The use of spectral methods in bidomain studies. A Fourier transform method is developed for solving the bidomain coupled differential equations governing the intracellular and extracellular potentials on a finite sheet of cardiac cells undergoing stimulation. The spectral formulation converts the system of differential equations into a "diagonal" system of algebraic equations. Solving the algebraic equations directly and taking the inverse transform of the potentials proved numerically less expensive than solving the coupled differential equations by means of traditional numerical techniques, such as finite differences; the comparison between the computer execution times showed that the Fourier transform method was about 40 times faster than the finite difference method. By application of the Fourier transform method, transmembrane potential distributions in the two-dimensional myocardial slice were calculated. For a tissue characterized by a ratio of the intra- to extracellular conductivities that is different in all principal directions, the transmembrane potential distribution exhibits a rather complicated geometrical pattern. The influence of the different anisotropy ratios, the finite tissue size, and the stimuli configuration on the pattern of membrane polarization is investigated.


Finite element methods for the biomechanics of soft hydrated tissues: nonlinear analysis and adaptive control of meshes. This chapter addresses computationally demanding numerical formulations in the biomechanics of soft tissues. The theory of mixtures can be used to represent soft hydrated tissues in the human musculoskeletal system as a two-phase continuum consisting of an incompressible solid phase (collagen and proteoglycan) and an incompressible fluid phase (interstitial water). We first consider the finite deformation of soft hydrated tissues in which the solid phase is represented as hyperelastic. A finite element formulation of the governing nonlinear biphasic equations is presented based on a mixed-penalty approach and derived using the weighted residual method. Fluid and solid phase deformation, velocity, and pressure are interpolated within each element, and the pressure variables within each element are eliminated at the element level. A system of nonlinear, first-order differential equations in the fluid and solid phase deformation and velocity is obtained. In order to solve these equations, the contributions of the hyperelastic solid phase are incrementally linearized, a finite difference rule is introduced for temporal discretization, and an iterative scheme is adopted to achieve equilibrium at the end of each time increment. We demonstrate the accuracy and adequacy of the procedure using a six-node, isoparametric axisymmetric element, and we present an example problem for which independent numerical solution is available. Next, we present an automated, adaptive environment for the simulation of soft tissue continua in which the finite element analysis is coupled with automatic mesh generation, error indicators, and projection methods. Mesh generation and updating, including both refinement and coarsening, for the two-dimensional examples examined in this study are performed using the finite quadtree approach. The adaptive analysis is based on an error indicator which is the L2 norm of the difference between the finite element solution and a projected finite element solution. Total stress, calculated as the sum of the solid and fluid phase stresses, is used in the error indicator. To allow the finite difference algorithm to proceed in time using an updated mesh, solution values must be transferred to the new nodal locations. This rezoning is accomplished using a projected field for the primary variables. The accuracy and effectiveness of this adaptive finite element analysis is demonstrated using a linear, two-dimensional, axisymmetric problem corresponding to the indentation of a thin sheet of soft tissue. The method is shown to effectively capture the steep gradients and to produce solutions in good agreement with independent, converged, numerical solutions.


Glycerol permeability of human spermatozoa and its activation energy. Glycerol has commonly been employed as a cryoprotectant in cryopreservation of human spermatozoa. However, the addition of glycerol into the sperm before freezing and the removal of glycerol from the sperm after freezing and thawing result in anisotonic environments to the cells, which can cause cell injury. To define optimal procedures for the addition/removal of glycerol and to minimize the cell injury, one needs to know the kinetics of glycerol permeation across the sperm plasma membrane at different temperatures. For this, one has to determine the permeability coefficient of glycerol (Pg) and its activation energy (Ea). Values of Pg at different temperatures and at different glycerol concentrations were determined by measuring the time required for 50% spermolysis in hyperosmotic glycerol solutions which were hypotonic with respect to electrolytes. Value of the Ea was determined assuming an Arrhenius type temperature dependence of Pg. A dual fluorescent staining technique (propidium iodide and 6-carboxyfluoroscein diacetate) and flow cytometry were used to measure the spermolysis. The values of Pg in 0.5, 1.0, 1.5, and 2.0 M glycerol at 22 degrees C are 1.62, 1.88, 1.68, and 1.54 x 10(-3) cm/min, respectively. The values of Pg in 1 M glycerol at 0, 8, 22, and 30 degrees C are 0.33, 0.54, 1.88, and 2.60 x 10(-3) cm/min, respectively. The value of Ea is 11.76 kcal/mol.


Deterioration of cold-stored tissue specimens due to lipid peroxidation: modulation by antioxidants at high subzero temperatures. It is often necessary to store tissue specimens in subzero conditions for assay in batches. During storage at -20 degrees C we found that sufficient lipid peroxidation occurred in rat liver homogenates in phosphate-buffered saline to affect subsequent malondialdehyde assays. This peroxidation did not occur at -196 degrees C. The ratio of oxidized to reduced glutathione increased with storage at -20 degrees C and the level of conjugated dienes increased progressively. The addition of a specific free radical scavenger, superoxide dismutase (200 u/ml) reduced the level of malondialdehyde (P < 0.001) during -20 degrees C storage for periods of 28 days but failed to prevent the changes in the glutathione ratio or dienes. Storage in a less specific free radical scavenger, 0.25 molar sucrose/EDTA, instead of phosphate-buffered saline totally prevented the malondialdehyde production over similar storage periods.


Noradrenaline content of the tissue and nerve in the rabbit ear after freezing injury. The aim of this study was to investigate the development of the demarcation line in the rabbit ear upon injury by experimental freezing and thawing. For this purpose the sequential changes in noradrenaline (NA) content in the tissue and nerve of the ear were determined by liquid chromatography. Frostbite was inflicted with a glass bottle filled with liquid nitrogen and specimens were taken from the injured area, the probable demarcation line area and the healthy area 1, 3, and 7 days after frostbite. Control samples were taken from the normal contralateral ear. Tissue NA levels in the injured area and the probable demarcation line area were significantly lower than those in corresponding areas of the control ear after 1 day. Day 3 NA levels in the demarcation line area were 90% higher than those on Day 1 in this area and were not significantly different from Day 3 levels in the control ear. By Day 7, NA levels in the demarcation line area were down to 70% of the Day 3 levels. NA levels in the central nerve at the probable demarcation line were much higher than those in the control ear nerve and also showed a peak on Day 3. In conclusion, the results suggest that NA is released from the adrenergic nerves and the reaction at the probable demarcation line is strongest on the third day.


Acute respiratory failure and ECMO.

Acute respiratory failure and ECMO. In recent years, we have experienced advances in treatments for severe ARDS. One that holds promise for these critically ill adult patients is ECMO, which can provide gas exchange and lung rest for the patient in severe reversible respiratory failure. Advances in ECMO techniques, appropriate patient selection and the development of heparinized tubing will all improve the potential for survival in patients who are placed on ECMO therapy in the future.


Circumcision--an update.

Circumcision--an update. Circumcision will likely continue to be a frequently performed procedure during the neonatal period. Rather than allowing it to be an emotion-laden issue, clinicians should keep abreast of ongoing developments in the field and be able to present thorough, objective counseling. Informed parental refusal requires no less.


Circadian relations among cardiovascular variables of young adults. Every 4 hours for 24 hours, 14 clinically healthy young individuals (6 women and 8 men), 26 +/- 4 years of age, measured systolic (S) and diastolic (D) blood pressure (BP) by sphygmomanometer and heart rate by ECG and did impedance cardiography under usual living conditions. Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were calculated. Time series of SBP, DBP, HR, SV, CO and TPR were analyzed by single and population-mean cosinor. A circadian cardiovascular rhythm is demonstrated by rejection of the zero amplitude assumption in the population-mean cosinor test for SBP, DBP, HR, SV, CO and TPR (P < 0.01). TPR peaks around 0400 (-61 degrees from local midnight), in antiphase with all other variables, their acrophase occurring around 1600 (-240 degrees). A circadian rhythm of statistical significance or of borderline statistical significance is found for all variables except TPR in women. Circadian rhythm characteristics were otherwise mostly similar in men and women with a statistically significant gender difference found by parameter tests only for the MESOR and amplitude of SBP.


Age, gender and circadian or circasemidian blood pressure and heart rate variation of children. Systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) of clinically healthy children (24 boys and 15 girls) 3 to 7 years of age were measured with a standard mercury sphygmomanometer at 3-hour intervals for 24 hours in April 1991. The children slept and/or rested from 2100 to 0700 and napped from 1230 to 1530; they had meals at 0730, 1200 and 1800. A statistically significant circadian and about 12-hour (circasemidian) component of variation is documented for SBP and DBP of boys and girls and for HR of boys. No gender difference was found for the circadian and circasemidian components. A positive correlation with age is found for the MESOR and circadian amplitude of SBP and DBP (p < 0.05); a negative correlation with age is found for the MESOR of HR (p < 0.001).


Rats grouping and the circadian and ultradian synchronization of their carbon dioxide emission by a light-dark 12:12 h alternation. Carbon dioxide emission (VCO2) was continuously recorded during 19 consecutive days in 25 Sprague Dawley young male rats placed in the same "respiratory chamber", grouped by 5 (G) and then separated (S). All rats were in controlled environmental conditions (20 degrees C temperature, humidity, ventilation, food and water ad libitum) and submitted to a light (100 lux)-dark alternation (LD 12:12). The curves obtained with the respiratory chamber CO2 concentration sampled every 20 minutes were analyzed for circadian periods, amplitudes, phases, ultradian peak oscillation intervals and amplitudes, and VCO2 time variations at L-->D and D-->L light transitions. Analysis of variance and t test show circadian amplitudes significantly (P < 0.001) higher (by 40.9%) than in S; moreover, ultradian peak amplitudes were higher in G than in S (by 78.0% in L and 105.8% in D). The circadian and ultradian (tau > 40 min) period intervals were not significantly different in G and in S. Circadian phase differences between L-->D and D-->L were significantly greater in S (by 50.3 min) but not in G. Light transitions did not significantly modify ultradian phases in G and in S. This data shows a better LD 12:12 synchronization in G than in S, resulting mostly from an increased respiratory amplitude modulation due to interindividual interactions.


Age-variant and age-invariant rhythmicities in the cortical and hippocampal electrical activities of neonatal rats. The neocortical and hippocampal electrical activities were studied in 8, 15, 22, and 29-day-old rats. Segments of EEG recorded for 4 hours were analyzed by means of fast Fourier transformation. The sleep-wake activity stages were determined. The developments in the neocortical and hippocampal EEG activities were characterized by the gradual appearance of adult-like EEG waves and a shift towards higher frequencies in the theta wave range of the hippocampal electrical activity. The power value in the theta range, however, exhibited age-invariant rhythmicities with cycle lengths of about 9.5-11 and 16-22 min. The manifestation of such an age-invariant rhythm can be interpreted as an electrical manifestation of the rest-activity cycle originally described by KLEITMAN25.


