Iatrogenic secondary post‐partum haemorrhage: Apropos of two uncommon cases

In this article we would like to highlight uterine pseudoaneurysm as a cause of secondary post‐partum haemorrhage following Caesarean section. We would like to stress Doppler ultrasound scan as the initial screening modality for this condition. We also describe angioembolization as the prudent treatment option for this condition rather than resorting to surgery.     

Clinical pharmacology research in the pediatric patient: the challenge continues

For most of the 20th century, most drugs labeled by the United States Food and Drug Administration (USFDA) have not been adequately studied in the pediatric population. This lack of data has necessitated the continued dependence of practitioners on sub-optimal prescribing data placing pediatric patients at great risk of serious therapeutic misadventures. Recently, the USFDA has enacted and begun to enforce the Final Rule of 1997 which became effective on 1 April 1999. This rule is the culmination of the persistent efforts of numerous professional organizations, clinicians, academicians, the USFDA and others, to ensure the ready availability of appropriate data for medications intended for or that will be used in children. Unlike the 1994 Rule which voluntarily required pharmaceutical manufacturers to submit pediatric data, the Final Rule mandates submission of such data and, most importantly, empowers the USFDA to afford incentives and penalties for non-compliance including possible removal of already marketed products. This overview addresses many of the important components which must be included in the performance of a comprehensive clinical pharmacologic evaluation serving as the foundation for optimal dosing across the broad age range encompassing pediatric practice. Furthermore, the possible risk and/or benefits of the study must be reasonably defined prior to undertaking the study and clearly shared with the patient's caregivers. Consent should always be obtained from the caregiver and, when appropriate, assent obtained from the underage child. To facilitate such clinical investigations and to foster collaborative efforts with innovators and clinical research programs, the National Institutes of Health through the National Institute of Child Health and Human Development of the NIH established a network of Pediatric Pharmacology Research Units. These units have worked closely together and with other pediatric research centers to facilitate USFDA labeling of a number of commonly used medications. All of these very positive efforts highlight the many challenges that remain for the pediatric investigator and practitioner while underscoring the very positive environment in support of these efforts.     

Transepithelial paracellular leakiness induced by chronic phorbol ester exposure correlates with polyp-like foci and redistribution of protein kinase C-alpha

Although exposure of LLC-PK1 epithelial cell sheets to phorbol esters (TPA) causes a near immediate and total decrease of transepithelial electrical resistance (TER), continuation of exposure for 3 to 4 days results in a tachyphylactic response as TER begins to return to control levels. Recovery of TER is maximal by 5 to 6 days, but reaches only 70 to 80% of control level. A reciprocal change in the transepithelial flux of D-mannitol indicates that the TER decrease is indicative of an increase in tight junction permeability. Exposure of cell sheets to TPA for several days also results in the appearance of multilayered polyp- like foci (PLFs) across the otherwise one cell layer thick cell sheets. The pattern of penetration of the electron dense dye, ruthenium red, from the apical surface, across the tight junction and into the lateral intercellular space indicates that the tight junctions of the cell sheet become uniformly leaky after acute exposure to TPA. However, when exposure is continued for several days, only the junctions of cells in the PLFs manifest leakiness. The decrease in TER following acute TPA exposure correlates with the translocation of protein kinase C-alpha (PKC alpha) into a membrane-associated compartment. With exposure of several days, only a trace of PKC alpha is visible by Western immunoblot, and this is in the membrane-associated compartment. Immunofluorescent microscopy indicates that the trace of PKC alpha seen in the Western immunoblots is ascribable distinctly to cells of the PLFs. Monolayer areas between PLFs show no discernible immunofluorescent signal. The data therefore indicate that tight junction barrier function may be restored in certain areas by the down regulation of PKC alpha from the membrane-associated compartment. Failure to down regulate may result in the paracellular leakiness and abnormal cell architecture of the PLFs. Possible implications of this model for in vivo epithelial tumor promotion are discussed.      

Sputum tumour necrosis factor-alpha and leukotriene concentrations in cystic fibrosis

It is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to lung injury. Tumour necrosis factor-alpha (TNF-alpha) may play a part in that process and in the generation of leukotrienes. Therefore, the relationships between sputum TNF-alpha, leukotriene concentration, and lung function abnormalities in 16 children with cystic fibrosis were investigated. Each subject provided sputum samples and performed spirometry. TNF-alpha was measured by enzyme linked immunosorbent assay; individual leukotrienes were separated using high performance liquid chromatography and quantified by radioimmunoassay. The geometric mean concentration of TNF-alpha was 129.7 pg/ml and 95% confidence interval 48.2 to 348.3. Mean (SEM) leukotriene B4 (LTB4) was 97.8 (22.9) pmol/g and total cysteinyl leukotrienes were 60.9 (14.8) pmol/g. Mean (SD) forced expiratory volume in one second (FEV1) of the group was 53 (15)% of predicted and forced vital capacity (FVC) was 65 (14)% of predicted. There was a significant positive correlation between TNF-alpha and both LTB4 and the total cysteinyl leukotriene sputum content. An inverse relationship existed between TNF-alpha and FEV1 and FVC. Moreover, a negative correlation was observed between sputum LTB4 and FEV1 and FVC. These results suggest that TNF-alpha and the leukotrienes may participate in the airways inflammation and airflow obstruction observed in cystic fibrosis subjects and support the hypothesis that TNF-alpha upregulates the 5-lipoxygenase pathway in vivo.     

