Arousal responses to inspiratory resistive loading during REM and non-REM sleep in normal men after short-term fragmentation/deprivation

The arousal response to inspiratory resistive loading in normal men is known to be high during REM sleep compared to non-REM sleep. We investigated whether we could observe the same pattern, i.e. brisk arousal from REM sleep compared to non-REM sleep, in normal subjects who had undergone short-term sleep fragmentation/deprivation prior to the investigation. The arousal response to the repeated application of an external inspiratory resistance of 25 cm H2O/l/s was determined during REM and non-REM sleep in 10 healthy men after a single night with 4 hours of acoustically fragmented sleep. The percentage of arousals to non-arousals occurring within 2 minutes of the load application was significantly higher during REM sleep than during either of the non-REM sleep stages 2 and 3/4 and decreased significantly from stage REM to stage 2 and from stage 2 to stage 3/4. The mean time to arousal in REM was significantly shorter than in non-REM stage 3/4. The duration of sleep (comparing the results of the first with the second half of the sleep period time) did not modify the arousal response in stages 2 and 3/4. Despite short-term sleep fragmentation/deprivation the night before the study, the arousal response to external inspiratory resistive loading was brisker during REM than non-REM sleep in the healthy subjects studied. The responses were of the same magnitude as those induced in prior studies without pretest sleep disturbance. This is different from what is seen in patients with sleep apnea, where breathing disorders are worst during REM sleep and sleep fragmentation/deprivation leads to rapid deterioration of arousal responses to the spontaneously occurring airway occlusions.     

The effects of learning on the ventilatory responses to inspiratory threshold loading

Progressive threshold loading (PTL) is frequently used to assess inspiratory muscle endurance in health and disease. We and others have noted a systematic increase in endurance with the first few exposures to the task in subjects previously na?ve to PTL, which may not be related to conditioning of the muscles themselves. The purpose of this study was to investigate the mechanisms responsible for this increased endurance by examining the ventilatory responses to 3 PTL tests, each > 24 h apart, in 18 healthy subjects. During PTL, threshold pressure (Pth) was increased by approximately 10% every 2 min until task failure. Subjects were allowed to adopt any breathing pattern. Respiratory muscle strength (maximal inspiratory pressure [PImax]) was unchanged over successive tests while maximal Pth (Pthmax) during PTL increased (69 +/- 17, 77 +/- 16, and 86 +/- 11% of PImax, respectively, p < 0.05) (mean +/- SD), indicating that the increased Pthmax could not be attributed to improved respiratory muscle strength. Breathing pattern changed with successive tests, so that for comparative loads inspiratory time (TI), respiratory frequency (f ), and duty cycle (TI/Ttot) decreased. This change in breathing pattern did not alter respiratory muscle efficiency (respiratory muscle V O2/work), which was similar in each test (2.4 +/- 2.2%), but perceived effort (Borg Score), which was maximal at task failure in each test, decreased at comparative loads with successive tests. Thus, Pthmax during initial tests appeared to be limited by discomfort rather than respiratory muscle function. These findings suggest that the increased Pthmax with successive tests is a consequence of differences in the breathing pattern adopted, reflecting neuropsychological rather than respiratory muscle conditioning. Measurements from PTL should only be used to assess respiratory muscle performance after allowing time for learning.     

Defensiveness and perception of external inspiratory resistive loads in asthma

This paper introduces a model which incorporates fetal thymus organ culture (FTOC) from NOD mice to replicate thymic development of diabetogenic T cells. NOD fetal pancreas organ culture (FPOC) co-cultured with 13-16 day NOD FTOC for an additional 14-21 days produced less insulin than FPOC cultured alone. Insulin production from the FTOC of non-diabetic strains C57BL/6 and BALB/c was not inhibited by co-culture with FTOC from their syngeneic counterparts. Sections of the NOD co-cultures showed peri-islet infiltration with lymphocytes. Insulin reduction by FTOC/FP co-culture was prevented by co-culture of the NOD FT with FT from immunologically incompetent C.B-17 SCID/SCID mice. Co-culture of NOD FP with NOD FT prior to the development of T cells prevented generation of diabetogenic FTOC. Thus, early exposure of NOD T cell precursors to the thymic stromal elements of C.B-17 SCID/SCID FT or to islet antigens can negatively select for diabetogenic T cells or activate immuno-regulatory cells that can suppress diabetogenic T cell activity. The addition of blocking F(ab')2 fragments of anti-CD3epsilon monoclonal antibody to NOD FTOC/FP co-cultures prevented insulin reduction, implicating a role for TcR-mediated recognition in this "in vitro IDDM" model. The addition of activating whole anti-CD3epsilon caused the complete ablation of insulin production in FTOC/FP co-cultures from all strains tested. Transfer of unprimed syngeneic FTOC cells to prediabetic NOD mice prevented the onset of IDDM while transfer of islet-cell primed FTOC/FP cells slightly increased disease incidence. These data suggest that while diabetogenic T cells are present in the FT, they are normally suppressed, even after organ culture. However, these cells can induce the destruction of islet cells, in vitro and in vivo, if they are appropriately activated with pancreatic tissue.     

