Cross-lip vermilion "tri-tailed" flap to correct the "whistling lip" deformity.
Explore the source record for details and available documents.
Cleft Lip↗
Biomedical subjects
A Weinberg
Publications and source records attributed to A Weinberg.
Preformed IgG antibodies against major histocompatibility complex class II antigens are major risk factors for high-grade cellular rejection in recipients of heart transplantation.
BACKGROUND: Preformed anti-HLA antibodies reacting specifically with donor lymphocytes have been associated with acute vascular rejection and early cardiac allograft failure. However, the effect of preformed anti-HLA antibodies directed against allogeneic major histocompatibility complex (MHC) class I or II antigens of a donor panel on heart transplantation outcome has not been extensively studied. METHODS AND RESULTS: The study group consisted of 68 patients who received cardiac transplants between 1989 and 1996 and who were at high risk for developing anti-HLA antibodies before transplantation. The effect of preformed antibodies against allogeneic MHC class I or class II antigens on the development of early high-grade cellular rejection and on cumulative annual rejection frequency was determined. Both patients with left ventricular assist devices and retransplantation candidates had a similar increase in the frequency of IgG anti-MHC class II antibodies (IgG anti-II) compared with control subjects (P<0.0001), whereas the frequency of IgG anti-MHC class I antibodies (IgG anti-I) was elevated only in patients with left ventricular assist devices. Pretransplantation IgG anti-II predicted early development of high-grade cellular rejection (P=0.006) and higher cumulative annual rejection frequency (P<0.001) in both of these sensitized patient groups. Among retransplantation recipients, a match between donors 1 and 2 at HLA-A additionally predicted an earlier time to a high-grade cellular rejection. CONCLUSIONS: These results emphasize the importance of specifically screening heart transplantation candidates for the presence of IgG antibodies directed against MHC class II molecules and suggest that strategies aimed at their reduction may have an impact on the onset and frequency of high-grade cellular rejections after transplantation.
Adolescent↗
Is early kinetic positioning beneficial for pulmonary function in multiple trauma patients?
Body positioning (kinetic therapy) is known to improve oxygenation in patients with impaired pulmonary function and ARDS. We have used body positioning prophylactically in trauma patients whose injury and pattern predispose to ARDS. This retrospective study reports the effects of early prophylactic (group P) versus late (group L) axial rotation on pulmonary function and the incidence of ARDS. Both groups were comparable in age, injury severity and the degree of thoracic injury. Systemic oxygenation was significantly better and the incidence of ARDS significantly lower in group P (group P: 34.3 per cent, group T: 74.1 per cent, P < 0.05). There was a tendency towards a lower incidence of pneumonia and a better survival in group P, which did not reach statistical significance. The duration of kinetic therapy and of ventilation was comparable in both groups. In this retrospective evaluation early prophylactic kinetic therapy was associated with a significantly lower incidence of ARDS compared with that instigated later.
Adult↗
Early nonsurgical removal of chemically injured tissue enhances wound healing in partial thickness burns.
Chemical burns are slow healing injuries and their depth is difficult to assess. Tissue destruction continues as long as active material is present in the wound site. The routine therapy for treatment of full thickness chemical burns is early excision; it shortens hospitalization and reduces morbidity. However, presently there is no specific treatment for chemical burns of partial thickness. This study examined several treatment modalities for partial thickness chemical burns: surgical excision; laser ablation and chemical debridement with Debridase or trypsin-linked to gauze. Chemical burns were inflicted with nitrogen mustard (NM -- a nitrogen analog to sulfur mustard -- mustard gas) in an experimental guinea pig model. Debridase was most effective and reduced significantly lesion area of burns after 'humid' exposure to 2 mg NM. The healing action of Debridase was also evident in the significantly higher histopathological score of biopsies from local tissue obtained on day 5. Laser ablation was most effective and accelerated healing of burn lesions after 'dry' exposure to 5 mg NM. The histopathology score of the laser treated burns was higher on day 4 compared to untreated controls. It is concluded that for partial thickness chemical burns early nonsurgical removal of the damaged tissues accelerates wound healing.
Administration, Topical↗
Cytokine production in varicella-zoster virus-stimulated cultures of human blood lymphocytes.
