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Biomedical subjects

P Cohen

Publications and source records attributed to P Cohen.

At least 19 recordsLinked to original sources
PubMed2007

Comorbid personality disorder and treatment use in a community sample of youths: a 20-year follow-up.

OBJECTIVE: The impact of comorbid personality disorder (PD) on subsequent treatment and psychotropic drug use was examined in a representative sample of over 700 individuals. METHOD: Axis I disorders and PD were assessed by self- and mother-report at mean ages 13 and 22 years, and by self-report at mean age 33. Mothers reported treatment use by participants before mean age 33; participants reported treatment and psychotropic drug use at mean age 33. RESULTS: Individuals with multiple axis I disorders without PD, axis I disorder-PD comorbidity, and single disorders were compared simultaneously to individuals not diagnosed. Overall, odds of subsequent and past year treatment or psychotropic drug use or both were highest when PD co-occurred with a mood, an anxiety, a disruptive, or a substance use disorder. CONCLUSION: Co-occurring personality pathology may contribute to elevated mental health service use, including use of psychotropic drugs, among young adults in the community.

Adolescent↗
PubMed2006

Antiviral effects on bacteriophages and rotavirus by cranberry juice.

Studies were undertaken to investigate the antiviral effects of comestible juices, especially cranberry juice, on non-related viral species. After exposure of bacteriophage T2 to a commercially available cranberry (Vaccinium macrocarpon) juice cocktail (CJ), virus infectivity titer was no longer detectible. After a 60-min exposure to orange (OJ) and grapefruit juices (GJ), phage infectivity was reduced to 25-35% of control, respectively. Similar data were observed for the bacteriophage T4. CJ inactivation of phage T4 was rapid, dose-dependent, and occurred at either 4 or 23 degrees C. Neither pH nor differences in sugar/carbohydrate levels among the juices may be ascribed to the recognized antiviral effects. Further studies were performed to identify the occurrence of antiviral activity by CJ to a mammalian enteric virus. The treatment of the simian rotavirus SA-11 with a 20% CJ suspension was sufficient to inhibit hemagglutination. Under scanning and transmission electron microscopy, CJ was observed to inhibit the adsorption of phage T4 to its bacterial host cells and prevented the replication of rotavirus in its monkey kidney (MA-104) host cells, respectively. The data suggest, for the first time, a non-specific antiviral effect towards unrelated viral species (viz., bacteriophages T2 and T4 and the simian rotavirus SA-11) by a commercially available cranberry fruit juice drink.

Antiviral Agents↗
PubMed2006

Vasculitis restricted to the lower limbs: a clinical and histopathological study.

BACKGROUND: Rare cases of vasculitis restricted to the lower limbs have been reported, but the characteristics, outcome and response to treatment of this entity are not well known. OBJECTIVE: To describe the clinical, complementary examinations and response to treatment of this rare entity in the first retrospective series, and to compare data with historical pooled cases. METHODS: Retrospective analysis of all biopsy-proven cases observed over a 10-year period in four French tertiary medical units. Diagnosis of vasculitis restricted to the lower limb required the absence of any clinical symptom and complementary test finding, suggesting major extramuscular visceral involvement. RESULTS: 11 patients were included. Vasculitis restricted to the lower limb was associated with disabling muscle pain of the calves. Fever was present in 50% of cases; ankle arthralgia in 50% and skin involvement in 40%. MRI was the cornerstone of the diagnosis, showing hyperintense signal in T2 weight and in T1 weight after gadolinium injection. MRI findings correlated well with clinical outcome and were useful in guiding biopsy. Muscle biopsy was consistent with a polyarteritis nodosa-type vasculitis in only 40% cases, whereas a leucocytoclastic vasculitis was seen for all other cases. Treatment with corticosteroids was effective in all cases, but there were relapses requiring immunosuppressive agents in 54% of cases. CONCLUSION: Vasculitis of the calf muscles must be considered for patients with calf pain and with a biological inflammatory syndrome.

Adult↗
PubMed2006

Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis.

Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer.

Animals↗
PubMed2006

Eukaryotic organisms in Proterozoic oceans.