Abnormal neural response to feedback on planning and guessing tasks in patients with unipolar depression

BACKGROUND: It has been suggested that patients with unipolar depression show abnormal responses to negative feedback in the performance of cognitive tasks. Positron emission tomography (PET) has previously identified blood flow abnormalities in depressed patients during cognitive performance. We have also used PET to identify regions where there is differential neural response to performance feedback in normal volunteers. In this study we aimed to test the hypothesis that blood flow in these regions, the medial caudate and ventromedial prefrontal cortex, would be abnormal in depressed patients. METHODS: Six patients with unipolar depression and six matched controls were scanned using PET while performing cognitive tasks in the presence and absence of feedback. RESULTS: Compared with controls, depressed patients failed to show significant activation in the medial caudate and ventromedial orbitofrontal cortex. Blood flow was lower and a differential response, observed in normals, under different task and feedback conditions was not seen in the patients. DISCUSSION: The findings suggest that the behavioural response to feedback in depressed patients is associated with an abnormal neural response within the medial caudate and ventromedial orbitofrontal cortex, regions implicated in reward mechanisms. We argue that the observed abnormalities may depend on a combination of psychological factors, with both cognitive and emotive components.     

Estimation of respiratory muscle endurance using an inspiratory threshold loading device in patients with chronic pulmonary emphysema and in elderly subjects

We studied respiratory muscle endurance with an inspiratory threshold loading (ITL) device using Martyn's method (2-min incremental loading test) in 9 patients with chronic pulmonary emphysema (CPE patients) and in 9 elderly subjects with no lung disease (NE subjects), and their endurance was compared with that of 9 normal young subjects (NY subjects). In 11 cases (8 CPE patients and 3 NE subjects) a treadmill exercise test was performed and cardiopulmonary parameters obtained from the ITL and treadmill tests were compared. The maximum weight tolerated for 2 minutes (Wmax) and the mean peak inspiratory mouth pressure/maximum inspiratory mouth pressure ratio at the maximum load (Ppk/MIP at Max Load) were used as indices of respiratory muscle endurance. CPE patients had significantly decreased Wmax compared with those of NE and NY subjects. Wmax in all cases positively correlated with Ppk/MIP at Max Load, and endurance time of both the ITL and treadmill tests. During both tests, SaO2 significantly decreased, and heart rate and mean blood pressure significantly increased. There was less change in SaO2 and heart rate during the ITL test than during the treadmill test, and neither arrhythmias nor ST changes on ECG were observed during the ITL test. These results indicate that the ITL test can be easily and safely employed in CPE patients and elderly subjects to estimate respiratory muscle endurance.     

The effects of pulmonary rehabilitation combined with inspiratory muscle training on pulmonary function and inspiratory muscle strength in elderly patients with chronic obstructive pulmonary disease]

It has been suggested that pulmonary rehabilitation compined with inspiratory muscle training (IMT) might improve pulmonary function and respiratory muscle strength in elderly patients with chronic obstructive pulmonary disease (COPD). To test this hypothesis, inspiratory muscle strength (PImax), expiratory muscle strength (PEmax) and resting pulmonary function were measured in 13 elderly patients with COPD (aged 70.3 +/- 2.7 years). Inspiratory muscle training (IMT) was performed for 15 min twice a day, using a pressure threshold device, for a total of 12 weeks. The inspiratory threshold was set at 15% of maximal inspiratory pressure (PImax) for each individual. Pulmonary rehabilitation was performed for 12-h sessions over a 12-week period. Patients with COPD were assigned randomly to two groups: pulmonary rehabilitation combined with IMT (group A) (n = 7), and conventional pulmonary rehabilitation only (group B) (n = 6). Functional residual capacity (FRC) decreased significantly from 4.3 +/- 0.4 L at baseline to 3.9 +/- 0.4 L after rehabilitation (p < 0.01), Vp significantly increased from 4.6 +/- 0.8 L/sec at baseline to 5.1 +/- 0.7 L/sec after rehabilitation (p < 0.05) and the PImax increased significantly from 51.5 +/- 5.4 cmH2O at baseline to 80.9 +/- 7.0 cmH2O after rehabilitation (p < 0.02) in group A. However, these variables did not change in group B. There was no improvement in the 10-minutes walking distance of group A, but there was a significant increase in that of group B. It can be concluded that pulmonary rehabilitation combined with IMT improves pulmonary function and inspiratory muscle strength in elderly patients with COPD.     