Estimates of responder cell frequency (RCF) based on limiting dilution analyses are laborious, and alternative means to quantitate cell-mediated immunity to immunogens are desirable. It was shown that levels of interleukin (IL)-2 in the supernatant of varicella-zoster virus-stimulated blood lymphocytes from immune adults peaked at 48 h of culture and correlated partially with estimates of RCF (r = .74, P = .003). Levels of gamma-interferon, IL-4, and IL-10 increased through the first 4 days of culture, and gamma-interferon levels showed some correlation with peak IL-2 levels (r = .48, P = .03). Nevertheless, correlations between levels of these cytokines and RCF did not reach statistically significant levels.
Adult↗
Severity of psychiatric disorder in day hospital and in-patient admissions.
This study assessed whether severity of psychiatric disorder varies across day hospital and in-patient units according to local need, and whether severity of disorder predicts length of stay and therefore costs. Data were collected for a consecutive series of 2230 in-patients and 712 day patients using the Social Behaviour Scale (data completed by nurses) and diagnosis and Clinical Global Impression (CGI) (completed by doctors). Severity of illness of subjects admitted to in-patient units, but not to day hospitals, was associated with under-privileged area score (UPA). Length of in-patient stay is most accurately predicted by Clinical Global Impression and six other variables relating to diagnosis, demographic status and individual hospital. Improved resource allocation for mental health services could be achieved if severity of disorder was routinely collected.
Adult↗
Rapid ganciclovir susceptibility assay using flow cytometry for human cytomegalovirus clinical isolates.
Rapid, quantitative, and objective determination of the susceptibilities of human cytomegalovirus (HCMV) clinical isolates to ganciclovir has been assessed by an assay that uses a fluorochrome-labeled monoclonal antibody to an HCMV immediate-early antigen and flow cytometry. Analysis of the ganciclovir susceptibilities of 25 phenotypically characterized clinical isolates by flow cytometry demonstrated that the 50% inhibitory concentrations (IC50s) of ganciclovir for 19 of the isolates were between 1.14 and 6.66 microM, with a mean of 4.32 microM (+/-1.93) (sensitive; IC50 less than 7 microM), the IC50s for 2 isolates were 8.48 and 9.79 microM (partially resistant), and the IC50s for 4 isolates were greater than 96 microM (resistant). Comparative analysis of the drug susceptibilities of these clinical isolates by the plaque reduction assay gave IC50s of less than 6 microM, with a mean of 2.88 microM (+/-1.40) for the 19 drug-sensitive isolates, IC50s of 6 to 8 microM for the partially resistant isolates, and IC50s of greater than 12 microM for the four resistant clinical isolates. Comparison of the IC50s for the drug-susceptible and partially resistant clinical isolates obtained by the flow cytometry assay with the IC50s obtained by the plaque reduction assay showed an acceptable correlation (r2 = 0.473; P = 0.001), suggesting that the flow cytometry assay could substitute for the more labor-intensive, subjective, and time-consuming plaque reduction assay.
Antigens, Viral↗
Measurement of induced cytokines in AIDS clinical trials using whole blood: a preliminary report. ACTG Inducible Cytokines Focus Group. AIDS Clinical Trials Group.
Measures of immune function have become increasingly important as endpoints in AIDS clinical trials, with respect to both modulation and reconstitution of immunity by experimental therapies. Measurement of immune function in this setting requires the development of robust analytic approaches suitable for the clinical laboratory. Experiments were performed to evaluate the suitability of using cultured heparinized ("whole") blood for induction of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), two cytokines critical in AIDS pathogenesis. TNF-alpha expression ranged from 229 to 769 pg/ml in lipopolysaccharide (LPS)-stimulated cultures and was not detected in unstimulated cultures. IFN-gamma expression ranged from 0 to 112,000 pg/ml in phytohemagglutinin A (PHA)-stimulated cultures and from 0 to 789 pg/ml in antigen-stimulated cultures. The mean coefficient of variation observed in three weekly determinations was 0.47 for TNF-alpha and ranged from 0.12 to 1.73 for IFN-gamma. These values indicate that sample sizes of 8, 24, and 29 subjects would be sufficient to detect twofold changes in LPS-induced TNF-alpha and in PHA- and antigen-induced IFN-gamma respectively, if two baseline and two treatment determinations were obtained, and if the interpatient variability of changes in true levels from baseline to follow-up is negligible compared to the variability in the three weekly measurements. Measurement of LPS-induced TNF-alpha and mitogen- or antigen-induced IFN-gamma can be performed simply and reproducibly in human immunodeficiency virus-infected persons by the whole-blood culture method. Further studies are warranted to determine the effect of overnight shipping on assay reproducibility and to determine the extent to which responses can be reliably detected in subjects with low CD4 cell numbers.
