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Biomedical subjects

D Shapiro

Publications and source records attributed to D Shapiro.

At least 19 recordsLinked to original sources
PubMed2007

Clinical Trial of the Pan-Caspase Inhibitor, IDN-6556, in Human Liver Preservation Injury.

Cold ischemia/warm reperfusion (CI/WR) injury remains a problem in liver transplantation. The aim of the current study was to assess the utility of the pan-caspase inhibitor IDN-6556 on CI/WR injury during human liver transplantation. This report is a post hoc analysis of a Phase II, multi-center, randomized, placebo-controlled, double-blinded, parallel group study. Subjects were assigned to four treatment groups: Group 1 (Organ storage/flush: Placebo-Recipient: Placebo); Group 2 (Organ storage/flush: 15 microg/mL-Recipient: Placebo); Group 3 (Organ storage/flush: 5 microg/mL-Recipient: 0.5 mg/kg); and Group 4 (Organ storage/flush: 15 microg/mL-Recipient: 0.5 mg/kg). Liver cell apoptosis was assessed by serum concentrations of the apoptosis-associated CK18Asp396 ('M30') neo-epitope, TUNEL assay and caspase 3/7 immunohistochemistry. Liver injury was assessed by serum AST/ALT determinations. Serum markers of liver cell apoptosis were reduced in all groups receiving drug as compared to placebo. However, TUNEL, caspase 3/7 positive cells and serum AST/ALT levels were only consistently reduced in Group 2 (drug exposed to organ only). This reduction in serum transaminases was significant and observed across the study. In conclusion, IDN-6556 when administered in cold storage and flush solutions during liver transplantation offers local therapeutic protection against CI/WR-mediated apoptosis and injury. However, larger studies are required to confirm these observations.

Adult↗
PubMed2005

Damped and thermal motion of laser-aligned hydrated macromolecule beams for diffraction.

We consider a monodispersed Rayleigh droplet beam of water droplets doped with proteins. An intense infrared laser is used to align these droplets. The arrangement has been proposed for electron- and x-ray-diffraction studies of proteins which are difficult to crystallize. This paper considers the effect of thermal fluctuations on the angular spread of alignment in thermal equilibrium, and relaxation phenomena, particularly the damping of oscillations excited as the molecules enter the field. The possibility of adiabatic alignment is also considered. We find that damping times in a high-pressure gas cell as used in x-ray-diffraction experiments are short compared with the time taken for molecules to traverse the beam and that a suitably shaped field might be used for electron-diffraction experiments in vacuum to provide adiabatic alignment, thus obviating the need for a damping gas cell.

Chemistry, Physical↗
PubMed2004

Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease.

BACKGROUND: Azathioprine is a useful agent in the management of inflammatory bowel disease. Its use is limited by its side-effect profile. Marrow toxicity occurs in approximately 3.2% of patients and is known to be associated with diminished thiopurine methyltransferase enzyme activity resulting from genetic polymorphisms. AIM: To evaluate the cost-effectiveness of screening for thiopurine methyltransferase gene polymorphisms prior to initiation of azathioprine therapy. METHODS: Analysis of the literature was undertaken to calculate the expected frequency of leucopenia and its relationship with thiopurine methyltransferase polymorphisms in a model of theoretical inflammatory bowel disease patients. Decision analysis was then applied to assess the cost of a pre-treatment genotyping strategy, taking account of direct costs and cost per life-year saved. RESULTS: In 1000 inflammatory bowel disease patients treated with azathioprine, 32 will develop myelosuppression and one will die because of this. Of those who develop myelosuppression during azathioprine therapy, 32% are attributable to lower thiopurine methyltransferase activity. Pre-treatment genotyping costs pound 347 per life-year saved for a 30 year old and pound 817 per life-year saved for a 60 year old. This compares favourably with other health care technologies. CONCLUSION: The use of pre-treatment screening for thiopurine methyltransferase polymorphisms in inflammatory bowel disease patients commencing azathioprine therapy represents good value for money.

Adult↗
PubMed2003

Exposure to the 'SIDA dans la Cité' AIDS prevention television series in Côte' d'Ivoire, sexual risk behaviour and condom use.

