Intestinal effects of iron deficiency anemia in children.

A group of 11 children with iron deficiency anemia were studied with respect to intestinal structure and function. In six cases there were histological abnormalities of intestinal mucosa in varying degrees consisting of villous damage, increased activity in the crypts, increased lymphoplasmocytic infiltration and changes in the surface epithelium. Ultrastructurally, microvilli lesions, mitochondrial changes and an increase in lysosomes were observed. Relative malabsorption of iron and d-xylose malabsorption were present in a minority of patients. Functional and structural changes were correlated. Our results suggest that these changes are due to impairment of cell metabolism.     

44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.     

Are general practitioner hospitals cost-saving? Evidence from a rural area of Norway

OBJECTIVE: We aimed to determine whether general practitioner GP hospitals, compared with alternative modes of health care, are cost- saving. METHODS: Based on a study of admissions (n = 415) to fifteen GP hospitals in the Finnmark county of Norway during 8 weeks in 1992, a full 1-year patient throughput in GP hospitals was estimated. The alternative modes of care (general hospital, nursing home or home care) were based on assessments by the GPs handling the individual patients. The funds transferred to finance GP hospitals were taken as the cost of GP hospitals, while the cost of alternative care was based on municipality and hospital accounts, and standard charges for patient transport. RESULTS: The estimated total annual operating cost of GP hospitals was 32.2 million NOK (10 NOK = 1 Pound) while the cost of alternative care was in total 35.9 million NOK. Sensitivity analyses, under a range of assumptions, indicate that GP care in hospitals incurs the lowest costs to society. CONCLUSION: GP hospitals are likely to provide health care at lower costs than alternative modes of care.      

Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats

The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5. The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site-specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-2, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy.     

Chromosome 22q11.2 deletion and phenotypic features in 30 patients with conotruncal heart defects

This report describes the dysmorphic features and frequency of 22q11.2 deletion (del22q11) in 30 Turkish patients with conotruncal heart defects (CTHDs). Fluorescence in situ hybridization (FISH) analysis revealed deletions in the 22q11.2 region in nine (30%) individuals. The CTHDs in this group were tetralogy of Fallot (four cases), double-outlet right ventricle (DORV) (two cases), transposition of great arteries (two cases), and ventricular septal defect (VSD) associated with other CTHDs (one case). The frequency of del22q11 in the study group was relatively high because many of the patients with dysmorphic findings also had cardiac anomalies involving the pulmonary artery, ductus arteriosus, or the aortic arch and its main branches. Twenty of the 30 patients exhibited several dysmorphic findings. Two of the nine patients with del22q11 exhibited no apparent dysmorphic features other than sacral dimple. Interestingly, one of the patients with del22q11 had a phenotypic appearance similar to that seen in oculo-auriculo-vertebral spectrum (OAVS). This individual had left microtia, atresia of the external meatus, mandibular asymmetry, and peripheral facial nerve paralysis. His mental development was normal and there were no abnormalities on ophthalmological examination. The CTHDs in this patient were situs inversus dextrocardia, DORV, pulmonary stenosis, and VSD. Radiographs of this patient showed platybasia, complete fusion of C2-C3, and posterior fusion of the T1-T2 vertebrae. This particular case indicates that the phenotypic features of del22q11 and OAVS may overlap.     

Kinetics of antagonism at histamine-H1 receptors in isolated rabbit arteries

Summary Kinetics of antagonist-induced decrease of histamine-H₁ receptor-mediated steady-state responses in isolated rabbit arteries were studied in the presence of histamine-H₂ receptor antagonist famotidine. Data were fitted using a model which describes competition kinetics at the receptor level. Estimated rate and equilibrium constants were evaluated for their dependence on tissue, agonist and antagonist concentrations, using (+)-brompheniramine as antagonist. In large arteries (thoracic and arcus aorta), rate constants were observed to be modified by agonist and/or antagonist concentrations, suggesting a diffusion-controlled process. In relatively small (common carotid and iliac) arteries, estimated equilibrium constants (and consequently the rate constants) were found to diverge despite the invariance of equilibration times between arteries, leading us to include the effects of spare receptors in our evaluation. A model describing the effects of receptor reserve on the estimated equilibrium dissociation constant was developed and stimulated and the results then compared with those that had been experimentally estimated. The reserve hypothesis was experimentally verified in common iliac artery (where EC₅₀ K _A) using the irreversible antagonist phenoxybenzamine. A rationalized rule for the optimization of experimental design for in-vitro disequilibrium-competition experiments was proposed. Common carotic artery was found to be favorable for the present design in view of its reserve properties. In addition, competition reaction seems to be the rate-determining step in this artery. Rate and equilibrium constants of mepyramine, (+)-brompheniramine, diphenhydramine and antazoline were therefore determined in the common carotid artery and were compared with those obtained from independent experiments. Results suggest that the estimated parameters reflect drug-receptor interaction.This work constitutes a part of the PhD thesis of H. O. Onaran Send offprint requests to T. A. Bökesoy at the above address     

Intestinal permeability in kwashiorkor

Intestinal permeability can be assessed non-invasively using the lactulose-rhamnose (L-R) test, which is a reliable measure of small intestinal integrity. AIMS: To determine risk factors for abnormal intestinal permeability in kwashiorkor, and to measure changes in L-R ratios with inpatient rehabilitation. DESIGN: A case-control study of 149 kwashiorkor cases and 45 hospital controls. The L-R test was adapted to study kwashiorkor in Malawi, with testing at weekly intervals during nutritional rehabilitation. Urine sugars were measured by thin layer chromatography in London. RESULTS: The initial geometric mean L-R ratios (x100) (with 95% confidence interval) in kwashiorkor were 17.3 (15.0 to 19.8) compared with 7.0 (5.6 to 8.7) for controls. Normal ratios are < 5, so the high ratios in controls indicate tropical enteropathy syndrome. Abnormal permeability in kwashiorkor was associated with death, oliguria, sepsis, diarrhoea, wasting and young age. Diarrhoea and death were associated with both decreased L-rhamnose absorption (diminished absorptive surface area) and increased lactulose permeation (impaired barrier function) whereas nutritional wasting affected only L-rhamnose absorption. Despite, clinical recovery, mean L-R ratios improved little on treatment, with mean weekly ratios of 16.3 (14.0 to 19.0), 13.3 (11.1 to 15.9) and 14.4 (11.0 to 18.8). CONCLUSION: Abnormal intestinal permeability in kwashiorkor correlates with disease severity, and improves only slowly with nutritional rehabilitation.     

Evaluation of research ethics committees in Turkey

In Turkey, there was no legal regulation of research on human beings until 1993. In that year "the amendment relating to drug researches" was issued. The main objectives of the regulation are to establish a central ethics committee and local ethics committees, and to provide administrative control. There are no compulsory clinical ethics lectures in the medical curriculum, so it is also proposed that research ethics committees (RECs) play a central educational role by helping physicians to be aware of moral problems and by contributing to the training of research teams.     

The experience of the research ethics committees in Turkey

In this article the experience of the research ethics committees in Turkey, which are nearly ten years old, is introduced. Although the legislation related to Research on Human Beings by using Drugs and Chemical Substances, issued on 29th January 1993 by the Ministry of Health, there are a lot of problems about RECs, for example the central ethics committee has no medical ethicist as a member, and there is no ethical concept other than "consent" in their operational procedures. Membership characteristics of the ECs, and their specialty areas described functions of the ECs, the forms used, and the major items used for the evaluation of the proposals are explained. Finally the ethics committee of the Turkish Medical Association is also introduced as another model of ECs in Turkey.