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Biomedical subjects

R Kessler

Publications and source records attributed to R Kessler.

At least 109 records · Page 6Linked to original sources

Blood vessel invasion is a major prognostic factor in resected non-small cell lung cancer.

BACKGROUND: We examined the prognostic value of histologic indices in non-small cell lung cancer with particular interest in major blood vessel invasion. METHODS: We studied 593 patients who had curative resection between November 1983 and December 1988. We determined the histology, T and N status, peritumoral lung tissue invasion, tumor stroma, necrosis, mitotic rate, and blood vessel invasion. RESULTS: The median patient survival of the whole series was 3.2 years, with a 5-year survival of 38.9%. In univariate analysis, a high T stage, a high percentage of necrosis, blood vessel invasion, and N stage significantly worsened the survival. In multivariate analysis, only blood vessel invasion and, less significantly, T stage and lymph node metastasis remained independent prognostic factors. CONCLUSIONS: These results highlight the negative prognostic value of blood vessel invasion in non-small cell lung cancer and suggest that blood vessel invasion, T stage, and node metastasis are three unrelated and distinctive characteristics of resected non-small cell lung cancer.

Analysis of Variance↗

Pneumonectomy for chronic infection is a high-risk procedure.

BACKGROUND: The purpose of this study was to estimate operative risk, and to identify indicators of adverse prognosis, in patients undergoing pneumonectomy for chronic infection. METHODS: Twenty-five patients aged 41 +/- 15 years underwent pneumonectomy (three completions) for chronic infection: sequelae of tuberculosis, 15; cystic bronchiectasis, 9; and radiation pneumonitis, 1. Eight patients had aspergilloma (7 after tuberculosis, 1 with radiation pneumonitis). RESULTS: Operative mortality was 4%. Operative blood loss was estimated at 1,983 +/- 1,424 mL, ranging from 150 to 5,600 mL. A single patient required reexploration. Eight patients (32%) had empyema, and a further 3 (12%) had bronchopleural fistula; thoracoplasty was required for 10 (40%). Sequelae of tuberculosis heralded increased operative bleeding (t = 2.884; p < 0.005). Incidence of empyema or bronchopleural fistula was increased in patients with sequelae of tuberculosis (chi 2 = 3.896; p < 0.05), patients with aspergilloma (chi 2 = 4.588; p < 0.05), patients in whom the parenchymal cavities were entered (chi 2 = 11.5; p < 0.001), and those in whom blood loss was in excess of 1,000 mL (chi 2 = 4.911; p < 0.05). CONCLUSIONS: We conclude that pneumonectomy is a high-risk procedure, especially in patients with sequelae of tuberculosis.

Adolescent↗

Severe global amnesia presenting as Wernicke-Korsakoff syndrome but resulting from atypical lesions.

A female alcoholic presented with Wernicke's encephalopathy subsequent to administration of diazepam and glucose (without thiamine) for treatment of withdrawal seizures. Nystagmus and cerebellar ataxia quickly resolved when administered thiamine, although severe global amnesia consistent with Korsakoff's syndrome persisted. Magnetic resonance imaging (MRI) revealed infarction of the right temporal lobe with hippocampal atrophy, but no lesions of thalamus or atrophy of mammillary bodies. Positron emission tomography (PET) confirmed decreased cerebral metabolic rates for glucose (CMRglu) in the right temporal lobe corresponding to MRI findings, but also significant metabolic asymmetry of dorsal thalamus, i.e. reduced CMRglu in left versus right. This patient is unique in that neuroradiological findings revealed intact mammillary bodies and suggest asymmetrical dysfunctions (structural right temporal and functional left diencephalic) to produce her profound amnesia.

Alcohol Amnestic Disorder↗

Proteolysis of human calcitonin in excised bovine nasal mucosa: elucidation of the metabolic pathway by liquid secondary ionization mass spectrometry (LSIMS) and matrix assisted laser desorption ionization mass spectrometry (MALDI).

