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1.
Int J Cosmet Sci ; 39(5): 500-510, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28488331

ABSTRACT

OBJECTIVE: Terminalia ferdinandiana extracts are potent growth inhibitors of many bacterial pathogens. They may also inhibit the growth of malodour-producing bacteria and thus be useful deodorant components, although this is yet to be tested. METHODS: Terminalia ferdinandiana fruit and leaf solvent extracts were investigated by disc diffusion and liquid dilution MIC assays against the most significant bacterial contributors to axillary and plantar malodour formation. Toxicity was determined using the Artemia franciscana nauplii bioassay. Non-targeted HPLC separation of the methanolic leaf extract coupled to high-resolution time-of-flight (TOF) mass spectroscopy was used for the identification and characterization of individual components in the extract. RESULTS: The T. ferdinandiana leaf extracts were the most potent bacterial growth inhibitors. The leaf methanolic extract was particularly potent, with low MIC values against C. jeikeium (233 µg mL-1 ), S. epidermidis (220 µg mL-1 ), P. acnes (625 µg mL-1 ) and B. linens (523 µg mL-1 ). The aqueous and ethyl acetate leaf extracts were also potent growth inhibitors of C. jeikeium and S. epidermidis (MICs < 1000 µg mL-1 ). In comparison, the fruit extracts were substantially less potent antibacterial agents, although still with MIC values indicative of moderate growth inhibitory activity. All T. ferdinandiana leaf extracts were non-toxic in the Artemia franciscana bioassay. Non-biased phytochemical analysis of the methanolic leaf extract revealed the presence of high levels of and high diversity of tannins and high levels of the flavone luteolin. CONCLUSION: The low toxicity of the T. ferdinandiana leaf extracts and their potent growth inhibition of axillary and plantar malodour-producing bacteria indicate their potential as deodorant components.


Subject(s)
Bacteria/drug effects , Deodorants/pharmacology , Odorants , Plant Extracts/pharmacology , Terminalia/chemistry , Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Bacteria/growth & development , Bacteria/metabolism , Chromatography, High Pressure Liquid , Humans , Mass Spectrometry , Microbial Sensitivity Tests
2.
Dis Esophagus ; 26(5): 457-64, 2013 Jul.
Article in English | MEDLINE | ID: mdl-22676713

ABSTRACT

Fistula formation between the pericardium and the gastrointestinal tract is rare. Enteropericardial fistulae may present dramatically, many have prodromal symptoms even though they are not symptoms usually associated with esophageal disease. Prompt diagnosis and expedient surgery can result in survival. We describe three cases of enteropericardial fistulae diagnosed during emergency surgery for sepsis or hemorrhage. All had previous surgery though the details were not available to the operating surgeons because of the time that had passed since their original operation. All three patients survived, albeit with prolonged hospital stay and repeated surgery. A review of the English language literature revealed 95 cases (Table 1). Fifty-eight had a history of previous surgery, particularly fundoplication or esophagectomy. Ten had advanced malignancy and were treated conservatively. All eight patients with fistulae, which were iatrogenic or due to foreign bodies, survived without aggressive surgery. For more extensive pathology, a successful outcome was achieved in 32 of the 36 cases when the upper gastrointestinal (GI) tract was defunctioned because of the presence of major sepsis or because the healthy vascularized tissue was transposed into the area at risk for further fistula formation. Where less aggressive surgery was performed only 12 of 27 patients survived (P < 0.0001). Esophageal surgeons need to be aware of the late complications and associated atypical symptoms of historical procedures which are no longer in common usage. Where an enteropericardial fistula is present, defunctioning of the upper GI tract or repair with transposition of vascularized tissue gives a better chance of a successful outcome. [Table: see text].


Subject(s)
Fistula/diagnosis , Fistula/therapy , Intestinal Fistula/diagnosis , Intestinal Fistula/therapy , Pericardium , Adult , Anti-Bacterial Agents/therapeutic use , Drainage , Echocardiography , Esophagostomy , Fistula/complications , Gastrostomy , Hematemesis/etiology , Humans , Intestinal Fistula/complications , Jejunostomy , Male , Melena/etiology , Middle Aged , Pericardial Effusion/diagnostic imaging , Pericardial Effusion/etiology , Pericarditis/drug therapy , Pericarditis/etiology , Sepsis/drug therapy , Sepsis/etiology
3.
Drug Alcohol Depend Rep ; 9: 100203, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38035048

