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Biomedical subjects

H Shapiro

Publications and source records attributed to H Shapiro.

At least 19 recordsLinked to original sources

Duration and distance of exposure are important predictors of transmission among community contacts of Ontario SARS cases.

We report attack rates and contact-related predictors among community contacts of severe acute respiratory syndrome (SARS) cases from the 2003 Toronto-area outbreak. Community contact data was extracted from public health records for single, well-defined exposures to a SARS case. In total, 8662 community-acquired exposures resulted in 61 probable cases; a crude attack rate of 0.70% [95% confidence interval (CI) 0.54-0.90]. Persons aged 55-69 years were at higher risk of acquiring SARS (1.14%) than those either younger (0.60%) or older (0.70%). In multivariable analysis exposures for at least 30 min at a distance of <or=1 m increased the likelihood of becoming a SARS case 20.4-fold (95% CI 11.8-35.1). Risk related to duration of illness in the source case at time of exposure was greatest for illness duration of 7-10 days (rate ratio 3.4, 95% CI 1.9-6.1). Longer and closer proximity exposures incurred the highest rate of disease. Separate measures of time and distance from source cases should be added to minimum datasets for the assessment of interventions for SARS and other emerging diseases.

Adolescent↗

Detecting antibodies with similar reactivity patterns in the HLDA8 blind panel of flow cytometry data.

The blind panel collected for the 8th Human Leucocyte Differentiation Antigens Workshop (HLDA8; ) included 49 antibodies of known CD specificities and 76 antibodies of unknown specificity. We have identified groups of antibodies showing similar patterns of reactivity that need to be investigated by biochemical methods to evaluate whether the antibodies within these groups are reacting with the same molecule. Our approach to data analysis was based on the work of Salganik et al. (in press) [Salganik, M.P., Milford E.L., Hardie D.L., Shaw, S., Wand, M.P., in press. Classifying antibodies using flow cytometry data: class prediction and class discovery. Biometrical Journal].

Antibodies↗

Fluorouracil induces apoptosis and surface molecule modulation of peripheral blood leukocytes.

Little is known about the direct effect of chemotherapy on normal peripheral blood leukocytes (PBL) or its contribution to leukopenia. We examined 5'-fluorouracil's (5FU) effect on PBL apoptosis and adhesion molecules' expression in a single-drug solid-tumor model. Possible apoptosis mediators were examined. The study included 32 colorectal cancer patients; apoptosis was determined by annexin-V binding and light-scatter morphology before and after drug infusion. CD18, CD11a, CD11b, and CD63 membranal levels were assayed by flow cytometry. Apoptosis was increased post-5FU administration in neutrophils (PMN), monocytes and lymphocytes (P < 0.05). Levels of Fas receptor and activated caspase 3 did not vary indicating that the process was not mediated by caspase 3 in the timeframe studied. Reduced CD63 on monocytes and decreased CD18 expression on PMN and non-apoptotic monocytes were observed (P < or = 0.05). CD11a,b expression did not vary. Decreased CD18 and CD63 levels were demonstrated in apoptotic and non-apoptotic PBL implying a more direct association with the drug itself.

Antigens, CD↗

A novel treatment for constipation-predominant irritable bowel syndrome using Padma Lax, a Tibetan herbal formula.

BACKGROUND AND AIMS: Padma Lax, a complex Tibetan herbal formula for constipation was evaluated for safety and effectiveness in treating constipation-predominant irritable bowel syndrome in a 3-month double-blind randomised pilot study. METHODS: Patients were recruited from Hadassah Hospital's Gastroenterology clinic, using the Rome I Criteria for irritable bowel syndrome, and the international consensus criteria for constipation. Symptom severity was evaluated monthly by patients and gastroenterologist, using categorical and numerical rating scales. A patient diary recorded daily stool habit and trial medication. RESULTS: In 61 patients, (34 Padma Lax, 27 placebo), significant improvement was demonstrated after 3 months in the Padma Lax group compared to placebo in constipation, severity of abdominal pain, and its effect on daily activities, incomplete evacuation, abdominal distension and flatus/flatulence. A global assessment indicated that significantly more Padma Lax patients, compared to placebo, rated the current treatment superior to previous therapies tried for irritable bowel. Laboratory parameters displayed no clinically significant changes. Side effects, primarily loose stools in 7 Padma Lax patients responded well to lowering treatment dosage from 2 to 1 capsule/day. CONCLUSIONS: Padma Lax is a safe and effective treatment for constipation-predominant irritable bowel syndrome and may offer an alternative to the current multi drug approach.

