Impact of operator technique and device on infrared emission detection tympanic thermometry.

Preliminary data on the use of infrared emission detection (IRED) tympanic thermometers suggest that operator technique may be important in IRED readings. No systematic investigation of specific technique and available IRED devices has previously been performed. In a prospective, blinded trial, 40 healthy adult subjects using six IRED thermometers with two techniques were examined in random sequence. Differences between IRED tympanic, oral, and rectal temperatures were compared using ANOVA. Significant differences were observed between all temperatures, the IRED devices, and the method of probe insertion. Differences between oral or rectal temperatures and IRED tympanic readings were reduced by an ear tug (as for routine otoscopy) for all but one device. An "ear tug" results in increased IRED readings that may improve accuracy of tympanic thermometers using IRED.


Enalapril-induced cough in the emergency department.

A case of enalapril-induced cough is reported. In the Emergency Department, the patient initially was misdiagnosed with bronchial asthma and, later, with early congestive heart failure, despite normal physical examination and investigations. The cough subsided within 5 days of cessation of enalapril. It is important to recognize this side effect in patients taking enalapril.


Determination of prehospital blood glucose: a prospective, controlled study.

To determine if emergency medical personnel can effectively rule out hypoglycemia in the prehospital setting. During a 10-week period, emergency medical personnel determined the fingerstick glucose on all prehospital patients with altered mental status using the Chemstrip bG. Statistical comparisons were made to serum glucose levels performed by hospital laboratory personnel on blood samples obtained prior to glucose administration. A serum glucose level less than 60 mg/dL was considered a positive test for hypoglycemia. 170 consecutive patients with altered mental status (AMS) ranging in age from 13 to 90 years were enrolled. Of these patients, 158 were normal or hyperglycemic, 12 were hypoglycemic, and one patient was hypoglycemic but had only a borderline negative fingerstick test. Thus, a sensitivity of 91.7% and a negative predictive value of 99.3% were obtained. The specificity was 92.4%, and positive predictive value was 47.8%. The Chemstrip bG may be used safely in the prehospital setting to rule out hypoglycemia.


Fat embolism syndrome in a child with muscular dystrophy.

Fat embolism syndrome is a relatively common complication of orthopedic trauma. Once thought to be rare in children, it probably occurs with a similar frequency as in adults, but is often subclinical. Clinically apparent fat embolism syndrome may exhibit neurologic, pulmonary, and cutaneous manifestations. It often resolves without sequelae if it is recognized promptly and supportive treatment is provided. We present a pediatric case of fat embolism syndrome and review the literature on its diagnosis and management in children.


Atlanto-occipital dislocation.

Reported is the case of a 29-year-old woman who sustained an atlanto-occipital dislocation (AOD). This patient survived the initial resuscitation to expire some 72 hours later. Survival of patients with AOD is being reported with increasing frequency and with good neurologic recovery in many cases. Emergency physicians should be aware of this injury and the methods of initial evaluation and stabilization in order to maximize the potential for patients with these serious injuries. Radiographic features of AOD are outlined and the potential hazards of longitudinal traction are emphasized.


Infant botulism: a case series and review of the literature.

Little has been written about infant botulism in the emergency medicine literature, despite increasing references in the pediatric journals. We describe three cases diagnosed at The Children's Hospital in Denver, Colorado, over an 8-month period. A review of the literature follows, to discuss the clinical manifestations, differential diagnosis, diagnostic workup and treatment of the disease.


Emergency medical recognition and management of idiopathic anaphylaxis.

Idiopathic anaphylaxis (IA) is a diagnosis of exclusion that is made when no identifiable causative factors can be found for an episode of anaphylaxis. IA is a potentially life-threatening disease that is the result of a nonimmunologic mast cell activation syndrome. Acute presentation and treatment of these patients is most often in the emergency department and is clinically the same as anaphylaxis from allergens. Since these episodes are unpredictable and often recurrent, these patients are at risk of death if not identified on acute presentation and managed appropriately. As an increasing number of patients are being diagnosed with IA, they will be presenting to emergency departments with initial and recurrent episodes of IA. Therefore, increased awareness of IA and coordinated care is needed so that the morbidity and mortality of this potentially fatal disease can be kept at a minimum.


Cocaine-associated dissection of the thoracic aorta.

Patients present to emergency departments with a variety of complications related to cocaine abuse. Emergency physicians must be aware of the life- and limb-threatening complications to avoid undue mortality and morbidity. We present the case of a patient with aortic dissection who developed the acute onset of abdominal pain 5 minutes after subcutaneous cocaine use. Four previous reports of cocaine-associated aortic dissection are reported in the literature. These cases and other reports of intra-abdominal vascular injuries related to cocaine use are reviewed. Cocaine's mechanism of action as it relates to aortic dissection and some of the pharmacologic agents available for treatment are discussed.


Techniques of nasotracheal intubation with the fiberoptic bronchoscope.

When nasotracheal intubation with a fiberoptic bronchoscope is performed, the tube may be blocked in the nasal cavity or larynx, resulting in several complications including epistaxis and hoarseness. We review the causes and complications of tube blockage and discuss optimal techniques for minimizing it.


Magnesium: clinical considerations.

Magnesium is gaining recognition as a clinically important electrolyte. Hypomagnesemia has been associated with a variety of disorders including seizures, malignant ventricular dysrhythmias, and sudden death. The emergency department patients who are most likely to be magnesium deficient include alcoholics, patients who take diuretics, and those in diabetic ketoacidosis. Hypokalemia and hypocalcemia may represent unrecognized hypomagnesemia. Clinical trials and case reports also document increasing interest in magnesium as an effective therapeutic agent for potentially life-threatening problems such as torsade de pointes, digitalis toxicity, bronchospasm, and alcohol withdrawal. We present an overview of hypomagnesemia, review the current literature, and focus on the role of magnesium in the acute care setting and the implications for the emergency physician.


Time factors in VDT-induced myopia and visual fatigue: an experimental study.

In an experimental design with two matched groups (n = 13 and n = 17) working 2 and 4 hr respectively, followed by a 15-min restitution time, the study examined the effect of continuous VDT work on 1) visual acuity, refraction and oculomotor functions (ZCSV: zone of clear, single vision) and 2) the effect of 15-min restitution time on the oculomotor functions (ZCSV). In both groups there were a significant reduction in visual acuity, refraction changes in myopic direction and reduced ciliar and vergence muscle capacity. The ZCSV changes were temporary and a 15-min restitution period restored approximately half of the ZCSV changes. There were no significant differences between 2 or 4 hr of VDT work on any of the variables examined.


A study on optimum load for physical work.

Five healthy men were chosen as experimental subjects and were divided into groups at random. The subjects walked with a load in a shoulder-waist-back manner on the treadmill at the speed of 5, 7 and 9 km h-1. The parameters measured were as follows: oxygen expenditure, energy consumption, heart rate and self appraisal. Based on the experimental results and analysis of multiple regression, the authors suggested that physical loading should not exceed 25 kg (i.e. roughly equal to 39% of average body weight of male Chinese), when the walking speed was at 5 km h-1. The suitable loading at physical work would be 20 kg (i.e. equal to 31% of the average body weight of male Chinese).


A comparative study of the myoelectric amplitude characteristics for weight-holding tasks.

This study was conducted to examine the effects of load, time, and gender on five amplitude measures of the myoelectric signal (MES) for 10 male and 10 female subjects engaged in upper extremity weight-holding tasks. The results indicated that: (1) measures of amplitude variability (e.g.: standard deviation) are more sensitive to changes in load and time than the full-wave rectified integral and root-mean square indices; (2) both load and time had a significant effect on MES indices, suggesting that amplitude measures may be used as a tool for evaluating the degree of muscular loading and fatigue; (3) females have higher muscular exertion values than males under the same experimental conditions, indicating that females are subjected to higher levels of stresses than males for the same amount of workload. The implications of the results are discussed.


Work stress of women in sewing machine operation.

