Relationship between atrial septal defects and asthma-like dyspnoea: the impact of transcatheter closure.

BACKGROUND: Patients with atrial septal defects (ASD) are often misdiagnosed as asthma patients and accordingly receive erroneous bronchodilator treatment. In order to characterise their symptoms of dyspnoea to explain this clinical observation, we investigated the prevalence of asthma-like symptoms in patients with secundum ASD who then underwent successful percutaneous closure. METHODS: A total of 80 ASD patients (74 % female, mean age 46.7 ± 16.8 years, median follow-up 3.0 [2.0-5.0] years) retrospectively completed dyspnoea questionnaires determining the presence and extent of cough, wheezing, chest tightness, effort dyspnoea and bronchodilator use on a 7-point scale (0 = none, 6 = maximum) before and after ASD closure. The Mini Asthma Quality of Life (Mini-AQLQ) and Asthma Control Questionnaire with bronchodilator use (ACQ6) were administered. RESULTS: A total of 48 (60 %) patients reported cough, 27 (34 %) wheezing, 26 (33 %) chest tightness and 62 (78 %) effort dyspnoea. Symptom resolution or reduction was found in 64 (80 %) patients after ASD closure. Asthma symptom scores decreased significantly on the Mini-AQLQ and ACQ6 (both p < 0.001). The number of patients using bronchodilators decreased from 16 (20 %) to 8 (10 %) patients after ASD closure (p = 0.039) with less frequent use of bronchodilators (p = 0.015). CONCLUSIONS: A high prevalence of asthma-like symptoms and bronchodilator use is present in ASD patients, which exceeds the low prevalence of bronchial asthma in this study population. Future prospective research is required to confirm this phenomenon. The presence of an ASD should be considered in the differential diagnosis of patients with asthma-like symptoms, after which significant symptom relief can be achieved by ASD closure.

Consider obstructive sleep apnea in patients with oropharyngeal vascular malformations.

INTRODUCTION: Patients with oropharyngeal vascular malformations with complaints of upper airway obstruction were referred to a sleep specialist to investigate the existence of obstructive sleep apnea (OSA). METHODS: Demography, complaints, localization, and extent of the malformation were noted. The Epworth Sleeping Scale (ESS) and a polysomnography were performed to analyze the existence of OSA. RESULTS: Thirteen patients with vascular malformations in the upper oropharyngeal tract were referred, with a mean age of 49 years (range, 20-77 years). The male: female ratio was 7:6. In 2 patients the ESS was missed, and in the other 11 patients the mean ESS was 11.7 (range, 4-23). After polysomnography, 11 of the 13 patients (85%) were diagnosed with OSA, of whom 7 patients had severe OSA. CONCLUSION: Patients with oropharyngeal vascular malformations with complaints of upper airway obstruction have a high risk of OSA, and should be referred to a sleep specialist.

Recurrent acute pulmonary oedema after aortic and mitral valve surgery due to trachea malacia and obstructive sleep apnoea syndrome.

In this report we describe a patient with recurrent episodes of acute pulmonary oedema after aortic and mitral valve surgery. The first episode of pulmonary oedema was caused by mitral valve dysfunction. The second episode of pulmonary oedema was not clearly associated with a mitral valve problem, but reoperation was performed in the absence of another explanation. After the third episode of acute pulmonary oedema occurred, the diagnosis of obstructive sleep apnoea syndrome (OSAS) was considered and confirmed. After starting treatment with continuous positive airway pressure (CPAP) during his sleep the patient had no further episodes of acute respiratory failure. Our case demonstrates that acute pulmonary oedema after cardiothoracic surgery can be caused or at least be precipitated by OSAS and should be suspected in patients with unexplained episodes of (recurrent) pulmonary oedema. (Neth Heart J 2008;16:310-2.).

Effects of treatment of obstructive sleep apnea on circadian hemodynamics.

