Updated evidence of the effectiveness and safety of transanal drainage tube for the prevention of anastomotic leakage after rectal low anterior resection: a systematic review and meta-analysis.

BACKGROUNDS: Anastomotic leakage (AL) represents a major complication after rectal low anterior resection (LAR). Transanal drainage tube (TDT) placement offers a potential strategy for AL prevention; however, its efficacy and safety remain contentious. METHODS: A systematic review and meta-analysis were used to evaluate the influence of TDT subsequent to LAR as part of the revision of the surgical site infection prevention guidelines of the Japanese Society of Surgical Infectious Diseases (PROSPERO registration; CRD42023476655). We searched each database, and included randomized controlled trials (RCTs) and observational studies (OBSs) comparing TDT and non-TDT outcomes. The main outcome was AL. Data were independently extracted by three authors and random-effects models were implemented. RESULTS: A total of three RCTs and 18 OBSs were included. RCTs reported no significant difference in AL rate between the TDT and non-TDT groups [relative risk (RR): 0.69, 95% confidence interval (CI) 0.42-1.15]. OBSs reported that TDT reduced AL risk [odds ratio (OR): 0.45, 95% CI 0.31-0.64]. In the subgroup excluding diverting stoma (DS), TDT significantly lowered the AL rate in RCTs (RR: 0.57, 95% CI 0.33-0.99) and OBSs (OR: 0.41, 95% CI 0.27-0.62). Reoperation rates were significantly lower in the TDT without DS groups in both RCTs (RR: 0.26, 95% CI 0.07-0.94) and OBSs (OR: 0.40, 95% CI 0.24-0.66). TDT groups exhibited a higher anastomotic bleeding rate only in RCTs (RR: 4.28, 95% CI 2.14-8.54), while shorter hospital stays were observed in RCTs [standard mean difference (SMD): -0.44, 95% CI -0.65 to -0.23] and OBSs (SMD: -0.54, 95% CI -0.97 to -0.11) compared with the non-TDT group. CONCLUSIONS: A universal TDT placement cannot be recommended for all rectal LAR patients. Some patients may benefit from TDT, such as patients without DS creation. Further investigation is necessary to identify the specific beneficiaries.

Feasibility of transanal minimally invasive surgery for total pelvic exenteration for advanced primary and recurrent pelvic malignancies.

BACKGROUND: The purpose of this study was to clarify the efficacy and safety of transanal minimally invasive surgery (TAMIS) for total pelvic exenteration (TPE) in advanced primary and recurrent pelvic malignancies. METHODS: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of TAMIS for TPE. Surgery was performed between September 2019 and April 2023. The median follow-up period was 22 months (2-45 months). RESULTS: Fifteen consecutive patients were included in this analysis M:F = 14:1 and median (range) age was 63 (36-74). Their diagnoses were as follows: primary rectal cancer (n = 5; 33%), recurrent rectal cancer (n = 4; 27%), primary anorectal cancer (n = 5; 33%), and gastrointestinal stromal tumor (n = 1; 7%). Bladder-sparing TPE was selected for two patients (13%). In nine of 15 patients (60%) the anal sphincter could be successfully preserved, five patients (33%) required combined resection of the internal iliac vessels, and two (13%) required rectus muscle flap reconstruction. The median operative time was 723 min (561-1082), and the median intraoperative blood loss was 195 ml (30-1520). The Clavien-Dindo classifications of the postoperative complications were as follows: grade 0-2 (n = 11; 73%); 3a (n = 3; 20%); 3b (n = 1; 7%); and ≥ 4 (n = 0; 0%). No cases of conversion to laparotomy or mortality were observed. The pathological results demonstrated that R0 was achieved in 14 patients (93%). CONCLUSIONS: The short-term outcomes of this initial experience proved that this novel approach is feasible for TPE, with low blood loss, acceptable postoperative complications, and a satisfactory R0 resection rate.

The advanced lung cancer inflammation index predicts outcomes in patients with Crohn's disease after surgical resection.

