Accurate thermochemistry at affordable cost by means of an improved version of the JunChS-F12 model chemistry.

The junChS-F12 composite method has been improved by means of the latest implementation of the CCSD(F12*)(T+) ansatz and validated for the thermochemistry of molecules containing atoms of the first three rows of the periodic table. A thorough benchmark showed that this model, in conjunction with cost-effective revDSD-PBEP86-D3(BJ) reference geometries, offers an optimal compromise between accuracy and computational cost. If improved geometries are sought, the most effective option is to add MP2-F12 core-valence correlation corrections to CCSD(T)-F12b/jun-cc-pVTZ geometries without the need of performing any extrapolation to the complete basis set limit. In the same vein, CCSD(T)-F12b/jun-cc-pVTZ harmonic frequencies are remarkably accurate without any additional contribution. Pilot applications to noncovalent intermolecular interactions, conformational landscapes, and tautomeric equilibria confirm the effectiveness and reliability of the model.

Hemodialysis associated hypoxia extends into the post-dialysis period.

To investigate whether hypoxia extends into the post-hemodialysis period, nine clinically stable-end stage renal disease patients were dialyzed against bicarbonate and one against an acetate batch, all with bioincompatible dialyzers. None had clinical evidence of cardiopulmonary overload on the day of the study. Using an oximeter with internal memory, oxygen saturation was monitored continuously at the beginning, during, and for four hours after hemodialysis. Hypoxia was defined as oxygen saturation less than 85%. Three patients had no hypoxia during or after dialysis. Hypoxia occurred in five patients both during and after dialysis, and in two patients only in the post-dialysis period. Episodes of hypoxia were of longer duration and severity in post-dialysis period. We conclude that significant hypoxia can occur in the post-hemodialysis period.

Use of fiberoptic bronchoscopy in the diagnosis of bronchogenic carcinoma. A study in patients with idiopathic pleural effusions.

We reviewed our experience with 115 patients with pleural effusion in whom bronchogenic carcinoma was suspected who underwent fiberoptic bronchoscopy (FOB) to identify those for whom the procedure was useful. In 6 of 12 patients with hemoptysis, 8 of 12 with a mass or infiltrate, and 8 of 18 with atelectasis with negative fluid cytology and 3 of 7 with cytology positive, FOB was useful in diagnosis. Sixty-six patients had an isolated cytology-negative effusion. Seven of 18 with massive effusion had FOB detecting cancer. Fiberoptic bronchoscopy usually was nondiagnostic in lesser-sized effusions (47 of 48). Using outcome for those with nondiagnostic FOB, we established operating characteristics for the procedure. We conclude that FOB is useful in diagnosing bronchogenic carcinoma in such patients when there is hemoptysis, accompanying lung mass or infiltrate, atelectasis, the effusion is massive, or in cytology-positive effusions without obvious primary tumor. Due to the low prevalence of bronchogenic carcinoma in patients with effusions of lesser size, we suggest that in this group FOB not be routinely performed.

Pleural effusion in yellow nail syndrome: chemical pleurodesis and its outcome.

Two cases of yellow nail syndrome (a triad of yellow dystrophic nails, chronic lymphedema and pleural effusion) are described which demonstrate long-term control of recurrent pleural effusions by tetracycline pleurodesis. Neither patient developed problems as a result of the procedure enabling us to conclude that tetracycline pleurodesis is effective in managing reaccumulating pleural fluid in yellow nail syndrome and may avoid loss of lung function due to pleural peel.

Simultaneous legionellosis and invasive aspergillosis in an immunocompetent patient newly treated with corticosteroids.

Invasive pulmonary aspergillosis (IPA), although unusual, has been recognized in the immunocompetent host. Several cases of IPA with rapidly progressive respiratory failure have been reported in patients receiving short-term corticosteroid therapy for chronic obstructive pulmonary disease. Atypical pneumonia caused by dual infection with Legionella pneumophila and Mycoplasma pneumoniae has also been reported. We report an unusual case of simultaneous L pneumophila pneumonia and IPA in an asthma patient with suspected allergic bronchopulmonary aspergillosis newly treated with corticosteroids.

Utility of pleural fluid analysis in predicting tube thoracostomy/decortication in parapneumonic effusions.

