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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 37 records · Page 2Linked to original sources

Reduced-intensity allogeneic stem cell transplantation in relapsed and refractory Hodgkin's disease: low transplant-related mortality and impact of intensity of conditioning regimen.

A total of 40 patients with relapsed/refractory Hodgkin's disease (HD) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) from an HLA-identical sibling (n=20) or a matched unrelated donor (n=20). The median age was 31 years (range 18-58). Disease status at allo-SCT was refractory relapse (n=14) or sensitive relapse (n=26). The conditioning regimens were fludarabine-cyclophosphamide+/-antithymocyte globulin (n=14), a less intensive regimen, and fludarabine-melphalan (FM) (n=26), a more intensive one. The two groups had similar prognostic factors. The median time to neutrophil recovery (ie absolute neutrophil count >/=500/microl) was 12 days (range 10-24). The median time to platelet recovery (ie platelet count >/=20 000/microl) was 17 days (range 7-132). Day 100 and cumulative (18-month) transplant-related mortalities (TRMs) were 5 and 22%. Twenty-four patients (60%) are alive (14 in complete remission or complete remission, unconfirmed/uncertain) with a median follow-up of 13 months (4-78). In all, 16 patients expired (TRM n=8, disease progression n=8). FM patients had better overall survival (73 vs 39% at 18 months; P=0.03), and a trend towards better progression-free survival (37 vs 21% at 18 months; P=0.2). RIC allo-SCT is feasible in relapsed/refractory HD patients with a low TRM. The intensity of the preparative regimen affects survival.

Adolescent↗

Differences in infantile growth patterns in Turner syndrome girls with and without spontaneous puberty.

OBJECTIVE: The role of prepubertal estrogen in child growth was modeled using Turner's syndrome, comparing growth patterns of girls who later did or did not enter puberty spontaneously. The hypothesis was that TS patients with normal prepubertal estrogen levels would have a different growth pattern from those with subnormal estrogen levels. STUDY DESIGN: Growth data from 78 full-term patients with Turner's syndrome were collected retrospectively. 24/78 later developed spontaneous puberty, (+Pub), and their growth data were compared to TS patients without spontaneous puberty (-Pub). A nonlinear mixed model was fitted using the bi-exponential model. RESULTS: The growth velocity difference between the -Pub and +Pub groups suggests an early infantile growth advantage in the -Pub group, which disappears before the end of the first year of life; growth velocity remains similar (+/- 1 cm/y) for the next 6 years and declines at age 7-8 years in the +Pub group faster than it does in the -Pub group. Bi-exponential analysis showed that both the 1st (restrictive) and 2nd exponent (forward) were different (p = 0.0003). CONCLUSIONS: Comparison of girls with or without spontaneous puberty suggests a role for estrogen in child growth. Estrogens restrict infantile growth, as well as growth during the mid-childhood spurt.

Adolescent↗

Clinical characteristics and mid-term prognosis of acute coronary syndrome in HIV-infected patients on antiretroviral therapy.

OBJECTIVES: Acute coronary syndromes (ACSs) and coronary artery disease are emerging complications in HIV-infected patients on highly active antiretroviral treatment. The aim of this study was to determine the mid-term prognosis of ACS in HIV-infected patients. METHODS: We evaluated the clinical characteristics and follow-up profile [38+/-15 months; mean+/-standard deviation (SD)] of ACS in 20 HIV-infected patients (mean +/-SD: age 44+/-8 years; range 35-65 years). All had coronary angiograms performed mean time 3+/-48 h after the onset of symptoms. RESULTS: Eighteen patients were on antiretroviral therapy, of whom 13 patients were on regimens including protease inhibitors (mean duration+/-SD: 19+/-13 months). Fifteen patients had a first episode of ST segment elevation ACS and five had non-ST segment elevation ACS. Tobacco consumption (80%) and hypercholesterolaemia (50%) were the most frequent cardiovascular risk factors. During initial hospitalization, four patients were treated with thrombolysis, two had primary coronary angioplasty and seven had secondary coronary angioplasty. At follow up, 10 patients (50%) had had 18 cardiovascular events: one cardiovascular death, seven episodes of recurrent myocardial ischaemia in four patients, three pulmonary oedemas in two patients, and seven revascularization procedures in five patients. CONCLUSIONS: This preliminary report highlights the risk of ACS and related complications in HIV-infected patients and raises questions regarding the implications of antiretroviral treatment.

Adult↗

Intracranial arterial dolichoectasia is associated with enlarged descending thoracic aorta.

