Double ventricular response by a single ventricular extrastimulus to the inner loop of reentry in a patient without apparent heart disease.

In a patient without apparent heart disease, a ventricular extrastimulus delivered from the left ventricular apex where the electrogram was recorded 30 ms after the onset of the QRS complex during VT advanced the second QRS complex, but not the first QRS complex. The morphology of the second QRS complex was the same as that of VT. The postpacing interval was the same as the cycle length of the VT. These findings indicated that the site of stimulation was at the inner loop of the reentry circuit of the VT. A ventricular extrastimulus with a shorter coupling interval advanced the first and second QRS complexes, indicating that the ventricle was activated by antidromic and orthodromic activation from the extrastimulus. Radiofrequency ablation at that site of stimulation terminated the VT and no further VT could be induced.

Short tone burst-evoked myogenic potentials on the sternocleidomastoid muscle: are these potentials also of vestibular origin?

OBJECTIVES: To show that short tone bursts (STBs) evoke myogenic potentials from the sternocleidomastoid muscle (SCM) that are of vestibular origin. DESIGN: Evoked potential activity was recorded from the SCMs of normal volunteers and from patients with vestibulocochlear disorders. SETTING: This outpatient study was conducted at the Department of Otolaryngology, University of Tokyo, Tokyo, Japan. SUBJECTS: Nine normal volunteers and 30 patients (34 affected ears) with vestibulocochlear disorders were examined. INTERVENTION: Diagnostic. OUTCOME MEASURES: Sound-evoked myogenic potentials in response to STBs were recorded with surface electrodes over each SCM. Responses evoked by STBs in patients were compared with responses evoked by clicks. RESULTS: In all normal subjects, STBs (0.5, 1, and 2 kHz) evoked biphasic responses on the SCM ipsilateral to the stimulated ear; the same was true for clicks. Short tone bursts of 0.5 kHz evoked the largest responses, while STBs of 2 kHz evoked the smallest. In patients with vestibulocochlear disorders, responses to STBs of 0.5 kHz were similar to responses evoked by clicks. Thirty (88%) of the 34 affected ears demonstrated the same results with 0.5-kHz STBs and with clicks. Responses were present in patients with total or near-total hearing loss and intact vestibular function. Conversely, patients with preserved hearing but with absent or severely decreased vestibular function had absent or significantly decreased myogenic potentials evoked by STBs. CONCLUSIONS: Short tone bursts as well as clicks can evoke myogenic potentials from the SCM. Myogenic potentials evoked by STBs are also probably of vestibular origin.

Isolation of peptides from an enzymatic hydrolysate of food proteins and characterization of their taste properties.

Soybean protein, casein, bonito protein and chicken protein, each as foodstuff protein, were hydrolyzed with four proteinases; namely, pepsin, trypsin, alpha-chymotrypsin and bromelain. Since the chicken protein hydrolysate with bromelain possessed the most favorable umami taste, eleven peptides were isolated from the chicken protein hydrolysate by successive chromatography on ODS, Amberlite IR-120B, Amberlite IRA-410 and AG-50W; their structures were Asp-Ala, Asp-Val, Glu-Glu, Glu-Val, Ala-Asp-Glu, Ala-Glu-Asp, Asp-Glu-Glu, Asp-Glu-Ser, Glu-Glu-Asn, Ser-Pro-Glu, and Glu-Pro-Ala-Asp. Many of them did not show any umami taste by themselves, but Glu-Glu, Glu-Val, Ala-Asp-Glu, Ala-Glu-Asp, Asp-Glu-Glu, and Ser-Pro-Glu were recognized to enhance the umami taste of 0.02% 5'-inosine monophosphate (IMP). A combination of these peptides, especially 0.5% each of Glu-Glu, Glu-Val, Asp-Glu-Glu and Glu-Glu-Asn, with 0.02% IMP produced a delicious "full" umami taste.

Vestibular evoked myogenic potentials in acoustic tumor patients with normal auditory brainstem responses.

In order to clarify the utility of the vestibular evoked myogenic potential (VEMP) in detecting acoustic tumors, we report two patients who were found to have normal auditory brainstem responses (ABRs) and abnormal VEMPs. To record VEMPs, electromyographic responses to brief loud clicks (0.1 ms at 95 dBnHL) were amplified and averaged on the sternocleidomastoid muscle ipsilateral to the stimulated side. The stimulation rate was 5 Hz and the analysis time 50 ms. The first case was a 54-year-old woman in whom VEMPs were absent on the affected side while caloric tests and ABRs were normal. The second case was a 58-year-old woman whose VEMPs were absent on the affected side while caloric tests revealed a 22% canal paresis and normal ABRs. These results and previous studies suggested that the VEMP could reflect a function different from those evaluated by the ABR or the caloric test. We concluded that the VEMP can provide useful information in diagnosing acoustic tumors.

