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Biomedical subjects

M Simpson

Publications and source records attributed to M Simpson.

At least 19 recordsLinked to original sources

Influence of fluid intake pattern on short-term recovery from prolonged, submaximal running and subsequent exercise capacity.

The aim of this study was to examine if the pattern of fluid intake with a carbohydrate-electrolyte solution during 4 h recovery from prolonged, submaximal running would influence the subsequent endurance capacity. Seven well-trained athletes aged 19.8 +/- 0.3 years (mean +/- s(mean)) took part in the study, which had university ethical committee approval. They ran at 70% VO2 max on a level treadmill for 90 min (T1), or until volitional fatigue, whichever came first, on two occasions, at least 7-10 days apart. Four hours later, the subjects ran at the same speed for as long as possible (T2), as a measure of their endurance capacity. During the 4 h rehydration recovery period, the runners were allowed to drink a carbohydrate-electrolyte solution (6.9% Lucozade-Sport; sodium, 24 mmol l(-1); potassium, 2.6 mmol l(-1); calcium, 1.2 mmol l(-1); osmolality, 300 mOsm kg(-1)) ad libitum on one occasion. On the other occasion, the volume of the same fluid was prescribed from calculations of the body mass loss during T1 (2.6% of pre-exercise body mass). All subjects completed the 90 min run during T1 on both trials. However, during T2, in the prescribed intake trial, the exercise time to exhaustion was 16% longer (P< 0.05) than during T2 in the ad libitum trial (69.9 +/- 9.1 vs 60.2 +/- 10.2 min). Although there was no difference between conditions in the total volume ingested (1499 +/- 155 vs 1405 +/- 215 ml), the volume of carbohydrate-electrolyte solution ingested in the fourth hour of the rehydration recovery period was greater in the prescribed intake trial than in the ad libitum trial (258 +/- 52 vs 78 +/- 34 ml; P< 0.05). The amount of glucose ingested in this period during the prescribed intake trial was also greater than during the ad libitum trial (17.8 +/- 3.6 vs 5.4 +/- 2.4 g; P< 0.05). There was a higher blood lactate concentration at the start of T2 in the prescribed intake trial than in the ad libitum trial (1.12 +/- 0.20 vs 0.94 +/- 0.09 mmol l(-1); P< 0.05), but there were no differences in blood glucose, plasma insulin, free fatty acid concentrations or urine volume between trials. The results of this study suggest that drinking a prescribed volume of a carbohydrate-electrolyte solution after prolonged exercise, calculated to replace the body fluid losses, restores endurance capacity to a greater extent than ad libitum rehydration during 4 h of recovery, even though the total volumes ingested were the same between trials.

Adult

Itraconazole maintenance treatment for histoplasmosis in AIDS: a prospective, multicenter trial.

PURPOSE: To study the efficacy and safety of maintenance treatment with itraconazole for disseminated histoplasmosis in patients with AIDS. PATIENTS AND METHODS: This was a prospective, multicenter, open-label study conducted at university-based hospitals participating in the AIDS Clinical Trial Group (ACTG). Forty-six AIDS patients with mild to moderate disseminated histoplasmosis who had successfully completed 12 weeks of induction treatment with itraconazole were treated with itraconazole, 200 mg once daily (42 patients) or 400 mg once daily (4 patients). Patients were followed at monthly intervals with clinical and laboratory assessment for relapse or toxicity. Primary outcome measures were relapse of histoplasmosis and survival. Secondary outcome measures included drug-limiting toxicity and changes in serum and urine Histoplasma polysaccharide antigen (HPA) levels. RESULTS: Two patients relapsed during a median follow-up period of 87 weeks. The 1-year relapse-free rate was estimated to be 95.3% (95% CI, 85.3%-99.7%). One relapse may have been related to poor adherence to treatment and the second to concurrent administration of rifampin. From the start of maintenance treatment, the estimated 1-year survival rate was 73.0% (95% CI, 67.5%-77.9%). Five patients discontinued treatment because of suspected drug toxicity, three of whom had possible or probable hepatotoxicity. Median serum and urine HPA levels declined significantly during treatment. The only patient in whom antigen levels rose >2 U developed clinical relapse 1 week later; antigen levels were unavailable in the other relapsing patient. CONCLUSIONS: Itraconazole, 200 mg daily, is effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. It is generally well tolerated, but clinicians should be alert for drug interactions and possible hepatotoxicity.

