Effect of nicotine, silver acetate, and ordinary chewing gum in combination with group counselling on smoking cessation.

Four hundred and ninety six smokers participated in a randomised comparison of the effect of silver acetate, nicotine, and ordinary chewing gum on smoking cessation. All were motivated to stop smoking abruptly and all had smoked at least 10 cigarettes a day for at least five years. Side effects and taste acceptability were related to outcome after six months. The participants attended nine meetings over a year, at which lectures, support, and advice about stopping smoking were given. Tobacco abstinence was confirmed by measurement of carbon monoxide in expired air. The chewing gums were used for 12 weeks. After 12 weeks there was a trend towards more abstainers in the nicotine group (59%) than in the silver acetate (50%) and ordinary (45%) chewing gum groups that was not quite significant (p = 0.07). At 26 and 52 weeks the number of cigarette abstainers was similar in the three treatment groups. Subjects in the nicotine chewing gum group had a longer mean time before relapse than those in the silver acetate and ordinary chewing gum groups. Mean success rates for all subjects combined at 12, 26, and 52 weeks were 52.8%, 39.7%, and 23.3%. The side effects of nicotine and silver acetate chewing gum were generally mild and transient, and unimportant except for mouth irritation from silver acetate, which had a negative effect on outcome, and the low taste acceptability of nicotine, which had a strong negative influence on the success rate. The results suggest a short term effect on nicotine chewing gum on smoking cessation, but the abstinence rates after one year were generally disappointing.     

Blood pressure and excretion of sodium, potassium, calcium and magnesium in 8- and 9-year old boys from 19 European centres

We have measured systolic and diastolic blood pressure and excretions of sodium, potassium, calcium and magnesium in groups of about 50 8- and 9-year-old boys from 19 European centres using standardized methods for the measurement of blood pressure and collection of urine, and by carrying out all analyses in one laboratory. Weight, height, pulse rate and environmental temperature were also studied. Mean systolic blood pressure ranged from 91 to 105 mm Hg and diastolic blood pressure from 51 to 66 mm Hg. Mean 24-h excretion of sodium was between 91 and 146 mmol/d, that of potassium between 29 and 60 mmol/d, that of calcium between 1.5 and 2.6 mmol/d and that of magnesium between 2.7 and 4.2 mmol/d. Mean sodium excretion tended to be lower and potassium excretion tended to be higher in the boys from the north-western parts of Europe. Relations between either systolic or diastolic blood pressure and electrolyte excretions were generally weak or absent. Most remarkable is that only the association between mean diastolic blood pressure and 24-h magnesium excretion (partial regression coefficient (b +/- s.e., -5.04 +/- 2.08 mm Hg/mmol/d) was statistically significant after adjusting for differences in creatinine excretion and environmental temperature. Mean systolic blood pressure was not significantly related with any of the variables measured. The partial regression coefficient (b +/- s.e.) for diastolic blood pressure on weight was 0.186 +/- 0.062 mm Hg/kg, on height 0.165 +/- 0.056 mm Hg/cm, on pulse rate 0.364 +/- 0.100 mm Hg/beats per min and on outside temperature -0.25 +/- 0.07 mm Hg/degrees C.     

Interspecies comparison of cellular localization of the cyanide metabolizing enzyme rhodanese within olfactory mucosa

The observation of high levels of xenobiotic metabolizing enzyme activity in the olfactory mucosa has produced speculation on the functional significance of these enzymes in the nose. Hypothesized roles include protection of the nasal epithelium, lung, and other downstream tissues, and termination or modification of olfactory responses. The enzyme rhodanese metabolizes cyanide, which is a commonly inhaled toxicant and an odorant and therefore of interest to both toxicologists and olfactory neurobiologists. The cellular localization of this enzyme within the olfactory mucosa will have important consequences for its ability to protect specific cells, as well as its ability to alter the concentration of inhaled cyanide at receptors, and therefore could provide clues as to its function in this tissue. We have compared the distribution of this enzyme in two species, the rat and the cow, using immunohistochemical localization techniques employing species-specific polyclonal antisera raised in our laboratory. In the rat, rhodanese-like immunoreactivity was greatest within the apical portion of the sustentacular cells, the basal cells, and the duct cells of Bowman's glands. Very little to no reaction was observed in the acinar cells of Bowman's glands. In the cow, however, the acinar cells and duct cells of Bowman's glands showed intense immunoreactivity with little to no reaction observed in the sustentacular or basal cells. The differences in localization of rhodanese in these two species may have important implications for cell types at risk during inhalation of cyanide or organonitrile compounds metabolized to cyanide within the nasal mucosa. In addition, the difference in distribution in the two species emphasizes the importance of considering enzyme activity and localization in the determination of an appropriate animal model for study of both nasal toxicology and olfactory responsiveness in humans.     

Streptococci from root canals in teeth with apical periodontitis receiving endodontic treatment.

