Morphometric subaxial lateral mass evaluation allows for preoperative optimal screw trajectory planning.

PURPOSE: Lateral mass (LM) fixation has become a standard in cervical spine instability treatment; however, maximal biomechanical stability combined with low morbidity remains a challenge. We evaluated our own patient cohort for bicortical screw placement and complication rates and investigated optimal screw trajectories with preoperative multiplanar computed tomography (CT) scans. METHODS: Fifty-five patients were retrospectively evaluated after LM fixation at various subaxial cervical spine levels with a modified Magerl technique. Postoperative CTs and clinical records were used to determine LM anatomy, screw lengths, bicortical screw percentages, and complication rates. Additionally, 3D CT subaxial cervical spine data sets from 45 additional subjects with clinical indications for cervical spine imaging were evaluated. Subject LM geometries (thickness) were evaluated at different sagittal angulations (strict sagittal, 20°, 30° and the optimal angulation) for the optimal screw trajectories at the C3-C7 segments. RESULTS: In total, 284 LM screws were placed, with a mean screw length of 16 mm and an 88% bicortical bone purchase. Additionally, a 3.8% malplacement rate was observed. LM thickness varied substantially between each subaxial cervical level and at each of the investigated angulations. The optimal angulation, at which LM thickness was maximal, increased continuously from C3 (14°) to C7 (38°). This increase permitted 8% (C3) to 39% (C7) gains in screw length compared with the strict sagittal plane assessments. CONCLUSIONS: The optimal LM trajectory varied for each subaxial segment. The knowledge of LM geometry allows for safe, long and even bicortical screw placements using preoperative sagittal CT imaging evaluations.

Recurrence and increased proliferation rate of a solitary fibrous tumor in the central nervous system--case report and review of the literature.

Meningeal solitary fibrous tumors (SFTs) were at first estimated as rare benign tumors which can be cured by total resection. To date, only 37 patients with intracranial SFTs have been reported. Therefore, the natural history of this tumor entity needs more enlightenment. The authors report a case of a 77-year-old female in whom a SFT with infiltration of the transversal sinus was subtotally resected. After a short time, interval tumor recurrence was seen, 2 years and 6 months later second surgery was performed. Immunohistologically, in both specimens typical features for SFT with positivity for CD34, vimentin and BCL-2 and negative for epithelial membrane antigen was seen. No signs for malignancy occurred in the second resection. Notably the MIB-1 index increased from 1 to 5%. In conclusion, consequent long-time follow-up for SFTs are necessary, especially after incomplete tumor resection.

[Lymphoproliferative disease following kidney transplantation]. / Lymphoproliferative Erkrankungen nach Nierentransplantation.

HISTORY AND CLINICAL FINDINGS: A 31-year-old male patient was referred because of a worsening graft function 56 months after an allogenic kidney transplantation for interstitial nephritis. He had complained about diffuse abdominal pain and watery diarrhea during the preceding week. Correction of volume status did not result in an improvement of kidney function. Bacterial or viral enteritis could be excluded as well as a mucosa-associated lymphatic tissue lymphoma (MALT-lymphoma). Shortly thereafter, the patient developed a subileus. INVESTIGATIONS: Kidney biopsy showed a low degree nephrosclerosis and some interstitial fibrosis, but no signs of rejection. The abdominal CT scan showed enlarged lymph nodes partially obstructing the intestinal lumen. Histology showed an EBV-negative, highly aggressive B-blastic lymphoma. DIAGNOSIS: EBV-negative post-transplant lymphoproliferative disease (PTLD). TREATMENT AND COURSE: Because of the advanced lymphoma stage immunosuppressive therapy was reduced and immunochemotherapy according to the CHOP-protocol (cyclophosphamide, doxorubicin, vincristine, prednisone) in combination with rituximab (R-CHOP) was started. After 4 chemotherapy cycles the patient was in complete remission and another 2 therapy cycles were given for consolidation. The patient remained free of disease during the actual follow-up of 8 months. CONCLUSION: PTLD can present with unspecific abdominal symptoms including diarrhea and with signs of graft dysfunction.

Blockade of leucocyte function-associated antigen-1 (LFA-1) decreases lymphocyte trapping in the normal pulmonary vasculature: studies in the isolated buffer-perfused rat lung.