Acquired Immunodeficiency Syndrome↗
Effect of shipment, storage, anticoagulant, and cell separation on lymphocyte proliferation assays for human immunodeficiency virus-infected patients.
Lymphocyte proliferation assays (LPA), which can provide important information regarding the immune reconstitution of human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral therapy, frequently involve shipment of specimens to central laboratories. In this study, we examine the effect of stimulant, anticoagulant, cell separation, storage, and transportation on LPA results. LPA responses of whole blood and separated peripheral blood mononuclear cells (PBMC) to different stimulants (cytomegalovirus, varicella-zoster virus, candida and tetanus toxoid antigens, and phytohemagglutinin) were measured using fresh specimens shipped overnight and frozen specimens collected in heparin, acid citrate dextrose (ACD), and citrate cell preparation tubes (CPT) from 12 HIV-infected patients and uninfected controls. Odds ratios for positive LPA responses were significantly higher in separated PBMC than in whole blood from ACD- and heparin-anticoagulated samples obtained from HIV-infected patients and from ACD-anticoagulated samples from uninfected controls. On separated PBMC, positive responses were significantly more frequent in fresh samples compared with overnight transportation for all antigens and compared with cryopreservation for the candida and tetanus antigens. In addition, viral antigen LPA responses were better preserved in frozen PBMC compared with specimens shipped overnight. CPT tubes yielded significantly more positive LPA results for all antigens, irrespective of the HIV patient status compared with ACD, but only for the candida and tetanus antigens and only in HIV-negative controls compared with heparin. Although HIV-infected patients had a significantly lower number of positive antigen-driven LPA responses compared with uninfected controls, most of the specimen processing variables had similar effects on HIV-positive and -negative samples. We conclude that LPA should be performed on site, whenever feasible, by using separated PBMC from fresh blood samples collected in either heparin or ACD. However, if on-site testing is not available, optimal transportation conditions should be established for specific antigens.
Adult↗
Expression of the peptide antibiotic human beta-defensin 1 in cultured gingival epithelial cells and gingival tissue.
Human beta-defensin-1 (hBD-1) is a member of the family of small cationic antimicrobial peptides that have been identified in several mucosal epithelia. Because human gingival epithelium is a site that is constantly challenged by oral microorganisms, we examined the expression of hBD-1 in human gingival epithelial and fibroblast cell cultures and tissue samples. Cell cultures were challenged with cell wall extracts of Porphyromonas gingivalis or Fusobacterium nucleatum, Escherichia coli lipopolysaccharide, tumor necrosis factor alpha, or phorbol myristate acetate. hBD-1 mRNA was detected in unstimulated and stimulated cultures by reverse transcription (RT)-PCR using several primer sets specific for hBD-1. Gingival epithelial cells, but not gingival fibroblasts, expressed a product of the predicted size for hBD-1 mRNA. The sequence of the PCR product was identical to that of hBD-1. hBD-1 mRNA expression was not significantly modulated by any of the stimulants tested. Human gingival tissues from noninflamed and inflamed sites were also analyzed by RT-PCR. hBD-1 mRNA was expressed in all tissue samples. The relative expression of hBD-1 mRNA was similar in noninflamed and inflamed tissues obtained from each of four patients undergoing treatment for periodontitis. However, the relative expression of hBD-1 mRNA varied in gingival biopsies obtained from 15 different normal individuals, and the relative hBD-1 expression was unrelated to interleukin-8 expression. Our findings show the constitutive expression of hBD-1 mRNA in cultured epithelial cells and gingival tissues but not gingival fibroblasts. These findings suggest that expression of hBD-1 may play a role as part of the innate host defenses in maintaining normal gingival health.
