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1.
Microorganisms ; 8(4)2020 Mar 27.
Article in English | MEDLINE | ID: mdl-32230755

ABSTRACT

One-day-old chicks were assigned one of four dietary treatments in a 2 × 2 factorial design in which the main effects were diet (adequate vs. low protein) and the addition of protease (0 vs. 200 g/1000 kg of feed). Chick performance (days 0-14) was recorded and their excreta were analyzed for short chain fatty acids, ammonia, and composition of the microbiota using 16S rRNA gene sequencing. Birds fed the low protein diet had lower body weight gain and poorer overall feed conversion ratio (FCR) (p 0.04); however, these parameters were not affected by the inclusion of protease (p 0.27). Protease inclusion did not affect any particular bacterial genus in the excreta, but it increased the total number of observed OTUs (p = 0.04) and Faith's phylogenetic diversity (p = 0.05). Abundance of Proteus and Acinetobacter were lower in the excreta of chicks fed the low protein diet (p = 0.01). Abundance of Bacteroides was associated with poorer FCR, while Proteus was associated with improved FCR (p 0.009). Although diet had a stronger impact than protease on chick performance, both diet and protease yielded some changes in the intestinal microbiotas of the birds.

2.
BJS Open ; 4(2): 260-267, 2020 04.
Article in English | MEDLINE | ID: mdl-32003132

ABSTRACT

BACKGROUND: Peritoneal mesothelioma (PM) is a rare primary neoplasm of the peritoneum with an increasing incidence worldwide. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promise as a treatment strategy. A national PM multidisciplinary team (national PM MDT) video-conference meeting was established in the UK and Ireland in March 2016, aiming to plan optimal treatment, record outcomes and provide evidence for the benefits of centralization. This article reports on the activities and outcomes of the first 2·5 years. METHODS: Between March 2016 and December 2018, patients with PM, referred to peritoneal malignancy centres in Basingstoke, Birmingham, Manchester and Dublin, were discussed by the national PM MDT via video-conference. The MDT was composed of surgeons, radiologists, specialist nurses and pathologists. Patients were considered for CRS and HIPEC if considered fit for surgery and if radiological imaging suggested that complete surgical cytoreduction could be achieved. Morbidity and mortality following surgery were analysed. Survival analysis following MDT discussion was conducted. RESULTS: A total of 155 patients (M : F ratio 0·96) with a mean(s.d.) age of 57(17) years were discussed. To date, 22 (14·2 per cent) have had CRS and HIPEC; the median Peritoneal Cancer Index for the surgical group was 17·0. Complete cytoreduction was achieved in 19 patients. Clavien-Dindo grade I-II complications occurred in 16 patients; there was no grade III-IV morbidity or 30-day in-hospital mortality. The median follow-up for the whole cohort was 18·7 months, and the 2-year survival rate from time of first review at the national PM MDT was 68·3 per cent. CONCLUSION: The centralized national PM MDT was effective at selecting patients suitable for CRS and HIPEC, reporting a good outcome from patient selection.


ANTECEDENTES: El mesotelioma peritoneal (peritoneal mesothelioma, PM) es una neoplasia primaria del peritoneo muy poco frecuente, con una incidencia creciente en todo el mundo. La cirugía citorreductora (cytoreductive surgery, CRS) con quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC) se ha mostrado prometedora como estrategia de tratamiento. En marzo de 2016, se organizó una reunión por videoconferencia del equipo multidisciplinar nacional de PM (national PM multi-Disciplinary Team, MDT) en el Reino Unido e Irlanda, con el objetivo de planificar un tratamiento óptimo, registrar los resultados y proporcionar evidencia de los beneficios de la centralización. Este manuscrito presenta las actividades y los resultados de los primeros 2,5 años. MÉTODOS: Entre marzo de 2016 y diciembre de 2018, 155 pacientes con PM, remitidos a centros de cirugía oncológica peritoneal en Basingstoke, Good Hope Hospital en Birmingham, Christie Hospital en Manchester y Mater Misericordiae en Dublín, fueron discutidos en el National PM MDT a través de una videoconferencia. El MDT estaba compuesto por cirujanos, radiólogos, enfermeras especializadas y patólogos. Los pacientes fueron considerados para CRS e HIPEC si se determinaba que eran aptos para la cirugía y si las imágenes radiológicas sugerían que se podía lograr una citorreducción quirúrgica completa. Se analizó la morbilidad y mortalidad después de la cirugía. Se realizó un análisis de supervivencia tras la discusión en el MDT. RESULTADOS: En total, se discutieron 155 pacientes (tasa varón/mujer 0,96) con una edad media de 57 ± 17 años. Hasta el momento, 22 (14,2%) habían sido sometidos a CRS y HIPEC y la mediana de PCI en el grupo quirúrgico fue de 17,0. La citorreducción completa se logró en 19 (86,4%), las complicaciones de Clavien-Dindo grado I/II ocurrieron en 16/22, sin morbilidad de grado III/IV, ni mortalidad a los 30 días. La mediana de seguimiento fue de 15,0 meses y la supervivencia a los 2 años desde el momento de la revisión en el National PM MDT fue del 66,7%. CONCLUSIÓN: El National PM MDT centralizado fue eficaz en la selección de pacientes adecuados para CRS e HIPEC, presentando un buen resultado a partir de dicha selección.


