Exertional rhabdomyolysis and heat stroke : beware of volatile anesthetic sedation

In view of the enormous popularity of mass sporting events such as half-marathons, the number of patients with exertional rhabdomyolysis or exercise-induced heat stroke admitted to intensive care units (ICUs) has increased over the last decade. Because these patients have been reported to be at risk for malignant hyperthermia during general anesthesia, the intensive care community should bear in mind that the same risk of life-threatening rhabdomyolysis is present when these patients are admitted to an ICU, and volatile anesthetic sedation is chosen as the sedative technique. As illustrated by the three case studies we elaborate upon, a thorough diagnostic work-up is needed to clarify the subsequent risk of strenuous exercise, and the anesthetic exposure to volatile agents in these patients and their families. Other contraindications for the use of volatile intensive care sedation consist of known malignant hyperthermia susceptibility, congenital myopathies, Duchenne muscular dystrophy, and intracranial hypertension

Exertional rhabdomyolysis : relevance of clinical and laboratory findings, and clues for investigation

Some degree of exertional rhabdomyolysis (ER), striated muscle breakdown associated with strenuous exercise, is a well-known phenomenon associated with endurance sports. However in rare cases, severe and/or recurrent ER is a manifestation of an underlying condition, which puts patients at risk for significant morbidity and mortality. Selecting the patients that need a diagnostic work up of an acute rhabdomyolysis episode is an important task. Based on the diagnostic work up of three illustrative patients treated in our hospital, retrospectively using the 'RHABDO' screening tool, we discuss the clinical and biochemical clues that should trigger further investigation for an underlying condition. Finally, we describe the most common genetic causes of this clinical syndrome

Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise

The mechanism of chemotherapy-induced acceleration of ovarian aging is not fully understood. We used doxorubicin, a widely used cancer chemotherapeutic, in a variety of in vivo xenograft, and in vitro models to investigate the impact of chemotherapy-induced aging on the human ovary. Doxorubicin caused massive double-strand-DNA-breaks in primordial follicles, oocytes, and granulosa cells in a dose dependent fashion as revealed by accumulating γH2AX foci. This damage was associated with apoptotic oocyte death and resulted in the activation of ATM. It appeared that the repair response enabled a minor proportion of oocytes (34.7%) and granulosa cells (12.1%) to survive while the majority succumbed to apoptotic death. Paradoxically, inhibition of ATM by KU-55933 resulted in improved survival, probably via prevention of downstream activation of TAp63α. Furthermore, doxorubicin caused vascular and stromal damage in the human ovary, which might impair ovarian function both pre- and post-menopausally. Chemotherapy-induced premature ovarian aging appears to result from a complex process involving both the germ- and non-germ cell components of the ovary. These effects may have clinical implications in aging both for premenopausal and postmenopausal cancer survivors

Oocyte activation: The impact of calcium signals on fertilization

Fertilization is triggered by changes in intracellular calcium concentration. In mammals, these transients in ooplasmic calcium concentration take the form of repetitive spikes, so called calcium oscillations (Ca2+-oscillations). These oscillations are important for relieve of meiotic arrest and to induce all the other events of oocyte activation. Although a surface mediated way of oocyte activation has been proposed, there is now substantial evidence to suggest that the sperm cell induces these Ca2+-oscillations by introducing a sperm specific phospholipase C, PLC., in the ooplasm. Ca2+-oscillations are also observed after intracytoplasmic sperm injection ( ICSI), a successful technique in human assisted reproduction. In the rare cases that no fertilization is observed following ICSI, this may be due to a deficiency in PLC.. However, artificial activating the oocytes after ICSI by increasing the calcium concentration can restore fertilization rates in these cases and support further development, as evidenced by successful pregnancies. Further evaluation of the current protocols for assisted oocyte activation is appropriate and investigation of the future application of PLC. is warranted

Cystitis: symptomatology in women with suspected uncomplicated urinary tract infection