PURPOSE: Two calcitonins, i.e. human calcitonin (hCT) and, for comparison, salmon calcitonin (sCT), were chosen as peptide models to investigate nasal mucosal metabolism. METHODS: The susceptibility of hCT and sCT to nasal mucosal enzymes was assessed by in-and-out reflection kinetics experiments in an in vitro model based on the use of freshly excised bovine nasal mucosa, with the mucosal surface of the mucosa facing the peptide solution. The kinetics of CT degradation in the bulk solution was monitored by HPLC. Peptide sequences of the main nasal metabolites of hCT were analyzed by using both liquid secondary ionization mass spectrometry (LSIMS), following HPLC fractionation of the metabolites, and matrix-assisted laser desorption ionization mass (MALDI) spectrometry. For sCT, the molecular weights of two major metabolites were determined by LC-MS with electrospray ionization. RESULTS: Both CTs were readily metabolized by nasal mucosal enzymes. In the concentration range studied metabolic rates were higher with hCT than with sCT. Presence of endopeptidase activities in the nasal mucosa was crucial, cleaving both calcitonins in the central domain of the molecules. CONCLUSIONS: Typically, initial metabolic cleavage of hCT in nasal mucosa is due to both chymotryptic- and tryptic-like endopeptidases. The subsequent metabolic break-down follows the sequential pattern of aminopeptidase activity. Tryptic endopeptidase activity is characteristic of nasal sCT cleavage.

Amino Acid Sequence↗

Bronchogenic cancer in the elderly: operative risk and long-term prognosis.

Surgery for bronchogenic cancer raises the question of benefit to elderly patients. The present study reviews a cohort of 223 patients aged 70 years and more (range: 70-84), who underwent thoracotomy for pulmonary malignancy over a 10-year period. The aim of the study was to evaluate both operative risk and 5-year survival. Medical history was negative in 29% of the patients; 26% had a history of cardio-vascular disease, and 19% had a history of malignancy in complete remission. Tumor histology was squamous-cell carcinoma for 70.4%, adenocarcinoma for 24.2%, large-cell carcinoma for 3.6%, and small-cell carcinoma for 1.3% of the patients. 48.4% of patients were in stage I, 17.2% in stage II, and 30.3% in stage III. Exploratory thoracotomy was carried out in 5.8% of patients. A resection was achieved in 210 patients (pneumonectomy in 28.5%, lobectomy in 71.5%). Operative mortality was 7.2% for the whole series, 10% after pneumonectomy and 6.6% after lobectomy. Mortality was similar below and above 75 years. Overall 5-year survival was 32.9% (45.7% for stage I, 36.3% for stage II, and 13.8% for stage III). Survival was not influenced by age, symptomatic or asymptomatic presentation, medical history, and in particular not by history of malignant disease. Although operative mortality is slightly increased when compared to younger patients, long-term results legitimize surgery for bronchogenic cancer in the elderly.

Aged↗

Psychological and hypnotic preparation for anesthesia and surgery: an individual differences perspective.

Multiple reviews indicate that psychological preparation for surgery can provide psychological, physiological, and economic benefit to the patient. Research demonstrating that hypnosis adds to this benefit is both limited and encouraging. The content and status of this literature, however, are confusing, with little coherent theoretical basis to account for the contradictions and inconsistencies across multiple studies whose methodologies often limit generalization. A model is presented regarding pertinent individual differences that include patient coping styles, prior medical experiences, and hypnotic ability, as well as differences in types of coping demanded by different surgical procedures. This model (a) helps explain some of the confusion, (b) offers a theoretical focus for patient assessment as well as development and selection of preparation strategies, and (c) clarifies future research goals.

Adaptation, Psychological↗

In situ activation of mouse alveolar macrophages by aerosolized liposomal IFN-gamma and muramyl tripeptide.

Interferon-gamma (IFN-gamma) was entrapped with an efficiency of 30-40% in muramyl tripeptide-containing liposomes by a freeze-thawing procedure. A microcytotoxicity assay was developed to measure the tumoricidal activity of mouse alveolar macrophages (AM) against tumoral target cells with a colorimetric viability test. Free IFN-gamma and liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) were found to be only slightly effective to activate in vitro AM, whereas encapsulation of both INF-gamma and MTP-PE within the same liposomes produced higher activation of AM. Aerosolized IFN-gamma and liposomal immunomodulators enhanced antitumor properties of AM recovered in mice 24 h postinhalation. Whereas free IFN-gamma also induced a substantial activation of peritoneal macrophages, liposomal encapsulation significantly reduced the systemic activity of inhaled immunomodulators. This approach provides a useful model for the compartmentalized organ-specific activation of AM in mice.