Recommended criteria for surgical drainage of parapneumonic effusions include evidence of frank purulence, a glucose level less than 40 mg/dl, a pH of less than 7.00, or an LDH greater than 1,000 IU/L. To test the utility of these criteria, we reviewed the three-year experience of three Rochester, NY, hospitals. We identified 133 patients undergoing thoracentesis for putative parapneumonic effusions. Of 91 patients with neutrophilic exudates, 43 met one or more criteria for tube thoracostomy: 48 did not. Twenty-one of the 43, including 9 with frank empyema, underwent immediate drainage. Of the 22 who did not, 11 eventually required tube thoracostomy and/or decortication. Of the 48 not meeting any of the criteria, 7 also came to surgery. Using whether the patients eventually underwent surgery as a measure of outcome, we calculated for those patients not undergoing immediate drainage the sensitivity, specificity, positive predictive values, and negative predictive values for each of the criteria. The four criteria have relatively high specificity ranging from 82 to 96 percent, but have low sensitivity varying from only 18 percent for a positive Gram stain to 53 percent for a fluid LDH greater than 1,000 IU/L. We conclude that these criteria have limited usefulness in predicting the need for eventual chest tube drainage/decortication. Patients not meeting the criteria require close follow-up as well.

Assessment of rebreathing O2 consumption in humans with normal and diseased lungs.

We investigated sources of error in estimating steady-state O2 consumption (VO2ss) by calculating O2 uptake from an anesthesia bag containing O2, He, and N2 during 10-20 s of rebreathing (VO2rb). In 11 normal resting subjects, VO2rb calculated with end-tidal sampling overestimated VO2ss by 16 +/- 15% (SD) (P less than 0.003). This error was proportional to the increase in pulse rate during rebreathing, so that pulse-corrected VO2rb slightly underestimated VO2ss by 2.1 +/- 12.2% (P = 0.66) in the six subjects who rebreathed 28% O2 in the rebreathing bag but significantly underestimated VO2ss by 7.5 +/- 6.7% (P less than 0.04) in the six subjects who rebreathed 21% O2 in the rebreathing bag. During exercise, VO2rb underestimated VO2ss by 4 +/- 12% (P less than 0.001) and by 7 +/- 6% at O2 consumptions greater than 2,000 ml/min if O2 in the rebreathing bag was kept above 20% throughout rebreathing. We found that VO2rb calculated with end-tidal gas concentrations underestimated VO2ss by 1-43% in patients with moderate-to-severe obstructive lung disease, with even greater errors when mixed expired samples were used. The magnitude of the discrepancy correlated poorly with abnormalities in standard pulmonary function tests. Based on these data, VO2rb closely approximates VO2ss in normal subjects, provided hypoxia during rebreathing is avoided and cardiac acceleration from rebreathing is taken into account during resting measurement.

Chronic persistent cough. Experience in diagnosis and outcome using an anatomic diagnostic protocol.

Irwin and co-workers have designed an anatomic approach to the diagnosis and treatment of cough. In their hands, diagnosis was consistently determined and treatment successful almost without exception, if sustained. We reviewed the results of a similar approach in 139 consecutive and unselected patients referred to pulmonary specialists in two community hospitals. Thirty-nine patients demonstrated hyperreactive airways (HA) by carbachol inhalation and/or eucapnic hyperventilation of cold air. Twenty-seven of 78 without HA had postnasal drip, and 13 of 78 had a persistent cough following acute upper airway inflammation. Other less common diagnoses included chronic bronchitis, gastro-esophageal reflux, occupational bronchitis, interstitial lung disease, and psychologic causes. We were able to find the cause of cough 88 percent of the time. Treatment adjusted for noncompliance was not always a success. While all patients with HA improved, 8 percent of patients without HA or specific diagnosis did not have an improvement in their cough upon retrospective inquiry. Based on this analysis, we find that the diagnosis and treatment of cough may not be as successful as originally reported using Irwin's approach.

Acute respiratory distress syndrome with pulmonary calcification in two patients with B cell malignancies.

Two patients, one with B cell lymphoma and hypercalcemia and the other with multiple myeloma and hypercalcemia developed acute progressive respiratory insufficiency characteristic of the adult respiratory distress syndrome (ARDS). Both were intubated and placed on mechanical ventilation. Lung compliance deteriorated and became refractory to mechanical inflation. Examination of the lungs at post mortem examination disclosed widespread calcification within alveolar septa and diffuse alveolar damage with hyaline membrane formation consistent with ARDS. Although ARDS has been described with lymphomatous involvement of the lungs, its development in association with metastatic calcification in B cell malignancy has not been previously reported.

