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Biomedical subjects

M Law

Publications and source records attributed to M Law.

At least 19 recordsLinked to original sources
PubMed1998

A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors.

OBJECTIVE: To describe a syndrome of peripheral lipodystrophy (fat wasting of the face, limbs and upper trunk), hyperlipidaemia and insulin resistance in patients receiving potent HIV protease inhibitor therapy. DESIGN: Cross-sectional study. SETTING: Outpatient clinic of a university teaching hospital. PATIENTS: HIV-infected patients either receiving at least one protease inhibitor (n=116) or protease inhibitor-naive (n=32), and healthy men (n=47). INTERVENTIONS AND MAIN OUTCOME MEASURES: Lipodystrophy was assessed by physical examination and questionnaire and body composition by dual-energy X-ray absorptiometry. Fasting triglyceride, cholesterol, free fatty acid, glucose, insulin, C-peptide and fructosamine levels, other metabolic parameters, CD4 lymphocyte counts, and HIV RNA load were also assessed. RESULTS: HIV protease inhibitor-naive patients had similar body composition to healthy men. HIV protease inhibitor therapy was associated with substantially lower total body fat (13.2 versus 18.7 kg in protease inhibitor-naive patients; P=0.005), and significantly higher total cholesterol and triglyceride levels. Lipodystrophy was observed clinically in 74 (64%) protease inhibitor recipients after a mean 13.9 months and 1(3%) protease inhibitor-naive patient (P=0.0001). Fat loss occurred in all regions except the abdomen after a median 10 months. Patients with lipodystrophy experienced a relative weight loss of 0.5 kg per month and had significantly higher triglyceride, cholesterol, insulin and C-peptide levels and were more insulin-resistant than protease inhibitor recipients without lipodystrophy. Patients receiving ritonavir and saquinavir in combination had significantly lower body fat, higher lipids and shorter time to lipodystrophy than patients receiving indinavir. Three (2%) patients developed new or worsening diabetes mellitus. CONCLUSION: A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance is a common complication of HIV protease inhibitors. Diabetes mellitus is relatively uncommon.

Adult↗
PubMed1998

Predictors of progression in long-term nonprogressors. Australian Long-Term Nonprogressor Study Group.

It is now apparent that a proportion of individuals (5-8%) remains clinically free of HIV-1 disease with normal levels of CD4+ lymphocytes (> or =500/microl) for more than 8 years following infection. However, the proportion of these individuals who ultimately progress to AIDS remains to be established. We determined the virological and immunological characteristics of a cohort of long-term nonprogressors in Australia and examined the role of these factors in predicting disease progression. Individuals with documented asymptomatic HIV-1 infection for at least 8 years with CD4+ lymphocyte counts >500 cells/microl were recruited from hospital clinics and general practices serving the eastern area of Australia. CD4+ lymphocyte count, rate of CD4+ lymphocyte change, CD8+ lymphocyte count, beta2-microglobulin, immune complex dissociated (ICD) HIV-1 p24 antigen, and plasma HIV-1 RNA were measured at baseline and multiple visits at 6-month intervals over an average period of 2 years. Up to November 1996, 67 study participants were recruited, of whom 72% had been infected with HIV-1 for at least 10 years. HIV-1 RNA correlated with beta2-microglobulin, ICD p24 antigen, and the ability to isolate virus in culture but not with levels of CD4+ or CD8+ lymphocytes. Serum beta2-microglobulin was a stronger predictor of CD4+ lymphocyte decline than HIV-1 RNA and the only factor significantly associated with CD4+ lymphocyte decline. These findings show that the serum concentration of beta2-microglobulin is a strong predictor of immunological progression in people with long-term asymptomatic HIV-1 infection and provides additional prognostic information to HIV-1 RNA in determining the risk of disease progression.

Adolescent↗
PubMed1998

A universal virus inactivant for decontaminating blood and biopharmaceutical products.

Removal of virus infectivity from blood and biopharmaceutical products prepared from blood is an issue of considerable importance. For biopharmaceutical products, removal can usually be achieved by a series of fractionation steps or by inactivation with a suitable reagent. Irrespective of the methods that are chosen it is vital that the biological activity of the product is not impaired. For blood and unfractionated plasma or serum, the problem is even more challenging. Selective inactivation of the genome is the key step in the preparation of killed virus vaccines. Viruses belonging to all the recognised families can be inactivated by imines. In this paper it is shown that the biological properties of several proteins, including the cell growth-promoting factors in calf serum, are not impaired using conditions which ensure the inactivation of > 10(15) infectious units of poliovirus and foot-and-mouth disease virus (FMDV). Also shown is that both viruses can be inactivated by imines at 4 degrees C, thus providing a method for removing infectivity from protein preparations which are unstable at higher temperatures. The RNA extracted from FMDV inactivated at 4 degrees C was not degraded and contained no hidden breaks but nevertheless was non-infectious. However, it could be amplified by PCR using primers corresponding to the gene coding for a portion of the viral RNA polymerase, but not from that coding for VP1, one of the structural proteins, showing that alteration of a base or bases had occurred in that region. Surprisingly, it could be translated in the rabbit reticulocyte system although some of the products were different from those obtained with unmodified RNA.