Subject(s)
Cytoreduction Surgical Procedures/methods , Mesothelioma/surgery , Patient Care Team , Peritoneal Neoplasms/surgery , Videoconferencing , Adult , Aged , Combined Modality Therapy , Female , Humans , Hyperthermic Intraperitoneal Chemotherapy , Ireland , Male , Mesothelioma/drug therapy , Mesothelioma/mortality , Mesothelioma/pathology , Middle Aged , Patient Selection , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Retrospective Studies , Survival Analysis , Treatment Outcome , United Kingdom
3.
Can Commun Dis Rep ; 43(1): 21-24, 2017 Jan 05.
Article in English | MEDLINE | ID: mdl-29770043

ABSTRACT

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: ​: Pork is a known, although infrequent, source of human Escherichia coli O157:H7 infection. E. coli O157:H7 infections often result in clinically severe illness with serious complications in humans. WHAT IS ADDED BY THIS REPORT?: ​: During July-October 2014, an outbreak of 119 cases of E. coli O157:H7 infections associated with exposure to contaminated pork products occurred in Alberta, Canada. E. coli O157:H7-contaminated pork and pork production environments and mishandling of pork products was identified at all key points in the implicated pork distribution chain. Measures to control the outbreak included product recalls, destruction of pork products, temporary food facility closures, targeted interventions to mitigate improper pork-handling practices, and prosecution of a food facility operator. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: ​: Pork should be considered in public health E. coli O157:H7 investigations and prevention messaging, and pork handling and cooking practices should be carefully assessed during regulatory food facility inspections.

4.
Arch Intern Med ; 151(10): 1954-60, 1991 Oct.
Article in English | MEDLINE | ID: mdl-1929683

ABSTRACT

In a double-blind randomized study, we evaluated the effects of 25 mg vs 50 mg of hydrochlorothiazide in 51 elderly patients (aged 68.9 +/- 7.0 years) with isolated systolic hypertension (blood pressure, 160 to 239 mm Hg systolic and less than 90 mm Hg diastolic). Dose levels could be increased to twice daily to control blood pressure. The reductions in blood pressure (25.4/6.8 mm Hg and 28.9/7.4 mm Hg) and proportion of patients in whom blood pressure was controlled (78% and 89%) were similar in the lower- and higher-dose groups during the titration phase. However, serum potassium level was reduced more in the higher-dosage (0.57 mmol/L) than the lower-dosage (0.17 mmol/L) group. There were no significant changes in blood pressure during a 24-week maintenance phase. No patient required withdrawal from the study because of adverse effects, and cognitive-behavioral function was well preserved. We conclude that hydrochlorothiazide is effective and well tolerated in older patients with isolated systolic hypertension, many of whom may be effectively treated with 25 mg of hydrochlorothiazide once daily.