Acetylmuramyl-Alanyl-Isoglutamine↗

Pulmonary hypertension in the obstructive sleep apnoea syndrome: prevalence, causes and therapeutic consequences.

"Cor pulmonale" is a classic feature of the "Pickwickian syndrome". Earlier studies have reported a high prevalence of pulmonary hypertension (PH) in obstructive sleep apnoea (OSA) patients, but this has not been confirmed by recent studies with a more adequate methodology, including larger groups of patients. The first part of this review is devoted to the prevalence of PH in OSA; most recent studies agree on prevalence of 15-20%. The second (and major) part of the study deals with the causes and mechanisms of PH in OSA. Pulmonary hypertension is rarely observed in the absence of day-time hypoxaemia, and the severity of nocturnal events (apnoea index (AI), apnoea+ hypopnoea index (AHI) does not appear to be the determining factor of PH. Diurnal arterial blood gas disturbances and PH are most often explained by the presence of severe obesity (obesity-hypoventilation syndrome) and, principally, by association of OSA with chronic obstructive pulmonary disease (the so called "overlap syndrome"). Bronchial obstruction is generally of mild-to-moderate degree and may be asymptomatic. The final part of the review analyses the therapeutic consequences of the presence of PH in OSA patients. Pulmonary hypertension, which is generally mild-to-moderate, does not need a specific treatment. When nasal continuous positive airway pressure (CPAP) fails to correct sleep-related hypoxaemia, supplementary oxygen must be administered. In patients with marked daytime hypoxaemia (arterial oxygen tension (Pa,O2), < or = 7.3 kPa (55 mmHg) conventional O2 therapy (nocturnal + diurnal) is required.

Adult↗

Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients.

We have investigated pulmonary hemodynamics in a large series of consecutive, unselected patients with obstructive sleep apnea syndrome (OSAS). The aims of this study were to evaluate the frequency of pulmonary artery hypertension (PH) in OSAS and to analyze, as far as possible, its mechanisms. Two hundred twenty patients were included on the basis of a polysomnographic diagnosis of OSAS (apnea+hypopnea index > 20). PH, defined by a resting mean pulmonary artery mean pressure (PAP) of at least 20 mm Hg, was observed in 37 of 220 patients (17%). Patients with PH differed from the others with regard to pulmonary volumes (vital capacity [VC], FEV1) and the FEV1/VC ratio that were significantly lower (p < 0.001); PaO2 (64.4 +/- 9.3 vs 74.7 +/- 10.1 mm Hg; p < 0.001); PaCO2 (43.8 +/- 5.4 vs 37.6 +/- 3.9 mm Hg; p < 0.001), apnea+hypopnea index (100 +/- 33 vs 74 +/- 32; p < 0.001), and mean nocturnal arterial oxygen saturation (SaO2) (88 +/- 6% vs 94 +/- 2%; p < 0.001). Patients with PH were also more overweight (p < 0.001). Multiple regression analysis showed that 50% of the variance of PAP could be predicted by an equation including PaCO2 (accounting for 32% of the variance), FEV1 (12%), airway resistance (4%), and mean nocturnal SaO2 (2%). In conclusion, PH is observed, in agreement with previous studies, in less than 20% of OSAS patients. PH is strongly linked to the presence of an obstructive (rather than restrictive) ventilatory pattern, hypoxemia, and hypercapnia, and is generally accounted for by an associated obstructive airways disease. In this regard, the severity of OSAS plays only a minor role.

Adult↗

[Iatrogenic pulmonary artery hypertension].

