Meso-Rex shunt using deep femoral vein conduit: first report.

The Meso-Rex shunt (MRS) procedure was first described in 1992 by de VILLE et al. for the treatment of extrahepatic portal vein obstruction (EHPVO) in paediatric liver transplant patients. This technique provides more physiological relief of portal hypertension compared to the porto-systemic shunts, which can lead to long-term complications such as hyperammonaemia and hepato-pulmonary syndrome. Different conduits as autologous and cryopreserved veins or prosthetic grafts have been previously reported. We present herein the first case of a MRS using the autologous deep femoral vein in a 17-year-old female patient affected by EHPVO from unknown reasons.

Directed mutagenesis of dihydrofolate reductase.

Three mutations of the enzyme dihydrofolate reductase were constructed by oligonucleotide-directed mutagenesis of the cloned Escherichia coli gene. The mutations--at residue 27, aspartic acid replaced with asparagine; at residue 39, proline replaced with cysteine; and at residue 95, glycine replaced with alanine--were designed to answer questions about the relations between molecular structure and function that were raised by the x-ray crystal structures. Properties of the mutant proteins show that Asp-27 is important for catalysis and that perturbation of the local structure at a conserved cis peptide bond following Gly-95 abolishes activity. Substitution of cysteine for proline at residue 39 results in the appearance of new forms of the enzyme that correspond to various oxidation states of the cysteine. One of these forms probably represents a species cross-linked by an intrachain disulfide bridge between the cysteine at position 85 and the new cysteine at position 39.

Visceral and testicular calcifications as part of the phenotype in pseudoxanthoma elasticum: ultrasound findings in Belgian patients and healthy carriers.

Occasionally calcifications in abdominal organs, breasts and testicles have been reported in pseudoxanthoma elasticum (PXE) patients. In the present study, an ultrasound evaluation was performed of the abdomen and--in male patients--of the testicles in 17 PXE patients and 17 heterozygous carriers. Blood samples were taken to evaluate calcium load, liver and kidney function. Calcifications in liver, kidneys and spleen were detected in 59% of the patients and in 23.5% of healthy carriers. Parameters of kidney and liver function were normal in both groups, suggesting that the calcifications have no direct effect on organ function. Testicular ultrasound revealed parenchymous calcifications in all males investigated. Widespread, small hyperechogenic foci resembling testicular microlithiasis were seen. In some carriers, focal calcifications were identified. The current data suggest that visceral and testicular calcifications are part of the phenotype of PXE patients. Their presence in some of the healthy carriers are suggestive of subclinical manifestations in these relatives. The natural history and long-term effects of the parenchymal calcifications remain to be elucidated. As testicular microlithiasis may be associated with a higher risk for malignancy, regular clinical and ultrasound follow-up seems indicated in these patients.

Crystallization and preliminary X-ray studies of recombinant human granulocyte-macrophage colony stimulating factor.

Human granulocyte-macrophage colony stimulating factor (hGM-CSF) is an important regulator of growth and differentiation for mononuclear and polymorphonuclear phagocytes. Here we report the crystallization and preliminary X-ray studies of Escherichia coli-expressed hGM-CSF. The crystals are orthorhombic, with the space group P212121, and have unit cell dimensions a = 46.62 A, b = 58.73 A and c = 126.42 A. Recombinant hGM-CSF crystals diffract X-rays to 2.4 A resolution and are thus suitable for X-ray structural studies.

Granulocyte-macrophage colony-stimulating factor mimicry and receptor interactions.

Development of small molecular mimics of larger polypeptide ligands is an important approach to pharmacophore design. One strategy for the development of such mimics is analysis of alternative ligands that bind to the same site as the native ligand. These allow examination of the structural and chemical constraints for binding within the setting of diverse backbone geometries. The use of antireceptor antibodies as alternative ligands has allowed the development of biologically active peptides in several ligand-receptor systems. This technology has been applied to the study of interactions between human granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor (GM-CSFR). GM-CSF is one of a family of signal-transducing cytokines and growth factors characterized by a four-helix bundle core structure. The GM-CSFR is comprised of an alpha-chain (GM-CSFR alpha) specific for GM-CSF, and a beta-chain (beta c) shared with the interleukin-3 and interleukin-5 receptors. At least two sites on GM-CSF have been implicated in the GM-CSF-GM-CSFR alpha/beta c ternary complex. In studies summarized here, synthetic peptide analogs of GM-CSF sequences were designed and used to map neutralizing epitopes. One neutralizing epitope corresponded to the A helix of GM-CSF, and a synthetic analog displayed biological activity as a GM-CSF antagonist in vitro, suggesting interaction with the GM-CSFR alpha/beta c complex. A second peptide comprising the B and C helices was recognized by monoclonal neutralizing antibodies and similarly displayed antagonist activity. Recombinant antibody (rAb) technology was also employed. An expression library of rAbs from mice immunized with neutralizing anti-GM-CSF antibodies was developed and screened with a neutralizing anti-GM-CSF monoclonal antibody. One clone which displayed receptor binding activity exhibited structural similarity with epitopes on GM-CSF previously implicated as interaction sites with the neutralizing monoclonal antibody. A synthetic peptide analog of the rAb inhibited GM-CSF bioactivity. Critical contact residues were predicted on the basis of structural similarity of the rAb peptide and GM-CSF. These studies indicate the feasibility of using rAbs in bioactive peptide design, providing lead compounds and information regarding contact residues for drug design.

Pseudoxanthoma elasticum: similar autosomal recessive subtype in Belgian and Afrikaner families.