Subject(s)
Hydrochlorothiazide/administration & dosage , Hypertension/drug therapy , Aged , Double-Blind Method , Drug Administration Schedule , Humans , Hydrochlorothiazide/adverse effects , Hypertension/blood , Male , Middle Aged , Potassium/blood
5.
Endocrinology ; 137(7): 2676-82, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8770886

ABSTRACT

Insulin-like growth factor (IGF)-binding protein (IGFBP) proteases modulate IGF action by cleaving IGFBPs into fragments with lower affinity to IGFs, thereby increasing the levels of free IGFs. We have previously documented that prostate-specific antigen (PSA), a serine protease of the kallikrein family, is an IGFBP-3 protease. In this study, we characterized the potential IGFBP proteolytic activity of nerve growth factor (NGF gamma-subunit), which shares high sequence homology with PSA. [125I]IGFBP-3 was cleaved by NGF (but not other kallikreins) at a 3-fold lower concentration than that of PSA, thus proving NGF to be a more potent IGFBP protease than PSA. NGF-generated, lower mol wt IGFBP-3 fragments, detected by immunoblotting and cross-linking to IGFs, had a lower affinity to IGFs than intact IGFBP-3. Unlike PSA, which cleaves primarily IGFBP-3 and -5, NGF also displayed potent proteolytic activity against IGFBP-4 and -6. These data suggest that NGF may be involved in the growth of cells by more than one mechanism. In addition to binding to its receptors, NGF is capable of cleaving IGFBPs and, thus, enhancing IGF action. This synergistic action between NGF and IGF may have important implications on cell growth, development, and repair in the brain and other tissues.


Subject(s)
Endopeptidases/metabolism , Nerve Growth Factors/metabolism , Protease Inhibitors/pharmacology , Blotting, Western , Glycosylation , Humans , Insulin-Like Growth Factor Binding Protein 3/metabolism , Kallikreins/antagonists & inhibitors , Kallikreins/chemistry , Kallikreins/metabolism , Kinetics , Nerve Growth Factors/chemistry , Peptide Fragments/chemistry , Peptide Fragments/isolation & purification , Prostate-Specific Antigen/chemistry , Prostate-Specific Antigen/metabolism , Recombinant Proteins/metabolism , Sequence Homology, Amino Acid , Substrate Specificity
6.
J Clin Endocrinol Metab ; 83(8): 2843-8, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9709957

ABSTRACT

The insulin-like growth factor (IGF)-binding proteins (IGFBPs) carry IGFs in serum and regulate their activity and bioavailability. The main IGFBP in serum, IGFBP-3, is known to form a 150-kDa complex with IGFs and the acid-labile subunit (ALS). We investigated the binding of IGFBP-3 to additional association proteins in human serum (IGFBP-3 APs). Ligand blots, column chromatography, and affinity cross-linking experiments revealed the specific binding of IGFBP-3 to at least three novel serum proteins. These techniques demonstrated the presence of proteins with molecular masses of 70, 100, and 150 kDa that bind IGFBP-3 with high affinity. Serum ALS migrated separately (at 88 kDa) from the novel IGFBP-3 APs (as evident by Western immunoblot), and bound IGFBP-3 weakly (by reverse ligand blots). We also demonstrated that large amounts of one of the IGFBP-3 APs and small amounts of ALS were coimmunoprecipitated with IGFBP-3 from human serum. Similar to ALS, these IGFBP-3 APs are acid labile and lose their IGFBP-3 binding capacity after exposure to low pH. We conclude that there are several serum proteins in addition to ALS and IGFs that bind IGFBP-3 with high affinity. These IGFBP-3 APs may serve as an additional reservoir of IGFBP-3 or modulate its functions.


Subject(s)
Blood Proteins/metabolism , Insulin-Like Growth Factor Binding Protein 3/blood , Autoradiography , Blood Proteins/analysis , Blood Proteins/chemistry , Blotting, Western , Chromatography , Cross-Linking Reagents , Electrophoresis, Polyacrylamide Gel , Female , Humans , Hydrogen-Ion Concentration , Immunosorbent Techniques , Insulin-Like Growth Factor I/metabolism , Iodine Radioisotopes , Male , Molecular Weight , Pregnancy , Recombinant Proteins/metabolism
7.
J Clin Endocrinol Metab ; 81(3): 1141-6, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8772589

