The urological care and outcome of pregnancy after urinary tract reconstruction.

OBJECTIVE: To assess the obstetric and urological outcomes during and after pregnancy following urinary tract reconstruction, as pregnancies after such surgery can have a significant effect on the function of the reconstructed urinary tract, and the reconstruction can significantly affect the delivery of the fetus. PATIENTS AND METHODS: We retrospectively reviewed the obstetric and urological history of 11 patients (12 pregnancies; 10 singletons and one twin) with previous urinary reconstruction, delivered between 1989 and 2003. Antepartum and postpartum urological function and obstetric outcomes were investigated. RESULTS: All the patients had some difficulty with clean intermittent catheterization (CIC) during pregnancy, and four needed continuous indwelling catheters. During pregnancy 10 women had several bladder infections and all received antibiotic suppression. There were eight Caesarean sections, two vaginal deliveries and one combined delivery. Six Caesareans were elective and three were emergent. The use of CIC returned to normal in all patients after delivery. CONCLUSIONS: Women with a urinary reconstruction can have successful pregnancies. The complexity of the surgery and the concern for possible emergency Caesarean section resulted in most patients having an elective Caesarean delivery before term. Antibiotic prophylaxis is recommended and patients may require indwelling dwelling catheters while pregnant but normal CIC can be resumed after delivery.

Evidence for the role of demyelination, HLA-DR alleles, and cytokines in the pathogenesis of parvovirus B19 meningoencephalitis and its sequelae.

OBJECTIVE: To review the clinical and pathological features of parvovirus B19 meningoencephalitis and its sequelae in 12 previously published cases, and to perform additional tests to determine the pathogenesis of the disease. METHODS: Cases were reviewed and available serum and cerebrospinal fluid (CSF) tested for antiganglioside antibodies and a range of cytokines. In situ hybridisation for parvovirus B19 DNA was performed on postmortem brain tissue in two cases. HLA-DRB1 typing was undertaken on genomic DNA extracted from peripheral blood leucocytes. RESULTS: Cerebellar involvement was suggested either clinically or pathologically in four cases. In the two cases with postmortem histology, there was marked atrophy of the molecular and granular layers of the cerebellum with focal loss of Purkinje cells. Brain scanning by MRI or CT was done in six cases during the acute phase. Three were abnormal with evidence of demyelination. Three had markedly enlarged ventricles, in two of which there was high signal intensity from the white matter on both T1 and T2 weighted images. The three cases with abnormal brain scans had long term neurological sequelae (mental retardation, personality change, altered affect). In situ hybridisation on available postmortem brain tissue was negative in the two cases tested. All cases in which HLA-DR alleles were determined carried at least one of the following alleles: HLA-DRB1*01, *04, *07, *09, *15, *16. Available serum and CSF was tested for antiganglioside antibodies (all negative) and for a panel of cytokines, which had a similar profile in both serum (n = 5) and CSF (n = 1) during the acute phase. Cytokines that were consistently detectable were IL-6 (mean 726.20 pg/ml), TNFalpha (50.64 pg/ml), IFNgamma (39.64 pg/ml), GM-CSF (216.12 pg/ml), and MCP-1 (154.43 pg/ml); IL-1beta, IL-5, and IL-13 were undetectable. CONCLUSIONS: HLA-DR associations, an increased cytokine response, and benefit from immunomodulatory treatment (in one case) support a role for the immune response in the pathogenesis of parvovirus B19 meningoencephalitis.

Does GH replacement therapy in adult GH-deficient patients result in recurrence or increase in size of pituitary tumours?

OBJECTIVE: Hypopituitary GH-deficient patients have an increased cardiovascular mortality and GH replacement in this population has resulted in considerable therapeutic benefit. GH replacement involves administration of a potentially mitogenic substance to patients with a previous or residual pituitary tumour. Our objective was to evaluate whether GH replacement results in an increase in the size of pituitary tumours. METHODS: This was a non-randomised observational study on patients recruited from the endocrine clinic. All subjects had GH deficiency, proven on an insulin tolerance test and were divided into those who were or were not receiving long-term GH replacement. Comparison of change in pituitary size was made with interval radiological imaging of the pituitary. RESULTS: Seventy-five patients (40 men and 35 women) were in the study, 47 were on long-term GH replacement and there were 28 controls. The average length of treatment for the treated group was 3.6 patient years. Thirty-nine patients in the treated group had at least 2 years of GH treatment between imaging studies of the pituitary. Two patients in the treated group had an increase in pituitary size (non-functioning adenomas) and two in the control group (one functioning and one non-functioning adenoma adenoma). None of these four patients required further treatment. There was no statistically significant difference between the two groups. CONCLUSION: Using a representative cohort of hypopituitary patients attending an endocrine clinic, GH replacement was not associated with an increased pituitary tumour recurrence rate. Although the results are not conclusive, in the period of observation GH had little adverse effect but longer studies are required to be certain.