Effects of dantrolene sodium on progression of left ventricular hypertrophy induced by pressure overload in rats.

We studied the long-term effects of dantrolene sodium (D), a specific sarcoplasmic reticulum (SR) Ca2+-release inhibitor, on the progression of left ventricular pressure-overloaded hypertrophy in rats. We treated abdominal aorta-constricted rats with one of two doses of D for 4 weeks. The extent of hypertrophy was expressed as the ratio of left ventricle to body weight. Hemodynamic parameters were measured by using a microtip catheter manometer. Although a low dose of D (500 mg/L in drinking water) decreased blood pressure to normal levels, the progression of cardiac hypertrophy was not inhibited. In contrast, a high dose of D (5 mg/kg, i.p.) also reduced blood pressure and inhibited the progression of cardiac hypertrophy. Dantrolene sodium had no effect on cardiac function in sham-operated rats. Thus control of Ca2+ release from the SR might be crucial in regulating the progression of cardiac hypertrophy, the final mediator possibly being intracellular Ca2+ concentration.

Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC), cardiac troponin T (cTnT), alpha-tropomyosin (alpha TM), cardiac myosin binding protein C (cMBPC), ventricular myosin essential light chain (vMLC1) and ventricular myosin regulatory light chain (vMLC2) genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients. Family studies showed that an Arg145Gly mutation was linked to HCM and a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnI is the seventh HCM gene.

Effects of a platelet activating factor antagonist on oedema formation following burns.

Deep dermal burns covering 30 per cent of the total body surface area were prepared by immersing the backs of rabbits in hot water at 80 degrees C for 20 s, to determine whether platelet activating factor (PAF) was involved in the onset of oedema following burns and to evaluate the effect of TCV-309, a potent PAF antagonist. The PAF antagonist, which was infused soon after the burn, blocked oedema formation in the wound and significantly (P < 0.001) inhibited PAF increase (P < 0.05) in the damaged tissue in a dose-dependent manner. This was confirmed by immunohistochemistry. In contrast, the superoxide dismutase content in the group treated with a high dose of TCV-309 was significantly (P < 0.01) higher than that of the control group. These findings suggest that administration of large doses of a PAF antagonist immediately after injury prevents oedema of burn wounds and the subsequent onset of burn shock by suppressing PAF and superoxide radical formation.

The influence of severe bone loss on mitral annular calcification in postmenopausal osteoporosis of elderly Japanese women.

We assessed the influence of aging bone calcium metabolism on mitral annular calcification (MAC) and aortic valve calcification (AVC) in 239 septua- and octogenarians (62 men, 177 women; 80.2 +/- 4.4 years). Osteoporosis was diagnosed by vertebral bone fracture. Both MAC and AVC were derived by 2-dimensional echocardiography. Bone mineral content (BMC) of the lumbar vertebral body was obtained by single-energy quantitative computed tomography using a calibration phantom. Serum calcium, phosphorus, parathyroid hormone, calcitonin, and osteocalcin were examined. Patients were classified into 3 age-matched groups in each sex: Group-C included patients with MAC (-) and AVC (-) (n = 96); Group-A was those with AVC (+) and MAC (-) (n = 80); Group-M consisted of those with MAC (+) and AVC (-) or AVC (+) (n = 63). Osteoporosis-frequency and BMC in women were significantly higher (p < 0.01) and lower (p < 0.001) respectively than those in men. Among men, osteoporosis-frequency and BMC showed no difference between the 3 groups. Among women, osteoporosis-frequency (52%) and BMC (32 +/- 23 mg/cm3) in Group-M were higher (NS) and significantly less (p < 0.01) than those (37%, 49 +/- 36) in Group-C, respectively. In both sexes, serum examinations revealed no differences between the 3 groups. These results suggest that: 1) MAC in elderly women can be attributed to ectopic calcium deposits, related to the severe bone loss caused by postmenopausal osteoporosis; 2) there is no significant relationship between the incidence of MAC or AVC and the humoral factors of calcium metabolism; and 3) AVC may be mainly caused by pressure or stress loading.

Hyperkalaemia with renal tubular dysfunction by sulfamethoxazole-trimethoprim for Pneumocystis carinii pneumonia in patients with lymphoid malignancy.