The study examined the work stresses of 107 women who were engaged in sewing machine operation in small garment manufacturing units. Of the three types of sewing machines (motor-operated, full and half shuttle foot-operated), 74% of the machines were foot-operated, where throttle action of the lower limb is required to move the shuttle of the machine. The motor-operated machines were faster than the foot-operated machines. The short cycle sewing work involves repetitive action of hand and feet. The women had to maintain a constant seated position on a stool without backrest and the body inclined forward. Long-term sewing work had a cumulative load on the musculo-skeletal structures, including the vertebral column and reflected in the form of high prevalence of discomfort and pain in different body parts. About 68% of the women complained of back pain, among whom 35% reported a persistent low back pain. Common sewing work accident is piercing of the needle through the fingers, particularly the right forefingers. Unsatisfactory man-machine incompatibility, work posture and fatigue, improper coordination of eye, leg and hand are the major problems of the operators. The design mis-match of the work place may be significantly improved by taking women's anthropometric dimensions in modifying the workplace, i.e. the seat surface, seat height, work height, backrest, etc.


Objectives to direct the training of emergency medicine residents on off-service rotations; radiologic imaging 2: contrast and imaging techniques.

Interpretation of radiologic images is an essential skill for the emergency physician. This is the second of two sets of objectives for an off-service rotation in radiology. The first covered the interpretation of plain films. This series addresses commonly used imaging modalities such as contrast media, ultrasound, computed tomography, nuclear medicine, and magnetic resonance imaging. This set of objectives may be used to guide a one-month radiology rotation or to serve as part of a teaching program integrated with didactic training and emergency department experience.


Measurement of the car steering wheel turning force of persons with cervical cord injuries.

Steering wheel turning force was measured in persons with cervical cord injuries for evaluation of their ability to drive a car. Seventeen subjects were divided into two groups according to their functional level: Group I (comprising 11 subjects of functional level C6) and Group II (comprising 6 subjects of functional level C7-C8). A device for hand fastening was attached to a steering wheel, which was mounted onto the rotation shaft of a Cybex machine, and the torque for turning the wheel with the right hand at a constant speed was measured. Persons with cervical cord injuries showed characteristically higher left-turning torque than right-turning torque. Mean values and standard deviation of the two groups were: 0.52 +/- 0.16 kgf-m (left-turning) and 0.40 +/- 0.12 kgf-m (right-turning) for Group I; and 0.81 +/- 0.16 kgf-m (left-turning) and 0.76 +/- 0.15 kgf-m (right-turning) for Group II. Subjects in Group I had a turning torque lower than 0.30 kgf-m (the lowest wheel turning torque shown by Japanese cars equipped with a power-steering system) at a turning angle range of between 0-135 degrees in left-turning and 45-200 degrees in right-turning.


Noise in multiple-workstation open-plan computer rooms: measurements and annoyance.

Computers in the workplace have become very prevalent. As with the introduction of any new technology, unanticipated problems often develop. Noise in open-plan computer rooms and annoyance and perceived deterioration in performance associated with it also appears to be a problem that may be similarly categorized. An experimental investigation was undertaken as a result of frequent user complaints about the difficulty of concentrating and performing their work in the computer rooms of a large service organization. Two typical computer rooms were investigated. Noise levels were measured at random times during the working hours. The noise spectrum was found to be almost similar in both facilities. The 10-second A-weighted noise level for all frequencies ranged between 53 and 62 dB. Most noise energy was either in the high-frequency bands (above 2,000 Hz) or low-frequency bands (below 500 Hz). The highest noise energy levels were recorded at 8,000 Hz (between 64 and 73 dB). Least noise energy levels were recorded between 500 and 2,000 Hz (between 35 and 44 dB). The noise spectrum, thus, was substantially different from those of open-plan offices. Eighty-nine percent of the users questioned indicated their tasks required concentration. Fifty percent of all respondents rated the noise level between extremely annoying and unbearable and intolerable (scale values between 22 and 25 on a 25-point scale; 1 being noticeable but not objectionable and 25 being unbearable and intolerable); 10% of the respondents considered the noise very annoying; 20% of the respondents considered the noise levels moderately annoying; the remaining respondents did not seem to have a major problem. Conversational sound and computer-printer beeping sounds were reported to be most annoying by 90% of the respondents who considered the noise levels annoying. Constant arrival and departure of users, sound from keyboards, and ventilation equipment also appeared to be major contributing factors.


Perceived workload and performance of shift workers.

The present paper is based on the results of a study conducted to investigate whether the relationship between perceived workload and quality of performance, if any, holds true if controlled for shift system, type of task, age, and skill level of the workers. The sample of the study comprised 279 blue-collar workers of a jute industry operating under fixed three-shift system. The subjects were all males selected by random sampling method. The method of data collection was a field study through questionnaire. The collected data were analyzed by employing zero-order and partial correlation coefficients. The results indicate that workload and performance were negatively correlated but the strength of the relationship reduced substantially when the effects of the control variables were partialled out simultaneously. It was concluded that the control variables had joint effect on the relationship between workload and performance but skill level of the employees appeared to be the variable having the greatest contaminating effect.


Immunological properties of a radioiodinated monoclonal antibody and its F(ab')2mu fragments directed against the polymorphic epithelial mucin of human breast cancer.

The purification of the IgM monoclonal antibody 436 against a breast tumor antigen from mouse ascitic fluid is reported. The purified immunoglobulin was radioiodinated and the resulting product assessed for its binding capacity and binding specificity. Purified IgM-436 served for F(ab')2 mu preparation which was tested for its antigen binding capacity. Radioiodinated IgM-436 and its F(ab')2 mu retained their immunological activity which was never lower than those of the corresponding cold products.


CA-549 serum levels in breast cancer monitoring.

CA-549 serum levels were assessed in 288 patients, 156 with early breast cancer (after surgery) and 132 with advanced breast cancer. CA-549 was abnormal (> 12 U/ml) in 25/156 patients (16%) without clinical signs of disease after surgery (median 9 U/ml), in 49/60 patients (82%) with disease in progression (P) (median 50 U/ml), in 19/27 patients (70%) with stationary disease (NC) (median 14 U/ml), in 25/33 patients (76%) with partial remission (PR) (median 18 U/ml) and in 4/12 patients (33%) with complete remission (CR) (median 9 U/ml). CA-549 serum levels correlated mainly with the extent of disease and secondarily with the prevalent metastatic site, higher values being observed in patients with visceral involvement (median 32.5 U/ml). CA-549 serum levels were also assessed in 51 patients at the start of treatment and at the time of objective evaluation: the results underline the concordance of CA-549 behavior with the clinical outcome in 71% of the cases. We conclude that CA-549 is a useful marker for monitoring breast cancer patients during the advanced stages of the disease.


Plasmatic fibronectin in malignancies.

Plasmatic fibronectin has been studied in tumor patients on the basis of the role that unspecific opsonin may play in tumor growth and spreading. Alterations in fibronectin levels might be used as a biological marker and our purpose has been to evaluate the significance of this test in the biological diagnosis of cancer. When comparing the levels found in the control group (22.86 +/- 1.40 mg/dl) and in tumor patients (23.80 +/- 1.90 mg/dl), we observed no difference in the overall group. However, in relation to the localization of tumors, a significant increase was found in breast cancer (31.83 +/- 3.83 mg/dl) and a significant decrease in squamous cell carcinoma of the head and neck (9.56 +/- 1.68 mg/dl). These results suggest that plasmatic fibronectin could be useful as a biomarker in some types of tumors. Our conclusion was confirmed by analysis of ROC curves related to every one of the studied tumors.


Serum prolactin levels in women with gross cystic breast disease.

