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Biomedical subjects

R H Hyland

Publications and source records attributed to R H Hyland.

At least 19 recordsLinked to original sources

Sustained improvement in asthma with long-term use of formoterol fumarate.

Inhaled formoterol fumarate, a long acting beta 2 agonist, produces bronchodilatation that is sustained for approximately 12 hours. To determine whether such bronchodilator effects are maintained and asthma control sustained during chronic administration, we monitored airflow indices and clinical control in 112 asthmatic patients who self administered formoterol twice daily for periods ranging from 9 to 12 months. Subjects were recruited immediately following completion of a 3-month double-blind comparison of formoterol, 12 micrograms, bid versus salbutamol, 200 micrograms, qid. Assessments were conducted at baseline, 3, 6, and 9 months, where baseline represents the final visit of the 3-month comparative study. Patients were asked to complete diary cards and twice daily PEFR for a 2-week period before each assessment. Throughout the follow-up study, there was no indication of worsening of asthma control or deteriorating lung function. For the patients who continued to receive formoterol, the previous improvement in asthma control and lung function was maintained at the level reached in the 3-month study. There was an improvement in flow rates and asthma symptoms in the group switched from salbutamol to formoterol by the first clinic visit. This improvement in asthma control and lung function was maintained over the subsequent 6 months. Formoterol was well tolerated during the study period. We conclude that prolonged use of formoterol fumarate twice daily results in sustained improvement in symptoms and flow rates in asthma with no evidence of tachyphylaxis.

Adolescent

Aerosol pentamidine for secondary prophylaxis of AIDS-related Pneumocystis carinii pneumonia. A randomized, placebo-controlled study.

OBJECTIVE: To assess the safety and efficacy of aerosol pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). PARTICIPANTS: Patients recovering from a first confirmed episode of AIDS-related P. carinii pneumonia who had no evidence of either another active AIDS-defining opportunistic infection or another pulmonary abnormality were considered eligible for the study but were included only if they had received no immunomodulators or antiretroviral agents other than zidovudine within 30 days of entry. One hundred sixty-two patients were randomized and started on the study drug. INTERVENTION: Patients were randomly assigned to receive aerosol pentamidine, 60 mg per dose, or placebo, delivered using a hand-held, patient-triggered, ultrasonic nebulizer. The induction phase of treatment consisted of 5 doses over 14 days, followed by a maintenance phase beginning on day 21 and consisting of one dose every 2 weeks. RESULTS: Thirty-two cases of P. carinii pneumonia were diagnosed before the termination of the trial; 27 cases occurred among 78 patients receiving placebo and 5 occurred among 84 patients receiving aerosol pentamidine. Estimates of the cumulative relapse rate of P. carinii pneumonia by 24 weeks were 50% and 9% for the placebo and pentamidine groups, respectively (P less than 0.001). Adverse reactions attributed to the study drug occurred in 15 of 78 patients receiving placebo and in 28 of 84 patients receiving pentamidine (P = 0.04). These were all mild or moderate in severity and did not preclude continued administration of the study drug. CONCLUSION: Intermittent therapy with aerosol pentamidine is highly effective and well tolerated as secondary prophylaxis for AIDS-related P. carinii pneumonia.

Acquired Immunodeficiency Syndrome

A three-month comparison of twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma.

We compared the efficacy of inhaled formoterol, a long-acting beta 2-agonist, with inhaled albuterol in 145 stable adult asthmatics in a 12-wk multicenter trial. Patients were allocated in randomized double-blind fashion to maintenance therapy with either formoterol 12 micrograms twice a day or albuterol 200 micrograms four times a day in addition to their other asthma medications. Patients were allowed to use "rescue" 100-micrograms albuterol puffs on an as-needed basis. Mean baseline FEV, in the morning before bronchodilator was 2.14 +/- 0.76 L and 1.98 +/- 0.71 L for the formoterol and albuterol groups, respectively, these values being used as baseline covariates in subsequent analysis of predrug and postdrug FEV1. Measured at each clinic visit, morning predrug FEV1 rose significantly with formoterol treatment and was significantly greater at all visits than in the albuterol group, the greatest difference being in Week 8 (2.40 +/- 0.77 versus 1.92 +/- 0.66 L, p less than 0.001). Morning FEV1 30 min postdrug was significantly higher in the formoterol group at Weeks 2 and 8, the trend not reaching statistical significance at other times. Diurnal variation in prebronchodilator peak flow rates was significantly reduced in the formoterol group throughout the trial (17 versus 42 L/min at Week 12, p less than 0.0001). The number of asthma episodes per week was significantly less in the formoterol group during Weeks 4, 8, and 12 as were the number of sleep disruptions during Weeks 2, 4, 6, 8, and 12. Significantly more rescue albuterol was required in the albuterol group by Week 2 and throughout the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation

A comparison of enprofylline and theophylline in the maintenance therapy of chronic reversible obstructive airway disease.

