Cylindrical spirals of myofilamentous origin associated with exertional cramps and rhabdomyolysis

We describe the presence of cylindrical spirals on muscle biopsy from a 31-year-old man who developed rhabodomyolysis following a long run. He had a prior history of exertional cramps and myoglobinuria. His maternal grandfather had similar symptoms. Transmission electron micrographs demonstrated continuity between the lamellae of the cylindrical spirals and native myofilaments. Whether these unusual structures confer a derangement in myofilament function is uncertain.     

Localization of IGF-I and IGF-I Receptor mRNA inSparus aurataLarvae

Studies of the ontogeny of IGF-I mRNA during embryonic and larval development of the gilthead sea breamSparus auratashowed its expression during these early developmental stages. The present study appliesin situhybridization to localize IGF-I and IGF receptor mRNAs in 16-day larvae ofS. aurata.Paraffin sections were hybridized with homologous RNA probes labeled by [³⁵S]UTP. IGF-I mRNA expression was found mainly in chondrocytes, in both the gill arches and cranial cartilage, in skeletal muscle, in the brain, in the pancreas, in the retina, and in the epithelial cells surrounding the lens. A strong positive reaction for IGF receptor mRNA was found in skeletal muscle, in the pancreas, and in the lymphoid tissue found in the intertubular tissue of the kidney. Signals were less intense in brain and chondrocytes. It is suggested that in teleosts, as in higher vertebrates, IGF-I may be involved in the regulation of tissue growth and differentiation in an autocrine/paracrine manner.     

Laparoscopic appendicectomy — A successful operation in adults and children

Laparoscopic appendicectomy has been the subject of several encouraging reports, but has not as yet gained widespread acceptance. We present a series of 159 consecutive laparoscopic appendicectomies performed, over a 4 yr period, in both adults and children. We find the procedure as safe as its open counterpart, with patients fit to leave hospital within the same time period. Perforated appendices were amenable to this procedure, and the location of the appendix did not alter the outcome. Children responded as well as adults post-operatively. Obesity may be an indication for this form of treatment. Removal of displaced faecoliths associated with perforated appendicitis is a difficult technical problem in less than 5 per cent of patients.     

Deliberating about Bioethics

In some sense, bioethics was built on conflicts. Abortion, physician-assisted suicide, patients’ demand for autonomy all are staple and contentious issues. And the controversies continue to proliferate. What forum best serves such debates? A look at political theories of democracy can help answer that question. The most promising for bioethics debates are theories that ask citizens and officials to justify any demands for collective action by giving reasons that can be accepted by those who are bound by the action. This conception has come to be known as deliberative democracy.     

Safety pharmacology of the respiratory system: Techniques and study design

The known effects of drugs from a variety of pharmacologic/therapeutic classes on the respiratory system and worldwide regulatory requirements support the need for conducting respiratory evaluations in safety pharmacology. The objective of these studies is to evaluate the potential for drugs to cause secondary pharmacologic or toxicologic effects that influence respiratory function. Changes in respiratory function can result either from alterations in the pumping apparatus that controls the pattern of pulmonary ventilation or from changes in the mechanical properties of the lung that determine the transpulmonary pressures (work) required for lung inflation and deflation. Defects in the pumping apparatus are classified as hypo- or hyperventilation syndromes and are evaluated by examining ventilatory parameters in a conscious animal model. The ventilatory parameters include respiratory rate, tidal volume, minute volume, peak (or mean) inspiratory flow, peak (or mean) expiratory flow, and fractional inspiratory time. Defects in mechanical properties of the lung are classified as obstructive or restrictive disorders and can be evaluated in animal models by performing flow-volume and pressure-volume maneuvers, respectively. The parameters used to detect airway obstruction include peak expiratory flow, forced expiratory flow at 25 and 75% of forced vital capacity, and a timed forced expiratory volume, while the parameters used to detect lung restriction include total lung capacity, inspiratory capacity, functional residual capacity, and compliance. Measurement of dynamic lung resistance and compliance, obtained continuously during tidal breathing, is an alternative method for evaluating obstructive and restrictive disorders, respectively, and is used when the response to drug treatment is expected to be immediate (within minutes post-dose). The species used in the safety pharmacology studies conducted in our laboratory are the same as those used in toxicology studies since pharmacokinetic and toxicologic/pathologic data are available in these species. These data can be used to help select test measurement intervals and doses and to aid in the interpretation of functional change. The techniques and procedures for measuring respiratory function parameters are well established in guinea pigs, rats, and dogs.     

Diagnostic accuracy of progressive supranuclear palsy in the Society for Progressive Supranuclear Palsy brain bank.

Diagnostic accuracy has been addressed previously for Parkinson's disease in a brain bank collection, but accuracy of progressive supranuclear palsy (PSP) has not been addressed in a similar setting. Clinical and genetic features of pathologically confirmed cases of PSP were compared with misdiagnosed cases to determine ways to improve diagnostic accuracy. Medical records were reviewed for 180 cases sent to the Society of Progressive Supranuclear Palsy Brain Bank that had standardized neuropathologic evaluations as well as determination of apolipoprotein E and tau genotypes. Of the 180 cases studied, 137 had PSP and 43 had other pathologic diagnoses. Corticobasal degeneration (CBD), multiple system atrophy (MSA), and diffuse Lewy body disease (DLBD) accounted for 70% of the misdiagnosed cases. History of tremor, psychosis, dementia, and asymmetric findings were more frequent in misdiagnosed cases. The frequency of H1 tau haplotype (93 vs. 80%) and H1H1 genotype (86 vs. 66%) were significantly greater and APOE epsilon4 carrier state was significantly less (17 vs. 41 %) in PSP compared with misdiagnosed cases. Pathologic evaluation of clinically diagnosed PSP remains important for definitive diagnosis, and CBD, MSA, and DLBD are the disorders most likely to be misdiagnosed as PSP. Tremor, psychosis, early dementia, asymmetric findings, absence of H1 haplotype, and presence of APOE epsilon4 should raise questions about a diagnosis of PSP.