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Biomedical subjects

J John

Publications and source records attributed to J John.

At least 19 recordsLinked to original sources

Abnormal signal-averaged electrocardiogram (SAECG) in obesity.

OBJECTIVE: The occurrence of small high-frequency electrocardiogram (ECG) potentials (1 to 20 microV) seen at the end of the QRS complex and into the ST segment have been correlated with increased risk for ventricular arrhythmias and sudden cardiac death. Computer-assisted analysis of these "late potentials" by signal-averaged electrocardiography (SAECG) has been studied and utilized to predict the likelihood of ventricular arrhythmias in various clinical states. Obesity is associated with significant cardiovascular morbidity and sudden death. Ventricular arrhythmias are postulated causes. We studied the occurrence of late potentials in a randomly selected group of obese patients and healthy volunteers. RESEARCH METHODS AND PROCEDURES: We performed SAECG on 105 subjects. Of these, 62 were obese ambulatory patients with body mass index (BMI) of >30 kg/m2, whereas 43 were healthy asymptomatic volunteers with a BMI of <30 kg/m2. Patients with a history of clinical heart disease and pulmonary disease, electrolyte abnormalities, recent hospitalizations, or abnormal screening ECG or taking medications known to alter the QRS interval were excluded. At least 250 beats were analyzed with a noise level of <0.50 microV. Criteria of a late potential include QRS duration >114 ms, high-frequency low amplitude >38 ms, and root-mean-square voltage <20 microV. Patients were divided into four subgroups based on BMI values. The prevalence of SAECG abnormalities in each BMI subgroup was studied. We utilized multiple logistic regression analysis to study the effect of obesity, hypertension, and diabetes mellitus on abnormal SAECG results. RESULTS: Compared to age- and sex-matched healthy volunteers with BMI of <30 kg/m2, obese patients with BMI of >30 kg/m2 had significantly more abnormalities on SAECG (4.6% vs. 55%). In the obese group, the prevalence and number of abnormalities increased with increase in BMI (35% in the BMI 31 to 40 kg/m2 subgroup, 86% in the BMI 41 to 50 kg/m2 subgroup, and 100% in patients with BMI of >50 kg/m2). Multiple logistic regression analysis shows that BMI is an independent predictor variable of abnormal SAECG results in obese patients (n = 62) with BMI of >30 kg/m2 as well as in all study subjects (n = 105). BMI also predicts abnormality of each abnormal SAECG criterion in both obese and all subjects. Hypertension was found to influence the QRS duration alone in obese and all subjects. DISCUSSION: Obesity is associated with increased occurrence of abnormal SAECG results. These abnormalities are found both in obese patients with and without hypertension and/or diabetes. Obesity is an independent predictor variable of abnormal SAECG results. A history of hypertension predicts abnormality of QRS duration only.

Body Mass Index↗

The redistributive effect of health care finance in twelve OECD countries.

The OECD countries finance their health care through a mixture of taxes, social insurance contributions, private insurance premiums and out-of-pocket payments. The various payment sources have very different implications for both vertical and horizontal equity and on redistributive effect which is a function of both. This paper presents results on the income redistribution consequences of the health care financing mixes adopted in twelve OECD countries by decomposing the overall income redistributive effect into a progressivity, horizontal inequity and reranking component. The general finding of this study is that the vertical effect is much more important than horizontal inequity and reranking in determining the overall redistributive effect but that their relative importance varies by source of payment. Public finance sources tend to have small positive redistributive effects and less differential treatment while private financing sources generally have (larger) negative redistributive effects which are to a substantial degree caused by differential treatment.

Cross-Cultural Comparison↗

Equity in the finance of health care: some further international comparisons.

This paper presents further international comparisons of progressivity of health care financing systems. The paper builds on the work of Wagstaff et al. [Wagstaff, A., van Doorslaer E., et al., 1992. Equity in the finance of health care: some international comparisons, Journal of Health Economics 11, pp. 361-387] but extends it in a number of directions: we modify the methodology used there and achieve a higher degree of cross-country comparability in variable definitions; we update and extend the cross-section of countries; and we present evidence on trends in financing mixes and progressivity.

Cross-Cultural Comparison↗

Circumferential fingernail.

We describe a Brazilian girl with a congenital circumferential nail on her left ring finger associated with other bony and soft tissue abnormalities of the affected limb. The tubular nail plate resembling a punch biopsy has been described as a circumferential nail, an extremely rare congenital malformation that can be associated with other congenital anomalies. In our review of the literature, there have only been two previous reports of this unusual condition affecting the fingernails.

Child↗

Effect of NMDA lesion of the medial preoptic neurons on sleep and other functions.

