Somatic and cognitive domains of depression in an underserved region of Ecuador: some cultural considerations.

Not enough research efforts on depression have been carried out up to now in Latin America. The knowledge that has resulted from research activities in the United States or Europe offers limited generalizability to other regions of the world, including Latin America. In the Andean highlands of Ecuador, we found very high rates of moderate and severe depressive symptoms, a finding that must be interpreted within its cultural context. Somatic manifestations of depression predominated over cognitive manifestations, and higher education level was protective against depression. These findings call for an appreciation of culturally-specific manifestations of depression and the social factors that influence them. These factors must be further studied in order to give them the deserved priority, allocate resources appropriately, and formulate innovative psychosocial interventions.

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1.

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have shown that transgenic mice expressing R192Q or S218L FHM1 mutations have increased SD frequency and propagation speed; enhanced corticostriatal propagation; and, similar to the human FHM1 phenotype, more severe and prolonged post-SD neurological deficits. The susceptibility to SD and neurological deficits is affected by allele dosage and is higher in S218L than R192Q mutants. Further, female S218L and R192Q mutant mice were more susceptible to SD and neurological deficits than males. This sex difference was abrogated by ovariectomy and senescence and was partially restored by estrogen replacement, implicating ovarian hormones in the observed sex differences in humans with FHM1. These findings demonstrate that genetic and hormonal factors modulate susceptibility to SD and neurological deficits in FHM1 mutant mice, providing a potential mechanism for the phenotypic diversity of human migraine and aura.

Migraine and vasodepressor syncope in a large family.

We evaluated a 47-year-old woman for recurrent migraine and syncope. The patient had 7 children (not examined by the authors), all of whom also experienced migraine and syncope. The patient's father, now deceased, had reportedly experienced migraine and episodes of feeling faint. All 5 of the patient's siblings reported migraine, and 4 of the 5 reported syncope. The case of our patient, which we discuss herein, suggests a genetic link between these 2 conditions, both of which include vascular dysregulation in their pathogenesis. To our knowledge, the medical literature contains no previous description of familial associations of combined migraine and syncope.

Volume and shape in feature space on adaptive FCM in MRI segmentation.

Intensity non-uniformity (bias field) correction, contextual constraints over spatial intensity distribution and non-spherical cluster's shape in the feature space are incorporated into the fuzzy c-means (FCM) for segmentation of three-dimensional multi-spectral MR images. The bias field is modeled by a linear combination of smooth polynomial basis functions for fast computation in the clustering iterations. Regularization terms for the neighborhood continuity of either intensity or membership are added into the FCM cost functions. Since the feature space is not isotropic, distance measures, other than the Euclidean distance, are used to account for the shape and volumetric effects of clusters in the feature space. The performance of segmentation is improved by combining the adaptive FCM scheme with the criteria used in Gustafson-Kessel (G-K) and Gath-Geva (G-G) algorithms through the inclusion of the cluster scatter measure. The performance of this integrated approach is quantitatively evaluated on normal MR brain images using the similarity measures. The improvement in the quality of segmentation obtained with our method is also demonstrated by comparing our results with those produced by FSL (FMRIB Software Library), a software package that is commonly used for tissue classification.

EXPRESSION AND IMMUNOLOGICAL CHARACTERIZATION OF HERV-K TRANSMEMBRANE ENVELOPE PROTEIN IN HUMAN BREAST CANCER

The human endogenous retrovirus K (HERV-K) env gene encodes envelope protein comprising surface (SU) and transmembrane (TM) domains. Having shown the exclusive expression of SU in human breast cancer and the stimulation of SU-specific immune responses in patients with breast cancer, our research here confirmed and extended the data by investigating the expression of HERV-K TM envelope domain and the induction of specific immune responses against TM in breast cancer patients. We found HERV-K TM mRNA and protein expression only in human breast cancer cells but not in normal controls. The specific immune responses against TM domain were induced in mice determined by enzyme-linked immunosorbent assay (ELISA) and IFN-γ enzyme-linked immunosorbent spot (ELISPOT) assay. Furthermore, ELISA detected higher titers of anti-HERV-K TM Env IgG antibodies in sera of breast cancer patients. In addition, the magnitude of the anti-HERV TM B cell response was correlated with the disease stage. Peripheral blood mononuclear cells (PBMCs) before and after in vitro stimulation (IVS) with HERV-K TM from patients with breast cancer as well as healthy controls were tested for T cell responses against HERV-K TM domain by ELISPOT assay. Breast cancer patients (n=21) had stronger HERV-K TM-specific cellular responses than healthy controls (n=12) (P < 0.05). These findings suggest, for the first time, that HERV-K TM expression was enhanced in human breast cancer cells and was able to induce specific B cell and T cell immune responses in breast cancer patients. This study provides support for HERV-K TM as a promising source of antigen for anti-tumor immunotherapy, prevention, diagnosis, and prognosis.

