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To ensure that patients are appropriately prepared for surgical procedures in a welcoming environment, the Sir Mortimer B. Davis Jewish General Hospital, a McGill University affiliated teaching hospital located in Montreal, is redesigning and relocating its existing presurgical screening clinic so that it provides additional services and is more patient friendly. Given the services being added, limited space, and the desire of senior management to minimize overtime costs, physician idle time, and excessive patient waiting times, we apply simulation optimization to the operations of the redesigned clinic. The simulation optimization is then used to evaluate the effect of possible design decisions to be made by senior management, to ensure that the resulting clinic meets their goals. In contrast to existing research which generally limits clinic optimization to just a few facets, we simultaneously optimize the clinic's multiple objectives at a fine-grained level with respect to individual decision variables for the start time of each physician, the appointment time of each patient, and the start, break, and lunch times of each staff member. To perform the optimization, we apply a simple heuristic to a simulation model of the clinic. We show, with this simple heuristic, that simultaneously optimizing the clinics's multiple objectives by adjusting decision variables at this more granular level can significantly reduce physician idle time, staff overtime, and excessive patient waiting. This in turn makes it possible to evaluate design decisions in context of optimized operations. These results suggest the usefulness of this approach to other multi-activity clinics such as cancer treatment clinics. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a chronic granulomatous disease with a wide spectrum of symptoms. Genome-wide association studies in European populations have reported significant associations between sarcoidosis and single-nucleotide polymorphisms (SNPs) located in the intergenic region between the C10ORF67 and OTUD1 genes on chromosome 10p12, and the ANXA11 gene (chromosome 10q22). We carried out fine-mapping at 10p12 and 10q22 to assess associations of genetic variants in these regions with sarcoidosis risk in African-American women, based on 486 sarcoidosis cases and 943 age- and geography-matched controls in a nested case-control study within the Black Women's Health Study. There were no significant associations with variants of the ANXA11 gene (P=0.17). Haplotypic analyses of the C10ORF67-OTUD1 intergenic region revealed a strong inverse association of the variants rs1398024 and rs11013452 with sarcoidosis (odds ratio=0.52; P=0.01). Both SNPs are located inside an ∼300 kb low recombination region of chromosome 10p12, suggesting that both SNPs are tagging the same causal variant. Our top SNP (rs11013452) is located inside a smaller linkage disequilibrium block in HapMap YRI, further narrowing the position of the causal SNP to a region of ∼8 kb on chromosome 10p12. The present findings confirm the potential importance of the 10p12 locus in the etiology of sarcoidosis. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-II (IGF-II) has been shown to promote pancreatic β-cell survival. We evaluated the effect of co-encapsulating islets and bioengineered IGF-II-producing cells on islet cell survival. IGF-II or green fast protein (GFP) genes were transferred into TM4 cells, and purified using a neomycin resistance gene, leading to pure cell cultures (TM4-IGF-II or TM4-GFP) with a stable overexpression of the transferred gene. Islets were co-encapsulated with TM4-IGF-II or TM4-GFP, or encapsulated alone in alginate microcapsules. Rat and mouse islet cell survival was studied in vitro and in vivo, respectively. After 12 days in culture, islet viability (dual staining, acridine orange/propidium iodide) was 83% with TM4-IGF-II, compared with 51% (P<0.05) and 41% (P<0.001) with TM4-GFP and islets alone, respectively. The study of islet necrotic centers and the evaluation of islet function, using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay, yielded similar results. From 125 days after transplantation, more diabetic mice maintained normoglycemia when they were transplanted with islets co-encapsulated with TM4-IGF-II (4/7). A significant difference for the maintenance of normoglycemia was observed between recipients of islets co-encapsulated with TM4-IGF-II versus islets alone (P=0.023), or with TM4-GFP (P=0.048). In conclusion, the co-encapsulation of islets with bioengineered IGF-II-producing cells promotes islet cell survival. [ABSTRACT FROM AUTHOR]

High body mass index (BMI) and use of hormone replacement therapy (HRT) increase the risk of postmenopausal breast cancer. It has been shown that BMI modifies the effect of HRT, as its influence is most pronounced in lean women. We investigated the influence of BMI and HRT on prognosis in 2640 postmenopausal women diagnosed with breast cancer in Sweden in 1993-1995, taking into account HRT and mammography before diagnosis. Logistic and Cox regression were used. In non-users of HRT, obese women (BMI >30) compared with normal weight women (BMI <25) had a similar prognosis (hazard ratio (HR) 1.1, 95% confidence interval (CI) 0.8-1.6), despite larger tumours found in obese women. Obese HRT users had less favourable tumour characteristics and poorer prognosis compared with normal weight women (HR 3.7, 95% CI 1.9-7.2). The influence of BMI on breast cancer prognosis was similar whether diagnosed by mammographic screening or not. We found a similar prognosis of postmenopausal breast cancer-specific death regardless of BMI in non-users of HRT, but among HRT users obesity was associated with a poorer breast cancer prognosis. [ABSTRACT FROM AUTHOR]

