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Biomedical subjects

S D Mark

Publications and source records attributed to S D Mark.

At least 55 records · Page 3Linked to original sources

Nocturnal enuresis.

Nocturnal enuresis is common. Although its aetiology remains unclear recent evidence increasingly supports the lack of a normal nocturnal increase in ADH leading to nocturnal polyuria exceeding functional bladder capacity. Sleep patterns are probably normal although an arousal disorder might be a factor. Treatment should follow careful evaluation to determine if one is dealing with 'uncomplicated' or 'complicated' enuresis. Complicated enuresis requires further investigation. 'Uncomplicated enuresis' always requires reassurance and patient and parent education. Resource centres such as ERIC can provide information and advice. Active treatment should be tailored to the patients age, motivation and parental wishes. Behavioural modification techniques yield the highest long-term cure rate but require the most commitment and are rarely successful before the age of 7-8 years. Pharmacotherapy has been revolutionized by DDAVP which gives a response rate of up to 70% relatively free from side-effects but at the price of a high relapse rate after medication. Imipramine is less expensive than DDAVP but may be fatal in overdose. Anticholinergics should be reserved for those patients with significant diurnal symptoms or those who fail first-line pharmacotherapy. Overall patients and parents should be reassured by the high spontaneous cure rate.

Adolescent↗

Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P4501A2 activity in humans.

Heterocyclic aromatic amines (HAAs) are formed when meat juices are pyrolyzed. In humans HAAs are activated in vivo by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) to mutagens or carcinogens. While activity of NAT2 is noninducible, exposure to cigarettes, polycyclic aromatic hydrocarbons, and cruciferous vegetables has been shown to induce CYP1A2 activity in humans. To date, it is unknown if pan-fried meat, which is consumed at high levels in the United States, is capable of inducing CYP1A2. In order to address this issue, we measured CYP1A2 and NAT2 activities in 66 healthy nonsmokers (33 males and 33 females) in a controlled metabolic feeding study. The study was designed to minimize the influence of known inducers of CYP1A2. Subjects consumed meat pan-fried at a low temperature (100 degrees C) for 7 days followed by 7 days of meat pan-fried at a high temperature (250 degrees C). The low temperature-cooked meat had undetectable levels of HAAs while the high temperature-cooked meat contained high amounts of HAAs [9.0 ng/g of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2.1 ng/g of 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and 32.8 ng/g of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)]. In contrast, total polycyclic aromatic hydrocarbon content was similar in both meat samples (10.7 ng/g in low temperature-cooked meat and 10.1 ng/g in high temperature-cooked meat). At the end of each period, subjects were tested for CYP1A2 and NAT2 enzyme activity by caffeine metabolism phenotyping. NAT2 activity remained unchanged throughout the study while CYP1A2 activity increased in 47 of 65 (72%) of the subjects after consuming high temperature-cooked meat (P < 0.0002), suggesting induction by some compound(s) formed during high temperature cooking. If HAAs are shown to be human carcinogens in epidemiological studies, then meat cooked at high temperatures may pose an increased cancer risk because it contains both inducers of CYP1A2 and procarcinogens MeIQx, DiMeIQx, and PhIP known to be activated by this enzyme.

Carcinogens↗

The effect of vitamin and mineral supplementation on esophageal cytology: results from the Linxian Dysplasia Trial.

The population of Linxian in China has one of the world's highest rates for esophageal/gastric cardia cancer, as well as documented nutritional deficiencies. To determine whether dietary supplementation with a multi-vitamin multi-mineral preparation could reduce the risk of esophageal cancer and favorably influence precursor lesions, 3,318 individuals age 40-69 with cytologically determined grade 1 or grade 2 esophageal dysplasia were randomly assigned to receive either an active multi-vitamin multi-mineral supplement or a placebo. Pills were distributed at monthly visits and incident cancers or deaths were recorded. At 30 and 72 months subsequent to randomization all living participants without a known incident cancer were asked to undergo repeat cytological examination of their esophagus. Based on these procedures participants were classified as having no dysplasia, dysplasia grade 1, dysplasia grade 2 or near cancer dysplasia. Diagnoses of cancer were based on the cytology findings plus available histologic, radiologic and clinical materials. At the end of the study there was little overall difference in cumulative risk of esophageal cancer between those receiving vitamin/mineral supplementation and those receiving placebo. There was, however, a significant increase in reversion to non-dysplastic cytology among the group receiving the active treatment. The odds of not having any dysplasia at the two post-randomization screens was 1.23 times higher in the active treatment group than in the placebo group. Within each treatment group higher categories of dysplasia were associated with higher rates of cancer.

Adult↗

Clam cystoplasty for the overactive bladder: a review of 23 cases.

