Increased exhalation to inhalation ratio during breathing enhances high-frequency heart rate variability in healthy adults.

Heart rate variability (HRV) is a well-established surrogate of cardiac and emotional health that reflects the balance between sympathetic and parasympathetic activity of the autonomic nervous system. We examined the impact of manipulating exhalation to inhalation ratio (E:I) on HRV, without altering the intrinsic breathing rate of healthy individuals. We hypothesized that a longer exhalation relative to inhalation (E:I > 1) would shift HRV metrics in a direction consistent with increased parasympathetic activity. Twenty-eight individuals (16 young [6M, age = 21-28];12 older adults [6M, age = 66-80]) completed a task during which they paced breathing according to their intrinsic respiratory rate, but altered onset of exhalation and inhalation according to 1:1 sound cue (equal exhalation and inhalation duration) or 2:1 cue (exhalation twice as long as inhalation). Paced 1:1 breathing followed these task conditions to examine residual effects. Estimates of actual E:I ratio based on thoracic movement were 1.08(0.16) for 1:1 task and 1.33(0.20) for 2:1 task, which were significantly different from one another. HRV metrics derived from electrocardiogram included root mean square of the successive differences between normal heartbeats (RMSSD) and high-frequency (HF) HRV. Analyses of HRV metrics by block showed that RMSSD and HF-HRV were higher in the 2:1 task condition compared to 1:1. Time series analysis showed that HF-HRV increased after the end of the 2:1 task block and remained elevated for four minutes. These findings suggest that longer duration of exhalation relative to inhalation, without altering breathing rate, acutely increased RMSSD and HF-HRV, consistent with enhancement of cardiac vagal tone.

Electron transport in the membrane of lutoids from the latex of Hevea brasiliensis.

1. An antimycin-insensitive NADH-cytochrome c oxidoreductase (E.C. 1.6.99.3) activity can be demonstrated in the membrane of lutoids isolated from the latex of Hevea brasiliensis. This electron transport system can also use ferricyanide as an electron acceptor, but is unable to oxidize NADPH. 2. Two beta-type cytochromes are present in the membranes. Cytochrome beta563 is partially reduced by NADH and ascorbate, but is not reducible by NADPH. It shows a double peak at 555 and 561 nm at 77 degrees K. A second cytochrome, cytochrome beta561, seems to be reducible by hydrosulfite only. 3. In the reduced state, these cytochromes do not combine with CO. The occurrence of cytochrome P-450 could not be demonstrated. 4. The role of the NADH oxidation system is considered in relation to the biosynthesis of polyisoprene compounds in the latex.

High-dose carboplatin and recombinant granulocyte-macrophage colony-stimulating factor in advanced-stage recurrent ovarian cancer.

PURPOSE: We investigated whether carboplatin myelosuppression could be favorably modulated by the administration of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in patients with advanced-stage ovarian cancer. PATIENTS AND METHODS: Thirty-four patients with advanced-stage recurrent ovarian cancer were treated with high-dose carboplatin (800 mg/m2 per 35-day cycle) and rGM-CSF. rGM-CSF was administered as a daily subcutaneous injection starting 72 hours after the carboplatin dose and continuing until 7 days beyond the WBC nadir. rGM-CSF was administered in a phase I fashion. Seven patients were treated at an rGM-CSF dose of 3 micrograms/kg, 11 at 5 micrograms/kg, 10 at 10 micrograms/kg, and six at 20 micrograms/kg. RESULTS: rGM-CSF-related toxicities that were not dose-related included nonneutropenic fever, rib pain, acute hypersensitivity reaction, and pericarditis. At the rGM-CSF dose of 20 micrograms/kg, debilitating malaise was seen in four of six patients and this was the dose-limiting toxicity. Patient tolerance of the 3-micrograms/kg and 5-micrograms/kg doses was good, but tolerance was limited for the 10-micrograms/kg dose. Febrile neutropenia was seen in four of seven patients at 3 micrograms/kg, two of 11 at 5 micrograms/kg, two of 10 at 10 micrograms/kg, and one of six at 20 micrograms/kg. Cumulative carboplatin myelotoxicity was blunted only in respect to WBC count, and not for platelets or RBCs. Gastrointestinal bleeding was seen in seven patients. The administered dose-intensity of carboplatin averaged 134 mg/m2/wk for the cohort, or 670 mg/m2 per 35-day cycle. There were two clinical complete responses and eleven partial responses, for a response rate of 38%. CONCLUSION: rGM-CSF appears to be effective and tolerable at 5 micrograms/kg/d administered subcutaneously, if given with carboplatin doses up to approximately 600 mg/m2 over 35 days. The use of rGM-CSF with high-dose carboplatin is associated with a substantial response rate in poor-prognosis ovarian cancer patients.