In a Swedish population-based case-control study, smoking showed no convincing association with risk of postmenopausal breast cancer - regardless of timing or level of smoking exposure - either overall or among subgroups. [ABSTRACT FROM AUTHOR]

Diabetes results from an insufficient insulin-secreting beta cell mass. Restoration of beta cell mass through pharmaceutically induced endogenous beta cell mass expansion may revolutionise diabetes therapy. However, it remains to be determined whether the induced beta cell mass expansion is under homeostatic regulation. Beta cell mass expansion rates were derived from three separate studies of continuous stimulation of islet neogenesis, including the partial duct obstruction of euglycaemic Syrian hamsters, administration of a pentadecapeptide with the same amino acid sequence as residues 104–118 of islet neogenesis-associated protein (INGAP104–118) to euglycaemic Syrian hamsters, as well as to euglycaemic CD-1 mice. The incidence of islet neogenesis, average beta cell size, and beta cell replication and apoptotic rates were determined. Partial duct obstruction led to a ∼2.5-fold increase in endocrine tissue at day 56 ( p<0.05). From day 0 to day 7 the average rate of change of islet area was 12.7% per day, and this rate decreased to 5.3% per day from day 7 to day 42, and to 2.8% per day from day 42 to day 56. Administration of INGAP104–118 to adult hamsters led to a 31% increase in total beta cell mass at day 30 ( p=0.031). From day 0 to day 10 the average rate of beta cell mass expansion was 148 μg/day, whereas from day 10 to day 30 it decreased to 45 μg/day. INGAP104–118 administration to adult CD-1 mice resulted in an approximately twofold increase in beta cell mass after 31 days ( p=0.021). However, at day 90, there was no significant difference vs age-matched control mice ( p=0.30), even though the neogenic beta cell mass was approximately fourfold greater ( p=0.026). Beta cell replication was decreased by 56% ( p<0.048), whereas beta cell apoptosis was fourfold greater ( p<0.003) in 90-day INGAP104–118-treated mice compared with age-matched control mice. These data indicate that in the presence of ongoing islet neogenesis, homeostatic regulatory mechanisms intervene to regulate beta cell mass according to the prevailing metabolic requirements. [ABSTRACT FROM AUTHOR]

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a critical role in promoting the survival of pancreatic beta cells. Akt becomes activated in isolated human islets following overnight culture despite significant levels of cell death. The aim of the current study was to identify the cause of the observed increase in Akt phosphorylation in isolated islets. We hypothesised that a factor secreted by the islets in culture was acting in an autocrine manner to activate Akt. In order to identify the stimulus of the PI3K/Akt pathway in culture, we examined the effects of different culture conditions on Akt phosphorylation and islet survival during the immediate post-isolation period. We demonstrated that islet-conditioned medium induced Akt phosphorylation in freshly isolated human islets, whereas frequent medium replacement decreased Akt phosphorylation. Following overnight culture, islet-conditioned medium contained significantly elevated levels of insulin, indicating that insulin may be responsible for the observed increase in Akt phosphorylation. Indeed, treatment with an anti-insulin antibody or with inhibitors of insulin receptor/IGF receptor 1 kinase activity suppressed Akt phosphorylation, leading to decreased islet survival. In addition, dispersion of islets into single cells also suppressed Akt phosphorylation and induced islet cell death, indicating that islet integrity is also required for maximal Akt phosphorylation. Our findings demonstrate that insulin acts in an autocrine manner to activate Akt and mediate the survival of isolated human islets. These findings provide new information on how culturing islets prior to transplantation may be beneficial to their survival by allowing for autocrine activation of the pro-survival Akt pathway. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the phenotypic plasticity of pancreatic islets of Langerhans. Quiescent adult human islets were induced to undergo a phenotypic switch to highly proliferative duct-like structures in a process characterized by a loss of expression of islet-specific hormones and transcription factors as well as a temporally related rise in the expression of markers of both duct epithelial and progenitor cells. Short-term treatment of these primitive duct-like structures with the neogenic factor islet neogenesis-associated protein (INGAP104–118) induced their reconversion back to islet-like structures in a PI3-kinase-dependent manner. These neoislets resembled freshly isolated human islets with respect to the presence and topological arrangement of the four endocrine cell types, islet gene expression and hormone production, insulin content and glucose-responsive insulin secretion. Our results suggest that adult human islets possess a remarkable degree of morphogenetic plasticity. This novel observation may have important implications for understanding pancreatic carcinogenesis and islet neogenesis.Cell Death and Differentiation (2005) 12, 702–712. doi:10.1038/sj.cdd.4401617 Published online 8 April 2005 [ABSTRACT FROM AUTHOR]