Background: Although cystitis in women is very common in general practice, its evolution in symptoms has not been clearly studied. Qualitative research has pointed to other than the classic symptomatology. Methods: This was a prospective observational study of the symptomatology at presentation and the evolution of the symptoms in treated women with suspected uncomplicated urinary tract infection (UTI). Women consulting their general practitioner (GP) for dysuria, urgency, or frequency produced a urine sample (for bacteriologic processing) and kept a diary until the end of the symptoms. Exclusion criteria included complaints >1 week, fever, vaginal discharge, and known pathology. Results: Of the 300 asked to participate, 148 (49%) returned the diary. Although none of the patients developed acute pyelonephritis, a substantial number of the women had such complaints as feeling feverish (33% in culture-positive group, 38% in culture-negative group), back pains (44% vs. 56%), and feeling weak and tired (71% vs. 65%). Differences between the culture-positive and culture-negative groups were not statistically significant except for the duration of symptoms, which was shorter in the culture-positive group (4 vs. 6 days). More severe symptoms at inclusion were correlated with a longer duration of these symptoms. Conclusions: The spectrum of complaints in women with suspected uncomplicated UTI is broad and comprises a number of symptoms usually associated with an upper UTI. The occurrence of these symptoms should not automatically prompt GPs to prescribe broad-spectrum antibiotics. Moreover, the duration of symptoms exceeding the recommended duration of antibiotic therapy does not indicate therapy failure and, thus, the need for changing antibiotic therapy

Doctrine Formulation and Distrust

Legal scholars exhaustively debate the substantive wisdom of Supreme Court decisions and the appropriate methods for interpreting legal texts but rarely consider the more pragmatic need to craft rules that will be faithfully implemented by the lower court judges who have the last word in the overwhelming majority of cases. Political scientists, in contrast, invest tremendous effort seeking to determine whether lower courts “comply” with Supreme Court directives, but find themselves unable to explain why their own studies generally find high levels of compliance. This Article argues that part of the answer lies in the Court\u27s ability to craft legal doctrines that both shape a trial court\u27s initial decision and increase the efficacy of appellate monitoring. After identifying numerous strategies for increasing lower court control, this Article argues that appreciating the links between them helps illuminate recent developments in three areas of public law: the constitutional law of punitive damages;the rules governing “officer suits” brought under 42 U.S.C. § 1983;and the concept of “reasonable” searches and seizures under the Fourth Amendment. Reprinted by permission of the publisher

Cognitive Information Processing

Contains reports on three research projects.Center for Advanced Television StudiesAmerican Broadcasting CompanyAmpex CorporationColumbia Broadcasting Systems (until 5/86)Harris Corporation (until 5/86)Home Box OfficeKodak (from 1/87)Public Broadcasting ServiceNational Broadcasting CompanyRCA CorporationTektronixZenith (from 5/86)3M Company (until 5/86)International Business Machines, Inc.Defense Advanced Research Agency (Contract N00014-85-K-0213

Doctrine Formulation and Distrust

Legal scholars exhaustively debate the substantive wisdom of Supreme Court decisions and the appropriate methods for interpreting legal texts but rarely consider the more pragmatic need to craft rules that will be faithfully implemented by the lower court judges who have the last word in the overwhelming majority of cases. Political scientists, in contrast, invest tremendous effort seeking to determine whether lower courts “comply” with Supreme Court directives, but find themselves unable to explain why their own studies generally find high levels of compliance. This Article argues that part of the answer lies in the Court\u27s ability to craft legal doctrines that both shape a trial court\u27s initial decision and increase the efficacy of appellate monitoring. After identifying numerous strategies for increasing lower court control, this Article argues that appreciating the links between them helps illuminate recent developments in three areas of public law: the constitutional law of punitive damages;the rules governing “officer suits” brought under 42 U.S.C. § 1983;and the concept of “reasonable” searches and seizures under the Fourth Amendment. Reprinted by permission of the publisher