Molecular basis of severe myoclonic epilepsy in infancy

Severe myoclonic epilepsy (SMEI) or Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel alpha-1 subunit. Recently, we generated and characterized a knock-in (KI) mice with an SCN1A nonsense mutation that appeared in three independent SMEI patients. The SCN1A-KI mice well reproduced the SMEI disease phenotypes. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. In heterozygous knock-in mice, trains of evoked action potentials in inhibitory neurons exhibited pronounced spike amplitude decrement late in the burst but not in pyramidal neurons. We further showed that in wild-type mice the Nav1.1 protein is expressed dominantly in axons and moderately in somata of parbalbumin (PV) – positive inhibitory interneurons. Our immunohistochemical observations of the Nav1.1 are clearly distinct to the previous studies, and our findings has corrected the view of the Nav1.1 protein distribution. The data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. These information should contribute to the understanding of molecular pathomechanism of SMEI and to develop its effective therapies.     

Kindling of the visual cortex in cats: comparison with amygdaloid kindling

Kindling of the primary visual cortex (VC) was compared with that of the amygdala in cats. VC kindling was basically similar to kindling of the amygdala in that daily electrical stimulation can lead to the development of a generalized convulsion in most subjects, a growth of afterdischarges in their configuration and duration, and a reduction of the afterdischarge threshold. The kindling response of the VC differed from that of the amygdala in a number of respects, i.e., a high afterdischarge threshold, a different pattern of behavioral seizure development, an abrupt growth of electroclinical seizures coincident with the onset of a generalized convulsion, an intersubject variability in seizure susceptibility, and a marked seizure instability. In VC kindling the afterdischarge propagation into the amygdala was not observed until the generalized convulsion developed, and the early involvement of afterdischarge was seen in the pulvinar, lateral geniculate body, and superior colliculus. These data suggest that a neural mechanism different from amygdaloid kindling may participate in VC kindling, and that the subcortical structures of the visual system are involved in the preferential pathway for a seizure generalization from the VC.     

Three-dimensional identification of hemangiomas and feeding arteries in the head and neck region using combined phase-contrast MR angiography and fast asymmetric spin-echo sequences.

OBJECTIVE: To evaluate a proposed technique for the 3-dimensional (3D) detection of hemangiomas, including vascular malformation and their feeding arteries, in the head and neck. The new technique combines phase-contrast magnetic resonance angiography (PCMRA) without contrast medium and 3D fast asymmetric spin-echo (FASE) sequences. METHODS: The technique was applied to 3 patients having hemangiomas in the head and neck region. In 1 patient the image obtained with the proposed technique was compared to that obtained by standard contrast angiography. RESULTS: In all 3 patients, the 3D presence of the hemangiomas and the feeding arteries were well defined in images created by the proposed technique. Additionally, the characterization of the hemangioma's 3D structure and distribution of the feeding arteries coincided with those observed using contrast angiography in the case for which contrast angiography was also performed. CONCLUSIONS: Preliminary experience shows that the proposed technique combining 3D-FASE and 3D-PCMRA is useful to visualize both the 3D structure of hemangiomas and to identify the 3D distribution of the feeding arteries without using contrast medium.     

Isolated rupture of radial collateral ligament of the small finger dip joint repaired with a bone suture anchor: a case report.

Isolated rupture of radial collateral ligament of the small finger DIP joint is a rare injury. We treated this lesion using a bone suture anchor with excellent results.     

Studies on isolated smooth muscle cells. IX. Application of papain for isolation of single smooth muscle cells from guinea-pig taenia coli

To prepare single smooth muscle cells from the taenia coli of guinea pig, the application of papain to the enzymatic solution was examined under two conditions: 1) the isolation in a modified Tyrode solution (containing 0.18 mM Ca2+: 0.18 mM Ca2+-Tyrode solution) and 2) the isolation in a high-K+ Tyrode solution (Na+ was replaced by K+, and Ca2+ was not added: high-K+ Tyrode solution). The presence of papain during collagenase digestion reduced contamination of broken cells and cell debris. In the case of the high-K+ Tyrode solution, papain increased the yield of single cells significantly. The cells were contracted in a dose-dependent manner by Ca2+ in the high-K+ Tyrode solution and by carbachol in 0.18 mM Ca2+-Tyrode solution; furthermore, the contractions were antagonized by verapamil and atropine, respectively. Treatment with papain did not affect cell sensitivity to the stimulants. Therefore, our results suggest that the addition of papain is useful for the isolation of single cells to investigate the physiological and pharmacological characteristics of smooth muscle.     

Carpentier-Edwards pericardial aortic valve in middle-aged patients comparison with the St. Jude medical valve

Objective The objective of the present study was to compare long-term results of single aortic valve replacement (AVR) with mechanical (St. Jude Medical valves: standard) and biologic (the Carpentier-Edwards pericardial) prostheses. Method: Between 1995 and 2002, 95 patients who underwent single AVR with mechanical (n=46) or biologic (n=49) prostheses were enrolled in this study. The mean age at the operation was 54.0±9.6 years (range: 20 to 69 years) with the mechanical and 68.8±7.1 years (range: 44 to 85 years) with the biologic prosthesis. Results: The 9-year actuarial survival rate, which was calculated by taking perioperative mortality into account, was 90.3±4.6% for patients with mechanical valves and 87.6 ±4.8% for patients with bioprostheses, with no difference between the two groups (p=0.342). The 9-year freedom rate from thromboembolism, reoperation, endocarditis was 94.8+3.6%, 100% and 97.8 ±2.2% for patients with mechanical valves and 98.0 ±2.0%, 97.5 ±3.4% and 95.0 ±3.4% for those with bioprostheses, respectively. After 9 years, freedom from cardiac death averaged 97.8% in the group with mechanical valves compared with 95.3% in those with bioprostheses (p=0.541). Conclusion: We conclude that the mid-term durability of the Carpentier-Edwards pericardial valve in the aortic position for the elderly is excellent. Nevertheless, the risk of tissue valve reoperation progressively increases with time, and a longer follow-up may be necessary to provide its value compared with the mechanical valves in a country like Japan with a high life expectancy. (Jpn J Thorac Cardiovasc Surg 2005; 53:465-469)     

