Biomedical subjects
Publications and source records attributed to S Smith.
A male child presented with recurrent respiratory infections, otitis media, and oral ulceration and was found to be neutropenic. Investigations showed hypogammaglobulinaemia with normal serum IgM and a novel deletion in the gene for CD40 ligand on his X chromosome. Intravenous gammaglobulin did not lead to resolution of his neutropenia; G-CSF was also necessary.
Using an exercise device that integrates maximal voluntary static contraction (MVC) of knee extensor muscles with dynamic knee extension, we compared progressive muscle fatigue, i.e., rate of decline in force-generating capacity, in normoxia (758 Torr) and hypobaric hypoxia (464 Torr). Eight healthy men performed exhaustive constant work rate knee extension (21 +/- 3 W, 79 +/- 2 and 87 +/- 2% of 1-leg knee extension O2 peak uptake for normoxia and hypobaria, respectively) from knee angles of 90-150 degrees at a rate of 1 Hz. MVC (90 degrees knee angle) was performed before dynamic exercise and during < or = 5-s pauses every 2 min of dynamic exercise. MVC force was 578 +/- 29 N in normoxia and 569 +/- 29 N in hypobaria before exercise and fell, at exhaustion, to similar levels (265 +/- 10 and 284 +/- 20 N for normoxia and hypobaria, respectively; P > 0.05) that were higher (P < 0.01) than peak force of constant work rate knee extension (98 +/- 10 N, 18 +/- 3% of MVC). Time to exhaustion was 56% shorter for hypobaria than for normoxia (19 +/- 5 vs. 43 +/- 7 min, respectively; P < 0.01), and rate of right leg MVC fall was nearly twofold greater for hypobaria than for normoxia (mean slope = -22.3 vs. -11.9 N/min, respectively; P < 0.05). With increasing duration of dynamic exercise for normoxia and hypobaria, integrated electromyographic activity during MVC fell progressively with MVC force, implying attenuated maximal muscle excitation. Exhaustion, per se, was postulated to related more closely to impaired shortening velocity than to failure of force-generating capacity.
Our objective was to test the short-term efficacy and feasibility of two stress-reduction approaches for the treatment of hypertension in older African Americans, focusing on subgroup analysis by sex and by high and low risk on six measures of hypertension risk: psychosocial stress, obesity, alcohol use, physical inactivity, dietary sodium-potassium ratio, and a composite measure. The study involved a follow-up subgroup analysis of a 3-month randomized, controlled, single-blind trial conducted in a primary care, inner-city health center. Subjects were 127 African American men and women, aged 55 to 85 years, with diastolic pressure of 90 to 104 mm Hg and systolic pressure less than or equal to 179 mm Hg. Of these, 16 did not complete follow-up blood pressure measurements. Mental and physical stress-reduction approaches-the Transcendental Meditation technique and progressive muscle relaxation, respectively-were compared with a life-style modification education control and with each other. Both systolic and diastolic pressures changed from baseline to follow-up for both sexes and for high and low risk level (defined by median split) on the six measures of hypertension risk. Compared with education control subjects, women practicing the Transcendental Meditation technique showed adjusted declines in systolic (10.4 mm Hg, P < .01) and diastolic (5.9 mm Hg, P < .01) pressures. Men in this treatment group also declined in both systolic (12.7 mm Hg, P < .01) and diastolic (8.1 mm Hg, P < .001) pressures compared with control subjects. Women practicing muscle relaxation did not show a significant decrease compared with control subjects, and men declined significantly in diastolic pressure only (6.2 mm Hg, P < .01). For the measure of psychosocial stress, both the high and low risk subgroups using the Transcendental Meditation technique declined in systolic (high risk, P = .0003; low, P = .06) and diastolic (high risk, P = .001; low, P = .008) pressures compared with control subjects, whereas for muscle relaxation, blood pressure dropped significantly only in the high risk subgroup and only for systolic pressure (P = .03) compared with control subjects. For each of the other five risk measures, Transcendental Meditation subjects in both the high and low risk groups declined significantly in systolic and diastolic pressures compared with control subjects. Effects of stress reduction on blood pressure were found to generalize to both sexes and diverse risk factor subgroups and were significantly greater in the Transcendental Meditation treatment group. These effects (along with high compliance) even in individuals with multiple risk factors for hypertension clearly warrant longer-term investigation in this and other populations.
