Stage-directed treatment guidelines.
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Carcinoma, Non-Small-Cell Lung↗
Biomedical subjects
M Goldberg
Publications and source records attributed to M Goldberg.
Surgical approaches in special situations.
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Antineoplastic Combined Chemotherapy Protocols↗
Specific interchain cross-linking of antibodies using bismaleimides. Repression of ligand leakage in immunoaffinity chromatography.
The extensive use of antibody-containing affinity columns in the purification of biologically active compounds (e.g., genetically engineered proteins) is severely hampered by the leaching of antibody (or portions thereof) from the immunoaffinity resin during elution of the target antigen. One of the major problems in this context is the combined use of reducing (i.e., thiols) and chaotropic (e.g., detergents and denaturants) agents in the elution step, which causes the disassociation of heavy and/or light chains from the immobilized antibody, thereby contaminating the resultant product. In order to overcome this problem, we have cross-linked the four antibody chains at their sites of disulfide interlinkage, thus producing a single antibody chain. To accomplish this, interchain disulfide bonds were reduced, and the resultant thiol groups were cross-linked by using bifunctional SH-specific reagents (particularly bismaleimides). Cross-linking of up to 95% of the available SH groups produced was achieved with concomitant retention of antigen-binding activity. The cross-linked antibody was immobilized onto CNBr-activated Sepharose, and the resultant column was found to be substantially more stable to harsh elution conditions than similar columns which contain the un-cross-linked antibody.
Antibodies↗
Factors affecting plasma bilirubin in preterm infants ventilated for respiratory distress syndrome.
OBJECTIVE: To evaluate the contribution of various factors to plasma bilirubin level in preterm infants with a birth weight of < 1500 gm in need of mechanical ventilation for respiratory distress syndrome (RDS) during their first week of life. METHODOLOGY: A total of 50 very low birth weight (< 1500 gm) preterm infants consecutively admitted to the neonatal intensive care unit were studied. Plasma bilirubin levels were determined every 8 hours for the first week of life. Data relating to daily body weight, daily fluid intake, age at onset of gavage feeds, daily caloric intake, and grade of intraventricular hemorrhage (IVH) were collected. Data relating to mechanical ventilation were collected every 4 hours as follows: fractional inspired O2, arterial PO2, arterial PCO2, and mean airway pressure. An arterial/alveolar PO2 ratio and a corrected oxygenation index were computed for the first 2 days of life. A bilirubin index (BI), defined as the ratio of peak plasma bilirubin level to birth weight1/3, was used to study the association between bilirubin and the above variables. A BI was also used as a criterion for starting and discontinuing phototherapy. Multiple linear regression analysis was used to model BI. RESULTS: IVH (p < 0.0001), age at onset of gavage feeds (p < 0.003), oxygenation index (p < 0.007), and gestational age (p < 0.05) made a significant contribution to variations in BI (37.16%, 43.71%, 48.99%, and 53.33%, respectively). CONCLUSION: Hyperbilirubinemia in ventilated preterm infants with RDS is most likely multifactorial; entities quite distinct from RDS (such as nutrition and IVH) may significantly contribute to its variation.
Aging↗
Geographical distribution of respiratory cancer in New Caledonia.
All cases of primary respiratory cancers diagnosed between 1/1/78 and 12/31/81 in the French territory of New Caledonia, where nickel has been mined and smelted for more than one hundred years, were recorded. The successive addresses of each case were noted. The distribution of stays between mining zones and others was compared to an expected distribution based on censuses. A significant excess was observed in mining zones, both for the number of stays and for the number of person-years. The excess was observed for primary lung cancer only. The data seem to indicate that people with lung cancer have spent a larger part of their life in a mining zone. The reason for that phenomenon cannot, however, be assessed clearly. This could be due to the geographical environment, i.e., the presence of nickel and asbestos in the soil of some parts of the territory; the observed relationship could also be due, in part, to the effects of urbanization leading to increased tobacco consumption.
