Use of opioid analgesics in a patient with chronic abdominal pain.

Pethidine is the most commonly used opioid in hospitals in the UK, but it lacks potency, has a short duration of action and a narrow therapeutic index. These points are illustrated by a case history of a patient prescribed pethidine for chronic abdominal pain. Misplaced fears of the side-effects of morphine result in its underuse in the management of chronic pain with consequential restriction of patients' functional ability.

Home oximetry studies for diagnosis of sleep apnea/hypopnea syndrome: limitation of memory storage capabilities.

BACKGROUND: Memory oximeters enable diagnostic studies for sleep apnea hypopnea syndrome (SAHS) to be performed in the home. However, memory capabilities may be limited. STUDY OBJECTIVES: To compare a pulse oximeter used at home with an 8-h memory, storing data every 12 s, and in the laboratory, with on-line recording every 2 s. DESIGN: Prospective cohort study. SETTING: Patients' homes and a sleep laboratory. PATIENTS: One hundred patients with suspected SAHS. MEASUREMENTS: Home oximetry and a laboratory full polysomnography. The number of >/= 4% dips in pulse oximetric saturation (SpO(2)) was calculated for each study. Daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS) score. RESULTS: The mean dips per hour were 5.3/h (range, 0 to 53/h) for home studies and 13.4/h (range, 0 to 106/h) for laboratory studies; the relationship between home and laboratory studies was as follows: home = (0.4 x laboratory) - 0.01 +/- 11.2; r(2) = 0.64. Mean difference was 8.4/h (- 2.5 to + 77.9/h), which correlated with the mean of the measurements. At a cutoff point of 10/h, 52 studies were both negative and 13 studies were both positive. Nineteen home studies were false-negatives. Sensitivity was 0.41, and specificity was 1.0. In these 19 studies, 7 patients had an ESS score > 10 and 4 patients had an ESS score > 14. To confirm that differences were due to different sampling rates, 16 additional patients had on-line data and stored data collected simultaneously in the laboratory. Mean dips per hour were 3.2/h (range, 0.1 to 18.3/h) for the stored data and 8.34/h (0.2 to 22.8/h) for on-line data; the relationship being stored was as follows: 0.5 on-line - 1.17 +/- 2.6; r(2) = 0.69. Mean difference was 5.2/h (0.04 to 15.4 h), which correlated with the mean of the measurements. CONCLUSION: Home studies using a memory storage pulse oximeter may underestimate the number of hypoxic dips, probably due to sampling rates. Clinically significant hypoxic SAHS may therefore be missed.

Hypersomnia following uvulopalatopharyngoplasty for snoring.

This report describes three cases who underwent uvulopalatopharyngoplasty for severe snoring and who subsequently developed progressive excessive daytime sleepiness. All three cases were shown to have sleep fragmentation as a result of non-apnoeic episodic upper airway narrowing. These cases raise the possibility that increased upper airway resistance during sleep may be exacerbated or even caused by uvulopalatopharyngoplasty. Ideally, sleep-disordered breathing should be carefully excluded before this surgery is offered as treatment for severe snoring.

Characterisation of an oxidative response inhibitor produced by Streptococcus pneumoniae.

BACKGROUND: Pneumonia caused by infection with Streptococcus pneumoniae is still a major clinical problem. Reactive oxygen species contribute to the killing of these bacteria by polymorphonuclear leucocytes (PMNs). Defence mechanisms of Str pneumoniae which counter reactive oxygen species are characterised. METHODS: PMNs were stimulated with phorbol myristate acetate (PMA) in the presence and absence of Str pneumoniae and supernatants from them, and superoxide (O2-) production was measured by the reduction of ferricytochrome c. RESULTS: Streptococcus pneumoniae, but not Klebsiella pneumoniae or Staphylococcus aureus, inhibited PMA stimulated superoxide production by PMNs. Washed PMNs which had been preincubated with Str pneumoniae autolysis phase supernatants also exhibited depressed H2O2 production in response to PMA. The inhibitory activity was not attributable to non-specific cytotoxicity as assessed by release of the cytoplasmic enzyme lactate dehydrogenase, nor did the supernatants inhibit PMA stimulated degranulation of PMNs. Fractionation of the autolysis phase supernatants revealed inhibitory activity in both the fractions greater than and less than 10 kD. Like pneumolysin the inhibitory activity was heat sensitive. However, both a parent and pneumolysin negative mutant Str pneumoniae, and autolysis phase supernatants from them, inhibited PMN superoxide production. Antisera to pneumolysin failed to abrogate the inhibitory effect of intact Str pneumoniae or autolysis phase supernatants from types 1 or 14 Str pneumoniae. CONCLUSIONS: The inhibitory effect of Str pneumoniae on the respiratory burst of PMNs is not shared by two other common lung pathogens. The existence of a novel inhibitor of the PMN respiratory burst, distinct from pneumolysin, has been demonstrated. The inhibitor is specific for the respiratory burst and is active both in the logarithmic phase of growth and during autolysis.

