Cellular uptake of amelogenin, and its localization to CD63, and Lamp1-positive vesicles.

Proteins of the developing enamel matrix include amelogenin, ameloblastin and enamelin. Of these three proteins amelogenin predominates. Protein-protein interactions are likely to occur at the ameloblast Tomes' processes between membrane-bound proteins and secreted enamel matrix proteins. Such protein-protein interactions could be associated with cell signaling or endocytosis. CD63 and Lamp1 are ubiquitously expressed, are lysosomal integral membrane proteins, and localize to the plasma membrane. CD63 and Lamp1 interact with amelogenin in vitro. In this study our objective was to study the molecular events of intercellular trafficking of an exogenous source of amelogenin, and related this movement to the spatiotemporal expression of CD63 and Lamp1 using various cell lineages. Exogenously added amelogenin moves rapidly into the cell into established Lamp1-positive vesicles that subsequently localize to the perinuclear region. These data indicate a possible mechanism by which amelogenin, or degraded amelogenin peptides, are removed from the extracellular matrix during enamel formation and maturation.

Drift and scaling in estimation of distribution algorithms.

This paper considers a phenomenon in Estimation of Distribution Algorithms (EDA) analogous to drift in population genetic dynamics. Finite population sampling in selection results in fluctuations which get reinforced when the probability model is updated. As a consequence, any probability model which can generate only a single set of values with probability 1 can be an attractive fixed point of the algorithm. To avoid this, parameters of the algorithm must scale with the system size in strongly problem-dependent ways, or the algorithm must be modified. This phenomenon is shown to hold for general EDAs as a consequence of the lack of ergodicity and irreducibility of the Markov chain on the state of probability models. It is illustrated in the case of UMDA, in which it is shown that the global optimum is only found if the population size is sufficiently large. For the needle-in-a haystack problem, the population size must scale as the square-root of the size of the search space. For the one-max problem, the population size must scale as the square-root of the problem size.

Typical and atypical chronic lymphocytic leukemia differ clinically and immunophenotypically.

We compared the features of 17 cases of atypical chronic lymphocytic leukemia (aCLL) with those of a clinical control group of 24 cases of CLL. Quantitative flow cytometric data, available for 12 cases, were compared with an immunophenotypic control group of 58 cases using a relative fluorescence indexfor CD5, CD23, CD79b, and surface immunoglobulin light chain (sIg). Compared with the clinical control group, patients with aCLL had a higher mean WBC count and a lower platelet count. Patients with aCLL had a significantly higher probability of disease progression. Compared with an immunophenotypic control group of 58 CLL cases, 12 cases of aCLL demonstrated significantly higher expression of CD23. There was no significant difference in expression of sIg, CD79b, or CD5 between the groups. CD38 expression was noted in only 1 (9%) of 11 tested cases; 2 (18%) of 11 cases had trisomy 12. aCLL can be distinguished from typical CLL morphologically, clinically, and immunophenotypically. Atypical morphologic features in CLL seem to be a marker of aggressive clinical behavior.

Cumulant dynamics of a population under multiplicative selection, mutation, and drift.

We revisit the classical population genetics model of a population evolving under multiplicative selection, mutation, and drift. The number of beneficial alleles in a multilocus system can be considered a trait under exponential selection. Equations of motion are derived for the cumulants of the trait distribution in the diffusion limit and under the assumption of linkage equilibrium. Because of the additive nature of cumulants, this reduces to the problem of determining equations of motion for the expected allele distribution cumulants at each locus. The cumulant equations form an infinite dimensional linear system and in an authored appendix Adam Prügel-Bennett provides a closed form expression for these equations. We derive approximate solutions which are shown to describe the dynamics well for a broad range of parameters. In particular, we introduce two approximate analytical solutions: (1) Perturbation theory is used to solve the dynamics for weak selection and arbitrary mutation rate. The resulting expansion for the system's eigenvalues reduces to the known diffusion theory results for the limiting cases with either mutation or selection absent. (2) For low mutation rates we observe a separation of time-scales between the slowest mode and the rest which allows us to develop an approximate analytical solution for the dominant slow mode. The solution is consistent with the perturbation theory result and provides a good approximation for much stronger selection intensities.

Maternal and neonatal outcomes in pregestational and gestational diabetes mellitus, and the influence of maternal obesity and weight gain: the DEPOSIT study. Diabetes Endocrine Pregnancy Outcome Study in Toronto.

