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Biomedical subjects

J Mills

Publications and source records attributed to J Mills.

At least 109 records · Page 6Linked to original sources

Sex differences in learning and memory in mice: effects of sequence of testing and cholinergic blockade.

Sexual dimorphism in spatial and cued navigation using the Morris water maze was examined in C57BL/6 mice both with and without administration of scopolamine, a cholinergic blocker. In Exp. 1, female and male mice learned to perform first a spatial, then a cued, navigation task. Both performed a spatial task similarly; males, however, performed a cued task better than females. In Exp. 2, the sequence of navigation testing was reversed. Both performed similarly on a cued task; however, males performed a spatial task better than females. In both experiments, females were more sensitive than males to the effects of scopolamine. No significant confounding sex differences were found in either spontaneous activity or passive avoidance retention. These data indicate that sex differences in spatial and cued tasks are dependent on the sequence of task presentation and implicate a role for the cholinergic system in these differences.

Animals↗

Maternal smoking, alcohol drinking, caffeine consumption, and fetal growth: results from a prospective study.

In a prospective study of 712 pregnancies, we examined associations between maternal smoking, alcohol, and caffeine consumption and fetal growth. We interviewed patients at entry into care [12.9 +/- 4.3 (standard deviation) weeks], and at 28 and 36 weeks of gestation. We found the expected reductions in adjusted birthweight among women who smoked throughout pregnancy: 168 gm [95% confidence limits (CL) = -326, -10] for low/moderate amounts (< or = 15 cigarettes per day); 288 gm (95% CL = -491, -84) for heavy smoking (> 15 cigarettes per day). We also found a decrease in birthweight (-179 gm; 95% CL = -364, 7) among smokers who reported quiting early in pregnancy. First trimester alcohol consumption (average: four drinks per week) was associated with a 155-gm reduction in fetal growth (95% CL = -324, 15), even after adjustment for number of cigarettes smoked. The association, observed with all types of alcohol consumption, was stronger among smokers (-270 gm) but was also present in nonsmokers (-115 gm). Caffeine consumption showed no relation to fetal growth, even among heavy consumers, although they were relatively few. This study implicates heavy maternal smoking at any point in pregnancy, including solely in the early months, and possibly moderate alcohol drinking as causes of low birthweight.

Adult↗

Recombinant baculovirus-expressed NS3 proteinase of hepatitis C virus shows activity in cell-based and in vitro assays.

Recombinant baculoviruses have been constructed which express the hepatitis C virus (HCV) NS3 proteinase and its substrates in insect cells. The expressed proteinase has been shown to carry out trans-cleavage at the NS3/4A, NS4A/4B, NS4B/5A and NS5A/5B junctions in a cell-based assay. When assayed in a cell-free system using in vitro translated substrates, the proteinase could perform trans-processing of the NS4A/4B and NS5A/5B junctions, but only when coexpressed with NS4A, either as an NS3-4A precursor or by co-infection of cells with NS3- and NS4A-expressing recombinant baculoviruses. Possible reasons for the absolute requirement of the NS3 proteinase for NS4A in vitro are discussed.

Animals↗

Client-centred practice: what does it mean and does it make a difference?

During the past 15 years, occupational therapists in Canada, through the Canadian Association of Occupational Therapists, have worked to develop and implement guidelines for practice of a client-centred approach to occupational therapy. One of the difficulties with the current Guidelines for the Client-Centred Practice of Occupational Therapy is the lack of a definition and discussion of the concepts and issues fundamental to client-centred practice. In this paper, key concepts of client-centred practice: individual autonomy and choice, partnership, therapist and client responsibility, enablement, contextual congruence, accessibility and respect for diversity are discussed. Two practice examples are used to illustrate these ideas and raise issues about obstacles to the practice of client-centred occupational therapy. Research evidence about the effectiveness of client-centred concepts in enhancing client satisfaction, functional outcomes and adherence to health service programmes is reviewed.

Canada↗

HIV infection of monocyte-derived macrophages in vitro reduces phagocytosis of Candida albicans.

