Molecular bases of beta-thalassemia in the Eastern Province of Saudi Arabia

beta-thalassemia is a group of heterogeneous recessive disorders common in many parts of the world. Al-Qatif and Al-Hassa oases in the Eastern Province of Saudi Arabia are regions known for high frequency of these disorders. Using two molecular methods, based on multiplexing-amplification refractory system and reverse hybridization principles, the spectrum of beta-thalassemia in the region was studied. Sixty-nine subjects with known beta-thalassemia disease and volunteers with high hemoglobin $A(2)(HbA(2))$ and low mean corpuscular volume (MCV) were included in this study. Ten mutations were detected in 91% of the subjects under study. Six of these mutations had previously been observed while the other four mutations are reported here for the first time. In addition, four of the mutations accounted for 76.8% of the subjects studied. IVSII-1 (G > A), IVSI-5 (G > A), and codon 39 (C > T) mutations were found to be the most frequent. However, the frequencies of different mutations reported here are slightly different from those reported earlier. A number of these mutations were also found in the neighboring countries, which can be explained in terms of gene flow.     

Characterization of the action of S 21403 (mitiglinide) on insulin secretion and biosynthesis in normal and diabetic beta-cells

S 21403 (mitiglinide) is a new drug for type 2 diabetes mellitus (T2DM). Its action on insulin release and biosynthesis was investigated in several experimental systems utilizing pancreas from normal and T2DM animals. At high concentrations (10 microM), S 21403, like classical sulphonylurea, induced insulin release in the absence of glucose. In contrast, at therapeutic (0.1-1.0 microM) concentrations, S 21403 amplified insulin secretion glucose dose-dependently and with similar magnitude in normal and diabetic GK rat islets. In perfused GK rat pancreas, S 21403 induced normal kinetics of insulin secretion including first-phase response. The effect of S 21403 was strongly modulated by physiological factors. Thus, 0.1 microM adrenaline inhibited S 21403-induced insulin release. There was marked synergism between S 21403 and arginine in GK rat islets, combination of the two normalizing insulin secretion. In primary islet cultures from normal rats or prediabetic Psammomys obesus, prolonged exposure to S 21403 did not induce further depletion of insulin stores under normal or 'glucotoxic' conditions. Proinsulin biosynthesis was not affected by 2-h exposure of rat or prediabetic P. obesus islets to 1 microM S 21403. Yet, 24-h exposure of rat islets to S 21403 resulted in 30% increase in proinsulin biosynthesis at 8.3 mM glucose. Amplification by S 21403 of glucose-induced insulin secretion in diabetic GK beta-cells with restoration of first-phase response, a strong synergistic interaction with arginine and marked inhibition by adrenaline, make it a prime candidate for successful oral antidiabetic agent.     

Effect of green tea in the prevention and reversal of fasting-induced intestinal mucosal damage

OBJECTIVE: Epidemiologic studies have suggested that high consumption of green tea protects against the development of chronic active gastritis and decreases the risk of stomach cancer. The effect of green tea on the intestinal mucosa was not studied previously, so we examined the effects of green tea on the intestinal mucosa of fasting rats in a controlled experimental setting. METHODS: Two sets of experiments were performed. In the recovery set, rats were fasted for 3 d, after which they were allowed free access to water, black tea, green tea, or vitamin E for 7 d. On day 8, the animals were killed, and small bowels were removed for histologic examination. In the pretreatment set, rats were allowed a normal diet, but the water supply was replaced with green tea, black tea, or vitamin E for 14 d. They were subsequently fasted for 3 d. On day 4, the rats were killed, and small bowels were removed for histologic examination. RESULTS: In the recovery set, fasting for 3 d caused shortening of villi, atrophy, and fragmentation of mucosal villous architecture, with a significant (P < 0.0001) reduction in the length and surface area of the villi. Ingestion of green tea and, to a lesser extent, vitamin E for 7 d helped in the recovery of villi to normal. In the pretreatment set, drinking green tea, black tea, or vitamin E for 14 d before fasting protected intestinal mucosa from damage. CONCLUSION: The mucosal and villous atrophy induced by fasting was reverted to normal by the ingestion of green tea and, to a lesser extent, vitamin E. Black tea ingestion had no effect. In addition, ingestion of black tea, green tea, and vitamin E before fasting protected the intestinal mucosa against atrophy.     

