End-to-side nerve grafts: experimental study in rats

The effectiveness of the end-to-side nerve graft in comparison with the end-to-end cable-graft was determined in rat sciatic nerve transection models. Sixty Sprague-Dawley rats were randomly divided into four groups with different reconstructive methods for two branches of the sciatic nerve: Group I, median nerve graft with end-to-side neurorrhaphy; Group II, median and ulnar nerve grafts with end-to-end neurorrhaphy; Group III, no repair; and Group IV, sham operation. Between Groups I and II, there were no significant differences in the functional, electrophysiologic, and histologic evaluations. In retrograde tracing of the spinal cord and dorsal root ganglia, the number of double-labeled neurons was significantly higher in Group I. End-to-side nerve grafts show good functional recovery, require less graft, and are easy to perform. The authors find this method to be an effective alternative in facial nerve reconstruction and of great value in various kinds of peripheral nerve surgery.     

Immunisation of male mice with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes suppresses fertility in vivo

Immunisation against mammalian gonadotrophin releasing hormone (GnRH-I) linked to large carrier proteins has been shown to disrupt fertility. However, various studies have shown that the carrier protein causes epitope suppression of the hapten response, resulting in short-lived immunoneutralisation, followed by a return of fertility. A range of strategies has been used to resolve this, with limited success. The aim of this study was to construct a plasmid DNA vaccine encoding GnRH-I and T-helper epitopes. A 498 bp long vaccine construct in pcDNA3.1+ was administered to male mice in conjunction with a Hemagglutinating Virus of Japanese Envelop (HVJ-E) vector or in saline solution. The vaccine efficacy was evaluated in terms of GnRH-I specific IgG antibody response, serum testosterone levels, testicular spermatogenesis and the ability to produce offspring. The vaccine appeared to induce higher anti-GnRH-I IgG antibody response and insult the fertility axis, which was characterised by a drop of epididymal sperm counts, reduction of serum testosterone levels, suppressed testicular spermatogenesis and a significant decrease in litter numbers compared to control animals. The end-point vaccine efficacy was much higher in the HVJ-E vector mediated immunisation, than in saline alone.     

Nerve bypass grafting for the treatment of neuroma-in-continuity: an experimental study on the rat

The treatment of neuroma-in-continuity is controversial. To bypass neuroma-in-continuity with a nerve graft using end-to-side neurorrhaphy is considered to be theoretically a good option. To test this therapeutic modality, we performed a nerve bypass graft in a neuroma-in-continuity rat model. An obstructive neuroma-in-continuity was created in a transected peroneal nerve by interposition using the aponeurosis of the spinal muscles. In the experimental animals, (1) immediate, (2) 3-week delayed, or (3) no ulnar nerve bypass graft was performed. The peroneal functional index (PFI), conduction velocity, tibialis anterior muscle weight, and histomorphometric analyses were performed and compared with control (simply cut and repair) animals. On postoperative day 70, the recoveries of the PFI values, conduction velocity, and tibialis anterior muscle weight in the bypassed animals showed no significant differences as compared with the control animals, and the extent of these recoveries in the bypassed animals were significantly superior to those in the no-graft animals. In the histomorphometric analysis, the mean percent nerve in the bypassed animals was significantly larger than that in the no-graft animals. In conclusion, this technique may be a good alternative to the current therapeutic techniques for neuroma-in-continuity when there is a significant retained function.     

Partial gastrectomy using natural orifice translumenal endoscopic surgery (NOTES) for gastric submucosal tumors: early experience in humans

Background

Transvaginal endoscopic gastric surgery is one of the cutting edge procedures in the field of natural orifice translumenal endoscopic surgery (NOTES). Its feasibility has been shown sporadically in bariatric cases but not in oncologic conditions. The authors report their early experience with hybrid transvaginal NOTES gastrectomy for gastric submucosal tumors (SMTs).

Methods

Two female patients with SMTs in the distal stomach participated in this institutional review board (IRB)-approved study. Surgical indication was determined according to the National Comprehensive Cancer Network (NCCN) sarcoma guidelines, and the study adhered to the following oncologic principles: no direct handling of the lesion, full-thickness resection, and reasonable surgical margins. The study protocol required a minimum of two laparoscopic ports to ensure procedural safety and aforementioned oncologic appropriateness. Under laparoscopic guidance, a transvaginal route was created and secured with a 50-cm flexible overtube. A gastrointestinal endoscope was introduced, and the perigastric dissection was performed using an insulation-tipped diathermy knife (IT knife) and needle knife. This process was assisted with two laparoscopic graspers. After perigastric mobilization, the transvaginal endoscope was replaced with a digital stapling device, and partial gastrectomy was accomplished. The resected specimen was isolated and delivered through the vagina, and the vaginal wound was closed under direct vision. Outcomes measurements included surgical results, pain scoring, and clinical outcomes.

Results

Both operations were completed successfully in compliance with the aforementioned oncologic principles. The operating time was 365 and 170 min, respectively. The estimated blood loss was negligible. A minilaparotomy for specimen delivery was successfully avoided in both cases. A minimal vaginal incision was added for one patient at retrieval. Postoperatively, both patients reported no pain and recovered rapidly. The final diagnosis was hemorrhagic lipoma and gastrointestinal stromal tumor (GIST), respectively.