Animals↗
PubMed1998

The prediction of criminal and violent recidivism among mentally disordered offenders: a meta-analysis.

A meta-analysis was conducted to examine whether the predictors of recidivism for mentally disordered offenders are different from the predictors for nondisordered offenders. Effect sizes were calculated for 35 predictors of general recidivism and 27 predictors of violent recidivism drawn from 64 unique samples. The results showed that the major predictors of recidivism were the same for mentally disordered offenders as for nondisordered offenders. Criminal history variables were the best predictors, and clinical variables showed the smallest effect sizes. The findings suggest that the risk assessment of mentally disordered offenders can be enhanced with more attention to the social psychological criminological literature and less reliance on models of psychopathology.

Adolescent↗
PubMed1997

N-Type calcium channels in the developing rat hippocampus: subunit, complex, and regional expression.

The expression of multiple classes of voltage-dependent calcium channels (VDCCs) allows neurons to tailor calcium signaling to functionally discrete cellular regions. In the developing hippocampus a central issue is whether the expression of VDCC subtypes plays a role in key phases such as migration and synaptogenesis. Using radioligand binding and immunoblotting, we show that some N-type VDCCs exist before birth, consistent with a role in migration; however, most N-VDCC subunit expression is postnatal, coinciding with synaptogenesis. Immunoprecipitation studies indicate that the increased expression of N-VDCCs in early development occurs without subunit switching because there is no change in the fraction of beta3 subunits in the N-VDCC alpha1B-beta3 heteromers. Fluorescence imaging of cell surface N-VDCCs during this period reveals that N-VDCCs are expressed on somata before dendrites and that this expression is asynchronous between different subfields of the hippocampus (CA3-CA4 before CA1-CA2 and dentate gyrus). Our data argue that N-VDCC expression is an important cue in the genesis of synaptic transmission in discrete hippocampal subfields.

Animals↗
PubMed1997

Acute toxicity in pelvic radiotherapy; a randomised trial of conformal versus conventional treatment.

BACKGROUND: A prospective, randomized clinical trial to assess the effect of reducing the volume of irradiated normal tissue on acute reactions in pelvic radiotherapy accured 266 evaluable patients between 1988 and 1993. PURPOSE: This is the definitive analysis to assess the differences between the conformal and conventional arms of the trial. MATERIALS AND METHODS: In both arms, patients were treated with 6 MV X-rays using a 3-field technique (in all but 5 cases) consisting of an anterior and two wedged lateral or posterior oblique fields; in the conventional arm, rectangular fields were employed, whereas in the conformal arm, the fields were shaped with customized blocks drawn according to the beam's-eye-view of the target volume. The most common dosage was 64 Gy in 2-Gy fractions 5 times a week, although a subgroup (of ca. bladder patients) were treated with 30-36 Gy in once-a-week 6 Gy fractions. Each patients completed a comprehensive acute toxicity scoring questionnaire concentrating on bowel and bladder problems, tiredness and nausea, before the start of treatment, weekly during and for 3 weeks after the end of treatment and then monthly for a further 2 months. compliance was excellent. RESULTS: There were no differences between the patients in the two arms with respect to age, gender, tumour type (52% prostate, 41% bladder, 5% rectum, 2% other) fractionation/dosage, anterior field size, weight, or baseline symptoms. Substantial differences in normal-tissue volumes (rectum, bladder, etc.) were achieved: median high-dose volume (HDV) of 689 cm3 for the conformal technique versus 792 cm3 for the conventional. A clear pattern of an increase in symptoms during RT, followed by a decrease after RT, was observed for the patient group as a whole. However, a very extensive analysis has not revealed any (statistically) significant differences between the two arms in level of symptoms, nor in medication prescribed. The disparity between our findings and those of other, non-randomized studies is discussed. CONCLUSIONS: The data on late effects must be collected and analyzed before any definite conclusions can be drawn on the benefits of conformal therapy in the pelvis.

Aged↗
PubMed1997

Spinal cord compression in prostate cancer: treatment outcome and prognostic factors.

