Scrofuloderma (tuberculosis colliquativa cutis)

Summary A 16-year-old girl presented with long-standing purulent sinuses to the skin overlying the lacrimal ducts, which had evolved into ulcers and resulted in hypertrophic scarring. The ulcers were serpiginous, with an uneven soft floor, and undermined edges. Histological examination revealed non-caseating tuberculoid granulomas in the dermis. Cultures for Mycobacterium tuberculosis were positive. Chest X-ray did not show pulmonary involvement. Antituberculous therapy with isoniazid 300mg/day and rifampicin 600mg/day achieved a great improvement within 5 weeks of being started. A further improvement was seen at 4 months and complete resolution had occurred by 9 months. To the best of our knowledge, there are no other documented cases of scrofuloderma over the lacrimal system. The delay in the diagnosis emphasizes the importance of maintaining a high level of awareness.     

Serum levels of interleukin-6 and tumour-necrosis-factor-alpha are not correlated to disease activity in patients with rheumatoid arthritis after treatment with low-dose methotrexate

Abstract. Cytokines are major mediators of inflammatory responses in rheumatoid arthritis. Some of them have been shown to correlate with the disease activity and thus are proposed to be used for monitoring patients. Therefore the effects of a low-dose therapy with methotrexate on serum concentrations of interleukin-6 (IL-6) and tumour-necrosis-factor-alpha (TNF-α) were examined in eight patients with seropositive rheumatoid arthritis. Serum levels of IL-6 and TNF-α were significantly elevated in patients compared to healthy controls. Before the onset of MTX treatment IL-6 concentrations were correlated to the c-reactive protein ( P < 0·05) but the correlation was abolished after treatment. For TNF-α no correlations neither before nor after treatment were observed. Both cytokines remained substantially elevated after MTX treatment despite a clear reduction in disease activity. Thus we suggest that one of the effects of MTX might be the inhibition of some of the actions of IL-6 and TNF-α.     

Influence of the force--frequency relationship on haemodynamics and left ventricular function in patients with non-failing hearts and in patients with dilated cardiomyopathy

In isolated human myocardium it was shown that a positive force-frequencyrelationship occurs in non-failing myocardium; however, theforce-frequency relationship was found to be inverse in myocardiumfrom failing human hearts. In order to investigate the clinicalrelevance of these experimental findings, the influence of heartrate changes on haemodynamics and left ventricular functionwas studied in eight patients without heart failure and in ninewith failing dilated cardiomyopathy (NYHA II–III). Rightventricular pacing was performed at a rate slightly above sinusrate and at 100, 120 and 140 beats. min^–1 Haemodynamicparameters were obtained by right heart catheterization andby high-fidelity left ventricular pressure measurements. Leftventricular angiography was performed at basal pacing rate andat 100 and 140 beats. min^–1 With increasing heart rate,cardiac index increased in patients with normal left ventricularfunction from 2·9 ± 0·2 to 3·5 ±0·21. min^–1. m^–2 (P<0·01) and decreasedcontinuously in patients with dilated cardiornyopathy from 2·6± 0·1 to 2·2 ± 0·11. min^–1. m^–2 (P<0·05). With increasing heart rate,the maximum rate of left ventricular pressure rise increasedin non-failing hearts from 1388 ± 86 to 1671 ±88 mmHg. s^–1 (P<0·01) and did not change infailing hearts. Ejection fraction decreased from 27 ± 3% to 19 ±2% in patients with dilated cardiomyopathy (P<0·05)when the pacing rate was changed from 84 ± 2 beats. min^–1to 140 beats. min^–1, which was associated with a significantlyincrease in end-systolic volume without significantly changesin end-diastolic volume. In patients with normal left ventricularfunction, when the pacing rate was changed from 85 ±3 beats. min^–1 to 140 beats. min^–1, end-diastolicvolume decreased significantly by 13%, whereas left ventricularend-systolic volume and ejection fraction did not significantlychange. Left ventricular systolic and end-diastolic pressuresdid not significantly change with pacing tachycardia in eithergroup. The frequency-related changes in left ventricular volumesand pressures indicate that the differrent haemodynamic effectsof pacing tachycardia in both groups of patients result predominantlyfrom frequency effects on myocardial function and not from frequencyeffects on preload or afterload. These data indicate that recentexperimental findings of positive force-frequency effects innon-failing and negative force-frequency effects in failinghuman myocardium are relevant for the intact heart.     

HOW INDEPENDENT ARE MULTIPLE ‘INDEPENDENT’ DIAGNOSTIC CLASSIFICATIONS?

Multiple performances of diagnostic tests are commonly employed in clinical practice and epidemiologic research to assess test reliability, to increase sensitivity or specificity, or to correct for misclassification bias. An assumption almost universally made in this context is the assumption of independence of test results conditional on the true value. For dichotomous diagnostic tests, for example, disease present or absent, this assumption is usually not tenable, however, since there is typically a continuum of the traits that underly diagnosis and individuals in the vicinity of the (implicit or explicit) diagnostic cutpoint (such as the threshold of clinical detectibility) are more likely to be misclassified than other individuals. This paper assesses the magnitude of the resulting correlation of diagnostic errors as a function of the distribution of the underlying trait, the magnitude of the measurement error and the diagnostic threshold. It is concluded that errors of diagnostic tests can be strongly correlated even if errors in perception of the underlying trait are independent. It is illustrated by numerical examples that such positive correlation of diagnostic errors can substantially inflate commonly employed indices of reliability, such as the kappa coefficient.     

In-Vivo Immune Responses of Breast- and Bottle-fed Infants to Tetanus Toxoid Antigen and to Normal Gut Flora

The effects of breast and bottle-feeding on serum immunoglobulin levels and specific antibody responses have been examined in 30 infants on five occasions from 6 days until 9 months of age. No significant differences were found on any sample occasion between the two feeding groups in total immunoglobulin levels of G, M and A classes or in class-specific antibody responses to tetanus toxoid vaccine. This suggests that the capacity of the two groups to make serum antibodies develops similarly. Concentrations of antibodies to commensal Escherichia coli 'O'lipopolysaccharide antigens, however, were significantly greater in the bottle-fed group, and it is suggested that this difference is due to an increase in the exposure of the systemic immune system to these gut antigens in the bottle-fed infants. There are several possible explanations for this increased exposure and the resulting effects on the infants'immune system. These experiments also illustrate a possible role of breast milk in stimulating the immune system.