Interference with the oxidative response of neutrophils by Streptococcus pneumoniae.

BACKGROUND: Pneumococcal infections are still a major clinical problem. Polymorphonuclear leucocytes (neutrophils) are considered to have a key role in the host's defence against Streptococcus pneumoniae but the mechanisms by which they kill the pneumococcus remain unclear. As reactive oxygen species are regarded as a major antimicrobial defence of phagocytes an attempt has been made to establish their role in the response of neutrophils to S pneumoniae. METHODS: S pneumoniae isolated from patients with bacteraemic pneumococcal pneumonia were incubated with neutrophils in suspension and superoxide production was measured by reduction of ferricytochrome c. RESULTS: S pneumoniae did not stimulate superoxide production alone or in the presence of normal human serum. Spontaneous superoxide production by neutrophils was actually abrogated by S pneumoniae, as was the powerful respiratory burst stimulated by phorbol myristate acetate. This phenomenon depended on both the dose and the viability of the bacteria. With S pneumoniae in the logarithmic phase of growth inhibitory activity was confined to the organisms themselves but with organisms undergoing autolysis it was also present in filtered supernatants, suggesting that the inhibitory activity can be attributed to a factor released during autolysis. CONCLUSIONS: S pneumoniae can interfere with the respiratory burst of neutrophils. This property may help to explain the pathogenicity of the organism.

An assessment of sputum induction as an aid to diagnosis of respiratory infections in the immunocompromised child.

Sputum induction using nebulised hypertonic saline was performed in two groups of immunocompromised children, one group with symptoms of respiratory infection and one group without. The asymptomatic group were bone marrow transplant (BMT) recipients, all seropositive for cytomegalovirus infection (CMV). Organisms were identified in three of 14 induced sputum specimens obtained from the symptomatic group (CMV N = 1, Haemophilus influenzae N = 2), but in none of 12 specimens from the asymptomatic group. Adverse effects encountered were minor. Four symptomatic patients with negative induced sputum samples underwent bronchoalveolar lavage, and no further organisms were identified. Sputum induction can be a useful adjunct to the diagnosis of respiratory pathogens in this group of patients.

Sputum induction as an aid to diagnosis of active cytomegalovirus infection following bone marrow transplantation.

An 8-year-old boy received an allogeneic bone marrow transplant (BMT) for relapsed T cell acute lymphoblastic leukaemia. Because he was seropositive for cytomegalovirus (CMV), serial virological specimens were taken throughout the transplant period, and included those obtained by sputum induction. Sixty-one days following BMT he became unwell, and was found to have mild tachypnoea and reduced oxygen saturations. All investigations were negative, apart from that obtained by sputum induction, which was positive for CMV. He received appropriate therapy with good response. We conclude that the technique of sputum induction can be applied to aid diagnosis of active CMV infection following BMT.

Open lung biopsy in patients with non-Hodgkin's lymphoma and pulmonary infiltrates.

Patients with non-Hodgkin's lymphoma (NHL) are at increased risk for pulmonary infection with opportunistic pathogens associated with diminished cell mediated immunity. Open lung biopsy (OLB) frequently is recommended for diagnosis of pulmonary infiltrates in patients with NHL, but its usefulness for patient management and outcome has not been evaluated for patients with NHL. We reviewed the results of 20 consecutive OLB in 19 patients with previously diagnosed non-Hodgkin's lymphoma at Stanford University Medical Center during a nine-year period. Fifteen patients had known active lymphoma at time of OLB, and no patient had granulocytopenia. Ten of the 20 OLBs yielded specific diagnoses. A greater proportion of patients with stage I or II disease had specific diagnoses than patients with more advanced NHL. Five of 14 patients considered to have had a life threatening illness at the time of OLB had specific diagnoses from OLB vs five of six patients considered clinically stable. Chest roentgenograms that had discrete masses or nodules correlated with ability to establish a specific diagnosis by OLB. For patients in whom the results of OLB were nonspecific, management appeared unaffected by the OLB. The OLB in NHL appeared most useful for detecting recurrent NHL in clinically stable patients with discrete nodules or masses on chest roentgenogram. Pneumocystis pneumonia was the only infection identified by OLB.

