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Regulation and function of the fetal adrenal gland in sheep.

It is now known that in some species (sheep, cow, pig, llama) the fetal adrenal cortex is capable of secreting cortisol both early and late in gestation, but not during some, variable, intermediate time period. In the sheep the fetal adrenal can secrete cortisol, and respond quickly to ACTH, both between 40-90 days of gestation, and from 120-150 days (term), but not between 90-120 days. The inability to secrete cortisol in this 'off' period is due to lack of adequate pituitary ACTH at this time to maintain expression of P-450(17 alpha and P-450scc. Recent experiments demonstrate that the fetal pituitary does secrete adequate amounts of ACTH to keep these genes expressed, in the 40-90 day period. The question now becomes, therefore, what regulates the triphasic secretion pattern of ACTH during fetal sheep development.

Adrenal Glands

Genetic variation and differentiation of three Schistosoma species from the Philippines, Laos, and Peninsular Malaysia.

Electrophoretically-detected allozyme variation is described in strains of Schistosoma japonicum (4 Philippine strains), S. mekongi (Laos), and an undescribed anthropophilic S. japonicum-like schistosome from Peninsular Malaysia. Result, together with those reported previously for 8 other strains (S. japonicum, China, Formosa, Japan, Philippines; S. mekongi, 2 substrains; Malaysian schistosome, 2 strains) permit a composite genetic characterization of 15 strains of Asian schistosomes at 9-18 presumptive loci. The proportion of polymorphic loci (P) and the mean heterozygosity per locus (H) were zero in all strains. Although this was expected for strains that had been in laboratory culture for up to 50 years, we expected to detect variation in strains based on 10-50 recently field-collected infected snails. We expected S. japonicum to be as variable as S. mansoni (P = 0.13 (0-0.33), H = 0.04, 18 loci, 22 strains) as it is believed to reproduce sexually, has an evolutionary history of several million years, inhabits a wide geographic range, coevolved with a genetically variable intermediate snail host, and has a diversity of mammalian hosts. No differences were detected between the 5 S. japonicum strains from Leyte and Luzon (Philippines), between the 3 S. mekongi strains, or between the 3 Malaysian schistosome strains; these groups and the remaining S. japonicum strains representing Mindoro (Philippines), China, Formosa, and Japan each have distinctive multilocus electromorphic patterns. Nei's genetic distances (D) were calculated to estimate interstrain and interspecific divergence. Interstrain genetic distances in S. japonicum averaged greater than 0.3; much higher than those reported previously for S. mansoni (D = 0.06, D(max) = 0.24). S. japonicum (Mindoro) was moderately differentiated from the Leyte-Luzon strains (D = 0.29, 12 loci). Estimates of the S. japonicum China-Philippine distance (D greater than 0.4, 11 loci) are high for conspecific populations and further studies of the still poorly characterized Chinese parasite may reveal that these are, in fact, separate species. S. japonicum is shown to be only distantly related to S. mekongi and the Malaysian schistosome (D greater than 1); the latter is closely related to, but genetically quite distinct from, S. mekongi (D = 0.61 +/- 0.275, 11 loci) and warrants recognition as a new species. The medical significance of the isogenic nature of the Asian schistosome strains and their evolutionary divergence are discussed.

Animals

Risk factors for severe measles.

A retrospective study on measles was carried out in 522 children admitted to the Department of Pediatrics, Sumber Waras Hospital, Jakarta during the period of January 1982-December 1986. Most of the subjects (91.1%) came from lower socio-economic levels, living in unfavorable environmental conditions in crowded housing. The predominant age group was 2-5 years; complications were observed in 82.6% and mortality in 10.3%. The most common complications and cause of deaths were bronchopneumonia (94.4%), encephalopathy (88.9%) and diarrhea (25.9%) or combinations thereof. The outcome of measles infections is determined by the presence of malnutrition and complications which is influenced by the nutritional intake, exposure, susceptibility and constitution of the patients. The household characteristics (socio-economic, socio-cultural and health facilities available) influence the above mentioned interactions through intermediate variables of nutrition (feeding pattern, food supplements), constitution, age) and treatment. Research and intervention on measles can be designed and planned based on this model of interactions.