Purification and Characterization of Phosphoribosylpyrophosphate Synthetase from Rubber Tree Latex.

Phosphoribosylpyrophosphate synthetase (PRS; EC 2.7.6.1) from Hevea brasiliensis Mull. Arg. latex was located in the cytosol. After purification, its apparent molecular weight under nondenaturing conditions was estimated at 200,000 [plus or minus] 10,000; a single band at 57,000 [plus or minus] 3,000 was detected after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme seemed to be a homotetramer. Its affinity constants were estimated at 200 [plus or minus] 30 [mu]M for adenosine triphosphate and 40 [plus or minus] 2 [mu]M for ribose-5-phosphate. The purified enzyme proved to be functional in a paraphysiological medium (cytosol deproteinized by ultrafiltration). Optimum pH was 7.5 in buffer and 6.5 in a paraphysiological medium. No PRS activity was detected in the absence of the Mg2+ ion. Of the numerous compounds tested, only Mn2+, phosphoribosylpyrophosphate, and inorganic phosphate affected the enzymatic reaction. Mn2+ (inhibitor constant = 20 [mu]M) and phosphoribosylpyrophosphate (inhibitor constant = 30 [mu]M) were inhibitors. PRS responded allosterically (Hill's coefficient = 2.3) to ribulose-5-phosphate in the presence of a physiological concentration of inorganic phosphate (10 mM). These results are set in the physiological context of laticifers.

Ethylene-Induced Increase in Glutamine Synthetase Activity and mRNA Levels in Hevea brasiliensis Latex Cells.

Ethylene, used as a stimulant of latex production in Hevea brasiliensis, significantly activates the regenerating metabolism within the laticiferous cells. In this context, attention was focused on glutamine synthetase (GS; EC 6.3.1.2), a key enzyme in nitrogen metabolism. A specific and significant activation of the cytosolic glutamine synthetase (GScyt) in the laticiferous cells after ethylene treatment parallels the increase of latex yield. A marked accumulation of the corresponding mRNA was found, but in contrast, a slight and variable increase of the polypeptide level is at the limit of detection by western blotting. The GS response to ethylene might be mediated by ammonia that increases in latex cytosol following ethylene treatment. The physiological significance for such a regulation by ethylene of the GScyt is discussed in terms of the nitrogen requirement for protein synthesis associated with latex regeneration.

Surgical revascularization after fibrinolysis in acute myocardial infarction. Long-term follow-up.

One hundred twenty-eight patients with myocardial infarction who underwent operation for myocardial revascularization and 147 patients who received medical therapy were followed up for up to 6 years: all patients had received treatment with intravenous streptokinase. In the surgical group, 91.5% of the patients had the region related to the infarction revascularized, and in 82.8% of them the mammary artery was used. Statistically significant differences were not detected between the groups according to infarct size, clinical features, and left ventricular ejection fraction. However, there was a higher risk in the surgical group, as compared with that in the medical group, in terms of anatomic characteristics: 99.2% versus 77.1% of the patients showed more than 70% residual obstruction at the "culprit" coronary artery (p < 0.001, 95% confidence interval 14.1% to 30.1%) and 76.8% versus 40.7% showed multivessel coronary disease (p < 0.001, 95% confidence interval 23.7% to 48.5%). In-hospital survival was 95.3% in the surgical group and 89.1% in the medical group (p = 0.096, 95% confidence interval -0.2% to 12.6%). Significantly higher survivals were obtained for the surgical group both during the first (93% +/- 2.3% versus 80.3% +/- 3.3%, p = 0.005) and the sixth (86.4% +/- 3.4% versus 68.4% +/- 4.3%, p = 0.003) year of follow-up. Statistically significant differences were also obtained when in-hospital deaths were excluded. A Cox regression model with 13 variables showed that only age (p = 0.0422) and medical treatment (p = 0.0194) correlated independently with mortality. It is concluded that in this nonrandomized study, operation led to a significantly higher survival both on a medium- and long-term basis, when compared with that obtained for patients receiving medical therapy.

