Diverse biological processes coordinate the transcriptional response to nutritional changes in a Drosophila melanogaster multiparent population.

BACKGROUND: Environmental variation in the amount of resources available to populations challenge individuals to optimize the allocation of those resources to key fitness functions. This coordination of resource allocation relative to resource availability is commonly attributed to key nutrient sensing gene pathways in laboratory model organisms, chiefly the insulin/TOR signaling pathway. However, the genetic basis of diet-induced variation in gene expression is less clear. RESULTS: To describe the natural genetic variation underlying nutrient-dependent differences, we used an outbred panel derived from a multiparental population, the Drosophila Synthetic Population Resource. We analyzed RNA sequence data from multiple female tissue samples dissected from flies reared in three nutritional conditions: high sugar (HS), dietary restriction (DR), and control (C) diets. A large proportion of genes in the experiment (19.6% or 2471 genes) were significantly differentially expressed for the effect of diet, and 7.8% (978 genes) for the effect of the interaction between diet and tissue type (LRT, Padj. < 0.05). Interestingly, we observed similar patterns of gene expression relative to the C diet, in the DR and HS treated flies, a response likely reflecting diet component ratios. Hierarchical clustering identified 21 robust gene modules showing intra-modularly similar patterns of expression across diets, all of which were highly significant for diet or diet-tissue interaction effects (FDR Padj. < 0.05). Gene set enrichment analysis for different diet-tissue combinations revealed a diverse set of pathways and gene ontology (GO) terms (two-sample t-test, FDR < 0.05). GO analysis on individual co-expressed modules likewise showed a large number of terms encompassing many cellular and nuclear processes (Fisher exact test, Padj. < 0.01). Although a handful of genes in the IIS/TOR pathway including Ilp5, Rheb, and Sirt2 showed significant elevation in expression, many key genes such as InR, chico, most insulin peptide genes, and the nutrient-sensing pathways were not observed. CONCLUSIONS: Our results suggest that a more diverse network of pathways and gene networks mediate the diet response in our population. These results have important implications for future studies focusing on diet responses in natural populations.

Trade-off acquisition and allocation in Gryllus firmus: a test of the Y model.

Many models of life history evolution assume trade-offs between major life history traits; however, these trade-offs are often not found. The Y model predicts that variation in acquisition can mask underlying allocation trade-offs and is a major hypothesis explaining why negative relationships are not always found between traits that are predicted to trade-off with one another. Despite this model's influence on the field of life history evolution, it has rarely been properly tested. We use a model system, the wing dimorphic cricket, Gryllus firmus as a case study to test the assumptions and predictions of the Y model. By experimentally altering the acquisition regime and by estimating energy acquisition and energy allocation directly in this species, we are able to explicitly test this important model. Overall, we find strong support for the predictions of the Y model.

A prospective study of complications after tracheostomy for assisted ventilation.

A prospective study of 40 patients having elective tracheostomy for ventilatory assistance used fiberoptic bronchoscopy and radiologic examination to assess tracheal healing after extubation. Ten percent of patients had bleeding complications of tracheostomy and 17.5 percent had tracheostomy management problems. Sixteen percent of survivors had asymptomatic stomal site tracheal narrowing and 8 percent required tracheal resection for symptomatic stomal site tracheal stenosis, 16 percent had asymptomatic tracheal defects at the cuff site. Stomal healing was seen to consist of gradual stomal shrinkage, resolution of tracheitis, and approximation of divided tracheal rings. No statistically significant correlation was demonstrated between various factors operative during ventilatory assistance and subsequent tracheal healing. All patients should have routine endoscopic or radiologic tracheal assessment after-tracheostomy.

Percutaneous trephine lung biopsy: evolving role.

The Steele trephine was employed to perform 134 transthoracic biopsies in 120 patients. Resultant cores of tissue and "lung juice" provided a diagnosis in 89 percent (107) of the patients. Complications occurred in 41 percent (49) of the patients, the incidence being greatest in those with diffuse parenchymal disease. Most complications were of a minor nature. Although the precise role of trephine lung biopsy in the physician's diagnostic armamentarium remains to be defined, there is no doubt that it is a useful and safe technique in the elucidation of intrathoracic disease.