Acute Disease

Ego and superego alterations in borderline structures: their effect on the process and outcome of treatment.

The intermediate variable establishing the link between pathological structural alterations and aetiopathogenic factors, whether constitutional or acquired, might correspond to mental substructures derived from defensively altered and pathologically internalized object relations. Some basic postulates, connected to this central thesis, guided a brief, introductory critical review of two controversial areas in the treatment of borderline structures: (a) the relationship between mental models and developmental theories and (b) the relationship between mental models and therapeutic approaches. Since the axis of this paper centred around the limitations determined by structural alterations produced by defences, I then outlined some aspects of the treatment of a patient with severe character pathology, laying particular stress on: (a) the clinical manifestations of ego and superego alterations and their influence on the process and outcome of treatment; (b) the impediments and complications stemming from early superego precursors, with reference, in particular, to the therapeutic frame and psychoanalytic tactics; and, finally (c) the limitations and vicissitudes of the interplay of specific and diatrophic (non-specific) aspects of the analytic work in the task of promoting emotional growth.

Adult

Elevated platelet-derived microparticle levels during unstable angina.

OBJECTIVE: To use fluorescent-activated flow cytometry coupled with activation-dependent and -independent platelet-specific monoclonal antibodies in a pilot study to assess the degree and time course of platelet activation events in patients presenting within 24 h of onset of Canadian Cardiovascular Society class 4 angina. BACKGROUND: Although activated platelets play a key role in the pathogenesis of unstable angina, the development of simple assays to quantify platelet activation events directly is lacking. METHODS: Blood samples were drawn from six unstable angina patients from the coronary care every 4 h over a 24 h period into a fixative and analyzed the following day. All patients were on acetylsalicylic acid and heparin. Comparisons were made with six healthy, medication-free volunteers. Platelets were defined by flow cytometry as positive for fluorochrome-labelled monoclonal antibody to glycoprotein Ib (AP1) and within the single intact platelet window defined by scatter characteristics. The presence of the fluorochrome-labelled activation-specific monoclonal antibody (KC4.1 for anti-P-selectin, PAC-1 for activated glycoprotein IIb/IIIa) was used to determine the percentage of activated platelets. Platelet activation-dependent microparticles were identified by gating on AP1-positive events and defining microparticles (percentage of total platelet events) as being smaller (forward size scatter) than single intact platelets. RESULTS: There was a marked, sixfold increase in microparticle generation (17 +/- 7% versus 2.8 +/- 1.4%) in the unstable angina patients (P = 0.001) compared with healthy volunteers. Further assessment of six coronary care unit patients with nonischemic cardiac disorders demonstrated a highly variable intermediate level of microparticle generation (11 +/- 7%). No differences in activated glycoprotein IIb/IIIa expression were noted for the various groups and P-selectin expression was lower in the unstable angina patients (6 +/- 2% versus 12 +/- 3%, (P = 0.007). CONCLUSIONS: This pilot study suggests that measuring circulating platelet microparticle levels is a simple yet useful parameter for the assessment of platelet activation in unstable angina compared with activation markers on intact whole platelets. Despite antiplatelet and antithrombin therapy, significant platelet activation occurred in these patients over the initial 24 h. Flow cytometry may be a useful tool in assessing the efficacy of newer therapeutic modalities.

Adult

[Cytologic diagnosis of myxoid liposarcomas of soft tissues].

Myxoid sarcomas are characterized by the presence of branching capillaries in preparations around which lipogenesis is proceeded (unilocular and multilocular). Fat is chemically neutral. The cell content is represented by two basic kinds of cells: 1. stellate lipoblast -- a cambial element of the tumor, and 2. mature lipocyte -- a terminal stage of the differentiation of stellate lipoblast. Moreover, variable intermediate forms demonstrating the stage of lipoge nesis may be encountered. The differential diagnosis between the former and intramuscular myxoma and neurinoma (Antony B type) was made. The work is based on the analysis of 10 cases of myxoid liposarcomas.