Colonic Diseases, Functional↗

The prognostic value of DNA ploidy in small renal cell carcinoma.

The objective was to study the prognostic value of Deoxyribonucleic Acid (DNA) ploidy status in small renal cell carcinomas (RCC). The nuclear DNA content of renal cell carcinoma tissues from patients who underwent radical or partial nephrectomy has been analyzed by flow cytometry. The results of the DNA ploidy have been correlated to the size of tumors and disease progression. Of the 50 patients with RCC studied, 8 (16%) progressed. Tumors with non-diploid DNA patterns were found in 24 (48%) of the 50 patients and in 4 of the 8 patients who progressed. Overall the median tumor size in our series was 50 mm. A tumor diameter of 50 mm or less was measured in 26 patients (group I) and above 50 mm in 24 (group II). Non-diploid DNA patterns were found in 11 (42.3%) and 13 (54.2%) patients in groups I and II, respectively. This difference between the groups was not significant. Only one patient in group I (3.8%) developed metastatic disease and died 72 months after the operation. In group II, 7 patients (29.2%) presented tumor progression and 5 died of metastatic disease. The survival probability in group I was 95% at 5 and 8 years (95% CI 70% to 99%) and for group II 94% at 5 years (95% CI 67%-99%) and 67% at 8 years (95% CI 39%-83%). DNA ploidy is an inaccurate predictor of tumor behavior in patients with RCC, even in small tumors. Tumor size is a more significant predictor of outcome.

Adult↗

Preliminary observations of transtracheal augmented ventilation for chronic severe respiratory disease.

OBJECTIVE: Evaluate the potential safety and efficacy of transtracheal augmented ventilation (TTAV), which is the transtracheal delivery of high flows of a humidified air-oxygen blend. METHODS: The first of 2 observational studies evaluated patients before and after a 3-month intervention with the nocturnal (Noc) administration of TTAV at 10 L/min. Resting physiologic studies evaluated standard low-flow transtracheal oxygen (LFTTO), TTAV, and breathing without transtracheal flow via mouthpiece (MP). Patients also underwent nocturnal polysomnography, bronchoscopy, ventilatory drive evaluation, and treadmill exercise. The second study assessed the safety of Noc TTAV for up to 60 months. Each study evaluated 15 different transtracheal patients with severe lung disease. RESULTS: Pleural pressure-time index and respiratory duty cycle were significantly lower (p < 0.05) when comparing MP to TTAV. TTAV contributed more (p < 0.05) than LFTTO to the total volume delivered to the lung (V(L)). Arterial blood gases and (V(L)) were unaltered by TTAV. Sleep quality and nocturnal oxygenation with TTAV were similar to LFTTO, and Noc TTAV had no effect on ventilatory drive. Bronchoscopy showed no evidence of substantial injury. Treadmill exercise tests showed a longer exercise time (p < 0.005) and greater total work (p < 0.05) following Noc TTAV. During exercise, the changes in slope for heart rate and pH were less steep (p < 0.05) following Noc TTAV. The 3-month study and a long-term evaluation showed that Noc TTAV was well-tolerated and safe, with a reported high compliance. CONCLUSIONS: Patients with chronic hypoxemia and severe respiratory insufficiency may benefit from Noc TTAV.

Aged↗

The disconnect: infertility patients' information and the role they wish to play in decision making.