[Changes in LAK cell activity in chronic viral hepatitis and treatment with autologous LAK cell transfusion]. We investigated the activity of LAK cells in 10 patients with chronic persistent hepatitis, 20 patients with chronic active hepatitis, 21 patients with post-hepatitic cirrhosis and 21 normal persons. The values were 36.87 +/- 7.44, 30.38 +/- 5.36, 28.84 +/- 4.95 and 44.50 +/- 4.75 respectively (P < 0.05). The LAK cell activity in patients with chronic hepatitis was lower than that of normal persons, especially in those with chronic active hepatitis and post-hepatitic cirrhosis. The causes of lower LAK cell activity in patients with chronic hepatitis were less expression of IL2 receptors on precursors of LAK cells and existing serum LAK cell inhibition factors. We further studied 9 patients with chronic hepatitis B treated with autologous LAK cell transfusions. Factors favoring a more effective result were female sex, ALT elevation after treatment, activity of LAK cells > 10%, and inhibition factor of LAK effector cells existing in serum of patients, with inhibition rate < 50%. These factors might be used as the indications in selecting cases for treatment and predicting the effect of the treatment. As the number of cases observed was rather small, further investigation is needed.


[Hepatitis E in Hetian city. Analysis of 562 cases]. Between August and September 1987, 562 patients were hospitalized with acute non-A, non-B hepatitis. The male to female ratio was 1.4:1, and 75% of the patients was of 15-40 years of age. Jaundice developed in 87%. The overall case-fatality rate was 1.4%, but it was highest among pregnant women (5.2%) and newborn infants (24.2%). In general, the disease was self-limited with no evidence of chronic infection. Liver biopsies obtained during the acute illness showed portal inflammation and cytoplasmic cholestasis. Of 31 specimens of stool examined with a prototype ELISA for HEV antigen, 8 were found to be 'positive' and confirmed with immune electron microscopy (IEM). IEM examination of 'patients' stool revealed 27-32 nm viruslike particles. Inoculation of rhesus monkeys with patients stool containing virus-like particles produced acute hepatitis and the acute phase serum reacted with these particles in IEM, while preinoculation serum specimens were non-reactive.


[The determination of serum hepatitis B virus DNA by polymerase chain reaction in hepatitis B patients treated with alpha-interferon]. To clarify the status of HBV in serum of chronic hepatitis B (CHB) patients who were treated with alpha-interferon, we determined the serum HBV DNA before and after treatment in 15 CHB patients with polymerase chain reaction (PCR). Before treatment all the 15 patients were HBsAg and HBeAg positive. HBV DNA was also positive with dot-blot hybridization (DB), PCR, ethidium bromide (PCR-EB) and PCR Southern-blot hybridization (PCR-SBH). HBeAb was negative in all the 15 patients. 12 patients has the determination repeated 2 to 39 weeks after treatment, 7 out of the 12 patients became HBeAg negative and HBV DNA also negative with DB and PCR-EB. However, in 5 of the 7 patients HBV DNA was still positive with PCR-SBH. Seroconversion of HBeAb from negative to positive occurred in 4 of the 12, but HBV DNA of the 4 patients remained positive with PCR-SBH. After an interval of one and half year or more following treatment 12 patients repeated the examination, only 5 of the 12 patients became seronegative for HBeAg and HBV DNA with DB and PCR-EB, but in 4 of the 5 HBV DNA was positive with PCR-SBH. Two of the 5 were seropositive for HBeAb and HBV DNA with PCR-SBH. The mechanism of residual viraemia after alpha-interferon treatment in CHB patients is uncertain.


Circadian variation of abnormal heart beats in an elderly population and their relation to sudden cardiac death. The relationships between the circadian variation of abnormal heart beats and the circadian variation in sudden cardiac death warrant further discussion for the high correlations demonstrated here are difficult to ignore. In the healthy group abnormal beats showed a high correlation of their circadian variation with that of sudden cardiac death which is independent of heart rate. As a result the conclusion that the relationship of the circadian variations of abnormal heart beats and sudden cardiac death is merely dependent on a mutual dependence on activity is not supported here. The present data illustrates a strong association between arrhythmias and sudden cardiac death. The relationship of sudden cardiac death with abnormal heart beats demonstrated here, however, cannot confirm a causal role of the latter on the former for both may be responding to circadian variations of some underlying mechanism such as ischemia. Additionally the population studied here, although relatively comparable in terms of living conditions and other significant factors, was not strictly age-matched with those from the sudden cardiac death study warranting further caution in interpreting the association demonstrated here. The results from the unhealthy group, although somewhat limited, indicate that cardiovascular morbidity may alter the relationship of sudden cardiac death and abnormal heart beats. Such a result could be explained by the presence of other forms of heart disease which could be responsible for sudden cardiac death in the unhealthy group. An interesting question to ask concerning the data presented above is whether or not significant circadian variations in in the frequency of abnormal heart beats could have been demonstrated when exogenous factors such as meal times and activity were altered. The data on in hospital sudden cardiac death indicates that the circadian variation in sudden cardiac death is significantly altered by the radical changes in routine which accompany hospitalization. If the relationship between the circadian variation of sudden cardiac death and abnormal heart beats is as strong as the results presented here indicate, it is likely that the alteration of such exogenous factors would also change the circadian variation of abnormal heart beats. The results of the present study indicate that both the circadian variation in abnormal heart beats, and its relationship to sudden cardiac death, warrant further study.


[Effect of captopril on the exercise performance in patients with congestive heart failure]. We studied the effect of captopril on exercise performance in 30 patients with congestive heart failure using a randomized, double-blind and placebo-controlled method. 4-week captopril treatment can significantly increase the exercise tolerance time and work load, heart function, blood flow in exercising lower limbs as well as oxygen metabolic capacity. However, 3-day captopril treatment had no effect on exercise performance. A significant correlation was found between improvement in exercise performance and the pretreatment level of plasma angiotensin II. The increased levels of plasma prostaglandins E 2 and I 2 after captopril treatment were also correlated with improvement of exercise performance. The results indicated that long-term captopril treatment can increase exercise performance in congestive heart failure by improving both central and peripheral hemodynamics and metabolism. Certain vasomotor or endocrine factor may play a mediate role in the above changes.


[Bronchial carcinoid. A clinical, roentgenological and pathological study of 17 cases]. 17 cases with bronchial carcinoid were reported. 16 cases of them were proved pathologically after pulmonary resection, and the remaining one was confirmed histopathologically through bronchoscopic biopsy. 64.7% was under 40 years of age. The main clinical manifestations were cough, hemoptysis, fever and repeated pneumonitis. In one patient, the carcinoid was associated with Cushing's syndrome. Chest roentgenograms showed lesions centrally located in 12 cases, and peripherally located in 5 cases. Histological examination revealed 15 typical and 2 atypical carcinoid tumors. This disease was usually misdiagnosed as lung cancer, tuberculoma and benign tumors. Chest X-ray examination and fiberoptic bronchoscopic biopsy are helpful to the diagnosis of the disease. Pulmonary resection was performed in 16 cases. Two patients had hilar lymph node metastases, one of them had also involvement of pericardium. There was no operative mortality. In the follow-up study, the disease-free actuarial survival following pulmonary resection was 92.9% at 5 years. 2 patients died. One died of respiratory failure 4 months after pneumonectomy, the other died of pericardium involvement of carcinoid 8 months after operation. Resection is the only effective treatment for bronchial carcinoid.


[Study on anti-histone fraction antibodies in patients with rheumatic diseases]. By using Western blot method, we studied the antihistone fraction antibodies in sera of patients with rheumatic diseases. After analysed with SDS-PAGE, the histone could be separated into H1, H3, H2B, H2A and H4 fractions. The positive rate of anti-histone fraction antibodies was highest (82.1%) in systemic lupus erythematosus (SLE) patients, especially in active stage. In 28 SLE patients, the positive rates of anti-H2B, -H1, -H3, -H2A and -H4 were 78.6%, 60.7%, 50.0%, 35.7% and 7.1% respectively. The results revealed that the determination of anti-histone fraction antibodies was beneficial to the diagnosis of SLE.


[A study on phenytoin pharmacokinetics in 15 patients with refractory epilepsy]. Monitoring of serum concentration and studying of individual clinical pharmacokinetics of phenytoin (PHT) were made in 15 patients with refractory epilepsy who had taken PHT and other antiepileptic drugs for a long time. The results showed that 10 of them were tolerant to PHT and their effective doses were higher than the routine ones; 2 of them showed striking fluctuation of serum PHT concentration within 24 hours; In the remaining patients serum PHT concentration during menstruation was much lower than that during ovulation. According to their different characteristics we gave them reasonable and individualized adjustment in dose and time interval of taking PHT. The seizures of all the patients were controlled satisfactorily. It is suggested that some of the patients with refractory epilepsy may have special PHT pharmacokinetics.


[Clinical and pathological features of type I and III membranoproliferative glomerulonephritis]. Analysis and comparisons were made between the clinical and pathological data obtained from 42 cases of type I and 17 cases of type III membranoproliferative glomerulonephritis (MPGN). It was shown that type I MPGN differed from type III remarkably in following respects: (1) Nephrosis was a salient feature of type III while hypertension, impairment of renal function and hematuria were more common in type I. (2) Pathological glomerular sclerosis, tubular interstitial changes and crescents formation occurred frequently in type I but not in type III. (3) Long term prognosis for type III was much better than type I. It is concluded the type III MPGN is a distinct clinical entity which differs from the classical type I MPGN in many aspects.


[Flow cytometric analysis of bone marrow cell cycles in patients with hematologic diseases]. Cell cycle phases of bone marrow cells from 8 patients with iron deficiency anemia (IDA), 8 aplastic anemia (AA), 30 myelodysplastic syndrome (MDS), 41 acute leukemia (AL) before treatment, 8 acute leukemia in relapse, 17 acute leukemia in complete remission (CR), 12 chronic myelogenous leukemia (CML) and 4 chronic lymphocytic leukemia (CLL) were analysed with flow cytometry. The proportions of phases of S. G2 M in patients with IDA, refractory anemia, and refractory anemia with ring sideroblast were similar to these in normal controls (P > 0.05). However, they were significantly lower in patients with AA, refractory anemia with excess of blast (RAEB) and transformed RAEB than those in normal controls (P < 0.01, respectively), and CML patients than in normal controls (P < 0.05). The S G2M% was apparently higher in patients with CML than that in CLL (P < 0.01). But, there was no difference between in ALL and ANLL (P > 0.05). It was higher in patients with AL in CR and in relapse than AL before treatment (both P < 0.01). It was still lower in the former than that in normal controls. (P < 0.05). The clinical significance of cell cycle status was also discussed in this paper.