BACKGROUND AND PURPOSE: Spinal cord compression (SCC) is an important complication of metastatic prostate cancer. We have analysed patients treated at the Royal Marsden Hospital to assess treatment outcome and prognostic factors in this patients group. MATERIALS AND METHODS: We performed retrospective analysis of 69 patients with spinal cord compression and prostate cancer treated at the Royal Marsden Hospital. RESULTS: At presentation 40 (58%) patients were non-ambulant and 52% were catheterised. Diagnosis was established by myelography in 42% and magnetic resonance imaging (MRI) in 47% of patients. MRI detected significantly more patients with multiple sites of compression (51 versus 7%, P < 0.001). SCC was present at the initial diagnosis of prostatic cancer in 13 patients and 17 patients had received no hormone treatment prior to diagnosis. Following treatment 36 (52%) patients had a functional improvement of motor power with 25/40 (63%) non-ambulant patients becoming ambulant. Seventy-seven percent of patients who had eventual improvement had some improvement in power within 7 days. On multivariate analysis a single level of compression, no previous hormone therapy and a young age (<65 years) predicted for better outcome. When these factors were included an increased radiation dose (>30 Gy) or the addition of surgery did not improve the functional outcome. Following initial recovery; there was a 45% risk of developing a further episode of cord compression at the same or new site by 2 years with a median time to progression of 236 days (range 47-1215 days). The median survival was 115 days (range 5-2016 days) with 25% of patients surviving for 2 years. Patients with no prior hormone therapy had a median survival of 627 days (range 46-1516 days). Other predictors of improved survival on multivariate analysis were a single site of compression and a haemoglobin over 12 g. CONCLUSIONS: Treatment of SCC in prostate cancer results in improved motor function in the majority of patients. Long-term survival is possible, especially in good performance status patients with no prior hormone treatment. Survivors remain at high risk of subsequent neurological relapse. An early improvement in motor power is a strong predictor of subsequent functional improvement. MRI detects additional sites of asymptomatic SCC which makes it the investigation of choice.

Aged↗
PubMed1997

Fibroblast growth factor 2 in breast cancer: occurrence and prognostic significance.

This paper examines the expression of fibroblast growth factor 2 (FGF-2) in the malignant human breast. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assess the level of expression of FGF-2 in a series of 51 patients clinically followed up for a median of 84 months (Luqmani et al, 1992). Immunohistochemistry and Western blotting were used to show that the level of FGF-2 in breast tissues correlated with the amount of FGF-2 mRNA. FGF-2 was present in both malignant and non-malignant breast, although less was expressed in malignant tissues as determined by all three methods. Immunohistochemistry on frozen sections of breast tissue showed expression of FGF-2 in myoepithelial and epithelial cells in non-malignant samples and generally lower or undetectable levels of staining in malignant epithelial cells. The results obtained by immunohistochemistry correlated well with RT-PCR data showing similar levels of FGF-2 and FGF-2 mRNA expression in samples. No correlation was found between FGF-2 mRNA expression and T stage, nodal status or oestrogen receptor status. However, Kaplan-Meier survival plots show that higher levels of FGF-2 are associated with improved overall and disease-free survival. We suggest that FGF-2 expression may have value as a prognostic indicator in breast cancer.

Adult↗
PubMed1997

A comparison of intensive neurodevelopmental therapy plus casting and a regular occupational therapy program for children with cerebral palsy.

The purpose of this research was to evaluate the combined effect of intensive neurodevelopmental therapy (NDT) and casting in improving hand function, quality of upper-extremity movement and range of motion in children aged between 18 months and 4 years with cerebral palsy (CP). A randomized crossover design was used to evaluate the difference between intensive NDT plus casting and a less intensive regular occupational therapy (OT) program. Blinded assessments of hand function, quality of upper-extremity movement, and parents' perception of hand-function performance were carried out at baseline, 4 months (end of first intervention period), 6 months (after a 2-month 'washout' period), and 10 months (end of second intervention period). Analysis of the outcomes revealed no significant differences in hand function, quality of upper-extremity movement, or parents' perception of hand-function performance between the two treatment groups-intensive NDT plus casting or regular OT programs. There does not appear to be any beneficial effect of an increased amount of therapy for the children in this study.

Activities of Daily Living↗
PubMed1997

An appraisal of the efficacy and cost effectiveness of antenatal screening for hepatitis B.

