Evaluation of gemfibrozil therapy: predictive response from lipoprotein subfraction analysis.

Subjects with high-density lipoprotein cholesterol (HDL-C) values of less than 47 mg/dL (mean 35.6 +/- 5.5 mg/dL) were selected for this study to examine relationships between plasma lipids, lipoprotein components, and the outcome of gemfibrozil therapy. Changes in plasma lipoprotein subfractions were determined to better understand the previously observed variability of the responses in both HDL-C and triglycerides to gemfibrozil. Based on the data collected, an attempt was made to identify pretreatment lipid parameters that may be predictive regarding the efficacy of gemfibrozil therapy. Serum samples were analyzed at the outset and after the conclusion of 12 weeks of gemfibrozil therapy. Because the HDL-C response to therapy was highly variable, the data from patients were separated into two groups, responders (>20% increase in HDL-C) and nonresponders (<20% increase in HDL-C). The lipid components of lipoprotein subfractions were evaluated using multiple regression analysis yielding predictive models that show the relationship between specific lipoprotein subfractions and the percentage change in HDL-C and posttreatment triglyceride levels. Group classification was then predicted with 78% accuracy using specific lipoprotein subfractions to estimate an individual's percentage change in HDL-C. The major difference between the responder and nonresponder groups was their respective correlations between triglyceride-lowering and changes in HDL-C. In the responder group, there was a significant correlation between the changes in HDL-C and the lowering of triglycerides (r = 0.61, p = 0.03), whereas the nonresponder group showed no such correlation (r = 0.17, p = 0.52). The predictive model also proved to be highly accurate in forecasting the effectiveness of the triglyceride-lowering action of gemfibrozil in this group of patients.     

Patellofemoral joint: kinematic MR imaging to assess tracking abnormalities

The patellofemoral joint was imaged with magnetic resonance (MR) in the axial plane while the knee was positioned from 0 degrees to 32 degrees of flexion (nine positions). These multiple sequential images obtained within the early phases of flexion of the knee were viewed in a "cine-loop" format, producing a kinematic study that clearly demonstrated the relationship of the patella to the trochlear groove. Four healthy subjects and one patient with known bilateral subluxing patellae were studied. The preliminary results suggest that kinematic MR imaging of the patellofemoral joint is potentially useful for the evaluation of patellar tracking abnormalities.     

Immunohistochemical localization of steroidogenic enzymes and comparison with hormone production during follicle development in the pig

The steroidogenic enzymes, P450 aromatase (P450arom) and P450 17alpha-hydroxylase (P45017alpha), were precisely located within the healthy porcine follicle by immunohistochemistry. Enzyme distribution was examined throughout follicular development during natural oestrous cycles (n = 14 gilts) and was compared with steroid production by healthy whole and theca-only follicles. All follicles 2 mm or more in diameter were either fixed for immunohistochemistry (n = 380 of which 197 were assessed as healthy) or incubated as whole (n = 110) or theca-only (n = 110) follicles to measure steroidogenesis. P45017alpha was confined to the theca layer. The number of positive cells and staining intensity increased with follicle size. P450-arom was consistently detected in the granulosa layer of follicles measuring 6 mm or more in diameter and those cells furthest from the antrum were most strongly stained. P450arom was also detected in the theca layer of these large follicles. Whole and theca-only follicles produced oestradiol and androstenedione, and the levels of both hormones increased with follicle size (P<0.001). Whole follicles produced more oestradiol (P<0.001), but less androstenedione (P = 0.01) than theca-only follicles of the same size. Although granulosa cells contained P450arom and synthesized oestradiol, only theca cells contained P45017alpha. Theca cells therefore provided granulosa cells with androgen substrate. In addition, theca cells possessed P450arom, making them capable of independent oestradiol production, which may be required to trigger the LH surge. This study confirms the vital role of theca cells in follicular steroidogenesis in the pig.     

Adjunctive osteopathic manipulative treatment in the elderly hospitalized with pneumonia: a pilot study

To evaluate the benefit of osteopathic manipulative treatment in the elderly with pneumonia, the authors recruited 21 individuals older than 60 years who were hospitalized with acute pneumonia. Eleven patients were randomly assigned to the treatment group and ten to the control group. The treatment group received specific osteopathic manipulative treatment for somatic dysfunction and a standardized treatment protocol. Both groups received conventional therapy, and the attending physician was blind to group assignments. No significant difference existed between groups for age, sex, or severity of illness. Although the mean duration of leukocytosis, intravenous antibiotic treatment, and length of stay were shorter for the treatment group, these measures did not reach statistical significance. However, the mean duration of oral antibiotic use did reach statistical significance at 3.1 days for the treatment group and 0.8 day for the control group. Osteopathic manipulative treatment may reduce antibiotic use and length of stay; however, a larger study is needed to clarify this outcome.     

Marrow regeneration after mechanical depletion

The origin of marrow regeneration after mechanical depletion was reinvestigated in mouse chimeras. The results were compatible with the local origin of stem cells from remnants of incompletely removed marrow, but not with their origin from a common precursor of both bone and hemopoietic cell lines. In transplanted femurs depleted by a modified technique of in vivo evacuation of marrow, hemopoietic regeneration failed to occur. The presence of hemopoietic stem cells in the Haversian canals was thus excluded. The demonstration of ample hemopoiesis with minimal bone formation in nondepleted controls in which bone marrow initially became necrotic provided new evidence that osteogenesis was not a prerequisite of hemopoietic regeneration.     

Severe malabsorption in autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome successfully treated with immunosuppression

A 15 year old boy with autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome suffered recurrent episodes of severe intractable diarrhoea, steatorrhoea, and hypocalcaemia. The only treatment modality, which controlled the malabsorption syndrome, was immunosuppression with intravenous high dose methylprednisolone and oral methotrexate maintenance therapy.     

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.