Smallpox in aboriginal Australia: the early 1830s.
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Biomedical subjects
Publications and source records attributed to J Campbell.
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Nurses use theory to sharpen their observations and to facilitate their understanding of the human responses to which they direct their interventions. An assessment tool, derived from the nursing theory 'modelling and role-modelling', was developed by nurses at the University of Michigan Hospitals. This tool appears to elicit the data necessary to assess and diagnose the health status of clients. This article describes the assessment tool, why it was developed, the objectives in utilization of the tool and suggestions for implementation.
Physiological characterization of the APR-11 variant of Streptococcus faecalis ATCC 9790 revealed that the variant has reduced sensitivity to glucose catabolite repression. This reduced sensitivity was indicated by the synthesis of enzymes for catabolism of lactose or arginine in cultures growing at 0.1, 40, or 70 MPa in media with levels of glucose highly repressive for the parent strain. Reduced catabolite repression appeared to be due to reduced activity of the glucose-specific, phosphotransferase system in APR-11 cells. Conversion of pyruvate to lactate or to acetate and ethanol did not appear to be altered in the variant. The APR-11 variant produced a greater final yield of biomass than the parent at all pressures tested, and its barotolerance was especially marked in media with low levels of glucose and high levels of lactose in which derepression of the lactose catabolic system was necessary for full growth. Overall, the greater barotolerance of the APR-11 strain appeared to be due to its enhanced capacity for catabolism related to its reduced sensitivity to catabolite repression by glucose.
Serum antibodies to strains of avian paramyxovirus and flavivirus were detected in little blue penguins sampled at Port Campbell and Phillip Island, Victoria, Australia. No antibody to Newcastle disease virus (NDV) was detected in 267 sera collected, although one penguin captured for experimental studies had a hemagglutination-inhibition antibody titer of 2(4) to this virus. Experimental studies showed that the avian paramyxovirus designated APMV-IM and strain V4 of NDV were non-pathogenic for penguins, although the penguins could have been previously infected with these or similar virus strains. A flavivirus designated Saumarez reef virus, and an unnamed virus isolated from ticks on Macquarie Island, Southern Ocean were pathogenic causing disease and mortality in penguins inoculated with the viruses.
The neurotoxic effects and cerebrospinal fluid (CSF) pharmacokinetics of bleomycin were evaluated in beagles after chronic intraventricular administration twice a week for 8 consecutive weeks. Bleomycin was reasonably well tolerated at doses of 0.067 to 0.3 mg/week. Doses higher than 0.3 mg/week produced marked elevation of CSF protein levels and a necrotizing vasculitis within the central nervous system. Pharmacokinetic studies were performed approximately 1 month after the completion of the toxicity studies. [3H]inulin was used as a reference compound. Both [3H]inulin and bleomycin were cleared from the CSF more slowly than in previous studies and more slowly than in normal dogs, which suggests that bulk CSF absorption was reduced by the drug, probably secondary to protein-induced blockage of the arachnoid granulations through which CSF is normally absorbed. Because a "minimally toxic" dose of bleomycin (approximately 0.1 mg/week) produces a CSF C X t of only 1.9 mg/min/ml, we believe that a Phase I clinical trial would be too dangerous given the limited therapeutic potential that a dose of 0.1 mg/week could achieve.
The central nervous system toxicity and cerebrospinal fluid (CSF) pharmacokinetics of 3-[(4-amino-2-methyl-5-pyrimidinyl)ethyl]-1-(2-chloroethyl)-1- nitrosoureas, a (ACNU) were determined in beagles and compared to those for three other nitrosoureas, 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, and chlorozotocin. Of the four drugs, ACNU was tolerated best and at doses of 0.2 to 0.8 mg/week for 8 consecutive weeks. We found that the average half-time for CSF elimination of ACNU was 18 min (range, 12 to 38 min). This value exceeded the known rate of ACNU decomposition in aqueous solution (28 to 29 min), implying that the disappearance of ACNU from CSF was due to hydrolytic decomposition and cellular entry and/or transcapillary loss across central nervous system capillaries. The drug exposure integral (C X t) of ACNU in the CSF after a "toxic dose low" of 0.8 mg in the dogs would achieve the equivalent of in vitro cell kills in excess of 3 logs for rat 9L and human glioma 126 cells. As a potential therapeutic agent for meningeal neoplasia, the major limiting factor may be that the CSF elimination of ACNU is rapid compared to its equilibration time from ventricle to spinal- and cerebral convexity-subarachnoid space. Based on these results, we have instituted clinical Phase I trials of intra-CSF ACNU.