We prospectively studied pregnancy outcome in 428 women with gestational diabetes mellitus (DM) and 196 women with pregestational DM, with particular reference to the influence of maternal obesity and excessive weight gain. These were consecutive singleton pregnancies delivered in our institution over 5 years. After controlling for multiple risk factors, including maternal BMI and pregnancy weight gain, women with pregestational DM were at increased risk (compared to those with gestational DM) for Caesarean delivery (OR 3.6, 95%CI 2.3-5.6), shoulder dystocia or cephalopelvic disproportion (OR 2.2, 95%CI 1.3-3.6), and gestational hypertension or toxaemia (OR 3.0, 95%CI 1.7-5.4). The offspring of these women were also at increased risk for admission to the neonatal intensive care unit (OR 4.0, 95%CI 2.3-6.8), large-for-gestational-age birthweight (OR 3.5, 95%CI 2.2-5.6), and preterm birth before 37 weeks (OR 3.8, 95%CI 2.5-5.9). Maternal obesity, and, to a lesser degree, excessive weight gain, were also independent risk factors for all these adverse maternal and neonatal outcomes, regardless of the type of DM, except for shoulder dystocia/cephalopelvic disproportion.

Using a neural network to screen a population for asthma.

PURPOSE: To use a neural network to rank a population according to individual likelihood of asthma based on their responses to a respiratory questionnaire. METHODS: A final diagnosis of asthma can be made only after full clinical assessment but limited resources make it impossible to offer this to complete populations as part of a screening programme. Prioritisation is required so that review can be offered most promptly to those most in need. A stratified random sample of 180 from 6825 respondents to a community survey underwent clinical review. They were categorised according to likelihood of asthma by three independent experts whose opinions were combined into a single probability label for each patient. A neural network was trained to relate questionnaire responses to probability labels. The trained network was applied to the whole community to produce a ranking order based on likelihood of asthma. A screening threshold could then be set to correspond to available resources, and patients above this level with no recorded evidence of asthma diagnosis could be assessed clinically. Using the known probability labels from the training set, it was possible to derive the expected proportion of true asthmatics in any set of patients. RESULTS: If the screening threshold had been set to capture the top 10% of the ranked population (n = 683), then 239 patients above this threshold had no evidence of diagnosis and would need assessment. Of these, it would be expected that 74% would have the diagnosis confirmed. CONCLUSIONS: This approach allows prioritisation of a population where resources for diagnostic examination are limited.

Cervical length as a predictor of pre-term birth in twin gestations.

The aim of this study was to determine the predictive value of cervical length as a risk factor for spontaneous pre-term birth in twin gestations. A retrospective chart review was carried out on patients with twin pregnancies referred to our multiples' clinic. Cervical length was measured by transvaginal ultrasonography. Patients with an indicated pre-term delivery or intervention were excluded from the analysis. Outcomes included preterm delivery < 28 and < 35 weeks gestation. After extracting the data, 2 x 4 tables were constructed. Likelihood ratios were then generated for cervical lengths < or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm, and > 3.0 cm. Because of the limited number of measurements taken < 25 weeks gestation, we elected to collapse the tables, thereby achieving more meaningful results. For measurements taken before 30 weeks gestation, a shorter cervix did predict delivery < 28 weeks gestation (likelihood ratios for cervical lengths < or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm, and > 3.0 cm were 4.43, 1.94, 0.97, and 1.02, respectively). The probability of preterm delivery < 35 weeks gestation increased with decreasing cervical length (likelihood ratios for cervical length < or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm, and > 3.0 cm were 2.58, 1.66, 1.38, and 0.81, respectively). A shorter cervix measured before 30 weeks gestation was a stronger predictor of preterm delivery < 28 weeks compared to < 35 weeks gestation. Cervical length was not predictive of preterm delivery if measured after 30 weeks. Cervical length is predictive of preterm delivery < 28 weeks and < 35 weeks gestation when measured before 30 weeks gestation. No trend was seen when measured after 30 weeks gestation. A prospective study is currently underway to confirm these results.

Bell's palsy and tinnitus during pregnancy: predictors of pre-eclampsia? Three cases and a detailed review of the literature.

