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Biomedical subjects

P A Turner

Publications and source records attributed to P A Turner.

At least 19 recordsLinked to original sources

Seasonality and factors associated with cryptosporidiosis among individuals with HIV infection.

The seasonality and factors associated with Cryptosporidium infection were assessed in a cohort of HIV-infected patients in Los Angeles County to better define the epidemiology of cryptosporidiosis among individuals with HIV. Data were analysed from a cohort of 4247 patients > or = 13 years of age with HIV infection enrolled from four outpatient facilities in Los Angeles, 1990-6. Cryptosporidiosis was diagnosed in 120 (2.8%) patients. Among the 1296 individuals with complete follow-up until death, cryptosporidiosis occurred in 69 (5.3%). The seasonal rate of cryptosporidiosis showed a modest bimodal trend with the highest rates occurring in March-May and September-October. There was no difference in the rate of cryptosporidiosis for the periods of heaviest rainfall (December-March) and low rainfall (April-November). Infection rates were higher among males (1.59 per 100 person-years) than females (0.92) and lower in blacks (0.98) than other racial/ethnic groups (1.80). A significant trend of decreasing cryptosporidiosis was observed with increasing age, with the highest rate (2.34) in the 13-34 year age group. A strong association between cryptosporidiosis and CD4+ count was noted. These data suggest that cryptosporidiosis among HIV-infected individuals in Los Angeles County exhibits a modest spring and fall seasonality. This pattern of occurrence of cryptosporidiosis appears temporally unrelated to local rainfall patterns. Our findings suggest that HIV-infected men, individuals in younger age groups and those with CD4+ lymphocyte counts < 100 x 10(6)/l are at increased risk of cryptosporidiosis. Blacks with HIV infection appear less likely than other racial/ethnic groups to be diagnosed with Cryptosporidium infection. These results may provide insight into possible routes of transmission and sources of cryptosporidiosis infection in individuals with HIV.

Adolescent

POU transcription factors control expression of CNS stem cell-specific genes.

Multipotential stem cells throughout the developing central nervous system have common properties. Among these is expression of the intermediate filament protein nestin and the brain fatty acid binding protein (B-FABP). To determine if common mechanisms control transcription in CNS stem cells, the regulatory elements of these two genes were mapped in transgenic mice. A 257 basepair enhancer of the rat nestin gene is sufficient for expression throughout the embryonic neuroepithelium. This enhancer contains two sites bound by the class III POU proteins Brn-1, Brn-2, Brn-4, and Tst-1. Only one of the two POU sites is required for CNS expression. An adjacent hormone response element is necessary for expression in the dorsal midbrain and forebrain. The regulatory sites of the B-FABP gene are strikingly similar to those of the nestin gene. A hybrid POU/Pbx binding site is recognized in vitro by Pbx-1, Brn-1 and Brn-2. This site is essential for expression in most of the CNS. In addition, a hormone response element is necessary for forebrain expression. Both the nestin and B-FABP genes therefore depend on POU binding sites for general CNS expression, with hormone response elements additionally required for activity in the anterior CNS. These data indicate that regulation by POU proteins and hormone receptors is a general mechanism for CNS stem cell-specific transcription.

Animals

A multidimensional scaling analysis of the techniques that physiotherapists use.