Patient compliance during drug therapy for hypertension

A retrospective study has been conducted examining the relationship between patient compliance and race among diagnosed hypertensives in NHANES II 1976-1980. The study includes the review/analysis of 403 blacks and 2,011 nonblacks. Patient compliance was measured using the frequency that patients took their hypertensive medication.^ A statistically significant trend of increasing compliance as age increased was found (p =.000) in blacks, nonblacks, and the study group. The number of times a person spoke with a doctor about high blood pressure was found to be statistically significant (p ==.000) in nonblacks and the study group. ^

Involvement of heparin-like glycosaminoglycans and expression of a novel heparan sulfate binding protein (p24) during human placentation and in a model for human implantation

Previous studies in our laboratory have indicated that heparan sulfate proteoglycans (HSPGs) play an important role in murine embryo implantation. To investigate the potential function of HSPGs in human implantation, two human cell lines (RL95 and JAR) were selected to model uterine epithelium and embryonal trophectoderm, respectively. A heterologous cell-cell adhesion assay showed that initial binding between JAR and RL95 cells is mediated by cell surface glycosaminoglycans (GAG) with heparin-like properties, i.e., heparan sulfate and dermatan sulfate. Furthermore, a single class of highly specific, protease-sensitive heparin/heparan sulfate binding sites exist on the surface of RL95 cells. Three heparin binding, tryptic peptide fragments were isolated from RL95 cell surfaces and their amino termini partially sequenced. Reverse transcription-polymerase chain reaction (RT-PCR) generated 1 to 4 PCR products per tryptic peptide. Northern blot analysis of RNA from RL95 cells using one of these RT-PCR products identified a 1.2 Kb mRNA species (p24). The amino acid sequence predicted from the cDNA sequence contains a putative heparin-binding domain. A synthetic peptide representing this putative heparin binding domain was used to generate a rabbit polyclonal antibody (anti-p24). Indirect immunofluorescence studies on RL95 and JAR cells as well as binding studies of anti-p24 to intact RL95 cells demonstrate that p24 is distributed on the cell surface. Western blots of RL95 membrane preparations identify a 24 kDa protein (p24) highly enriched in the 100,000 g pellet plasma membrane-enriched fraction. p24 eluted from membranes with 0.8 M NaCl, but not 0.6 M NaCl, suggesting that it is a peripheral membrane component. Solubilized p24 binds heparin by heparin affinity chromatography and $\sp{125}$I-heparin binding assays. Furthermore, indirect immunofluorescence studies indicate that cytotrophoblast of floating and attached villi of the human fetal-maternal interface are recognized by anti-p24. The study also indicates that the HSPG, perlecan, accumulates where chorionic villi are attached to uterine stroma and where p24-expressing cytotrophoblast penetrate the stroma. Collectively, these data indicate that p24 is a cell surface membrane-associated heparin/heparan sulfate binding protein found in cytotrophoblast, but not many other cell types of the fetal-maternal interface. Furthermore, p24 colocalizes with HSPGs in regions of cytotrophoblast invasion. These observations are consistent with a role for HSPGs and HSPG binding proteins in human trophoblast-uterine cell interactions. ^

A prospective cohort study evaluating the state of medical readiness in the United States Air Force and risk factors to improve the medical readiness posture