Adhesion molecules regulate the migration of lymphocytes in lymphoid and non-lymphoid organs. In the lung, little is known about lymphocyte sticking and migration through the pulmonary vascular endothelium in physiological or pathological situations. Therefore the isolated buffer-perfused rat lung was used to investigate the mobilization of lymphocytes out of the normal lung into the venous effluent and to the bronchoalveolar space. The lymphocyte subset composition was characterized in the venous effluent, the lung tissue and the bronchoalveolar lavage (BAL) using immunocytology. Lymphocytes continuously left the normal lung at a total of 5.0 +/- 0.7 x 106 cells within the first hour of perfusion. The injection of 200 x 106 lymphocytes via the pulmonary trunk increased the venous release of lymphocytes by 170%. To investigate the effect of LFA-1 and CD44 on the adhesion of lymphocytes to the pulmonary endothelium, lymphocytes preincubated with an anti-LFA-1 MoAb, which blocks the interaction of LFA-1 and intercellular adhesion molecule-1 (ICAM-1), or lymphocytes preincubated with an anti-CD44 MoAb, were injected. The injection of LFA-1-blocked lymphocytes led to an increase by 70% of injected cells recovered in the perfusate within the first hour, whereas anti-CD44 treatment of injected lymphocytes had no effect. The LFA-1-blocked lymphocytes showed higher numbers of T and B cells in the effluent. Thus, the present experiments demonstrate that LFA-1 influences the trapping of lymphocytes in the vasculature of the healthy rat lung.

Endotoxin priming of the cyclooxygenase-2-thromboxane axis in isolated rat lungs.

Enhanced prostanoid generation has been implicated in vascular abnormalities occurring during endotoxemia and sepsis, and the lung is particularly prone to such events. Prostanoids are generated from arachidonic acid (AA) via cyclooxygenase (COX)-1 or -2, both isoenzymes recently demonstrated to be expressed in different lung cell types. Upregulation of COX may underlie the phenomenon that endotoxin [lipopolysaccharide (LPS)]-exposed lungs show markedly enhanced vasoconstrictor responses to secondarily applied stimuli (priming). Isolated rat lungs were perfused with a physiological salt buffer solution in the absence and presence of 1.5% rat plasma and exposed to different concentrations of LPS (1,000 or 10,000 ng/ml) during a 2-h priming period. No change in physiological variables was noted during this period, although enhanced baseline liberation of both thromboxane (Tx) A(2) and PGI(2) as well as of tumor necrosis factor (TNF)-alpha was evident compared with that in control lungs in the absence of LPS. LPS priming caused a significant elevation in AA-induced pulmonary arterial pressure, ventilation pressure, and lung weight gain. Concomitant increased levels of TxA(2) were found in the buffer perfusate. All changes were largely suppressed by three selective, structurally unrelated COX-2 inhibitors (NS-398, DUP-697, and SC-236) in both buffer- and buffer-plasma-perfused lungs. Anti-TNF-alpha neutralizing antibodies were ineffective under conditions of buffer perfusion. In the presence of plasma components, manyfold augmented TNF-alpha generation was noted, and anti-TNF-alpha antibodies significantly suppressed the increase in ventilation pressure but not in the vascular pressor response and lung edema formation. We conclude that the propensity of LPS-primed lungs to respond with enhanced vasoconstriction, edema formation, and bronchoconstriction to a secondarily applied stimulus proceeds nearly exclusively via COX-2 and increased Tx formation, with TNF-alpha generation being involved in the change in bronchomotor reactivity in the presence of plasma constituents. In context with recent immunohistological investigations, LPS-induced upregulation of the COX-2-thromboxane synthase axis in vascular and bronchial smooth muscle cells is suggested to underlie these events.

Rat pulmonary cyclooxygenase-2 expression in response to endotoxin challenge: differential regulation in the various types of cells in the lung.

