Biomedical subjects
Publications and source records attributed to A Gordon.
Although many of the factors that contribute to anorexia nervosa are not within the physician's control, early detection and prompt initiation of treatment may improve patient outcome. A high level of suspicion and a willingness to address the issue can serve our patients well.
BACKGROUND: Congenital alveolar rhabdomyosarcoma (RMS) is extremely rare and invariably fatal with current therapy. Its clinical presentation is unusual and is distinct from RMS in older children, with > 50% of patients presenting with multiple cutaneous metastases. To the authors' knowledge, the biology of this condition has not been studied to date. METHODS: The clinical and pathologic findings of four cases of congenital RMS are presented along with those of other cases found in the literature. Molecular analysis was undertaken to detect the characteristic chromosomal translocations of alveolar RMS in three cases with suitable material. RESULTS: To the authors' knowledge, there are no recorded survivors of congenital alveolar RMS. Clinical and histopathologic findings in four patients with congenital alveolar RMS are detailed along with treatment responses. It now is recognized that tumor specific translocations can be detected in the majority of cases of alveolar RMS using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. However, detailed molecular analysis using RT-PCR was unable to detect the presence of either the classic t(2;13) or variant t(1;13) translocation in three cases analyzed at the molecular level. CONCLUSIONS: To the authors' knowledge the optimal treatment for this rare tumor is not known. The longest survivor in the current series underwent myeloablative therapy with peripheral stem cell support, suggesting that more intensive treatment may be of value in this rare condition. None of the three tumors analyzed by RT-PCR harbored characteristic RMS translocations. The molecular biology of this highly malignant and aggressive congenital tumor appears to be different from alveolar RMS in older children and warrants further investigation.
To better understand cellular responses in human lymphoblastoid cell TK6 after exposure to C-ion (22 keV/micrometer) and Fe-ion (1000 keV/micrometer), both protein induction and cell-cycle progression have been extensively analyzed by the recently developed techniques. While proceeding this line of analyses, we realized the importance of studying low-dose effect, in relation to the genetic alterations. Adaptive response by 5~20 cGy of such C- or Fe-ion irradiation to both lethal and mutagenic effects of the challenging X-ray exposure (1~3 Gy) was difficult to be seen in this TK6 cells, but surprisingly, a relatively high level of p53 and its related proteins induction was observed after low-dose irradiations of heavy-ions. Here, we focus to introduce the above results of genetic and biochemical studies to elucidate the adaptive response.
BACKGROUND: Beneficial training outcomes have been reported in patients with chronic heart failure (CHF) following leg exercise training. However, data from more comprehensive training programs are limited. The aim of this study was to test the hypothesis that exercise training applying the concept of comprehensive local muscle training can improve aerobic and functional working capacity as well as quality of life in patients with CHF. METHODS: Twenty-four men and women [age 63+/-9 years (mean+/-S.D.)] with stable, moderate chronic heart failure (left ventricular ejection fraction 30+/-10%), were investigated in a randomized controlled study with a training group of 16 patients and a control group of 8 patients. The training was performed as an aerobic resistance training by activating all the main muscle groups, one at a time. The patients exercised for 1 h, three times per week for 8 weeks. RESULTS: Patient groups did not differ at baseline. Peak oxygen uptake (8%, P<0.03), the distance walked in a 6-min walking test (11%, P<0.002), the health-related quality of life (P<0.001) and plasma norepinephrine levels at rest (32%, P<0.003) and at submaximal intensities (P<0.03) improved after training. No changes were found in the control group, except for decreased peak oxygen uptake (P<0.02) and quality of life scores (P<0.03). CONCLUSIONS: Since comprehensive physical training activating a minor muscle mass at a time markedly improves exercise capacity and quality of life and reduces catecholamine levels, it can be recommended for the rehabilitation of patients with CHF under supervision of a physical therapist.
Dendritic-cell (DC) trafficking and function in tumors is poorly characterized, with studies confined to myeloid DCs (DC1s). Tumors inhibit DC1 migration and function, likely hindering specific immunity. The role of plasmacytoid DCs (DC2s) in tumor immunity is unknown. We show here that malignant human ovarian epithelial tumor cells express very high levels of stromal-derived factor-1, which induces DC2 precursor (preDC2) chemotaxis and adhesion/transmigration, upregulates preDC2 very late antigen (VLA)-5, and protects preDC2s from tumor macrophage interleukin-10-induced apoptosis, all through CXC chemokine receptor-4. The VLA-5 ligand vascular-cell adhesion molecule-1 mediated preDC2 adhesion/transmigration. Tumor preDC2s induced significant T-cell interleukin-10 unrelated to preDC2 differentiation or activation state, and this contributed to poor T-cell activation. Myeloid precursor DCs (preDC1s) were not detected. Tumors may weaken immunity by attracting preDC2s and protecting them from the harsh microenvironment, and by altering preDC1 distribution.
