Biomedical subjects
A Williams
Publications and source records attributed to A Williams.
PrP deposition, microglial activation, and neuronal apoptosis in murine scrapie.
The present study investigated the relationship among PrP deposition, microglial activation, vacuolation, and neuronal death in the hippocampus of the 301V/VM murine scrapie model (mean incubation period 117 +/- 1 days). PrP deposition was first detected after 30 days and microglial activation after 60 days. Vacuolation in the CA1 and CA2 pyramidal layer was present from 90 days onward. Only occasional in situ end labeling (ISEL)-positive neurons were present in the hippocampus of scrapie-infected mice from 75 days postinoculation (d.p.i.), except at 105 d.p.i. when relatively large numbers of apoptotic, ISEL-positive neurons in the CA1 hippocampal region were observed. Terminally ill animals showed almost complete loss of CA1 pyramidal neurons. Electron microscopy of the CA1 region at 105 days confirmed that these neurons were dying by apoptosis. These data suggest that microglial activation in scrapie is a response to abnormal PrP deposition rather than a response to neuronal cell loss.
National audit on the practice and training in breech deliveries in the United Kingdom.
OBJECTIVE: To assess training in breech delivery in the United Kingdom at the level of registrar. METHOD: Three hundred and nineteen registrars in obstetrics and gynecology in the United Kingdom replied to a postal questionnaire. RESULTS: The various indications of cesarean section in breech presentation answered by respondents were: pre-term labor, pelvimetric measurement of inlet/outlet less than 11.5 cm, primigravida, no spontaneous labor, estimated fetal weight less than 2.5 kg or more than 3.5 kg, non-progression of labor in active phase, non-delivery after one hour of active pushing in second stage. A total of 190 respondents (60%) felt that they had been given sufficient training in vaginal breech delivery but only 125 respondents (39%) had the training in the United Kingdom. CONCLUSION: There is a high rate of cesarean section in breech presentation due to inadequate training of junior staff in vaginal breech delivery.
Hand infections in the diabetic patient.
Between 1984 and 1994, 23 diabetic patients were admitted to a university hospital/Department of Veterans Affairs (DVA) Medical Centre with a primary or secondary diagnosis of hand infection. We also identified 726 patients admitted to all DVA Medical Centres during the years 1989 through 1994 with co-diagnoses of diabetes mellitus and hand infection. Contrary to previously published literature, most diabetic hand infections are non-specific, confined to the soft tissues, and respond to broad spectrum parenteral antibiotic therapy. When surgery is necessary, most patients do not require amputation.
Valuing health status using VAS and TTO: what lies behind the numbers?
It is well known that different methods of eliciting the valuations attached to various health states, such as the Visual Analogue Scale (VAS) and the Time Trade Off (TTO), yield different results. This study gathers qualitative data from a group of 43 respondents who had previously taken part in a large scale national study which set out to elicit the values attached by individuals to various health states using both the VAS and the TTO techniques. The findings of this study raised three questions which are of particular interest here: (1) Why are some states that are rated better than dead on the VAS often rated as worse than dead in TTO? (2) Why are some respondents unwilling to trade off any time at all in order to avoid a health state that they place below full health on the VAS? (3) Why are TTO valuations of older respondents for the more severe health states lower than those of the younger age groups? This study has uncovered qualitative evidence on each of these three key issues. Regarding the first question, many respondents did not appear to interpret a better than dead VAS score as a strict preference for spending 10 years in a health state over immediate death. Several different factors appeared to contribute towards this, an important one being the tendency of respondents to ignore the duration of the health state during the VAS task. Regarding the second question, there is evidence of the existence of a "threshold of tolerability" below which states would have to fall before some respondents would be willing to give up any time at all on the TTO. Regarding the last question, it appears that older respondents are less likely to find the worse than dead TTO scenario plausible than those in the younger age groups. However, whilst this may explain why older respondents attach lower worse than dead valuations to health states, it does not appear to account for the entire difference in TTO valuations between the two age groups. In addition, it appears that older respondents may be less prepared to live for the next 10 years in a diminished health state.
The bifurcate coracoacromial ligament: an arthroscopic variant.
A 28-year-old woman underwent shoulder arthroscopy. Bursoscopy revealed a bifurcate appearance of the coracoacromial ligament (CAL). We believe this case report is the first description of this appearance, which represents a normal variant. Several cadaveric studies have documented a bifurcate CAL to be seen frequently at dissection. Presumably, the bifurcate segment of the CAL usually lies out of view from inspection within the subacromial bursa, thereby accounting for the rarity of the appearance we describe.
The assessment of acute confusion as part of nursing care.
