Clinical,pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families

We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7 ± 3.1 years (mean ± SD), and loss of ambulance occurred at 38.5 ± 2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca²⁺-binding domain. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1493–1501, 1998     

Association between Changes in the Systolic Blood Pressure from Evening to the Next Morning and Night Glucose Variability in Heart Disease Patients

Objectve To assess the impact of glycemic variability on blood pressure in hospitalized patients with cardiac disease. Methods In 40 patients with cardiovascular disease, the glucose levels were monitored by flash continuous glucose monitoring (FGM; Free-Style Libre™ or Free-Style Libre Pro; Abbott, Witney, UK) and self-monitoring blood glucose (SMBG) for 14 days. Blood pressure measurements were performed twice daily (morning and evening) at the same time as the glucose level measurement using SMBG. Results The detection rate of hypoglycemia using the FGM method was significantly higher than that with the 5-point SMBG method (77.5% vs. 5.0%, p＜0.001). Changes in the systolic blood pressure from evening to the next morning [morning - evening (ME) difference] were significantly correlated with night glucose variability (r=0.63, P＜0.001). A multiple regression analysis showed that night glucose variability using FGM was more closely correlated with the ME difference [r=0.62 (95% confidence interval, 0.019-0.051); p＜0.001] than with the age, body mass index, or smoking history. Night glucose variability was also more closely associated with the ME difference in patients with unstable angina pectoris (UAP) than in those with acute myocardial infarction (AMI) or heart failure (HF) (r=0.83, p=0.058). Conclusion Night glucose variability is associated with the ME blood pressure difference, and FGM is more accurate than the 5-point SMBG approach for detecting such variability.     

Orally administered levofloxacin as prophylaxis against pacemaker infection

OBJECTIVES: Despite paying careful attention to surgical details and sterile procedures, infection often occurs after pacemaker implantation. The prophylactic use of intravenously or orally administered antibiotics should therefore be considered. The present study aimed to evaluate the efficacy of orally administered levofloxacin (LVFX) as prophylaxis against pacemaker infection. METHODS: Thirty-nine patients who underwent permanent pacemaker implantation or pacemaker generator replacement due to battery depletion were included in the present study. Patients were divided into two groups (groups 1 and 2) and administered different antibiotics accordingly. Group 1 included 19 patients (75.7+/-9.3 years of age; 10 men and nine women) who were intravenously administered 2 g of cefazolin daily for five days postoperatively. Group 2 included 20 patients (73.7+/-14.4 years of age; 10 men and 10 women) who were orally administered 200 mg of LVFX 2 h before surgery and then 400 mg daily for five days thereafter. RESULTS: In group 1, the mean white blood cell concentrations before, and one, four and seven days after surgery were 4979+/-1330/mm(3), 6453+/-1200/mm(3), 5463+/-1303/mm(3) and 5632+/-1154/mm(3), respectively, and in group 2, they were 5931+/-1316/mm(3), 7062+/-1774/mm(3), 5708+/-1402/mm(3) and 5345+/-1506/mm(3), respectively. In group 1, the mean blood C-reactive protein concentrations before, and one, four and seven days after surgery were 0.27+/-0.34 mg/dL, 0.48+/-0.48 mg/dL, 1.04+/-0.99 mg/dL and 0.52+/-0.48 mg/dL, respectively, and in group 2, they were 0.43+/-0.54 mg/dL, 0.52+/-0.27 mg/dL, 0.61+/-0.42 mg/dL and 0.56+/-0.63 mg/dL, respectively. The inflammatory parameters showed similar responses in both groups. CONCLUSIONS: Orally administered LVFX following permanent pacemaker implantation can prevent pacemaker infection as successfully as intravenously administered cefazolin.     

Three-dimensional stereotactic surface projection study of freezing of gait and brain perfusion image in Parkinson's disease.

Gait disturbance is a cardinal symptom in patients with Parkinson's disease. Among the gait disturbances, freezing of gait is a unique and troublesome symptom, but its mechanism is unclear. We compared brain perfusion images using three-dimensional stereotactic surface projection analysis of N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography between Parkinson's disease patients with freezing of gait and those without. Twenty-four cases (freezing of gait group) with Parkinson's disease with freezing of gait, and 31 Hoehn and Yahr stage-matched cases (no freezing of gait group) with Parkinson's disease without freezing of gait were studied. Bilateral Brodmann area 11 perfusion of the freezing of gait group decreased significantly compared to that of the no freezing of gait group. The Brodmann area 11 may play important roles in gait, and impairment in this region may have a close relationship with freezing of gait in Parkinson's disease.     