OBJECTIVE: To determine the preferred role in medical decision making of women undergoing fertility treatments and to establish whether their knowledge of treatments is adequate to inform their choices. METHODS: Self-report survey of 404 women undergoing fertility treatments in 2 university hospitals and a private fertility clinic in Canada. RESULTS: The women had been in fertility treatment for 2.3 +/- 2.6 years; 67.8% reported taking fertility drugs. Most (61.7%) women wanted to share knowledge equally with their doctors about possible fertility treatments. However, about half wanted to decide alone or mostly by themselves about the acceptability of treatment risks and benefits (56%), what treatments should be selected (49.8%), and when to conclude treatments (54.3%). In addition, 55.1% of the women did not know their personal eventual chances of pregnancy with fertility treatment or thought it was 50% or greater. Over half of the women (57.2%) who had taken fertility drugs were unaware of a possible link between fertility drugs and increased ovarian cancer risk. The majority of women (61.8%) who knew of this possible association reported that they learned about it from the print media. Women who knew of the association had a poor understanding of the strength of the evidence or the ability to detect or treat ovarian cancer successfully, and 88.3% thought they could reduce cancer risk by following their doctors' advice. CONCLUSIONS: Despite these women's wishes to actively participate in fertility treatment decisions, they lacked the necessary information to do so meaningfully. Public health policymakers, professional and advocacy organizations, physicians, other healthcare providers, and women themselves must find ways to improve the general public's and patients' understanding about fertility treatment outcomes and risks.

Female↗

The diagnostic significance of polyclonal lymphocytosis in pleural effusions.

AIM: To evaluate the diagnostic contribution and clinical relevance of analysing subpopulations of lymphocytes in pleural effusions. METHODS: Forty patients (age >60 years) with newly diagnosed, polyclonal, lymphocyte-rich pleural effusions were evaluated. The following data were collected: demographic characteristics, associated diseases, fluid type, fluid white blood cells count, differential morphology and immunephenotyping, and final diagnosis. RESULTS: Of the 33 patients for whom biochemical data were available, 18 had exudative effusion, while 15 had transudate. Thirty-three fluids contained mostly T cells and only one was B-cell rich. (The lymphocytes of five patients with malignant epithelial cells in the effusion were not subtyped.) Thirty-two of the 33 T-cell rich fluids contained mainly CD4+ lymphocytes. The most common causes of pleural effusion were congestive heart failure (17 patients) and epithelial malignant diseases (eight patients), while none of the patients had tuberculosis. Since most effusions were CD4+ rich, no correlation could be detected between lymphocyte subtyping and diagnosis or the biochemical type of the fluids. Congestive heart failure was significantly associated with transudates, while malignant diseases correlated with exudates. CONCLUSIONS: Most patients with pleural polyclonal lymphocytosis, especially those with transudates, have congestive heart failure. The presence of exudative, lymphocyte-rich effusion is an indication for further evaluation, since it is most commonly associated with malignancy. The clinical value of lymphocyte subtyping is low and this procedure should not be used routinely.

Aged↗

Analysis of enzyme kinetics in individual living cells utilizing fluorescence intensity and polarization measurements.

BACKGROUND: The Cellscan mark-S (CS-S) scanning cytometer was used for tracing enzymatic reactions in the same individual cells under various physiological conditions over periods of minutes. On-line reagent addition and changes in the experimental conditions (buffers, ions, substrates and inhibitors) were performed. METHODS: Kinetic events were monitored by fluorescence intensity (FI) and fluorescence polarization (FP) measurements of fluorescein diacetate (FDA) and chloromethyl fluorescein diacetate (CMFDA) intracellular hydrolysis. FP measurements have been used to assess the intracellular marker's mobility restrictions. RESULTS: Kinetic measurement along 1000 s of FDA labeled individual Jurkat T cells, indicated variation of 65% for FI(t) and approximately 10% for FP(t). While FI increased linearly with time, FP(t) decreased nonlinearly and asymptotically, reaching a constant value. The FP(t) of CMFDA-labeled cells was different from that of FDA-labeled cells. Average cellular Km of 3.9 microM was calculated from individual cell FDA hydrolysis curves. CONCLUSIONS: (1) Analysis of the reaction kinetics of intracellular enzymes can be refined by using FP measurements of the products of fluorogenic substrates in addition to the FI measurements. (2) Subpopulations or individual cells could be classified according to their reaction rates. (3) A specific dependence of FP(t) on type of enzyme substrate is suggested.