Aims/hypothesis. We have provided evidence that glucagon-like peptide-1, a potential therapeutic agent in the treatment of diabetes, activates phosphatidylinositol-3 kinase/protein kinase B signalling in the pancreatic beta cell. Since this pathway promotes cell survival in a variety of systems, we tested whether glucagon-like peptide-1 protects beta cells against cell death induced by elevated glucose and/or non-esterified fatty acids. Methods. Human islets and INS832/13 cells were cultured at glucose concentrations of 5 or 25 mmol/l in the presence or absence of palmitate. Apoptosis was evaluated by monitoring DNA fragmentation and chromatin condensation. Wild-type and protein kinase B mutants were overexpressed in INS832/13 cells using adenoviruses. Nuclear factor-κB DNA binding was assayed by electrophoretic mobility shift assay. Results. In human pancreatic beta cells and INS832/13 cells, glucagon-like peptide-1 prevented beta cell apoptosis induced by elevated concentrations of (i) glucose (glucotoxicity), (ii) palmitate (lipotoxicity) and (iii) both glucose and palmitate (glucolipotoxicity). Overexpression of a dominant–negative protein kinase B suppressed the anti-apoptotic action of glucagon-like peptide-1 in INS832/13 cells, whereas a constitutively active protein kinase B prevented beta cell apoptosis induced by elevated glucose and palmitate. Glucagon-like peptide-1 enhanced nuclear factor-κB DNA binding activity and stimulated the expression of inhibitor of apoptosis protein-2 and Bcl-2, two anti-apoptotic genes under the control of nuclear factor-κB. Inhibition of nuclear factor-κB by BAY 11-7082 abolished the prevention of glucolipotoxicity by glucagon-like peptide-1. Conclusions/interpretation. The results demonstrate a potent protective effect of glucagon-like peptide-1 on beta cell gluco-, lipo- and glucolipotoxicity. This effect is mediated via protein kinase B activation and possibly its downstream target nuclear factor-κB. [ABSTRACT FROM AUTHOR]

We investigated the relation between lifetime physical activity and bone mineral density (BMD) in South African women using data collected in a case-control study of breast cancer in relation to BMD. Subjects (n = 144) were of black African or mixed ancestral origin, and <60 years of age (mean age 42.6 ± 8.9 years). Cases had newly diagnosed breast cancer (n = 62) and controls were referred for conditions unrelated to BMD or breast cancer (n = 82). Physical activity data consisting of household, occupational and leisure-time activity, and activity for transport, were collected via questionnaire at 4 life stages (epochs), viz. 14–21, 22–34, 35–50, and 50+ years of age. Total energy (MET hrs) and peak strain scores were calculated. Lumbar spine and total proximal femur BMD were measured using dual-energy x-ray absorptiometry. BMD measures were similar between groups, therefore data were combined. BMD measures were unrelated to total lifetime physical activity. However, the major determinants of total proximal femur BMD included age, transport activity including walking and bicycling between the ages of 14 and 21 years, and current weight (adjusted r2 = 0.33, P < 0.0001). The major determinants of lumbar spine BMD included age, household energy expenditure between the ages of 14 and 21 years, and current weight (adjusted r2 = 0.23, P < 0.0001). Total peak bone strain score for activities between 14–21 years of age was also significantly correlated with lumbar spine BMD (r = 0.18, P < 0.05). Intraclass correlation coefficients to assess tracking of activity through epochs 1, 2, and 3 were high for total energy expenditure (0.96; 95%CI: 0.94–0.97), household (0.98; 95%CI: 0.97–0.99) and occupational activity (0.78; 95%CI: 0.71–0.84) and activity for transport (0.92; 95%CI: 0.89–0.94). These data suggest that walking or activities resulting in impact loading at a young age are associated with higher BMD in later years. In addition, our findings suggest tracking of physical activity over time. [ABSTRACT FROM AUTHOR]

