Associations between smoking and adenocarcinomas and squamous cell carcinomas of the uterine cervix (United States).

OBJECTIVES: Few studies of smoking and cervical carcinoma have addressed the rare cervical adenocarcinomas or used DNA-based tests to control for human papillomavirus (HPV) infection. METHODS: This multicenter case-control study included 124 adenocarcinoma cases, 307 community controls (matched on age, race, and residence to adenocarcinoma cases), and 139 squamous carcinoma cases (matched on age, diagnosis date, clinic, and disease stage to adenocarcinoma cases). Participants completed risk-factor interviews and volunteered cervical samples for PCR-based HPV testing. Polychotomous logistic regression generated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for both histologic types. RESULTS: Eighteen percent of adenocarcinoma cases, 43% of squamous carcinoma cases, and 22% of controls were current smokers. After control for HPV and other questionnaire data, adenocarcinomas were consistently inversely associated with smoking (e.g. current: OR = 0.6, 95% CI 0.3-1.1; > or = 1 pack per day: OR = 0.7, 95% CI 0.4-1.3), while squamous carcinomas were positively associated with smoking (e.g. current: OR = 1.6, 95% CI 0.9-2.9; > or = 1 pack per day: OR = 1.8, 95% CI 1.0-3.3). Results in analyses restricted to HPV-positive controls were similar. CONCLUSION: Smoking has opposite associations with cervical adenocarcinomas and squamous carcinomas. Although both histologic types are caused by HPV and arise in the cervix, etiologic co-factors for these tumors may differ.

Evaluation of self-collected cervicovaginal cell samples for human papillomavirus testing by polymerase chain reaction.

As human papillomavirus (HPV) becomes accepted as the central cause of cervical cancer, longitudinal studies are shifting focus away from causality to a more detailed investigation of the natural history of HPV infections. These studies commonly require repeated samples for HPV testing over several years, usually collected during a pelvic exam, which is inconvenient to the participants and costly to the study. To alleviate the inconvenience and cost of repeated clinic visits, it has been proposed that women collect cervicovaginal cells themselves, hopefully increasing participation in the natural history studies. We evaluated the technical feasibility of self-collection of cervicovaginal cells using a Dacron swab for HPV DNA detection. We compared the self-collected swab sample and two clinician-administered swab samples (one from the endocervix and another from the ectocervix) from a total of 268 women participating in a case-control study of adenocarcinoma and squamous cell carcinomas of the uterine cervix (111 cases and 157 controls). HPV DNA was detected and genotyped using an L1 consensus PCR assay. The overall agreement between the clinician- and self-collected swabs was excellent [88.1%; kappa = 0.73 (95% confidence interval (CI), 0.61-0.85)]. The correlation was highest between the two clinician-administered swabs [kappa = 0.81 (95% CI, 0.69-0.93)] but was still excellent when comparing either clinician-administered swab to the self-administered sample [kappa = 0.75 (95% CI, 0.63-0.87) and 0.67 (95% CI, 0.55-0.79) for ectocervix and endocervix, respectively]. The type-specific agreement between samples was higher for high-risk, or cancer-associated, HPV genotypes than for low risk, noncancer-associated HPV genotypes when comparing the self-administered swab sample to the clinician-administered swab sample (kappa = 0.78 for high-risk versus 0.66 for low-risk HPV infections, t = -1.45, P = 0.15). The decrease in agreement for low risk types was largely attributable to an increased detection of these types in the self-administered sample (McNemar's chi2 = 6.25, P = 0.01 for clinician- versus self-administered swab comparisons). The agreement did not vary significantly by age, menopausal status, case status, or clinic center. We have demonstrated that a self-collected Dacron swab sample of cervicovaginal cells is a technically feasible alternative to clinician-administered cervical cell collection in natural history studies of HPV and cervical cancer.

An experimental evaluation of theory-based mother and mother-child programs for children of divorce.

This study evaluated the efficacy of 2 theory-based preventive interventions for divorced families: a program for mothers and a dual component mother-child program. The mother program targeted mother-child relationship quality, discipline, interparental conflict, and the father-child relationship. The child program targeted active coping, avoidant coping, appraisals of divorce stressors, and mother-child relationship quality. Families with a 9- to 12-year-old child (N = 240) were randomly assigned to the mother, dual-component, or self-study program. Postintervention comparisons showed significant positive program effects of the mother program versus self-study condition on relationship quality, discipline, attitude toward father-child contact, and adjustment problems. For several outcomes, more positive effects occurred in families with poorer initial functioning. Program effects on externalizing problems were maintained at 6-month follow-up. A few additive effects of the dual-component program occurred for the putative mediators; none occurred for adjustment problems.

