Tuberculosis. Current therapeutics

Due to the constant decline in incidence up to the mid eighties, eradication of tuberculosis appeared to be an attainable objective in developed countries. Since then multiple factors (HIV epidemic, poor social conditions in certain unfavored areas, population migrations, urbanization) have led to an increased frequency, making an excellent knowledge of tuberculosis a priority for all physicians. Multi-resistant mycobacteria have also made their appearance leading to numerous clinical and experimental studies which provide new insights into the correct management of patients with tuberculosis. Despite these recent changes, the classical treatment for tuberculosis remains the same in most cases, allowing nearly-certain cure when applied correctly in patients infected with a susceptible bacteria, including those with HIV infection or extrapulmonary localizations. On the contrary, the spontaneous aggravation of multi-resistant tuberculosis, even in some cases being treated, emphasizes the need to test the strain's susceptibility to the antituberculous agents used. Certain new antibiotics, including fluoroquinolones, may play an important role in some cases. The contribution of surgery, isolation and strict compliance must also be emphasized. Resistant strains may also led to renewed indications for the Calmette-Guérin vaccine.     

Long-term depression of synaptic transmission in the cerebellum: cellular and molecular mechanisms revisited

In recent studies, it has been shown that information about scatterer spacing can be obtained from analyzing the phase of the ultrasound echo from various media. Such information proves to be useful when examining the ultrasonic backscatter from well-organized tissue, such as the liver. By quantifying the deviations in scatterer spacing and/or varying degrees of regularity, conclusions may be drawn about the underlying pathology of the tissue. This paper examines the physical basis of how the scatterer locations affect the phase of the data. Computer simulations were performed that mimic various scattering conditions and that display the effects of differing degrees of regularity, as well as increases in a diffuse random background scattering component. Results of studies on a phantom are also included to investigate and display the phase response under well-controlled scattering conditions. Finally, in vivo data taken from liver scans were analyzed. In this work, it was shown that the phase of the backscattered signal holds valuable information regarding the pathological state of liver tissue. It is suggested that this simple examination of the phase can be refined into a technique to be used as a method to consistently detect the onset of pathological change.     

Levamisole treatment of a child with severe aphthous stomatitis and neutropenia

The treatment of a 12-year-old girl with a lifelone history of recurrent infections and aphthous stomatitis is reported. A profound neutropenis, first noted at the age of 2 years, occurring at least every month was observed together with multiple mouth ulcers a sore throat and swelling of the jugular glands. Levamisole, originally described as an anthelmintic, has a beneficial effect on the symptoms of recurrent aphthous stomatitis. After levamisole treatment aphthous stomatitis was milder and in the 1-year follow-up period the patient was asymptomatic several times during a phase of obvious neutrophil depression. The child no longer complained of a sore throat with swelling of the jugular glands and the recurrent staphylococcal infections of the skin disappeared. After therapy a marked increase in monocytes at the moment of neutropenia was observed.     

Sex steroid metabolism and menstrual irregularities in the exercising female. A review

This article aims to clarify why, and by which mechanisms, exercise may influence the normal menstrual cycle. Therefore, the vast amount of literature on this subject is reviewed and a critical appraisal of the most widespread hypotheses if offered. The strikingly low body mass which frequently accompanies exercise-related menstrual irregularities (ERMI) has led some authors to develop a hypothesis which postulates that a critical percentage of body fat is essential to trigger normal menstruation. The relevance of any reference to anorexia nervosa to support this view lacks consistency: female athletes differ in many ways from patients with anorexia nervosa, not least in their excellent physical status which is essential to deliver first-class performances. ERMI is not identical to the so-called female athlete triad, a complicated pathology that involves ERMI, premature osteoporosis and disordered eating. ERMI itself does not seem to have any substantial pathological effects as long as attention is paid to preventing osteoporosis or stress fractures which may result from prolonged hypo-estrogenaemia. In the female athlete with ERMI who wishes to conceive, the accompanying subfertility may necessitate a response other than a prompt reduction in training intensity, as this is hardly a first choice for any top athlete. During recent years, a number of prospective studies have greatly contributed to our understanding of the complexity of the mechanisms involved in ERMI. Older hypotheses, such as those considering hyperprolactinaemia as the cornerstone of ERMI, have now been firmly rejected. The present hypotheses emphasise the importance of caloric deficiency and limited energy availability, although they still fail to identify the actual mechanism that causes ERMI. There is, however, evidence that ERMI is produced by a disturbance of the hypothalamic gonadotrophin-releasing hormone oscillator. This disturbance is caused by either an insufficient estrogen or progesterone feedback or by an imbalance of local opioid peptide and catecholamine activities mediated by gamma-aminobutyric acid (GABA), corticotrophin-releasing hormone and insulin-like growth factor-1. More recent experiments have also linked ERMI with changes in steroid metabolism, in particular, an increasing activity of catecholestrogens possibly leading to enhanced intracerebral noradrenaline (norepinephrine) levels that may interfere with normal gonadotrophin release. This article demonstrates that the outcome of the many studies of ERMI is characterised by much controversy and numerous methodological flaws. The importance and complexity of some recent findings necessitate a comprehensive study which links older and newer findings within a critical perspective.     

The potential risk factors associated with acute viral hepatitis in children under 5 years old]

In studies of the effects of salt intake on blood pressure (SBP, MBP, DBP), influences on heart rate (HR) are usually neglected even though the longterm load on both left ventricle (LV) and systemic arteries (SA) is better related to the product of HR x SBP (or MBP) than to pressure alone. After all, altered salt intakes often induce considerable volume-related changes in HR, and the heart operates more economically at low HR and high stroke volume (SV). Thus, about 3/4 of LV metabolism is used for the build-up of systolic tension, while the cost for SV expulsion, or for SV increases, is far lower. Moreover, low HR prolongs the diastolic period, so important for LV coronary supply. Against this background we have used results from studies in both rats and man, in which both BP and HR were followed during marked changes in salt intake, to explore how this affected the HR x SBP (or HR x MBP) product. Briefly, in ordinarily salt-resistant organisms, whether normo- or hypertensive, salt intake increases, which in man ranged from 10-20 to 250-300 mM (in rats over 100-fold), if anything reduced the computed longterm load (HR x SBP, or MBP) on LV and SA, as consequences of an efficient reflex volume control. By contrast, in salt-sensitive man, HR reflex reductions to increased salt intake were almost absent despite substantial SBP elevations, suggesting the influence of a CNS suppression of bulbar reflex centres combined with CNS neurohormonal interference with renal salt volume excretion, as in SHR.     

Diffuse interstitial pneumopathy associated with limited Sj?gren's syndrome (author's transl)

Diffuse interstitial pneumopathy was found to be associated with limited Sj?gren's syndrome (i.e. without connective tissue involvement) in 5 women aged from 48 to 83 years. The respiratory symptoms (dyspnoea, unproductive cough and crepitations) appeared before the dry-eye-and-mouth syndrome was diagnosed in two patients and several years afterwards in three. Respiratory function studies showed a mixed restrictive and obstructive syndrome, perturbed Co transfer and increased total expiratory airways resistance. These changes reflected the underlying pathology, as revealed by bronchial and lung biopsies, which consisted of lymphocyte and plasmocyte infiltration and fibrosis of the interalveolar septa, peribronchial spaces and bronchial glands. Abnormal respiratory function tests in 5 other patients without any respiratory symptom suggest that subclinical and subradiological lesions of the lungs and bronchi are not uncommon in Sj?gren's syndrome.