Serum prolactin (PRL) concentrations at baseline and after TRH stimulation were determined in 15 healthy women and in 51 premenopausal patients suffering from Gross Cystic Breast Disease. All women were in the luteal phase of the menstrual cycle and patients were divided into three groups according to cyst type at presentation. Basal hormone levels were within the normal range in the control group and in the three cystic breast disease groups. The maximum PRL response to TRH stimulation was significantly higher (p < 0.001) in patients with type I cysts (low Na+/K+ intracystic ratio and apocrine epithelium) than in patients with type II cysts (high Na+/K+ intracystic ratio and flattened epithelium), type III cysts (intermediate Na+/K+ intracystic ratio and mixed epithelium) and in normal women. Serum PRL concentrations corresponding to samples obtained 60 and 90 minutes after stimulation remained higher in the first group of patients. These results led us to consider the existence of an altered central regulation of PRL secretion in patients with type I cysts at presentation.


The diagnostic value of mucinous carcinoma-associated antigen (MCA) tests in breast carcinomas.

MCA (Mucinous Carcinoma-Associated Antigen) levels of 176 breast carcinoma patients were tested postoperatively by serial determination. One hundred forty-one patients had non-progressive disease (PD-) while 35 were in the progressive phase (PD+); in the latter the diagnosis was confirmed by means of current diagnostic procedures. One hundred seventeen of the 141 PD-patients showed MCA levels below cutoff whereas 27 of the 35 PD+ cases showed high values. The difference in the incidence of elevated MCA levels between PD- and PD+ groups was statistically significant (p < 0.05). The overall diagnostic efficacy of MCA assays showed 77% sensitivity and 82% specificity.


Evaluation of the behavior of carcinoembryonic antigen in cirrhotic patients.

Benign liver diseases are a cause of increased serum levels of CEA. We studied the behavior of CEA in 86 patients with liver cirrhosis who underwent extensive clinical and laboratory evaluation. We found abnormal CEA levels in 38.4% of the patients (28.6% Child's grade A, 40.6% Child's B, and 42.4% Child's C) with a mean of 4.75 ng/ml. Significant differences were found between patients and controls. There was a trend towards higher levels of CEA in more severe cirrhosis according to Child's classification, although this was not significant. We found significant correlations between CEA and some liver tests, including glycocholic acid (r = 0.264., p = 0.012), a marker of severity in liver diseases. The increase of CEA in these patients is probably due to alterations in its metabolic processing caused by hepatocellular dysfunction. Moderate elevations of serum CEA can be expected in cirrhotic patients independently of malignancy.


Simultaneous determination of urinary CEA, ferritin and TPA in Egyptian bladder cancer patients.

Urinary carcinoembryonic antigen (CEA), ferritin (Fer) and tissue polypeptide antigen (TPA) were determined in 328 cases (106 with bladder cancer, 152 with non-malignant urinary tract disease and 70 healthy controls). CEA was determined by the kit supplied by Roche Diagnostica (CEA EIA Doumab 60), ferritin by the Tandem-E Fer kit supplied by Hybritech and TPA by the Prolifigen TPA-IRMA kit supplied by Sangtec Medical. The results of this work revealed that combined determination of urine CEA and Fer, CEA and TPA or Fer and TPA showed higher sensitivity than determination of the individual markers. There was no significant difference between combined and individual marker determination with respect to false positivity in non-malignant urinary tract diseases. At 97% specificity, the sensitivities of urine CEA, Fer and TPA were 82.1%, 71.7% and 90.6%, respectively, while combined urine CEA & Fer, CEA & TPA and Fer & TPA showed sensitivities of 92.5%, 99.1% and 98.1%, respectively. When the specificity was related to the entire non-cancer group (patients with benign urinary tract diseases and normal controls), some reduction in the sensitivities of the combined markers was noted compared to the normal group only. In conclusion, combined determination of urine markers is superior to determination of individual markers in the diagnosis of bladder cancer.


Neuron-specific enolase and embryology of the trabecular meshwork of the rat eye: an immunohistochemical study.

Neuron-specific enolase (NSE) is a unique form of the glycolytic enzyme enolase found exclusively in neurons and neuroendocrine tissues. Immunohistochemical techniques in which antineuron-specific enolase antibodies are used have made it possible to map out derivatives of the neural crest in humans. By using affinity-purified antibodies against NSE, we investigated whether the contribution of the neural crest cells to the development of the anterior ocular structures in the rat is similar to that in man. We found that filtration structures in rats show morphologically striking similarities with the analogous region of the human eye. Hence, the rat eye, with certain reservations, is a suitable model for experimental studies on ocular diseases that are characterized by chamber angle anomalies or congenital glaucoma.


Tissue polypeptide antigen (TPA) in chronic active hepatitis and mild liver diseases.

Tissue polypeptide antigen (TPA) is a non-specific tumor marker with a broad reactivity. Increases in TPA are also observed in benign liver diseases. We conducted this study to evaluate the usefulness of TPA serum level determination in 15 patients with chronic active hepatitis (CAH) and in 30 patients with mild liver diseases (MLD) diagnosed at the time of evaluation. TPA levels were abnormal in 73.3% of CAH patients and in 40% of MLD patients. CAH patients had significantly higher TPA levels than MLD patients (p = 0.006). There was a significant correlation between TPA and ASAT (r = 0.581 p < 0.00001), suggesting that cytolysis plays an important role in the increase in TPA. A TPA value of twice the normal level will unlikely be due to MLD (specificity 90%). TPA can be used in the clinical characterization of these patients and in the selection of patients for biopsy.


[Clinical experience with the omnicarbon valve prosthesis].

Between January 1985 and March 1990, isolated valve replacements with the Omnicarbon valve were performed in 90 patients aged 34-72 years. There were 53 aortic valve replacements (AVR) and 37 mitral valve replacements (MVR). The cumulative follow-up was 320 patient-year (py) with a mean follow-up of 3.7 +/- 1.4 years. There were 3 operative and hospital mortalities (3.3%), resulting from retrograde aortic dissection during cardiopulmonary bypass, postoperative renal failure, and rupture of infective pseudoaneurysm in ascending aorta. Seven patients died during the late postoperative period, 4 due to valve-related causes. Two of these patients died of prosthetic valve endocarditis (PVE), while the others died of thromboembolism (including valve thrombosis). The overall actuarial survival rate at 6 years was 86.3% (98.8% for AVR, and 82.1% for MVR). There were 2 thromboembolic events (one mesenteric artery thrombosis, and the other valve thrombosis). The linearized incidence of thromboembolism was 0.63%/py. PVE occurred in 3 patients (0.94%/py). One patient (0.31%/py) was found to have a valve dehiscence due to aortitis syndrome. There were no instances of anticoagulant-related hemorrhage, or valve-related hemolysis. The actuarial rate of freedom from valve-related mortality at 6 years was 93.5% (100% for AVR, and 88.1% for MVR). On the basis of a follow-up period of 6 years, good clinical results and a low incidence of valve-related complications can be demonstrated with Omnicarbon valve.


[Emergency coronary artery bypass grafting in patients with severe pump failure complicating acute myocardial infarction].

Thirty patients with severe pump failure (Killip's degree III or more) complicating acute myocardial infarction (MI) underwent emergency coronary bypass grafting (CABG). Average age was 66 years old and CABG was performed 2.6 days after the onset of MI. The patients were divided into two groups according to the mechanisms that can bring about severe pump failure: 19 patients had large MI alone (G-I). The other 11 patients had severe ischemia occurring either at areas distant from the site of coronary occlusion or in the previous area at risk (G-II). To estimate the ventricular wall motion quantitatively, the left ventricular wall was divided into 17 segments. Each segment was graded on a four-point scale: akinesis, 3; severe hypokinesis, 2; hypokinesis, 1; normal 0. Wall motion score was estimated by summing the number of asynergic segments score. In G-I, Cardiac index (CI (l/min/m2)) increased from 2.03 +/- 0.91 to 2.68 +/- 0.73 and pulmonary wedge pressure (PCWP (mmHg)) decreased from 28 +/- 5 to 15 +/- 5, 72 hours after the surgery (p < 0.01). In G-II, CI increased from 2.17 +/- 0.78 to 3.17 +/- 1.01 and PCWP decreased from 29 +/- 6 to 13 +/- 5 after the surgery (p < 0.01). There was no difference in preoperative and postoperative hemodynamics between two groups. The wall motion score at the risk area did not change postoperatively (from 16 +/- 7 to 17 +/- 9 in G-I, from 15 +/- 8 to 11 +/- 5 in G-II).(ABSTRACT TRUNCATED AT 250 WORDS)


[Coronary revascularization using only arterial grafts in patients with left main coronary artery stenosis].