Cyclooxygenase (Cox), the key enzyme of prostanoid synthesis, consists of the two isoforms Cox-1 and Cox-2, both recently noted to be constitutively expressed in rat lungs with a distinct profile of cellular distribution. The responsiveness of pulmonary Cox-1 and Cox-2 expression to intravascular endotoxin lipopolysaccharide (LPS) administration was investigated in isolated, ventilated rat lungs, buffer-perfused with or without admixture of rat plasma. Immunohistochemical staining intensity was measured by a previously described method of silver enhancement and epipolarization image analysis. Both the Cox-1 mRNA, quantified in the whole lung homogenate, and the cellular localization of Cox-1 were unchanged in response to LPS. In contrast, time- and dose-dependent up-regulation of Cox-2 mRNA (lung homogenate) occurred, and differential LPS reactivity at the cellular level was observed. Up-regulation of Cox-2 in cell types expressing this enzyme already under baseline conditions was noted in bronchial epithelial cells, bronchial and vascular smooth muscle cells, cells within the BALT and myocytes of the large hilar veins. De novo induction of Cox-2 occurred in endothelial cells and the majority of alveolar macrophages. Down-regulation of Cox-2 was observed in perivascular and peribronchial macrophage-like cells. Moreover, differential impact of plasma components was noted: for the large majority of cells, CD14 surface expression correlated with Cox-2 responsiveness to LPS independent of plasma, whereas the presence of plasma components was a prerequisite for the LPS response in CD14-negative cells. LPS did not provoke physiological changes in the perfused lungs, but markedly enhanced baseline prostanoid generation. We conclude that LPS-induced Cox-2 regulation occurs in a complex, cell-specific manner, which may be relevant for pathogenetic sequelae in septic lung injury and acute respiratory failure.

Identification of a penta- and hexapeptide of islet amyloid polypeptide (IAPP) with amyloidogenic and cytotoxic properties.

Pancreatic amyloid is found in more than 95 % of type II diabetes patients. Pancreatic amyloid is formed by the aggregation of islet amyloid polypeptide (hIAPP or amylin), which is a 37-residue peptide. Because pancreatic amyloid is cytotoxic, it is believed that its formation is directly associated with the development of the disease. We recently showed that hIAPP amyloid formation follows the nucleation-dependent polymerization mechanism and proceeds via a conformational transition of soluble hIAPP into aggregated beta-sheets. Here, we report that the penta- and hexapeptide sequences, hIAPP(23-27) (FGAIL) and hIAPP(22-27) (NFGAIL) of hIAPP are sufficient for the formation of beta-sheet-containing amyloid fibrils. Although these two peptides differ by only one amino acid residue, they aggregate into completely different fibrillar assemblies. hIAPP(23-27) (FGAIL) fibrils self-assemble laterally into unusually broad ribbons, whereas hIAPP(22-27) (NFGAIL) fibrils coil around each other in a typical amyloid fibril morphology. hIAPP(20-27) (SNNFGAIL) also aggregates into beta-sheet-containing fibrils, whereas no amyloidogenicity is found for hIAPP(24-27) (GAIL), indicating that hIAPP(23-27) (FGAIL) is the shortest fibrillogenic sequence of hIAPP. Insoluble amyloid formation by the partial hIAPP sequences followed kinetics that were consistent with a nucleation-dependent polymerization mechanism. hIAPP(22-27) (NFGAIL), hIAPP(20-27) (SNNFGAIL), and also the known fibrillogenic sequence, hIAPP(20-29) (SNNFGAILSS) exhibited significantly lower kinetic and thermodynamic solubilities than the pentapeptide hIAPP(23-27) (FGAIL). Fibrils formed by all short peptide sequences and also by hIAPP(20-29) were cytotoxic towards the pancreatic cell line RIN5fm, whereas no cytotoxicity was observed for the soluble form of the peptides, a notion that is consistent with hIAPP cytotoxicity. Our results suggest that a penta- and hexapeptide sequence of an appropriate amino acid composition can be sufficient for beta-sheet and amyloid fibril formation and cytotoxicity and may assist in the rational design of inhibitors of pancreatic amyloid formation or other amyloidosis-related diseases.

Vasoregulatory prostanoid generation proceeds via cyclooxygenase-2 in noninflamed rat lungs.

