[An older female patient with refractory anemia and hemochromatosis]. / Eine ältere Patientin mit refraktärer Anämie und Hämochromatose.

CASE HISTORY AND CLINICAL FINDINGS: A 69-year-old woman was admitted because of a normocytic anemia. One year before an acute B19 parvovirus infection had been diagnosed, but the anemia was attributed to intestinal bleeding caused by a dysplastic colonic polyp. However, anemia persisted despite polypectomy. There was an excessive elevation of serum ferritin. ADDITIONAL EXAMINATIONS: A bone marrow biopsy and aspirate led to the diagnosis of a myelodysplastic syndrome (pure sideroblastic anemia). Ultrasound demonstrated advanced fibrosis of the liver. Fibrosis in association with severe parenchymatous siderosis was also demonstrated by histology. Analysis of the hemochromatosis gene (B-HFE, nt 845, G/A) was negative. DIAGNOSIS, THERAPY AND CLINICAL COURSE: The patient had secondary hemochromatosis due to a myelodysplastic syndrome. An acute infection with parvovirus B19 had been noted at the time of the first admission, one year before MDS was diagnosed. At that time, hemochromatosis had already caused fibrosis of the liver. However, complete regression of organ siderosis was achieved by deferoxamine administration. The myelodysplastic syndrome itself did not show any progression even 7 years after the diagnosis was established. CONCLUSION: Our case demonstrates the uncommon association between sideroblastic anemia and secondary hemochromatosis. Acute parvovirus infection may induce severe anemia in myelodysplastic syndromes. In acute B19 parvovirus infections an underlying hematologic disease should be excluded.

[Tracheobronchopathia osteochondroplastica: an uncommon cause of retention pneumonia in an elderly patient]. / Tracheobronchopathia osteochondroplastica: eine ungewöhnliche Ursache einer Retentionspneumonie.

A 79 years old patient without preexisting pulmonary disease was admitted due to pneumonia and hemoptysis. Despite intravenous antibiotic therapy he did not recover and still suffered from fever and dyspnea six days later. Fiberoptic bronchoscopia was performed in order to exclude poststenotic pneumonia. However, macroscopically a "rock-garden" trachea, the characteristic picture of osteochondroplastic tracheobronchopathy, was seen with multiple whitish irregularly shaped nodules in the trachea, except in the pars membranacea, involving both sides of the bronchial system and producing subtotal stenosis. Although cytologic examination suggested adenocarcinoma, histology confirmed the diagnosis of osteochondroplastic tracheobronchopathy. Repeated CT scans as well as control bronchoscopy served as a means of excluding simultaneous carcinoma. The case presented here demonstrates that even progressive tracheobronchopathy may remain asymptomatic for a long time until subtotal stenosis or impaired clearing mechanisms may lead to retention pneumonia. Cytologic examination may give false positive results suggesting malignant disease. However the typical macroscopic picture as well as histology should lead to the correct diagnosis.

[A young man with adynamia, subepicardial ischemia and sleep apnea]. / Ein junger Mann mit Adynamie, Aussenschichtischämie und nächtlicher Apnoe.

HISTORY AND CLINICAL FINDINGS: A 44-year-old manager presented himself for the assessment of nocturnal apnoea. He reported increasing lack of drive and nightly angina pectoris. INVESTIGATIONS: Polysomnography indicated obstructive apnoea and hypopnoea with a respiratory disturbance index of 29.1, while the ECG showed T wave inversion in all leads. There was severe hypothyroidism with atrophic thyroid tissue. DIAGNOSIS, TREATMENT AND COURSE: The patient had an obstructive sleep apnoea syndrome (OSAS), hypothyroidism with myxoedema, hypopnoea and myocardial ischaemia. He was treated with negative peak airway pressure (nCPAP) ventilation, administration of L-thyroxine and initiation of anti-anginal medication, which relieved his symptoms. The severe hypothyroidism was thought to be the most important cause of his respiratory disorder and angina. CONCLUSION: This case illustrates the connection between hypothyroidism and OSAS. Hypothyroidism must be excluded in patients with OSAS, regardless of the patient's age.

Phase II study of anti-CD4 idiotype vaccination in HIV positive volunteers.