HIV-1 infection of peripheral blood monocyte-derived macrophages (MDMs) is unrelated to the level of CD4 expression on the surface of the cell, is associated with considerable donor variability, causes minimal cytopathology, and results in peak viral antigen production after 2 weeks of infection. Phagocytosis of opsonized Candida albicans by MDMs infected in vitro with several strains of HIV was compared with that of uninfected cells from the same donors; the proportion of MDMs containing the fluorescein isothiocyanate-labeled yeast was determined by flow cytometry and phase contrast microscopy. The intracellular localization of C. albicans was confirmed by confocal microscopy. Using paired MDMs from nine donors, 81% of uninfected and 53% of HIV-infected MDMs phagocytosed C. albicans. In addition, the number of yeast per cell was significantly higher in uninfected MDMs than in HIV-infected cells (mean 6.1 versus 2.5). These findings may partially explain the high incidence of mucocutaneous candidiasis in HIV-infected patients with advanced disease.

AIDS-Related Opportunistic Infections↗

HIV replication in chronically infected macrophages is not inhibited by the Tat inhibitors Ro-5-3335 and Ro-24-7429.

Human immunodeficiency virus infects different cell types including CD4+ lymphocytes and monocyte-derived macrophages (MDMs). We have examined the activity of the HIV-1 Tat inhibitors Ro-5-3335 and Ro-24-7429 in cultured human peripheral MDMs. Monocytes were isolated from HIV-seronegative donors by gradient centrifugation and plastic adherence. MDMs and unfractionated peripheral blood mononuclear cells (PBMCs) were infected with HIV Ba-L and then treated with drug either immediately (acute infection) or after 4 days (PBMCs) or 14 days (MDMs) (chronic infection). Inhibition of HIV replication by each drug was assessed by quantitation of HIV p24 antigen in culture supernatant using an enzyme immunoassay. In acutely infected MDMs, Ro-5-3335 (10 microM) and Ro-24-7429 (10 microM) resulted in 77% and 99% mean inhibition, respectively, of HIV replication with a clear dose response at lower concentrations; chronically infected MDMs were much less susceptible to these drugs, with both compounds inhibiting p24 antigen production by less than 50% at 10 microM. The drugs had no deleterious effect on cell viability at any concentration tested. In acutely infected PBMCs Ro-5-3335 and Ro-24-7429 resulted in 68% and 68.5% mean inhibition at 10 microM; when the compounds were added 4 days after infection inhibition was less than 50% compared with controls. Thus, the Tat inhibitors were effective in inhibiting acute HIV infection in MDMs but not in chronically infected cells, findings that differ from those of published studies using continuous lymphoblastoid cell lines.

Antigens, Viral↗

Retrotrapezoid nucleus muscarinic receptor subtypes localized by autoradiography.

Microinjection of muscarinic receptor subtype antagonists into the region of the cat retrotrapezoid nucleus (RTN) decreases blood pressure (greatest efficacy; M2 subtype) and both baseline phrenic activity and CO2 sensitivity (greatest efficacy; M3/M1 subtype). Here we examine, in cat medullary sections at the level of the RTN, the effects of the same antagonists on binding of the high affinity muscarinic agonist quinuclidinyl benzilate (QNB). 3H-QNB binding was saturated and highly specific at 1 nM concentration and stable over 30 to 120 min (Kd, 0.49 nM; Bmax, 136 fm/mg protein). Studied biochemically, we found IC50 values for whole sections of 4.9 x 10(-6) M (M1 antagonist pirenzepine); 1.0 x 10(-6) M (M2 antagonist AFDX); and 0.64 x 10(-7) M (M3 antagonist DAMP; P < 0.03 vs PZ). Densitometric analysis of whole medullary cross section autoradiograms resulted in similar IC50 values as in the biochemical approach. Specific analysis of the RTN region demonstrated the presence of 3H-QNB binding and similar competition by the antagonists. Average IC50 values determined by densitometry were 14 x 10(-6) M (pirenzepine); 1.3 x 10(-6) M (AFDX; P < 0.01 vs PZ); and 0.53 x 10(-7) M (DAMP; P < 0.01 vs PZ). All three subtypes of muscarinic receptors identifiable via pharmacological antagonists appear to be present in the RTN region but we could not distinguish a subtype-specific pattern of receptor distribution.

Adamantane↗

The use of psychiatric services before imprisonment: a survey and case register linkage of sentenced prisoners in Melbourne.