A cohort of 418 United States Air Force (USAF) personnel from over 15 different bases deployed to Morocco in 1994. This was the first study of its kind and was designed with two primary goals: to determine if the USAF was medically prepared to deploy with its changing mission in the new world order, and to evaluate factors that might improve or degrade USAF medical readiness. The mean length of deployment was 21 days. The cohort was 95% male, 86% enlisted, 65% married, and 78% white.^ This study shows major deficiencies indicating the USAF medical readiness posture has not fully responded to meet its new mission requirements. Lack of required logistical items (e.g., mosquito nets, rainboots, DEET insecticide cream, etc.) revealed a low state of preparedness. The most notable deficiency was that 82.5% (95% CI = 78.4, 85.9) did not have permethrin pretreated mosquito nets and 81.0% (95% CI = 76.8, 84.6) lacked mosquito net poles. Additionally, 18% were deficient on vaccinations and 36% had not received a tuberculin skin test. Excluding injections, the overall compliance for preventive medicine requirements had a mean frequency of only 50.6% (95% CI = 45.36, 55.90).^ Several factors had a positive impact on compliance with logistical requirements. The most prominent was "receiving a medical intelligence briefing" from the USAF Public Health. After adjustment for mobility and age, individuals who underwent a briefing were 17.2 (95% CI = 4.37, 67.99) times more likely to have received an immunoglobulin shot and 4.2 (95% CI = 1.84, 9.45) times more likely to start their antimalarial prophylaxsis at the proper time. "Personnel on mobility" had the second strongest positive effect on medical readiness. When mobility and briefing were included in models, "personnel on mobility" were 2.6 (95% CI = 1.19, 5.53) times as likely to have DEET insecticide and 2.2 (95% CI = 1.16, 4.16) times as likely to have had a TB skin test.^ Five recommendations to improve the medical readiness of the USAF were outlined: upgrade base level logistical support, improve medical intelligence messages, include medical requirements on travel orders, place more personnel on mobility or only deploy personnel on mobility, and conduct research dedicated to capitalize on the powerful effect from predeployment briefings.^ Since this is the first study of its kind, more studies should be performed in different geographic theaters to assess medical readiness and establish acceptable compliance levels for the USAF. ^

A case-control study of hepatitis C virus and its interaction with hepatitis B virus on the development of hepatocellular carcinoma in the USA

Objective. The aim of this study was to assess the independent risk of hepatitis C virus (HCV) infection in the development of hepatocellular carcinoma (HCC). The independent risk of hepatitis B virus (HBV), its interaction with hepatitis C virus and the association with other risk factors were examined.^ Methods. A hospital-based case-control study was conducted between January 1994 and December 1995. We enrolled 115 pathologically confirmed HCC patients and 230 nonliver cancer controls, who were matched by age ($\pm$5 years), gender, and year of diagnosis. Both cases and controls were recruited from The University of Texas M. D. Anderson Cancer Center at Houston. The risk factors were collected through personal interviews and blood samples were tested for HCV and HBV markers. Univariate and multivariate analyses were performed through conditional logistic regression.^ The prevalence of anti-HCV positive is 25.2% in HCC cases compared to 3.0% in controls. The univariate analysis showed that anti-HCV, HBsAg, alcohol drinking and cigarette smoking were significantly associated with HCC, however, family history of cancer, occupational chemical exposure, and use of oral contraceptive were not. Multivariate analysis revealed a matched odds ratio (OR) of 10.1 (95% CI 3.7-27.4) for anti-HCV, and an OR of 11.9 (95% CI 2.5-57.5) for HBsAg. However, dual infection of HCV and HBV had only a thirteen times increase in the risk of HCC, OR = 13.9 (95% CI 1.3-150.6). The estimated population attributable risk percent was 23.4% for HCV, 12.6% for HBV, and 5.3% for both viruses. Ever alcohol drinkers was positively associated with HCC, especially among daily drinkers, matched OR was 5.7 (95% CI 2.1-15.6). However, there was no significant increase in the risk of HCC among smokers as compared to nonsmokers. The mean age of HCC patients was significantly younger among the HBV(+) group and among the HCV(+)/HBV(+) group, when compared to the group of HCC patients with no viral markers. The association between past histories of blood transfusion, acupuncture, tattoo and IVDU was highly significant among the HCV(+) group and the HBV(+)/HCV(+) group, as compared to HCC patients with no viral markers. Forty percent of the HCC patients were pathologically or clinically diagnosed with liver cirrhosis. Anti-HCV(+) (OR = 3.6 95% CI 1.5-8.9) and alcohol drinking (OR = 2.7 95% CI 1.1-6.7), but not HBsAg, are the major risk factors for liver cirrhosis in HCC patients.^ Conclusion. Both hepatitis B virus and hepatitis C virus were independent risk factors for HCC. There was not enough evidence to determine the interaction between both viruses. Only daily alcoholic drinkers showed increasing risk for HCC development, as compared to nondrinkers. ^

Development and testing of a procedure for systematically assigning gestational age for clinical and research use

