Photo quiz. Envenomation from a spider bite.
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Biomedical subjects
Publications and source records attributed to L L Ross.
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This open-label, multicenter, single-arm clinical trial assessed the 48-week efficacy of a twice-daily triple nucleoside reverse-transcriptase inhibitor regimen containing a lamivudine (150 mg)-zidovudine (300 mg) combination tablet (COM) and abacavir (ABC; 300 mg) in 87 antiretroviral therapy-experienced, protease inhibitor-naive patients infected with human immunodeficiency virus type 1 (HIV-1). At baseline, the median plasma HIV-1 RNA level was 3.10 log(10) copies/mL, and the median CD4 cell count was 506 cells/mm(3). An intent-to-treat&rcolon;observed analysis showed that, at weeks 24 and 48 of treatment, HIV-1 RNA level was <400 copies/mL in 48 (76%) of 63 and 45 (82%) of 55 patients, respectively, and <50 copies/mL in 37 (59%) of 63 and 31 (56%) of 55 patients, respectively. Previous zidovudine or lamivudine use and presence at baseline of the M184V reverse-transcriptase mutation did not impact virologic response. Median CD4 cell counts were maintained above baseline throughout the study. COM plus ABC was generally well tolerated.
Although a rare diagnosis, with few reports in the literature, calcific myonecrosis is a diagnosis that must be entertained in individuals presenting with expanding masses in the muscle compartments occurring years after an initial injury. The authors report a previously healthy 66-year-old man with an expanding right lower extremity mass felt initially to be an abscess. Despite presumably appropriate antimicrobial therapy, the lesion continued to expand, causing pain and loss of function. The patient subsequently underwent extensive debridement and free muscle flap transfer with an excellent outcome. This patient serves to remind us that, although calcific myonecrosis is an uncommonly encountered condition, it must be maintained in the differential diagnosis of an expanding muscle compartment mass.
OBJECTIVE: The authors examined brain activity associated with the internal monitoring of performance to test the hypothesis that error-related activity in the anterior cingulate cortex is impaired in patients with schizophrenia. METHOD: Seventeen patients with schizophrenia and 16 healthy comparison subjects underwent event-related functional magnetic resonance imaging during a continuous performance task; stimulus degradation was used to increase error rates. RESULTS: Comparison subjects, but not schizophrenic patients, showed error-related activity in the anterior cingulate cortex, and this difference in brain activity was significantly different across the two groups. Patients also showed less slowing of reaction time after error commission. CONCLUSIONS: Lower error-related activity in the anterior cingulate cortex and less performance adjustment after error commission are consistent with the hypothesis that disturbances in anterior cingulate cortex function are related to a specific alteration in an evaluative component of executive functioning-the internal monitoring of performance.
Event-related functional MRI and a version of the Stroop color naming task were used to test two conflicting theories of anterior cingulate cortex (ACC) function during executive processes of cognition. A response-related increase in ACC activity was present when strategic processes were less engaged, and conflict high, but not when strategic processes were engaged and conflict reduced. This is inconsistent with the widely held view that the ACC implements strategic processes to reduce cognitive conflicts, such as response competition. Instead, it suggests that the ACC serves an evaluative function, detecting cognitive states such as response competition, which may lead to poor performance, and representing the knowledge that strategic processes need to be engaged.