Phenotypic change of adult pancreatic islets has been implicated in the development of certain pancreatic cancers and in islet transplant failure. The aim of this study was to characterize intracellular events that mediate changes in adult islet phenotype. Using an in vitro islet-to-duct transformation model, canine islets were induced to undergo phenotypic transformation to duct-like epithelial structures through a two-stage process. Stage one was characterized by widespread islet cell apoptosis associated with the formation of cavitary spaces within the islets. During this stage, c-Jun N-terminal regulated kinase (JNK) and caspase-3 activities were elevated, while extracellular signal-regulated kinase (ERK) and Akt activities were decreased. The second stage of the process was characterized by an inversion in the balance in activity between these signal transduction pathways and by a concomitant decrease in apoptosis. The transformed islets were no longer immunoreactive for islet cell hormones, but expressed the duct epithelial cell marker CK-AE1/AE3. In contrast to islet cells, these duct epithelial cells were highly proliferative. To clarify the role of the identified changes in signal transduction events, we performed additional studies using pharmacological inhibitors of enzyme activity and demonstrated that inhibition of JNK and caspase-3 activity prevented cystic transformation. Our results indicate that the balance in signaling activity between ERK/Akt and JNK/caspase-3 appears to be an important regulator of islet cell death and differentiation.Cell Death and Differentiation (2003) 10, 987-996. doi:10.1038/sj.cdd.4401266 [ABSTRACT FROM AUTHOR]

Objectives: Numerous studies, but not all, have yielded positive associations between adult height and risk of breast cancer. There are few data on black women. We evaluated adult height in relation to breast cancer in data from the Black Women's Health Study, a prospective cohort study of 64,530 African-American women aged 18-69 years at baseline in 1995.Methods: A total of 910 cases of breast cancer were analyzed: 700 prevalent cases reported at baseline and 210 incident cases that occurred during the first 2 years of follow-up. A comparison group of controls frequency-matched on 5-year category of birth year was chosen from among participants who had not developed breast cancer. Odds ratios (OR) were calculated for various categories of adult height compared to a reference category of height less than or equal to 61 inches (155 cm), with control for current age, age at menarche, and years of education.Results: Increased height was associated with an increased risk of breast cancer overall (p trend = 0.001); the OR for the highest category of height, > 69 inches (175 cm), was 1.6 (95% confidence interval 1.1-2.3). The association was stronger among premenopausal women and women who had less than 16 years of education. Results were similar for prevalent and incident cases.Conclusion: The present findings indicate that height is associated with breast cancer risk in African-American women. [ABSTRACT FROM AUTHOR]

The incidence of adenocarcinoma of the pancreas has risen steadily over the past 4 decades. Since pancreatic cancer is diagnosed at an advanced stage, and because of the lack of effective therapies, the prognosis of such patients is extremely poor. Despite advances in our understanding of the molecular biology of pancreatic cancer, the systemic treatment of this disease remains unsatisfactory. Conventional chemotherapy has not produced dramatic improvements in response rates or patient survival. New treatment strategies are clearly needed. This paper reviews emerging therapies for pancreatic carcinoma. A more profound understanding of the molecular biology of cell growth and proliferation, as well as of neoplastic cell transformation, has led to advances in several areas, including the use of somatostatin analogues and antiandrogens as adjuvant therapy; inhibition of tumour growth and metastasis by inhibitors of matrix metalloproteinases and angiogenesis, and by small molecules such as retinoids, which interfere with progression through the cell cycle; immunotherapy with monoclonal antibodies; disruption of intracellular signal transduction with farnesyltransferase inhibitors; and finally gene therapy with specifically designed vaccines. [ABSTRACT FROM AUTHOR]

Background: We undertook the present analyses to determine whether family history of colorectal cancer in a parent or sibling modifies the inverse association of nonsteroidal anti-inflammatory drug (NSAID) use with colorectal cancer risk.Methods: We used data from two case-control studies of colorectal cancer. The hospital-based Case Control Surveillance Study included 1526 patients with primary colorectal cancer, 4192 cancer controls and 6036 noncancer controls. A population-based study conducted in Massachusetts enrolled 1201 incident cases of colorectal cancer and 1201 community controls. Data on NSAID use and risk factors for colorectal cancer were collected by interview.Results: In both studies there was a reduction in the odds ratios among subjects who used NSAIDs regularly continuing into the previous year, regardless of family history. In the Case Control Surveillance data, the odds ratio was 0.4 (95% CI 0.2-0.9) among subjects with a family history and 0.5 (95% CI 0.4-0.7) among subjects without a family history. The comparable odds ratios in the Massachusetts data were 0.5 (95% CI 0.3-0.9) and 0.7 (95% CI 0.6-0.9).Conclusions: These data indicate that regular continuing NSAID use is associated with a reduced risk of colorectal cancer among persons with a family history of the disease, as well as those without such a history. [ABSTRACT FROM AUTHOR]