Although increasing use is being made of arterial grafts (internal thoracic arteries and right gastroepiploic artery) for coronary revascularization, application to left main coronary artery (LMT) patients is frequently not possible. During the period from December 1989 to July 1991, coronary revascularization was conducted on 9 LMT patients using only arterial grafts and no venous grafts. The bypass grafts were 6 left internal thoracic artery grafts, 9 right internal thoracic artery grafts and 9 right gastroepiploic artery grafts, a total of 24 grafts and an average of 2.7 bypasses per patient. There were no operated deaths, but five patients required IABP support after cardiopulmonary bypass. They had more than 90% stenotic lesions of left main coronary artery. In contrast, four patients with less than 90% stenotic lesion were uneventful. The cause of these catastrophic hemodynamics was considered reduced blood flow by graft spasm. All patients could be functionally placed in New York Heart Association Class I or II. Postoperative stress tests were made on eight patients and the results were normal in seven. Eight patients have had postoperative angiograms. Twenty-one of 22 grafts were patent. The present results demonstrate that an arterial bypass is possible even on LMT patients by IABP support.


[Postoperative conduction disturbances in patients with retrograde continuous cold blood cardioplegia].

Two hundred twenty-seven patients who underwent open heart surgery with retrograde continuous cold blood cardioplegia (RC-CBCP) were investigated to manifest the incidence of postoperative conduction disturbances (CD) and to determine factors related to the occurrence of CD. The incidence of CD in patients with RC-CBCP was 16.7%, which was lower than that (24.4%) in 41 patients with antegrade continuous cold blood cardioplegia. In addition, the CD resolved by the time of hospital discharge in 65% of the patients. There were no patients with new complete atrioventricular block requiring a pacemaker. The development of postoperative CD was related to topical cooling with slushed ice and lower myocardial temperature of the left ventricle, but not to kinds of diseases, duration of aortic cross-clamp, or the distribution of RC-CBCP evaluated from myocardial temperature at the end of initial infusion of cold cardioplegic solution. Furthermore, terminal warm blood cardioplegia reduced the occurrence of CD. We conclude that the occurrence of CD in patients with RC-CBCP is lower than that in patients with antegrade cardioplegia, and is most related to local hypothermia with slushed ice. This suggests that the most likely mechanism for the development of CD would be ischemic or reperfusion injury to the specialized conduction system with the disturbance of microcirculation because of rouleaux formation in CBCP at very low myocardial temperature.


[Coronary revascularization with bilateral internal thoracic artery grafts].

Thirty-two patients underwent coronary revascularization with bilateral internal thoracic artery (ITA) grafts. Each patient received 2.7 grafts in average including double ITA grafts. Seventeen patients had the right ITAs as free grafts. The other sixteen were treated with 13 autologous veins and 9 right gastroepiploic arteries in addition. Fifty-five grafts out of 56 (98.2%) were proved to be patent at the time of hospital discharge. The postoperative morbidity included three reoperations for bleeding and one perioperative inferior myocardial infarction. One patient died of colon perforation after surgery and another died of cerebral infarction late after surgery. These results exhibited that coronary artery bypass grafting with bilateral ITA grafts had relatively low risks and could contribute to complete revascularization in patients with diseased coronary arteries.


[Experimental study on coronary bypass grafts--functional and pathologic comparison of late changes in various coronary grafts].

The internal thoracic artery (ITA) has excellent long-term patency when used as a conduit for coronary artery bypass (CAB), but there are still some problems, such as flow capacity and limited graft length of the ITA. This study was performed to evaluate the functional and pathologic late changes in left ITA grafts (LITAG), vein grafts (VG), ITA-vein (ITA-VG) and ITA-ITA composite grafts (ITA-ITAG) in a canine model of coronary artery bypass. Twenty-nine adult mongrel dogs underwent bypass of the left circumflex coronary artery (CX) with one of the above grafts. More than five months postoperatively (mean follow up period 245 +/- 78 days), changes in graft flow (CX flow in control group), mean aortic pressure (AoP), left ventricular end diastolic pressure (LVEDP), diastolic pressure time index/tension time index (DPTI/TTI), left atrial pressure (LAP) and right atrial pressure (RAP) with atrial pacing were compared with control group, and postmortem specimens were examined microscopically. With atrial pacing, AoP and RAP did not change in any group. Increases in graft flow, LVEDP and LAP with decrease in DPTI/TTI were observed in ITAG and ITA-ITAG groups, but these changes were similar to control group. On the other hand, increases in LVEDP and LAP with decreases in graft flow and DPTI/TTI were observed in VG and ITA-VG groups, and these changes were different from control group. No atherosclerotic change without anastomotic site was observed in any ITA which was used in ITAG, ITA-ITAG and ITA-VG groups, while intimal thickening and irregular dilatation were observed in al veins which were used in VG and ITA-VG groups. In conclusion, this study shows that ITA is a excellent conduit for CAB because of sufficient flow capacity and no atherosclerosis without anastomotic site in a long-term period. And to elongate ITA as a CAB graft, ITA-ITAG could be more appropriate than ITA-VG.


[The surgical treatment for the Stanford type A aortic dissection].

Twenty-nine patients who underwent operation at Shinshu University Hospital for the Stanford type A dissecting aneurysm were analysed. The patients were operated on in the acute stage within 2 weeks after onset. In 13 of these 26 acute cases, the graft replacement of the ascending and arch of the aorta was performed (group A). The patients were operated under a separate perfusion to the brain and the distal anastomosis to the proximal portion of the descending aorta was performed using the method of open distal anastomosis. In other 13 cases, the graft replacement of the ascending aorta was performed (group B). Operative mortality rate was 19% in this series (group A: 23%, group B: 15%). There was no significant difference in their operative mortality of acute stage. And there was also no significant difference in their post operative course of acute stage operations. We concluded that the graft replacement of the ascending and arch of the aorta was better than the graft replacement of the ascending aorta alone for the patients with Stanford type A acute aortic dissection.


[A clinical study of the analysis and ranking of the determinant factors for non-blood open heart surgery].

We analyzed the determinant factors as to whether open heart surgery with non-blood transfusion may be indicated or not, according to the formula based on the quantitative theory (class II). Extracorporeal circulation with non-blood priming were indicated on 106 patients using Cell Saver apparatus in our department, they were divided into two groups; blood transfusion group (group I): 38 patients, and non-blood transfusion group (group II): 68 patients. These two groups were compared for study in terms of age, preoperative body weight (BW), the body surface area (BSA), preoperative Hct value (Hct), calculated Hct value (Hct(C)) at the start of extracorporeal circulation (ECC), the aortic cross-clamping time (AXT), the total extracorporeal circulation time (TECCT) and total bleeding amount. The followings are described in the ranking of importance. 1) The amount of blood loss in ICU: less than 400 ml. 2) Hct(C): more than 30%. 3) The amount of blood loss after ECC: less than 130 ml. 4) Hct: more than 40%. 5) BW: more than 55 kg. 6) The total bleeding amount: less than 600 ml. 7) TECCT: less than 90 min. 8) AXT: less than 50 min. In addition, prospective factors which should be considered preoperatively are determined in the following ranking. 1) Hct. 2) Hct(C). 3) BW. From these results, the amount of blood loss in ICU, Hct and Hct(C) were found to be reliable critical in any case as determinant factors for open heart surgery with non-blood transfusion.


[Distribution of thymic tissue in the mediastinal adipose tissue removed at the thymectomy in 47 patients with myasthenia gravis].

