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Biomedical subjects

B Jacobs

Publications and source records attributed to B Jacobs.

At least 19 recordsLinked to original sources

[Diabetes mellitus and massive lower leg edema without heart failure].

ANAMNESIS AND CLINICAL FINDINGS: The 47-year-old male patient was admitted to the hospital because of newly diagnosed diabetes and elevated liver function tests (gamma glutamyl transferase 303 U/l). On admission the patient reported a reduction of appetite, which had increased during the past 2 weeks, fatigue, muscular weakness, polyuria and polydypsia. On physical examination the patient was moderately overweight, the blood pressure was normal. There were leg edema, which had not responded to previous treatment. There were no additional signs of right heart failure. INVESTIGATIONS: On admission there were hypokalemia and increased parameters of cholestasis. Cortilsol concentration was elevated (1744 microg/l). Hypokalemia which was refractory to treatment raised the differential diagnosis of Conn's syndrome or ectopic secretion of ACTH, although these conditions are frequently associated with arterial hypertension. Cushing's syndrome was finally diagnosed despite of the lack of classical symptoms. Underlying reason was an adenocarcinoma of the pancreas with ectopic secretion of ACTH. TREATMENT AND COURSE: Therapy was targeted to control the excessive secretion of cortisol. A treatment attempt with subcutaneous somatostatin and the adrenal enzyme inhibitor ketoconazole failed to control increased cortisol secretion. Bilateral surgical adrenalectomy was performed because of the patient's progressively deteriorating clinical condition. The patient developed a lethal septic shock after surgery, most likely due to the cortisol-induced immunosuppression. CONCLUSION: 1. In patients presenting with muscular weakness, leg oedema refractory to treatment, hypokalemia and hyperglycemia hypercortisolism should be ruled out even in the absence of typical clinical signs. 2. Massive hypercortisolism (as present in ectopic ACTH secretion) is not necessarily associated with arterial hypertension.

Adenocarcinoma↗

Effects of sleep deprivation and recovery sleep upon cell proliferation in adult rat dentate gyrus.

Numerous behavioral and environmental factors modulate the production of new cells in the adult mammalian brain. Although sleep loss has previously been shown to dramatically suppress brain cell proliferation, the effect of recovery sleep after a period of sleep deprivation is not known. Using the disk-over-water paradigm, adult male Sprague-Dawley rats were sleep deprived for 48 h. Separate groups were then allowed either an 8 h period of recovery sleep or an additional 8 h of sleep deprivation. A third group of rats served as a control, and were not sleep deprived. At 54 h, all rats received an injection of 5-bromo-2'-deoxyuridine (200 mg/kg, i.p.) and were killed 2 h later. When compared with control rats, a 36% reduction in cell proliferation was observed in the dentate gyrus of rats subjected to 56 h of sleep deprivation. A similar reduction in proliferation (39%) was observed in rats allowed an 8 h period of recovery sleep. In both deprivation groups, the magnitude of suppression of cell proliferation was approximately twice as large in the posterior hippocampus as it was in the anterior hippocampus. These data confirm previous results that an extended period of sleep deprivation exerts a strong suppressant effect on cell proliferation in the rat dentate gyrus, and demonstrate that this suppression of cell proliferation shows no evidence of recovery for at least 8 h following a 48 h period of sleep deprivation.

Analysis of Variance↗

A structured assessment of newly qualified medical graduates.

INTRODUCTION: While there is extensive published experience with the assessment of procedural skills in undergraduate students, this is limited in newly qualified medical graduates at the time of entry to the pre-registration (internship) year. The few studies that have been published suggest that these skills are frequently deficient when objectively tested. We therefore chose to assess the competence of a group of South African medical graduates on entry to their pre-registration year. METHODS: A total of 58 graduates of South African medical schools were assessed. Each subject participated in a 7-station objective structured clinical examination (OSCE); 6 of these assessed individual competence in phlebotomy, intramuscular injection, female pelvic examination, bladder catheterisation, tracheal intubation and prescription writing, while competence in cardiopulmonary resuscitation was assessed in a seventh station in randomly allocated teams of 3 candidates. Candidates' opinions of their own competence was sought by questionnaire. RESULTS: There was a wide variation in competence between subjects and across the range of tasks studied. Mean scores ranged from 85.4% for phlebotomy to 55.3% for prescription writing. The average score across all stations was 67.5%, and no student obtained an overall cut-off score of 85% or more, which was established using a modified Angoff method. Subjects' assessment of their own performance was unduly optimistic; most believed that they had demonstrated competence despite clear shortcomings in technique. Objective scores for subjects who had been exposed to a structured skills laboratory programme were not significantly higher than for those who had not, although their self-assessed performance was indeed higher. DISCUSSION: Most of the South African medical graduates who participated in this study were unable to satisfactorily perform technical procedures appropriate to the house officer on entry to the pre-registration year. This is in line with the conclusions of the few studies published in other countries. We suggest that the learning outcomes of undergraduate medical programmes should include an explicit statement of the competencies required for practice in the pre-registration year, and that these should be adequately taught and rigorously assessed before graduation.

