Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695.

We have created early-onset transgenic (Tg) models by exploiting the synergistic effects of familial Alzheimer's disease mutations on amyloid beta-peptide (Abeta) biogenesis. TgCRND8 mice encode a double mutant form of amyloid precursor protein 695 (KM670/671NL+V717F) under the control of the PrP gene promoter. Thioflavine S-positive Abeta amyloid deposits are present at 3 months, with dense-cored plaques and neuritic pathology evident from 5 months of age. TgCRND8 mice exhibit 3,200-4,600 pmol of Abeta42 per g brain at age 6 months, with an excess of Abeta42 over Abeta40. High level production of the pathogenic Abeta42 form of Abeta peptide was associated with an early impairment in TgCRND8 mice in acquisition and learning reversal in the reference memory version of the Morris water maze, present by 3 months of age. Notably, learning impairment in young mice was offset by immunization against Abeta42 (Janus, C., Pearson, J., McLaurin, J., Mathews, P. M., Jiang, Y., Schmidt, S. D., Chishti, M. A., Horne, P., Heslin, D., French, J., Mount, H. T. J., Nixon, R. A., Mercken, M., Bergeron, C., Fraser, P. E., St. George-Hyslop, P., and Westaway, D. (2000) Nature 408, 979-982). Amyloid deposition in TgCRND8 mice was enhanced by the expression of presenilin 1 transgenes including familial Alzheimer's disease mutations; for mice also expressing a M146L+L286V presenilin 1 transgene, amyloid deposits were apparent by 1 month of age. The Tg mice described here suggest a potential to investigate aspects of Alzheimer's disease pathogenesis, prophylaxis, and therapy within short time frames.

Surgical treatment of right ventricular myxoma in infancy.

Myxomas are the most common of all primary cardiac tumors in adults. They are extremely rare in infancy. We report on a 5-month-old infant who was admitted in a state of cardiogenic shock. Echocardiography showed a right ventricular myxoma completely occluding the right ventricular outflow tract. prompt surgical removal of the tumor resulted in a excellent outcome.

Acute hypoglycaemic coma--a rare, potentially lethal form of early onset Sheehan syndrome.

This case emphasizes the importance of intensive obstetric management that is required when confronted with prolonged postpartum haemorrhage. Anticipation of the possibility of acute hypoglycaemic coma as an initial manifestation of Sheehan syndrome and prompt recognition may prevent disastrous consequences, including maternal death.

Renal papillary necrosis in a child with rheumatic carditis treated with aspirin.

A child with rheumatic carditis developed acute renal failure due to renal papillary necrosis while receiving a short course of aspirin treatment. It is suggested that in this child the aspirin therapy predisposed the renal medulla to hypoxic damage induced by the carditis and congestive heart failure. It is therefore recommended that children receiving aspirin or other nonsteroidal anti-inflammatory drugs, even for a short time, be closely observed and the drug discontinued of hypoxia is evident. Moreover, during illnesses tending to cause hypoxia such as carditis, aspirin or other nonsteroidal anti-inflammatory drugs are best avoided since they are additional risk factors for renal damage.

Advanced papillary adenocarcinoma of unknown origin as tumor previa during late pregnancy.

A 41-year-old woman with advanced abdominal adenocarcinoma presented at term pregnancy. The tumor was presented as previa and obstructed the delivery. A cesarean section was performed and a healthy child was born. At surgery diffuse metastatic disease was detected throughout the pelvis and abdomen and was partially resected. Combined chemotherapy consisting of cis-platinum, adriamycin and cytoxan was administered for 5 months. At second-look laparotomy no residual disease was found. We present an unusual presentation of metastatic abdominal undifferentiated carcinoma treated as ovarian cancer.