Effects of lisinopril upon cardiac hypertrophy, central and peripheral hemodynamics and neurohumoral factors in spontaneously hypertensive rats.

OBJECTIVE: Left ventricular function (LVF) after reversal of left ventricular hypertrophy (LVH) with antihypertensive therapy is still controversial. The present study was undertaken in spontaneously hypertensive rats (SHR) to determine whether LVF of the regressed heart with lisinopril is normally maintained. DESIGN: We compared cardiac function of SHR after reversal of LVH induced by lisinopril with that observed in control SHR and also with effects after a 4-week washout period. METHODS: Administration of lisinopril began at 15 weeks of age and continued for 20 weeks. Cardiac index, renal blood flow, leg muscle blood flow, plasma renin activity, atrial natriuretic peptide level, and norepinephrine concentration were determined. RESULTS: Lisinopril decreased body weight, blood pressure and left ventricular weight and increased leg muscle blood flow; cardiac index and renal blood flow were unaltered. Although norepinephrine concentration was unchanged, plasma renin activity increased and atrial natriuretic peptide decreased in treated SHR. Peak left ventricular pumping ability during volume loading was comparable in the two groups. After a 4-week washout period, left ventricular mass and blood pressure increased but remained lower than controls; cardiac index at rest and during volume loading was similar in the two groups. CONCLUSIONS: These data indicate that LVF of the regressed heart induced by lisinopril was well preserved at rest, during volume loading and also after spontaneous recurrence of hypertension in SHR.

Lisinopril reduces cardiac hypertrophy and mortality in rats with aortocaval fistula.

We evaluated the effects of lisinopril (1 mg/kg per day) on hemodynamics, cardiac hypertrophy, and neurohumoral factors in Wistar rats with an abdominal aortocaval fistula. After 4 weeks of treatment, the results were compared with values obtained for untreated rats with a fistula and for sham-operated rats. Volume loading induced biventricular hypertrophy, hemodynamic signs of high-output heart failure (increased cardiac output, left ventricular end-diastolic pressure, and pulse pressure), and impaired renal function (decreased renal blood flow and kidney weight; increased blood urea nitrogen). Lisinopril did not affect these cardiorenal hemodynamics, but decreased left ventricular mass and mortality rate (both P < 0.05). Lisinopril attenuated the increase in plasma norepinephrine, and increased plasma renin activity (both P < 0.05). Thus, lisinopril reduced left ventricular mass and mortality in rats with high-output heart failure without changing the cardiorenal hemodynamics. Neurohumoral inhibition may play a role in the beneficial effects of lisinopril.

Cardioprotective effects of quinapril after myocardial infarction in hypertensive rats.

Although angiotensin-converting enzyme inhibitors are beneficial for patients with congestive heart failure, the appropriate timing and dosage in acute myocardial infarction are still controversial. We examined the hemodynamic effects of quinapril administered before acute myocardial infarction in spontaneously hypertensive rats (SHR). Quinapril (10 mg/kg per day in drinking water) was started 1 week before infarction and continued for 4 weeks after infarction (total duration 5 weeks). The hemodynamic parameters were evaluated by cardiac catheterization 4 weeks after coronary ligation. Sham-operated SHR served as controls. After infarction, left ventricular end-diastolic and right atrial pressures were increased (P < 0.01) and blood pressure and cardiac index were decreased (P < 0.01); the magnitude of blood pressure reduction was similar in the treated and untreated rats with infarction. Quinapril improved these hemodynamic parameters significantly and decreased left and right ventricular weight. These results suggest that a prior treatment with quinapril in SHR with acute myocardial infarction is hemodynamically beneficial.

[Effect of active oxygen on cytoplasmic Ca2+ sequestration mechanism].