ABSTRACT

We have previously described a case of tumor-associated hypoglycemia secondary to the production of high molecular weight insulin-line growth factor (IGF)-II in a child with congenital neuroblastoma. The child's hypoglycemia resolved with GH therapy and has continued to be well controlled for 1 yr. This represents one of the first cases of nonislet cell tumor hypoglycemia (NICTH) treated successfully with long-term exogenous GH. We now present an in-depth analysis of the IGF axis in this patient, before and after GH treatment. Although IGF-II levels at presentation were in the normal range, they were inappropriate for the patient's low GH state. Furthermore, the percentage of "big" IGF-II was elevated, as was the level of the IGF-IIE peptide, which is normally cleaved in the processing of the mature peptide. On the initial evaluation, GH levels failed to rise in response to hypoglycemia, IGF-I levels were low, IGF binding protein-3 (IGFBP-3) levels were suppressed, and IGFBP-2 levels were elevated. We have shown that baseline IGFBP-3 levels were low by RIA and immunoblotting and have demonstrated that this decrease was not associated with IGFBP protease activity. We have also demonstrated the baseline suppression of the acid labile subunit (ALS) of the 150K ternary complex by a novel immunoblot assay. The ratio of IGFs to IGFBP-3 was dramatically elevated, presumably leading to hypoglycemia. Furthermore, the percentage of serum IGF-I and IGF-II present as part of a binary (50K) complex with IGFBPs was also increased. GH therapy resulted in a normalization of the levels of blood sugars, IGFBP-3, ALS, IGFBP-2, and IGF-I, as well as the IGF/IGFBP-3 ratio. In summary, we have presented evidence that the hypoglycemia in this patient resulted from tumor production of high molecular weight IGF-II, which suppressed GH secretion, leading to the described derangements in the IGF binding proteins. We speculate that as a result of the decreased IGFBP-3 and ALS levels, the IGF population was shifted from the stable 150K complex to lower molecular weight complexes with IGF binding proteins, increasing IGF availability to tissues due to rapid turnover of these low molecular weight complexes. We demonstrated the reversal of the abnormalities in the IGFBP levels with GH treatment, corresponding to the clinical response of euglycemia.


Subject(s)
Growth Hormone/therapeutic use , Hypoglycemia/blood , Neuroblastoma/complications , Somatomedins/metabolism , Adenoma, Islet Cell/complications , Carrier Proteins/blood , Child, Preschool , Endopeptidases/blood , Female , Glycoproteins/blood , Humans , Hypoglycemia/etiology , Insulin-Like Growth Factor Binding Proteins/blood , Neuroblastoma/congenital
8.
Hypertension ; 15(4): 348-60, 1990 Apr.
Article in English | MEDLINE | ID: mdl-2318517

ABSTRACT

We compared the efficacy and adverse effects of antihypertensive drug regimens in 690 men past age 60 with diastolic blood pressure 90-114 mm Hg and systolic blood pressure less than 240 mm Hg. They received either a low (25-50 mg) or high (50-100 mg) dose of hydrochlorothiazide daily. Of 644 patients who completed the hydrochlorothiazide titration, 375 (58.2%) were responders (diastolic blood pressure less than 90 and less than or equal to 5 mm Hg below baseline) and 92.8% of these completed a 6-month maintenance period. Blood pressure was reduced from 157.6/98.5 mm Hg by 18.3/9.5 mm Hg with low dose hydrochlorothiazide and by 20.4/9.6 mm Hg with high dose hydrochlorothiazide; more patients achieved goal blood pressure with the high dose. Whites and blacks responded equally. Serum potassium less than 3.5 mmol/l occurred in 104 of 321 (32.3%) of the high dose versus 62 of 333 (18.6%) of the low dose hydrochlorothiazide patients. The 269 nonresponders to hydrochlorothiazide were randomly assigned in a double-blind study to receive hydralazine, methyldopa, metoprolol, or reserpine in addition to hydrochlorothiazide; 79.2% responded to the addition of the second drug and 87.3% of these completed a 6-month maintenance phase. Overall, there were no significant efficacy differences among the step 2 regimens. We conclude that the lower dose of hydrochlorothiazide was nearly as effective as the higher dose, and the addition of a second drug was effective and generally well tolerated in elderly patients.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Aged , Aging/physiology , Antihypertensive Agents/adverse effects , Blood Pressure/drug effects , Diuretics/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Heart Rate , Humans , Hydrochlorothiazide/administration & dosage , Hydrochlorothiazide/adverse effects , Hydrochlorothiazide/therapeutic use , Hypertension/blood , Hypertension/physiopathology , Male , Middle Aged , Osmolar Concentration , Potassium/blood , Racial Groups
9.
Hypertension ; 15(4): 361-9, 1990 Apr.
Article in English | MEDLINE | ID: mdl-2318518