Open lung biopsy in patients with Hodgkin's disease and pulmonary infiltrates.

Although open lung biopsy (OLB) is frequently employed for diagnosis of pulmonary lesions in patients with Hodgkin's disease, the actual efficacy of the procedure in establishing a diagnosis in these patients, and its effect on their treatment and clinical outcome, have not been evaluated. We reviewed the results of OLB in 41 patients with previously diagnosed Hodgkin's disease (17 with stage II disease, 10 with stage III, and 14 with stage IV) who had pulmonary opacification on chest roentgenogram. Nineteen (46%) diagnoses were specific and 22 nonspecific. The most common specific diagnosis was Hodgkin's disease (12 patients); the others were Pneumocystis carinii pneumonia (3), solitary fungal granuloma (2), cytomegalovirus pneumonia (1), and primary lung adenocarcinoma (1). Specific diagnoses were made in 11 (69%) of 16 patients with discrete nodules or masses but in only eight (32%) of the 25 patients with non-nodular radiographic opacification. Eleven (58%) of 19 patients who were asymptomatic or had had symptoms for longer than 4 wk had specific diagnoses, compared to one of six patients (17%) symptomatic for 1 wk or less. Survival of hospitalization correlated more with stage of Hodgkin's disease than with specific diagnosis. However, treatment was changed after biopsy in 22 (54%) of the patients. The results suggest that OLB can be helpful in the management of patients with Hodgkin's disease and pulmonary infiltrates, both in establishing a diagnosis and in assisting the patients' management. OLB appears to be more helpful in patients with Hodgkin's disease than in patients with acute nonlymphocytic leukemia or the acquired immunodeficiency syndrome and pulmonary infiltrates.

Effect of bronchial challenge on breathing patterns and arterial oxygenation in stable asthma.

The effect of histamine or methacholine inhalational challenge on breathing patterns and oxygen saturation was investigated in ten stable asthmatic patients. We used the respiratory inductive plethysmograph to record respiratory timing and minute ventilation along with an ear oximeter to measure oxygen saturation (SaO2). As FEV1 fell during the challenge procedure, SaO2 also fell (average 3 percent). Furthermore, with histamine challenge, expiratory time (Te), inspiratory time (Ti), and breath period (Ttot) all increased; minute ventilation probably also fell. These changes in breathing pattern and SaO2 were reversed by inhalation of a beta 2-agonist. However, no such changes in breathing patterns were observed with methacholine challenge despite a similar fall in FEV1. Bronchial challenge produces hypoxia in stable asthmatic patients, which might result from a combination of hypoventilation with alteration in alveolar ventilation/perfusion relationships.

Is nocturnal asthma caused by changes in airway cholinergic activity?

A randomised, double blind, placebo controlled crossover trial of high dose nebulised ipratropium was carried out in 10 asthmatic patients with documented nocturnal bronchoconstriction. Patients received nebulised saline or ipratropium 1 mg at 10 pm and 2 am on two nights. Absolute peak flow (PEF) rates were higher throughout the night after the patients had received ipratropium (at 2 am, for example, mean (SEM) PEF was 353 after ipratropium and 285 l/min after placebo). The fall in PEF overnight, however, was similar with ipratropium and placebo. Patients were given a further 1 mg nebulised ipratropium at 6 am on both nights. There was a significant overnight fall in PEF on the ipratropium night even when comparisons were made between the times that maximal cholinergic blockade would be expected, PEF falling between 11.30 pm and 7.30 am from 429 to 369 l/min. The percentage increase in PEF, though not the absolute values, was greater after ipratropium at 6 am than at 10 pm. These results confirm that ipratropium raises PEF throughout the night in asthmatic patients, but suggest that nocturnal bronchoconstriction is not due solely to an increase in airway cholinergic activity at night.

Do sleep studies contribute to the management of patients with severe chronic obstructive pulmonary disease?