BACKGROUND: Intracranial arterial dolichoectasia (IADE) is defined as an increase in length and diameter of the intracranial arteries and is present in 12% of stroke patients. The pathophysiology is unknown; some data suggest that IADE is not merely a complication of atherosclerosis, but a distinct arteriopathy characterized by loss of elastic tissue in the media. OBJECTIVE: To investigate the relationship between IADE and transesophageal echocardiography (TEE) variables such as ascending and descending thoracic aorta diameters. METHODS: The sample included 154 patients with brain infarction (BI) and with measurement of the descending thoracic aorta on TEE. IADE was diagnosed by consensus between two neurologists. Information on demographic characteristics and risk factors was collected using a structured questionnaire, and a carotid ultrasound scan was performed. RESULTS: IADE was identified in 23 of the 154 stroke patients (15%). The mean diameter (+/-SD) of the descending thoracic aorta was significantly higher in the IADE(+) than in the 131 IADE(-) stroke patients (mean +/- SD 26.6 +/- 3.6 vs 24.8 +/- 2.7 mm). The proportion of IADE increased regularly with the quartiles of descending thoracic aorta diameter: 5%, 13%, 18%, and 24% (test of linear trend, p = 0.02). The adjusted OR (95% CI) of IADE associated with a 1 mm increase in descending thoracic aorta diameter was 1.22 (95% CI, 1.02 to 1.45). CONCLUSION: Patients with intracranial arterial dolichoectasia (IADE) have larger descending thoracic aorta diameters than non-IADE patients, suggesting that the underlying process causing IADE also affects the descending thoracic aorta.

Aged↗

Laparoscopically guided distal ventriculoperitoneal shunt placement.

In standard techniques for performing ventriculoperitoneal shunts, the peritoneal catheter is threaded more or less blindly into the peritoneal cavity. Using laparoscopic techniques allows accurate peritoneal placement, without a large incision, even in replacement procedures and in patients with previous abdominal operations. We performed 28 laparoscopically guided ventriculoperitoneal shunt placements and shunt revisions in 24 patients with hydrocephalus (aged 6-80 years). Sixteen of 24 patients (67%) had previous abdominal surgery. Laparoscopic shunt placement was successful in all patients. Mean operative time was 63 +/- 34.9 minutes (range 15-150 minutes). In 2 patients, broken and disconnected distal parts of previously inserted shunts were removed from the abdomen. One shunt was removed following infection and other one was revised due to shunt malfunction. Three patients required revision of the cranial part of the shunt. Laparoscopically guided distal ventriculoperitoneal shunt placement provides definite patient benefits: it allows shunt placement under direct vision, associated with reduced trauma to the abdominal wall, and avoids a consequent risk of intra-abdominal adhesions.

Adolescent↗

Electrically conductive 2D-PAN-containing surfaces as a culturing substrate for neurons.

In the present contribution we report on a novel route to synthesize 2D-polyaniline (2D-PAN) on sulfonated-poly(styrene) (SPS) templates by allowing first monomer assembly followed by chemical oxidation to achieve polymerization. We show that Aplysia neurons grown on 2D-PAN exhibit an unusual growth pattern and adhesion to this conducting substrate that is manifested by the formation of giant lamellipodia. The lamellipodial domains are characterized by small gap between the plasma membrane and the 2D-PAN substrate (ca. 30 nm) and actin rich skeleton resembling the skeleton of growth cones. This behavior is characteristic to uniform substrates containing only 2D-PAN. However, in patterned substrates containing additionally poly(L-lysine) Aplysia neurons prefer to extend new neurites on the poly(L-lysine) domains.

Actins↗

Multiple microembolic borderzone brain infarctions and endomyocardial fibrosis in idiopathic hypereosinophilic syndrome and in Schistosoma mansoni infestation.

We report two cases of multiple distal borderzone ischaemic strokes associated with hypereosinophilia due to idiopathic hypereosinophilic syndrome in one patient and to acute Schistosoma mansoni infestation in the other. Endomyocardial fibrosis (EMF) was documented pathologically, in one case at autopsy and in the other after cardiac surgery; and by cardiac CT, with initially negative echocardiography, in one patient. These observations suggest that so called borderzone infarcts may be due to microembolisms and that, in the context of hypereosinophilia, EMF diagnosis warrants complete cardiac investigation including cardiac CT and repeat echocardiography.

Adult↗

[Quantification of longitudinal myocardial velocities by Doppler tissue imaging during dobutamine echocardiography].

