Physician assistants as inpatient caregivers. A new role for mid-level practitioners.
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Hospitalists↗
Biomedical subjects
R Kessler
Publications and source records attributed to R Kessler.
Effects of ras transformation on the induction of the IL-1 receptor related T1 gene in response to mitogens, anisomycin, IL-1 and TNFalpha.
The T1 gene gives rise to two transcripts encoding a 62 kDa membrane-bound and a 37 kDa secreted protein with similarity to the type I IL-1 receptor. It is weakly expressed in proliferating but not in resting fibroblasts and is strongly induced during the entry of quiescent cells into the cell cycle. Here we show that the T1 gene is also transcriptionally activated in response to the treatment of fibroblasts with cycloheximide and anisomycin. These protein synthesis inhibitors are known to stimulate the JNK and p38/RK signal transduction pathways. We provide evidence that anisomycin triggers T1 gene induction through the stimulation of the p38/RK MAP kinase. This observation is in line with our finding that physiological activators of the p38/RK pathway, the proinflammatory cytokines IL-1 and TNFalpha, stimulate T1 gene expression efficiently. Growth factor mediated T1 gene induction is a delayed early event, requiring ongoing protein synthesis. In contrast, anisomycin induces T1 gene expression at concentrations which block translation completely. Thus, transcriptional induction of the T1 gene via the p38/RK pathway is an immediate early event not requiring de novo protein synthesis. The T1 gene is strongly induced by various mitogens in quiescent NIH3T3 fibroblasts but not in ras transformed NIH3T3 cells. In contrast, all of the three tested agent which activate the p38/RK pathway, IL-1, TNFalpha, and anisomycin led to strong T1 gene expression in normal and ras transformed NIH3T3 cells alike. Thus, the T1 gene can be induced through the activation of at least two MAP kinase pathways: signaling through the ERK pathway can occcur in normal but not in ras transformed NIH3T3 cells, whereas the signaling through the p38/RK pathway is not affected by ras transformation.
3T3 Cells↗
[Oncocytoma. A contribution to differential diagnosis of laryngeal tumors].
Oncocytomas of the minor salivary glands are uncommon epithelial tumors. Their occurrence is controversial because the formation of metastases and histological criteria of malignancy such as hypercellularity in connection with nuclear pleomorphism and local aggressive growth, have been described in only single cases. We report a case of a 66-year-old woman who was found to have an oncocytic adenoma localized in her left laryngeal vestibular ligament. Because no signs of malignancy could be found in our case the tumor was classified histologically as primary benign. We emphasize that thorough histological examination of oncocytic tumors and close clinical supervision are necessary. A general overview of the available literature and the histological classification of oncocytomas is given.
Adenoma, Oxyphilic↗
Bronchopulmonary aspergilloma: a reappraisal.
BACKGROUND: Classically, most complications observed after operations for aspergilloma occurred in patients with sequelae of tuberculosis. Because the incidence of tuberculosis has declined over the past two decades, aspergilloma is expected to develop with increasing frequency in patients without previous tuberculosis. Therefore, our hypothesis was that operative outcome should have improved during the most recent years in comparison with our previous experience. METHODS: Operative outcome of 12 recently accrued patients was evaluated and compared with a historic control group of 55 patients, previously reported by the same center. RESULTS: As expected, only 17% of patients of the present series had a history of tuberculosis, compared with 57% in the former series. Postoperatively, there was no mortality. Major morbidity has decreased, although this difference is not statistically significant: bleeding decreased from 44% to 9% of patients; space problems decreased from 47% to 18%; and prolonged hospital stay (>30 days) decreased from 32% to 9%. CONCLUSIONS: Our results support a trend toward improved postoperative outcome of operations for aspergilloma owing to a decreased incidence of aspergilloma growing in tuberculous cavitations.
Adolescent↗
Improved selection of winners: a working hypothesis for neoadjuvant chemotherapy.