Adult↗
Evaluation of a commercial PCR kit for diagnosis of cytomegalovirus infection of the central nervous system.
We evaluated the AMPLICOR cytomegalovirus (CMV) PCR kit for the diagnosis of neurologic CMV infections on 43 positive and 112 negative archived cerebrospinal fluid specimens originally tested by an in-house PCR method. The AMPLICOR kit showed sensitivity and specificity of 95 and 100%, respectively, versus the home-grown assay, indicating its utility in this clinical setting.
Base Sequence↗
Flow cytometric determination of ganciclovir susceptibilities of human cytomegalovirus clinical isolates.
A flow cytometric assay has been developed for the measurement of susceptibilities to ganciclovir of laboratory strains and clinical isolates of human cytomegalovirus (HCMV). The assay uses fluorochrome-labeled monoclonal antibodies to HCMV immediate-early and late antigens to identify HCMV-infected cells and flow cytometry to detect and quantitate the number of antigen-positive cells. By this assay, the 50 and 90% inhibitory concentrations (IC50 and IC90, respectively) of ganciclovir for the AD169 strain of HCMV were 1.7 and 9.2 microM, respectively, and the IC50 for the ganciclovir-resistant D6/3/1 derivative of the AD169 strain was greater than 12 microM. The ganciclovir susceptibilities of 17 HCMV clinical isolates were also determined by flow cytometric analysis of the effect of ganciclovir on late-antigen synthesis in HCMV-infected cells. The average IC50 of ganciclovir for drug-sensitive HCMV clinical isolates was 3.79 microM (+/-2.60). The plaque-reduction assay for these clinical isolates yielded an average IC50 of 2.80 microM (+/-1.46). Comparison of the results of the flow cytometry assays with those obtained from the plaque-reduction assays demonstrated acceptable bias and precision. Flow cytometric and plaque-reduction analysis of cells infected with ganciclovir-resistant clinical isolates failed to show a reduction in the percentage of late-antigen-positive cells or PFU, even at 96 microM ganciclovir. The flow cytometric assay for determining ganciclovir susceptibility of HCMV is quantitative, and objective, and potentially automatable, and its results are reproducible among laboratories.
Antigens, Viral↗
Epithelial antimicrobial peptides: review and significance for oral applications.
Epithelial tissues provide the first line of defense between an organism and the environment. Disruption of this barrier leads to bacterial invasion and subsequent inflammation. This is precisely the situation existing in the human oral cavity, where tissues are constantly exposed to a variety of microbial challenges that can lead to bacterially induced periodontal diseases, and to infections of the oral mucosa by bacteria, fungi, and viruses. With the recent discoveries of host-derived peptide antibiotics in mammalian mucosal epithelium, a new line of investigation is emerging to test the hypothesis that one class of these peptides, called "beta-defensins", functions to protect the host against microbial pathogenesis at these critical, confrontational sites. In that light, impairment of beta-defensin activity has recently been implicated in chronic bacterial infections in cystic fibrosis patients. The first direct evidence of expression of defensin peptides in the oral mucosa was the identification of a novel epithelial beta-defensin in mammalian tongue. It was shown to be upregulated in inflammation, suggesting that it participates in host defense. It is theorized that epithelial cell-derived antimicrobial peptides function to keep the natural flora of micro-organisms in a steady state in different niches such as the skin, the intestines, the airway, the endocervix, and the mouth. There is now evidence indicating that normal gingival epithelial cells and tissues express two beta-defensins, hBD-1 and the newly described hBD-2. In addition, a cathelin-class antimicrobial peptide, designated LL-37 and found in human neutrophils, is also expressed in skin and gingiva. It is highly likely that these and/or other epithelial antimicrobial peptides play an important role in determining the outcome of the host-pathogen interaction at the oral mucosal barrier, and that they may have important future applications in antibiotic treatment.
Amino Acid Sequence↗
Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF.
