Was Osler Verdeutsched?

William Osler, considered one of the preeminent American physicians at the turn of the century, studied in North America and in Europe. His later influence in molding the teaching and the specialty of internal medicine is still felt. One may ask to what extent his ideas were generated or influenced by his extensive German experiences? Most certainly his exposure to pathology in Germany was profound and lasting. While there can be no doubt that Osler was a Germanophile throughout his career, one has to conclude that his academic influences were more English and not exclusively German. He was cosmopolitan and used and promulgated good ideas wherever he found them.

Effect of hematin in porphyric neuropathy.

Early, intravenous administration of hematin in a patient with acute intermittent porphyria and severe quadriparesis may have produced partial but remarkable improvement of neuropathy, and resulted in simultaneous decline of porphyrin precursors in the blood. Intermittent, biweekly hematin infusions given 1 month after the onset of the porphyric relapse had no effect on recovery of the residual neuropathy. We believe hematin may be effective in the treatment of porphyric neuropathy, if administered before irreversible neuronal damage has occured.

Pseudo-porphyria in a patient with hepatocellular carcinoma.

An elderly woman was found to have hepatocellular carcinoma and, incidental to this, markedly elevated levels of porphobilinogen in urine and serum. The delta-aminolevulinic acid levels in urine and serum were normal, but there was a distinct increase of porphyrins in urine and feces. Neither the patient nor her family gave a history suggestive of a clinical porphyria. The patient died from the carcinoma without ever exhibiting porphyric symptoms. It is assumed that the hepatocellular carcinoma produced the excessive amounts of porphobilinogen.

Spa therapy for heart disease Bad Nauheim (circa 1900).

The development of Bad Nauheim, a German spa that over 2 centuries became dominant in the attraction of patients with heart disease is described. Here, patients experienced a regimen of saline baths and mostly static exercises developed by the Schotts, 2 physician brothers. Concomitant with the bathing and exercises, there was a social atmosphere conducive to relaxation. Many visiting physicians were impressed that there were improvements in the patients' cardiac status. One skeptical exception was Sir James Mackenzie, whose views are synopsized. The reported improvements may have had a modicum of a physiologic base, from recent investigations on the nature of heart failure, and may have anticipated the current use of exercise in cardiac rehabilitation.

Effects of sulfinpyrazone on early graft closure after myocardial revascularization.

The effect of sulfinpyrazone on the incidence of early postoperative closure of saphenous vein bypass grafts was compared with placebo in a prospective randomized study of 255 eligible patients. Treatment with sulfinpyrazone (800 mg/day) was started 24 hours after operation in 130 patients; 125 patients received placebo. Graft blood flow was measured at operation in 96 percent of all patients. Graft angiography was performed between the 7th and 14th postoperative days. There was no significant difference between the two groups in graft blood flow, number and diameter of the grafted arteries, left ventricular filling pressure or ejection fraction. During the study 73 patients (41 on sulfinpyrazone, 32 on placebo therapy) were excluded because graft angiography was contraindicated or because of concomitant use of anticoagulant or antiplatelet drugs. The incidence rate of early graft closure in the remaining 182 patients (43.1 grafts) was 3.8 percent (8 or 212) in the sulfinpyrazone group and 9.1 percent (20 of 219) in the placebo group (p less than 0.025). The incidence of graft closure for the sulfinpyrazone and placebo groups classified according to the recipient coronary arteries was: (1) left anterior descending artery; 3 of 98 versus 11 of 111; p less than 0.05; (2) left circumflex coronary artery: 3 of 50 versus 5 of 43; difference not significant; (3) right coronary artery: 2 of 64 versus 4 of 65; difference not significant. The incidence of closure in grafts with a flow of less than 30 ml/min did not differ significantly in the sulfinpyrazone and placebo groups (4 of 26 versus 6 of 22). These results suggest that sulfinpyrazone reduces the incidence of early graft closure in grafts with a flow rate greater than 30 ml/min.

Environmental chemical exposures and disturbances of heme synthesis.

Porphyrias are relatively uncommon inherited or acquired disorders in which clinical manifestations are attributable to a disturbance of heme synthesis (porphyrin metabolism), usually in association with endogenous or exogenous stressors. Porphyrias are characterized by elevations of heme precursors in blood, urine, and/or stool. A number of chemicals, particularly metals and halogenated hydrocarbons, induce disturbances of heme synthesis in experimental animals. Certain chemicals have also been linked to porphyria or porphyrinuria in humans, generally involving chronic industrial exposures or environmental exposures much higher than those usually encountered. A noteworthy example is the Turkish epidemic of porphyria cutanea tarda produced by accidental ingestion of wheat treated with the fungicide hexachlorobenzene. Measurements of excreted heme precursors have the potential to serve as biological markers for harmful but preclinical effects of certain chemical exposures; this potential warrants further research and applied field studies. It has been hypothesized that several otherwise unexplained chemical-associated illnesses, such as multiple chemical sensitivity syndrome, may represent mild chronic cases of porphyria or other acquired abnormalities in heme synthesis. This review concludes that, although it is reasonable to consider such hypotheses, there is currently no convincing evidence that these illnesses are mediated by a disturbance of heme synthesis; it is premature or unfounded to base clinical management on such explanations unless laboratory data are diagnostic for porphyria. This review discusses the limitations of laboratory measures of heme synthesis, and diagnostic guidelines are provided to assist in evaluating the symptomatic individual suspected of having a porphyria.