This study assesses factors associated with viewing of 'SIDA dans la Cite', a weekly television soap opera on AIDS in Côte d'Ivoire, and the relationship between 'SIDA dans la Cite' viewing, sexual risk behaviour and condom use. The study uses across-sectional survey of 2150 respondents aged 15-49 in three regions. Logistic regression analysis was used to assess the effect of'SIDA dans la Cite' exposure on condom use. The results show that 65% of the sample had seen at least one 'SIDA dans la Cite' episode. Among viewers, 27% of males and 41% of females had seen ten or more episodes. Persons who had risky sexual partners were particularly likely to watch the programme. Women who had seen ten or more episodes were 1.4 times more likely than non-viewers to have used a condom in last sex. Men who had seen ten or more episodes were 2. 7 times more likely to have used a condom. We conclude that television soap operas on AIDS, such as 'SIDA dans la Cite',can be an important tool for promoting condom use. The programme was most appealing to viewers who engaged in risky behaviour, who are the core transmitters of the virus. HIV prevention programmes that provide continuous information, through multiple media channels or through series of broadcasts, are likely to have the greatest impact on condom use.

Adolescent↗
PubMed2001

Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib.

BACKGROUND: In comparing aspirin, nonselective nonsteroidal antiinflammatory agents (NSAIDs), and cyclooxygenase (COX)-2 inhibitors, variation in platelet inhibitory effects exists that may be associated with differential risks of cardiovascular (CV) thrombotic events. Among the randomized, controlled trials with the COX-2 inhibitor rofecoxib, one study demonstrated a significant difference between rofecoxib and its NSAID comparator (naproxen) in the risk of CV thrombotic events. A combined analysis of individual patient data was undertaken to determine whether there was an excess of CV thrombotic events in patients treated with rofecoxib compared with those treated with placebo or nonselective NSAIDs. METHODS AND RESULTS: CV thrombotic events were assessed across 23 phase IIb to V rofecoxib studies. Comparisons were made between patients taking rofecoxib and those taking either placebo, naproxen (an NSAID with near-complete inhibition of platelet function throughout its dosing interval), or another nonselective NSAIDs used in the development program (diclofenac, ibuprofen, and nabumetone). The major outcome measure was the combined end point used by the Antiplatelet Trialists' Collaboration, which includes CV, hemorrhagic, and unknown deaths; nonfatal myocardial infarctions; and nonfatal strokes. More than 28 000 patients, representing >14 000 patient-years at risk, were analyzed. The relative risk for an end point was 0.84 (95% CI: 0.51, 1.38) when comparing rofecoxib with placebo; 0.79 (95% CI: 0.40, 1.55) when comparing rofecoxib with non-naproxen NSAIDs; and 1.69 (95% CI: 1.07, 2.69) when comparing rofecoxib with naproxen. CONCLUSIONS: This analysis provides no evidence for an excess of CV events for rofecoxib relative to either placebo or the non-naproxen NSAIDs that were studied. Differences observed between rofecoxib and naproxen are likely the result of the antiplatelet effects of the latter agent.

Aged↗
PubMed2001

Facial and autonomic activity in depression: social context differences during imagery.

Previous research indicates that depressed patients show reduced facial expression as well as a lack of social context differences in frowning in response to sad imagery. The present study examined social context differences in facial electromyogram (EMG), self-reported emotion, skin conductance level and heart rate in 21 depressed and 22 non-depressed women assessed by the Beck Depression Inventory. Subjects were asked to imagine happy and sad situations both with and without visualizing other people. Depressed subjects showed a lack of social context differences in EMG-brow activity during sad imagery while heart rate was increased during sad-social compared to sad-solitary imagery. In contrast, non-depressed subjects showed increased EMG-brow activity during sad-social compared to sad-solitary imagery but no social context differences in heart rate. EMG-cheek activity and heart rate were increased during happy-social compared to happy-solitary imagery in depressed and non-depressed subjects. Skin conductance level was reduced in depressed compared to non-depressed subjects during baseline but failed to respond to imagery. Social context differences in heart rate and a lack thereof of frowning during sad imagery may indicate an altered psychosocial functioning in depression.

