Prevalence and penetrance of ZFPM2 mutations and deletions causing congenital diaphragmatic hernia.

Zinc finger protein, FOG2 family member 2 (ZFPM2) (previously named FOG2) gene defects result in the highly morbid congenital diaphragmatic hernia (CDH) in humans and animal models. In a cohort of 275 CDH patient exomes, we estimated the prevalence of damaging ZFPM2 mutations to be almost 5%. Genetic analysis of a multigenerational family identified a heritable intragenic ZFPM2 deletion with an estimated penetrance of 37.5%, which has important implications for genetic counseling. Similarly, a low penetrance ZFPM2 frameshift mutation was observed in a second multiplex family. Isolated CDH was the predominant phenotype observed in our ZFPM2 mutation patients. Findings from the patients described herein indicate that ZFPM2 point mutations or deletions are a recurring cause of CDH.

Training and validation of standardized patients for unannounced assessment of physicians' management of depression.

OBJECTIVE: Standardized patients (SPs) have been developed to measure practitioner performance in actual practice settings, but results have not been fully validated for psychiatric disorders. This study describes the process of creating reliable and valid SPs for unannounced assessment of general-practitioners' management of depression disorders in Iran. METHOD: Ten psychology and nursing students (potential SPs) took part in a five-session course involving training in dialogue and body language. Five scenarios, along with corresponding checklists representing common presentations of mood disorders in primary-care settings, were developed by an expert group. The SPs' role-play performance of their respective scenario was videotaped and scored independently by three psychiatrists according to an observational rating scale to assess validity. The role-play was repeated after 1 week with the same scenario and the same doctor, to assess test-retest reliability. The reliability of each checklist to be used by the SPs was assessed by testing interrater reliability between groups of SPs. RESULTS: The cutoff score for the SPs' portrayal validity was 90% or above for all SPs. Mean interrater reliability for the checklists was acceptable for the SPs watching the same videos and filling in the checklists, while the mean kappa for assessing concurrent validity in filling in the checklists was lower. The test-retest performance for assessing reliability resulted in a mean kappa of 0.72. All SPs except one, who was not recruited, performed acceptably well. CONCLUSION: The authors have demonstrated a thorough validation of the technique of using standardized patients in the portrayal of depressive disorders in primary-care settings in Iran, which creates confidence in employing this technique to evaluate doctors' performance, for example, after an educational intervention. Similar methods of validation can be used for SPs' portrayal of other psychiatric disorders.

Fluid retention in cirrhosis: pathophysiology and management.

Accumulation of fluid as ascites is the most common complication of cirrhosis. This is occurring in about 50% of patients within 10 years of the diagnosis of cirrhosis. It is a prognostic sign with 1-year and 5-year survival of 85% and 56%, respectively. The most acceptable theory for ascites formation is peripheral arterial vasodilation leading to underfilling of circulatory volume. This triggers the baroreceptor-mediated activation of renin-angiotensin-aldosterone system, sympathetic nervous system and nonosmotic release of vasopressin to restore circulatory integrity. The result is an avid sodium and water retention, identified as a preascitic state. This condition will evolve in overt fluid retention and ascites, as the liver disease progresses. Once ascites is present, most therapeutic modalities are directed on maintaining negative sodium balance, including salt restriction, bed rest and diuretics. Paracentesis and albumin infusion is applied to tense ascites. Transjugular intrahepatic portosystemic shunt is considered for refractory ascites. With worsening of liver disease, fluid retention is associated with other complications; such as spontaneous bacterial peritonitis. This is a primary infection of ascitic fluid caused by organisms originating from large intestinal normal flora. Diagnostic paracentesis and antibiotic therapy plus prophylactic regimen are mandatory. Hepatorenal syndrome is a state of functional renal failure in the setting of low cardiac output and impaired renal perfusion. Its management is based on drugs that restore normal renal blood flow through peripheral arterial and splanchnic vasoconstriction, renal vasodilation and/or plasma volume expansion. However, the definitive treatment is liver transplantation.

Effects on readiness to change of an educational intervention on depressive disorders for general physicians in primary care based on a modified Prochaska model--a randomized controlled study.