Cardiopulmonary Resuscitation↗

Social marketing of pre-packaged treatment for men with urethral discharge (Clear Seven) in Uganda.

We implemented social marketing of pre-packaged treatment for men with urethral discharge (Clear Seven) in Uganda, and studied its feasibility, acceptability and effectiveness as a possible means to treat STDs and thereby prevent HIV. Clear Seven was distributed at private health care outlets in three rural districts and two divisions of the capital. Comparisons were made with a pre-intervention period in the same sites plus one additional rural district. There were almost universally positive attitudes to Clear Seven. Cure rate (84% versus 47%), treatment compliance (93% versus 87%), and condom use during treatment (36% versus 18%) were significantly higher among Clear Seven users (n=422) than controls (n=405). Partner referral was similar but fewer Clear Seven partners were symptomatic when seeking treatment. Distribution of socially marketed pre-packaged treatment for male urethritis should be expanded in sub-Saharan Africa. Consideration should be given to developing similar kits for women.

Acquired Immunodeficiency Syndrome↗

Cost-effectiveness analysis of the russian treatment scheme for tuberculosis versus short-course chemotherapy: results from Tomsk, Siberia.

SETTING: Tomsk Oblast, Siberia. OBJECTIVE: To assess the cost-effectiveness of individualised Russian treatment and short-course chemotherapy (SCC) regimens for new WHO Category I tuberculosis patients. DESIGN: Analysis of costs incurred by the provider, the household and society as a whole for both treatment approaches, and a sensitivity analysis for SCC with hospitalisation for 2 weeks (patients theoretically at low risk of defaulting) and 2 months (patients theoretically at risk of defaulting). Outcomes were measured as cost per case cured and year of life saved, with cure rates based on a locally conducted trial. RESULTS: The cost per cure using the individualised Russian treatment was US $2,295, vs. US $1,901 when using SCC. The costs per year of life saved were respectively US $123 and US $103. The cost per cure was US $1,457 for SCC with 2 months hospitalisation and US $556 for SCC with 2 weeks hospitalisation, with costs per year of life saved of US $79 and US $30, respectively. CONCLUSION: Major financial savings for both the provider and the household, with cure rates similar to those obtained with the Russian treatment scheme, can be achieved in Tomsk when embarking on SCC with 2 weeks and 2 months hospitalisation.

Adult↗

Multicentre controlled trial of parenting groups for childhood antisocial behaviour in clinical practice.

OBJECTIVE: To see whether a behaviourally based group parenting programme, delivered in regular clinical practice, is an effective treatment for antisocial behaviour in children. DESIGN: Controlled trial with permuted block design with allocation by date of referral. SETTING: Four local child and adolescent mental health services. PARTICIPANTS: 141 children aged 3-8 years referred with antisocial behaviour and allocated to parenting groups (90) or waiting list control (51). INTERVENTION: Webster-Stratton basic videotape programme administered to parents of six to eight children over 13-16 weeks. This programme emphasises engagement with parental emotions, rehearsal of behavioural strategies, and parental understanding of its scientific rationale. MAIN OUTCOME MEASURES: Semistructured parent interview and questionnaires about antisocial behaviour in children administered 5-7 months after entering trial; direct observation of parent-child interaction. RESULTS: Referred children were highly antisocial (above the 97th centile on interview measure). Children in the intervention group showed a large reduction in antisocial behaviour; those in the waiting list group did not change (effect size between groups 1.06 SD (95% confidence interval 0.71 to 1.41), P<0.001). Parents in the intervention group increased the proportion of praise to ineffective commands they gave their children threefold, while control parents reduced it by a third (effect size between groups 0.76 (0.16 to 1.36), P=0.018). If the 31 children lost to follow up were included in an intention to treat analysis the effect size on antisocial behaviour was reduced by 16%. CONCLUSIONS: Parenting groups effectively reduce serious antisocial behaviour in children in real life conditions. Follow up is needed to see if the children's poor prognosis is improved and criminality prevented.

