Search PubMed⌕ Search

Biomedical subjects

M Macaluso

Publications and source records attributed to M Macaluso.

At least 37 records · Page 2Linked to original sources

Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis.

Here we report the effects of gentamicin treatment on cystic fibrosis transmembrane regulator (CFTR) production and function in CF airway cells and patients with CF with premature stop mutations. Using immunocytochemical and functional [6-methoxy-N- (3-sulfopropyl) quinolinium (SPQ)-based] techniques, ex vivo exposure of airway cells from stop mutation CF patients led to the identification of surface-localized CFTR in a dose-dependent fashion. Next, five patients with CF with stop mutations and five CF control subjects were treated with parenteral gentamicin for 1 wk, and underwent repeated in vivo measures of CFTR function (nasal potential difference [PD] measurements and sweat chloride [Cl(-)] testing). During the treatment period, the number of nasal PD readings in the direction of Cl(-) secretion was increased approximately 3-fold in the stop mutation patient group compared with controls (p < 0.001), and four of five stop mutation patients with CF had at least one reading during gentamicin treatment with a Cl(-) secretory response of more than -5 mV (hyperpolarized). A response of this magnitude was not seen in any of the CF control subjects (p < 0.05). In an independent series of experiments designed to test the ability of repeat nasal PDs to detect wild-type CFTR function, evidence of Cl(-) secretion was seen in 88% of control (non-CF) nasal PDs, and 71% were more than -5 mV hyperpolarized. Together, these results suggest that gentamicin treatment can suppress premature stop mutations in airway cells from patients with CF, and produce small increases in CFTR Cl(-) conductance (as measured by the nasal PD) in vivo.

Adolescent↗

Partner type and condom use.

OBJECTIVES: To examine the association between type of sexual partnership and condom use consistency. DESIGN: A prospective follow-up study of women attending two urban clinics for sexually transmitted diseases (STD). METHODS: Sexual diaries recording barrier method, partner initials and partner type for each act of intercourse were kept by 869 women. Condom use by partner type was evaluated in three ways in the entire group: among women who encountered multiple partners, during months in which women encountered multiple partners, and within sexual partnerships that changed status during the study. RESULTS: Consistency of condom use was higher with new and casual partners than with regular partners in the entire group and among women who encountered multiple partners. In months in which partners of different types were encountered, condom-use consistency was higher with new and casual partners than with regular partners. Consistent condom use decreased in partnerships that changed status from new to regular. The female condom was used more often with regular partners than with new or casual partners in the entire study group, among women who encountered multiple partners, and during months in which a woman achieved consistent use with her regular partner. CONCLUSIONS: This study provides strong evidence that condom use behavior is modified by partner type. Observations about condom use and partner type made in cross-sectional or retrospective surveys also hold in the present longitudinal analyses of individual women and of partnerships that change status. The female condom may be an important option for achieving consistent protection within stable partnerships.

Adolescent↗

Safety and acceptability of a baggy latex condom.

A total of 104 couples participated in a randomized crossover trial to compare a new baggy condom with a straight-shaft condom produced by the same manufacturer. Participants completed a coital log after using each condom. All couples used five condoms of each type. Among 102 couples who did not report major deviations from the protocol, the breakage rate was eight of 510 (1.6%) for the baggy condom, and six of 510 (1.2%) for the standard condom (rate difference, RD = 0. 4%, 95% confidence interval of the RD, CI = -1.0%; +1.8%). Slippage was reported in 50 baggy condom logs and in 58 standard condom logs; the slippage rate was 50 of 510 (9.8%) for the baggy condom, and 58 of 510 (11.4%) for the standard condom (RD = -1.6%, 95% CI = -5.4%; +2.2%). Slippage was most often partial (<1 inch) and may not indicate condom failure. Severe slippage rates were 11 of 510 (2.2%) for the baggy condom, and 18 of 510 (3.5%) for the standard condom (RD = -1.4%, 95% CI = -3.4%; +0.7%). The findings support the conclusion that the two condoms are equivalent with respect to breakage and slippage. The participants appeared to prefer the baggy condom, suggesting that the new product may be more acceptable to the public than the traditional straight-shaft condoms, and may be easier to use consistently over long time periods.

Adolescent↗

Birth control method choice and use of barrier methods for sexually transmitted disease prevention among low-income African-American women.