Oral contraceptives as risk factors for cervical adenocarcinomas and squamous cell carcinomas.

To assess the hypothesis that oral contraceptives (OCs) increase the risk of cervical adenocarcinomas, we conducted a six-center case-control study of 124 patients with adenocarcinomas, 139 with squamous cell carcinomas, and 307 population controls. Women between the ages of 18 and 69 who were newly diagnosed with cervical adenocarcinomas between 1992 and 1996 were eligible. Healthy female controls and a second case group of incident cervical squamous cell carcinomas were matched to the adenocarcinoma cases. All participants were interviewed regarding OCs, other risk factors for cervical carcinoma, and utilization of cytological screening, and a PCR-based test determined HPV genotype of cervical samples for both case groups and controls. Use of OCs was positively and significantly associated with adenocarcinomas and positively but weakly associated with squamous cell carcinomas. Associations between OCs and invasive adenocarcinomas (n = 91), squamous cell carcinoma in situ (n = 48), and invasive squamous cell carcinomas (n = 91) disappeared after accounting for HPV infection, sexual history, and cytological screening, but a positive association remained between current use of OCs and cervical adenocarcinoma in situ (n = 33). This association persisted after stratification by screening and sexual history and after restriction according to HPV status, but small numbers made it difficult to exclude detection bias, selection bias, or residual confounding by HPV as potential explanations Current OC use was associated with cervical adenocarcinomas in situ, but we saw no other evidence that OCs independently increase the risk of cervical carcinomas.

Symptom study in context: effects of marital quality on signs of Parkinson's disease during patient-spouse interaction.

Hypokinesia, the inability to initiate or maintain movement, represents one of the most disabling aspects of Parkinson's disease (PD), and displays intriguing moment-to-moment variability from environmental stressors. Correlates of orofacial hypokinesia (characteristics of spontaneous eye blink and speech) were coded from videotaped interactions for PD patients in maritally distressed and nondistressed dyads. Significant changes occurred only for the patients in distressed relationships on the two strongest neurophysiologic measures of orofacial hypokinesia, rate and duration of spontaneous eye blink. Further analyses suggest two possible explanations for these temporal symptom changes. Distressed spouses may exacerbate symptoms by exposing the patient to negativity. Alternately, nondistressed spouses may compensate for the demands of the interactional task by assuming a greater share of the conversation relative to the patient's contribution. Results are linked to existing literature; the role of social and familial support in chronic illness is discussed.

The effects of maternal alcohol consumption and cigarette smoking during pregnancy on acoustic cry analysis.

During the last trimester of pregnancy, 127 primiparous Irish mothers were interviewed to ascertain their history of alcohol and tobacco use. Confounding effects due to other drugs were not a factor in this sample. Mothers consumed an average of .21 ounces absolute alcohol (AA) per day, with 62% classified as moderate drinkers, 10.6% as heavy drinkers, and 26% as nondrinkers. Neurobehavioral status was measured using acoustic characteristics of the infant's cry, collected on the third day of life. Multiple regression analysis showed that more ounces AA per day was related to more dysphonation and higher first formant, while more cigarette smoking was related to higher pitch, higher second formant, and more variability in the second formant. Analysis of variance comparisons of these 3 alcohol groups demonstrated significant cry effects on infants of heavy drinking mothers.

Intravenous gamma-glutamyl-tyrosine elevates brain tyrosine but not catecholamine concentrations in normal rats.

A number of clinical situations may benefit from intravenous supplements of tyrosine (Tyr). In total parenteral nutrition (TPN), the supply of Tyr is limited by its poor solubility. In both rats and infants maintained on pediatric TPN, plasma Tyr levels are approximately 30% of normal, and in rat brains Tyr concentrations are similarly reduced. We reported previously that supplementing a TPN solution with the soluble peptide, gamma-glutamyl-Tyr [Glu(Tyr)], normalizes plasma Tyr and doubles brain Tyr in rats. To assess more fully the behavior of intravenous Glu(Tyr) in vivo, 20 mmol/L Glu(Tyr) was infused into the inferior vena cava of rats at rates increased every 2 hours over an 8-hour period (300 to 450 mumol Glu(Tyr)/kg body weight/h). The surgical procedure for catheterization is described. At the maximum rate of infusion, plasma Tyr and Glu(Tyr) concentrations reached mean plateau values of 326 and 252 mumol/L, respectively. Brain Tyr concentrations were 71 and 264 nmol/g wet weight in control rats infused with heparinized saline (SAL group) and rats infused with Glu(Tyr) (PEP group) respectively. No differences were found in concentrations of norepinephrine (NE), dopamine (DA), or homovanillic acid (HVA) in prefrontal cortex (PFC), striatum (STR), or remaining brain (RB) tissue in PEP and SAL rats. We did not detect undergraded Glu(Tyr) in the brain, and less than 0.5% of infused Glu(Tyr) appeared in the urine.