BACKGROUND: The Prochaska model of readiness to change has been proposed to be used in educational interventions to improve medical care. OBJECTIVE: To evaluate the impact on readiness to change of an educational intervention on management of depressive disorders based on a modified version of the Prochaska model in comparison with a standard programme of continuing medical education (CME). METHODS: This is a randomized controlled trial within primary care practices in southern Tehran, Iran. The participants included 192 general physicians working in primary care (GPs) were recruited after random selection and randomized to intervention (96) and control (96). Intervention consisted of interactive, learner-centred educational methods in large and small group settings depending on the GPs' stages of readiness to change. Change in stage of readiness to change measured by the modified version of the Prochaska questionnaire was the RESULTS: The final number of participants was 78 (81%) in the intervention arm and 81 (84%) in the control arm. Significantly (P < 0.01), more GPs (57/96 = 59% versus 12/96 = 12%) in the intervention group changed to higher stages of readiness to change. The intervention effect was 46% points (P < 0.001) and 50% points (P < 0.001) in the large and small group setting, respectively. CONCLUSIONS: Educational formats that suit different stages of learning can support primary care doctors to reach higher stages of behavioural change in the topic of depressive disorders. Our findings have practical implications for conducting CME programmes in Iran and are possibly also applicable in other parts of the world.

Prevalence of coronary artery disease risk factors in Iran: a population based survey.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of mortality, morbidity, and disability with high health care cost in Iran. It accounts for nearly 50 percent of all deaths per year. Yet little is known about CAD and CAD risk factors in the Iranian population. We aimed to assess the prevalence of different CAD risk factors in an Iranian population. METHODS: A descriptive cross sectional survey was conducted involving 3000 healthy adults at 18 years of age or above who were recruited with cluster random sampling. Demographic data and risk factors were determined by taking history, physical examination and laboratory tests. RESULTS: The average age was 36.23 +/- 15.26. There was 1381 female (46%) and 1619 male (54%) out of which 6.3% were diabetic, 21.6% were smoker, and 15% had positive familial heart disease history. 61% had total cholesterol level > 200 mg/dL, 32% triglyceride > 200 mg/dl, 47.5% LDL-c > 130 mg/dl, 5.4% HDL-c < 35 mg/dl, 13.7% systolic blood pressure > 140 mmHg, 9.1% diastolic blood pressure > 90 mmHg and 87% of them were physically inactive. CONCLUSION: Clinical and Para-clinical data indicated that Iranian adult population are of a high level of CAD risk factors, which may require urgent decision making to address national control measures regarding CAD.

Meningeal-cutaneous relationships in anencephaly: evidence for a primary mesenchymal abnormality.

The pathogenesis of cranial and spinal dysraphia has been controversial. Studies of spinal dysraphia have shown that the relationships of the pia and dura to the cutaneous layers were best understood as the result of a primary abnormality of mesenchymal structures, with the nervous system lesions occurring as a result of exposure of the bare spinal cord on the body surface. This study was undertaken to determine if the relationship of the cutaneous layers in anencephaly were similar to those found in spinal dysraphia. We reviewed serial histologic sections of the cranial structures of 10 anencephalic fetuses autopsied at The Johns Hopkins Hospital. We found the dura to be continuous with the deep dermis and the pia continuous with the superficial dermis and epidermis, the same arrangement observed in myelomeningocele. The development of eyes and cranial nerves, the absence of a bony calvarium, and the meningeal-cutaneous relationships found in this study support the idea that anencephaly can originate as an abnormality of mesenchymal structures and that the brain is secondarily lost to injury in utero because of its exposed position.

High dose intramuscular methylprednisolone in experimental Staphylococcus aureus endophthalmitis.

We attempted to determine whether treatment using intramuscular methylprednisolone plus intravitreal vancomycin decreased ocular inflammation and preserved retinal function better in experimental Staphylococcus aureus (S. aureus) endophthalmitis than treatment with intravitreal vancomycin alone. Sixteen rabbits received intravitreal inoculations in both eyes with S. aureus and the rabbits were divided into two groups (group I and group II) of eight rabbits each. Group I rabbits were treated with one injection of intravitreal vancomycin in each eye at either 24, 36, 48 or 72 hours after bacterial inoculation followed by seven consecutive days of high dose intramuscular methylprednisolone (30 mg/kg per day). Group II rabbits were treated with only one intravitreal injection of vancomycin in each eye at equivalent time intervals as in Group I. Clinical evaluations of ocular inflammation were performed by slit-lamp biomicroscopy and indirect ophthalmoscopy. Electroretinography (ERG) was performed eight days after bacterial inoculation to assess retinal function in all eyes. The combination of intramuscular methylprednisolone and intravitreal vancomycin resulted in a degree of ocular inflammation equal to eyes treated with intravitreal vancomycin alone at all treatment intervals. ERG responses were not significantly different in either group. A single intravitreal injection of vancomycin plus daily intramuscular methylprednisolone for seven days were found neither to decrease ocular inflammation nor preserve retinal function better than a single intravitreal injection of vancomycin in our experimental model of S. aureus endophthalmitis.