The geological record of protists begins well before the Ediacaran and Cambrian diversification of animals, but the antiquity of that history, its reliability as a chronicle of evolution and the causal inferences that can be drawn from it remain subjects of debate. Well-preserved protists are known from a relatively small number of Proterozoic formations, but taphonomic considerations suggest that they capture at least broad aspects of early eukaryotic evolution. A modest diversity of problematic, possibly stem group protists occurs in ca 1800-1300 Myr old rocks. 1300-720 Myr fossils document the divergence of major eukaryotic clades, but only with the Ediacaran-Cambrian radiation of animals did diversity increase within most clades with fossilizable members. While taxonomic placement of many Proterozoic eukaryotes may be arguable, the presence of characters used for that placement is not. Focus on character evolution permits inferences about the innovations in cell biology and development that underpin the taxonomic and morphological diversification of eukaryotic organisms.

Biological Evolution↗
PubMed2006

A "field change" of inhibited apoptosis occurs in colorectal mucosa adjacent to colorectal adenocarcinoma.

BACKGROUND: Colorectal cancer is associated with a "field change" of increased proliferation throughout the colonic and rectal mucosa. Both proliferation and apoptosis are disrupted during carcinogenesis. Whether altered apoptosis contributes to this field change of microscopic abnormality is, however, unclear. Bcl-xL is an anti-apoptotic protein that inhibits apoptosis by preventing release of cytochrome c, a recognised pathway to cell death. AIM: To determine whether Bcl-xL inhibition of apoptosis is increased in colorectal mucosa adjacent to colorectal adenocarcinoma over that in normal non-neoplastic colorectal mucosa. PATIENTS: PATIENTS undergoing surgical resection for neoplastic (adenocarcinoma) or non-neoplastic disease of the colorectum (rectal prolapse, diverticular disease or volvulus). METHODS: Formalin-fixed, paraffin-wax-embedded surgical colorectal resection specimens were immunostained for Bcl-xL protein. Labelling indices were determined by counting the proportion of positively stained cells in mucosal crypts. RESULTS: 85 patients were studied. Bcl-xL immunostaining was most marked in the upper third of mucosal crypts. It occurred in a minority of samples from non-neoplastic colorectal mucosa, but was seen in most mucosal samples adjacent to colorectal adenocarcinoma. Significant increases (p<0.001) were observed in Bcl-xL labelling indices in the mucosa at 1 cm (n = 46, median labelling index 31.8%, interquartile range 8.3-43.9%) and at 10 cm (n = 52, median labelling index 22.0%, interquartile range 0.0-36.3%) from colorectal carcinoma, compared with normal, non-neoplastic colorectal mucosa (n = 22, median labelling index 0.0%, interquartile range 0.0-0.0%). CONCLUSIONS: The findings are consistent with a field change of inhibited apoptosis in mucosa adjacent to colorectal carcinoma.

Adenocarcinoma↗
PubMed2006

Comparison of the effects of fasting morning, fasting evening and fed bedtime administration of tenatoprazole on intragastric pH in healthy volunteers: a randomized three-way crossover study.

BACKGROUND: The effectiveness of proton pump inhibitors is influenced by meals and administration time. AIM: To compare the effects on intragastric acidity of times of dosing of tenatoprazole, a novel imidazopyridine-based proton pump inhibitor with a prolonged plasma half-life. METHODS: This randomized three-period crossover study included 12 Helicobacter pylori-negative healthy subjects, who received tenatoprazole 40 mg either fasting at 7.00 AM, fasting at 7.00 PM or fed at 9.30 PM for 7 days, with a 2-week washout between periods. Twenty-four hour intragastric pH was monitored on day 7 of each period. RESULTS: On day 7, median 24-h pH was 4.7, 5.1 and 4.7 after breakfast, dinner and bedtime dosing, respectively (P = 0.11), whereas night-time pH was 4.2, 5.0 and 4.4 (P = 0.13). The mean 24-h percentage of time over pH 4 was 62, 72 and 64 after breakfast, dinner and bedtime dosing, respectively (N.S.), and 54, 68 and 56 during night-time (P = 0.06). Nocturnal acid breakthrough incidence decreased from 100% at baseline to 83%, 55% and 75% after 7.00 AM, 7.00 PM and 9.30 PM dosing, respectively (P = 0.18), and its mean duration dropped from 6.2 to 2.8, 1.0 and 2.2 h, respectively (P < 0.05). CONCLUSION: Seven-day administration of tenatoprazole provides a prolonged duration of acid suppression, especially during the night-time, with little effect of food or time of dosing.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

Effectiveness of written guidelines on the appropriateness of thromboprophylaxis prescriptions for medical patients: a prospective randomized study.