We have shown that viruses are associated with 80 to 85% of asthma exacerbations in school-age children in the community. We hypothesize that viral infections are also associated with severe attacks of asthma precipitating hospital admissions. To investigate this, we conducted a time-trend analysis, comparing the seasonal patterns of respiratory infections and hospital admissions for asthma in adults and children. During a 1-yr study in the Southampton area of the United Kingdom, 108 school-age children monitored upper and lower respiratory symptoms and took peak expiratory flow rate (PEFR) recordings. From children reporting a symptomatic episode or a decrease in PEFR, samples were taken for detection of viruses and atypical bacteria. A total of 232 respiratory viruses and four atypical bacteria were detected. The half-monthly rates of upper respiratory infection were compared with the half-monthly rates for hospital admissions for asthma (International Classification of Diseases [ICD] code 493) for the same time period for the hospitals serving the areas from which the cohort of schoolchildren was drawn. The relationships of upper respiratory infections and hospital admissions for asthma with school attendance were studied. Strong correlations were found between the seasonal patterns of upper respiratory infections and hospital admissions for asthma (r = 0.72; p < 0.0001). This relationship was stronger for pediatric (r = 0.68; p < 0.0001) than for adult admissions (r = 0.53; p < 0.01). Upper respiratory infections and admissions for asthma were more frequent during periods of school attendance (87% of pediatric and 84% of total admissions), than during school holiday periods (p < 0.001). These relationships remained significant when allowance was made for linear trend and seasonal variation using multiple regression analysis (p < 0.01). Not surprisingly, school attendance, because it is a major factor in respiratory virus transmission, was found to be a major confounding variable in children. This study demonstrates that upper respiratory viral infections are strongly associated in time with hospital admissions for asthma in children and adults. Rhinoviruses were the major pathogen implicated, and the majority of viral infections and asthma admissions occurred during school attendance.
BACKGROUND: Maladaptive behaviours are frequently present in individuals with learning disabilities; however, their prevalence varies between studies and the aetiology, classification and most appropriate management of such behaviors remain unclear. The aims of the study were twofold: firstly to determine the prevalence of maladaptive behaviours, and secondly to develop a classification typology. METHOD: A population of 2202 adults with learning disabilities was surveyed to determine the prevalence of maladaptive behaviours. These were subjected on the basis of 13 behavioural characteristics to cluster analysis. The clusters were further examined in respect of secondary variables. RESULTS: Over 60% of individuals demonstrated the presence of at least one maladaptive behaviour and in 40% this problem was of either severe degree or frequent occurrence. Men were more likely to demonstrate physical aggression, property destruction, tantrums and verbal abuse than women. Although some severe maladaptive behaviours diminished with age, many persisted through all age groups. Six behavioural clusters were devised which demonstrated face validity and which differed in respect of demographic and developmental variables, and the prevalence of maladaptive habits and autistic symptoms. CONCLUSIONS: These findings demonstrate a high prevalence of maladaptive behaviours and 'objectionable habits' among people with learning disabilities. A classification of behavioural symptoms may be possible on the basis of symptom clusters.
PURPOSE: The outcome for patients with recurrent medulloblastoma has historically been poor, with most patients dying of disseminated disease. Here, we report on seven patients with recurrent medulloblastoma, most heavily pretreated with a variety of chemotherapeutic agents, including parenteral etoposide (VP-16), who showed responses to the administration of repeated courses of low-dose oral VP-16. PATIENTS AND METHODS: Seven patients age 4 to 16 years were treated with VP-16 after neuroradiographic and clinical evidence of tumor progression. Six had received prior irradiation. All seven had been pretreated with a variety of chemotherapeutic agents and schedules, including parenteral VP-16. VP-16 was administered orally as repeated 21-day courses at 50 mg/m2/d with a 7-day interval between courses. Evaluation consisted of neuroradiographic and clinical examination after completion of every two courses of therapy. Complete blood cell counts were performed weekly. RESULTS: The major toxicity of oral VP-16 was hematologic, with two patients requiring platelet transfusions due to thrombocytopenia and two requiring RBC transfusions. All seven patients developed treatment-related neutropenia. Two patients were supported with granulocyte colony-stimulating factor (G-CSF) between courses. One patient developed infectious epididymitis after course 2 and required intravenous antibiotics; this illness was complicated by Clostridium difficile colitis. There was one episode of fever associated with neutropenia. There were no treatment-related deaths. Of seven patients assessed, six have demonstrated partial responses (PRs) and the remaining patient had stable disease (SD). CONCLUSION: This report demonstrates the activity of oral VP-16 in the treatment of a small cohort of pretreated patients with recurrent medulloblastoma. This form of administration of oral VP-16 was well tolerated and produced modest toxicity.