BACKGROUND AND AIMS: During the last decades several angiogenic factors have been characterized but so far it is unknown whether local muscle exercise training increases the expression of these factors in patients with moderate heart failure. Expression of the major putative angiogenic factor vascular endothelial growth factor (VEGF) at the level of messenger RNA (mRNA) and/or protein was therefore studied before and after 8 weeks of training in patient with chronic heart failure. METHODS: VEGF mRNA and protein concentrations were determined in skeletal muscle biopsies before and after 8 weeks of one-legged knee extension training in patients with chronic heart failure (New York Heart Association II-III). RESULTS: Exercise training increased the citrate synthase activity and peripheral exercise capacity by 46% and 36%, respectively, in parallel with a two-fold increase in VEGF at both the mRNA (P = 0.03) and protein (P = 0.02) levels CONCLUSION: The increase in VEGF gene expression in response to exercise training indicates VEGF to be one possible mediator in exercise-induced angiogenesis and may therefore regulate an important and early step in adaptation to increased muscle activity in patient with chronic heart failure.
This paper reports 3-dimensional confocal microscopy observations on how nephrogenic aggregates form from the NCAM- and Pax2-positive caps (4-5 cells deep) of condensed metanephric mesenchyme surrounding the duct tips of the mouse kidney. Aggregates of 6-8 cells are first seen at approximately E12.5-12.75 immediately proximal to this cap, closely abutting the duct surface. As the tip advances, NCAM expression is maintained in the cap but is otherwise restricted to aggregates whose cells rapidly epithelialise, forming tubules that invade the duct epithelium. Pax2 expression studies shows how the rind of nephrogenic blastemal cells forms: as duct tips extend towards the kidney surface, the associated Pax2+ cells form patches of cells on the kidney surface. These observations revise our knowledge of the timing and process of nephron initiation.
Rhabdomyosarcoma in children is a "small round blue cell tumour" that displays skeletal muscle differentiation. Two main histological variants are recognised, alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma. Whereas consistent chromosome translocations characteristic of ARMS have been reported, no such cytogenetic abnormality has yet been described in ERMS. We have used multiple colour chromosome painting to obtain composite karyotypes for five ERMS cell lines and one PAX-FOXO1A fusion gene negative ARMS. The cell lines were assessed by spectral karyotyping (SKY), tailored multi-fluorophore fluorescence in situ hybridisation (M-FISH) using series of seven colour paint sets generated to examine specific abnormalities, and comparative genomic hybridisation (CGH). This approach enabled us to obtain karyotypes of the cell lines in greater detail than previously possible. Several recurring cytogenetic abnormalities were demonstrated, including translocations involving chromosomes 1 and 15 and chromosomes 2 and 15, in 4/6 and 2/6 cell lines respectively. All six cell lines demonstrated abnormalities of chromosome 15. Translocations between chromosomes 1 and 15 have previously been recorded in two primary cases of ERMS by conventional cytogenetics. Analysis of the translocation breakpoints may suggest mechanisms of ERMS tumourigenesis and may enable the development of novel approaches to the clinical management of this tumour.
BACKGROUND: Promising treatments for alcoholics include naltrexone (NTX), cue exposure combined with urge-specific coping skills training (CET), and communication skills training (CST). This study investigated the effects of combining these elements as treatment adjuncts. METHODS: A 2 x 2 design investigated the effects of CET combined with CST, as compared with an education and relaxation control treatment, during a 2-week partial hospital program (n = 165) followed by 12 weeks of NTX (50 mg/day) or placebo during aftercare (n = 128). Drinking outcomes were assessed at 3, 6, and 12 months after discharge from the partial hospital. Process measures included urge, self-efficacy (confidence about staying abstinent in risky situations), and self-reported coping skills. Medically eligible alcohol-dependent patients were recruited. RESULTS: Among those compliant with medication on at least 70% of days, those who received NTX had significantly fewer heavy drinking days and fewer drinks on days that they drank than those receiving placebo during the medication phase but not during the subsequent 9 months. CET/CST-condition patients were significantly less likely to report a relapse day and reported fewer heavy drinking days at the 6- and 12-month follow-ups than patients in the control treatment. Interactions of medication with behavioral treatments were not significant. Process measures showed that NTX resulted in lower weekly urge ratings, and those in CET/CST used more of the prescribed coping skills after treatment, reported fewer cue-elicited urges, and reported more self-efficacy in a posttest role-play test. Drinking reductions at 3, 6, and 12 months correlated with more use of coping skills, lower urge, and higher self-efficacy. CONCLUSIONS: The results suggest the probable value of keeping alcoholics on NTX for longer periods of time and the importance of increasing compliance with NTX. They also support the earlier promising effects of CET and CST as adjuncts to treatment programs for alcoholics by maintaining treatment gains over at least a year. The value of the urge-specific and general coping skills and of self-efficacy and urge constructs was demonstrated in their association with drinking outcomes.
