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Biomedical subjects

M McGuire

Publications and source records attributed to M McGuire.

At least 37 records · Page 2Linked to original sources

Chronic intermittent hypoxia increases haematocrit and causes right ventricular hypertrophy in the rat.

Chronic continuous hypoxia increases haematocrit and causes right ventricular hypertrophy and pulmonary hypertension. In obstructive sleep apnoea, the exposure to hypoxia is intermittent rather than continuous but the effects of chronic intermittent hypoxia on haematocrit and right ventricular mass are unclear. Wistar rats were exposed to alternating periods of hypoxia and normoxia twice per min for 8 h per day for 5 weeks in order to mimic the intermittent hypoxia of obstructive sleep apnoea in humans. Haematocrit was significantly raised at day 7, 14, 21, 28 and 35 of the treatment period. At the end of the treatment, there was a significant increase in right ventricular mass. Therefore, chronic intermittent hypoxia increases haematocrit and right heart mass. These results suggest that the raised haematocrit and pulmonary arterial pressure observed in some cases of obstructive sleep apnoea in humans may be caused by intermittent nocturnal hypoxaemia.

Animals↗

Upper tract recurrences following radical cystectomy: an analysis of prognostic factors, recurrence pattern and stage at presentation.

PURPOSE: We study the incidence and pattern of upper tract recurrences following radical cystectomy for bladder cancer, and analyze the prognostic factors. MATERIALS AND METHODS: A retrospective study was performed on 529 patients who underwent radical cystectomy and urinary diversion at Memorial Sloan-Kettering Cancer Center between July 1989 and June 1997. Data related to upper tract recurrence were analyzed. RESULTS: Of the 529 patients 16 (3%) had upper tract recurrence. Median followup was 16.9 months for the entire group and 49.1 months for patients with upper tract recurrence, with a median time to recurrence of 37.2 months. Of 12 upper tract recurrences 7 (58%) were locally advanced at surgery (p3a or greater with or without lymph node metastasis) and 5 of 16 patients with recurrence (31.3%) had bilateral tumors (2 synchronous and 3 metachronous). Overall survival from the time of diagnosis of upper tract recurrence after radical cystectomy was poor, with a median of 10 months (confidence interval 1 to 19). CONCLUSIONS: The incidence of upper tract recurrence following radical cystectomy is low (3%). However, the incidence of bilateral tumors (31.3%) and locally advanced stage at the time of operation (58%) is higher than expected for upper tract tumors in the general population. Survival of patients with upper tract recurrence is poor, with a median of 10 months.

Adult↗

Treatment attrition among alcohol-dependent men: is it related to novelty seeking personality traits?

"Dropouts" are a major concern when monitoring treatment efficacy in clinical trials. Alcohol-dependent patients are especially prone to discontinuing treatment, perhaps because of impulsive behavior. The Tridimensional Personality Questionnaire (TPQ) measures a trait-like quality, novelty seeking, which may reflect impulsiveness. We tested the hypotheses that higher TPQ Novelty Seeking subscale scores would be associated with increased rates of treatment dropout and increased risk for dropping out earlier. A total of 170 alcohol-dependent men who participated in a double-blind, placebo-controlled pharmacotherapeutic trial for decreasing relapse drinking completed the TPQ and were monitored until treatment dropout. Logistic regression and Cox proportional hazards models were used to (1) describe the relationship between the TPQ Novelty Seeking score and the dichotomous outcome variable, treatment dropout; and (2) assess the effects of a number of potential confounding covariates on the relationship between the risk factor, novelty seeking, and the time to the outcome event. The mean Novelty Seeking score was significantly higher among study dropouts compared with nondropouts (p = 0.003). Higher Novelty Seeking scores were associated with a higher adjusted odds ratio for dropping out (adjusted odds ratio = 1.07, 95% confidence interval [CI] = 1.00-1.15) and a higher adjusted hazard rate for dropping out earlier (adjusted hazard rate = 1.05, 95% CI = 1.00-1.09). The TPQ Novelty Seeking subscale score may identify a subgroup of alcohol-dependent men who are at risk for dropping out of treatment. This information may be useful for developing treatment plans to encourage these high-risk patients to remain in treatment.

Adult↗

Jamaican Symmetry Project: long-term study of fluctuating asymmetry in rural Jamaican children.