OBJECTIVES: The object of this study was to investigate the diversity among streptococcal species isolated from root canals in conjunction with endodontic therapy and to characterize their production of extracellular proteins. STUDY DESIGN: Consecutive root canal samples (RCS) taken as bacteriological controls during root canal treatment of teeth with apical periodontitis were analyzed in a total of 100 clinical cases. Bacteria were isolated and classified by selective media and gas liquid chromatography. Streptococcal strains were identified by carbohydrate fermentation, hydrolysis of aesculin/arginine, and production of enzymes. Releases of extracellular proteins by streptococci and Enterococcus spp in fluid culture media were examined with SDS-PAGE and 2-dimension gel electrophoresis (2 DE). Extracellular proteins produced were quantified and qualitatively analyzed. Specific proteins were targeted with Western immunoblot assays. Comparisons were made with type strains. RESULTS: Of a total of 241 bacterial strains recovered in the first samples submitted, Streptococcus gordonii, S anginosus, and S oralis were the most frequently isolated streptococci. In 49 of 89 resubmitted samples showing bacterial growth, S gordonii and S oralis still predominated among streptococci. Other common bacterial isolates were Enterococcus spp, Lactobacillus paracasei, and Olsenella uli. Quantitative and qualitative differences in extracellular protein production were observed among clinical isolates and laboratory streptococcal strains. In similar conditions for growth, S intermedius, S anginosus, S oralis, and S gordonii were strong producers of extracellular proteins (>3.0 microg/mL), while Enterococcus spp and S mutans were weak. Whole cell protein extracts showed a different profile from that of extracellular proteins. The chaperone protein DnaK was recognized to be produced extracellularly by S gordonii, S oralis, S anginosus, and S parasanguis. CONCLUSIONS: Being strong producers of extracellular proteins and by virtue of common presence in teeth undergoing endodontic therapy, S gordonii, S anginosus, and S oralis may be of pathogenic significance in posttreatment apical periodontitis.     

Fusion of bone marrow-derived stem cells with cardiomyocytes in a heterologous in vitro model.

OBJECTIVE: Recent studies have demonstrated that transplanted bone marrow-derived stem cells (BMCs) possess a broad differentiation potential and are able to form new cardiomyocytes. However, the identity of BMCs as true cardiomyocytes is still ambiguous. Therefore, we investigated the fate of transplanted fluorescence labeled BMCs and cardiomyocytes in co-culture. METHODS: For cell tracking we used two different fluorescent probes, Vybrant/DiO and Vybrant/DiI. BMCs were taken from human sternal marrow, purified using a Ficoll-gradient-centrifugation, treated with 5-azacytidine and stained with Vybrant/DiO. Furthermore, isolated spontaneous beating cardiomyocytes of neonatal rats (CM) were labeled with Vybrant/DiI. Thereafter, the BMCs were transplanted into CM-cultures and investigated on day 1, 4, 7, 14 and 28 using two-color fluorescence phenotyping by laser-scanning-cytometry (LSC). Two-color positive cells were harvested by patch-clamp technique and beta-MHC mRNA expression was analyzed by single-cell PCR. RESULTS: Two different morphological phenotypes were observed by LSC. First, isolated DiO labeled BMCs without contact or with direct cell contact to DiI labeled CMs. Second, some BMCs and CMs were double positive for DiO/DiI spontaneously forming hybrids. This population increased by 18% from day 1 to 4 and decreased only slightly until day 28. Additionally, few two-color positive cell formations expressed both human and rat specific beta-MHC mRNA as well as only human beta-MHC mRNA indicating that cell-fusion and transdifferentiation has occurred. CONCLUSION: These observations provide in vitro evidence for spontaneous cell fusion and transdifferentiation of BMCs in co-culture, raising the possibility that the observed phenomenons may contribute to development or maintenance of these cell types.     

Basal cell carcinoma. An epidemiologic study in a defined population.

BACKGROUND. The incidence of basal cell carcinoma (BCC) in a defined population is unknown. METHODS. The incidence of histologically diagnosed cases of BCC in a defined population of a city in southern Sweden was studied. Four 2-year periods were examined from 1970 to 1986. Cases from 1970 and 1980 were reexamined microscopically. RESULTS. From 1970 to 1986, the age-standardized incidence of BCC was doubled. BCC was equally common in male and female patients. It was possible to trace another BCC in the medical history of 41% of the patients. The risk of development of BCC increased rapidly with age greater than 55 years. Approximately two-thirds of the tumors were found in the head and neck region. There was a possible increase in superficial multicentric tumors on the trunk but otherwise an essentially unchanged pattern in type and distribution. CONCLUSIONS. The age-standardized incidence of histologically diagnosed BCC was doubled from 1970 to 1986. The rapid increase should be taken into consideration when planning allocation of medical resources.     