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Carcinoma, Bronchogenic↗
Future developments in professional hypnosis training: a review and critique of available training with consideration for development of a nationally coordinated program.
This article seeks to review current training models of hypnosis within a framework of basic distinctions between 2 primary goals of professional training programs and 3 primary aspects of professional training models. We focus on a description and critique of available training programs in the context of progress which has been achieved in the teaching of professional hypnosis. Programs within and the United States, Australia, and the Netherlands are reviewed, along with efforts to implement an "Americanized" version of training which incorporates desirable aspects of these latter programs. Suggestions are also made for what might be gained from adoption of a nationally coordinated program of training in professional hypnosis.
Adolescent↗
Successful treatment of adults with severe Hantavirus pulmonary syndrome with extracorporeal membrane oxygenation.
OBJECTIVE: To describe our experience with the use of extracorporeal membrane oxygenation (ECMO) as a rescue therapy in adult patients with severe cardiopulmonary failure from Hantavirus pulmonary syndrome. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Patients with confirmed Hantavirus infection, who developed severe cardiopulmonary failure in which conventional therapy was assessed as being unsuccessful. INTERVENTIONS: Records of previous patients treated for Hantavirus pulmonary syndrome were reviewed and findings consistent with 100% mortality were found. MEASUREMENTS AND MAIN RESULTS: Findings associated with a 100% mortality rate were a) cardiac index of <2.5 L/min/m2; b) serum lactate concentration of >4.0 mmol/L (normal range 0.0 to 2.2); c) pulseless electrical activity or ventricular fibrillation or ventricular tachycardia; and d) refractory shock despite fluid resuscitation, and vasoactive medications. From 1994 to 1996, seven patients were admitted with confirmed Hantavirus pulmonary syndrome and severe cardiopulmonary failure. Three of the seven patients had at least two of the four criteria for a 100% mortality rate listed above, and appeared to be failing optimal conventional therapy. These three patients received support with venoarterial ECMO. The first patient was placed on ECMO during cardiac arrest and died. The next two patients who received ECMO for Hantavirus pulmonary syndrome survived after relatively short, uncomplicated ECMO runs, and were discharged without complications. CONCLUSIONS: ECMO successfully provided cardiopulmonary support in two patients with severe Hantavirus pulmonary syndrome who survived with a good outcome. Our experience suggests that ECMO is a beneficial therapy for patients critically ill with Hantavirus pulmonary syndrome.
Acute Disease↗
Tissue engineered bone repair of calvarial defects using cultured periosteal cells.
Periosteum has been demonstrated to have cell populations, including chondroprogenitor and osteoprogenitor cells, that can form both cartilage and bone under appropriate conditions. In the present study, periosteum was harvested, expanded in cell culture, and used to repair critical size calvarial defects in a rabbit model. Periosteum was isolated from New Zealand White rabbits, grown in cell culture, labeled with the thymidine analog bromodeoxyuridine for later localization, and seeded into resorbable polyglycolic acid scaffold matrices. Thirty adult New Zealand White rabbits were divided into groups, and a single 15-mm diameter full-thickness calvarial defect was made in each animal. In group I, defects were repaired using resorbable polyglycolic acid implants seeded with periosteal cells. In group II, defects were repaired using untreated polyglycolic acid implants. In group III, the defects were left unrepaired. Rabbits were killed at 4 and 12 weeks postoperatively. Defect sites were then studied histologically, biochemically, and radiographically. In vitro analysis of the cultured periosteal cells indicated an osteoblastic phenotype, with production of osteocalcin upon 1,25(OH)2 vitamin D3 induction. In vivo results at 4 weeks showed islands of bone in the defects repaired with polyglycolic acid implants with periosteal cells (group I), whereas the defects repaired with untreated polyglycolic acid implants (group II) were filled with fibrous tissue. Collagen content was significantly increased in group I compared with group II (2.90 +/- 0.80 microg/mg dry weight versus 0.08 +/- 0.11 microg/mg dry weight, p < 0.006), as was the ash weight (0.58 +/- 0.11 mg/mg dry weight versus 0.35 +/- 0.06 mg/mg dry weight, p < 0.015). At 12 weeks there were large amounts of bone in group I, whereas there were scattered islands of bone in groups II and III. Radiodensitometry demonstrated significantly increased radiodensity of the defect sites in group I, compared with groups II and III (0.740 +/- 0.250 OD/mm2 versus 0.404 +/- 0.100 OD/mm2 and 0.266 +/- 0.150 OD/mm2, respectively, p < 0.05). Bromodeoxyuridine label, as detected by immunofluorescence, was identified in the newly formed bone in group I at both 4 and 12 weeks, confirming the contribution of the cultured periosteal cells to this bone formation. This study thus demonstrates a tissue-engineering approach to the repair of bone defects, which may have clinical applications in craniofacial and orthopedic surgery.