OBJECTIVE: To assess the effectiveness of providing doctors with written thromboprophylaxis prescription aids based on current recommendations. DESIGN: A prospective trial of specific anticoagulant prescription forms: a 1-day survey before and after the intervention in each centre. SETTING: 30 Internal Medicine departments of Assistance Publique-Hôpitaux de Paris. SUBJECTS: All inpatients were included, except those who were either admitted or discharged on the day of the survey, and those receiving curative anticoagulant treatment. INTERVENTIONS: The study included three parts: (i) a 1-day baseline survey; (ii) over the following 3-month period, departments were randomized into two groups: all practitioners in wards allocated to the intervention group were required to systematically use specific anticoagulant prescription forms, whilst doctors in the control group continued prescribing according to their usual practices and (iii) a 1-day postintervention survey. MAIN OUTCOME MEASURE: The proportion of prescriptions in accordance with the recommendations. RESULTS: 1,469 patients were included. The intervention produced a significant reduction in the frequency of over-prescriptions, from 25% to 14% of the patients who did not meet the guideline criteria (adjusted OR: 0.3; 95% CI: 0.1-0.8). Using specific forms did not improve under-prescription of anticoagulants. A little over 60% of the patients who met guideline criteria for thromboprophylaxis were prescribed anticoagulants in both intervention and control wards, either at baseline or after intervention. CONCLUSIONS: Multitargeted interventions using a variety of means and strategies should still be considered to improve prescriptions that may have a significant impact on health expenses and, most importantly, on patients outcomes.

Aged↗
PubMed2006

Peritoneal mucinous cystadenocarcinoma of probable urachal origin: a challenging diagnosis.

This report describes the case of a mucinous cystadenocarcinoma of probable urachal origin that presented with mass effect, precipitating deep venous thrombosis and pulmonary embolism. The patient presented with acute symptoms of leg swelling, pain and dyspnoea, and a vague awareness of lower abdominal distension. Computer tomography showed a cystic mass closely related to the anterior abdominal wall and the superior aspect of the bladder. A 1500 cm(3) cyst adherent to the dome of the urinary bladder was resected on laparotomy. Partial cystectomy was not carried out in the belief that the cyst represented a benign lesion. Subsequent imaging has shown cystic changes in the anterior bladder wall, and the patient has been referred for partial cystectomy.

Adult↗
PubMed2006

Identification of novel genes that co-cluster with estrogen receptor alpha in breast tumor biopsy specimens, using a large-scale real-time reverse transcription-PCR approach.

The estrogen receptor alpha (ERalpha) plays a critical role in the pathogenesis and clinical behavior of breast cancer. To obtain further insights into the molecular basis of estrogen-dependent forms of this malignancy, we used real-time quantitative reverse transcription (RT)-PCR to compare the mRNA expression of 560 selected genes in ERalpha-positive and ERalpha-negative breast tumors. Fifty-one (9.1%) of the 560 genes were significantly upregulated in ERalpha-positive breast tumors compared with ERalpha-negative breast tumors. In addition to well-known ERalpha-induced genes (PGR, TFF1/PS2, BCL2, ERBB4, CCND1, etc.) and genes recently identified by cDNA microarray-based approaches (GATA3, TFF3, MYB, STC2, HPN/HEPSIN, FOXA1, XBP1, SLC39A6/LIV-1, etc.), an appreciable number of novel genes were identified, many of, which were weakly expressed. This validates the use of large-scale real-time RT-PCR as a method complementary to cDNA microarrays for molecular tumor profiling. Most of the new genes identified here encoded secreted proteins (SEMA3B and CLU), growth factors (BDNF, FGF2 and EGF), growth factor receptors (IL6ST, PTPRT, RET, VEGFR1 and FGFR2) or metabolic enzymes (CYP2B6, CA12, ACADSB, NAT1, LRBA, SLC7A2 and SULT2B1). Importantly, we also identified a large number of genes encoding proteins with either pro-apoptotic (PUMA, NOXA and TATP73) or anti-apoptotic properties (BCL2, DNTP73 and TRAILR3). Surprisingly, only a small proportion of the 51 genes identified in breast tumor biopsy specimens were confirmed to be ERalpha-regulated and/or E2-regulated in vitro (cultured cell lines). Therefore, this study identified a limited number of genes and signaling pathways, which better delineate the role of ERalpha in breast cancer. Some of the genes identified here could be useful for diagnosis or for predicting endocrine responsiveness, and could form the basis for novel therapeutic strategies.

Biopsy↗
PubMed2005

Transcutaneous oxygen tension in arms of women with unilateral postmastectomy lymphedema.

