Prognostic factors in patients with surgically resected stages I and II non-small cell lung cancer.

BACKGROUND: About one-third to one-half of patients with early stages of non-small cell lung cancer (NSCLC) succumb to their disease. In this study, we attempted to identify prognostic factors that predict outcome in patients with stages I and II NSCLC. METHODS: A retrospective evaluation of 454 patients with surgically resected stages I and II NSCLC was performed to determine the impact of various clinical, laboratory, and pathological factors on patient outcome such as overall survival (OS) and event-free survival (EFS). RESULTS: Patients older than 65 years had shorter EFS and OS than younger patients (p = 0.002). Patients with preoperative hemoglobin less than or equal to 10 g% had shorter EFS and OS compared to patients with a hemoglobin greater than 10 g% (p = 0.001). Expectedly, OS and EFS were shorter in patients with stage II as compared to stage I patients (p < 0.001). In a multivariate analysis, age, hemoglobin level, and stage remain significant predictors for EFS and OS. CONCLUSIONS: Older age, anemia, and higher stage are important prognostic factors in patients with surgically resected stage I and II NSCLC.

Antagonism of cortical excitation of striatal neurons by glutamic acid diethyl ester: evidence for glutamic acid as an excitatory transmitter in the rat striatum.

Rat striatal cells that were excited by cortical stimulation were found to respond to cortical stimulation with an average latency of 12 msec. Each response consisted of a variable number of spikes with, on the average, a less than 1:1 relationship between the stimulus and the number of spikes generated. Iontophoretic application of glutamic acid diethyl ester (GDEE), a substance reported to be a glutamate antagonist, at currents of +50 to +125 nA in the vicinity of neurons exicted by cortical stimulation, almost totally suppressed the excitation in 90% of the cells, and this suppression was fully reversible. All cells were excited by glutamate. GDEE also suppressed neuronal excitation produced by iontophoretic aspartate, glutamate and DL-homocysteic acid. It is concluded from this study that an excitatory amino acid, either aspartic or glutamic, may function as the transmitter in the corticostriate projection.

Mass spectographic analysis of stimulated release of endogenous amino acids from rat hippocampal slices.

Amino acids released from in vitro rat hippocampal slices following stimulation of the Schaffer's collateral pathway, were collected by micro-perfusion and analysed by chemical ionization mass spectrometry, with isotope ratiodetermination as the quantitative technique, through the use of stable, isotopically labeled internal standards. Stimulation at 10 pulses/sec resulted in a doubling of the release of aspartic acid over the resting level and about a 60% increase in glutamate release, which is in essential agreement with studies utilizing K+ depolarization-evoked release from slices.

GDEE antagonism of iontophoretic amino acid excitations in the intact hippocampus and in the hippocampal slice preparation.

Glutamic acid diethylester (GDEE) reversibly antagonized excitations produced by glutamate and aspartate but not those produced by acetylcholine when applied iontophoretically to rat CA1 hippocampal neurons in penthrane (methoxyfluorane) anesthetized rats and to CA1 neurons in in vitro slice preparations. GDEE did not appear to differentiate between the excitations produced by glutamate aspartate and appeared to be a more potent antagonist than has previously been reported. CA1 cells were remarkably sensitive to acetylcholine; 5-50 nA being sufficient to produce marked amino acid-like excitations, which were unrelated to the pH of the acetylcholine. The nature of the responses to applied substances was virtually identical between the intact animal and the in vitro slice preparation. A description of the in vitro technique is given as an Appendix.

Diurnal blood pressure patterns in normotensive and hypertensive children and adolescents.