We present two cases of Bell's palsy, and another with tinnitus, all in association with pre-eclampsia in the third trimester of pregnancy. We also systematically reviewed the published literature on both Bell's palsy and tinnitus in pregnancy and the puerperium using Medline from January 1966 to October 1998, and searched through the references from review articles and original research publications for further studies. Studies were limited to those published in the English language. We then pooled the rates of occurrence for Bell's palsy according to trimester of pregnancy, and postpartum, as well as the associated prevalence of pre-eclampsia or gestational hypertension. We found that the majority of cases of Bell's palsy arose during the third trimester (pooled event rate 71.1%, 95% confidence interval (CI) 64.1-77.2), while almost none arose in the first trimester. During the postpartum period, the distribution of Bell's palsy was 21.3% (95% CI 15.7-28.1) of all cases, with the majority arising within days of delivery. Gestational hypertension or pre-eclampsia was present in 22.2% of cases (95% CI 12.5-36.4), well above the 5% rate in the general population. Only one paper provided data on tinnitus in pregnancy, with the distribution equal across all three trimesters. When compared to non-pregnant controls, the odds ratio for the development of tinnitus during pregnancy was 2.8 (95% CI 1.0-8.1). In conclusion, Bell's palsy, and perhaps, tinnitus, occur more frequently during the third trimester of pregnancy. Both may be presenting prodromal signs of underlying early pre-eclampsia. The pathophysiologic mechanism relating these two entities to pre-eclampsia is also discussed.

CD5- B-cell lymphoproliferative disorders presenting in blood and bone marrow. A clinicopathologic study of 40 patients.

We studied 40 patients with CD5- B-cell lymphoproliferative disorders (B-LPDs) presenting in blood or bone marrow and 28 control patients with CD5+ B-cell chronic lymphocytic leukemia (CLL). Fifteen study patients had morphologic features typical of CLL. The 15 patients with CD5- CLL were older and had lower absolute lymphocyte counts and more advanced-stage disease at diagnosis than controls. Ten study patients had morphologic features suggesting mantle cell lymphoma (MCL); 3 were later given a diagnosis of MCL based on lymph node biopsy results. The 10 patients with CD5- MCL were older and at a more advanced stage than CLL control patients. The remaining 15 study patients were given the following diagnoses: circulating non-Hodgkin lymphoma, 5; splenic lymphoma with villous lymphocytes, 5; lymphoplasmacytoid lymphoma, 3; and CLL/pro-lymphocytic leukemia, 2. For the patients with CD5- B-LPDs with morphologic features and manifestations resembling CLL, we prefer the term CD5- CLL variant because of clinical and immunophenotypic differences. Patients with CD5- B-LPDs with atypical nuclear morphologic features may represent the leukemic phase of MCL. Since CD23 is expressed in most patients with CD5- B-LPD, its use in subclassifying these disorders seems limited.

Satisfaction with obstetric care. Patient survey in a family practice shared-call group.

OBJECTIVE: To examine patients' satisfaction with their obstetric care in a family medicine shared-call group. DESIGN: A survey was given to a convenience sample of patients who came to see their doctors over a 6-week period. SETTING: Brameast Family Practice in Brampton, Ont, where eight doctors participate in a shared obstetrics call group with 16 other physicians, each taking call 1 day in 23 days. PARTICIPANTS: Mothers in the practice who had delivered in the previous 8 months. MAIN OUTCOME MEASURES: Demographic data, interventions during delivery, and satisfaction ratings. RESULTS: Of the 70% of women who responded, 96% were delivered by a doctor other than their own. Eighty-eight percent of these women were satisfied with their medical care at delivery and 96% were satisfied with their prenatal care. Nearly 79% said they would choose this shared-call group again. CONCLUSIONS: This pilot study demonstrated a high level of patient satisfaction with obstetric care, despite the fact that most patients were delivered by a doctor other than their own. Family practice groups sharing obstetric call offer a feasible alternative for physicians who wish to avoid the interference with lifestyle and office appointments that practising obstetrics usually entails.

Thoracic involvement with pheochromocytoma: a review.

Pulmonary manifestations of pheochromocytoma are infrequent and are not well documented. A MEDLINE search in the English language revealed no cases of endobronchial involvement from a pheochromocytoma. We report a case of endobronchial metastases in a 37-year-old woman known to have a recurrent extra-adrenal pheochromocytoma. She presented with symptoms of wheezing and a nonproductive cough for 8 months and was being treated for asthma. A flexible bronchoscopy with endobronchial biopsy established the diagnosis. The patient underwent a Nd-YAG laser photoresection (LPR) to ablate the tumor, which was followed by placement of a Wallstent (Pfizer Medical Technology Group; Rutherford, NJ). She remains well 18 months later, having required multiple palliative LPRs. To our knowledge, this is the first reported case of endobronchial pheochromocytoma. The pulmonary manifestations of this rare disease and their management are reviewed.