To compare the efficacy and side effects of two xanthine derivatives in the maintenance therapy of reversible obstructive airway disease, 242 patients were assigned in randomized, double-blind fashion to receive either oral enprofylline or theophylline for 5 weeks in addition to their usual maintenance regimens. After a week of placebo xanthine therapy, enprofylline-treated patients received 150 mg of this drug twice daily (b.i.d.) for 3 days, 300 mg b.i.d. for 2 weeks, and 450 mg b.i.d. for 2 weeks. Theophylline was administered in identical doses, except that the final dosage increase was not made if plasma theophylline was 12 mg/ml or higher. At 300 mg b.i.d., both drugs significantly increased morning peak expiratory flow rate (PEFR), the mean increase above baseline being significantly higher for theophylline-treated patients (29.9 +/- 37.2 L/min) than for enprofylline-treated patients (17.4 +/- 36.9 L/min) (p = 0.023). At 450 mg b.i.d., improvement in morning PEFR was not significantly different between theophylline-treated (31.5 +/- 44.4 L/min) and enprofylline-treated groups (23.5 +/- 48.4 L/min). Evening PEFR, FEV1, and asthma symptom scores also improved significantly, demonstrating no significant difference between groups. The incidence of side effects was also similar between groups. We conclude that both enprofylline and theophylline offer useful bronchodilatation in the maintenance therapy of asthma, enprofylline, 450 mg b.i.d., being approximately equivalent to theophylline, 300 or 450 mg b.i.d.

Adolescent

The malignancy-sarcoidosis syndrome.

In a retrospective review of six patients with malignancy preceding sarcoidosis, we found four cases of malignant lymphoproliferative disease (LD) and one case each of ovarian cancer and breast cancer. The median interval from onset or relapse of malignancy to sarcoidosis was nine months. Of the four patients with LD, sarcoidosis appeared within six months of termination of chemotherapy for three of the patients and 15 months after allogeneic bone marrow transplantation for the fourth patient. At the time of diagnosis of sarcoidosis, there was no clinical or pathologic evidence of malignancy in the chest. We conclude that in contradistinction to the previously described syndrome of sarcoidosis preceding LD, there exists a syndrome of sarcoidosis following malignancy with or without chemotherapy.

Adult

Pulmonary complications following bone marrow transplantation.

Pulmonary complications are a common cause of morbidity and mortality after bone marrow transplantation. Some of these complications are infectious and related to the degree of ongoing immunosuppression, and thus vary with the posttransplant marrow reconstitution and the need for continued immunomodulating drugs. Noninfectious complications are related to previous chemotherapy, the transplantation protocol and conditioning regimen, and, in allogeneic transplants, the presence of graft-versus-host disease. The various complications are classified based on their timing after the transplant procedure. A diagnostic and therapeutic approach is outlined and the prognosis is discussed.

Bone Marrow Transplantation

Pulmonary complications of AIDS: a clinical strategy.

Infectious and noninfectious forms of pulmonary disease are the most common complications of acquired immune deficiency syndrome (AIDS), and many are amenable to treatment. We describe the clinical and radiologic features of the most common causes of lung disease in AIDS patients and review the drugs available for treatment. In addition, we provide a strategy for the clinical assessment and management of patients with human immunodeficiency virus infection who have lung infiltrates.

Acquired Immunodeficiency Syndrome

Management of chronic ventilatory insufficiency with electrical diaphragm pacing.

We have had experience with diaphragm pacing in 24 patients at the Toronto Western Hospital. Fourteen patients have undergone bilateral implants to treat chronic ventilatory insufficiency (CVI) caused by traumatic tetraplegia at the C1/2 level (eight patients), neurogenic apnea (five) and one case of neonatal apnea. Unilateral stimulators for nocturnal pacing have been implanted in five patients with central alveolar hypoventilation (sleep apnea) and five patients who suffered CVI resulting from various etiologies. Of the patients who were ventilatory dependent, 80% were successfully weaned and in the entire series, 58% of the patients are living. Diaphragm pacing was successful in 67%, partially successful in 8% and ineffective in 25%. The major complications were: death by pneumonia, failure of the radio receivers, and infection. Diaphragm pacing is the treatment of choice for patients who are ventilator dependent and tetraplegic from upper cervical trauma or in some cases of neurogenic apnea; it may be life saving for patients who suffer central alveolar hypoventilation.

Adolescent

Corticosteroids as adjunctive therapy in treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.

10 patients with the acquired immunodeficiency syndrome whose respiratory failure due to Pneumocystis carinii pneumonia (PCP) was deteriorating rapidly had 7 days of intravenous methylprednisolone added to their antibiotic regimen. 8 similar patients were treated with antibiotic therapy alone. 9 of the 10 methylprednisolone-treated patients survived their episode of PCP, compared with 2 of the 8 conventionally treated patients. Clinical improvement was evident within 2 days of the start of steroid therapy, and in none of the 10 patients did clinical deterioration or recurrence of PCP occur on cessation of steroid therapy. In 1 steroid-treated patient disseminated herpes zoster developed 2 days after discontinuation of methylprednisolone. Methylprednisolone seems to be a useful adjunctive therapeutic agent for patients with AIDS in whom Pneumocystis carinii is the sole respiratory pathogen.