INTRODUCTION: The role of obstructive sleep apnea syndrome (OSAS) in the etiology of daytime hypertension is still an issue of debate, which is fed by the high prevalence of the syndrome in hypertensive patients. In this study the anti-hypertensive effect of short-term treatment of obstructive sleep apnea with nasal continuous positive airway pressure (nCPAP) was assessed. PATIENTS AND METHODS: In eight patients with documented OSAS (mean apnea index 62 apneas/h), two 24-h continuous finger blood pressure registrations (Portapres) were performed. At baseline and after 3 weeks of treatment with nCPAP. Ten hypertensive control subjects were studied. Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were assessed by pulse contour analysis. RESULTS: Hemodynamics were highly reproducible in the controls. nCPAP therapy improved apnea-activity in all OSAS patients. This was associated with a reduction of nighttime systolic (SBP), mean arterial (MAP) and diastolic blood pressure (DBP). Treatment also reduced daytime MAP by -11 mm Hg (ranging from -27 to 1; P < 0.05), and DBP by -7 mm Hg (-24 to 3; P < 0.05). CO was significantly increased in daytime by 9% (-4 to 25; P < 0.05), whereas TPR was reduced by -15% (-34 to 3; P < 0.05). CONCLUSIONS: Treatment of OSAS caused a reduction in daytime MAP and DBP, associated with a reduction of vascular resistance. These findings are consistent with the hypothesis of a reduced sympathetic outflow at night after therapy of obstructive sleep apnea, carrying over to the day.

[Infections with Mycobacterium kansasii in the Academic Medical Center in Amsterdam: the changing clinical spectrum since the start of the HIV epidemic]. / Infecties met mycobacterium kansasii in het Academisch Medisch Centrum in Amsterdam: het klinisch beeld sinds het begin van de HIV-epidemie.

OBJECTIVE: Inventory of patients with a Mycobacterium kansasii infection. DESIGN: Descriptive, retrospective. SETTING: Academic Medical Centre, Amsterdam, the Netherlands. METHOD: Review of the medical records of all patients with a bacteriologically confirmed infection with M. kansasii from January 1987 until the end of December 1996. RESULTS: M. kansasii was isolated from 17 patients. Of 15 HIV-tested patients 13 were seropositive. Their median CD4 count was 10 x 10(6)/l. Ten HIV-positive individuals used trimethoprim-sulfamethoxazole prophylaxis. In 1 HIV-seropositive and in 1 HIV-seronegative patient no chest X-rays were made. Caverns were present in none of 12 HIV-positive patients and in 1 of 3 HIV-negative patients. Of the HIV-positive patients 1 fulfilled the criteria for pulmonary infection of the American Thoracic Society (ATS). According to these criteria 9 of the HIV-positive patients were colonized with M. kansasii. In 6 of these patients there were indications of infection: regression of pulmonary infiltrates with therapy (n = 3), positive histology and culture of lung tissue at autopsy (n = 1), and dissemination (n = 2). Disseminated infection occurred in a total of 4 HIV-infected patients. CONCLUSION: HIV-infected patients are at an increased risk for M. kansasii infection. Trimethoprim-sulfamethoxazole does not offer protection against this infection. The diagnostic criteria of the ATS are not applicable to these patients. M. kansasii infection confirmed by isolation in an HIV-positive individual should always be treated.

[Characterization of 100 patients with tuberculosis treated in the Academic Medical Center in Amsterdam]. / Karakterisering van 100 patiënten met tuberculose behandeld in het Academisch Medisch Centrum te Amsterdam.

OBJECTIVE: To inventory both clinical and demographical data of patients with tuberculosis in the AMC, as well as diagnostic procedures, response to therapy and rate of resistance. DESIGN: Retrospective, descriptive. SETTING: The Academic Medical Center. Amsterdam, the Netherlands. METHOD: The medical records of all patients with a bacteriologically confirmed infection with Mycobacterium tuberculosis complex between January 1993 and December 1995 were studied. RESULTS: 70 out of 100 patients with tuberculosis were not born in the Netherlands. Out of 50 patients tested 18 were HIV positive. The most common abnormality seen on X-rays of non-HIV positive patients were caverns. The X-ray of HIV positive patients showed no abnormalities in 39%; there was no correlation with CD4 cell count. In 74% of the patients with pulmonary tuberculosis the diagnosis was made by culture of the sputum. Treatment consisted of INH, rifampicin, pyrazinamide and ethambutol. Twelve patients were infected with resistant strains, of which two were multidrug resistant. Four patients died of tuberculosis. CONCLUSION: Tuberculosis was seen mostly among immigrants. Only half the patients with tuberculosis were tested for presence of HIV antibodies. Culture and staining of sputum played a key role in the diagnosis of tuberculosis. Multiresistant tuberculosis was present in 2% of the patients. Death due to tuberculosis in this population was 4%.