A clam enterocystoplasty was performed for refractory urge incontinence due to either idiopathic instability (13 patients) or neuropathic hyperreflexia (10 patients). Twelve patients became dry and appliance free. Of the remaining 11 wet patients, seven developed low pressure reservoirs, of whom five had stress incontinence and two had overflow incontinence. The other four patients had persistent symptomatic involuntary phasic contractions and ongoing urge incontinence. The magnitude of the surgery and the voiding dysfunction associated with the relative lack of motivation of elderly patients made the operation less successful and more hazardous in those over the age of 65. Successful outcome could be improved by careful patient selection and by performing an antistress incontinence procedure, such as implantation of an artificial urinary sphincter cuff or a cystourethropexy, where there is associated bladder outlet incompetence.

Adolescent↗

Carcinoma in situ of the testis followed by an overt malignant teratoma of the testis within 12 months.

A case of bilateral metachronous testicular non-seminomatous germ cell tumour (NSGCT) is presented. The second tumour was preceded by carcinoma in situ, diagnosed at the time of the first orchidectomy. The patient was placed under active surveillance and 1 year later the second testis tumour developed. A second orchidectomy was performed and testosterone replacement begun. Carcinoma in situ of the testis is discussed.

Adult↗

Estimating the causal effect of smoking cessation in the presence of confounding factors using a rank preserving structural failure time model.

Estimating the causal effect of quitting smoking on time to death or first myocardial infarction requires that one control for the differences in risk factors between individuals who elect to quite at each time t versus those who elect to continue smoking at time t. In this paper we examine the limitations of standard time varying Cox proportional hazards models to yield tests and estimates of this effect. Implementing the method of G-estimation proposed by Robins, we perform an observational analysis of data from the Multiple Risk Factor Intervention Trial (MRFIT) and estimate the causal effect of cigarette cessation while controlling for such time varying confounders as angina. We reject the null hypothesis of no effect of quitting on time to failure, and estimate that by quitting smoking, an individual increases by 50 per cent his time to death or first myocardial infarction (MI).

Adult↗

A method for the analysis of randomized trials with compliance information: an application to the Multiple Risk Factor Intervention Trial.

The standard approach to analyzing randomized trials ignores information on postrandomization compliance. Application of these methods results in estimates that may lack the desired causal interpretation. We employ a new method of estimation and analyze data from the Multiple Risk Factor Intervention Trial (MRFIT) to estimate the causal effect of quitting cigarette smoking. Our procedure utilizes a method proposed by Robins and Tsiatis and allows us to take advantage of postrandomization smoking history without requiring untenable assumptions about the comparability of compliers and noncompliers. We contrast the performance of our method and the standard intent-to-treat analysis in the MRFIT data and in simulated data in which compliance rates are varied.

Adult↗

Flow cytometric analysis of nuclear DNA content in ovarian tumors. Association of ploidy with tumor type, histologic grade, and clinical stage.

The authors undertook a prospective, flow cytometric study of nuclear DNA ploidy in 140 fresh ovarian tumors. There were 43 benign tumors, 27 borderline tumors, and 70 malignant tumors. Results of DNA ploidy analysis were compared to age at diagnosis, menopausal status, tumor size, histologic type, grade, and International Federation of Gynecology and Obstetrics (FIGO) stage. Although the majority of benign tumors were diploid, 19% were aneuploid. Among the benign tumors, DNA ploidy was significantly associated with tumor type and tumor size. All borderline tumors were diploid. Of the 70 malignant tumors, 64% were aneuploid. In the malignant tumors, DNA aneuploidy had significant univariate associations with histologic type, grade, and FIGO stage. By multivariate analysis, DNA aneuploidy remained significantly associated with stage and grade, both known predictors of survival in ovarian cancer. These results indicate that DNA ploidy varies with the aggressive potential of an ovarian cancer and may, at the time of initial diagnosis, provide additional information about tumor prognosis.

Adult↗

A flow cytometric study of 137 fresh hydropic placentas: correlation between types of hydatidiform moles and nuclear DNA ploidy.

Hydropic placentas may be classified by histopathology into hydropic abortus, partial hydatidiform mole, and complete hydatidiform mole. We studied 142 hydropic placentas: 39% were complete hydatidiform moles, 35% partial hydatidiform moles, and 26% hydropic abortuses. Villous vesicle size was predictive of histologic diagnosis. We determined DNA ploidy in 137 cases. Seventy-three percent of hydropic abortuses were diploid and 11% were triploid. Ninety percent of partial moles were triploid or near-triploid; one partial mole was haploid and one diploid. Of the complete moles, 50% were diploid, 43% were tetraploid, 3.6% polyploid, and 1.7% triploid. Partial moles had lower pre-evacuation beta-hCG levels than complete moles. Persistent tumor followed 33% of complete moles and 12% of partial moles. Although the numbers were small, no patient with a diploid, tetraploid, aneuploid, or haploid partial mole developed persistent disease. Among complete moles, the pre-evacuation beta-hCG level was not predictive of persistence (P = .15). Subdividing complete moles by ploidy, we found that tetraploid moles were associated with higher pre-evacuation beta-hCG levels than were diploid moles. However, tetraploidy was not associated with increased persistent tumor among complete moles. Although most partial moles were triploid and most complete moles were diploid or tetraploid, there was wider DNA heterogeneity among molar gestations than previously reported. In this series, DNA ploidy was not an independent predictor of persistence in complete moles.