Mortality in patients with acute intermittent porphyria requiring hospitalization: a United States case series.

Acute intermittent porphyria (AIP) is a genetic disorder in which patients may have life threatening attacks of neurologic dysfunction. This study examined the prognosis during the past 50 years of patients in the United States who required hospitalization for porphyric attacks. The cumulative survival was determined for 136 patients with AIP who were hospitalized for porphyric attacks between 1940 and 1988. Diagnosis was established on the basis of clinical symptoms, in combination with increased urinary excretion of porphobilinogen. The patient group had an average age of 32 years (range 9 to 75) at diagnosis and consisted of 43 males and 93 females. At follow-up, 19 males (44%) and 31 females (33%) were decreased. The standardized mortality ratio for the 136 patients, compared to an age-matched hypothetical population experiencing USA 1970 Census Death Rates was 3.2, with a 95% confidence interval of 2.4-4.0. Most deaths occurred during the initial porphyric attack (20% of deaths) or a subsequent attack (38% of deaths). Suicide was also common (five deaths). Comparison was made between 50 patients who were diagnosed before 1971, the year in which hematin therapy became available, and 86 patients who were diagnosed afterward. There was improved survival in the latter group, particularly after 10 years from the time of diagnosis, but this did not reach statistical significance. In conclusion, the proportionate increase in mortality due to symptomatic AIP was three-fold compared to the general population during the past 50 years. The major cause of the increased mortality was the porphyric attack itself.

Severe hemolysis with a fabric-worn cloth-covered aortic valve prosthesis.

A patient developed severe hemolytic anemia one year after insertion of a cloth-covered aortic valve prosthesis (Starr-Edwards No. 2320). The cloth over the three struts was disrupted but showed coverage with mostly organized collagen. Hemolysis stopped after replacement with a porcine heterograft. Fabric wear seems to augment the hemolysis in patients with cloth-covered artificial valves.

Electrocardiographic changes after cervical laminectomy.

Striking T-wave inversions were observed in the postoperative electrocardiograms of a 64-year-old woman following an extensive cervical laminectomy. Except for the presence of a trace amount of CK-MB in a single serum specimen all her enzyme and isoenzyme studies were negative, and her clinical course was not suggestive of myocardial ischemia. Coronary angiography, including an ergonovine study, done 6 mth following the laminectomy were normal. Because of the nature of this patient's neurogenic origin of these T-wave changes is suspected.

Relation between serum digoxin concentration and the electrocardiogram.

The relation between serum digoxin concentration and the electrocardiogram was assessed by correlating computerized measurements of electrocardiographic parameters (PR, QRS, QT and QTc intervals, ST segment, and T-wave amplitude) with the serum digoxin concentration in 97 patients on digoxin maintenance therapy and in 40 nondigitalized control subjects. None of the patients had unstable ischemic heart disease, electrolyte disorders, medication known to influence the ST segment, and/or the presence of a bundle-branch block or ventricular hypertrophy. We found a trend toward lengthened PR interval and shortened QT and QTc intervals in digitalized versus nondigitalized patients. Increasing serum digoxin concentrations were associated with progressive depression of the ST segment and decreased T-wave amplitude (p less than 0.001). A normal ST segment in four leads (I, aVF, V5, V6) excluded the presence of a serum digoxin concentration greater than 1.3 ng/ml in our patients, whereas severe ST-segment depression with a J point of greater than or equal to 100 microV was a strong indicator for the presence of a serum digoxin concentration greater than 2.0 ng/ml in our selected patient population (specificity 99%, sensitivity 30%, predictive accuracy 85%). We conclude that computerized electrocardiographic analysis of the ST segment may provide clinically useful information for the management of selected patients on digitalis therapy and may therefore increase the diagnostic yield of the electrocardiogram in predicting the presence of higher serum digoxin concentrations in a small but significant percentage of patients.

[Haemolysis after heart valve replacement (author's transl)]. / Hämolyse nach Herzklappennersatz

Intravascular haemolysis is frequently seen in patients after heart valve replacement, but is often compensated. The cause of the haemolysis is traumatic damage of the red cells. It is more often seen after aortic, than after mitral replacement, because the transvalvular pressure gradient is higher and is more severe in ball valves than in disc valves. If substitution therapy with iron, folic acid, or even red cells fails, re-operation should be seriously considered.

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