Primary pulmonary infection caused by Mycobacterium terrae complex.

The Mycobacterium terrae complex, consisting of three saprophytic species, M. terrae, M. nonchromogenicum, and M. triviale, rarely causes human disease. Only six cases of respiratory infection involving the complex have been documented worldwide. A case of primary pulmonary disease in a previously healthy young woman caused by M. terrae complex is described.

Utility of fiberoptic bronchoscopy in patients with hemoptysis and a nonlocalizing chest roentgenogram.

The need for fiberoptic bronchoscopy in the patient with hemoptysis and a normal or nonlocalizing chest roentgenogram remains a subject of debate. Currently, diagnostic fiberoptic bronchoscopy is recommended as the investigative procedure of choice. To develop predictors that identify the patient in whom fiberoptic bronchoscopy is most likely to be diagnostic, we reviewed our community's experience with this population over a five-year period. We identified 196 patients with hemoptysis and a normal or nonlocalizing chest roentgenogram who underwent fiberoptic bronchoscopy. Three quarters were active or previous smokers. We examined the relationship of advancing age, sex, smoking, nonspecific roentgenographic findings and the amount, duration, and previous bouts of hemoptysis to the incidence of a diagnostic fiberoptic bronchoscopy. Twelve patients (6 percent) had bronchogenic carcinoma and 33 (17 percent) another specific cause for the hemoptysis identified by fiberoptic bronchoscopy. By univariate and discriminant analyses, we found that the three factors of age of 50 years or more, male sex, and smoking of 40 pack-years or more best predicted a diagnosis of malignancy. Bleeding in excess of 30 ml daily was associated with an increase in overall diagnostic yield. The presence of two of the three factors associated with malignancy or bleeding in excess of 30 ml daily (or both) identified 100 percent of the patients with bronchogenic carcinoma and 82 percent of all of the diagnostic fiberoptic bronchoscopic procedures. use of these criteria in selecting the patient for fiberoptic bronchoscopy could have reduced our use of the bronchoscope by 28 percent, with the remaining patients safely observed.

Can postoperative pulmonary complications after elective cholecystectomy be predicted?

To determine predictors of postoperative morbidity in elective cholecystectomy patients, the authors examined prospectively the consequences of age, sex, active and past smoking, respiratory history, obesity, type of surgical incision, and preoperative pulmonary function, upon the incidence of postoperative pulmonary complications and length of hospitalization. They identified 31 (14.8%) complications in 209 patients; 21 had atelectasis, 8 purulent bronchitis, and 2 pneumonia. These patients averaged 1.5 days longer in the hospital (p less than 0.001 by analysis of variance) than control patients. Abnormal spirometry (MEFV) and the single-breath nitrogen test (SBN2) were significant predictors of postoperative pulmonary complications (p less than 0.001 by discriminant analysis method). Active smoking and history of respiratory disease were associated with abnormal small airway function (p less than 0.001 by chisquare test), but did not predict postoperative morbidity. By analysis of variance, only a reduction in preoperative FVC emerged as predictive of prolonged hospitalization (p less than 0.001). These results were used to determine if the selection of patients by preoperative pulmonary function testing permits more cost-effective administration of respiratory therapy (RT) services. Neither the MEFV nor SBN2 had sufficient specificity to enhance the cost effectiveness of postoperative RT.

Inhaled metaproterenol is superior to inhaled cromolyn in protecting against cold-air-induced bronchospasm.

