Outcome of Perthes'' disease in unselected patients after femoral varus osteotomy and splintage

PURPOSE: To study the incidence, cause, recovery time, and prevention of diplopia following subcutaneous injection of botulinum A toxin for the treatment of facial spasms. METHODS: Patients who experienced diplopia after botulinum A toxin injections had their deviations examined in detail. When the muscle that caused diplopia was identifiable, the injection closest to that muscle was omitted in the next treatment in an attempt to prevent diplopia. RESULTS: Of 250 patients receiving about 1500 sets of injections, 25 (1.7%) incidents of diplopia occurred in 10 patients. Excluding two patients who declined further treatment after having diplopia on their first botulinum A toxin treatment, seven of the remaining eight patients had multiple incidents of diplopia. The most common pattern of diplopia was "uncertain diagnosis." The most common identifiable cause of diplopia was paresis of the inferior oblique muscle. Omission of the injection into the central portion of the lower eyelids in the next treatment prevented recurrence of diplopia in only one of the four patients. No significant correlation between botulinum A toxin doses injected and times to recovery was noted. CONCLUSIONS: Diplopia following botulinum A toxin treatment is uncommon. Seven patients (3% of patients studied) had 22 episodes of diplopia (88% of episodes). When diplopia occurs, it tends to recur on reinjection, sometimes with a prolonged recovery time. This response may not be dose dependent. The extraocular muscles of some patients may be more susceptible to chemodenervation than others, or botulinum A toxin may diffuse to extraocular muscles more easily in some patients than in others.     

Ethical care at the end of life

In treating dying patients, who by virtue of their physical and emotional situation are frail and vulnerable, physicians must meet a high standard of professional, ethical care. Such a standard is based upon a philosophy of care that recognizes the patients' inherent worth as human beings and their uniqueness as individuals. The ethical and virtuous physician will practice in accordance with the principles of biomedical ethics that form the foundations of thought and treatment approaches in this area and will seek to do the best for the patient and the family. "Doing the best" includes respecting autonomy through gentle truth-telling, helping the patient and family to set treatment goals, and providing for symptom control, continuing attentive care and accompaniment throughout the course of the illness. Total care includes physical, emotional and spiritual aspects, is sensitive to cultural values and is best provided by an interdisciplinary team. Practices of symptom control in routine care and in crisis situations, as well as the cessation and non-initiation of treatment, will have as their goals the relief and comfort of the patient. The ethical physician will not act with the intention of bringing about the death of the patient, whether by ordering medication in excess of that required for symptom control, administering a lethal injection or any other means.     

Examination of metabolic pathways and identification of human liver cytochrome P450 isozymes responsible for the metabolism of barnidipine, a calcium channel blocker

1. In a human liver microsomal system, barnidipine was converted into three primary metabolites, an N-debenzylated product (M-1), a hydrolyzed product of the benzyl-pyrrolidine ester (M-3) and an oxidized product of the dihydropyridine ring (M-8). 2. Involvement of CYP3A in the three primary metabolic pathways was revealed by the following studies: (a) inhibition of CYP3A, (b) a correlation study using 10 individual human liver microsomes and (c) cDNA-expression studies. The secondary metabolites, M-2 and M-4 (pyridine forms of M-1 and M-3), were most likely generated from M-8 but were unlikely from M-1 or M-3. Involvement of CYP3A in the secondary pathways of metabolism is also suggested. 3. The possibility of interactions between barnidipine and coadministered drugs was examined in vitro. The formation rate of the primary metabolites was little affected by warfarin, theophylline, phenytoin, diclofenac and amitriptyline at concentrations of 200 microM, but was inhibited by glibenclamide, simvastatin and cyclosporin A. IC50 for the latter drugs was estimated to be > 200, 200 and 20 microM respectively, which was roughly > 200, 6000 and 50 times higher than their respective therapeutic plasma levels, suggesting that interactions with cyclosporin A, a CYP3A inhibitor, are of possible clinical relevance.     

Flow cytometric analysis of leukocytes in the human female reproductive tract: comparison of fallopian tube, uterus, cervix, and vagina

PROBLEM: The tissues of the human female reproductive tract (Fallopian tube, uterus, cervix, and vagina) may play different roles in the provision of mucosal immunity. The purpose of this study was to develop a uniform method suitable for quantitative comparison of the leukocytes from all these tissues. METHOD OF STUDY: Tissues, typically 0.5-1.0 g, were dispersed by enzyme treatment. A flow cytometric gating procedure based on CD45-positivity and low far-red autofluorescence permitted unfractionated, freshly dispersed cells to be phenotyped with respect to T lymphocytes, B lymphocytes, macrophages, and granulocytes. RESULTS: Reproductive tract tissues contain leukocytes that represent approximately 6-20% of the total number of cells, with the Fallopian tubes and uterus containing a higher proportion of leukocytes than the cervix and vagina. The uterine endometrium from post-menopausal women has fewer leukocytes than does uterine endometrium from pre-menopausal women. T lymphocytes are a major constituent (30-60%) of leukocytes from all tissues. The Fallopian tube contains granulocytes as another major constituent; granulocytes are significantly less numerous in the other tissues. All tissues contain B lymphocytes and macrophages as clearly detectable but minor components. CONCLUSIONS: Three-color flow cytometry is an appropriate method for quantitative comparison of leukocytes from the different tissues of the female reproductive tract, during all phases of the menstrual cycle and within post-menopausal samples. Results indicate that the tissues differ from each other, particularly with respect to the large number of granulocytes in the Fallopian tubes.     