AIM: Precise biomarkers for predicting prognosis could help to identify high-risk Crohn's disease (CD) patients to facilitate better follow-up during the postoperative course. In this study, the primary aim is the identification of the most reliable nutrition marker that predicts surgical relapse in CD patients. METHOD: We first evaluated the predictive value of various nutrition markers for postoperative surgical relapse in CD patients and identified the advanced lung cancer inflammation index (ALI) as a promising biomarker. Then, we assessed the clinical significance of preoperative ALI in CD patients using two cohorts. RESULTS: Preoperative ALI showed the highest correlation with reoperation rate compared with other nutritional parameters in CD patients receiving surgical resection (sensitivity 53%, specificity 86%, area under the curve 0.71). Lower levels of preoperative ALI were significantly correlated with the presence of perianal disease. A lower level of preoperative ALI was an independent prognostic factor for reoperation rate after an intestinal resection (hazard ratio 3.37, 95% CI 1.38-10.12, P = 0.006), and the prognostic impact of preoperative ALI was successfully validated in an independent cohort using the same cut-off value. CONCLUSION: Preoperative ALI might be useful for postoperative management of CD patients.

Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction.

We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (Cmin) was ≥15-30 µg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7-10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial Cmin compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial Cmin ≥15 µg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34-13.15). In patients with 15-30 µg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 µg/ml. In conclusion, achievement of Cmin of 15-30 µg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients.

The effectiveness of fascial closure with antimicrobial-coated sutures in preventing incisional surgical site infections in gastrointestinal surgery: a systematic review and meta-analysis.

The aim of this study was to conduct a systematic review and meta-analysis of the efficacy of fascial closure using antimicrobial-sutures specifically for the prevention of surgical site infections (SSIs) in gastrointestinal surgery, as part of the revision of the SSI prevention guidelines of the Japanese Society of Surgical Infectious Diseases (JSSI). We searched CENTRAL, PubMed and ICHUSHI-Web in May 2023, and included randomized controlled trials (RCTs) comparing antimicrobial-coated and non-coated sutures for fascial closure in gastrointestinal surgery (PROSPERO No. CRD42023430377). Three authors independently screened the RCTs. We assessed the risk of bias and the GRADE criteria for the extracted data. The primary outcome was incisional SSI and the secondary outcomes were abdominal wall dehiscence and the length of postoperative hospital stay. This study was supported partially by the JSSI. A total of 10 RCTs and 5396 patients were included. The use of antimicrobial-coated sutures significantly lowered the risk of incisional SSIs compared with non-coated suture (risk ratio: 0.79, 95% confidence intervals: 0.64-0.98). In subgroup analyses, antimicrobial-coated sutures reduced the risk of SSIs for open surgeries, and when monofilament sutures were used. Antimicrobial-coated sutures did not reduce the incidence of abdominal wall dehiscence and the length of hospital stay compared with non-coated sutures. The certainty of the evidence was rated as moderate according to the GRADE criteria, because of risk of bias. In conclusion, the use of antimicrobial-coated sutures for fascial closure in gastrointestinal surgery is associated with a significantly lower risk of SSI than non-coated sutures.

Optineurin is potentially associated with TDP-43 and involved in the pathogenesis of inclusion body myositis.

AIMS: Increasing evidences suggest a similarity in the pathophysiological mechanisms of neuronal cell death in amyotrophic lateral sclerosis (ALS) and myofibre degeneration in sporadic inclusion body myositis (sIBM). The aim of this study is to elucidate the involvement of ALS-causing proteins in the pathophysiological mechanisms in sIBM. METHODS: Skeletal muscle biopsy specimens of five patients with sIBM, two with oculopharyngeal muscular dystrophy (OPMD), three with polymyositis (PM), three with dermatomyositis (DM), three with neurogenic muscular atrophy, and three healthy control subjects were examined. We analysed the expression and localization of familial ALS-causing proteins, including transactive response DNA binding protein-43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), Cu/Zn superoxide dismutase (SOD1) and optineurin (OPTN) by immunohistochemistry. RESULTS: TDP-43, OPTN and, to a lesser extent, FUS/TLS were more frequently accumulated in the cytoplasm in patients with sIBM and OPMD than in patients with PM, DM, neurogenic muscular atrophy, or healthy control subjects. SOD1 was accumulated in a small percentage of myofibres in patients with sIBM and OPMD, and to a very small extent in patients with PM and DM. Confocal microscopy imaging showed that TDP-43 proteins more often colocalized with OPTN than with FUS/TLS, p62 and phosphorylated Tau. CONCLUSIONS: These findings suggest that OPTN in cooperation with TDP-43 might be involved in the pathophysiological mechanisms of skeletal muscular degeneration in myopathy with rimmed vacuoles. Further investigation into these mechanisms is therefore warranted.

