Muscle function in 164 men and women aged 20--84 yr

PURPOSE: The purpose of the present study was to investigate the effect of aging in men and women on muscle functional properties, i.e., muscle force and force per unit of cross-sectional area (force/CSA). METHODS: A total of 164 volunteers participated in this study and were divided into five groups according to their chronological age as follows: 20s (20--39 yr old), 40s, 50s, 60s, and 70s (70--84 yr old). Isokinetic (0, 60, 180, and 300 degrees.s(-1)) knee extensor and flexor peak torque, and CSA of the quadriceps femoris (QF) muscle of the mid-thigh were measured. RESULTS: Peak torque during knee extension and flexion was inversely related to age in both men and women. This was the case irrespective of the speed of contraction in both genders (men: r = -0.797 to -0.756, all P < 0.001, women: r = -0.639 to -0.530, all P < 0.001). A significant correlation was observed between CSA of QF and peak torque during isometric knee extension in men (r = 0.827, P < 0.001) and women (r = 0.657, P < 0.001). During isometric contraction, the force/CSA exhibited a significant decrease with increasing age in men (r = -0.518, P < 0.001) but not in women (r = -0.207, NS). CONCLUSION: These results thus suggest that muscle strength losses would be mainly due to a decline in muscle mass in both genders, whereas age-related decline in muscle function in men may also be the result of neural factors, such as muscle recruitment and/or specific tension.     

Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice

Germ-line mutations of the human TSC2 tumor suppressor gene cause tuberous sclerosis (TSC), a disease characterized by the development of hamartomas in various organs. In the Eker rat, however, a germ-line Tsc2 mutation gives rise to renal cell carcinomas with a complete penetrance. The molecular mechanism for this phenotypic difference between man and rat is currently unknown, and the physiological function of the TSC2/Tsc2 product (tuberin) is not fully understood. To investigate these unsolved problems, we have generated a Tsc2 mutant mouse. Tsc2 heterozygous mutant (Tsc2+/-) mice developed renal carcinomas with a complete penetrance, as seen in the Eker rat, but not the angiomyolipomas characteristic of human TSC, confirming the existence of a species-specific mechanism of tumorigenesis caused by tuberin deficiency. Unexpectedly, approximately 80% of Tsc2+/- mice also developed hepatic hemangiomas that are not observed in either TSC or the Eker rat. Tsc2 homozygous (Tsc2-/-) mutants died around embryonic day 10.5, indicating an essential function for tuberin in mouse embryonic development. Some Tsc2-/- embryos exhibited an unclosed neural tube and/or thickened myocardium. The latter is associated with increased cell density that may be a reflection of loss of a growth-suppressive function of tuberin. The mouse strain described here should provide a valuable experimental model to analyze the function of tuberin and its association with tumorigenesis.     

Dietary prevention of azoxymethane-induced colon carcinogenesis with rice-germ in F344 rats.

The modifying effect of dietary administration of defatted rice-germ and gamma-aminobutyric acid (GABA)-enriched defatted rice-germ on azoxymethane (AOM)-induced colon carcinogenesis was investigated in two experiments with male F344 rats. In the first experiment (the pilot study), the effects of the defatted rice-germ, the GABA-enriched defatted rice-germ and rice-germ on AOM-induced (15 mg/kg body wt once a week for 3 weeks) formation of aberrant crypt foci (ACF) were examined. The latter two preparations (2.5% in the diet) significantly inhibited ACF formation (P < 0.005). In the second experiment, a long-term study of the effects of rice-germ was done. One group was treated with AOM alone, four groups received the carcinogen and were fed the diets containing 2.5% rice-germ or 2.5% GABA-enriched defatted rice-germ for 5 (initiation phase) or 30 weeks (post-initiation phase), two groups were treated with rice-germ or GABA-enriched defatted rice-germ alone and one group was kept on the basal diet. At the termination of the study, dietary exposure to rice-germ during the initiation phase significantly reduced the incidence of colonic adenocarcinoma (71 versus 29%, P < 0.01). GABA-enriched defatted rice-germ or rice-germ during the post-initiation phase also decreased the frequency of colonic adenocarcinoma (71 versus 20%, GABA-enriched defatted rice-germ feeding, P < 0.01; 27%, rice-germ feeding, P < 0.01). These data suggest that constituents of rice-germ are possible dietary preventatives for human colon cancers.     

Bilateral nonpalpable breast carcinomas in a patient withbrca2 germ line mutation and past history of osteosarcoma

A 34-year-old premenopausal woman developed asynchronous bilateral nonpalpable breast cancers at the age of 32 and 34 years. She had undergone amputation of her left lower leg because of osteosarcoma at the age of 16. Her mother had been diagnosed with breast cancer at the age of 45. The clinicopathological features of the two breast tumors in this patient closely resembled each other; both were nonpalpable, and detectable only by helical CT scan. Histologically, they consisted mainly of an intraductal component with small grade 3 invasive foci. In addition, both tumors estrogen receptor (ER) status was negative, and both were positive for c-erbB-2 protein on immunohistochemical staining. A missense germ line mutation ofBRCA2 (exon 25 codon 3118; Met31 1 8Thr) was detected in this patient. These data may provide useful information on the carcinogenesis and biological behavior of breast cancers which develop in patients withBRCA2 germ line mutations.     

Effect of ipriflavone on bone in elderly hemiplegic stroke patients with hypovitaminosis D.