A clinical phase II trial of postinfectional idiotype vaccination was performed in early stage HIV + volunteers. The mAb 13B8.2 is directed against the CDR3-homologous CD4/D1 region implicated in HIV-gp120 binding. We have previously shown that this mAb induces HIV-gp120 cross-reactive immunity. In addition, the mAb 13B8.2 was well tolerated in a clinical phase-Ia trial. In this phase-II trial, 158 patients with 350-500 CD4+ cells/microl blood were randomised to receive either 1.2 mg of alum-precipitated mAb 13B8.2 or placebo. The mAb was well tolerated evoking predominantly local side effects. Multivariant analysis of clinical study endpoints demonstrated a significant response in the verum group (intend-to-treat analysis). Titres of HIV-1 neutralisation in vitro were raised along with HIV/gp120 antigen binding titres. Our data indicate that patients treated with the idiotype vaccine will produce an augmented specific anti-viral immune response. The vaccine might thus have a positive impact on the course of HIV disease.

Thrombotic microangiopathies and HIV infection: report of two typical cases, features of HUS and TTP, and review of the literature.

Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are thrombotic microangiopathies increasingly reported in patients with HIV infection. However, characteristic features of thrombotic microangiopathies associated with HIV disease have not been defined yet. The typical courses of HUS and TTP in two patients are presented. The data as well as the analysis of cases published in the literature demonstrate the association of thrombotic microangiopathies with late-stage HIV disease. Moreover, differences between HUS and TTP can be detected. Patients with HUS present with more severe immunologic deterioration. Although clinical symptoms are fewer, HUS implicates a very poor prognosis. Life expectancy rarely exceeded 1 year after diagnosis. HUS and TTP should therefore be added to the international AIDS classification.

[Post infection antiidiotype vaccination against HIV: results of a phase Ia pilot study]. / Postinfektionelle Antiidiotyp-Vakzination gegen HIV: Ergebnisse einer Phase-Ia-Pilotstudie.

The mAb IOT4A against the HIV-gp 120 binding site on CD4 was shown to elicit the production of specific anti-idiotypes in rabbits neutralising HIV-1 in vitro. This study was designed in order to determine the safety and efficacy of the mAb IOT4A for the immunization of HIV+ volunteers. 10 patients in stages WR2-WR4B of HIV-disease were given six s.c. injections of the mAb IOT4A as an alum precipitate (each 3 patients receiving 0.6 or 1.2 mg, 4 patients receiving 2.4 mg). 6 patients subsequently received a booster immunization with the same dose of the mAb IOT4A. The immunization schedule was accompanied by monitoring clinical, immunologic and virologic parameters. No systemic toxic or allergic effects of the idiotype vaccine were observed. 8/10 vaccinees displayed a delayed-type hypersensitivity at the location of antibody administration beyond the third injection. The relative and absolute CD4 count showed a sustained increase in 8/10 patients at the end of the booster immunization and an additional raise after booster immunization in 6/6 patients. 624 antigen levels became negative in 2/2 patients during vaccination. In 4/10 patients in increase in HIV/gp 120 antigen binding titres was observed. HIV neutralisation titer remained stable throughout the observation period, and no progression in HIV disease was observed in all patients included in this study. The administration of the mAb IOT4A as a vaccine in HIV-infected volunteers was well tolerated. The mAb ITO4A induced the production of specific anti-idiotypes, that might have been of clinical benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Neutralization of HIV-1 by anti-idiotypes to monoclonal anti-CD4. Potential for idiotype immunization against HIV.

Anti-idiotypic antibodies were raised in rabbits against a panel of 11 murine mAb directed to the human CD4 receptor. Selection of mAb for vaccination was based on inhibition studies demonstrating that these mAb recognized CD4/V1 epitopes implicated in HIV-1-gp120 binding. Purified antisera showed high titer anti-Id activity and reacted specifically with Ag-combining site-related Id of the mAb used for their generation. Anti-Id either detected a private Id of the immunizing mAb or displayed a partial cross-reactivity with Id of other mAb to CD4. Eight anti-Id to six different mAb were shown to recognize determinants of recombinant HIV-1-gp120 or of HIV-1-gp160 as shown by ELISA and radioimmunoprecipitation assay. These anti-Id were capable of inhibiting HIV infection up to 100% in a MT-4 cell assay in vitro. In addition to neutralizing infectivity of cell-free virus, anti-Id to two mAb--the mAb IOT4a and 7.3F11--were also shown to inhibit HIV-induced syncytia formation up to 100%. Anti-Id to the mAb IOT4a, 7.3F11, and to the mAb anti-Leu3a interfered with rgp120 binding to cellular CD4 as assessed by flow cytometry. These results demonstrated that mAb specific for both CDR2- and CDR3-like regions of CD4 were capable of inducing HIV-1-gp120 cross-reacting anti-Id neutralizing HIV-1 in vitro. These studies may have implications for the development of a gp120 internal image based vaccine against HIV.