Absorptiometry, Photon↗
Antiproliferative properties of human alveolar macrophages.
OBJECTIVE: The aim of our study was to determine whether macrophages from lung cancer patients could acquire antitumoral properties in an in vitro model. METHODS: We isolated macrophages from bronchoalveolar lavages performed in two groups of patients: patients with lung cancer and patients with lung infection. All patients were smokers. We used the inhibition of incorporation of 3H-thymidine by U937 tumoral cells as an in vitro cytostatic assay. RESULTS: When stimulated by gamma interferon, alveolar macrophages either from lung cancer patients or from patients with lung infection induced cytostasis of proliferating U937 tumoral cells. This effect could be reproduced by using the supernatants of cultures of activated macrophages. When using optimal doses, gamma interferon showed an increased activity as compared with lipopolysaccharide. The combination of these two compounds was no more effective than gamma interferon alone in cancer patients. A macrophage/U937 tumoral cell ratio of 1/1 was sufficient to achieve a near-maximal cytostatic effect. CONCLUSIONS: Our results demonstrate that it is possible to activate, in vitro, alveolar macrophages from lung cancer patients by stimulation with gamma interferon. These macrophages acquire antiproliferative properties against a sensitive tumoral cell line.
Bronchoalveolar Lavage Fluid↗
Effect of lung volume reduction surgery on gas exchange and pulmonary hemodynamics at rest and during exercise.
Lung volume reduction surgery (LVRS) has become an extended surgery for emphysema in order to improve the dyspnea of severely affected patients. Because resection of lung areas may reduce the vascular bed, which is an important factor of pulmonary hypertension in emphysematous patients, especially during exercise, the aim of our study was to assess the outcome of pulmonary hemodynamics and gas exchange at rest and during exercise after LVRS. Nine patients had right heart catheterization before and 3 to 12 mo (mean, 4.5 mo) after LVRS. FEV1 increased from 705 to 1,005 ml (p < 0.05) after LVRS. PaO2, PaCO2 and mean pulmonary artery pressure (Ppa) did not change after LVRS, either at rest or during exercise. However, a significant overall decrease of the respiratory swings of the pulmonary artery diastolic pressure (DeltaPd) at rest (median value, from 12 to 8 mm Hg, p < 0.01) and during exercise (from 20 to 15 mm Hg, p < 0.05) was observed. There was a significant correlation between the change in resting Ppa (Ppa before minus Ppa after LVRS) and the change in resting DeltaPd (r = 0.73, p < 0.03), and also between the change in exercising Ppa and the change in resting DeltaPd (r = 0.80, p < 0.02). Significant correlations were also found between the change in exercising Ppa and the change in exercising PaO2 (r = -0.70, p < 0.05), and between the change in exercising Ppa and the change in exercising PaCO2 (r = 0.76, p < 0. 03). We conclude that pulmonary hemodynamics in most cases are not impaired by LVRS either at rest or during exercise. The possible mechanisms influencing hemodynamics after a lung volume reduction procedure are discussed.
