Coffee consumption and mortality in Japan with 18 years of follow-up: the Jichi Medical School Cohort Study.

OBJECTIVE: Coffee consumption can be expected to reduce mortality due to cardiovascular diseases and cancer. This study tested the hypothesis of an inverse association between coffee intake and all-cause mortality and mortality due to cancer, coronary heart disease, or stroke. STUDY DESIGN: Prospective cohort study. METHODS: We analyzed data from the Jichi Medical School Cohort Study, Japan, enrolling 9946 subjects (men/women: 3870/6,076, age: 19-93 years) from 12 communities. A food frequency questionnaire assessing the subjects' daily coffee consumption was used. RESULTS: During an average follow-up of 18.4 years, the total number of deaths was 2024, including 677 for cancer, 238 for coronary heart disease, and 244 for stroke. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality and cause-specific mortality due to cancer, coronary heart disease, and stroke. Overall, no significant association was shown between coffee consumption and all-cause mortality. In the cause-specific mortality analyses, stroke mortality was significantly lower in those who consumed 1-2 cups of coffee daily (HR [95% CI]: 0.63 [0.42-0.95]) than in those who do not consume coffee, and this association occurred only in men. CONCLUSION: This study showed no significant association between coffee consumption and all-cause mortality. A U-shaped association between coffee consumption and stroke mortality with a 37% lower stroke mortality, only significant in men who consume 1-2 cups of coffee daily was observed. It is necessary to examine the possibility of intervention studies to reduce stroke mortality through coffee consumption.

Effects of a calcium supplement on bone mineral density in male cyclists.

AIM: The purpose of this study was to maintain or improve bone density in male road cyclists through provision of calcium and vitamin D3 supplementation ingested before cycling. METHODS: Participants were male cyclists (N=17), with a mean (±SD) age of 42.7 (9.4) years. Measurements of lumbar spine and hip areal bone mineral density (aBMD) were performed at the start and end of a cycling season. Cyclists were randomized into the calcium supplement (CAL) or the control group (CON) group based on lumbar spine T-scores. The CAL group was instructed to consume 1600 mg calcium and 1000 IU vitamin D3 prior to cycling for the 5-month period. RESULTS: Femoral trochanter aBMD significantly decreased during the 5 month cycling season. There was no difference in aBMD between CAL and CON groups. CONCLUSION: Negative effects of competitive cycling on aBMD in hip structures can be observed within 5 months. Calcium and vitamin D3 ingested prior to cycling does not ameliorate this effect. This proof of concept paper provides evidence that more work is needed to find mechanisms to protect cyclists from destructive bone loss in hip structures.

Egg yolk protein and egg yolk phosvitin inhibit calcium, magnesium, and iron absorptions in rats.

Egg yolk decreases the absorption of iron. The effects of egg yolk protein and egg yolk phosvitin on the absorption of calcium, magnesium, and iron were investigated by in vivo studies. Male Wistar rats were fed purified diets containing casein, soy protein, or egg yolk protein for 14 d. The apparent absorptions of calcium, magnesium, and iron in the rats fed the yolk protein-based diet were lower than those in rats fed the casein- and soy protein-based diets. The apparent phosphorus absorption and the apparent protein digestibility in the yolk protein group were lower than those in the casein and soy protein groups. In the feces of the yolk protein group, serine comprised more than 30% of the amino acids. The addition of egg yolk phosvitin to the casein diets at levels of 1% and 2% (w/w) produced effects on calcium and magnesium absorptions similar to those produced by the diet containing yolk protein. The tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) pattern suggested that phosphopeptide fragments having molecular masses of 28, 22, and 15 kDa were evident in the contents of the small intestine of the rats fed phosvitin diets. These results indicate that yolk protein, when compared with casein and soy protein, decreases calcium and magnesium absorption via the resistance of phosvitin to proteolytic action.

Chronic hypernatremia derived from hypothalamic dysfunction: impaired secretion of arginine vasopressin and enhanced renal water handling.