A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side, correlating with the degree of paralysis and vitamin D deficiency due to malnutrition, sunlight deprivation, and immobilization-induced hypercalcemia, and increases the risk of hip fracture. We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [1alpha(OH)D3; vitamin D3] administration on bone mineral density preservation as compared with untreated controls. In a randomized and prospective study of 103 patients with hemiplegia after stroke (the mean duration of illness was 4.8 yr), 68 (34 patients in each group) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo, whereas the remaining 35 patients received no drug. Bone mineral density on the hemiplegic side decreased by 1.4% in the ipriflavone group, 3.8% in the vitamin D3 group, and 5.4% in the control group (P < .0001, ipriflavone v vitamin D3 and control). At baseline, all three groups of patients showed a 25-hydroxyvitamin D insufficiency, increased serum ionized calcium, and low levels of 1, 25-dihydroxyvitamin D, suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1, 25-dihydroxyvitamin D. After treatment, the serum 1, 25-dihydroxyvitamin D level increased by 139.9% in the ipriflavone group and by 26.9% in the vitamin D3 group. Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group, whereas no changes occurred in the other two groups. One patient in the untreated group suffered a hip fracture, compared with none in the ipriflavone and vitamin D3 groups. These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1, 25-dihydroxyvitamin D concentration.     

Laboratory and clinical studies on clarithromycin in the field of pediatrics

Laboratory and clinical studies on clarithromycin (TE-031, A-56268), a new macrolide antibiotic, were carried out in the field of pediatrics. The results obtained are summarized as follows: 1. Serum concentrations, urinary concentrations and urinary recovery rates were determined upon oral administration on fasting of TE-031 at doses of 5 mg/kg granules in 1 case and tablets in 2 cases, and 10 mg/kg granules in 1 and 15 mg/kg granules in 1. Peak serum levels were obtained at 30 minutes in 2 cases, at 1 hour in 2 cases and at 2 hours in 1 case after administration of the drug with a range of 2.29-7.10 micrograms/ml with half-lives of 2.2-7.5 hours. Urinary recovery rates in 6 hours after administration ranged from 7.1-34.5%. 2. MICs of TE-031 against 49 clinical isolates (Streptococcus pyogenes 5 strains, Streptococcus pneumoniae 9, Staphylococcus aureus 3, Branhamella catarrhalis 4, Haemophilus influenzae 14, Haemophilus parainfluenzae 7, and Campylobacter jejuni 7) were compared with those of josamycin (JM), erythromycin (EM), and ampicillin (ABPC). The antibacterial activity of TE-031 was superior to those of JM and equal to those of EM. 3. Fifty-five pediatric patients with acute infectious diseases (scarlet fever 3 cases, pharyngitis and tonsillitis 15, pertussis 2, pneumonia 10, bronchitis 14, Campylobacter enteritis 11) were treated with TE-031 at daily doses of 10-35 mg/kg t.i.d. as a rule. The efficacy rates were 96% clinically and 72% bacteriologically. 4. Side effects or abnormal laboratory test values were not observed. 5. None of children refused TE-031.     

Serum creatine phosphokinase elevation in patients treated with intravenous magnesium sulfate.

OBJECTIVE: During the treatment of pre-term labor with magnesium sulfate, we noted an abnormal elevation of maternal serum creatine phosphokinase. This study was aimed at evaluating the relationship between tocolysis with MgSO4 and maternal serum CPK elevation, which represents the possible damage of muscles by magnesium sulfate. METHODS: Clinical records of 45 women treated with magnesium sulfate and beta-sympathomimetics for the treatment of pre-term labor were retrospectively examined. RESULTS: Serum CPK was abnormally elevated in 32 out of 45 cases (71.1%), but in only one out of 21 in the control group. In three cases, the decrease of serum creatine phosphokinase after cessation of magnesium sulfate was demonstrated, despite the continuous infusion of beta-sympathomimetics. CONCLUSION: Magnesium sulfate may cause muscular damage and abnormal elevation of maternal serum creatine phosphokinase. Special attention must be paid to patients when drugs acting on muscle cells, for example succinyl choline, are going to be used.     

Upper airway function and non-intubated, assisted ventilation

The influence of upper airway patency on ventilation assisted by chest negative pressure ventilation (CNPV) or nasal intermittent positive pressure ventilation (nIPPV) was studied as follows. 1) In seven patients with chronic respiratory failure (PaCO2 more than 50 Torr), the increase in tidal volume (VT) induced by CNPV was larger during mouth breathing than during nose breathing in the awake state. On CNPV transcutaneous PCO2 (PtcCO2) decreased during awake state, but increased during NREM sleep. 2) In four patients with chronic respiratory failure (PaCO2 more than 60 Torr), nIPPV induced the leakage of air from mouth in more than 20 cmH2O of nasal mask pressure during sleep. PtcCO2 increased during sleep, especially during REM sleep in spite of nIPPV. The change in PtcCO2 during REM sleep on nIPPV comparing awake state was 16.1 +/- 1.4 torr and comparing REM sleep in usual sleep was -6.0 +/- 1.4 Torr. 3) Upper airway resistance (UAR) was measured in two patients with tracheostomy. An increase in UAR was associated with a linear decrease in VT during nIPPV, although associated with a curvilinear decrease in VT during CNPV. These results indicate that the efficiency of CNPV and nIPPV depends on the patency of upper airway.