The aetiology of posttraumatic stress disorder in four ethnic groups in outpatient psychiatry

BACKGROUND: PTSD is one of few diagnoses to be defined by its aetiology. At treatment centres specialising in a certain type of trauma, like war, torture or sexual abuse, the aetiology may be regarded as self-explanatory. Recent surveys of general populations reveal high rates of PTSD, often following exposure to multiple traumatic events. Traumas are frequently overlooked in general psychiatric settings and PTSD is underestimated. Such findings indicate the need to conceptualise trauma in terms of multiple events and to examine the aetiology of PTSD amongst patients in everyday psychiatric practice. The present study examines aetiological factors of PTSD in three minority groups at a general psychiatric outpatient clinic. Arabs, Iranians and Turks selected from an entire year's cohort of patients-and a sample of Swedish patients of similar age and gender distribution. METHODS: Histories were collected from 115 patients, both regarding their own traumas and traumas involving relatives and close friends, by means of a questionnaire. A self-rating instrument for PTSD, with no reference to a specific trauma, was used in order to study the relationship between trauma and PTSD outcome. RESULTS: Of the patients, 89% had experienced at least one trauma, and 77% multiple traumatic events. The prevalence of probable PTSD varied between ethnic groups: Iranians 69%, Arabs 59%, Turks 53% and Swedes 29%. In a logistic regression analysis, probable PTSD outcome was associated with multiplicity of relatives' traumas (OR = 3.14), multiplicity of own traumas (OR = 2.56) and belonging to an ethnic minority (OR = 2.44), but not with gender. No patient without a trauma history was positively assessed for probable PTSD. CONCLUSION: The symptomatic syndrome of probable PTSD does not appear in the absence of extreme trauma, lending empirical support to the definition of PTSD. Prevalence increases with multiplicity of traumas, including those involving a relative or close friend. The high prevalence of probable PTSD found in this study warrants screening for trauma among patients, their relatives and close friends, in outpatient psychiatry.     

Management and outcome of patients with combined vaginal septum, bifid uterus, and ipsilateral renal agenesis (Herlyn-Werner-Wunderlich syndrome)

Objective

Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare müllerian anomaly consisting of uterine didelphy, hemivaginal septum, and ipsilateral renal agenesis. The purpose of this study was to evaluate the natural history and outcome of patients with HWWS.

Methods

With ethics review board approval, all patients with uterine/vaginal anomalies were reviewed between 1982 and 2004. Patients with cloacal and/or anorectal anomalies were excluded. Presenting symptoms, preoperative investigations, operative management, and long-term follow-up were assessed.

Results

Of 80 patients identified with uterine/vaginal anomalies, 12 had HWWS. Median age at presentation was 13 years. Most patients (11/12) in this series presented with either abdominal pain and/or pelvic masses. Two patients had intra-abdominal abscesses. Seven patients were menstruating at presentation with 4 of these patients having dysmenorrhea. Symptom duration ranged from 0.5 to 12 months. Diagnosis was confirmed by ultrasound (n = 11), computed tomographic scan (n = 3), and/or magnetic resonance imaging (n = 2). Operative management included vaginal septectomy and drainage of the hematocolpos/hematometrocolpos. One patient required salpingectomy for pyosalpinx. Follow-up ultrasounds revealed no recurrent collections. Median follow-up was 3 years (2 months to 16 years). Eleven patients were asymptomatic after treatment. One patient complained of irregular menses.

Conclusion

This is one of the largest reviews of HWWS in pediatric patients to date. Good long-term outcome occurs after vaginal septectomy. This diagnosis should be suspected in females with a pelvic mass and ipsilateral renal agenesis.     

On the pathogenesis of maturity-onset diabetes mellitus

Conclusions At the 6th IDF Congress in Stockholm in 1967, a hypothesis for the pathogenesis of maturity-onset diabetes under the title ‘What is inherited — what is added?’ was put forward. Investigations over the past 10 years, on the whole, tend to confirm our concept that the capacity of the pancreatic beta-cell to respond to a standardized glucose infusion with insulin production, to a major degree, is genetically controlled. Therefore, our original idea that impaired insulin response to glucose is a marker of genetic diabetes in all its stages (prediabetes, chemical diabetes, manifest diabetes) seems plausible. Accordingly, a malfunction in the transmission of information about the blood glucose level in the extracellular fluid to those sites in the cells which regulate insulin release, would be the primary defect in genetic diabetes. Our studies suggest that, due to increased sensitivity of the liver to insulin in the portal vein, most prediabetics retain a relatively normal — although somewhat low — glucose tolerance. This compensatory mechanism becomes insufficient and glucose intolerance is precipitated, e.g., when the demand for insulin release is increased. This occurs when the sensitivity of the body for insulin diminishes as in the case of obesity, acromegaly and pregnancy and, maybe, also during the process of aging.     

IgG subclasses, barrier function for albumin and production of immunoglobulin G in the central nervous system

Cerebrospinal fluids from patients with neurological diseases have been studied. It appeared that the detectability of immunoglobulin G subclasses 1, 2, 3, 4, and the occurrence of oligoclonal bands in the IgG region increased with increasing concentration of IgG in the spinal fluid. No specific pattern emerged in the different disease groups. Formula: see text.