[Serum concentrations of amitriptyline and its metabolites and clinical effect in depressive patients]. The serum concentrations of amitriptyline and its 3 metabolites--nortriptyline, 10-hydroxy-amitriptyline and 10-hydroxy-nortriptyline were determined in 18 depressive patients treated with amitriptyline for 6 weeks. The relationships between the serum concentrations and the clinical effects were statistically analyzed and showed significant correlations. The authors suggest that the total TAD serum concentration (280 ng/ml) can be used as the index for clinical efficacy, so far as the above data are concerned.


[A comparative study of rapid and non-rapid cycling types in bipolar affective disorder]. It was a prospective and comparative study on the two types of bipolar affective disorder--rapid cycling (RC) and nonrapid cycling (NRC). Each group contains 51 cases separately. Both of the two types are included in bipolar disorder, so they have a lots in common in respect of clinical phenomenology. But the episode frequency of some patients in RC group is characterized as extremely rapid cycle. And there are more premorbid psychosocial factors in RC group than that in NRC group. In contrast with NRC, the RC is more common in type II bipolar disorder. We think that RC is a clinical subtype in bipolar affective disorder, having a close bearing on type II. For the function of HPT axis, we investigated the premorbid thyroid history and observed its changes, but no abnormal signs were found. Plasma level of TSH was determined among some cases in the two types, all the results are in normal range, and the average level of TSH was not significantly different between the groups.


[A correlative study on post-stroke depression and CT, physical, psychological and social parameters]. 58 acute hospitalized CVD patients were selected as study group. Each patient was administered a series of standardized quantitative measures. As a result, we found a significant difference between hemisphere (L: 55% vs R: 28% P < 0.05), and the difference was result from the highest incidence rate of PSD observed in the left anterior CVD subgroup. Meanwhile, those with left anterior lesion (cortical and subcortical) had the greater severity of depression than any other lesions. A strong negative correlation between the severity of depression and AP% was observed for left CVD group. The result of multiple stepwise regression analysis not only support the notions mentioned above but also shown up that a few factors other than location of the lesion had impact on the PSD. Finally, authors discussed the heterogenous causes of PSD and think probably biological etiology involved in the formation of PSD.


[Active music therapy for senile depression]. 68 cases with senile depression were divided randomly into two groups--test group and control group. Patients of both groups received same antidepressive drugs while for the patients in the test group active music therapy was provided everyday in addition and the course of music therapy was 8 weeks. Patients in the test group showed improvement of their symptoms at the end of first week while most patients in the control group were getting somewhat better at the 3rd-4th week. The effectiveness of combined treatment in the test group is better than that in the control group. Patients in the test group became calm and active and the atmosphere on the ward appeared to be somewhat harmonized so that it was beneficial to the nursing care.


[Comparative studies of brain CT scan in schizophrenia]. CT Scan was undertook to 48 schizophrenics and 30 healthy volunteers. The results revealed that: the incidence rate of CT abnormalities was higher in schizophrenics than in normal control; the incidence rate of CT abnormalities in winter-born schizophrenics was higher than in non-winter-born patients; the incidence rate of abnormalities was higher in familial type schizophrenics than in sporadic type; the incidence rate in negative symptom schizophrenics was higher than in positive symptom patients.


[The patterns of the health care seeking behavior and related factors in the schizophrenic patients]. Three hundreds schizophrenic out-patients, from 6 different socioculture background psychiatric facilities in Hunan were investigated by structured interview with definite schedule. The results show that after the recognition of the problem by decision maker, 45% subjects were delayed at least one month for help-seeking, 61.3% subjects first visited the non-psychiatric agencies, and 74.3% subjects has counselled with non-psychiatric doctors or healers at least one time, especially to the healer providing superstitious or religious therapy. The help-seeking styles mainly attributes to the lower socioeconomic status of the family, inconvenient referral to the psychiatric facilities, especially if the decision maker is a female, rural resided under-educated person knowing nothing of modern psychiatry. Based on these findings, the authors urge to improve scientific psychiatric care knowledge in population, develop the resource of mental health service to facilitate the radical change of help seeking behavior of the population.


[A comparative study on 8 high and low density families of schizophrenia]. The writers select 8 families with high density of schizophrenia from Wuhan local data of psychiatric epidemiology. Among first degree relative of each family there are 3 or more than 3 sufferers. The selection is compared with 8 low density families of schizophrenia chosen by random. The comparison indicates that the total suffering ratio in high density families and their 1st. 2nd and 3rd degree relatives suffering ratio differ notably from the total suffering ratio of the low density families and their corresponding relatives (P < 0.01, respectively). There is also marked difference on the full brother or sister suffering ratio. The ratio of consanguineous marriage, course of illness and prognosis are also different between the high density family group and the low group. The result suggests that the high density group has high heredity- ability. But it is hard to explain the genetic mode through general analytic method. The writers agree with Mr Jiang sanduo's opinion that schizophrenic is a polygenic disease with a major dominant gene.


[A research on near-death experiences of survivors in big earthquake of Tangshan, 1976]. 81 survivors with Near-Death Experiences (NDEs) in a severe earthquake (Tangshan, 1976) were reviewed. Among them 40 NDE phenomena were found and strange bodily sensation, thought unusually vivid, loss of emotions, unusually bodily sensations, life seemed dream, feeling of being dead, feeling of peace or cuphoria, life review or "panoramic memory" and thinking unusually fast comprised more than half of the group. It seemed that our observation was somewhat different from that of pasricha (India) and Greyson. In our series, the survivors with more than 7 scores on Greyson's NDE scale account for 32 cases, and in whom, the cognitive and transcendental types comprise the great part. This findings suggest that the components, sequences and types of NDE might be correlated to races, regions, psychological and cultural backgrounds, and kinds of event.


[Clinical studies of the treatment of hypertensive cerebral hemorrhage by simple serotaxic exsuction]. 51 cases of hypertensive cerebral hemorrhage (Group A) treated with exsuction on the basis of the medical conservative therapy are reported. And meanwhile a control group of 51 cases (Group B) is treated only with conservative therapy. Comparison of the result of these two groups shows that complete absorption of hematoma in Group A appears 2 weeks earlier than that of group B; both the mortality rate and the disability rate are significantly lower in the former. Follow-up study shows that most cases of group A enjoy their lives very well. Indication of exsuction, operation maneuvers, operation methods and the correlation between the volume and site of hematoma and curative effect are discussed.


[Experimental study of erythrocyte deformation]. A laser diffraction system was used to study the deformation of RBC. This work indicated: 1. There was a decreased tendency accompanied with age increased, especially at pre-elderly period. 2. The deformability of patients with acute ischemic stroke was significantly decreased. This result emphasized that DI value should be considered as a peculiar index for diagnosis and treatment. 3. Abnormal calcium accumulation in RBC may play a crucial role in governing RBC deformability. It provided one of the basis of potential therapy of calcium antagonist. 4. The quantitative relation of deformation and SOD activity of RBC need to be researched.


[An experimental study of arginine vasopressin on acute ischemic brain edema in gerbils (1)]. The purpose of this experiments is to study the role of arginine vasopressin (AVP) in acute ischemic brain edema of mongolian gerbils. The results showed that the contents of AVP in ischemic cortex, hypothalamus and striatum increased remarkably in 15-120 minutes after ischemia, while the contents of AVP had no change in pons-medulla which was not affected from ischemia, and there was relationship between the contents of AVP in cortex and the ischemic cortical edema. Intracerebroventricular injection (ICV) of AVP exacerbated the ischemic cortical edema and it showed dose-response correlation. While ICV of AVP antiserum significantly decreased ischemic cortical edema. These suggested that AVP was involved in the pathophysiologic process of acute ischemic brain edema. The increasing of AVP contents in ischemic brain regions could exacerbate the formation of ischemic brain edema.


[Non-activated platelet cytoplasmic ionized calcium in patients with acute ischemic stroke and healthy controls]. Non-activated platelet cytoplasmic ionized calcium was measured in Aequorin-loaded Gel-filtered platelets in 43 patients with acute ischemic stroke and 32 healthy controls. Platelet cytoplasmic ionized calcium is 2,596 +/- 0,674 mumol/L in controls, 3,370 +/- 1,339 mumol/L in the patients with acute ischemic stroke. Platelet cytoplasmic ionized calcium is increased in the stroke patients as compared to controls (P < 0.01). This indicates that there may be a lower threshold in platelet of stroke patient for activation. Moreover, increased platelet cytoplasmic ionized calcium may be a risk factor for thrombus propagation and aggravation of clinical manifestation.


[Diagnostic value of magnetic resonance imaging in multiple sclerosis]. Brain MRI findings in 16 clinical cases of MS were compatible with multiple lesions in the brains in 14 cases. Cerebral lesions were detected in 12 cases without symptoms or signs referable to the cerebral hemispheres. When compared with t*he findings CT scannings, evoked potentials, and oligoclonal bands in the CSF, MRI findings appeared to be the most effective means for confirming the diagnosis of MS, but they would not indicated the course, the times of relapse and the activity of the disease process.


[Factors affecting prognosis of cryptococcal meningitis]. By analyzing 26 cases of clinic data in cryptococcal meningitis. The author found that the poor prognosis in cryptococcal meningitis depends on following factors: 1. younger age of patients, 2. abrupt onset, 3. course prolonged over 6 weeks, 4. complicated extracerebral cryptococcal infections and many underlying disease, 5. used corticosteroids and antibiotics longtime, 6. higher CSF pressure and lower CSF cells count most of which is neutrophilic leukocyte.


[A follow-up study of 420 cases of cerebral cysticercosis]. 420 patients with cerebral cysticercosis, including 97 with intracranial hypertension, were treated by praziquantel 30-50 mg/kg a day, 7-10 days a course. Of the 420 patients, 252, 144 and 24 were treated for one, two and three courses respectively. 1-6 years' follow-up study showed 366 were completely recovered (87.14%) and 399 had effect (95.00%); 12 had inefficacy and 9 died (5.00%). It is believed that the serious acute allergic reactions might be eliminated by "desensitization" of a small dose of praziquantel; intracranial hypertension can be lowered by intrathecal injection of dexamethasone; and ventricular and intra-ocular cysticercosis can also be treated by praziquantel.


Multiple organ failure syndrome.

