High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema.

OBJECTIVE: To determine the feasibility, safety and efficacy of bilevel positive airway ventilation (BiPAP) in the treatment of severe pulmonary edema compared to high dose nitrate therapy. BACKGROUND: Although noninvasive ventilation is increasingly used in the treatment of pulmonary edema, its efficacy has not been compared prospectively with newer treatment modalities. METHODS: We enrolled 40 consecutive patients with severe pulmonary edema (oxygen saturation <90% on room air prior to treatment). All patients received oxygen at a rate of 10 liter/min, intravenous (IV) furosemide 80 mg and IV morphine 3 mg. Thereafter patients were randomly allocated to receive 1) repeated boluses of IV isosorbide-dinitrate (ISDN) 4 mg every 4 min (n = 20), and 2) BiPAP ventilation and standard dose nitrate therapy (n = 20). Treatment was administered until oxygen saturation increased above 96% or systolic blood pressure decreased to below 110 mm Hg or by more than 30%. Patients whose conditions deteriorated despite therapy were intubated and mechanically ventilated. All treatment was delivered by mobile intensive care units prior to hospital arrival. RESULTS: Patients treated by BiPAP had significantly more adverse events. Two BiPAP treated patients died versus zero in the high dose ISDN group. Sixteen BiPAP treated patients (80%) required intubation and mechanical ventilation compared to four (20%) in the high dose ISDN group (p = 0.0004). Myocardial infarction (MI) occurred in 11 (55%) and 2 (10%) patients, respectively (p = 0.006). The combined primary end point (death, mechanical ventilation or MI) was observed in 17 (85%) versus 5 (25%) patients, respectively (p = 0.0003). After 1 h of treatment, oxygen saturation increased to 96 +/- 4% in the high dose ISDN group as compared to 89 +/- 7% in the BiPAP group (p = 0.017). Due to the significant deterioration observed in patients enrolled in the BiPAP arm, the study was prematurely terminated by the safety committee. CONCLUSIONS: High dose ISDN is safer and better than BiPAP ventilation combined with conventional therapy in patients with severe pulmonary edema.

Fatal haemoptysis induced by invasive pulmonary aspergillosis in patients with acute leukaemia during bone marrow and clinical remission: report of two cases and review of the literature.

We describe two patients with acute leukaemia who died of massive haemoptysis caused by invasive pulmonary aspergillosis (IPA). The fatal event occurred during the period of bone marrow remission which followed chemotherapy-induced neutropenia. This is a rare complication. We were able to find additional 17 similar cases in the English literature, which we review. Clinically, the picture consisted of unremitting fever with profound and prolonged neutropenia, cough and dyspnoea. Both our patients were treated with broad-spectrum antibiotics, fluconazole and amphotericin B. An upper lobe infiltrate in one case, and a progressive pleural effusion in the other, were late findings on chest radiographs during the period of bone marrow recovery. Both patients succumbed to sudden massive haemoptysis during the period of bone marrow and clinical improvement. In conclusion, patients with acute non-lymphoid leukaemia are at significant risk for IPA-induced fatal haemoptysis during bone marrow and clinical remission. A high index of suspicion should be sustained throughout the entire clinical course. In view of the potential fatal outcome, aggressive diagnostic and treatment efforts are mandatory.

Acoustic rhinometry in the evaluation of nasal obstruction.

Acoustic rhinometry (AR) is a recently developed objective technique for assessment of geometry of the nasal cavity. The technique is based on the analysis of sound waves reflected from the nasal cavities. It measures cross-sectional areas and nasal volume (NV). To obtain dependable assessments of nasal resistance by rhinomanometry or cross-sectional area measurements by AR, it is essential that the structural relations of the compliant vestibular region remain undisturbed by the measuring apparatus. The use of nozzles in making these measurements carries a great risk of direct distortion of the nasal valve. We used a nasal adapter that does not invade the nasal cavity and a chin support that stabilizes the head. In 51 healthy nasal cavities, the average minimum cross-sectional area (MCA) was 0.62 cm2 at 2.35 cm from the nostril and 0.67 cm2 at 2 cm from the nostril, respectively, before and after topical decongestion of the nasal mucosa. The MCA and NV findings in this group were significantly higher than MCA and NV (P < 0.001) in people with structural or mucosal abnormalities before mucosal decongestion. After mucosal decongestion, the MCA and NV were significantly higher in healthy nasal cavities than in nasal cavities with structural abnormalities (P < 0.001) but were not higher than nasal cavities with mucosal abnormalities (MCA, P = 0.05; NV, P = 0.06). A nozzle was applied in 20 healthy nasal cavities after mucosal decongestion, and a significantly higher MCA was found compared to measurements made with the nasal adapter (P = 0.02). We conclude that the nasal adapter, which does not invade the nasal cavities, avoids the distortion of the nasal valve and gives more accurate results.

The role of acoustic rhinometry in nasal provocation testing.