Event-related potentials to inspiratory flow-resistive loads in young adults: stimulus magnitude effects

Event-related potentials were recorded to brief presentations of four levels of inspiratory flow-resistive loads in young adults. We labeled the loads according to the level of resistance they provided subjectively: sub-threshold (0.34 cmH2O/l per s), near-threshold (4.01 cmH2O/l per s), intermediate (10.4cmH2O/l per s), and near-occlusion (57.5 cmH2O/l per s). No discernible ERPs were elicited by the undetected, sub-threshold stimulus but late components of the ERP (P2, N2, and P3) were observed to each of the three larger stimuli. They were related, in part, to behavioral judgments obtained during the stimulus periods. Both the latency and amplitude of the ERP components varied systematically as a function of stimulus magnitude, in a manner comparable to that observed in ERP paradigms using auditory and visual stimuli. Thus, the data show that event-related potentials to breathing are sensitive to physiologic effects of resistive loads present at the onset of inspiration. Respiratory ERPs may be used to infer sensory and perceptual responses to increases in airflow resistance and, accordingly, may relate to the perception of airflow obstruction in patient populations.     

Immediate effects of group therapy upon response to social reinforcement among juvenile delinquents.

Using a paper-and-pencil measure of the degree of effective assimilation or recognition of interpersonal approval and disapproval statements as reward and punishment events, a group of 89 institutionalized delinquent male adolescents tested immediately following a 1-hour group-therapy session were compared with an identical group tested immediately prior to their weekly group-therapy session. Analysis of variance and Cochran-Cox tests revealed that the posttherapy group scored significantly (p     

Immediate eradication of Helicobacter pylori in patients with previously documented peptic ulcer disease: clinical and economic effects

The introduction of adenovirus 5 E1A into the SKOV3ip1 ovarian cancer cell line was shown previously to suppress HER2/neu expression and reduce the malignant potential of these cells (Yu et al., Cancer Res., 53: 891-898, 1993). In this report, we show that reduction of p185 in cells stably expressing E1A protein was coincident with increased sensitivity to cytotoxic agents. The LD50 of cisplatin was reduced 6-fold, and the LD50 of paclitaxel and doxorubicin was reduced 10-fold in E1A-expressing cells compared with control cells. The growth of SKOV3ip1 and control cells was unchanged in the presence of 150 ng/ml of tumor necrosis factor-alpha, whereas the growth of E1A-expressing cells was reduced by 30 to 40%. When we used a physiologically obtainable concentration of paclitaxel (0.5 microM), DNA laddering consistent with apoptotic cell death was seen after a 24-h exposure in the E1A-expressing cells, whereas laddering and DNA fragmentation were only detected in DNA from control cells after longer exposure (48 h) at a 20-fold higher concentration of paclitaxel. The SKOV3ip1 cells do not express p53 protein; hence, the induction of apoptosis by paclitaxel is through a p53-independent pathway. Despite their diverse mechanisms of action, the cytotoxic effects of cisplatin, doxorubicin, paclitaxel, and tumor necrosis factor-alpha were enhanced by the expression of E1A proteins in the SKOV3ip1 ovarian cancer cells. This suggests that these agents share a common final pathway of cell killing, which may represent a potential therapeutic target in resistant ovarian cancers.     

Work place challenge: spirometric response in polyurethane (isocyanate) paint workers

As many as 159 patients with pneumonia (all men aged 18-39) were examined. Functional activity of monocytes was studied in an integral test with nitroblue tetrazolium as was nonspecific cellular antiviral resistance by the level of viral damage to the monocytes and lymphocytes. The progression of pneumonia was found to be accompanied by a decrease in the number of phagocytizing mononuclears and the activity of phagocytosis. Nonspecific cellular antiviral resistance is significantly impaired. The proportion of monocytes and lymphocytes containing viral inclusions increases several-fold. The treatment of patients is accompanied by positive dynamics of indicators of functional status of monocytes and nonspecific cellular antiviral resistance. By the time of discharge from hospital the impaired functions of immunocompetent cells fail to completely restore.     