Adult

Risk factors and clinical outcomes between fungal and bacterial keratitis: a comparative study.

PURPOSE: Previous studies on fungal and bacterial keratitis were descriptive single case series analysis. We conducted a hospital-based retrospective study to evaluate fungal and bacterial keratitis using a case-control design to compare risk factors and clinical outcomes. METHODS: Twenty-nine cases of culture-positive fungal keratitis seen over a 5-year period were compared to 51 cases of culture-positive bacterial keratitis seen over a 21 months period. Using bacterial keratitis as the reference group, case-control odds ratios (OR) for predisposing factors and cohort relative risks (RR) for clinical outcomes associated with fungal keratitis were derived. Mantel-Haenszel adjustment procedures were used to examine the respective roles of confounding and intermediate variables. RESULTS: Compared to bacterial keratitis, fungal keratitis was significantly more likely to be associated with ocular trauma (OR = 2.69, 95% confidence interval [CI], 1.06-6.86) but significantly less likely to be associated with contact lens wear (OR = 0.16, 95% CI, 0.04-0.67) and preexisting ocular diseases (OR = 0.23, 95% CI, 0.07-0.72). Fungal keratitis was more likely to perforate than bacterial keratitis (RR = 5.28, 95% CI, 1.35-20.66) and to require penetrating keratoplasty (OR = 5.86, 95% CI, 2.06-16.69). CONCLUSIONS: Fungal keratitis appears more likely to result from ocular trauma, whereas bacterial keratitis is more likely to result from contact lens wear and pre-existing ocular diseases. Fungal keratitis is more likely than bacterial keratitis to result in perforation and require penetrating keratoplasty.

Adolescent

Variable expression of intermediate filament proteins during embryonic development of human optic nerve.

The intermediate filament protein composition of human optic nerve and tract was analyzed by two-dimensional gel electrophoresis. Optic nerves were analyzed at 15, 19, 22, and 24 weeks of embryonic development and the results were compared with the composition of adult optic nerve. The optic tract was analyzed at the later stages of development. The proteins were visualized by Coomassie blue staining and immunoblotting with specific antibodies to glial fibrillary acidic protein (GFAP) and vimentin. The 70K and 150K neurofilament proteins were first observed at 24 weeks. At 15 weeks of development, only trace amounts of GFAP were observed and vimentin was the predominant intermediate filament protein. In contrast, there was more than twice as much GFAP as vimentin in the adult optic nerve. The results also showed that the ratio of GFAP to vimentin is higher in the optic tract than in the optic nerve during development, whereas in adult tissue, the ratio is the same for the two regions. In pathological situations with axonal dropout, a complete loss of neurofilament proteins was observed. The amounts of both GFAP and vimentin were the same for both the normal and involved optic nerve. These results are discussed in terms of the development of the optic nerve.

Glial Fibrillary Acidic Protein

Nonrandom frequency patterns of synonymous substitutions in homologous mammalian genes.

All 69 homologous coding sequences that are currently available in four mammalian orders were aligned and the synonymous positions of quartet and duet (fourfold and twofold degenerate) codons were divided into three classes (that will be called conserved, intermediate, and variable) according to whether they show no change, one change, or more than one change, respectively. We observed (1) that the frequencies of conserved, intermediate, and variable positions of quartet and duet codons are different in different genes; (2) that the frequencies of the three classes are significantly different from expectations based on a random substitution process in the majority of genes (especially for GC-rich genes) for quartet codons and in a minority of genes for doublet codons; and (3) that the frequencies of the three classes of positions of quartet codons are correlated with those of duet codons, the conserved positions of quartet and duet codons being, in addition, correlated with the degree of amino acid conservation. Our main conclusions are that synonymous substitution frequencies: (1) are gene-specific; (2) are not simply the result of a stochastic process in which nucleotide substitutions accumulate at random, over time; and (3) are correlated in quartet and duet codons.

Animals

Intermediate-term outcome of variable dose mitomycin C filtering surgery.

