[Red fingers].
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
R Speich
Publications and source records attributed to R Speich.
Low specificity of the bacterial index for the diagnosis of bacterial pneumonia by bronchoalveolar lavage.
The bacterial index (BI) as defined by the sum of log10 colony-forming units (cfu) of microorganisms per milliliter of bronchoalveolar lavage (BAL) fluid, i.e., a multiplication of the single cfu/ml, has been used to distinguish between polymicrobial pneumonia (BI> or =5) and colonization (BI<5). Since many false-positive results are to be expected using this parameter, the diagnostic value of the BI was studied prospectively by obtaining bacteriologic cultures of BAL fluid in 165 consecutive unselected patients. In 27 cases the diagnosis of bacterial pneumonia was established on clinical criteria. In 133 patients pneumonia could be excluded, and in five patients the diagnosis remained unclear. Using a cut-off of > or = 10(5) cfu/ml BAL fluid, sensitivity and specificity for the diagnosis of pneumonia were 33% (9/27) and 99% (132/133), respectively. Sensitivity was mainly influenced by prior treatment with antibiotics, being 70% (7/10) in untreated and 12% (2/17) in treated patients. Applying the BI methodology at a cut-off of > or =5, however, resulted in an unacceptably high rate of 16 additional false-positive results, thus lowering the specificity to 87% (116/133; P<0.0001) while increasing the sensitivity to only 41% (11/27; P = 0.77). In conclusion, given the high rate of false-positive results, the methodology of the BI is of doubtful value for the diagnosis of bacterial pneumonia by BAL in an unselected patient group. By applying the absolute number of cfu/ml BAL fluid, however, positive bacteriologic cultures of BAL fluid are highly specific for the diagnosis of pneumonia. Their sensitivity is limited by previous antibiotic therapy.
Adolescent↗
Efficacy, safety, and tolerance of piperacillin/tazobactam compared to co-amoxiclav plus an aminoglycoside in the treatment of severe pneumonia.
An open, randomized, multicenter study was conducted to compare the efficacy and safety of piperacillin/tazobactam and co-amoxiclav plus aminoglycoside in the treatment of hospitalized patients with severe community-acquired or nosocomial pneumonia. Of the 89 patients who entered the study, 84 (94%) were clinically evaluable. A favorable clinical response was observed in 90% of the piperacillin/ tazobactam group and in 84% of the co-amoxiclav/aminoglycoside group (not significant). The bacteriological efficacy was comparable in both groups (96% vs. 92%; not significant). There was only one fatal outcome in the piperacillin/tazobactam group compared to six in the co-amoxiclav/aminoglycoside group regimen (P=0.058). The adverse event rate was non-significantly lower in the piperacillin/ tazobactam group compared to the co-amoxiclav/aminoglycoside group (2% vs. 7%; P=0.32). Piperacillin/tazobactam is safe and highly efficacious in the treatment of serious pneumonia in hospitalized patients. It compares favorably with the combination of co-amoxiclav/aminoglycoside.
Aged↗
A 54-year-old man with increasing dyspnea on exertion and a previous diagnosis of emphysema. Case 1, discussed at the Zurich University Hospital, October 31, 1996.
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Blood Chemical Analysis↗
Established acute respiratory distress syndrome: benefit of corticosteroid rescue therapy.
UNLABELLED: The mortality of the acute respiratory distress syndrome (ARDS) is still very high. There is some evidence based on case series suggesting that corticosteroids may be beneficial in the chronic fibroproliferative state of the disease. In a retrospective study we analysed the data of 31 non-trauma ARDS patients who had been on mechanical ventilation for at least 7 days. Thirteen cases received corticosteroids at a dosage equivalent to 100-250 mg methylprednisolone at the discretion of the attending physician in charge. Apart from corticosteroid administration, supportive care was identical in the treated and non-treated patient subgroups. Both groups were comparable regarding the relevant demographic, clinical and physiologic data, Apache-II score, radiological score, lung injury score and multiple organ failure score. Mortality in the treatment group was 38% (5/13) as opposed to 67% (12/18) in the untreated group (p = 0.117). There was a significant improvement in the PaO2/FIO2 ratio from a median of -26 to +5 mm Hg measured in a 48-hour period before and after corticosteroid treatment (p = 0.039). The response to corticosteroid therapy could not be predicted on the basis of clinical or physiologic data. Five patients responded within 48 h, and 3 showed a delayed response after 5-6 days. There were no significant complications attributable to corticosteroid treatment. CONCLUSIONS: Although the data of this first comparative study were retrospective, they suggest a beneficial effect of corticosteroid treatment in patients with established fibroproliferative ARDS. A prospective clinical trial, however, is highly warranted in order to fully elucidate the true effect of this therapeutic approach under controlled conditions.