Adult↗
PubMed2001

Hormone profiles in young adults with epilepsy treated with sodium valproate or lamotrigine monotherapy.

PURPOSE: Treatment with sodium valproate (VPA) may be associated with polycystic ovarian syndrome (PCOS) in some women with epilepsy. By comparing hormone profiles in young adults taking VPA or lamotrigine (LTG) as monotherapy, this study aimed to explore whether a pharmacologic effect of VPA could be responsible for this observation. METHODS: Hormone profiles in men and women taking VPA (n = 40) or LTG (n = 36) monotherapy for epilepsy were compared. None of the women were receiving hormonal contraception or replacement. Patients gave details of seizure type and frequency, menstrual cycle, and medical and drug history. Body mass index was calculated, and fasting insulin, glucose, cholesterol, triglycerides (TG), high- and low-density lipoproteins, testosterone, dihydroepiandosterone (DHEA), androstenedione, sex hormone-binding globulin (SHBG), free androgen index (FAI), luteinising hormone (LH), follicle-stimulating hormone (FSH), and antiepileptic drug (AED) concentrations were measured. RESULTS: There were no differences between treatment groups for both sexes in age and seizure control. Only four obese VPA-treated women were hyperinsulinaemic (p = 0.05); three with abnormal menstrual cycles; one with raised testosterone. Testosterone (p = 0.02), FAI (p = 0.03), and TG (p = 0.02) levels were higher, however, in women taking the drug. Obese patients of both sexes (p = 0.01) and VPA-treated men (p = 0.03) had higher insulin concentrations. CONCLUSIONS: VPA therapy may be associated with subclinical elevation in fasting insulin levels. Testosterone and TG levels were higher in VPA-treated women compared with the levels in those taking LTG. However, only a minority of obese females exhibited biochemical characteristics suggestive of PCOS. Biochemical screening may allow women at risk of developing PCOS to avoid VPA.

Adult↗
PubMed2001

Striking a chord: moods, blood pressure, and heart rate in everyday life.

The objective of this study was to assess the relation between the intensity of single moods and of mood combinations on blood pressure (BP) and heart rate (HR). The subjects were 203 healthy registered nurses, all women, who were studied on two work and two off days. Ambulatory BP and HR were recorded every 20 min. On each occasion subjects rated their moods on a 5-point scale. Graded increases in BP and HR were shown with higher ratings of negative moods and decreases for a mood related to energy level. Little change was observed for a positive mood. These effects depended on concurrent changes in other moods. A positive mood countered the effects of a negative mood, whereas two negative moods resulted in unique patterns of BP and HR. The energy level mood moderated the cardiovascular effects of positive and negative moods. Ambulatory methods provide a way of probing into the nature and consequences of everyday emotional experiences.

Adult↗
PubMed2000

Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group.

BACKGROUND: Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis. METHODS: We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers). RESULTS: Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups. CONCLUSIONS: In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.

Adult↗
PubMed2000

Reduced facial expression and social context in major depression: discrepancies between facial muscle activity and self-reported emotion.

The expression of emotion is determined by emotion and the presence and absence of others, i.e. social context. The present study examined social context differences in facial muscle activity and self-reported emotion of 11 major depressed and 11 non-depressed patients. Subjects were asked to imagine happy and sad situations with and without visualizing other people. Facial muscle activity over the brow and cheek region was reduced in depressed compared to non-depressed patients during happy and sad imagery whereas self-reported emotion showed no group differences. In both subject groups, happy imagery induced increased smiling and self-reported happiness whereas sad imagery induced increased frowning and self-reported sadness. Smiling and self-reported happiness were increased during happy-social compared to happy-solitary imagery in both groups. In contrast, frowning showed a lack of social context differences, although self-reported sadness was increased during sad-social vs. sad-solitary imagery in both groups. Reduced facial muscle activity in depression may indicate psychomotor retardation whereas the lack of social context differences in frowning may suggest social disengagement and an inhibition of sad facial expression in the presence of others.