Previous reports suggest that skin blood flow is reduced in arms of women with lymphedema due to breast cancer treatment. Since tissue oxygenation depends on blood flow, we sought to determine if transcutaneous oxygen tension (TcPO2) is also reduced and if so, if therapy that reduces edema has a beneficial effect. TcPO2 was measured in fibrotic areas of affected arms and in corresponding sites on non-affected arms of 15 women with unilateral arm lymphedema before and after CDP therapy sequences. Fibrosis was assessed by indentation recovery times (IRT) after applying an indenter-like device to tissue. Volumes and edema percentages were determined from circumferences using automated software calculations. Treatment significantly (p < 0.01) reduced arm edema from 28.6 +/- 22.9% to 18.1 +/- 17.7% (mean +/- SD) and fibrotic segment edema from 42.6 +/- 30.1% to 25.0 +/- 20.4%, and softened fibrotic tissue judged by reductions in IRT (88.7 +/- 60.7 sec vs. 23.1 +/- 38.8 sec, p < 0.001). TcPO2 did not differ between arms initially and did not change with treatment, being 60.1 +/- 8.8 mmHg at the start and 61.8 +/- 9.2 mmHg at the end of treatment. Thus, despite significant amounts of initial edema, TcPO2 was not initially less in affected arms nor was it changed by therapy that improved both edema and fibrosis.

Aged↗
PubMed2004

Short-term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus-related polyarteritis nodosa.

OBJECTIVE: To assess the efficacy and safety of lamivudine, an antiviral agent that strongly inhibits hepatitis B virus (HBV) DNA replication, combined with plasma exchanges after short-term corticosteroids for HBV-related polyartertitis nodosa (PAN). METHODS: Ten patients (8 men, 2 women, mean +/- SD age 50.4 +/- 14.4 years) with previously untreated HBV-related PAN were included in a multicenter, prospective, observational trial. Oral prednisone (1 mg/kg/day) was given for 1 week, then tapered and withdrawn within 1 week. Then, lamivudine (100 mg/day or less in the case of renal insufficiency) was started for a maximum of 6 months. Plasma exchanges were performed simultaneously and scheduled as follows: 3/week for 3 weeks, 2/week for 2 weeks, then 1/week until hepatitis B e antigen (HBeAg) to anti-HBe antibody (HBeAb) seroconversion was obtained or until 2-3 months of clinical recovery was sustained. The primary trial endpoint was clinical recovery from HBV-PAN at 6 months. The secondary endpoint was loss of detectable serum HBeAg and HBV DNA, and HBeAg to HBeAb seroconversion at 9 months. RESULTS: One death, attributed to catheter-related septicemia, was recorded. At 6 months, all 9 survivors had achieved clinical recovery and by 9 months, 6 of 9 (66%) had seroconverted. CONCLUSION: The strategy of short-term steroids followed by lamivudine and plasma exchanges effectively led to recovery from HBV-PAN. Because of its oral administration and good safety profile, lamivudine should henceforth be considered the antiviral agent of choice to treat HBV-related PAN.

Administration, Oral↗
PubMed2004

Modern diagnostics in chronic myeloproliferative diseases (CMPDs).

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.

Blood Cell Count↗
PubMed2004

IL-10 gene therapy is therapeutic for dextran sodium sulfate-induced murine colitis.

The transfer of genes encoding immunoregulatory proteins is a promising new strategy in the treatment of intestinal inflammation. Previous work has demonstrated that daily systemic interleukin (IL)-10 therapy is able to prevent disease onset in animal models of colitis but is not sufficient to treat established disease. This study investigates the therapeutic efficacy of an adenovirus encoding IL-10 (AdvmuIL-10) in the treatment of experimental colitis. Colitis was induced in BALB/c mice by the addition of dextran sodium sulfate to the drinking water for 7 days. A single systemic injection of AdvmuIL-10, empty cassette vector (Adv0), or saline vehicle was administered on day 4 after the onset of colitis. The addition of DSS to the drinking water led to an acute, dose-dependent colitis. A single injection of AdvmuIL-10 led to a marked reduction in both stool markers of inflammation (IL-1beta, IL-6, and TNFRII) and serum IL-6. Furthermore, the histological colitis score was significantly reduced in mice receiving AdvmuIL-10 compared to controls (4.9 +/- 1.1 Vs 9.1 +/- 1.2, respectively; P < 0.05). A single systemic injection of AdvmuIL-10 is therapeutic in mice with established DSS colitis. Gene therapy strategies using adenoviral vectors encoding IL-10 may prove to be a potent therapy for chronic inflammation of the colon such as Crohn's disease.

