also blocked this increase in dopamine turnover, indicating that critical modulatory effects of (+)HA966 on FG7142-induced changes in dopamine turnover are occurring at the level of mesoprefrontal dopamine neuron cell bodies. Systemic (+)HA966 and clonidine, but not propranolol or D-cycloserine, prevented FG7142-associated spatial working memory deficits in rats and monkeys. These results support the idea of a critical range of dopamine turnover for optimal prefrontal cortical cognitive functioning, with excessive dopamine turnover leading to cognitive impairment. These studies also provide evidence for the regulation of prefrontal cortical dopamine turnover and cognition by multiple neurotransmitter systems and suggest that the VTA is an important regulatory site for these effects.
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The selective activation of the prefrontal cortical dopamine system by mild stress can be mimicked by anxiogenic beta-carbolines such as FG7142. To investigate the functional relevance of elevated levels of dopamine turnover in the prefrontal cortex, the current study examined the effects of FG7142 on the performance of spatial working memory tasks in the rat and monkey. FG7142 selectively increased prefrontal cortical dopamine turnover in rats and significantly impaired performance on spatial working memory tasks in both rats and monkeys. Spatial discrimination, a task with similar motor and motivational demands (rats), or delayed response performance following zero-second delays (monkeys) was unaffected by FG7142. Further, biochemical analysis in rats revealed a significant positive correlation between dopamine turnover in the prefrontal cortex and cognitive impairment on the delayed alternation task. The cognitive deficits in both rats and monkeys were prevented by pretreatment with the benzodiazepine receptor antagonist, RO15-1788, which blocked the increase in dopamine turnover and by the dopamine receptor antagonists, haloperidol, clozapine, and SCH23390. These findings indicate that excessive dopamine activity in the prefrontal cortex is detrimental to cognitive functions mediated by the prefrontal cortex.
OBJECTIVE: Gonadal vein recruitment by collateral veins in patients with renal cell carcinoma is not routinely searched for during abdominal computed tomography. We performed a retrospective view to determine the incidence of gonadal vein recruitment for collateral venous drainage in patients with renal cell carcinoma and we discuss its potential importance. PATIENTS AND METHODS: Abdominal CT examinations were available for 58 of 95 patients with renal cell carcinoma identified during a 3-year-period. The presence of collateral veins and recruitment of the ipsilateral gonadal vein was recorded and correlated with the estimated blood loss at surgery. RESULTS: Eighteen of 58 tumours were small (less than 5 cm). Multiple (greater than three) collateral renal capsular veins were noted in 26 of 58 patients and few (less than three) were noted in 11. Recruitment of the gonadal vein (range 4-18 mm, mean 8 mm) was seen in 18 of 58 patients (31%) who all had multiple collaterals. Gonadal vein recruitment was only seen in patients with tumours greater than 5 cm. Mean estimated blood loss at surgery was significantly different (P < 0.01) in 18 of 58 patients (mean, 1078 ml) with gonadal vein recruitment compared to 40 of 58 patients (mean 304 ml) without distinct visualization of the gonadal vein and compared to 22 of 40 patients with large tumours (mean 368 ml). CONCLUSION: Gonadal vein recruitment signifies well-developed arteriovenous shunting and high flow collateral venous drainage pathways and may be used as an index of tumour vascularity. This finding may have clinical potential in triaging patients toward pre-operative renal embolization.
Dopamine (DA) D1 receptor compounds were examined in monkeys for effects on the working memory functions of the prefrontal cortex and on the fine motor abilities of the primary motor cortex. The D1 antagonist, SCH23390, the partial D1 agonist, SKF38393, and the full D1 agonist, dihydrexidine, were characterized in young control monkeys, and in aged monkeys with naturally occurring catecholamine depletion. In addition, SKF38393 was tested in young monkeys experimentally depleted of catecholamines with chronic reserpine treatment. Injections of SCH23390 significantly impaired the memory performance of young control monkeys, but did not impair aged monkeys with presumed catecholamine depletion. Conversely, the partial agonist, SKF38393, improved the depleted monkeys (aged or reserpine-treated) but did not improve young control animals. The full agonist, dihydrexidine, did improve memory performance in young control monkeys as well as in a subset of aged monkeys. Consistent with D1 receptor mechanisms, agonist-induced improvements were blocked by SCH23390. Drug effects on memory performance occurred independently of effects on fine motor performance. These results underscore the importance of DA D1 mechanisms in cognitive function, and provide functional evidence of DA system degeneration in aged monkeys. Finally, high doses of D1 agonists impaired memory performance in aged monkeys, suggesting that excessive D1 stimulation may be deleterious to cognitive function.