ABSTRACT

This study was designed to determine whether blood pressure reduction, per se, causes adverse effects on cognitive and behavioral function in elderly hypertensive patients. Men with mild-to-moderate diastolic hypertension who had passed their 60th birthday were entered into the trial. After a placebo washout period, they were assigned in a randomized, double-blind manner to one of two groups receiving hydrochlorothiazide (either 25 mg once or twice daily or 50 mg once or twice daily). Responders entered a 1-year maintenance period. Nonresponders were randomly assigned to double-blind treatment with hydralazine, methyldopa, metoprolol, or reserpine added to the diuretic therapy. During the placebo and treatment periods, patients underwent a battery of psychometric tests designed to assess cognitive function, motor skills, memory, and affect. A separate questionnaire assessed the patient's ability to perform activities of daily living. A subset of patients blindly being treated with placebo received the same battery of tests as a control for practice effect. The results showed that there was similar improvement on the psychometric tests between those patients whose blood pressure was successfully reduced and the placebo-treated control group. Therefore, the practice effect did not obscure a true deterioration in function. There were no substantive differences between the lower and higher doses of diuretic or among the four drugs added to the diuretic, although there were qualitative differences in side effects. We conclude that blood pressure reduction, per se, does not adversely affect cognitive and behavioral function in elderly hypertensive patients and that antihypertensive treatment is safe and effective in these patients.


Subject(s)
Antihypertensive Agents/therapeutic use , Behavior/drug effects , Cognition/drug effects , Hypertension/drug therapy , Activities of Daily Living , Affect/drug effects , Aged , Drug Therapy, Combination , Humans , Hydrochlorothiazide/therapeutic use , Hypertension/physiopathology , Hypertension/psychology , Male , Middle Aged , Psychometrics
10.
Proc Biol Sci ; 243(1308): 187-94, 1991 Mar 22.
Article in English | MEDLINE | ID: mdl-1675797

ABSTRACT

The responses of intestinal tissues to ionizing radiation can be described by comparing irradiated cell populations qualitatively or quantitatively with corresponding controls. This paper describes quantitative data obtained from resin-embedded sections of neutron-irradiated mouse small intestine at different times after treatment. Information is collected by counting cells or structures present per complete circumference. The data are assessed by using standard statistical tests, which show that early mitotic arrest precedes changes in goblet, absorptive, endocrine and stromal cells and a decrease in crypt numbers. The data can also produce ratios of irradiated: control figures for cells or structural elements. These ratios, along with tissue area measurements, can be used to summarize the structural damage as a composite graph and table, including a total figure, known as the Morphological Index. This is used to quantify the temporal response of the wall as a whole and to compare the effects of different qualities of radiation, here X-ray and cyclotron-produced neutron radiations. It is possible that such analysis can be used predictively along with other reference data to identify the treatment, dose and time required to produce observed tissue damage.


Subject(s)
Intestine, Small/radiation effects , Animals , Female , Intestine, Small/pathology , Mice , Models, Biological , Neutrons , Radiation Tolerance , X-Rays
11.
Am J Cardiol ; 78(11): 1236-41, 1996 Dec 01.
Article in English | MEDLINE | ID: mdl-8960581