Cervical MRI of subacute myelo-optico-neuropathy.

STUDY DESIGN: Case study. OBJECTIVES: Subacute myelo-optico-neuropathy (SMON) is a severe neuro-degenerative disorder caused by poisoning due to over-dose and prolonged oral administration of clioquinol; this disorder was more frequent during 1957-1970. It is characterized by axonal degeneration and gliosis in the cervical gracile fasciculus. Recently, copper-deficient myelo-neuropathies presenting similar symptoms (that is, painful dysesthesia/paresthesia in the lower limbs, ataxia, spastic paraplegia, autonomic disorders and visual impairment) were reported. Magnetic resonance imaging (MRI) of these patients detected T2-weighted hyperintensities in the cervical spinal cord. An unbalanced zinc-copper metabolism was suggested as one of the candidate pathogenesis of clioquinol toxicity because of its metal-chelating ability. The aim of this study was to present MRI findings of old SMON patients and to compare them with those of current copper-deficient myelo-neuropathies. SETTING: Japan. METHODS: We conducted and analyzed cervical and brain MRIs of seven old SMON patients who contracted the disorder during the 1960s. Serum iron, magnesium, copper, zinc and ceruloplasmin levels were also measured. RESULTS: Cervical T2-weighted MRIs showed mild volume loss and faint hyperintensities in the dorsal columns, which might reflect residual gliosis. Brain fast fluid-attenuated inversion-recovery images and tractography were normal. Current levels of serum copper and zinc were within almost normal ranges. CONCLUSION: Although fainter, the abnormal T2 MRI signals we observed were similar to and occurred in the same locations as those reported in copper-deficient myelo-neuropathy patients. We suggest that these findings are useful to study the mechanism of clioquinol toxicity before using it to treat neurodegenerative diseases such as Alzheimer's disease.

Implementation of a hospital-wide project for appropriate antimicrobial prophylaxis.

The aim of this study was to confirm the effect of implementing a hospital-wide project for appropriate use of antimicrobial prophylaxis (AMP) to reduce the rate of antibiotic-resistant organisms. Fifteen different manuals for each surgical department have been simultaneously implemented since February 2007. Compliance rate was compared between pre- and postintervention periods (3 months for each period). As an effect of this intervention, we analyzed changes in the rates of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus among organisms isolated postoperatively. The number of operations was 1,627 in both periods. Among patients whose surgeries were longer than 3 h in duration, 75% received an additional intraoperative antimicrobial dose in the postintervention period and 23% in the preintervention period (P < 0.001). Although most patients received postoperative AMP with an interval of q12 h in the preintervention period, 63% of the patients received AMP with an interval of q8 h in the postintervention period. The duration of AMP use was reduced from 2.4 ± 1.9 to 1.6 ± 1.5 days (P < 0.001). Forty-seven percent of patients discontinued AMP within 24 h and 81% within 48 h. Isolation rates of P. aeruginosa among all gram-negative organisms significantly decreased from 13% (68/538 patients) to 7.3% (37/509 patients) (P = 0.004). Execution of a hospital-wide project to promote the appropriate use of AMP, including shortening the duration of AMP use, was useful to decrease the rate of P. aeruginosa isolated postoperatively.

[Anomalous origin of the right coronary artery from the ascending aorta].

The patient was a 77-year-old man. In June 2008, he underwent off-pump coronary artery bypass (OPCAB) for unstable angina Intraoperative epiaortic echo showed an anomalous origin of theright coronary artery from the ascending aorta 4 cm above the sinotubular junction (STJ). The right coronary artery traveled through the planned proximal anastomotic site of the saphenous vein graft (SVG). If diagnosis of the anomalous origin of the right coronary artery had not been made, there would have been a high likelihood that the right coronary artery could have been injured. Thus, the usefulness of epiaortic echo was reaffirmed. An anomalous origin of the coronary artery is a rare congenital anomaly and its incidence is approximately 1%. An anomalous origin of the right coronary artery is very rare from the ascending aorta 4 cm above the STJ and only a few cases have been reported. An anomalous origin of the coronary artery can cause serious complications affecting the prognosis after open heart surgery. Thus, such an anomalous origin needs to be considered in preoperative evaluation.

Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease.