ABSTRACT

Background: Co-use of alcohol and cannabis is highly prevalent and may be associated with negative outcomes. The intersection between alcohol and cannabis use remains poorly understood. The present study assessed this intersection and the moderating effects of sex on the daily levels of high-risk alcohol and cannabis co-use. Methods: A secondary analysis of an experimental pharmacology study specifically designed to recruit individuals using both alcohol and cannabis was conducted. Thirty-three non-treatment seeking subjects (19 M/14F) reporting high-risk levels of alcohol and cannabis use completed a 30-day Timeline Follow-back (TLFB) assessment for alcohol and cannabis use, resulting in a total of N = 990 observations. Logistic models tested the probability of same day cannabis use as predicted by alcohol use (any use, total drinking, and binge drinking), sex, and alcohol use by sex interactions. Results: Drinking any alcohol on a given day was associated with a significant increase in the likelihood of same-day cannabis use (b = 0.61, p = 0.001) as was amount of alcohol consumed on a given day (b = 0.083, p = 0.012). These relations were significantly moderated by sex (b = 1.58, p<0.001; b = 0.14, p = 0.044). Male-identifying individuals demonstrated an increased probability of concurrent cannabis use with any alcohol use on a given day, and this relationship increased linearly as the number of drinks consumed increased. Conclusions: The present study investigated the patterns associated with co-using alcohol and cannabis in individuals reporting high-risk levels of both alcohol and cannabis use. The sex-dependent findings suggest that males are at higher risk for co-using alcohol and cannabis compared with females.

4.
Eat Weight Disord ; 17(2): e101-8, 2012 Jun.
Article in English | MEDLINE | ID: mdl-23010779

ABSTRACT

Few well-controlled trials have evaluated the effects that macronutrient composition has on changes in food cravings during weight loss treatment. The present study, which was part of the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial, investigated whether the fat and protein content of four different diets affected changes in specific food cravings in overweight and obese adults. A sample of 811 adults were recruited across two clinical sites, and each participant was randomly assigned to one of four macronutrient prescriptions: 1) low fat (20% of energy), average protein (15% of energy); 2) moderate fat (40%), average protein (15%); 3) low fat (20%), high protein (25%); 4) moderate fat (40%), high protein (25%). With few exceptions, the type of diet that participants were assigned did not differentially affect changes in specific food cravings. Participants assigned to the high-fat diets, however, had reduced cravings for carbohydrates at month 12 (p<0.05) and fruits and vegetables at month 24. Also, participants assigned to high-protein diets had increased cravings for sweets at month 6 and month 12 (ps<0.05). Participants in all four dietary conditions reported significant reductions in food cravings for specific types of foods (i.e., high fat foods, fast food fats, sweets, and carbohydrates/starches; all ps<0.05). Cravings for fruits and vegetables, however, were increased at month 24 (p<0.05). Calorically restricted diets (regardless of their macronutrient composition) yielded significant reductions in cravings for fats, sweets, and starches whereas cravings for fruits and vegetables were increased.


Subject(s)
Caloric Restriction , Diet, Reducing , Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Food Preferences , Overweight/diet therapy , Weight Loss , Adult , Age Factors , Aged , Biomarkers/blood , Body Mass Index , Dietary Proteins/administration & dosage , Feeding Behavior , Female , Follow-Up Studies , Humans , Male , Middle Aged , Obesity/diet therapy , Self Report , Sex Factors , Surveys and Questionnaires , Treatment Outcome
5.
Open Forum Infect Dis ; 5(9): ofy202, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30255113

ABSTRACT

BACKGROUND: Hepatitis C is now curable for most individuals, and national goals for elimination have been established. Transmission persists, however, particularly in nonurban regions affected by the opioid epidemic. To reach goals of elimination, barriers to treatment must be identified. METHODS: In this open cohort of all individuals diagnosed with active hepatitis C from 2010 to 2016 at a large medical center, we identified patient and clinic characteristics associated with our primary outcome, sustained virologic response (SVR). We performed a subgroup analysis for those with documented substance misuse. RESULTS: SVR was achieved in 1544 (41%) of 3790 people with active hepatitis C. In a multivariable Poisson regression model, SVR was more likely in individuals diagnosed outpatient (incident rate ratio [IRR], 1.7; 95% confidence interval [CI], 1.5-2.0), living in close proximity to the medical center (IRR, 1.2; 95% CI, 1.1-1.3), with private insurance (IRR, 1.1; 95% CI, 1.0-1.3), and with cirrhosis (IRR, 1.4; 95% CI, 1.3-1.5). Achieving SVR was less likely in those qualifying as indigent (IRR, 0.8; 95% CI, 0.8-0.9) and those with substance misuse (IRR, 0.8; 95% CI, 0.7-0.9). In the subgroup analysis of those with substance misuse, SVR rates were higher in those linked to the infectious diseases clinic, which has embedded support services, than those linked to the gastroenterology clinic, which does not (IRR, 1.4; 95% CI, 1.1-1.9). CONCLUSIONS: Social determinants of health including proximity to care and poverty impacted achievement of SVR. Those with substance misuse, a high-priority population for treatment of hepatitis C, had better outcomes when receiving care in a clinic with embedded support services.