Postexercise energy expenditure in response to acute aerobic or resistive exercise

The association between adherence to medical recommendations and health outcomes (physical, role, and social functioning, energy/fatigue, pain, emotional well-being, general health perceptions, diastolic blood pressure, and glycohemoglobin) was examined in a 4-year longitudinal, observational study of 2125 adult patients with chronic medical conditions (hypertension, diabetes, recent myocardial infarction, congestive heart failure) and/or depression. Change score models were evaluated, controlling for disease and comorbidity. Patient adherence was associated minimally with improvement in health outcomes in this study. Only 11 of 132 comparisons showed statistically significant positive effects of adherence on health outcomes. We conclude that the relationship between adherence and health outcomes is much more complex than has often been assumed.     

Blood pressure and heart rate response to apomorphine in urethane anesthetized rats

The mechanisms involved in the hypotensive effect of apomorphine were studied in urethane anesthetized rats. The intravenous injection of apomorphine (0.01-0.75 mg/kg) produced a dose dependent fall in mean blood pressure. At the higher doses used (0.5-0.75 mg/kg) a marked bradycardia accompanied the hypotensive effect. These cardiovascular effects were prevented by pretreating the animals with pimozide (0.01-0.1 mg/kg). Low doses of haloperidol (0.03-0.3 mg/kg) did not antagonize the hypotensive action of apomorphine. Higher doses of haloperidol (1-3 mg/kg) reduced markedly the mean blood pressure. Atropine (1 mg/kg) partially antagonized the decrease in mean blood pressure induced by apomorphine and prevented completely the bradycardia. Hexamethonium (10 mg/kg) reduced the mean blood pressure and when apomorphine was administered, a residual hypotensive effect and no bradycardia was observed. It is concluded that the cardiovascular actions of apomorphine are central in origin and mainly due to the stimulation of a dopamine receptor. A probable peripheral effect could not be discarded.     

Secretory protein 7B2 response to oral glucose loading and intravenous glucagon injection in patients with diabetes mellitus

Serum 7B2 concentrations in control subjects and patients with diabetes mellitus were measured following a 75 g oral glucose load and following intravenous glucagon infusion. In response to oral glucose, serum 7B2 levels increased in the controls (n = 10) and in the diabetic patients (n = 7). The increment of the serum 7B2 level was smaller in the diabetic patients than the controls. During the 75 g oral glucose tolerance test (75g OGTT), serum 7B2 levels were significantly positively correlated with serum C-peptide levels. In contrast, following intravenous glucagon infusion, serum 7B2 levels increased only in diabetic patients treated with oral hypoglycemic agents (n = 20) and did not increase in controls (n = 5): the group having the highest insulin secretion activity in the present study, nor in diet or insulin-treated diabetic patients. No correlation between serum 7B2 levels and serum CPR levels was observed in the intravenous glucagon infusion study. These data suggest that an extra-pancreatic source which produces the observed serum 7B2 increase following oral glucose intake can not be excluded and that 7B2 may not be secreted concomitantly with insulin from the pancreatic beta cell in response to intravenous glucagon injection.     

Time course evolution of ventilatory responses to inspiratory unloading in patients

Inspiratory muscle unloading decreases ventilatory drive. In this study, we examined the time course of this effect in patients with chronic obstructive pulmonary disease receiving two modes of ventilatory support: pressure support ventilation (PSV), during which each cycle was assisted, and biphasic positive airway pressure (BIPAP), set up in such a manner that one spontaneous breath took place between two consecutive pressure-assisted breaths. The first breath following the switch from spontaneous breathing to PSV was associated with an increase in tidal volume (VT) and a drop in mean transdiaphragmatic pressure (mean Pdi) and inspiratory work (WI) performed per liter but with unchanged values of esophageal occlusion pressure at 100 ms (Pes 0.1), diaphragmatic electrical activity (EMGdi), and WI performed by breath. The same phenomena were observed for the assisted breath of BIPAP as compared with the preceding spontaneous breath. During the subsequent breaths of PSV, Pes 0.1, EMGdi, and WI performed per breath decreased progressively up to the sixth to eighth breaths, and VT returned to pre-PSV values. We conclude that in patients with chronic obstructive pulmonary disease the decrease in ventilatory drive associated with PSV takes place from the first breath onwards but requires six to eight breaths to be fully achieved. During BIPAP, as a consequence of the kinetics of the PSV-induced downregulation of ventilatory drive, assisted breaths following spontaneous breaths are characterized by an enhanced inspiratory efficiency.     