In this report, the distribution of thymic tissue in the mediastinal adipose tissue was examined histologically in 54 patients with myasthenia gravis underwent extended thymectomy. In fourty-seven of 54 patients, the mediastinal adipose tissues were removed from 6 different parts adjacent to the thymus, i.e., right upper, right middle, right lower, left upper, left middle, and left lower, respectively. Upper area means of around the upper pole of thymus, middle area means of around hilum and lower area means of around from lower pole of thymus to diaphragma. In the mediastinal adipose tissue, thymic tissue was found outside the thymus lobes in 41 (75.9%) of 54 patients. The each prevalence (percent of occurrence) of 6 areas were as follows: 15.0% in the right upper area, 21.4% in the right middle area, 19.0% in the right lower area, 17.5% in the left upper area, 66.7% in the left middle area and 33.3% in the left lower area. There was significant differences in the prevalence of the left middle area according to the other 5 areas (p < 0.01). There were no significant differences in the prevalences among sex, Osserman type, duration of the disease, pre-operative treatment and histological findings or removal thymus. There were significant differences in the prevalence of all according to the proportion of thymic tissue in the thymus (0.01 < P < 0.05). In conclusion, it is suggested that for the removal of all thymic tissue, the sufficient procedure required utmost care especially to the left middle area around thymus.(ABSTRACT TRUNCATED AT 250 WORDS)


[Evaluation of the correlation with preoperative left ventricular end-systolic volume index and postoperative exercise tolerance in the patient with aortic regurgitation].

Twenty-three male patients (49 +/- 11 years old) undergoing aortic valve replacement (AVR) for aortic regurgitation received the exercise tolerance test using bicycle ergometer at more than one year after AVR. Preoperative left ventricular end-systolic volume index (LVESVI) significantly correlated with tolerance time, peak VO2, anaerobic threshold (AT) during the exercise, and with serum noradrenaline (NAd) levels at rest. Then patients were divided into two groups: those with preoperative LVESVI < or = 70 ml/M2 (13 patients, group A), and those with LVESVI > 70 ml/M2 (10 patients, group B). All patient in group A achieved more than 75 W of the exercise, however only one in group B achieved this level. The increase of VO2 in group B with an increasing exercise was significantly suppressed compared to group A, and then, the peak VO2 levels in group B were significantly lower than in group A (A: 20.9 +/- 3.7, B: 11.4 +/- 3.9 ml/kg/min). In addition group B showed a less increase of AT levels (A: 10.6 +/- 2.9, B: 6.8 +/- 2.3 ml/kg/min). In contrast, serum lactate and NAd levels in group B increased significantly at 50 W of the exercise compared to group A (A: 12.5 +/- 3.7, 332.3 +/- 104.2; B: 17.5 +/- 5.7 mg/dl, 746.7 +/- 324.3 pg/ml, respectively) though a significant difference of NAd levels before the exercise was observed between the both groups (A: 173.7 +/- 34.2, B: 329.0 +/- 132.1). In conclusion, group A showed a better exercise tolerance physiologically and biochemically compared to group B.(ABSTRACT TRUNCATED AT 250 WORDS)


[Examination of post operative split lung function using quantitative xenon 133 (133Xe) inhalation scan].

133Xe inhalation scan and ordinary lung function testing were performed three times in 34 patients undergoing pulmonary resection: before surgery, and one and six months postoperatively. Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1.0) were used as spirometric parameters. From the 133Xe inhalation scan, a split lung capacity (right to left, upper, middle and lower) and T1/2 (time required for half of the inhalation of 133Xe gas to be expired) were calculated by computer and used as indices of split lung capacity and ventilation, respectively. Results obtained from this study are as follows. 1) The predicted postoperative lung functions were calculated using preoperative spirometric respiratory function and 133Xe inhalation data according to the formula reported by Ali and associates. At sixth postoperative month, both predicted FVC (r = 0.895, p < 0.001) and FEV1.0 (r = 0.897, p < 0.001) correlated highly with those actually observed. These results appear to be very useful for preoperative evaluation of operative indications and the choice of surgical methods. 2) The ratios of observed to predicted lung capacity in the post operative state were examined by splitting the right and left lung and the means +/- S.D. (%) were as follows. One month after surgery, operated side; 80.5 +/- 9.7%, opposite side; 119.2 +/- 11.7%. Six months after surgery, operated side; 111.0 +/- 5.6%, opposite side; 96.7 +/- 16.4%. The post operative T1/2 values on the operated sides were about 2.4 times the preoperative values at one month after surgery but had recovered to the preoperative values by the six postoperative month.(ABSTRACT TRUNCATED AT 250 WORDS)


[A case report of Lucas-Schmidt IIA type Cor triatriatum in neonate].

Lucas-Schmidt IIA type of Cor triatriatum has been rarely reported. Since it shows the same hemodynamics as Darling IIb type TAPVC, it is important as a emergent surgical case in early infancy. We reported a male neonate with IIA type Cor triatriatum. He was admitted to our hospital because of cyanosis and dyspnea since birth. The echocardiographic examinations revealed the accessory chamber behind the left atrium and atrial septal defect. The view from the right atrium revealed that there was no direct connection between the accessory chamber and the true left atrium, and we diagnosed it Lucas IIA type Cor triatriatum. The abnormal diaphragma was resected, and the atrial septum was corrected with a Xenomedica patch. The patient had an uneventful postoperative course, and was discharged on the 25th postoperative day.


[Successful repair of traumatic aortic arch rupture].

The most common site of traumatic aortic tear is at the isthmus, and there have been few reports of successful surgical repair of traumatic rupture of the aortic arch. We have experienced a 18-year-old patient who sustained a blunt chest trauma in a traffic accident. After admission to our hospital, his general condition became stabilized by conservative therapy. But the chest X-ray showed widening of mediastinum and aortography demonstrated leakage of contrast media outside of the aortic arch lumen between the innominate and the left common carotid arteries. The patient underwent reconstructive surgery for the innominate artery with a part of the aortic arch using prosthetic graft with the aid of hypothermic retrograde total body perfusion. He has recovered without any neurological deficit, although the retrograde perfusion time exceeded 100 minutes. It is suggested that the technique of "retrograde total body perfusion" may provide longer time to perform aortic arch repairs than the conventional circulatory arrest does.


[A case of mitral valve replacement in the first three months of life for congenital mitral valve regurgitation].

Mitral valve replacement with 19 mm St. Jude Medical mechanical valve was successfully performed for congenital mitral regurgitation in an infant aged 3 months. The infant had undergone ligation of ductus arteriosus at the first month of age. Ten days after the operation, he was discharged, though having systolic murmurs. One month later, however, he was re-admitted for progressive heart failure. After hospitalization, he had to be supported mechanical ventilation. The second operation was needed for intractable heart failure, that was considered to be caused by mitral regurgitation, on an emergency basis without cardiac catheterization. The mitral valve was hypoplastic and the leaflet and chordae were gelatinous. Therefore, mitral valvuloplasty was considered to be impossible, and consequently mitral valve replacement was chosen. Postoperatively the patient's condition remarkably improved. Anticoagulation therapy with sodium warfarin and dipyridamole was maintained after operation. At present the patient is growing without any symptom.


[A rare case of mediastinal neuroblastoma with pectus excavatum in a 4-month-old boy--a surgical report].

Screening of neuroblastoma is commonly performed on 6-month-old infants; therefore, its discovery in children younger than that age is extremely rare. However, a 4-month-old boy with pectus excavatum was found to also have mediastinal neuroblastoma after close examination. This 7 kg child had no apparent symptoms, yet revealed an egg-sized shadow along the right atrium in the chest X-ray film, and along the right side of the vertebrae on CT. Due to the increase in the size of the tumor after two months of observation, we suspected malignant neurogenic tumor and performed a thoracotomy. With a right posterolateral thoracotomy we removed the dark-brown, elastic tumor measuring 6 x 4 x 3 cm and located along the right side of the vertebrae from III through VIII ribs. The origin was the thoracic sympathicus and the pathological diagnosis of the tumor was neuroblastoma with rosset formation. After conducting a post-operative chemotherapy (Jame's protocol), no evidence of recurrence was observed at 33 months after surgical treatment. We summarized the previously reported seven surgically treated cases of Stage I mediastinal neuroblastoma at less than 12 months of age. Among the 2500 pectus excavatum surgeries that have been held at our department, non has been found to have mediastinal neuroblastoma.