Canine tracheal injury by neodymium-YAG laser irradiation.

The relationship between endoscopic graded neodymiumyittrium aluminum garnet (Nd-YAG) laser intensity and the magnitude of effects on the tracheal wall was studied in two mongrel dogs. The dogs were anesthetized and graded Nd-YAG laser burns of 50, 100, and 200 Joules (J) were produced on the distal tracheal walls with a laser fiber inserted through a bronchoscope. One dog was killed immediately after injury and the other 24 hours later. At the time of killing, the trachea was excised and prepared for light microscopic (LM) and scanning electron microscopic (SEM) examination. We found that the injury produced by the 50 J intensity beam was confined to the mucosa and submucosa, with no destruction of the tracheal cartilage; by contrast, transmural penetration of the trachea was observed at intensities of 100 and 200 J. These results indicate that a strong correlation exists between laser intensity and the magnitude of the resulting tracheal injury. We suggest that the intensity of a Nd-YAG laser, endoscopically directed perpendicular to the tracheal wall, should not exceed 50 J in order to minimize the risk of perforating the tracheal wall.

Aspiration biopsy in the diagnosis of pulmonary disease.

We reviewed the results of 146 aspiration lung biopsies (ALB) performed on 140 patients over a five-year period. A negative fiberoptic bronchoscopy in patients with a pulmonary mass lesion or infiltrate was the major indication for ALB in this group. Seventy-two patients had various malignant chest lesions, 63 had benign or inflammatory pulmonary disease. A definite diagnosis was not obtained in the remaining five patients. The diagnostic accuracy of ALB was 73.6 percent in malignant disease and 17.5 percent in benign disease with no false positive results. Of 50 patients ultimately proven to have unresectable cancer, 46 (92.6 percent) were spared the necessity of exploratory thoracotomy for diagnosis by prior ALB. Complications included pneumothorax in 30 percent necessitating chest tube drainage in 14.3 percent. Minor hemoptysis occurred in 3.4 percent, hemothorax in 0.68 percent and subcutaneous emphysema in 1.36 percent. There were no deaths directly attributable to the procedure. We conclude that ALB is a valuable procedure in the diagnosis of malignant chest lesions, sparing exploratory thoracotomy for histologic diagnosis in many patients.

The value of submucous needle aspiration in the prediction of surgical resection line of bronchogenic carcinoma.

The fiberoptic bronchoscope was used to perform a series of SMNAs from the tumor site in the bronchial tree toward the carina to decide on an appropriate surgical line of resection in 20 patients. The line of resection was examined histologically for tumor invasion. Of the 20 patients who underwent surgery 16 had lobectomies and four had pneumonectomies. Eighteen patients had no evidence of tumor invasion at the surgical resection site. Of the remaining two, one had a cancer-positive SMNA proximal to the resection line and demonstrated tumor cells in the surgical resection line. The second demonstrated tumor cells in the right lower and upper lobes with sparing of the right bronchus intermedius. This patient underwent lobectomy with subsequent resection of the remaining right upper lobe. On the basis of this experience we conclude that SMNA is effective in predicting the optimal surgical line of resection in lung carcinoma.

Guidewire catheter change in central venous catheter biofilm formation in a burn population.

This study was designed to assess the risk of colonization and biofilm formation of central venous catheters left in situ for seven days vs those changed over a guidewire at three days and removed at seven days. Colonization was determined using scanning and transmission electron microscopy and compared to a special scraping/sonication culture method. Thirty-one catheters were examined, and no difference was found between catheters left in situ (9 of 16 colonized) and those changed over a guidewire (11 of 15 colonized). Colonization rates rose significantly from 4 of 15 catheters at the time of guidewire change to 11 of 15 at 7 days (p less than 0.001). Of the catheters defined as colonized by SEM, the special culture technique showed bacterial growth in only 35 percent, making a negative culture result of dubious value in ruling out catheter colonization. No beneficial effect of guidewire changes in reducing colonization could be demonstrated.