As abnormalities in diurnal ambulatory blood pressure (BP) have been associated with hypertensive target organ damage in adults, we investigated the diurnal systolic BP (SBP) and diastolic BP (DBP) patterns of 54 normotensive children, age 13.4 +/- 3.0 years, and 45 untreated borderline and mildly hypertensive children, age 14.4 +/- 2.6 years. Subjects wore the SpaceLabs 90207 ambulatory BP monitor for 24 h. BP was measured q 15 min from 08.00-21.00 h then q 30 min from 21.00-08.00 h. Nocturnal BP fall, the night-day ratio and cusum derived measures were calculated from time-weighted daytime and night-time SBP and DBP. The groups were compared using analysis of covariance with adjustment for age, race, gender and body mass index. The influence of age, gender and race on the diurnal BP profile was also examined. Nocturnal SBP fall was greater in hypertensive compared to normotensive subjects (17.1 +/- 6.7 vs 14.6 +/- 7.1 mm Hg; unadjusted mean +/- s.d., P = 0.022). Normotensive and hypertensive groups did not differ in nocturnal DBP fall or SBP or DBP night-day ratio. Race appeared to influence the diurnal BP pattern as black subjects had less nocturnal SBP fall (12.9 +/- 6.9 vs 17.1 +/- 6.5 mm Hg; P < 0.005) and a higher night-day SBP ratio (90.1 +/- 5.3 vs 86.7 +/- 4.6%; P < 0.005) than white subjects. In conclusion, hypertensive children and adolescents have a similar diurnal BP pattern as their normotensive counterparts, except that the entire BP profile is shifted upward with a greater absolute fall in SBP at night. Race also appears to influence the diurnal BP profile of normotensive and hypertensive children and adolescents.

Advanced prostate cancer activates coagulation: a controlled study of activation markers of coagulation in ambulatory patients with localized and advanced prostate cancer.

Cancer and increased age are risk factors for coagulation activation. Patients with advanced prostate cancer, which usually presents in the seventh to eighth decade of life, are likely to be at increased risk for thrombosis. We report results of a controlled study of changes in specific and sensitive markers of coagulation activation in patients with prostate cancer. Complete blood count, prothrombin time, partial thromboplastin time, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT) and quantitative D-dimers (DD) were measured in 30 patients of advanced prostate cancer (androgen ablated), in 30 newly diagnosed localized prostate cancer patients, in 30 healthy age-matched volunteers, and in 20 healthy young volunteers. Plasma F1 + 2 (P < 0.05) and DD (P < 0.05), but not TAT, were significantly elevated in healthy elderly males (mean age, 77 years) when compared with healthy young volunteers (mean age, 35 years). F1 + 2, TAT and DD were significantly elevated in advanced prostate cancer when compared with healthy age-matched controls (P < 0.001). In conclusion, advanced prostate cancer patients have significantly increased levels of sensitive markers of coagulation activation compared with healthy age-matched controls. This data can be used to plan studies to determine the risk of clinically significant coagulopathy and the role of primary prophylaxis in patients with advanced prostate cancer.

Femoral strength is better predicted by finite element models than QCT and DXA.

Clinicians and patients would benefit if accurate methods of predicting and monitoring bone strength in-vivo were available. A group of 51 human femurs (age range 21-93; 23 females, 28 males) were evaluated for bone density and geometry using quantitative computed tomography (QCT) and dual energy X-ray absorptiometry (DXA). Regional bone density and dimensions obtained from QCT and DXA were used to develop statistical models to predict femoral strength ex vivo. The QCT data also formed the basis of a three-dimensional finite element (FE) models to predict structural stiffness. The femurs were separated into two groups; a model training set (n = 25) was used to develop statistical models to predict ultimate load, and a test set (n = 26) was used to validate these models. The main goal of this study was to test the ability of DXA, QCT and FE techniques to predict fracture load non-invasively, in a simple load configuration which produces predominantly femoral neck fractures. The load configuration simulated the single stance phase portion of normal gait; in 87% of the specimens, clinical appearing sub-capital fractures were produced. The training/test study design provided a tool to validate that the predictive models were reliable when used on specimens with "unknown" strength characteristics. The FE method explained at least 20% more of the variance in strength than the DXA models. Planned refinements of the FE technique are expected to further improve these results. Three-dimensional FE models are a promising method for predicting fracture load, and may be useful in monitoring strength changes in vivo.