The efficacy and safety of laparoscopic nephrectomy in patients with three or more comorbidities

OBJECTIVES: Laparoscopic surgery for kidney treatment is a common procedure. However, the efficacy of this procedure in patients with several comorbidities has not been well investigated. We conducted a retrospective comparison of results of laparoscopic surgery between patients with several comorbidities and patients with no comorbidity to access the efficacy and safety of this procedure. METHODS: The subjects were 20 patients with three or more comorbidities (group A) and 46 patients with less than three comorbidities (group B). These 66 patients were 48 men and 18 women with a mean age of 62.3 years (age range, 24-83 years). The data from these two groups were compared for American Society of Anesthesiology (ASA) physical status score, previous surgical history, duration of surgery, estimated blood loss, tumor size, complications during and after surgery, conversion rates, time to oral intake, and length of hospital stay. RESULTS: The initial ASA score and age were significantly higher for the patients with comorbidities (P < 0.0001, P = 0.0008, respectively). All other variables before, during, and after surgery were similar for both laparoscopic groups. However, the incidence of atelectasis of laparoscopy was higher than that of open surgery. CONCLUSIONS: Laparoscopic nephrectomy for patients with comorbidities is safe and minimally invasive. Further investigation to prevent atelectasis is necessary.     

Surgical outcomes of partial nephrectomy for renal cell carcinoma: A joint study by the Japanese Society of Renal Cancer

OBJECTIVE: A joint study was undertaken by the Japanese Society of Renal Cancer to investigate the present status of partial nephrectomy in Japan and to speculate about what may be the indications for partial nephrectomy in patients with renal cell carcinoma. METHODS: Data were tabulated for 469 patients from participating medical institutions and various clinical factors were investigated with regard to disease progression (local recurrence and distant metastasis). RESULTS: Disease progression was observed in 21 patients (4.5%). No significant relation to disease progression was observed for sex, laterality, tumor histology, grade and tumor size. Although patients with solitary tumors displayed excellent prognosis irrespective of tumor diameter, patients with multiple tumors displayed a high likelihood of disease progression. Patients older than 77 years old and patients with imperative indication were found to have a poorer prognosis. CONCLUSION: In patients with solitary tumors, partial nephrectomy can be actively performed, even if the patient displays elective indications and the tumor is >4 cm in diameter. In patients displaying multiple tumors with imperative indications, the decision whether to perform partial nephrectomy should be made by the patients and their physicians after considering the impact on curability and the quality of life.     

A pilot study of the assessment of the quality of life, functional results, and complications in patients with an ileal neobladder for invasive bladder cancer

OBJECTIVE: To assess the functional results, health-related quality of life (QOL) outcomes, and complications in patients with an ileal neobladder in comparison to those with cutaneous diversion (ileal conduit and cutaneostomy). METHODS: Between September 1992 and February 2003, we consecutively performed an ileal neobladder (the Studer method) in 30 patients and cutaneous diversion in 38 patients. In August 2004, questionnaires were mailed to 54 patients. The questionnaire included the validated health-related quality of life (QOL) questionnaire, SF-36 General Health Survey, and a urinary incontinence questionnaire. We also evaluated the functional results in patients with an ileal neobladder and the postoperative complications in patients with both urinary diversions. RESULTS: The data from 41 patients (21 ileal neobladder procedures and 20 cutaneous diversions) were available for the analysis. No differences in the overall QOL were observed between the two groups. Complete daytime and night-time urinary continence was achieved in the 21 patients (100%) and 13 patients (61.9%), respectively. The mean value of the maximum flow rate was 15 +/- 12 mL/min in the 21 neobladder patients. There were 19 early complications in 18 patients (60.0%) and seven late complications in six patients (20.0%) with an ileal neobladder. However, there were 15 early complications in 14 patients (36.8%) and eight late complications in six patients (15.8%) with cutaneous diversions. CONCLUSION: The findings regarding the health-related QOL and the frequency of complications in the neobladder group and those in the cutaneous diversion group were similar. However, the functional results and the status of urinary continence in the neobladder patients were satisfactory.     

Early onset of ganciclovir-resistant cytomegalovirus infection in a lung-transplant recipient.

Ganciclovir resistance in cytomegalovirus (CMV) is an increasing problem in lung-transplant recipients with adverse clinical outcomes. We experienced the successful treatment of ganciclovir-resistant CMV infection in a lung-transplant recipient still receiving CMV prophylaxis. A 24-year-old woman with lymphangioleiomyomatosis underwent a living-donor lobar lung transplantation. She was a primary CMV mismatch (D+/R-) patient. She recovered from her postoperative complications, and was about to be discharged. However, she suffered ganciclovir-resistant CMV infection during prophylactic therapy. She was successfully treated with foscarnet, and is now alive without recurrence 18 months after surgery.