We analyzed the disorder of water metabolism in a 32 year-old female with chronic hypernatremia. She had meningitis at 4 years, and ventriculo-peritoneal shunt operation at 13 years because of normal pressure hydrocephalus. At 14 years hypernatremia of 166 mmol/l was initially found and thereafter hypernatremia ranging from 150 to 166 mmol/l has been persisted for the last 18 years. Physical and laboratory findings did not show dehydration. Urine volume was 750-1700 ml per day and urinary osmolality (Uosm) 446-984 mmol/kg, suggesting no urinary concentrating defect. Plasma arginine vasopressin (AVP) levels ranged from 0.4 to 1.2 pmol/l despite hyperosmolality of 298 through 343 mmol/kg under ad libitum water drinking. There was no correlation between plasma osmolality (Posm) and plasma AVP levels, but Uosm had a positive correlation with Posm (r=0.545, P < 0.05). Hypertonic saline (500 NaCl) infusion after a water load increased Uosm from 377 to 679 mmol/kg, and plasma AVP from 0.2 to 1.3 pmol/l. There was a positive correlation between Posm and plasma AVP levels in the hypertonic saline test (r=0.612, P<0.05). In contrast, an acute water load (20 ml/kg BW) verified the presence of impaired water excretion, as the percent excretion of the water load was only 8.5% and the minimal Uosm was as high as 710 mmol/kg. Urinary excretion of aquaporin-2 remained low in concert with plasma AVP levels. No abnormality in pituitary-adrenocortical function was found. These results indicate that marked hypernatremia is derived from partial central diabetes insipidus and elevated threshold of thirst, and that enhanced renal water handling may contribute to maintenance of body water in the present subject.

[Hyperbaric oxygen as an adjunctive treatment for descending necrotizing mediastinitis: report of a case].

We report a case of 59-year-old man of descending necrotizing mediastinitis (DNM) secondary to peritonsillar abscess. A 59-year-old man with diabetes mellitus was admitted to a local hospital because of cervical swelling related to a peritonsillar abscess. Despite administration of antibiotics, swelling of the neck, dysphagia and dyspnea deteriorated. Therefore he was urgently undergone a tracheotomy and transferred to our hospital by an ambulance. The surgery consisted with neck and anterior mediastinal drainage through neck and cervical collar incision. Culture of drainage fluid showed clostridium difficile. On postoperative day 5, we started hyperbaric oxygen therapy (HBOT). After lavage and HBOT, the patient improved by degrees, and discharged on postoperative day 82. DNM is a rare but serious complication of otopharyngeal and deep neck infection that spreads down to the mediastinum through the cervical-facial planes. Its mortality rate remains high even with aggressive surgical drainage and appropriate antibiotics. Our patient was successfully treated with urgent surgical drainage, antibiotics and HBOT. HBOT might be of great value as an adjunctive management to control this fatal infection.

Biosorption of actinides from dilute waste actinide solution by egg-shell membrane.

Removal of radioactive elements from the effluent and waste aqueous solutions is an important problem. In previous laboratory batch experiments, hen egg-shell membrane (ESM) was stable as an insoluble protein and was very capable of binding heavy metal ions from aqueous solution. Batch laboratory pH profile, time dependency, and capacity experiments were performed to determine the binding of uranium (U) and thorium (Th) to ESM. Batch pH profile experiments indicated that the optimum pH for binding these actinides was approx 6.0 (U) or 3.0 (Th). The adsorption isotherms were developed at pH 5.0 (U) or 3.0 (Th) at 25 degrees C, and the adsorption equilibrium data fitted both Langmuir and Freundlich models. The maximum uptakes by the Langmuir model were about 240 mg U/g and 60 mg Th/g dry weight ESM. In addition, their adsorption capacities increased as salt concentration increased. ESM could also accumulate uranium from dilute aqueous solution by adjusting to the optimum pH. These results showed that ESM was effective for removing actinides from solution and would be useful in filtration technology to remove actinides from aqueous solution.

Licorice-induced hypokalemic myopathy and hypokalemic renal tubular damage in anorexia nervosa.

A patient with a history of anorexia nervosa developed licorice-induced hypokalemic myopathy. With potassium replacement, high CPK blood level and myopathic signs returned to normal. However, the patient manifested persistent hypokalemia and impaired renal function to concentrate and acidify the urine. Renal biopsy demonstrated intense degeneration and vacuolation of tubules with a normal glomerus which was consistent with hypokalemic nephropathy. Prolonged hypokalemia in anorexia nervosa is sometimes attributed to surreptitious purging or taking diuretics, but it is necessary to check the urine pH, the urine-specific gravity, and the urine potassium level in order to find underlying renal damage even after hypokalemic myopathy is treated successfully.