Prostanoids have been implicated in the regulation of lung vascular tone both under physiological and inflammatory conditions. The conversion of arachidonic acid (AA) to prostaglandin H2 is catalyzed at least by two isoforms of cyclooxygenase, named Cox-1 and Cox-2. Cox-1 is thought to be ubiquitously expressed, enrolled in physiological processes, whereas Cox-2 is mostly assumed to be dynamically regulated, responding to inflammatory conditions. We have recently shown by immunohistochemistry that Cox-2 is constitutively expressed in control rat lungs, with a predominant localization in smooth muscle cells of partially muscular vessels. We now asked whether Cox-2 is basically involved in the physiological regulation of pulmonary vascular tone. Isolated perfused rat lungs were challenged with intravascular bolus application of free AA to elicit thromboxane-related vasoconstrictor responses and to investigate the effects of three different selective Cox-2 inhibitors (NS-398, DUP697, SC-236). AA induced the liberation of prostaglandin I2 and thromboxane A2 into the intravascular space, and it provoked marked pulmonary artery pressure responses and concomitant lung edema formation. All events were dose-dependently inhibited by 1 to 50 micromol/liter NS-398, whereas control vasoconstrictor responses to angiotensin II and the stable thromboxane analogue U46619 were not affected by this agent. Similarly, marked inhibition of the AA elicited pressor response was achieved by 25 micromol/l DUP697 and by 10 micromol/l SC-236. These data suggest a physiological role of Cox-2 rather than Cox-1 in the regulation of vascular tone in rat lungs.

Detection of multiple vascular endothelial growth factor splice isoforms in single glomerular podocytes.

Glomerular podocytes are major determinants of filtration permselectivity in the glomerulus. Although the molecular mechanisms determining the characteristics of the glomerular filtration unit are incompletely understood, vascular endothelial growth factor (VEGF) has been implicated. To analyze this process in situ, we established a method that allows exploration of in vivo mRNA expression of podocytes using single-cell reverse transcriptase-polymerase chain reaction (RT-PCR). Microdissected mouse glomeruli were held in a patch-clamp apparatus, and single podocytes were harvested by aspiration. After lysis, the cells were reverse transcribed, and PCR was performed (45 cycles). The podocyte nature of the material was confirmed by detection of podocyte-specific mRNA (glomerular epithelial protein 1 and Wilms' tumor protein 1). Using specific oligonucleotide primers, VEGF was detected in mRNA obtained from renal cortex, single microdissected glomeruli, cultured murine podocytes, and single podocytes in situ. All cells examined expressed three VEGF isoforms (121, 165, and 189). These differ in their capacity for binding to extracellular matrix and could have different potencies regulating glomerular endothelial permeability. Our approach should allow a semiquantitative, isoform-specific evaluation of VEGF mRNA expression in podocytes during nephrogenesis and in glomerular disease.

Loss of lifetime due to radiation exposure-averaging problems.

A new method is presented for assessing a years of life lost (YLL) due to stochastic effects caused by the exposure to ionizing radiation. The widely accepted method from the literature uses a ratio of means of two quantities, defining in fact the loss of life as a derived quantity. We start from the real stochastic nature of the quantity (YLL), which enables us to obtain its mean values in a consistent way, using the standard averaging procedures, based on the corresponding joint probability density functions needed in this problem. Our method is mathematically different and produces lower values of average YLL. In this paper we also found certain similarities with the concept of loss of life expectancy among exposure induced deaths (LLE-EID), which is accepted in the recently published UNSCEAR report, where the same quantity is defined as years of life lost per radiation induced case (YLC). Using the same data base, the YLL and the LLE-EID are calculated and compared for the simplest exposure case-the discrete exposure at age a. It is found that LLE-EID overestimates the YLL, and that the magnitude of this overestimation reaches more than 15%, which depends on the effect under consideration.

Defective endogenous opioid response to exercise in type I diabetic patients.