Lower limb and back pain in Guillain-Barré syndrome and associated contrast enhancement in MRI of the cauda equina.

UNLABELLED: This study assesses the frequency of lower limb and back pain in children with Guillain-Barré syndrome and reviews the magnetic resonance imaging results of those undergoing spinal imaging. Over an 8-y period, nine children presented with various combinations of severe back pain, leg pains, impairment of gait and bladder dysfunction. Guillain-Barré syndrome was confirmed on clinical examination and peripheral electrophysiology (n = 8). Magnetic resonance imaging in four patients, following contrast injection, showed enhancement of the cauda equine and, additionally, of the cervical nerve roots in one of the patients. A further patient, who was not scanned with contrast, had abnormal thickening of the lumbar roots. Carbamazepine and steroids were effectively used for analgesia in three cases. All the patients recovered. CONCLUSION: Guillain-Barré syndrome should be considered in the differential diagnosis of children presenting with back and/or leg pain. Early diagnosis ensures prompt monitoring for autonomic dysfunction and respiratory compromise.

MRI of the brain in HIV-positive patients: what is the value of routine intravenous contrast medium?

Our purpose was to assess the value of routine administration of intravenous gadolinium-DTPA (Gd-DTPA) for cranial MR in a series of human immunodeficiency virus (HIV)-positive patients. Two radiologists retrospectively reviewed 150 consecutive examinations of 104 patients. All patients underwent unenhanced and contrast-enhanced images. Each radiologist independently assessed first the unenhanced images alone and then the pre- and postinjection images together. Then both reviewed the complete study and produced a consensus report. The history, investigations and management were collated separately and were unknown to the radiologists. Contrast-enhanced T1-weighted images showed new focal abnormalities, not seen on the T2-weighted or unenhanced images in 15 (14 %) patients, but almost always in the context of abnormal unenhanced images. In only 2 patients (2 %) did contrast medium reveal abnormalities when the unenhanced study had been considered normal. In only 1 of these (1 %) was the new finding, cytomegalovirus diffuse ependymal enhancement, of clinical importance, although the diagnosis of encephalitis was made on routine examination of cerebrospinal-fluid. The other revealed a toxoplasma lesion in a patient known to have resolving disease. Meningeal disease not suspected on the unenhanced images was shown in 2 patients (2 %). In these case the unenhanced images were abnormal in other respects. Intravenous Gd-DTPA was helpful to the radiologist in making a radiological diagnosis in 11 patients (11 %), usually by improving characterisation of a lesion seen on the unenhanced images. The contribution of intravenous Gd-DTPA in this series does not warrant recommending its use in every case.

Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end.

The multisubunit protein, dynactin, is a critical component of the cytoplasmic dynein motor machinery. Dynactin contains two distinct structural domains: a projecting sidearm that interacts with dynein and an actin-like minifilament backbone that is thought to bind cargo. Here, we use biochemical, ultrastructural, and molecular cloning techniques to obtain a comprehensive picture of dynactin composition and structure. Treatment of purified dynactin with recombinant dynamitin yields two assemblies: the actin-related protein, Arp1, minifilament and the p150(Glued) sidearm. Both contain dynamitin. Treatment of dynactin with the chaotropic salt, potassium iodide, completely depolymerizes the Arp1 minifilament to reveal multiple protein complexes that contain the remaining dynactin subunits. The shoulder/sidearm complex contains p150(Glued), dynamitin, and p24 subunits and is ultrastructurally similar to dynactin's flexible projecting sidearm. The dynactin shoulder complex, which contains dynamitin and p24, is an elongated, flexible assembly that may link the shoulder/sidearm complex to the Arp1 minifilament. Pointed-end complex contains p62, p27, and p25 subunits, plus a novel actin-related protein, Arp11. p62, p27, and p25 contain predicted cargo-binding motifs, while the Arp11 sequence suggests a pointed-end capping activity. These isolated dynactin subdomains will be useful tools for further analysis of dynactin assembly and function.

Heterotopic pancreas as lead point in intussusception: new variant of vitellointestinal tract malformation.

