Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function

Adult mammalian CNS neurons do not normally regenerate their severed axons. This failure has been attributed to scar tissue and inhibitory molecules at the injury site that block the regenerating axons, a lack of trophic support for the axotomized neurons, and intrinsic neuronal changes that follow axotomy, including cell atrophy and death. We studied whether transplants of fibroblasts genetically engineered to produce brain-derived neurotrophic factor (BDNF) would promote rubrospinal tract (RST) regeneration in adult rats. Primary fibroblasts were modified by retroviral-mediated transfer of a DNA construct encoding the human BDNF gene, an internal ribosomal entry site, and a fusion gene of lacZ and neomycin resistance genes. The modified fibroblasts produce biologically active BDNF in vitro. These cells were grafted into a partial cervical hemisection cavity that completely interrupted one RST. One and two months after lesion and transplantation, RST regeneration was demonstrated with retrograde and anterograde tracing techniques. Retrograde tracing with fluorogold showed that approximately 7% of RST neurons regenerated axons at least three to four segments caudal to the transplants. Anterograde tracing with biotinylated dextran amine revealed that the RST axons regenerated through and around the transplants, grew for long distances within white matter caudal to the transplant, and terminated in spinal cord gray matter regions that are the normal targets of RST axons. Transplants of unmodified primary fibroblasts or Gelfoam alone did not elicit regeneration. Behavioral tests demonstrated that recipients of BDNF-producing fibroblasts showed significant recovery of forelimb usage, which was abolished by a second lesion that transected the regenerated axons.     

Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia type 1 patients in northwestern Europe and Mediterranean countries

Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disease caused by a deficient activity of the enzyme fumarylacetoacetase (FAH). To investigate the molecular heterogeneity of tyrosinemia, the geographic distribution and the genotype–phenotype relationship, we have analyzed the FAH genotype of 25 HT1 patients. Mutation screening was performed by PCR amplification of exons 1-14 of the FAH gene, followed by SSCP analysis and direct sequencing of the amplified exons. Fourteen different mutations were found, of which seven were novel, viz. Three missense mutations (G158D, P261L, F405H), a deletion of three nucleotides causing a deletion of serine (DEL366S) and three splice site mutations: IVS2+1(g-t), IVS6-1(g-c), IVS8-1(g-c). The splice site mutations IVS6-1(g-t) and IVS12+5(g-a) were frequently found in countries around the Mediterranean and northerwestern Europe, respectively. No clear correlation between the genotype and the three major HT1 subtypes could be established. Hum Mutat 12:19–26, 1998. © 1998 Wiley-Liss, Inc.     

Assessment of referral patterns for CT KUB in a tertiary setting

The purpose of this study was to assess the referral patterns and the use of unenhanced renal tract CT (CT KUB) for investigating patients presenting with clinically suspected renal colic. We retrospectively reviewed 500 consecutive CT KUB studies requested for suspected renal colic carried out at a single institution between December 2006 and July 2007. Follow‐up radiology reports and discharge summaries on the hospital clinical Intranet were also reviewed. Studies were analysed for characteristics including patient demographics, referring clinical team, time of referral, final diagnosis and requirement for further imaging. The majority of requests were from Emergency (ED) or Urology Departments (49%, 245 out of 500, and 37%, 186 out of 500, respectively). The positive rate for urolithiasis was 67% (337 out of 500), the negative rate was 25% (123 out of 500), and 8% (40 out of 500) of patients had alternative significant findings. Female patients were more likely to have a negative study than male patients (35 versus 20%, P < 0.0001) and more likely to have alternative significant pathology (12 versus 6%, P < 0.0001). Patients referred by specialities other than Urology and ED were more likely to be female and have a negative or alternative finding (P < 0.0001). CT KUB is a widely used first method of investigation for patients with suspected renal colic with a high positive predictive value allowing rapid diagnosis and intervention. However, given the high rate of negative or alternative findings on CT KUB in young women, especially those referred by specialities other than ED or Urology, ultrasound should be considered as an alternative imaging method to minimise unnecessary radiation exposure.     

Ureaplasma Urealyticum or Mycoplasma Hominis Infections and Semen Quality of Infertile Men in Abidjan

Objective To determine the prevalence of U. urealyticum and M. hominis in semen samples collected from men admitted in clinic for infertility, and to compare the quality of these semen samples.
Methods A total of 1 058 semen samples collected were investigated. Sperm semiological assays were performed according to the guidelines of the World Health Organisation （WHO）. Semen were examined by Mycoplasma IST for the detection of mycoplasma. Semen culture on agar media was used to detect other microorganisms. Chlamydia was detected using direct fluorescent assay （DFA） of Clamydia Trachomatis.
Results Among 1 058 semen samples, microorganisms were detected in 638 （60.3%）. The infected sperms consisted of mycoplasma alone in 507 cases （47.9%）, mycoplasma and other microorganisms in 98 （9.3%）, giving in all 605 （57.2%） samples infected with mycoplasma. The last 33 （3.1%） consisted of other microorganisms alone. The frequency of U. urealyticum, M. hominis and mixed genital infections detected in semen samples of infertile men were 39%, 23.8% and 5.6%, respectively. The rates of abnormal semen parameters recorded among patients infected with mycoplasma were for volume （22.2%-25%）, viscosity （29.6%-43.5%）, pH （64.7%-72.9%）, motility （80.8%-93.8%）, morphology （36.3%-47.9%）, sperm concentration （53.3%-58.3%） and leukocyte count （51.4%-58.3%）.
Conclusion Frequency of U. urealyticum infection was higher than that of M. hominis. Mycoplasma infections were associated with disorders of pH, motility and sperm concentration. In addition M. hominis infection affected spermatozoa morphology. Therefore, screening of U. urealyticum clinically relevant in Abidjan. and M. hominis for routine semen analysis is     

The influence of Helicobacter pylori infection on gastrin and somatostatin values present in serum

BACKGROUND/AIMS: Recent studies on the role of Helicobacter pylori in pathogenesis of duodenal ulcers have focused on the mechanism by which H. pylori infections causes exaggerated gastrin release. METHODOLOGY: We compared the gastrin and somatostatin serum values between two groups of patients; 37 H. pylori-positive ones and 29 H. pylori-negative ones. We applied radioimmunoassay technique to determine the gastrin and somatostatin values in serum. H. pylori was confirmed by urease test and by histopathological color according to Giemsa. RESULTS: The level of gastrin in the serum of Helicobacter pylori-positive patients with chronic gastritis were significantly higher in relation to H. pylori-negative patients. The somatostatin concentration in the sera of H. pylori-positive patients with duodenal ulcer (16.27 +/- 9.49 pg/mL) were less in comparison with those without duodenal ulcer (23.25 +/- 13.59 pg/mL). CONCLUSIONS: The results suggest that H. pylori infection suppresses the somatostatin secretion.