Cytotoxicity of ethanol in primary cultures of rat midbrain neurons

Primary cultures of midbrain neurons were obtained from 15-day-old rat fetuses. Neuron cultures were exposed to ethanol (27 mM, 43 mM and 120 mM) for 24 h and evaluated by light microscopy, a viability measure, and protein content. Ethanol concentrations of 43 and 120 mM appeared to affect the cultures both in terms of cell viability and protein. This effect was independent of any osmotic effect, when sucrose was run as a control. We conclude that primary cultures of midbrain neurons are sensitive to relatively low concentrations of ethanol, compared to cell culture preparations used by other investigators.     

Botulinum Toxin Urethral Sphincter Injection Resolves Urinary Retention after Pubovaginal Sling Operation

The management of prolonged urinary retention following pubovaginal sling surgery typically involves transvaginal urethrolysis for anatomical urethral obstruction. Brubaker [1] recently reported on urethral sphincter abnormalities as a cause of postoperative urinary retention following either Burch suspension or a pubovaginal sling procedure. We report a case of functional urethral obstruction and detrusor acontractility following pubovaginal sling surgery that was successfully treated by botulinum A toxin urethral sphincter injection.     

The Clinical Conundrum of Corticotropin-independent Autonomous Cortisol Secretion in Patients with Bilateral Adrenal Masses

Background Management of patients with bilateral adrenal masses and corticotropin (ACTH)-independent Cushing syndrome (CS) or subclinical CS is problematic. We report our experience with adrenal venous sampling (AVS) in the evaluation of 10 patients with bilateral masses who had ACTH-independent CS or subclinical CS. Patients and Methods Ten patients (9 women, 1 man, mean age 56.4 years) with bilateral adrenal masses and ACTH-independent CS (n = 3) or subclinical CS (n = 7) underwent AVS. Autonomous cortisol secretion was documented in all cases with suppressed serum ACTH concentrations and lack of cortisol suppression with dexamethasone administration. Adrenal venous sampling was performed on the second day of dexamethasone administration. Cortisol and epinephrine levels were measured from each adrenal vein (AV) and from a peripheral vein (PV). Results Mean (± SD) maximal diameter of the adrenal masses on computed tomography was 3.3 ± 1.3 cm (range: 1.2–6.0 cm). Successful catheterization was confirmed with AV:PV epinephrine gradients. A cortisol AV:PV gradient >6.5 was consistent with a cortisol-secreting adenoma in 11 adrenal glands; 5 patients had clinically important bilateral autonomous cortisol hypersecretion, 3 had bilateral cortisol-secreting adenomas, and 2 had ACTH-independent macronodular adrenal hyperplasia. Adrenal venous sampling-guided adrenalectomy was completed in all 10 patients—2 patients had total bilateral adrenalectomy and 2 others had subtotal bilateral adrenalectomy. During a mean follow-up of 36.1 months (range: 0.7–123 months), CS or clinically important cortisol secretory autonomy did not recur. Conclusions Adrenal venous sampling contributed to the localization of autonomous hypercortisolism in the setting of ACTH-independent CS or subclinical CS in patients with bilateral adrenal masses. Presented at the Annual Meeting of the International Association of Endocrine Surgeons, Montreal, Canada, August 26–29, 2007. J. A. Carney is an Emeritus Member of the Department of Laboratory Medicine and Pathology.     

Analysis of Hurthle cell neoplasms of the thyroid by interphase fluorescence in situ hybridization.

Recent studies have indicated that numerical chromosomal abnormalities including changes in p53 and cyclin D1 may be involved in Hurthle cell tumorigenesis. We analyzed a series of Hurthle cell neoplasms of the thyroid to evaluate the diagnostic and prognostic utility of numerical anomalies by DNA fluorescent probes for cyclin D1 and p53 gene loci and chromosomes 5, 7, 11, 12, 17, and 22. Interphase fluorescence in situ hybridization (FISH) analysis was performed on paraffin-embedded tissue sections from 10 Hurthle cell adenomas, 19 Hurthle cell carcinomas, and 7 normal thyroid tissues used as controls. Directly labeled fluorescent DNA probes for the centromere region of chromosomes 7, 11, 12, and 17 and locus-specific probes for chromosomes 5 and 22, cyclin D1, and p53 were utilized for dual-probe hybridizations. Sixty percent (6 of 10) Hurthle cell adenomas and 63% (12 of 19) Hurthle cell carcinomas showed chromosome gains. Twenty percent (2 of 10) Hurthle cell adenomas and 26% (5 of 19) Hurthle cell carcinomas showed chromosome losses. Normal thyroid tissues used as controls showed no chromosomal abnormalities. Among Hurthle cell tumors with chromosomal abnormalities, adenomas averaged 2.7 gains and 0.3 losses per case, and carcinomas averaged 3.3 gains and 0.6 losses per case. The two adenomas with chromosome losses each showed loss of one chromosome, whereas the five carcinomas with losses averaged 1.8 losses per case. Chromosome 22 was the most common loss identified, occurring in three of the 11 patients who died of disease. These results indicate that chromosomal imbalances as gains are common in both benign and malignant Hurthle cell neoplasms, but Hurthle cell carcinomas tend to have more chromosome losses than adenomas. Among Hurthle cell carcinomas in this study, chromosome losses were identified only from patients who died of disease. The loss of chromosome 22 may have prognostic value in Hurthle cell carcinoma of the thyroid.     