Transplant fine needle aspiration (FNA) cytology has been suggested as a method for monitoring intrarenal changes of acute rejection after transplantation. We studied this technique by sampling dog renal allografts daily with simultaneous FNA's and core needle biopsies from the time of transplantation to complete rejection. Individual FNA's were analyzed by the increment method, subtracting peripheral white blood cell counts from aspirated white blood cell counts to define the composition and extent of interstitial mononuclear infiltrate. The increment for each mononuclear cell type was corrected by a factor related to its immunologic relevance and the new values summed to produce the total corrected increment, an index of rejection. FNA findings were compared to histologic sections graded 0 to 4 according to the extent of mononuclear infiltrate that was present. FNA sample adequacy was assessed by the aspirate sampling index (ASI), the concentration of renal tubular cells per high power microscopic field. Mean FNA increments for all mononuclear cell groups increased as rejection progressed histologically. Mean total corrected increment ranged from 0.9 with no rejection to 9.8 with grade 4 rejection (R = 0.73; p = 0.001). Mild and moderate infiltrates were detected more accurately when ASI was at least 0.25, while denser infiltrates could be detected in samples with lower ASI. These findings indicate FNA can identify the mononuclear infiltrate associated with acute rejection and the FNA score correlates with the magnitude of the infiltrate if the parenchymal component of the sample is large enough. The ASI is of value in evaluating the samples and reducing the likelihood of false-negative interpretations.
The impact of mass treatment with praziquantel on 241 individuals, 131 males and 110 females in Napu Valley, Indonesia was studied. The pre-treatment overall stool positive cases ranged from 43% to 79%, the highest in the 20-29 age group. Post-treatment follow-up study showed that the cases dropped to 2.5%. Significant reduction was seen in liver rate from 68% to 51% and in the age groups 0-9, 10-19, there was a significant decrease in liver enlargement after treatment, but not significant differences were seen in spleen rate in all age groups. This might be due to the early stage of Schistosoma infection in younger age groups where complete resolution of fibrosis might occur.
The St. Francis Boys' Homes early intervention program for inadequately coping fourth-, fifth-, and sixth-grade students depends upon school teachers' nominations and employs their descriptions of pupil characteristics. In the interest of behavioral science, as well as the potential screening-in, selective placement, predictor purpose, and clinical gain within the tailored treatment program, the teachers completed a 99-item, favorable and unfavorable item description of 852 youths who were participating for 45 days in "Passport for Adventure." This large array of items yielded 14 first-order and four second-order factors, many of which have been found in the extensive literature. These measures of 14 first-order factors obtained through ratings by numerous teachers in 122 school settings demonstrated the wide span of the usual teacher's perception of youths in a formative period of their lives. It included interpersonal and intrapersonal descriptors. Most prior studies entered analysis with a low number of items and therefore could describe only a few simpler dimensions and could name them with less certainty. In addition, the factor analysis was sometimes unrealistically orthogonal and not finally hand rotated for clearest simple structure. This study gives a more comprehensive understanding of what teachers can and do perceive within and among their students, made manifest by a more extensive sampling of behavior.
Fifty-nine patients with end-stage renal disease undergoing long-term dialysis were studied prospectively for joint disease. Radiographic assessment allowed division of patients into 3 groups: group 1 included 12 patients with renal osteodystrophy and erosions of the metacarpophalangeal, proximal interphalangeal, distal interphalangeal, shoulder, wrist, and knee joints; group 2 had 11 patients with renal osteodystrophy without articular erosions; group 3 included 36 patients without osteodystrophy or erosions. Clinical manifestations were frequent in patients of group 1 and included episodes of arthralgias of the metacarpophalangeal, wrist, proximal interphalangeal, and knee joints. Patients of groups 1 and 2, particularly those of group 1, had a longer mean duration of dialysis and a higher mean serum alkaline phosphatase level compared with group 3 patients. The study indicates that there is a relatively high incidence (20%) of erosive arthropathy in dialysis patients. Renal osteodystrophy, more specifically, secondary hyperparathyroidism, and duration of dialysis are important factors in the development of this articular disorder.
The rat foetus, in contrast with the maternal liver and placenta, has little or no ability to hydrolyse di-(2-methoxyethyl)-phthalate (DMEP) to mono-2-methoxyethyl)-phthalate (MMEP). At short times after the administration of DMEP to the dam on the 14th day of gestation, however, both the di- and mono-ester are present in the foetus. Clearance of total phthalate from the foetus and placenta, is rapid and the foetal burden is reduced by 96% between 45 min and 4 h. Although MMEP, when injected into the dam at the same molar dose level, crosses the placenta, its concentration in the foetus is lower than the after the injection of DMEP, MMEP (2.49 mmol kg-1), is no teratogenic when administered as an aqueous solution of the sodium salt on day 8, 10, 12 or 14 of gestation, in contrast with the same molar dose of the liquid DMEP. The alcohol, 2-methoxyethanol (ME), when administered as a single injection at this dose level (2.49 mmol kg-1), however, is highly teratogenic and its effects cannot be differentiated clearly from those of DMEP. These results, which indicate the possibility that ME, derived by metabolism of DMEP, may be the teratogenic agent, suggest that both the rate of hydrolysis to the monoester and the chemical properties of the liberated alcohol, could be important determinant factors in the teratogenic activities of different phthalate diesters.