In a prospective study of 1122 women attending a sexually transmitted disease (STD) clinic in Alabama, consistent use of the male condom and vaginal microbicide/spermicides was promoted to reduce STD risk. This analysis evaluated: 1) baseline characteristics that may influence birth control method choice; and 2) the association of birth control method and other baseline characteristics with consistency of barrier use during follow up. Birth control method was associated with sociodemographic variables, sexual, and reproductive history. Women who adopted user-independent methods (tubal ligation, implants, injectable hormones) appear to have completed their family plan. Oral contraceptive users were of higher socioeconomic status and at lower STD risk. Barrier method users and women who used no method were young and at higher STD risk. Consistency of condom/spermicide use increased in all groups. Barrier method users were more likely than other women to use condoms and spermicides during the study. Women who used no birth control method at baseline experienced the largest increase in barrier use during follow up, although their barrier use rates were lower than in other groups. The synergism between the intention to prevent pregnancy and the intention to prevent STD should be considered in the design of interventions promoting condom use.

Adolescent↗

Validity and coverage of estimates of relative accuracy.

PURPOSE: Studies comparing test accuracy often restrict the confirmation procedure to subjects classified as positive by either test. Relative sensitivity (RSN) and relative false-positive rate (RFP) are two estimable comparative measures of accuracy. This article evaluates the influence of sample size, disease prevalence, and test accuracy on the validity of point estimates of RSN and RFP, and on the coverage of their confidence intervals (CI). METHODS: For each combination of sample size, disease prevalence, test accuracy, and interdependence between tests 1,000 samples were generated using computer simulations. The percent bias in the RSN and RFP estimates was measured by comparing the means of the 1,000 values computed in each simulation (log-transformed) with their theoretical values. Coverage of the estimated CI was measured by computing the proportion that actually included the theoretical values. Application of these methods was illustrated with data from a study comparing mammography and physical examination in screening for breast cancer. RESULTS: RSN estimates were valid if the true number of diseased cases exceeded 30, and RFP estimates were valid if the number of nondiseased subjects exceeded 200. When the numbers of diseased and nondiseased subjects exceeded 150 each, the 95% CI of RSN and RFP provided adequate coverage of the parameters (95 +/- 2%). CONCLUSION: Sample size is the most important variable for the validity and coverage of RSN and RFP estimates. For small samples, validity and coverage of RSN and RFP also depend on the accuracy of each test and on the degree of interdependence between the tests.

Adult↗

Alternative strategies for selecting population controls: comparison of random digit dialing and targeted telephone calls.

PURPOSE: This project was carried out to identify a valid framework for selecting controls to be used in a population-based case-control study of breast cancer, and to compare participation rates and characteristics between women contacted using a standard random digit dialing (RDD) strategy and those who were sent a letter of presentation prior to telephone contact (targeted telephone calls, TTC). METHODS: Twelve hundred women, ages 20-74, were sampled from the Department of Motor Vehicles (DMV) and Health Care Financing Administration (HCFA) records. Women for whom telephone numbers were obtained (N = 771) were randomly assigned to RDD or TTC. The respondents participated in a brief telephone interview. Odd ratios (OR) and their 95% confidence intervals (CI) were used to estimate differences in characteristics of the respondents between the two contact strategies. RESULTS: Telephone numbers were obtained for 79% of women aged > or = 55 years and for only 38% of women aged < 55 years. Interviews were obtained for 48% of women for whom we obtained telephone numbers, and for 77% of women for whom eligibility was confirmed via telephone contact. Participation of target women appeared to be higher for the TTC than the RDD group (42% vs. 35%, p = 0.054). Among respondents who were > or = 55 years old, those in the TTC group were 80% more likely (OR = 1.8, 95% CI: 0.9-3.4) to report a serious medical condition than women in the RDD group, 60% less likely (OR = 0.4, 95% CI: 0.2-1.0) to report having used oral contraceptives, and 80% less likely (OR = 0.2, 95% CI: 0.1-0.5) to report having had breast surgery. CONCLUSIONS: Characteristics of respondents differed according to method of contact. These differences, along with the sampling frame used, should be considered when interpreting findings of case-control studies.

Adult↗

Localized folate and vitamin B-12 deficiency in squamous cell lung cancer is associated with global DNA hypomethylation.