Epidemiologic Methods↗
Incidence of pleural mesothelioma in New Caledonia: a 10-year survey (1978-1987).
All cases of primary pleural cancers that were reported during a 10-y period (i.e., 1978-1987) in New Caledonia were recorded and compared with five cancer registers. There was an excess of primary pleural cancers in the area of New Caledonia, and it was particularly evident among the Melanesian ethnic group. Neither geographical nor occupational factors accounted for these results, but an environmental factor could not be excluded.
Adult↗
Reanalysis of the Harvard Six Cities Study, part I: validation and replication.
Because the results of the Harvard Six Cities Study played a critical role in the establishment of the current U.S. ambient air quality objective for fine particles (PM(2.5)), the U.S. Environmental Protection Agency, industry, and nongovernmental organizations called for an independent reanalysis of this study to validate the original findings reported by Dockery and colleagues in the New England Journal of Medicine (vol. 329, pp. 1753-1759) in 1993. Validation of the original findings was accomplished by a detailed statistical audit and replication of original results. With the exception of occupational exposure to dust (14 discrepancies of 249 questionnaires located for evaluation) and fumes (15/249), date of death (2/250), and cause of death (2/250), the audit identified no discrepancies between the original questionnaires and death certificates in the audit sample and the analytic file used by the original investigators. The data quality audit identified a computer programming problem that had resulted in early censorship in 5 of the 6 cities, which resulted in the loss of approximately 1% of the reported person-years of follow-up; the reanalysis team updated the Six Cities cohort to include the missing person-years of observation, resulting in the addition of 928 person-years of observation and 14 deaths. The reanalysis team was able to reproduce virtually all of the original numerical results, including the 26% increase in all-cause mortality in the most polluted city (Stubenville, OH) as compared to the least polluted city (Portage, WI). The audit and validation of the Harvard Six Cities Study conducted by the reanalysis team generally confirmed the quality of the data and the numerical results reported by the original investigators. The discrepancies noted during the audit were not of epidemiologic importance, and did not substantively alter the original risk estimates associated with particulate air pollution, nor the main conclusions reached by the original investigators.
Air Pollutants↗
Reanalysis of the Harvard Six Cities Study, part II: sensitivity analysis.
Following the validation and replication of the Harvard Six Cities Study (Krewski et al., this issue), we conducted a wide range of sensitivity analyses to explore the observed associations between long-term exposure to fine particle or sulfate air pollution and mortality. We examined the impact of alternative risk models on estimates of risk, taking into account covariates not included in the original analyses. These risk models provided a basis for identifying covariates that may confound or modify the association between fine particle or sulfate air pollution and mortality, and for identifying sensitive population subgroups. The possibility of confounding due to occupational exposures was also investigated. Residence histories were coded for the study subjects and were used to examine temporal patterns of exposure and risk. Our sensitivity analyses showed the mortality risk estimates for fine particle and sulfate air pollution to be highly robust against alternative risk models of the Cox proportional hazards family, including models with additional covariates from the original questionnaires not included in the original published analyses. There was limited evidence of departures from the proportional hazards assumption. Flexible exposure-response models provided some evidence of departures from linearity at both low and high sulfate concentrations. Incorporating information on changes over time in cigarette smoking and body mass index had little effect on the association between fine particles and mortality. There was limited evidence of variation in risk with attained age, gender, smoking status, occupational exposure to dust and fumes, marital status, heart or lung diseases, or lung function. However, air pollution risk did appear to decreasing with increasing educational attainment. Extensive adjustment for occupation using aggregate indices of occupational "dirtiness" and occupational exposure to known lung carcinogens had little impact on the mortality risks associated with particulate air pollution. Our evaluation of population mobility indicated that relatively few subjects moved from their original city of residence. Attempts to identify critical exposure time windows were limited by the lack of marked interindividual variation in temporal exposure patterns throughout the study period. Overall, this extensive sensitivity analysis both supported the conclusions reached by the original investigators and demonstrated the robustness of these conclusions to alternative analytic approaches.