Adolescent↗

Estimating exposure effects by modelling the expectation of exposure conditional on confounders.

In order to estimate the causal effects of one or more exposures or treatments on an outcome of interest, one has to account for the effect of "confounding factors" which both covary with the exposures or treatments and are independent predictors of the outcome. In this paper we present regression methods which, in contrast to standard methods, adjust for the confounding effect of multiple continuous or discrete covariates by modelling the conditional expectation of the exposures or treatments given the confounders. In the special case of a univariate dichotomous exposure or treatment, this conditional expectation is identical to what Rosenbaum and Rubin have called the propensity score. They have also proposed methods to estimate causal effects by modelling the propensity score. Our methods generalize those of Rosenbaum and Rubin in several ways. First, our approach straightforwardly allows for multivariate exposures or treatments, each of which may be continuous, ordinal, or discrete. Second, even in the case of a single dichotomous exposure, our approach does not require subclassification or matching on the propensity score so that the potential for "residual confounding," i.e., bias, due to incomplete matching is avoided. Third, our approach allows a rather general formalization of the idea that it is better to use the "estimated propensity score" than the true propensity score even when the true score is known. The additional power of our approach derives from the fact that we assume the causal effects of the exposures or treatments can be described by the parametric component of a semiparametric regression model. To illustrate our methods, we reanalyze the effect of current cigarette smoking on the level of forced expiratory volume in one second in a cohort of 2,713 adult white males. We compare the results with those obtained using standard methods.

Analysis of Variance↗

Epithelial ovarian tumors of borderline malignancy.

Between January 1975 and January 1987, 80 patients underwent primary surgery at Brigham and Women's Hospital for epithelial ovarian tumors of borderline malignancy. Surgical staging revealed 52 (65%) patients with stage IA, 2 (2.5%) with stage IB, 10 (12.5%) with stage IC, 4 (5%) with stage II, 11 (13.8%) with stage III, and 1 (1.2%) with stage IV. All 37 patients with mucinous tumors had stage I disease, whereas 13 (33%) of 39 patients with serous tumors had stage II-IV disease. The mean sizes of mucinous and serous ovarian tumors were 18.7 and 10 cm, respectively. At initial surgery, 48 (60%) patients had a total abdominal hysterectomy with bilateral salpingo-oophorectomy and 16 (20%) had an oophorectomy. Sixteen (20%) patients underwent cystectomy, 6 (37.5%) of whom subsequently had an oophorectomy. All 10 patients treated by cystectomy alone have remained disease free. CA-125 levels were normal in 5 patients with stage I disease, but were elevated in 6 of 8 patients with more advanced tumors. Current disease status was determined in 72 patients (90%); 69 (95.8%) are alive and disease free, 1 (1.4%) patient is alive with tumor, and 2 (2.8%) patients died, free of disease.

Adult↗

Flexible cystoscopy as an adjunct to extracorporeal shockwave lithotripsy.

Ancillary procedures associated with extracorporeal shockwave lithotripsy (ESWL) include placement and subsequent removal of double pigtail ureteric stents. A simple new technique has been developed for the insertion of these stents. Using the flexible cystoscope, the procedure is performed on an out-patient basis under local anaesthesia. Placement of the stents was successful in 30/34 patients and removal was successful in 14/14 patients.

Adult↗

Hydatidiform moles. Application of flow cytometry in diagnosis.

Hydropic chorionic villi are found in hydropic abortuses, partial hydatidiform moles (PM), and complete hydatidiform moles. Partial and complete moles have the potential for persistent trophoblastic disease. The vast majority of partial moles are triploid and generally follow a benign clinical course. Complete moles are diploid and distant metastasis and choriocarcinoma may develop. The authors determined the nuclear ploidy by flow cytometry of 31 placentas, 19 of which appeared hydropic either on obstetric ultrasonography or gross examination. Of ten complete moles classified by histologic criteria, ten were diploid, whereas five of seven histologically classified PM were triploid. The remaining two cases classified as PM were diploid; one most likely represented a regressing complete mole; the other a hydropic abortus. All 14 control placentas were diploid. In all cases in which karyotypic analysis was performed, the flow cytometric determination of ploidy was confirmed. It was concluded that DNA flow cytometric analysis is a rapid, accurate, and cost-effective means for assaying nuclear ploidy in these tissues, and as such, offers an informative supplement to the histological interpretation of hydropic placentas.

Abortion, Spontaneous↗