It is established that obesity is an important risk factor for hypertension, but there is little information on this relationship among highly educated black women. We assessed the relationship of body mass index (weight (kg)/height[SUP2](m)) to prevalent hypertension among US black women who had completed college, and among less educated women as well. The data were collected in 1995 in the Black Women's Health Study: 64530 African-American women aged 21 to 69 years enrolled by completing mailed health questionnaires; 44% of the participants had completed college. We compared the 9394 participants who reported a diagnosis of hypertension treated with a diuretic or antihypertensive drug (cases) with 9259 participants of similar ages who did not have hypertension (controls). Multivariate odds ratios were estimated by logistic regression. The odds ratio for treated hypertension increased with increasing body mass index at every educational level. Among college-educated women, the odds ratio for hypertension was 2.7 for overweight women (index 27.3-32.3) and 4.9 for severely overweight women (index ≥ 32.3), relative to women with a body mass index <22.8. The prevalences of obesity and hypertension were high among the college-educated women, although not as high as among women with fewer years of education. About a quarter of the difference in the prevalence of hypertension across educational levels was explained by the difference in the proportions who were overweight or severely overweight. These results document a high prevalence of obesity and hypertension, and a strong association of obesity with hypertension, among highly educated US black women. [ABSTRACT FROM AUTHOR]

Objectives: Renal cell cancer has been associated with hypertension or with drugs to treat it in several studies. We assessed whether the association is explained by more frequent detection of early renal cell cancer among persons being treated for hypertension.Methods: The data were collected in our Case-Control Surveillance Study, in which patients aged 20 to 69 years were interviewed in hospitals in Baltimore, Boston, New York, and Philadelphia during 1976-1996. We compared 134 incident cases of renal cell cancer who were being treated with drugs for hypertension to 193 untreated cases with respect to the route to diagnosis and the stage.Results: The relative risk estimate for having been diagnosed incidentally during a routine examination or workup for another condition, relative to having been diagnosed because of symptoms of renal cell cancer, was 1.3 (95 percent confidence interval, 0.7-2.5). The estimate for diagnosis at stage I or II relative to stage III or IV was 1.2 (0.7-2.1).Conclusion: In Case-Control Surveillance Study data, the relative risk estimate for renal cancer among users of various classes of antihypertensive drugs is 1.8 or 1.9. The present results suggest that this association can, at most, be explained only partially by the selective diagnosis of renal cell cancer among persons being treated for hypertension. [ABSTRACT FROM AUTHOR]

Rhinophyma, the end stage in the development of rosacea, is characterized by sebaceous hyperplasia, fibrosis, follicular plugging, and telangiectasis. Although it is commonly considered a cosmetic problem, it can also cause gross airway obstruction. Many patients suffer psychic trauma as a result. Basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and sebaceous carcinoma (SC) have been reported previously in association with rhinophyma. It would appear that the incidence of malignancy in rhinophyma is significantly greater than in the skin of normal noses. It is the purpose of this report to discuss and emphasize the need for histologic examination of all the surgically removed tissue in patients with rhinophyma. Early surgical treatment is advocated even in minimal rhinophyma, this can result in gratification for both the patient and the surgeon. Four illustrative cases are presented. [ABSTRACT FROM AUTHOR]

Two cases of malignant fibrous histiocytoma are presented. The clinicopathologic findings are also reported. The disease was of fast growing pattern and the outcome of one of the cases very rapid. The relative literature is reviewed and the histogenesis is emphasized. [ABSTRACT FROM AUTHOR]

Proposes that a Just-In-Time (J-I-T) or Kanban method of Japanese inventory management can improve productivity of the marketing channel. Terms commonly used to describe logistic functions; Concept of physical distribution; Comparison between channel management and physical distribution; Information on J-I-T technique; Description of the inventory control theory; Functions of inventory; Factors of inventory which is commonly associated with customer service.

Partial pancreatic duct obstruction in the hamster leads to the induction of endocrine-cell differentiation and new islet formation. We prepared cytosolic extracts from the partially obstructed pancreas and identified one, which when administered i.p., produced significant increases in the incorporation of tritiated thymidine by ductular and islet cells, as well as a corresponding increase in islet mass. In this study, we evaluate the ability of this extract to reverse streptozotocin diabetes mellitus. Hamsters were treated i. p. twice daily for 7 weeks with either 0.9% NaCl (saline) ( n=10) or a cytosol extract ( n=10) prepared previously from partially obstructed hamster pancreata. All animals in the cytosol group survived vs only 60% of the saline group ( p=0.02). Random blood glucose levels were greater than 22.2 mmol/l in 90% of the saline group vs 40% in the cytosol group ( p<0.05). Pancreatic tissue from the surviving saline animals and from persistently hyperglycaemic cytosol-treated animals, showed intra-cytoplasmic vacuolation of islet cells, a characteristic lesion of sustained hyperglycaemic states. Vacuolation was not observed in normoglycaemic extract treated animals. Islets in hyperglycaemic animals demonstrated a profound decrease or absence of immunoreactive insulin, compared to an abundance of immunoreactive beta cells in cytosol-treated animals that reverted to normoglycaemia. In this group, single cells or nests of cells stained for insulin or glucagon cells were identified in ductal epithelium in association with cells budding from the duct. Morphometric analysis of pancreata in reverted cytosol-treated animals showed a new population of small islets compared with saline controls and an increased islet mass. In summary, streptozotocin diabetes can be reversed by new islet formation induced by local pancreatic growth factors, the exact nature of which remains to be determined. [ABSTRACT FROM AUTHOR]