Age Factors↗
Effects of halothane anesthesia on renal function in normal man.
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Adult↗
Adjunctive clonazepam treatment of tic symptoms in children with comorbid tic disorders and ADHD.
The treatment of seven children and adolescents with a tic disorder and concomitant attention-deficit hyperactivity disorder (ADHD) is reviewed. Symptoms of ADHD were treated successfully with clonidine; however, patients experienced persistent tics. The patients were treated with the adjunctive use of clonazepam. The addition of clonazepam resulted in a further decrease in tic frequency and severity without affecting the coexisting ADHD symptoms. These cases suggest that clonazepam may be a useful adjunctive pharmacological intervention in treating tics in children with comorbid ADHD.
Adolescent↗
Improved burn scar assessment with use of a new scar-rating scale.
The subjective assessment of scar appearance is a widely used method in the evaluation of burn outcomes and the efficacy of treatment methods. The purpose of this study is to design a numeric scar-rating scale with better interrater reliability than has previously been reported. The rating scale assesses scar surface, thickness, border height, and color differences between a scar and the adjacent normal skin. Eight raters were trained with use of a standardized set of photographs that provide examples of the scores to be assigned to each level of severity of each scar characteristic. The raters then rated 10 photographs of different scars, referring to the teaching set of pictures for comparison. The intraclass correlation (interrater reliability) was 0.94, 0.95, 0.90, and 0.85 for scar surface, border height, thickness, and color, respectively. This rating system has proved to be a useful tool for the evaluation of scar surface, thickness, border height, and color.
Burns↗
Apoptosis in human and rat dental pulp.
Apoptotic cells were visualized in human premolar and rat molar pulps using either the TUNEL method, which stains DNA strand breaks by in situ nick end labeling, or labeling sections with an anti-transglutaminase antibody. Apoptotic cells were evident at the periphery of the pulp, mostly in a sub-odontoblastic location, and were more numerous in the crown than in the root region of the pulp. Most odontoblasts were unlabeled. A few apoptotic nuclei in the pulp of rat molars displayed the characteristics of chromatin condensation, as observed by electron microscopy. Many cell debris resembling apoptotic bodies were also observed. The 3 methods support the occurrence of apoptosis in the dental pulp. As this phenomenon was observed in healthy teeth apoptosis is probably involved in the regulation of the pulp cell population.
Animals↗
A dose-escalation study of large doses of naloxone for treatment of patients with acute cerebral ischemia.
A dose-escalation study was performed in 27 patients to determine the highest safe and potentially optimal dose of naloxone for treatment of acute cerebral ischemia. All patients received a bolus of naloxone followed by a continuous 24 hour infusion at an hourly rate 50% of the bolus. Loading doses ranged from 2.5 to 200 mg/m2. Total patient doses ranged from 52.3 to 4978 mg. No major dose-related side effects occurred. This study was not designed to determine naloxone's efficacy in stroke, but transient or sustained improvement was observed in 13 patients. Three patients' neurological condition worsened within three hours after the naloxone was discontinued. Our experience suggests that further therapeutic trials of naloxone are worthwhile.
Acute Disease↗
Preincubation with intravenous lipid emulsion reduces chemotactic motility of neutrophils in cord blood.
Neutrophils from cord blood of healthy term infants were isolated and incubated for 30 min with varying concentrations of intravenous lipid emulsion (ILE) solution (4, 8, 20 mg/ml). In vitro assay of chemotaxis was performed after incubation for 120 min with endotoxin-activated serum (EAS). Neutrophil random motility was unchanged after ILE incubation yet chemotactic factor (EAS)-stimulated motility was significantly reduced in a dose-related pattern.