PURPOSE: Trabeculectomy with adjunctive mitomycin C is associated with high success rates in studies with follow-up of less than 1 year. This report evaluates the visual and intraocular pressure (IOP) outcome in eyes after trabeculectomy with adjunctive mitomycin C 1 to 3 years after surgery in a predominantly white group (98.1%). METHODS: The records of 157 eyes of 157 consecutive patients, aged 18 or older, who underwent mitomycin C trabeculectomies for uncontrolled glaucoma of various causes were reviewed. All surgeries were performed between April 1991 and June 1993. The concentration of mitomycin C varied from 0.2 to 0.5 mg/ml and was applied for 30 seconds to 5 minutes (only one patient received 0.2 mg/ml). Of the 157 eyes, 110 eyes were at high risk for failure (previous surgeries or inflammatory glaucoma). Thirty-nine eyes had preoperative IOP < or = 21 mmHg. RESULTS: The mean preoperative IOP was 29.4 +/- 10.3 mmHg. This was reduced to 13.0 +/- 7.6 mmHg at 1 year, 11.5 +/- 6.4 mmHg at 2 years, and 13.4 +/- 7.3 mmHg at 3 years. Cumulative survival rate by life-table analysis was 94.2% +/- 1.9% at 1 year, 92.1% +/- 2.4% at 2 years, and 88.7% +/- 4.0% at 3 years, where failure was defined as reoperation for control of IOP. Complications included cataract formation-progression (n = 31), hyphema (n = 26), choroidal detachment (n = 21), hypotony maculopathy (n = 5), and endophthalmitis (n = 2). Vision deteriorated in 29 eyes and improved by 2 or more Snellen visual acuity lines in 29 eyes. CONCLUSION: The IOP reduction after mitomycin C filtering surgery is sustained in the intermediate-term, 1 to 3 years, follow-up period.

Adult

A prospective randomized study comparing short- and intermediate-term perioperative outcome variables after spinal or general anesthesia for lumbar disk and laminectomy surgery.

General or regional anesthesia may be used for lumbar laminectomy. To determine whether one method is superior, 122 patients were randomly assigned to receive either a standard general anesthetic (GA) or spinal anesthesia (SA) supplemented with intravenous (IV) propofol sedation. Data from the intraoperative period through hospital discharge were collected and compared. Demographically, both groups were similar. Total anesthesia (131.0 +/- 4.3 vs 106.6 +/- 3.2 min) and surgical times (81.5 +/- 3.6 vs 67.1 +/- 2.8 min) were longer in the GA group. Intraoperative hemodynamics were similar between groups except that the incidence of increased blood pressure was more frequent with GA (26.2% vs 3.3%). Blood loss was less during SA (133 +/- 18 mL vs 221 +/- 32 mL). Postanesthesia care unit (PACU) heart rates and mean arterial pressures were higher in the GA group. Peak pain scores in the PACU were higher after GA compared with SA (58 +/- 4 vs 22 +/- 3) as were the number of patients who required analgesics. Severe nausea was more common in the GA group both in the PACU and during the 24 h after surgery. Analgesic requirements after discharge from the PACU, urinary retention, and days in the hospital did not differ between groups. This study suggests that SA may be superior to GA both intraoperatively and postoperatively for lumbar spine procedures lasting less than 2 h.

Adult

Noninvasive identification of severe coronary artery disease using exercise radionuclide angiography.

The ability of exercise radionuclide angiography to predict the risk of having significant left main or three vessel coronary artery disease was examined in 681 patients who underwent both radionuclide and coronary angiography. There were significant differences in multiple variables between patients with or without such disease. Logistic regression analysis identified seven variables as independently predictive of the presence of left main or three vessel disease. Using these variables, low, intermediate and high probability groups could be identified. The four most important variables--the magnitude of exercise ST segment depression, peak exercise ejection fraction, peak exercise rate-pressure product and sex of the patient--can provide practical estimates of the risk of having left main or three vessel disease. Exercise radionuclide angiography can provide a clinically useful noninvasive estimate of the risk of having significant left main or three vessel disease.

Angiography

A variable risk clinical prognostic compartmental model.