Detection by electron microscopy of a small subband 13q14.11 deletion in an hereditary retinoblastoma.

High-resolution banding, specific for electron microscopy, was applied to chromosomes of synchronized blood lymphocytes obtained from a child with bilateral retinoblastoma. Ultrastructural analysis of the subbands in region q14.1, after synchronization and immunochemical banding, showed that the deletion in the abnormal chromosome 13 corresponds to subband 14.11, thus evidencing that the retinoblastoma gene is located within subband q14.11. This first application to a diagnostic problem of immunochemical banding suggests that, coupled with electron microscopy, this banding provides a higher resolution than that obtained with light microscopy and should be useful to pinpoint important localizations.

Absence of the left pericardium diagnosed by computed tomography.

A case report of left pericardial absence in a 12-year-old boy is described. The suspected diagnosis was not shown either by cross-sectional echocardiography or angiography, but was correctly established by computed tomography (CT), showing the effectiveness of this diagnostic test for diagnosis of pericardial defects.

Transcatheter occlusion of patent ductus arteriosus using coil embolization.

We studied 31 procedures of coil embolization for occlusion of ductus arteriosus, attempted in 29 patients. The mean age was 4.8+/-3.4 years (1-16 years) and the mean diameter of ductus was 1.8+/-0.7 mm (0.8-3.1 mm). Femoral artery approach was used and aortogram in 90 degrees lateral view was performed. Through a Judkin right coronary catheter, the coil was delivered for occlusion of the ductus. In 5 cases, 2 coils were delivered using retrograde and anterograde techniques. Successful placement of coil was accomplished in 29 procedures. Coils 0.038 inch (diameter)-5 cm (length)-5 mm (helical diameter) (Cook, Inc) were used in 16 procedures, coils 0.035 inch-5 cm-5 mm in 9, coil 0.038 inch-8 cm-8 mm in 1, two coils 0.038 inch-5 cm-5 mm in 2, coils 0.038 inch-5 cm-5 mm+0.038 inch-5 cm-8 mm in 1, and 2 coils 0.035 inch-5 cm-5 mm in 2. Aortogram 20 min after the occlusion, showed residual shunt in 9. Coil migration occurred in a ductus type B in the following day. One patient developed severe haemolysis, due to a change in the coil position, 12 h after the procedure. Echodopplercardiogram 4 to 6 h after the procedure showed a residual shunt in 5 patients, 24 h after in 3 and 30 days after, in 1(3.8%). Heparin therapy started 10 days after occlusion of the ductus, caused reappearance of the shunt in 1 patient. This technique is simple and effective, but complications may occur hours or days after successful ductus occlusion.

Acute myocardial infarction treated with intravenous streptokinase: 6-year follow-up.

Our objective was to investigate variables which, although occurring during the acute period, could influence the medium (1st year) and long-term (6th year) survival of infarcted patients. Of a total of 332 patients treated consecutively and prospectively according to the same protocol which included intravenous streptokinase, 305 survived the hospital phase and represent the study population. Mean patient age was 55.6 +/- 10 years and mean follow-up time was 3.33 years, with 1008.59 patient-years. The clinical course of the group was analyzed according to the following variables: left ventricle ejection fraction, hypotension per/peri streptokinase infusion, CK-MB peak, previous myocardial infarction, number of obstructed coronaries, reinfarction, sex, 'definitive' treatment, residual obstruction, age, pain/streptokinase infusion interval, patency of the 'culprit' coronary and infarct location. Overall, patient survival was 93.8 +/- 1.4% during the 1st year and 83.7 +/- 2.6% at the 6th. The following groups showed significantly different (log-rank) survivals: (a) 1st year: 94.6% for absence and 82.6% for presence of reinfarction (P = 0.0451); 97.9% for inferior and 91.4% for anterior infarct location (P = 0.044); 96.4% for ejection fraction > 50% and 90.6% for ejection fraction < or = 50% (P = 0.0187); 96.5% for angioplasty/surgery and 90.1% for clinical treatment (P = 0.0028); 95.5% for absence and 80.6% for presence of previous infarct (P = 0.0001). (b) 6th year: 88.3% for ejection fraction > 50% and 73.9% for ejection fraction < or = 50% (P = 0.028); 87.4% for < or = 65 and 66.4% for > 65 years (P = 0.0114); 89.6% for aggressive and 76.8% for conservative treatment (P = 0.013); 86.6% for absence and 60.7% for presence of previous infarct (P = 0.0009).