OBJECTIVE: To determine the frequency of mild/atypical herpes simplex virus encephalitis (HSVE) among patients with CSF specimens submitted to a university diagnostic virology laboratory for HSV PCR. BACKGROUND: HSVE is the most commonly recognized cause of acute sporadic encephalitis in the United States. Recognized clinical features are based on autopsy- or brain biopsy-confirmed cases. This is likely to produce ascertainment bias for features associated with severe disease and under-recognition of mild or atypical cases. Amplification of HSV DNA by PCR from CSF provides a sensitive and specific method for diagnosis of HSVE. METHODS: Results of all HSV CSF PCR tests sent to a university diagnostic virology laboratory (January 1, 1993, to December 31, 1996) were reviewed. Clinical information was prospectively collected and retrospectively reviewed. Patients with positive HSV CSF PCR tests were classified as having meningitis, encephalitis, or neonatal infection. Encephalitis was considered typical or atypical based on published criteria. RESULTS: A total of 7.6% of 1,224 CSF specimens were positive for HSV DNA. CSF HSV DNA-positive patients had meningitis (52%), encephalitis (26%), neonatal infection (17%), or nonclassifiable disease (5%). A total of 17% of HSVE patients had mild or atypical disease characterized by the absence of focal findings and slow progression in the absence of antiviral therapy. Atypical HSVE was associated with HSV-2 infection (two of the four patients), immunosuppression by steroid therapy or coexisting HIV infection (three of the four patients), or disease predominantly involving the nondominant temporal lobe (two of the four patients). CONCLUSIONS: Approximately one-fifth of HSVE patients have mild or atypical disease. CSF PCR for HSV DNA should be performed in patients with febrile encephalopathy even in the absence of focal features, initial CSF pleocytosis, or abnormal CT. Mild or atypical HSVE may be associated with infection with either HSV-1 or HSV-2. Mild or atypical HSVE was frequently associated with immunocompromise or asymmetric HSV infection affecting predominantly the nondominant temporal lobe.
DNA, Viral↗
CSF and MRI findings in patients with acute herpes zoster.
OBJECTIVE: To explore MRI and CSF findings in patients with herpes zoster (HZ) and to correlate the findings with clinical manifestations of the disease. METHODS: Fifty immunocompetent patients (mean age, 59 years; range, 17 to 84 years) with HZ of fewer than 18 days duration participated. None had clinical signs of meningeal irritation, encephalitis, or myelitis. In 42 patients (84%), the symptoms constituted pain and rash only. Six patients (12%) had motor paresis, and three patients (6%) had ocular complications. One to three CSF samples were obtained from 46 patients (the first sampling taken 1 to 18 days from onset of rash), and 16 patients (all with either trigeminal or cervical HZ) underwent MRI of the brain. The clinical follow-up continued at least 3 months. RESULTS: CSF was abnormal in 28/46 patients (61%): pleocytosis (range, 5 to 1,440 microL) was detected in 21, elevated protein concentration in 12, varicella zoster virus (VZV) DNA in 10, and immunoglobulin G antibody to VZV in 10. These changes were more common in patients with acute complications, although they did not predict development of postherpetic neuralgia (PHN). In 9/16 patients (56%), MRI lesions attributable to HZ were seen in the brainstem and cervical cord. At 3 months, 5/9 patients (56%) with abnormal MRI had PHN, whereas none of the 7 patients with no HZ-related lesions on MRI had any remaining pain. CONCLUSIONS: Subclinical extension of viral inflammation into the CNS occurs commonly in HZ. This finding may have implications for treatment of HZ and prevention of various associated complications.
Acute Disease↗
Platelet transfusions are associated with the development of anti-major histocompatibility complex class I antibodies in patients with left ventricular assist support.
