Ca2+ clearance in visual motion-sensitive neurons of the fly studied in vivo by sensory stimulation and UV photolysis of caged Ca2+

In motion-sensitive visual neurons of the fly, excitatory visual stimulation elicits Ca(2+) accumulation in dendrites and presynaptic arborizations. Following the cessation of motion stimuli, decay time courses of the cytosolic Ca(2+) concentration signals measured with fluorescent dyes were faster in fine arborizations compared with the main branches. When indicators with low Ca(2+) affinity were used, the decay of the Ca(2+) signals appeared slightly faster than with high affinity dyes, but the dependence of decay kinetics on branch size was preserved. The most parsimonious explanation for faster Ca(2+) concentration decline in thin branches compared with thick ones is that the velocity of Ca(2+) clearance is limited by transport mechanisms located in the outer membrane and is thus dependent on the neurite's surface-to-volume ratio. This interpretation was corroborated by UV flash photolysis of caged Ca(2+) to systematically elicit spatially homogeneous step-like Ca(2+) concentration increases of varying amplitude. Clearance of Ca(2+) liberated by this method depended on branch size in the same way as Ca(2+) accumulated during visual stimulation. Furthermore, the decay time courses of Ca(2+) signals were only little affected by the amount of Ca(2+) released by photolysis. Thus Ca(2+) efflux via the outer membrane is likely to be the main reason for the spatial differences in Ca(2+) clearance in visual motion-sensitive neurons of the fly.     

Non-response to ovarian stimulation in normogonadotrophic, normogonadal women: a clinical sign of impending onset of ovarian failure pre- empting the rise in basal follicle stimulating hormone levels

The most important aspect of diminished ovarian reserve is the associated decline in reproductive potential. Assessment of ovarian reserve is mainly based on measurement of early follicular phase follicle stimulating hormone (FSH) concentration. The objective of this study was to report the identification of a group of 12 infertile women initially diagnosed as having unexplained or anovulatory infertility, who had a normal baseline hormonal profile and did not respond to repeated ovarian stimulation with gonadotrophins. All developed ovarian failure within a relatively short time span. Non-response to ovarian stimulation was defined by failure to achieve development of follicles >12 mm and failure to raise oestradiol concentration >350 pmol/l in two successive cycles of human menopausal gonadotrophin (HMG) doses of up to five ampoules per day for 5-8 days. Within a mean of 9 months following the failed attempts of ovarian stimulation the mean day 3 FSH concentrations rose from 5.4 +/- 2.7 IU/l to 53.5 +/- 19.7 IU/l. In these patients, day 3 FSH concentration failed to indicate the low ovarian reserve manifested only by lack of clinical response to treatment with gonadotrophins which was the first sign of impending ovarian failure. We conclude that women with normal early follicular phase serum FSH concentrations who do not respond to ovarian stimulation by HMG are at risk of developing ovarian failure within several months.      

Evaluation of the COBAS TaqMan 48 real-time PCR system for quantitation of hepatitis B virus DNA

The purpose of this study is to evaluate the usefulness of the new real-time PCR COBAS TaqMan 48 analyzer, comparing it to the existing COBAS AMPLICOR HBV MONITOR based on conventional PCR technology. The study used 104 samples from different patients. No differences were found in the sensitivity of the tests. There was an excellent correlation between the sample with a viral load within the dynamic range of the two tests (r = 0.938). The COBAS TaqMan test has a wider linear range, and this fact enables quantifying of the viral load without diluting the sample.     

Quality of life outcomes after minimally invasive repair of pectus excavatum utilizing a new set of metallic bars and stabilizers

Background/PurposeThe aim of the study was to evaluate the postoperative quality of life (QoL) of patients who underwent minimally invasive repair of pectus excavatum (MIRPE) with a newly designed bar and bar stabilizers.MethodsWe conducted a prospective randomized study in which patients were operated either with standard perpendicular stabilizers (control group) or with the newly designed oblique stabilizers (intervention group). All patients were evaluated 6 months after the operation with the Pectus Excavatum Evaluation Questionnaire (PEEQ).ResultsThere were 16 patients in the control group and 14 in the intervention group. Mean age was 17 (SD: 3.3, range 14–27) years. There were no demographic differences between groups. Two patients in the control group and one in the intervention group were repaired with two bars instead of one. There was one reoperation in each group. There was a significant difference between the pre- and postoperative scores, in both groups, in the patient body image domain (control group: 9.5 to 3; p < 0.01; intervention group 10 to 3; p < 0.01), as well as in the psychosocial domain (control group: 13.5 to 24, p < 0.01; intervention group: 15 to 24, p < 0.01). With regards to the patients' perception of physical difficulties before and after MIRPE, the difference between pre- and postoperative scores was greater in the intervention group (8 to 12, p < 0.01) than in the control group (10 to 11, p = 0.04). The mean length of stay was 4.5 and 5 days in the intervention group and the control group, respectively.ConclusionOur study showed that patients who underwent MIRPE with the newly designed bars and stabilizers had non-inferior outcomes than patients reported in the literature who underwent MIRPE with standard bars and stabilizers. We found slightly better outcomes in patients in the intervention group compared to the control group, but larger studies will be needed to confirm if those differences are statistically significant.Level of evidenceII     

Gastro-Gastric Fistulas and Marginal Ulcers in Gastric Bypass Procedures for Weight Reduction

