Morphology of peripheral airways in current smokers and ex-smokers

To investigate the effect of smoking status on pulmonary function and pathologic changes in the peripheral airways, we studied 97 patients who underwent thoracotomy for coin lesions. The patients were divided into 4 groups: nonsmokers (n = 9), current smokers (n = 51), and those who had ceased smoking for less than (n = 18) or more than (n = 19) 2 yr prior to surgery. We found that current smokers had evidence of air-flow obstruction with abnormal lung volumes when compared with nonsmokers. Ex-smokers had lung volumes similar to those of nonsmokers, but showed evidence of obstruction, with the FEV1/FVC between the values found for nonsmokers and current smokers. Examination of the small airways showed that the membranous bronchioles of current smokers and ex-smokers displayed only increased goblet cell metaplasia when compared with those in nonsmokers; the respiratory bronchioles of current and ex-smokers showed increases in intraluminal and airway wall inflammatory cells, wall fibrosis, and pigment deposition. We conclude that patients who currently smoke cigarettes have reduced lung function that is associated with abnormalities of airway structure. Although those who have stopped smoking have function that is closer to the nonsmoking group, there is no apparent difference in structural change between current and ex-smokers.     

Clinical and prognostic aspects of adrenocortical neoplasms in childhood

BACKGROUND: A retrospective study of 54 children was undertaken to define the clinical presentation and secretory patterns of adrenal tumors and to evaluate the outcome of surgical resection and medical therapy. PROCEDURES: Different factors were studied in univariate and multivariate analysis by using the Cox proportional hazard model. RESULTS: Median age at diagnosis was 4 years. Boys and girls were affected equally. The disease was revealed by virilization (61%) or by a palpable mass (39%) with a 0.1-5.5 year delay from initial symptoms. At initial examination, we found that 76% of children were virilized. Ninety-four percent of the tested tumors secreted androgens, which were associated with glucocorticoids in 36%. Adrenal tumors in children were smaller than in adults. Half of them measured less than 10 cm. There were recurrences in 40% of children. The survival rate at 5 years was 49%, 70% if resection was microscopically complete and 7% if not (P < 0.001). CONCLUSIONS: In children, rare adrenal tumors have different diagnostic and prognostic characteristics than in adults; however, recurrences remain frequent. The efficacy of chemotherapy, mainly o,p'-DDD (Mitotane), remains to be evaluated in comparative trials.     

The fate of cryopreserved sperm acquired during vasectomy reversals

PURPOSE: Intraoperative sperm banking has been recommended during vasectomy reversal. These specimens are maintained as insurance for possible future intracytoplasmic sperm injection. We evaluated the fate of specimens collected intraoperatively from 48 vasectomy reversal patients. MATERIALS AND METHODS: Of 75 men 48 (64.0%) agreed to intraoperative sperm banking during vasectomy reversal. A total of 135 vials of epididymal sperm, 81 vials of testicular tissue and 13 vials of vasal sperm were cryopreserved. RESULTS: Among couples who stored sperm 10 (20.8%) voluntarily discarded the specimens within 4 months of vasectomy reversal. Specimens from 31 couples (64.5%) remain in storage. Seven couples (14.6%) have used frozen sperm for intracytoplasmic sperm injection. In 3 of these couples the men were azoospermic after surgery, 2 men had 10,000 to 15,000 sperm per ml. in the ejaculate with limited motility and 2 had 1 to 2 million sperm per ml. with limited motility. The 7 women who underwent intracytoplasmic sperm injection ranged between 37 and 39 years old, which was older than the mean age of the remaining study group (32.7 years). With intracytoplasmic sperm injection fertilization was achieved in all cases and 20 of 47 eggs (42.5%) developed into embryos. Of 7 women 4 achieved biochemical pregnancies (57.1%) and 2 (28.6%) delivered newborns with epididymal sperm. Natural pregnancy occurred in 7 of 16 vasectomy reversal couples (43.7%) who were followed at least 18 months postoperatively but the time to pregnancy averaged 1 year. CONCLUSIONS: Cryopreservation of sperm collected at vasectomy reversal is recommended for patients undergoing vasoepididymostomy or vasovasostomy. The couples who used the cryopreserved sperm for intracytoplasmic sperm injection included husbands whose postoperative ejaculate remained azoospermic or severely oligospermic and wives who were approaching 40 years old. Only a limited number of couples (14.6% of the study group) have used the cryopreserved sperm but the delivered newborn rate (28.6%) was comparable to other intracytoplasmic sperm injection data. The natural pregnancy rate after vasectomy reversal was 43.7% but the time to pregnancy after surgery was lengthy (average 1 year). These findings may be helpful for counseling couples who are planning vasectomy reversal surgery and may be considering intraoperative sperm banking.     