This study was undertaken to determine the effects of the destruction of the medial preoptic area (mPOA) neurons by N-methyl D-aspartic acid (NMDA), on sleep-wakefulness (S-W), locomotor activity, body weight, rectal temperature, and food and water intake in rats. The NMDA lesion of the mPOA produced long-lasting insomnia with marked reduction in the deeper stages of sleep, including paradoxical sleep. The reduction in the duration of sleep episodes in the lesioned rats indicated their inability to maintain sleep. The insomnia resulting from a decreased sleep pressure did not alter the sleep-initiating ability. Though the day-night distribution of sleep remained largely unaffected, there was an increase in locomotor activity during the light period. There was no increase in food intake to compensate for the high energy expenditure resulting not only from hyperactivity but also from hyperthermia in the mPOA-lesioned rats. Thus, body weights of the rats were reduced even without any change in food and water intake. However, the changes in body temperature and locomotor activity after the mPOA neuronal loss may not have exerted a major influence on S-W, as the alterations in all these parameters had different time courses.

Animals↗

Recovery of sleep after fetal preoptic transplantation in medial preoptic area-lesioned rats.

Changes in sleep after fetal preoptic (POA) tissue transplantation were studied in rats which had been made insomniac by a medial preoptic area (mPOA) lesion. Two days after the N-methyl D-aspartic acid (NMDA) lesion of the mPOA, fetal POA tissues (obtained from 14- to 17-day-old fetuses) were transplanted into the lesioned mPOA. Insomnia was less marked in these animals, as compared to nontransplanted lesioned rats, even on the 4th day after transplantation. The quantum of sleep nearly attained the prelesion level by the 20th day. Body weight also showed recovery after transplantation. Rectal temperature, which was increased by the lesion of the mPOA, remained unaltered even after the transplantation. These results suggest that the recovery of sleep and rectal temperature may follow different time courses. Surviving transplanted neurons were seen at the site of lesion on postmortem examination. Humoral interaction between the host and the transplant may be responsible for the early recovery of sleep, though the establishment of neural connections between the host and transplant might have contributed to the later recovery. This is the first study to show the recovery of sleep function in insomniac animals after fetal preoptic tissue transplantation. However, the specificity of the POA fetal tissue, in comparison with other neural tissues to promote sleep recovery, remains to be established.

Animals↗

Dominant selection of hematopoietic progenitor cells with retroviral MDR1 co-expression vectors.

When transferring the human multidrug resistance 1 (MDR1) cDNA, FMEV retroviral vectors mediate high-dose multidrug resistance and, thus, background-free selection in primary human hematopoietic progenitor cells. Here, we analyzed strategies for co-expression of a second gene from an FMEV:MDR1 vector. When linking the cDNAs with the internal ribosomal entry site (IRES) of poliovirus or retroviral splice signals, almost all multidrug-resistant hematopoietic colonies simultaneously coexpressed the 3' positioned second gene, neomycin-phosphotransferase (neoR). The IRES strategy allowed functional co-transfer of a 4.2-kb lacZ-neoR fusion gene, resulting in a total proviral genome size of 11 kb, corresponding to the packaging limit of retroviral vectors. Preselection based on multidrug resistance elevated the expression of the second gene in IRES constructs, but not in splice vectors. Moreover, three intriguing observations were made. First, up to 30% of cells preselected for functional transfer of the 3' positioned cDNA (neoR) showed infunctional MDR1; this occurred irrespective of the linking principle and was associated with instability of the MDR1 transcription unit. Second, the levels of multidrug resistance achieved with the co-expression vectors were moderately lower (15-30% reduced) than those mediated by the monocistronic counterpart. Third, transduction with FMEV:MDR1 co-expression vectors still resulted in high-dose cancer drug resistance and background-free selection of hematopoietic progenitor cells (including primary human CD34+ colony-forming units). Thus, for the first time, we describe MDR1 co-expression vectors that maintain their desired function in early and primary human hematopoietic cells. However, careful interpretation of the data reveals that further vector improvements are required to obtain clinically useful MDR1 co-expression vectors.

Antigens, CD34↗

FMEV vectors: both retroviral long terminal repeat and leader are important for high expression in transduced hematopoietic cells.