Following the essentially 'hands-on' origin of the physiotherapy profession a century ago, the range of techniques available to practitioners has expanded considerably. While this expansion of techniques has been of research interest, the main focus has been upon individual techniques, thus neglecting the fundamental question of the use of techniques in combination. In addition, researchers have tended to treat the profession as homogeneous, thus overlooking possible differences in technique usage. The present study addressed these questions. It postulated that ordered combinations of techniques usage would be employed, and that a typology would exist that differentiates the profession according to patterns of use. The study comprised a questionnaire survey of 230 clinical physiotherapists in England. This sought information on the range and frequency of techniques used over the previous six months. Descriptive analysis indicated a high frequency of use of several techniques, notably exercise therapy, passive mobilisation techniques and ultrasound. A feature of the analysis was the use of two multivariate procedures, multidimensional scalogram analysis (MSA) and smallest space analysis (SSA). The SSAs revealed a clear structure concerning combinations of techniques used, and the MSAs provided a coherent typology based upon this usage. One feature of the techniques in combination that emerged was the frequent use of passive mobilising techniques, which was associated with equally frequent use of electrotherapy techniques. In contrast, respondents who employed neurological or respiratory techniques made little use of electrotherapy. Regarding the typology, differentiation of the profession according to use of particular combinations of techniques indicated probable specialisms. The specialist areas identified were neurological physiotherapy, respiratory physiotherapy and musculo-skeletal physiotherapy. The results reinforce the need for both future research and physiotherapy education to address the issue of techniques in combination. Finally, and on the basis of the analyses, elements of a theoretical model are advanced that may provide directions for future research.

England

Incidence and factors associated with extrapulmonary cryptococcosis among persons with HIV infection in Los Angeles County.

OBJECTIVE: To determine the incidence and factors associated with extrapulmonary cryptococcosis among a cohort of persons with HIV in Los Angeles County. DESIGN: Records-based cohort study. METHODS: Data were analysed from a cohort of 3836 persons aged > or = 13 years with HIV infection enrolled from four outpatient facilities in Los Angeles from 1990 to 1995. The potential association between cryptococcosis and demographic risk behavior and clinical factors was assessed. Possible seasonal clustering was evaluated and an estimate of survival following cryptococcosis was calculated. Multivariate analysis was performed using a Cox proportional hazards approach. RESULTS: Cryptococcosis was identified in 112 patients (2.9%) representing a crude incidence rate of 1.7 cases per 100 person-years experience. The rate of cryptococcosis was higher among men than women (1.9 and 0.6, respectively; P < 0.01) and in Hispanics than in whites (2.3 and 1.2, respectively, P < 0.01). A significant trend of decreasing cryptococcosis was observed with increasing age (P < 0.01). Cryptococcosis increased with declining CD4+ lymphocyte count, with risk being greatest at CD4+ cell counts below 100 x 10(6)/l (P < 0.001). In bivariate analysis persons with a history of antifungal medication had a marginally lower rate of cryptococcosis, but this difference was not statistically significant. The rate of cryptococcosis was significantly higher in fall and winter months [rate ratio (RR), 1.45; 95% confidence interval (CI), 1.0-2.3; P = 0.05]. After controlling for other variables, cryptococcosis was more common in men than women (adjusted RR, 3.2; 95% CI, 1.0-10.4) and in Hispanics than whites (adjusted RR, 1.6; 95% CI, 0.9-2.7). Both CD4+ count and age continued to be strongly associated with the occurrence of cryptococcosis. After controlling for other factors a substantial protective effect was observed for antifungal therapy (adjusted RR, 0.48; 95% CI, 0.29-0.79). CONCLUSION: Our data suggest that HIV-infected men, Hispanics, persons aged under 45 years and those with CD4+ counts under 100 x 10(6)/l have an increased risk of extrapulmonary cryptococcosis. A fall-winter seasonality in the occurrence of cryptococcosis may exist. Significant primary protection against cryptococcal disease is afforded by antifungal therapy. These results may provide insight into possible routes of transmission and sources of cryptococcal infection and help guide both primary prophylaxis and early recognition and diagnosis in persons likely to be at increased risk.

AIDS-Related Opportunistic Infections

Test of a mosquito eggshell isolation method and subsampling procedure.