Eucapneic hyperventilation of cold air (EHCA) provokes bronchospasm in asthmatics. Although inhaled cromolyn powder and sympathomimetic solutions have attenuated the bronchospasm induced by EHCA, comparison of both drugs in solution has not been performed. We performed a prospective double-blind study comparing cromolyn solution, metaproterenol solution, and placebo (normal saline) given prior to EHCA. Eight asthmatics defined by a 20% reduction in forced expiratory volume in 1s (FEV1) after EHCA consented to the study. Patients were tested on 3 separate occasions at a similar time of day. Each session began with a determination of FEV1 followed by a randomized double-blind treatment. A repeat FEV1 (pre-EHCA) was performed 20 min after drug inhalation. Twelve minutes of EHCA was performed consisting of 4 min of tidal breathing, 4 min of eucapneic hyperventilation (60-70% of the predicted MVV) and a final 4 min of tidal breathing. FEV1 was performed immediately, 5 min, and 10 min after EHCA. The lowest value was defined as the post-EHCA FEV1. The pre-EHCA FEV1 was significantly larger after metaproterenol pretreatment compared to the pre-EHCA FEV1 following cromolyn (p = 0.01) and saline (p = 0.04). Metaproterenol pretreatment had a significant protective effect in comparison to placebo pretreatment (p less than 0.01). No other paired comparisons (cromolyn vs. placebo, cromolyn vs. metaproterenol) achieved statistical significance at a 0.05 level. In conclusion, metaproterenol is superior to cromolyn in protecting against cold-air-induced bronchospasm.

Transthoracic needle biopsy of lung in nonhospitalized patients.

To confirm the safety of transthoracic needle biopsy of the lung (TNB) in the outpatient setting, we reviewed our experience with 106 such procedures over three years. We compared the operating characteristics and morbidity with the 65 similar procedures we were asked to perform on hospitalized patients during the same period. Outpatients did not differ from inpatients in mean age, sex, incidence of clinically apparent COPD, size and location of lesion, or number of needle passes. The operating characteristics of the biopsy were the same for the two groups. Pneumothorax occurred in 29 (27 percent) of 106 outpatient and 26 (40 percent) of 65 inpatient TNBs. Few pneumothoraces not present upon completion of biopsy developed during four hours of observation or later. The requirement for chest tube drainage was similar for both groups, 5.7 and 4.6 percent, respectively. With appropriate caution, TNB can be performed safely on an outpatient basis and the cost of an uncomplicated procedure reduced by 27 percent.

Chronic effects of direct vasodilation (pinacidil), alpha-adrenergic blockade (prazosin) and angiotensin-converting enzyme inhibition (captopril) in systemic hypertension.

Chronic responses of systemic hemodynamics and blood pressure counterregulatory ("pseudo-tolerance") mechanisms were investigated in matched groups of patients with essential hypertension after 1 month of vasodilator therapy with pinacidil (a direct arterial dilator), prazosin (an alpha 1-adrenergic blocking drug) or captopril (an angiotensin-converting enzyme inhibitor). For equivalent decreases in mean arterial pressure compared with placebo baseline (approximately 8 mm Hg supine and 12 mm Hg upright), prazosin and captopril did not increase cardiac index or heart rate. In contrast, marked decreases in systemic vascular resistance with pinacidil (approximately 25%, p less than 0.05) were accompanied by reflex increases in cardiac index (approximately 20%, p less than 0.05). Activity of the sympathetic nervous system, measured by supine and upright plasma norepinephrine (NE), increased approximately 50% with pinacidil and prazosin (p less than 0.001 each), whereas captopril decreased supine plasma NE by 12% (p less than 0.05) and did not change upright plasma NE. All 3 drugs caused an expansion of height-adjusted blood volume (approximately 14%). Pinacidil and prazosin caused reversible weight gains of 0.9 and 0.7 kg, respectively, whereas captopril reversibly decreased body weight by 0.8 kg (p less than 0.05), suggesting differential effects of the 3 drugs on interstitial fluid volume. During chronic therapy, all 3 drugs may require concomitant diuretic therapy, whereas concomitant sympatholytic therapy may be required with the potent vasodilator pinacidil. Captopril may be associated with the lowest cardiac risk because of its lack of stimulatory effects on the sympathetic nervous system and cardiac index.

Cardiac output by rebreathing in patients with cardiopulmonary diseases.

Noninvasive estimates of cardiac output by rebreathing soluble gases (Qc) can be unreliable in patients with cardiopulmonary diseases because of uneven distribution of ventilation to lung gas volume and pulmonary blood flow. To evaluate this source of error, we compared rebreathing Qc with invasive measurements of cardiac output performed by indicator-dilution methods (COID) in 39 patients with cardiac or pulmonary diseases. In 16 patients with normal lung volumes and 1-s forced expiratory volumes (FEV1), Qc measured with acetylene [Qc(C2H2)] overestimated COID insignificantly by 2 +/- 9% (SD). In subjects with mild to moderate obstructive lung disease, Qc(C2H2) slightly overestimated COID by 6 +/- 15% (P = 0.11). In patients with restrictive disease or combined obstructive and restrictive disease, Qc(C2H2) underestimated COID significantly by 9 +/- 14% (P less than 0.04). The magnitude of the discrepancy between Qc and COID correlated with size of the volume rebreathed and an index of uneven ventilation calculated from helium mixing during rebreathing that determined a dead space to inspired volume ratio (VRD/VI). Rebreathing volumes less than 40% of the predicted FEV or VRD/VI of 0.4 or greater identified all subjects with a discrepancy between Qc(C2H2) and COID of 20% or greater.