ABSTRACT

An abnormal plasma lipid and lipoprotein profile is an independent and strong predictor of mortality and morbidity from coronary artery disease (CAD). We report on plasma lipid and lipoprotein profiles with respect to race, age, obesity, blood pressure (BP), smoking, and drinking history in 1,292 male veterans with a diastolic BP of 95 to 109 mm Hg while off antihypertensive medications. Blacks had 24% (p <0.001) lower triglycerides than whites. In contrast, the following parameters were higher in blacks than in whites by the indicated percentages: high-density lipoprotein (HDL) cholesterol, 16% (p <0.001); HDL2 cholesterol, 36% (p <0.001); apolipoprotein (Apo) A1, 8% (p <0.001); HDL/low-density lipoprotein (LDL), 18% (p = 0.018); HDL2/LDL, 36% (p = 0.031); HDL2/HDL3, 21% (p <0.001); and Apo A1/Apo B, 15% (p <0.001). Triglycerides were unchanged up to age 60, but were lower by 24% (p <0.001) in those aged > or = 70. Apo A1 levels were higher (p <0.001), whereas LDL cholesterol was lower (p <0.008) in moderate alcohol consumers versus abstainers. Triglycerides were higher (p <0.001), whereas HDL, HDL2 cholesterol, and Apo A1 were lower (p <0.001) with increasing obesity. Moderate alcohol consumption had a strong favorable effect on HDL, HDL2, and HDL3 cholesterol among subjects of normal weight, but this effect was diminished in obese subjects. Total and LDL cholesterol were higher by 6.4% (p = 0.001) and 9.4% (p <0.003), respectively, whereas HDL cholesterol remained unchanged in those with diastolic BP of 105 to 109 mm Hg versus those with diastolic BP of 95 to 99 mm Hg. We conclude that hypertensive black men have lipid and lipoprotein profiles indicative of less CAD risk than white men. Chronic moderate alcohol consumption correlates with a favorable plasma lipid and lipoprotein profile in normal, but not obese, men. Obesity is associated with an adverse plasma lipid and lipoprotein profile. Thus, race, alcohol intake, and obesity may be important modifiers of CAD in untreated hypertensive men.


Subject(s)
Black People , Hypertension/blood , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , White People , Apolipoprotein A-I/blood , Apolipoproteins B/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Coronary Disease/etiology , Coronary Disease/prevention & control , Humans , Hypertension/complications , Hypertension/ethnology , Male , Regression Analysis , Renin/blood , Risk Factors
12.
J Endocrinol ; 164(2): 215-23, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10657857

ABSTRACT

The IGF axis has been implicated in the pathogenesis of benign prostatic hyperplasia (BPH) via the paracrine action of IGFs and IGF-binding proteins (IGFBPs). In this study, we examined the regulation of cell growth and IGFBP-3 secretion by transforming growth factor-beta (TGF-beta) in prostatic stromal cell (PC-S) cultures from histologically normal tissues and tissues from BPH. PC-S cultures were treated with varying doses of TGF-beta1. Forty-eight hour conditioned media (CM) from these cultures were subjected to Western immunoblotting and ligand blotting for detection and quantification of IGFBPs. IGFBPs-2, -3 and -4 were detected in the CM from normal PC-S cultures. In CM from BPH PC-S, IGFBP-3 levels were 2-fold lower at baseline than in the normal PC-S CM, in addition to the differences in IGFBPs-2 and -5 which we have previously reported. In response to TGF-beta1, a 15-fold increase in the levels of IGFBP-3 was observed in normal PC-S CM, while a mere 2-fold increase was observed in BPH PC-S CM (P<0.001). These findings were confirmed by specific immunoblotting and immunocytochemistry. IGFBP-3 mRNA levels detected by Northern blotting of total RNA extracted from similar cultures showed the induction of IGFBP-3 expression by TGF-beta1 in normal PC-S and its lack of induction in BPH PC-S. Cell growth inhibition in response to TGF-beta1 correlated with the IGFBP-3 concentrations found in CM. Normal PC-S showed a 60% decrease in cell number after 10 days in media with 1 ng/ml TGF-beta1, compared with the untreated control. The decrease in proliferation observed in comparably treated BPH cells was only 20% (P<0.001). In conclusion, BPH PC-S had a reduced IGFBP-3 response to TGF-beta1 and demonstrated decreased TGF-beta1-induced growth inhibition relative to normal PC-S. We hypothesize that in normal PC-S, TGF-beta exerts its anti-proliferative effects by stimulating the production of IGFBP-3, which acts as an inhibitory factor, either by inhibiting IGFs or directly by interacting with cells, and that this process is altered in BPH PC-S.