6.
Neoplasia ; 17(3): 306-16, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25810015

ABSTRACT

A substantial proportion of colorectal cancers (CRCs) are interval CRCs (I-CRCs; i.e., CRCs diagnosed soon after a colonoscopy). Chromosomal instability (CIN) is defined as an increase in the rate of which whole chromosomes/large chromosomal fragments are gained or lost and is observed in 85% of non-hereditary CRCs. The contribution of CIN to the etiology of I-CRCs remains unknown. We established a fluorescence in situ hybridization (FISH) approach to characterize CIN by enumerating specific chromosomes and determined the prevalence of numerical CIN in a population-based cohort of I-CRCs and control (sporadic) CRCs. Using the population-based Manitoba Health administrative databases and Manitoba Cancer Registry, we identified an age, sex, and colonic site of CRC matched cohort of I-CRCs and controls and retrieved their archived paraffin-embedded tumor samples. FISH chromosome enumeration probes specifically recognizing the pericentric regions of chromosomes 8, 11, and 17 were first used on cell lines and then CRC tissue microarrays to detect aneusomy, which was then used to calculate a CIN score (CS). The 15th percentile CS for control CRC was used to define CIN phenotype. Mean CSs were similar in the control CRCs and I-CRCs; 82% of I-CRCs exhibited a CIN phenotype, which was similar to that in the control CRCs. This study suggests that CIN is the most prevalent contributor to genomic instability in I-CRCs. Further studies should evaluate CIN and microsatellite instability (MSI) in the same cohort of I-CRCs to corroborate our findings and to further assess concomitant contribution of CIN and MSI to I-CRCs.


Subject(s)
Chromosomal Instability , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Age Factors , Aged , Cell Line, Tumor , Chromosome Aberrations , Chromosomes, Human, Pair 11 , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 8 , Colorectal Neoplasms/epidemiology , Female , Humans , In Situ Hybridization, Fluorescence , Karyotype , Male , Microsatellite Instability , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prevalence , Sensitivity and Specificity , Sex Factors
7.
Am J Cardiol ; 71(10): 766-72, 1993 Apr 01.
Article in English | MEDLINE | ID: mdl-8456751

ABSTRACT

Previous studies of the natural history of coronary disease generally relied on estimates of percent stenosis derived from visual assessment of the coronary angiogram. In a study of 26 patients, serial quantitative angiography was performed 3 years apart to determine changes in both absolute measurements of the luminal diameter and relative percent stenosis. Initially, the mean minimal diameter of 74 coronary obstructions was 1.94 +/- 0.09 mm, the mean "normal" reference diameter was 3.06 +/- 0.11 mm, and the mean percent stenosis was 37%. At follow-up, there was a mild reduction of 0.12 +/- 0.04 mm (6%) in the minimal diameter (p < 0.005), and an increase in percent stenosis to 39% (p = 0.03). The average diameter of 85 arterial segments without a focal obstruction either initially or at follow-up showed mild but significant progression (-0.11 +/- 0.04 mm; p = 0.02). Using a minimal change of 0.27 mm in arterial diameter as a categoric variable, progression occurred in 26% of 74 arterial segments, no significant change in 65%, and regression in 9%. The only significant determinant of disease progression was the initial severity of disease. Obstructed arteries with a larger initial minimal diameter and presumably milder disease progressed more rapidly than did those with a smaller diameter (r = -0.42; p = 0.0002). There was no effect of age on the rate of progression (r = 0.02; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Image Processing, Computer-Assisted , Cardiac Catheterization , Constriction, Pathologic/diagnostic imaging , Coronary Artery Disease/epidemiology , Coronary Artery Disease/therapy , Coronary Vessels/pathology , Follow-Up Studies , Humans , Male , Middle Aged , Pilot Projects , Time Factors
8.
Hum Pathol ; 31(2): 255-9, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10685645

