Persistent hypermethioninaemia with dominant inheritance

Summary A clinically benign form of persistent hypermethioninaemia with probable dominant inheritance was demonstrated in three generations of one family. Plasma methionine concentrations were between 87 and 475 µmol/L (normal mean 26 µmol/L; range 10–40 µmol/L); urinary methionine and homocystine concentrations were normal. Plasma homocystine, cystathionine, cystine and tyrosine were virtually normal. The concentrations in serum and urine of metabolites formed by the methionine transamination pathway were normal or moderately elevated. Methionine loading of two affected family members revealed a diminished ability to catabolize methionine, but the activities of methionine adenosyltransferase and cystathionine -synthase were not decreased in fibroblasts from four affected family members. Fibroblast methylenetetrahydrofolate reductase activity and its inhibition byS-adenosylmethionine were also normal, indicating normal regulation ofN ⁵-methyltetrahydrofolate-dependent homocysteine remethylation. Serum folate concentrations were not increased.The findings in this family differ from those previously described for known defects of methionine degradation. Since the hepatic and fibroblast isoenzymes of methionine adenosyltransferase differ in their genetic control, this family's biochemical findings appear consistent with a mutation in the structural gene for the hepatic methionine adenosyltransferase isoenzyme.     

Fever and pneumonia in a steroid treated patient with systemic lupus erythematosus

Systemic lupus erythematosus is reported to affect the lungs in almost half of patients, but pleuritis is most commonly encountered. Acute pneumonitis is an uncommon but recognized manifestation of SLE. Infection and drug reactions are more frequently diagnosed. The case discussed below permits consideration of the dilemmas typical of the SLE patient who presents with an acute pulmonary process.     

Drug hepatotoxicity

Drug-induced liver disease is a relatively common, but often unrecognized, cause of liver injury, primarily because the diagnosis is often not entertained clinically. In addition, drugs are great imitators, capable of producing nearly any clinical scenario and histopathologic lesion. Thus, when dealing with a liver biopsy from a patient with an undiagnosed liver disease, the diagnosis of drug hepatotoxicity is made by first having a high index of suspicion, and then by careful correlation of histopathologic findings with both clinical and laboratory data and with a search for appropriate precedents in the medical literature.     

Will the use of low-molecular-weight heparin (enoxaparin) in patients with acute coronary syndrome save costs in Canada?

BACKGROUND: One-year follow-up data from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial show that use of low-molecular-weight heparin (enoxaparin) compared with unfractionated heparin in patients hospitalized with unstable angina or non-Q-wave myocardial infarction is associated with a 10% reduction in the cumulative 1-year risk of death, myocardial infarction, or recurrent angina. Given the higher acquisition cost of enoxaparin relative to unfractionated heparin, we assessed whether the reduced use of revascularization procedures and related care makes enoxaparin a cost-saving therapy in Canada. METHODS AND RESULTS: We analyzed cumulative 1-year resource use data on the 1259 ESSENCE patients enrolled in Canadian centers (40% of the total ESSENCE sample). Patient-specific data on use of drugs, diagnostic cardiac catheterization, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, and hospital days were available from the initial hospital stay and cumulative to 1 year. Hospital resources were costed with the use of data from a teaching hospital in southern Ontario that is a participant in the Ontario Case Costing Project. During the initial hospital stay, use of enoxaparin was associated with reduced use of diagnostic catheterization and revascularization procedures, with the largest effect being reduced use of percutaneous transluminal coronary angioplasty (15.0% vs 10.6%; P =.03). At 1 year, the reduced risk and costs of revascularization more than offset increased drug costs for enoxaparin, producing a cost-saving per patient of $1485 (95% confidence interval $-93 to $3167; P =.06). Sensitivity analysis with lower hospital per diem costs from a community hospital in Ontario still predicts cost savings of $1075 per patient over a period of 1 year. CONCLUSIONS: The acquisition and administration cost of enoxaparin is higher than for unfractionated heparin ($101 vs $39), but in patients with acute coronary syndrome, the reduced need for hospitalization and revascularization over a period of 1 year more than offsets this initial difference in cost. Evidence from this Canadian substudy of ESSENCE supports the view that enoxaparin is less costly and more effective than unfractionated heparin in this indication.     

