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Biomedical subjects

A Weinberg

Publications and source records attributed to A Weinberg.

At least 55 records · Page 3Linked to original sources

Viability and functional activity of cryopreserved mononuclear cells.

Factors that influence viability and function of cryopreserved peripheral blood mononuclear cells (PBMC) were identified on 54 samples from 27 AIDS Clinical Trial Units. PBMC viability ranged from 1 to 96% with a median of 70%, was higher in laboratories with experienced staff, and was not significantly associated with CD4 cell number. Function of cryopreserved PBMC, measured by lymphocyte proliferation, was associated with viability. Preparations with viability greater than or equal to 70% had consistent proliferative responses and were suitable for functional analyses.

Cell Division↗

Shipment impairs lymphocyte proliferative responses to microbial antigens.

Lymphocyte proliferation assays (LPAs) are widely used to assess T-lymphocyte function of patients with human immunodeficiency virus infection and other primary and secondary immunodeficiency disorders. Since these assays require expertise not readily available at all clinical sites, specimens may be shipped to central labs for testing. We conducted a large multicenter study to evaluate the effects of shipping on assay performance and found significant loss of LPA activity. This may lead to erroneous results for individual subjects and introduce bias into multicenter trials.

Candida↗

Inducible expression of human beta-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier.

Human gingival epithelial cells (HGE) express two antimicrobial peptides of the beta-defensin family, human beta-defensin 1 (hBD-1) and hBD-2, as well as cytokines and chemokines that contribute to innate immunity. In the present study, the expression and transcriptional regulation of hBD-2 was examined. HBD-2 mRNA was induced by cell wall extract of Fusobacterium nucleatum, an oral commensal microorganism, but not by that of Porphyromonas gingivalis, a periodontal pathogen. HBD-2 mRNA was also induced by the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and phorbol myristate acetate (PMA), an epithelial cell activator. HBD-2 mRNA was also expressed in 14 of 15 noninflamed gingival tissue samples. HBD-2 peptide was detected by immunofluorescence in HGE stimulated with F. nucleatum cell wall, consistent with induction of the mRNA by this stimulant. Kinetic analysis indicates involvement of multiple distinct signaling pathways in the regulation of hBD-2 mRNA; TNF-alpha and F. nucleatum cell wall induced hBD-2 mRNA rapidly (2 to 4 h), while PMA stimulation was slower ( approximately 10 h). In contrast, each stimulant induced interleukin 8 (IL-8) within 1 h. The role of TNF-alpha as an intermediary in F. nucleatum signaling was ruled out by addition of anti-TNF-alpha that did not inhibit hBD-2 induction. However, inhibitor studies show that F. nucleatum stimulation of hBD-2 mRNA requires both new gene transcription and new protein synthesis. Bacterial lipopolysaccharides isolated from Escherichia coli and F. nucleatum were poor stimulants of hBD-2, although they up-regulated IL-8 mRNA. Collectively, our findings show inducible expression of hBD-2 mRNA via multiple pathways in HGE in a pattern that is distinct from that of IL-8 expression. We suggest that different aspects of innate immune responses are differentially regulated and that commensal organisms have a role in stimulating mucosal epithelial cells in maintaining the barrier that contributes to homeostasis and host defense.

Adolescent↗

Comparison of PCR, antigenemia assay, and rapid blood culture for detection and prevention of cytomegalovirus disease after lung transplantation.

The goal of this study was to evaluate serial cytomegalovirus (CMV) blood culture, antigenemia testing, and qualitative and quantitative plasma CMV PCR for their ability to predict CMV disease and thus to direct preemptive therapy after lung transplantation. Forty-one patients provided 414 samples for blood culture, 290 samples for antigenemia testing, and 432 samples for PCR. Seven patients developed 11 episodes of CMV disease. CMV PCR had sensitivity, specificity, and positive predictive and negative predictive values of 79, 99, 84, and 99%, respectively, compared with 48, 99, 85, and 98%, respectively, for antigenemia testing, and 8, 100, 100, and 97%, respectively, for culture. Only quantitative CMV PCR correlated with disease stage: asymptomatic patients had a mean of 1,500 CMV DNA copies/ml, whereas patients who developed CMV disease had 5,087 copies/ml 12 to 4 weeks before symptoms and 32,000 copies/ml at diagnosis. Furthermore, CMV PCR-measured DNA increased 5- to 10-fold immediately preceding symptoms. PCR and antigenemia test values decreased with anti-CMV therapy. CMV DNA (as detected by PCR), but not antigenemia, persisted in patients who later developed recurrent CMV disease. The data indicate that lung transplant recipients will benefit from monitoring of CMV disease by plasma CMV PCR.

Adult↗

Expression of the antimicrobial peptide, human beta-defensin 1, in duct cells of minor salivary glands and detection in saliva.

