Ultrastructure of the aqueous lining layer in hamster airways: is there a two-phase system?

For particle retention and clearance, the structure and surface properties of the airway lining layer are important. Due to difficulties of its preservation, structural analysis has been hampered, and, hence, the existence of two distinct and continuous phases and how much osmiophilic material is available are unclear. It was the objective of this study to investigate the ultrastructure of the aqueous lining layer in the intrathoracic conducting airways of hamsters. By means of transmission electron microscopy, we investigated the ultrastructure of the airway lining layer in hamsters whose lungs have been fixed by the application of fixative dissolved in nonpolar fluorocarbon, either by instillation via the trachea or injection into the gas exchange parenchyma, together with intravascular perfusion of aqueous fixatives. The results were compared to lungs fixed by intravascular perfusion only. In twelve hamsters, the airway lining layer was found to consist of an aqueous phase and was coated by an osmiophilic film that follows fairly closely the upper-extending contours of cilia protruding from epithelial cells. Substantially less osmiophilic material was preserved in extrapulmonary airways and when nonaqueous fixative was injected. We found that the aqueous lining layer of the intrathoracic airways in hamsters essentially surrounds and covers the cilia, the microvilli, and any other structures like macrophages or deposited particles contained in it and is coated by an osmiophilic film of variable thickness. In healthy animals, a gel phase is expected to be very thin, not clearly separated from the periciliary fluid, and located just beneath the osmiophilic film.

[The appearance of Sweet's syndrome during the transition from a myelodysplastic syndrome to erythroleukemia]. / Auftreten eines Sweet-Syndroms beim Ubergang von einem myelodysplastischen Syndrom in eine Erythroleukämie.

HISTORY AND CLINICAL FINDINGS: Two months after being diagnosed as having refractory anaemia with an excess of blasts in transformation (RAEB-T), a 62-year-old man presented in the emergency room with fever (40 degrees C) for two weeks and scattered deep-red macular indolent efflorescences over the chest, back, face and thighs. Other than splenomegaly there were no significant findings on physical examination. INVESTIGATIONS: Erythrocyte sedimentation rate was increased to 38 mm in the first hour. Haemoglobin concentration and platelet count were at the lower limits of normal, white cell count within the normal range. Differential count: 60 erythroblasts per 100 leukocytes and 33.5 blast cells. Two skin biopsies revealed massive oedema in the upper corium and focal erythrocyte extravasations. There were perivascular and perifollicular inflammatory infiltrates in the deeper layers and elastosis of the corium. There was no leukocytoclastic vasculitis. These findings established the diagnosis of Sweet syndrome and erythroleukaemia. TREATMENT AND COURSE: The erythroleukaemia was treated symptomatically and the skin changes gradually receded under prednisone, 1 mg/kg, but new spots occurred when the prednisone dose was halved. Candida oesophagitis occurred as a complication of the erythroleukaemia. Chest radiogram showed diffuse infiltrates in both upper lobes of the lung. Despite intensive antimycotic and antibiotic treatment the patient died 10 days later from pulmonary aspergillosis. CONCLUSION: This case report describes the rare occurrence of Sweet syndrome during the transformation from a myelodysplastic Syndrome to erythroleukaemia.

[Disseminated toxoplasmosis in AIDS]. / Disseminierte Toxoplasmose bei AIDS.

Within one year a 46-year-old HIV-positive man developed Pneumocystis carinii pneumonia, candida oesophagitis and recurrent mucocutaneous herpes simplex infections. He finally developed a constant fever without any infection-localizing features. There was pancytopenia, increased activities of the transaminases, lactate dehydrogenase, amylase and lipase, as well as diffuse ST-segment changes in the ECG and discrete pulmonary infiltrates. The anti-toxoplasmosis titre was 8 IU/ml. Despite extensive diagnostic tests no firm diagnosis could be established. The pulmonary infiltrate and the fever regressed under antibiotic treatment with co-trimoxazole. Two months later his general condition deteriorated again with some disorientation and subfebrile temperature, epididymitis and renewed rise in abnormal laboratory values. For the first time computed tomography showed some punctate contrast-medium concentrations in the subcortical area and the medulla. The patient died on the same day. Histological material obtained at the time of autopsy revealed pseudocysts with Toxoplasma gondii and necrotizing inflammation in the brain, myocardium and lungs, as well as the entire gastrointestinal and urogenital tracts. In addition, cytomegalovirus infection of the lung and adrenals was demonstrated. Anti-toxoplasmosis IgG titre, determined postmortem, again registered a marked rise to 251 IU/ml. This suggests that there was reactivation of the toxoplasmosis as part of the immunosuppression process.