We investigated the effect of 0.05% topical cyclosporine (Cys) on the ocular surface and tear functions in dry eye patients with chronic GVHD (cGVHD) in a prospective comparative study. Thirty eyes of 15 patients refractory to baseline treatment were recruited and the patients assigned for topical Cys treatment group (14 eyes of 7 patients) and control group (12 eyes of 6 patients) respectively. Two patients dropped out because of intolerable irritation while using topical Cys eye drops. Visual analog scale symptom scores, corneal sensitivity, Schirmer I test value, tear film break-up time (TBUT), tear evaporation rate and ocular surface vital staining scores were recorded at baseline and at the end of the following one month. Conjunctival impression and brush cytology were performed before and after the treatment. After topical Cys treatment, significant improvements were found in symptom scores, corneal sensitivity, tear evaporation rate, TBUT, vital staining scores, goblet cells density, conjunctival squamous metaplasia grade, inflammatory cell numbers and the MUC5AC expression. Our study suggests that 0.05% topical Cys may be an effective treatment for dry eye patients with cGVHD. The improvements in the ocular surface and tear functions resulted presumably from the decreased inflammation, increased goblet cell density and MUC5AC mRNA expression. Bone Marrow Transplantation (2008) 41, 293-302; doi:10.1038/sj.bmt.1705900; published online 5 November 2007.

Aphasia during the acute phase in ischemic stroke.

OBJECTIVES: We investigated the incidence, clinical characteristics, outcome and factors associated with aphasia and early improvement in acute ischemic stroke. METHODS: We consecutively studied 855 patients with acute ischemic stroke who were admitted to our hospital within 48 h after onset and who were not comatose on admission. Assessment of aphasia was performed on admission (day 0) and day 10. We examined the incidence, severity, and subtypes of aphasia, and compared the clinical background of patients with and without aphasia on admission, and also those with and without early improvement by day 10. In addition, we investigated the independent factors associated with the presence of aphasia on admission and with early improvement. RESULTS: Of the 855 patients, 130 (15.2%) had aphasia on admission. The National Institutes of Health Stroke Scale (NIHSS) on admission (OR 1.21; 95% CI 1.17-1.26) was a significant and independent factor associated with the presence of aphasia on admission. Early improvement was seen in 56 of 121 aphasic patients (46.3%) who were still alive on day 10. A history of hypercholesterolemia (OR 3.27; 95% CI 1.14-9.39) was a significant and independent factor associated with early improvement in aphasia during the acute phase and NIHSS on admission (OR 0.95; 95% CI 0.90-0.99) was marginally significant. CONCLUSION: It is difficult to predict the outcome of aphasia within the first few days after the onset of ischemic stroke.

Ostomy creation with fewer sutures using tissue adhesives (cyanoacrylates) in inflammatory bowel disease: a pilot study.

Introduction Fistula formation around the ostomy site is a stoma-related complication often requiring surgical intervention. This complication may be caused by sutures or may develop as a complication of inflammatory bowel disease. Before conducting a clinical trial, we set out to investigate the safety of ostomy creation with fewer sutures using tissue adhesives in this pilot study. Methods Patients with inflammatory bowel disease who required surgery with ostomy creation at the Hyogo College of Medicine between January 2014 and December 2015 were enrolled. Safety was assessed by evaluating the incidence of stoma-related complications. Ostomy was restricted to loop ileostomy and was created with two sutures and tissue adhesives. Results A total of 14 patients were enrolled. Mean body mass index was 18.9 ± 2.0 kg/m2. There were no cases of ostomy retraction and no severe adverse events were observed. Conclusions This pilot study demonstrates that ostomy creation using tissue adhesives is safe. Although retraction and adverse events were not observed, even in patients with inflammatory bowel disease who generally exhibit delayed wound healing, the body mass index was extremely low in this series. This study does not strongly recommend ostomy creation with tissue adhesives; further studies are needed to clarify the efficacy and safety of the procedure.

Immediate interlocking nailing versus external fixation followed by delayed interlocking nailing for Gustilo type IIIB open tibial fractures.