Fluctuating asymmetry, small deviations from perfect bilateral symmetry, is negatively correlated with health and positively correlated with sexual selection in human adults, but the accumulation, persistence, and fitness implications of asymmetries during childhood are largely unknown. Here, we introduce the Jamaican Symmetry Project, a long-term study of fluctuating asymmetry and its physical and behavioral correlates in rural Jamaican children. The project is based on an initial sample of 285 children (156 boys and 129 girls), aged 5 to 11 years. We describe the design of the project and the methodology of measuring 10 paired morphometric traits. All traits except hand width showed fluctuating asymmetry. Fluctuating asymmetries of the legs tended to be related and were less than half as great as fluctuating asymmetries of the arms and ears. Therefore the legs may show high developmental stability resulting from selection for mechanical efficiency. A fluctuating asymmetry composite score revealed that boys have significantly lower fluctuating asymmetry than girls and that this effect resides mainly in the elbows. There were significant positive relationships between composite fluctuating asymmetry and age, height, and weight, but multiple regression analyses showed that age was negatively related to fluctuating asymmetry, whereas body size was positively correlated. These findings are compared with results from recent English studies.

Analysis of Variance↗

The influence of streptozotocin diabetes and metformin on erythrocyte volume and on the membrane potential and the contractile characteristics of the extensor digitorum longus and soleus muscles in rats.

The effects of streptozotocin (STZ) diabetes and the antihyperglycaemic agent metformin on the contractile characteristics of the limb skeletal muscles and on erythrocyte volume were examined in rats. After 8 weeks of diabetes, the tetanic tension of the extensor digitorum longus (EDL) muscle decreased and the half-relaxation time of the soleus muscle increased. Endurance decreased in both muscles. Metformin treatment of the diabetic rats did not prevent the development of these contractile changes. Diabetes induced depolarisation in the EDL and soleus muscles. Following exposure to insulin, both muscles repolarized. Metformin treatment of control rats induced depolarisation in the EDL and soleus muscles, but in the depolarised EDL and soleus muscles of the diabetic rats metformin treatment caused no further depolarisation. The muscles of metformin-treated control and diabetic rats hyperpolarized in the presence of insulin. Diabetes caused an increase in the volume of the blood erythrocytes. This was prevented by metformin treatment.

Animals↗

Location of the phosphate binding site within Clostridium symbiosum pyruvate phosphate dikinase.

Pyruvate phosphate dikinase (PPDK) catalyzes the interconversion of ATP, Pi, and pyruvate with AMP, PPi, and PEP in three partial reactions: (1) E + ATP --> E.ATP --> E-PP.AMP, (2) E-PP.AMP + Pi --> E-PP.AMP.Pi --> E-P.AMP.PPi, and (3) E-P + pyruvate --> E-P.pyruvate --> E.PEP. The Clostridium symbiosum PPDK structure consists of N-terminal, central, and C-terminal domains. The N-terminal and central domains catalyze partial reactions 1 and 2 whereas the C-terminal and central domains catalyze partial reaction 3. The goal of the present work is to determine where on the N-terminal domain catalysis of partial reactions 1 and 2 occurs and, in particular, where the Pi binding site is located. Computer modeling studies implicated Arg337 as a key residue for Pi binding. This role was tested by site-directed mutagenesis. The R337A PPDK was shown to be impaired in catalysis of the forward (kcat 300-fold lower) and reverse (kcat 30-fold lower) full reactions. Time courses for the single turnover reactions were measured to show that catalysis of partial reaction 1 is 5-fold slower in the mutant, catalysis of the second partial reaction is 140-fold slower in the mutant, and catalysis of the third partial reaction is unaffected. With the exception of the mutation site, the crystal structure of the R337A PPDK closely resembles the structure of the wild-type protein. Thus, the altered kinetic properties observed for this mutant are attributed solely to the elimination of the interaction between substrate and the guanidinium group of the Arg337 side chain. On the basis of these findings we propose that the Pi binding site is located within the crevice of the PPDK N-terminal domain, at a site that is flanked by the ATP beta-P and the Mg2+ cofactor.

Alanine↗

Use of formal and informal sources of mental health care among older African-American public-housing residents.

BACKGROUND: Elderly residents of public housing have high rates of psychiatric disorders, but most of those in need of care do not use any mental health service. This study examines the use of formal and alternative informal sources of mental health care in a sample of elderly African-American public-housing residents. METHOD: Data from an epidemiological survey of six Baltimore public-housing developments for the elderly (weighted N = 818) were analysed to examine the utilization of mental health services by older African-American residents. Logistic regression analyses were used to determine correlates of using formal and informal sources by those needing mental health care. RESULTS: Thirty-five per cent of subjects needed mental health care. Less than half (47%) of those in need received any mental health care in the previous 6 months. Residents in need were more likely to use formal (38.5%) than informal sources (18.6%) for care. The strongest correlates of using formal providers were substance use disorder (OR = 15.62), Medicare insurance (OR = 10.31) and psychological distress (OR = 10.27). The strongest correlates of using informal sources were perceiving little or no support from religious/spiritual beliefs (OR = 21.65), cognitive disorder (OR = 19.71) and having a confidant (OR = 15.07). CONCLUSIONS: Contrary to elderly African-Americans in general, those in public housing rely more on formal than informal sources for mental health problems. Nevertheless, both sources fail to fill the gap between need and met need. Interventions to increase identification, referral and treatment of elderly public-housing residents in need should target general medical providers and clergy and include assertive outreach by mental health specialists.

