Summary measures of the insulin resistance syndrome are adverse among Mexican-American versus non-Hispanic white children: the Corpus Christi Child Heart Study

BACKGROUND: Mexican-American (MA) adults are known to have a greater burden of diabetes and insulin resistance than non-Hispanic white (NHW) people. In this report, we examined data obtained from MA and NHW third-grade children for evidence of a pattern consistent with the insulin resistance syndrome. In addition, we developed two summary measures characterizing insulin resistance syndrome to compare measures of this syndrome among our population. METHODS AND RESULTS: Data regarding fasting insulin, triglycerides, HDL cholesterol, systolic blood pressure, and body mass index (BMI) were available for 403 third-grade children. Median levels of insulin and glucose were significantly higher in MA boys and girls than in NHW boys and girls. Risk factors characterizing insulin resistance, including levels of insulin, triglycerides, systolic blood pressure, HDL cholesterol, and BMI were categorized as above or below the total population median. MA children were more likely than NHW children to have three or more adverse risk factors (55% versus 37%). When risk factors were converted to Z scores, and the five Z scores were summed for each individual, MA boys and girls had higher mean scores than NHW boys and girls (means for boys, 0.65 versus -0.97, P<.0001; girls, 0.52 versus -0.30, P<.04). Principal components analysis was used to create a summary score or index representing the insulin resistance syndrome. This summary score was significantly higher among MA boys and girls than NHW boys and girls (means for boys, 0.34 versus -0.72, P<.0001; girls, 0.35 versus -0.04, P=.056). CONCLUSIONS: Our results support the hypothesis that MA children exhibit a greater degree of the insulin resistance syndrome than NHW children, especially among boys. We conclude that some of the factors responsible for the increased risk of NIDDM seen among MA adults are demonstrable in childhood.     

Human papillomavirus type in anal epithelial lesions is influenced by human immunodeficiency virus

PURPOSE: To evaluate limbal conjunctival Langerhans cell density in ocular cicatricial pemphigoid patients versus normal controls. Langerhans cells obviously play a major role in T-cell activation and are involved in corneal and conjunctival inflammatory diseases. METHODS: We used a protease (Dispase II) on inferior limbal conjunctival biopsies to separate the epithelium from the substantia propria and performed indirect immunofluorescence to analyze CD1a+ (a specific Langerhans cell surface antigen) cell density on flat-mounted epithelial sheets obtained from 30 normal controls and 11 patients presenting with ocular cicatricial pemphigoid. RESULTS: This technique was quick and reproducible. The mean Langerhans cell density in normal limbal conjunctiva was 272 +/- 37 cells/mm2. It was significantly higher in ocular cicatricial pemphigoid patients: 386 +/- 43 cells/mm2 (p = 0.001). CONCLUSIONS: Conjunctival Langerhans cell density in ocular surface inflammatory diseases can best be evaluated by indirect immunofluorescence, following epithelial sheet separation from the substantia propria, using Dispase II.     

What alters physicians'' decisions to admit to the coronary care unit?

OBJECTIVES: To determine the endometrial response and bleeding patterns in post-menopausal women who were given a sequential hormone replacement regimen with estradiol 2 mg and dydrogesterone 10 mg. METHODS: One-hundred-and-eighty-eight (188) post-menopausal women with amenorrhea of 6 months or longer, with FSH/estradiol (E2) levels in the post-menopausal range and normal endometrium were entered in the study. All patients received a daily dose of 2 mg E2 during day 1-14 of each 28 day cycle and 2 mg E2 combined with 10 mg dydrogesterone during cycle day 15-28. The total duration of treatment was 12 months (13 cycles of 28 days). RESULTS: The rate of adequate progestational response (secretory or atrophic) in the 146 patients who remained in the study for at least 356 days with 90% study medication compliance and received an endometrial biopsy after 13 cycles of study medication was 97.2%. Three patients had proliferative endometrium and one simple hyperplasia. Cyclic bleedings in the 153 women who remained on study medication for at least 76 days occurred in over 85% of all cycles; the day of onset occurring regularly on day 13 or 14 of the combined period; the mean duration of bleeding per cycle was approximately 5 days with most patients having (very) slight bleeding. Sixty percent of patients had no intermittent bleedings over the whole 12-month study period. The average incidence of intermittent bleeding in the remaining patients was only 2.7 and generally of very slight quantities and of short duration. Per evaluable cycle the percentage of patients with an intermittent bleeding varies from 4.6 to 9.8%. Only two patients discontinued therapy because of bleeding problems. A clear decrease in the incidence of typical menopausal symptoms, i.e. hot flushes and night sweats was observed by the first visit after 6 weeks of treatment. CONCLUSIONS: The endometrial safety of 2 mg E2 sequentially combined with 10 mg dydrogesterone is very good as determined by the histologic response of the endometrium. The incidence of cyclic bleedings with this combination therapy is very high as is the regularity of day of onset and duration of bleeding. Blood loss during intermittent bleedings was mild and of short duration.     