Measurements of viscosity of synthetic erythrocyte suspensions.

Measurements were made of the viscosity of suspensions of synthetic erythrocytes composed of hemoglobin solutions encapsulated in liposomes, as a function of shear rate, temperature, suspension concentration, lipid membrane composition, and the viscosity of the suspending medium. It was found that the viscous behavior of the synthetic erythrocyte suspensions was non-Newtonian and nearly the same as that of suspensions of natural erythrocytes prepared similarly, with the major difference being that synthetic erythrocyte suspensions are somewhat more viscous. Suspensions of Fluosol FC-43 prepared similarly were found to be essentially Newtonian fluids, and substantially different and more viscous than either erythrocyte suspension. The higher viscosity of synthetic erythrocyte suspensions probably accounts for the ability of these suspensions to maintain normal systemic vascular resistance in transfusion experiments, in spite of the fact that synthetic erythrocytes are smaller than natural erythrocytes.

Use of sunflower seeds in grower diets for pullets and subsequent performance as affected by aureomycin and pelleting.

In two experiments the effects of unhulled sunflower seeds (USFS) were evaluated at levels of 19 and 38% in corn-based diets for pullets between 10 and 19 wk of age. As an additional treatment a .09%-lysine monohydrochloride supplement was added to the 38% USFS-containing diet in Experiment 2. Isonitrogenous grower diets made up of corn and soybean meal or largely oats served as control diets. During the productive phase, layers were fed a high oats diet as mash (both experiments) or in pelleted form (Experiment 2). One half of the hens in each study were fed layer diets containing Aureomycin at 100 g per ton for 1 wk during each 28-day period to monitor the effect on egg production. Treatments during the laying phase were superimposed on the previous growing phase treatments. Pullets fed the 38% USFS diet in Experiment 1 were significantly lighter (P less than .01) at 19 wk of age and reached 50% egg production 2 days later than those on the control corn-soy diet. However, subsequent overall laying performance for 14 28-day periods was not significantly affected by the growing treatments. Neither growth nor laying performance was influenced by the treatments imposed during the rearing period of the second experiment. The two supplies of USFS varied considerably in crude fiber (14.6 vs 25.8%) and ether extract components (42.4 vs. 29.0%, respectively). The discrepancy in growth response to USFS of the two experiments was possibly related to the difference in the ether extract portions of the oil seeds. Egg production rate was significantly increased by Aureomycin only when the diet was pelleted.

Appearance of D-alloisoleucine in the blood plasma of laying hens.

Two strains of laying chickens were used to investigate the effects of amino acid additions, including D-alloisoleucine, to a low protein corn-soy diet on plasma free amino acids and egg albumen amino acid composition. Intake of .1% D-alloisoleucine with the L-form in the mixture resulted in appearance of this compound in the plasma but not in egg albumen. The concentration of plasma valine was significantly increased when the amino acid (.2% D-L) was added to the 10% protein diet. Threonine and arginine additions did not increase the concentration of the respective amino acid in the plasma significantly. The amino acid composition of egg albumen remained unaffected by dietary supplementation. Production data along with amino acid composition of egg albumen showed that the laying hen reduces production rather than altering amino acid composition of egg albumen protein in its response to reduced uptake. No apparent strain differences were noted.

Effect of copper with three levels of sulfur containing amino acids in diets for turkeys.

The effects of adding copper or methionine to low-protein practical diets for turkeys were studied in two experiments involving an initial total of 2,496 day-old tom poults. In Experiment 1, 0 or 120 ppm copper were added to diets providing about 75, 85, or 100% of the National Research Council (NRC, 1977) requirements for sulfur amino acids (SAA) as supplemented by DL-methionine. Experiment 2 involved four levels of copper (0, 60, 120, and 240 ppm) added to diets containing three levels of SAA (75, 100, or 125%, NRC, 1977). Sixty ppm of copper improved 8-week body weight, while the effects of 120 and 240 ppm copper were growth depressing but not beyond 8 weeks of age. Increasing the methionine content of the diets to the 100% level for SAA (1977) consistently improved weight gain of younger birds. The improved body weight from methionine additions for the older turkeys (16 to 24 weeks) however, was significant only in Experiment 1. Copper did not influence the methionine requirement in these experiments.

Pathogenesis of age-related macular degeneration: embryologic concept.

Age-related macular degeneration (ARMD) is a bilateral progressive process which deprives millions of elderly individuals of central vision. Although numerous risk factors have been enumerated, embryonic implication, in relation to ARMD is an area that has been neglected to my knowledge. I address this new issue for the first time.