Adult↗
PubMed2000

Autonomic reactivity of panic patients during a CO2 inhalation procedure.

The objectives of this study were to compare continuous subjective and physiological responses of panic disorder patients and normal controls during 5% CO2 inhalation. Psychophysiological responses of panic disorder patients (n = 42) and controls (n = 25) were monitored during baseline (20 min), 5% CO2 inhalation (20 min), and recovery (20 min). The data were compared at baseline and over periods of the experiment using analysis of variance. A subgroup of patients who experienced panic attacks during the CO2 inhalation (n = 12) were significantly different from the other subjects on baseline heart rate and on variability of systolic and diastolic blood pressure, skin conductance, and breathing variability (length and number of breathing pauses and length of breathing cycle variability). Inspection of the data showed that elevation in blood pressure and breathholding were present during some of the panic attacks, suggesting that some attacks may represent a complex psychophysiological response with elements of a "freezing" reaction, well described in animal experiments, which can quickly shift to a "fight/flight" reaction that is usually characterized by an increase in heart and breathing rate. However, some patients had only minimal changes in breathing and others had minimal psychophysiological changes during the time they indicated that they had a panic attack. Panic attacks are not homogeneous and may be characterized by a variety of physiological and cognitive responses. This may indicate that biological mechanisms of panic include abnormality in many functionally connected areas of the brain responsible for complex psychophysiological reactions to multiple threatening situations.

Administration, Inhalation↗
PubMed2000

Preservation of fertility and ovarian function and minimizing gonadotoxicity in young women with systemic lupus erythematosus treated by chemotherapy.

BACKGROUND: Premature ovarian failure (POF) is a common long-term consequence of chemotherapy. Whereas the cytotoxic-induced damage is reversible in other tissues of rapidly dividing cells such as bone marrow, gastrointestinal tract and thymus, it appears to be progressive and irreversible in the ovary, where the number of germ cells is limited, fixed since the fetal life, and cannot be regenerated. The gonadal toxicity of cyclophosphamide is well known. In patients with lupus nephritis, premature ovarian failure (POF) was reported in half of all treated women after cyclophosphamide pulse therapy, affecting 100% of those older than 30 y, about 50% of the patients between the ages of 20-30y and only 13% of the patients younger than 20y of age. Following our preliminary encouraging experience in women with lymphoma, whereby the temporary induction of a prepubertal hormonal milieu, during chemotherapy, has significantly decreased the risk of POF, we have administered a monthly injection of gonadotropin-releasing hormone agonistic analogue (GnRH-a) to eight young women in parallel to alkylating agent chemotherapy. MATERIALS AND METHODS: A monthly intramuscular depot injection of 3.75 mg D-TRP6-GnRH-a (Decapeptyl C.R.) was administered after informed consent to eight women with autoimmune, severe connective tissue diseases (seven SLE patients and one woman with nephrotic syndrome) in parallel to chemotherapy, for up to six months. The institutional committee for human experimentation approved the protocol. The concentrations of FSH, LH, progesterone, and 17-beta-estradiol (E2) were measured before, during and after the GnRH-a/chemotherapy treatment. A transvaginal (or transabdominal) sonography (TVS) was performed on each patient before and after treatment. These eight treated patients (study group) were compared to a group of nine women similarly treated by cyclophosphamide pulses (CPT) or chlorambucil for SLE/connective tissue disease but were not referred for the GnRH-a adjuvant treatment. RESULTS: Whereas none of the eight women receiving GnRH-a in parallel to alkylating agent chemotherapy (cyclophosphamide (7) or chlorambucil (1)) suffered POF and hypergonadotropic amenorrhea, five of the nine ( > 50%) patients treated by alkylating agents (cyclophosphamide (8) or chlorambucil (1)) experienced POF. Whereas two of these five women were 35 y old, the other three were < or = 23 y old at the time of the chemotherapeutic insult. CONCLUSIONS: Our present results, extrapolating this encouraging experience from hematological malignant diseases to severe connective tissue diseases, such as SLE associated nephropathy or others, suggests that the beneficial effect of GnRH-a co-treatment may be exploited towards preservation of future fertility and ovarian function in every young woman of reproductive age, exposed to alkylating agents, such as cyclophosphamide and chlorambucil.