Social interaction and symptom sequences: a case study of orofacial bradykinesia exacerbation in Parkinson's disease during negative marital interaction.

Evidence is rapidly accumulating that disease symptoms are influenced by psychological factors, and most potently, by familial relationships. This case study demonstrated the detrimental influence of negative marital interaction on orofacial bradykinesia and speech productivity in a 74 year old male Parkinson's disease patient. An increase in bradykinesia symptoms followed a series of specific negative comments by the wife during a conversation; these symptoms showed partial reversal during a subsequent conversation with a lab assistant. The analytic method and data summary strategies used to determine this relationship are discussed relative to their possible utility for other disorders.

Contraceptive practice of Irish married and single first-time mothers.

This study surveys 100 married and 100 unmarried primiparous mothers, attending the National Maternity Hospital, Dublin, with regard to their contraceptive practice, their planning of their pregnancy and the timing of their first antenatal visit. Nineteen per cent of the married women, but 64% of the unmarried women, had never used any contraceptive method. The contraceptive pill was the most popular method for both groups, but while three in five of the married women had at some time used the pill, only a little more than one in five of the unmarried women had ever used it. One quarter of the women who had used contraception reported that their pregnancy was the result of a failure in their contraceptive method. Eighty-nine per cent of the single group and 20% of the married had not planned their pregnancy. None of the married women, but almost a quarter of the single, delayed their first antenatal visit until after they were 20 weeks pregnant.

PIP: This study surveys 100 married and 100 unmarried primiparous mothers, attending the National Maternity Hospital, Dublin, Ireland, with regard to their contraceptive practice, their planning of their pregnancy and the timing of their 1st antenatal visit. 19% of the married women, but 64% of the unmarried women, had never used any contraceptive method. The contraceptive pill was the most popular method for both groups, but while 3/5 of the married women had at some time used the pill, only a little more than 1/5 of the unmarried women had ever used it. 1/4 of the women who had used contraception reported that their pregnancy was the result of a failure in their contraceptive method. 89% of the single group and 20% of the married had not planned their pregnancy. None of the married women, but almost 1/4 of the single, delayed their 1st antenatal visit until after they were 20 weeks pregnant. Very significantly, the results for the married subgroup suggest that the widespread failure of single women to use contraception is related more to their unmarried status than to prevailing cultural norms or religious doctrine prohibiting artificial contraception. The present data do not provide an explanation of the striking difference between the married and the single women in the sample with regard to the time of their 1st attendance at an antenatal clinic. It is possible that the delay is partly due to a psychological resistance to acknowledging a pregnancy.

The relationship between depression and hopelessness. Implications for current theories of depression.

In both Beck's cognitive theory of depression and Brown & Harris's sociopsychological model, hopelessness is given unwarranted universality and centrality. Empirical evidence contradicting this element of the two theories has been ignored, and two new investigations are presented which suggest the existence of 'non-hopeless' depression. A more complete account of the heterogeneous nature of depression is now required.

The crystal structure of ribonuclease B at 2.5-A resolution.

The glycosylated form of bovine pancreatic ribonuclease, RNase B, was crystallized from polyethylene glycol 4000 at low ionic strength in space group C2 with unit cell dimensions of a = 101.81 A, b = 33.36 A, c = 73.60 A, and beta = 90.4 degrees. The crystals, which contained two independent molecules of RNase B as the asymmetric unit, were solved by a combination of multiple isomorphous replacement and molecular replacement approaches. The structures of the two molecules were refined to 2.5-A resolution and a conventional R factor of 0.22 using a constrained-restrained least squares procedure (CORELS). Complexes were also investigated of RNase B plus ruthenium pentaamine and between RNase B and a substrate analogue iodouridine. The polypeptide backbones of the two molecules of RNase B in the asymmetric unit were found to be statistically identical and their differences from RNase A to be statistically insignificant. The carbohydrate chains of both molecules extended into solvent cavities in the crystal lattice and appear to be disordered for the most part. The oligosaccharides appear to exert no influence on the structure of the protein. Iodouridine was observed to bind identically in the pyrimidine site of both RNase B molecules and in a way apparently the same as that previously observed for RNase A. Ruthenium pentaamine bound at histidine 105 of both RNase B molecules in the asymmetric unit, but at a number of secondary sites as well. An array of bound ions was observed by Fo-Fc difference Fourier syntheses. These ions were proximal to lysine and arginine residues at the surface of the proteins while a pair of strong ion binding sites were seen to fall exactly in the active site clefts of both RNase B molecules in the asymmetric unit.