A model for predicting the occurrence of disease endpoints from a knowledge of baseline variables and intermediate events is described and illustrated with numerical examples. Maximum likelihood equations are developed and maximum likelihood estimates of coefficients in risk functions of variables included in a stepwise upward procedure are applied to a small set of data for illustrative purposes.

Adult

Composite pheochromocytoma/ganglioneuroma of the adrenal gland associated with multiple endocrine neoplasia 2A: case report with immunohistochemical analysis.

We report a case of composite pheochromocytoma/ganglioneuroma arising in a background of diffuse and nodular medullary hyperplasia in the adrenal gland of a 34-year-old man with multiple endocrine neoplasia 2a (MEN 2a). Cells were histologically classified as chromaffin or chromaffin-like (small typical-appearing pheochromocytoma cells), neuron-like (possessing ganglion cell morphology), and intermediate. We speculate that these cell types may represent a spectrum of differentiation of a neoplastic clone, with the intermediate cells representing a transitional stage between chromaffin cells and neurons. All three cell types in the composite tumor and all chromaffin cells in both nodular and nonnodular areas of the remaining medulla were strongly immunoreactive for tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. In contrast, neuron-like cells (and to a variable extent intermediate cells) displayed selective loss of expression of phenylethanolamine-N-methyltransferase (PNMT), the enzyme that synthesizes epinephrine. Proliferative activity of the composite tumor and both the nodular and nonnodular medulla was studied by staining for the endogenous cell proliferation antigen Ki-67, using monoclonal antibody MIB-1. MIB-1 labeling was highest in Schwann cell areas of the composite tumor, followed by chromaffin-like cells in the composite tumor and in the separate nodules. Labeling was absent in neuron-like cells, consistent with the cells' postulated status as terminally differentiated derivatives of a chromaffin cell precursor, and was highly variable in nonnodular areas of the medulla. The latter observation suggests topographical variation in signals that drive chromaffin cell proliferation in MEN.

Adrenal Gland Neoplasms

Analysis of hair samples of mummies from Semma South (Sudanese Nubia).

Hair samples from 76 burials at Semna South (Sudanese Nubia) were examined using a variety of techniques. Electrophoresis and fluorescence microscopy indicated some oxidation of the cuticule and keratin protein had taken place. However, the cuticular structure and the lack of fluorescence of the cortex indicate that the low humidity and non-alkaline conditions preserved the physical and chemical properties of the hair well. Pigmentation, even allowing for oxidation of melanin, showed a higher proportion of lighter samples than is currently associated with the Nubian area. Hair form analysis showed medium diameter and scale count; the curling variables were intermediate between European and African samples. There was a high ratio of maximum to minimum curvature (a measure of irregularity), approached only by Melanesian samples. Meroitic and X-group burial types were not statistically significantly different (largely due to sample sizes), but the X-group, especially males, showed more African elements than the Meroitic in the curling variables. Principal components analysis showed the Semna sample to be significantly different from seven populations examined earlier.

Anthropology, Physical

The importance of process variables analysis in the assessment of long-term oxygen therapy by concentrator.

The aim of the present study was to evaluate process variables and intermediate outcomes involved in long-term oxygen therapy (LTOT) by concentrator with the purpose of identifying which of those factors would be the most influential in the final health outcome of the therapy. A cross-sectional survey was carried out on a random sample of 111 patients receiving LTOT by concentrator in Catalonia (Spain). Patients were interviewed and assessed at home by a trained physician, and the variables collected were arterial oxygen saturation, performance of the concentrators, and patient compliance. Sixty-two patients participated in the study. Overall, LTOT was appropriately prescribed in 36 patients, of whom only 29 were able to correct their level of hypoxaemia. Patient compliance with treatment was considered adequate in 19 of those 29 patients. Thus, only 19 of 62 patients (31%) fulfilled those criteria needed to achieve the expected clinical benefits. Strategies for improving the effectiveness of medical interventions or technologies ought to consider those factors of the therapeutic process which might influence the expected health outcomes in a specific health-care context.

Aged

Distribution of cytokeratin polypeptides in syringomas. An immunohistochemical study on paraffin-embedded material.