BACKGROUND: Preformed anti-human leukocyte antigen (HLA) antibodies delay heart transplantation in patients with left ventricular assist devices (LVAD) because of difficulty in finding crossmatch-negative donors. These antibodies may also be associated with adverse outcome after transplantation. METHODS: In a retrospective analysis of 40 patients with LVAD at Columbia-Presbyterian Medical Center between 1990 to 1996, age, sex, diagnosis, race, duration of support, transfusions, and infections were studied by univariate and multivariate analysis as predictors for development of either anti-HLA class I (anti-I) or anti-HLA class II (anti-II) immunoglobulin G (IgG) or M (IgM) antibodies. RESULTS: Eighteen (45%) patients had development of anti-I and 20 (50%) had development of anti-II antibodies over the study period. Median time for LVAD support was 142 days (range 35 to 439). Only total number of perioperative platelet transfusions predicted the development of anti-I IgG antibodies (p = .04). No other associations were found for development of anti-I IgM or anti-II antibodies of either IgG or IgM specificity. Patients who had development of anti-I IgG received a mean of 13.9 (SE +/- 2.6) units of platelets compared with a mean of 7.7 (SE +/- 2.3) units in those who did not (p = .01). By Kaplan-Meier analysis, at the median duration of follow-up, 8% of patients receiving < 6 units were predicted to have development of anti-I antibodies compared with 63% receiving > 6 units (p = .002). In the last 7 patients, leukocyte filters were used to decrease the antigenic load during platelet and red blood cell transfusions. Only 1 of 7 (14%) patients had development of anti-HLA antibodies compared with 31 of 33 (94%) in whom filters were not used (p < .005). CONCLUSIONS: These results indicate that platelet transfusion during LVAD implantation is a risk factor associated with development of HLA class I IgG antibodies. Use of leukocyte filters during platelet transfusion may decrease the risk of development of anti-HLA antibodies.
Antibody Formation↗
Does prior infection with varicella-zoster virus influence risk of adult glioma?
To evaluate a possible association between varicella-zoster virus infection and glioma, the authors asked adults with glioma (n = 462) whose tumors were diagnosed between August 1, 1991, and March 31, 1994, and age-, sex-, and ethnicity-matched controls (n = 443) about their histories of chickenpox or shingles. Cases were significantly less likely than controls to report a history of either chickenpox (odds ratio = 0.4, 95% confidence interval (CI) 0.3-0.6) or shingles (odds ratio = 0.5, 95% CI 0.3-0.8). To obtain serologic support for these findings, the authors conducted double-blind enzyme-linked immunosorbent assays for immunoglobulin G antibodies to varicella-zoster virus among 167 self-reporting subjects for whom blood samples were available. Cases and controls reporting no history of chickenpox were equally likely to test positive (73% vs. 75%), but among those reporting a positive history, cases were less likely than were controls to test positive (71% vs. 85%). Despite the misclassification, an odds ratio of 0.6 was obtained using either serologic data (95% CI 0.3-1.3) or reported history of chickenpox (95% CI 0.3-1.1) in this subgroup of subjects. This suggests that adults with glioma were less likely than controls either to have had prior varicella-zoster virus infection or to have an immunoglobulin G antibody response adequate to indicate positivity. Since either explanation suggests novel mechanisms for brain tumor pathogenesis, these findings require corroboration and elaboration.
Adult↗
Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM.
We report an association between X-linked immunodeficiency with hyper-IgM (XHIM) and carcinomas affecting the liver, pancreas, biliary tree, and associated neuroectodermal endocrine cells. The tumors were fatal in eight of nine cases and in most instances were preceded by chronic cholangiopathy and/or cirrhosis. An additional group of subjects with XHIM had chronic inflammation of the liver or bile ducts but no malignancy. Many patients with XHIM were infected with cryptosporidia. CD40 is normally expressed on regenerating or inflammed bile duct epithelium. A CD40+ hepatocellular carcinoma cell line, HepG2, susceptible to cryptosporidia and CMV infection became resistant when cell surface CD40 was cross-linked by a CD40 ligand fusion protein. Apoptosis was triggered in HepG2 cells if protein synthesis was blocked by cycloheximide or if the cells were infected by cryptosporidia. Ligation of CD40 on biliary epithelium may contribute to defense against infection by intracellular pathogens. We propose that the CD40 ligand mutations that cause XHIM deprive the biliary epithelium of one line of defense against intracellular pathogens and that malignant transformation in the biliary tree follows chronic infection or inflammation. The resulting tumors may then progress without check by an effective immune response. Patients with XHIM who have abnormal liver function tests should be considered at increased risk for cholangiopathy or malignancy.
Adolescent↗