Production of Aedes vigilax, the common salt-marsh mosquito, can be assessed by determining eggshell densities found in soil. In this study, 14 field-collected eggshell samples were used to test a subsampling technique and compare eggshell counts obtained with a flotation method to those obtained by direct examination of sediment (DES). Relative precision of the subsampling technique was assessed by determining the minimum number of subsamples required to estimate the true mean and confidence interval of a sample at a predetermined confidence level. A regression line was fitted to cube-root transformed eggshell counts obtained from flotation and DES and found to be significant (P < 0.001, r2 = 0.97). The flotation method allowed processing of samples in about one-third of the time required by DES, but recovered an average of 44% of the eggshells present. Eggshells obtained with the flotation method can be used to predict those from DES using the following equation: DES count = [1.386 x (flotation count)0.33 - 0.01]3.

Aedes

The relationship between the density of Aedes vigilax (Diptera: Culicidae) eggshells and environmental factors on Kooragang Island, New South Wales, Australia.

Knowledge of oviposition sites selected by wetland mosquitoes could improve mosquito control and guide wetland rehabilitation practices to avoid creating or exacerbating a mosquito problem. Two studies that enumerated Aedes vigilax eggshells found in salt marsh soil on the western portion of Kooragang Island in New South Wales, Australia, allowed an evaluation of oviposition sites. In one study, the density of eggshells found in samples collected from a large area was related to environmental factors, including distance from nearby drainage channels, vegetation cover, elevation, and terrain characteristics. Multiple-regression analysis suggested eggshell densities were positively correlated with the presence of depressions and ponds, vegetation cover, and distance from culverts, but negatively related to elevation. In another study, eggshell density was related to relative elevation and vegetation species within each of two 400-m2 plots on Kooragang Island. In all but one instance, samples from bare soil contained fewer eggshells than samples with vegetation cover at both plots. Eggshell density did not differ between the two dominant vegetation species, Sarcocornia quinqueflora and Sporobolus virginicus, although bare soil of one plot had a mean eggshell density similar to that of soil with S. quinqueflora cover. Eggshells were at highest density at intermediate elevations at one plot but at low elevations at the other.

Aedes

Emerging patterns of HIV transmission: the value of alternative surveillance methods.

OBJECTIVE: To assess the current patterns of HIV transmission in Los Angeles County and determine if AIDS surveillance data accurately reflect these patterns. DESIGN: Records-based cohort study. METHODS: The demographic and HIV risk characteristics of persons considered to be recently infected with HIV (CD4+ count > 700 x 10(6)/l) were determined and compared with the characteristics of persons meeting the Centers for Disease Control and Prevention (CDC) 1993 AIDS case definition. Data were obtained for patients with HIV infection enrolled from four HIV outpatient clinics and analyzed between August 1991 and July 1993. RESULTS: The patient cohort included 1857 persons with HIV infection; 1096 (59.1%) met the CDC 1993 AIDS case definition and 134 (7.2%) had a CD4+ lymphocyte count > 700 x 10(6)/l. The median CD4+ count for the group presumed to be recently infected was 809 x 10(6)/l. Persons considered recently infected with HIV were more likely than those meeting the AIDS case definition to be female (26.1 and 14.5%, respectively; P < 0.001), black (28.4 and 18.2%, respectively; P = 0.001), or male homosexual injecting drug users (IDU; 6.7 and 3.4%, respectively; P = 0.05). After controlling for confounding variables by logistic regression, persons recently infected were more likely to be female [adjusted odds ratio (OR), 3.4; 95% confidence interval (CI), 1.8-6.5; P < 0.001], black (adjusted OR, 1.6; 95% CI, 1.1-2.5; P = 0.02) or male homosexual IDU (adjusted OR, 2.4; 95% CI, 1.1-5.2; P = 0.02) than persons with AIDS. CONCLUSIONS: Our results suggest that the HIV epidemic in Los Angeles County is currently advancing into different subpopulations and indicate that the current patterns of HIV transmission in the County are not fully reflected in standard AIDS surveillance activities. However, our data must be interpreted cautiously because of potential selection and misclassification biases. These findings illustrate the benefits of alternative surveillance mechanisms in detecting important changes in HIV transmission and defining groups at risk, especially in jurisdictions without HIV reporting.