We have developed a beagle dog model to study the pharmacology and toxicology of anticancer drugs administered through the 3rd or lateral ventricles. A Foltz-type reservoir was implanted SC and connected by tube into a cerebral ventricle. Drugs were administered directly into the reservoir; CSF sampling of drugs administered into the ventricle was achieved directly by tapping the reservoir or by percutaneous puncture of the cisterna magna. In the current study, we evaluated the CSF pharmacokinetics and CNS toxicity of two inhibitors of polyamine metabolism, alpha-difluoromethylornitine (DFMO) and methylglyoxal bisguanylhydrazone (MGBG). Both drugs were judged too toxic to justify intrathecal or intraventricular studies with these agents in patients.
Ethyl carbamate (EC) and two related carcinogens, ethyl N-hydroxycarbamate (ENHC) and vinyl carbamate (VC), caused species-specific increases in sister-chromatid exchange (SCE) formation in the bone marrow cells of rodents. Mice exposed to 400 mg/kg of EC had SCE increases of 6-times-baseline, while rats, Chinese hamsters, and golden hamsters showed 3- to 4-times-baseline increases in response to this dose. Lesser, but still significant, differences were found for ENHC and VC; the severest effects consistently occurred in mice. Control bone marrow cell-cycle kinetics among the rodent species were similar. Mouse strains A and C57BL/6, which have high and low susceptibilities to EC induction of lung adenomas, respectively, showed nearly identical levels of SCE induction after in vivo exposure to these carbamates. However, testing of VC, a possible metabolite of EC, in vitro revealed strain-dependent liver enzyme (Aroclor-induced S-9 fraction) capabilities to convert VC to genotoxic products. SCE induction, gene mutation for 6-thioguanine and ouabain resistance, and cytotoxicity in Chinese hamster V79 cells were significantly greater when A strain S-9 enzymes were used as compared with C57BL/6 strain S-9 enzyme preparations. No effect on SCE of reseeding, compared with no reseeding, of VC-treated V79 cells was observed. At a concentration of 25 micrograms/ml, VC caused 6-times-baseline induction of SCE in the presence of A strain S-9 mix and 4-times-baseline induction in the presence of C57BL/6 strain S-9 mix. These in vitro strain-dependent patterns of response are relevant to the current theory that VC may be a proximate carcinogenic metabolite of EC.
Recent studies have suggested genetic linkage between the major histocompatibility complex and affective disorder. We tested this hypothesis in a large pedigree of bipolar affective disorder in which 22 of 37 relatives were interviewed and HLA typing was carried out on 20. The findings provided no evidence for linkage between affective disorder and HLA antigens. Our findings are discussed along with those of other linkage studies bearing on this question.
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The effects of a purported animal model of depression (inescapable shock, IS) was tested on: (a) escape behavior, (b) regional brain levels of norepinephrine (NE), serotonin (5-HT), and dopamine, and (c), the response of the cerebromicrovasculature to metabolic demand as mimicked by manipulation of arterial CO2 content (PaCO2). Multidisciplinary research has implicated central biogenic amines in the regulation of cerebromicrocirculation. IS treatment resulted in increased escape latency and lowered levels of NE and 5-HT in the locus coeruleus but not in terminal fields in distant regions. This treatment also did not alter cerebral blood flow or capillary permeability in distant regions when compared with control rats. Thus, the discrete changes in NE and 5-HT in locus coeruleus induced by IS treatment is not reflected in changes in cerebral blood flow and the effective permeability of the blood-brain barrier.
The purposes of this study were 1) to document ankle and subtalar motion during gait in 20 healthy subjects and in 25 patients with rheumatoid arthritis (RA) and 2) to determine stride characteristics with and without the use of an extended University of California Biomechanics Laboratory orthosis in RA patients with painful ankle and hindfoot deformity. An insole foot-switch system and ankle and subtalar electrogoniometers measured stride characteristics and dynamic range of motion (ROM). Arthritic patients demonstrated less ROM than healthy subjects except for ROM of hindfoot valgus. Arthritic patients also had slower gait velocity and less single limb support (SLS) time. In five new and five current orthotic wearers, a significant increase (p less than .01) in velocity and SLS time occurred with shoes and a further significant increase (p less than .01) occurred with the orthosis. Nine of 10 patients reported a decrease in ankle and hindfoot pain after using the orthosis. This study demonstrates the value of an orthosis for the treatment of arthritic patients with ankle and hindfoot pain and deformity.
Although pubertal development is unusual in 46,XY gonadal dysgenesis, it may occur in association with gonadal tumors. The authors report a case of 46,XY gonadal dysgenesis in a 17-year-old girl remarkable for H-Y+ phenotype and bilateral gonadoblastomas accompanied by dysgerminomatous change and nearly complete female secondary sex development. Endocrinologic activity of the gonads was indicated by marked decrease in sex steroid production after gonadectomy. Occurrence of gonadal neoplasia in this case is consistent with the observation that neoplastic transformation is likely in H-Y+ cases of 46,XY gonadal dysgenesis.