An automatic, optically isolated, biphasic constant current stimulator adapter for artefact suppression.

A stimulator adapter is described that automatically generates true biphasic constant current pulses from the single pulse output of a standard stimulator. Variations in the width or amplitude of the driving pulse are automatically duplicated in the biphasic pulses generated, permitting great ease of control of stimulating parameters. The device is simple, small in size and has a low current drain, permitting battery operation.

Local erythema multiforme-like drug reaction following intravenous mitomycin C and 5-fluorouracil.

A localized skin reaction occurred within 4 weeks following IV administration of mitomycin C and 5-FU. Erythematous papules appeared proximal to the forearm site used for drug administration that histologically resembled an erythema multiforme-like drug reaction. A localized hypersensitivity reaction to mitomycin C is suspected.

A microvolume molecular filter.

A microvolume polymer membrane filter based on Amicon hollow fibers in described which permits separation of low molecular weight compounds from proteins, and can be used for desalting volumes of 100 microliter or less, or to separate cellular protein debris from perfusates during release studies. The filter has the advantage of being reusable and having almost no void volume.

Prospective study of circulating angiogenic markers in prostate-specific antigen (PSA)-stable and PSA-progressive hormone-sensitive advanced prostate cancer.

OBJECTIVES: To prospectively describe and compare circulating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in two groups of advanced prostate cancer patients undergoing androgen deprivation. The first patient group (n = 21) consisted of patients with stable serum prostate-specific antigen (PSA) and the second group (n = 20) consisted of patients with a rising serum PSA during androgen deprivation. METHODS: Patients with diabetes or active heart disease or those receiving anticoagulants were excluded. Circulating VEGF and bFGF were measured in platelet-poor plasma. bFGF was also measured in urine. Platelet factor 4 protein (PF4) assays were performed to evaluate platelet activity in platelet-poor plasma samples. Commercially available enzyme-linked immunosorbent assay kits were used for all assays, and all tests were performed in duplicate. RESULTS: The median age of this study population was 75 years (range 58 to 85). Median plasma VEGF measured in the PSA-stable group was 801.5 pg/mL and in the PSA-rising group was 655.5 pg/mL (P = 0.464). Circulating bFGF was undetectable in plasma, but 4 patients in the PSA-stable group had measurable urine levels. Platelet-poor plasma PF4 assays in all patients were less than 3 IU/mL (normal range 0 to 10). CONCLUSIONS: Our pilot study suggests elevated plasma VEGF levels in advanced prostate cancer do not increase during failure of androgen deprivation therapy. Most of the advanced cancer patients in this study expressed plasma VEGF. This suggests its potential role as a surrogate marker for response assessment during antiangiogenic therapy in this stage.

Evaluation of four newer antimicrobial agents in the Avantage susceptibility test system.

Antimicrobial elution disks containing amoxicillin-clavulanic acid (Augmentin), cefotetan, ciprofloxacin, or norfloxacin were tested in the Avantage automated susceptibility test system. Performance was compared against an agar diffusion procedure in a three-site collaborative study. Results of 1,500 comparison with amoxicillin-clavulanic acid showed a full accord (agreement of both systems) of 93.6% and an essential accord (agreement excluding minor discrepancies) of 97.6%. Results for cefotetan showed a full accord of 95.1% and an essential accord of 98.3% by the two methods. Results for both ciprofloxacin and norfloxacin were in full accord for more than 98% of tests with gram-negative bacilli and staphylococci, but tests with enterococci gave 38 and 26.1% minor discrepancies (the result of one method was resistant or susceptible and the result of the other method was intermediate), respectively. The results indicated that the Avantage test system is accurate and reliable and provides appropriate determination of bacterial susceptibility with the four antibiotics tested.

IgG anticardiolipin antibody titer > 40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study.