A clinicopathologic study of 42 patients with granulomatous gastritis. Is there really an "idiopathic" granulomatous gastritis?

Idiopathic granulomatous gastritis (IGG) is a diagnosis made only by excluding other causes of granulomatous gastritis, such as infection, foreign bodies, and systemic granulomatous diseases. Recently, several investigators have questioned the existence of IGG. We reviewed the slides and clinical data of all cases of granulomatous gastritis seen at the Cleveland Clinic between 1975 and 1994. In addition to routine hematoxylin and eosin stains, slides from all cases were stained with Ziehl-Neelsen, Gomori's methenamine silver, and Giemsa stains. Clinical information and follow-up were available for 42 patients. The clinicopathologic diagnoses of the 42 patients with granulomatous gastritis were as follows: Crohn's disease (n = 23), three of whom had concomitant chronic active gastritis with Helicobacter pylori infection; sarcoidosis (n = 9), four of whom had concomitant chronic active gastritis with H. pylori infection; chronic active gastritis with H. pylori infection and no other systemic illness (n = 2); distal esophageal adenocarcinoma and chronic active gastritis (n = 2); mucosa-associated lymphoid tissue (MALT) lymphoma with chronic active gastritis and presumed H. pylori infection (n = 2); peptic ulcer complications (n = 2); hypertrophic gastropathy with chronic active gastritis (n = 1); and possible Crohn's disease (n = 1). We conclude that (a) in most cases of granulomatous gastritis, a diagnosis of Crohn's disease or sarcoidosis could be established; (b) the background inflammatory pattern was helpful in suggesting a diagnostic category for granulomatous gastritis; (c) granulomatous gastritis is not associated with H. pylori per se; however, if known cases of Crohn's disease and sarcoidosis are excluded, an association between H. pylori and granulomatous gastritis cannot be ruled out; and (d) IGG, if it exists, is extremely rare.

Giant bilateral extra-adrenal myelolipoma.

We report a case of a giant bilateral extra-adrenal myelolipoma. To our knowledge this is only the second reported case of either giant or bilateral extra-adrenal myelolipoma and the first in which both features are present. The tumor is also notable for having areas of fibromyxoid degeneration histologically similar to those seen in low-grade fibromyxoid sarcomas. This feature, previously unreported, expands the differential diagnosis of extra-adrenal myelolipomas.

Evaluation of an AIDS education model for women drug users in jail.

This paper reports outcome evaluation results of an AIDS education program for drug-using women in jail, of whom the majority were current drug injectors, had high-risk sexual partners, and never used condoms for insertive sex. The women participated in four small-group health/HIV education sessions. Education participants and controls were followed-up 7 months after their release from jail; the two groups did not differ significantly on drug- or sex-related HIV risk behaviors at follow-up. However, being in drug dependency treatment (primarily methadone maintenance) at follow-up was associated with reduced heroin use, crack use, drug dealing, and criminal activity. Although improved HIV education in jail is important, better networks of community resources, including more accessible community drug dependency treatment, also must be developed to support drug-dependent women after their release from jail.

Correlates of cocaine/crack use among inner-city incarcerated adolescents.

Inner-city male adolescents in jail in New York City (N = 427) were interviewed to examine correlates of cocaine or crack use. Twenty-three percent had used cocaine or crack in the month before arrest and 32% reported lifetime use. Substantial rates of robbery, murder, other violent crime, weapons possession, and drug dealing were found. However, type of crime, including violent crime, was not related either to cocaine/crack use or to drug dealing. Current cocaine/crack users were more likely to use alcohol, marijuana, and intranasal heroin; to have multiple previous arrests; to be out of school; to be psychologically distressed; to have been sexually molested as a child; to have substance abusing parents; and to have cocaine/crack-using friends. They were also more likely to have frequent sex with girls, to be gay or bisexual, and to engage in anal intercourse. The findings should be considered in developing more effective drug abuse prevention and treatment interventions, and HIV prevention education, for incarcerated at-risk adolescents.

Outcomes of intensive AIDS education for male adolescent drug users in jail.