Geometric changes of the nasal airway in response to allergen challenge were measured by acoustic rhinometry (AR) and the sensitivity of the method was compared with that of rhinomanometry. Ten asymptomatic patients who suffered from ragweed allergic rhinitis were challenged out of season. The use of a custom-made noninvasive nasal adapter was an important feature of the measurement technique. A dose-dependent decrease in nasal cross-sectional area was found at and posterior to the entrance to the nasal valve. Both rhinometric and rhinomanometric methods were equivalent in sensing the changes in nasal patency due to allergen exposure (p = 0.73). Acoustic rhinometry, however, was simpler, more quickly performed and more comfortable for the subjects than was rhinomanometry by body plethysmography. AR is an alternative objective method for measurement of nasal mucosal responses, as in allergen challenge.

Noninvasive positive pressure ventilation in acute asthmatic attack.

Asthma is characterised by reversible airway obstruction. In most patients, control of disease activity is easily achieved. However, in a small minority, asthma may be fatal. Between the two extremes lie patients with severe asthmatic attacks, refractory to standard treatment. These patients are at an increased risk of recurrent severe attacks, with respiratory failure, and mechanical ventilation. Invasive mechanical ventilation of the asthmatic patient is associated with a higher risk of complications and, therefore, is a measure of last resort. Noninvasive positive pressure ventilation (NPPV) is another treatment modality that may be beneficial in patients with severe asthmatic attack who are at an increased risk of developing respiratory failure. These patients have the potential to benefit from early respiratory support in the form of NPPV. However, reports of NPPV in asthmatic patients are scarce, and its usage in asthmatic attacks is, therefore, still controversial. Only a few reports of NPPV in asthma have been published over the last decade. These studies mostly involve small numbers of patients and those who have problematic methodology. In this article we review the available evidence for NPPV in asthma and try to formulate our recommendations for NPPV application in asthma based on the available evidence and reports.

Evidence for a major gene affecting the transition from normoglycaemia to hyperglycaemia in Psammomys obesus.

We investigated the mode of inheritance of nutritionally induced diabetes in the desert gerbil Psammomys obesus (sand rat), following transfer from low-energy (LE) to high-energy (HE) diet which induces hyperglycaemia. Psammomys selected for high or low blood glucose level were used as two parental lines. A first backcross generation (BC(1)) was formed by crossing F(1) males with females of the diabetes-prone line. The resulting 232 BC(1) progeny were assessed for blood glucose. All progeny were weaned at 3 weeks of age (week 0), and their weekly assessment of blood glucose levels proceeded until week 9 after weaning, with all progeny maintained on HE diet. At weeks 1 to 9 post weaning, a clear bimodal distribution statistically different from unimodal distribution of blood glucose was observed, normoglycaemic and hyperglycaemic at a 1:1 ratio. This ratio is expected at the first backcross generation for traits controlled by a single dominant gene. From week 0 (prior to the transfer to HE diet) till week 8, the hyperglycaemic individuals were significantly heavier (4--17%) than the normoglycaemic ones. The bimodal blood glucose distribution in BC(1) generation, with about equal frequencies in each mode, strongly suggests that a single major gene affects the transition from normo- to hyperglycaemia. The wide range of blood glucose values among the hyperglycaemic individuals (180 to 500 mg/dl) indicates that several genes and environmental factors influence the extent of hyperglycaemia. The diabetes-resistant allele appears to be dominant; the estimate for dominance ratio is 0.97.

Polysomnography in patients with intracranial tumors before and after operation.

OBJECTIVE: To evaluate the breathing and sleep patterns in patients with brain tumors before and after operation, and assess their relation to the location and size of the tumor, as well as to the post-operative outcome. METHODS: Polysomnographic studies were performed in 11 patients with intracranial tumors (nine supra- and two infratentorial) before and after surgery. RESULTS: Pre-operatively, the mean apnea-hypopnea index (AHI) was 23.3. Six patients demonstrated signs of obstructive sleep apnea (SA) and one had mixed obstructive and central type SA. After operation, the mean AHI decreased to 8.1(P < 0.05). The duration of random eye movement sleep stage increased after tumor removal (P < 0.04). No relation was found between the characteristics of the tumor, nor the post-operative outcome and SA. CONCLUSIONS: Patients with brain tumors often suffer from SA and this can further worsen their symptoms related to increased intracranial pressure. Removal of the tumor results in a substantial decrease in sleep-related disturbances and may thus play a role in clinical recovery.

Distinctive genetic signatures in the Libyan Jews.

Unlinked autosomal microsatellites in six Jewish and two non-Jewish populations were genotyped, and the relationships among these populations were explored. Based on considerations of clustering, pairwise population differentiation, and genetic distance, we found that the Libyan Jewish group retains genetic signatures distinguishable from those of the other populations, in agreement with some historical records on the relative isolation of this community. Our methods also identified evidence of some similarity between Ethiopian and Yemenite Jews, reflecting possible migration in the Red Sea region. We suggest that high-resolution statistical methods that use individual multilocus genotypes may make it practical to distinguish related populations of extremely recent common ancestry.