[A case of Stanford type A acute aortic dissection complicated with clotted false lumen and saccular aneurysm formation].

A 59-year-old farmer was admitted with severe anterior chest and back pain. As MRI showed a Stanford type A dissection, operation was performed. Surgical intervention revealed the clotted false lumen of the ascending aorta without intimal tear, and it was transected and primarily reconstructed with Teflon felt bolsters. Three months later MRI disclosed disappearance of the dissected lumen in the ascending and descending aorta. During the following two years and three months, a saccular aneurysm of the distal arch was found to be increased in size rapidly. The second operation was attempted to close the intimal defect with patch. As a whole this was a rare case of DeBakey type III acute aortic dissection complicated with proximal extension, clotted false lumen and saccular aneurysm formation at the site of the intimal tear.


[Surgical treatment of infected left atrial myxoma--a case report].

A 22-year-old man had undergone dental therapy following an intermittent fever, and the bacteriological examination by blood culture identified Streptococcus viridans. A left atrial myxoma was echocardiographically found out and the tumor was surgically resected with uneventful postoperative course. Multiple foci and Gram-positive cocci within the typical myxoma were revealed histopathologically. Reviewing previous reports on infected cardiac myxoma, the coexistence of cardiac myxoma and a confirmed positive blood culture has been considered diagnostic criteria for "infected cardiac myxoma". But, from the surgical viewpoint, the demonstration of infecting organisms within the tumor is essential for accurate diagnosis. Infected atrial myxoma has an extremely high incidence of systemic embolization, and its bacterial foci could be the source of persistent bacteremia. Therefore, in clinical situations suggesting infected cardiac myxoma, we recommend performing open heart surgery to prevent both the embolization and the infective progression into other cardiac valves, as soon as possible.


[Surgical treatment of ventricular tachycardia after total correction of tetralogy of Fallot].

A 38-year-old man with total repair of tetralogy of Fallot at the age of 16 suffered from paroxysmal ventricular tachycardia. His first attack of sustained ventricular tachycardia was recognized at the age of 37 and it was refractory for medical therapy. Electrophysiologic study demonstrated two morphological types of clinical ventricular tachycardias, one originated from the outflow tract of the right ventricle and the other from the area around the patch for closure of ventricular septal defect. He underwent cryosurgical ablation for ventricular tachycardia and patch-closure for residual shunt of ventricular septal defect following the failure of electrical ablation. All of clinical ventricular tachycardias disappeared postoperatively without antiarrhythmic drugs.


[One-staged repair for coarctation of the aorta and annuloaortic ectasia with severe aortic regurgitation in a patient with Turner syndrome].

A 27-year-old woman with Turner syndrome was admitted to NCVC for congestive heart failure. 2-D echocardiography and magnetic resonance imaging (MRI) disclosed annuloaortic ectasia with severe aortic regurgitation and coarctation of the aorta. One staged operation by a modified Bentall procedure and extra-anatomical bypass grafting from the ascending aorta to the infrarenal abdominal aorta was successfully performed. The postoperative course was uneventful. The pressure gradient between upper and lower extremities decreased as to be 30 mmHg compared with preoperative 60 mmHg.


[A case of coronary artery-pulmonary artery fistula in tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries (MAPCA)].

A case of four year old girl with tetralogy of Fallot, pulmonary atresia, major aortopulmonary collateral arteries and coronary artery to pulmonary artery fistula is reported. The patient was misdiagnosed as truncus arteriosus, pulmonary stenosis and major aortopulmonary collateral arteries (MAPCA) preoperatively. The ligation of MAPCAs was carried out through left thoracotomy as an initial procedure, because we believed that the area fed by MAPCAs had dual blood supply. However, the patient demonstrated pulmonary infarction post operatively. This complication forced us to postpone an intracardiac repair. At the time of intracardiac repair, after mentioned diagnosis was established and a Rastelli type operation and ligation of coronary-pulmonary artery fistula were carried out. A 18 mm Carpentier-Edwards valved conduit was used as an extracardiac conduit. 1) We experienced a rare association of coronary artery fistula in TOF with PA. 2) The MAPCAs functioning as a sole source of blood-supply to the lung should be precisely diagnosed preoperatively and uniforcalized before an intracardiac repair.


[A case of chronic fibrosing mediastinitis].

This case report describes a 32-year-old male patient with superior vena cava syndrome due to chronic fibrosing mediastinitis involving superior vena cava, bilateral brachiocephalic, subclavian, and internal jugular veins. Although the ringed ePTFE graft was placed between left internal jugular vein and right atrium twice, it occluded each time. Pathological examination of the removed specimen showed invasion of the fibrous tissue into the lumen of the graft at the anastomotic site and severe fibroelastosis in the intima of the jugular vein. The third reconstruction of the venous system with the ringed ePTFE substitute was done in the same manner. Postoperative venography demonstrated the patent graft and the interruption at the midportion of the left internal jugular vein. The patient remains free from the symptoms one year and nine months after the last operation.


[A case report of isolated tricuspid valve endocarditis in a non-addicted adult person without underlying cardiac disease].

We report a rare case of isolated tricuspid valve endocarditis. A 46-year-old man who was non-addicted, non-alcoholic and had no underlying cardiac disease was admitted to our hospital for persistent pyrexia. Appropriate intravenous antibiotics therapy was unable to control the repeated infection and destruction of his tricuspid valve progressed. The patient was referred to our surgical division where on intraoperative inspection, tricuspid valve endocarditis was found to involve the entire anterior leaflet and part of the posterior leaflet. Following complete debridement of the infectious lesion, tricuspid valvuloplasty was not considered to be possible. So we performed tricuspid valve replacement using a mechanical valve (CARBOMEDICS 27 mm). His postoperative course was uneventful and he had no ventricular arrhythmia. After prophylactic antibiotic administration for 3 weeks, he was afebrile for 2 weeks without any medication. Thereafter he was discharged and has been free from any complications for over 1 year.


[An electron microscopic study on osteoblastoma--ultrastructure and fine localization of alkaline phosphatase].

Three cases of osteoblastoma were studied by electron microscopy. They included two cases of conventional osteoblastoma and one case of aggressive osteoblastoma. In conventional osteoblastoma, ultrastructural features and location of alkaline phosphatase activity of the osteoblast-like cell were similar to those of normal osteoblast. On the other hand, aggressive osteoblastoma cell (case 3) showed different structure from those of a normal osteoblast; the nucleus of the tumor cell showed irregular surface with a small degree of heterochromatin, and poorly developed cytoplasmic organellae. Cytochemically, alkaline phosphatase activity was noted not only on the cytoplasmic membrane, but on the abundant vesicles in the cytoplasm. From these findings we conclude that the aggressive osteoblastoma cells are more immature in morphology and show increased synthesis of alkaline phosphatase.


[Anatomical study of radiocarpal joint--degenerative change and morphometry].

The present investigator studied following degenerative changes of the articular cartilage of the radiocarpal joint: the ruptures of the scapholunate and the lunotriquetral interosseous ligaments (S-L lig., L-T lig.), the shape of the scaphoid and the lunate fossa of the distal radius. We studied 120 wrist joints from 74 cadaveric specimens (age 20-97, average age 68). The cartilaginous changes were correlated significantly with age (p < 0.01). The cartilaginous changes were most commonly found in the ulnar demarcation of the lunate, next commonly, in the radiodorsal demarcation of the scaphoid fossa, thirdly, in the radiodorsal demarcation of the scaphoid and finally, in the radial demarcation of the scaphoid fossa. Clearly, the cartilaginous changes in the ulnar demarcation of the lunate intensified proportionally as the ulnar variance increased (p < 0.05) and as the radial inclination decreased (p < 0.05). The S-L lig. and the L-T lig. ruptures increased as the age of the specimens increased. The cartilaginous changes of the interosseous ligament rupture group were stronger than those of the non ligament rupture group (p < 0.01). The concavity of the scaphoid fossa in the dorsovolar direction exhibited an S shaped curve, a convexity on the dorsal side and a concavity on the volar side. The other concavities exhibited a smooth concave curve. From these results, it was concluded that the stability of the wrist joint in extention and the cartilaginous changes of the radioscaphoid joint were due to the volar concavity of the scaphoid fossa of the radius.