Cell Movement↗
Multimodality therapy in surgically resectable early non-small cell lung cancer.
Lung cancer is a global epidemic. Unfortunately only a fraction of patients can undergo curative surgery and in these, only one-third survive five years. The remainder die of locoregional and distant metastatic disease. With advances in chemotherapy for systemic control and radiation therapy for local control, responses and survivals have shown promise in extensive inoperable disease. In order to attempt to extend survival in extensive local but operable disease (Stage IIIa), these treatment modalities were added to the surgical regimen either before (neoadjuvant, induction) or after (adjuvant) surgery. Several small phase III trials substantiated the benefits. Since early lung cancer (Stage I and II) recur in 30% of instances to distant sites as well as regionally, multimodality therapies have recently been encouraged in global trials in an attempt to prolong time to recurrence and survival in this latter group of patients. A review follows:
Carcinoma, Non-Small-Cell Lung↗
[Consensus on antimicrobial sensitivity tests in gram-positive cocci. Subcommittee on Antimicrobials, SADEBAC (Argentinian Society of Clinical Bacteriology), Argentinian Association of Microbiology].
Antimicrobial susceptibility testing is mainly performed in Argentina by disk diffusion method, following National Committee for Clinical Laboratory Standards (NCCLS) recommendations. We worked out new recommendations for the reporting and interpretation of this test when dealing with gram-positive cocci, in accordance to local trends and epidemiology. General considerations for performing the diffusion assay, quality control, and an update on susceptibility testing for gram-positive cocci are reported in this first document. The present update should be considered as a group of recommendations summarized by Argentinean experts and as the result of a consensus meeting coordinated by the Subcomisión de Antimicrobianos of the Sociedad Argentina de Bacteriología Clínica (Asociación Argentina de Microbiología). Experts in antimicrobial agents were convened in order to prepare this final document. These recommendations take into account local needs, affordability and availability to be used in current practice, tending to contribute to the correct antimicrobial treatment election, according to the particular microorganism and the infection sites.
Algorithms↗
[Consensus for antimicrobial susceptibility testing for Enterobacteriaceae. Subcommittee on Antimicrobials, SADEBAC (Argentinian Society of Clinical Bacteriology), Argentinian Association of Microbiology].
Taking into account previous recommendations from the National Committee for Clinical Laboratory Standards (NCCLS), the Antimicrobial Committee, Sociedad Argentina de Bacteriología Clínica (SADEBAC), Asociación Argentina de Microbiología (AAM), and the experience from its members and some invited microbiologists, a consensus was obtained for antimicrobial susceptibility testing and interpretation in most frequent enterobacterial species isolated from clinical samples in our region. This document describes the natural antimicrobial resistance of some Enterobacteriaceae family members, including the resistance profiles due to their own chromosomal encoded beta-lactamases. A list of the antimicrobial agents that should be tested, their position on the agar plates, in order to detect the most frequent antimicrobial resistance mechanisms, and considerations on which antimicrobial agents should be reported regarding to the infection site and patient characteristics are included. Also, a description on appropriate phenotypic screening and confirmatory test for detection of prevalent extended spectrum beta-lactamases in our region are presented. Finally, a summary on frequent antimicrobial susceptibility profiles and their probably associated resistance mechanisms, and some infrequent antimicrobial resistance profiles that deserve confirmation are outlined.
Anti-Bacterial Agents↗
[Arterial hypertension in Thio (New Caledonia)].
The high blood pressure is one of the main cardiovascular risk factors in New Caledonia as it is every where. A study carried out in THIO from August 1985 to August 1988 displayed a frequency and a seriousness not frequent (17.8 p.c. of hypertensives in the population over 30 years of age by applying strict criteria), noticeably in the Melanesian ethnic group and mainly in the women. Such a result ought to instigate complementary epidemiological surveys, but also to urge on an active policy of screening, prevention and treatment.
Adult↗