Child↗

Extracellular signal-regulated kinase 1/2-mediated phosphorylation of cytosolic phospholipase A2 is essential for human eosinophil adhesion to fibronectin.

We examined the role of p38, p42, and p44 mitogen-activated protein kinase (MAPK) isoforms and cytosolic phospholipase A(2) (cPLA(2)) activation in human eosinophil adhesion to plate-coated fibronectin (FN). In the control state, eosinophil adhesion was maximal, with 10 microg/ml FN at 30 min, and decreased after 60-90 min. Western blot analysis demonstrated that p44/42 MAPK (extracellular signal-regulated kinase (ERK)1/2) and cPLA(2) were phosphorylated during adhesion to FN, whereas p38 MAPK phosphorylation was unchanged. Preincubation of eosinophils with U0126 or PD98059, two structurally unrelated MAPK kinase inhibitors, or arachidonic trifluoromethyl ketone, a cPLA(2) inhibitor, blocked eosinophil adhesion to FN. By contrast, eosinophil adhesion was unaffected by SB203580, a p38 MAPK inhibitor. Pretreatment of eosinophils with okadaic acid, a serine/threonine phosphatase inhibitor, at the concentrations that induced ERK1/2 and cPLA(2) phosphorylation caused an increase in maximal eosinophil adhesion to FN for >60 min. MAPK kinase inhibition but not p38 inhibition also blocked FN-mediated F-actin redistribution in eosinophils and prevented cPLA(2) phosphorylation caused by adhesion to FN. These results demonstrate that ERK1/2 mediating cPLA(2) activation is essential for eosinophil adhesion to FN.

Actins↗

Regional dendritic and spine variation in human cerebral cortex: a quantitative golgi study.

The present study explored differences in dendritic/spine extent across several human cortical regions. Specifically, the basilar dendrites/spines of supragranular pyramidal cells were examined in eight Brodmann's areas (BA) arranged according to Benson's (1993, Behav Neurol 6:75-81) functional hierarchy: primary cortex (somatosensory, BA3-1-2; motor, BA4), unimodal cortex (Wernicke's area, BA22; Broca's area, BA44), heteromodal cortex (supple- mentary motor area, BA6beta; angular gyrus, BA39) and supramodal cortex (superior frontopolar zone, BA10; inferior frontopolar zone, BA11). To capture more general aspects of regional variability, primary and unimodal areas were designated as low integrative regions; heteromodal and supramodal areas were designated as high integrative regions. Tissue was obtained from the left hemisphere of 10 neurologically normal individuals (M(age) = 30 +/- 17 years; five males, five females) and stained with a modified rapid Golgi technique. Ten neurons were sampled from each cortical region (n = 800) and evaluated according to total dendritic length, mean segment length, dendritic segment count, dendritic spine number and dendritic spine density. Despite considerable inter-individual variation, there were significant differences across the eight Brodmann's areas and between the high and low integrative regions for all dendritic and spine measures. Dendritic systems in primary and unimodal regions were consistently less complex than in heteromodal and supramodal areas. The range within these rankings was substantial, with total dendritic length in BA10 being 31% greater than that in BA3-1-2, and dendritic spine number being 69% greater. These findings demonstrate that cortical regions involved in the early stages of processing (e.g. primary sensory areas) generally exhibit less complex dendritic/spine systems than those regions involved in the later stages of information processing (e.g. prefrontal cortex). This dendritic progression appears to reflect significant differences in the nature of cortical processing, with spine-dense neurons at hierarchically higher association levels integrating a broader range of synaptic input than those at lower cortical levels.

Adult↗

A surrogate method for assessment of beta(2)-integrin-dependent adhesion of human eosinophils to ICAM-1.