Doppler tissue imaging has been suggested to be a valuable method for the diagnosis of myocardial ischaemia during dobutamine echocardiography. The authors studied this mode of investigation in 49 consecutive patients (average age 60 +/- 12 years) referred for dobutamine stress echocardiography and who had undergone coronary angiography. The stress echo was carried out according to a standard protocol (5 to 40 m g/kg/min +/- atropine) with additional acquisition of 3 apical views (4, 2 and 3 chambers) with colour Doppler tissue imaging. Analysis of systolic and diastolic myocardial velocities was performed afterwards from digitised data. The different Doppler tissue parameters were measured in 12 left ventricular segments (excluding the apical segments) for each dosage of dobutamine: peak systolic velocity (S), Q-S duration, systolic velocity time integral (ITVS), peak early diastolic velocity (E), peak end diastolic velocity (A). These parameters were analysed throughout the stress for each segment without significant coronary stenosis to define normal values. ROC curves were constructed to determine threshold values of relative changes of velocity (between maximal dobutamine dosage and basal conditions) to improve detection of ischaemia in a segment with coronary stenosis (vessel diameter reduction > or = 70%). Similar diagnostic performances were observed with different systolic and diastolic parameters. The feasibility of measurement of diastolic velocities was, however, reduced (from 29% to 49%). The diagnostic accuracy of each parameter was the same for each vessel territory. A satisfactory concordance was observed between 2D echocardiography and Doppler tissue imaging for the detection of significant coronary stenosis in an analysis by vascular territory. The authors conclude that analysis of myocardial velocities during dobutamine stress echocardiography is feasible. It may be a useful complement for the detection of coronary stenosis during pharmacological stress echocardiography.

Coronary Stenosis↗

Comparative bioequivalence studies with Estradot and Menorest transdermal systems.

OBJECTIVES: To compare the relative bioavailability of Estradot, a small size, new generation estradiol transdermal system (ETS) to Menorest, in healthy postmenopausal women. METHODS: In two open-label, single center, randomized, crossover, bioequivalence studies, healthy postmenopausal women aged 40-65 years received treatment with all the test regimens. In Study 1 (single-dose study), patients wore 5 cm(2) (50 microg/day), 10 cm(2) (100 microg/day) Estradot and 29 cm(2) (100 microg/day) Menorest for 84 h. In Study 2 (multiple-dose study), patients wore a regimen of four consecutive treatments with a 5 cm(2) (50 microg/day) new generation patch, Estradot and a 14.5 cm(2) (50 microg/day) patch, Menorest. Blood samples were drawn at various time-points in both studies. Estradiol and estrone serum levels were determined by gas chromatography/mass spectrometry or radioimmunoassay methods. Skin irritation (erythema and edema), patch adherence and local skin reaction were assessed following patch removal. RESULTS: In Study 1, baseline-uncorrected C(max) for estradiol for Estradot 50 and 100 microg/day and Menorest 100 microg/day was 54.8, 106.2 and 101.6 pg/ml, respectively, and C(max) for estrone was 75.6, 97.0 and 98.3 pg/ml, respectively. In Study 2, the baseline-uncorrected mean maximum serum concentration (C(max)) for estradiol for Estradot 50 microg/day and Menorest 50 microg/day patches was 56.7 and 52.7 pg/ml, respectively, and C(max) for estrone was 41.7 and 41.3 pg/ml, respectively. No significant skin irritation was observed in either study, but Estradot caused less skin irritation than Menorest. CONCLUSIONS: Estradot produced comparable serum concentrations of estradiol and estrone and caused less skin irritation than Menorest.

Administration, Cutaneous↗

Segmental tibial fractures: an assessment of procedures in 27 cases.

Twenty-seven patients (two women) with segmental tibial fractures (19 open) were treated in our institution with a mean age of 38.9 years (range 22-67 years) and a mean Injury Severity Score of 11.5 (9-34). Sixteen fractures were stabilised initially with an interlocking nail, seven with an external fixator, one with a hybrid external fixator, two cases were plated and one was treated in plaster. The mean size of the segment was 11.5 cm (range 4-20 cm). Soft tissue coverage was required in 17 cases. There were three cases of compartment syndrome, six cases of superficial infection and four deep infection cases (two of which required amputation). In four cases, excision of the non-viable segment was necessary. Overall, 13 patients were subjected to a second operative procedure (OP) (four external fixators were replaced with the AO solid tibial nail, two Ilizarov bone transports following excision of the dead bone segment, 2 below knee amputations, 3 exchange reamed nailings, 1 LISS plate application for stability and 1 ring fixator for compression of a fracture). Five patients underwent third procedure (two Ilizarov for bone transport, two exchange nailing, and one bone grafting). The mean time to union of the proximal segment was 38.8 weeks (range 10-78 weeks) and 41.4 weeks (range 12-65 weeks) for the distal segment, respectively. The treatment of segmental tibial fractures poses many problems to the surgeon due to the precarious blood supply of the intermediate segment. The risk of non-union delayed union, infection and additional procedures is high as seen in this series of patients.

Adult↗

Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography: optimal diagnostic models using off-line tissue Doppler in the MYDISE study.