Plasma beta-endorphin (beta-E) concentration was determined before, during, and after a standardized incremental exercise test to maximal capacity in eight type I diabetic patients and eight normal control subjects. Diabetic patients were studied under normoglycemic and hyperglycemic conditions in a single-blind random fashion to differentiate between the effects of acute hyperglycemia and of diabetes per se on the beta-E response to exercise. The perceived magnitude of leg effort elicited by exercise was evaluated using a category scale. Whereas plasma beta-E concentrations increased in control subjects with increasing workload, causing significantly higher beta-E levels at the end of exercise than at the beginning (P < .001), no such increase could be observed in the diabetic patients under normoglycemic and hyperglycemic conditions. In addition, baseline plasma beta-E concentrations were significantly lower in normoglycemic (P < .01) and hyperglycemic (P < .001) diabetic patients than in control subjects. Even during the recovery period, patients' beta-E levels remained significantly lower than those of control subjects. At submaximal levels of power output, the perceived intensity of leg effort was significantly higher in normoglycemic and hyperglycemic diabetic patients than in control subjects. We conclude that in type I diabetic patients, the ability of the endogenous opioid system to respond to exercise-induced stress is impaired under hyperglycemic and even under normoglycemic conditions. Considering the effect of endogenous opioids on stress tolerance, such changes may compromise exercise performance in diabetic patients.

Effect of autonomic neuropathy on ventilatory response to progressive hypercapnia in dialysis patients.

The impact of autonomic neuropathy (common in patients on haemodialysis) on ventilatory response to hypercapnia has been studied. We investigated cardiac reflex tests in 20 patients on chronic haemodialysis (8 patients were found with and 12 without neuropathy of the autonomic nervous system). Using the hyperoxic CO2-rebreathing method (according to Read), we tested the above-mentioned two groups of patients and compared them with 14 healthy control subjects. Accumulation of CO2 in blood with hyperoxic CO2 rebreathing stimulates central chemoreceptors, and therefore causes a progressive rise in minute ventilation. In patients with autonomic neuropathy (n = 8), ventilatory response to increasing pCO2 was significantly lower than that in the controls (1.7 +/- 0.3 versus 3.2 +/- 0.5 l/min/mmHg, P < 0.001). On the other hand ventilatory response in patients without autonomic damage (n = 12) showed no significant difference when compared to controls (3.1 +/- 0.8 l/min/mmHg). There were no differences in lung function, arterial blood gas analysis, blood chemistry, duration on dialysis, and demographic data when comparing the patients with and those without autonomic damage. Our analysis shows different patterns of ventilatory response to increasing pCO2 in patients on haemodialysis. Autonomic neuropathy has to be considered when rebreathing tests are interpreted. The clinical relevance of these findings needs further investigation.

The effect of aminophylline on the force-length characteristics of the diaphragm.

The aim of our study was to evaluate the effect of aminophylline on the contractile function of the human diaphragm during varying muscle fiber length. Ten healthy subjects were studied during maximal sniff maneuvers and bilateral phrenic nerve twitch stimulations, with and without intravenous infusion of aminophylline in a randomized fashion. The transdiaphragmatic pressures generated at various baseline lung volumes, from residual volume to 90% of total lung capacity, were recorded before and after the induction of diaphragm exhaustion. At all levels of lung volume, aminophylline did not have an effect on the contractility of the fresh diaphragm. In the exhausted diaphragm, however, the pressure values, induced by sniffs and twitch stimulations, were significantly improved by aminophylline. This positive effect on diaphragm contractility was also impressive at 60, 75, and 90% of total lung capacity. This indicates that aminophylline significantly improves the contractile function of the exhausted human diaphragm, even if the muscle fibers are shorter than optimal. This effect occurs regardless of the neuronal firing rate, whether it is low (twitch stimulation) or high (sniff maneuver).

Effect of lung transplantation on diaphragmatic function in patients with chronic obstructive pulmonary disease.