Airflow and pressure characteristics of three different tracheostoma valves.

Tracheoesophageal speakers can achieve speech without digital occlusion by using a tracheostoma valve. Laryngectomized patients who are successful with this device can regain considerable freedom. However, little is known about which valve suits the patient best. Valve aerodynamics may give a guideline for its use. Three major tracheostoma valves, each divided into four subtypes, were repeatedly measured in this study. Dynamic pressure and airflow rate signals were sampled through an analog-digital interface into a computer. Considerable aerodynamic differences were observed between the tested valves. The maximum airflow rates, closing pressures, and resistances at low velocities were compared. The presented data may help increase the successful use of tracheostoma valves in tracheoesophageal speakers. Patient factors and additional valve factors should always be taken into account. Further clinical study to validate the clinical relevance of the data is needed.

Cytokine profiles in bronchoalveolar lavage fluid and blood in HIV-seropositive patients with Pneumocystis carinii pneumonia.

Concentrations and ex vivo production of interleukin 1 beta (IL-1), tumour necrosis alpha (TNF), interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors (sTNF-receptors, P55 and P75) were measured in bronchoalveolar lavage (BAL) fluid and blood in 23 HIV-seropositive (HIV+) patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy HIV-seronegative (HIV-) controls and asymptomatic HIV+ subjects. Concentrations of the proinflammatory cytokine IL-1 beta were increased in BAL fluid of HIV+ patients with PCP (184 +/- 47 pg mL-1) compared with undetectable levels in healthy control subjects (P = 0.0001). In plasma of these patients higher concentrations of the anti-inflammatory cytokine IL-1RA were found during acute PCP than after recovery (2.1 +/- 0.7 vs. 0.5 +/- 0.2 ng mL-1, P = 0.01). No correlations could be found between cytokine concentrations and clinical severity of the infection. Corticosteroid treatment did not influence cytokine concentrations in BAL or blood, nor did it suppress the production in alveolar cells. In whole-blood cultures, however, lipopolysaccharide (LPS)-stimulated production was significantly suppressed for IL-1 (1.3 vs. 5.5 ng mL-1, P = 0.009) and for IL-6 (0.6 vs. 2.5 ng mL-1, P = 0.01). The overall data show that in HIV+ patients with PCP (similar to what we had found previously in HIV-patients with PCP) proinflammatory cytokines are more prominently present in BAL, whereas anti-inflammatory reaction is predominant in the circulation.

Pneumocystis carinii pneumonia in HIV-negative patients with haematologic disease.

Since 1990, Pneumocystis carinii pneumonia (PCP) was diagnosed in 15 adult HIV-negative haematologic patients in our hospital. None of them had received PCP prophylaxis. All except one had been treated with prednisone. Symptoms usually started after stopping or tapering. In six patients the diagnosis of PCP was delayed because of confounding bacterial isolates from blood, sputum or urine leading to unsuccessful antibiotic treatment. PCP was diagnosed by demonstrating pneumocysts in bronchoalveolar lavage fluid. In four patients additional fungal or viral pathogens were identified. The infections were not clustered. The patients were treated with co-trimoxazole and, in case of a pO2 < 60 mmHg, with prednisone. Three patients died (20%); they all had a coinfection with cytomegalovirus and/or aspergillus. The others recovered completely. There were no relapses. Primary PCP prophylaxis should be considered in patients with lympho-proliferative disease and exposure to prednisone.

A chemoreflex model of relation between blood pressure and heart rate in sleep apnea syndrome.