A graphing method was developed and tested to estimate gestational ages pre-and postnatally in a consistent manner for epidemiological research and clinical purposes on feti/infants of women with few consistent prenatal estimators of gestational age. Each patient's available data was plotted on a single page graph to give a comprehensive overview of that patient. A hierarchical classification of gestational age determination was then applied in a systematic manner, and reasonable gestational age estimates were produced. The method was tested for validity and reliability on 50 women who had known dates for their last menstrual period or dates of conception, and multiple ultrasound examinations and other gestational age estimating measures. The feasibility of the procedure was then tested on 1223 low income women with few gestational age estimators. The graphing method proved to have high inter- and intrarater reliability. It was quick, easy to use, inexpensive, and did not require special equipment. The graphing method estimate of gestational age for each infant was tested against the last menstrual period gestational age estimate using paired t-Tests, F tests and the Kolmogorov-Smirnov test of similar populations, producing a 98 percent probability or better that the means and data populations were the same. Less than 5 percent of the infants' gestational ages were misclassified using the graphing method, much lower than the amount of misclassification produced by ultrasound or neonatal examination estimates. ^

Certified nurse midwives effects on catecholamine levels and maternal anxiety during labor

Studies of nurse midwifery care in the last twenty one years have reported excellent birth outcomes (Levy, Wilkenson and Marine, 1971; Platt et al. 1985; Stone et al. 1976). These outcomes are frequently attributed to the special support offered during labor and delivery by nurse midwives. This supportive style is thought to decrease catecholamine levels by reducing maternal anxiety. This prospective observational study evaluated catecholamine levels, anxiety levels, in-hospital costs, obstetrical practices and outcomes between low risk, term, labor and delivery primigravida patients managed by obstetrical residents (n = 55) or by certified nurse-midwives CNM (n = 59). The two groups were similar with regard to obstetrical risk factors present at admission. Each group was selected over the same period of time between March 23, 1994 and November 2, 1994. Specific catecholamines evaluated were epinephrine and norepinephrine. Obstetrical and newborn characteristics were also compared. This study did not prove that there is a decreased level in stress as indicated by lower levels of epinephrine and norepinephrine in nurse-midwife patients compared to obstetrical resident patients after adjusting for the use of epidural anesthesia. There was also no difference found in the perceived anxiety levels between the two groups. This study did confirm that nurse-midwives and obstetrical residents have different practice styles. Nurse-midwife patients had fewer augmented deliveries, fewer operative deliveries, less blood loss, fewer episiotomies and fewer third and fourth degree lacerations. The physician's choice to utilize more interventions such as continuous fetal monitoring and epidural anesthesia did not improve outcomes. The hospital cost of the nurse-midwife patients in this study was 35 percent lower than the physician patients. ^

An investigation of the pica practices of pregnant women in Houston and Prairie View, Texas

Pregnant African American women are at higher risk of having a preterm delivery and/or a low birthweight infant. Many factors are associated with adverse pregnancy outcomes but a food habit that deserves further study in the causal process is pica, a craving for, and ingestion of, nonnutritive substances such as laundry starch, clay, dirt, or ice. This food habit is more common in the African American population but has not been adequately studied in relation to preterm and/or low birth weight infants.^ Mothers (n = 281) with infants less than one year of age who participated in the Special Supplementary Food Program for Women, Infants, and Children (WIC) at clinics in Houston and Prairie View, Texas were interviewed regarding pica practices during pregnancy, dietary practices, and some demographic indices. Hospital records were abstracted for health information on the mothers and infants, including birthweight and gestational age at birth of the infant.^ The subjects were 88.6% African American, 6.8% Hispanic, and 4.6% Caucasian. Overall prevalence of pica was 76.5%. Pica prevalence by substance(s) was as follows: ice 53.7%; ice and freezer frost 14.6%; other substances such as baking soda, baking powder, cornstarch, laundry starch, and clay or dirt 8.2%; and 23.5% reported no pica. The women who reported ice/freezer frost pica had a higher percentage of illegal drug use and alcohol use during pregnancy. The women who reported other pica substances had the lowest mean educational level, highest gravidity, and a higher percentage smoked during pregnancy.^ There were no significant differences in nutrient intakes measured by the mean 24-hour dietary recalls between women who reported ice pica (n = 103) and women who denied pica (n = 50). The women who reported ice/freezer frost pica or other pica substances had more food cravings and food dislikes during pregnancy than those who reported ice pica or no pica.^ There were no differences in mean birthweight or mean gestational age at birth of infants born to mothers from the three pica groups and the no pica group but regression analyses revealed a possible relationship between pica, low maternal hemoglobin at delivery, and preterm birth. ^

