A Family Demonstrating Inheritance of the Leach Phenotype: a Gerbich-Negative Phenotype Associated with Elliptocytosis

One third of very weakly Rh-immunized women show no increase in their level of Rh immunization during pregnancy and after delivery. Administration of 300 micrograms of Rh immune globulin at 6-week intervals does not alter the incidence of lack of progression of Rh immunization in such women. Thirty-three Rh-positive women who ultimately delivered ABO-compatible babies, had Kleihauer fetal transplacental hemorrhage (TPH) screening tests carried out at 2-week intervals during pregnancy and shortly after delivery. One third of the 33 women had no detectable TPH or a TPH of 0.01 ml of fetal red cells. We conclude that one third of weakly Rh-immunized women failed to show any progression of their Rh immune response during pregnancy or after delivery because they were exposed to too few fetal red cells (0.01 ml or less) to produce such a response.     

Defining the anatomic perfusion bed of an occluded coronary artery and the region at risk to infarction: A comparative study in the baboon, pig and dog

To assess selectively the effectiveness of therapeutic interventions to reduce infarct size, it is important to assess both ultimate infarct size as well as the size of the region of myocardium at risk to infarction. The anatomically defined perfusion bed of an occluded artery has generally been assumed to be synonymous with the region at risk of infarction. This assumption was tested by delineating the anatomic perfusion bed of an occluded artery with microvascular dyes and by examining the relation of the anatomic perfusion bed to the region of acute ischemic injury. In 8 baboons, 12 pigs and 15 dogs a major branch of the left anterior descending or left circumflex coronary artery was occluded. At 2 and 30 minutes after occlusion the eplcardial area of ischemic injury was determined by epicardial S-T segment mapping. The boundary of epicardial S-T segment elevation was resolved to within 1 mm and marked directly on the ventricular surface. The heart was then excised and the perfusion bed of the occluded artery was delineated by either (1) injecting different colored silicone rubber microvascular dyes into the previously occluded artery as well as the adjacent perfusion beds (direct method), or (2) injecting dye only into the adjacent perfusion beds (defect method).

Serial cross-sections of the left ventricle from the direct and defect dye-perfused hearts in all three species showed the perfusion bed of the occluded artery to be readily demarcated. Microscopic examination demonstrated no evidence of capillary anastomoses and minimal inter-digitation of capillaries at the perfusion bed boundaries. In dye-perfused hearts, the baboon and the pig showed no evidence of precapillary anastomoses between perfusion beds; however, the dog demonstrated numerous epicardial collateral channels. The epicardial area of the anatomic perfusion bed correlated closely with the epicardial area of S-T segment elevation at 2 minutes after occlusion in the baboon (r = 0.97), pig (r = 0.99) and dog (r = 0.96). The epicardial area of S-T segment elevation did not change through the 30 minute period of occlusion in the baboon and the pig, but in the dog it showed a progressive and variable reduction reflecting the gradual recruitment of existing collateral channels from adjacent perfusion beds.

It is concluded that the techniques of direct and defect dye delineation accurately define the anatomic perfusion bed of an occluded coronary artery. This anatomic perfusion bed corresponds to the region of myocardium undergoing acute ischemic injury and hence the region at risk to infarction immediately after coronary occlusion in the three species studied.     

Extrapulmonary sarcoidosis

Sarcoidosis can affect any organ in the body. Frequently extrapulmonary manifestations of the disease are the major cause of morbidity. Treatment of extrapulmonary sarcoidosis often requires consideration of alternative immunosuppressive agents, topical therapy, or therapy that is not specifically directed against the granulomatous inflammation of the disease. This article reviews the clinical presentation and therapy of extrapulmonary sarcoidosis.     

Fine-needle aspiration may miss a third of all malignancy in palpable thyroid nodules: a comprehensive literature review

BACKGROUND: Fine-needle aspiration (FNA) is currently the primary diagnostic procedure in diagnosing thyroid malignancy and guides surgeons on patient selection for thyroidectomy for thyroid nodules. Diagnostic sensitivity is reported to be approximately 80%; however, patients with negative FNA results do not necessarily undergo surgery and are often not considered in statistical analysis. This may lead to bias in previous reported sensitivity of FNA. The aim of this study was to assess the diagnostic performance attributes of FNA based on a comprehensive review and summary of previous literature. METHODS: A comprehensive review of published literature from 1966 to 2005 was performed, using structured selection and appraisal methods to include all studies that have assessed the sensitivity of FNA for detecting thyroid malignancy in palpable thyroid nodules. A statistical modeling study was designed to estimate the possible true sensitivity and specificity of FNA. RESULTS: Twelve studies fulfilled inclusion criteria and were included in the review. Only 1 study had greater than 25% of patients with negative FNA results who proceeded to thyroidectomy. Statistical modeling indicated that the sensitivity of FNA is highly dependent on the risk of malignancy in the patients with negative FNA results who did not undergo thyroidectomy; in the "same risk" scenario, where the risk of malignancy in the whole group with negative FNA result was assumed to be the same as that in patients with negative FNA results who underwent surgical biopsy; sensitivity could be as low as 66% (confidence interval [CI]: 65-68%). CONCLUSION: Based on existing reports, the true diagnostic attributes of FNA for thyroid malignancy in palpable nodules are uncertain and FNA could miss up to a third of all thyroid malignancy. Further research is required to investigate the incidence of malignancy in FNA negative cases and to determine the additive effect of clinical judgment.     