Older adults who become acutely confused when hospitalized present challenges to nurses because of their increased care needs and risk for injury. This study evaluated the feasibility of introducing the NEECHAM Confusion Scale as part of usual nursing care as a first step in improving nurses' ability to assess, prevent, and manage acute confusion in hospitalized older adults. By addressing several of the factors that influence adoption and continuation of a new practice, this study found that staff nurses could successfully use the NEECHAM Confusion Scale.
Donor pretreatment with leflunomide has an adverse effect on rat cardiac allograft survival.
The effect of leflunomide (Lef) donor pretreatment (DPT) on rat cardiac allograft survival was investigated. In untreated Lewis recipients of untreated DA hearts, median graft survival was 5 days. DPT (Lef 5 or 10 mg/kg per day for 30 days) reduced median graft survival to 4.0 and 4.5 days, respectively. In immunosuppressed (Lef 5 mg/kg for 10 or 30 days) Lewis recipients of untreated DA hearts, median graft survival was 21 and 33 days, respectively. DPT with Lef 5 mg/kg per day for 5 days or 30 days reduced median graft survival to 12 and 23.5 days, respectively (p < 0.05). DPT with Lef resulted in earlier graft rejection but the histological appearance at the time of rejection was the same as in untreated controls. DPT with Lef resulted in a 40% reduction in MHC class II-positive cells in the heart. Histological examination of rejecting hearts showed no obvious difference in the nature of the rejection process between DPT and untreated control hearts. The paradox between class II reduction but earlier rejection indicates that DPT is exerting a deleterious effect through some unrecognized property of the graft.
Antiretroviral therapy: factors associated with adherence.
Clinical effectiveness of the new highly active antiretroviral therapies depends in large part on patients' ability to adhere to demanding medication regimens because the suboptimal drug levels associated with nonadherence are, in turn, associated with the development of antiretroviral resistance. However, definitions of adherence are inconsistent, and the concept is difficult to measure. Adherence to medical and health regimens is the outcome of a dynamic process of human behavior and interaction. Factors influencing this process include characteristics of the regimen, the provider, the patient, and society.
HIV therapeutics: confronting adherence.
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ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents.
The 55-kilodalton (kDa) protein from the E1B-region of adenovirus binds to and inactivates the p53 gene, which is mutated in half of human cancers. We have previously shown that the replication and cytopathogenicity of an E1B, 55-kDa gene-attenuated adenovirus, ONYX-015, is blocked by functional p53 in RKO and U20S carcinoma lines. We now report that normal human cells were highly resistant to ONYX-015-mediated, replication-dependent cytolysis. In contrast, a wide range of human tumor cells, including numerous carcinoma lines with either mutant or normal p53 gene sequences (exons 5-9), were efficiently destroyed. Antitumoral efficacy was documented following intratumoral or intravenous administration of ONYX-015 to nude mouse-human tumor xenografts; efficacy with ONYX-015 plus chemotherapy (cisplatin, 5-fluorouracil) was significantly greater than with either agent alone.
Vascular adhesion protein-1 and intercellular adhesion molecule-1 mediate T-cell binding to human hepatocellular carcinoma.
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Segregation analysis of ovarian cancer using diathesis to include other cancers.
Despite the recent cloning of BRCA1, BRCA2 and the mismatch repair genes, it will still be a long time before it is possible to specify any individual's risk for ovarian cancer based on her genotype. Most women concerned about their risk on the basis of one or two affected relatives do not belong to extensive ovarian cancer families. Risk calculations depend on a reliable genetic model for ovarian cancer derived, ideally, from the population from which an individual is drawn. We have carried out a segregation analysis using data collected from consecutive ovarian cancer patients in two different centres in the UK. Complex segregation analysis was carried out with the addition of diathesis as a separate parameter allowing other cancers, associated with ovarian cancer, to be taken into account. The use of diathesis in the derivation of this alternative model is described. Analysed under joint likelihood without diathesis, the gene frequency is 0.0028 and penetrance to age 70 years is 50%. This is in agreement with other published models. Incorporating diathesis into the model under joint likelihood gives similar parameters for a single locus model but gives the best fit with a two locus model where both genes are rare.
End-to-side neurorrhaphy: a histologic and morphometric study of axonal sprouting into an end-to-side nerve graft.
This study investigated axonal regeneration in a denervated nerve graft sutured end-to-side with a main peripheral nerve trunk. To demonstrate morphologic changes, the peroneal nerve was severed in a rat and coapted end-to-side to the posterior tibial nerve. The integrity of the epineurial and perineurial sheath was altered in four different groups. Histologic evaluation 30 days after operation showed axonal regeneration in the nerve graft in all groups. Morphometric analysis of cross sections of the grafted nerve elucidated the importance of severance of the perineurium in end-to-side neurorrhaphy.
A new animal model to investigate axonal sprouting after end-to-side neurorrhaphy.