WHERE ARE THE GATES IN GAP JUNCTION CHANNELS?

1. In the formation and function of gap junction channels two types of gates ought to be discriminated: the docking gate and the channel gates proper. The docking gate is involved in the transformation of a closed hemichannel to a patent gap junction channel. By definition the trigger mechanism for this gate and maybe even the gate itself is contained within the extracellular loops of the gap junction proteins, the connexins. The channel gates proper determine the open and closed states of the complete gap junction channels. 2. Probing the docking gate by mutagenesis of connexins and by synthetic peptides indicates that this gate is the consequence of complex interactions between a large fraction of the amino acids comprising the extracellular loops. Probably both inter- and intra-molecular interactions are involved, and disulfide exchange may be entailed in the stabilization of the open and closed states. 3. Of the various effectors on the channel gate(s) the voltage effects have obtained the most scrutiny to date. The response of gap junction channels and hemichannels is diverse, the various channels respond differently to transjunctional and membrane potential. No equivalent to the S4 segment representing the voltage sensor in other voltage dependent ion channels is present in the connexin sequences, instead mutations in various segments of connexins have been reported to affect the voltage dependence of gap junction channels. To understand the complexity of voltage effects on gap junction channels, non-connexin peptides may need to be considered as voltage sensors or as modifiers thereof.     

Case-control study of risk factors for cervical neoplasia in Denmark. II. Role of sexual activity,reproductive factors,and venereal infections

Sexual, reproductive and venereal risk factors for cervical neoplasia were investigated in a population-based case-control study of 586 women with histologically verified, cervical squamous-cell carcinoma in situ, and 59 women with invasive squamous-cell cervical cancer, diagnosed from 1985 to 1986 in Copenhagen. Cases were identified from the computerized Danish Cancer Registry. An age-stratified control group (n=614) was drawn at random from the female population in the study area by means of the Danish Central Population Register. A structured questionnaire was mailed to cases as well as controls. Increasing number of sexual partners exerted a significant effect on the risk both for carcinoma in situ, and invasive cancer, independently of age at first intercourse and other potential confounders. Conversely, the association with early age at first intercourse became statistically insignificant after allowance for other risk factors, although an increasing risk was still observed with decreasing age at sexual debut. Early age at first episode with genital warts was a significant risk factor for carcinoma in situ, perhaps indicating a possible increased susceptibility of the cervix epithelium during adolescence. A history of genital warts was a good predictor of risk for carcinoma in situ, whereas a history of previous gonorrhea was associated with an increased risk for invasive carcinoma. Women with multiple births had a significantly increased adjusted risk, especially for carcinoma in situ, although some association was also observed with invasive cervical cancer. The study supports the hypothesis of cervical neoplasia being a sexually transmitted disease, and that carcinoma in situ and invasive cervical carcinoma, to a high degree, have similar patterns of risk factors.Drs Kjaer, Engholm, and Lynge are with the Danish Cancer Registry. Dr Dahl is with the Department of Surgery, Slagelse Hospital, Denmark. Dr Bock is with the Department of Gynecology, Rigshospitalet, Copenhagen, Denmark. Dr Jensen, formerly with the Danish Cancer Registry, is deceased. Address correspondence to Dr Kjaer, Danish Cancer Registry, Institute of Cancer Epidemiology, Danish Cancer Society, Rosenvengets Hovedvej 35, Box 839, Copenhagen. Denmark. The Danish Cancer Society supported this study through grants.     

Effect of thoracic epidural etidocaine 1.5% on somatosensory evoked potentials, cortisol and glucose during cholecystectomy

The effect of thoracic (T7-8) epidural etidocaine 1.5%, 9 ml, and continuous per- and postoperative epidural infusion of etidocaine 1.5%, 4 ml/h, on early (less than 500 ms) somatosensory evoked potentials (SEPs), and cortisol and glucose in plasma during cholecystectomy, was examined in ten patients. Spread of analgesia (pin-prick) was T3 (T1-T3) to L2 (T11-L3) 35 min after injection of etidocaine, and T3 (T2-T4) to T12 (T8-L4) 3 h after surgical incision (median (range)). Before operation, epidural etidocaine had no significant effects on peak-to-peak amplitude of SEPs to electrical stimulation at the L1, T10 or T6 dermatomal level (P greater than 0.09). SEPs were abolished in only two patients at T6, and no patient had SEPs abolished at T10 or L1. The plasma concentrations of cortisol and glucose were significantly increased 20 min after surgical incision and remained increased throughout the study. No correlation was found between the block-induced decrease in the peak-to-peak amplitude at T6 or T10 and increase in plasma cortisol, except for a negative correlation at T10 and the initial increase in cortisol (Rs = 0.72, P = 0.03). In conclusion, thoracic epidural administration of 9 ml of etidocaine 1.5% does not provide total afferent somatic blockade assessed by SEP and the stress response to cholecystectomy.