Rapidly progressive hepatic alveolar echinococcosis in an ABO-incompatible renal transplant recipient.

We report on the case of an ABO-incompatible renal re-transplant recipient maintained on an intensified immunosuppressive regimen for recurrent cellular rejection episodes and transplant glomerulopathy who presented with rapidly growing hepatic tumors, radiologically suggestive of hemangiosarcoma. Upon resection and pathological work-up, the lesions revealed alveolar echinococcosis, a rare but potentially life-threatening parasitosis. Usually infection with Echinococcus multilocularis remains asymptomatic for extended periods of time and can go unrecognized for years. In the case presented, we observed an atypically rapid growth pattern of E. multilocularis that might have been due to the extent of the immunosuppressive regimen, which included repetitive anti-CD20 treatments. Retrospectively performed serological studies with enzyme-linked immunosorbent assays known to provide high sensitivity and specificity for the detection of echinococcosis in the general population, yielded ambiguous results in our immunocompromised host, which could be, in part, explained by B-cell depletion and its effects on antibody production and indirect actions on cellular immunity. In conclusion, this is the first report to our knowledge of hepatic alveolar echinococcosis in a renal transplant recipient. This case documents an altered clinical course of the parasitosis and the challenge of serological diagnostic tools under an intensified regimen of immunosuppressive agents, including rituximab.

[Disseminated histoplasmosis with involvement of mediastinum and skin in an immunocompetent patient]. / Disseminierte Histoplasmose mit Befall des Mediastinums und der Haut bei immunkompetenter Patientin.

HISTORY AND ADMISSION FINDINGS: A 29-years-old Brazilian woman was admitted to hospital because of progressive dyspnoea, shivering and fever. She reported a noticeable swelling at the right mandible and an ulcerative tumor at the side of the nose. INVESTIGATIONS: Laboratory tests showed normocytic, normochromic anemia with an elevation of the inflammatory parameters. Radiology showed an enlargement of the upper mediastinum. Computed tomography revealed extensive, confluent lymphoma. There were groups of cervical lymph nodes, especially in the area of the right jaw. Bronchoscopy showed extensive space-occupying lesions with severe inflammation of the trachea. DIAGNOSIS: Bronchial biopsy revealed necrotizing, granulomatous inflammation with dense infiltration of lymphatic cells. Small and spheroidal pathogens were seen within giant cells. Grocott-silver stain was positive, indicating histoplasmosis. Histological work-up of the ulcerating tumor at the side of the nose also showed Histoplasma capsulatum. TREATMENT AND COURSE: 8 weeks after starting specific treatment with oral itraconazole the inflammatory parameters had fallen to normal and computed tomography showed regression of the mediastinal bulge. CONCLUSION: Large mediastinal and cervical lymphatic masses with space-occupying bronchial lesions suggest should, in the differential diagnosis, consider not only malignant tumor but also infections. If the patient had been abroad (in this case in Brazil), pathogens like Histoplasma capsulatum, which is not present in Europe, have to be considered. In this immunocompetent patient the severe progression and dissemination of the disease, involving mediastinum, throat and skin, is most unusual.

Low sodium and furosemide-induced stimulation of the renin system in man is mediated by cyclooxygenase 2.

The aim of this study was to examine the effects of highly selective inhibition of cyclooxygenase 2 (COX-2) with rofecoxib on the renin system during long-term stimulation and after short-term stimulation. Six healthy male volunteers received, in a randomized crossover design, a low-sodium diet for days 1 through 9 with or without 25 mg rofecoxib twice daily on days 5 through 9 and, in addition, 20 mg of furosemide intravenously on day 8. Plasma renin activity increased 2 to 3 times over baseline with a low-sodium diet and 5 times over baseline 30 minutes after intravenous furosemide; it was still elevated nearly 5 times on day 9. These effects were completely blocked by rofecoxib. Plasma aldosterone and urinary aldosterone concentrations basically reflected the findings with plasma renin activity. Urinary sodium excretion decreased during a low-sodium diet and increased after intravenous furosemide without being significantly affected by rofecoxib. We have concluded that low-sodium and furosemide-stimulated renin and aldosterone secretion is completely blocked in healthy volunteers during COX-2 inhibition with rofecoxib, suggesting that intact COX-2 is of major importance for stimulation of the renin system under these conditions in man.

