A new method using F-waves to measure muscle fiber conduction velocity (MFCV)

OBJECTIVE: First, to propose a new technique for measuring muscle fiber conduction velocity (MFCV). Second, to ascertain the validation of the new method that uses F-waves (F-MFCV) in healthy volunteers. Third, to examine the relationship between F-MFCV and motor nerve conduction velocity (MCV) in the same subjects. SUBJECTS AND METHODS: F-waves reflecting single motor units were recorded with a multi-channel surface electrode array and weak electrical stimulation to the median or ulnar nerves in 21 healthy volunteers. F-MFCVs of the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) were calculated from the F-wave peak latency in each channel. MFCV during minimal voluntary contraction (V-MFVC) was measured in the same muscles. RESULTS: There was no significant difference between F-MFCV and V-MFCV in the muscles tested The mean F-MFCV value was similar to recently reported MFCV values generated by minimal voluntary contraction. No significant differences were found between the APB and ADM F-MFCVs, whereas the MCV of the ulnar nerve was faster than that of the median nerve. CONCLUSION: The MFCV in a single motor unit could be measured with a multi-channel surface electrode array by recording F-waves induced by weak stimulation. Since V-MFCV generated by minimal voluntary contraction is explained by the size principle, V-MFCV reflects small and slow conducting motor unit. There was no significant difference between F-MFCV and V-MFCV. It seemed that F-MFCV also reflected small motor unit. The reason for the lack of difference in the F-MFCVs of the ADM and APB is considered to be a relatively slow F-MFCV. Moreover, MCV reflected the speed of the fastest nerve fiber, whereas F-MFCV did not.     

Suppressive effect of leflunomide metabolite (A77 1726) on metalloproteinase production in IL-1beta stimulated rheumatoid synovial fibroblasts

Leflunomide, an isoxazol derivative structurally unrelated to other immunomodulatory drugs, has proven to be efficacious in the treatment of rheumatoid arthritis (RA). This study was conducted to elucidate the mechanism by which leflunomide mediated antirheumatic effects. We investigated the effects of A77 1726, leflunomide's active metabolite, on mitogen-activated protein kinase (MAPK) activation in IL-1beta-stimulated rheumatoid synovial fibroblasts. The effects of A77 1726 on the secretion of matrix metalloproteinases (MMPs) from rheumatoid synovial fibroblasts were also examined. A77 1726 partially suppressed IL-1beta-induced ERK1/2 and p38 kinase activation. In contrast, A77 1726 efficiently suppressed IL-1beta-stimulated JNK1/2 kinase activation. Although no suppressive effect was demonstrated on MMP-2, A77 1726 markedly inhibited MMP-1, 3, and 13 secretions from IL-1beta-stimulated rheumatoid synovial fibroblasts. Tissue inhibitor of metalloproteinases-1 (TIMP-1) was constitutively produced from rheumatoid synovial fibroblasts and the suppressive effects of A77 1726 on TIMP-1 production were minimal. Our results suggest that the suppression of the MAPK signalling pathway and MMP synthesis in rheumatoid synovial fibroblasts is a possible mechanism for the inhibitory activity of leflunomide against rheumatoid arthritis.     

Hypofluorescent spots in indocyanine green angiography of peau d‘orange and fundus

Purpose. Hypofluorescent spots were seen inindocyanine green (ICG) angiography of peau dorangefundus in eyes with angioid streaks. Origin of the hypofluorescentspots were examined with attention to their correlationwith a peau dorange appearance of the central fundususing a computer-assisted image comparison system. Methods. ICG angiography was performed in 5 patientshaving peau dorange appearance of fundus using ascanning laser ophthalmoscope (SLO) and a digitalvideo-fundus camera. The same central fundus areas corresponding to hypofluorescent spots in an ICGangiogram were then digitally identified in afluorescein angiogram and in a red-free picture in all10 eyes of the 5 patients. Monochromatic lightobservation was also performed with a dark fieldobservation using a SLO to see subretinal orintrachoroidal pigment clumping. Results. In no patient, the areas identified withhypofluorescent spots did show relevant changes ina fluorescein angiogram or a red-free picture. SLOexamination revealed not perfusion defect at the sameareas. The dark field observation showed no pigmentclumping at the peripapillary and papillomacularbundle regions where hypofluorescent spots were seen.Conclusions: Hypofluorescent spots seen in ICGangiograms did not show exact consistency with peau dorange changes in their location and shape. Perfusion defects or blocking by pigments were not acause of hypofluorescent spots. The scatteredhypofluorescent spots were considered to be relevantwith irregular affinity of the fundus to ICG dye.     

Calcaneus Bone Mineral Density is Lower Among Men and Women with Lower Physical Performance

Fracture risk is influenced by both bone strength and by falls. Measures of physical function and performance are predictors of falls. However, the interrelationships among bone mineral density (BMD), regular physical activity, and measures of physical performance are not well known. We studied 447 community-dwelling Japanese people aged 40 years and over (96 men and 351 women) to examine the association of calcaneus BMD with measures of physical performance (grip strength, walking speed, chair stand, and functional reach) and regular physical activity. Calcaneus BMD decreased with age by approximately 25% in men and 42% in women. Measures of physical performance decreased with age by approximately 30% in both genders, however, performance on the chair stand test declined by approximately 60%. There were only minimal differences in performance measures and calcaneus BMD between people with and those without regular physical activity in both genders, and most differences were not significant. However, there were significant BMD increases of 3–6% per standard deviation (SD) increase in all performance measures for women and a 7% increase in BMD per SD increase in grip strength for men, after adjusting for age. These associations remained after additional adjustment for body mass index and regular physical activity. These findings suggest that bone density and physical function decline markedly in both men and women with age, and that low BMD and poor function tend to occur together, which would increase fracture risk more than either risk factor alone. Received: 9 August 1999 / Accepted: 4 February 2000     

Coronary artery bypass surgery in a patient with myasthenia gravis

A 73-year-old man with myasthenia gravis required quadruple coronary artery bypass grafting due to triple-vessel disease. Anesthetic management was performed with general anesthesia using a reduced dose of muscle relaxant with the aid of a neuromuscular transmission monitor. He was extubated 14 hrs after surgery without difficulty under this monitor. His postoperative course was uneventful. A patient with myasthenia gravis who required coronary artery bypass surgery was successfully performed by the deliberate preoperative evaluation of patient's myasthenic and cardiac status, and by the careful perioperative management.     

Morphological change in the MNNG-treated rat gastric mucosa

To investigate the process of carcinogenesis in gastric cancer, we studied the histological features of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated rats. Samples of the gastric mucosa from both MNNG-treated and control rats were histologically examined every 2 months, for 10 months. In 40% of the MNNG-treated rats, atrophy in the gastric mucosa was observed after 2 months, and regenerative epithelium was observed after 4 months, followed by adenomatous proliferation and disappearance of the tight junction electron microscopically after 6 months. A small intestinal cancer had developed in 2 rats at 6 months. While gastric cancer had developed in 3 rats at 8 months, and in one of these 3 rats, peritoneal dissemination was observed macroscopically and histologically. These results suggested that adenomatous proliferation and disappearance of the tight junction observed electron microscopically were characteristic pathological features of precancerous lesions in the stomach in MNNG-treated rat.     

Primary gastric lymphoma: a clinicopathological study

A retrospective study of 25 patients treated for primary gastric lymphoma was made to investigate a number of problems related to treatments and report the factors influencing prognosis. In the 5-year-survival rate according to Working Formulation classification, either survival rate of low-grade type or intermediate-grade type was higher than that of high-grade type. Both the 5-year-survival rate of cases without lymph node metastasis and that of cases that involved perigastric lymph nodes were higher than that of cases that involved distant gastric lymph nodes. Those surviving five years after perigastric lymph node metastasis had received D3 or D4 dissection and postoperative multicombined chemotherapy. Tumors invading only to the submucosal layer had received D2 dissection and were not treated by postoperative multicombined chemotherapy, and recurrence was not recognized in these cases. Of 9 cases infiltrating into the musclaris propria or serosa without lymph node metastasis, 8 cases were treated by postoperative multicombined chemotherapy and were alive without recurrence, but one case without postoperative multicombined chemotherapy died by recurrence. Therefore, adequate therapy for gastric lymphoma with infiltrating into submucosal layer is gastrectomy with D2 lymph node dissection, and postoperative multicombined chemotherapy is not necessary. The cases with perigastric lymph node metastasis, or the cases with invading from muscularis propria to serosa require D3 or D4 lymph node dissection with postoperative multicombined chemotherapy. But the cases with distant gastric lymph node metastasis or invading adjacent structure or high-grade type histologically (WF classification) require preoperative chemotherapy.     

No Improvement of Adult Height in Non-growth Hormone (GH) Deficient Short Children with GH Treatment

It is still in doubt whether the standard-dose growth hormone (GH) used in Japan (0.5 IU/kg/week, 0.167 mg/kg/week) for growth hormone deficiency is effective for achieving significant adult height improvement in non-growth hormone deficient (non-GHD) short children. We compared the growth of GH-treated non-GHD short children with that of untreated short children to examine the effect of standard-dose GH treatment on non-GHD short children. GH treatment with recombinant human growth hormone (rhGH) was started before the age of 11 yr in 64 boys and 76 girls with non-GHD short stature registered at the Foundation for Growth Science who have now reached their adult height. In 119 untreated boys and 127 untreated girls whose height standard deviation score (SDS) was below –2 SD at the age of 6 yr, height growth was followed until 17 yr. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, in both sexes. Adult height and adult height SDS were significantly greater in the untreated group than in the GH-treated group, in both sexes, although the change in height SDS did not differ significantly. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, so 57 boys and 57 girls whose height SDS at the age of 6 yr in the untreated group closely matched the height SDS before GH treatment in the GH-treated group were chosen for comparison. Height SDS did not differ significantly between the GH-treated group before GH treatment and the untreated group at the age of 6 yr, nor were there differences between these subgroups in adult height, adult height SDS, or height SDS change, in either sex. The effect of GH treatment is reported to be dose-dependent and doses over 0.23 mg/kg/week are reported to be necessary to improve adult height in non-GHD short children. Currently, the GH dose is fixed at 0.175 mg/kg/week in Japan, and we expected to find, and indeed concluded, that ordinary GH treatment in Japanese, non-GHD short children does not improve adult height.     

A dose-finding study of glycosylated G-CSF (Lenograstim) combined with CHOP therapy for stem cell mobilization in patients with non-Hodgkin's lymphoma

BACKGROUND: Peripheral blood stem cell (PBSC) reinfusion has been widely used for hematopoietic reconstitution after high-dose chemotherapy. However, the optimal dose of granulocyte colony-stimulating factor (G-CSF) for PBSC mobilization in combination with chemotherapy for autograft remains unknown. METHODS: To find the optimal dose of glycosylated G-CSF (lenograstim) for PBSC mobilization in combination with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), we conducted a dose-finding study on 43 newly diagnosed patients who had unfavorable prognostic factors. They received four to six courses of cyclophosphamide, doxorubicin, vincristine and prednisolone combined with lenograstim every 2 weeks (biweekly CHOP therapy). PBSC apheresis was started after the third course of biweekly CHOP therapy. Lenograstim was given daily from day 3 until the day of the last apheresis. The optimum dose of lenograstim was assessed based on mobilization efficacy and safety profiles at a daily single dose of 2, 5 and 10 microg/kg for eight patients in each level. RESULTS: The collected number of CD34+ cells in the first apheresis products was higher in the 5 microg/kg group than in the 2 microg/kg group (median, 4.22 x 10(6) vs 2.49 x 10(6) CD34+ cells/kg, P = 0.051). The highest dose of 10 microg/kg (median, 2.99 x 10(6) CD34+ cells/kg) failed to show a dose dependence in PBSC mobilization. The efficacy and safety of the 5 microg/kg dose were further confirmed in an additional 19 patients. CONCLUSIONS: The present study suggests that the recommended dose of lenograstim for PBSC mobilization with CHOP therapy in untreated NHL is 5 microg/kg.