We measured the concentrations of folate and vitamin B-12 in paired tissue samples of squamous cell cancer (SCC) and adjacent grossly normal-appearing uninvolved bronchial mucosa (from which SCC developed and also "at risk" of developing SCC) of the lung in 12 subjects to determine the involvement of these vitamins in 1) lung carcinogenesis and 2) global DNA methylation. The folate concentrations were significantly lower in SCCs than in uninvolved tissues (p = 0.03). The vitamin B-12 concentrations were also significantly lower in SCCs than in uninvolved tissues (p = 0.02). The radiolabeled methyl incorporation (inversely related to the degree of in vivo DNA methylation) was significantly higher in SCCs than in uninvolved tissues (p < 0.0001). The correlation between folate and radiolabeled methyl incorporation was inverse and statistically significant in SCCs (p = 0.03). The correlation between vitamin B-12 and radiolabeled methyl incorporation also was inverse and statistically significant in SCCs (p = 0.009). The relationship between tissue vitamin B-12 and DNA methylation was minimal in uninvolved tissues. The relationship between folate and DNA methylation, however, was inverse in uninvolved tissues. In the multiple regression models that included both vitamins, only folate was inversely associated with radiolabeled methyl incorporation in uninvolved and cancerous tissues. These results suggested that folate might be the limiting vitamin for proper DNA methylation in SCC as well as in tissues at risk of developing SCC. Several possible mechanisms of folate deficiency, including inactivation of the vitamin by exposure to carcinogens of cigarette smoke and underexpression or absence of folate receptor in SCCs and associated premalignant lesions, are discussed in light of these findings.

Aged↗

Effectiveness of an intervention promoting the female condom to patients at sexually transmitted disease clinics.

OBJECTIVES: This study evaluated a behavioral intervention designed to promote female condoms and reduce unprotected sex among women at high risk for acquiring sexually transmitted diseases (STDs). METHODS: The effect of the intervention on barrier use was evaluated with a pretest-posttest design with 1159 female STD clinic patients. RESULTS: Among participants with follow-up data, 79% used the female condom at least once and often multiple times. More than one third of those who completed the study used female condoms throughout follow-up. Use of barrier protection increased significantly after the intervention, and high use was maintained during a 6-month follow-up. To account for attrition, the use of protection by all subjects was projected under 3 conservative assumptions. The initial visit and termination visit projections suggest that use increased sharply after the intervention and declined during follow-up but remained elevated compared with the baseline. CONCLUSIONS: Many clients of public STD clinics will try, and some will continue, to use female condoms when they are promoted positively and when women are trained to use them correctly and to promote them to their partners. A behavioral intervention that promotes both female and male condoms can increase barrier use.

Adolescent↗

Prostate-specific antigen in vaginal fluid as a biologic marker of condom failure.

Forty women participated in three clinic visits during which they were exposed to their partner's semen (10 microL, 100 microL, and 1 mL). At each visit they took vaginal fluid samples before exposure to their partner's semen, immediately after, and at 1, 24, and 48 h after exposure. PSA was measured with an enzyme-linked immunoassay. The mean PSA level for preexposure swabs ranged between 0.43 and 0.88 ng/mL. The mean PSA levels were 193 immediately after exposure to 10 microL, 472 after 100 microL, and 19,098 after 1 mL. The PSA levels declined within 1 h, and returned to background at 48 h. The findings confirm that our procedure is a sensitive and specific method for detecting recent semen exposure, and indicate that PSA levels depend on exposure intensity and time since exposure. Application of this method in condom efficacy studies provides objective evidence of condom failure that enhances the interpretation of self-report.

Adult↗

Determinants of reinfection with Chlamydia trachomatis.

BACKGROUND AND OBJECTIVES: Epidemiologic studies of chlamydial infections may often miss factors associated with the acquisition of infection. GOAL: To evaluate factors associated with risk for initial and recurrent Chlamydia trachomatis infections. STUDY DESIGN: A retrospective study of patients attending a sexually transmitted disease clinic and, within this retrospective cohort, a nested case-control study. RESULTS: Among initial-negative subjects the crude incidence rate was 11.5 per 1,000 months of follow-up. Among initial-positive subjects, the crude incidence rate was 28 per 1,000 months of follow-up (RR = 1.8, 95% CI: 1.4-2.2). The increase in risk of infection associated with prior infection was independent of age. In the case-control study, a reduced risk of recurrent infection was associated with tubal ligation, hormonal contraception, and barrier contraception. CONCLUSIONS: As well as targeting sexually active adolescents, prevention programs should recommend repeat testing for all women with prior chlamydial infection, irrespective of age. Furthermore, issues related to personal control of health may modify risk for infection.

Adult↗

Prospective study of barrier contraception for the prevention of sexually transmitted diseases: study design and general characteristics of the study group.

