Arteriovenous perfusion with the pulmonary assist membrane oxygenator.

The feasibility of employing a recently developed pulmonary assist membrane oxygenator for partial respiratory support in arteriovenous perfusion was studied using small mongrel dogs rendered hypoxic by oxygen depression. The unit is employed along with the conventional ventilation techniques (such as CPAP and PEEP) when the latter alone cannot maintain adequate gas exchange in the lung. The results indicate that poorly oxygenated arterial blood can be upgraded to life-sustaining levels when the bypass flow rate through the oxygenator is in the range of 18-33% of the total cardiac output. No cardiovascular derangements were noted at these arteriovenous flow rates for perfusion periods of four to six hours. The present results demonstrate the feasibility of providing partial support to pulmonary function using the pulmonary assist membrane oxygenator.     

The Synergistic Action of Antibodies.: A Method to Increase the Sensitivity of the Lymphocyte Microcytotoxicity Test

Abstract. A method, based on the synergistic action of two antibody systems, is suggested as a lymphocyte cross-match test. To donor lymphocytes in the serum of the recipient a rabbit anti-human lymphocyte antibody, in sublytic quantities, is added before the addition of the complement. Results obtained with this test in tissue typing sera are compared to the lymphocyte microcytotoxicity test. It could be shown that the new test is more sensitive than the ordinary microcytotoxicity test.     

French hormones: progestins and therapeutic variation in France

Western medicine is seen as universally valid, but in reality it displays a wide range of national and local variability. Our paper focuses on one such case of local variation: the widespread use of progestins in France to treat various pre-menopausal conditions as well as for contraception. The case of progestins allows us to explore how specific styles of research may come to dominate a particular local medical culture, and how they are influenced by changing criteria of scientific validity and wider social relations. We argue that in the 1980s and 1990s a single prestigious research-oriented Parisian hospital service played a dominant role in the transformation of progestins into scientifically validated medical practice. This status was not called seriously into question until recently when foreign research on a different form of hormone therapy suggested that risk was associated with their use. We also propose that both the research around and medical use of progestins in France was shaped by the positive attitude of many French women, including feminists, to hormonal therapies and to the non-surgical specialty most closely associated with hormones, medical gynaecology.     

An empirical evaluation of Tukey's control chart for use in health care and quality management applications

Recently in this journal, F. Alemi (Qual Manage Health Care. 2004;13(4):216-221) proposed the use of Tukey's Control Chart because of the unique benefits associated with nonparametric inferential statistics including robust performance with (1) low N sizes, (2) nonnormal data, and (3) the presence of outliers, However, an assumption that applies to virtually all inferential statistical procedures (parametric and nonparametric) is that the observations in question are independent from each other. Unfortunately, there is good reason to suspect violation of this assumption when evaluating quality processes over time (as is often the case in health care settings). In this article, the power (ability to detect real changes in a data process) and type I error (probability of false positives) performance of Tukey's Control Chart technique is empirically evaluated. When observations are not independent, Tukey's Control Chart technique demonstrates unacceptable type I error performance. Additionally, regardless of whether observations are independent, the technique demonstrates low power to detect real effects unless the effects are quite large.     

Severely compromised quality of life in women and those of lower socioeconomic status waiting for joint replacement surgery

OBJECTIVE: To determine health-related quality of life (HRQOL), psychological distress, physical function, and self efficacy in persons waiting for lower-limb joint replacement surgery. METHODS: A total of 214 patients on a waiting list for unilateral primary total knee or hip replacement at a large Australian public teaching hospital completed questionnaires after entry to the list. HRQOL and psychological distress were compared with available population norms. RESULTS: Average HRQOL was extremely poor (mean +/- SD 0.39 +/- 0.24) and much lower (>2 SD) than the population norm. Near death-equivalent HRQOL or worse than death-equivalent HRQOL were reported by 15% of participants. High or very high psychological distress was up to 5 times more prevalent in the waiting list sample (relative risk 5.4 for participants ages 75 years and older; 95% confidence interval 3.3, 9.0). Women had significantly lower HRQOL, self efficacy, and physical function scores than men. After adjusting for age and sex, significant socioeconomic disparities were also found. Participants who received the lowest income had the poorest HRQOL; those with the least education or the lowest income had the highest psychological distress. Low self efficacy was moderately associated with poor HRQOL (r = 0.49, P < 0.001) and more strongly associated with high psychological distress (r = -0.55, P < 0.001). CONCLUSION: Patients waiting for joint replacement have very poor HRQOL and high psychological distress, especially women and those from lower socioeconomic backgrounds. Lengthy waiting lists mean patients can experience extended and potentially avoidable morbidity. Interventions to address psychological distress and self efficacy could reduce this burden and should target women and lower socioeconomic groups.     

p57Kip2 (cdkn1c): sequence, splice variants and unique temporal and spatial expression pattern in the rat pancreas

The cyclin-dependent kinase (CDK) inhibitor p57Kip2 (CDKN1C) is a negative regulator of cell proliferation, binding to a variety of cyclin-CDK complexes and inhibiting their kinase activities in vitro. The p57Kip2 gene is imprinted and the maternal allele is expressed in terminally differentiated cells, including human beta-cells. Somatic loss of p57Kip2 expression is associated with increased beta-cell proliferation in the focal form of Hyperinsulinism of Infancy. We cloned and sequenced the rat ortholog of p57Kip2, and demonstrate that it is highly homologous to the mouse gene. However, the human and rodent genes are quite divergent. Despite having highly homologous C- and N-terminal domains, the mid-portion of the human gene is entirely different from that of its rodent counterparts. Expression of p57Kip2 was evaluated during fetal and postnatal development, and a highly cell-specific, temporal and spatial expression profile was found. In contrast to other tissues, the expression pattern in rat pancreas was entirely opposite from that previously reported in man, with high levels of expression in rodent exocrine cells, but no expression in beta-cells during any stage of development. These findings demonstrate that p57Kip2 expression is highly regulated. In the pancreas, the functional significance of this gene appears to be quite different in humans when compared with rodents, suggesting that a better understanding of the function of this protein may provide new insights into the mechanisms involved in the control of human beta-cell mass.     

Long-term stability study of L-adrenaline injections: Kinetics of sulfonation and racemization pathways of drug degradation

Injectable formulations of L-adrenaline are commonly used in emergency medicine. Despite numerous studies, the comparative contribution and kinetics of the L-adrenaline inactivation pathways during storage have not been conclusively evaluated. We examined the kinetics of L-adrenaline degradation in a prospective study and determined the extent of drug inactivation by different pathways during and beyond the stipulated product shelf-life in 42 batches of adrenaline ampules stored under controlled conditions. The content of L-adrenaline and degradation products was determined with a chiral high-performance liquid chromatography (HPLC) assay, and the degradation products were identified by mass spectrometric detection as D-adrenaline and L- and D-adrenaline sulfonate. The kinetics of the content change with storage was analyzed simultaneously for L-adrenaline and the degradation products using kinetic modeling. The lower acceptable level of adrenaline content in the formulation stated by US Pharmacopoeia (90% as a sum of L- and D-isomers) was attained after 2.0 years of storage, at which time the content of the therapeutically active L-isomer amounted to as low as 85%. The modeling revealed significant differences in the degradation kinetics in the formulations produced before and after 1997, whose cause remained unidentified in this study.