We have reported previously that cellophane wrapping of the hamster pancreas is a stimulus that leads to the induction of duct epithelial cell proliferation, followed by endocrine cell differentiation and new islet formation. Reg is a candidate gene that has been reported to be expressed in regenerating pancreatic islets, suggesting a role in islet growth. We examined Reg gene expression in the cellophane-wrap model by isolating total RNA from hamster pancreata at various times after wrapping. Northern blot analysis using a rat cDNA Reg probe showed no expression of Reg in control non-wrapped hamster pancreas, whereas a strong signal was detected in control wrapped rat pancreas. Using reverse transcription of RNA followed by polymerase chain reaction (PCR) we amplified, isolated and sequenced a 194 base pair product which showed homology to rat Reg in both control and wrapped hamster pancreas. When the PCR product was used as a probe for Northern blot analysis, no signal was detected in control non-wrapped pancreata. In contrast, a strong signal was detected 1 and 2 days after wrapping, which then returned to basal between 4 and 6 days after wrapping. A similar temporal pattern was observed using in situ hybridization to localize the Reg gene. One- and 2-day wrapped but not control pancreas expressed Reg in acinar cells, but not in islets. In conclusion, (a) Reg expression is low in the control hamster pancreas; (b) in the cellophane-wrap model of islet neogenesis, increased Reg mRNA is found within acinar tissue; (c) Reg gene may thus be involved as an acinar paracrine effector of duct cell proliferation in the initial step of islet neogenesis, but may also participate in the inflammatory response to traumatic stimuli. [ABSTRACT FROM AUTHOR]

The small leucine-rich bone proteoglycans, biglycan and decorin, can be purified by chromatography on hydroxyapatite columns, demonstrating their potential affinities for bone apatite. To determine their effects on in vitro apatite formation and growth, a mixture of the chondroitin-sulfate (CS) bone proteoglycans, or purified fractions of the dermatan sulfate (DS) containing proteoglycans, DS-decorin and DS-biglycan obtained from skin and articular cartilage, respectively, were analyzed in a gelatin gel diffusion system in which apatite formation occurs in the absence of proteins in a 3.5 day period. Low concentrations of the bone CS-proteoglycan mixture and low DS-biglycan concentrations (5–25 μg/ml) increased apatite formation relative to proteoglycan-free controls at 3.5 days. The CS-proteoglycan mixture was less effective at 50 μg/ml than at 10 μg/ml. DS-biglycan was similarly most effective at 5–25 μg/ml. At 5 days, when apatite growth and proliferation were assessed, 10 and 50 μg/ml of both CS-bone proteoglycan and DS-biglycan increased mineral yields. DS-decorin, in contrast, had no significant effect on mineral accumulation at any of these concentrations. In seeded growth experiments, 1 and 10 μg/ml CS-proteoglycan and 10 and 50 μg/ml DS-biglycan were significant effective inhibitors of mineral accretion, whereas DS-decorin showed no tendency to inhibit seeded growth. Using molar extinction coefficients to determine concentrations, the binding of DS-biglycan and DS-decorin to apatite (specific surface 54 m2/g) was determined using a Langmuir adsorption isotherm model. DS-biglycan had a greater affinity for apatite than DS-decorin (0.285 ml/μmol versus 0.0098 ml/μmol). DS-biglycan binding was more specific with fewer binding sites (3.5 μmol/m2 compared with 18.2 μmol/m2 for DS-decorin). Data suggest that of the small proteoglycans, biglycan may play a more significant role than decorin in the regulation of mineralization. [ABSTRACT FROM AUTHOR]