APACHE↗
Single pulmonary nodule after cardiac catheterization.
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Aged↗
Bronchiolitis obliterans after lung transplantation: a review.
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Animals↗
[Ulcer + ulcer].
We report on an elderly woman suffering from an acutely bleeding duodenal ulcer. Apart from old age and a history of gastrointestinal ulcer there were no risk factors detectable. However, clinical examination revealed that the patient had put a diclofenac hydroxyethylpyrrolidine plaster, which had been prescribed for lower back pain, inadvertently on a large ulcus cruris. The diclofenac serum concentration was 80 mu/l corresponding to a therapeutic serum level. This case demonstrates that false application of new pharmaceutical formulation may lead to inadvertent side-effects.
Administration, Topical↗
[Clinical single case study (n-of-1 trial)].
We conducted a single case (N-of-1) randomized trial in two patients. In the first case with bronchiolitis obliterans after lung transplantation a beneficial effect of inhaled steroids could be documented. The second patient suffered from symptoms compatible with HIV-associated M. Addison improving after cortisone, but the adrenocortical function was normal. Because the patient required the cortison treatment to be continued, we performed a n-of-1 trial which demonstrated the inefficacy of cortisone. This experience underscores the feasibility and usefulness of N-of-1 randomized clinical trials in medical practice.
Addison Disease↗
Salvage therapy with mycophenolate mofetil for lung transplant bronchiolitis obliterans: importance of dosage.
BACKGROUND: Bronchiolitis obliterans (BO) is the most important long-term complication of lung transplantation. Treatment of this condition is often unsuccessful. METHODS: A patient presented with early BO. Despite OKT3 and the addition of methotrexate, the patient needed persistently high doses of prednisone to maintain lung function at a moderate level. Only the substitution of azathioprine by mycophenolate mofetil (MMF, 3 g/day) made it possible to reduce the dose of prednisone. RESULTS: Reduction of the dose of MMF to 2 g/day resulted in a deterioration of lung function, which improved impressively after MMF was increased again to 3 g/day. CONCLUSIONS: MMF may be a valuable therapy for lung transplant BO. However, the use of a high dose, i.e., 3 g/day, may be crucial.
Adult↗
[Diagnostic process in internal medicine: decision analysis or intuition?].
The diagnostic process is a hypothesis-testing approach under conditions of uncertainty. Experience-based intuition plays an important role in complex clinical situations. Serious cognitive errors may be avoidable if possible heuristic problems are considered. Probabilistic reasoning according to Bayes' theorem, especially for determination of pretest probability, is crucial for coping with uncertainty and the myriad available diagnostic tests and procedures. Their proper interpretation depends on fundamental test variables such as sensitivity, specificity and likelihood ratio. Computers and neural networks cannot replace cognitive reasoning and probabilistic strategies in daily clinical practice. Decision analysis is pivotal, particularly when the aim is to maintain high-quality medical care at a time of limited resources.
Decision Making, Computer-Assisted↗
[Primary pulmonary hypertension. Clinical aspects, follow-up and prognostic factors].