Adult↗
PubMed1999

Diagnostic categories of dental anxiety: a population-based study.

This study aimed to use a population-based sample to assess the psychological validity of the Seattle system for diagnosing dentally anxious individuals. This system consists of four diagnostic types in which such individuals are categorized according to the main source of their fear regarding dental treatment. Subjects were 1420 randomly selected adults aged 18 years and over who took part in a two-stage mail survey. The questionnaires contained measures of dental anxiety and standardized measures of general anxiety and fearfulness. Allocation to the Seattle categories was based on responses to four diagnostic items. Overall, 16.4% of the sample were dentally anxious. Their distribution across the four Seattle types was as follows: type I (simple conditioned phobia)--49.6%; type II (fear of catastrophe)--7.8%; type III (generalized anxiety)--19.4% and type IV (distrust of dentists)--9.9%. The remaining 13.3% could not be categorized. Judging by their scores on measures of dental anxiety, these subjects were borderline cases. Scores on the measures of anxiety and fearfulness indicated that the diagnostic system was valid and identified sub-groups of the dentally anxious population which were internally consistent. However, all subjects indicated extreme fear of dental treatment and were broadly similar in terms of their cognitive and behavioral responses to dental care. Of particular interest was the distribution of diagnoses according to age. Younger subjects were more likely to be categorized as type I, while older subjects were more likely to be categorized as type III. Overall, the results indicate that dental anxiety is a complex fear with a number of components.

Adolescent↗
PubMed1999

Nicotine reduces the frequency of anger reports in smokers and nonsmokers with high but not low hostility: an ambulatory study.

Two studies were conducted to determine the anger-attenuating effects of nicotine as a function of trait hostility. The 1st study examined the effects of nicotine on diary ratings of anger during a 24-hr period in a natural setting in 30 smokers and 30 nonsmokers. Participants took part in 2 monitoring sessions involving the administration of a nicotine patch and a placebo patch. Participants were categorized as high or low on trait hostility on the basis of their scores on the Cook-Medley Hostility scale. Administration of the nicotine patch, compared with the placebo patch, resulted in a significant reduction in diary reports of anger from 24% to 13% in high-hostile participants. In low-hostile participants, nicotine had no effect on reports of anger during the day. The anger-palliative effects of nicotine were greatest among participants more frequently reporting anger on the placebo-patch day. These effects were independent of smoking status and gender. The 2nd study, which was restricted to high-hostile smokers (n = 19) and nonsmokers (n = 23), found that, compared with a placebo patch, administration of nicotine resulted in significant reductions in reports of anger in smokers and nonsmokers. The results of these 2 studies clearly link nicotine to reduced reports of anger in high-hostile individuals.

Administration, Cutaneous↗
PubMed1999

Bone density and antiepileptic drugs: a case-controlled study.

This case-controlled study explored the relationship between bone mineral density (BMD) and long-term treatment with antiepileptic drugs (AEDs) in older adults with epilepsy. Seventy-eight patients (47 post-menopausal females, 31 males, aged 47-76 years) with epilepsy participated in the study. Each had only ever received treatment with either enzyme-inducing (n = 52) or non-inducing (n = 26) AEDs. Individuals were matched for age, sex, height and weight with a drug-naive control. All patients underwent bone densitometry at the lumbar spine and femoral neck and had blood sampling and urine collected for a range of bone markers. Male patients had lower BMD than controls at the lumbar spine (P < 0.01) and neck of the femur (P < 0.005). Female patients had significantly reduced bone density at the femoral neck (P < 0.05) only. AED usage was independently associated with an overall reduction in bone density at femoral sites and contributed to just over 5% of the variance at the femoral neck. Duration of treatment and type of AED were not independent factors for reduction in BMD. This case-controlled study supports the hypothesis that long-term AED therapy is an independent risk factor for reduced BMD in epileptic patients. Adults receiving treatment for epilepsy are at higher risk of osteoporosis and should be offered bone densitometry.

Adult↗