Synthesis and structure-activity relationships of new 9-N-alkyl derivatives of 9(S)-erythromycylamine

A series of new 9-N-alkyl derivatives of 9(S)-erythromycylamine has been synthesized by reductive alkylation of erythromycylamine with aliphatic aldehydes and sodium cyanoborohydride. Alternative syntheses employing hydrogenation methods have also been developed. These new 9-N-alkyl derivatives possess excellent antimicrobial activity in vitro and in vivo, especially when administered orally to treat experimental infections in mice. From structure-activity studies, 9-N-(1-propyl)erythromycylamine (LY281389) was selected as the most efficacious derivative. These methods have also been extended to the synthesis of some 9-N,N-dialkyl derivatives of erythromycylamine.     

Energy metabolism and requirements in different ethnic groups

Some studies on energy metabolism of men and women in Third World countries suggested that their basal metabolic rate (BMR) is lower compared to BMRs of people in Northern European and American countries. It is, however, not clear whether this results from ethnic factors, climate or adaptation to, for instance, a low energy intake. A study on energy requirements of people from Third World countries has therefore been performed. People with different ethnic backgrounds participated; they were divided into four ethnic groups: 8 African males, 7 Asian males of Mongolian origin (Asian-M), 8 Asian males of Caucasian origin (Asian-C) and 7 European males, who formed the control group. The participants from outside Europe had spent at least 3 months in the Netherlands. All participants consumed a diet (12 per cent of energy from protein, 22 per cent from fat and 66 per cent from carbohydrate) during 8 d. The dietary energy given to each individual was estimated to maintain energy equilibrium during the experiment. The last 3 nights and 2 days were spent in an indirect whole-body calorimeter. Two 24-h energy expenditure (24hEE) measurements were performed on each subject. The environmental temperature inside the calorimeter was 22.0-24.5 degrees C. Physical activity was light, mainly sedentary, with 75 min bicycling at 15 W. The Asian subjects had a significantly lower body weight and fat-free mass than the Europeans. Energy requirement (ER), 24hEE and EE during the night (8 h sleep) was lower in the Asian and African subjects compared to the Europeans, but the difference only reached significance for the Asian-C and African males. When ER, 24hEE and EE-night were expressed in relation to body weight and fat-free mass the Asian groups showed a higher ER and higher EE than the Europeans. This result is contrary to findings of others and may be caused eg, by a higher body weight and fat-free mass of the European controls. Comparison of EE-night with BMR estimated from FAO/WHO/UNU equations showed that the EE-night was consistently lower by about 9 per cent. This suggests that EE during the night may not be predicted by the BMR estimated by widely used equations. This study does not give conclusive evidence that an ethnic factor is involved in energy metabolism in humans.     

Regulation of G-PROTEIN mRNA abundancy and cAMP accumulation after long-term opioid incubation in primary cultures of astroglia from the rat cerebral cortex.

Primary astroglial cultures were incubated with delta (10(-6) M DPDPE) or kappa (10(-5) M U-50,488H) receptor agonists for 5 days. Thereafter, the acute inhibitory actions of delta or kappa receptor agonists on forskolin stimulated cAMP accumulation were assayed. The G alpha s, G alpha i-1 and G alpha i-2 mRNA levels were quantified after 5 days of either delta or kappa receptor agonist treatment using a solution hybridization, RNase protection assay. Pronounced effects were observed after 5 days of kappa receptor agonist [10(-5) M U-50,488H] incubation. This treatment resulted in an attenuation in the acute inhibitory action of delta and kappa receptor agonists. Furthermore, a decreased stimulatory action of forskolin was seen. Similar effects were also seen after delta receptor stimulation. We also investigated the effects after 24 h and 3 days of incubation with the kappa receptor agonist (10(-5) M) U-50,488H. The 24 h incubation resulted in a decreased sensitivity to the acute inhibitory action of delta and kappa receptor agonists in the astroglial cultures. This effect was further accentuated after the 3 days of incubation with 10(-5) M U-50,488H. No significant change was seen in the basal accumulation of cAMP after incubation with the kappa agonist U-50,488H. However, after 5 days of incubation with the delta agonist DPDPE, a significantly increased basal accumulation of cAMP was seen in the astroglial cultures. After 5 days of delta or kappa agonist incubation, an increase in G alpha s mRNA level and a decrease in G alpha i-2 mRNA level was seen compared with controls. No statistically significant alterations in the amount of G alpha i-1 mRNA were seen. The data obtained in the present study indicate that the effects of long-term opioid treatment alters the sensitivity of glial cell opioid receptors. Furthermore, long term opioid treatment induces alterations in glial G-protein mRNA levels.     

Post-traumatic osteolysis of the distal extremity of the clavicle]

Post-traumatic osteolysis of the acromial extremity of the clavicle is a rare condition, usually occurring sometime after an injury to the shoulder. Three cases of PTOAC and one case of athlete's osteolysis are reported. The semiology is summed up, as well as the differential diagnoses and the associated forms. This is a benign disease, which should be suggested by the clinical findings and diagnosed on the radiographs, which demonstrate early signs of osteolysis. The treatment is mainly based on immobilization.     