Multiple organ failure syndrome. Tissue injury, whether from infection, blood or volume loss, trauma, or inflammation such as pancreatitis, induces local and systemic responses. The systemic responses include shock, reperfusion, systemic inflammation (hypermetabolism) with primary organ dysfunction, and secondary organ dysfunction that either becomes progressive and leads to death or from which the patient recovers and enters into a period of prolonged rehabilitation. Each of these responses has its pathogenesis and treatments that are appropriate and effective. The research indicates that the responses may contribute to the development of cell and organ injury and to progressive multiple organ failure syndrome and death, particularly in the case of the systemic inflammatory response. Current therapy is designed to rapidly remove the cause of injury, resuscitate the microcirculation, and institute nutrition therapy to prevent single and generalized nutrient deficiencies and promote repair and healing. Newer therapies are designed to modulate the inflammatory response itself to minimize its injury potential and promote tissue repair and recovery of the patient. Genetic regulation of metabolism is also a pathogenetic mechanism. Its role in these responses is just starting to be understood--new therapies will need to await this understanding. Once the patient begins to recover, rehabilitation tends to be long and problematic. Nonetheless, significant survival rates are now occurring, with continued improvements expected in response to the newer therapeutic approaches. Planned rehabilitation thus becomes an important component of effective recovery. Professionals trained in critical care and well versed in cellular and molecular biology provide the milieu within which continued improvements in prevention, therapy, and outcome will continue to occur.


Insulin autoantibodies in patients with autoimmune diseases. Insulin antibodies (IAA) can be detected in the serum of the majority of newly diagnosed IDDM patients prior to insulin therapy. In first degree relatives of IDDM patients, IAA are associated with an increased risk of development of IDDM. However, the disease specificity of IAA, detected by radiobinding assays, has not been addressed. We thus tested sera from patients with autoimmune disease for IAA. One of 29 (3%) patients with Graves' disease and five of 27 (19%) patients with SLE had IAA levels exceeding the range for normal controls. IAA were not detected in sera from 29 patients with Addison's disease, 15 patients with pernicious anaemia or 10 patients with increased gamma globulins. Non-specific binding of 125I-labelled insulin was increased in serum from 14 (21%) samples from patients with Graves' disease, 10 (37%) patients with SLE, one (3.2%) of 29 patients with Addison's disease and two (13%) of 15 patients with pernicious anaemia. The increased non-specific binding most likely relates to immunoglobulin binding as it was also found in eight of 10 patients with oligoclonal or polyclonal increase in gamma globulins. Our findings suggest that moderate elevations of IAA are not uncommon in patients with SLE, in whom increased non-specific binding of insulin is also common. This observation is of importance in preclinical diabetes screening studies.


Postprandial hypotension in patients with non-insulin-dependent diabetes mellitus. This study attempted to determine whether postprandial hypotension (PPH) is associated with diabetes mellitus by 24-h ambulatory blood pressure monitoring (24-h ABPM) and by monitoring blood pressure during 75-g oral glucose tolerance test (75-g OGTT) in 15 normal subjects and 35 patients with non-insulin-dependent diabetes mellitus. When we defined PPH as a postprandial decrease in systolic blood pressure of greater than 20 mmHg, the incidence of PPH in diabetics was 37% by 24-h ABPM and 20% by 75-g OGTT. The incidence of proliferative retinopathy and proteinuria was greater in diabetics with PPH than in those without PPH. All of the patients with PPH had somatic and autonomic neuropathy. The C-peptide response was lower in diabetics with PPH than in those without PPH. We revealed the presence of PPH in diabetics, and found that PPH was closely related to disease severity, especially diabetic autonomic neuropathy.


Is diabetes always diabetes?

Is diabetes always diabetes? Diabetes is always taken to be a life-long diagnosis. In order to re-examine this question, 75 g glucose tolerance tests (OGTT) were performed twice on 37 previously confirmed diabetic patients (mean duration of diabetes of 4.6 years; range 1-15 years) with normal glycosylated haemoglobin levels on regular review. Weight loss since institution of a healthy diet was 7.6 +/- 4.8 kg (+/- SE). Normal glucose tolerance was found in 27% of patients and impaired glucose tolerance in 21% with no significant change on rechallenge. HbA1 was 6.3 +/- 1.5% (+/- SD) (normal < 7.5%) in patients with normal glucose tolerance compared to 7.0 +/- 0.9% (+/- SD) in those with impaired glucose tolerance, P < 0.05. The response of the OGTT in these patients varied with dietary intake and weight. Such individuals could be regarded as having perfectly controlled diabetes or alternatively to have been cured. The definition of diabetes should be reviewed to allow people to escape the diagnosis where permanent change in dietary habits is established.


Diabetic nephropathy: duplex Doppler ultrasound findings. To evaluate the correlations among Doppler sonographic findings, morphologic sonographic findings, and laboratory findings representing renal functional status, duplex Doppler sonography of the kidney was performed in 32 patients with diabetes mellitus. Resistive indices obtained in the region of the arcuate or the interlobar arteries in patients with elevated serum creatinine levels were significantly higher than those in patients with normal serum creatinine levels (P < 0.05). Also, there was a significant correlation between the resistive indices and creatinine clearance levels (correlation coefficient, -0.828). There was a significant difference between the serum creatinine levels of patients with normal renal cortical echogenicity and those with increased cortical echogenicity (P < 0.05). Analysis of the Doppler spectrum of the intrarenal arteries in conjunction with careful evaluation of the renal cortical echogenicity may be helpful in sonographic prediction of the renal functional status in patients with diabetes mellitus.


Micral-Test: a qualitative dipstick test for micro-albuminuria. Micro-albuminuria is a very sensitive predictor of the development of renal disease in insulin- and non-insulin-dependent diabetes mellitus. A reliable dipstick test for routine screening for micro-albuminuria is, therefore, desirable. Such a test has been developed by Boehringer Mannheim, Germany, and marketed as Micral-Test. It is an immunological slide-test with semi-quantitative properties. To evaluate its performance as a screening test we compared it with a turbidimetric immuno-assay. In 396 urine specimens from 132 patients, sensitivity was 91% and specificity 96% for a discriminating albumin level of 20 mg/l. Correlation with quantitative values was reasonable (r = 0.73). We also tested for micro-albuminuria, defined as mean albumin excretion rate of > or = 20 micrograms/min, determined with the turbidimetric immuno-assay in timed overnight urines on three consecutive days, whereas Micral-Test was considered to be positive for micro-albuminuria if the albumin concentration in one of the three urine samples was > or = 20 mg/ml. In 132 patients, the sensitivity of Micral-Test was 82% and the specificity 86%. Albumin excretion rate in all false-negative results was < 50 micrograms/min. We therefore concluded that Micral-Test is a useful qualitative screening test for micro-albuminuria in diabetic patients.


Possible relevance of lipid peroxidation and thromboxane production to the initiation and/or evolution of microangiopathy in non-hyperlipidemic type 2 diabetes mellitus. To investigate the possible relevance of free radicals and prostanoids to the mode of initiation and/or evolution of microangiopathy in diabetes mellitus, we measured serum lipid peroxides (LPO), an accepted index of intravascular free radicals, and plasma 11-dehydrothromboxane B2 (11-dehydro-TXB2), a stable metabolite of vasoactive thromboxane A2 released from platelets, in 95 patients with normolipidemic type 2 (non-insulin-dependent) diabetes mellitus at different stages of the disease. In general, either LPO or 11-dehydro-TXB2 was significantly greater in the patients, as a group, than in the matched controls (3.82 vs. 2.65 nmol/ml, P < 0.01 for LPO; and 17.3 vs. 5.8 pg/ml, P < 0.01 for 11-dehydro-TXB2). In patients, both LPO and 11-dehydro-TXB2 increased according to the severity of their diabetic retinopathy. A highly significant positive correlation existed between the LPO values and 11-dehydro-TXB2 in the patients (r = 0.64, P < 0.0001), while there was no such relationship in the controls (r = 0.18, P = NS). No difference in serum levels of apolipoproteins A-I, A-II, B, C-II, C-III, or E was observed between the patients and controls. Short-term glycemic control (25 cal/kg of standardized body weight/day, for 8 weeks) resulted in a small but significant reduction in LPO (4.2 vs. 4.6 nmol/ml, control; P < 0.05) without alteration in 11-dehydro-TXB2. There was a tendency towards deterioration in LPO according to the improvement in glycemic control. These results appear consistent with the view that, in addition to LPO, the release of TXA2 from activated platelet in the human circulation could be an important factor for the initiation and/or evolution of microangiopathy in diabetic patients even when they are not apparently hyperlipidemic. Further, the results of the present study emphasize the notion that more tight control of serum lipids is worthy of serious consideration in preventing the advance of diabetic microangiopathy.


Glucagon-glucose (GG) test for the estimation of the insulin reserve in diabetes. The residual B-cell function was examined by means of the plasma C-peptide response 6 min after a combined injection of glucagon and glucose (GG test) or conventional glucagon test (G test) in four insulin-dependent diabetic patients (IDDM group), in 18 diabetic patients treated with insulin (Insulin group), 31 treated with oral hypoglycemic agents (SU group) and 27 treated with diet only (Diet group) and in 22 borderline cases. By GG test, 6-min C-peptide values of the IDDM group were 0.27 +/- 0.05 nM (n = 4) and were significantly lower than those of the Insulin group (0.89 +/- 0.09 nM, n = 12), the SU group (1.42 +/- 0.10 nM, n = 13), the Diet group (2.47 +/- 0.22 nM, n = 11) and the borderline cases (3.38 +/- 0.22 nM, n = 11). Patients with a 6-min C-peptide concentration below 0.75 nM by GG test appeared to be insulin-requiring patients. In the G test, plasma C-peptide concentrations at 6 min were 0.35 +/- 0.08 nM in the IDDM group (n = 2), 0.72 +/- 0.20 nM in the Insulin group (n = 7), 1.08 +/- 0.09 nM in the SU group (n = 20), 1.40 +/- 0.19 nM in the Diet group (n = 17) and 2.05 +/- 0.21 nM in the borderline cases (n = 12). Some of the Diet group patients showed extremely low C-peptide responses. When comparing the GG test and G test in individual cases, a greater C-peptide response was seen with the GG test in all cases except for IDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Low toxic derivatives of istamycin B: synthesis and preliminary evaluation. 3-O-Demethylistamycin B derived from istamycin B was one of the most potent aminoglycoside antibiotics against various bacteria. 3-O-Demethylistamycin B, however, showed considerable acute toxicity in mice. The authors attempted to prepare the derivatives of istamycin B having high potency and low toxicity. The selective N-acylation or N-amidination at the C-2 position of istamycin B could not improve the acute toxicity. The replacement of the amino group at the C-2 position of istamycin B by a hydroxyl group markedly decreased the acute toxicity. Among 2'-deamino-2'-hydroxyistamycins, 4-N-(beta-alanyl)-2'-deamino-3-O-demethyl-2'-hydroxyistamycin B0 (9d) showed good antibacterial activity against Gram-positive and Gram-negative bacteria and a low acute toxicity in mice.