This study demonstrates computed tomographic (CT) findings of morning glory syndrome. CT examination of the orbits was performed in three patients. Images of 2-mm-thick sections were acquired at 2-mm intervals without use of contrast material. Excellent demonstration of coloboma was achieved in each case. Because both magnetic resonance imaging and ultrasonography have limitations in imaging of coloboma, CT is the imaging method of choice in diagnosis of this disorder.
Lead has been recognized for years as an environmental pollutant of concern for young children. Nonetheless, many children in the United States still experience high body burdens of lead. Reducing exposure to lead must include an assessment of all potential sources of lead and a definition of routes of exposure. In this paper, the relationships between soil lead and blood lead concentrations in residents in communities with high soil lead concentrations resulting from past mining and ore processing (milling) activities are compared to those derived from studies in urban communities or communities with operating smelters. The impact of mine waste-derived lead in soil (usually in the form of lead sulfide) on blood lead is less than that for lead in soil derived from smelter, vehicle, or paint sources. Possible reasons for a reduced impact of lead sulfide on blood lead in children in mining communities include the following: lead from mining sources contributes less to lead in the immediate environment of children than lead from other sources; mine wastes typically are of larger particle size, which decreases the bioavailability of lead in the gastrointestinal tract; and lead sulfide is absorbed less in the gastrointestinal tract compared to other lead species. A reduced impact of mine waste-derived lead on blood lead may be important from a regulatory point of view. Expensive cleanup actions for lead-contaminated soils in mining communities based on acceptable soil lead concentrations derived from smelter or urban communities may be questionable in terms of reducing blood lead in children.
In 1981, a hepatitis B vaccine demonstration project was initiated among Yupik Eskimos of southwest Alaska to demonstrate that, under field conditions, the vaccine was safe, immunogenic, and efficacious. Laboratory tests for serologic markers of hepatitis B virus infection (HBsAg, anti-HBs, and anti-HBc) performed on sera collected in May 1981 from 3,988 residents of 17 remote Eskimo villages revealed that 2,645 (66.3%) had no evidence of hepatitis B virus infection. Because of a limited supply of vaccine, specific criteria for selection were used so that those at highest risk of infection would be immunized first. In November 1981, the first dose of vaccine was administered to 1,693 carefully selected individuals. The second dose was administered to 1,678 (99.1%) of those who received the first dose, and the final dose was administered to 1,630 persons (96.3%). Serologic follow-up showed the vaccine to be safe (0.4% experienced minor adverse reactions) and immunogenic (97.4% developed antibody). Vaccine-induced antibody levels were significantly higher for persons less than 30 years of age (p less than 0.001) and for females (p less than 0.001). Vaccine recipients were also protected from hepatitis B virus infection (p = 0.002). This public health measure proved to be feasible and effective in this remote arctic population despite difficult conditions for delivery and administration of this temperature-sensitive vaccine. This strategy for immunization is now being applied on a larger scale in Alaska as part of a program for the primary prevention of this infection and its sequelae.
To determine the risk of hepatitis B virus infection for rural hospital employees, we obtained serum and a completed questionnaire from each of 2,064 employees of 11 rural hospitals. Only 96 (4.7%) employees had hepatitis B virus markers. Increased marker prevalence was significantly associated with prior residence in a city with a population of greater than 100,000 (odds ratio, 2.9; 95% confidence interval, 1.6 to 5.2) and increasing blood contact (odds ratio, 1.6; confidence interval, 1.2 to 2.3); however, the association with blood contact was not significant when we limited analysis to the 836 employees who had never lived in a city. We conclude that the risk of hepatitis B virus infection for these rural hospital employees is low, probably because the incidence of hepatitis B in rural areas is low.