Acquired Immunodeficiency Syndrome

Idiopathic small airways pathology in patients with graft-versus-host disease following allogeneic bone marrow transplantation.

In a retrospective analysis (July 1979 to March 1984) of 120 allogeneic adult bone marrow transplant recipients, we identified seven patients with small-airway disease for whom no microbiologic agent was detected. Six had pulmonary function studies demonstrating air flow obstruction. Five of the seven patients had an open-lung biopsy showing pathologic changes within small airways; these varied from early bronchiolar wall damage to bronchiolitis obliterans. The inflammatory cell infiltrate was peribronchiolar, and consisted of polymorphonuclear leukocytes and lymphocytes in varying proportions. Three of the seven patients recovered following increased immunosuppressive therapy; the other four died. Because all seven patients had acute and chronic graft-versus-host disease, in the absence of any identifiable pathogen, we postulate that small-airway damage represents one of the facets of graft-versus host-disease. An additional analysis of 26 patients with respiratory symptomatology and available histologic material supports the hypothesis that small-airway disease in bone marrow transplant patients represents a risk factor for the subsequent development of respiratory opportunistic infections.

Bone Marrow Transplantation

Small-airways disease in recipients of allogeneic bone marrow transplants. An analysis of 11 cases and a review of the literature.

In a retrospective review of 116 consecutive allogeneic bone marrow transplants (BMT), severe obstructive airways disease was identified in 11 patients. Lung pathology demonstrated bronchiolitis in 9 patients and physiologic studies showed small-airways disease consistent with bronchiolitis in the other 2. None of the 5 patients with associated infection survived, while 3 of the 6 patients without an identified pathogen stabilized or improved. Analysis of the 11 cases presented and all 25 cases reported in the literature (1982 to 1985) supports the conclusion that graft-versus-host disease is a major risk factor for bronchiolitis in BMT recipients. Among the proposed mechanisms for the development of bronchiolitis after allogeneic BMT, the 2 most likely are graft-versus-host disease directly causing bronchiolitis, and increased immunosuppressive therapy given for graft-versus-host disease predisposing to viral bronchiolitis. The available evidence would suggest that it is prudent to obtain serial pulmonary function tests even in asymptomatic patients post-BMT, and particularly in those with chronic graft-versus-host disease, in the hope that early detection will allow for early intervention that will arrest or reverse the progression of the obstructive airways disease.

Adolescent

Prevention of acute pulmonary edema after bone marrow transplantation.

In a retrospective review of 21 bone marrow transplantation procedures (BMT), we identified ten episodes of acute pulmonary edema coinciding with significant weight gain in the second week after BMT. When we prospectively observed nine consecutive BMT recipients, six patients developed acute pulmonary edema associated with significant (p less than 0.05) weight gain and an increase in echocardiographically determined left ventricular end diastolic diameter. These findings led to a prospective prophylactic intervention study of 30 consecutive BMT patients. Prophylactic intervention consisting of reduced fluid volume of parenteral alimentation, and diuretic therapy was instituted at any clinical sign of fluid overload. No episode of pulmonary edema occurred. The dramatic difference--acute pulmonary edema occurred in 16/30 untreated vs 0/30 treated cases--suggests that this post-BMT complication is critically related to fluid balance and can be prevented by careful clinical examination, close monitoring of weight change, avoidance of fluid overload and the appropriate use of diuretic therapy.

Adult

Pulmonary tumor embolism: a critical review of clinical, imaging, and hemodynamic features.

Pulmonary tumor embolism is a common finding at autopsy but is generally perceived as a difficult diagnosis to make ante mortem. After a retrospective review of 164 reported cases of pulmonary tumor embolism, we identified a typical profile of clinical, laboratory, and imaging features that may permit confident clinical diagnosis in most patients with this condition. The clinical features include a documented or suspected underlying malignancy, acute to subacute onset of dyspnea, and signs of cor pulmonale. Supportive laboratory features are hypoxemia or increased alveolar-arterial oxygen gradient, and invasive or noninvasive evidence of pulmonary artery hypertension. Typical imaging findings are normal chest radiographs; multiple, subsegmental, peripheral perfusion defects on ventilation-perfusion lung scans; and delayed filling with or without subsegmental filling defects but without a thrombus on pulmonary angiogram. Radiolabeled monoclonal antibody imaging and pulmonary microvascular cytology sampling techniques are promising diagnostic tests for early diagnosis of pulmonary tumor embolism.

Adult

Diphenylhydantoin-induced lymphocytic interstitial pneumonia.

A patient developed diffuse lymphocytic interstitial pneumonia after receiving diphenylhydantoin therapy for 14 months. Withdrawal of medication resulted in reversal of the disease process. This case illustrates the value of combined transbronchial biopsy and bronchoalveolar lavage sampling in establishing a diagnosis, and the utility of serial bronchoalveolar lavage in monitoring disease evolution.

Aged