AIMS: To develop optimal methods for the objective non-invasive diagnosis of coronary artery disease, using myocardial Doppler velocities during dobutamine stress echocardiography. METHODS AND RESULTS: We acquired tissue Doppler digital data during dobutamine stress in 289 subjects, and measured myocardial responses by off-line analysis of 11 left ventricular segments. Diagnostic criteria developed by comparing 92 normal subjects with 48 patients with coronary disease were refined in a prospective series of 149 patients referred with chest pain. Optimal diagnostic accuracy was achieved by logistic regression models, using systolic velocities at maximal stress in 7 myocardial segments, adjusting for independent correlations directly with heart rate and inversely with age and female gender (all p<0.001). Best cut-points from receiver-operator curves diagnosed left anterior descending, circumflex and right coronary disease with sensitivities and specificities of 80% and 80%, 91% and 80%, and 93% and 82%, respectively. All models performed better than velocity cut-offs alone (p<0.001). CONCLUSION: Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography is best performed using diagnostic models based on segmental velocities at peak stress and adjusting for heart rate, and gender or age.

Adult↗

Age-related patterns of fertility in captive populations of birds and mammals.

We have analyzed birth records from the International Species Inventory System database of zoo animals to describe patterns of fertility as a function of age in birds and mammals. Unlike age at death, fertility in captive populations is partly controlled by animal keepers depending on availability of space and potential mates and on the aims of captive propagation programs. Thus, fertility records must be considered carefully to avoid potential age-specific biases. The zoo data suggest that fertility declines from a peak at young adult ages in most species. The rate of decline in reproductive function is correlated with the rate of somatic aging, indicated by the increase in mortality rate with age, and with the age at peak fertility. Over the sample as a whole, these patterns do not differ systematically between the sexes, nor do they differ between birds and mammals. While it is clear that the demographic consequences of aging of the reproductive system follow a different course than the aging of somatic tissue, the rates of each are correlated either through functional connections or through parallel evolutionary responses to common selective factors.

Aging↗

A clinical and molecular study of a Bedouin family with dysmegakaryopoiesis, mild anemia, and neutropenia cured by bone marrow transplantation.

OBJECTIVES: Familial thrombocytopenia is a relatively rare and heterogeneous group of clinical and genetic syndromes of unknown etiology. Recently, mutations in a few hematopoietic transcription factors were implicated in dysmegakaryopoiesis with and without dyserythropoietic anemia. The aim of the present study was to describe the clinical and hematologic picture of members of a Bedouin family with severe congenital thrombocytopenia associated with neutropenia and anemia and to determine the possible involvement of hematopoietic transcription factor genes in their disease. PATIENTS AND METHODS: Four members of a Bedouin family presented with severe bleeding tendency, including intracranial hemorrhage in three. Three of the four were successfully treated with allogenic human leukocyte antigen (HLA)-matched bone marrow transplants. Measurements of serum erythropoietin and thrombopoietin levels, bone marrow electron microscopy, and megakaryocytic colony were grown for each patient in addition to DNA amplification and single-strand conformation polymorphism of each exon of the NF-E2, Fli-1, FOG-1, and Gfi-1b in genes. RESULTS: Bone marrow studies revealed dysmegakaryopoiesis and mild dyserythropoiesis. A low number of bone marrow megakaryocyte colony-forming units was found, as well as a slightly elevated serum thrombopoietin level. No mutation was identified in any of the transcription factor genes examined. CONCLUSIONS: A unique autosomal recessive bone marrow disorder with prominent involvement of megakaryocytes is described. Defects were not identified in transcription factors affecting the common myeloid progenitor.

Anemia↗

Methods of reducing loss of efficiency due to discreteness of distributions.

All models of this paper involve R x C contingency tables in which the total frequency is fixed (full multinomial model), or in which the row totals are fixed (product multinomial model). For the most part, we assume that the column categories are ordered. For the full multinomial model the null hypothesis of interest is independence, i.e., the (ij)th cell probability is the product of the marginal probabilities of the ith row and jth column. In the product multinomial model the null hypothesis is that the R multinomial distributions have the same vector of cell probabilities. Our review includes (1) a careful listing of two-sided and one-sided alternatives, and (2) methodology to reduce the loss of efficiency of tests because of the discreteness of the model (The methodologies discussed are efficient in several senses. Tests are exact. Tests have very favorable and robust power properties. Tests make use of back-up statistics, thereby providing a finer grid of p-values. In some special cases, e.g., a 2 x C table and a one-sided alternative, conditional p-values are found, within seconds, simply by entering row frequencies into a given website. Thus, computational efficiency is exceptional.), and (3) a critique of some exact linear permutation tests (that are conditional on row and column margins) for both two-sided and some one-sided alternatives. Furthermore, recommendations as to which tests to use for specific alternatives are made.

Data Interpretation, Statistical↗