Two cases of intussusception are reported with heterotopic pancreatic tissue attached to and draining into the ileum. The first patient, a boy aged 16 months, presented with ileoileal intussusception. The diagnosis was confirmed on ultrasound scan. Laparotomy and resection were performed. A 12-mm nodule of heterotopic pancreatic tissue was identified in the ileal serosa at the apex of the intussusceptum, fully formed with acinar tissue, islets, and draining duct. The second patient, also a boy aged 16 months, presented with obstructed ileocolic intussusception in which the lead point at surgery resembled a Meckel's diverticulum. Histopathology revealed a similar 10-mm nodule of fully formed pancreatic tissue in the ileal serosal tissues, with some acinar tissue extending through the wall of the intestine alongside ductal structures. In both cases there was ectopic gastric mucosa either in the distal part of the draining duct or in the small intestine itself at the opening. Heterotopic pancreas is a rare cause of intussusception. We propose that this lesion is of vitellointestinal tract origin, conceptually similar to a Meckel's diverticulum but without a diverticulum as such. Heterotopic pancreatic tissue occurring alone is more common in the proximal small intestine, duodenum, and stomach than in the ileum, and it is often asymptomatic.

Self-regulated polymerization of the actin-related protein Arp1.

The actin-related protein Arp1 (or centractin, actin RPV) is the major subunit of dynactin, a key component of the cytoplasmic dynein motor machinery [1] [2] [3]. Of the ubiquitously expressed members of the Arp superfamily, Arp1 is most similar to conventional actin [4] [5] [6] and, on the basis of conserved sequence features, is predicted to bind ATP and possibly polymerize. In vivo, all cytosolic Arp1 sediments at 20S [7] suggesting that it assembles into oligomers, most likely dynactin - a multiprotein complex known to contain eight or nine Arp1 monomers in a 37 nm filament [8]. The uniform length of Arp1 polymers suggests a novel assembly mechanism that may be governed by a 'ruler' activity. In dynactin, the Arp1 filament is bounded by actin-capping protein at one end and a heterotetrameric protein complex containing the p62 subunit (D.M. Eckley, S.R. Gill, J.B.B., J.E. Heuser, T.A.S., unpublished observations) at the other [8]. In the present study, we analyzed the behavior of highly purified, native Arp1. Arp1 was found to polymerize rapidly into short filaments that were similar, but not identical, in length to those in dynactin. With time, these filaments appeared to anneal to form longer assemblies but never attained the length of conventional actin filaments.

Magnetic resonance imaging features of pituitary yttrium-90 rod implantation.

Intersellar implantation of yttrium-90 rods was a common treatment for a variety of pituitary tumours in the 1960s and 1970s. The magnetic resonance (MR) imaging features in three patients with implants (two for growth hormone-secreting and one for prolactin-secreting pituitary adenomas) are presented: the implants appeared as low signal cylinders with no image distortion, in contradistinction to CT where the implants generate beam hardening and back projection artefacts. Confident evaluation of the pituitary fossa for residential tumour and sequelae of therapy could be made on MR. It is the imaging technique of choice in the follow-up of patients treated with yttrium-90 implants.

Evaluation of fluorodeoxyglucose positron emission tomography in the management of soft-tissue sarcomas.

We performed a retrospective analysis to evaluate the ability of whole-body F-fluorodeoxyglucose positron emission tomography (FDG PET) to identify local recurrence and pulmonary metastases in patients with soft-tissue tumours after treatment. We compared the results of FDG PET with those of MRI for the detection of local recurrence, and with CT of the chest for pulmonary metastases. We assessed 62 patients of mean age 51 years, who had 15 types of soft-tissue sarcoma, after a mean follow-up of 3 years 2 months. For the detection of local disease, 71 comparisons showed that the sensitivity and specificity of FDG PET were 73.7% and 94.3%, respectively; there were 14 true-positive and five false-negative results. MRI had a sensitivity and specificity of 88.2% and 96.0% respectively. For the identification of lung metastases, 70 comparisons showed that the sensitivity and specificity of FDG PET were 86.7% and 100%, with 13 true-positive results and two false-negative results. CT of the chest had a sensitivity and specificity of 100% and 96.4%. Thirteen other sites of metastases were identified by FDG PET. FDG PET can identify both local and distant recurrence of tumour as a one-step procedure and will detect other metastases. It seems that all three methods of imaging are needed to define accurately the extent of disease, both at initial staging and during follow-up.