Estrogen modulation: tiered testing for human hazard evaluation. American Industrial Health Council, Reproductive and Developmental Effects Subcommittee

Recent concerns about the potential of certain chemicals to modulate estrogen-regulated processes have led to questions as to how chemicals should be tested for such effects. Therefore, AIHC has developed a comprehensive, resource-efficient, and flexible tiered strategy for estrogen modulation (EM) testing. Levels of evaluation include Tier 0, in which exposure, along with alerts based on structure-activity, persistence, bioaccumulation, and other data, are assessed to prioritize chemicals for preliminary testing. In Tier I, short term in vitro, ex vivo, and/or in vivo assays are used to obtain a preliminary indication of EM potential. Among these, an in vivo response assay is considered the most reliable at this time. However, none of these tests are intended for risk assessment, but rather to aid in choosing chemicals for further testing and in guiding the extent of that testing. Tier II is aimed at risk assessment and involves whole animal tests that contain EM-sensitive end points (e.g., two-generation reproduction study). Tier III consists of hypothesis-driven research reserved for situations where targeted research can reduce levels of uncertainty. This tiered approach provides a framework for the strategic and effective application of EM test methods to address specific information needs on a case by case basis.     

Development of invasive adenocarcinoma in a long-standing Kock continent ileostomy: report of a case

The first case of adenocarcinoma developing in a continent ileostomy is reported. A healthy, 39-year-old man with a continent ileostomy for 17 years developed subacute obstructive symptoms and was found on endoscopy to have a large adenocarcinoma involving the intussusception valve. At operation, he was found to have a large tumor originating in the valve, extending through the reservoir, and involving the afferent ileal limb. A number of metastatic lymph nodes were identified in the mesentery of the small bowel. He underwent excision of the pouch and formation of an end ileostomy. He is currently undergoing adjuvant chemotherapy. Biochemical and morphologic changes in the ileal pouch, both in the pelvis and the continent ileostomy, are discussed. The implications of this apparent de novo cancer arising in an ileal pouch are discussed.     

Mechanisms of the cochlear nucleus octopus cell's onset response: synaptic effectiveness and threshold

Octopus cells are one of the principal cell types in the mammalian posteroventral cochlear nucleus. These cells respond to the onset of a toneburst with a precisely timed spike followed by little, if any, sustained activity. While experimental studies have partially characterized the cell, the mechanisms of this onset response are not well understood. The present study involved a model-based investigation that analyzed the responses of a compartmental model of the octopus cell in terms of synaptic effectiveness and dynamic spike threshold. The simulations demonstrate that properties of the onset response (first-spike latency, temporal precision of the first spike, and sustained firing rate) can be predicted from the values of these cell properties for a wide range of model configurations. These relationships were further analyzed through the development of mathematical expressions for synaptic effectiveness and dynamic spike threshold. This computational analysis resulted in a relatively simple explanation of the onset response, as well as predictions of the responses of octopus cells to nontonal, complex stimuli.     

The fate of retained gallstones following laparoscopic cholecystectomy in a prairie dog model

By extrapolation to zero time, the initial and final slopes of data sets which probably demonstrate the existence of accelerated repopulation during radiotherapy can be used to estimate the lower limits of the initial tumour hypoxic fraction. The slow repopulation phase (initial slope) is assumed to reflect treatment in mixed oxic and hypoxic conditions and the later fast repopulation (final slope) phase that of a well-oxygenated cell population. The method assumes that accelerated repopulation in tumours results from an improvement in oxygen status during radiotherapy, but quantitative knowledge of repopulation factors is not required in the calculations. Using the data of (a) Withers et al. (for head and neck squamous cell cancer) and (b) Maciejewski & Majewski (for bladder cancer), the lower limits of initial hypoxic fraction appear to be between 10 and 52%, the exact values depending on the value assumed for the oxygen-enhancement ratio (OER) of the hypoxic compartment. The analysis also suggests that the half-life of effective tumour reoxygenation is probably less than 5 days.     