Effects of the active oxygen on the extrusion mechanism of once-increased cytoplasmic Ca2+, which causes various physiological phenomena, were investigated using different kinds of culture cells. First we found that, in response to stimulation with vitamin K (VK), various culture cells showed a decrease in cytoplasmic Ca2+ concentration. On the presumption that this phenomenon might be related to the oxidizing action of VK, we performed the same experiments using oxidizing agents such as H2O2 or KO2. They also showed a decrease in cytoplasmic Ca2+ concentration. Furthermore, they suppressed the increase of cytoplasmic Ca2+ by vasopressin. It would be inferred from these results that the active oxygen may act upon some site of the cellular signal transduction system of cell membrane to lower the cytoplasmic Ca2+ level.

Acute thallotoxicosis: neuropathological and spectrophotometric studies on an autopsy case.

Acute thallotoxicosis has been studied in an autopsy case with characteristic neurological symptoms. Pathologic findings were composed of a rarefaction in cerebral white matter, swelling and fragmentation in peripheral nerve fibers and some chromatolytic changes in neurons of cranial nerves and spinal cord. Trace amounts of thallous salt were measured in the tissues from the brain, liver and kidney using spectrophotometric technique. The locus of thallium affection is assumed to be a mitochondrial membrane with a specific affinity to the thallous ion.

Histochemical demonstration of phenobarbital by immunocytochemistry.

A method for the demonstration of the topographical distribution of phenobarbital at the cellular level in various tissues was established. Mice that had been exposed to various doses of phenobarbital by intraperitoneal injection were killed, and their tissues were fixed with 0.1 M phosphate buffer solution (pH 7.4) containing paraformaldehyde and glutaraldehyde. Thereafter, paraffin and frozen sections were made and stained by the indirect immunoperoxidase method using antisera obtained from commercial sources and used for the immunochemical assay of the blood level of phenobarbital in clinical medicine. A specific positive reaction was observed solely in testing the intoxicated tissues, and this reaction was inhibited when phenobarbital was added to the antisera. The minimal sensitivity of the positive reaction, which can be discerned by observing the stained slides macroscopically, was in the range of 10 mg/kg. Thus, the diagnosis of phenobarbital intoxication in the forensic autopsy can be made by immunohistochemistry. A positive reaction was found in various tissue cells, including nerve cells, myelin sheaths, glia cells, hepatocytes, cells of the alveolar and bronchial wall, epithelial cells of the distal part of the renal tubules, and so forth. Endothelial cells of the capillaries in all tissues gave a strong positive reaction. The immunocytochemical electron microscopy of the hepatocytes revealed that the positive reaction in the cytoplasm was located solely in the intraluminal space of the smooth endoplasmic reticulum. These results indicate some interesting aspects of the pharmacokinetics of phenobarbital in vivo. It is expected that the antisera, which are used widely for the assay of the blood concentration of various drugs (phenobarbital, amphetamines, morphine, and so forth), may be regarded as excellent reagents for immunocytochemistry. This clearly indicates that morphological evidence in toxicology, which had so far remained obscure, can be easily obtained by applying these antisera against various drugs.

[Internal carotid artery occlusion related to seat belt shoulder strap: report of two cases].

Two cases of traumatic internal carotid artery occlusion probably related to the seat belt shoulder strap are reported. Case 1. A 20-year-old woman was driving and was struck on the right front side of her car by another car. There were neither bruises, abrasions on her neck, nor weakness in her extremities. About 4 hours later, she developed left hemiplegia, and CT scan taken on the following day revealed low density areas in the capsulostriatal area on the right. The right carotid angiography revealed occlusion of the internal carotid artery about 3 cm distal to the bifurcation. Case 2. A 43-year-old man was driving and was struck on the front of his car by a hard iron railing. He sustained a sternum fracture, but there was no disturbance of consciousness or paresis of the extremities. His neck was unremarkable externally. About 50 days later, he developed left hemiplegia. CT scan and MRI revealed a massive infarction in the distribution of the right middle cerebral artery territories. The carotid angiography revealed occlusion of the right internal carotid artery about 3 cm distal to the bifurcation. In each cases, the driver was wearing a three-point shoulder seatbelt when the car was struck on the front or on the right front. Previous experimental studies have revealed in these situations the neck is flexed right anteriorly, and then quickly overextended left posteriorly. The overextension of the neck probably injured the intima of the internal carotid artery ipsilateral to the shoulder fixed in the seatbelt, resulting in the subsequent occlusion by a thrombus.