Subject(s)
Insulin-Like Growth Factor Binding Protein 3/metabolism , Prostatic Hyperplasia/pathology , Transforming Growth Factor beta/pharmacology , Blotting, Western , Cell Division/physiology , Cells, Cultured , Female , Humans , Immunohistochemistry , Male , Prostatic Hyperplasia/metabolism , Stromal Cells/cytology , Stromal Cells/pathology
13.
J Endocrinol ; 152(3): 455-64, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9071967

ABSTRACT

The IGFs are mitogenic agents which are closely linked to regulatory processes in carbohydrate metabolism. Because limited information is available on the occurrence of the IGF system in the pancreatic beta-cell milieu, we evaluated the presence of IGFs, IGF receptors, and IGF-binding proteins (IGFBPs) in the beta-cell lines beta TC3 and HIT T-15. Serum-free conditioned media (SFCM) from beta TC3 cells contained IGF-II at concentrations greater than 100 ng/ml. High (15 kDa) and low (7.5 kDa) molecular weight IGF-II were detected both by column chromatography followed by RIA and by immunoblotting. GH (10-1000 ng/ml) conditioning of beta TC3 cells stimulated IGF-II secretion in a dose-dependent manner. IGF-II mRNA was detected in beta TC3 cells using Northern blots, and also showed a GH-dependent relationship. IGF-II peptide was detected in SFCM from HIT cells, albeit at lower concentrations. To evaluate the presence of IGF receptors in beta-cell lines, affinity cross-linking studies were performed on beta TC3 cells, demonstrating type I IGF receptors which bound iodinated IGF-II with high affinity, iodinated IGF-I with lesser affinity, and had minimal appreciable binding to iodinated insulin. Type II IGF receptors were not detected. SFCM from beta TC3 and HIT cells was subjected to Western ligand blotting, which disclosed the presence of two major IGFBPs of 29 kDa and 24 kDa, characteristic of IGFBP-2 and IGFBP-4. The identity of the specific IGFBPs was confirmed by immunoprecipitation and Northern blotting. Varying the glucose concentration had no significant effect on the levels of IGFBPs, nor did preconditioning with GH, IGF-I, IGF-II, insulin, or glucagon. Levels of both IGFBPs in beta TC3 cell-conditioned media increased in the presence of dexamethasone at concentrations of 10(-6) M or greater. In summary, we present evidence that beta-cell lines comprise an environment for GH and IGF action. We speculate that IGFs, their receptors and binding proteins function as a complex interactive system which regulates beta-cell growth and function.


Subject(s)
Insulin-Like Growth Factor Binding Proteins/analysis , Insulin-Like Growth Factor II/analysis , Islets of Langerhans/chemistry , Receptors, Somatomedin/analysis , Animals , Blotting, Northern , Cell Line , Culture Media, Conditioned/chemistry , Dexamethasone/pharmacology , Dose-Response Relationship, Drug , Glucocorticoids/pharmacology , Growth Hormone/pharmacology , Insulin-Like Growth Factor Binding Protein 2/analysis , Insulin-Like Growth Factor Binding Protein 4/analysis , Insulin-Like Growth Factor II/metabolism , Islets of Langerhans/drug effects , Protein Binding , Receptors, Somatomedin/metabolism , Stimulation, Chemical
14.
Ann Thorac Surg ; 44(5): 550-1, 1987 Nov.
Article in English | MEDLINE | ID: mdl-3675061

ABSTRACT

Anatomical complications of myocardial infarction include ventricular septal defect and mitral regurgitation. Another unusual complication of myocardial infarction is described, and its diagnosis and surgical management are discussed.


Subject(s)
Coronary Disease/etiology , Fistula/etiology , Heart Diseases/etiology , Myocardial Infarction/complications , Coronary Disease/surgery , Coronary Vessels , Fistula/surgery , Heart Diseases/surgery , Heart Ventricles , Humans , Male , Middle Aged
15.
Avian Dis ; 43(4): 798-803, 1999.
Article in English | MEDLINE | ID: mdl-10611999

ABSTRACT

In a flock of 12,000 bobwhite quail (Colinus virginianus) and 7200 chukar partridge (Alectoris chukar), the owner had 100% morbidity and 40%-50% mortality in birds between the ages of 2 and 4 wk. Affected birds were stunted and anorexic and had yellow/green diarrhea. Two- and 4-wk-old birds submitted for necropsy all had slight nasal discharge. Histopathologic examination revealed mild (bobwhite) to severe (chukar) rhinitis. Immunohistochemistry was positive for Chlamydia psittaci in all birds. Chlamydia psittaci organisms were demonstrated histopathologically in hematoxylin and eosin and Gimenez-stained slides. Management sanitation and treatment with chlortetracycline stopped further excessive losses. The owners were also infected. Treatment by their local physician with tetracycline alleviated symptoms.