On the binocular summation of chromatic contrast

The binocular summation of chromatic contrast was investigated under a variety of stimulus conditions. Binocular and monocular contrast detection thresholds were measured using 0.5 cpd Gabor patches. It was found that, using stimuli which contained combinations of chromatic and luminance contrast, binocular detection could take place independently in luminance-contrast- and chromatic-contrast-sensitive mechanisms. It was also found that, with chromatic stimuli, levels of binocular summation were above those expected from probability summation between the eyes, and thus showed evidence for binocular neural summation within chromatic detection mechanisms. The implications of these results for (a) the binocularity of chromatic detection mechanisms, and (b) the suggested link between stereopsis and binocular neural summation, are discussed.     

Use of exercise myocardial perfusion imaging to guide and assess the effectiveness of medical therapy in coronary artery vasospasm

A computed tomography (CT) scan of the head is often routine for patients with new-onset psychosis to rule out somatic causes. Charts of 127 such patients admitted to a major military medical center were examined. Most patients were young and otherwise in good health. Relationships were examined between CT scan findings and demographic variables, seizure history, neurological abnormalities, and discharge diagnosis. None of the 127 patients had an abnormal scan; four had incidental findings. Incidental findings were strongly associated with ethnic minority status but not with neurologic abnormalities, seizure history, or diagnosis. Findings suggest that routine CT scans for all newly psychotic military patients may not be warranted.     

Role of cross-linking agents in determining the biochemical and pharmacokinetic properties of Mgr6-clavin immunotoxins

Several immunotoxins (ITs) were synthesized by the attachment of clavin, a recombinant toxic protein derived from Aspergillus clavatus, to the monoclonal antibody Mgr6 that recognizes an epitope of the gp185(HER-2) extracellular domain expressed on breast and ovarian carcinoma cells. Conjugation and purification parameters were analyzed in an effort to optimize the antitumor activity and stability of the ITs in vivo. To modulate the in vitro and in vivo properties of the immunotoxins, different coupling procedures were used and both disulfide and thioether linkages were obtained. Unhindered and hindered disulfide with a methyl group linkage ethyl S-acetyl 3-mercaptopropionthioimidate ester hydrochloride (AMPT) or ethyl S-acetyl 3-mercaptobutyrothioimidate ester hydrochloride (M-AMPT) were obtained by reaction with recombinant clavin, while the monoclonal antibody Mgr6 was derivatized with ethyl 3-[(4-carboxamidophenyl)dithio]propionthioimidate ester hydrochloride (CDPT). To achieve higher hindrance (a disulfide bond with a geminal dimethyl group), Mgr6 was derivatized with the N-hydroxysuccinimidyl 3-methyl-3-(acetylthio)butanoate (SAMBA) and clavin with CDPT. To evaluate the relevance of the disulfide bond in the potency and pharmacokinetic behavior of the ITs, a conjugate consisting of a stable thioether bond was also prepared by derivatizing Mgr6 with the N-hydroxysuccinimidyl ester of iodoacetic acid (SIA) and clavin with AMPT. The immunotoxins were purified and characterized using a single-step chromatographic procedure. Specificity and cytotoxicity were assayed on target and unrelated cell lines. The data indicate that the introduction of a hindered disulfide linkage into ITs has little or no effect on antitumor activity and suggest that disulfide cleavage is essential for activity; indeed, the intracellularly unbreakable thioether linkage produced an inactive IT. Analysis of IT stability in vitro showed that the release of mAb by incubation with glutathione is proportional to the presence of methyl groups and increases exponentially with the increase in steric hindrance. Analysis of the pharmacokinetic behavior of ITs in Balb/c mice given intravenous bolus injections indicated that ITs with higher in vitro stability were eliminated more slowly; i.e., the disulfide bearing a methyl group doubled the beta-phase half-life (from 3.5 to 7.1 h) compared with that of the unhindered, while a geminal dimethyl protection increased the elimination phase to 24 h. The thioether linkage showed its intrinsic stability with a beta-phase half-life of 46 h. The thioether linkage also increased the distribution phase from 17 to 32 min. The in vitro characteristics and in vivo stability of Mgr6-clavin conjugates composed of a methyl and dimethyl steric hindered disulfide suggest clinical usefulness.