Predictive value of bronchoalveolar lavage in excluding a diagnosis of Pneumocystis carinii pneumonia during prophylaxis with aerosolized pentamidine.

We assessed the negative predictive value of bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia (PCP) during prophylaxis with aerosolized pentamidine. On the basis of the assumption that undiagnosed and untreated PCP would progress and become clinically apparent, for 3 months we prospectively followed 34 consecutive cases in which BAL had not detected PCP. All patients were immunodeficient, had a symptomatic human immunodeficiency virus infection, and were evaluated for possible PCP during prophylaxis with aerosolized pentamidine. No transbronchial biopsies were performed. In 32 of 34 cases, a diagnosis of PCP could be excluded because of other definite diagnoses or improvement during the follow-up. Despite negative results of an examination of their BAL fluid, two patients received empirical treatment that was active against PCP; these patients were regarded as possibly having undiagnosed PCP. Thus, the negative predictive value of BAL alone was at least 94% (32 of 34 cases) in excluding a diagnosis of PCP during prophylaxis with aerosolized pentamidine.

[Diagnosis and course of patients with HIV infections and exclusion of Pneumocystis carinii pneumonia]. / Diagnose und Verlauf nach Ausschluss einer Pneumocystis-carinii-Pneumonie bei HIV-Infizierten.

30 patients infected with HIV (20 men, 10 women; mean age 34 [26-54] years), suspected of having Pneumocystis carinii (Pc) pneumonia, had undergone bronchoalveolar lavage which proved negative for Pc. They were then kept under observation for 5 months. No transbronchial biopsy was performed. 27 patients were in stage IV of the HIV infection, and 14 had been on pentamidine prophylaxis. The most frequent diagnosis with the bronchial lavage was bacterial infection (19 patients), next most frequent was mycobacterial infection (6, atypical in 5). A neoplasia (Kaposi sarcoma; non-Hodgkin lymphoma) was found in two, with pulmonary involvement. The diagnosis remained unclear in only three patients who were treated as for Pc pneumonia. The remaining 27 patients did not receive any treatment against Pc. Nonetheless, there were no cases of Pc pneumonia in the 5 months of observation so that bronchoalveolar lavage has a negative predictive value of 90% (27 of 30), high enough to make additional bronchial biopsy unnecessary.

[The lung as a reflection of internal medicine diseases]. / Die Lunge als Spiegelbild internmedizinischer Krankheiten.

The lungs are called "mirror of internal medicine" because they are often involved in multisystem diseases. The morphologic changes of the lungs are uncharacteristic and the classification is only possible in relation to other manifestations of multisystem diseases. In this article clinical syndromes with pulmonary manifestations will be reviewed. Congestive heart failure and congenital diseases may lead to pulmonary features. Most cardial pleural effusions are transudates except postcardiac injury syndrome causes pleural exsudates. Almost all connective tissue diseases may affect the lungs and the pleura. Scleroderma, systemic lupus erythematodes, vasculitis, polymyositis, Sharp's syndrome, Wegener's granulomatosis, Goodpasture and Sjögren's syndrome, rheumatoid arthritis, ankylosing spondylitis and sarcoidosis are discussed. There is an association of gastroesophageal reflux and asthma. Acute pancreatitis may cause an adult respiratory distress syndrome. Endocrine and hematologic diseases seldom cause pulmonary changes. Many malignant tumors are going along with metastasis in the lungs. Renal insufficiency causes "fluid lung", nephrotic syndrome pleural effusions. Finally different drugs induce pulmonary diseases.

[Histiocytosis X. Clinical aspects and course in 5 patients]. / Histiocytosis X. Klinik und Verlauf bei fünf Patienten.

