Time-dependence of urinary neopterin, a marker of cellular immune activity

Neopterin, a marker of cellular immune system activation, is produced by human macrophages after induction by interferon gamma (secreted by T-lymphocytes) and is eliminated mostly in urine. We have documented the circadian rhythm of urinary neopterin in five healthy young men (about 25 years old), using voidings collected during 48 h at fixed 4-h intervals. We repeated the experiment three times, one week apart. Neopterin was measured by high-performance liquid chromatography (HPLC). We clearly show a peak of the excretion of neopterin in the early morning (around 0630 hours +/- 2 h), with total variability (peak-trough difference) reaching 51%. Neopterin is commonly assayed in urinary fractions, so it is imperative to use urine specimens collected at the same time of day--e.g., the first morning urines--to avoid misinterpretation in follow-up of patients.     

Prevalence of magnesium and potassium deficiencies in the elderly

Concentrations of magnesium and potassium in erythrocytes and plasma were determined in a population of 381 unselected elderly men and women, most of them in their eighties. The effects of biological factors (age, sex, weight) and a large set of pathological conditions, malignant or not, were examined. Analyses of variance showed a relation between age and concentrations of plasma potassium and between weight and concentrations of plasma magnesium. The chi-square test showed correlations between low concentrations of plasma magnesium and diabetes, abuse of alcohol and tobacco, and also between low values for erythrocyte magnesium and hypertension. Low values for plasma potassium were correlated with hypertension whereas high values were correlated with cardiovascular disease. Although some of the differences in the mean concentrations observed were statistically significant, these differences were always small. Most interesting was the distribution of the concentrations of the cations. This study shows that assays of both of these cations in erythrocytes were better than assays in plasma to evidence a deficiency. Indeed, about 20% of the studied population had low concentrations of both erythrocyte potassium and magnesium, whereas 2 and 10% had low values for plasma potassium and magnesium, respectively. This study underlines the large prevalence of magnesium and potassium deficiencies in the elderly, an observation we could not attribute to pathology or treatment. Routine electrolyte studies therefore appear to be justified in aged human subjects.     

Fortuitous discovery of the association of true and false aneurysm of the left ventricle after cardiogenic shock]

The authors report the fortuitous diagnosis of a true and a false left ventricular aneurysm in a 77 year old man with severe ischaemic heart disease and calcific aortic stenosis, admitted for cardiogenic shock. The association of these two forms of aneurysm is very rare. Clinical and paraclinical diagnosis is difficult. Conventional left ventriculography is the investigation of reference but the diagnosis has been facilitated by Technetium 99 cardiac scintigraphy and color Doppler echocardiography. Surgery may be considered in cases of true aneurysm especially in patients with left ventricular failure, but the indication is formal in cases of false aneurysm.     

Septicemia following maxillary sinusitis: a rare complication of nasotracheal intubation

A case of septicaemia due to gram-negative bacilli secondary to maxillary sinusitis occurring is reported in a patient intubated through the nose. The search of a purulent nasal discharge and the portable X-ray film were important in establishing the diagnosis. Removing the tube and antibiotics usually give a prompt recovery.     

Lack of specificity of protected distal bronchial samples in the bacteriological diagnosis of nosocomial pneumonia caused by gram negative bacilli

Lower respiratory tract secretions (LRS) were sampled during a two year period in patients undergoing mechanical ventilation using a method previously described by Matthew et al. Only those LRS positive for gram-negative bacilli were reported in this study. The patients were separated in two groups: those with nosocomial pneumonia due to gram-negative bacilli (NP+ group) and those without (NP- group). The species most often isolated from LRS were: Pseudomonas aeruginosa (25%), Proteus (20%), Escherichia coli (18%), Klebsiella pneumoniae (10%), Acinetobacter calcoaceticus (8%) and Haemophilus influenzae (7%). The spectrum of gram-negative species was not statistically different in either group of patients. The numbers of gram-negative bacilli isolated from each LRS were more important in the NP+ group (p less than 0.001), but so was the duration of mechanical ventilation before each LRS (p less than 0.01). In this group also, a specific bacteriological diagnosis with only one species was possible in 3 out of the 13 cases; a tentative diagnosis only was possible in 10 cases: in 6 cases, the responsibility of two (or more) species was suggested. The susceptibility to antibiotics of gram-negative bacilli isolated from LRS was moderate. A third generation cephalosporin together with amikacin seemed to be the best choice of antibiotics when no specific bacteriological diagnosis could be made with the LRS.     

o,P'-DDD (mitotane) treatment for Cushing's syndrome: Adrenal drug concentration and inhibition in vitro of steroid synthesis

Summary o,p'-DDD is an inhibitor of adrenal steroid synthesis currently used for therapy of Cushing's syndrome. Conflicting data have been published on the relationship between the plasma level of the drug and its clinical and biological effects. The levels of o,p'-DDD and o,p'-DDE in various tissues obtained from treated patients have been measured and are compared with data on in vitro steroidogenesis in adrenal tissues from the same patients. o,p'-DDD was found in all samples and o,p'-DDE in half of them, both levels being high when the tissue lipid concentration was high. There was considerable variability in lipid content from one tissue to another and within a tissue from one sample to another; only the drug to lipid ratio seems able to provide a reproducible index of drug entry into a tissue. No relationship was found between the tissue concentration of the drug and the total dose administered or inhibition of the steroid biosynthetic step studied.     

Disruption of the circadian patterns of serum cortisol in breast and ovarian cancer patients: relationships with tumour marker antigens.

Few data are available on the circadian rhythmicity in cancer patients. Since monitoring the disease usually implies the follow-up of blood concentrations of a number of biological variables, it would be of value to examine the profile of the circadian variations of serum cortisol and tumour marker antigens. This we did in 33 cancer patients (13 breast cancer patients and 20 ovarian cancer patients). The profiles of serum cortisol were documented, since this hormone is considered as a strong marker of circadian rhythms. This study shows that 8 out of 13 breast cancer patients and 15 out of 20 ovarian cancer patients had deeply altered cortisol circadian patterns. The modifications were either high levels along the 24 h scale and/or erratic peaks and troughs and/or flattened profiles. Within 24 h, variations of tumour marker antigens as large as 70% were observed but no typical individual circadian patterns could be found. No relationship between cortisol subgroups and concentration of tumour marker antigens at 8 h could be observed (Kolmogorov-Smirnov''s test). The question thus arises as to the origin of these alterations, and whether they are related to a cause or a consequence of the disease, and their possible incidence upon therapeutic designs.     

Polymeric multilayer capsules delivering biotherapeutics

Polymeric multilayer capsules have emerged as a novel drug delivery platform. These capsules are fabricated through layer-by-layer sequential deposition of polymers onto a sacrificial core template followed by the decomposition of this core yielding hollow capsules. The resulting nanometer thin membrane is permselective, allowing diffusion of water and ions but excluding larger molecules. Moreover, the sequential fabrication procedure allows a precise fine-tuning of the capsules’ physicochemical and biological properties. These properties have put polymeric multilayer capsules under major attention in the field of drug delivery. In this review we focus on polymeric multilayer capsule mediated delivery of biotechnological macromolecular drugs such as peptides, proteins and nucleic acids.