Adolescent

Anal intercourse and disclosure of HIV infection among seropositive gay and bisexual men.

Human immunodeficiency virus (HIV)-infected gay and bisexual men (n = 609) randomly selected from two HIV outpatient clinics in Los Angeles completed confidential, self-administered questionnaires at the clinics, reporting sexual activities and disclosure during the previous 2 months. Approximately 9% had engaged in unprotected insertive anal intercourse with one or more partners. This activity was 3.27 times more likely to have occurred with seropositive partners than with partners who were seronegative or whose serostatus was unknown. Fourteen men (2.3% of total sample) had engaged in unprotected insertive anal sex with 25 seronegative or unknown serostatus partners who were not informed of their risk of infection. Thirty-three men (5.4% of total sample) had engaged in this activity with 37 seropositive partners who were informed. Clinicians and other health professionals can play an important role in helping to control the HIV epidemic by discussing with seropositive patients the importance of using safer sex and informing sexual partners. Such discussion should include information about the potentially negative health effects of unprotected sex between seropositive persons.

Adult

Increased density of HLA-DR antigen on monocytes of patients infected with the human immunodeficiency virus.

Monocytes and macrophages play an important role in the pathogenesis of the acquired immunodeficiency syndrome (AIDS). Dysfunction of these cells contributes to the immunocompromised state that characterizes AIDS, and they probably serve as a reservoir for the human immunodeficiency virus (HIV). HIV-infected macrophages may also be responsible for the infection of many CD4-positive lymphocytes by means of cell to cell contact during the initiation of immunological responses. The efficiency of this process would be enhanced by activation of the macrophages, since that is accompanied by increased expression of class II major histocompatibility (HLA-DR) antigen. Using a direct blood antibody marking procedure in conjunction with flow cytometry, we have analyzed the expression of HLA-DR antigen on the surfaces of monocytes present in the peripheral blood of HIV-infected patients. In contrast to the results reported by other investigators who purified the monocytes using Ficoll-Hypaque centrifugation prior to antibody marking, we found that the percentage of monocytes expressing HLA-DR antigen was identical in the patients and normal controls. However, a subpopulation of monocytes was detected in the blood of the majority of the patients that was expressing increased levels of HLA-DR antigen. It was also found that the proportion of monocytes with a high density of HLA-DR antigen on their surfaces negatively correlated with the absolute numbers of CD4-positive lymphocytes present in the peripheral blood of the patient. These findings support the postulated role of monocytes and macrophages in the HIV infection and ultimate destruction of CD4-positive lymphocytes.

Acquired Immunodeficiency Syndrome

Does diazepam really reduce the cardiotoxic effects of intravenous bupivacaine?

The effect of diazepam on the cardiovascular toxicity of bupivacaine was investigated in a rat model. Under chloral hydrate (400 mg/kg intraperitoneal) anesthesia, unilateral femoral venous and bilateral femoral arterial cannulae were placed for administration of drugs, for blood sampling, and for continuous qualitative monitoring of arterial blood pressure. Lead II ECG was continuously recorded and a tracheostomy performed to increase FIO2 by use of a "T-piece." Four groups of 24 to 36 rats each were studied. All rats received IV bupivacaine 2 mg/kg, within 10 seconds. Group I, the control group, received only bupivacaine. Groups II and III received IV diazepam 0.2 mg/kg, or diazepam vehicle in an equivalent volume, respectively. Five minutes after this pretreatment, groups II and III received IV bupivacaine 2 mg/kg. Group IV was given diazepam, 0.2 mg/kg, 30 seconds after injection of 2 mg/kg bupivacaine. A marked respiratory and metabolic acidosis occurred in all rats but was significantly worse in groups II and III. No rat in the study became hypoxemic. Serious arrhythmias (ventricular or supraventricular tachycardia) were noted in all groups, but the incidence was significantly higher in the group of rats given diazepam pretreatment than in the other three groups. It is concluded that IV diazepam 0.2 mg/kg given 5 minutes before administration of IV bupivacaine 2 mg/kg increases the incidence of serious cardiac arrhythmias. Second, this increase is not solely due to increased acidosis, because the rats receiving the vehicle (group III) developed equivalent acidosis but did not develop increased arrhythmias.