A retrospective study is presented of all patients with primary pulmonary hypertension (PPH) observed at Zürich University Hospital between 1980 and 1990. In 16 of the 36 patients (23 females/13 males, median age 40) there was a known risk factor for PPH: HIV infection (8), use of anorectic agents (7), liver cirrhosis (1). In 20 cases no risk factor could be found. In 4 of them PPH was diagnosed before the study period. We calculated an incidence of PPH in north-east Switzerland of about 1.5 cases per million per year. The clinical course in the 20 patients without known risk factors for PPH was analyzed in more detail: treatment consisted of oral anticoagulation (15) and vasodilators (7); the median survival was 48 (1-307) months. Only 7 patients (35%) are still alive. Prognosis of PPH correlated with the severity of hemodynamics. The median survival in patients with pulmonary vascular resistance of < 1000 versus > or = 1000 dyn.sec.cm-5 was 151 (106-307) months versus 13 (1-73) months (p < 0.001), with mean pulmonary artery pressure of < 50 versus > or = 50 mm Hg it was 151 (73-307) versus 13 (1-106) months (p = 0.0015), with right atrial pressure of < 10 versus > or = 10 mm Hg it was 90 (4-307) versus 3 (1-60) months, and with mixed venous O2-saturation of > or = 62% versus < 63% it was 119 (4-307) versus 14 (1-106) months (p = 0.024). PPH is a rare disease with a poor prognosis depending mainly on the severity of hemodynamic changes. However, despite this fact, the clinical course of individual patients may be unexpectedly favourable. Treatment of PPH is limited, and lung transplantation remains the most promising therapeutic approach. In this regard the quality of life aspect is of great importance.
Adolescent↗
Hyperthyroidism and pulmonary hypertension.
OBJECTIVES: To identify patients with hyperthyroidism and coincidental pulmonary hypertension and to document reversibility of pulmonary hypertension after treatment of hyperthyroidism. DESIGN: Patients with hyperthyroidism referred for transthoracal echocardiography for any reason that showed elevated pulmonary arterial pressures were collected. After therapy for the thyreotoxic state with documented normalization of thyroid hormone (IT4), pulmonary arterial pressure was measured again noninvasively. SETTING: An out-patient tertiary referral centre. SUBJECTS: The medical records were used to identify, retrospectively, patients with hyperthyroidism and pulmonary hypertension over a three-year period (April 1993 to April 1996). INTERVENTIONS AND MAIN OUTCOME MEASURES: Systolic pulmonary artery pressure (PAPs) was determined by adding up right ventricular systolic pressure (RVSP) and mean right atrial pressure (RAP) measured by continuous-wave Doppler echocardiography according to standard techniques. All patients were treated for hyperthyroidism to normal IT4 levels. After successful therapy. Doppler echocardiography was repeated. RESULTS: Four patients with pulmonary hypertension showing elevated PAPs of 40 +/- 11 mmHg were identified. After therapy. PAPs decreased in all patients to a mean of 25 +/- 6 mmHg. CONCLUSION: The observation of four patients with pulmonary hypertension and hyperthyroidism is striking and suggests a possible pathogenetic link of these disorders.
Adult↗
Simplified sample processing combined with a sensitive one-tube nested PCR assay for detection of Pneumocystis carinii in respiratory specimens.
Early diagnosis of Pneumocystis carinii pneumonia, a life-threatening complication in immunosuppressed patients, may lower morbidity and mortality. We have developed a one-tube nested PCR assay for the detection of P. carinii in respiratory specimens. Four primers were selected from the sequence of the small-subunit rRNA gene of P. carinii to amplify a 265-bp fragment, and their specificities for P. carinii were confirmed by both theoretical evaluations (by computer-assisted comparison with the sequences in GenBank) and empirical evaluations (with DNA from medically important fungi and diagnostic samples). The assay was optimized for routine diagnostic use. Processing of the clinical samples is rapid and simple (digestion with proteinase K directly in PCR buffer at room temperature in the presence of 10% Chelex 100 and no further purification steps). Bovine serum albumin (1 mg/ml) and glycerol (10%) in the amplification buffer reduced the number of samples inhibitory to the PCR, as assessed by control reactions containing a size-modified target. A total of 749 clinical specimens (312 bronchoalveolar lavage, 403 sputum or induced sputum, and 34 other specimens) from 507 patients (295 human immunodeficiency virus [HIV]-infected and 164 non-HIV-infected patients and 48 patients whose HIV status was unknown) were tested by PCR, and the results were compared with those of an indirect immunofluorescence assay (IFA). Concordant results were obtained for 732 samples (646 negative and 86 positive). There were 17 discrepant results: 12 were PCR positive and IFA negative, and 5 were PCR negative and IFA positive. After resolution of the discrepant results by review of the patients' clinical data, the sensitivity and specificity were 94.8 and 99.1%, respectively, for PCR and 93.8 and 100%, respectively, for IFA. In conclusion, the short procedure time and the technical ease of this PCR assay render it suitable for implementation in routine diagnostic laboratories.