Background: Gastro-gastric fistulas and marginal ulcers are frequent and serious complications of gastric compartmentalization procedures for obesity. Methods: The authors analyzed 810 patients after 911 operations for gastro-gastric fistulas and marginal ulcers over an 8-year period. All patients underwent a form of gastric bypass, in which a pouch is constructed along the lesser curvature of the stomach. The outlet of the pouch was restricted with a prosthetic band. In the first 189 patients (Group I), the pouch and stomach were stapled in continuity or partially divided. In the next 222 patients (Group II), segments were stapled and separated by transection. In the remaining 492 cases (Group III), in addition to transection of the stomach, a limb of jejunum was interposed between the pouch and excluded stomach. Stapled anastomoses were done in Group I and II patients and a portion of Group III patients. The remaining patients underwent hand-sewn anastomosis. Results: Gastro-gastric fistulas occurred in 49% of the patients in Group I, 2.6% of those in Group II, and 0% of those in Group III. In stapled anastomosis, the incidence of marginal ulceration in Groups I, II, and III were 8.5%, 5.4%, and 5.1%, respectively. In a subset of Group III patients, in whom a two-layer, hand-sewn anastomosis was done, the incidence was 1.6% when the outer layer was not absorbable and 0% when both layers were absorbable. Conclusions: Gastro-gastric fistulas and marginal ulcerations are likely the result of breakdown of the mucosa resulting from migrating staples and other foreign material. Lack of integrity of the gastric lining facilitates the action of the gastric digestive process. Transection of gastric segments with interposition of jejunum prevents gastro-gastric fistula formation. An intact serosa appears to block the digestion of bowel wall by gastric enzymes. Our early data suggest that the use of absorbable sutures at the gastrojejunostomy significantly decreases the incidence of marginal ulceration.     

Combining Clozapine with ECT

We describe the safe and effective use of the combination of clozapine and ECT in a patient with schizophrenia who had lost responsiveness to clozapine alone. We suggest further investigation to define the role of combined clozapine-ECT treatment in the management of treatment-resistant schizophrenia.     

Obesity Surgery Poly-parametric Patient Auto-evaluation

A simple auto-evaluation sheet is presented for the proper assessment of the patient's condition after surgery. Stress is put not only on weight loss, but on other important factors as well.     

Abnormalities in the serum insulin-like growth factor-1 axis in women with hyperandrogenism

Objective: To study the insulin-like growth factor-1 (IGF-1) axis in hirsute women.

Design: Controlled clinical study.

Setting: Tertiary care institutional hospital.

Patient(s): Forty hirsute women and 17 women with normal menstrual cycles.

Intervention(s): Basal and ACTH-stimulated samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after a single 3.75-mg IM dose of triptorelin. Controls did not receive triptorelin for ethical reasons.

Main Outcome Measure(s): Serum GH, IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, glucose, total testosterone, sex hormone-binding globulin, E₂, and gonadotropin levels. Basal and ACTH-stimulated steroid precursors were measured.

Result(s): Patients with idiopathic hirsutism were identified by normal serum androgen levels (n = 17). Those with functional ovarian hyperandrogenism (n = 15) were identified by an increase in the serum testosterone level that normalized during gonadal suppression, whereas those with functional adrenal hyperandrogenism (n = 8) were identified by an initial increase in the testosterone level that persisted during gonadal suppression. The adrenal hyperandrogenism group had increased IGF-1 levels compared with the control, idiopathic hirsutism, and ovarian hyperandrogenism groups. Patients with ovarian hyperandrogenism had normal IGF-1 concentrations, but their IGFBP-3 concentrations were lower than those of controls. No differences were observed in GH levels between any of the groups. These results persisted when the influence of age was corrected for.

Conclusion(s): The IGF-1 axis appears to be involved in the pathogenesis of hyperandrogenism, especially in patients with adrenal hyperandrogenism, who have a clear increase in IGF-1 levels. Moreover, patients with ovarian hirsutism have decreased IGFBP-3 concentrations, which might enhance IGF-1 bioavailability.     

Análisis de la concentración sérica del ADN tumoral en el cáncer de pulmón no microcítico y avanzado: ¿es útil como factor pronóstico?

INTRODUCTION: Presence of circulating DNA in the serum of patients with cancer makes detection of tumour-specific genetic alterations feasible. OBJECTIVE: To study serum DNA concentration in patients diagnosed as having advanced Non-Small Cell Lung Cancer (NSCLC) and to evaluate its relationship with age, histology, stage, response, time-to-progression (TTP), and survival. METHODS: Serum DNA from 78 patients was purified and spectrophotometrically quantified. RESULTS: No significant correlations were found between serum DNA concentration and age, histology, response and survival. There was a significant correlation with respect to stage (IIIB = 408.75 ng/ml; IV = 478.74 ng/ml; p = 0.02). When patients were grouped according to DNA concentration, significant correlation with TTP was found; establishing a cut-off point at 500 ng/ml ([DNA] < 500 ng/ml TTP = 7.25 months, 95%CI: 3.5-5.25; [DNA ] > or = 500 ng/ml TTP = 4.25 months, 95%CI: 2-6.5; p = 0.05). CONCLUSIONS: Using the present method, DNA concentration quantification appears to be simple, but with certain deficiencies due to inter-sample variability and low specificity. This is because total DNA concentration is measured without distinguishing as to whether it is tumour-related. We suggest that there is a correlation between DNA concentration and prognosis which enables an analysis of the natural history of the disease.