Effect of N omega-nitro-L-arginine on ventilatory response to hypercapnia in anesthetized cats

The effect of intravenous administration of 40 mg/kg N omega-nitro-L-arginine (L-NNA), an inhibitor of the synthesis of nitric oxide (NO), on the ventilatory response to CO2 was studied in anesthetized cats. The ventilatory response to CO2 was assessed during normoxia by applying square-wave changes in end-tidal PCO2 of approximately 1 kPa. Each CO2 response was separated into a fast peripheral and slow central component characterized by a CO2 sensitivity (Sp and Sc, respectively), time constant, time delay, and an offset (apneic threshold). L-NNA reduced Sp, Sc, and the apneic threshold significantly by approximately 30%. However, the ratio Sp/Sc was not changed. It is argued that the reduction in Sp and Sc, Sp/Sc remaining constant, may be due to a potent inhibitory action of L-NNA on the brain stem respiratory-integrating centers and on the neuromechanical link between these centers and respiratory movements. It is concluded that NO plays an important role in the control of breathing.     

Pharyngeal patency in response to advancement of the mandible in obese anesthetized persons

BACKGROUND: During anesthesia in humans, anterior displacement of the mandible is often helpful to relieve airway obstruction. However, it appears to be less useful in obese patients. The authors tested the possibility that obesity limits the effectiveness of the maneuver. METHODS: Total muscle paralysis was induced under general anesthesia in a group of obese persons (n = 9; body mass index, 32 +/- 3 kg[-2]) and in a group of nonobese persons (n = 9; body mas index, 21 +/- 2 kg[-2]). Nocturnal oximetry confirmed that none of them had sleep-disordered breathing. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. A static pressure-area plot allowed assessment of the mechanical properties of the pharynx. The influence of mandibular advancement on airway patency was assessed by comparing the static pressure-area relation with and without the maneuver in obese and nonobese persons. RESULTS: Mandibular advancement increased the retroglossal area at a given pharyngeal pressure, and mandibular advancement increased the retropalatal area in nonobese but not in obese persons at a given pharyngeal pressure. CONCLUSION: Mandibular advancement did not improve the retropalatal airway in obese persons.     

Effect of antiarrhythmic therapy with intravenous loading dose of amiodarone: evidence for an altered response in diabetic patients

This article investigates the evidence we have for the existence of proto-surgery in ancient Egypt during the Dynastic Period (c.3200-323 BC). Climate and chance have preserved medical literature as well as paleoarcheological specimens and these artefacts, along with extant Greek and Roman treatises appear to support the conclusion that proto-surgery was practised in ancient Egypt (the prefix proto-designates an original or early form). Elements of proto-surgical development including analgesia and sedation, the incision, trephination, proto-surgery of trauma, mythical proto-surgery and antisepsis, drawing on primary sources, surviving artefacts and modern commentary are discussed. Where appropriate comparisons are made with proto-surgery in ancient Mesopotamia and the Bronze Age Aegean.     

Occult lumbar lateral spinal stenosis in neural foramina subjected to physiologic loading

PURPOSE: To measure the effect of extension, flexion, lateral bending, and axial rotation loads applied to the spine on the anatomic relationship of the spinal nerves in the neural foramen to the ligamentum flavum and the intervertebral disk, anc to determine the effect of disk degeneration on the response to loading. METHODS: Cadaveric lumbar motion segments were examined with CT and MR imaging, loaded with pure moment forces, frozen in situ, reexamined with CT, and sectioned with a cryomicrotome. The morphology of the intervertebral disks was classified on the basis of the appearance of the cryomicrotome sections. The neural foramina were classified as having no evident stenosis, as being stenotic, as having occult stenosis, or as showing resolved stenosis on the basis of the images and sections before and after loading. The stenotic and nonstenotic foramina were stratified by disk level, intervertebral disk classification, and type of loading applied. The effect of spinal level, disk type, and load type on the prevalence of stenosis was studied. RESULTS: On average, extension, flexion, lateral bending, and axial rotation resulted in the ligamentum flavum or intervertebral disk contacting or compressing the spinal nerve in 18% of the neural foramina. Extension loading produced the most cases of nerve root contact, and lateral bending produced the fewest cases. Each of the loading types resulted also in diminished contact between the spinal nerve and the intervertebral disk or ligamentum flavum in some cases. Disk degeneration significantly increased the prevalence of spinal stenosis. All foramina associated with advanced disk degeneration and half of the foramina associated with disks having radial tears of the annulus fibrosus either developed occult stenosis or were stenotic before loading. CONCLUSIONS: The study supports the concept of dynamic spinal stenosis; that is, intermittent stenosis of the neural foramina. Flexion, extension, lateral bending, and axial rotation significantly changed the anatomic relationships of the ligamentum flavum and intervertebral disk to the spinal nerve roots.