Effect of routine administration of analgesia on energy expenditure in critically ill patients.

Measurement of gas exchange using portable metabolic carts to indirectly determine energy expenditure (EE) has been a recent advance in the nutritional management of mechanically ventilated, critically ill patients. Although administration of large doses of morphine has been shown to significantly decrease EE, the influence on EE of morphine given in routine amounts to critically ill patients has not been studied previously. We examined the effect of morphine administration (given as bolus IV injections of 0.10 mg/kg every two hours and continuous IV infusion at 0.05 mg/kg/hr) on EE during rest and various ICU activities in seven mechanically ventilated patients. Morphine administration resulted in a significant reduction in resting EE and total EE of 6.0 and 8.6 percent, respectively. However, EE associated with activities (ie, chest x-ray examination and chest physiotherapy) were not significantly affected by morphine administration. Both bolus and continuous IV morphine infusion had similar effects on EE. Administration of routine doses of morphine significantly decreases total EE in critically ill patients. This should be considered an important factor influencing measurements of EE.

Biofilms on right heart flow-directed catheters.

This study was designed to detect biofilm and bacteria on right heart flow-directed catheters using scanning electron microscopy and culture following scraping and dispersion of biofilm by sonication. We examined 20 consecutive catheters removed from 18 critically ill patients, an average of 2.6 days after insertion. On scanning electron microscopy, all catheters were found to be covered by a biofilm, with bacteria visible on 50 percent of them. Cultures of specimens from 40 percent of the catheters grew skin organisms (Staphylococcus warneri, Diphtheroid), anaerobes (Propionibacterium), and other potential pathogens (Proteus vulgaris, Enterobacter cloacae). Combination of the two techniques produced a bacterial detection rate of 75 percent. This study demonstrates that the presence of biofilm with bacterial adherence is common on right heart flow-directed catheters. The phenomenon could play a significant role in endogenous infection in critically ill patients.

Primary alveolar hypoventilation managed by negative-pressure ventilators.

A girl who had a history of repeated apnea was found to have absent chemical drive to ventilation and, on sleep monitoring, both central and obstructive types of apnea. She is currently undergoing successful mechanical ventilation at night with negative-pressure ventilators.

Reversible ventilation and perfusion abnormalities in unilateral obstructed lung.

An intraluminal carcinoid tumor obstructing the left mainstem bronchus produced hypoxemia through alteration in ventilation/perfusion matching. Studies of regional lung function using 133-xenon (133Xe) and a multiprobe computerized instrumentation system documented a reduction of perfusion to 22 percent and ventilation to 6 percent of the total. There was negligible washout of intravenously injected 133Xe from the left lung consistent with air trapping. Four days after left mainstem bronchial sleeve resection, perfusion, ventilation and washout of injected xenon had significantly improved and by four months postresection, all measurements were virtually normal, although complete restoration of perfusion in relation to ventilation was delayed. Regional lung function studied with a multiprobe system in this patient provided a clinical model for the study of ventilation and perfusion inter-relationships in large airway obstruction and demonstrated that a prolonged time may be required for return of perfusion to normal.

Alterations in pulmonary mechanics and gas exchange during routine fiberoptic bronchoscopy.

Pulmonary function and arterial blood gases were measured in 35 patients undergoing routine diagnostic flexible fiberoptic bronchoscopy (FFB) either through an 8-mm endotracheal tube (ETT) or transnasally in order to investigate whether FFB changes lung function in a way which may explain why hypoxemia commonly occurs during this procedure. In these patients with moderate airway obstruction, functional residual capacity (FRC) increased significantly after inserting the ETT, after placing the FFB in the airway through the ETT, and after inserting the flexible bronchoscope transnasally. The mean increase in FRC was 30 percent in the intubated group before FFB insertion and 17 percent in the transnasal group. Removal of the FFB and ETT caused FRC to return toward the control value. Insertion of the ETT-FFB combination or transnasal FFB did not change PaO2 substantially, although following the examination, PaO2 was decreased significantly in the transnasal group but not in the intubated group. The PaO2 decreased significantly in both groups following removal of the ETT and transnasal FFB. These results suggest that placement of an FFB or ETT-FFB combination in the airway in spontaneously breathing subjects elevates FRC.