X-ray studies of nucleotide binding and pyridoxal phosphate labeling of the gene 5 DNA unwinding protein.

X-ray diffraction studies have been carried out using difference Fourier methods to evaluate the reaction or interaction of an affinity label and 5'-phosphate nucleotides with the gene 5 DNA binding protein in the crystalline state. In the first case the crystalline protein was reacted with pyridoxal phosphate. Pyridoxal phosphate, which has served as an affinity label for nucleotide binding sites on other enzymes, demonstrated a major site of substitution at the center of the protein's DNA binding cleft adjacent to lysine 46 as well as two other reaction sites near residues implicated in DNA binding. Difference Fourier maps of crystals exposed to 5'-dAMP, 5'-dCMP and 5'-dTMP indicated that phosphate groups were associated with most lysine and arginine side-chains on the surface of the protein but that the nucleoside portion of the ligands were generally disordered. In several cases, however, more specific binding of the nucleotides appeared to have occurred and these sites were primarily within the proposed DNA binding cleft of the protein. In particular, binding was observed near tyrosine 34, phenylalanine 73 and within the curl of the DNA binding loop containing tyrosine 26.

Comparative effects of polymyxin B and compound 48/80 on histamine metabolism in rat muscle and gastric tissue.

Polymyxin B, administered in vivo, increased histidine decarboxylase (HDC) activity and histamine (HM) concentrations in muscle tissue homogenates and supernatants. When administered in vitro it increased HDC activity and HM concentrations in both muscle and gastric tissue. The stimulatory effect on muscle was similar to that obtained with compound 48/80, but 48/80, unlike polymyxin B, did not affect gastric tissue. In vitro additions of alpha-fluoromethylhistidine inhibited both in vivo and in vitro stimulatory effects of polymyxin B. The results of these studies show that the action of compound 48/80 and of polymyxin B are similar, and that both affect HM synthesis in a manner that requires further elucidation.

Differential response of muscle and gastric histidine decarboxylase to compound 48/80 and dietary calcium.

Previous work from this laboratory had indicated that in vivo, histidine decarboxylase (HDC) activity was stimulated by compound 48/80 in rat leg muscle, and that high dietary calcium had a stimulating effect on gastric HDC activity. In the present investigations the 48/80 effect was also observed in vitro in leg muscle extracts from rats, chicks, and guinea pigs. Compound 48/80 had no effect in vitro on histamine metabolism of gastric tissue homogenates in any of the animal species studied. A dietary effect of high calcium intake was noted in rat gastric tissue but not in rat leg muscle. In vitro addition of 48/80 and/or calcium had no stimulatory effect on bacterial HDC or on muscle carnosinase activity. These findings, in conjunction with a comparison of stomach and leg muscle mast cell populations, confirm an HDC stimulatory role for 48/80 in muscle, in addition to its histamine-releasing function from mast cells.

Enhanced carnosine (beta-alanyl-L-histidine) breakdown and histamine metabolism following treatment with compound 48/80.

We have previously suggested that carnosine may serve as a reservoir for histidine to be used as a source of histamine in the trauma response of rats. In this study we report the effect of stimulation of histamine-forming capacity by compound 48/80 on muscle carnosinase (C'ASE) and histidine decarboxylase (HDC) activities as well as on muscle carnosine and histamine concentrations. Male rats (180 g) were injected i.p. with 5 mg/kg bw of compound 48/80 and C'ASE and HDC activities as well as carnosine, histidine and histamine concentrations were monitored over a 72 h period post-injection. This treatment resulted in an 120% increase in muscle HDC activity and an 110% increase in muscle histamine concentration at 15 min post-injection, followed by an 80% increase in muscle C'ASE activity at 1 h and a 100% reduction in muscle carnosine concentration at 24 h post-injection when compared to control animals injected with 0.9% saline. Histidine concentration was not affected by treatment. The time frame of response, a rapid increase in muscle HDC activity and in muscle histamine concentration followed by an increase in muscle C'ASE activity and a later decrease in muscle carnosine concentration, suggests that carnosine is hydrolysed to liberate histidine and that carnosine, as a reservoir for histidine, is mobilized to maintain a constant muscle concentration of histidine for histamine synthesis.

Levels of measured hopelessness in physically-ill patients.

Beck et al.'s Hopelessness Scale was administered to a group of 60 general hospital patients suffering from a variety of physical disorders. The group consisted of 30 chronically- and 30 acutely-ill patients. The mean Hopelessness Scale score for the whole group was 3.75 (SD 2.7). This mean score did not differ significantly from the mean Hopelessness Scale score obtained from a large sample from the general population. However it was significantly lower than the mean score of 40 clinically-depressed psychiatric hospital patients. No significant differences were found between the levels of measured hopelessness of the chronically ill and acutely ill.