Black or African American↗

The influence of streptozotocin-induced diabetes and the antihyperglycaemic agent metformin on the contractile characteristics and the membrane potential of the rat diaphragm.

After 2 months of streptozotocin-induced diabetes in rats, the membrane potential of the diaphragm muscle when measured in vitro at 30 degrees C was unchanged but the tetanic tension, the half-relaxation time of the isometric twitch and the fatigue resistance were each reduced. Treatment of the diabetic rats with the antihyperglycaemic agent metformin prevented the decrease in half-relaxation time and the greater degree of fatigue in the diaphragms. The possibility that changes in H+ and cyclic AMP concentrations in the diabetic muscles contributed to the decreased contractile function and that metformin acted by attenuating these changes is discussed.

Animals↗

General exercise training improves ventilatory and peripheral muscle strength and endurance in chronic airflow limitation.

We studied the impact of a 6-wk supervised, multimodality endurance exercise training program (EXT) on strength and endurance of ventilatory and peripheral muscles in patients with chronic airflow limitation (CAL), and determined whether potential improvements contributed to relief of exertional breathlessness (B) and perceived leg effort/discomfort (LE), respectively. Twenty breathless patients with stable CAL (FEV1 = 41 +/- 3% predicted; mean +/- SEM) were tested at 6-wk intervals at baseline, after a nonintervention control period (pre-EXT), and post-EXT. Measurements included: pulmonary function tests (PFTs), maximal inspiratory/expiratory pressures (MIP, MEP), inspiratory muscle endurance (V(LIM)), quadriceps strength and endurance, exercise endurance, and submaximal cycle exercise with cardioventilatory and symptom responses. Measurements at baseline and pre-EXT were identical. Post-EXT, PFTs did not change; exercise endurance measured on the treadmill, cycle ergometer, arm ergometer, and by 6-min walk distance increased 40 +/- 8%, 43 +/- 10%, 12 +/- 5%, and 34 +/- 9%, respectively (p < 0.05); quadriceps strength increased 21 +/- 5% (p < 0.01); MIP and MEP increased 29 +/- 11% and 27 +/- 11%, respectively (p < 0.05); V(LIM) increased almost threefold (p < 0.05). At isotime near end-exercise, B, LE, carbon dioxide production (VCO2), oxygen consumption (VO2), ventilation, and breathing frequency (F) all fell after EXT (p < 0.05): deltaB correlated with deltaF (r = 0.58, p < 0.01). Increased MIP and V(LIM) did not correlate with improved breathlessness or exercise endurance. Similarly, changes in quadriceps strength and endurance did not correlate with changes in LE or exercise endurance. In conclusion, general nonspecific EXT improved ventilatory and peripheral muscle function in severe CAL, but such improvements did not appear to contribute significantly to reduced exertional symptoms and enhanced exercise performance.

Aged↗

Cost reduction with maintenance ECT in refractory bipolar disorder.

A case report of outpatient maintenance electroconvulsive therapy (ECT) is presented in a patient with bipolar disorder type I refractory to conventional medication treatment but responsive to ECT. A cost comparison is made showing substantial savings when outpatient maintenance ECT is used in lieu of inpatient hospitalization with ECT. A detailed life chart illustrating multiple medication trials that failed to stabilize the patient accompanies the financial summary. This case highlights the advantages of outpatient maintenance ECT for bipolar depression particularly with regard to safety, efficacy, and significant health care cost reduction.

Adult↗

Need and unmet need for mental health care among elderly public housing residents.

Epidemiologic survey data from elderly residents of six public housing developments were used to determine the prevalence of need and unmet need for mental health care. Thirty-seven percent of this predominantly African American sample needed mental health services, and 58% of those who needed care had unmet needs. Logistic regression analyses showed that males, older residents, those with no Medicare insurance, and those with more Activities of Daily Living (ADL) impairments were at greater risk of both needing mental health care and receiving no mental health care services. Findings suggest the need for targeted interventions that would increase service utilization and potentially reduce the likelihood of eviction or placement in more restrictive settings.