The dimensions of proteoglycan aggregates, aggregated monomers, and nonaggregated monomers, and the proportion of aggregated monomers found in the different zones of bovine rib growth plate have been defined by the electron microscopic monolayer technique. Growth plates were divided into the following 1 mm thick transverse slices; the hypertrophic zone, the lower proliferative zone, the upper proliferative zone, a transitional zone, and epiphyseal cartilage. Proteoglycans prepared by associative extraction followed by equilibrium density gradient centrifugation under associative conditions were examined by electron microscopy. Proteoglycan aggregate size decreased sharply in the lower proliferative and hypertrophic zones, as indicated by decreases in hyaluronate filament length and in the number of monomers per aggregate. Aggregated proteoglycan monomers did not show evidence of proteolytic degradation. Nonaggregated monomers were shorter than aggregated monomers, but their mean length did not decrease in the lower proliferative and hypertrophic zones. However, the proportion of nonaggregated monomers increased in these zones. Thus, before the cartilage matrix mineralized in the lower proliferative zone and as the cartilage matrix began to mineralize in the hypertrophic zone, proteoglycan aggregate size decreased and the proportion of aggregated monomers decreased. These changes in matrix proteoglycans may be one of the events that allow cartilage mineralization. [ABSTRACT FROM AUTHOR]

Well-characterized bovine nasal proteoglycan A1 fraction (aggregate) and proteoglycan D1 fraction (subunit) have been shown to be effective inhibitors of hydroxyapatite (HA) formation in two in vitro test systems: (a) the transformation of amorphous calcium phosphate (ACP) to crystalline HA, and, (b) the direct precipitation of HA from low-concentration calcium phosphate solutions. A1 or D1 in solution slowed the transformation kinetics in system (a) without affecting the time to the onset of conversion. In system (b), A1 or D1 in solution increased the time to the onset of HA formation without affecting the HA formation kinetics. In both test systems A1 was a more effective inhibitor than D1, although the difference was not great. In both systems the inhibitory effect was proportional to the A1 or D1 solution concentration. The action of solutions of low and high molecular weight neutral dextrans on both test systems showed that high molecular weight and/or extended spatial molecular conformation has a much stronger correlation with inhibitory ability than solution viscosity. Proteoglycans have been implicated as playing a role in regulating biological mineralization particularly in the epiphyseal growth plate. Our study suggests that just enzymatic cleavage of aggregate into subunit is not sufficient to allow mineralization to occur, since we find that D1 itself is a potent inhibitor of HA formation. Further degradation and/or removal of D1 appears to be necessary for calcification to take place. [ABSTRACT FROM AUTHOR]

It has been suggested, based on animal experiments and limited human data, that the antihypertensive drug hydralazine might be carcinogenic, and among the sites of concern are the lung and colon. To assess the possible relationship between the use of hydralazine and lung and colorectal cancers in humans, we compared 1006 cases of lung cancer with 3531 hospital control subjects, and 972 cases of colorectal cancer with 3276 controls. Data were collected by interview in hospitals in the United States and Canada. Overall, 1.1% of the lung cancer cases, 1.6% of the colorectal cancer cases, and 1.5% of the controls had used hydralazine. Compared with those who had never used hydralazine, the relative risk estimate of lung cancer for those who first took the drug at least 18 months before hospital admission was 1.1 (95% confidence interval 0.4-2.9). The estimate for use for at least 1 year was 1.4 (0.5-3.8) and for use for at least 5 years the estimate was 0.9 (0.2-4.3). The corresponding relative risk estimates for colorectal cancer were 1.2 (0.5-2.5) for any use, 1.7 (0.8-3.7) for use for at least one year, and 2.4 (0.8-6.9) for five or more years of use. Other antihypertensive treatments and risk factors, including cigarette smoking in the analysis of lung cancer, were taken into account in these estimates. Although the effect of use after long latent intervals could not be evaluated, the results provide no support for the hypothesis that hydralazine use increases the risk of lung cancer. There is also no evidence that hydralazine increases the risk of colorectal cancer, but an effect after extended durations of use cannot be ruled out. [ABSTRACT FROM AUTHOR]

In a case-control study of 1881 women with breast cancer and 1523 controls with benign conditions, 65 cases (3.5%) and 64 controls (4.2%) reported having used a drug that contained rauwolfia, giving a rate ratio estimate of 0.8 (95% confidence interval, 0.5-1.1). Use that ended more than a year previously was negatively associated with breast cancer (rate ratio, 0.5; 95% confidence interval, 0.2-0.9). The risk of breast cancer did not vary significantly according to duration of use. Nor did it vary within strata of varying base-line risk, such as age at first pregnancy. The data suggest that rauwolfia alkaloids do not increase the risk of breast cancer. [ABSTRACT FROM AUTHOR]