Conclusion

Our initial experience with human transvaginal NOTES gastrectomy showed it to be feasible and safe for gastric SMTs. It is a complex but promising surgical alternative for female oncologic patients undergoing partial gastric resection.     

Postictal mania versus postictal psychosis: differences in clinical features, epileptogenic zone, and brain functional changes during postictal period

PURPOSE: To clarify the differences between postictal mania (PIM) and postictal psychosis (PIP). METHODS: Five patients with PIM were compared to 17 patients with PIP, with respect to clinical, epileptological, electrophysiological, and neuroimaging features. PIM was distinguished from PIP by the symptoms observed in the postictal period based on the ICD-10 criteria. RESULTS: Postictal manic episodes lasted for a longer period than postictal psychotic episodes. Patients with PIM had more recurrent postictal episodes than patients with PIP. The age at onset of epilepsy in patients with PIM was older than that in patients with PIP. PIM was associated with frontal lobe and temporal lobe epilepsies, whereas PIP was associated with temporal lobe epilepsy. The estimated epileptogenic zone was on the language dominant side in PIM, whereas there was no predominant hemispheric laterality in PIP. Electroencephalography (EEG) performed during the early period of postictal manic and psychotic episodes showed decreased frequency of interictal epileptiform discharges in both PIM and PIP. Single-photon emission computed tomography (SPECT) during postictal manic and psychotic episodes showed increased perfusion in the temporal and/or frontal lobes in both PIM and PIP. Three patients with PIM showed increased perfusion during postictal episodes on bilateral or the language nondominant side, which were contralateral to the estimated epileptogenic zone, whereas three patients with PIP showed increased perfusion on the areas, which were ipsilateral to the estimated epileptogenic zone. CONCLUSIONS: PIM has a distinct position among the mental disorders observed in the postictal period.     

HLA Class I markers in Japanese patients with carbamazepine‐induced cutaneous adverse reactions

Carbamazepine (CBZ) is frequently used for treating epilepsy, but this drug causes cutaneous adverse drug reactions (cADRs) that may range from mild to severe. It is reported recently that the human leukocyte antigen HLA‐B*1502 is associated with Stevens‐Johnson syndrome (SJS) induced by CBZ in Han Chinese. We examined HLA class I in 15 Japanese patients who fulfilled the diagnostic criteria for CBZ‐induced cADRs (mild in 10 and severe = SJS in 5). HLA‐B*1518, HLA‐B*5901 and HLA‐C*0704 alleles showed higher relative risks (above 10.0) for severe cADRs. The haplotype (HLA‐A*2402‐B*5901‐C*0102) had high relative risk (16.09) for severe cADRs. In patients with severe cADRs, frequencies of HLA‐A*1101, HLA‐A*3303, HLA‐B*1501, HLA‐B*4403, HLA‐B*5101, HLA‐B*5201, HLA‐C*0702, and HLA‐C*1202 alleles are relatively lower than in the Japanese population. These data may suggest that HLA‐B*5901 is one of the candidate markers for CBZ‐induced SJS in Japanese.     

An overview of regular dialysis treatment in Japan (as of 31 December 2004)

A statistical survey of 3932 nationwide hemodialysis (hereafter, dialysis) facilities was carried out at the end of 2004, and 3882 facilities (98.73%) responded. The population undergoing dialysis at the end of 2004 was 248 166, an increase of 10 456 patients (4.4%) from that at the end of 2003. The number of dialysis patients per million people was 1943.5. The crude death rate of dialysis patients from the end of 2003 to the end of 2004 was 9.4%. The mean age of patients who underwent dialysis in 2004 was 65.8 years, and that of the total dialysis population was 63.3 years. The percentage distribution of patients who underwent dialysis according to a newly underlying disease showed that 41.3% of patients had diabetic nephropathy and 28.1% had chronic glomerulonephritis. The frequency of calcium carbonate use for dialysis patients was 75.1% and that of sevelamer hydrochloride use was 26.2%. The frequency of sevelamer hydrochloride use does not necessarily have a strong correlation with the dose of calcium carbonate. Patients who received high doses of sevelamer hydrochloride tended to have a low concentration of arterial blood HCO(3-). Approximately 15% of dialysis patients used an intravenous vitamin D preparation, generally maxacalcitol. The longer the patients had been on dialysis, the higher the frequency of use of an intravenous vitamin D preparation. When the concentration of serum intact parathyroid hormone (PTH) was more than 200 pg/mL, the frequency of use of an orally administered vitamin D preparation decreased; but that of intravenous vitamin D preparation increased. The percentage of dialysis patients who received percutaneous ethanol injection therapy (PEIT) was 1.4%. The percentage was more than 50% in the patients who had been on dialysis for more than 10 years. The percentage of patients who received PEIT again was 35.0%. The percentage of patients who had been on hemodialysis for more than 10 years and received PEIT again was more than 50%.     