PURPOSE: To compare immediate interlocking nailing with external fixation followed by delayed interlocking nailing, for Gustilo type IIIB open tibial fractures. METHODS: 23 patients with Gustilo IIIB open tibial fractures were treated with either immediate unreamed interlocking nailing (n=9) or external fixation followed by delayed unreamed interlocking nailing (n=14). Patient age, sex ratio, fracture site, fracture type, and severity were similar in both groups. The time to union, deep infection rate, and nonunion rate in the 2 groups were compared. RESULTS: In the immediate and delayed nailing groups, respective mean times to union were 21 (standard deviation [SD], 14) months and 14 (SD, 8) months; nonunion rates were 44% (4/9) and 36% (5/14), and deep infection rates were 22% (2/9) and 7% (1/14). All corresponding differences were not statistically significant. CONCLUSION: Prospective, randomised, multicentre studies are needed to assess whether there are significant differences between the 2 treatment methods.

Role of nitric oxide in the cerebellar degeneration during methylmercury intoxication.

To investigate the role of nitric oxide in the cerebellar degeneration during methylmercury intoxication, interaction of the change in nitric oxide synthase activity and degeneration of the granular layer neurons was examined in rats after methylmercury administration. Both reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and anti-nitric oxide synthase antibody staining, and measurement of glutamate, and nitrite and nitrate levels in the cerebrospinal fluid were performed after oral administration of 5 mg/kg of methylmercury for 12 days. Nitric oxide synthase activity in the cerebellum was also assayed by monitoring the conversion of arginine to citrulline. Methylmercury levels in the blood and the cerebellum gradually increased up to day 13 after the initial methylmercury administration, and neurological disturbances, such as hindleg crossing and abnormal gait, were observed from day 17 after administration. Although a significant decrease in the number of granular layer neurons was recognized at day 84, no such decrease either in NADPH-diaphorase or anti-nitric oxide synthase antibody positive neurons was seen. Glutamate levels in the cerebrospinal fluid transiently increased at day 9 and finally decreased at day 84. Also a transient increase in both nitrite and nitrate levels in the cerebrospinal fluid and nitric oxide synthase activity in the cerebellum was seen prior to the start of degeneration of the granular layer neurons. These results suggest that nitric oxide may play an important role in the degeneration process of the granular layer neurons during methylmercury intoxication.

Role of superoxide dismutase and nitric oxide on the interaction between brain and systemic circulation during brain ischemia.

To elucidate the critical role of superoxide dismutase (SOD) and nitric oxide in brain injury and systemic circulation during brain ischemia, we performed bilateral carotid artery ligation (BCAL) on rats and evaluated the effects of NG-monomethyl-L-arginine (L-NMMA) and a long-acting SOD derivative (SMA-SOD). After administration of L-NMMA, specific inhibitor against nitric oxide synthase (NOS), most of BCAL rats died within 6 h while no BCAL rats without L-NMMA died at all. Administration of SMA-SOD exhibited no effect on the life span of BCAL rats. Magnetic resonance imaging (MRI) and microscopic analysis for the ischemic brain revealed that, although administration of L-NMMA showed no significant effect on the ischemic brain of BCAL rats, SMA-SOD effectively prevented the ischemic changes based on permeability edema in the frontal lobe. Measurement of changes in the blood flow of the ischemic brain revealed that administration of L-NMMA decreased the blood flow in the BCAL rats while no remarkable changes were seen after administration of SMA-SOD. Urinary secretion of NO2-/NO3-, the metabolites of nitric oxide, was increased by challenging BCAL, and the presence of L-NMMA or SMA-SOD diminished this elevation. Blood pressure was increased by performing BCAL to rats, and administration of L-NMMA showed further elevation of the blood pressure. On the contrary, administration of SMA-SOD decreased post-ischemic hypertension. These results suggest that SOD may play a protective role for brain ischemia by suppressing increased vascular permeability, while nitric oxide showed beneficial effect on the ischemic brain by increasing the blood flow in the ischemic brain.

Down regulation of a harmful variant protein by replacement of its normal protein.