Status epilepticus and multiple organ system dysfunction

Recent reports have suggested the possible association of status epilepticus and multiple organ system failure. The purpose of this case control study was to investigate this association and to identify factors that predispose individuals with status epilepticus (SE) or aborted status epilepticus (ASE) to develop multiple organ system failure (MOSF) or multiple organ system dysfunction (MODS).^ For the purpose of the study, definitions of SE, ASE, MOSF, and MODS were operationalized as follows: SE was defined as any seizure lasting for a duration of $\ge$30 minutes or intermittent seizures lasting for $\ge$30 minutes from which the patient does not regain consciousness. ASE was defined as any seizure lasting for a duration of $\ge$10 minutes but $<$30 minutes and which was aborted as a result of a medical intervention. MOSF was defined as the failure of $\ge$2 organ systems in the same patient; organ system failure was said to be present whenever standard MOSF criteria were met. MODS was defined as the dysfunction of $\ge$2 organ systems in the same patient; organ system dysfunction was said to be present, whenever the monitor(s) of that organ's function exceeded the normal range for the physiological or laboratory parameters.^ Medical records of 686 individuals between the age of 5 and 44 years, with history of seizures needing hospitalization at the Texas Children's Hospital or Methodist Hospital, Houston, Texas, between 1991-95 were reviewed and 100 individuals with SE/ASE were identified. Of these 100 individuals with SE/ASE, 45 developed MOSF/MODS during their hospitalization and 9 of these individuals died. Using multivariate analyses, it was found that adult individuals who had an "acute" etiology of their seizure disorder (OR = 5.23; 95%CI: 0.41, 66.24) and children who had a "remote" etiology of their seizure disorder (OR = 3.92; 95%CI: 0.53, 29.22), were more likely to develop MOSF/MODS compared with those who had other etiologies of the seizure disorder. Individuals with SE lasting more than one hour were more likely to develop MOSF/MODS compared with individuals with SE lasting less than 1 hour (OR = 6.51; 95%CI: 1.63, 25.92). Individuals who presented with the SE/ASE episode as their first seizure episode were more likely to develop MOSF/MODS compared to those with a previous history of seizure episodes (OR = 1.78; 95%CI: 0.36, 8.82).^ The major limitations of this study includes the relatively small sample size and the study being performed in only two institutions. However, this is the first study of this kind and should therefore be viewed as largely exploratory in nature. Future studies should investigate the relationship of the risk factors identified in this study using a larger number of institutions and patients. ^

The door of the tomb is open: Participatory action research to assess the impact of strengthened community capacity on maternal health care in rural Mali

This participatory action-research project addressed the hypothesis that strengthened community and women's capacity for self-development will lead to action to address maternal health problems and the prevention of maternal morbidity and mortality in Mali. Research objectives were: (1) to undertake a comparative cross-sectional study of the association of community capacity with improved maternal health in rural areas of Sanando, Mali, where capacity building interventions have taken place in some villages but not in others. (2) to describe women's maternal health status, access to and use of maternal health services given their residence in program or comparison communities.^ The participatory action research project was an integrated qualitative and quantitative study using participatory rural appraisal exercises, semi-structured group interviews and a cross-sectional survey.^ Factors related to community capacity for self-development were identified: community harmony; an understanding of the benefits of self-development; dynamic leadership; and a structure to implement collective activities.^ A distinct difference between the program and comparison villages was the commitment to train and support traditional birth attendants (TBAs). The TBAs in the program villages work in the context of the wider, integrated self-development program and, 10 years after their initial training, the TBAs continue to practice.^ Many women experience labor and childbirth alone or are attended by an untrained relative in both program and comparison villages. Nevertheless a significant change is apparent, with more women in program villages than in comparison villages being assisted by the TBAs. The delivery practices of the TBAs reveal the positive impact of their training in the "three cleans" (clean hands of the assistant, clean delivery surface and clean cord-cutting). The findings of this study indicate a significant level of unmet need for child spacing methods in all villages.^ The training and support of TBAs in the program villages yielded significant improvements in their delivery practices, and resulting outcomes for women and infants. However, potential exists for further community action. Capacities for self-development have not yet been directed toward an action plan encompassing other Safe Motherhood interventions, including access to family planning services and emergency obstetric care services. ^