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Genetic and infectious prion diseases.

Enriching fractions from Syrian hamster (SHa) brain for scrapie prion infectivity led to the discovery of the prion protein (PrP). Prion diseases include scrapie of sheep and bovine spongiform encephalopathy of cattle as well as Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome (GSS) of humans. Transgenic (Tg) mice expressing both SHa and mouse (Mo) PrP genes were used to probe the molecular basis of the species barrier and the mechanism of scrapie prion replication. Bioassays of brain extracts from two scrapie-infected Tg lines showed that the prion inoculum determines that prions are synthesized de novo, even though the cells express both PrP genes. Studies with artificial prions produced from chimeric Mo/SHaPrP transgenes underscore the concept that inoculated prion dictates which prion will be replicated. Discovery of mutations in the PrP genes of humans with GSS and familial CJD established that prion diseases are both genetic and infectious. Transgenic mice expressing high levels of MoPrP-P101L, corresponding to the GSS point mutation (P102L) in human PrP, spontaneously develop neurologic dysfunction, spongiform degeneration, and astrocytic gliosis. Inoculation of brain extracts prepared from these Tg (MoPrP-P101L) mice produced neurodegeneration in recipient animals after prolonged incubation times. These results are in accord with those of other studies and argue that prions are devoid of foreign nucleic acid. Structural investigations of cellular prion protein (PrPC) and prion protein scrapie (PrPSc) suggest that the difference may be conformational. Conditions that diminished the beta-sheet content of PrPSc were the same as those identified previously that inactivate prion infectivity. Whether prion diversity as reflected by distinct "strains" producing different patterns of PrPSc accumulation is due to different conformers of PrPSc remains to be established. Advances in the purification and characterization of both PrPC and PrPSc seem to have identified the central event in PrPSc synthesis and prion propagation, ie, the unfolding of PrPC followed by its refolding into PrPSc. These findings underscore the fundamental features of prion structure and propagation that differentiate prions from other transmissible pathogens.

Animal Diseases↗

A clinical and radiological study of chronic lower spinal arachnoiditis.

A critical evaluation revealed no distinct clinical complex of symptoms related to the radiological picture of chronic adhesive arachnoiditis in the lower lumbar sac in 72 patients. In all cases the arachnoiditis was diagnosed by myelography with water soluble contrast media and, in 16 cases, verified by operation and microscopy. The assumed cause of arachnoiditis was, in more than half of the cases, the combination of myelography and operation in close relation, and, in ten cases, a previous operation.

Adolescent↗

Inadvertent injection of corticosteroid into the choroidal vasculature.

A 21-year-old woman with pars planitis was treated with a subtenon's depot corticosteroid injection that was complicated by the appearance of the corticosteroid suspension within the choroidal vasculature. White, flocculent material was observed in the anterior chamber and 24 hours later this settled on the iris surface. Similar material was located in the major choroidal vessels. Two months after the incident, the choroid was normal appearing but the pars planitis was unchanged.

Adult↗

Unusual complications of coronary artery bypass graft surgery.

Complications after coronary artery bypass grafting are myriad and are to a certain extent operator dependent. The investigators report 2 unusual cases of inadvertent aortocoronary fistula after coronary artery bypass grafting that escaped routine detection. In conclusion, the development of heart failure led to the detection of this rare complication.

Aged↗

Phrenic nerve injury after coronary artery grafting: is it always benign?

BACKGROUND: The purpose of this study was to evaluate the effect of phrenic nerve injury (PNI) occurring during coronary artery bypass grafting in patients with major chronic obstructive pulmonary disease (COPD). METHODS: Over a 42-month period, 1,303 patients underwent primary coronary artery bypass grafting. Sixty-seven (5.14%) had major COPD, and 29 (43.3%) of these 67 sustained PNI (group I). These patients were matched for age and ejection fraction with 29 CABG patients with COPD but without PNI (group II), 29 patients without COPD but with PNI (group III), and 29 patients with neither COPD nor PNI (group IV). The groups were compared on the basis of preoperative and operative factors and immediate and midterm morbidity and mortality. RESULTS: There were no significant differences between the groups with respect to hypertension, diabetes, ejection fraction, number of grafts, internal mammary artery use, cardiopulmonary bypass time, and ischemic time. Postoperatively, group I had a longer total hospitalization (group I, 11.7 days; group II, 7.8 days; group III, 7.8 days; and group IV, 6 days; p = 0.0001) and stay in the intensive care unit (I, 3.6 days; II, 2.2 days; III, 2.1 days; and IV, 1.2 days; p = 0.0023). More patients in group I required reintubation (I, 37.9%; II, 3.4%; III, 6.9%; and IV, 0%; p < 0.0001). Mean follow-up was 32.8 months (range, 7 to 48 months). Group I had more hospital readmissions (I, 78; II, 50; III, 61; and IV, 28; p < 0.007) and lower cumulative survival (I, 60.6%; II, 93%; III, 96.8%; and IV, 100%; p < 0.0015) compared with the other groups. CONCLUSIONS: In patients with COPD, PNI during coronary artery bypass grafting has a major negative impact on immediate and midterm results.

Aged↗

Postoperative chylothorax.

Between July 1987 and May 1995, 11,315 patients underwent general thoracic surgical procedures at our institution. In 47 of these patients (0.42%), postoperative chylothorax developed. There were 32 men and 15 women with a median age of 65 years (range 21 to 88 years). Initial operation was for esophageal disease in 27 patients, pulmonary disease in 13, mediastinal mass in six, and thoracic aortic aneurysm in one. All patients were initially treated with hyperalimentation, cessation of oral intake, medium chain triglyceride diet, or a combination. Nonoperative therapy was successful in 13 cases (27.7%), and oral intake was resumed a median of 7 days later (range 2 to 15 days). Reoperation was required in the remaining 34 cases. The reoperation rate varied according to the type of initial operation. Twenty-four of the 27 patients (88.9%) who had undergone an esophageal operation required reoperation, versus only five of 13 patients (38.5%) who had undergone pulmonary resection (p < 0.001). Lymphangiography was performed in 16 patients and identified the site of the leak in 13. The thoracic duct was ligated in 32 of the 34 patients who required reoperation (94%). The remaining two patients were treated with mechanical pleurodesis and fibrin glue. Reoperation was successful in 31 of the 34 patients (91.2%). The single death among the 47 patients (2.1%) occurred in the reoperated group. Complications occurred in 18 patients (38.3%). Factors that predicted the need for reoperation were initial esophageal operation and average daily postoperative drainage greater than 1000 ml/day for 7 days. We conclude that postoperative chylothorax is an infrequent complication. Some cases can be managed without operation; however, we recommend early reoperation when drainage is greater than 1000 ml/day or if the chylous fistula occurs after an esophageal operation. The fistula can usually be controlled by ligation of the thoracic duct.

Adult↗

PRIMARY REFLUX.

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Congenital Abnormalities↗