Information about contact with psychiatric services before imprisonment was obtained for a stratified random sample of sentenced prisoners, who were not receiving prison psychiatric care, in Melbourne's three metropolitan prisons. The sample of 158 men and 31 women was matched with the longitudinal person-linked records of state psychiatric service use in the Victorian Psychiatric Case Register (VPCR). Records of contact with the state services were found for 54 men (34%) and 19 women (61%), including records of in-patient treatment for 25 men (16%) and 15 women (48%). For 64% of individuals with a positive match, the case-note diagnoses were substance use disorders only. Diagnoses of psychotic disorders were recorded for four prisoners, and mood disorders for another six. In addition, clinicians conducted standardized diagnostic interviews and enquired about treatment and personal history. A further 24 prisoners reported specialist psychiatric treatment outside the state treatment sector. This study links the findings from an interview survey of psychiatric morbidity in prisoners with the records available in the VPCR, and emphasizes a number of matters important to the public health. The high rates of previous treatment for substance abuse disorders, the apparent pool of prisoners with largely untreated major depression, and the service needs of those with chronic psychotic disorders are discussed.

Adolescent↗

Diagnostic X-ray and ultrasound exposure and risk of childhood cancer.

In a population-based case-control study of 642 childhood cancer cases and the same number of matched controls in Shanghai, China, we evaluated the relationship between diagnostic X-ray (preconception, pre- and post-natal) and antenatal ultrasound exposure and the subsequent risk of developing three major types of childhood cancer (acute leukaemia, lymphoma and brain tumours) and all childhood neoplasms combined. Consistent with previous studies, prenatal X-ray exposure was found to be associated with an 80% increased risk of childhood cancers, although the estimation was based on 4% and 2% exposed cases and controls and was only marginally statistically significant (P = 0.08). Post-natal X-ray exposure was also linked with a small elevation in the risk of all cancers and the major categories of malignancies in children. Little evidence, however, was found to relate parental preconception X-ray exposure with the subsequent cancer risk in offspring, regardless of the exposure window and the anatomical site of X-ray exposures. This study adds further to the growing literature indicating that antenatal ultrasound exposure is probably not associated with an increased risk of childhood cancer.

Adolescent↗

A rapid screen test for in vitro susceptibility of clinical herpes simplex virus isolates.

A rapid screening test for antiviral susceptibility to acyclovir and foscarnet was evaluated in 320 herpes simplex virus (HSV) isolates from 197 patients. Of the isolates tested (16% HSV-1, 84% HSV-2), 60% were resistant in vitro to acyclovir and 5% were resistant to foscarnet using the plaque reduction assay. The rapid screening test, requiring only 3 days to yield a preliminary susceptibility result, was highly associated with the results of the plaque reduction assay for acyclovir and foscarnet (P < or = .001 for each) and with the clinical response to antiviral therapy (P < .001, P = .001, respectively).

Acyclovir↗

Correlation between response to acyclovir and foscarnet therapy and in vitro susceptibility result for isolates of herpes simplex virus from human immunodeficiency virus-infected patients.

In vitro susceptibility testing of herpes simplex virus (HSV) isolates will play an increasingly important role in guiding the clinical management of immunocompromised hosts who have lesions that are poorly responsive to therapy with standard antiviral agents. We assessed the correlation between the in vitro susceptibility result using a plaque reduction assay in Vero cells and the response to antiviral therapy with acyclovir or foscarnet for 243 clinical isolates of HSV collected from 115 human immunodeficiency virus-infected patients. The in vitro results and clinical responses were highly associated for both acyclovir and foscarnet (P < 0.001 and P < 0.001, respectively). The predictive values of a susceptible result (50% effective concentrations, < 2 micrograms/ml for acyclovir and < 100 micrograms/ml for foscarnet) for complete healing of lesions were 62% for acyclovir and 82% for foscarnet; the predictive values of a resistant result for failure to heal were 95% for acyclovir and 88% for foscarnet. Thus, in vitro testing has clinical utility in guiding therapy, although the 1 to 2 weeks required to derive a definitive result by the plaque reduction assay is a major limitation.

Acyclovir↗

Prognosis in cystic fibrosis treated with continuous flucloxacillin from the neonatal period.