To compensate for the hypoprotein and hypoalbuminemia of familial amyloidotic polyneuropathy (FAP) patients, 800 ml of fresh frozen plasma (FFP) was intravenously administered and change in total and variant transthyretin (TTR) levels were measured in the plasma. After injection of FFP, total plasma TTR levels were elevated and variant TTR levels decreased from 24 to 48 h, accompanied by an elevation of plasma total protein, albumin levels and TTR levels. To elucidate the mechanism of this phenomenon, a large amount of purified normal TTR from normal human plasma was intravenously injected in mice and FAP patients. By intravenous injection of 3 mg of the purified TTR to C57Black6, the expression of TTR mRNA decreased from 6 to 24 h post injection, and gradually increased up to 48 h post injection. After injecting 400 mg of normal TTR in each of 3 FAP patients, total plasma TTR levels were elevated and variant TTR levels decreased significantly from 24 to 48 h. These results suggested that down regulation of the harmful protein by replacement of its normal form of the protein occurred by this method. This phenomenon should be applied as the basis for one of the useful methods for decreasing the harmful proteins in the circulation.

Adult T cell leukemia following HTLV-I-associated myelopathy/tropical spastic paraparesis: case reports and implication to the natural course of ATL.

Adult T cell leukemia (ATL) is the T cell malignancy caused by human T lymphotropic virus type I (HTLV-I), and HTLV-I is also the causative agent of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although HTLV-I causes both diseases, concomitant occurrence is reported to be rare. This paper describes two cases of HAM/TSP that developed into lymphoma-type ATL after the onset of HAM/TSP. In one case, the same HTLV-I infected clone could be detected by polymerase chain reaction in peripheral blood obtained when the patient was diagnosed as HAM/TSP. This finding showed that the HTLV-I clone already existed at the stage of HAM/TSP. Since frequent detection of clonal proliferation of HTLV-I infected cells has been reported previously in patients with HAM/TSP, careful follow-up is needed for patients with HAM/TSP.

Animal model of oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset polyalanine disorder characterized clinically by progressive ptosis, dysphagia, and limb weakness and pathological hallmarked by unique intranuclear inclusions in the muscles. It is caused by heterozygous expansion of a 10-alanine stretch to 12-17 alanine residues in the N-terminus of the poly(A)-binding protein, nuclear 1 (PABPN1). Although PABPN1 is a major component of the inclusions in OPMD, the associated pathogenic mechanism is undetermined. No animal models of OPMD have been discovered in nature; therefore, we generated transgenic mice expressing human PABPN1 (hPABPN1) using a chicken beta-actin (CAG) promoter. While transgenic mice lines expressing normal hPABPN1 did not show myopathic changes, lines expressing high levels of expanded hPABPN1 with a 13-alanine stretch showed myopathy phenotype with aging. The latter mice disclosed intranuclear inclusions consisting of aggregated mutant hPABPN1 and scattered rimmed vacuoles restricted in the muscles. In particular, the nuclear inclusions closely resembled those of OPMD muscles on electron microscopy, and myopathic changes were more prominent in the eyelid and pharyngeal muscles. The results demonstrated that we had established the first transgenic OPMD model mouse. Recently, two other transgenic mice expressing mutated hPABPN1 with a 17-alanine stretch have been generated; however, the transgenic mouse using its natural promoter did not show myopathy phenotype, and the other using the human skeletal actin (HSA1) promoter disclosed quite different intranuclear inclusions from those of human OPMD muscles. Our transgenic OPMD model mouse appears to have more dramatic alterations in myofiber viability, but is useful for elucidating of molecular mechanisms and establishing therapeutic trials.

Structural proteins of the opaque muscle fibers in Duchenne muscular dystrophy.

We studied the structural proteins of the "opaque fibers" (OFs) in muscle biopsies from 12 patients, aged 4 to 24 years, with Duchenne muscular dystrophy. The electrophoretic patterns of myofibrillar proteins indicated three groups of opaque fibers: the first (OF a) had an almost normal electrophoretogram, the second (OF b1) showed a clear decrease of 55,000 dalton protein (desmin), and the third (OF b2) exhibited a great reduction in alpha-actinin and desmin. The data suggest that some OFs are pathologic fibers in the degenerative process of Duchenne dystrophy.

Minamata disease (organic mercury poisoning): neuroradiologic and electrophysiologic studies.

We studied 10 patients with Minamata disease (organic mercury poisoning) who have been followed for over 20 years. CT revealed a bilateral, symmetric, low-density area in the visual cortex and diffuse atrophy of the cerebellar hemispheres and vermis, especially the inferior vermis. Computerized quantitative analysis of the tremor of these patients showed a peculiar frequency of 7.075 Hz on postural tremor and 7.501 Hz on action tremor. On studies of short-latency somatosensory evoked potential, all patients showed a lack of the N20 component, the potential of the somatic sensory area.