BACKGROUND: Anticardiolipin antibodies (aCL) have been associated with an increased risk of stroke and thrombo-occlusive events. Little is known about the influence of aCL on recurrent thrombo-occlusive events. METHODS: Consecutively identified patients (n = 132) with focal cerebral ischemia [stroke = 112, transient ischemic attack (TIA) = 20] harboring aCL of at least 10 GPL units at the time of their index event were prospectively followed to estimate the effect of aCL titer on time to and risk of subsequent thrombo-occlusive events (stroke, TIA, deep venous thrombosis, pulmonary embolism, myocardial infarction) and death. On the basis of prior literature, we divided patients into those with aCL < or = 40 GPL (n = 111; mean age, 63 +/- 14 years; mean follow-up, 1.95 years) and those with aCL > 40 GPL (n = 21; mean age, 54 +/- 20 years; mean follow-up, 1.50 years). RESULTS: There was no difference between groups for prevalence of hypertension, diabetes mellitus, cigarette smoking, atrial fibrillation, prior TIA, or sex. The GPL > 40 group was younger (54 +/- 20 versus 63 +/- 14 years; P = .055), had more prior strokes [9/21 (48%) versus 27/111 (20%); P = .030], more frequent subsequent thrombo-occlusive events and death [15/21 (71%) versus 51/111 (48%); P = .030], and a shorter median time (years) to event (0.15 versus 0.61, log rank P = .005). The risk ratio for recurrent event and death with GPL > 40 obtained from Cox proportional hazards models, adjusted for prior strokes, prior TIAs, hypertension, diabetes mellitus, atrial fibrillation, and cigarette smoking was 1.9 (95% confidence interval, 1.0 to 3.5; P = .051). CONCLUSIONS: Our data suggest that subsequent thrombo-occlusive events and death after focal cerebral ischemia associated with IgG aCL may occur sooner and more frequently with GPL > 40.

Clinical laboratory evaluation of the Abbott MS-2 automated antimicrobial susceptibility testing system: report of a collaborative study.

The MS-2 system (Abbott Diagnostics, Division of Abbott Laboratories, Dallas, Tex.) was evaluated for its efficacy in determining the susceptibilities of both clinical and selected challenge (nonfastidious, facultative, and aerobic) isolates. The MS-2 results were compared with standard Kirby-Bauer disk diffusion and microdilution results by using fresh clinical isolates. For gram-positive isolates other than enterococci, overall agreement between MS-2 and reference results was 93 to 98%. With enterococci, MS-2 agreement with disk diffusion was 68% but with microdilution was 86% (agreement between disk diffusion and microdilution was 73%). The main discrepancies with enterococci were with cephalothin, penicillin, gentamicin, and kanamycin. With clinical gram-negative isolates, the overall agreement was 91 to 93%, with most discrepancies occurring with Enterobacter spp. and beta-lactam antibiotics (MS-2 versus disk diffusion, 84%; MS-2 versus microdilution, 84%; disk diffusion versus microdilution, 87%) and with Serratia spp. and colistin (false-susceptible results). The agreement of MS-2 results with established reference antibiograms of a special collection of challenge strains was 91 to 97% for the gram-positive cocci and 86 to 98% for the gram-negative strains. (With Enterobacter spp., agreement was 86%, but was greater than 90% for all other organism groups.) Of the 98 finite MS-2 minimum inhibitory concentrations (MICs) that could be directly compared with microdilution MICs, 77 (79%) were within +/- 1 well of the geometric mean microdilution MIC. MS-2 analysis time ranged from 2.8 to 6.5 h (mean, 4.2 h). On the basis of these results, we conclude that the MS-2 can be expected to yield rapid and accurate results with most nonfastidious, facultative, and aerobic pathogens.

Molecular epidemiologic surveillance of salmonellosis in Arkansas.