New hydroxybenanomicins produced by Actinomadura. A soil microorganism, Actinomadura sp. MH193-16F4, produces an antifungal antibiotic benanomicin A and several related compounds. Among them, benanomicin A is the best candidate as a chemotherapeutic agent in terms of antifungal activity, toxicity and water-solubility. Three novel hydroxyl congeners, 3'-hydroxybenanomicin A, 7-hydroxybenanomicin A and 7-hydroxybenanomicinone have been isolated from the culture broth of the MH193-16F4 strain or its mutant. Interestingly, 3'-hydroxy-benanomicin A was as effective as benanomicin A, but the 7-hydroxy congeners were inactive. The inactive congeners differ from benanomicin A and 3'-hydroxyenanomicin A in their conformational structures at C-5 and C-6.


The sensitivity of clinical bacteria isolated in Scotland to the oral cephalosporin, cefdinir. The minimum inhibitory concentration (MIC) of cefdinir (CI-983, FK-482), cephalexin cefuroxime, cefixime and ceftazidime were determined against clinical isolates. Cefdinir was as effective as cefixime against Haemophilus and Moraxella (Branhamella) strains and both were more effective than cefuroxime. Against streptococci, cefdinir was much more effective than cefixime and had similar efficacy to cefuroxime. Against staphylococci, cefdinir had the lowest MIC50 of all of the drugs tested. The efficacy of these antibiotics was tested against Escherichia coli K12 strains harbouring 16 of the new extended-spectrum plasmid-mediated beta-lactamases, and cefdinir was more effective than ampicillin, cephalexin, cefuroxime, ceftazidime and aztreonam.


Sub-inhibitory concentrations of brodimoprim inhibit adhesion of E. coli to human uroepithelial cells. Bacterial adhesion to mucosal surfaces is a prerequisite for infection. Several antibiotics at sub-inhibitory concentrations (sub-MICs) have been shown to affect the adhesive ability of bacteria, usually decreasing adherence in vitro. The aim of the present study was to investigate the effect of brodimoprim, a broad-spectrum antibiotic, on E. Coli adhesiveness to uroepithelial cells. Sub-inhibitory concentrations of brodimoprim, up to 1/16 MIC, significantly reduced the percentage of adhesion of E. Coli to epithelial cells. At these concentrations, brodimoprim strongly diminished the adhesiveness of E. Coli, causing the growth of filamentous shapes lacking in pili and therefore unable to adhere to epithelial cells.


Cefaclor as a prophylactic agent for recurrent urinary infections: a comparative trial with macrocrystalline nitrofurantoin. Eighty women with recurrent urinary infections (a median of seven episodes per year) were randomized to twelve months prophylaxis with cefaclor 250 mg or macrocrystalline nitrofurantoin 50 mg, at night. Seventy-three patients (37 given cefaclor and 36 given macrocrystalline nitrofurantoin) were assessable for efficacy. The incidence of radiological abnormalities in the two treatment groups was 23% and 30% respectively. Ninety-five percent of the patients taking cefaclor were symptomatically improved during the twelve months of prophylaxis and 86% remained abacteriuric; corresponding figures in the group taking macrocrystalline nitrofurantoin were 86% and 85% respectively. There were 88 breakthrough infections in patients taking cefaclor (6 resistant strains), and 9 in those patients taking macrocrystalline nitrofurantoin (6 by resistant strains). The mean interval between symptomatic episodes on prophylactic therapy increased by 5.6-fold in patients taking cefaclor, and 4.3-fold in those taking macrocrystalline nitrofurantoin. Resistant coliforms were found in only 3 out of 37 patients studied after twelve months prophylaxis; these organisms did not proceed to cause infections. All 80 patients were assessable for adverse events: 5 out of 39 taking cefaclor (12.8%) reported an event "probably" associated with the antibiotic, and 3 (7.7%) stopped taking the drug for various reasons; corresponding figures for macrocrystalline nitrofurantoin were 17.1% and 9.8% respectively. Patients with a radiological abnormality responded well to long-term low-dose prophylaxis with either agent. Cefaclor seems to offer an alternative to macrocrystalline nitrofurantoin for the prophylaxis of recurrent urinary infections in women.


Effects of bezafibrate on biosynthesis of cholesterol and on degradation of native and acetylated low-density lipoproteins in incubated human monocytes. The effects of bezafibrate on 14C-acetate incorporation into non-saponifiable lipids and on degradation of native and acetylated [125I] low-density lipoproteins (LDL) in cultured human monocytes has been evaluated. The presence of bezafibrate in the incubation medium resulted in a decrease of labelled acetate incorporation into non-saponifiable lipids. In parallel with the decrease in sterol synthesis, bezafibrate produced an increase in total and specific degradation of native low-density lipoproteins, whereas the degradation of acetylated low-density lipoproteins was not affected by the drug. These data, though obtained with concentrations of bezafibrate in the incubation medium greater than those encountered in ordinary therapeutic conditions, support the hypothesis that bezafibrate inhibits cholesterol biosynthesis and increases removal of low-density lipoproteins by activating the specific receptor pathway.


Anti-inflammatory action of AGF44, a ganglioside ester derivative. Gangliosides (GA) have been shown to promote axonal sprouting and growth of injured peripheral nerves, and enhance functional biochemical and morphologic recovery after CNS damage. Moreover, it has recently been shown that the natural ganglioside mixture (GM1 + GD1a + GD1b + GT1b) from bovine brain is endowed with powerful anti-inflammatory activity in rodents. Here we report that the novel semisynthetic ganglioside derivative AGF44, the isopropyl ester of monosialoganglioside GM1, displays a potent anti-inflammatory activity when orally or topically administered in various models of acute inflammation. AGF44 was effective (0.5-5 mg/kg p.o. or 0.5% gel topical application) in reducing rat paw oedema induced by either carrageenin, histamine, bradykinin, serotonin, nystatin or kaolin. Moreover, crossed confrontation with the effects elicited by other anti-inflammatory agents revealed that AGE44 seems to act through a different pathway than NSAIDs, steroids or antihistaminic/antiserotoninic agents.


[Adjuvant hormonal therapy in lymph node-negative breast carcinoma patients in the postmenopause]. The effect of adjuvant treatment with tamoxifen on recurrence and survival rates was determined in a prospective randomized trial in 98 postmenopausal women (mean age 62.7 [49-77] years) with lymph node-negative breast cancer who had undergone modified radical mastectomy with axillary lymphadenectomy. The tamoxifen group (n = 48) received 10 mg of the drug twice daily for one year. After a mean period of 8 (6-11) years the tamoxifen group had a significantly higher rate of survival without recurrence than the control (no tamoxifen) group (83% vs 61.5%, P = 0.02) and a higher overall survival rate (95% vs 81.9%, P = 0.05). These results indicate that adjuvant tamoxifen favourably influences the prognosis for postmenopausal women with lymph node-negative breast cancer after radical mastectomy with axillary lymphadenectomy.


[Extracorporeal shockwave therapy in endoscopic therapy-refractory gallstones]. Extracorporeal shock-wave lithotripsy (ESWL) was undertaken in 36 patients (12 men, 24 women; mean age 70.9 +/- 2.4 years) with extra- or intrahepatic bile duct stones which could not be removed endoscopically. Stone fragmentation was successful in 32 patients with stones in the choledochal duct and in one with stones in the left hepatic duct. Fragmentation failed in two patients with stones in the left hepatic duct and one with stones in the cystic duct. 26 of the 36 patients were free of stone after spontaneous passage (n = 3) or after endoscopic removal of the residual concrements (n = 23). Complications occurred in only five patients during or after ESWL (cardiac arrhythmias, respiratory failure, pancreatitis, cholangitis).--These data point to ESWL being clearly preferable to surgical intervention in bile duct stones refractory to endoscopic treatment, especially in the elderly with an increased perioperative risk.


[Cocaine poisoning from transport of the drug in the gastrointestinal tract (the body-packer syndrome)]. Three days after arriving in Switzerland from Bolivia a 35-year-old man presented at a casualty department. He was anxious, agitated and hallucinating, and he expressed delusional ideas of being poisoned. As a general physical examination was without abnormal findings he was thought to suffer from a psychiatric disorder. It was only when he had evacuated in stool a long oval foreign body, packed in plastic sheeting and filled with a dark paste, that cocaine poisoning due to cocaine transport in the gastrointestinal tract (body packer syndrome) was suspected. Plain X-ray of the abdomen revealed numerous regular structures of poor X-ray contrast and the urine contained cocaine metabolites, confirming the tentative diagnosis. As the patient's state of consciousness deteriorated and he had a grand mal seizure, an emergency laparotomy was performed. 78 packages (two of them had opened) were removed by gastro- and caecotomy. Total cocaine weight was 650 g. He was discharged from hospital after 11 days, free of symptoms.


[Hemosuccus pancreaticus due to a pressure ulcer in pancreatolithiasis]. Ultrasound examination in a 32-year-old man with epigastric pain and slightly elevated serum amylase level (66 U/l) revealed cysts in the head and tail of the pancreas as well as nonhomogeneous pancreas parenchyma as signs of chronic pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) additionally showed pancreatolithiasis. Melena occurred 7 months later, haemoglobin concentration decreasing to 8.7 g/dl. Endoscopy revealed bleeding into the duodenum via the papilla major. Angiography excluded vessel rupture. Haemostasis was achieved by occlusion of the pancreatic duct with fibrin glue, but the procedure had to be repeated twice within the next 8 months. Three months later ERCP was performed because of melena with massive haematemesis (haemoglobin level 6.5 g/dl). Stones were no longer demonstrated. At the previous location a pressure ulcer was now demonstrated, together with fresh blood in the pancreatic duct. After the stones had passed the ulcer healed and the patient has been symptom-free for over 13 months.


Characterization of the insulin resistance in liver cirrhosis: a comparison with non-insulin dependent diabetes mellitus. To characterize the mechanisms of insulin resistance in liver cirrhosis (LC), we estimated the peripheral tissue sensitivity and responsiveness to insulin using the euglycemic clamp technique and determined the insulin binding to erythrocytes in patients with compensated LC as well as in patients with non-insulin dependent diabetes mellitus (NIDDM). The insulin dose-response curves of the glucose metabolic clearance rates (MCR) were shifted to the right and downward both in patients with LC and NIDDM, indicating a reduced sensitivity and responsiveness to insulin. In the cirrhotics, MCR at the maximally effective insulin level, an index of insulin responsiveness, was correlated with fasting insulin levels (r = -0.57, P < 0.01) and sigma BG in 75 gOGTT (r = -0.43, P < 0.05), but no correlations were found between them and the diabetics. Although specific insulin bindings to erythrocytes were significantly lower in patients both with LC and NIDDM, Scatchard analysis revealed a significant decrease in the number of insulin receptors in the cirrhotics, and a decrease in the empty-site affinity in the diabetics. These findings suggest that insulin resistance in LC consists of a combination of binding and postbinding defects. The latter defect may be caused by basal hyperinsulinemia and contribute to the development of glucose intolerance. Although binding and postbinding abnormalities are also found in NIDDM, the mechanisms of insulin resistance in LC and NIDDM may be different.