Adélie penguin (Pygoscelis adeliae) males and females, nesting in Antarctica, alternate attendance at the nest with absences of many days to forage at sea. We investigated the importance of tactile input from egg and chicks on prolactin levels by observing nest attendance patterns and obtaining blood samples (1) during the first nest exchange of the incubation stage, (2) from birds whose incubation period was artificially increased or decreased by about 10 days, and (3) from birds whose nests had failed. Prolactin levels in females after 8 to 11 days of absence from the breeding colony did not differ from those in incubating males and did not change after females resumed incubation. Moving eggs between nests resulted in nests in which chicks hatched after about 26, 36 (normal), or 46 days. Duration of incubation did not affect prolactin levels in the parents measured during incubation, at the pip stage, hatch stage, or early brood stage. Adults first left their chicks unguarded on about the same calendar date, regardless of chick age. However, chicks from long incubation nests averaged 8 days younger when they were left unguarded than chicks from control or short-incubation nests. In females, there was no effect of nest failure on prolactin levels. In males, prolactin levels were slightly lower after nest failure than in males tending nests. Testosterone was significantly higher in males after nest failure than in males still tending nests. Prolactin is elevated in Adélie penguins as part of the program of cyclical hormonal changes that accompany the lengthy reproductive season and is relatively independent of tactile input. Sustained prolactin secretion is probably required for the maintenance of parental behavior in offshore feeding species that must be absent from the nest for many days at a time.
Unique in the history of academic medicine in the 20th century was the 1993 merger of two medical schools, Hahnemann University and The Medical College of Pennsylvania, to create Allegheny University of the Health Sciences, the largest private medical school in the United States. During the early, most critical phase of the merger process, the two faculties were brought together to plan and submit an application for The Robert Wood Johnson Foundation's Generalist Physician Initiative (GPI). This action had a profound and lasting impact on the merger of the two schools and the educational enterprise that subsequently evolved. The GPI grant was awarded to the merged school in the midst of this complex merger rife with major changes, all with their attendant fears and frustrations. During and just after the merger, at a time when faculty and staff were somewhat uncertain about the direction of the university, the GPI provided a focus with a clear set of goals and objectives. Despite the unprecedented changes occurring in the organization and personal and professional concerns, faculties from the two institutions were able to join in pursuing the generalist initiative and its associated curriculum reform. This single, pervasive effort was a significant factor in forming a unified faculty of a united school of medicine. This sense of unity was put to the test when, in July 1998 the university, along with its affiliated hospital system, filed for bankruptcy. The goals of this extraordinary action were to sell the hospitals to another organization, thereby removing from the university the burden of supporting hospital-based clinical programs and allowing the university to emerge as a freestanding academic institution focusing on its core mission of education and the principles embodied in the GPI.
Two novel assays, a restriction fragment length polymorphism (RFLP) assay and an assay based on the 5'-nuclease activity of Taq DNA polymerase, were developed for screening viral variants in lamivudine-treated patients' sera containing <1,000 copies of the hepatitis B virus (HBV) genome per ml. Both assays were designed to detect single-nucleotide changes within the HBV DNA polymerase gene that are associated with lamivudine resistance in vitro and have been used to screen a number of patients' sera for variant virus. Results obtained with these assays and standard sequencing technology were compared with regard to throughput, ability to detect individual virus species present at low concentrations, and ability to detect, distinguish, and quantitate wild-type (wt) and HBV tyrosine methionine(552) aspartate aspartate motif variants in mixed viral populations. Unlike DNA sequencing, both assays are amenable to high-throughput screening and were shown to be able to quantitatively detect variant virus in the presence of a background of wt virus. As with DNA sequencing, both new assays incorporate a PCR amplification step and are able to detect the relatively low amounts of virus found in lamivudine-treated patients' sera. However, these assays are far less labor intensive than the DNA-sequencing techniques presently in use. Overall, the RFLP assay was more sensitive than DNA sequencing in detecting and determining the ratios of wt to variant virus. Furthermore, the RFLP assay and 5'-nuclease assay were equally sensitive in the detection of mixed viral species, but the RFLP assay was superior to the 5'-nuclease assay in the quantitation of mixed viral species. These assays should prove useful for further understanding of virological response to therapy and disease progression.