We consider the Born-Oppenheimer problem near conical intersection in two dimensions. For energies close to the crossing energy we describe the wave function near an isotropic crossing and show that it is related to generalized hypergeometric functions 0F3. This function is to a conical intersection what the Airy function is to a classical turning point. As an application we calculate the anomalous Zeeman shift of vibrational levels near a crossing.
Recordings of membrane potential (Em) and intracellular [Cl-] ([Cl-]i) were made from the smooth muscle of human umbilical and placental arteries, using double-barrelled, ion-sensitive microelectrodes. In both arteries, [Cl-]i was above equilibrium with Em. In the umbilical artery, [Cl-]i was 33.8+/-0.9 mM (+/-SD, n=19) and Em -54.9+/-1.3 mV and in the placental artery respectively 35.1+/-0.7 mM (n=17) and -50.6+/-0.9 mV. In both arteries, [Cl-]i was reduced and Em hyperpolarised significantly by successive additions of 100 microM 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulphonic acid (DIDS), 10 microM bumetanide and 1 mM acetazolamide, thus revealing the presence of Cl-/HCO3- exchange, (Na+K+Cl) cotransport and "pump III". In the presence of all three inhibitors, [Cl-]i was in equilibrium with Em. As in earlier studies on rat arterial smooth and cardiac muscle, pump III was unaffected by DIDS, bumetanide, metolazone and the removal of Na+, partly inhibited by chlorothiazide and fully inhibited by ethacrynic acid. The results are discussed in terms of the possibility that of chloride accumulating systems may regulate vasomotor tone in the foetoplacental unit.
A parental questionnaire was used to investigate the outcome for children who had had ischaemic stroke, who were seen at Great Ormond Street Hospital, London between 1990 and 1996. The results of functional assessments carried out by a physiotherapist and an occupational therapist, and of quantitative evaluations carried out by a neuropsychologist were used for validation where possible. The relationship between clinical and radiological factors and outcome were examined. The children were aged between 3 months and 15 years at the time of stroke (median age 5 years) and the period of follow-up ranged from 3 months to 13 years (median duration 3 years). Of the 90 children for whom data were obtained, 13 (14%) had no residual impairments. Outcome was good in 37 children (40%) and poor in 53 (60%) (defined according to whether impairments interfered with daily life). Agreement, as measured by Cohen's kappa, was good or very good between the parents' responses and the qualitative measures provided by the medical professionals and the therapists, but only fair to moderate for the quantitative measures provided by the neuropsychologists. This may reflect different parental perceptions of the physical and cognitive aspects of outcome. Younger age at time of the stroke was the only significant predictor of adverse outcome.
Unprotected sex is a critical issue in the Hispanic community, with the incidence of new Hispanic acquired immune deficiency syndrome (AIDS) cases three times that of non-Hispanic Whites. The researchers used focus groups to examine: (a) whether newly immigrated Mexican men and women in the Southeast United States discussed human immunodeficiency virus (HIV)/sexually transmitted disease (STD) prevention with each other, and (b) how condom use was discussed. For the women, communication was safe sex, and for the men, trust was safe sex. Both communication and trust were dependent on timing in the relationship. Participants could not discuss condoms in a new or established relationship because of issues of trust. This study highlights the complexity of HIV/STD prevention and suggests that trust and timing should be considered within the cultural context of condom introduction.