To determine whether studies of breathing and oxygenation during sleep are clinically useful, we have assessed whether the detection of excess nocturnal hypoxemia in patients with chronic obstructive pulmonary disease (COPD) is of prognostic importance. Ninety-seven patients with COPD were followed for 32 to 108 (median, 70) months after studies of overnight oxygenation. Significant relationships (p less than 0.001) were obtained between mean oxygen saturation (SaO2) asleep and awake. There was similarly a significant relationship between lowest SaO2 asleep and awake, but this relationship was improved by the inclusion of awake arterial carbon dioxide tension (PaCO2). The patients who were more hypoxic at night than predicted from these regression relationships had similar survivals to the patients who were less hypoxic at night than predicted, whether excess nocturnal hypoxia was defined in terms of mean or lowest SaO2 during sleep. In the 66 patients who did not subsequently receive long-term oxygen therapy, none of the indices of nocturnal oxygenation was related to survival, the only significant predictor of survival being daytime arterial oxygen tension (PaO2). For all 97 patients, both mean nocturnal SaO2 and lowest SaO2 during sleep were related to survival (p less than 0.05), and percent predicted vital capacity was also related to survival (p less than 0.05). Neither of the oxygen saturations during sleep significantly added to the more readily and cheaply measured percent predicted vital capacity in determining survival in these patients. Thus, in patients with COPD, excess nocturnal hypoxemia is not associated with an impaired prognosis, and so studies of oxygenation during sleep cannot be recommended in the routine clinical management of these patients.

The sleep hypopnea syndrome.

We have observed patients who clinically have the obstructive sleep apnea syndrome but have no apneas, instead having recurrent nocturnal hypoventilation. There is disagreement about the definition and significance of such sleep-related hypopneas. We have thus analyzed breathing patterns, oxygenation and sleep records of 50 consecutive patients referred with the clinical features of the sleep apnea syndrome and found to have abnormal breathing during sleep to determine: (1) the best definition of hypopnea, and (2) how frequently patients have the clinical features of the sleep apnea syndrome without recurrent apneas. Hypopnea definitions based on decreases in thoracoabdominal movement yielded hypopnea frequencies that were significantly closer to desaturation and arousal frequencies than hypopnea definitions based on flow reduction. The best hypopnea definition was that of a 50% reduction in thoracoabdominal movement lasting for 10 s. This was validated in 33 normal subjects, all of whom had fewer than 11 hypopneas/h, and fewer than 14 apneas plus hypopneas/h of sleep. Thirty-two of the 50 patients had 10 or more apneas/h, the remaining 18 having 9 to 98 hypopneas/h such that all patients had more than 16 apneas plus hypopneas/h. Patients with recurrent hypopneas were clinically indistinguishable from and had a similar frequency of 4% desaturations (zero to 104/h) and arousals (7 to 98/h) to the patients with frequent apneas. This study confirms that hypopneas are clinically important and that the "sleep apnea syndrome" may occur in the absence of recurrent apneas.

Unique differences in infectivity and seroreactivity of Toxoplasma harvested from mice infected for different lengths of time.

For use in experiments, Toxoplasma of the RH strain are usually harvested from mouse peritoneal cavities 48 hr (2-day Toxoplasma) or more after intraperitoneal inoculation. In this report we show that Toxoplasma harvested at 24 hr (1-day Toxoplasma) after inoculation are much more infective for and replicate to a greater degree within mouse resident peritoneal macrophages in vitro and are much more resistant to the cidal activity of activated mouse peritoneal macrophages and resident rat peritoneal macrophages than are 2-day Toxoplasma. Ingestion of 1-day Toxoplasma by macrophages did not trigger the respiratory burst as measured by reduction of nitroblue tetrazolium (NBT), but coating 1-day Toxoplasma with specific antibody did result in reduced NBT. However, coating 1-day Toxoplasma with specific antibody did not markedly decrease infectivity for macrophages in vitro, unlike decreased infectivity observed when 2-day Toxoplasma are coated with specific antibody. Use of 1-day Toxoplasma in the dye test resulted in a 5-fold decrease in titer of specific antibody in human sera. Use of Toxoplasma harvested 24 hr after infection may serve as a new tool to probe virulence factors of Toxoplasma and of host cells' antimicrobial mechanisms.

Breathing patterns during sleep in patients with nocturnal asthma.

Breathing patterns early and late in the night, at the same sleep stage, were compared in six healthy subjects and 15 adults with nocturnal asthma, to try to identify changes of overnight bronchoconstriction, and breathing patterns at different sleep stages, to see whether there were changes related to sleep stages that were indicative of bronchoconstriction. Despite an average 31% fall in FEV1 overnight in the patients with asthma, neither breathing frequency nor expiratory time, which might be expected to change during bronchoconstriction, was different early in the night from late in the night, nor did they differ between sleep stages. There was no evidence of asynchronous movement of the chest and abdomen in any patient. This study did not identify any abnormality of breathing pattern that would indicate the development of nocturnal asthma without the need to awaken the patient.