OBJECTIVES: Administrative data from Manitoba, Canada document variation in procedure utilization rates over a period of 15 years. With coronary angiography and cardiovascular surgery centralized in the capital, Winnipeg, previous analyses from 1977 to 1983 found angiography and coronary artery bypass surgery (CABS) rates to be higher for residents of Winnipeg. Residents of the Western region had consistently lower rates; this variation in regional access appeared due to physician practice patterns. In this study all angiography patients were followed from 1987 to 1992 and rates of CABS and percutaneous transluminal coronary angioplasty (PTCA) calculated. METHODS: Cox proportional hazard multivariate regression models with five sociodemographic variables and two clinical variables (time from angiography to revascularization, and comorbidities) also were examined. RESULTS: Consistent regional variation was documented; rates in the Western region remain consistently low. A "funnel effect" is found; the fewer patients from a region referred for angiography, the fewer patients from that region who have CABS or PTCA. CONCLUSIONS: Implications of the persistence of these findings are discussed. Individuals in Western Manitoba probably have some of the lowest rates of coronary artery bypass surgery and percutaneous transluminal coronary angioplasty in North America.
Stereotypies are high-frequency, highly repetitive, nonfunctional behaviors that are also often characterized as rhythmic. Rhythmicity suggests that the behavior is periodic, occurring at fixed intervals. Few studies, however, have rigorously demonstrated periodicity in stereotypy. This study examined various topographies of stereotypy in 9 participants and used spectral methods to detect existence of periodicties. Two general patterns emerged in the spectral analysis. Participants who engaged in stereotypic rocking showed peaks in their power spectra; participants who engaged in other topographies of stereotypy did not show peaks. Thus, it appears that although some stereotypies--notably, rocking--have a periodic component, rhythmicity does not appear to be a characteristic of stereotypy in general.
The current environment in which medicine is taught and practiced requires that medical schools pay increased attention to the faculty member's roles, rewards, career development, and productivity. Medical schools must make strategic decisions about the allocation of resources that can nurture their faculties and support the activities in academic and community settings in which faculty are involved. From 1993 to 1995 Allegheny University of the Health Sciences (formerly Medical College of Pennsylvania and Hahnemann University) designed a comprehensive system for the professional development of faculty. This system is based upon expanded categories of faculty academic activity and scholarship. New programs were implemented to reorient faculty toward conducting and documenting the expanded array of scholarly activities. The main characteristics of the new system are the establishment of formally defined performance expectations, the vertical alignment of the individual faculty member's objectives with the department's mission and the school's mission, and an increasing emphasis upon faculty interdependence, accountability, and use of sound business practices. The authors describe these and other aspects of the design of the new system in detail and report initial results and lessons learned from the system's implementation, evaluation, and dissemination throughout the university. The long-term success of this comprehensive professional development program will be assessed over time by observing how this institution advances its mission in a well-planned and cost-effective manner that retains talented, productive, and professionally fulfilled faculty.
We used subtractive screening of a cDNA library prepared from corneoscleral rims after cauterizing rat corneas. We identified 76 clones whose corresponding mRNA increased during the wound healing process in an in vivo model of injury which damages the corneal epithelium, stroma, and endothelium. Of these clones, 31 sequences encode known proteins. Another 45 clones are novel sequences based on comparison with the GenBank/EMBL databases. Changes in the level of expression of the novel genes, and a selected number of the known genes, were examined by in situ hybridization 22 and 72 hr after corneal injury. The majority produced a 'wound pattern' of expression such that the mRNAs were highly induced in all cell types adjacent to the wound site at 22 hr post injury. This signal decreased in intensity with distance from the wound site. In a subset of corneoslceral rims examined by in situ hybridization, the mRNAs for these genes were also highly induced in the limbal epithelium, where the progenitor corneal epithelial stem cells reside. By 72 hr, when acute tissue damage had been repaired, the induced mRNA was only faintly present in the thickened epithelium. Our results provide a useful framework for further studies defining the pathophysiological roles of the known and novel proteins encoded by the isolated cDNA clones.
This study compared the effects of multiple versus single deadline contingencies on distribution of unit-mastery test taking by students in four university classes taught using the personalized system of instruction. Rate of test taking was most uniform when multiple deadlines were imposed throughout the course. When deadlines were infrequent, a scalloped pattern of test taking developed.