OBJECTIVES: The purpose of the study was to conduct and evaluate an intensive AIDS education program for incarcerated male adolescent drug users. METHODS: The study was conducted in New York City's main jail facility for detained and sentenced male youths aged 16-19 years. A four-session, group-oriented AIDS education program based on Problem-Solving Therapy was conducted. The program was voluntary and all youths on designated dormitories were invited to participate. The evaluation compared youths participating in the AIDS education with waiting list controls who were discharged or transferred before they could be offered the education. Behavioral outcomes for AIDS education participants and controls were determined at a five month follow-up after release from jail. Behaviors were measured through personal interviews at baseline and follow-up. RESULTS: High rates of HIV risk behaviors were documented, including alcohol, marijuana and cocaine/crack use that may predispose youths to sexual risk-taking: practice of heterosexual anal sex; multiple and high-risk sexual partnerships; and no, or inconsistent, use of condoms. Education participants as compared with controls were significantly more likely to increase their condom use, to increase positive attitudes towards condoms, and possibly to decrease high-risk sexual partnerships. However, other sexual risk variables and substance use were unchanged. CONCLUSION: Intensive AIDS education provided in jail can be useful in reducing certain HIV risk behaviors of criminally-involved male adolescents.

Condom use among criminally-involved adolescents.

Condom use was studied for 421 sexually active, minority male adolescents who were currently in jail in New York City. Over three-quarters of the youths were users of alcohol and marijuana and about one-quarter were users of cocaine or crack, but drug injectors were rare. In the six months before arrest they had multiple sexual partners and about one-third had engaged in anal intercourse. Inconsistent condom use was the norm, with 17% reporting that they never used condoms and only 15% reporting that they used condoms every time for insertive sex. In multivariate analysis, more frequent condom use was independently predicted by gay/bisexual preference, greater acceptability and accessibility of condoms, partners' receptivity to use, self-initiation of use, and self-efficacy of avoiding AIDS. Condoms were used less frequently with steady than with causual partners, and rarely for anal or oral sex. AIDS prevention curricula addressing these factors should be delivered to high risk adolescents while they are temporarily accessible in jail.

PIP: Studies have found criminally-involved male adolescents to be highly sexually active, involved in unprotected sexual activities with multiple partners, and heavy consumers of alcohol and drugs extensively, behaviors which are conducive to HIV exposure and transmission. This paper reports findings on the sex behavior and condom use of 421 sexually active, minority male adolescents incarcerated at the Adolescent Reception Center on Rikers Island during February 1991-February 1992. The volunteers were aged 16-19 years (median age, 17.8 years), 98.8% were Black or Hispanic, 95.2% were heterosexual, 3.3% were bisexual, and 1.4% were gay. Each young man was compensated with $10 credited to his commissary accounts for participation in a 90-minute personal interview. 38.0% had been arrested for robbery, 27.3% for drug offenses, 16.9% for property crimes, and 13.5% for weapons offenses. 9.0% were in for murder. 74.8% were detained, while the remained had been sentenced. During the month before arrest, 81.0% consumed alcohol, 76.0% smoked marijuana, and approximately 25% used cocaine or crack cocaine, but IV drug use was rare. Only 1% of the sample reported ever using IV drugs. They had an average of three partners each during the 6 months before arrest, although few had identifiable high-risk partners. 17% reported never using condoms and 15% reported using condoms every time for insertive sex. Inconsistent condom use was therefore the norm. 15.9% had ever had a STD. Multivariate analysis found more frequent condom use to be independently predicted by gay/bisexual preference, greater acceptability and accessibility of condoms, partners' receptivity to use, self-initiation of use, and self-efficacy of avoiding AIDS. Condoms were used less frequently with steady than with casual partners, and rarely for anal or oral sex. 30% of heterosexual and 60% of gay/bisexual youths reported engaging in anal intercourse. 83% of the sample believed that it is hard to get HIV from sex. Most believed that they had already changed their behavior to reduce their risk, such as reducing the number of sex partners, being more selective of sex partners, and/or increasing condom use. AIDS prevention messages should be conveyed to these adolescents while they are a captive audience.

Postpartum ultrasonographic findings associated with placenta accreta.

Postpartum ultrasonographic examination of a patient with a retained placenta showed findings consistent with placenta accreta. The diagnosis was confirmed after surgery with histopathologic examination of the uterus. This case illustrates the possible clinical application of ultrasonography in the postpartum diagnosis of placenta accreta.