End-to-side neurorrhaphy is a technique that may provide a solution for the problem of distal target reinnervation without injury to the original donor nerve. The technique drew extensive attention after Viterbo reported his experiments in 1992; however, to date, the animal models used to elucidate the process of lateral axon sprouting had the disadvantage of substantial injury to the donor nerve, raising questions about the origin of axons reinnervating the nerve graft. In this report, a new model in the rat is introduced, in which the donor nerve is not damaged and an additional target can be innervated via a nerve graft. The saphenous nerve represents the axonal conduit; the proximal end is coapted end-to-side to the sciatic nerve at the site of a perineurial window. The distal end is passed through the adductor muscles and coapted distally in an end-to-end fashion with the obturator nerve. In one group, a partial neurectomy was performed at the site of coaptation, which led to a lower Sciatic Functional Index (SFI). In the second group, the creation of a perineurial window yielded a normal SFI after end-to-side neurorrhaphy. Compared to the partial neurectomy group, the perineurial window end-to-side neurorrhaphy resulted in significantly less axons in the graft. The new model has the following advantages: (a) minimal injury to the donor nerve; (b) provision of a single additional target (gracilis) whose functional recovery can be assessed morphologically and behaviorally; (c) an opportunity to understand lateral sprouting by providing a non-injury model in which axonal invasion of the graft can originate from nodal axonal outgrowth; and (d) establishment of a noninjury model that can have widespread clinical applications.
Hemolytic uremic syndrome following taipan envenomation with response to plasmapheresis.
We report a case of hemolytic uremic syndrome (HUS) in a 33 year old male who was bitten by a taipan, with apparent massive envenomation. The microangiopathic hemolytic anemia (MAHA) and thrombocytopenic aspects of his HUS appeared to respond to plasmapheresis, but his anuric renal failure persisted. He also had prolonged severe muscular paralysis which gradually began to resolve over the course of two weeks. At this point he suffered a cardiac arrest sustaining severe and subsequently fatal hypoxic brain injury. This case raises the possibility that the taipan venom may have induced HUS by damaging the renal endothelium. His cardiac arrest was not apparently related to his HUS.
Retrospective analysis: are fever and altered mental status indications for lumbar puncture in a hospitalized patient who has not undergone neurosurgery?
Although nosocomial meningitis is rare in nonsurgical patients, lumbar punctures are frequently performed on hospitalized medical patients who develop delirium and/or fever. A retrospective review was undertaken to determine the yield of lumbar puncture in this setting and to compare it with the yield for suspected community-acquired meningitis. Of 232 lumbar punctures studied, 51 (22%) were performed to rule out nosocomial meningitis, while 181 (78%) were done to rule out community-acquired meningitis. No lumbar puncture performed for suspected nosocomial meningitis was positive, while results of 26 (14%) of those done for suspected community-acquired meningitis were abnormal (P < .01). Patients whose lumbar punctures were positive more often had headache or meningeal signs than those whose lumbar punctures were negative, and only 11 patients (22%) who had lumbar punctures performed for suspected nosocomial meningitis had headache or meningeal signs. We conclude that lumbar punctures performed for suspected nosocomial meningitis in nonsurgical patients have a low yield and that in some low-risk patients without headache or meningeal signs, lumbar puncture may be unnecessary.
Evaluating the goodness of fit in models of sparse medical data: a simulation approach.
BACKGROUND: Epidemiological studies of rare events, which are common in the medical literature, often involve modeling sparse data sets. Assessing the fit of these models may be complicated by the large numbers of observed zeros in the data set. METHODS: Poisson models, fitted as generalized linear models, were used to investigate the referral patterns of patients suffering from end-stage renal failure in south west Wales. The usual method for assessing the goodness of fit is to compare the deviance with a chi 2 distribution with appropriate degrees of freedom. However, this test may be invalid when the data set is sparse, as the deviance values may be unusually low compared to the degrees of freedom. This would suggest that there is a problem with underdispersion when, in fact, the large numbers of zeros in the data set make the comparison with the chi 2 distribution unreliable. A simulation approach is advocated as an alternative method of assessing model fit in these situations. RESULTS: Three models are considered in detail here. The first modelled the total referrals in each of the 245 wards in the study area and included two explanatory variables. These observations were not unusually sparse and both the chi 2 goodness of fit test and the simulation methodology outlined here suggested that the model did not fit. The second model included the population 'at risk' as an offset and the model improved considerably. Both the chi 2 test and the simulation approach suggested that this model did fit. Finally, the data were disaggregated into five age groups providing 1225 observations and a very sparse data set. According to the chi 2 goodness of fit test, the deviance was very low suggesting that the model was underdispersed. Using simulated data, it was shown that the deviance was not unusually low and that the model fitted the data reasonably well. CONCLUSION: In cases where the data set being modelled is sparse, it is useful to test the goodness of fit of a Poisson model using a simulation approach, rather than relying on the chi 2 test.