Energy expenditure associated with CPAP and T-piece spontaneous ventilatory trials. Changes following prolonged mechanical ventilation.

The use of portable metabolic carts to assess energy expenditure (EE) by measuring oxygen consumption (VO2) and carbon dioxide production (VCO2) has recently been applied to patients undergoing weaning from mechanical ventilation. The VO2 and EE can be used to estimate changes in the work of breathing (WOB) associated with different weaning strategies. The purpose of this study was to use VO2 and EE to assess changes in the WOB when assisted mechanical ventilation (AMV) was replaced with two spontaneous ventilatory trial (SVT) techniques: continuous positive airway pressure (CPAP) and T-piece. Nine difficult-to-wean patients were studied during the initial weaning period following 26 +/- 18 days (mean +/- SD) of mechanical ventilatory support. The VO2 and EE during all AMV were 296 +/- 75 ml/min and 2069 +/- 519 kcal/day, respectively. Compared to the baseline AMV levels, during CPAP overall VO2 and EE increased 14 percent and 13 percent, respectively, and during T-piece overall VO2 and EE increased 20 percent and 19 percent, respectively. Respiration rate (f) increased and tidal volume (VT) decreased during both SVTs compared to AMV although no significant change in minute ventilation was seen. The WOB, as judged from changes in VO2, was only 5 percent higher during T-piece compared to CPAP; however, patients tolerated an average of only 141 +/- 45 min on T-piece vs 165 +/- 29 minutes on CPAP. We conclude that during the initial weaning stages in patients who have received prolonged mechanical ventilatory support, the WOB associated with SVTs is increased compared to AMV but that the WOB associated with T-piece is not significantly greater than that for CPAP.

Caval catheter haemodialysis.

We describe a five-year experience using vena caval access for haemodialysis utilizing the McIntosh double-lumen catheter. A description of the catheter, method of insertion and of its performance including complications in 88 patients is given. The McIntosh catheter is a rapid, simple, effective and safe means of obtaining access for short-term haemodialysis.

Hemodynamic and pathologic effects of prostacyclin on oleic acid-induced pulmonary injury.

Oleic acid (OA) injection into the lungs of dogs produces pulmonary edema and decreased cardiac output, and the result is combined hypoxic and stagnant hypoxia. Prostacyclin (PGI2) has some effects that may be beneficial in the alleviation of hypoxia. We studied 18 anesthetized dogs that were divided into three groups: (1) Six dogs acted as controls and did not receive OA or PGI2, (2) six dogs received OA but no PGI2, and (3) six dogs were first given OA and 1 hour later an infusion of PGI2 (100 ng/kg/min) was started and continued for 4 hours. All dogs were killed at the end of the study and their lungs were removed for weighing and preparation for microscopic examination. Compared with controls, OA caused a low cardiac output, high systemic and pulmonary vascular resistance, and increased right-to-left intrapulmonary shunt. The group that received OA and PGI2 demonstrated a well-maintained cardiac output and a low systemic vascular resistance. Right-to-left intrapulmonary shunt, however, increased in these dogs compared with the dogs not given PGI2. All animals given OA had similar wet/dry lung weights and histologic appearances. Our results suggest that the only beneficial effect of PGI2 in OA-induced lung injury is to improve the stagnant hypoxia, but this is associated with an aggravation of the hypoxic hypoxia. The result of these competing effects appears to be a mild overall improvement in oxygen delivery as suggested by the slightly higher mixed venous PO2 in the group that received PGI2.

Collateral ventilation during high-frequency oscillation in dogs.