In obstructive sleep apnea syndrome (OSAS), pronounced low-frequency (LF) oscillations of blood pressure and interbeat interval (I) occur during recurrent apneas. We investigated the time relations between LF oscillations of diastolic pressure (D) and I in 12 patients with OSAS by means of spectral analysis. A high coherency between I and D was found, allowing a description of the relation by gain and phase. Oscillations in I and D were almost in counterphase in the LF range. Simple physiological models were implemented to interpret the observed features of LF oscillations. Model 1 describes the vagal and sympathetic influence by the carotid body chemoreflex on the circulation. From derivation of the frequency response of this model, gain and phase relations were obtained as would be expected from the action of the chemoreflex. We found that a range of phase relations can be induced by this reflex, depending on the relative vagal and sympathetic efferent influence on the circulation. This range of phase relations was indeed observed in 10 patients. Extended models that also included the orienting reflex (model 1a) or the baroreflex and a mechanical influence of breathing on the circulation (model 2) could not fit the data without a major contribution of the chemoreflex. We conclude that the relation between LF oscillations in I and D in OSAS can be explained by assuming that stimulation of the carotid body chemoreflex is the main source of these oscillations.

Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population.

The composition of human immunodeficiency virus type 1 (HIV-1) clonal populations at different stages of infection and in different compartments was analyzed. Biological HIV-1 clones were obtained by primary isolation from patient peripheral blood mononuclear cells under limiting dilution conditions, with either blood donor peripheral blood lymphocytes or monocyte-derived macrophages (MDM) as target cells, and the biological phenotype of the clones was analyzed. In asymptomatic individuals, low frequencies of HIV-1 clones were observed. These clones were non-syncytium inducing and preferentially monocytotropic. In individuals progressing to disease, a 100-fold increase in frequencies of productively HIV-1-infected cells was observed as a result of a selective expansion of nonmonocytotropic clones. In a person progressing to AIDS within 19 months after infection, only syncytium-inducing clones were detected, shifting from MDM-tropic to non-MDM-tropic over time. From his virus donor, a patient with wasting syndrome, only syncytium-inducing clones, mostly non-MDM-tropic, were recovered. Parallel clonal analysis of HIV-1 populations in cells present in bronchoalveolar lavage fluid and peripheral blood from an AIDS patient revealed a qualitatively and quantitatively more monocytotropic virus population in the lung compartment than in peripheral blood at the same time point. These findings indicate that monocytotropic HIV-1 clones, probably generated in the tissues, are responsible for the persistence of HIV-1 infection and that progression of HIV-1 infection is associated with a selective increase of T-cell-tropic, nonmonocytotropic HIV-1 variants in peripheral blood.

Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS: a randomized European multicenter open label study.

Fifty-nine human immunodeficiency virus type-1-infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on (a) survival to discharge, (b) need for mechanical ventilation, and (c) survival at day 90. CS was given within 24 h of standard therapy as intravenous methylprednisolone 2 mg/kg body weight daily for 10 days. All patients received cotrimoxazole as standard treatment. Inclusion criteria were a PaO2 less than 9.0 kPa (67.5 mm Hg) and/or a PaCO2 less than 4.0 kPa (30.0 mm Hg) while breathing room air. During the acute episode of PCP, 9 (31%) of the 29 control patients died versus 3 (10%) of the 30 CS patients; p = 0.01. Mechanical ventilation was necessary in 15 patients; 12 (41%) in the control group and 3 (10%) in the CS group; p = 0.01. The 90-day survival was 69% in controls versus 87% in CS patients; p = 0.07. Based on these data we conclude that adjunctive CS therapy for moderate to severe PCP in AIDS patients reduces the acute mortality and the need for mechanical ventilation.

Can the course of high dose cotrimoxazole for Pneumocystis carinii pneumonia in AIDS be shorter? A possible solution to the problem of cotrimoxazole toxicity.

Fifty consecutive patients with confirmed PCP received a high dose of cotrimoxazole for 14 d, or until development of intolerance, directly followed by reduced dose maintenance therapy. Seven individuals died during the high dose course. Twenty (47%) of the 43 survivors showed toxicity reactions that necessitated dose reduction to maintenance level on average after 9.6 d. Thirteen of these 20 individuals tolerated the reduced dose, and seven did not. No further cases of toxicity were observed. In 43 survivors only one early relapse (day 17) was observed in a patient who had received full dose treatment for 14 d. We conclude (1) that extending high dose cotrimoxazole therapy beyond 2 weeks is usually unnecessary, provided that reduced dose maintenance therapy is given directly, and (2) that dose reduction on appearance of toxicity signs during the second week of treatment is safe and allows two-thirds of patients to be maintained on cotrimoxazole with satisfactory results.

ELISA of ceruloplasmin and alpha-2-macroglobulin in paired bronchoalveolar lavage fluid and serum samples.

Bronchoalveolar lavage fluid (BALF) was analysed to obtain information on leakage of proteins from the blood into the respiratory lumen and on local synthesis. Albumin, ceruloplasmin and alpha-2-macroglobulin were measured in paired BALF and serum samples from patients with acute pneumonitis or asthma. Ceruloplasmin (CP) and alpha-2-macroglobulin (A2M) were measured by ELISAs thereby avoiding concentration of BALF. The quotients 10(3) ([protein]BALF)/(protein]serum), Qprotein, were calculated as well as the relative coefficients of excretion, RCE: Qprotein/Qalbumin. The QCP and QA2M increased parallel to Qalbumin in patients with pneumonitis and QCP increased parallel with Qalbumin in the asthma patients. This indicates that abnormal leakage of proteins from the blood rather than local synthesis cause the increased concentrations of these proteins in the BALF. Increased values for the RCE of CP and A2M were observed at normal Qalbumin. We therefore conclude that the determination of CP and A2M yields more detailed information on leakage of proteins from the blood into the airway compartment than that of albumin.

Gallium-67 lung scintigraphy in patients with acquired immune deficiency syndrome (AIDS).

Fifteen 67Ga lung scans were obtained from 11 men with AIDS to detect opportunistic lung infection. Results were compared with clinical findings, chest radiographs, CO-transfer and transbronchial biopsies or BAL. Clinical symptoms were least helpful in diagnosing pneumonia. Chest radiographs were normal in six of eight normal 67Ga studies and abnormal in four of seven abnormal scans. In four cases the X-ray showed equivocal abnormalities, twice corresponding to a normal and twice to an abnormal scan. Once the X-ray was normal, but the scan showed diffuse abnormalities. CO-transfer in patients with a normal scan was higher (55-68%) than in patients with an abnormal scan (22-44%). Biopsy or BAL revealed P. carinii in five of six patients. Cytomegalo-virus was isolated once. All six patients had abnormal 67Ga scans. 67Ga lung scintigraphy is a sensitive indicator of active lung disease in AIDS, especially when chest X-rays are normal or equivocal.

Intravenous naphazoline intoxication.

Nine pale perspiring drug addicts with drowsiness, nausea, headache, normal blood pressure and marked sinus bradycardia with premature ventricular beats were seen at the Casualty Department soon after alleged i.v. cocaine administration. Eight were treated with atropine, as the bradycardia suggested intoxication with a parasympathomimetic compound. Seven were discharged in good condition after a few hours' observation. One patient developed a blood pressure of 150/120 mmHg after atropine. Subsequently, a hemiparesis was found and an intracerebral haematoma was evaluated at surgery. Another patient was admitted forthwith to the CCU. He did not receive any medication and recovered within two days. Urinalysis of these two patients disclosed contents of naphazoline, a powerful alpha-adrenergic agent. Samples of the alleged cocaine contained 97% naphazoline HCl. A conscious rabbit was injected with naphazoline and thereafter with atropine. I.v. naphazoline doubled mean arterial pressure (MAP) and reduced heart rate (HR) from 167 to 30 beats/min. Atropine doubled HR, but caused a marked rise in MAP, too, stressing the adverse effects of atropine in these cases. When confronted with patients after alleged cocaine abuse, the role of substitute drugs, especially alpha-adrenergic compounds, should be considered as this should influence the therapeutic approach.