Blunt chest trauma and suspected aortic rupture: reliability of chest radiograph findings

The chest radiographs of 86 patients with suspected aortic rupture from blunt chest trauma were reviewed. Seventy-three patients had no evidence of aortic rupture on aortography or surgical exploration, and 13 patients had surgically confirmed rupture. Sixteen radiographic findings were analyzed for sensitivity and specificity in detecting aortic rupture. The following findings were not statistically significant: hemothorax on either side; rib fractures on either side; pneumothorax on either side; lung contusion; widened left paravertebral stripe; and widening of the mediastinum, along with an increased ratio of mediastinal width to chest width. The most helpful findings leading to suspicion of aortic rupture included nasogastric tube or tracheal deviation to the right at the T4 level; depression of the left mainstem bronchus; and loss of the aortic contour or knob and left apical cap. False positives and false negatives occurred with each radiographic sign, indicating that there is no single finding that is absolutely reliable in predicting or excluding significant injury in every patient with suspected aortic rupture. Analysis of combinations of findings found that when the aortic contour and knob are normal and the nasogastric tube and trachea are not deviated, there was no case of aortic rupture in four consecutive years of experience. These four signs can be used to exclude aortic rupture.     

Vasoactive intestinal polypeptide gene expression in the developing human gastrointestinal tract.

Expression of vasoactive intestinal polypeptide has been shown, by immunocytochemistry and biochemical assay, to follow the craniocaudal neural colonization of the mammalian gut. The aim of this study was to use in situ hybridization to see if it could provide more information on vasoactive intestinal polypeptide gene expression in the developing human gut. Immunocytochemistry of vasoactive intestinal polypeptide and, to visualize the total innervation, protein gene product 9.5 was also applied. By 8 weeks of gestation, protein gene product 9.5-immunoreactive neurons had colonized the gut lengthwise (17% of intestinal muscle area) but not transversely. Vasoactive intestinal polypeptide immunoreactivity was first detected at 9 weeks of gestation in a few nerve fibers of the upper gut, the origin of which could not be determined. Vasoactive intestinal polypeptide-immunoreactive ganglion cells were not seen until 18 weeks of gestation, whereas in situ hybridization showed messenger RNA in ganglion cells of the upper gut at 9 weeks. An adultlike pattern of peptide gene products (e.g., 2.5% and 3.1% of intestinal mucosal or muscle area, respectively) was detected by 20 weeks' gestation. The finding that the vasoactive intestinal polypeptide gene is expressed first in the upper human gut is consistent with craniocaudal neuronal colonization and maturation.     

How many joints in the hands and wrists should be included in a score of radiologic abnormalities used to assess rheumatoid arthritis?

Numerous methods for reading abnormalities of rheumatoid arthritis in hand and wrist radiographs have been proposed over the past several decades. There are many differences among these methods, one of the more striking of which is the variation in the number of joints that are scored. In this study, we tested the number of joints that need to be read in order to represent abnormalities accurately and reproducibly, using the scores of multiple observers. Thirteen rheumatologists and radiologists each read a set of 41 hand and wrist films from patients with rheumatoid arthritis. Ten of 13 readers scored 27 joints in each hand and wrist; the other 3 readers scored fewer areas. Fourteen combinations of joints were selected based on the frequency of involvement and the technical adequacy of routine films in assessing a given area. After testing these 14 different combinations, 1 scheme, which included 17 areas read for erosions and 18 areas read for joint space narrowing, was tested further. The correlation coefficients for 10 intraobserver scores derived from this modified scheme compared with the original scores were between 0.981 and 0.997. Seventy-one of 78 interobserver comparisons were better using the new scheme than using the original scheme. These data indicate that the simplified scheme, using a combination of 17 joints to score erosions and 18 to score joint space narrowing, more accurately reflects the extent of abnormalities perceived by a panel of experts than does the original scheme. This abbreviated number of joints shortens the amount of time required to read a set of films and simplifies the scoring of films, since a number of areas that are difficult to read are eliminated from radiographic assessment.