Animals↗
A case report of a double-blind, randomized trial of inhaled steroids in a patient with lung transplant bronchiolitis obliterans.
Lung transplant bronchiolitis obliterans syndrome (BOS) is the most significant long-term cause of morbidity and mortality after lung transplantation. Although augmented immunosuppression is used by most centers, reported on treatment to reverse BOS are largely anecdotal. We performed a double-blind, randomized, controlled trial (RCT) with ten treatment pairs of 2 weeks duration each comparing inhaled fluticasone propionate (2 x 1,000 micrograms/day) with placebo in a patient with BOS grade 2 who previously showed an improvement in lung function after inhaled steroids. The Baseline Dyspnea Index and the Modified Medical Research Council Dyspnea Scale showed a significant improvement during fluticasone treatment compared with the placebo period (2.7 +/- 0.2 vs. 2.0 +/- 0.3; p = 0.043; and 1.7 +/- 0.2 vs. 2.4 +/- 0.2; p = 0.043). The patient correctly identified fluticasone and placebo, respectively, in eight of ten trial pairs (p = 0.016). The values of forced expiratory volume in 1 s were significantly higher during the fluticasone period (1,207 +/- 10 ml; 95% confidence interval, CI, 1,187-1,227 ml) compared to the placebo period (1,150 +/- 6 ml; 95% CI 1,138-1,162 ml; p = 0.0012). In conclusion, this n-of-1 RCT suggests the efficacy of high-dose inhaled fluticasone in our patient with lung transplant BOS. We propose to conduct a multicenter RCT of high-dose inhaled steroids. Until further data are available, this treatment modality should be offered to patients with lung transplant BOS.
Administration, Inhalation↗
HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study.
To assess the clinical and echocardiographic time course, prognosis, and possible etiology of HIV-associated primary pulmonary hypertension (PPH), we prospectively followed all 19 patients in whom PPH was diagnosed in our centers. Women (12 cases) and injecting drug use (16 cases) predominated; the median CD4 lymphocytes count was 83/microliter (range, 1 to 740). Matched control subjects without PPH were identified within the Swiss HIV Cohort Study. Frozen serum samples of both groups were then reanalyzed for autoimmune parameters, neopterin, beta-2-microglobulin, and thyroid-stimulating hormone. The median follow up of the patients was 1.3 yr. Follow-up Doppler echocardiography was available in 13 patients. The RVSP-RAP pressure gradient decreased by 3.2 mm Hg for those six patients who received antiretroviral treatment but increased by 19.0 mm Hg for untreated patients (p = 0.026). PPH was the cause of eight of 17 deaths. The probability of surviving was significantly decreased in patients with PPH in comparison with the control subjects; the median survival was 1.3 versus 2.6 yr (p < 0.05). Patients with PPH had significantly higher anticardiolipin IgM, anti SS-B, and neopterin, but all other laboratory values did not differ between cases and control subjects. In conclusion, HIV-associated PPH contributed significantly to mortality. Antiretroviral treatment may exert a beneficial effect on the pressure gradient. A possible role of an autoimmune phenomenon in the pathogenesis could not be substantiated.
Adult↗
Inhalation of the nitric oxide synthase cofactor tetrahydrobiopterin in healthy volunteers.
Pulmonary endothelial dysfunction is the hallmark of acute lung injury. Impaired pulmonary endothelial nitric oxide (NO) production in this event has been described. Tetrahydrobiopterin (BH4) is an essential cofactor for NO synthase and modulator of its activity. At high local concentrations, BH4 provokes local vasodilation in vivo in healthy individuals. At lower concentrations, BH4 selectively and locally restores disturbed NO-dependent vasodilation in patients with endothelial dysfunction. In this preliminary study, we therefore investigated the feasibility of BH4 inhalation in five healthy human volunteers. Inhalation of buffered, aqueous BH4-dihydrochloride solution was well tolerated; despite the buffer, BH4 stability was completely preserved. Resorption of inhaled BH4 was demonstrated by significantly increased BH4 levels in plasma and urine. Inhaled BH4 did not alter pulmonary function and had no effect on systemic hemodynamic values. Our data demonstrate that inhalation is a novel method for local BH4 administration, offering a basic therapeutic tool for investigation of restoration of impaired NO-dependent vasodilation due to pulmonary endothelial dysfunction.
Administration, Inhalation↗