The distribution of cytokeratin (CK) polypeptides expressed in syringomas (12 cases) was compared with that in normal eccrine sweat ducts using immunohistochemical techniques on paraffin-embedded tissue. Intradermal and intraepidermal segments of the eccrine duct showed reactivity with an antibody to CK1/5/10/11 in all cell layers, whereas CK19 expression was restricted to the luminal cell layer. CK14 was expressed in all cells of the eccrine duct except for the peripheral cells of the intraepidermal duct. Expression of CK5/6 was seen in the basal cells of the dermal duct and of the lower intraepidermal duct (sweat duct ridge) exclusively. Reactivity with an antibody to CK1 was found in the intermediate cells of the uppermost part of the eccrine dermal duct. In addition, this antibody gave a strong staining of the peripheral cells of the intraepidermal duct, leaving basal cells of the sweat duct ridge and luminal cells unstained. In syringoma, CK distribution was essentially comparable with that found in the uppermost part of the dermal duct and in the sweat duct ridge. Namely, ductal luminal cells expressed CK1/5/10/11, CK19, and variably CK14. Intermediate cells of ductal structures and solid nests were homogeneously stained by antibodies to CK1 and CK1/5/10/11, whereas CK14 was expressed heterogeneously. The basal or outermost layer of ductal structures and solid nests was reactive with antibodies to CK1/5/10/11, CK5/6, and CK14. With regard to CK expression, the results indicate that syringoma represents a tumor differentiating toward both the uppermost part of the dermal duct and the lower intraepidermal duct (sweat duct ridge) of the eccrine sweat gland.

Adenoma

Metabolic capacity and myosin expression in single muscle fibres of the garter snake.

1. The transversus abdominis muscle of the garter snake contains fibres of three types: tonic (T), slower twitch (S) and faster twitch (F). Fibre types can be determined by anatomical criteria in living preparations. Individual fibres identified as T, S or F were excised from the muscle and subdivided for two types of biochemical examination. Enzymes of energy metabolism were assayed using quantitative microfluorometric methods. Myosin heavy chain composition was determined by gel electrophoresis. In separate experiments, twitch time-to-peaks of F and S fibres were measured to assess the range of contraction times present within the muscle's twitch fibre population. 2. Metabolic subgroups of fibres were delineated by the relative activities of adenylokinase (AK), lactate dehydrogenase (LDH) and beta-hydroxyacyl-CoA-dehydrogenase (beta OAC). The metabolic subgroups corresponded to the anatomical fibre types. Type F fibres had high levels of enzymes associated with glycolytic (LDH) and high-energy phosphate (AK) metabolism. Type T fibres had high levels of the oxidative enzyme beta OAC. Type S fibres had both types of enzyme activity in intermediate and variable amounts. 3. Three myosin heavy chain isoforms were present in the muscle. Type F and type T fibres each expressed a single isoform, denoted F and T respectively. Type S fibres expressed significant quantities of two isoforms: an isoform unique to this fibre type (denoted S) and the F isoform. 4. Electrophoretic mobility and antibody reactivity of the F myosin heavy chain isoform resembled that of mammalian fast-twitch myosin. By the same criteria, the T isoform resembled mammalian slow-twitch myosin. The S isoform exhibited intermediate characteristics: its antibody reactivity was similar to mammalian fast-twitch myosin, but its electrophoretic mobility was that of mammalian slow-twitch myosin. 5. Based on whole-muscle analysis, two myosin alkali light chains, denoted ALC1 and ALC2, and one myosin regulatory light chain were present. Gel patterns suggested that ALC1 and ALC2 exist as both homodimers and heterodimers. 6. The population of type S fibres within a given muscle exhibited a much wider range of twitch contraction times than did the population of type F fibres. Diversity of contractile properties among type S fibres may result, in part, from differential co-expression of two myosin heavy chain isoforms, together with highly variable ratios of enzymes from two major metabolic pathways. 7. The clear biochemical distinction among fibre types indicates that each type possesses a unique and limited range of physiological properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals