A family of Emery-Dreifuss muscular dystrophy with extreme difference in severity

This report describes two patients, a father and son, with autosomal dominant Emery-Dreifuss muscular dystrophy. Although the father had the common phenotype, the son had a severe phenotype including early onset of weakness and fatal cardiomyopathy in childhood. Among the patients with severe phenotype of autosomal dominant Emery-Dreifuss muscular dystrophy, he is the first to have familial onset, and in the severe end of this disease spectrum.     

Limited mediastinal lymph node dissection for non-small cell lung cancer according to intraoperative histologic examinations

BACKGROUND: Although radioisotopic procedures are commonly used to detect sentinel lymph nodes in breast cancer surgery, these procedures are often problematic and not necessarily suitable for lung cancer surgery. METHODS: Our previous study revealed that the mediastinal sentinel lymph node, defined as the regional mediastinal lymph node, consisted of nodes 2, 3, or 4 in right upper lobe cancers; 3, 7, or 8 in right lower lobe cancers; 4, 5, or 7 in left upper lobe cancers; and 4, 7, or 8 in left lower lobe cancers. On the basis of these findings, we pathologically investigated one representative lymph node at each of the 3 levels dissected during surgical intervention in 69 patients with non-small cell lung cancer from September 1993 through December 2002. Fifty-eight patients with lung cancer underwent lobectomies with limited mediastinal lymph node dissection according to this strategy. RESULTS: Mediastinal lymph node recurrence was observed in only one patient during 41 +/- 25 months (maximum, 98 months) of follow-up. The cancer-specific 5-year survivals were 96.6% in patients with pathologic stage IA disease (n = 31) and 67.4% in patients with stage IB disease (n = 16). CONCLUSION: These results suggested that limited mediastinal lymph node dissection is applicable to patients with non-small cell lung cancer whose regional mediastinal lymph nodes are not metastatic.     

Extension of radiofrequency ablation of the liver by transcatheter arterial embolization with iodized oil and gelatin sponge: results in a pig model

PURPOSE: To determine whether transcatheter arterial embolization (TAE) with iodized oil and gelatin sponge particles can be used to expand radiofrequency (RF)-induced coagulation necrosis, the morphology and histologic characteristics of ablation lesions were evaluated in the normal pig liver after three different TAE procedures. MATERIALS AND METHODS: Ten consecutive animals with 33 ablation lesions produced with an RF ablation system were randomly assigned to one of three treatment groups and a control group: a group treated with TAE with iodized oil, a group treated with TAE with gelatin sponge, a group treated with TAE with iodized oil and gelatin sponge, and a control group in which TAE was not performed. After the completion of ablation, the lesions were excised for gross and histologic examination. RESULTS: The longest and shortest diameters of ablation lesions were greatest in the group treated with TAE with iodized oil and gelatin sponge, followed by the groups treated with TAE with gelatin sponge and TAE with iodized oil (P < .05 vs controls, respectively). The hemorrhagic rim was also widest in the group treated with TAE with iodized oil and gelatin sponge (P < .05 vs controls), and it spread toward the liver periphery like a segmental hemorrhagic area adjacent to the ablation lesion. Histochemical staining for lactate dehydrogenase, maleate dehydrogenase, and nicotinamide adenine dinucleotide diaphorase showed what appeared to be 100% cellular destruction in all the ablation lesions and their hemorrhagic rims. CONCLUSION: RF ablation combined with TAE with iodized oil and gelatin sponge induces the greatest area of coagulation necrosis accompanied by peripherally spreading segmental necrosis in normal pig liver tissue.     

Cut-off level of docetaxel, paclitaxel and gemcitabine in histoculture drug response assay for non-small cell lung cancer

Cut-off levels of docetaxel (DOC), paclitaxel (PAC), and gemcitabine (GEM) in histoculture drug response assay are determined by data acquisition of non-small cell lung cancer. Inhibition rates were 47.5 +/- 22.2% in DOC (n=181), 66.6 +/- 25.1% in PAC (n=57), and 25.4 +/- 18.4% in GEM (n=63), respectively. Cut-off levels were determined as 50% in DOC, 60% in PAC, and 30% in GEM. The positive rates such as 47.5% in DOC, 68.4% in PAC, and 33.3% in GEM were obtained.     

Docetaxel therapy against anthracycline resistant breast cancer]

To evaluate the efficacy of docetaxel therapy against anthracycline-resistant breast cancer, twenty patients were treated with docetaxel. Of the 20 patients pretreated with anthracycline, 17 were clinically anthracycline-resistant and the remaining three were refractory to anthracycline on histoculture drug response assay. Nine patients had loco-regional recurrence and 11 had distant +/- loco-regional recurrence. Docetaxel (49-60 mg/m2) was administered every 4 weeks, and was infused 1-13 times (median; 3 times). Of the 19 evaluable patients, eight (42%) showed partial response with the docetaxel therapy. Durations of the response ranged from 1 to 8 months (median; 4 months). Major adverse effects of the therapy were alopecia, neutropenia, and leucocytopenia. Hypersensitivity reaction was observed in one case. In addition, severe adverse effects such as grade 2 pneumonia and grade 4 diarrhea were found in one patient each. In conclusion, although the adverse effects are not negligible, docetaxel therapy is effective against anthracycline-resistant breast cancer.     

Beitrag zur Kenntnis der Lungensyphilis der Neugeborenen und Erwachsenen

Ohne ZusammenfassungHiezu Taf. III.     

Revised optimal cut-off point of waist circumference for the diagnosis of metabolic syndrome in Japanese women and the influence of height

AIM: We reevaluated waist circumference as a diagnostic criterion of metabolic syndrome (MetS) in Japanese. METHODS: We enrolled 5,571 subjects (3,148 men and 2,423 women) who had health check-ups in our center. The criterion was reevaluated using the positive predictive value of a receiver-operating characteristics (ROC) curve at 10 different hypothesized lengths of waist circumference with or without a cluster of risk factors. We also drew ROC curves based on the atherosclerotic findings of clinical examinations. RESULTS: Based on the ROC curves, the optimal waist circumference cut-off was 85 cm in men and 80 cm in women. Using this 80 cm cut-off point in women, misdiagnosis rates of MetS were lowered (-19.1--56.6%) compared to the cut-off point currently in use. Integrating the influence of height, namely by using a waist-to-height(2) ratio, misdiagnosis rates in shorter populations were decreased in both men and women. CONCLUSION: These data suggested an optimal waist circumference cut-off to improve the diagnostic probability of MetS in Japanese women of 80 cm, as well as the utility of an easily detected anthropometric index such as a waist-to-height (cm x 100/cm) or waist-to-height(2) (cm x 10,000/cm(2)) ratio, determined as 51 in men and 52 in women, or 30 in men and 33 in women, respectively.     

A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment

Background

To date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy.

Methods

We randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear (62 patients) or four intratympanic injections with dexamethasone (Dex; 58 patients). The primary outcome was the proportion of patients showing hearing improvement (10 decibels or greater in pure-tone average hearing thresholds) 8?weeks after treatment. The secondary outcomes included the change in pure-tone average hearing thresholds over time and the incidence of adverse events.

Results

In the IGF-1 group, 66.7% (95% confidence interval [CI], 52.9-78.6%) of the patients showed hearing improvement compared to 53.6% (95% CI, 39.7-67.0%) of the patients in the Dex group (P?=?0.109). The difference in changes in pure-tone average hearing thresholds over time between the two treatments was statistically significant (P?=?0.003). No serious adverse events were observed in either treatment group. Tympanic membrane perforation did not persist in any patient in the IGF-1 group, but did persist in 15.5% (95% CI, 7.3-27.4%) of the patients in the Dex group (P?=?0.001).

Conclusions

The positive effect of topical IGF-1 application on hearing levels and its favorable safety profile suggest utility for topical IGF-1 therapy in patients with sudden deafness.

Trial registration

UMIN Clinical Trials Registry Number UMIN000004366, October 30^th, 2010.

     

Inhibition of platelet aggregation by low concentrations of sodium fluoride. Significance of the intracellular calcium ion concentration.

Sodium fluoride activates platelets but its mechanism of action has not yet been completely identified. We examined the effect of a low concentration of sodium fluoride (which could not cause aggregation) on thrombin-induced changes in the intracellular calcium ion concentration ([Ca2+]i). In the presence of 1 mM extracellular Ca2+, preincubation with a low concentration of sodium fluoride decreased the peak of the thrombin-induced elevation of [Ca2+]i, when measured with aequorin. When [Ca2+] was measured using fura-2, preincubation caused no marked changes in its peak, but the later changes that were thought to mainly reflect extracellular Ca2+ influx were inhibited. The inhibitory mechanism of sodium fluoride appears to depend on reducing extracellular Ca2+ influx. Aequorin appears to reflect [Ca2+]i near the cell membrane and is thus easily affected by the extracellular Ca2+ influx.     

Analysis of adhesive proteins on the surface of platelets from the patients with lung cancer: studies in histological type and clinical stage]

Flow cytometry was used to detect platelet-associated fibrinogen (PA-Fbg), platelet-associated fibronectin (PA-FN) and platelet-associated thrombospondin (PA-TSP) on the surface membrane of platelets and plasma (P)-TSP in 30 patients with lung cancer (16 case of adenocarcinoma and 14 of squamous cell carcinoma). ELISA was used to analyze beta-TG and PF4. In the lung cancer group, beta-TG and PF4 were higher than those of a normal control group. PA-Fbg values were correlated with beta-TG and PF4 values. Each adhesive protein had a higher value in the patient than in the normal control group, and the degree of the increase was related to the progression of clinical disease stage. In the squamous cell carcinoma group, the P-TSP value was significantly elevated. Platelet size increased as the clinical stage of the disease progressed. These results suggest the following: 1. An increase in PA-Fbg can indicate the presence of activated platelets. 2. In patients with lung cancer, activated platelets appear in the blood, and their numbers increase as the clinical stage of the disease progresses. 3. Differences in histologic type led to differences in binding adhesive protein.