Long-term effects of jejunal pouch added to Roux-en-Y reconstruction after total gastrectomy

Background. Jejunal pouch reconstruction after total gastrectomy has been demonstrated to ameliorate postgastrectomy symptoms, with the process of adaptation taking several months. In contrast to the short-term effects of pouch reconstruction, there are few reports about the long-term consequences (more than 2 years after surgery). Methods. In this study, 22 patients with jejunal pouch (PRY group) and 12 patients without jejunal pouch (RY group) who survived for more than 2 years without any recurrence and were available for follow-up were compared. Patients in the two groups were compared 2 years after surgery in terms of postgastrectomy symptoms, and improvements in body weight and nutritional parameters. Results. Eating capacity at a single meal compared with that in the pre-illness state was significantly better in the PRY group than in the RY group. The total score on the gastrointestinal symptom rating scale (GSRS) in the PRY group was less than that in the RY group (3.17 vs 5.25). The GSRS score for reflux syndrome in the PRY group was significantly better than that in the RY group. Assessment according to Cuschieri's gradings revealed that the total score in the PRY group was lower than that in the RY group (2.73 vs 5.92). Among the various symptoms examined, the incidence of dietary restriction and that of heartburn were significantly lower in the PRY group. Conclusion. We conclude that, 2 years after total gastrectomy, the pouch reconstruction had alleviated postgastrectomy symptoms to a greater extent than simple Roux-en-Y reconstruction, but the effectiveness could be improved. The long-term effects of pouch reconstruction should be examined more precisely with an adequate and valid scoring system for determining quality of life. Received: May 15, 2001 / Accepted: August 29, 2001     

Calpain activation in plasma membrane bleb formation during tert-butyl hydroperoxide-induced rat hepatocyte injury

BACKGROUND & AIMS: The mechanism of plasma membrane blebbing (dissociation of the lipid bilayer from the membrane cytoskeleton) in hepatocyte injury is not known. The aim of this study was to investigate the role of calpain, a calcium-dependent cytosolic protease, in bleb formation induced by oxidative stress. METHODS: Hepatocytes from Wistar rats were injured with tertbutyl hydroperoxide in the presence or absence of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or a specific calpain inhibitor, calpeptin (Z-Leu-nLeu-H). Bleb formation was examined by phase-contrast and transmission electron microscopies. Intracellular calcium concentration was measured using Fura-2. Western blot analyses were performed for cytoskeletal proteins (talin, alpha-actinin, and vinculin) and the intermediate (activated) and proactivated forms of calpain mu. RESULTS: tert-Butyl hydroperoxide induced a sustained increase in intracellular calciu, bleb formation, and, ultimately, hepatocyte death. Talin and alpha-actinin were degraded in a time- dependent manner, although no apparent changes of actin filament were observed. Before the cytoskeletal protein degradation, the intermediate form of calpain mu appeared as its proactivated form decreased. In addition, calpeptin or EGTA inhibited not only calpain mu activation but also cytoskeletal protein degradation and bleb formation. CONCLUSIONS: In tert-butyl hydroperoxide-treated hepatocytes, the activation of calpain promotes membrane blebbing via degradation of cytoskeletal proteins. (Gastroenterology 1996 Jun;110(6):1897-904)     

Experimental Striatal Degeneration Induced by Kainic Acid Administration: Relevance to Morphological Changes in Huntington's Disease

Abstract: In an attempt to reproduce the characteristic neuronal degeneration pattern in the striatum of human patients with Huntington's disease, the histological and ultra-structuralfeatures of the degeneration of medium-sized nerve cells in the striatum and its processes are described in young rats induced by a direct injection of a small amount of kainic acid into the striatum. A light microscopic examination revealed initial edema and necrotic changes at the site of injection. The area surrounding the needle track showed neuronaland dendritic swelling and eosinophilic neurons without the apparent involvement of the passing axons. Later changes consisted of a marked neuronal loss particularly of the smallcells with consequent severe astrocytosis. Electron microscopy showed specific neuronal alterations in the form of ballooned Golgi apparatuses, swelling of the endoplasmic reticulum, dendritic swelling, proliferated neurofilaments and aggregation of polysomes together with a marked disruption of neuropil. Neuronal debris and small dense bodies appeared. The majority of neuronal loss consisted of medium-sized nerve cells: Type I. Some spheroid bodies and lipid droplets were also observed.     

Microsatellite instability in adult T-cell leukaemia

Microsatellite instability (MSI) is thought to represent a defect of the DNA mismatch repair system which has been implicated in the tumourigenesis of several human malignancies. We investigated MSI in acute/ lymphomatous adult T-cell leukaemia (ATL; n =22) using 54 highly polymorphic dinucleotide short-tandem repeat sequences. The corresponding control DNA from each individual was obtained from the peripheral blood in either chronic phase ( n =5) or when complete remission was achieved ( n =17). 10/22 (41%) patients had MSI, six of whom showed MSI in multiple loci; four loci had MSI in multiple samples. The incidence of MSI in ATL was found to be higher than in other haematological malignancies, indicating MSI as a feature of ATL, which may be involved in the progression of the disease.