STUDY OBJECTIVE: Identify risk factors for work disability among adults with asthma treated by pulmonary and allergy specialists. DESIGN: Cross-sectional survey, including retrospective work history data. PARTICIPANTS: Sixty-eight pulmonary and 16 allergy internal medicine subspecialists maintaining a registry of patient visits for asthma; 698 registered patients aged 18 to 50 years, of whom 601 (86%) were studied. MEASURES: Computer-assisted, telephone-administered structured interview assessing asthma severity, perceived general health status, asthma quality of life, demographics, and work history. Complete work disability defined as total work cessation attributed to asthma; partial work disability defined as change in job, duties, or reduction in work hours attributed to asthma. RESULTS: Complete cessation of work due to asthma was reported by 40 (7%; 95% confidence interval [CI], 5 to 9%) and partial work disability by 53 (10%; 95% CI, 7 to 12%) of 550 subjects with a history of labor force participation. Severity of asthma score predicted both complete disability (odds ratio [OR], 7.9; 95% CI, 4.2 to 15 per 10-point increment) and partial disability (OR 2.6; 95% CI, 1.6 to 4.2). Taking illness severity into account, job conditions, occupation, and work exertion carried a combined disability OR of 3.9 (95% CI, 1.7 to 8.6). CONCLUSIONS: Work disability is common among adults with asthma receiving specialist care. Severity of disease is a powerful predictor, but not the sole predictor of disability in this group. Working conditions, including job-related exposures, are associated with added disability risk even after taking illness severity into account.
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We have analysed the deficiencies of paper medical records in facilitating the care of patients with diabetes and have developed an electronic medical record that corrects some of them. The diabetes electronic medical record (DEMR) is designed to facilitate the work of a busy diabetes clinic. Design principles include heavy reliance on graphic displays of laboratory and clinical data, consistent color coding and aggregation of data needed to facilitate the different types of clinical encounter (initial consultation, continuing care visit, insulin adjustment visit, dietitian encounter, nurse educator encounter, obstetric patient, transplant patient, visits for problems unrelated to diabetes). Data input is by autoflow from the institutional laboratories, by desk attendants or on-line by all users. Careful attention has been paid to making data entry a point and click process wherever possible. Opportunity for free text comment is provided on every screen. On completion of the encounter a narrative text summary of the visit is generated by the computer and is annotated by the care giver. Currently there are about 7800 patients in the system. Remaining challenges include the adaptation of the system to accommodate the occasional user, development of portable laptop derivatives that remain compatible with the parent system and improvements in the screen structure and graphic display formats.
Expression of a major thyroid autoantigen, thyroid peroxidase (TPO) was studied using the baculovirus-insect cell expression system. Human TPO cDNA modified so as to code for the extracellular fragment of the protein was placed under the control of the strong polyhedrin promoter in baculovirus transfer vector pBlueBacIII and cotransfected with linearized AcMNPV viral DNA. Expression in two insect cell lines Spodoptera frugiperda (Sf9) and Tricoplusia ni (High Five) was investigated and levels of recombinant TPO (rTPO) monitored by RIA and SDS-PAGE followed by Western blotting. Both insect cell lines expressed rTPO, but higher levels (30 mg/l culture medium) were obtained with High Five cells. Culture medium rTPO was purified and its glycosylation and immunoreactivity analysed. Lectin-affinity blotting and treatment with glycosidases indicated that both high mannose and complex-type sugar residues were associated with the recombinant protein. Studies with an ELISA based on biotinlabelled rTPO and an immunoprecipitation assay based on 125I-labelled rTPO indicated that the rTPO and native TPO showed similar reactivity to TPO autoantibodies (r = 0.96, P < 0.001, n = 50 and r = 0.99, P < 0.001, n = 80 respectively). In addition, rTPO expressed in High Five cells showed enzyme activity comparable with that of native TPO when the heme biosynthesis precursor delta-aminolevulinic acid was included in the culture medium. Overall, our studies indicate that the High Five insect cell line provides a useful system for the expression of relatively high levels of rTPO which should be suitable for structural analysis of TPO and TPO-TPO autoantibody complexes.
Cognitive ERPs and EEG spectral differences were compared in three groups of children: nonreferred controls, those with a dominant hyperactivity/impulsivity factor (ADHD-Im), and those with a dominant inattentive factor (ADHD-Ia). The results from the ERP analyses indicated that the P250, P350, and P500 components differed between the groups. The most marked differences were seen with respect to the amplitude of the P500 components. In addition, the topographic foci of the P500 components for the CON and ADHD-Im groups were symmetrical, but the ADHD-Ia group featured P250 and P350 components that were biased away from the right hemisphere. Nevertheless, the P500 was found to be an effective discriminator between the groups. The combined spectral and ERP results suggest that the attention disordered children have difficulty adjusting their level of physiological arousal, and are defective with respect to controlled (or effortful) processing.