[Histochemical study of adrenergic nerve fibers in the skeletal muscle of the rat].

The distribution of adrenergic nerve fibers in the vessels, nerves, and skeletal muscles of the rat was studied by the glyoxylic acid fluorescence method and by electron microscopy. The changes in catecholamine fluorescence were investigated after decentralization, lumbar sympathectomy, and femoral nerve ligation. Catecholamine fluorescence was mainly localized in the arteries, and arterioles in the perimysium of the skeletal muscle. Sometimes, a spot-shaped catecholamine was seen in the metarteriole and capillary. Adrenergic nerve fibers ran parallel with femoral nerve fibers. After lumbar sympathectomy catecholamine fluorescence disappeared, the fluorescence in the quadriceps femoris muscle did not disappear even after ligation of the femoral nerve. Unmyelinated nerve fibers were identified adjacent to the capillary, whereas adrenergic nerve fibers were seen approaching to the quadriceps femoris muscle within a gap of 300 nm.


[Reinnervation after direct neurotization in cross innervated rats--a study of spinal anterior horn cells by horseradish peroxidase method].

This experiment was performed to clarify the progress of the reinnervation of the denervated muscle after direct neurotization using cross innervation. In this study 79 rats were used. The common peroneal nerve was cut and neurotized into the previously denervated gastrocnemius muscle. At different stages after neurotization, evoked M-waves of the neurotized muscle, and muscle weights were analyzed. Histological findings of the neurotized and denervated gastrocnemius muscles, and the number of spinal anterior horn cells labeled by the horseradish peroxidase method, were also studied. The labeled cells of the neurotized gastrocnemius muscle were located in the spinal level between L3 and L5, which was almost the same site as that of the anterior tibial muscle in normal rats. This finding showed that the denervated gastrocnemius muscle was reinnervated by the implanted common peroneal nerve. The labeled cells of the neurotized gastrocnemius muscle started to appear 2 weeks after neurotization, and the number of cells were almost the same as in the control side from 3 weeks to the end of the experiment. The fixed formed M-wave was observed in some cases 3 weeks after neurotization and in all cases at 6 weeks and thereafter. Four weeks after neurotization and denervation, the weight of neurotized muscle was significantly heavier than that of denervated muscle. The histological findings of the gastrocnemius muscle 3 months after neurotization were almost normal. These results showed that the reinnervation of denervated muscle after direct neurotization using cross innervation began after 2 weeks and the neurotized muscle started to regain its function 3 weeks after the neurotization. The present study also suggested that the muscle power of the neurotized muscle recovered fully resulting from increasing number of labeled spinal anterior horn cells.


Evidence for a conserved 95-120 kDa subunit associated with and essential for activity of V-ATPases.

Vacuoles purified from Saccharomyces cerevisiae bearing the vph1-1 mutation had no detectable bafilomycin-sensitive ATPase activity or ATP-dependent proton pumping. Furthermore, the vacuolar H(+)-ATPase (V-ATPase) nucleotide binding subunits were no longer associated with vacuolar membranes yet were present at wild-type levels in yeast whole-cell extracts. The VPH1 gene was cloned by screening a lambda gt11 expression library with antibodies directed against a 95 kDa vacuolar integral membrane protein and independently cloned by complementation of the vph1-1 mutation. Deletion disruption of the VPH1 gene revealed that the VPH1 gene is required for vacuolar H(+)-ATPase assembly and vacuolar acidification but is not essential for cell viability or for targeting and maturation of vacuolar proteases. VPH1 encodes a predicted polypeptide of 840 amino acid residues (95.6 kDa) with putative membrane-spanning regions. Cell fractionation and immunodetection demonstrate that Vph1p is a vacuolar integral membrane protein that co-purifies with V-ATPase activity. Vph1p has 42% identity to the 116 kDa polypeptide of the rat clathrin-coated vesicles/synaptic vesicle proton pump, 42% identity to the TJ6 mouse immune suppressor factor, 42% identity to the Caenorhabditis elegans proton pump homologue and 54% identity to the predicted polypeptide encoded by the yeast gene STV1 (Similar To VPH1, identified as an open reading frame next to the BUB2 gene.


Evolution and isoforms of V-ATPase subunits.

The structure of V- and F-ATPases/ATP synthases is remarkably conserved throughout evolution. Sequence analyses show that the V- and F-ATPases evolved from the same enzyme that was already present in the last common ancestor of all known extant life forms. The catalytic and non-catalytic subunits found in the dissociable head groups of both V-ATPases and F-ATPases are paralogous subunits, i.e. these two types of subunits evolved from a common ancestral gene. The gene duplication giving rise to these two genes (i.e. those encoding the catalytic and non-catalytic subunits) pre-dates the time of the last common ancestor. Similarities between the V- and F-ATPase subunits and an ATPase-like protein that is implicated in flagellar assembly are evaluated with regard to the early evolution of ATPases. Mapping of gene duplication events that occurred in the evolution of the proteolipid, the non-catalytic and the catalytic subunits onto the tree of life leads to a prediction of the likely quaternary structure of the encoded ATPases. The phylogenetic implications of V-ATPases found in eubacteria are discussed. Different V-ATPase isoforms have been detected in some higher eukaryotes, whereas others were shown to have only a single gene encoding the catalytic V-ATPase subunit. These data are analyzed with respect to the possible function of the different isoforms (tissue-specific, organelle-specific). The point in evolution at which the different isoforms arose is mapped by phylogenetic analysis.


Structure and function of V-ATPases in endocytic and secretory organelles.

Chromaffin granules and clathrin-coated vesicles are major sources for V-ATPases of mammalian cells. Studies of these organelles have helped us to understand the structure and function of the enzyme. It was shown that V-ATPases are composed of distinct catalytic and membrane sectors containing several subunits. The subunit stoichiometry was determined to be 3A, 3B, 1C, 1D, 1E, 6c (proteolipids), 1Ac115 and ?Ac39. Additional subunits are likely to be discovered. Resolution and reconstitution of the enzyme revealed that the catalytic and membrane sectors are interdependent for their partial activity. The catalytic sector has no ATPase activity when detached from the membrane sector, and the membrane sector when depleted of the catalytic sector does not conduct protons. The mechanistic significance of these properties is discussed.


Structure, function and regulation of the coated vesicle V-ATPase.

The coated vesicle V-ATPase plays an important role in both receptor-mediated endocytosis and intracellular membrane traffic by providing the acidic environment required for ligand-receptor dissociation and receptor recycling. The coated vesicle V-ATPase is a macromolecular complex of relative molecular mass 750,000 composed of nine subunits arranged in two structural domains. The peripheral V1 domain, which has a relative molecular mass of 500,000, has the subunit structure 73(3)58(3)40(1)34(1)33(1) and possesses all the nucleotide binding sites of the V-ATPase. The integral Vo domain of relative molecular mass 250,000 has a subunit composition of 100(1)38(1)19(1)17(6) and possesses the pathway for proton conduction across the membrane. Reassembly studies have allowed us to probe the role of specific subunits in the V-ATPase complex while chemical labeling studies have allowed us to identify specific residues which play a critical role in catalysis. From both structural analysis and sequence homology, the vacuolar-type H(+)-ATPases resemble the F-type H(+)-ATPases. Unlike the F1 and Fo domains of the F-type ATPases, however, the V1 and Vo domains do not appear to function independently. The possible relevance of these observations to the regulation of vacuolar acidification is discussed.


V-ATPases in phagocytic cells.