The oral cavity is exposed to a variety of environmental insults. Salivary secretions play a critical role in maintaining oral health via innate host defense mechanisms and secretion of secretory IgA. Human beta-defensins (hBD) are antimicrobial peptides that are a component of the innate immune response; they are expressed in epithelia and are proposed to have a role in mucosal defense. hBD-1 mRNA is constitutively expressed in numerous mucosal tissues, including human gingiva and submandibular and parotid glands. Our objective was to detect the expression and localization of hBD-1 peptide in human salivary glands and in saliva. Minor salivary gland tissue was obtained from biopsies of patients with mucoceles (n = 20). hBD-1 peptide was detected by immunohistochemistry; expression was localized to the ductal cells and not the acinar cells of these glands. The peptide was located apically, toward the lumen in the duct cells. Further evaluation showed stronger hBD-1 expression in ducts with periductal inflammation, as indicated by the immunostaining of serial sections with anti-CD45 specific for B- and T-lymphocytes. Statistical analysis showed a strong correlation of hBD-1 staining and inflammation. Results of immunolocalization suggest that hBD-1 functions to protect salivary glands from retrograde infection, that expression of the peptide is enhanced in inflamed sites, and that post-transcriptional regulatory mechanisms may be involved in hBD-1 peptide expression. Western immunoblot analysis also detected hBD-1 peptide in unstimulated, whole, acidified saliva from normal volunteers. However, hBD-1 peptide associated with salivary mucin resulted in loss of the detection in a dot-immunoblot assay. Association of hBD-1 with salivary mucin may facilitate peptide distribution and adherence to oral surfaces and aid its function within the oral cavity.

Adult↗

Improving screening for melanoma by measuring similarity to pre-classified images.

A new method that can dramatically improve the sensitivity and especially the specificity of skin naevi screening for melanoma by physicians is introduced. The method is based on measuring the similarity to previously classified naevi images. As more naevi are being classified, the power of the method is enhanced. Thus physicians can benefit from experience accumulated by others and the screening can be performed effectively by physicians with less experience.

Dysplastic Nevus Syndrome↗

Slowed glycogen utilization enhances exercise endurance in patients with heart failure.

OBJECTIVES: The objective of the study was to investigate the impact of alteration of glycogen stores and metabolism on exercise performance in patients with heart failure. BACKGROUND: In normal subjects, muscle glycogen depletion results in increased exertional fatigue and reduced endurance. Skeletal muscle biopsies have revealed reduced glycogen content in patients with congestive heart failure (CHF). Whether glycogen depletion contributes to reduced endurance and abnormal ventilation in these patients is unknown. METHODS: Bicycle exercise tests with measurement of respiratory gases were performed following dietary manipulations to induce glycogen depletion (60% protein, 40% fat) and slow glycogen utilization (60% carbohydrate, 30% fat, 10% protein) in 13 patients with CHF (left ventricular ejection fraction 22+/-6%; age 48+/-9 years) and 7 control subjects (age 45+/-5 years). Maximal exercise, exercise at 75% of peak workload until exhaustion and 1-min cycles of supramaximal exercise at 133% of peak were performed on three occasions over a two-week period. RESULTS: Significant changes in resting respiratory quotients (RQs) in normal (Baseline: 0.78+/-0.03; Depleted: 0.69+/-0.05) and CHF subjects (Baseline: 0.84+/-0.05; Depleted: 0.72+/-0.05) were observed (both p<0.05). Peak Vo2 (oxygen consumption) in both groups was unchanged. The ventilatory response to exercise was analyzed by correlating CO2 production (V(CO2)) to minute ventilation (VE) in each test. The slopes of these correlations were not affected in either group. With glycogen depletion, exercise endurance was reduced from 17 to 6.1 min (57+/-19%) in normal subjects versus a reduction of 9.4 to 8.1 min (11+/-19%) in patients (p<0.05). With slowed glycogen use, CHF patients increased exercise endurance from 9.4 to 16.5 min (65%) versus 17 to 20.6 min (18%) in normal subjects (p<0.05). CONCLUSIONS: Glycogen depletion minimally affects maximal exercise performance, endurance or ventilation in CHF patients, whereas slowed glycogen utilization markedly enhances exercise endurance. Therapeutic interventions that increase or slow use of glycogen stores may have clinical benefit.

Adult↗

Outcome after orthotopic cardiac transplantation in adults with congenital heart disease.