Plasma norepinephrine and age as determinants of systemic hemodynamics in men with established essential hypertension.

Two primary predictor variables, age and supine plasma norepinephrine, were studied with respect to their influences on supine hemodynamic variables in 52 white men with essential hypertension who were 23 to 67 years of age and had been off active therapy for at least 4 weeks. Plasma norepinephrine was related to age (r = 0.39, p less than 0.01), correlated closely with mean arterial pressure (MAP; r = 0.54, p less than 0.0002) and systemic vascular resistance (r = 0.49, p less than 0.0005), and was related inversely to cardiac output (r = -0.26, p less than 0.06) and stroke volume (r = -0.31, p less than 0.05). Age correlated weakly with MAP (r = 0.31, p less than 0.05) and more strongly with systemic vascular resistance (r = 0.46, p less than 0.005) but was negatively related to cardiac output (r = -0.41, p less than 0.005) and heart rate (r = -0.33, p less than 0.05). Weight did not correlate with any of the hemodynamic variables. Partial regression techniques yielded significant residual correlations between age-adjusted plasma norepinephrine and MAP (r = 0.42, p less than 0.005) or systemic vascular resistance (r = 0.38, p less than 0.005). Residual correlations with cardiac output (r = -0.34, p less than 0.05), heart rate (r = -0.36, p less than 0.02), and systemic vascular resistance (r = 0.33, p less than 0.05) remained after adjusting age for the corresponding plasma norepinephrine values. These correlations demonstrate the independent effects of sympathetic nervous activity and the aging process on the systemic vasoconstriction and decreased cardiac function observed in essential hypertension.

Increased plasma norepinephrine and sympathetic nervous activity in essential hypertensive and uremic humans: effects of clonidine.

We investigated the relationship between hypertension and increased sympathoadrenal activity in previously normotensive, stable maintenance hemodialysis patients (uremics) who developed hypertension subsequent to the onset of chronic renal failure. In age-matched groups, supine morning plasma norepinephrine (NE) concentrations (pg/ml) were elevated in uremics (401 +/- 26, p less than 0.00001, n = 23) and essential hypertensives (340 +/- 23, p less than 0.01, n = 29) compared to normal controls (260 +/- 18, n = 24). To further investigate the functional significance of increased sympathoadrenal activity in uremia, a subset of dialysis patients was studied during chronic clonidine therapy. Compared to placebo baseline, clonidine (mean dose 0.4 mg/day) caused parallel decreases in mean arterial pressure (MAP) (-8 +/- 2 mm Hg, p less than 0.05), heart rate (HR) (-13 +/- 3 b/min, p less than 0.05), plasma NE (-84 +/- 13 pg/ml, p less than 0.01), and plasma epinephrine (-24 +/- 4 pg/ml, p less than 0.01). Clonidine exerted balanced effects on cardiac output and systemic vascular resistance while blood volume and plasma renin activity were slightly increased. We conclude that the increased sympathoadrenal activity in uremia contributes to chronically increased arterial pressure in a pattern similar to essential hypertension. Central sympatholytic drugs are effective antihypertensive agents in uremia.

Distribution of Ca in different regions of heart muscle cell.

Electron microscopic autoradiographic investigations to study the localization of Ca in muscle were performed using heart muscle. The distribution of autoradiographic grains, originating from Ca-45 were compared above myofibrils and interfibrillar spaces of the ventricle, auricle and sinus node of the heart. Our aim was to get new data on the role of Ca in the mechanical activity of muscle with special consideration of the Ca content of interfibrillar spaces. The different distribution of grains in the muscle fibrils and interfibrillar spaces of various parts of the heart can be in connection with the different activities of these parts. The more Ca content in myofibrils of ventricle cells may be in connection with its greater mechanical activity and its work.