Multicenter clinical trial for evaluating methylprednisolone pulse treatment of idiopathic optic neuritis in Japan. Optic Neuritis Treatment Trial Multicenter Cooperative Research Group (ONMRG).

BACKGROUND: A randomized, controlled clinical trial was conducted in 1991 to compare an intravenous megadose of methylprednisolone with a control drug (mecobalamin) for treating acute idiopathic optic neuritis. CASES: Sixty-six cases from 22 clinical centers throughout Japan were examined to evaluate the treatment on visual function parameters, such as visual acuity, visual field, color vision, contrast sensitivity, and critical flicker frequency. OBSERVATIONS: The methylprednisolone pulse treatment group showed faster recovery of visual function, particularly the visual acuity at 1 week (P<.05), Humphrey field analyzer mean deviation at 3 weeks (P<.05), and color vision at 1 week (P<.05). Recovery of contrast sensitivity at several different spatial frequencies was significant in the pulse treatment group at 1 (P<.01), 2 (P<.05), and 4 weeks (P<.05) after the start of treatment. Visual function test results at 12 weeks and 1 year were essentially the same in the two treatment groups. Side effects appeared more frequently in the pulse treatment group than in the control (P<.05). CONCLUSIONS: Pulse treatment does not appear effective for idiopathic optic neuritis even though visual function in the pulse treatment group of this trial recovered more quickly during the initial phase compared to the controls. More effective and specific treatment should be established for optic neuritis.

Isolation and mapping of a human zinc finger gene (ZNF188) homologous to ZNF187, a serum-response-element binding protein.

From a human pancreas cDNA library we isolated and characterized a novel zinc finger gene encoding a protein homologous to ZNF187, a serum response element-binding protein. The full-length cDNA contained an open reading frame of 1,686 nucleotides encoding a predicted 562-amino-acid peptide that included an ATP-GTP binding site and seven C2H2 zinc finger domains. The consensus sequence of the C2H2 domains (CX2CX3FX5LX2HX3H) is common in the SRE-binding region present in Drosophila Krüppel proteins. An alternatively spliced form of the transcript found in the cDNA library lacked both the ATP-GTP binding site and any C2H2 zinc finger domains. We localized this gene (ZNF188) to chromosome band 7q22.1-->q22.3 by fluorescence in situ hybridization.

A 120-MHz ultrasound probe for tissue imaging.

Ultrasound transducers with center frequency above 100 MHz are expected to be used for future diagnostic tissue characterization because of their high lateral resolution. We have fabricated a 120-MHz transducer that consists of a ZnO piezoelectric film on a sapphire substrate that has a concave acoustic lens. The lateral resolution was calculated as 13 microns. The insertion loss of the transducer, defined as the difference between the received voltage and the transmitted one, was -45 dB. The 6-dB handwidth of the received signal was approximately 40 MHz. The transducer was mounted in a rod-shaped probe to ensure contact with in vivo tissue, because of the low penetration of ultrasound in the high frequency region. While the probe is rotated and moved along its axis mechanically, the transducer receives backscattered ultrasound from the surrounding tissue on a cylindrical plane that is kept a constant distance from the probe surface. The feasibility of this high-frequency tissue imaging probe has been demonstrated by obtaining preliminary images of an in vitro bovine kidney.

[Optic neuritis and vitamin C].

Twenty five patients with optic neuritis (ON) of unknown etiology were treated with a high dosage of intravenous vitamin C. We measured blood levels of vitamin A, B1, B2, B6, B12, C, E, folate and zinc. All levels were compared with the normal values of our laboratory. The blood level of vitamin C (p < 0.001) was significantly less than the mean value of the normal. The blood levels of vitamin E, B6 (p < 0.01) and zinc (p < 0.001) also significantly decreased. Intravenous administration of vitamin C was given in those patients with decreased blood level of vitamin C. In order to compare the effect on vision by this treatment, the amplitude of recovery of vision, the time needed to attain the maximum vision, and the speed of visual recovery were analyzed. The results were compared with groups receiving other treatments. That is, Group A received intravenous administration of high dosage of vitamin C, Group B, intravenous pulse administration of corticosterone, Group C, oral administration of corticosterone, and Group D, oral administration of vitamin B12. Vision was significantly improved in all groups. There was no significant difference in improvement of visual acuity. Intravenous administration of vitamin C can be evaluated as the method of choice for the treatment of patients with ON. A possible mode of action by vitamin C on free radicals is discussed.