Black or African American↗

Inhibition of prostate ductal morphogenesis by retinoic acid.

PURPOSE: To examine the effect of retinoic acid on prostate ductal morphogenesis. MATERIALS AND METHODS: Newborn male Balb/C mice were injected with 25 mg./kg. all-trans retinoic acid or vehicle alone. Animals were sacrificed at 60 days of age and prostate ductal morphology was quantitatively assessed by microdissection. Total prostate DNA was quantitated by DPA assay. RESULTS: The greatest effect was seen in the ventral prostate. Retinoic acid treated animals showed a 20% decrease in mean number of branch-points (p = 0.0006) with a corresponding 13% decrease in duct tips (p = 0.026). The combined ventral and dorsal prostate showed an effect with a 12% decrease in ductal branchpoints (p = 0.048). There was no effect on animal or organ weight and no effect on DNA content within the prostate. There was no difference in the prostate histology of treated and control animals. CONCLUSION: Retinoic acid administration in the newborn period inhibits mouse prostate ductal morphogenesis. This effect appears independent of an inhibition of overall growth.

Animals↗

Almitrine and doxapram decrease fatigue and increase subsequent recovery in isolated rat diaphragm.

The effects of almitrine bimesylate and doxapram HCl on isometric force produced by in vitro rat diaphragm were studied during direct muscle activation at 37 degrees C. Doxapram and almitrine ameliorate respiratory failure clinically by indirectly increasing phrenic nerve activity. This study was carried out to investigate possible direct actions of these agents on the diaphragm before and after fatigue of the fibers. Two age groups of animals were chosen [6-14 wk (group 1) and 50-55 wk (group 2)] because it is known that increasing age decreases a muscle fiber's resistance to fatigue. Muscle strips were isolated from both group 1 and group 2 and directly stimulated (2-ms pulse duration, 5-15 V) to produce twitch tensions of 1.3 and 2.1 N/cm2, respectively. At low concentrations, doxapram (</=20 microg/ml) and almitrine (</=12 microg/ml) had no effect on twitch contraction or 100-Hz tetanic tension. However, 40 microg/ml doxapram and 30 microg/ml almitrine increased twitch tension by 9.0 +/- 1.4 and 11.6 +/- 1.9%, respectively, in animals of group 2 (n = 5). A fatigue protocol consisting of low-frequency stimulation (30-Hz trains, 250-ms duration every 2 s for 5 min) caused a reduction of twitch tension in animals of group 1 (48 +/- 4% of control) and group 2 (28 +/- 4% of control). At 90 min postfatigue, the twitch tension recovered to 72 +/- 3 and 42 +/- 2% of control values in group 1 and group 2, respectively. In the presence of doxapram (20 microg/ml), there was a significant increase in the recovery of twitch tension at 90 min in group 1 and group 2 (84.5 +/- 3.2 and 80.1 +/- 2.8%, respectively) compared with controls at 90 min postfatigue. In the presence of almitrine (12 microg/ml), there was a full recovery from fatigue in group 1 animals (100% of control) and a recovery to 95.6 +/- 2.1% of control in group 2 animals at 90 min. These results demonstrate a significant improvement in the rapidity and magnitude of recovery from fatigue in the rat diaphragm muscle in the presence of both doxapram and, especially, almitrine. These effects may be due to changes in intracellular calcium, ADP/ATP ratios, or oxygen free radical scavenging.

Almitrine↗

Evidence-based periodontal treatment. Highlights from the 1996 World Workshop in Periodontics.

State-of-the-art periodontal therapy involves a wide range of diagnostic and treatment options. The 1996 World Workshop in Periodontics used an evidence-based approach to assess the efficacy of many of these options. This article describes the evidence-based approach and summarizes the findings of the workshop in the areas of diagnosis and nonsurgical and surgical periodontal therapy as well as dental implants.

Alveolar Bone Loss↗

Pseudarthrosis after postoperative wound infection in the lumbar spine.

This retrospective investigation attempts to define the incidence of fusion success after postoperative infection after a posterior lumbar fusion, as well as which risk factors may adversely affect arthrodesis after successful debridement. At an average follow-up of 37 months, 18 of 29 patients (62.1%) had a successful arthrodesis. Eighty-seven percent of patients whose fusion excluded the sacrum had a solid arthrodesis, compared with only 36% of those fusions including the sacrum. The fusion rate in female patients was 33.3%, compared with 82.4% in male patients. The rate of fusion with allograft bone was 17.2 versus 83.3% with autograft bone. Female sex, the use of allograft bone, and extension of the fusion mass to the sacrum significantly increase the incidence of nonunion after a postoperative deep spinal wound infection.

Adolescent↗