Experimental and epidemiologic evidence have suggested that phenacetin use increases the risk of transitional cell cancers of the urinary tract. The drug is no longer marketed but a commonly used metabolite, acetaminophen, has been linked recently to an increased risk of renal cancer. We assessed the relation of acetaminophen use to the risk of transitional cell cancer of the urinary tract and of renal cell cancer with data from a hospital-based study of cancers and medication use conducted from 1976-96 in the eastern United States. We compared 498 cases of transitional cell cancer and 383 cases of renal cell cancer with 8,149 noncancer controls and 6,499 cancer controls and controlled confounding factors with logistic regression. For transitional cell cancer, the relative risk (RR) estimate for regular acetaminophen use that had begun at least a year before admission was 1.1 (95 percent confidence interval [CI] = 0.6-1.9) based on noncancer controls, and 0.9 (CI = 0.5-1.6) based on cancer controls. RR estimates for use that lasted at least five years, and for nonregular use, were also close to 1.0. For renal cell cancer, the corresponding estimates were again close to 1.0. Our results suggest that acetaminophen, as used in present study population, does not influence the risk of transitional cell cancer of the urinary tract or of renal cell cancer. [ABSTRACT FROM AUTHOR]

The relation of induced and spontaneous abortion to the risk of breast cancer is evaluated in a hospital-based case-control interview study conducted in three cities in the United States from 1985 through 1995. Cases were 1,803 women aged 25 to 64 years with newly diagnosed invasive breast cancer; controls were 4,182 women of the same ages admitted for conditions unrelated to reproductive factors. Other breast cancer risk-factors were controlled through multiple logistic regression. The reference for all analyses was women who had never had an abortion, either induced or spontaneous. Among parous women, the relative risk (RR) estimate was 1.1 (95 percent confidence interval [CI] = 0.9-1.5) for induced abortion overall, 1.0 (CI = 0.7-1.4) for abortion before the first birth, and 1.3 (CI = 1.0-1.8) for abortion after at least one birth. Among nulliparous women, the relative risk estimate for induced abortion was 1.3 (CI = 0.9-1.9). There was no trend of increased risk with number of abortions, nor was there consistent evidence of an increased risk in any particular subgroup. Spontaneous abortion was not associated with increased risk of breast cancer, either among nulliparous women or among parous women. These findings provide little support for the hypothesis that induced abortion increases breast cancer risk overall or in particular subgroups. [ABSTRACT FROM AUTHOR]

Copyright of Folia Microbiologica is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Il Nuovo Cimento: A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article presents a study which examines the relation of diuretic use to the risk of invasive breast cancer with the use of the 30-year data from hospital-based case-control surveillance study in the U.S. It says that researchers used data collected from patients to collaborating hospitals in Boston, Massachusetts, New York, Philadelphia, Pennsylvania, and Baltimore, Maryland from 1976 through 2007. Researchers found that diuretics have a major public health impact on breast cancer.

The case of a young pregnant woman who developed an acute gigantomastia during pregnancy is presented, in addition to the unusual finding of bilateral axillary breasts. The condition was treated by simple mastectomy and immediate reconstruction with a subpectoral silicone implant. The literature is reviewed, and this rare combination of pathology is discussed. [ABSTRACT FROM AUTHOR]

The case of a young pregnant woman who developed an acute gigantomastia during pregnancy is presented, in addition to the unusual finding of bilateral axillary breasts. The condition was treated by simple mastectomy and immediate reconstruction with a subpectoral silicone implant. The literature is reviewed, and this rare combination of pathology is discussed. [ABSTRACT FROM AUTHOR]

While Medicare's discriminatory copayments for mental and physical health care are being eliminated, much remains to be done to achieve true parity within Medicare. Medicare needs to recognize and pay for such critical mental health services as case management, psychiatric rehabilitation, and assertive community treatment. Medicare must cover payments for all behavioral health professionals. Also the 190-day lifetime limit on inpatient psychiatric hospital days under Medicare must be removed. We envision a time-in the not too distant future-when Medicare provides a mental health benefit that includes vital community services. [ABSTRACT FROM AUTHOR]

A rare case of squamous cell carcinoma arising in sebaceous cysts is described. This neoplasm most often arises on the scalp of elderly people in long existing cysts. Unroof-ing of the growing tumor leads to the formation of an ulcer with the tumor at its base. Wide excision, with a split thickness skin graft applied on the periosteum is the treatment of choice. [ABSTRACT FROM AUTHOR]

A rare case of necrotizing fascitis of the scalp as a consequence of permanent waving is described. One should be aware of this or other complications in compromised patients. [ABSTRACT FROM AUTHOR]

A method for construction of a dynamic, articulated external fixator for fingers is presented. This fixator allows early mobilization of the operated finger in order to preserve joint and soft tissue mobility. [ABSTRACT FROM AUTHOR]

A system which can be used for injection or infiltration of large volumes of fluid is described. This consists of a syringe which fills automatically from a reservoir through an inlet/outlet valve. [ABSTRACT FROM AUTHOR]

A method of making a fine suction cannula from an intravenous transfusion needle is described. This has been used in general plastic surgery, microsurgery and suturing in the emergency room. [ABSTRACT FROM AUTHOR]