[A case of advanced esophageal cancer made resectable by preoperative combination therapy with 5-FU and CDDP].

The authors experienced a case of advanced esophageal cancer made resectable by combination therapy with 5-FU and CDDP as a neoadjuvant chemotherapy. The patient was a 69-year-old-man suffering from esophageal cancer of A3.N4 (+).Pl0.M0 at stage IV. At this case was diagnosed to be radically unresectable, this form of combination therapy was used. The patient showed PR after 2 courses and the operation could then be conducted. The intraoperative findings revealed fibrous fusion of tumor with the aorta, but no direct invasion. The metastatic lymph nodes were necrotized and reduced. It was evaluated as Grade 3 in accordance with the "Histologic criteria for the effects of anticancer chemotherapy." The postoperative course was favorable without recurrence. This therapy caused no adverse reactions and seems effective as a neoadjuvant chemotherapy for advanced esophageal cancer.

Effect of glycemic control on calcium and phosphorus handling and parathyroid hormone level in patients with non-insulin-dependent diabetes mellitus.

The present study was undertaken to determine whether improvement of hyperglycemia alters calcium and phosphorus handling, parathyroid hormone (PTH) secretion and bone turnover in patients with non-insulin-dependent diabetes mellitus (NIDDM). We measured serum and urinary mineral levels, serum intact PTH and osteocalcin on admission and at discharge (38 +/- 3 days later, Means +/- SEM) in 28 patients with poorly-controlled NIDDM (63 +/- 2 years old, 13 males and 15 females). During the hospitalization period, glycemic control was markedly improved. Serum calcium levels remained unchanged, but serum phosphorus increased. Urinary calcium and phosphorus excretion decreased. Serum intact PTH decreased from mid-normal (30.0 +/- 2.2 ng/l) to low normal values (24.0 +/- 1.3 ng/l) (P < 0.01, normal values: 10-65 ng/l). Serum osteocalcin increased from 4.14 +/- 0.35 to 4.92 +/- 0.40 micrograms/l (P < 0.01, normal values: 2.5-13 micrograms/l). On admission, urinary calcium and phosphorus excretion showed a positive correlation with urinary glucose excretion. Serum calcium levels showed a negative correlation with serum intact PTH (r = -0.46, P < 0.05). Moreover, the change in serum calcium during the hospitalization was negatively correlated to the change in serum intact-PTH (r = -0.45, P < 0.05). Serum phosphorus concentrations showed a positive correlation with the renal threshold for phosphorus excretion on admission (r = 0.86, P < 0.01). These results indicate that hyperglycemia causes excess urinary calcium and phosphorus excretion in patients with NIDDM. In response to urinary calcium loss, PTH secretion is mildly stimulated. Bone formation seems to be suppressed in the hyperglycemic state in spite of increased PTH secretion.

Changes in pH affect Cl- removal and AVP action in collecting tubules.

We examined what mechanisms are involved in the alteration by chloride (Cl-) removal of arginine vasopressin (AVP)-induced cellular cAMP production, and cellular free calcium ([Ca2+]i) mobilization in rat renal papillary collecting tubule cells in culture, using two buffer systems: bicarbonate and non-bicarbonate buffers. The first study was performed in the bicarbonate-supplemented buffer. Removal of Cl-, which was replaced by methylsulfonate or gluconate, increased cellular pH (pHi) from 7.19 to 7.26. AVP increased cellular cAMP production in a dose-dependent manner; 1 x 10(-9) and 1 x 10(-7) M AVP-induced increases in cellular cAMP production were significantly enhanced by the Cl- removal. Also, 1 x 10(-7) M AVP-mobilized [Ca2+]i was augmented by the Cl- removal (181.3 vs. 224.5 nM, P < 0.05). The second study was carried out with the Krebs-Ringer buffered saline (KRB). Removal of Cl- lowered pHi from 7.20 to 7.09. AVP-induced increases in cellular cAMP production were significantly reduced in the Cl(-)-free KRB compared to those in the KRB. The reduction was obtained with KRB containing less than 25 mM Cl-. Similar results were obtained with 2 x 10(-8) M forskolin, a diterpene activator of adenylate cyclase. 1 x 10(-7) M AVP-mobilized [Ca2+]i was also diminished by the Cl(-)-free KRB. These results indicate that Cl- depletion affects the cellular response to AVP mediated via the changes in pHi in renal papillary collecting tubule cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancement of vascular action of arginine vasopressin by diminished extracellular sodium concentration.