Hyperkalaemia with renal tubular dysfunction by oral therapy of sulfamethoxazole-trimethoprim (co-trimoxazole) is described in 2 elderly Japanese patients with lymphoid malignancy, who developed Pneumocystis carinii pneumonia and improved. A high dose of cotrimoxazole induced hyperkalaemia with the elevation of serum creatinine and blood urea, and increased urinary N-acetyl glucosaminase after several days of the drug administration in these patients; one patient became unconscious. Discontinuation of co-trimoxazole normalized serum potassium level and symptoms. A repeated low dose of the drug induced hyperkalaemia. Before the treatment of co-trixomazole, their serum levels of creatinine showed upper limits of normal ranges. In the present study, our cases suggested that patients receiving a high dose of co-trimoxazole should be evaluated for these potential complications during a course of treatment, particularly in elderly patients with preexisting renal dysfunction.

Inhibitory effect of dietary iron deficiency on the induction of putative preneoplastic foci in rat liver initiated with diethylnitrosamine and promoted by phenobarbital.

The effects of dietary iron deficiency on induction of putative preneoplastic, gamma-glutamyltransferase (GGT)-positive hepatocyte focal lesions in the liver of rats treated with diethylnitrosamine (DEN) followed by phenobarbital (PB) were investigated. Male Fischer 344 rats of 4 weeks old were placed on an iron deficient (ID) diet containing less than 5 p.p.m. of iron or an iron supplemented (IS) diet containing 180 p.p.m. of iron throughout experimental period of 12 weeks. Both groups of rats were administered 200 mg kg-1 body weight of DEN by a single intraperitoneal injection at Week 4 followed by PB mixed into each diet at a concentration of 0.05% from Week 6 to the final sacrifice at Week 12 when induction of GGT-positive foci was quantitatively analysed. On the ID and IS diets, respective numbers of GGT-positive foci were 6.3 and 14.2 cm-2. The sizes of foci were not altered by the iron content of the diet. The present results indicate that iron plays a role in the development of preneoplastic foci in the livers of rats initiated with DEN and promoted by PB especially in the initiation phase.

[Hypothalamic GH Deficiency and gelastic seizures in a 10-year-old girl with MELAS].

A case of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes, in which a pituitary growth hormone (GH) secretion deficiency of hypothalamic origin was revealed through neuro-endocrinological examinations, was described. The case was a 10-year-old girl, who had been suffering from generalized tonic seizures since age 5, four episodes of alternating hemiplegia since age 6, stunted growth since age 7, and simple partial motor seizures as well as gelastic seizures since age 8. Marked elevation of lactate and pyruvate in both serum and CSF, abundant ragged red fibers in biopsied muscle, and low density areas in the left occipital lobe and bilateral globus pallidus in addition to diffuse brain atrophy on CT scan and MRI of the head were demonstrated, although the activities of muscle enzymes complex I-IV were within normal ranges. Pituitary GH secretion was deficient under the loadings with insulin, L-DOPA, sleep, and a single growth hormone releasing factor (GRF) administration, but normal GH response was registered under the repetitive stimulation with GRF. Activities of other hormonal axes were normal. It is likely that short stature commonly observed in MELAS patients is due to hypothalamic dysfunction, which might be brought out by chronic ischemia and energy deficiency of the diencephalon based upon mitochondrial abnormality of that region. It is likely that gelastic seizure in this case is due to hypothalamic dysfunction.

Antitumor effect of forphenicinol, a low molecular weight immunomodifier, on murine transplantable tumors and microbial infections.

The antitumor activities of forphenicinol against murine transplantable tumors were examined. Ehrlich carcinoma was suppressed by treatment with 0.08 approximately 0.31 mg/kg/day of forphenicinol given for 10 days starting 5 days after tumor inoculation. IMC carcinoma was also suppressed by treatment with 0.5 approximately 5 mg/kg/day given for 5 days starting 8 days after the inoculation. The antitumor activity was dependent on the number of tumor cells inoculated, schedule of administration and dose. However, even in case of fast growing tumors such as L1210 and inoculation with a large number of tumor cells, forphenicinol markedly enhanced the antitumor effect of 6-mercaptopurine, aclacinomycin and cyclophosphamide. Forphenicinol showed a protective effect on Pseudomonas infection in mice.

Correlation between serum dopamine-beta-hydroxylase activity and dopamine-beta-hydroxylase and tyrosine hydroxylase activities in central and peripheral adrenergic neurons and adrenal glands.

Serum dopamine-beta-hydroxylase activity in spontaneously hypertensive rats and Wistar-Kyoto rats had a positive correlation with dopamine-beta-hydroxylase and tyrosine hydroxylase activities in mesenteric vessels, vas deferens, and adrenal glands at 14-16 weeks of age, a negative correlation with dopamine-beta-hydroxylase activity in locus coeruleus at 3 weeks and 14-16 weeks of age, and a positive correlation with tyrosine hydroxylase activity only at 3 weeks of age, but not at 14-16 weeks of age.