Penetration of cefsulodin into bronchial secretions

The objective of this study was to evaluate the penetration of cefsulodin, a new cephalosporin active against Pseudomonas aeruginosa, into the bronchial secretions. The study was carried out in 28 patients with respiratory infections; 11 patients received a single dose of 1 g i.v. (bolus); 17 patients received multiple doses of 1 g every 8 h for 48 h. Simultaneous samples of blood and bronchial secretions were collected 30 min and 1, 2, 4 and 6 h after injection. Bronchial secretions were obtained from 23 patients by means of fiberoptic bronchoscopy and in 5 tracheostomized patients (with severe respiratory insufficiency) through a tracheostomy cannula. The assays of cefsulodin were performed by means of the microbiological agar diffusion technique. The results of the study showed a noticeable penetration of the drug into the bronchial secretions, with a mean peak reaching 3.1-5.3 micrograms/ml at the 3rd or 4th hour, a slow elimination and residual levels at 6 h ranging between 2.0 and 6.0 micrograms/ml. The rate of penetration was not influenced by the administration of multiple doses of the drug. The ratios between bronchial concentrations and simultaneous serum concentrations ranged between 10 and 30%, corresponding to the usual values found for other cephalosporins. In conclusion, this study provides satisfactory results and confirms the presence of bronchial levels capable of inhibiting P. aeruginosa.     

Subcellular localization of the human papillomavirus 16 E7 oncoprotein in CaSki cells and its detection in cervical adenocarcinoma and adenocarcinoma in situ

E7 is the major oncoprotein of high-risk human papillomaviruses (HPV) which causes cervical cancer. To date E7 oncoproteins have not been investigated in cervical adenocarcinoma. In this study we generated a rabbit monoclonal anti-HPV-16 E7 antibody, RabMab42-3, which recognizes a conformational epitope in the E7 carboxy-terminal zinc-finger resulting in a strong increase in the sensitivity for the detection of cell-associated HPV-16 E7 protein relative to conventional polyclonal anti-HPV-16 E7 antibodies. Using RabMab42-3, we show that the subcellular localization of endogenous HPV-16 E7 oncoprotein varies during the cell cycle in cervical cancer cells. Moreover, we demonstrate for the first time that the HPV-16 E7 oncoprotein is abundantly expressed in cervical adenocarcinoma in situ and adenocarcinoma, suggesting an important role of HPV-16 E7 for the development of these tumors. Our findings suggest that the HPV-16 E7 oncoprotein could be a useful marker for the detection of cervical adenocarcinoma and their precursors.     

Regional changes in the cholinergic system in mice lacking monoamine oxidase A

Elevated brain monoamine concentrations resulting from monoamine oxidase A genetic ablation (MAOA knock-out mice) lead to changes in other neurotransmitter systems. To investigate the consequences of MAOA deficiency on the cholinergic system, we measured ligand binding to the high-affinity choline transporter (CHT1) and to muscarinic and nicotinic receptors in brain sections of MAOA knock-out (KO) and wild-type mice. A twofold increase in [³H]-hemicholinium-3 ([³H]-HC-3) binding to CHT1 was observed in the caudate putamen, nucleus accumbens, and motor cortex in MAOA KO mice as compared with wild-type (WT) mice. There was no difference in [³H]-HC-3 labeling in the hippocampus (dentate gyrus) between the two genotypes. Binding of [¹²⁵I]-epibatidine ([¹²⁵I]-Epi), [¹²⁵I]-α-bungarotoxin ([¹²⁵I]-BGT), [³H]-pirenzepine ([³H]-PZR), and [³H]-AFDX-384 ([³H]-AFX), which respectively label high- and low-affinity nicotinic receptors, M1 and M2 muscarinic cholinergic receptors, was not modified in the caudate putamen, nucleus accumbens, and motor cortex. A small but significant decrease of 19% in M1 binding densities was observed in the hippocampus (CA1 field) of KO mice. Next, we tested acetylcholinesterase activity and found that it was decreased by 25% in the striatum of KO mice as compared with WT mice. Our data suggest that genetic deficiency in MAOA enzyme is associated with changes in cholinergic activity, which may account for some of the behavioral alterations observed in mice and humans lacking MAOA.     