BACKGROUND AND OBJECTIVES: The AIDS epidemic has brought barrier contraceptives to the forefront of public health research. A comprehensive evaluation of the efficacy of barrier contraceptive use in preventing sexually transmitted diseases (STDs), including AIDS, is necessary to inform both potential users and public health policy makers. This study was undertaken to evaluate the efficacy of condoms and vaginal spermicide products, used alone or in combination, in preventing gonorrhea and chlamydia among women attending an STD clinic. GOAL OF THIS STUDY: To describe the general characteristics of the study group and its follow-up experience. STUDY DESIGN: Women who met the eligibility criteria were invited to participate. The initial visit included an interview, a behavioral intervention promoting barrier methods, a physical examination, and instructions to complete a sexual diary. Participants received free barrier contraceptives and returned for six monthly follow-up visits. DESIGN RESULTS: Participants (n = 1,122) were low income, single (74%) black (89%) women with a median age of 24. The behavioral intervention led to the use of barrier protection in more than 70% of reported acts of vaginal intercourse. Barriers were used consistently (100% of sexual acts) during 51% of the months of follow-up. A total of 148 cases of gonorrhea (28 per 1,000 months) and 122 cases of chlamydia infection (23 cases per 1,000 months) were diagnosed during follow-up. CONCLUSION: This study represents a practical solution to a complex set of design considerations. The study protocol was successful in promoting consistent and proper use of barrier methods.

Adult↗

Correlates of herpes simplex virus seroprevalence among women attending a sexually transmitted disease clinic.

BACKGROUND: Infections by herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are common in the United States. Herpes simplex virus type 2 is transmitted sexually, and the prevalence of antibodies to HSV-2 has increased in recent years. GOALS OF THIS STUDY: The objective of the present study was to estimate the seroprevalence of HSV-1 and HSV-2 antibodies among women attending a sexually transmitted disease (STD) clinic and to evaluate factors associated with HSV-1 and HSV-2 seropositivity. STUDY DESIGN: The report describes a cross-sectional study conducted at an STD clinic. This study included 1,103 women between the ages of 18 and 35. Eighty-nine percent of the subjects were African Americans. The remaining subjects were white. RESULTS: The overall prevalence of HSV-1 and HSV-2 antibodies among study subjects was 72% and 64%, respectively. Both HSV-1 and HSV-2 seropositivity were related directly to age and were higher among African Americans than whites. The prevalence of HSV-2 antibodies also increased with the number of lifetime sexual partners, an early age at first coitus, a history of syphilis, and the absence of HSV-1 antibodies. Drug use and recent use of barrier contraception were unrelated to either HSV-1 or HSV-2. COMMENT: Despite efforts by the public health community to prevent AIDS by promoting safe sexual practices, the prevalence of HSV-2 seropositivity has increased in recent years. Increased numbers of partners and an early age at first coitus are important correlates of HSV-2 infection. Public health interventions to prevent HSV-2 infection should target teenagers. Women of reproductive age attending STD clinics may also comprise an important target for interventions to prevent perinatal herpes.

Adolescent↗

Mechanical failure of the latex condom in a cohort of women at high STD risk.

BACKGROUND AND OBJECTIVES: Mechanical failure may reduce the efficacy of condoms. Little is known about frequency and determinants of condom failure in groups at high risk of sexually transmitted diseases (STD). GOAL: To measure condom breakage and slippage rates and evaluate potential determinants of failure among women attending a public STD clinic. STUDY DESIGN: Women attending an STD clinic participated in a 6-month prospective study of barrier contraception for the prevention of STD. They completed sexual diaries that were reviewed at monthly follow-up visits. No data were collected from the male partners. Baseline characteristics of the participants and time-dependent behaviors were evaluated as potential determinants of condom failure. RESULTS: Of 21,852 condoms used by 892 women, 500 broke during intercourse (2.3%) and 290 slipped (1.3%). Breakage was more common among young, black, single nulliparae who engaged in high-risk behavior. Slippage was more common among married women with children. Failure rates decreased with condom use, with coital frequency, and with use of spermicides. CONCLUSION: User characteristics and experience are determinants of breakage and slippage, which are often regarded only as the effect of product design flaws. Attention to modifiable determinants of failure may improve user counseling and product labeling.

Adolescent↗

Mortality from cancer and other causes of death among synthetic rubber workers.