The present study was undertaken to examine the effects of diminished extracellular sodium concentration on the vascular action of arginine vasopressin (AVP) in cultured rat vascular smooth muscle cells (VSMC). The preincubation of cells with the 110 mM extracellular Na+ ([Na+]e) solution supplemented with 30 mM choline chloride for 60 minutes enhanced the effect of AVP- (1 x 10(-8) M) induced VSMC contraction. The treatment of 110 mM [Na+]e solution also enhanced the cellular contractile response to the protein kinase C (PKC) activators, phorbol 12-myristate 13-acetate and 1-oleoyl-2-acetyl-glycerol. Furthermore, preincubation with the 110 mM [Na+]e solution also potentiated the effect of 1 x 10(-8) M AVP, but not 1 x 10(-6) M, to increase the cytosolic-free Ca2+ ([Ca2+]i) concentration. The 110 mM [Na+]e media decreased the basal intracellular Na+ concentration and increased intracellular 45Ca2+ accumulation, basal [Ca2+]i and AVP-produced 45Ca2+ efflux. These effects of 110 mM [Na+]e solution to enhance the vascular action of AVP were abolished by using Ca(2+)-free 110 mM [Na+]e solution during the preincubation period. The preincubation with the 110 mM [Na+]e solution did not change either the Kd and Bmax of AVP V1 receptor of VSMC or the AVP-induced production of inositol 1,4,5-trisphosphate. The present in vitro results therefore indicate that the diminished extracellular fluid sodium concentration within a range observed in clinical hyponatremic states enhances the vascular action of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggravation of experimental allergic conjunctivitis by environmental chemical and physical factors.

The effects of trichlorfon (DEP, Dipterex, anticholinesterase pesticide) and paraquat dichloride (Gramoxon, inhibitor of superoxide dismutase) on passive anaphylactic reaction in guinea pig conjunctiva using Japanese cedar pollen were quantitatively studied. For estimation of allergic conjunctivitis, Evans blue after i.v. injection was extracted from conjunctiva and measured spectrophotometrically. Allergic conjunctivitis was apparently aggravated by extremely low dosages of organophosphorus pesticide (10(-5) mg/kg) and organochlorine herbicide (10(-4) mg/kg). The aggravation of allergic conjunctivitis was also observed after exposure to cathode ray tubes used in commercial television, possibly due to electromagnetic waves. IgE-mediated allergic reaction could be non-specifically potentiated by such environmental factors.

Functional electrical stimulation (FES) systems for restoration of motor function of paralyzed muscles--versatile systems and a portable system.

Multichannel functional electrical stimulation (FES) systems were developed to restore the motor functions of the paralyzed muscles, i.e. two kinds of versatile systems for laboratory use and a practical portable system were developed. The first microcomputer-based FES system was composed of an 8 bit microcomputer (PC-8801mkII) with a voice recognition board and 30 stimulation outputs, in which the voice commands were used for selecting a motion pattern, and for executing (start), (hold), (restart) and (stop) commands. In combination with the voice commands, a proportional control command detected from a head angle sensor was used for volitional control of motion. The second microcomputer-based FES system was composed of a 16 bit microcomputer (PC-9801 UV or compatible) with flexible control capabilities (e.g. respiratory sensors) for volitional control and with 64 stimulation outputs. An originally designed practical portable FES system was 89 x 145 x 31 mm in dimension and 380 g in weight. This paper describes the system configurations, the control methods of these FES systems and three examples of the clinical applications of the FES systems.