BACKGROUND: To date there are no data on the effects of lung transplantation on diaphragmatic function in patients with end stage chronic obstructive pulmonary disease (COPD). It is not known whether the relation between the transdiaphragmatic pressure (PDI) and lung volume is altered in recipients after transplantation as a result of changes in diaphragmatic structure caused by chronic hyperinflation. The effect of lung transplantation on diaphragmatic strength was determined in patients with COPD and the relation between postoperative PDI and lung volume analysed. METHODS: Diaphragmatic strength was assessed in eight double lung transplant recipients, six single lung transplant recipients, and in 14 patients with COPD whose lung function was similar to those of the transplant recipients preoperatively. PDI obtained during unilateral and bilateral phrenic nerve stimulation at 1 Hz (twitch PDI) at functional residual capacity (FRC) and during maximal sniff manoeuvres (sniff PDI) at various levels of inspiratory vital capacity (VCin) served as parameters for diaphragmatic strength. Sniff PDI assessed at the various VCin levels were used to analyse the PDI/lung volume relation. RESULTS: Lung transplantation caused a reduction in lung volume, especially in the double lung transplant recipients. As a consequence sniff PDI was higher in the double lung transplant recipients than in the patients with COPD at all levels of VCin analysed. However, sniff PDI values analysed at comparable intrathoracic gas volumes were not reduced in the patients with COPD when compared with those who underwent lung transplantation. Bilateral twitch PDI values were similar in the patients with COPD and in the lung transplant recipients. In the single lung transplant recipients unilateral twitch PDI values were similar on the transplanted and the non-transplanted side. The relation between PDI and lung volume was similar in the patients with COPD and in the lung transplant recipients. CONCLUSIONS: In patients with COPD lung transplantation leads to an increase the maximal sniff induced PDI values by placing the diaphragm in a more favourable position for pressure generation. Since patients with COPD and postoperative lung transplant recipients showed similar PDI/lung volume relations, this suggests that chronic pulmonary hyperinflation does not cause major functional alterations of the diaphragm.

Inspiratory muscle training in patients with Duchenne muscular dystrophy.

PURPOSE: The aim of this study was to assess the usefulness of a specific inspiratory muscle training in Duchenne muscular dystrophy (DMD). PATIENTS AND METHODS: Fifteen patients with DMD started 6 months of training the inspiratory muscles and 15 patients served as a control group. Pulmonary and inspiratory muscle function parameters were assessed 3 months before and at the beginning of training, in the first and third month of training, at the end, and 6 months after its cessation. Maximal sniff assessed esophageal and transdiaphragmatic pressure values served as indices for global inspiratory muscle strength and diaphragmatic strength, respectively. Inspiratory muscle endurance was assessed by the length of time a certain inspiratory task could be maintained. RESULTS: In 10 of the 15 patients, respiratory muscle function parameters improved significantly after 1 month of training. Further improvements were to be seen after 3 and after 6 months. Even 6 months after the end of training, those effects remained to a large extent. In the other five patients, there was no such improvement after 1 month of training, which was therefore discontinued. All these five patients had vital capacity values of less than 25 percent predicted and/or PaCO2 values of more than 45 mm Hg. The 15 control patients had no significant change in their respiratory muscle function parameters. CONCLUSION: We conclude that a specific inspiratory muscle training is useful in the early stage of DMD.

Diaphragmatic function in patients on continuous ambulatory peritoneal dialysis.

We investigated 8 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for diaphragmatic strength and the neuromechanical efficiency of the diaphragm while the abdomen was filled with dialysate and while it was empty. Maximum transdiaphragmatic pressure (Pdimax) served as parameter for diaphragmatic strength; diaphragmatic efficiency was assessed by simultaneously monitoring transdiaphragmatic pressure (Pdi) and diaphragmatic electromyogram (EMGdi) during room-air breathing and hyperoxic CO2-rebreathing. After instilling dialysate, Pdimax increased from 76.7 +/- 12.1 cmH2O to 92.2 +/- 16.3 cmH2O (P < 0.05). While the slopes of the regression lines relating minute ventilation (VE) to arterial CO2 tension, and the change in VE for a given change in Pdi during hypercapnic rebreathing were similar in both states, the slope of EMGdi vs Pdi was significantly steeper when the abdomen was filled (P < 0.05). The increase in Pdimax observed in the filled state may suggest an adaptive rightward shift in the diaphragm's force-length relationship in CAPD patients, although this mechanism is insufficient to prevent a reduction of neuromechanical efficiency of the diaphragm.

Endogenous opioid system during inspiratory loading in patients with type I diabetes.