The value of quantitative DNA flow cytometry of testicular fine-needle aspirates in assessment of spermatogenesis: a study of 137 previously maldescended human testes

In order to assess the suitability of DNA flow cytometry of fine-needle aspirates for quantiftring spermatogenesis, the results from DNA flow cytometry were compared to histological evaluation of testicular biopsies taken concomitantly from 171 previously maldescended testes. In 137 of 171 cases, sufficient material for flow cytometric as well as histological evaluation was obtained.
Histological analysis of surgical biopsy specimens revealed spermatogenesis including the spermatid stage in 117 of the 137 gonads. In six of the 117 gonads no haploid cells were found using flow cytometry. On the other hand, surgical biopsies failed to reveal spermatogenesis in five cases in which the corresponding aspirates contained haploid cells. Both methods therefore seem equally sensitive in detection of spermatogenesis.
Other types of histological patterns also corresponded to distinct DNA histograms.
Thus, in 11 of 12 cases with Sertoli-cell-only pattern in all tubules, at least 95% of the cells had a diploid DNA content. Furthermore, predominance of tubules with maturation arrest at the primary spermatocyte level corresponded to an increased proportion of tetraploid cells.
When compared to surgical biopsy, DNA flow cytometry of testiclar fine-needle aspirates is a more objective, easy and rapid method, which is more convenient for the patient. This study has indicatedthat DNA flow cytometry is a suitable method of quantitative assessment of spermatogenesis. One of the first target groups might be men with azoospermia. In such men, DNA flow cytometric analysis of fine-needle aspirates and surgical biopsy are apparently of equal sensitivity in detecting gonads with spermatogenesis. We conclude that DNA flow cytometry may become an alternative method for the quantification of spermatogenesis.     

Conservative treatment for acute rupture of the Achilles tendon

Summary Sixty-six patients with acute ruptures of the Achilles tendon were treated by immobilisation in a plaster cast for 12 weeks. Fifty-seven were followed up for a mean time of 70 months. Four re-ruptures occurred shortly after the initial treatment. Most patients had no or only slight complaints, three had moderate and one severe, problems. The activity level dropped slightly from 5.3 to 5.03 (Tegner score). The results are satisfactory with a low complication rate. The method is an alternative to operative repair, especially in patients declining operation and in those in whom operation or anaesthesia is contraindicated.

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Résumé Soixante-six malades ont fait l'objet d'une étude à long terme concernant le traitement non-chirurgical des ruptures aiguës du tendon d'Achille. Le recul moyen était de 70 mois. Les patients avaient été immobilisés dans un plâtre pendant 12 semaines. 4 ruptures itératives survinrent précocément (6%). La plupart des malades n'avaient pas ou peu de séquelles, trois seulement se plaignaient d'une gêne modérée et 1 d'une gêne importante. Le niveau d'activité avait légérement diminué, de 5.3 à 5.03 (selon le score de Tegner). Les résultats paraissaient satisfaisants dans l'ensemble, avec une taux peu élevé de ruptures itératives ou d'autres complications. La méthode constitue une alternative valable au traitement chirurgical, notamment chez les sujets qui ne veulent pas être opérés ou chez ceux qui présentent des contrindications à l'anesthésie ou à la chirurgie.

     

A simple method of chromosomal analysis for malignant solid tumors.

A case of essential thrombocythemia with a partial deletion of the long arm of chromosome 11, del(11)(q21) as a sole chromosomal anomaly is reported. Rearrangement of chromosome 11 at band 11q21 has been reported in six patients with chronic myeloproliferative disorders: four with post-polycythemic myelofibrosis, one with myelofibrosis with myeloid metaplasia, and one with Ph+ chronic myeloid leukemia in blastic phase. Except for the last patient, all patients had been treated with 32P and/or an alkylating agent prior to cytogenetic examination. This is the first report of the 11q21 abnormality in essential thrombocythemia seen at diagnosis.     

Otitis media in children born to human immunodeficiency virus-infected mothers.

Acute otitis media (AOM) is thought to occur frequently in children infected with human immunodeficiency virus (HIV). We compared experience with AOM of 28 HIV-infected children with that of 33 children who seroreverted to HIV antibody negative status by age 18 months. The mean number of episodes/year of AOM for children who seroreverted decreased from 1.33 in the first year of life to 0.13 in the third year, whereas the mean number of episodes/year in HIV-infected children increased from 1.89 to 2.40. By age 3 years, all HIV-infected children had experienced 1 or more episodes of AOM, and 80% had experienced 6 or more, whereas 75% of children who seroreverted had experienced 1 or more episodes, and none had had 6 or more. HIV-infected children with normal T4 lymphocyte counts had a mean of 1.18 episodes of AOM in the first year of life compared with 2.35 episodes in HIV-infected children with decreased counts (P = 0.023). HIV-infected children with low counts had a nearly 3-fold increased risk of recurrent AOM (47% vs. 18%).