ABSTRACT

This report describes a low-grade B-cell lymphoma of mucosa associated lymphoid tissue (MALT) involving the thymus of a 63-year-old woman with features suggestive of a connective tissue disease. Sections of the thymic lesion and of a lung biopsy performed at the same operation were examined histologically and by immunohistochemistry using the monoclonal antibodies CD45, CD20, CD79a, CD3, CD45RO, and AE1/AE3. Polymerase chain reaction (PCR) for immunoglobulin heavy chain gene rearrangement was also performed. The dense infiltrate of small lymphoid cells intimately admixed with ramifying epithelial elements, some of which had undergone cystic change, closely resembled a thymoma. The lymphoid infiltrate comprised centrocyte-like cells, small lymphocytes, plasma cells, and blasts. Most of the lymphoid cells were immunoreactive with the B-cell markers CD20 and CD79a, and PCR showed clonal immunoglobulin heavy chain gene rearrangement. The lung biopsy showed dense infiltration by small lymphoid cells, morphologically suggestive of lymphoid interstitial pneumonia. However, PCR showed a weak band in the amplification for immunoglobulin heavy chain gene rearrangement, identical to that within the thymus and suggesting either recirculation of cells to accumulated MALT or subhistological lymphoma. MALT lymphoma may rarely involve the thymus, and pathologists should be aware of this to avoid misdiagnosis as a thymoma. Immunohistochemical and/or molecular studies are of value in this regard. MALT lymphomas of the thymus, common with those arising in other organs, may develop in the setting of a connective tissue disease.


Subject(s)
Lymphoma, B-Cell, Marginal Zone/diagnosis , Thymus Neoplasms/diagnosis , Biopsy , Female , Humans , Immunohistochemistry , Lung/pathology , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, B-Cell, Marginal Zone/surgery , Middle Aged , Polymerase Chain Reaction , Thymus Neoplasms/pathology , Thymus Neoplasms/surgery
9.
Transfus Med Rev ; 12(3): 151-61, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9673000

ABSTRACT

The chromosomal locations of genes controlling the expression of some 200 antigens constituting the 23 established human blood group systems have been reviewed. Twenty-one of the these genes are located on 12 autosomes, and two are located on the X chromosome. Refined chromosomal positions, to a single cytogenetically distinguishable band, have been established for 13 of the 23 genes. For the remainder, continued investigation will achieve the same result. The genes (RD, MER2, and OK) controlling the expression of one low-incidence and two high-incidence erythrocyte antigens have also been presented. Of these, OK is the most likely candidate for blood group system status, because its chromosomal location distinguishes it from all established system genes except LE and LW, and, the product of the OK gene is different from those of LE and LW (Table 3). This issue will be considered at the next meeting (scheduled for July 1998) of the ISBT Working Party. Alternatively, RD and MER2 are not good candidates for blood group system status because RD and MER2 reside in chromosomal regions containing genes for other blood group systems. In addition, the products of RD and SC have similar biochemical characteristics, and the product of MER2 has not yet been defined (Table 3). The challenge remaining for blood group scientists is characterization of genes that control expression of the approximately 50 other known erythrocyte antigens. Most of these are members of the ISBT's 700 (low-incidence) or 901 (high-incidence) series. Because the current genetic information for each of these antigens (attained by serologic investigation) varies considerably, future studies will have to rely on "tools" from related disciplines to provide the additional information. Use of resources such as molecular biological protocols and GBD should facilitate the effort.


Subject(s)
Blood Group Antigens/genetics , Chromosome Mapping/methods , Genes/immunology , Chromosome Banding/methods , Humans
10.
J Clin Pathol ; 55(3): 184-9, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11896068

ABSTRACT

AIMS: In vitro transfection experiments show that the nm23 gene suppresses metastasis, although the evidence from clinical studies is contradictory. The purpose of this study was to investigate whether nm23 selectively influences systemic, pleural, and lymphatic metastasis in non-small cell lung cancer (NSCLC). METHODS: Forty two patients undergoing resection of NSCLC and lymph node sampling were enrolled prospectively. In each case, a bone marrow aspirate, pleural lavage, and lymph nodes were assessed using immunohistochemistry for epithelial antigens and morphology. The intensity of nm23-H1 immunoreactivity of the primary tumour was compared with the internal control of normal bronchial epithelium in 32 cases where available. The microvessel count (MVC) of each tumour was determined using immunohistochemistry for the endothelial cell marker CD34. RESULTS: Tumour cell dissemination was detected in the bone marrow in 18 patients, in the pleura in seven, and in the lymph nodes in 21. Increased immunoreactivity for nm23 was found in the primary tumour in six patients, with none having tumour cells in the bone marrow, compared with 12 of 26 patients who showed nm23 immunoreactivity equal to or less than the control (Fisher's exact test: p = 0.043). This effect was confirmed to be independent of the MVC on multivariate analysis. There was no significant difference in the incidence of pleural or lymphatic tumour cell dissemination between the two groups. CONCLUSION: nm23 appears to be a suppressor of systemic, but not lymphatic, metastasis in primary NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/secondary , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Monomeric GTP-Binding Proteins/metabolism , Neoplasm Proteins/metabolism , Neoplastic Cells, Circulating/metabolism , Nucleoside-Diphosphate Kinase , Transcription Factors/metabolism , Aged , Bone Marrow Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , NM23 Nucleoside Diphosphate Kinases , Neovascularization, Pathologic/metabolism , Pleural Neoplasms/secondary , Prospective Studies , Specimen Handling/methods
11.
J Clin Pharmacol ; 30(8): 755-63, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2401755