Subject(s)
Disease Outbreaks/veterinary , Psittacosis/epidemiology , Animals , Birds , Chlamydophila psittaci/isolation & purification , Colinus , Eyelids/pathology , Kentucky/epidemiology , Lung/pathology , Morbidity , Psittacosis/mortality , Psittacosis/therapy
16.
J Matern Fetal Neonatal Med ; 14(5): 324-8, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14986806

ABSTRACT

OBJECTIVE: To determine the utility of sonographic estimated fetal weight (EFW) in diagnosing intrauterine growth restriction (IUGR, birth weight < 10% for gestational age) in patients with chronic hypertension. METHODS: All pregnant patients with hypertension delivered during a 5-year period at three centers were identified retrospectively. Patients with gestational hypertension, pre-eclampsia, diabetes mellitus, fetal anomalies and absence of a sonographic examination within 3 weeks of delivery were excluded. Likelihood ratio (LR) and guidelines established by the Evidence-Based Medicine Working Group were used to determine whether sonographic EFW is a reliable diagnostic test to detect IUGR. RESULTS: At the three centers, there were 264 patients with chronic hypertension (122, 77 and 65 at centers I, II and III, respectively). The incidence of IUGR ranged from 13% to 27% but was similar at the three locations (p = 0.064). The LR (with 95% confidence interval (CI)) of detecting IUGR was 4.4 (95% CI 2.5, 7.7), 2.3 (95% CI 1.4, 3.7) and 6.1 (95% CI 2.7, 13.7) at centers I, II and III, respectively. Based on the proportions of abnormal growth, we required 253 and 71 newborns with fetal growth restriction at centers I and II, respectively, to have narrow confidence intervals around the clinically important LR of 10. The extremely low incidence of IUGR at center III (13%) precluded the estimation of required sample size. CONCLUSION: Use of Evidence-Based Medicine Working Group guidelines indicates that sonographic EFW is slightly to moderately useful in detecting fetal growth restriction in patients with chronic hypertension.


Subject(s)
Fetal Growth Retardation/diagnosis , Hypertension/physiopathology , Pregnancy Complications, Cardiovascular/physiopathology , Chronic Disease , Cohort Studies , Female , Fetal Weight , Humans , Hypertension/complications , Pregnancy , Retrospective Studies
17.
Eval Rev ; 22(6): 751-79, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10345197

ABSTRACT

This study reports on an evaluation of the effects of street lights on crime in several Indianapolis neighborhoods. Crime was measured in terms of calls for police service (CFS). Using a quasiexperimental design, we performed analyses on four multiblock areas, three intersections, and two aggregated address groups. Two control areas were matched to two multiblock areas that received enhanced lighting. Of the nine target areas, six showed evidence of lower CFS volumes after more lighting. We analyzed the mean weekly CFS in the pre- and postinstallation periods. Two lighted areas had a lower mean weekly CFS after installation. The more illuminated target area experienced a greater reduction in average CFS for property and miscellaneous crimes than did the control area.


Subject(s)
Crime/prevention & control , Lighting , Police/statistics & numerical data , Crime/statistics & numerical data , Data Collection , Female , Humans , Incidence , Indiana , Male , Reference Values , Risk Assessment , Statistics as Topic , Surveys and Questionnaires
18.
J AHIMA ; 70(2): 30-7; quiz 39-40, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10344961

ABSTRACT

The continued evolution of the CPR offers numerous career opportunities for HIM professionals. But a knowledge and understanding of the fundamental concepts is critical for those who would take advantage of these opportunities. The authors offer an overview of the differences and interaction between the CPR component parts, the basic clinical and business functions they support, and the technology used to implement the CPR.


Subject(s)
Computer Systems , Medical Records Systems, Computerized , Systems Integration , Databases, Factual , Education, Continuing , Medical Records Systems, Computerized/classification , Programming Languages , United States
19.
Ann Intern Med ; 133(7): 563, 2000 Oct 03.
Article in English | MEDLINE | ID: mdl-11015178
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