BACKGROUND: Advances in surgical and medical management have greatly improved long-term survival rates in patients with congenital heart disease (CHD). As these patients reach adulthood, myocardial dysfunction can occur, leading to cardiac transplantation. METHODS AND RESULTS: We reviewed the pretransplantation and posttransplantation courses of 24 patients >18 years old (mean age, 26 years; range, 18 to 56 years) with CHD who received a transplant between January 1985 and September 1998. The relation between preoperative and perioperative risk factors for complications and death was assessed. Single ventricle was the pretransplantation diagnosis for 12 patients (50%), and d-transposition of the great vessels was the diagnosis for 4 patients (16%). Twenty-two patients had a mean of 2 previous operations. At cardiac transplantation, additional surgical procedures were required to correct extracardiac lesions in 18 patients (75%). Refractory heart failure was present in 22 patients, significant cyanosis was present in 7, and protein-losing enteropathy was present in 4. There were 5 early deaths due to bleeding (n=3) and infection (n=2). The Kaplan-Meier survival rate after cardiac transplantation was 79% at 1 year and 60% at 5 years. No anatomic or surgical risk factor was predictive of death. The outcome of patients with CHD who received a transplant was compared with that for patients without CHD (n=788). Mean bypass and ischemic times were significantly longer in patients with CHD than in patients without CHD. Survival rates after transplantation did not differ significantly between patients with and those without CHD (P=0.83). CONCLUSIONS: Successful cardiac transplantation is obtainable in adults with complex CHD, with an outcome similar to that of patients without CHD. A detailed assessment of cardiac anatomy and careful surgical planning are essential to the pretransplantation and posttransplantation management of these patients.

Adolescent↗

[Plagiocephaly in children: etiology, differential diagnosis and helmet treatment].

Plagiocephaly in a head-and-neck irradiated rat model or rhomboid-shaped head, occurs in at least 1 in 300 live births. In most cases such asymmetry is not caused by synostosis of the unilateral coronal or lambdoid sutures, but is rather a deformity produced by intrauterine and/or postnatal deformational forces. Categorization and diagnosis of plagiocephaly as synostotic or deformational is reliably made by physical examination and computerized tomography. Its differential diagnosis is extremely important because prompt surgical correction is usually indicated for the synostotic type. In contrast, infants with deformational frontal or occipital plagiocephaly generally respond to helmet treatment. 10 infants with significant deformational plagiocephaly were treated with individual plastic helmets during the past 2 years and 4 other infants with plagiocephaly are currently being treated. In each instance, cranial asymmetry dramatically improved as the brain grew and the head filled out the helmet. There were no significant complications. Awareness of deformational plagiocephaly allows more accurate diagnosis and appropriate treatment, avoiding unnecessary surgical intervention in patients with positional molding.

Head Protective Devices↗

[Optimal timing for secondary surgery in polytrauma patients: an evaluation of 4,314 serious-injury cases].

INTRODUCTION: It has been argued that secondary operations in multiple trauma patients impose an additional systemic burden, representing an additional risk of organ dysfunction. We investigated whether the timing of a secondary operation of > 3 h duration is related with the development of organ dysfunction. METHODS: In a retrospective analysis, 4,314 polytrauma patients treated at our institution between January 1975 and January 1999 were investigated. Patients were divided according to the presence ( + MOF) or absence (-MOF) of organ failure (Goris' criteria). RESULTS: In both groups, the injury severity, rescue time, duration and incidence of primary operations were comparable. Secondary surgery in patients who later developed organ failure was significantly more often performed between day 2 and 4, whereas patients without organ failure were usually operated between day 6 and 8 (P < 0.0001). The initial laboratory data in these two groups were comparable. If patients with organ failure were operated on days 6-8, significantly worse initial laboratory data were determined, indicating that these patients were at high risk of developing MOF. CONCLUSION: In patients with severe trauma requiring secondary operations of > 3 h duration, performance of this operation should be avoided on post trauma days 2-4.

Adult↗

Amputated lower limbs as a bank of organs for other organ salvage.

Aggressive modern technologies have made it possible to attempt limb salvage in even the most extreme cases. However, it is imperative to remember that prolonged salvage attempts may lead to devastating complications. The decision-making is more problematic in patients with bilateral severely injured mangled lower limbs. In such a case, protocols like the MESS are no longer valid because of the implications of bilateral amputation. In these rare cases, we use a multi-team approach and modern micro-surgical reconstructive techniques in attempting to salvage at least one of the lower limbs. We present here our experience in six patients with bilateral mangled lower limbs where an amputated limb was the source of "spare parts" for the salvage of the contralateral limb. In each of the cases, after evaluation and planning, the harvesting of the required tissues (including skin, muscle, bone, nerve and blood vessels) from the amputated leg was performed and simultaneously, a reconstruction of the contralateral severely injured limb was done. These cases emphasize the importance of modern trauma care, not only the ability to treat multiply traumatized patients, but also the capability to execute sophisticated techniques during the acute phase of treatment with maximal cooperation between teams from different disciplines.

Adolescent↗

Long-term survival after cardiac retransplantation: a twenty-year single-center experience.