Binding, Competitive↗

The effect of storage on the expression of platelet membrane phosphatidylserine and the subsequent impacton the coagulant function of stored platelets.

BACKGROUND: Platelet concentrates (PCs) derived from whole blood and stored under standard blood bank conditions undergo changes that are referred to as the platelet storage lesion. This study assesses the effect of PC preparation and storage on the distribution of phosphatidylserine (PS) in the platelet membrane and the effect that this distribution may have on the thrombogenic potential of stored PCs. STUDY DESIGN AND METHODS: Fresh platelets and PCs donated by healthy donors were obtained. PCs derived from platelet-rich plasma were studied on Day 1, Day 3, and Day 6 of storage under blood bank conditions. RESULTS: Platelet aggregation after exposure to the platelet agonists ADP and epinephrine singly declined progressively, but, when ADP and epinephrine in combination and collagen and thrombin in combination were used as agonists, the decline in platelet aggregation was less marked. PS expression as measured by Annexin V binding (mean and SD) was 2.02 +/- 0.93 percent in fresh platelet samples and increased to 5.39 +/- 4.2 percent on Day 1, 22. 1 +/- 7.1 percent on Day 3, and 39.5 +/- 12.1 percent on Day 6. Platelet prothrombinase activity (mean +/- SD) as measured by thrombin generation increased from 1.49 +/- 0.7 micro per mL in fresh platelet samples to 3.68 +/- 1.1 micro per mL in Day 1 platelets (p<0.001), 5.15 +/- 2.5 micro per mL in Day 3 platelets (p<0.001), and 4.65 +/- 2.48 micro per mL in Day 6 platelets (p<0. 001). CONCLUSION: These results show that PS expression increases after preparation of PCs from platelet-rich plasma and rises progressively during platelet storage under blood bank conditions. Furthermore, the greater PS expression is associated with increased platelet- dependent thrombin-generating capacity.

Blood Coagulation↗

Clinical observations of axillary involvement for tubular, lobular, and ductal carcinomas of the breast.

BACKGROUND AND OBJECTIVES: Recently, there has been much interest in identifying primary breast cancer characteristics which have predictive value for axillary metastases. We studied breast cancer patients to determine variables associated with the incidence/extent of axillary involvement and to construct a modeled analysis. METHODS: Patients with invasive ductal, lobular, and tubular breast cancer (group 1, n = 15,719) were analyzed by tumor size and histology for the probability/extent of axillary metastases. A subgroup of patients was analyzed separately for any association of axillary involvement and other variables (group 2). RESULTS: In group 1, the incidence and extent (number of positive lymph nodes) of axillary metastases correlated significantly with histology and increasing tumor size of ductal and lobular histologies. Significant associations for < or = 10% axillary involvement in group 2 were age and S phase for tubular histology and differentiation for ductal histology. In a multivariate analysis, increasing tumor size was the only statistically significant correlate for axillary involvement (group 2) and for increasing number of positive nodes (group 1). CONCLUSIONS: A multivariate model of tumor size and age combined with staging techniques can successfully confirm or assess extent of axillary metastases in breast carcinoma.

Adenocarcinoma↗

A specific sign of pneumoperitoneum on sonography: enhancement of the peritoneal stripe.

OBJECTIVE: Failure to reveal pneumoperitoneum is a recognized weakness of abdominal sonography. Our objective is to describe a reliable and reproducible sign of pneumoperitoneum that was first identified in an animal model and then confirmed in patients who had undergone laparoscopy. SUBJECTS AND METHODS: We injected 300 ml of degassed water into the peritoneal cavity of a 15-kg anesthetized pig. Sonographic images were obtained of the anterior peritoneal area after intraperitoneal injection of a single bubble, a series of bubbles, and, subsequently, a 10-ml bolus of air. Later, abdominal sonography was performed in nine patients who had undergone laparoscopy. Close attention was paid to the anterior peritoneal area and signs of free air observed in the animal model. Ten healthy volunteers functioned as a control group. RESULTS: In the pig, minute amounts of intraperitoneal air showed on sonography as enhancement of the peritoneal stripe. Larger volumes of intraperitoneal air showed as enhancement of the peritoneal stripe associated with dirty shadowing or distal multiple reflection artifacts. The stripe enhanced each time it appeared in the reflection artifact. Intraluminal gas was associated with a normal thin peritoneal stripe, superficial and distinct from the underlying gas artifact. The patients who had undergone laparoscopy showed findings suggestive of small and large pockets of free air, as we saw in the pig model. The control group showed findings consistent with intraluminal gas only. CONCLUSION: On sonography, enhancement of the peritoneal stripe alone or with reflection artifacts involving the peritoneal stripe is an accurate sign of pneumoperitoneum.