Secretory regulation of 19-hydroxyandrostenedione in normal man. To evaluate the secretory regulation of 19-hydroxyandrostenedione (19-OH-AD), its plasma concentration was measured before and after stimulation and inhibition tests for the ACTH-adrenal axis and the renin-angiotensin system in 50 normal subjects. Basal levels of plasma 19-OH-AD did not correlate with either those of plasma renin activity (PRA) or the plasma aldosterone concentration (PAC), but positively correlated with those of plasma cortisol. Plasma 19-OH-AD was stimulated by 0.25 mg ACTH-(1-24) and was suppressed by 1 mg dexamethasone (DEX) as were plasma cortisol and PAC. On the other hand, with 2-h standing alone or iv 40 mg furosemide plus 2-h standing, plasma 19-OH-AD and cortisol did not increase but PRA and PAC did. With iv furosemide plus 2-h standing with 3 mg DEX pretreatment, plasma 19-OH-AD and cortisol did not respond either, but PRA and PAC increased. With 25 mg oral captopril following 1-h standing with 3 mg DEX pretreatment, plasma 19-OH-AD and cortisol did not change but PAC decreased. These results indicate that the secretion of 19-OH-AD is mainly under the control of the ACTH-adrenal axis rather than the renin-angiotensin system.


Plasma free fatty acids, inhibitor of extrathyroidal conversion of T4 to T3 and thyroid hormone binding inhibitor in patients with various nonthyroidal illnesses. In order to clarify the role of free fatty acid (FFA) in thyroid hormone abnormalities in patients with nonthyroidal illness, thyroid function, FFA, inhibitor of extrathyroidal conversion of T4 to T3 (IEC) and thyroid hormone binding inhibitor (THBI) were studied in 99 patients with various nonthyroidal illnesses including diabetes mellitus (DM) (n = 35), liver cirrhosis (LC) (n = 33), chronic obstructive pulmonary disease (COPD) (n = 17) and chronic heart failure (CHF) (n = 14). Patients were divided into three groups based on the level of serum T3: Group I (T3 < 50 ng/dl), Group II (50 < or = T3 < 80) and Group III (80 < or = T3). Serum T4, FT3 and the T3/T4 ratio decreased significantly in the order Group III, Group II and Group I (Group III > II > I). The plasma FFA level was 0.91 +/- 0.12 mmol/l in Group I (P < 0.05, vs. Group III), 0.65 +/- 0.06 in Group II and 0.54 +/- 0.04 in Group III, respectively. The incidence of positive IEC was 80.0% in Group I (P < 0.05, vs. Group III), 53.7% in Group II (P < 0.05, vs. Group III) and 34.2% in Group III. However, IEC was not correlated with the serum T3 concentration. The incidence of positive THBI was 80% in Group I (P < 0.05, vs. Group III), 68.3% in Group II and 47.4% in Group III, but THBI was not correlated with the serum T4 level. Positive correlations were observed among FFA, IEC and THBI (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Biochemical studies of the relationship between iodothyronine 5'-monodeiodinase and protein disulphide isomerase in rat liver. The relationship between type I iodothyronine 5'-monodeiodinase (5'-MD) and protein disulphide isomerase (PDI) was investigated by using a synthetic 18-amino acid peptide (LAP475c), which corresponds to the sequence of amino acids at position 373-390 of PDI including its active site, and anti-LAP475c antibody. Western blot analysis revealed that our anti-LAP475c antibody was highly specific for 57K protein in solubilized rat liver microsomal protein (SRLMP) that corresponded to PDI. Anti-LAP475c IgG (1:100 dilution) precipitated 46% of 5'-MD. These data suggest that PDI may play a regulatory role in the 5'-monodeiodination reaction.


Simultaneous administration of TRH and sulpiride caused additive but not synergistic PRL responses in normal subjects. In order to study the mode of action of TRH and sulpiride in man, we administered TRH (500 micrograms, iv) and sulpiride (DA D2 receptor antagonist, 100 mg, im) simultaneously to 6 normal females (20-21 yr). Normal females showed significantly greater PRL increments and AUC in response to the combined administration compared to a single administration of each agent (P < 0.05-0.01), while the increment and AUC in response to the combination did not exceed the sum of those responses to a single administration. In contrast, the combined administration of TRH and sulpiride did not elicit an enhanced response of plasma TSH. These results indicate that the sites of action of TRH and sulpiride might be different from each other, and these agents work additively with no interaction in human lactotrophs.


In vitro monitoring activation by the ligands and specific DNA-binding of the glucocorticoid receptors. The glucocorticoid receptor is a member of the steroid and thyroid hormone receptor superfamily and acts as a ligand-activated transcription factor. To reconstitute the molecular mechanisms underlying the cellular response to soluble receptor ligands, we have exploited a cell-free system that exhibits glucocorticoid-induced activation of the latent cytosolic glucocorticoid receptor to an active DNA-binding species. We demonstrate here that cytosol from a rat hepatoma cell, M1.19, contains glucocorticoid receptor-specific immunoreactivities and target DNA-binding activities. Moreover, specific DNA-binding activities of M1.19 cytosol were dose-dependently induced by dexamethasone treatment, and linearly correlated with the hormonal induction of chloramphenicol acetyltransferase activity at the corresponding concentrations. These results indicate that the cytosolic glucocorticoid receptor could be converted in a DNA-binding form under cell-free conditions and the ligand appears to play a crucial role in the direct control of the level of functional activity of a given ligand-receptor complex.


Adrenalectomy enhances the susceptibility of pancreatic islets to interleukin-1 beta: immunohistochemical study. To determine the importance of adrenal steroid in the effects of interleukin-1, we investigated changes in the number of islet cells reactive toward antiserum to insulin (anti-Ins) by intraperitoneal administration of recombinant human interleukin-1 beta (IL-1) in intact and adrenalectomized (ADX) rats. IL-1 significantly reduced serum insulin levels in ADX rats only, while it similarly decreased plasma glucose levels. In intact rats, IL-1 did not affect the number of islet cells reactive to anti-Ins, although cytoplasmic immunostaining tended to be reduced by IL-1 treatment. Only adrenalectomy decreased the number of islet cells immunostained by anti-Ins. Furthermore, IL-1 treatment significantly reduced the number of islet cells reactive to anti-Ins in ADX rats. The present study immunohistochemically supported our working hypothesis that the withdrawal of adrenal steroids by adrenalectomy enhances the islet cell sensitivity to exogenous administration of IL-1.


A case of primary hyperparathyroidism due to an oxyphil cell adenoma. A 59-year-old woman with primary hyperparathyroidism was found to have a parathyroid adenoma behind the left clavicle. Preoperatively, it appeared as a hypoechoic mass on ultrasonography, as a hot nodule on thallium scintigraphy, and as a high signal on T2-weighted magnetic resonance imaging. Histological, immunohistochemical and ultrastructural studies of the surgically resected tumor revealed a parathyroid adenoma composed mainly of oxyphil cells with production of a parathyroid hormone. Moreover, a multilocular lesion of lymphangiectasia was contained. Hypercalcemia was alleviated postoperatively. These observations corroborated a functioning parathyroid oxyphil cell adenoma. This is the first case report of functioning oxyphil cell adenoma of the parathyroid gland with lymphangiectasia in Japan.


Effects of age, sex and renal function on urinary insulin-like growth factor I (IGF-I) levels in adults. Insulin-like growth factor I (IGF-I) levels in urine were measured in adults using specific RIA after extraction with acid-ammonium sulfate. Mean (+/- SD) total urine IGF-I values were 267.9 +/- 112.9 ng/day and 167.8 +/- 73.2 ng/g creatinine (Cr) in 17 normal young adults. There was a positive correlation (r = 0.785, P < 0.001) between IGF-I values in early morning urine and those of 24 h urine when they were corrected by urinary Cr. IGF-I values in early morning urine were ranged from 60 to 1,100 ng/gCr with a mean value of 309.6 ng/gCr in 178 normal adults aged 21-80 yr. There was a consistent trend towards higher urinary IGF-I values in males during aging and this trend did not reach statistical significance until the sixth and seventh decades. There was a positive correlation (r = 0.465, P < 0.005) between urinary IGF-I values and age in males but not in females. Although urinary IGF-I values were higher in females than in males of the second and third decades, no sex difference was found in older adults. Urinary IGF-I values were correlated reversely with 24 h Cr clearance (CCr) and positively with urinary beta 2-microglobulin (beta 2-MG) levels in patients with renal dysfunction. These findings indicate that urinary IGF-I levels are influenced by age, sex and renal function in adults.


Effect of 1-desamino-8-D-arginine vasopressin (DDAVP) on vasopressin release and blood pressure during hemorrhage. Whether or not 1-desamino-8-D-arginine-vasopressin (DDAVP) reduces blood pressure or affects the release of arginine vasopressin (AVP) and renin is controversial, although evidence suggests AVP and renin are important in maintaining blood pressure during hemorrhage. We therefore investigated the effect of DDAVP on endogenous release of AVP and renin and on blood pressure during hemorrhage in dogs. In the control group the hemorrhage was performed at a rate of 0.4 ml.kg-1.min-1 for 40 min from the femoral artery. The plasma AVP concentration and renin activity (PRA) increased progressively in response to the hemorrhage, from 7.5 +/- 0.5 to 40.3 +/- 7.3 pg.ml-1, and from 11.8 +/- 1.5 to 20.5 +/- 4.2 ng.ml-1.h-1, respectively, while blood pressure decreased slightly. In the DDAVP group, intravenous infusion of DDAVP (2.5 ng.kg-1.min-1 for 40 min) and hemorrhage were simultaneously performed. The plasma DDAVP concentration increased progressively to 218 +/- 21.0 pg.ml-1. There was no significant difference, however, between the control and DDAVP groups in the response of AVP, PRA and blood pressure. The results suggested that DDAVP may not affect the release of AVP and renin or blood pressure during hemorrhage.