Is there a place for hospitalists in health-care reform?

A case of stone heart syndrome is reported in a pregnant 27 year old West African patient, who suffered syncopal symptoms shortly before cardiac arrest. The electrocardiographic features were those of asystole, but direct examination of the heart at emergency thoracotomy in the A&E department revealed tetanic contracture of the organ. At necropsy, the heart was of normal weight but showed areas of fibrosis surrounding the bundle of His. The discrepancy between the ECG features and the physiological state of the heart raises the possibility that other cases of apparent asystole may not be what they seem.     

Amniotic fluid lecithin/sphingomyelin ratio changes related to centrifugal force

Lecithin/sphingomyelin ratio (L/S ratio) in amniotic fluid has gained wide clinical acceptance as an index of fetal lung maturity. We determined L/S ratios of amniotic fluids centrifuged at various "g-forces." Our studies demonstrate that the L/S ratio value is highly dependent on the g-force used to prepare the fluid. We recommend standardization of the g-force, time, and temperature used in preparation of the amniotic fluid for L/S ratio determination.     

Thymus dependence and independence of intestinal pathology in a Trichinella spiralis infection: a study in congenitally athymic (nude) mice

The hypothesis that non-specific histopathological gut changes are thymus-dependent was tested in a helminth infection--the nematode Trichinella spiralis. The study was performed in congenitally athymic (nu/nu) mice and their thymus-bearing heterozygous litter-mates (+/mu). The non-specific histopathological changes of the small intestine were judged on villus/crypt ratio and mitotic index; for the specific (= immunological) reaction the number of pyroninophilic cells in the small intestine was used as criterion. T. spiralis induced non-specific histopathological reactions both in nu/nu and +/nu mice, whereas the number of pyroninophilic cells was only increased in +/nu mice. It was concluded that the immunological reaction was dependent on the immune status of the host, whereas the non-specific histopathological changes were not, i.e. they were thymus-independent.     

Inherited deficiency of the second component of complement (C2) with membranoproliferative glomerulonephritis

The occurrence of membranoproliferative glomerulonephritis in a 13 year old boy with inherited complete deficiency of the second component of complement (C2) is described here for the first time. Results of the complement studies and the associations of glomerulonephritis with complement deficiencies are discussed.     

Inhibition of sterol biosynthesis in L cells and mouse liver cells by 15-oxygenated sterols

Described herein are the chemical syntheses of 5alpha-cholest-8(14-en-3beta-ol-15-one, 14alpha-methyl-5alpha-cholest-7-en-3beta-ol-15-one, 3beta-methoxy-14alpha-methyl-5alpha-cholest-7-en-15-one, 3beta-methoxy-14alpha-methyl-5alpha-cholest-7-en-15beta-ol, 3beta-methoxy-14alpha-methyl-15alpha-ol, and 5alpha-cholest-8(14)-en-3beta, 7xi,15xi-triol. The effects of these compounds and of 5alpha-cholest-8(14)-en-3beta,15beta-diol, 5alpha-cholest-8(14)-en-3beta,15alpha-diol, 5alpha,14beta-cholest-7-en-3beta,15beta-diol, 5alpha,14beta-cholest-7-en-3beta, 15alpha-diol, 14alpha-methyl-5alpha-cholest-7-en-3beta,15beta-diol, and 14alpha-methyl-5alpha-cholest-7-en-3beta,15alpha-diol on sterol synthesis in L cells and primary cultures of fetal mouse liver cells grown in serum-free media have been studied. With the exception of 3beta-methoxy-5alpha-cholest-7-en-15-one, all of the compounds were found to be potent inhibitors of sterol synthesis. With a few exceptions, the concentrations required to cause a 50% reduction in sterol synthesis were similar to those required to cause a 50% reduction in the level of HMG-CoA reductase activity.     

Simulation studies of ultrasonic backscattering and B-mode images of liver using acoustic microscopy data

Data obtained from a scanning laser acoustic microscope (SLAM) were used to examine several aspects of ultrasonic backscattering from the liver. Phase interferograms from normal and abnormal human-liver specimens were digitized, and a series of algorithms was used to compute images of propagation velocity within the specimens. The propagation velocity images were then employed to simulate A- and B-mode results. These initial simulations were used to investigate how ultrasonic echo signals are related to tissue microstructure. Among the topics examined were B-mode speckling, frequency and beamwidth effects, and angulation dependencies.