OBJECTIVE: To identify risk factors for survival after cardiac retransplantation and compare the survival after retransplantation with that after primary cardiac transplantation. METHODS: A retrospective analysis of 952 patients undergoing cardiac transplantation for the treatment of end-stage heart disease at a single center between 1977 and October 1997. Of these, 43 patients (4.5%) underwent cardiac retransplantation for cardiac failure resulting from transplant-related coronary artery disease, rejection, and early graft failure. RESULTS: No significant difference in actuarial patient survival was found by Kaplan-Meier analysis at 1, 2, and 5 years between patients undergoing primary transplantation and those undergoing retransplantation 76%, 71%, and 60% versus 66%, 66%, and 51%, respectively (P =.2). Multivariable analysis identified a shorter interval between transplants and an initial diagnosis of ischemic cardiomyopathy as significant risk factors for death after retransplantation (P =.04 and.03, respectively). Since 1993, when our criteria for patient selection for retransplantation were revised on the basis of earlier experience to exclude patients with allograft dysfunction as a result of primary graft failure and those with intractable acute rejection occurring less than 6 months after transplantation, the survival has been significantly better (<1993 = 45%, 45%, and 33% versus >/=1993 = 94%, 94%, and 94% at 1, 2, and 4 years, respectively, P =.003). CONCLUSION: The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation, especially in patients with transplant-related coronary artery disease. Patient characteristics and other preoperative variables should assist in the rational application of retransplantation to ensure optimal use of donor organs.

Actuarial Analysis↗

Live virus survives excimer laser ablation.

OBJECTIVES: To determine whether live virus can withstand excimer laser ablation and pose a possible health hazard to medical personnel. DESIGN: Experimental study. METHODS: Fibroblasts infected with oral polio vaccine virus were ablated with an excimer laser. The plume was collected using a smoke evacuator and bubbled through viral culture media. MAIN OUTCOME MEASURES: The inlet tube from the smoke evacuator was swabbed and cultured for virus. Liquid from the bubble trap was also cultured. RESULTS: Live virus was shown in the material trapped from the laser plume. CONCLUSIONS: Oral polio vaccine virus can survive excimer laser ablation. Whether other more clinically relevant viruses, such as human immunodeficiency virus, can withstand ablation and remain infectious remains to be determined.

Cells, Cultured↗

Transposition of the great omentum for infected sternotomy wounds in cardiac surgery. Report of 16 cases and review of published reports.

The expanding indications for coronary artery bypass graft (CABG) and cardiac valves replacement have caused an increase in the number of sternal infections. The common treatment includes appropriate antibiotics, early debridement, and transposition of muscle flaps with or without skin grafts. When other treatments have proved unsatisfactory, we have used the great omentum for wound closure. During the last five years, 16 patients (10 women, six men, median age 63 years) underwent repair of infected sternotomy wounds by the transposition of the great omentum, after failure of pectoralis major or rectus abdominis muscle flaps (n = 9). Seven patients underwent transposition of the great omentum as the first choice. The omentum covers the sternal defect well and the closure was reliable.

Aged↗

Interstrain variation in the human cytomegalovirus DNA polymerase sequence and its effect on genotypic diagnosis of antiviral drug resistance. Adult AIDS Clinical Trials Group CMV Laboratories.

The polymerase (pol) coding sequence was determined for 40 independent clinical cytomegalovirus isolates sensitive to ganciclovir and foscarnet. Sequence alignments showed >98% interstrain homology and amino acid variation in only 4% of the 1, 237 codons. Almost all variation occurred outside of conserved functional domains where resistance mutations have been identified.

Antiviral Agents↗

Pituitary gland gumma in congenital syphilis after failed maternal treatment: a case report.

A preterm, very low birth weight infant was born to a mother with early latent syphilis who was treated 10 days and 3 days before delivery with 2.4 mU of benzathine penicillin. The infant had clinical, laboratory, and radiographic abnormalities consistent with congenital syphilis, ie, a Venereal Disease Research Laboratory test titer that was fourfold greater than was the maternal titer, hepatosplenomegaly, abnormal liver function tests, pneumonitis, osteochondritis of the long bones, and cerebrospinal fluid (CSF) examination showing a reactive Venereal Disease Research Laboratory test, pleocytosis, and elevated protein content. The infant died on the third day of life, and an autopsy revealed an evolving gumma of the anterior pituitary. Immunoglobulin M immunoblotting of serum and CSF was positive, and polymerase chain reaction detected Treponema pallidum DNA in endotracheal aspirate and CSF. This case highlights the pathologic abnormalities observed in congenital syphilis and focuses on the rare finding of an evolving anterior pituitary gumma. Furthermore, it documents the failure of maternal syphilis treatment during the last 4 weeks of pregnancy to cure fetal infection and supports the recommendation that all infants born to mothers with syphilis treated during the last 4 weeks of pregnancy should receive penicillin therapy.

Female↗