ABSTRACT

Cigarettes can be developed that heat rather than burn tobacco. Such products would be expected to have less "tar" and other combustion products than cigarettes that burn tobacco. With one product of this type, benzo(a)pyrene, N-nitrosamines, phenolic compounds, acetaldehyde, acrolein, hydrogen cyanide, and N-heterocyclic compounds have been reduced 10- to 100-fold compared to the Kentucky reference (1R4F) cigarette, a representative low-tar cigarette. The yields of nicotine and carbon monoxide from this new cigarette are less than the yields of 95% and 75%, respectively, of the cigarettes sold in the United States during 1988. Nicotine absorption from smoking this new cigarette is not significantly different from that of tobacco-burning cigarettes yielding equivalent levels of nicotine. The urine mutagenicity of smokers of new cigarettes is significantly less (P less than .05) than that of smokers of tobacco-burning cigarettes and is not significantly different (P greater than .10) from that of nonsmokers. We conclude that cigarettes which heat rather than burn tobacco can reduce the yield of tobacco combustion products. This simplification of smoke chemistry had no effect on nicotine absorption in smokers and resulted in a reduction of biological activity in smokers as measured by urine mutagenicity.


Subject(s)
Hot Temperature , Nicotine/analysis , Smoke/analysis , Smoking , Adult , Humans , Male , Middle Aged , Mutagenicity Tests , Nicotine/blood , Nicotine/pharmacokinetics , Plants, Toxic , Smoke/adverse effects , Nicotiana
12.
J Neurosci Methods ; 18(3): 269-76, 1986 Nov.
Article in English | MEDLINE | ID: mdl-2879077

ABSTRACT

A simplified method is described for the isocratic analysis of endogenous amino acid neurotransmitters contained in brain perfusates by high performance liquid chromatography (HPLC) with electrochemical detection (EC). Pre-column o-phthalaldehyde (OPA) tert-butylthiol derivatives of the amino acids were injected into a C18 3 microns column. After linear concentration curves for standard solutions were obtained, the content of 6 amino acid neurotransmitters was analyzed in push-pull perfusates obtained from the hypothalamus and cerebral cortex of the unrestrained rat. Each analysis which included the simultaneous quantification of aspartic acid, glutamic acid, glutamine, glycine, taurine and gamma-aminobutyric acid (GABA), was completed in less than 15 min. The sensitivity of the assay ranged from 1.0 to 5.0 pmol of each amino acid contained within a 20 microliters aliquot of each perfusion sample.


Subject(s)
Amino Acids/analysis , Brain Chemistry , Chromatography, High Pressure Liquid/methods , Electrochemistry/methods , Neurotransmitter Agents/analysis , Animals , Cerebral Cortex/analysis , Glutamates/analysis , Glutamic Acid , Hypothalamus/analysis , Rats , Taurine/analysis , gamma-Aminobutyric Acid/analysis
13.
Ann Thorac Surg ; 58(5): 1534-6, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7979692

ABSTRACT

We describe a patient who had lipothymoma with red cell aplasia, hypogammaglobulinemia, and lichen planus. Parathymic syndromes described in association with lipothymomas also include myasthenia gravis, hyperthyroidism, lymphangioma, aplastic anemia, chronic lymphocytic leukemia, and Hodgkin's disease. The behavior of lipothymoma is generally benign, although local recurrence was noted in 1 patient who had an incomplete resection. Lipothymoma should be considered in the diagnosis of mediastinal tumors and parathymic syndromes, and also in patients with cardiomegaly, phrenic nerve palsy, and a widened mediastinum.


Subject(s)
Agammaglobulinemia/complications , Lichen Planus/complications , Lipoma/complications , Red-Cell Aplasia, Pure/complications , Thymoma/complications , Thymus Neoplasms/complications , Adult , Humans , Lipoma/diagnostic imaging , Lipoma/pathology , Male , Radiography , Thymoma/diagnostic imaging , Thymoma/pathology , Thymus Neoplasms/diagnostic imaging , Thymus Neoplasms/pathology
14.
Ann Thorac Surg ; 57(5): 1095-100; discussion 1100-1, 1994 May.
Article in English | MEDLINE | ID: mdl-8179370