The role of antegrade and collateral flow in relation to left ventricular function post-thrombolysis.

UNLABELLED: The aim of the study was to analyze the relationship between antegrade and collateral flow degree to the "culprit" coronary artery, and between both variables and left ventricular systolic function. We analyzed five hundred patients with acute myocardial infarction, treated prospectively and consecutively within 6 h of evolution with intravenous streptokinase. The degree of antegrade (0-3) and collateral blood flow (0-3) were correlated with 18 other variables. RESULTS: (a) By simple regression analysis, antegrade flow degree correlated positively (p < 0.0001), and collateral flow degree negatively (p = 0.0073) with left ventricular ejection fraction; (b) By multiple regression analysis, antegrade flow degree (p = 0.0032), but not collateral flow degree (p > 0.1), correlated independently with left ventricular ejection fraction; (c) In the subgroup of patients with occluded "culprit" coronary artery, the mean ejection fraction was significantly higher for those with collateral flow 3 (60.2% +/- 13.3 in relation to those with collateral flow < 3 (53.9% +/- 13.1, p = 0.032, 95% CI. 11.96 to (0.53%). In conclusion, antegrade coronary flow degree, but not collateral flow degree, correlated significantly and independently with left ventricular ejection fraction. However, in the subgroup of patients with occluded "culprit" coronary artery, collateral flow 3 led to better left ventricular systolic function, in relation to collateral flow < 3.

Clinical and laboratory signs of reperfusion: are they reliable?

We studied 101 patients (88 men and 13 women, mean age 54.5 +/- 10 years) who arrived at the hospital during the first 6 hours of acute myocardial infarction evolution. Our objective was to assess the reliability of clinical and laboratory signs of recanalization using intravenous streptokinase as a thrombolytic agent. The mean time between the beginning of infusion and coronary arteriography was 53.83 +/- 43 hours. The positive predictive values for pain, arrhythmia, ST segment and enzymes were 97.9%, 94.2%, 91.8% and 90.8%, respectively; the negative predictive values were 46.8%, 40.8%, 37.2%, and 50% in the same order. Sensitivity was 65.7%, 62.8%, 58.4% and 77.6% and specificity 95.6%, 86.9%, 82.6% and 73.9%, respectively. The positive predictive value, calculated on the basis of the presence of each variable alone or in association showed a probability of recanalization of 76.9% for one sign, 84% for two, 96.3% for three and 100% for all four. When we compared the positive predictive values of each variable according to the interval between the beginning of pain and admission to the hospital (during the first 3 hours or between 3 and 6 hours) our results were 100%/94% for pain (P = NS), 97%/88% for arrhythmia (P = NS), 100%/75% for ST segment (P = 0.004), and 97%/80% for enzymes (P = 0.019). The same analysis applied to negative predictive values showing 22%/62% (P = 0.007), 17%/55% (P = 0.008), 21%/47% (P = NS), 27%/61% (P = NS) for pain, arrhythmia, ST segment and enzymes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Pheochromocytoma with echocardiographic features of obstructive hypertrophic cardiomyopathy. A case report.

The authors report a case of pheochromocytoma in which the echocardiographic features suggested obstructive hypertrophic cardiomyopathy. The angiographic study and the computed tomography showed the tumor and its arterial supply. One month after resection of the tumor the echocardiographic features showed a tendency to normalization. The preoperative echocardiographic aspect was probably due to excessive production of catecholamines by the tumor.

Progressive-addition lenses in the management of esotropia with a high accommodation/convergence ratio.

In 25 children esotropia due to abnormal synkinesis between accommodation and accommodative convergence was corrected with progressive-addition lenses. Twelve of the children had been wearing conventional bifocals; the other 13 were given progressive lenses for the first time. The near esodeviation was satisfactorily neutralized in most cases, and nearly all the children had some stereopsis. All adapted well and without difficulty to the progressive lenses.

Preschool vision testing with a new device, the Scolatest.

