A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk

Conventional risk factors have very low predictive power in identifying haemodialysis patients at high risk of vascular accidents. A role for apolipoprotein E isotypes was looked for in a small, but rigorously defined, cohort of longterm haemodialysis patients. In individuals with high vascular risk, as identified by higher common carotid intima/media thickness, we found an excess of apolipoprotein E4 alleles. This preliminary result requires confirmation in large patient cohorts.      

De novo generation of histamine in sputum and the effect of antibiotics

We have performed experiments to test the hypothesis that bacteria may contribute to the presence of histamine in sputum. Sputum samples obtained from 7 patients with exacerbations of chronic bronchitis and 7 patients with cystic fibrosis were incubated at 37 degrees C for 72 hours. Serial sputum histamine estimations, performed by a recently-developed HPLC technique, showed large, progressive increases in both groups of samples. Both the pre-heating of samples at 100 degrees C prior to incubation and the addition of antibiotics to the incubates substantially reduced these increases. These findings strongly suggest that bacteria may contribute to sputum histamine in infective lung disease.     

Serum concentrations of alkaline phosphatase isoenzymes and osteocalcin in normal pregnancy

We measured serum alkaline phosphatase isoenzymes and osteocalcin levels in 40 healthy women at 4-week intervals throughout uncomplicated pregnancies and 6 weeks after delivery in 17 women. Serum bone alkaline phosphatase was significantly higher in the third trimester than in early pregnancy (P less than 0.001), and this elevation was still apparent at the end of the puerperium, suggesting increased bone turnover. Serum osteocalcin was not detected (less than 0.2 micrograms/L) after the first trimester in the majority of women, and it reappeared within 48 h after delivery. The disappearance of osteocalcin after the first trimester and its rapid reappearance after delivery suggest placental clearance of this peptide. We conclude that serum osteocalcin measurements cannot be used as a marker of bone metabolism during pregnancy.     

Serum sialic acid concentration in patients with hypertriglyceridaemia showing the Frederickson's IIB phenotype.

1. Serum total sialic acid concentration, recently shown to be a cardiovascular risk factor, and also serum lipid-associated sialic acid concentration were measured in 15 patients with hypertriglyceridaemia (fasting serum triacyglycerol concentration > 2.3 mmol/l) showing a Frederickson's type IIB phenotype, 15 patients with hypercholesterolaemia showing a IIA phenotype and 15 age- and sex-matched normal control subjects. 2. Total serum sialic acid concentration was significantly raised in the hypertriglyceridaemic group (84.9 +/- 21.5 versus 64.9 +/- 20.8 mg/dl, P < 0.03, Mann-Whitney U-test) compared with the normal control group, as was serum lipid-associated sialic acid concentration (23.0 +/- 4.3 versus 12.0 +/- 3.2 mg/dl, respectively, P < 0.001, Mann-Whitney U-test). 3. Serum total sialic acid concentration was also significantly elevated in the hypertriglyceridaemic group as compared with the IIA phenotype hypercholesterolaemic group (84.9 +/- 21.5 versus 58.4 +/- 11.7 mg/dl, P < 0.03, Mann-Whitney U-test), as was serum lipid-associated sialic acid concentration (23.0 +/- 4.3 versus 14.9 +/- 4.7 mg/dl, P < 0.001, Mann-Whitney U-test). 4. We suggest that serum concentrations of both total sialic acid and lipid-associated sialic acid may be useful markers of cardiovascular risk which could, in part, be related to hypertriglyceridaemia.     

Tuberculosis of the pancreas: a case report

A 73-year-old female died of adult respiratory distress syndrome (ARDS) and multiple organ system failure (MOSF) after a routine cholecystectomy for acute cholecystitis. An autopsy revealed disseminated tuberculosis with a tuberculous abscess of the pancreas.     

Hodgkin disease: CT of the thymus

The computed tomography (CT) scans in two groups of patients with Hodgkin disease were reviewed to determine the frequency of thymic enlargement. In 50 CT scans from 50 patients with evidence of thoracic disease on CT scans who were examined for primary staging, the thymus was enlarged in 15 of 50 (30%). Fifty CT scans were obtained from 44 patients at the time of 50 separate episodes of known or suspected relapse. Relapse occurred in the mediastinum in 12 episodes, lung parenchyma in five, and both sites in one. Thymic enlargement thought to be due to involvement by disease was present in seven of 18 (38%). Mediastinal disease was associated with thymic enlargement in all but one patient in whom a thymic cyst developed after radiation therapy. Differentiation of thymic enlargement from enlarged superior mediastinal lymph nodes was easily made in all but two patients. Thymic enlargement in the absence of lymph node enlargement may indicate a different disease, since isolated Hodgkin disease of the thymus is uncommon. Primary thymic tumor should be considered initially, whereas after treatment, rebound hyperplasia of the thymus may be the cause of enlargement.