FMEV retroviral vectors combine the long terminal repeat of Friend mink cell focus-forming viruses with the 5' untranslated leader region of the murine embryonic stem cells virus. These modules were connected to achieve high transgene expression in hematopoietic progenitor and stem cells. Here, we report the cloning of safety-improved and versatile FMEV vectors allowing module-wise exchange of crucial elements for comparative studies. By transfer and expression of four different marker genes (neomycin phosphotransferase, lacZ, enhanced green fluorescent protein and truncated low affinity nerve growth factor receptor), we formally demonstrate that both the long terminal repeat and the leader contribute to the high expression of FMEV in transduced hematopoietic cells. Most prominent are the data recorded in the absence of selection in myelo-erythroid progenitor cells. Here, FMEV vectors mediate up to two orders of magnitude increased transgene expression levels when compared with vectors based on the Moloney murine leukemia virus.

5' Untranslated Regions↗

Symptom relief with amitriptyline in the irritable bowel syndrome.

Anti-depressants have been reported to be useful in the management of the Irritable Bowel syndrome. We studied the efficacy of amitriptyline for 12 weeks in a randomized double-blind placebo-controlled trial. Forty patients who met predefined criteria entered the trial. They received 25 mg amitriptyline for the first week, 50 mg for the second week and 75 mg nightly thereafter until the end of the 12th week. The drug and placebo groups were comparable in all major pretreatment variables. Amitriptyline was found to be significantly more effective than placebo in producing global improvement, increasing feelings of well-being, reducing abdominal pain and increasing satisfaction with bowel movements. Younger age and increasing extroversion predicted a better response to amitriptyline. Severity of depressive and anxiety symptoms and other personality variables did not influence outcome.

Adult↗

cis-Active elements of Friend spleen focus-forming virus: from disease induction to disease prevention.

The polycythemic strain of the Friend spleen focus-forming virus (SFFVp) is a replication-defective, acutely transforming retrovirus inducing a bistage erythroleukemia in susceptible mice. The first stage of the disease is an acute polyclonal erythroblastosis induced by the proliferation-promoting effect of gp55. gp55 is expressed from a spliced subgenomic message of SFFVp and stimulates the cellular receptor for erythropoietin. Using a selectable SFFVp that otherwise mimics the specificity of the disease, we demonstrate that the kinetics of the polyclonal expansion depends on the transcriptional strength of the retroviral cis-active elements. By exchanging gp55 for apathogenic genes, we show that SFFVp enhancer and splice signals can be successfully utilized for the development of retroviral vectors mediating very efficient transgene expression in hematopoietic cells. Apathogenic selectable SFFVp-based vectors carrying distinct enhancer alterations are a valuable tool to analyze transcriptional control of leukemia viruses in the absence of oncogenic proteins. Moreover they might have therapeutic potential.

Animals↗

Appendicitis among African patients at King Edward VIII Hospital, Durban, South Africa: a review.

This retrospective study of 645 black patients, carried out over a five year period, showed that appendicitis is twice as common in males as in females and that it occurs predominantly in young people (median age 20 years). The classical presentation of periumbilical pain (16%) was outnumbered by right iliac fossa pain (36%) and non-specific pain (27%). The majority perforated (43%) and appendiceal inflammation was second commonest (37%). The negative appendicectomy rate was 8.8% and there was a diagnostic error of 14%. Mortality was two per cent mainly from patients complicated by peritonitis. Hospital stay was 7 +/- 7 days, with the longest stay following peritonitis. A diagnosis of appendicitis should always be entertained in an African patient presenting with an acute abdomen and, where the diagnosis is in doubt, a laparotomy should be performed.

Adolescent↗

Hepatitis A virus: declining seroprevalence in children and adolescents in Southeast Asia.

The prevalence of hepatitis A virus (HAV) in a country largely reflects its standards of hygiene and socioeconomic conditions. Countries which undergo socioeconomic development show major change in HAV prevalence from high to low endemicity, and this is largely reflected in patterns of age-related seroprevalence. This paper presents age-related HAV seroprevalence patterns of SE Asian countries, and highlights how these patterns have changed over recent decades. Singapore, Thailand and Malaysia have experienced a decline in childhood and adolescent HAV seroprevalence, typical of countries which undergo socioeconomic development. By contrast, India has remained a country of high endemicity, with almost universal seroconversion in childhood. The Philippines and Vietnam show age-related seroprevalence patterns typical of high to moderate endemicity, while Indonesia shows significant regional variation in HAV seroprevalence. Populations within countries which exhibit major improvements in endemicity and age related HAV seroprevalence patterns are at risk of HAV epidemics, and a paradoxical increase in incidence tends to occur as seroconversion shifts from children to adults. The residents of these countries, a significant number of whom are at-risk, would benefit from a program of vaccination, as would non-infected individuals visiting high-risk areas.

Adolescent↗

Frozen shoulder--an algoneurodystrophic process?

