Limited distribution of pertussis toxin in rat brain after injection into the lateral cerebral ventricles.

In vivo administration of pertussis toxin is often used to study the involvement of guanine nucleotide binding proteins in signal transduction. Especially when it is administered in the brain the effect is often poor. This could be due to the fact that pertussis toxin does not reach the area of interest. To evaluate the extent to which pertussis toxin is distributed in rat brain after intraventricular injection, different techniques were used. Immunohistochemical studies with an antibody against pertussis toxin showed that immunoreactivity was limited to periventricular brain structures less than 0.5 mm from the lumen. The highest immunoreactivity was seen 16-24 h after injection. After 96 h the labeling was very weak. The proportion of guanine nucleotide binding proteins that were ADP-ribosylated by in vivo injection of pertussis toxin into the ventricles as assessed by in vitro [32P]-back-ADP-ribosylation was very low 48 h after the injection, in all regions studied. Direct injection of pertussis toxin into the brain caused a marked ADP-ribosylation localized to the region injected that was maximal at 72 h after injection. At 96 h there were also effects after control injections, indicating non-specific effects. Synaptosomal membranes and other membranes were equally affected by pertussis toxin. The results suggest that in studies regarding the effect of pertussis toxin treatment on signal transduction, the toxin must be injected very close to the brain region of interest and, furthermore, that the rats should be killed 48-72 h after injection. In case of lack of effect on the response of interest one should examine whether the ADP-ribosylation of pertussis toxin-sensitive guanine nucleotide binding proteins in the area of concern has been affected.     

Comparison of direct planimetry of mitral valve regurgitation orifice area by three-dimensional transesophageal echocardiography to effective regurgitant orifice area obtained by proximal flow convergence method and vena contracta area determined by color Doppler echocardiography

Direct measurement of anatomic regurgitant orifice area (AROA) by 3-dimensional transesophageal echocardiography was evaluated for analysis of mitral regurgitation (MR) severity. In 72 patients (age 70.6 ± 13.3 years, 37 men) with mild to severe MR, 3-dimensional transesophageal echocardiography and transthoracic color Doppler echocardiography were performed to determine AROA by direct planimetry, effective regurgitant orifice area (EROA) by proximal convergence method, and vena contracta area (VCA) by 2-dimensional color Doppler echocardiography. AROA was measured with commercially available software (QLAB, Philips Medical Systems, Andover, Massachusetts) after adjusting the first and second planes to reveal the smallest orifice in the third plane where planimetry could take place. AROA was classified as circular or noncircular by calculating the ratio of the medial-lateral distance above the anterior-posterior distance (≤1.5 compared to >1.5). AROA determined by direct planimetry was 0.30 ± 0.20 cm2, EROA determined by proximal convergence method was 0.30 ± 0.20 cm2, and VCA was 0.33 ± 0.23 cm2. Correlation between AROA and EROA (r = 0.96, SEE 0.058 cm2) and between AROA and VCA (r = 0.89, SEE 0.105 cm2) was high considering all patients. In patients with a circular regurgitation orifice area (n = 14) the correlation between AROA and EROA was better (r = 0.99, SEE 0.036 cm2) compared to patients with noncircular regurgitation orifice area (n = 58, r = 0.94, SEE 0.061 cm2). Correlation between AROA and EROA was higher in an EROA ≥0.2 cm2 (r = 0.95) than in an EROA <0.2 cm2 (r = 0.60). In conclusion, direct measurement of MR AROA correlates well with EROA by proximal convergence method and VCA. Agreement between methods is better for patients with a circular regurgitation orifice area than in patients with a noncircular regurgitation orifice area.     

Mixed gonadal dysgenesis in a patient with de novo tas(Y;19)(p11.3;q13.4) and 45,X mosaicism

We report a patient with a de novo telomeric association between chromosomes 19 and Y in conjunction with mixed gonadal dysgenesis. The patient was first admitted to the clinic because of abnormal external genitalia. Laparoscopic evaluation revealed (1) a rudimentary uterus, one fallopian tube, and a small gonad resembling an ovary on the right side, and (2) an immature fallopian tube, a vas deferens, and a gonad resembling a testis on the left side. Conventional cytogenetic analysis performed on cultivated peripheral blood cells, and tissue obtained from the phallus and a gonadal structure which resembled a testis revealed two different cell lines with the 46,X,tas (Y;19)(p11.3;q13.4) and 45,X karyotype. Y chromosome microdeletion analysis showed that the patient did not have any genomic deletions in the AZFa, b, c, or SRY regions on the long arm of the Y chromosome. This is the first report of a patient with mixed gonadal dysgenesis that is accompanied by a telomeric association between chromosomes 19 and Y with 45,X mosaicism.     

Effects of glutamine and curcumin on bacterial translocation in jaundiced rats

AIM: To investigate the effect of curcumin on bacterial translocation and oxidative damage in an obstructive jaundice model and compare the results to glutamine, an agent known to be effective and clinically used. METHODS: Twenty-four female Wistar-Albino rats, weighing 200-250 g, were randomly divided into three groups (8 in each group). After ligation of the common bile duct in all animals, GroupⅠ received oral normal saline, Group Ⅱ received oral glutamine and Group Ⅲ received oral curcumin for seven day...     