Mechanics of collateral channels during high-frequency oscillatory ventilation (HFOV) were assessed in eight anesthetized dogs, using a modification of Hilpert's technique. Base-line functional residual capacity was measured with a body plethysmograph, with inspiratory efforts induced by phrenic nerve stimulation. The resistance (Rcoll) and time constant (Tcoll) of collateral channels at five lung volumes were measured during HFOV and positive end-expiratory pressure (PEEP). Rcoll and Tcoll were significantly higher during HFOV (P less than 0.001); the differences did not correlate with resting lung volumes. The calculated static compliance of the wedged segment was similar during HFOV and PEEP (P greater than 0.005). Mean pressures measured in small airways during HFOV corresponded to the midline between the inflation and deflation limbs of the static pressure-volume curves, indicating similar pressure-volume characteristics of the respiratory system during HFOV and static conditions. We conclude that HFOV increases resistance to gas flow through collateral channels but that this pathway may still be important in gas exchange.

Comparison of plethysmographic methods for obtaining thoracic gas volume in anesthetized dogs.

Thoracic gas volume (TGV) cannot be measured in the body plethysmograph by the standard spontaneous breathing technique (SB) when there is a significant respiratory center depression. In this case, either external compression of the chest wall (EC) or phrenic nerve stimulation (PhN) can be used to induce the pressure-volume changes necessary to calculate TGV. In the present study we compared TGV measured in eight pentobarbital-anesthetized dogs by SB, EC, PhN, and the standard He-dilution method. EC and simulated PhN were also used to measure the volume of a lung model, and EC was used to measure the volume of isolated lung lobes. A method for fast and accurate plethysmographic calibration is also described. In the intact dogs, SB, PhN, and He-dilution techniques gave similar results, but EC overestimated TGV. In the isolated lobes and lung model EC accurately measured volume. We speculate that EC induces substantial intersegmental and/or interlobal gas movement in intact lungs and that the pressure drop due to airway resistance causes proximal airway pressure to underestimate alveolar pressure changes, which induces overestimation in calculated TGV. We conclude that PhN is the method of choice to measure plethysmographic TGV when the respiratory center is depressed and that EC overestimates TGV in intact dogs.

Laser fluorescence bronchoscope for localization of occult lung tumors.

A system for imaging occult bronchogenic carcinoma by the fluorescence of previously-injected, tumor-specific compound hematoporphyrin-derivative has been assembled and successfully used to locate a tumor 1 mm thick. The violet excitation source is a krypton ion laser coupled to fused quartz fiber light conductor. An electrostatic image intensifier attached to a standard flexible fiberoptic bronchoscope provides a bright image even at relatively low irradiance. A red secondary filter rejects most reflected background and autofluorescence. Sensitivity and contrast capability of the system should permit detection of a tumor less than 0.1 mm thick.

Nimodipine and chronic vasospasm in monkeys: Part 3. Cardiopulmonary effects.

A subarachnoid hemorrhage was induced in 30 cynomolgus monkeys by the placement of a 6- to 7-ml blood clot through a frontotemporal craniectomy (Day 0). The monkeys underwent a 1-week-long, randomized, blind trial comparing various doses of nimodipine to placebo, sham, and no treatment. The treatment groups were: nimodipine, 3 mg/kg every 8 hours (n = 6), 6 mg/kg every 8 hours (n = 6), and 12 mg/kg every 8 hours (n = 6); placebo (polyethylene glycol 400), 0.33 ml/kg every 8 hours (n = 6); and no treatment (n = 6). An additional sham group underwent craniectomy without clot placement (n = 6) so that 36 animals in total were operated upon. Differences in cardiopulmonary indices between Day 0 and Day 7 were compared within and between groups. No significant differences were obtained in the sham and no treatment groups. The nimodipine 6- and 12-mg/kg groups showed significant decreases in blood pressure (P less than 0.04 and P less than 0.015). Systemic vascular resistance was increased in the placebo and 3-mg/kg groups (P less than 0.02) and decreased in the 12-mg/kg group (P less than 0.015). Stroke index was increased in the 12-mg/kg group (P less than 0.05). Cardiac index and stroke index correlated positively with nimodipine dosage (r = 0.99, P less than 0.05). There were no pronounced changes in pulmonary artery wedge pressure, central venous pressure, alveolar-arterial oxygen pressure difference, arteriovenous oxygen content difference, and percentage of shunting.