The frozen shoulder syndrome and the Sudeck syndrome are clinically in many aspects similar. Radioisotope bone scan shows an increased uptake in the affected areas in both diseases, while standard radiographs show a progressive demineralization. With measurement of bone-mineral density by quantitative digital radiography these local decalcification processes were diagnosed in an early stage of the frozen shoulder syndrome: of 12 patients with primary frozen shoulder 10 had a bone-mineral density decrease of more than 21% in the humeral head of the affected shoulder compared to the unaffected side. In the control groups (n = 32) the difference between affected and unaffected side (left and right humerus of the healthy probands) was in only one case each above 21%. There are several indications in the literature assuming the frozen shoulder to be an algoneurodystrophic process. Our observation supports this hypothesis, and may possibly lead to earlier diagnosis and improved therapeutic management.

Bone Density↗

[Income, health, and health services utilization in Germany 1992].

Data from the 1992 wave of the Socioeconomic Panel were used to analyse the relation between incomes, need for and utilisation of health care in East- and West Germany employing methods coming from the economic measurement of income distributions. "Self assessed health" and "restricted activities of daily living" were employed as need indicators. Utilisation was measured by the number of "visits to physicians" and "days in hospital". Data was available for 6435 individuals (west) and 3928 individuals (east). Income was defined as equivalent net household income with an equivalence scale derived from the german social assistance program. Compared to the concentration of income all variables in the scope of this study were only marginally concentrated (i.e. equally distributed). A slight concentration of need amongst the lower income was overcompensated by utilisation. Thus a very small impact of the German health care system favouring lower income individuals was measured. The study shows methodological problems when combining data from regions with strongly different income levels instead of analysing them separately. A combined analysis tends to underestimate concentration.

Activities of Daily Living↗

Pulmonary clearance of 99mTc-DTPA in experimental surfactant dysfunction treated with surfactant instillation.

BACKGROUND: Breakdown of the alveolo-capillary barrier is a characteristic feature of respiratory distress syndrome. Restoration of alveolo-capillary barrier function may be an important aspect of surfactant replacement therapy. We examined the effect of surfactant instillation on alveolo-capillary barrier function in an experimental model of surfactant dysfunction by measuring pulmonary clearance of 99mTc-DTPA. METHODS: Nineteen rabbits were tracheotomized and mechanically ventilated. Surfactant dysfunction was induced by administration of a synthetic detergent in aerosol form. Detergent was given to 13 rabbits; seven rabbits were then treated with instillation of natural surfactant, whereas six rabbits received saline. Six rabbits were used as untreated controls. An aerosol of 99mTc-DTPA was administered to all animals and the pulmonary clearance was measured with a gamma camera. RESULTS: 99mTc-DTPA cleared from the lungs with a half-life of 71 +/- 22 min in the control animals, 21.4 +/- 7.4 min in the surfactant-treated animals and 5.8 +/- 1.5 min in the saline-treated animals. The difference in half-life between groups was highly significant (P < 0.001). There was no change in arterial oxygenation or compliance in controls or in animals treated with saline. In animals treated with surfactant, a small transient reduction in arterial oxygen tension and a more long-standing reduction in compliance were observed. CONCLUSION: Surfactant treatment thus significantly attenuated the effect of detergent treatment but did not restore alveolo-capillary transfer of 99mTc-DTPA to normal.

Animals↗

Surfactant dysfunction makes lungs vulnerable to repetitive collapse and reexpansion.

Reexpansion of collapsed lung creates intrapulmonary shear forces. In an earlier study we showed that application of a negative end-expiratory airway pressure (NEEP) to normal rabbit lungs in vivo produced tidal collapse and reexpansion with transient changes in compliance and gas exchange but no histologic damage. In the present study we examined NEEP in a model of surfactant perturbation produced by an inhaled aerosol of 2% and 5% dioctyl sodium sulfosuccinate (DOSS). DOSS increased alveolocapillary permeability without affecting compliance or oxygenation. Repeated collapse and reexpansion (RECOREX), caused by NEEP for 3 h was compared with ventilation with positive-end expiratory pressure (PEEP). Groups ventilated with PEEP maintained normal lung mechanics and morphology even if pretreated with DOSS. NEEP disturbed lung mechanics and gas exchange with persistent dose-related histologic damage in animals pretreated with DOSS. Lungs subjected to NEEP without DOSS had normal morphology. We conclude that perturbation of the surfactant system makes lungs vulnerable to injury by RECOREX. The combination of DOSS and NEEP might lead to leakage of plasma proteins into alveoli, causing inactivation of surfactants and increased shear forces with resulting lung damage. Similar mechanisms may accelerate lung damage in the respiratory distress syndrome.

Animals↗