OBJECTIVES: Salmonella serotype Newport and Salmonella serotype Typhimurium are the most commonly identified serotypes of Salmonella causing human disease in the state of Arkansas. The purpose of our study was to compare the results of standard and molecular epidemiologic methods of investigating human salmonellosis cases due to Salmonella serotype Newport and Salmonella serotype Typhimurium. METHODS: All isolates of Salmonella serotype Newport and Salmonella serotype Typhimurium collected and submitted to the Arkansas Department of Health between July 1, 1997 and June 30, 1998 were gathered and underwent pulsed-field gel electrophoresis (PFGE). Patients from whom the isolates were collected were contacted and completed a questionnaire. RESULTS: There were 84 patients from whom Salmonella serotype Newport was isolated and 83 from whom Salmonella serotype Typhimurium was isolated during the study period. In the 124 patients (74%) who completed the questionnaire, Salmonella serotype Newport was more likely to be the infecting agent in younger, white, and pet-owning patients (P < 0.05). The use of PFGE confirmed that approximately 20% of the organisms had genetic fingerprint patterns identical to those of at least one other individual in the state. One third of the patients from whom these isolates were obtained were linked by standard epidemiologic methods. CONCLUSIONS: The use of PFGE on our state's most common isolates provides additional confirmation that despite being linked by time of onset and location of residence, the majority of the human salmonellosis cases in our region are still sporadic. Low-level, intermittent transmission of these organisms through environmental contamination and contact with asymptomatically infected individuals would be likely vehicles of transmission in our state. Molecular techniques are important in surveillance systems that investigate human salmonellosis. Eighty-one percent of the Salmonella serotype Newport and 92% of the Salmonella serotype Typhimurium cases that appeared to be outbreak-related based upon time of onset and location were actually found not to be outbreak-related by PFGE. Using techniques such as PFGE will allow for more focused evaluations of potential outbreaks and will save the already limited financial and human resources that would otherwise be spent on investigations that are not warranted.

Enhancement of immunity against murine syngeneic tumors by a fraction extracted from non-pathogenic mycobacteria.

The data reported here demonstrate that a preparation extracted from nonpathogenic mycobacteria such as Mycobacterium smegmatis and hereafter referred to as interphase material protected mice against Ehrlich ascitic carcinoma, L-1210 leukemia, and another syngeneic lymphoid leukemia. Furthermore, mice treated by this preparation were much less susceptible to endotoxins than when stimulated by BCG (bacillus Calmette-Guerin) or M. smegmatis cells. Moreover, guinea pigs treated by interphase material administered in Freund's incomplete adjuvant showed an increased immune response, yet their sensitivity to tuberculin was much weaker than that of controls sensitized with Freund's complete adjuvant. Finally, resistance to Columbia SK virus infection could be demonstrated when interphase material was administered to mice prior to virus challenge.

Racial differences in breast cancer survival: the effect of residual disease.

BACKGROUND: A survival difference has been seen in numerous studies between African-American (AA) and Caucasian (C) women with breast cancer. The purpose of this study was to elucidate the differences in patient characteristics and outcomes between AA and C women with breast cancer in our population. METHODS: We performed a retrospective analysis of 1345 women with newly diagnosed breast cancer who were entered into our tumor registry from October 1980 to December 1998. RESULTS: The association between race and stage at presentation was significant, as was the difference in the overall median survival between C and AA women. The data revealed no significant differences in survival between C and AA women presenting with Stage I or II disease. However, the differences between the median survival times for AA and C women presenting with Stage III and IV disease were both highly significant. A significantly lower percentage of AA women became "disease free" after initial therapy as compared with C women (P < 0.001). Interestingly, when data were stratified by stage, only in Stage III and IV were there significant differences between the races for becoming disease free. CONCLUSIONS: AA women tend to present at a later stage and have poorer survival from later-stage disease as compared with C women. The poorer survival appears to be related to the decreased ability to achieve disease-free status in AA women with advanced disease. The underlying causes of this difference in treatment outcome need further evaluation.