OBJECTIVES: This study evaluated the mortality experience of workers from the styrene-butadiene rubber industry. Concerns about a possible association of 1,3-butadiene and styrene with lymphohaematopoietic, gastrointestinal, and lung cancers prompted the investigation. METHODS: A retrospective follow up study was conducted of 15,649 men employed for at least one year at any of eight North American styrene-butadiene rubber plants. Analyses used standardised mortality ratios (SMRs) to compare styrene-butadiene rubber workers' cause specific mortalities (1943-91) with those of the United States and Ontario general populations. RESULTS: On average, there were 25 years of follow up per subject. The standardised mortality ratio (SMR) was 87 (95% confidence interval (95% CI) 85 to 90) for all causes of death combined and was 93 (95% CI 87 to 99) for all cancers. There was an excess of leukaemia (SMR 131, 95% CI 97 to 174), restricted to hourly workers (SMR 143, 95% CI 104 to 191). For causes of death other than leukaemia, SMRs were close to or below the null value of 100. Results by work area (process group) were unremarkable for non-Hodgkin's lymphoma, multiple myeloma, and stomach cancer. Maintenance workers had a slight increase in deaths from lung cancer, and certain subgroups of workers had more than expected deaths from cancer of the large intestine and the larynx. CONCLUSION: This study found an excess of leukaemia that is likely to be due to exposure to butadiene or to butadiene plus other chemicals. Deaths from non-Hodgkin's lymphoma, multiple myeloma, and stomach cancer did not seem to be related to occupational exposure. The excess deaths from lung cancer among maintenance workers may be due in part to confounding by smoking, which was not controlled for, and in part to an unidentified occupational exposure other than butadiene or styrene. Increases in cancer of the large intestine and larynx were based on small numbers, did not seem to be due to exposure to butadiene or styrene, and may be chance observations.

Butadienes↗

Incidence of cervical intraepithelial neoplasia grade III, and cancer of the cervix uteri following a negative Pap-smear in an opportunistic screening.

BACKGROUND: To investigate the influence of screening history on the diagnosis of cervical intraepithelial neoplasia grade three (CIN III) and cervical cancer in an opportunistic screening program. DESIGN: Follow-up study of women with a negative Pap-smear at entry. MATERIALS: Records from 41212 women pertaining to cervical specimens in the Pathology Registry of the University Hospital in Tromsø. RESULTS: During the 175,673 person-years (pyr) of observation, 396 incident cases (379 of CIN III and 17 of cervical cancer) were identified. The age specific incidence rate was highest among women who were 25 to 29 years old (396 per 100,000 pyr). A Poisson multiple regression model yielded statistically significant positive associations between time since last negative Pap-smear and the incidence of CIN III and cervical cancer. Most CIN III cases were diagnosed subsequently to a CIN I or CIN II diagnosis. Including only women with a CIN III diagnosis directly after a negative Pap-smear in the analyses revealed that women with less than two years (Relative rate (RR)= 1.O; 95% CI 0.7-1.4) and three years (RR=0.8; 95% CI 0.4-1.4) since their last negative Pap-smear were not at an increased risk compared with the women with a negative Pap-smear within the last year. Women with three or more years since their last negative Pap-smear were at an increased risk (RR=1.3; 95% CI 0.6 3.2) for CIN III. No meaningful association between number of negative specimens and the risk of CIN III was revealed. CONCLUSION: This study indicates that time since last negative Pap-smear does, while number of such does not, influence the risk of CIN III and cervical cancer in an opportunistic screening.

Adult↗

Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group.

BACKGROUND: Toxicity limits the use of methotrexate. OBJECTIVE: To identify risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. DESIGN: Case-control study. SETTING: One private and five academic rheumatology practices. PARTICIPANTS: Methotrexate recipients with rheumatoid arthritis with and without lung injury. MEASUREMENTS: Potential risk factors examined were sociodemographic and lifestyle characteristics, medical history, clinical and ancillary features and treatment of rheumatoid arthritis before methotrexate therapy, and characteristics of methotrexate therapy. Cases of lung injury were defined according to the modified criteria of Searles and McKendry. RESULTS: Ninety-four percent of the study participants were white, and 67% were women. Case-patients (n = 29) were older than controls (n = 82) (61.5 compared with 54.5 years of age). The strongest predictors of lung injury, after adjustment for other variables, were older age (odds ratio [OR], 5.1 [95% CI, 1.2 to 21.1]), diabetes (OR, 35.6 [CI, 1.3 to infinity]), rheumatoid pleuropulmonary involvement (OR, 7.1 [CI, 1.1 to 45.4]), previous use of disease-modifying antirheumatic drugs (OR, 5.6 [CI, 1.2 to 27.0]), and hypoalbuminemia (OR, 19.5 [CI, 3.5 to 109.7]). Previous use of disease-modifying antirheumatic drugs and hypoalbuminemia had very large attributable risks. CONCLUSION: Knowledge of the risk factors that predispose patients with rheumatoid arthritis to the toxic effects of methotrexate on the lung may provide a rationale for monitoring high-risk patients and may facilitate their management.

Antirheumatic Agents↗