AIDS-Related Opportunistic Infections

Mastication and swallowing in patients with postirradiation xerostomia.

PURPOSE: Very little objective data has been reported on mastication and swallowing in xerostomic patients, which would substantiate presumed causal relationships between xerostomia and patient complaints. The purpose was to elucidate which components of mastication and swallowing were abnormal, and most directly related to xerostomia, and which appeared unaffected. METHODS AND MATERIALS: A retrospective analysis of timing events in mastication and swallowing was done using videofluoroscopic data for 15 cancer patients with xerostomia, and 20 normal controls. Scintigraphy was also used to determine oropharyngeal residue after a water swallow. Cancer treatment modalities included radiation therapy or chemoradiation therapy. RESULTS: For barium liquid and paste substances, timing measures were equivalent for controls and patients. Xerostomic patients took 46% longer to masticate a shortbread cookie, and timing for the initiation of swallowing was shorter, but duration of swallowing appeared unaffected. Oral and pharyngeal residues following the swallow were greater in the patient group. CONCLUSIONS: Xerostomia primarily affected mastication and oral manipulation of a dry, absorbent food material. Increased oral and pharyngeal residues after a water swallow are ambiguously related to xerostomia. The initiation and duration of the pharyngeal swallow was not abnormal.

Aged

Macrophage-dependent apoptosis of CD4+ T lymphocytes from HIV-infected individuals is mediated by FasL and tumor necrosis factor.

Apoptosis of bystander uninfected CD4+ T lymphocytes by neighboring HIV-infected cells is observed in cell culture and in lymphoid tissue of HIV-infected individuals. This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals. Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals. This macrophage-dependent killing targets CD4+, but not CD8+ T lymphocytes from HIV-infected individuals, and direct contact between macrophages and lymphocytes is required. Additional analyses indicated that the apoptosis-inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4+ T cells. These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4+ T cells in HIV-infected individuals.

Antibodies, Monoclonal

Chronic fatigue syndrome/myalgic encephalomyelitis as a twentieth-century disease: analytic challenges.

The challenges of chronic fatigue syndrome (often called myalgic encephalomyelitis, especially in the UK) (CFS/ME) to analytical and medical approaches are connected with our inability to understand its distressing somatic symptoms in terms of a single identifiable and understandable disease entity. The evidence for the roles of viral aetiologies remains inconclusive, as does our understanding of the involvement of the immune system. The history and social context of CFS/ME, and its relation to neurasthenia and psychasthenia are sketched. A symbolic attitude to the condition may need to be rooted in an awareness of psychoid levels of operation, and the expression and spread of CFS/ME may sometimes be aided by the ravages of projective identification. Psychic denial, sometimes violent, in sufferers (especially children and adolescents) and their families may be important in the aetiology of CFS/ME. We draw out common threads from psychodynamic work with five cases, four showing some symptomatic improvement, analytic discussions of three cases being presented elsewhere in this issue of JAP.

Adolescent

A body with chronic fatigue syndrome as a battleground for the fight to separate from the mother.

I describe the therapy of a 20-year-old women who believed that her difficulties in concentrating and remembering were caused by her "ME' (Myalgic encephalomyelitis, Chronic fatigue syndrome, or CFS). She had been fathered by a man who never left his own wife. Work with her dreams revealed a within-body drama in which she was locked in an unspeakable fight to the death with her mother. Her symptoms improved after parallels between a dream and an accident showed her own self-destructive hand in her story. Another dream, reflecting her first 'incestuous' affair, showed her search for her original father-self as someone separate from mother, and a later affair provided a between-body drama, helping her to own the arrogant and abject traits she had before seen only as her mother's. I show how we worked in the area of Winnicott's first 'primitive agony' as experienced by a somatizing patient, stuck in a too-close destructive relationship with her mother-body. I discuss how analytical work can be done with the primitive affects and conflicts against which the ME symptoms may be defending.

Adult

Effects of Helicobacter pylori vacuolating cytotoxin on primary cultures of human gastric epithelial cells.