ABSTRACT

From January 1982 to December 1986, 167 patients (121 men and 46 women) with non-small cell lung cancer and a clinically negative mediastinum were found to have N2 lymph node metastases at thoracotomy and underwent pulmonary resection. Ages ranged from 31 to 86 years (median, 66 years). Adenocarcinoma was present in 70 patients (41.9%), squamous cell carcinoma in 64 (38.3%), large cell carcinoma in 20 (12.0%), adenosquamous cell carcinoma in 7 (4.2%), and bronchoalveolar cell carcinoma in 6 (3.6%). Forty-seven patients (28.1%) underwent mediastinoscopy; all results were negative. Pneumonectomy was performed in 64 patients, bilobectomy in 4, lobectomy in 76, segmentectomy in 2, and wedge excision in 21. Twenty patients had an incomplete resection. Thirty-five patients (21.0%) had complications, and the operative mortality was 4.8% (8 of 167 patients). Sixty-seven patients (40.1%) received adjuvant radiation therapy. The 5-year survival for the 147 patients who underwent complete resection was 23.7%. In contrast, 19 of the 20 patients (95.0%) who underwent incomplete resection died within 3 years. Other factors that significantly affected the 5-year survival were the number and location of metastatic lymph node stations, age, type of resection, and whether adjuvant radiation therapy was administered. We conclude that, when N2 disease is found at thoracotomy, complete resection is warranted to achieve long-term survival.


Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lymphatic Metastasis , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Survival Rate
15.
Cancer Chemother Pharmacol ; 41(4): 299-306, 1998.
Article in English | MEDLINE | ID: mdl-9488599

ABSTRACT

A highly sensitive and specific assay for the quantitation of the anticancer agent dolastatin-10 (DOL-10) in human plasma is described. The method was based on the use of electrospray ionization-high-performance liquid chromatography/mass spectrometry (ESP-LC/MS). The analytical procedure involved extraction of plasma samples containing DOL-10 and the internal standard (DOL-15) with n-butyl chloride, which was then evaporated under nitrogen. The residue was dissolved in 50 microl mobile phase and 10 microl was subjected to ESP-LC/MS analysis using a C18 microbore column. A linear gradient using water/acetonitrile was used to keep the retention times of the analytes of interest under 5 min. The method exhibited a linear range from 0.005 to 50 ng/ml with a lower limit of quantitation (LLQ) at 0.005 ng/ml. Absolute recoveries of extracted samples in the 85-90% range were obtained. The method's accuracy (< or =5% relative error) and precision (< or =10% CV) were well within industry standards. The analytical procedure was applied to extract DOL-10 metabolites from samples obtained following incubation of the drug with an activated S9 rat liver preparation. Two metabolic products were detected and were tentatively identified as a N-demethyl-DOL-10 and hydroxy-DOL-10. Structural assignments were made based on the fragmentation patterns obtained using the electrospray source to produce collision-induced dissociation (CID). The method was also applied to the measurement of DOL-10 in the plasma of patients treated with this drug. Preliminary investigation of the pharmacokinetics suggested that drug distribution and elimination may be best described by a three-compartment model with t1/2alpha = 0.087 h, t1/2beta = 0.69 h and t1/2gamma = 8.0 h. Plasma clearance was 3.7 l/h per m2.


Subject(s)
Antineoplastic Agents/pharmacokinetics , Depsipeptides , Oligopeptides/pharmacokinetics , Antineoplastic Agents/blood , Atmospheric Pressure , Chromatography, High Pressure Liquid/methods , Humans , Mass Spectrometry/methods , Neoplasms/drug therapy , Oligopeptides/blood , Reference Standards , Tissue Distribution
16.
J Am Coll Surg ; 185(6): 525-9, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9404874

ABSTRACT

BACKGROUND: Many current methods of esophageal resection have drawbacks that result in inadequate proximal resection, inadequate lymphadenectomy, and difficult gastric and splenic access. We describe a technique that allows reliable and safe access to the chest, abdomen, and neck. STUDY DESIGN: From 1988 to 1995, 113 patients (82 men; mean age 65.3 +/- 4.5 years) with carcinoma of the esophagus or esophagogastric junction (middle third in 34, lower third in 41, and cardia in 38) underwent total thoracic esophagectomy. The histology was adenocarcinoma in 71 (62.8%), squamous cell carcinoma in 32 (28.3%), and undifferentiated carcinoma in 10 (8.9%) of the patients; 57 tumors (50.5%) were stage III. The esophagus and stomach were mobilized through a left thoracoabdominal incision. After completion of the esophageal resection, the fundus of the stomach was sutured to the esophageal stump to allow later delivery of the stomach into the neck. The esophagogastric anastomosis was performed with continuous single-layer absorbable suture through a left oblique cervical incision. RESULTS: The mean duration of the operation was 309.2 +/- 47.9 minutes. Hospital stay ranged from 5 to 49 days (median, 12 days). The perioperative mortality rate was 4.4%. Anastomotic leak occurred in six patients (5.3%), one of whom died. The proximal resection margin was microscopically free of tumor in all cases, and with a minimum followup period of 18 months, there has been no anastomotic recurrence in any patient. Actuarial survival at 1 year was 63.4% +/- 4.9%, at 3 years 41.4% +/- 5.9%, and at 5 years 22.7% +/- 6.3%. CONCLUSIONS: Total thoracic esophagectomy through the left chest with a separate left cervical incision allows clear access to the esophagus and stomach and good tumor clearance. This procedure may be performed with a low rate of anastomotic leakage, a very low mortality rate, and no anastomotic tumor recurrence.