We have developed and validated an inexpensive and equivalent method for measuring eosinophil adhesion by beta(2)-integrin to endothelial ICAM-1 using bovine serum albumin (BSA) as a surrogate for the immunoglobulin supergene. The number of adherent eosinophils on BSA or ICAM-1 coated microplates was quantified by residual eosinophil peroxidase activity. Non-stimulated eosinophils did not adhere to either BSA or ICAM-1. However, after IL-5 stimulation, either BSA or ICAM-1 caused comparable and concentration-dependent adhesion of eosinophils. Eosinophil adhesion was rapid and occurred within 15 to 30 min of incubation for either BSA or ICAM-1. Preincubation of cells with CD11b or CD18 antibody specifically decreased adhesion to either BSA or ICAM-1. IL-5, PAF and fMLP all induced adhesion of eosinophils to either BSA or ICAM-1 in a concentration-dependent manner, and the optimal IL-5, fMLP and PAF concentrations for adhesion to BSA were the same as for adhesion to ICAM-1. BSA-binding was specific for beta(2)-integrin; neither alpha-CD49d mAb directed against the alpha(4)-chain or alpha-CD29 directed against the common beta(1)-chain of VLA-4 blocked adhesion to BSA or ICAM-1 controls. The protein tyrosine kinase inhibitor, genistein, the phosphatidylinositol 3-kinase (PI-3 kinase) inhibitor, wortmanin, and mitogen-activated protein kinase kinase (MEK) inhibitor, U0126, all inhibited IL-5-induced eosinophil adhesion to either BSA or ICAM-1 comparably. These results indicate that BSA is a reliable and economical surrogate ligand for ICAM-1 adhesion to beta(2)-integrin-dependent adhesion to ICAM-1. Ligation characteristics of BSA are identical to those for soluble ICAM-1, and the assay is suitable for assessment of signal transduction pathways mediating adhesion.

Androstadienes↗

Physiologic and metabolic results of pancreatic cold storage with Histidine-Tryptophan-Ketoglutarate-HTK solution (Custodiol) in the porcine autotransplantation model.

UNLABELLED: Delayed graft function (DEGF) remains an obscure phenomenon in organ transplantation. For the optimal washing of the compounds of the different organ flush solutions, adequate temperature and equilibrium of electrolytes have to be provided. A total of 29 land-race pigs weighing 37.3-5.4 kg were included in this study. According to the model, the left hemipancreas was perfused with Histidine-Tryptophan-Ketoglutarate (HTK)-solution and autotransplanted after 24 h (G1, n = 13) and 48 h (G2, n = 4) of cold storage (CS). Results were compared with grafts perfused with UW-solution and autotransplanted after 24 h (G3, n = 8) and 48 h (G4, n = 4) CS respectively. Daily measurements of glycemia, glucosuria, amylase and lipase were carried out. HTK perfusion resulted in an increase in wet weight of the grafts after 24 h and 48 h CS (P = 0.031 vs UW). Postoperative glycemia levels in pancreases flushed with HTK-solution were higher after 48 h than after 24 h CS until the 6th postoperative day, when the glycemia returned to normal range (P = 0.02), suggesting a delayed endocrine graft function. The mean IVGTT values attained after full function were comparable in G1 and in G3 (-1.22 +/- 0.23 vs. -1.5 +/- 0.65). The rises in serum amylase and lipase levels were more pronounced after 48 h CS in both HTK and UW groups, (P = n.s.). Appearance of interstitial and intracellular edema after CS and reperfusion did not influence the function. CONCLUSION: HTK-solution is suitable for 24 h pancreatic preservation in vivo; the perfusion requires at least 4 min for electrolyte equilibration. Long preservation time (48 h) resulted in a transitory DEGF.

Animals↗

Canadian Acute Respiratory Illness and Flu Scale (CARIFS): development of a valid measure for childhood respiratory infections.