Adenoviridae↗
PubMed2004

Fibromyalgia: a randomised, controlled trial of a treatment programme based on self management.

OBJECTIVE: To evaluate the efficacy of a treatment programme for patients with fibromyalgia (FM) based on self management, using pool exercises and education. METHODS: Randomised controlled trial with a 6 month follow up to evaluate an outpatient multidisciplinary programme; 164 patients with FM were allocated to an immediate 6 week programme (n = 84) or to a waiting list control group (n = 80). The main outcomes were changes in quality of life, functional consequences, patient satisfaction and pain, using a combination of patient questionnaires and clinical examinations. The questionnaires included the Fibromyalgia Impact Questionnaire (FIQ), Psychological General Well-Being (PGWB) index, regional pain score diagrams, and patient satisfaction measures. RESULTS: 61 participants in the treatment group and 68 controls completed the programme and 6 month follow up examinations. Six months after programme completion, significant improvements in quality of life and functional consequences of FM were seen in the treatment group as compared with the controls and as measured by scores on both the FIQ (total score p = 0.025; fatigue p = 0.003; depression p = 0.031) and PGWB (total score p = 0.032; anxiety p = 0.011; vitality p = 0.013,). All four major areas of patient satisfaction showed greater improvement in the treatment than the control groups; between-group differences were statistically significant for "control of symptoms", "psychosocial factors", and "physical therapy" No change in pain was seen. CONCLUSION: A 6 week self management based programme of pool exercises and education can improve the quality of life of patients with FM and their satisfaction with treatment. These improvements are sustained for at least 6 months after programme completion.

Adult↗
PubMed2003

Prognosis and outcome of 26 patients with systemic necrotizing vasculitis admitted to the intensive care unit.

OBJECTIVES: To investigate presenting features, prognostic factors and outcomes of patients with systemic necrotizing vasculitis (SNV) admitted to the intensive care unit (ICU). METHODS: We retrospectively reviewed the medical records of all 210 SNV patients followed in our university hospital and admitted to the ICU between 1982 and 2001, with respect to clinical features, ICU disease severity scores (APACHE II and SAPS II), the Birmingham vasculitis activity score (BVAS), the five-factors score (FFS) and outcomes. RESULTS: Twenty-six patients (16 men, 10 women) with a mean age of 46.3+/-16.5 yr were included. The reasons for ICU admission were: active SNV, 20 (77%); infection, 3 (12%); others, 3 (12%). SNV was diagnosed in 11 (42%) patients in the ICU. The mean APACHE II and SAPS II scores were significantly higher for patients who died in the ICU (P = 0.01 and P = 0.01 respectively). After a mean follow-up of 31.4+/-29.2 months, the overall mortality rate was 39% (10 patients). Among patients admitted to the ICU with active SNV, BVAS calculated at ICU admission was significantly higher for non-survivors at the end of follow-up (26.9+/-13.0 vs 14.7+/-4.6, P = 0.02). CONCLUSION: The main reason for admitting SNV patients to the ICU was active vasculitis, which was often the first manifestation of SNV and led to its diagnosis. ICU disease severity scores at admission were associated with mortality in the ICU but did not predict long-term outcome, unlike BVAS, which accurately predicted long-term outcome but not ICU prognosis for patients admitted to the ICU with active SNV.

Adolescent↗
PubMed2003

The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel alpha,beta,gamma-ENaC.

The serum- and glucocorticoid-inducible kinase 1 (SGK1) has been identified as a signalling molecule up-regulated by aldosterone, which stimulates the renal epithelial Na(+) channel ENaC. It is therefore thought to participate in the antinatriuretic action of this hormone. More recently, two isoforms, SGK2 and SGK3, have been cloned. The present study was performed to establish whether SGK2 and SGK3 influence ENaC activity similarly to SGK1. Dual-electrode voltage-clamp experiments in Xenopus laevis oocytes expressing alpha,ss,gamma-ENaC with or without SGK1, SGK2 or SGK3 revealed a stimulatory effect of all three kinases on the amiloride-sensitive current (I(Na)). To establish whether the SGK isoforms exert their effects through direct phosphorylation, we replaced the serine at the SGK consensus site of alphaENaC (alpha(S622A)ENaC) by site-directed mutagenesis. alpha(S622A),beta,gamma-ENaC was up-regulated similar to wild-type ENaC, suggesting that SGK isoforms do not act via direct phosphorylation of the transport proteins. In conclusion, SGK2 and SGK3 mimic the function of SGK1 and are likely to participate in the regulation of ENaC activity.

Animals↗