Chemical systems for delivery of antiepileptic drugs to the central nervous system. The chemical delivery system (CDS) approach, a recently developed procedure conceived to enhance the specific central nervous system (CNS) uptake of drugs, has been applied to several antiepileptic agents. CDSs based on dihydropyridine<-->pyridinium salt type redox targetors, reversibly linked to the drug, were designed, synthesized and tested for some traditional (phenytoin, valproate) and potential (stiripentol) antiepileptic drugs, as well as some compounds (GABA, adenosine) with important roles in epileptogenesis. Physicochemical, in vitro stability, in vivo tissue distribution, activity and toxicity studies were performed for the new derivatives. The results of these investigations indicated that selected CDSs possessed properties required for delivering the drugs to the CNS. In vivo experiments indicated improved brain uptake and enhanced pharmacologic activity in some of the examined cases. On the other hand, no toxic side effects were registered during the studies. Properly developed CDSs could enhance the therapeutic indexes of the anticonvulsant drugs.


Anticonvulsant action of lamotrigine during ontogenesis in rats. The anticonvulsant actions of lamotrigine and phenytoin against pentylenetetrazol-induced seizures were compared in laboratory rats during ontogenesis. Both drugs (lamotrigine in doses of 2.5, 5, 10, and 20 mg/kg and phenytoin in doses of 5, 10, 30 and 60 mg/kg) were injected intraperitoneally 30 min before pentylenetetrazol. Phenytoin and lamotrigine did not affect the incidence or latency of minimal (i.e., predominantly clonic, nongeneralized) seizures, although pretreatment with phenytoin changed the pattern of this phenomenon from short (10-30-s) seizures to long-lasting 'status of minimal seizures'. Both drugs abolished selectively the tonic phase of major, i.e., generalized tonic-clonic seizures, usually without any influence on the clonic phase of these seizures. Only the highest dose of phenytoin in adult animals suppressed the generalized tonic-clonic seizures as a whole. The study did not reveal any change of action of lamotrigine or phenytoin against pentylenetetrazol-induced motor seizures throughout development.


EEG frequency and time domain mapping study of the cortical projections of temporal lobe amygdala afterdischarge during kindling in the cat. EEG frequency and time domain color maps were computed during amygdala kindling in cats. The pattern of the amygdala afterdischarge (AM/AD) propagation to the cortex was assessed as kindling evolved. Our results show that the AM/AD has 4 components that coincide with the activation of certain cortical areas during specific behavioral stages. The pattern of the cortical projection follows an asymmetrical temporo-fronto-occipital direction, the ipsilateral temporal lobe being the first activated zone, followed by the ipsilateral and contralateral prefrontal areas. The contralateral temporal activation is a late phenomenon. We conclude that the electrographic and behavioral manifestations of this model of complex partial epilepsy are asymmetrical during the whole process, including the convulsive stage.


Noise exposure-induced audiogenic seizure susceptibility in Sprague-Dawley rats. Parameters were evaluated for the optimum induction of audiogenic seizure susceptibility in Sprague-Dawley (SD) rats by noise exposure. The effect of maturation on this susceptibility was also examined. It was found that SD rats are most inducible between neonatal days 13 and 15 and that susceptibility requires a minimum of 2 days to develop. Noise exposure on day 14 results in universal susceptibility by day 20, but seizure severity is not maximal until days 32-36. Although susceptibility persists at high levels into adulthood, seizures in older rats revert to the wild-running-only type. Seizure latency (from stimulus onset to onset of wild running) becomes increasingly shorter during the prepubescent period (days 16-24) but is stable at older ages. The mean shortness of latency in adult seizures depends somewhat on the age when initial noise exposure occurred; day-14 noise exposures result in seizures with shortest latencies. Ontogenetic comparisons were made of susceptibility in these noise exposure-induced rats, genetically epilepsy prone rats (GEPRs, which are SD substrains)29 and noise exposure-induced Wistar (WI) rats28. It appears that epileptogenesis begins at virtually the same age in all four groups of rats but that considerable differences characterize the absolute severity of seizures and the age dependence of maximum seizure severity among the strains.


Effects of loreclezole on epileptic activity and on EEG and behaviour in rats with absence seizures. The antiepileptic profile of loreclezole, a new putative antiepileptic compound, has been determined in rats of the WAG/Rij strain, a genetic model of generalized absence epilepsy. In addition, the effects of 0, 5, 10 and 20 mg/kg loreclezole on the spectral content of the background EEG and on spontaneous behaviour of rats were investigated. Both the number of spike-wave discharges and their total duration dose-dependently decreased following administration of loreclezole. Furthermore, the behaviour of the animals was not markedly influenced and significant changes in the background EEG were not noticed after administration. These data suggest that the broad-spectrum antiepileptic loreclezole can be a valuable new drug in the treatment of absence epilepsy.


Panoramic imaging of brain pHi and CBF during penicillin and metrazole induced status epilepticus. Using real-time in vivo umbelliferone fluorescent imaging, cortical intracellular brain pH (pHi) and cortical blood flow (CBF) were measured in New Zealand white rabbits during generalized seizures induced by intravenous metrazole or sodium penicillin. In the former, brain pHi declined from 7.04 +/- 0.07 to 6.78 +/- 0.07 within 15 min of generalized seizures and remained at this level for 1 h. In the penicillin group, pHi fell from 7.05 +/- 0.10 to 6.81 +/- 0.07 and also remained at this level over 60 min. This brain acidosis was uniform across the brain's surface. With the onset of status epilepticus there was a hyperemia which occurred in a heterogeneous pattern with blood flow appearing to be greater adjacent to cortical vasculature and slower in border zones between surface blood vessels. In the metrazole group, there was evidence of vasomotor paralysis with loss of autoregulation involving both cortical surface vasculature and penetrating arterioles with their capillary beds.


7-Chlorokynurenic acid antagonizes the anticonvulsant activity of D-cycloserine in maximal electroshock seizures. This study evaluated the anticonvulsant activity of D-cycloserine against maximal electroshock seizures in rats. Systematically administered D-cycloserine (i.p.) inhibited maximal electroshock-induced tonic hindlimb extension in a dose-dependent manner with an ED50 of 153 mg/kg. No neurological deficit was detected at any dose of D-cycloserine. In contrast, L-cycloserine had no effect on the maximal electroshock seizures. Administration of the strychnine-insensitive glycine receptor antagonist 7-chlorokynurenic acid (100 nmol, i.c.v.) significantly antagonized the anticonvulsant activity induced by D-cycloserine. Centrally administered D-cycloserine (i.c.v.) induced significant anticonvulsant activity 1-2 h after administration with an approximate ED50 of 5 mumol. 7-Chlorokynurenic acid (100 nmol, i.c.v.) significantly antagonized the anticonvulsant activity of centrally administered D-cycloserine. L-Cycloserine (i.c.v., 2 h) induced no significant anticonvulsant activity. These results provide evidence that the anticonvulsant activity of D-cycloserine in maximal electroshock seizures may be mediated by strychnine-insensitive glycine receptors.


Interictal HM-PAO SPECT: a routine investigation in patients with medically intractable complex partial seizures? Single photon emission computed tomography (SPECT) is increasingly being used as an adjunctive technique in the localisation of epileptogenic foci prior to surgery. As yet, few studies have been undertaken to establish the clinical associations of areas of reduced cerebral perfusion. Sixty-three consecutive patients (15 male, 48 female; median age 30 years, range 14-57 years) with medically intractable complex partial seizures (median/month 8, range 1-36) were investigated as outpatients. All had normal high resolution computerised X-ray tomography (CT) of brain. Twenty-seven (47%) exhibited significant perfusion defects on SPECT scanning with a rotating gamma camera system using Tc-99 HM-PAO. There were no significant differences between patients with normal and abnormal scans in terms of age at scanning or at onset of epilepsy or number of seizures. Patients with perfusion defects did, however, have longer median histories of epilepsy than those with normal scans (normal: 10 years, abnormal: 22 years; P = 0.01). Patients with abnormal scans were no more likely to have suffered febrile convulsions in early childhood. The correlation of abnormal SPECT scans with routine surface EEG recordings was poor with only 41% of cases showing clear agreement between the site of hypoperfusion and focal epileptic activity. It is not yet possible to predict clinically those patients who will exhibit perfusion defects on interictal TC-99 HM-PAO SPECT scanning.


An assessment of serum and red blood cell folate concentrations in patients with epilepsy on lamotrigine therapy. Lamotrigine (LTG) is a new antiepileptic drug which is effective in refractory epilepsy and which has been shown to have weak antifolate properties in vitro. The effect of LTG on serum folate and red cell folate (RBC) concentrations was assessed in a series of 14 patients on short-term LTG treatment during a placebo-controlled double-blind study. A further 14 patients who had been treated with LTG for up to 5 years were also assessed. In the short-term double-blind study the baseline mean serum folate concentration was 2.7 ng/ml and mean RBC folate concentration was 295 ng/ml. After 12 weeks of LTG therapy mean concentrations were 3.3 ng/ml and 339 ng/ml respectively and corresponding levels after 12 weeks of placebo were 2.4 ng/ml and 288 ng/ml. Patients on chronic LTG therapy showed no significant difference in RBC folate concentrations compared to those prior to LTG therapy (346 compared to 407 ng/ml). Other biochemical and haematological parameters were unaltered by LTG therapy. Thus, neither short-term nor chronic LTG therapy appears to be associated with significant changes in serum or RBC folate concentrations.


Right ventricular conductance to establish closed-loop pacing. Innovations in pacing technology, which include the addition of rate-responsive features to programmable pacemakers, can improve the quality of life of patients suffering from sick sinus syndrome. Among the strategies providing rate-adaptive cardiac pacing, the most attractive is the physiological restoration of closed-loop chronotropic control. This paper describes how autonomic nervous system (ANS) control information is extracted from dynamic measures of myocardial contractile performance obtained from unipolar conductance measurements using the stimulation electrode in the right ventricular cavity. The pacemaker uses the ANS information to modulate pacing rate and restore normal physiological control of heart rate. A new algorithm, regional effective slope quantity (RQ), for isolating the ANS signal was developed. The resulting signal, ventricular inotropic parameter (VIP), is a normalized parameter proportional to the strength of the ANS inotropic signals to the myocardium. The efficacy of the ANS control concept was evaluated in multi-centre studies. Patients with AV block and VIP-controlled pulse generators performed defined exercise protocols. The ANS-controlled pacing rate and the spontaneous sinus rate were closely correlated. Blood pressure and subjective patient reports further indicated that good control of the cardiovascular circulation was achieved.