Possible role of pure human follicle-stimulating hormone in the treatment of severe male-factor infertility by assisted reproduction: preliminary report

OBJECTIVE: Experimental clinical trial assessing the potential of systemic follicle-stimulating hormone (FSH) to improve sperm fertilizing ability in in vitro fertilization (IVF). DESIGN: Retrospective clinical evaluation of severe male factor patients failing fertilization in IVF or showing severe sperm defects. SETTING: Academic tertiary clinical care unit. PATIENTS, PARTICIPANTS: Fourteen patients (41 cycles) who failed IVF, 22 patients (32 cycles) with severe quantitative and qualitative semen abnormalities indicating poor fertilization. INTERVENTIONS: Treatment: FSH 150 U IM three times a week for 3 months. MAIN OUTCOME MEASURE(s): Pretreatment and post-treatment evaluation of endocrine profile, basic semen analysis, and fertilization and pregnancy rates. Hypothesis: FSH treatment may improve spermatogenesis quality by its multiple actions on the Sertoli-gamete cell compartment without interfering with testicular hormonogenic function. RESULTS: No significant changes were observed in the endocrine profile or in semen parameters; individual cases showed improvements in sperm concentration and motility. Significant increase in fertilization rate of preovulatory oocytes was demonstrated; seven term pregnancies were achieved. CONCLUSIONS: A multicenter randomized, double-blind trial with crossover is needed to demonstrate the benefit of systemic FSH administration and if this effect is FSH exclusive.     

Histopathological changes of cervical tissue in women with systemic sclerosis

Systemic sclerosis is a connective tissue disease that can affect almost any organ of the body. The clinical aspects of systemic sclerosis on the reproductive system have been studied in large series, and an increased rate of cesarean section has been reported. For this reason, in the present study the histopathological features of cervical specimens of hysterectomyzed women with systemic sclerosis were evaluated. An increased frequency of vascular and stromal abnormalities in cervical specimens of women with systemic sclerosis were observed. Vascular medial hypertrophy, intimal thickening, and fibrosis were more often encountered in the cervical specimens of the patients with systemic sclerosis. Some of the histopathological features also showed correlation with the clinical profile of the disease. The patients with vascular medial hypertrophy in their cervical specimens were older, had a higher Rodnan score, and had longer duration of the disease. In contrast to vascular medial hypertrophy, periadventitial edema was found in the cervical specimens of the patients who were younger, had a lower Rodnan score, and had shorter duration of the disease. It was concluded that the problems that are seen in common obstetric and gynecological practices in patients with systemic sclerosis may be explained by these tissue abnormalities.     

Effect of sedation with midazolam or propofol on patient's comfort during cancer chemotherapy infusion: a prospective, randomized, double-blind study in breast cancer patients

Nausea, vomiting and anxiety related to administration of cancer chemotherapy remain significant problems. This randomized, clinical trial was undertaken to evaluate the effect of sedation on the patient's comfort during chemotherapy infusion in patients with breast cancer. Forty-five breast cancer patients were randomized into three groups: Group I--chemotherapy, control, Group II--midazolam+chemotherapy, and Group III--propofol+chemotherapy. Nausea occured in 87% and vomiting in 13% of the patients in the control group, while none of the sedated subjects had these side-effects, although 76% of them had experienced then during previous cycles of chemotherapy. Compared with the control group, post-chemotherapy anxiety scores also improved with the addition of midazolam or propofol. Eighty percent of the subjects declared that they would prefer the sedative-containing regimen for their further cycles. Sedation with midazolam or propofol may improve the patient's comfort, and provide better control of chemotherapy-related side effects during chemotherapy infusion in breast cancer patients.     

An in vivo platform for translational drug development in pancreatic cancer.

Effective development of targeted anticancer agents includes the definition of the optimal biological dose and biomarkers of drug activity. Currently available preclinical models are not optimal to this end. We aimed at generating a model for translational drug development using pancreatic cancer as a prototype. Resected pancreatic cancers from 14 patients were xenografted and expanded in successive groups of nude mice to develop cohorts of tumor-bearing mice suitable for drug therapy in simulated early clinical trials. The xenografted tumors maintain their fundamental genotypic features despite serial passages and recapitulate the genetic heterogeneity of pancreatic cancer. The in vivo platform is useful for integrating drug screening with biomarker discovery. Passages of tumors in successive cohorts of mice do not change their susceptibility to anticancer agents and represent a perpetual live bank, facilitating the application of new technologies that will result in the creation of an integrated stable database of tumor-drug response data and biomarkers.     

Issues in surgical treatment of thoraco-lumbar injuries associated with spinal cord injuries in children and adolescents

To evaluate standards of care in surgical treatment of thoracolumbar injuries (TLIs), we reviewed the cases of 79 surgically treated patients (39 males, 36 females) with TLIs and spinal cord injuries occurring from January 1985 to January 2000. We assessed radiographs of fracture-dislocation reductions; restorations of sagittal and coronal alignment of injured segments; instrumentation levels and strategies; operations, and reoperations. Mean age at time o f injury was 14.1 years. The majority of injuries were thoracic, and posterior spinal fusion with instrumentation was the most common index procedure performed. Mean follow-up was 23.4months. Reoperation rate was 20%.Problems in achieving fracture reduction, selecting correct instrumentation levels, restoring proper sagittal alignment, an d planning a nd performing surgeries were more prevalent in patients treated before 1990 but are still problematic, even with use of modern segmental instrumentation, and frequently require revision to improve function or relieve symptoms. These results indicate a wide range in standards of care in surgical treatment of TLIs.