Adult↗
[Bronchiolitis obliterans with organizing pneumonia. Retrospective study of 19 cases].
We report a series of 19 cases of bronchiolitis obliterans with organized pneumonitis (BOOP) observed in two pneumology units at the Strasbourg University Hospital between July 1987 and June 1997. Mean patient age was 60 years. Clinical features included dry cough, exercise-induced dyspnea, and a flu-like syndrome in three-quarters of the cases. Standard chest x-ray showed a diffuse non-systemized alveolar syndrome with a air bronchogram in 18 cases and an interstitial syndrome in one-third of the cases. computed tomography of the thorax visualized bronchial dilatations by traction of the alveolar syndrome in one-third of the cases. Pulmonary function tests showed moderate restriction. Lymphocytes predominated in bronchio-alveolar lavage fluid. Pathology examination of surgical lung specimens (5 cases), transbronchial biopsies (5 cases) and scan-guided transparietal punctures (4 cases) provided the diagnosis. In 5 cases the diagnosis was based on the radiological and clinical presentation and favorable course on corticosteroid therapy. Recurrence was observed at corticosteroid withdrawal or dose reduction in 7 cases. In this series, bronchiolitis obliterans with organized pneumonitis was probably secondary to rheumatoid arthritis (1 case), breast radiotherapy (3 cases), and drugs (amiodarone: 1 case: sotalol: 2 cases: betaxolol: 1 case). An association with betaxolol has not been previously reported in the literature.
Adult↗
[Chronic respiratory insufficiency: evaluation, evolution, prognosis].
Chronic respiratory failure (CRF) is a major cause of morbidity and mortality. It is estimated that in France at least 60,000 patients exhibit severe CRF and that about 15,000 patients die each year from CRF. Chronic obstructive pulmonary disease (COPD) (chronic obstructive bronchitis, emphysema and their association) is by far the first cause of CRF (90% of the cases). The clinical picture of CRF depends on the causal disease, but exertional dyspnea is observed in almost all patients. Pulmonary function testing allows to assess whether the ventilatory defect is obstructive (COPD), restrictive or mixed. Severe CRF is usually defined by a Pa02 < 55 mmHg, in a stable state of the disease, with or without hypercapnia (PaC02 > 45 mmHg). The two major complications of CRF are acute exacerbations of the disease, with clinical and gasometric worsening, and pulmonary hypertension which may lead with time to right heart failure. Prognosis is poor in CRF since the 5 year survival rate is of 50% in COPD patients. Under long-term oxygen therapy (LTOT) the survival rate has been somewhat improved, being of 60-65% at 5 years. The best prognostic indices in CRF complicating COPD are the level of FEV1, Pa02, PaC02, the level of pulmonary artery mean pressure (PAP) and age. In COPD patients under LTOT the best prognostic indices are PAP and age.
Chronic Disease↗
[Short-duration nocturnal hypoxemia and persistent pulmonary hypertension].
Can daily short-duration hypoxemia (4-8 hours) induce pulmonary hypertension and right ventricular hypertrophy? A clinical model of this type of hypoxemia does exist: isolated nocturnal hypoxemia in patients with obstructive sleep apnea syndrome (OSAS) or chronic obstructive pulmonary disease (COPD). By investigating the pulmonary hemodynamics of these patients, it should be possible to determine whether nocturnal hypoxemia alone can induce pulmonary hypertension. Although nocturnal hypoxemia (in OSAS as well as in COPD) can induce acute episodes of pulmonary hypertension, it would not appear that nocturnal hypoxemia alone would be sufficient to provoke permanent diurnal pulmonary hypertension. This is the conclusion of recent studies concerning diurnal pulmonary hemodynamics in OSAS and COPD patients exhibiting minimal hypoxemia during the day but significant nocturnal desaturation. The therapeutic consequences of these data, particularly in COPD are important: current evidence is insufficient to treat with nocturnal oxygen therapy COPD patients who have minimal diurnal hypoxemia but significant nocturnal desaturation.