Serial passage of the MS-1 strain hepatitis A virus (HAV) in marmosets was shown to increase the yield of virus and to shorten the incubation period from approximately 55 days in the first passage to 3-7 days in the ninth and higher passages. Intravenous inoculation of susceptible chimpanzees with MS-1 HAV was found to result in a typical course of disease in two animals who had received eighth marmoset-passage virus, including the occurrence of elevated ALT activity, presence of HAV antigen in liver and stool, and seroconversion to anti-HAV. Two chimpanzees inoculated with 20th passage MS-1 HAV (M001 liver homogenate) exhibited normal or nearly normal ALT activity and had no demonstrable or significant HAV in weekly liver biopsy specimens or in serial stool suspensions obtained during 64 days of observation. However, both animals seroconverted to anti-HAV within 2 weeks after inoculation, as did the animals who had received eighth passage MS-1 HAV. These findings suggest that subpassage of the MS-1 strain of HAV in marmosets resulted in the generation of an attenuated virus strain that was still capable of inducing a vigorous antibody response in intravenously infected chimpanzees. Serial propagation of wild and attenuated strains of HAV (HAS-15 and MS-1/M001, respectively) in FRhK-4 cells was associated with a significant decrease in the growth period for both viruses. Our studies have also shown that HAS-15 HAV can be recovered in maximum yield in later passages as early as 2 to 3 days after inoculation.
To determine the significance of certain serological test results commonly encountered in hepatitis B virus testing, we reviewed serological test data from nine studies of hepatitis B conducted between 1980 and 1982. Three tests, for hepatitis B surface antigen and for antibodies to hepatitis B surface antigen and hepatitis B core antigen (anti-HBs and anti-HBc), were used to measure hepatitis B virus infection risk in various populations. Two results, low levels of anti-HBs alone and low levels of anti-HBc alone, occurred at constant frequencies (2.72 and 0.4%, respectively), regardless of the prevalence of HBV infection in the population. Positivity for low levels of anti-HBs alone persisted for 1 year in less than one-half of those studied; in addition, response to hepatitis B virus vaccine was augmented in only one-third of this group. Positivity for low levels of anti-HBc alone did not persist in any of 11 persons studied. These findings indicate that presently available tests for anti-HBs and anti-HBc at low levels are often nonspecific and should be interpreted with caution.
Two chimpanzees with persistent non-A, non-B (NANB) hepatitis were superinfected with marmoset-passaged MS-1 HAV. Two control chimpanzees were also infected with marmoset-passaged HAV. Neither animal with persistent NANB hepatitis developed elevated alanine aminotransferase (ALT) activity, whereas both control chimpanzees exhibited ALT elevations within 3 weeks after inoculation. In addition, both NANB-infected chimpanzees demonstrated a delayed anti-HAV antibody response in which one animal failed to produce detectable IgM anti-HAV. With the exception of one stool, all serial liver biopsy specimens and daily stool suspensions from the superinfected chimpanzees were negative for HAV antigen. One chimpanzee with a chronic HBV infection was superinfected with non-A, non-B hepatitis and was shown to develop elevated ALT activity and hepatocyte ultrastructural alterations accompanied by a marked reduction in the titer of serum HBsAg. Our combined findings indicate that acute and persistent non-A, non-B hepatitis infections are capable of interferring with two distinctly different hepatotropic viruses. These results also suggest that in vitro detection of non-A, non-B hepatitis infection or virus(es) may be achieved by antibody-independent methodologies that employ the basic principle of viral interference.
Sera collected in 1973-1975 from 3053 residents of 12 selected Alaskan Eskimo villages were tested for evidence of hepatitis B virus infection. Overall, hepatitis B surface antigen (HBsAg) was found in 6.4% of those tested. Evidence of hepatitis B infection (positive for HBsAg or antibody to hepatitis B surface antigen (anti-HBs] varied considerably by village, from 4.6% to 69.9%, and increased with advancing age. The proportion with HBsAg was significantly higher in those under the age of 13 years, and the male/female ratio varied from 0.9 to 1.5 to 1.5 in the prepubertal, postpubertal-premenopausal, and postmenopausal age groups, respectively. The prevalence of hepatitis B e antigen (HBeAg) in HBsAg-positive persons decreased with advancing age, and conversely, the prevalence of antibody to hepatitis B e antigen (anti-HBe) increased with age. Hepatitis B infection was found to be sporadically distributed, with great village-to-village variation and further variation by household within most villages. The high HBsAg and HBeAg seropositivity observed in children suggests that children are both more recently infected with hepatitis B and are more involved in hepatitis B transmission in these villages.