The role of CT and MR in imaging the complications of sickle cell disease.

Sickle cell disease is the most common inherited haemoglobinopathy described. Complications of sickle cell disease (SCD) are due to chronic haemolysis of fragile red cells or secondary to vascular occlusion by sickled red cells with subsequent tissue infarction. Traditionally plain film radiography has been the mainstay in the assessment of patients with SCD, but increasingly magnetic resonance (MR) imaging and computed tomography (CT) are being used. In this review the imaging features of a range of complications of SCD are demonstrated with particular emphasis on CT and MR.

The use of prophylactic antibiotics in ultrasound-guided transrectal prostate biopsy.

The use of antibiotic prophylaxis for transrectal prostate biopsy significantly reduces the incidence of infective complications, but no recommendations exist as to the most appropriate antibiotic regimen. This study was designed to find out which antibiotics were used in different departments and the financial cost of each regimen. A postal survey of 144 hospitals in the UK and Ireland was undertaken. Respondents were asked the name(s), dose(s), route(s) of administration and timing of antibiotics given pre and post biopsy. The response rate was 73.6%. Thirteen different antibiotics were used in 48 different regimens. The most commonly used antibiotic was metronidazole (orally or rectally) in 55% of regimens followed by oral ciprofloxacin in 48% and intravenous gentamicin in 48%. Most regimens (89.7%) contained an oral antibiotic and 58.6% contained an intravenous antibiotic. The cheapest regimen cost 38.7p/patient and the most expensive pounds sterling 21.36/patient, calculated according to prices quoted in the British National Formulary, March 1996. We conclude that there is a lack of standardization in antibiotic prophylaxis for ultrasound-guided transrectal prostate biopsy with widely differing costs for the different regimens. A review of the literature shows that oral antibiotics are inexpensive, well tolerated and effective at reducing the incidence of urinary tract infection and fever following transrectal prostate biopsy. A regimen is proposed including ciprofloxacin or norfloxacin. The addition of oral metronidazole is a subject for further study.

Cyclosporine-related reversible posterior leukoencephalopathy: MRI.

Three patients aged 48, 11 and 40 years, two of whom were recent recipients of renal transplants and one of a bone marrow transplant, developed seizures, with cortical blindness in two cases. All were immunosuppressed with cyclosporine and were hypertensive at the onset of symptoms. MRI showed predominantly posterior signal changes in all three cases. The abnormalities were more conspicuous on fast FLAIR images than on conventional T2-weighted spin-echo images.

Imaging and pathological features of primary malignant rhabdoid tumours of the brain and spine.

In this article two cases of primary malignant extrarenal rhabdoid tumour are described. In the affected children the brain and the spinal cord were the primary sites of origin of the tumour. The imaging findings are presented and the pathology discussed. Although the imaging features are non-specific, rhabdoid tumour should be included in the differential diagnosis of childhood intracranial and spinal neoplasms.

Molecular requirements for bi-directional movement of phagosomes along microtubules.

Microtubules facilitate the maturation of phagosomes by favoring their interactions with endocytic compartments. Here, we show that phagosomes move within cells along tracks of several microns centrifugally and centripetally in a pH- and microtubule-dependent manner. Phagosome movement was reconstituted in vitro and required energy, cytosol and membrane proteins of this organelle. The activity or presence of these phagosome proteins was regulated as the organelle matured, with "late" phagosomes moving threefold more frequently than "early" ones. The majority of moving phagosomes were minus-end directed; the remainder moved towards microtubule plus-ends and a small subset moved bi-directionally. Minus-end movement showed pharmacological characteristics expected for dyneins, was inhibited by immunodepletion of cytoplasmic dynein and could be restored by addition of cytoplasmic dynein. Plus-end movement displayed pharmacological properties of kinesin, was inhibited partially by immunodepletion of kinesin and fully by addition of an anti-kinesin IgG. Immunodepletion of dynactin, a dynein-activating complex, inhibited only minus-end directed motility. Evidence is provided for a dynactin-associated kinase required for dynein-mediated vesicle transport. Movement in both directions was inhibited by peptide fragments from kinectin (a putative kinesin membrane receptor), derived from the region to which a motility-blocking antibody binds. Polypeptide subunits from these microtubule-based motility factors were detected on phagosomes by immunoblotting or immunoelectron microscopy. This is the first study using a single in vitro system that describes the roles played by kinesin, kinectin, cytoplasmic dynein, and dynactin in the microtubule-mediated movement of a purified membrane organelle.