Expression of myosin heavy chain isoforms in Duchenne muscular dystrophy patients and carriers

The expression of MHC isoforms in the skeletal muscles of nine patients with Duchenne muscular dystrophy (DMD) (from 2.5 to 15 yr of age) and three DMD carriers was studied using different specific anti-MHC MAbs. We also analyzed muscle fiber size and fiber reactivity with acridine orange and/or with a surface antigen marker. One-quarter of all fibers of DMD patients, or less with age, were of normal size and contained only adult slow MHC. Half of the muscle fibers contained adult and developmental MHCs. Only half of these fibers were representative of an active regenerative process. MHC co-expression also altered the proportion of normal fast or slow fibers. Adult fast MHCs were expressed as unique MHC only in small and very small fibers in the oldest DMD patients. In DMD carrier muscles, the greatest alterations in MHC expression were observed in patients with the most reduced dystrophin expression. However, MHC changes in dystrophin-positive fibers were similar to those observed in dystrophin-free fibers. In conclusion, disruptions or delays in the switching of all genes coding for adult fast and slow MHC and developmental MHC coincided with dystrophin deletion and with perturbations in its expression.     

Preconception care of diabetes. Glycemic control prevents congenital anomalies

To test the value of intensive management of diabetes before and during early pregnancy, 84 women recruited prior to conception were compared with 110 women who were already pregnant referred at 6 to 30 weeks' gestation. All underwent daily measurement of fasting and postprandial capillary blood glucose levels. Mean blood glucose levels during embryogenesis and organogenesis were within 3.3 to 7.8 mmol/L in 50% of preconception subjects and exceeded 10 mmol/L in 6.5%. One major congenital anomaly occurred in 84 infants (1.2%) of women treated before conception compared with 12 anomalies in 110 infants (10.9%) of mothers in the postconception group. Transient symptomatic hypoglycemia occurred during embryogenesis in 60% of women in the preconception group, with a median frequency of 2.7 episodes per week, but was not associated with excess malformations. We conclude that education and intensive management for glycemic control of diabetic women before and during early pregnancy will prevent excess rates of congenital anomalies in their infants.     

Patients presenting to family physicians after a fall: a report from the Ambulatory Sentinel Practice Network.

BACKGROUND. Patients who fall present a diagnostic challenge to family physicians. The diagnostic workup of these patients must be thorough enough to detect and treat important causes of the fall yet not subject patients to unnecessary tests. Previous studies have provided only limited guidance for primary care physicians because in general they occurred in settings other than primary care and focused on a single age group. METHODS. The Ambulatory Sentinel Practice Network (ASPN) conducted a 6-month study of primary care patients of all ages presenting after a fall, or with medical problems resulting from a fall. ASPN clinicians collected information about the history, physical examination findings, and follow-up of these patients. Causes of falls were grouped into three categories: external reasons for falling, internal reasons related to gait, and internal reasons unrelated to gait. RESULTS. Participating clinicians identified 431 patients who had falls out of the 256,680 seen for any reason during the study period. The patients ranged in age from 1 to 94 years. The rate of falls for patients increased rapidly after age 65 years. Most falls occurred for reasons external to the patient, but internal reasons, both nonlocomotor and locomotor, increased after age 65 years. No nonlocomotor causes for a fall were found in patients younger than 65 years of age. Also, the rate of hospitalization of patients seen for falls was greater in the geriatric age group. CONCLUSIONS. The results highlight the need for further research about falls, particularly those occurring in pediatric and young adult patients. Furthermore, correcting environmental hazards and modifying gait problems in the elderly by increasing lower extremity and truncal strength could decrease the risk of falling.     

Disseminated strongyloidiasis in AIDS: uncommon but important

Disseminated Strongyloides stercoralis infection is a rare and severe but treatable complication of AIDS. We present a case where this infection was successfully treated and review the available literature. Cases may present many years after they have left an area endemic for Strongyloides infection, emphasizing the need for a full travel history. Symptoms are typically gastrointestinal and pulmonary, with infiltrates often seen on chest radiography. Diagnosis requires stool examination and biopsy of affected sites. Treatment with repeated courses of thiabendazole (25 mg/kg twice daily for 5 days) was successful in our case, but maintenance regimens have not yet been defined. The relative rarity of this complication of AIDS suggests that, where both infections are present, disseminated strongyloidiasis only arises either when HIV-induced immunodeficiency is profound or, possibly, when it is accompanied by impaired granulopoiesis.     

Covert inhalation of tablet causing fatal pneumonia

Inhalation of foreign bodies is usually associated with acute respiratory symptoms. We report a case of an elderly woman who died from pneumonia due to covert tablet inhalation. Clinicians caring for the elderly should consider this as a possible cause for pneumonia which fails to respond to usual therapy.     

5-Lipoxygenase-activating protein is the target of a novel hybrid of two classes of leukotriene biosynthesis inhibitors.

An 18-kDa leukocyte membrane protein, termed 5-lipoxygenase-activating protein (FLAP), has recently been shown to be the target of two structurally distinct classes of leukotriene biosynthesis inhibitors. These classes of inhibitors are based on indole and quinoline structures and are represented by MK-886 and L-674,573, respectively. A novel class of hybrid structure based on the indole and quinoline classes of inhibitors, termed quindoles, has recently been developed. These compounds, exemplified by L-689,037, are potent inhibitors of leukotriene biosynthesis, both in vitro and in vivo. In the present study, we have developed and characterized a potent radioiodinated photoaffinity analogue of L-689,037, termed [125I]L-691,678. This compound was used in immunoprecipitation studies with FLAP antisera to show that the quindole series of leukotriene biosynthesis inhibitors interact directly with FLAP. In addition, we show that MK-886, L-674,573, and L-689,037 specifically compete, in a concentration-dependent manner, with both [125I]L-691,678 and [125I]L-669,083, a photoaffinity analogue of MK-886, for binding to FLAP. These results suggest that these three classes of leukotriene biosynthesis inhibitors share a common binding site on FLAP, providing further evidence that FLAP represents a suitable target for structurally diverse classes of leukotriene biosynthesis inhibitors.