Acidosis, Respiratory

The influence of diazepam on the pharmacokinetics of intravenous and epidural bupivacaine in the rhesus monkey.

Pretreatment of patients with diazepam has been reported to reduce the plasma half-life of epidurally administered bupivacaine. The concentrations of bupivacaine used to estimate its plasma half-life may be influenced by input into the vascular system (rate and extent of absorption from the epidural space) and disposition (distribution and elimination). We conducted a study in Rhesus monkeys in which the input function was known and the influence of intravenous diazepam on the disposition of intravenous bupivacaine could be delineated. Results indicated no differences in the primary pharmacokinetic parameters (i.e., total clearance and volume of distribution) for the disposition of bupivacaine. To determine whether the apparent disparity between these results and a previous study might be due to a diazepam-induced alteration in the input function, the influence of intravenous diazepam or saline on the mean absorption time of epidurally administered bupivacaine was also studied in monkeys. Epidural bupivacaine was completely absorbed whether the animals received intravenous saline or intravenous diazepam. No significant differences in pharmacokinetic parameters were found between animals pretreated with intravenous saline or intravenous diazepam and receiving an epidural injection of bupivacaine. The mean residence time of bupivacaine in the body (P less than 0.01) and plasma elimination half-life (P less than 0.005) were significantly longer after epidural administration than after intravenous administration. Intravenous diazepam does not alter the pharmacokinetics of intravenously or epidurally administered bupivacaine.

Absorption

Bupivacaine protein binding in the term parturient: effects of lactic acidosis.

The effects of lactic acidosis on bupivacaine serum protein binding was studied in a group of term parturients and a group of nonpregnant female control subjects. Groups were matched in age and health. Distribution characteristics of bupivacaine in pregnancy were determined. Bupivacaine protein binding was best characterized by the model for two classes of binding sites in all studies. The parturients exhibited a lower capacity for the high-affinity, low-capacity (alpha 1-acid glycoprotein) site and higher affinity for the low-affinity, high-capacity (albumin) site. Lactic acidosis decreased the affinity constant for the high-affinity, low-capacity site in the control group but did not change binding characteristics in the parturients. Free concentration of bupivacaine (Cu) was elevated at low total bupivacaine concentrations (Ct) (less than 10 micrograms/ml). No differences in Cu were detected at concentrations in the cardiotoxic range (greater than 20 micrograms/ml). The Cu values predicted by the estimated binding parameters from in vitro experiments were compared with actual Cu measured in nine parturients at delivery; they correlated significantly (r = 0.94). Distribution changes for bupivacaine in the parturients were consistent with known physiologic changes in body composition associated with pregnancy. Alterations that occur in serum protein binding during pregnancy should not result in increased risk of central nervous system or cardiovascular system toxicity since these alterations do not increase free tissue concentration.

Absorption

Diagnosis and management of viral infections.

With the introduction of new diagnostic techniques and the expanding choices of antiviral agents, clinical virology is rapidly becoming an important field in infectious diseases. While effective therapy for several respiratory viruses, cytomegalovirus, hepatitis B virus, and Epstein-Barr virus is not currently available, herpes simplex, varicella zoster, and influenza A associated diseases can be adequately treated in many cases at the present time. New agents such as interferon, other nucleoside analogues, and immunomodulators are being investigated for their role in the treatment of viral illnesses, and many such illnesses with high morbidity and mortality may soon have effective therapy.

Acyclovir