Although acute respiratory infection (ARI) is the most frequent clinical syndrome in childhood, there is no validated measure of its severity. Therefore a parental questionnaire was developed: the Canadian Acute Respiratory Illness Flu Scale (CARIFS). A process of item generation, item reduction, and scale construction resulted in a scale composed of 18 items covering three domains; symptoms (e.g., cough); function (e.g., play), and parental impact (e.g., clinginess). The validity of the scale was evaluated in a study of 220 children with ARI. Construct validity was assessed by comparing the CARIFS score with physician, nurse, and parental assessment of the child's health. Data were available from 206 children (94%). The CARIFS correlated well with measures of the construct (Spearman's correlations between 0.36 and 0.52). Responsiveness was shown, with 90% of children having a CARIFS score less than a quarter of its initial value, by the tenth day.

Acute Disease↗

A single center's clinical experience with quadruple immunosuppression including ATG or IL2 antibodies and mycophenolate mofetil in simultaneous pancreas-kidney transplants.

UNLABELLED: Acute rejection remains a major problem in simultaneous pancreas-kidney (SPK) transplant and occurs in 60-100% of the cases. With the introduction of mycophenolate mofetil (MMF) replacing azathioprine (AZA) as a basis immunosuppressant, reduced rates of rejection have been reported. This study investigates the frequency and clinical relevance of allograft rejection in SPK patients receiving antithymocyte globulin (ATG) or Basiliximab induction therapy and cyclosporine Neoral (CyA), MMF, steroid basis immunosuppression. Between December 1996 and October 1999, 21 consecutive patients (15 males, 6 females) received a SPK transplant at our institution with a mean +/- standard deviation (SD) age of 42 +/- 6 yr. Of these, 14 patients were treated with anti-thymocyte globulin (ATG) Fresenius (rabbit) 3-5 mg/kg for 6 +/- 2 d, cyclosporine Neoral (CyA) (trough levels 350-400 ng/mL), MMF 3 g/d and low dose steroid therapy. Seven SPK patients were treated with Basiliximab (Simulect, Novartis 20 mg on d 0 and d 4 post-transplant) instead of ATG. The patients had an average human leucocyte antigen (HLA) mismatch of 3.9/6 and a negative cross match. All patients remained on triple drug therapy. Three patients were switched to tacrolimus instead of Neoral for CyA intolerance. The mean +/- SD cold ischemia time (CIT) of the organs was 10.1 +/- 2.4 h for the pancreas and 10.5 +/- 2.6 h for the kidney. RESULTS: Biopsy-proven rejection occurred in the kidney of 1 ATG patient (8%), which responded to steroid bolus therapy. One of the patients (14%) with Basiliximab induction developed renal allograft rejection, which was resolved after a 6-d course of anti-CD3 mAb (OKT3) treatment. All patients (100%) were free from rejection in the pancreas, as measured by urine amylase levels and glycemic control without the need for exogenous insulin with a mean glycosylated hemoglobin (HBA1C) of 5.1 +/- 0.7%, and serum creatinine with a mean of 1.24 +/- 0.24 mg/dL in a mean follow-up period of 17 +/- 15 months (median 12, range 2 37). CONCLUSION: Triple drug immunosuppression including cyclosporine, MMF and low dose steroids with ATG or interleukin 2 (IL2) receptor antibodies induction therapy appears to be a very suitable immunosuppressive regimen for combined pancreas-kidney transplant (PKT) with a marked reduction in the incidence of rejection.

Adult↗

Feasibility of hospital-based blood banking: a Tanzanian case study.

The demand for blood transfusion is high in sub-Saharan Africa because of the high prevalence of anaemia and pregnancy related complications, but the practice is estimated to account for 10% of HIV infections in some regions. The main response to this problem by the international donor community is to establish vertically implemented blood transfusion services producing suitable (safe) blood at a cost of US$25-40 per unit. However, the economic sustainability of such interventions is questionable and it is argued here that hospital-based blood transfusion services operating at a basic adequate level are sufficient for low-income African countries. The results of a project aimed at improving such services in Tanzania are presented. The main findings are: (1) the cost per suitable blood unit produced was US$12.4; (2) at an HIV test sensitivity of 93.5% during the study period, discounted financial benefits of the interventions exceeded costs by a factor of between 17.2 and 37.1; (3) the cost per undiscounted year of life saved by use of these interventions was US$2.7-2.8; and (4) safe blood transfusion practices can be assured at an annual cost of US$0.07 per capita. Recommendations are made to ensure safe blood transfusion practices at hospital-based blood banks in Tanzania.

Actuarial Analysis↗