The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells

To assess the efficiency of nasally administered cartilage-specific collagens as vaccination against development of arthritis and to ameliorate already established chronic arthritis, experimental models which develop chronic arthritis, pristane-induced arthritis (PIA), and homologous collagen-induced arthritis (CIA) in the rat were selected. Cartilage-specific collagens type IX (CIX) and type II (CII) were used for vaccination intranasally. A single dose of 250 microg CII instilled intranasally in rats with established PIA ameliorated the disease. For the prevention of disease, the same dose given before immunization was found to be most effective. Most importantly, the disease was more severe if this dose was given three times. For treatment of PIA, CIX was found to be more effective than CII, whereas for treatment of CIA only CII was effective. The amelioration of CIA was associated with a marked suppression of delayed type hypersensitivity and the flare reaction to CII and lower levels of IgG2b anti-CII antibodies in serum, i.e., with suppression of the TH1 rather than the TH2 response to CII. These findings, that cartilage proteins, if given intranasally, can both prevent and ameliorate established chronic arthritis in rats, are of significant importance for possible use in rheumatoid arthritis. The identification of two different cartilage-specific proteins (CII and CIX) effective against a disease induced with a well-defined nonimmunogenic adjuvant such as pristane will be of value for enhancing the effectiveness of the treatment.     

Radiation down-regulates replication origin activity throughout the S phase in mammalian cells

An asynchronous culture of mammalian cells responds acutely to ionizing radiation by inhibiting the overall rate of DNA replication by approximately 50% for a period of several hours, presumably to allow time to repair DNA damage. At low and moderate doses, this S phase damage-sensing (SDS) pathway appears to function primarily at the level of individual origins of replication, with only a modest inhibition of chain elongation per se. We have shown previously that the majority of the inhibition observed in an asynchronous culture can be accounted for by late G1cells that were within 2-3 h of entering the S period at the time of irradiation and which then fail to do so. A much smaller effect was observed on the overall rate of replication in cells that had already entered the S phase. This raised the question whether origins of replication that are activated within S phase per se are inhibited in response to ionizing radiation. Here we have used a two-dimensional gel replicon mapping strategy to show that cells with an intact SDS pathway completely down-regulate initiation in both early- and late-firing rDNA origins in human cells. We also show that initiation in mid- or late-firing rDNA origins is not inhibited in cells from patients with ataxia telangiectasia, confirming the suggestion that these individuals lack the SDS pathway.     

Early onset of parturition induced by acute alcohol exposure in C57BL/6J mice: role of uterine PGE and PGF2alpha

These studies were designed to determine the effect of acute alcohol treatment on gestational length and to probe for a mechanism underlying alcohol-induced early onset of parturition (EOP) in mice. Experiment 1: alcohol increases the incidence of EOP. Pregnant C57BL/6J mice were given alcohol (0, 4, 5 or 6 g kg(-1), i.g.) on Gestational Day (GD) 10, 15, 16, 17 or 18. Deliveries were monitored every 6 h from GD 18. Results indicated that 6 g kg(-1) alcohol treatment on GD 17 or 18 increased the incidence of EOP. Experiment 2: prostaglandins (PGs) play roles in parturition. The purpose of Experiment 2 was to determine whether PGs mediate alcohol-induced EOP in mice. The results indicated that pretreatment on GD 17 with aspirin, a prostaglandin synthesis inhibitor, prevented alcohol-induced EOP. These data suggest that alcohol-induced EOP in mice may be mediated by PGs. Experiment 3: PGs are influenced by alcohol and are triggers of labour. Experiment 3 measured uterine PGs associated with the onset of alcohol-induced EOP in mice. Alcohol increased uterine PGE and PGF2alpha, with PGE levels higher than control before labour, and elevated PGF2alpha levels correlating with labour. Changes in gestational length have important implications for pregnancy outcome, as well as for normal fetal growth and development.