In this review published data are used to determine the benefits and costs of antenatal screening for hepatitis B carriers to prevent the later occurrence of hepatoma and chronic liver disease in their offspring. In Britain, babies born to carrier mothers have a 25% risk of perinatal infection and of becoming carriers themselves (the risk is 82% if their mothers are positive for the e antigen and 10% if negative). The carrier state increases the risk of hepatoma an estimated 86 times and the risk of chronic liver disease 20 times. Life table analysis showed that there is an 11% lifetime risk in carriers in Britain of dying from hepatoma (which results in seven years of life lost on average) and a 7% risk of chronic liver disease (14 years of life lost). Neonatal vaccination reduces the risk of the infant becoming a carrier by about 90%. Perinatal transmission occurs in 38 of every 100,000 neonates in Britain. Antenatal screening of all women and vaccinating babies of carrier mothers would prevent perinatal transmission in 34 of the 38 children (90%), or 255 per year in Britain. Of these 34, 8.4 children would be Chinese in ethnic origin, 4.2 African, 11.5 South Asian (from the Indian subcontinent), 2.0 Caribbean, and 7.3 would be white. Six deaths in the 34 from hepatoma or chronic liver disease caused by hepatitis B would then be prevented. The direct cost in Britain of screening all women, irrespective of ethnicity, at their first pregnancy only, would be 1300 pounds for each year of life saved (undiscounted) or 2500 pounds if screening at every pregnancy. Screening just Chinese, Africans, and South Asians, at first pregnancy only, would cost 330 pounds for each year of life saved but would prevent only 64% of these deaths. Vaccinating the infants of carrier mothers is likely also to prevent horizontal transmission of hepatitis B in early childhood and prevent the carrier state developing in an estimated three extra children for each child protected from vertical transmission. When this is taken into account the number of deaths prevented increases fourfold, reducing the cost for each year of life saved by 75%. Screening all women at first pregnancy only is an acceptably cost effective policy in Britain (1300 pounds for each year of life saved), actually preventing 45 deaths a year from hepatoma and chronic liver disease (or about 180 deaths if those horizontally infected are included), at a total cost of 540,000 pounds a year. It has the advantage of being comprehensive, equitable, and easier to implement than a policy based on screening of high risk ethnic groups.

Adolescent↗
PubMed1997

Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer.

PURPOSE: Vaginal dryness and dyspareunia are significant estrogen-depletion symptoms that affect many breast cancer survivors. The present trial was developed to evaluate the nonhormonal vaginal lubricating preparation, Replens, for alleviating these symptoms. MATERIALS AND METHODS: A double-blind, crossover, randomized clinical trial was developed. Patients received 4 weeks of Replens (Columbia Research Laboratories, Rockville Centre, NY) followed by a 1-week washout period followed by 4 weeks of a placebo lubricating product, or vice versa. Weekly patient-completed diaries were used for measuring efficacies and toxicities of therapy. RESULTS: The 45 assessable patients provided well-balanced treatment groups. During the first 4 weeks, average vaginal dryness decreased by 62% and 64% in the placebo and Replens groups, respectively (P = .3). Average dyspareunia scores also improved by 41% and 60%, respectively (P = .05). Crossover analysis indicated that the bulk of the beneficial effects appeared within the first 2 weeks of the first treatment and remained constant thereafter. Both treatments were relatively well tolerated. CONCLUSION: Both Replens and the placebo appear to substantially ameliorate vaginal dryness and dyspareunia in breast cancer survivors.

Adult↗
PubMed1997

Occupational therapy practice: focusing on occupational performance.

Changes in the health system require occupational therapy practitioners to focus their concerns on the long-term health needs of people and to help them develop healthy behaviors not only to improve their health, but also to minimize the health care costs associated with dysfunction. Occupational therapy practitioners must initiate efforts in the community to integrate a range of services that promote, protect, and improve the health of the public. This article shares the experiences of Canadian occupational therapy practitioners, who were challenged by their government nearly 15 years ago to establish a system that demonstrates effectiveness by improving the health of occupational therapy clients. By focusing on occupational performance, occupational therapy practitioners assist clients in becoming actively engaged in their life activities. This requires client-centered and family-centered practice and services that span from the agency or institution to the community. Occupational therapy practitioners must work collaboratively with persons in the client's environment (e.g., family members, teachers, independent living specialists, employers, neighbors, friends) to assist the client in obtaining skills and to make modifications to remove barriers that create a social disadvantage. A focus on occupational performance requires occupational therapy personnel to reframe how we think about occupational therapy to a sociomedical context and to take an active role in building healthy communities.

Canada↗
PubMed1996

CD8+ lymphocyte responses to antiretroviral therapy of HIV infection.