BACKGROUND: Many Helicobacter pylori strains produce a cytotoxin that induces cytoplasmic vacuolation in various types of eukaryotic cells. In contrast with the marked cell vacuolation that occurs in vitro in response to this cytotoxin, comparatively little epithelial vacuolation has been observed in the gastric mucosa of H pylori infected persons. AIMS: Experiments were performed to determine the susceptibility of human gastric epithelial cells in vitro to H pylori vacuolating cytotoxin activity. METHODS: Human gastric epithelial cells, harvested from upper gastrointestinal endoscopic biopsy specimens, were incubated overnight with broth culture supernatants from either a wild type cytotoxin producing (tox+) H pylori strain or an isogenic mutant strain that lacks cytotoxin activity. RESULTS: Prominent cytoplasmic vacuolation occurred in response to tox+ supernatant, but not supernatant from the isogenic mutant strain. Primary human gastric epithelial cells were significantly more sensitive to H pylori vacuolating cytotoxin activity than were either HeLa or AGS cells. Exposure of human gastric epithelial cells to high concentrations of tox+ supernatant for 48 hours caused lethal cell injury. CONCLUSIONS: These studies indicate that primary human gastric epithelial cells are highly sensitive to H pylori vacuolating cytotoxin activity.

Bacterial Proteins

Evaluation of an educational programme to improve the recognition of psychological illness by general practitioners.

BACKGROUND: Take Care is a commercially sponsored educational package for the detection and management of depression by all members of the primary health-care team. AIM: This study was designed to evaluate whether the educational package affects the recognition of psychological illness by general practitioners. METHOD: General practitioners working in 13 practices in North West England or Trent Regional Health Authorities took part the evaluation. Patients who scored more than eight on the depression or anxiety component of the Hospital Anxiety and Depression (HAD) scales, and who were thought by their general practitioner to have a totally physical problem or no illness, were deemed to have a psychological illness that had been 'missed' by the doctor. Changes in the proportion of missed cases before and after exposure to Take Care were estimated. RESULTS: When all practices were considered together, the general practitioners missed a depressive illness in 24.1% of patients before Take Care, and 17.1% afterwards; absolute decrease 7.0% [95% confidence interval (CI) -2.0 to -12.0%]. An improvement was seen in most practices (Wilcoxon matched-pair test P < 0.05). The programme was also associated with a small reduction in the overall proportion of episodes of anxiety missed by the doctor (absolute decrease 4.5%; 95% CI -1.0 to -8.0%) a reduction was found in most practices (Wilcoxon matched-pair test P < 0.05). There was no material difference in the diagnostic false-positive rate of the doctors before and after the introduction of the programme. CONCLUSION: Exposure to an educational package for depression was associated with improved recognition of psychological illness by general practitioners.

Clinical Competence

Chloropropionic acid-induced alterations in glucose metabolic status: possible relevance to cerebellar granule cell necrosis.

We have examined the effect of L- and D-2-chloropropionic acid (L-CPA and D-CPA) on the concentrations of pyruvate, lactate, glucose and beta-hydroxybutyrate in the blood at various times after doses which produce cerebellar granule cell necrosis. Blood pyruvate and lactate concentrations were reduced in these animals 4 h after dosing and remained below those of controls for up to 48 h. No changes were seen in concentrations of plasma glucose of beta-hydroxybutyrate at any time point. Similarly, no changes in cerebellar glucose, pyruvate or lactate were seen 24 h after 750 mg/kg L-CPA. Oxidation of [14C] pyruvate or [14C] glucose to [14CO2] by cerebellar slices from control rats was not altered by the presence of L- or D-CPA (1-10 mM for 2 h). Nor were these parameters affected in cerebellar slices from rats killed 24 h after a dose of 750 mg/kg L-CPA. We conclude that the activation of the pyruvate dehydrogenase complex is unlikely to be a critical factor in the selective toxicity of CPA to the cerebellum.

Animals

Permeability and microleakage of Class II resin composite restorations.

The aim of this study was to evaluate the variations in microleakage of large Class II (MOD) restorations over time. Three different combinations of dentine bonding agents and posterior resin composites which had previously shown promise were used: Vitrebond/Scotchbond 2 plus P50, Tripton plus Occlusin and Clearfil Photo Bond plus Clearfil Photo Posterior. Conventional Class II cavities were prepared in freshly extracted third molars. All gingival margins were terminated at the cemento-enamel junction. A fluid-under-pressure apparatus connected with the pulp chamber of each tooth was used to evaluate the permeability and marginal leakage of the restorations at 0.069 MPa. Microleakage was tested after insertion of restorations at 2, 15, 45, 150 min, after 1, 2, 7, 14 days, after 1, 2, 3 months, after thermal cycling and 10 months later, after occlusal loading. Finally, all specimens were exposed to silver nitrate solution to measure microleakage as dye penetration. Immediately after insertion of the restorations, all the materials showed a higher microleakage than after 1-2 days. After 4-8 weeks, all the restorations exhibited an increased permeability suggesting that hygroscopic expansion was not sufficient to keep pace with hydrolytic degradation of the restorations. Neither thermocycling or occlusal stresses increased the microleakage of the restorations.