Some forms of stereotyped human behavior seem to occur randomly in time. A dynamical analysis of several topographies demonstrates that while such stereotypies have the spectral characteristics of random noise, the rate at which each subject exhibits his/her stereotypy is to some extent predictable and, unlike uncorrelated noise, prediction accuracy declines with increasing prediction interval. Rhythmic stereotypies appear to be more predictable than nonrhythmic topographies but both show a similar decline in prediction accuracy. Furthermore, the distribution of interresponse times exhibits self-similar behavior. These results point to a deterministic, rather than stochastic, origin for the variability of observed rates of stereotyped behaviors.
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Our previous studies showed that stressing newborn animals by immobilization during the first 2 weeks of life caused significant changes in the capacity of adult rats to respond to stress as measured by the adrenal and circulating levels of catecholamines. In this report the effect of stress on the antibody response to the capsular polysaccharide of Type III Streptococcus pneumoniae (SSS-III) was investigated in two different strains of rats: Sprague-Dawley (SD) and Fischer (F) 344 rats. Animals were stressed 1 h each day for a total period of 10 days. Following this period of stress, animals were reared together along with littermate controls up to 40 days of age, when they were immunized with an optimally immunogenic dose of SSS-III. The results of experiments done with SD rats showed a substantial suppression of the antibody response when the response of the neonatally stressed animals was compared to the controls. In contrast, stressing adult SD animals for 10 days, followed by a 3-week recovery period prior to immunization with SSS-III, did not result in any significant (p greater than .05) suppression of antibody response. When F rats were used, the antibody response of the neonatally stressed rats was also significantly (p less than .05) lower than that of the controls. Thus, the effects of chronic, immobilization stress on antibody response can be long-lasting when the stressor is applied during the neonatal period.
In the rat, functional connections between the splanchnic nerve and the adrenal medulla are immature at birth and do not become fully competent until the first postnatal week. Neonatal administration of triiodothyronine (T3) accelerates this process, and the present study was undertaken to elucidate the underlying mechanisms. Rats were given T3 (0.1 mg/kg, s.c.) daily for 9 days beginning 1 day after birth. Preganglionic innervation of the adrenal medulla was examined by retrograde axonal transport of horseradish peroxidase (HRP). At 10 days of age, there was an increased number of labeled perikarya in the spinal cord of the hyperthyroid pups. Ultrastructural examination revealed a corresponding increase in synaptic density in the adrenal medulla and in the activity of choline acetyltransferase, a marker for preganglionic cholinergic nerve terminals. These effects were attenuated by 25 days of age, whereupon deficits in HRP-labeled neurons and adrenomedullary synapses were noted. Similarly, replication of chromaffin cells was enhanced transiently in the T3 group during the initial stage of hyperthyroidism, but subsequent long-lasting deficits in cell numbers were noted, along with a corresponding retardation of ontogeny of adrenal catecholamine biosynthesis and storage. Thus, neonatal hyperthyroidism accelerates synaptic development in the sympatho-adrenal axis but suppresses maturation of the target chromaffin cells, ultimately leading to impaired adrenomedullary function.
Adrenergic receptor binding characteristics were analyzed in the mutant mouse tottering (tg/tg), a single gene locus autosomal recessive mutation causing hyperinnervation by locus coeruleus neurons of their target regions, which results in epilepsy. Instead of the expected down-regulation of receptors due to the hyperinnervation, both [3H]prazosin (alpha 1-receptor) and [125I]iodopindolol (beta-receptor) binding were normal in the tg/tg hippocampus, spinal cord and slightly increased in the cerebellum. This lack of postsynaptic receptor modulation in the target cells, combined with increased levels of norepinephrine due to the aberrant axon growth, may the critical factors in the expression of the abnormal spike-wave absence seizures in the tg/tg mouse.