To investigate the activity of the endogenous opioid system in patients with insulin-dependent diabetes mellitus during ventilatory stress situations, we measured plasma beta-endorphin levels in six male and five female diabetic patients breathing against fatiguing inspiratory resistive loads. The patients had to generate with each inspiration an esophageal pressure (Pes) 80% of maximum until they were exhausted and could no longer develop target Pes. The loaded breathing run was repeated three times with a 1-min interval between each run. Duty cycle, tidal volume, and breathing frequency were constant in all tasks. For each run plasma beta-endorphin levels were measured, inspiratory effort sensation assessed using a modified Borg scale, and inspiratory muscle endurance evaluated by the length of time the task could be maintained (Tlim). A group of 11 sex-, age-, height-, and weight-matched healthy individuals served as control subjects. Tlim was significantly lower in the diabetic patients. Evaluating respiratory effort during the three test runs in control subjects at a time corresponding to the break point of loaded breathing in patients showed significantly lower Borg ratings in the control group than in the patient group. Baseline plasma beta-endorphin was significantly lower in the diabetic patients (10.6 +/- 2.1 versus 27.0 +/- 4.2 pg/ml, p < 0.01). Additionally, whereas resistive loaded breathing caused a further increase in plasma beta-endorphin concentration in the control group (p < 0.005), absolutely no increase was found in the diabetic patients. We conclude that the endogenous opioid system in insulin-dependent diabetic patients does not respond to stress caused by breathing against fatiguing inspiratory resistive loads.

Inspiratory muscle performance relative to the anaerobic threshold in patients with COPD.

Rehabilitation programmes in chronic obstructive pulmonary disease (COPD) require exercise training above the anaerobic threshold. However, not all COPD patients develop metabolic acidosis during exercise. The hypothesis of this study was that non-exercise variables, characterizing the mechanical load on the inspiratory muscles during breathing at rest, can be used to reliably predict which patients with COPD are not able to develop metabolic acidosis during exercise. Thirty participants with COPD performed a symptom-limited cycle ergometer test. The oesophageal pressure/time index (PTIoes: the product of pressure magnitude and duration), the mean rate of pressure development during inspiration (Poes/TI), and the mean airway resistance (Raw)/maximal oesophageal pressure (Poesmax) ratio served as indices for the mechanical load on the inspiratory muscles. The oxygen uptake (VO2) at which plasma standard bicarbonate was seen to decrease from its baseline value was taken as the anaerboic threshold (AT). Mean Raw was significantly higher in those patients in whom the AT could not be detected. No other lung function parameters measured at rest allowed the accurate selection of those patients who did or did not develop exercise metabolic acidosis. On the other hand, Raw/Poesmax, PTIoes and Poes/TI were significantly different in the two patient groups. Additionally, whereas in the patient group with identifiable AT exercise hyperpnoea produced a non-linear increase of Poes/TI with respect to PTIoes above the AT, in the patient group without identifiable AT there was a linear relationship between Poes/TI and PTIoes throughout exercise. We conclude that the determination of inspiratory muscle load indices at rest may be useful in pulmonary rehabilitation programmes, for identifying those patients with COPD who do not develop exercise induced metabolic acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of opioids on inspiratory muscle fatigue during inspiratory resistive loading.

The effect of opioids on inspiratory muscle function under high mechanical load is still unknown. Even less clear is the extent to which opioids influence the shift of the electromyographic power spectrum of the inspiratory muscles to lower frequencies during ventilatory stress. We studied seven healthy subjects breathing against high inspiratory threshold loads until exhaustion while keeping the minute ventilation constantly high. We compared runs with and without administration of 0.2 mg kg-1 of morphine sulphate intramuscularly; two subjects were given 30 mg morphine sulphate so that we could study the effect of higher opioid concentration. The endurance time (Tlim), the diaphragmatic electromyogram (EMG), the transdiaphragmatic pressures (Pdi) and the ventilatory effort sensation were analysed. Morphine did not have any effect on Tlim or on the effort sensation elicited by the inspiratory resistance in both concentrations. Analysing the spectral shifts of the diaphragmatic EMG, we did not find any significant difference in the decrease of the centroid frequency between drug and control runs. Furthermore, the activation pattern of the diaphragm and the intercostal muscles, evaluated from the percentage contribution of oesophageal and gastric pressures on the transdiaphragmatic pressure swings, did not change following the administration of morphine. Our study shows that morphine does not change the function of the inspiratory muscles during high-resistive breathing. Morphine does not affect the electromyographic power spectrum of the diaphragm during those resistive breathing runs, either. This points out that during stressful ventilatory situations, the shift of the electromyographic power spectrum is attributed to a peripheral (muscular) event consequent to muscle fatigue and not to the elaboration of endogenous opioids.