Composite Resins

Comparison of changes in bone mineral in idiopathic and secondary osteoporosis following therapy with cyclical disodium etidronate and high dose calcium supplementation.

OBJECTIVE: Our clinical practice has been to offer treatment with cyclical disodium etidronate and high dose calcium supplements (1500-1600 mg/day) to all female patients with osteoporosis who are unable or unwilling to take hormone replacement therapy (HRT), and male osteoporotics. In a retrospective study we compared the effect of this treatment on measures of bone mineral over a 12-month period in women with post-menopausal and secondary osteoporosis. We also assessed its effects in 10 male osteoporotics. DESIGN: A retrospective analysis of 83 consecutive patients with osteoporosis who completed 12 months of treatment with disodium etidronate and calcium and who had a dual energy X-ray absorptiometry (DEXA) scan at baseline and following 12 months of therapy. PATIENTS: The study included 73 women (45 post-menopausal and 28 secondary osteoporotics) and 10 men with established osteoporosis as shown by spinal and femoral bone mineral densities (BMD) > 2 standard deviations (SD) below young normals, and radiological evidence of osteoporosis. MEASUREMENTS: Each patient had routine biochemistry at baseline, an X-ray of thoracic and lumbar spine and a DEXA scan of lumbar spine (L2-L4) and femoral neck. The DEXA scan was repeated following 12 months of therapy. RESULTS: There was no difference between increase in spinal BMD in the post-menopausal (5.7%) versus secondary osteoporotic group (6.7%). There was a significant increase in spinal BMD at 12 months in the 10 male osteoporotics (9.0%, P < 0.01). No overall change in femoral neck BMD was noted. CONCLUSIONS: Cyclical disodium etidronate given with high dose calcium supplements is equally effective in increasing spinal bone mineral density in post-menopausal and secondary osteoporosis. It also results in a significant rise in spinal bone mineral density in male osteoporotics. Whether this produces a reduction in fracture rates is unknown.

Bone Density

Cervical cytology findings in women infected with the human immunodeficiency virus.

It has been suggested that immunocompromised, HIV-infected patients are at risk of developing HPV infection and SIL. The well documented role of HPV and SIL in cervical carcinogenesis should lead to frequent, careful evaluation of HIV infected women. Forty-four cervical smears from 23 patients (20 HIV and 3 AIDS) were reviewed. While 11 of the 23 patients produced negative smears, 11 had abnormal cytological findings on at least one occasion. Sixteen smears (36 percent) from 10 patients (43%) showed evidence of HPV and/or SIL. Two smears (two patients) were assigned to the benign epithelial atypia category. (One of these showed keratosis which may indicate HPV infection.) Six smears (three patients) represented either a severe Trichomonas, fungal (Candida sp.), or Herpes infection. Three smears were deemed unsatisfactory for diagnosis due to severe acute inflammation or obscuring blood. Five biopsies were available. In four, histologic findings supported the original cytologic diagnosis. One patient with a negative smear had a biopsy showing condyloma. This study further supports an association of HPV and/or cervical dysplasia with HIV. Careful evaluation and follow-up of HIV-infected women is essential.

Female

Body composition analysis in liver cirrhosis. The measurement of body fat by dual energy X-ray absorptiometry in comparison to skinfold anthropometry, bioelectrical impedance and total body potassium.

In this cross-sectional study of methods to determine total body fat in patients with abnormal body composition secondary to chronic liver disease, we have demonstrated that TBFDXA by four-site skinfold anthropometry was highly correlated to TBFDXA, with small SEE and no bias in patients with ascites, but a small and significant bias in patients without ascites. TBFBIA showed no bias but a weaker correlation with a large SEE. In the presence of fluid retention the correlation coefficient decreased. TBFTBK showed a highly significant bias, and the correlation was not as good as SFA, and decreased in the presence of fluid retention.

Absorptiometry, Photon