Chronic airflow obstruction in Fabry's disease

Seven patients with Fabry's disease, an x-linked sphingolipid storage disorder, were evaluated for the presence and extent of airway obstruction. All were found to have significant obstruction to airflow. In addition, evaluation of their airway epithelial cells obtained by bronchoscopy demonstrated that these cells contained inclusion bodies consistent with deposits of ceramide trihexoside, suggesting that part of their functional obstruction to airflow may be secondary to intrinsic airway disease. Although all of the study population had evidence of airflow obstruction, the impairment was much worse in those who smoked, implying that even mild cigarette smoking is particularly hazardous to patients with Fabry's disease.     

Cardiovascular Effects of the Supraglottic and Super-supraglottic Swallowing Maneuvers in Stroke Patients with Dysphagia

The prolonged voluntary closure of the glottis during the supraglottic and super-supraglottic swallowing techniques may create the Valsalva maneuver. The Valsalva maneuver has been associated with sudden cardiac death and cardiac arrhythmias. This study describes the effects of the supraglottic and super-supraglottic swallowing techniques on the cardiovascular system. Subjects included 23 patients from an acute inpatient rehabilitation hospital. Subject groups included recent stroke, dysphagia, and a history of coronary artery disease (Group 1, N = 11), recent stroke and dysphagia with no known coronary artery disease (Group 2, N = 4), and orthopedic diagnosis with no known dysphagia or coronary artery disease (Group 3, N = 8). Cardiac status was moni-tored for 4 hours during swallowing training, regular therapy sessions, and a meal. For Groups 1 and 2, 86.6% (13 out of 15) of the subjects demonstrated abnormal cardiac findings during the swallowing session including supraventricular tachycardia, premature atrial contractions, and premature ventricular contractions. Arrhythmia subsided within a few minutes after the session and did not occur during other activities. In Group 3 (control group), none of the subjects demonstrated abnormal cardiac findings except for bradycardia in one subject. It is suggested that the supraglottic and super-supraglottic swallow maneuvers may be contraindicated for patients with a history of stroke or coronary artery disease.     

Quantification of experimental myocardial infarction using nuclear magnetic resonance imaging and paramagnetic ion contrast enhancement in excised canine hearts

Determination of myocardial infarct size is important for clinical management of patients with ischemic heart disease and for research on limiting infarct size. Nuclear magnetic resonance (NMR) imaging permits tomographic depiction of the distribution of mobile tissue protons. NMR images have demonstrated high spatial resolution and contrast. To evaluate the potential of this technique in measuring myocardial infarct size, NMR imaging was performed in six canine hearts excised 24 hours after circumflex coronary artery ligation. Before sacrifice, the dogs received i.v. manganous chloride (0.05 mmol/kg). After NMR imaging, the heart were sectioned and the myocardial slices were stained with triphenyl tetrazolium chloride. The pathologically determined infarct size was compared with the infarct size measured by NMR imaging. The correlation was good (regression line slope 1.06; r = 0.94). We conclude that NMR imaging with paramagnetic contrast agents can be used to determine infarct size in excised hearts.     

A waterborne outbreak in Missouri of Escherichia coli O157:H7 associated with bloody diarrhea and death.

OBJECTIVE: To describe and determine the source of a large outbreak of Escherichia coli O157:H7 (ECO157) infections in Missouri. DESIGN: A case-control study and a household survey. SETTING: A small city in a rural Missouri township that had an unchlorinated water supply. PATIENTS: Case patients were residents of or visitors to Burdine Township with bloody diarrhea or diarrhea and abdominal cramps occurring between 15 December 1989 and 20 January 1990. MEASUREMENTS: Escherichia coli O157 was isolated from 21 stool specimens. All isolates were resistant to sulfisoxazole, tetracycline, and streptomycin; produced Shiga-like toxins I and II; and had one 60-megadalton plasmid. RESULTS: Among the 243 case patients, 86 had bloody stools, 32 were hospitalized, 4 died, and 2 had the hemolytic uremic syndrome. In the case-control study, no food was associated with illness, but ill persons had drunk more municipal water than had controls (P = 0.04). The survey showed that, during the peak of the outbreak, bloody diarrhea was 18.2 times more likely to occur in persons living inside the city and using municipal water than in persons living outside the city and using private well water (P = 0.001). Shortly before the peak of the outbreak, 45 water meters were replaced, and two water mains ruptured. The number of new cases declined rapidly after residents were ordered to boil water and after chlorination of the water supply. CONCLUSIONS: This was the largest outbreak of ECO157 infections, the first due to a multiply resistant organism, and the first shown to be transmitted by water. System-wide chlorination as well as hyperchlorination during repairs might have prevented this outbreak. Both bloody and nonbloody diarrhea may be common manifestations of this infection, which is probably underdiagnosed because of the failure of routine stool cultures to identify the organism. Cities with deteriorating water systems using untreated water risk widespread illness from contaminated drinking water.     

Correction in trans for Fabry disease: expression, secretion and uptake of alpha-galactosidase A in patient-derived cells driven by a high-titer recombinant retroviral vector.

Fabry disease is an X-linked metabolic disorder due to a deficiency of alpha-galactosidase A (alpha-gal A; EC 3.2.1.22). Patients accumulate glycosphingolipids with terminal alpha-galactosyl residues that come from intracellular synthesis, circulating metabolites, or from the biodegradation Of senescent cells. Patients eventually succumb to renal, cardio-, or cerebrovascular disease. No specific therapy exists. One possible approach to ameliorating this disorder is to target corrective gene transfer therapy to circulating hematopoietic cells. Toward this end, an amphotropic virus-producer cell line has been developed that produces a high titer (>10(6) i.p. per ml) recombinant retrovirus constructed to transduce and correct target cells. Virus-producer cells also demonstrate expression of large amounts of both intracellular and secreted alpha-gal A. To examine the utility of this therapeutic vector, skin fibroblasts from Fabry patients were corrected for the metabolic defect by infection with this recombinant virus and secreted enzyme was observed. Furthermore, the secreted enzyme was found to be taken up by uncorrected cells in a mannose-6-phosphate receptor-dependent manner. In related experiments, immortalized B cell lines from Fabry patients, created as a hematologic delivery test system, were transduced. As with the fibroblasts, transduced patient B cell lines demonstrated both endogenous enzyme correction and a small amount of secretion together with uptake by uncorrected cells. These studies demonstrate that endogenous metabolic correction in transduced cells, combined with secretion, may provide a continuous source of corrective material in trans to unmodified patient bystander cells (metabolic cooperativity).     

Core Motivations of Childhood Obsessive-Compulsive Disorder: The Role of Harm Avoidance and Incompleteness

Child Psychiatry & Human Development - In an effort to improve patient conceptualization and targeted treatment, researchers have sought to accurately classify OCD subtypes. To date, the most...