Primary pulmonary arterial hypertension (PPH) is a rare disorder with a predilection for young subjects (most commonly of 20-40 years) and of the female sex. The prognosis is very poor because the average life expectancy is of the order of two to three years from the time of diagnosis. Since the epidemic of PPH observed in Switzerland, Austria and Germany in the years between 1968 and 1970, following the arrival of a derivative of amphetamine, Aminorex, it was realised that certain medications, notably appetite suppressants, might play an initiating role. More recently, fenfluramine and dexfenfluramine have been incriminated: in a significant statistic of A-beclere's team, around 20% of cases of PPH were observed in patients who had taken fenfluramine or dexfenfluranime for more than three months. A very recent case-control study has shown that any use of anorexic drugs (mainly fenfluramine derivatives) was associated with an increased risk of PPH (odds ratio: 6/1), and particularly when the duration of treatment exceeds 3 months. Outside the group of appetite suppressants few medications are capable of favouring the development of PPH, the cases are sporadic and the relationship between cause and effect is hardly established.

Appetite Depressants↗

Pharmacokinetics and body distribution of liposomal zinc phthalocyanine in tumor-bearing mice: influence of aggregation state, particle size, and composition.

The pharmacokinetics and body distribution of zinc phthalocyanine (ZnPc) intravenously administered in liposomes composed of ZnPc, 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), and 1,2-dioleoylphosphatidylserine (OOPS) (1:90:10 or 1:70:30 w/w) to tumor (Meth A sarcoma) bearing mice were studied. It was found that aggregation of ZnPc in the liposomes (i) increases the clearance rate of the dye from plasma, (ii) lowers the maximal dye concentration in tumor tissue, and (iii) increases the maximal dye concentration in the liver. In addition, aggregated dye is hardly eliminated from the liver and monomeric dye is eventually completely eliminated from this organ. Liposomes in the size range of 48-123 nm, containing the dye with the same aggregation state, showed the same pharmacokinetics and body distribution of the dye. The PS-content of the ZnPc liposomes (POPC alone versus POPC/OOPS 7:3) did not influence tumor, liver, and plasma pharmacokinetics during the studied time intervals. Free flow electrophoretic analysis showed in lyophilisates of ZnPc liposomes containing aggregated ZnPc the presence of two distinct populations differing in size, aggregation state of the dye, and PC/PS and ZnPc/phospholipid ratio. The liposomal formulation with monomeric ZnPc has a compositional homogeneity and demonstrated selectivity and reached high uptake in tumors, 48 h after intravenous administration and appears promising for photodynamic therapy.

Animals↗

Gangliosides and spinal cord ischemia secondary to aortic cross-clamping in the rat model.

Gangliosides, complex glycolipids of the nervous system cell membranes, have been found effective both in reducing the degree of ischemic injury and in stimulating neuronal regeneration during the recovery period. In order to investigate their neuroprotective effect during spinal cord ischemia, 60 male Sprague-Dawley rats underwent occlusion of the thoracic aorta and both subclavian arteries for 13 min. In the postoperative period, function of hindlimbs was appraised, daily for 30 days, by a deficit score (0-15). The animals were then killed and spinal cord injury was assessed by a histologic score (0-3) based on the degree of gray and white matter gliosis, number of motor neurons, and white matter myelination. The rats received intraperitoneal injection of placebo (n = 29) or GM-1 30 mg/kg (n = 31) daily, from 2 days prior to surgery to 15 days after. The scores of each group for each day were analyzed by repeated measures analysis of variance. The rate of recovery was better for GM-1 (P < 0.001) from the 15th to the 30th day. A trend was seen toward lower scores in the GM-1 group (P = 0.056). Mean histologic scores (placebo = 1.14 +/- 0.23 SE, GM-1 = 1.58 +/- 0.22 SE) did not differ (Wilcoxon, P = 0.17). The present data support the hypothesis that functional improvement after spinal cord ischemia due to aortic occlusion is enhanced by the administration of gangliosides. Optical microscopy could document only irreversible injury and might not be sensitive enough to detect subtle changes during recovery of neural elements.

Animals↗

Early and long-term results after completion pneumonectomy.