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OBJECTIVE: To evaluate the efficacy and tolerability of 2 widely used topical alpha-hydroxy acids at low concentrations, 8% glycolic acid and 8% lactic (L-isoform) acid creams, in the treatment of photodamaged skin. DESIGN: A single-center, 22-week, double-blind, vehicle-controlled, randomized clinical trial assessed the overall severity of photodamage on the faces and forearms of volunteers, based on 7 individual clinical components of cutaneous photodamage. SETTING: The study was performed in an outpatient clinical research unit at the Massachusetts General Hospital, Boston. PATIENTS: Seventy-four women, aged 40 to 70 years, with moderately severe photodamaged facial skin were enrolled in the study. One subject withdrew from the study early because of skin irritation, and 6 subjects withdrew from the study for personal reasons. INTERVENTIONS: Glycolic acid, L-lactic acid, or vehicle creams were applied twice daily to the face and outer aspect of the forearms. MAIN OUTCOME MEASURES: Improvement in alpha-hydroxy acid-treated photodamaged skin as determined by patient self-assessments and physician evaluations of efficacy and irritancy. RESULTS: The percentage of patients using either 8% glycolic acid or 8% L-lactic acid creams on the face achieving at least 1 grade of improvement (using a scale from 0 through 9) in overall severity of photodamage was significantly greater than with the vehicle cream (76% glycolic acid, 71% lactic acid, and 40% vehicle; P < .05). On the forearms, after 22 weeks, treatment with glycolic acid cream was superior to the vehicle in improving the overall severity of photodamage and sallowness (P < .05). L-Lactic acid cream was significantly superior to the vehicle in reducing the overall severity of photodamage (P < .05), mottled hyperpigmentation (P < .05), sallowness (P < .05), and roughness on the forearms (P < .05) at week 22. CONCLUSIONS: Topical 8% glycolic acid and 8% L-lactic acid creams are modestly useful in ameliorating some of the signs of chronic cutaneous photodamage. These agents are well tolerated and available without prescription.
Blood urea nitrogen (BUN) rises disproportionately to serum creatinine in patients with prerenal azotemia whether due to impaired hemodynamics or excessive ureagenesis. To determine whether urinary urea nitrogen excretion rates can distinguish between these caused of hyperuremia we performed a cross-sectional observational study to compare urinary urea nitrogen excretion rates in a highly selected group of patients with prerenal azotemia. Patients who had stable serum creatinine levels, BUN: serum creatinine ratios exceeding 20:1, and progressive azotemia were identified from the hospital laboratory data base. Using conventional clinicolaboratory criteria, 27 patients were diagnosed with either renal hypoperfusion (group I; n = 17) or hyperureagenesis ((group II; n = 10). Random urine sampling for electrolytes, osmolality, creatinine, and urea nitrogen was followed by 24 h collection for creatinine clearance and urinary urea nitrogen. There were no significant differences in age, gender, absolute levels of BUN, or BUN: serum creatinine ratios between the groups. Creatinine clearance (ml/min/1.73 m2) (ml/s/1.73 m2) was lower in group I than in group II (21 +/- 16 vs 36 +/- 13; p < 0.05) (0.35 +/- 0.27 vs 0.60 +/- 0.22; p < 0.05). Twenty-four hour urinary urea nitrogen levels were significantly different (group I, 4.8 +/- 2.9 vs. group II, 13.6 +/- 3.2 gm; p < 0.001) (group I, 171 +/- 300 vs. group II, 486 +/- 114 mmol; p < 0.001). Random urine urea excretion indices were less discriminating but nevertheless still capable of separating the groups. Timed as well as random urine urea nitrogen determinations may assist in differentiating prerenal azotemia due to renal hypoperfusion from hyperureagenesis. Differentiation of these causes of prerenal azotemia might prevent iatrogenic overhydration of patients with azotemia incorrectly attributed to hemodynamic disturbances.
In order to improve the effectiveness and subtainability of the family planning programme, the National Family Planning Board has devised a strategy to shift users to longer-acting methods and increase the role of the private sector. To design interventions, a better understanding of existing services was thought to be necessary. This study examines the distribution of family planning service delivery points in Jamaica and the services offered by the public and private sectors through an examination of records and questionnaire interviews. The study found that, because of the concentration of private sector providers-the main outlets for longer-acting methods-in urban areas, rural areas had poor access to these methods. Because rural areas are not attractive to private sector providers, the public sector should recognize the need to continue to serve these areas.