To determine the reliability of results obtained in preschool children by school nurses with a new device for testing vision, the Scolatest, 153 children aged 4 to 5 years were presented with the Snellen E on the standard American Optical projector and with five letters of the Sheridan test (H, O, V, T and X) on the Scolatest. Another 212 children aged 3 to 4 years were presented with the Allen symbols on the projector and with the Pigassou symbols on the Scolatest. The tests with the projector were given at 6 m by an experienced pediatric orthoptist, those with the Scolatest at 2.5 m by a school nurse. The proportion of good responses was higher with the Pigassou symbols than with the Allen symbols. The results with the Sheridan letters and the Snellen E were similar up to 20/30; beyond 20/30 the Snellen E appeared unreliable. The four vision-testing systems were also presented by a school nurse at 2.5 m on the Scolatest to 102 children aged 4 to 5 years (Snellen E and the five Sheridan letters) and 80 children aged 3 to 4 years (Allen and Pigassou symbols). The proportions of good responses were more comparable. The results suggest that a working distance of 2.5 m should be used in testing vision in preschool children. Visual screening at this distance should test acuity beyond the 20/30 equivalence if results comparable to those at 20 feet with the 20/30 standard requirement are to be obtained.

Trilateral retinoblastoma: bilateral retinoblastoma with pinealoblastoma.

Bilateral retinoblastoma was diagnosed in a 12-month-old boy. The left eye was enucleated; the choroid and the optic nerve were not invaded by the tumour. The right eye had three lesions: one was photocoagulated, and the other two were irradiated. Two years later, symptoms and signs of intracranial hypertension prompted computerized tomography, which demonstrated a mass in the pineal region and secondary hydrocephalus. The right eye showed papilledema but no evidence of tumour activity in the three retinal scars. Radiation therapy and chemotherapy had only a transient effect, and the child died at 42 months of age. At autopsy the pineal region and the third ventricle were found to be replaced by a pinealoblastoma with retinomatous differentiation. Only 11 other cases of pinealoblastoma associated with bilateral (heritable) retinoblastoma have been reported. The embryologic relationship between the pineal gland and the retina has given rise to the concept of trilateral retinoblastoma, a concept important in the investigation and follow-up of patients with bilateral retinoblastoma.

Ocular manifestations of Kawasaki disease (mucocutaneous lymph node syndrome).

This paper describes nine patients, five girls and four boys aged 4 months to 7 years (mean 3 3/4 years), who had the clinical and laboratory features of Kawasaki disease (mucocutaneous lymph node syndrome). Eight of them had mild to moderate anterior uveitis, and one child showed choroidal, retinal and vitreous changes in one eye that caused a severe visual loss. Recognition of this disease is important, particularly since 1% to 2% of patients under 2 years of age die suddenly from coronary arteritis.

The oculocardiac reflex in strabismus surgery.

During strabismus surgery on 81 extraocular muscles in 49 children the cardiac response to calibrated traction on each of the muscles operated on was studied through the use of a microdisplacement transducer and the tachometer of a cardiac monitor. There was no significant difference in the frequency of induction of the oculocardiac reflex between the medial rectus and the other muscles or between the two eyes. However, quick traction provoked a reflex in 87% of instances, whereas progressive traction did so in only 51% of instances, a significant difference (p less than 0.05). Thus, because the oculocardiac reflex is frequent during strabismus surgery, cardiac monitoring during the operation and minimal, gentle manipulation of the extraocular muscles are important.

Corrected transposition of the great arteries with several associated anomalies in a 68-year-old patient.

Few patients with corrected transposition of the great arteries survive past 50 years of age because of the association with congenital defects, development of total atrioventricular block, and right ventricular dysfunction. We report the case of a male patient with dextrocardia in situs solitus and corrected transposition of the great arteries associated with a wide atrial septal defect and severe pulmonary valvar and subvalvar stenoses. The patient also developed a large aneurysm on the pulmonary artery, total atrioventricular block diagnosed 8 years earlier, symptoms of dysfunction of the systemic ventricle in the previous 2 years, insufficiency of the left atrioventricular valve, and aortic regurgitation. Despite all these associated anomalies, the patient developed class III cardiac decompensation only at the age of 68 years, which makes this case a rarity. The patient was clinically treated, and was discharged from the hospital in good condition.

Pompe's disease or type IIa glycogenosis.

This is the report of a five-month-old child presenting clinical evidence of Pompe's disease: severe hypotonicity, hyporeflexia and congestive heart failure. The ECG showed a short PR interval, the chest radiography disclosed marked cardiomegaly, and the echocardiogram revealed marked left ventricular hypertrophy - the most typical finding of this disease. A skeletal muscle biopsy led to final diagnosis, because in the histopathologic study marked increased glycogen accumulation was evident. Death occurred two months after symptom onset.