Hemodynamics↗
[Limitations of surgical treatment of primary bronchial cancers].
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Bronchial Neoplasms↗
Acute saline infusion induces extracellular acidification and activation of the Na+/H+ exchanger in man.
The effect of acute expansion of the extracellular fluid volume (ECV) with isotonic (0.9%) saline on the activity of the lymphocyte Na+/H+ antiport (NHE) was studied in a total of 18 healthy volunteers. Saline was infused at a constant rate so that 4 mmol kg-1 b.w. was administered over 2 h. NHE activity was measured by quantifying cytosolic pH (pHi) recovery following acidification of the cells with propionic acid and by pH clamping at various pHi values between 7.2 and 5.8 using nigericin. Both methods demonstrate NHE activation associated with intravenous saline infusion, the kinetic difference being a marked decrease in the Hill coefficient n from 3.28 +/- 0.21 (SEM) to 2.22 +/- 0.11 in the absence of changes in baseline pHi (7.14 +/- 0.02 vs. 7.08 +/- 0.02; P = 0.15), Vmax (42.8 +/- 2.7 vs. 48.1 +/- 2.8 mmol L-1 min-1; P = 0.08) and pK (6.32 +/- 0.04 vs. 6.35 +/- 0.02). NHE activation was associated with significant decreases in serum chloride (P = 0.016), calcium (P = 0.008), total cholesterol (P = 0.008), low-density lipoproteins (P = 0.016) and high-density lipoproteins (P = 0.008). Moreover, saline infusion induced extracellular acidification with a decrease in pH from 7.39 +/- 0.01 to 7.37 +/- 0.01 (P = 0.016), HCO3- from 23.3 +/- 0.43 mmol L-1 to 21.3 +/- 0.25 mmol L-1 (P = 0.008) and base excess from -1.03 +/- 0.38 mmol L-1 to -3.00 +/- 0.31 mmol L-1 (P = 0.008). Our results show for the first time that acute ECV expansion with isotonic saline is followed by an activation of the lymphocyte NHE. The underlying mechanism(s) remain to be investigated. However, the demonstration in our study of marked changes in acid-base balance induced by acute saline points to a possible inter-relationship of antiporter activation and extracellular acidification.
Acid-Base Equilibrium↗
Sleep-related hypoxaemia in chronic obstructive pulmonary disease: causes, consequences and treatment.
Worsening of hypoxaemia during sleep in patients with chronic obstructive pulmonary disease has been extensively investigated in the past 20 years owing to the development of polysomnography and to the advent of reliable transcutaneous oximeters. Sleep-related hypoxaemia is characteristic of rapid-eye-movement (REM) sleep but may be present during other sleep stages. There is a strong relationship between nocturnal O2 saturation and the level of daytime PaO2: the more pronounced daytime hypoxaemia, the more severe nocturnal hypoxaemia. Sleep-related hypoxaemia is due to a variable combination of alveolar hypoventilation and ventilation-perfusion mismatching, alveolar hypoventilation being the preponderant mechanism during REM sleep. The deleterious effects of sleep-related hypoxaemia include cardiac arrhythmias, 'hypoxaemic stress' on the coronary circulation and especially, peaks of pulmonary hypertension. The treatment of nocturnal hypoxaemia is conventional O2 therapy (both nighttime and daytime) in patients who exhibit marked daytime hypoxaemia (PaO2 < 55-60 mm Hg). At present data are not sufficient for justifying the use of isolated nocturnal O2 therapy in patients with nocturnal desaturation who do not qualify for conventional O2 therapy.
Clinical Trials as Topic↗
Sleep-related O2 desaturation and daytime pulmonary haemodynamics in COPD patients with mild hypoxaemia.