From January 1, 1978 to December 31, 1992, 37 patients underwent a completion pneumonectomy after a previous lobectomy (36 men and 1 woman; mean age, 60 years; range, 41 to 77 years). These account for 4.8% of 758 pneumonectomies. The purpose of the present study was to evaluate the operative results of completion pneumonectomy and long-term survival in patients with bronchogenic cancer. The initial lung resection had been performed for primary bronchogenic cancer in 23, metastatic thyroid adenocarcinoma in 1, and benign diseases in 13 (tuberculosis in 11, aspergilloma in 1, and bronchiectasis in 1). Completion pneumonectomy was required for bronchogenic cancer in 32 (15 stage I, 6 stage II, 11 stage III). One patient had relapsing metastatic thyroid carcinoma, 2 had bronchiectasis, and 2 had a venous infarction after lobectomy. Four patients (10.8%) died perioperatively of the following causes: 1 fatal intraoperative bleeding, 1 fatal postoperative bleeding, 1 pneumonia, and 1 malignant hypercalcemia. Median operative blood loss was 1,000 mL, and 19 patients experienced bleeding exceeding 1,000 mL (51%). Six patients had intraoperative vascular injury. Nonfatal surgical complications occurred in 9 patients (24%), including 5 clotted hemothoraces, 3 empyemas, and 1 bronchopleural fistula. Four patients had medical complications (2 pulmonary edemas, 1 sinus tachycardia, and 1 unexplained fever). Twenty-three had an uneventful straightforward recovery (62%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Are bilobectomies acceptable procedures?

BACKGROUND: Controversy about operative morbidity and oncologic value of bilobectomy has led to a review of our experience over the past 12 years. METHODS: The charts of 112 patients (100 men and 12 women with a mean age of 63 years) were reviewed for operative mortality and morbidity and long-term survival. Survival of patients with stage I or stage II disease was compared with that of stage-matched and age-matched groups having right pneumonectomy. RESULTS: Four patients (3.5%) died postoperatively. Nonfatal complications occurred in 55 patients (49%); the most frequent problem was pleural space disease (34%). Survival studies focused on the 96 patients with nonsmall cell bronchogenic cancer (44 in stage I, 32 in stage II, and 20 in stage IIIA). The overall 5-year survival rate was 40%; the 5-year survival rate was similar for stage I and stage II (41% for stage I, 50% for stage II, and 17% for stage IIIA). The incidence of local recurrence was significantly increased after bilobectomy for stage I cancer (chi 2 = 5.066; p < 0.05) compared with pneumonectomy but did not affect 5-year survival. Local recurrence and survival were similar after bilobectomy and pneumonectomy in stage II. CONCLUSIONS: These data demonstrate an increased morbidity after bilobectomy. Survival studies demonstrate an increased risk of local recurrence in patients with stage I disease, which might be partly explained by understaging.

Adenocarcinoma↗

Decortication is a valuable option for late empyema after collapse therapy.

BACKGROUND: Infection of previous collapse therapy spaces may raise challenging problems. This study evaluated a conservative surgical approach based on decortication. METHODS: Since 1979, 28 patients (mean age, 60 +/- 6 years) have presented at an average of 37 +/- 7 years after artificial pneumothorax for tuberculosis. Diagnosis of empyema was made on follow-up in 12 patients and on symptoms in 16 patients. Mean vital capacity was 66% +/- 16% of normal. Microorganisms were isolated in 13 patients (Aspergillus fumigatus in 5, Mycobacterium tuberculosis in 4, anaerobes in 4). Decortication was made in 24 patients, associated with thoracoplasty in 4, and with partial lung resection in 2 patients. Thoracoplasty alone was performed in 2 patients, and 2 patients underwent an extrapleural pneumonectomy. RESULTS: Both extrapleural pneumonectomies were complicated with empyema requiring thoracoplasty, resulting in one postoperative death. Operative mortality after decortication was nil. Mean intraoperative blood loss during decortication was 1,830 +/- 1,310 mL. All patients were extubated within 24 hours, except 1 patient who was ventilator-dependent preoperatively. Prolonged air leaks were common (mean duration of drainage, 16 +/- 11 days), but ultimately sealed. Existence of symptoms was predictive of prolonged air leaks (p < 0.01). CONCLUSIONS: We conclude that decortication may provide a one-stage cure avoiding the hazards of extrapleural pneumonectomy; the nonfunctioning remaining lung may resolve the space problem.

Aged↗