Characteristics of voluntary participants versus nonparticipants in a psychoeducation program for euthymic patients with bipolar disorder

We aimed to assess the participation rate and predictive factors of participation in psychoeducation programs for euthymic outpatients with bipolar disorder. Ninety-five consecutive euthymic outpatients with bipolar disorder treated with lithium were recruited in a university department of psychiatry. The participants and nonparticipants in a program of psychoeducation were compared for sociodemographic, clinical, and psychological characteristics. According to univariate statistics, a younger age, a higher education level, a shorter duration of illness, a better initial knowledge about lithium, and a less external locus of control were predictive of participation in the program. A binary logistic regression model showed that an external locus of control was an independent predictor of participation. Among bipolar patients, the older, the less educated, those who have less knowledge about their treatment, and those with a more external locus of control were less likely to participate in hospital-based psychoeducation programs.     

Recombinant thyrotropin in the diagnosis of congenital hypothyroidism

CONTEXT: A modern approach to congenital hypothyroidism requires a definitive diagnosis of the underlying mechanisms; this can be achieved within the first weeks of life. When uncertainty persists, treatment is commenced, and the definitive diagnosis of congenital hypothyroidism is deferred to the age of 3 yr. OBJECTIVES: The interruption of thyroid replacement treatment is perceived as risky by parents and physicians. The aim of this pilot study was to test the possibility of a definitive diagnosis during thyroid replacement treatment, using stimulation of thyroid tissue by recombinant human (rh)TSH. SUBJECTS: Eight patients, three boys and five girls, age 5-15 yr (mean, 9.5+/-3.7 yr), with congenital hypothyroidism that had been diagnosed by the neonatal screening program, and having their diagnosis verified between the ages of 3-4 yr, were reevaluated while on thyroid replacement therapy. INTERVENTIONS: Patients received im 0.6 mg/m2 rhTSH on two consecutive days. RESULTS: rhTSH pharmacokinetics, maximal concentration, t1/2, and area under the curve in children were different as compared with adults. In the patients with intact TSH receptors, free T4 levels decreased after the first and the second injection of rhTSH (P=0.0137 and P=0.0149, respectively). All eight children showed identical scintigraphy after rhTSH administration as compared with thyroid replacement withdrawal. CONCLUSIONS: The use of rhTSH is effective for definitive diagnosis of congenital hypothyroidism during thyroid replacement treatment, and no safety issues were encountered.     

Nocturnal calcium, phosphorus and parathyroid hormone in the diagnosis of concealed and subclinical hypoparathyroidism

CONTEXT: Circadian rhythms of plasma parathyroid hormone (PTH) show peak values at night, whereas serum calcium levels peak in the evening and display a nadir at night. HYPOTHESES: Subclinical hypoparathyroidism (HPT) can be detected by utilizing the knowledge of diurnal variations. Thalassemia major (TM) may provide a model system of subclinical HPT. DESIGN: Nocturnal plasma PTH and serum calcium values were determined in 13 TM patients with normal morning serum calcium levels as compared with the corresponding values in eight healthy control subjects. RESULTS: Six patients with TM presented a nadir serum calcium level of 8.3 mg/dl or lower (hypoCa TM) at 0200 h, whereas the remaining seven showed nadir levels of 8.4 mg/dl or higher (normoCa TM). Patients with hypoCa TM displayed a drop between peak and nadir of 1.2 +/- 0.5 mg/dl as compared with a considerably smaller fall of 0.3 +/- 0.7 mg/dl in control subjects (P < 0.05). NormoCa TM patients experienced comparable nocturnal variation to that of control subjects. Patients from both the hypoCa and normoCa TM groups presented significantly lower nocturnal PTH levels than those of control subjects and lost the nocturnal PTH variation characteristic of healthy subjects. A plot of all serum calcium against plasma PTH levels provides a clear distinction of the three groups. CONCLUSIONS: All 13 daytime normocalcemic TM patients presented a certain degree of HPT. The hypoCa TM group displayed a concealed HPT detected in all, except the morning sampling, whereas normoCa TM patients experienced sub clinical HPT observed in the absence of nocturnal HPT variation. Nocturnal measurements of serum minerals thus enhance the sensitivity of HPT diagnosis.