Cognitive function and treatment response in a randomized clinical trial of computer-based training in cognitive-behavioral therapy

Cognitive-behavioral therapy (CBT), because of its comparatively high level of cognitive demand, is likely to be challenging for substance users with limitations in cognitive function. However, it is not known whether computer-assisted versions of CBT will be particularly helpful (e.g., allowing individualized pace and repetition) or difficult (e.g., via complexity of computerized delivery) for such patients. In this secondary analysis of data collected from a randomized clinical trial evaluating computer-assisted CBT, four aspects of cognitive functioning were evaluated among 77 participants. Those with higher levels of risk taking completed fewer sessions and homework assignments and had poorer substance use outcomes.     

Endoscopic sphincterotomy and interval cholecystectomy are reasonable alternatives to index cholecystectomy in severe acute gallstone pancreatitis (GSP)

BACKGROUND: UK guidelines for gallstone pancreatitis (GSP) advocate definitive treatment during the index admission, or within 2 weeks of discharge. However, this target may not always be achievable. This study reviewed current management of GSP in a university hospital and evaluated the risk associated with interval cholecystectomy. METHODS: All patients that presented with GSP over a 4-year period (2002-2005) were stratified for disease severity (APACHE II). Patient demographics, time to definitive therapy [index cholecystectomy; endoscopic sphincterotomy (ES); Interval cholecystectomy], and readmission rates were analysed retrospectively. RESULTS: 100 patients admitted with GSP. Disease severity was mild in 54 patients and severe in 46 patients. Twenty-two patients unsuitable for surgery underwent ES as definitive treatment with no readmissions. Seventy-eight patients underwent cholecystectomy, of which 40 (58%) had an index cholecystectomy, and 38 (42%) an interval cholecystectomy. Only 10 patients with severe GSP had an index cholecystectomy, whilst 30 were readmitted for Interval cholecystectomy (p = 0.04). The median APACHE score was 4 [standard deviation (SD) 3.8] for index cholecystectomy and 8 (SD 2.6) for Interval cholecystectomy (p < 0.05). Median time (range) to surgery was 7.5 (2-30) days for index cholecystectomy and 63 (13-210) days for Interval cholecystectomy. Fifty percent (19/38) of patients with GSP had ES prior to discharge for interval cholecystectomy. Two (5%) patients were readmitted: with acute cholecystitis (n = 1) and acute pancreatitis (n = 1) , whilst awaiting interval cholecystectomy. No mortality was noted in the Index or Interval group. CONCLUSIONS: This study demonstrates that overall 62% (22 endoscopic sphincterotomy and 40 index cholecystectomy) of patients with GSP have definitive therapy during the Index admission. However, surgery was deferred in the majority (n = 30) of patients with severe GSP, and 19/30 underwent ES prior to discharge. ES and interval cholecystectomy in severe GSP is associated with minimal morbidity and readmission rates, and is considered a reasonable alternative to an index cholecystectomy in patients with severe GSP.     

A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days

Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial. Preclinical studies showed antitumour activity in a broad range of human tumour xenografts. A phase I trial was performed with a 7-day b.i.d. p.o. schedule. Twenty-one patients (median age 62 years, range: 39-73 years) were treated with doses of 100, 200 and 800 b.i.d. Dose-limiting toxicities were seen at 800 mg b.i.d.; grade 3 fatigue, grade 3 skin rash, grade 3 hyponatraemia and grade 4 hypokalaemia. Other toxicities included reversible raised creatinine (grade 2), reversible grade 3 abnormal liver function and grade 2 emesis. An 800 mg portion was investigated further in 12 patients, three of whom had MAG3 renograms. One patient with a rapid increase in creatinine on day 3 had a reversible fall in renal perfusion, with full recovery by day 14, and no changes suggestive of renal tubular damage. Further dose escalation was precluded by hypokalaemia. Seliciclib reached peak plasma concentrations between 1 and 4 h and elimination half-life was 2-5 h. Inhibition of retinoblastoma protein phosphorylation was not demonstrated in peripheral blood mononuclear cells. No objective tumour responses were noted, but disease stabilisation was recorded in eight patients; this lasted for a total of six courses (18 weeks) in a patient with ovarian cancer.     

The Story of the Texas Pain Society: Formation and Function of a Regional Pain Society

Abstract: The idea of forming a Texas Pain Society came to the Founders in 1987 due to disparity and deficiencies in the practice of pain management in the United States and, in particular, the State of Texas. The Founders considered very carefully the implication of forming such a society. They diligently mapped out the mission and goals of the Texas Pain Society in those early formative years. This report is the history of Texas Pain Society as the activities unfolded from 1989 to 2011. The reader may question why there is a need to tell such a story. We believe strongly that, with disparities of standards of practice in pain medicine and poor recognition of advances in pain management, this scenario is quite common in many states and countries. The practitioners of pain management in these regions certainly must have considered getting together and forming a consensus on the standards of practice in their communities. This historical report of the Texas Pain Society provides the relevant information necessary and the efforts to be made for a society’s mission to achieve its goals and have an ongoing impact in its own region. We hope that we have shed some light on a process for the formation of a regional pain society such as ours. ?