A new amino acid mixture permits new approaches to the treatment of phenylketonuria

A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance.     

Preoperative balloon occlusion: “the intravascular ligature”

The resection of cerebral arteriovenous malformations may be difficult or very hazardous when access to the feeding arteries is limited by overlying large draining veins. Properative occlusion of feeding arteries can be performed using detachable flow-directed balloons.     

Effects of a malpractice crisis on specialist supply and patient access to care

OBJECTIVE: To investigate specialist physicians' practice decisions in response to liability concerns and their perceptions of the impact of the malpractice environment on patient access to care. SUMMARY BACKGROUND DATA: A perennial concern during "malpractice crises" is that liability costs will drive physicians in high-risk specialties out of practice, creating specialist shortages and access-to-care problems. METHODS: Mail survey of 824 Pennsylvania physicians in general surgery, neurosurgery, orthopedic surgery, obstetrics/gynecology, emergency medicine, and radiology eliciting information on practice decisions made in response to rising liability costs. RESULTS: Strong majorities of specialists reported increases over the last 3 years in patients' driving distances (58%) and waiting times (83%) for specialist care or surgery, waiting times for emergency department care (82%), and the number of patients forced to switch physicians (89%). Professional liability costs and managed care were both considered important contributing factors. Small proportions of specialists reported that they would definitely retire (7%) or relocate their practice out of state (4%) within the next 2 years; another third (32% and 29%, respectively) said they would likely do so. Forty-two percent of specialists have reduced or eliminated high-risk aspects of their practice, and 50% are likely to do so over the next 2 years. CONCLUSIONS: Our data suggest that claims of a "physician exodus" from Pennsylvania due to rising liability costs are overstated, but the malpractice situation is having demonstrable effects on the supply of specialist physicians in affected areas and their scope of practice, which likely impinges upon patients' access to care.     

Estimating Australia's abortion rates 1985-2003

AIM: To estimate national rates of induced abortion in Australia from 1985 to 2003, using Medicare claim statistics for private patients and hospital morbidity statistics for public patients. DESIGN AND SETTING: Estimates were based on Australian and South Australian data collections relating to abortions. SA hospital morbidity statistics were compared with SA statutory notifications of abortions to estimate the accuracy of these collections. Medicare statistics on abortion procedures performed on private patients in South Australia were then compared with hospital morbidity statistics for private patients. National statistics on abortion derived from Medicare and hospital morbidity statistics were adjusted for inaccuracies found in these sources. MAIN OUTCOME MEASURES: Numbers of induced abortions in Australia for each year from 1985 to 2003; abortion rates per 1000 women aged 15-44 years. RESULTS: Abortion numbers based on Medicare claims by private patients overestimated by 18.7% the number of abortions derived from statutory notifications in South Australia during the period 1988-89 to 1999-00. Hospital morbidity data using principal diagnosis codes relating to medical abortion overestimated statutory notifications by 2.3% (mainly because of readmissions). National statistics were adjusted for these overestimations and for the estimated 14.1% of private patients who would not have submitted Medicare claims (based on surveys of private-clinic patients in New South Wales and Victoria). The estimated Australian abortion rate increased from 17.9 per 1000 women aged 15-44 in 1985 to a peak of 21.9/1000 in 1995, then declined to 19.7/1000 in 2003 (estimated number of abortions, 84,460). CONCLUSION: There are no data currently available for deriving accurate numbers of induced abortions in Australia. Suggestions are made for collection of national statistics.     

Impact of malpractice reforms on the supply of physician services

Context  Proponents of restrictions on malpractice lawsuits claim that tort reform will improve access to medical care. Objective  To estimate the effects of changes in state malpractice law on the supply of physicians. Design  Differences-in-differences regression analysis that matched data on the number of physicians in each state between 1985 and 2001 from the American Medical Association’s Physician Masterfile with data on state tort laws and state demographic, political, population, and health care market characteristics. Main Outcome Measure  Effect on physician supply of "direct" malpractice reforms that reduce the size of awards (eg, caps on damages). Results  The adoption of "direct" malpractice reforms led to greater growth in the overall supply of physicians. Three years after adoption, direct reforms increased physician supply by 3.3%, controlling for fixed differences across states, population, states’ health care market and political characteristics, and other differences in malpractice law. Direct reforms had a larger effect on the supply of nongroup vs group physicians, on the supply of most (but not all) specialties with high malpractice insurance premiums, on states with high levels of managed care, and on supply through retirements and entries than through the propensity of physicians to move between states. Direct reforms had similar effects on less experienced and more experienced physicians. Conclusion  Tort reform increased physician supply. Further research is needed to determine whether reform-induced increases in physician supply benefited patients.