OBJECTIVE: To evaluate the clinical usefulness of Doppler analysis of the uterine artery velocity waveform in the prediction of pre-eclampsia and its associated complications of intrauterine growth retardation and perinatal death. DESIGN: Quantitative systematic review of observational diagnostic studies using online searching of the MEDLINE database coupled with scanning of the bibliographies of primary and review articles including known unpublished studies. MATERIAL: Twenty-seven studies involving 12,994 subjects stratified into population subgroups at low and high risk of developing pre-eclampsia and its complications. OUTCOME MEASURES: The outcome measures studied were: 1. the development of pre-eclampsia; 2. intrauterine growth retardation; and 3. perinatal death. The main meta-analyses were the flow velocity waveform ratio +/- diastolic notch derived by transabdominal Doppler ultrasound as the measurement parameter. The analyses were conducted using likelihood ratio as a measure of diagnostic accuracy. A likelihood ratio of 1 indicates that the test has no predictive value for the outcome. Prediction for the outcome event is considered conclusive with likelihood ratios of > 10 or < 0 x 1 for a positive and negative test result, respectively. Moderate prediction can be achieved with likelihood ratios of 5-10 and 0 x 1-0 x 2 whereas likelihood ratios values of 1-5 and 0 x 2-1 would generate only minimal prediction. RESULTS: In the low risk population a positive test result, predicted pre-eclampsia with a pooled likelihood ratio of 6 x 4 (95% CI 5 x 7-7 x 1), while a negative test result had a pooled likelihood ratio of 0 x 7 (95% CI 0 x 6-0 x 8). For intrauterine growth retardation the pooled likelihood ratio was 3 x 6 (95% CI 3 x 2-4 x 0) for a positive test result and 0 x 8 (95% CI 0 x 8-0 x 9) for a negative test result. Using perinatal death as outcome measure, the pooled likelihood ratio was 1 x 8 (95% CI 1 x 2-2 x 9) for a positive test result and 0 x 9 (95% CI 0 x 8-1 x 1) for a negative test result. In the high risk population a positive test result predicted pre-eclampsia with a pooled likelihood ratio of 2 x 8 (95% CI 2 x 3-3 x 4), while a negative test had a likelihood ratio of 0 x 8 (95% CI 0 x 7-0 x 9). For intrauterine growth retardation the pooled likelihood ratio was 2 x 7 (95% CI 2 x 1-3 x 4) for a positive test result and 0 x 7 (95% CI 0 x 6-0 x 9) for a negative result. For perinatal death the pooled likelihood ratio was 4 x 0 (95% CI 2 x 4-6 x 6) for a positive test result and 0 x 6 (95% CI 0 x 4-0 x 9) for a negative result. CONCLUSION: Uterine artery Doppler flow velocity has limited diagnostic accuracy in predicting pre-eclampsia, intrauterine growth retardation and perinatal death.
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Data from a sexual offender treatment program operated by the Correctional Service of Canada at the Regional Psychiatric Center (Saskatoon) supported the conclusion that cognitive behavioral treatment can reduce sexual offense recidivism. The study compared 296 treated and 283 untreated offenders followed for a mean of 6 years after their release. An untreated comparison subject was located for each treated offender on three dimensions: (a) age at index offense, (b) date of index offense, and (c) prior criminal history. Data were analyzed using tests of proportion, survival analysis, and analysis of offender Criminal Career Profiles. Over a mean follow-up period of almost 6 years, convictions for new sexual offenses among treated offenders were 14.5% versus 33.2% for untreated offenders. During the follow-up period, 48% of treated offenders remained out of prison compared to 28.3% of untreated offenders. Time series comparisons of treated and comparison samples also showed that treated men reoffended at significantly lower rates after 10 years. A Criminal Career Profile (CCP) was constructed by taking the Age at First Conviction and plotting the offender's successive lengths of time free against time incarcerated. Pre- and posttreatment slopes of the CCP were lower for both groups posttreatment; however, the degree of change was significantly greater for the treated group, indicating a greater reduction in criminal activity among these offenders. Taken together, the results of all three analytic techniques supported the efficacy of appropriate correctional treatment for effective reduction of recidivism.
BACKGROUND AND OBJECTIVES: The widespread use of alternative and complementary therapies by the public provides a new challenge to medical education. No standardized curriculum is available for medical educators in this field. Providing an adequate background on these therapies and reliable, useful information to our learners was a task addressed by the Society of Teachers of Family Medicine (STFM) Group on Alternative Medicine over the past 2 years. METHODS: The group met at conferences and communicated via e-mail to develop a consensus of recommended knowledge, skills, and attitudes in complementary and alternative medicine for incorporation into the family practice residency training curriculum. CONCLUSION: This article suggests guidelines as developed by this STFM group to assist programs wishing to include formal training in complementary and alternative medicine in residency training.
OBJECTIVE: To determine attitudes with regard to ethics in the practice of psychiatry in South Africa. DESIGN: Cross-sectional survey. METHOD: The study utilised clinical vignettes, with gender and race of the patient as potential modifying variables in diagnosis and management. Open-ended questions pertaining to potential abuses were included. SETTING AND SUBJECTS: Questionnaires were mailed to all practising psychiatrists in South Africa in 1993 and 1994. OUTCOME MEASURES: Responses to questionnaire. RESULTS: A 40% response rate was obtained (N = 73). Patient race and gender did not influence diagnosis or have a marked impact on the prescription of treatment. Pressure from the patient's family on the psychiatrist did alter case management, as did the psychiatrist's age and gender in some instances. Racial discrimination, sexual misconduct and economic abuses were the most frequently cited areas of observed abuse. CONCLUSION: The development of an ethical framework for the practice of psychiatry in South Africa would appear to be of critical importance.