Clinical spectrum of mutations in SCN1A gene: severe myoclonic epilepsy in infancy and related epilepsies

Severe myoclonic epilepsy in infancy (SMEI) manifests very frequent generalized tonic-clonic seizures (GTC), accompanied by myoclonic seizures, absences and partial seizures [Dravet, C., 1978. Les épilepsie grave de l'enfant. Vie Méd. 8, 543-548; Dravet, C., Roger, J., Bureau, M., Dalla Bernardina, B., 1982. Myoclonic epilepsies in childhood. In: Akimoto, H., Kazamatsuri, H., Seino, M., Ward, A. (Eds.), Advances in Epileptology. Raven Press, New York, pp. 135-140; Dravet, C., Bureau, M., Oguni, H., Fukuyama, Y., Cokar, O., 2002. Severe myoclonic epilepsy of infancy (Dravet syndrome). In: Roger, J., Bureau, M., Dravet, C., Genton, P., Tassinari, C.A., Wolf, P. (Eds.), Epileptic Syndromes in Infancy, Childhood and Adolescence, third ed. John Libbey, London, pp. 81-103]. However, there is a group of severe epilepsy that has many characteristics common to SMEI except for myoclonic seizures. We reported this group of epilepsy as intractable childhood epilepsy with GTC (ICEGTC) [Watanabe, M., Fujiwara, T., Yagi, K., Seino, M., Higashi, T., 1989b. Intractable childhood epilepsy with generalized tonic-clonic seizures. J. Jpn. Epil. Soc. 7, 96-105 (in Japanese); Fujiwara, T., Watanabe, M., Takahashi, Y., Higashi, T., Yagi, K., Seino, M., 1992. Long-term course of childhood epilepsy with intractable grand mal seizures. Jpn. J. Psychiatr. Neurol. 46, 297-302]. Recently, mutations of the neuronal voltage-gated sodium channel alphasubunit type 1 gene (SCN1A) have been found in SMEI [Claes, L., Del-Favero, J., Ceulemans, B., Lagae, L., Van Broeckhoven, C., De Jonghe, P., 2001, De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am. J. Hum. Genet. 68, 327-1332]. Mutations in SCN1A are found in both SMEI and ICEGTC at high rates of 70-81%. The loci of the mutations seen in ICEGTC are quite similar to those found in SMEI, suggesting a genotypic continuity between these entities. The clinical spectrum of epilepsies harboring SCN1A mutations may be consisted of various phenotypes with GEFS+ on the mildest end and SMEI on the severest end of the spectrum.     

MULTIPLE INFLAMMATORY MYOGLANDULAR POLYPS OF THE COLON

The patient was a 35‐year‐old man who was observed after bone marrow transplantation for acute lymphocytic leukemia. Polyps were found by colonoscopy performed after a positive fecal occult blood test, and the patient was admitted for polypectomy. There were three polyps, which were all reddened and pedunculated and were, respectively, located in the transverse, descending, and sigmoid colons. Polypectomy was performed, and all lesions were histopathologically diagnosed to be inflammatory myoglandular polyps. Inflammatory myoglandular polyps have been reported to occur solitarily only, and this is the first report of multiple occurrence.     

Inhibition of Growth and Metastasis of Ovarian Carcinoma by Administering a Drug Capable of Interfering with Vascular Endothelial Growth Factor Activity

The present study investigates the relationship between in vivo growth/metastasis of tumor cells and their capacity to produce the vascular endothelial growth factor (VEGF), as well as the regulation of tumor growth/metastasis using an angiogenesis-inhibitory drug. Two cloned tumor cell lines designated OV-LM and OV-HM were isolated from a murine ovarian carcinoma OV2944. OV-LM and OV-HM cells grew in cultures at comparable rates. However, when transplanted s.c. into syngeneic mice, OV-HM exhibited a faster growth rate and a much higher incidence of metastasis to lymph nodes and lung. Histologically, intense neovascularization was detected in sections of OV-HM but not of OV-LM tumor. OV-HM and OV-LM tumor cells obtained from in vitro cultures expressed high and low levels of VEGF mRNA, respectively. A difference in VEGF mRNA expression was much more clearly observed between RNAs prepared from fresh OV-HM and OV-LM tumor masses: RNA from OV-HM contained larger amounts of VEGF mRNA, whereas RNA from OV-LM exhibited only marginal levels of VEGF mRNA. An angiogenesis-inhibitory drug, FR118487 inhibited the VEGF-mediated in vitro growth of endothelial cells but did not affect the expression in vitro of VEGF mRNA by OV-HM tumor cells. Intraperitoneal injections of FR118487 into mice bearing OV-HM tumors resulted in: (i) a subsequent growth inhibition of primary tumors; (ii) a marked decrease in neovascularization inside tumor masses expressing comparable levels of VEGF mRNA to those detected in control OV-HM masses; and (iii) almost complete inhibition of metastasis to lymph nodes and lung. These results indicate that growth/metastasis of tumor cells correlates with their VEGF-producing capacity and that an angiogenesis inhibitor, FR118487, inhibits tumor growth and metastasis through mechanism(s) including the suppression of VEGF function in vivo.