Abdominal Pain↗

Pleural effusion in patients with non-Hodgkin's lymphoma: a case-controlled study.

BACKGROUND: Pleural effusion is reported in up to 20% of patients with non-Hodgkin's lymphoma (NHL), most often at presentation. However, the prognostic implications of such findings are not clear. The majority of the information in the literature is based on minor observational studies or case reports. Therefore, a case-controlled study was performed to verify the clinical significance of pleural effusion in NHL. METHODS: Seventeen patients with pleural effusion at the time of presentation of NHL were identified. They were categorized by grade of NHL (based on the Working Formulation). Twenty-nine control patients with similar histopathologic characteristics who had Stage III/IV NHL without pleural effusion were matched to these cases by age, time of diagnosis, and treatment. RESULTS: Ten patients with intermediate grade NHL were matched with 23 controls. No statistically significant difference in complete remission or survival rates between these groups was found (P=0.69 and P=0.7, respectively). The remission and survival rates also were similar in the subgroup of patients and controls who were treated with aggressive chemotherapy. Similarly, no difference was found in these parameters between four cases and six matched controls with low grade lymphoma. No matched controls were found for the patients with high grade lymphoma, but these patients had an unfavorable outcome. Fourteen of the 17 studied patients had an exudative type of pleural effusion. Thoracentesis yielded a positive cytologic finding in every case. CONCLUSIONS: The presence of pleural effusion at the time of presentation of NHL does not adversely affect complete remission or survival rates.

Adult↗

Increased expression of neutrophil and monocyte adhesion molecules LFA-1 and Mac-1 and their ligand ICAM-1 and VLA-4 throughout the acute phase of myocardial infarction: possible implications for leukocyte aggregation and microvascular plugging.

OBJECTIVES: This study sought to evaluate expression of adhesion molecules on neutrophils and monocytes throughout the acute phase of myocardial infarction. BACKGROUND: Neutrophil and monocyte counts increase within days from onset of acute myocardial infarction. Because leukocytes are recruited to the involved myocardial region, we postulated that these activated cells would display an increased expression of adhesion molecules necessary for effective endothelial transmigration. METHODS: We measured the expression of neutrophil and monocyte lymphocyte function associated antigen-1 (LFA-1), Mac-1, very late after activation antigen-4 (VLA-4) and intercellular adhesion molecule-1 (ICAM-1) by flow cytometry throughout the acute phase of acute myocardial infarction in 25 patients and 10 age-matched control subjects. RESULTS: Expression of Mac-1 on neutrophils increased significantly, whereas no expression of VLA-4 and ICAM-1 was detected. The expression of LFA-1, Mac-1, VLA-4 and ICAM-1 on the monocyte cell membrane in patients with an acute myocardial infarction was increased compared with that in control subjects by 22% (on day 7), 67%, 13% and 44% (all on day 4), respectively (all p < 0.001). Elevated density of monocyte-specific CD14 in the AMI versus the control group was also shown (30%, p < 0.001). CONCLUSIONS: Increased expression of neutrophil and monocyte adhesion molecules may contribute to their adhesion to endothelium in the ischemic territory. This adhesion could feasibly precipitate vasoconstriction or add a local thrombotic effect due to tissue factor expression secondary to Mac-1 engagement. In addition, the manifestation of increased density of LFA-1 and Mac-1 by activated leukocytes with monocytes also expressing ICAM-1 suggests that leukocytes may form microaggregates that could cause microvascular plugging. This mechanism may facilitate the occurrence of the "no-reflow" phenomenon or slow coronary filling after acute myocardial infarction.

Aged↗