Histiocytosis X developed in five patients (one woman and four men) when aged between 15 and 44 years. The initial sign in four of them was eosinophilic granuloma of the bone, in one it was pulmonary involvement. In three patients the disease remained confined to bone, while in two it involved the lungs and central nervous system, respectively. Osteolysis regressed spontaneously in one of the men, while in the woman there has been no recurrence 8 years after resection of the focus. In another man an osteolytic focus in a rib was noted after a 9-year recurrence-free interval. The man with pulmonary and bone involvement received chemotherapy with vinblastine and prednisone: dyspnoea and cough disappeared, vital capacity improved and the interstitial lung changes regressed. The osteolytic foci were repeatedly irradiated in the man with bone and CNS involvement. This brought about considerable reduction in pain but no significant radiological changes of the foci. Two courses of chemotherapy were given over 12 years, once with vincristine and prednisone, afterwards with cyclophosphamide. This arrested the progression of the osteolytic foci, but each time they recurred when the drugs were stopped.

Low-dose zidovudine in combination with either acyclovir or lymphoblastoid interferon-alpha in asymptomatic HIV-infected patients: a pilot study.

The antiretroviral activity, tolerance and toxicity of two different antiviral drug combinations were assessed and compared in a randomized, crossover pilot study in 16 HIV-1 p24 antigenaemic subjects with asymptomatic HIV infection. Oral zidovudine 250 mg twice daily was combined with either oral acyclovir 800 mg twice daily or lymphoblastoid interferon-alpha 1.5 x 10(6) IU administered subcutaneously three times weekly. The 12-week treatment period was followed by a 4-week washout period and a further 12-week crossover phase. During the entire treatment period a decline in p24 antigen was observed in all patients. No significant differences were found between the two treatment regimens. No patient showed clinical progression of HIV infection. Three patients were withdrawn from the study, one due to serious anaemia and two due to severe clinical adverse events. Long-term efficacy and tolerance data in asymptomatic HIV-infected patients with these regimens would be valuable.

[Brain abscess as a complication of Osler's disease with lung involvement]. / Hirnabszess als Komplikation des Morbus Osler mit Lungenbeteiligung.

Eight months after sustaining a reversible left motor hemisyndrome, predominantly of the arm, a 47-year-old man known to have hereditary haemorrhagic telangiectasia (Osler's disease) again developed neurological symptoms (headache, vertigo, unsteady gait) with fever (up to 38.5 degrees C). Clinical features and findings on computed tomography indicated a cerebellar abscess. This was resected because it continued to enlarge despite antibiotic treatment with daily 2 g ceftriaxone and twice daily 0.5 g ornidazole. As another manifestation of Osler's disease further tests revealed an arteriovenous malformation (2.5 x 2.0 cm) in the right upper lobe of the lung, presumably the cause of the cerebral abscess. After wedge resection of the anterior upper lobe segment the further course was without complications.

[Primary sclerosing cholangitis]. / Die primär-sklerosierende Cholangitis.

In a 40-year-old patient unexplained recurrent attacks of epigastric colic with transient cholestatic icterus occurred over a 9-year period. When the patient was again hospitalised because of progressive pain-free icterus associated with mild pruritus (alkaline phosphatase 900 U/l, direct bilirubin 305 mumol/l, GOT 187 U/l, GPT 103 U/l) sonography revealed liver enlargement to 17 cm, extended intrahepatic bile ducts and an echodense area of about 1 cm size in the region of the bifurcation of the common hepatic duct. Fine-needle puncture did not yield clear cytological findings. Endoscopic retrograde cholangiopancreatography pointed to sclerosing cholangitis. This diagnosis was confirmed by liver punch biopsy. Since the patient did not agree to a liver transplantation, he was treated with 450 mg ursodeoxycholic acid twice daily, resulting in marked reduction of the liver parameters until severe cholangiosepsis and acute renal failure occurred about 4 months later. The septic condition and its complications could not be managed despite thorough intensive-care measures so that a liver transplant had to be performed after all. Histology of the explantate revealed a cholangiocarcinoma in the region of the bifurcation of the common hepatic duct. At first the patient's condition improved markedly but one and half months later the transplant was rejected and the patient died.