It has been hypothesized but not firmly established that sleep-related hypoxaemia could favour the development of pulmonary hypertension in chronic obstructive pulmonary disease (COPD) patients without marked daytime hypoxaemia. We have investigated the relationships between pulmonary function data, sleep-related desaturation and daytime pulmonary haemodynamics in a group of 94 COPD patients not qualifying for conventional O2 therapy (daytime arterial oxygen tension (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)). Nocturnal desaturation was defined by spending > or = 30% of the recording time with a transcutaneous O2 saturation < 90%. An obstructive sleep apnoea syndrome was excluded by polysomnography. Sixty six patients were desaturators (Group 1) and 28 were nondesaturators (Group 2). There was no significant difference between Groups 1 and 2 with regard to pulmonary volumes and Pa,O2 (8.4+/-0.6 vs 8.4+/-0.4 kPa (63+/-4 vs 63+/-3 mmHg)) but arterial carbon dioxide tension (Pa,CO2) was higher in Group 1 (6.0+/-0.7 vs 53+/-0.5 kPa (45+/-5 vs 40+/-4 mmHg); p<0.0001). Mean pulmonary artery pressure (Ppa) was very similar in the two groups (2.6+/-0.7 vs 2.5+/-0.6 kPa (19+/-5 vs 19+/-4 mmHg)). No individual variable or combination of variables could predict the presence of pulmonary hypertension. It is concluded that in these patients with chronic obstructive pulmonary disease with modest daytime hypoxaemia, functional and gasometric variables (with the noticeable exception of arterial carbon dioxide tension) cannot predict the presence of nocturnal desaturation; and that mean pulmonary artery pressure is not correlated with the degree and duration of nocturnal hypoxaemia. These results do not support the hypothesis that sleep-related hypoxaemia favours the development of pulmonary hypertension.
Aged↗
Five-year effects of nasal continuous positive airway pressure in obstructive sleep apnoea syndrome.
There have been very few studies assessing the long-term physiological effects of nasal continuous positive airway pressure (CPAP) for the obstructive sleep apnoea syndrome. We therefore investigated prospectively the evolution of lung function, arterial blood gases and pulmonary haemodynamics in patients with this syndrome treated with CPAP. Sixty five patients were included. The mean duration of home treatment with nasal CPAP was 64+/-6 months. Most of the patients (77%) were smokers at the baseline assessment. We observed a small, but significant, decrease in forced expiratory volume in one second (FEV1) from 80+/-21% at baseline (t0) to 76+/-21% of the predicted value at the follow-up evaluation (t5) (p<0.01). Arterial oxygen tension (P[a,O2]) for the group as a whole remained stable (9.4+/-1.5 kPa (71+/-11 mmHg) versus 9.4+/-1.2 kPa (71+/-9 mmHg)). However, P(a,O2) increased in the subgroup of patients with hypoxaemia at t0 (n=23), from 7.8+/-0.7 kPa (59+/-5 mmHg) to 8.9+/-1.2 kPa (67+/-9 mmHg). Arterial carbon dioxide tension (P[a,CO2]) for the group as a whole increased slightly, but significantly, from 5.2+/-0.7 kPa (39+/-5 mmHg) to 5.4+/-0.5 kPa (41+/-4 mmHg) (p<0.05). Mean pulmonary artery pressure (Ppa) at rest did not change (16+/-5 mmHg versus 17+/-5 mmHg; NS) nor did exercising Ppa. In the 11 patients with pulmonary hypertension at t0, Ppa was 24+/-5 mmHg at t0 versus 20+/-7 mmHg at t5 (NS). We conclude that the significant decrease of forced expiratory volume in one second after 5 yr follow-up was related to a high percentage of smokers and exsmokers in the study population. Daytime arterial oxygen tension and pulmonary artery pressure remained stable in an unselected series of 65 obstructive sleep apnoea syndrome patients treated for 5 yrs with nasal continuous positive airway pressure, unlike arterial carbon dioxide tension, which increased by a small, but significant, amount.
Female↗