CD8+ T lymphocytes may mediate important host responses to human immunodeficiency virus (HIV) infection by human leukocyte antigen (HLA)-restricted cytotoxicity and production of soluble HIV suppressor factors. CD8+ lymphocytes are also important for the suppression of many latent pathogens responsible for opportunistic disease in HIV-infected patients. There has been no systematic analysis of the responses of CD8+ lymphocyte counts to antiretroviral therapy. We compared CD8+ lymphocyte responses in seven trials of nucleoside or non-nucleoside analog reverse transcriptase inhibitors and in two trials of ritonavir, a HIV protease inhibitor. Nucleoside analog and non-nucleoside analog reverse transcriptase inhibitor monotherapy resulted in no substantial changes in CD8+ counts relative to baseline or placebo. Combination nucleoside analog therapy resulted in variable peak responses (-145 to +240 cells/mm3), which remained significantly above baseline for 0 to 12 weeks. In contrast, ritonavir monotherapy caused a peak increase of 892 CD8+ cells/mm3, which remained significantly above baseline for 32 weeks. There was a significant correlation (Rs 0.61, p = 0.01) between the peak CD4+ cell and CD8+ responses to each therapy, but no significant correlation between the peak viral load responses and peak CD8+ cell responses. These findings suggest that the greater CD8+ response seen with ritonavir may be due to its specific inhibition of HIV protease and also that the CD8+ response is dependent on new CD4+ cell production. The CD8+ lymphocyte proliferation observed with protease inhibitor therapy could result in improved suppression of HIV replication by the immune system and should be confirmed in a prospective trial comparing protease inhibitors with both nucleoside and non-nucleoside analog therapies.

Acetamides↗
PubMed1996

A novel target for the Wilms' tumour suppressor protein (WT1) is bound by a unique combination of zinc fingers.

All isoforms of the Wilms' tumour suppressor protein, WT1, contain four consecutive zinc fingers which facilitate DNA binding. The predominant WT1 transcript contains a 9 base pair insertion resulting in an additional three amino acids, lysine-threonine-serine (KTS), between zinc fingers 3 and 4. WT1 zinc fingers 2, 3 and 4 are highly homologous to the zinc fingers of the early growth response gene, EGR1. However, only WT1--KTS is capable of binding an EGR1 consensus site. In contrast, the previously described genomic fragment, +P5 (D1S3309E), is bound by both WT1--KTS and WT1 + KTS. In this study, the region within + P5 to which both WT1 -- KTS and WT1 + KTS bind was defined as 5'-GGAGAGGGAGGATC-3'. EGR1 did not bind + P5. By creating zinc finger deletions, we demonstrate that zinc finger 1, but not zinc finger 4, is critical for + P5 binding; whereas zinc finger 4, but not 1, is necessary for the binding of WT1 target sites within EGR1, PDGF A chain and IGF2 promoters. Thus, zinc finger usage can vary with target and + P5 may represent a novel type of WT1 binding site, the physiological relevance of which must be investigated.

Binding Sites↗
PubMed1996

Laparoscopic discectomy with anterior interbody fusion of L5-S1.

BACKGROUND: A laparoscopic approach to the spine for the performance of a minimally invasive discectomy was first described in 1991. Since that time, a number of approaches to laparoscopic discectomy have appeared in the literature. Although these reports demonstrate the ability to approach the spine through a laparoscopic technique, they do not address the issues of loss of disc space, lumbar instability, and the need for interbody fusion. METHODS: Described is a technique of laparoscopic discectomy with interbody fusion that has been performed successfully in 75 patients. Although a carbon fiber implant was utilized to aid in the fusion process, the technique can equally be performed using donor bone as the interbody support. In the 75 patients attempted, 73 procedures were successfully completed via the laparoscopic approach. One patient was converted to an open anterior approach due to extensive pelvic adhesions from prior surgery. A second patients procedure was aborted after the diagnostic laparoscopy demonstrated dense presacral scarring from a previous gynecological procedure. RESULTS: There were no major complications in the series. Two patients with high riding bladders sustained bladder lacerations that were recognized and repaired with simple suture closure. There were no bowel injuries, and more importantly, no major vessel injury. The patients were discharged from the hospital on an average within 36 hours, with a return to work averaging between 2-4 weeks depending on the patients type of work. Using a modified pain score for evaluation, post operative pain was reduced by 75%. CONCLUSIONS: From this study, it is concluded that laparoscopic discectomy with interbody fusion is not only feasible, but appears to give good results with follow up extending out beyond two years. Issues regarding the use of carbon fiber cages vs. bone and indications of the procedure are independent of the laparoscopic approach and are addressed extensively in the orthopedic literature. It can be concluded that when there is surgical indication for L5-S1 discectomy, that a laparoscopic approach with interbody fusion may become the procedure of choice.

Diskectomy↗