[Driver identification of the motorcycle in motorcycle/car accidents].

A series of motorcycle/car collision experiments and in-depth investigations involving motorcycle/car accidents with two riders were carried out in order to study the difference in behavior and injuries between the driver and the passenger of the motorcycle during a collision, and to provide general data for identifying their seat positions on the motorcycle in traffic accidents. In all the tests, two Hybrid II dummies were seated on the double seats of the motorcycle as riders. The motorcycle collided against the front door, front end or rear door of the passenger car at a speed of 50 km/h, at impact angles of 60 degrees, 90 degrees or 120 degrees. The speeds of the passenger car were tested at 0 km/h or 25 km/h. With different speeds of vehicles and different impact angles, the difference in rider behavior between the driver and the passenger was distinctly verified by analysis of high speed films. It is possible to distinguish the driver's injuries from the passenger's. The abrasion and/or contusions in the chest, face and groin area were severe for the drivers, but less serious for the passengers. The typical injuries of the driver can be expected in terms of the rider behavior during collision from 25 ms to about 150 ms after starting contact. The data and information can be used to clarify the question of who was driving in accident reconstruction.

[An experimental study on driver identification of passenger car in vehicle to vehicle accidents].

A series of full-scale vehicle-to-vehicle oblique collision experiments was carried out for providing general data to clarify the question of seating positions. In all test, two unrestrained anthropometric dummies (Hybrid II) were seated on front seats in passenger cars as occupants. The bullet car collided against the target car running with 25 km/h, at 50 km/h, at impact angles of 120 degrees and 150 degrees. Five impact configurations between occupant regions and interior of vehicle were evaluated: head-face/windshield, head-face/A-pillar, chest-abdomen/instrument panel, upper body/inside door and lower extremities/instruments panel. Comparative occupant injuries and vehicle response data were obtained from electronic instrumentation, high-speed movie films and visual observations. No characteristic driver injuries was observed in oblique collision experiments. The crush characteristics of the vehicle interiors and occupant behavior had significant effect in determining the actual injury once contact occurred. The differences of injuries in occupants occurred depend on impact configurations of vehicles. Therefore, on the driver identification, it is important to clarify kinematics of occupants during the impact by an analytical reconstruction. The data and information can be used to determine who was driving in actual traffic accidents for the forensic medicine expert.

[Biomechanical analysis of the pulmonary trauma by localized blunt force--thoracic force-deflection in pigs].

Thoracic force-deflection characteristics have been measured in the living little pigs as a step towards the analysis of thoracic injury in the field of forensic medicine. Mechanisms of injury by hand impact with a small stone were investigated by means of high speed video/camera and load cell. Initial velocity by hand impact ranges from 5.8 to 11.1 m/s, with corresponding peak force from 24 to 122 kgf. The thoracic force-deflection of the pig shows a progress change with increasing impact velocity, showing more of a spring-mass like response with an initial linear region of stiffness during a short interval immediately after the impact. Peak force up to 122 kgf was developed for 77 mm in the localized thoracic displacement with rib fractures and serious lung injury. A few rib fractures occurred with initial velocity near 9 m/s and displacement near 50 mm, these data suggest an outbreak limit of rib fractures of the little pig.

[Disseminated intravascular coagulation in the early stage after severe burn: the role of excessive thrombin generation].