Heel ultrasonography is not a good screening tool for bone loss after kidney and pancreas transplantation

BACKGROUND: Solid organ transplant recipients, particularly simultaneous pancreas kidney recipients, are at high fracture risk. We tested whether quantitative ultrasonography (QUS) of the heel predicts bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) in solid organ transplant recipients. METHODS: Thirty-eight transplant recipients (22 Female/16 Male) were studied. Spine and hip BMD was measured with a Hologic DXA scanner. 'Stiffness' of the heel was measured with a Lunar Ultrasound densitometer and compared with BMD by DXA. Contributing factors to bone loss were also assessed. RESULTS: Mean age was 43.1 +/- 1.3 yr. Simultaneous pancreas-kidney, kidney, and pancreas alone transplant recipients were assessed. Mean time post-transplantation was 3.0 +/- 0.6 yr. Mean DXA spine T-score was -1.15 +/- 0.22 (mean +/- SEM) and hip T-score was -1.22 +/- 0.20. There was no difference in mean T-score between women and men at the hip or spine. Mean right heel stiffness T-score was -0.97 +/- 0.25. There was no correlation between QUS and DXA at either the hip or spine in women or men. QUS had a false negative rate for identifying osteopenia or osteoporosis of 17% compared with DXA. The false positive rate for identifying osteopenia was 61%. CONCLUSIONS: The QUS is an unacceptable tool for identifying those at risk for bone loss after kidney or pancreas transplantation.     

Color Doppler sonography in the evaluation of erectile dysfunction: patterns of temporal response to papaverine.

Most studies of duplex Doppler sonography for the assessment of erectile dysfunction involve determination of peak systolic velocities 5 min after intracavernosal injection of papaverine. The purpose of this study was to determine the effect of the timing of Doppler measurements of flow after papaverine injection for establishing the presence of arterial and venous abnormalities. Color Doppler sonography was performed in 75 patients for evaluation of vasculogenic impotence. After intracavernosal injection of 60 mg of papaverine, measurements of peak systolic and end-diastolic velocities were obtained in each cavernosal artery at 5-min intervals for a total of 30 min. A peak systolic velocity of less than 25 cm/sec was used as the threshold for arterial insufficiency. An end-diastolic velocity of greater than 5 cm/sec was used to predict venous incompetence. Scanning was performed for direct assessment of dorsal venous flow. Thirty patients were subsequently evaluated by cavernosometry and cavernosography. In most patients (76%), maximum response to papaverine was achieved within the first 5 min. In eight patients, significant increases in systolic velocity were seen only after 5 min. In 10 patients, significant changes in end-diastolic velocity between 5 and 30 min resulted in diagnostic reclassification. Data acquisition for 30 min significantly improved the sensitivity (95%) and specificity (83%) for the prediction of venous incompetence in patients with correlative cavernosography. Transient, early dorsal vein flow was noted in normal subjects. Persistent dorsal vein flow had an 80% sensitivity and 100% specificity for venous incompetence. Our results suggest that, when using color Doppler sonography, gathering data for 30 min may improve the prediction of vasculogenic impotence.     

Color Doppler flow imaging

The performance requirements and operational parameters of a color Doppler system are outlined. The ability of an operator to recognize normal and abnormal variations in physiologic flow and artifacts caused by noise and aliasing is emphasized. The use of color Doppler flow imaging is described for the vessels of the neck and extremities, upper abdomen and abdominal transplants, obstetrics and gynecology, dialysis fistulas, and testicular and penile flow imaging.     

Practical selection criteria for unenhanced cranial CT in patients with acute headache

We studied clinical predictors of cranial computed tomography (CT) abnormalities in patients with acute or acutely worsened headache. Data were collected from chart review of 333 consecutive patients presenting to an emergency department and who were clinically selected for cranial CT. Patients with a positive neurologic examination were at 10.7 times greater risk for a positive CT than the rest of the sample (p<1.5 – 10⁻¹⁰). Using only neurologic examination to select patients for CT would have missed 30.3% of the positive scans. The amnesia, depressed sensorium, and hypertension variables had CT yields approximating 10% or greater even in the presence of a negative neurologic examination. Together with a positive neurologic examination, these variables detected 87.9% of the patients in this sample with positive scans; their absence had a negative predictive value of 98.0%. Of the four patients with positive scans who would have been missed using this strategy, one was discharged directly from the emergency department anyway and the other three developed positive neurologic examinations within 24 hours. One died of causes unrelated to the intracranial pathology. Positive neurologic examination, hypertension, history of amnesia, or a depressed sensorium provide reasonable initial guidelines to select for CT patients with an acute headache.     

The primary plasminogen-activator inhibitors in endothelial cells, platelets, serum, and plasma are immunologically related.

Monospecific antiserum to an unusually stable Mr 50,000 plasminogen-activator inhibitor (PAI) purified from cultured bovine aortic endothelial cells was employed in conjunction with reverse fibrin autography to determine whether human platelets, serum, and plasma contain immunologically related inhibitors. Reverse fibrin autography revealed the presence of a Mr 50,000 inhibitor in the platelet and serum samples but not in normal plasma. However, a Mr 50,000 inhibitor was detected in plasma obtained from individuals with increased PAI activity. In each case, treatment of the sample with the anti-inhibitor serum removed the Mr 50,000 inhibitor. The inhibitor present in each sample neutralized exogenously added tissue-type plasminogen activator in a rapid manner. Inhibition was associated with the formation of a NaDodSO4-resistant enzyme-inhibitor complex of Mr 120,000. Again, treatment of the samples with the anti-inhibitor serum removed both the inhibitory activity and the component in these samples that binds to tissue-type plasminogen activator. Thus, the rapidly acting PAI present in human platelets, serum, and patient plasma is immunologically related to the PAI synthesized by cultured bovine aortic endothelial cells. This molecule may be the physiologically relevant inhibitor of plasminogen activator in the vascular system and, as such, may serve an important role in regulating the initiation of vascular fibrinolysis.