Left ventricular segmental volume by conductance catheter and Cine-CT. The ability of the conductance catheter method to measure left ventricular segmental and total volume was evaluated by comparison with the Cine-CT technique. In the seven dogs studied, 19 conductance catheter and simultaneous Cine-CT runs were obtained. High correlation coefficients were found for total volume and segmental volumes, except in the basal segment. However, in most cases there was a significant variability in slope and intercept between animals. Both methods are promising tools for estimating dynamic segmental left ventricular volume, each having specific advantages such as a continuous signal (conductance catheter) or anatomic detail (Cine-CT). However, the results also show the need for further improvement of both methods.


Ventricular pressure-volume relations in vivo. A number of fundamental mechanical properties of cardiac muscle as well as of the total ventricle are discussed. These include: Starling's law, shortening deactivation, homeometric autoregulation, and so-called hyperactivation associated with a small amount of ejection. Whenever appropriate, muscle properties are related to those of the intact ventricle. The phenomenon of load-dependence of the end-systolic pressure-volume relationship (ESPVR) receives particular attention and is placed within the framework of shortening deactivation and homeometric autoregulation. However, this effect also leads to a more basic definition of myocardial contractility, based on the observed, rather parallel shift of the ESPVR with different afterload conditions. Using this definition, the conclusion is drawn that an increase in afterload is, in fact, met by the left ventricle increasing its inotropic state. Finally, within this approach, it is proposed that the value of end-systolic volume at a chosen constant end-systolic pressure (e.g. 13 kPa or 100 mmHg) be used to characterize changes in myocardial contractility in patients after an intervention. The way of obtaining this parameter is explained.


Determination of left ventricular volume using a conductance catheter in the diseased human heart. To validate the accuracy of human left ventricular (LV) volume measured by the conductance catheter method, conductance volume was compared with LV volume measured by biplane angiography in 19 patients with ischaemic heart disease. Angiographic LV volumes were calculated frame by frame and matched with instantaneous conductance volumes. Calibration was determined by both gain constant, 1/alpha, and parallel conductance, alpha V c. The gain constant, 1/alpha, was the ratio of stroke volume measured by the thermodilution method to that measured by the conductance catheter. The parallel conductance, alpha Vc, was estimated by the saline injection method. There was a good correlation between the corrected conductance volume (Vcc) and the angiographic volume (V angio) such that Vcc = 0.94 V angio + 5.3 ml, r = 0.94, P < 0.001. There were no differences in the correlation coefficients between normal and depressed hearts. Compared with the angiographic data, LV end-diastolic volume, end-systolic volume and ejection fraction were determined accurately by the conductance catheter. We conclude that the conductance catheter method, corrected for gain constant and parallel conductance, can accurately and continuously estimate the LV volume throughout the cardiac cycle in the diseased human heart.


Single and dual excitation of the conductance-volume catheter analysed in a spheroidal mathematical model of the canine left ventricle. The conductance method employs a multi-electrode catheter to generate an electrical field and measure intracavitary segmental conductances. Left ventricular (LV) volumes are calculated using an algorithm which assumes the electrical field to be homogeneous. This assumption may be violated leading to a non-linear relation between conductance-derived and true volumes. In addition, this relation may vary between segments. A new method is introduced which uses a more homogeneous field. Volume estimates using the conventional single excitation and the new dual excitation method were compared in a mathematical model of a canine LV, which was varied over a large volume range. With single excitation the slope factors, relating conductance-derived and true volumes, varied from 0.50 to 0.76 between segments and was 0.65 for total LV volume. Using dual excitation the segmental slope variability was reduced (range: 0.74-0.77) and the slope factor for total volume increased to 0.76. The linearity of the relation between conductance-derived and true volume was improved with dual excitation and extended over a larger range.


Improvement in intracardiac impedance volumes by field extrapolation. The measurement of volume by electrical impedance is complicated by non-homogeneous current distribution resulting from small current sources, by the irregular shape of the ventricle, and by loss of current to surrounding anatomical structures. A mathematical technique, field extrapolation, was developed to partially correct the current distribution. The technique mathematically transforms measured potentials into the potential distribution which would result from infinitely distant current sources. The linear correlation coefficient between impedance stroke volume or cardiac output using field extrapolation and thermodilution stroke volume or cardiac output was 0.83 (n = 86) in 11 dogs and 0.76 (n = 92) in 12 patients. The average linear correlation coefficient between impedance stroke volume and integrated aortic flow in four dogs was 0.83 +/- 0.09 (n = 49) using field extrapolation.


The end-systolic pressure-volume relationship in young animals using the conductance technique. Evaluation of ventricular performance by the end-systolic pressure-volume relationship (ESPVR) has been extensively performed in the adult heart using the conductance technique. We undertook this study to validate the conductance technique and to generate ESPVRs in the small heart. To validate the technique, we simultaneously measured left ventricular volume by the conductance catheter and biplane cineangiography in nine piglets during changes in volume and contractility. Raw conductance volumes correlated highly with cineangiographic volumes (R = 0.97), and the slope was near identity (1.11 +/- 0.04). However, 'alpha Vc-corrected' volumes correlated less well (R = 0.85), probably because of errors induced by the saline technique for alpha Vc. We evaluated the ESPVR in nine lambs by inferior vena cava (IVC) occlusion, aortic occlusion, and volume infusion at rest and during changes in contractility. Reliable and linear ESPVRs were obtained in almost all IVC and aortic occlusions but not in volume infusions. Neither slope (Ees) nor position (V14) significantly changed over time or with dobutamine, but both changed after propranolol, supporting studies showing a limited contractile reserve in the newborn. However, Ees was 25% less steep when generated by IVC occlusion as compared to aortic occlusion. We conclude that the ESPVR can be reliably generated in the small heart using the conductance technique, but that it is sensitive to the loading technique.


Continuous measurement of the pressure-volume relationship in experimental heart failure produced by rapid ventricular pacing in conscious dogs. The contractile function of the left ventricle has been defined within the framework of the pressure-volume relationship. We employed a conductance catheter, together with a high-fidelity micromanometer, to obtain accurate pressure and volume data continuously on a beat-to-beat basis in conscious dogs. Reproducibility of conductance volumetry was proven by repeated in situ measurements of left ventricular volume on separate days in the same dog. Heart failure, produced by rapid ventricular pacing, was characterized by impaired systolic shortening, depressed contractility indices and incomplete left ventricular relaxation. The magnitude of the cardiotonic effects of dobutamine was significantly attenuated after development of heart failure. Dobutamine improved left ventricular early relaxation but did not affect chamber distensibility. In heart failure, the load sensitivity of relaxation was enhanced and the force-frequency response attenuated. This may elucidate the mechanisms of early diastolic dysfunction and the deleterious effect of an increase in heart rate in the failing heart. Thus, the conductance catheter provided a reliable and simple method of obtaining left ventricular volume continuously in conscious dogs.


Left ventricular filling after long-term angiotensin converting enzyme inhibition in congestive heart failure. As a rule, left ventricular relaxation is impaired in patients with coronary artery disease and congestive heart failure. In addition, the passive elastic properties in early and late diastole change when the ventricle dilates. Diastolic properties of the left ventricle were studied in 11 patients with congestive heart failure class II-IV (NYHA) before and 3 months after 10-20 mg enalapril was added to their regimen of salt restriction, a diuretic and occasionally digitalis. Haemodynamic studies were performed using radionuclide angiography and simultaneous pressure-volume measurements. Systemic vascular resistance decreased from 1479 to 1182 dynes.s.-1 cm-5 (P < 0.05) and left ventricular end-diastolic pressure from 19.2 to 15.9 mmHg (P < 0.05). Left ventricular end-diastolic volume index decreased from 130 +/- 22 to 81 +/- 22 ml (P < 0.01). Indices of early diastolic relaxation, such as peak filling rate (1.43 +/- 0.46 to 1.49 +/- 0.84 EDV/s), time to peak filling rate (460 +/- 70 to 490 +/- 70 ms), peak negative dP/dt (-903 +/- 190 to -891 +/- 190 mmHg/s) and tau, the time constant of isovolumic pressure decay (58.7 +/- 14.4 to 48.4 +/- 15.2 ms) did not change significantly. In nine patients pressure-volume loops shifted to the left in all patients but one due to reduction in end-systolic and end-diastolic volume. The steepness of the diastolic part of the pressure-volume relationship increased, indicating an increase in chamber stiffness. The stiffness constant increased about 25% towards a more normal value. The alteration in stiffness seemed to be mainly due to the change of the geometry of the ventricle and not to a major change in the visco-elastic properties of the ventricular wall. In conclusion, regression of remodelling induced by enalapril does not change diastolic function parameters in patients with chronic congestive heart failure beyond the changes caused by regression of ventricular dilation.


Clinical evaluation of left heart function by conductance catheter technique. Methods to obtain pressure-volume loops in humans and their application to clinical diagnosis and treatment of cardiac disease are discussed. The method employs a conductance catheter, micromanometer, and inferior vena caval balloon occluder to reversibly and rapidly vary venous return. Multiple cardiac cycles measured during this manoeuvre are used to derive a variety of systolic and diastolic function indices, as well as estimates of vascular loading, and cardiac energetics. Strengths and weaknesses of the method as well as pressure-volume indexes themselves are briefly discussed. Lastly, three clinical examples are presented which serve to demonstrate how pressure-volume analysis can provide useful clinical information regarding diagnosis and/or treatment in subjects with heart failure symptoms.


Cardiodynamic changes during passive tilt and acute nitrate therapy. In six patients with normal left ventricles and seven post-myocardial infarction patients cardiodynamic changes during tilt and acute nitrate medication were investigated. The conductance catheter was used for on-line registration of left ventricular volumes and a microtip manometer for high-fidelity pressure recordings. We analysed left ventricular end-diastolic volume index (EDVI) ejection fraction (EF), cardiac index (CI), heart rate (HR), end-systolic pressure (ESP) and end-diastolic pressure (EDP) in the supine position and 30 s after passive upright tilt. Supine and standing measurements were performed without medication and 2 min after acute nitrate medication (0.8 mg sublingual nitroglycerin). After unloading by upright tilt there was a similar reduction of average EDVI in the control group (-18 +/- 7 ml.m2) and in the post-infarction group (-21 +/- 18 ml.m2). The effect of nitroglycerin on EDVI (-12 +/- 4 ml.m2 control, -7 +/- 6 ml.m2 post-infarction) was less than the effect of upright tilt. EF in the control group improved by +8 +/- 5% (in absolute values) during passive tilt; the combined effect of tilt and nitrate was +12 +/- 6% EF (p < 0.05). In the post-infarction group EF did not change significantly during tilt and/or nitrate therapy. In the patients with normal regional ventricular function, CI during tilt was maintained at a constant level. In the post-infarction group the reduction in CI was not significant. Although the reduction in EDVI was similar in the control and infarction groups, the infarction group did not respond to the cardiodynamic change by increasing EF.(ABSTRACT TRUNCATED AT 250 WORDS)