The pathogenesis of disseminated intravascular coagulation (DIC) in the early stage after burn injury remains still unclear. We investigated 12 burn injured patients by serial determination of anti-thrombin III (AT-III) activities and thrombin-antithrombin III complex (TAT) levels. Of these patients 4 developed DIC (DIC group) and the others had no hematological complications (non-DIC group). The mean levels of TAT increased markedly and peaked at 6 hr; the increment being more pronounced in DIC group (p less than 0.001). A significant correlation was recognized between TAT and Burn Index (r = 0.871, p less than 0.001). We also observed low AT-III activities those inversely related to Burn Index (r = 0.875, p less than 0.001), whereas closely correlated with serum albumin levels (r = 0.864, p less than 0.001), suggesting that this depression might be caused by both massive infusion and shifts of plasma into the extravascular space rather than consumption. These findings suggest that massive thrombin generation and decrease of anticoagulant activity, correlated to the severity of burns, might concurrently develop. Non-DIC group may remain to latent activation of coagulation cascade where anticoagulants could inactivate thrombin generated. This compensatory mechanism may fail in severe burn patients who have Burn Index of more than 90, developing DIC with high levels of TAT (316.3 +/- 104.5 ng/ml) and low AT-III activities (19.5 +/- 8.7%).

[A case of severe tetanus associated with sympathetic overactivity].

A case of severe tetanus showing clinical features compatible with sympathetic overactivity (SOA) is reported. A 64-year-old man was admitted to our hospital 6 days after injury. The clinical signs of SOA developed on the second day in ICU. Through the clinical investigation of this case, we found out and insisted on some new concepts about the clinical features of SOA. 1. Lability of arterial pressure is parallel to that of catecholamine level in serum. 2. Two different types in SOA were found. One is dominantly lable type of Adrenaline and another is of Noradrenaline. 3. Drawing a sharp line between 2 types by assessment of circulatory data from Swan-Ganz catheter is significant for deciding therapeutic lines.

[A clinical study of pulmonary edema on paraquat poisoning by double indicator dilution method using heat and sodium].

We studied the formation of pulmonary edema on 9 patients with paraquat poisoning using thermal-sodium double indicator dilution method for the measurement of lung water. In survivors group (n = 4) extravascular thermal volume (EVTV) was not almost changes. In non-survivors group (n = 5) EVTV increased about three times as much as that in survivors group on 32 hours after admission. EVTV was correlated with PCP-PCOP in both survivors group and non-survivors group (n = 64, r = 0.665, p less than 0.01). But EVTV in non-survivors group was higher than that in survivors group within same PCP-PCOP. In non-survivors group delta EVTV/delta (PCP-PCOP) in 24 hours after admission was correlated with initial PCP-PCOP (r = 0.984, p less than 0.01). We propose that the formation of pulmonary edema on paraquat poisoning is mainly due to the increased capillary permeability, influenced by the increased pressure gradient of capillary barrier.

Evaluation of a simple loop-mediated isothermal amplification test kit for the diagnosis of tuberculosis.

OBJECTIVE: A new loop-mediated isothermal amplification (LAMP) test kit, including a simple DNA extraction device for the detection of Mycobacterium tuberculosis complex, was developed for commercial use and evaluated for its usefulness in diagnosing tuberculosis (TB). DESIGN: The LAMP test was performed using untreated and N-acetyl-L-cysteine (NALC) NaOH-treated sputum specimen. The efficiency of the kit was compared with other conventional laboratory examinations, including other nucleic acid amplification (NAA) tests. RESULTS: The sensitivity of LAMP using raw sputum (direct LAMP) in smear- and culture-positive specimens was 98.2% (95%CI 94.9-99.4), while the sensitivity in smear-negative, culture-positive specimens was 55.6% (95%CI 43.4-68.0). The diagnostic sensitivity of direct LAMP for the diagnosis of individuals with TB was 88.2% (95%CI 81.4-92.7). The sensitivity values of direct LAMP were slightly, but not statistically significantly lower than those of Cobas Amplicor MTB and TRC Rapid MTB, while the sensitivity of the LAMP test using NALC-NaOH treated sputum was significantly lower than other NAA tests (P < 0.05) for smear-negative, culture-positive specimens. The new commercial version of the LAMP kit was easy to handle and yielded results within 1 h of receiving sputum specimens. CONCLUSIONS: This test is considered a promising diagnostic tool for TB, even for peripheral laboratories with limited equipment, such as those in developing countries.