Subject(s)
Adenocarcinoma/surgery , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/surgery , Esophagectomy/methods , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophagectomy/statistics & numerical data , Esophagogastric Junction/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Postoperative Complications/epidemiology , Prospective Studies
17.
J Affect Disord ; 66(2-3): 273-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11578682

ABSTRACT

BACKGROUND: Panic disorder (PD) symptomatology has been reported to be altered by hormonal events or treatments which affect estrogen levels. Coryell et al. [Arch. Gen. Psychiatry, 39 (1982) 701-703; Am. J. Psychiatry, 143 (1986) 508-510] have suggested that the increased cardiovascular risk associated with PD is significantly greater in males, alluding to a potential cardioprotective effect of female hormones in the context of panic attacks. In the present study, we were, therefore, interested in elucidating the role of estrogen in modulating the behavioural and cardiovascular responses induced by the panicogenic agent pentagastrin, a cholecystokinin-B (CCK(B)) receptor agonist. METHODS: A double-blind cross-over placebo-controlled design with randomization of the order of a 3-day pretreatment of ethinyl estradiol (EE) (50 microg/day) or placebo was used to assess the effect of a 30-microg i.v. bolus injection of pentagastrin on panic symptom intensity and on increases in heart rate (DeltaHR), systolic (DeltaSBP) and diastolic (DeltaDBP) blood pressure following each pretreatment. Subjects were 9 male healthy controls and 11 male PD patients. RESULTS: EE pretreatment did not significantly reduce the pentagastrin-induced panic symptom scale (PSS) scores and had no effect on DeltaDBP or DeltaSBP. EE did, however, attenuate the pentagastrin-induced increase in HR in both PD patients and healthy controls. LIMITATIONS: Only male subjects were included in the present study; however, we are currently investigating the influence of female gonadal hormones on the panic response to pentagastrin in female PD patients and healthy controls. CONCLUSION: Our results suggest that estrogens may display cardioprotective effects in the context of panic attacks.


Subject(s)
Ethinyl Estradiol/pharmacology , Panic/drug effects , Pentagastrin , Adult , Arousal/drug effects , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Panic Disorder/diagnosis , Panic Disorder/psychology , Premedication
18.
Psychiatry Res ; 101(3): 237-42, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11311926

ABSTRACT

Clinical observation, as well as epidemiological and research data, suggest that female gonadal hormones influence the course of panic disorder (PD). Panicogenic agents such as pentagastrin are useful tools with which to study the pathophysiology of panic attacks. Nine women with PD were randomly assigned to receive, in a crossover design, a 3-day pretreatment with medroxyprogesterone acetate (MP) prior to an injection of pentagastrin, and a 3-day pretreatment with a placebo prior to another injection of pentagastrin. The panic response and the anxiety response to pentagastrin were decreased after MP pretreatment. These preliminary results support the use of laboratory models for investigations of the interactions between progestins and anxiety.


Subject(s)
Anti-Anxiety Agents/pharmacology , Medroxyprogesterone Acetate/pharmacology , Panic Disorder/metabolism , Pentagastrin/administration & dosage , Progesterone Congeners/pharmacology , Adult , Anti-Anxiety Agents/administration & dosage , Anxiety/chemically induced , Anxiety/prevention & control , Cross-Over Studies , Double-Blind Method , Female , Humans , Injections , Medroxyprogesterone Acetate/administration & dosage , Panic Disorder/chemically induced , Progesterone Congeners/administration & dosage , Psychiatric Status Rating Scales , Treatment Outcome
19.
Eur J Cardiothorac Surg ; 16(3): 261-5, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10554840