All newborn infants in East Anglia are screened for cystic fibrosis by blood immunoreactive trypsin assay at 7 days. Thirty eight infants with cystic fibrosis were randomised to treatment with either continuous oral flucloxacillin 250 mg/day (group P, n = 18) or with episodic antimicrobials as clinically indicated (group E, n = 20). Their progress was monitored from diagnosis to 24 months by a nurse coordinator who visited all infants regularly, at home and in hospital, to collect anthropometric, dietary, clinical, and microbiological data. Mean (range) age of confirmation of diagnosis was 5.7 weeks (1-14 weeks). There was no significant difference in birth weight, genotype, immunoreactive trypsin concentration, neonatal history, symptoms at diagnosis, pancreatic enzyme supplementation, or parental smoking history between the groups. Infants in group E had more frequent cough and a greater number of Staphylococcus aureus isolates than infants in group P. More infants of group E were admitted to hospital, had higher admission rates during the second year (19 v 5), for longer periods (6.4 v 2.2 days), despite receiving more than double the number of courses of antibiotics than group P infants (in addition to flucloxacillin). Continuous prophylactic flucloxacillin from early diagnosis of cystic fibrosis is associated with improved clinical progress during the first two years of life.

Bacterial Infections↗

Workload measurement: A survey of computerized data collection.

The results of a national survey which examined current computer usage and occupational therapist direct entry of Workload Measurement Data is presented. Results indicated an almost equal distribution of departments using computers versus not using computers. A variety of software packages are used for the purposes of collecting workload measurement data, but the majority of departments use customized in-house programmes. The most common method of data entry was a clerk in a central location, however, a number of departments are considering a switch to therapist direct entry. Advantages and disadvantages of both methods were described by survey respondents.

Canada↗

Thrombocytopenia secondary to high valproate levels in children with epilepsy.

We reviewed the frequency of valproate-induced thrombocytopenia in children with epilepsy in our institution. Sixty-four (21%) of 306 children taking valproate developed thrombocytopenia. Thirty-two of these 64 patients had at least one platelet count lower than 100 x 10(3)/mm3. Eight patients developed signs of bleeding. Low platelet levels were typically noted in patients with serum valproate levels of over 140 micrograms/mL, and reduction of the medication dose usually resulted in a prompt increase in the number of platelets. Only one patient developed thrombocytopenia unrelated to high serum drug levels, and her platelet count did not improve until the drug was discontinued. Neither the age of the patient nor the use of additional antiepileptic medication correlated with the platelet count. However, duration of valproate use was related. These data suggest that, although valproate may cause thrombocytopenia via more than one mechanism, by far the most common factor is the presence of high valproate levels. Thus, the medication can be safely lowered in most patients with thrombocytopenia rather than discontinued altogether. Platelet counts should probably be monitored more carefully in patients known to have higher drug levels.

Carbamazepine↗

The epidemiology of attempted suicide in the Oxford area, England (1989-1992).

The epidemiological and clinical characteristics of attempted suicide in Oxford, United Kingdom, between 1989 and 1992 are reported on the basis of data collected as part of the WHO/EURO Multicentre Study of Parasuicide in Europe. Some further findings for the period 1976-1992 are also described. Rates of attempted suicide were particularly high among females aged 15-19 years. There was a very marked association in males and females between attempted suicide and both lower socioeconomic status and unemployment. The percentage of first-time attempters entering the attempted suicide population remained steady between 1976 and 1992, with approximately two-thirds of attempters each year making their first attempts. There was a great increase in the use of paracetamol (acetominophen) for self-poisoning between 1976 and 1992, this being involved in 14.3% of overdoses in 1976 and 43.2% in 1992. On the basis of the Oxford rates, there are approximately 100,000 general hospital admissions for attempted suicide each year in England and Wales, approximately 19,000 involving teenagers (mostly girls). Oxford has a similar pattern of attempted suicide to that in the rest of the UK. The findings indicate that the UK has one of the highest rates of attempted suicide in Europe.

Adolescent↗

Treatment of herpes simplex and varicella zoster infections.

The introduction of antiviral agents such as acyclovir has had a remarkable impact on management of patients with viral infections. In this article the authors outline the management of herpes simplex and varicella zoster infections, giving specific guidelines for treatment with acyclovir.

Acyclovir↗

HIV-related respiratory disease.

The lungs are a primary target for the opportunistic infections and malignancies affecting those with HIV infection. In the patient whose HIV infection is undiagnosed, PCP is the commonest clue to its presence. Early diagnosis prevents morbidity and mortality. Less commonly, interstitial lung disease and tuberculosis, often "primary" or clinically atypical, will be the clue to underlying HIV infection. Other pulmonary complications are usually a late manifestation of HIV infection, which has usually (but not always) already been diagnosed.

AIDS-Related Opportunistic Infections↗