Severe hypertension and massive osteoporosis as presenting symptoms of Cushing's syndrome.

Though Cushing's syndrome is a well-known clinical problem in terms of side effects of steroid therapy, endogenous Cushing's syndrome is a relatively rare diagnosis. We treated a 27-year-old patient who presented with severe hypertension and massive osteoporosis. We could diagnose a central Cushing syndrome by endocrinological function tests which, in retrospect, existed undiagnosed for more than 5 years. However, magnetic resonance imaging did not display an adenoma neither of the hypophysis nor of the adrenal glands. During explorative surgery, a cylindric microadenoma of the pituary gland was found and excised. After surgery, the blood pressure returned to normal, making further antihypertensive treatment unnecessary.

Identification of a novel Ran binding protein 2 related gene (RANBP2L1) and detection of a gene cluster on human chromosome 2q11-q12.

The giant 358-kDa protein Ran binding protein 2 (RanBP2/Nup358) is localized at the cytoplasmic side of the nuclear pore complex and likely constitutes the Ran-GTP binding site at the cytoplasmic face of the complex. RanBP2/Nup358 furthermore acts as a chaperone for red/green opsin molecules. Here, we report on the physical mapping of human RanBP2 between markers D2S340 and D2S1893. A duplication of the 5'-end sequence of RanBP2 occurs within 3 Mb distal to RanBP2. Detailed sequence analysis resulted in primers specific for this distal duplication. Polymerase chain reaction-based screening of cDNA libraries indicates that this transcript, called RanBP2alpha (HGMW-approved symbol RANBP2L1), is expressed in several tissues. Screening of a fetal brain cDNA library yielded a 4057-bp partial cDNA clone for RanBP2alpha. Its 5'-end is almost identical to RanBP2, whereas its 3'-part is distinct from RanBP2. Northern blot analysis using a probe of the 3'-untranslated sequence of RanBP2alpha detected in several tissues an 8-kb transcript representing the full length of the transcript. In pancreas and placenta, an additional transcript of 14 kb was detected. PAC clones containing the bona fide RanBP2 sequences were localized to 2q11-q12 by FISH analysis, and a region of high similarity was detected on 2p11-p12. In summary, we have identified a RanBP2 gene cluster on 2q11-q12 together with a novel gene termed RanBP2alpha, with high sequence similarity to RanBP2.

Construction of a gene map of the nephronophthisis type 1 (NPHP1) region on human chromosome 2q12-q13.

A gene for the autosomal recessive kidney disorder juvenile nephronophthisis (NPH) is located on chromosome 2q between markers D2S1893 and D2S1888. Recently, the presence of large homozygous deletions was described in the majority of NPH patients. We constructed an integrated YAC/PAC contig of 54 markers and 30 PAC clones that encompasses this deletion and the flanking inverted duplication. Thirty-six novel sequence-tagged site markers were generated for this region of 2-3 Mb, 22 of which represent PAC ends. Ten of 18 multiplex NPH families show a homozygous deletion for 8 consecutive markers. BlastN database search and expressed sequence tag (EST) mapping led to the localization of 18 EST clones to the integrated contig, representing 11 putative transcribed sequences. Seven EST clones were localized to the NPHP1 region between D2S1893 and D2S1888. Two EST clones, zc07a11 from a human parathyroid tumor library and yy63e10 from a multiple sclerosis lesion library, are located in the deletion region. PCR amplification experiments indicate that zc07a11 represents a chimeric cDNA. Through FISH analysis the NPHP1 deletion region was localized to 2q12-q13. In summary, our study provides a high-resolution physical map of the NPHP1 region with 7 precisely localized expressed sequences, 2 of which have recently been shown to be part of a gene for NPH. These data will alleviate the identification of further genes of a homozygous gene deletion syndrome in patients with NPH and oculomotor apraxia and will be instrumental in the characterization of the molecular mechanism leading to the large homozygous deletion in this region. The data furthermore provide an important step toward the construction of a sequence-ready PAC contig of this region.