ABSTRACT

OBJECTIVE: Anastomotic recurrence is a major cause of late mortality following oesophago-gastrectomy (OG) for carcinoma of the oesophagus and oesophago-gastric junction using either the Ivor Lewis or left thoraco-abdominal approach with intra-thoracic anastomosis. The aim of this study was to determine whether the more extensive total thoracic oesophagectomy (TTO) with cervical anastomosis would reduce the anastomotic recurrence rate while maintaining acceptable operative morbidity and mortality. METHODS: From January 1988 to December 1996, 108 total thoracic oesophagectomies and 66 oesophago-gastrectomies were performed with curative intent in 174 patients (125 males, mean age 62.4 years) with carcinoma (squamous cell carcinoma in 34 and adenocarcinoma in 140) of the middle (31 patients) and lower (44 patients) oesophagus and oesophago-gastric junction (99 patients). RESULTS: Minor complications occurred in 37 (34%) total thoracic oesophagectomy and 18 (27%) oesophago-gastrectomy patients, major complications in 15 (14%) and 5 (8%) and peri-operative death in 5 (4.6%) and 7 (11%) patients, respectively. Anastomotic leakage occurred in 10 (9%) total thoracic oesophagectomy and 5 (8%) oesophago-gastrectomy patients, and was fatal in 1 (1%) and 4 (6%). There was no incidence of tumour at or within 5 mm of the proximal limit in the total thoracic oesophagectomy group and this was reflected in the complete absence of anastomotic recurrence. In the oesophago-gastrectomy group there was a positive proximal resection margin in 13 (20%) and 13 anastomotic recurrences (22% of peri-operative survivors). The 5-year survival (including operative mortality) was 29% for total thoracic oesophagectomy compared with 21% for the other techniques (P = 0.028 log rank test). Median survival was 25.2 months after total thoracic oesophagectomy and 15.8 after oesophago-gastrectomy. CONCLUSIONS: Total thoracic oesophagectomy can be performed in oesophageal cancer patients with comparable morbidity to that of lesser resections. Incomplete proximal resection and anastomotic recurrence did not occur in this series of 108 total thoracic oesophagectomies and this is reflected in an increased medium term survival. The improved survival is most apparent for tumours of the oesophago-gastric junction.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/methods , Esophagogastric Junction/surgery , Gastrectomy/methods , Neoplasm Recurrence, Local/mortality , Adenocarcinoma/diagnosis , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adult , Aged , Anastomosis, Surgical/methods , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/mortality , Esophagectomy/mortality , Esophagogastric Junction/pathology , Female , Gastrectomy/mortality , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/diagnosis , Prognosis , Proportional Hazards Models , Prospective Studies , Survival Analysis , Survival Rate
20.
Eur J Cardiothorac Surg ; 18(6): 656-61, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11113671

ABSTRACT

OBJECTIVES: This study compares the posterior auscultatory triangle thoracotomy incision (muscle sparing) with full posterolateral thoracotomy (where latissimus dorsi muscle is always cut across its full width), with particular attention to the difference between latissimus dorsi muscle strength, post operative pain and chronic wound related symptoms. METHODS: Ten patients who had undergone auscultatory triangle thoracotomy (ATT) at least 1 year previously were matched with ten patients who had undergone posterolateral thoracotomy (PLT). Each pair was matched for age, sex, dominant hand, side of the operation, time since operation and presence or absence of history of previous muscle training. Latissimus dorsi muscle strength was assessed by testing the shoulder adduction strength through an arc of 90-0 degrees using isokinetic technique. Early post-operative pain was assessed indirectly by calculating the analgesic requirement in the first 5 post-operative days. A subjective assessment of chronic post-thoracotomy pain was made using a questionnaire presented to the patients at the time of muscle testing. Variability of the torque curves, recorded as coefficient of variance at the time of muscle strength testing, provided objective measurements of chronic pain. Data were analysed using two sample t-tests. RESULTS: All patients reported at least one chronic post-thoracotomy symptom. There was no significant difference between the two groups in terms of acute or chronic wound pain and other long term wound related symptoms. Shoulder adduction strength was 24% greater in ATT than PLT (95% confidence limits=1-43%, P=0.04). CONCLUSIONS: All thoracotomy patients have long term wound related symptoms. This situation is not improved by performing a muscle sparing incision. However thoracotomy through the triangle of auscultation can preserve latissimus dorsi strength which is compromised in a posterolateral thoracotomy incision. We therefore recommend that a muscle sparing thoracotomy be considered for patients where preservation of muscle strength is deemed important, providing the operation is not compromised due to inadequate access.


Subject(s)
Muscles/physiopathology , Muscles/surgery , Pain, Postoperative/physiopathology , Thoracotomy/methods , Adolescent , Adult , Aged , Biomechanical Phenomena , Drainage , Female , Humans , Male , Middle Aged , Multivariate Analysis , Thoracotomy/statistics & numerical data , Time Factors
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