A multidisciplinary survey of the clinical and genetic characteristics of 26 Belgian and 32 Afrikaner families with biopsy-proven pseudoxanthoma elasticum (PXE) was undertaken. The major PXE phenotype emerging from this study is very similar in both patient groups and is characterized by severe ophthalmologic manifestations with variable, mild cutaneous and vascular symptoms. In the families with more than one affected relative, segregation analysis is compatible with autosomal recessive inheritance in both groups. It is suggested that the PXE phenotype of these Belgian and Afrikaner patients is distinct from the other recognized PXE subtypes. The phenotypic resemblance in both patient groups raises the question whether a similar genetic mechanism is involved.

Ventricular taps in the neonate under ultrasonic guidance. Technical note.

A method of ultrasonically guiding ventricular taps in children is described. The needle is introduced through a needle guide in the ultrasound field of a sectorscanner. The direction of the needle is accurately determined and the needle itself is clearly visualized on the television monitor during its introduction into the brain. The results of seven punctures are presented. All these punctures were successful at the first attempt, and no complications occurred.

Floating thrombi: diagnosis and follow-up by duplex ultrasound.

The clinical features and evolution of floating thrombi (FT) diagnosed by duplex ultrasound were examined. In 76 consecutively diagnosed above-knee deep venous thromboses the prevalence of FT was 18%. Of 44 FT diagnosed in 39 patients, 18 (39%) were located in the common femoral, 12 (26%) in the popliteal and seven (15%) in the external iliac veins. Serial duplex examinations revealed that 31% of FT in the iliofemoral segment disappeared 33% remained unchanged and 36% adhered to the vein wall within 2 weeks following diagnosis. After 3 months, 87% of the floating segments had disappeared, irrespective of the localization or therapeutic regimen. Thirteen patients experienced pulmonary embolism before (12/13) or following (4/13) diagnosis of floating thrombosis; three of four superficial femoral vein FT embolized. Fifteen per cent of the patients with FT died during the study period and 28% of the thrombi were associated with a malignant neoplasm; the incidence of malignancy was 60% in superficial and 39% in common femoral vein FT.

Ultrasound and CT changes of liver parenchyma in acute schistosomiasis.

Acute schistosomiasis in travellers to endemic regions often remains unrecognized. Early diagnosis is important to avoid progression to chronic disease. Diagnosis is based on clinical, epidemiological and laboratory data. The role of imaging techniques as diagnostic tools remains to be established in acute clinical schistosomiasis. We describe hypodense nodules in the liver on ultrasound and CT scanning in a patient with acute schistosomiasis (Katayama syndrome). To our knowledge this is the first description of nodular hepatic lesions in acute schistosomiasis.

[Echographically controlled ventricle punctures]. / Echografisch geleide ventrikelpuncties.

Ventricular taps are performed either for diagnostic or for therapeutic purposes. They are not free of risks. A new technique is presented, in which the placement of the needle is echographically monitored. Fifteen punctures were done in five children. All punctures were successful at first attempt, and were uneventful.

Safety and sample adequacy of renal transplant surveillance biopsies.

PURPOSE: To report on the safety and adequacy of surveillance biopsy for detecting subclinical lesions in clinically stable renal grafts. MATERIALS AND METHODS: We established an in-patient surveillance biopsy program with the elective performance of a renal transplant biopsy during the first year after renal transplantation. All biopsies in our centre were performed or supervised by the same operator. Patients were admitted to the hospital the day of biopsy and were discharged after 24h of observation. All patients were biopsied in supine position, using a 16-gauge needle with a spring-loaded gun (Bard) under real-time ultrasound guidance. Complication rates were retrospectively scored using the patients' charts and blood counts before and after biopsy. Major complications were defined as those requiring an intervention for resolution, a transfusion of blood products or an invasive procedure (angiography or surgery), and those that led to acute renal obstruction or failure, septicaemia, graft loss or death. In all other cases complications were considered minor. An adequate biopsy was defined as the presence of 7 or more glomeruli and at least one artery in the biopsy specimen. RESULTS: We performed 282 surveillance biopsies in 248 patients between January 2006 and December 2011. None of the complications were major. We observed 6% minor complications (n = 17). 5.6% (n = 16) of the complications were related to bleeding, with macroscopic haematuria as the most common condition (n = 10; 3.5%), followed by pain (n = 6; 2.1%) eighter due to a perinephric hematoma (n = 5) or a subcutaneous hematoma (n = 1). The biopsies contained a median number of 9 glomeruli (range 0-39) with 70% of biopsies containing at least 7 glomeruli and one artery. CONCLUSION: The procedure for taking surveillance biopsies was proven to be safe. There were no major complications and only rare minor complications. The majority of the samples were adequate for histological examination.

Contrast-enhanced ultrasonography in hepatosplenic sarcoidosis.

We report a case of a 38-year-old woman with atypical pain in the left lower hemi-abdomen. On abdominal B-mode ultrasonography the liver was normal; the spleen showed multiple subcentimetric hypoechoic nodules. A multidetector CT-examination revealed multiple small low-attenuation nodules in the liver and the spleen, suggestive for metastatic disease. Contrast-enhanced ultrasound (CEUS) revealed two hypoechoic nodules in the liver that were visible in the portal phase and disappeared in the late phase. The focal splenic lesions were visible as irregular hypo-enhancing nodules. An MRI examination, including T1, T2 and contrast-enhanced images, could not confirm the exact nature of the lesions. A core biopsy of a splenic nodule yielded non-caseating epithelioid cell granulomas. Different complementary examinations were normal and hepatosplenic sarcoidosis was diagnosed. The pain in the left lower hemi-abdomen was ascribed to irritable bowel syndrome.