V-ATPases in phagocytic cells are known to mediate the acidification of most intracellular organelles. Proton-pump-mediated acidification of these organellar compartments is vital to numerous cell processes, including receptor recycling, protein processing and sorting and microbial degradation. Recent studies have suggested a role for V-ATPases in cytoplasmic pH homeostasis. The present discussion will review the current knowledge regarding the presence of V-ATPases in both the plasmalemmal and organellar membranes of phagocytic cells, the regulation of proton pump activity in these locations and the functional significance of pump-mediated proton translocation.


The osteoclast proton pump differs in its pharmacology and catalytic subunits from other vacuolar H(+)-ATPases.

Osteoclasts are multinucleated cells derived from the mononuclear phagocyte system in the hematopoietic bone marrow. Their function is to resorb bone during skeletal growth and remodeling. They perform this function by acidifying an enclosed extracellular space, the bone resorbing compartment. Analysis of proton transport by inside-out vesicles derived from highly purified chicken osteoclast membranes has revealed the presence of a novel type of multisubunit vacuolar-like H(+)-ATPase. Unlike H(+)-ATPases derived from any other cell type or organelle, proton transport and ATPase activity in osteoclast vesicles are sensitive to two classes of inhibitors, namely V-ATPase inhibitors [N-ethyl-maleimide (NEM) and bafilomycin A1] and vanadate (IC50 100 mumol l-1), an inhibitor previously found to affect only P-ATPases. The osteoclast V-ATPase morphologically resembles vacuolar proton pumps and contains several vacuolar-like subunits (115 x 10(3), 39 x 10(3) and 16 x 10(3)M(r)), demonstrated by Western blot analysis. Subunits A and B of the catalytic domain of the enzyme, however, differ from that of other V-ATPases. In osteoclasts, subunit A has an M(r) of 63 x 10(3) instead of 67 x 10(3)-70 x 10(3); in contrast, monocytes, macrophages and kidney microsomes, which contain a vanadate-insensitive H(+)-ATPase, express the classical subunit A (70 x 10(3)M(r)). Moreover, two types of 57 x 10(3)-60 x 10(3)M(r) B subunits are also found: they are differentially recognized by antibodies and one is expressed predominantly in osteoclasts and the other in bone marrow cells and in kidney microsomes. Preliminary cloning data have indicated that the B subunit expressed in osteoclasts may be similar to the brain isoform. The osteoclast proton pump may, therefore, constitute a novel class of V-ATPase, with a unique pharmacology and specific isoforms of two subunits in the catalytic portion of the enzyme.


Polarized targeting of V-ATPase in kidney epithelial cells.

The membrane-associated V-ATPase that plays an important role in the regulation of acid-base balance by the kidney is a multisubunit enzyme that is densely packed into specialized membrane domains in intercalated cells. Intercalated cells can be separated into at least two subtypes, A-cells and B-cells, based on their morphological features, the distribution of V-ATPase, and the presence or absence of a basolateral chloride/bicarbonate anion exchanger (AE1) exclusively in B-cells. A-cells secrete protons into the tubule lumen, whereas B-cells secrete bicarbonate. The relative amounts of V-ATPase and AE1 in the plasma membranes of A- and B-cells are modulated under different acid-base conditions and provide a sensitive means by which urinary acidification can be controlled. The mechanisms governing the movement of acid-base transporting proteins between intracellular vesicles and the plasma membrane are under investigation. The microtubular apparatus of the cell is involved in maintaining both apical and basolateral polarity of the enzyme, and different isoforms of V-ATPase subunits may also be involved in the selective targeting of V-ATPase to different membrane domains.


Energization of sodium absorption by the H(+)-ATPase pump in mitochondria-rich cells of frog skin.

The frog skin in vivo is capable of active transepithelial H+ secretion (JH) which is matched by Na+ absorption (JNa). Studies in vitro demonstrate that JH is generated by an H(+)-ATPase pump localized in apical membranes of mitochondria-rich (MR) cells, whereas JNa occurs through an amiloride-sensitive pathway in principal (P) cells. The H+ pump is sensitive to inhibitors of carbonic anhydrase (e.g. acetazolamide) and to specific inhibitors of mitochondrial F1F0 H(+)-ATPase (oligomycin) and vacuolar (V)-type H(+)-ATPase (N-ethylmaleimide) and to inhibitors of both these types of H(+)-ATPases (dicyclohexylcarbodiimide, DCCD). JH is independent of external K+, which differentiates it from gastric H+/K(+)-ATPase and is strictly dependent on aerobic metabolism. The proton pump is primarily implicated in whole-body acid-base regulation. Acute stimulation of JH in response (seconds-minutes) to an acid load involves insertion of H+ pumps (exocytosis) from a cytosolic pool into the apical membrane. The chronic response (days) to metabolic acid load involves morphological changes (increased apical membrane surface area and number of MR cells). Whole-cell patch-clamp recordings of membrane capacitance and current fluctuations from MR cells demonstrate that a respiratory acid load and aldosterone produce rapid exocytotic insertion of DCCD-sensitive conductive membrane. A secondary role of the H+ pump is to energize sodium absorption (JNa) via principal cells from dilute solutions in the absence of a permeant anion under open-circuit conditions. The apparent 1:1 stoichiometry between JH and JNa is a result of transepithelial electrical coupling between these electrogenic fluxes. The H+ pump in MR cells generates a transepithelial current (serosa to apical) which acts as a physiological voltage-clamp to hyperpolarize the apical membrane of P cells. This hyperpolarization can facilitate passive Na+ entry across the apical membrane against a threefold chemical gradient. Since both JH and JNa are sensitive to membrane potential, inhibition or activation of one will produce similar effects on the transport of the other ion. For example, inhibition of JH by ethoxzolamide will reduce JNa. Conversely, blocking JNa with amiloride also inhibits JH. These effects can be avoided or reversed if variations in membrane potential are prevented by voltage-clamping the epithelium. A paradoxical activation of JNa is observed when JH is stimulated by an acid load (CO2), despite inhibition of Na+ channel activity by H+ in P cells.(ABSTRACT TRUNCATED AT 400 WORDS)


V-ATPases of the plasma membrane.

V-ATPases reside in high densities on the plasma membrane in specialized types of insect and vertebrate cells. They provide unique biochemical and electrophysiological properties that allow them to function in energizing the plasma membrane in insects, and in cellular acid excretion in vertebrates.


Ion transport in parasitic protozoa.

Many parasitic protozoa go through complex life cycles in the course of which they adapt to widely different environments; ion transport processes are expected to play a role both in pathogenicity and in adaptation. So far, studies on ion transport have been virtually limited to Leishmania, Plasmodium and Entamoeba. The distribution of ion pumps in the former two organisms generally appears to conform to the picture established for other protozoa, i.e. a proton-motive P-ATPase in the plasma membrane provides the driving force for H(+)-coupled secondary-active transport, a proton-motive V-ATPase in the digestive vacuoles is responsible for vacuolar acidification, and an F-ATPase (ATP synthase) is found in the mitochondria. The situation in Entamoeba, an archaic organism that lacks mitochondria, could be different from that in the two other parasites in that a V-ATPase may be present and active both in the plasma membrane and in the membranes of the endocytic vesicles.


The insect V-ATPase, a plasma membrane proton pump energizing secondary active transport: molecular analysis of electrogenic potassium transport in the tobacco hornworm midgut.

Goblet cell apical membranes in the larval midgut of Manduca sexta are the site of active and electrogenic K+ secretion. They possess a vacuolar-type ATPase which, in its immunopurified form, consists of at least nine polypeptides. cDNAs for the A and B subunits screened by monoclonal antibodies to the A subunit of the Manduca V-ATPase or by hybridisation with a cDNA probe for a plant V-ATPase B subunit have been cloned and sequenced. There is a high degree of identity to the sequences of the respective subunits of other V-ATPases. The M. sexta plasma membrane V-ATPase is an electrogenic proton pump which energizes, by the electrical component of the proton-motive force, electrogenic K+/nH+ antiport, resulting in net electrogenic K+ secretion. Since the midgut lacks a Na+/K(+)-ATPase, all solute fluxes in this epithelium seem to be energized by the V-ATPase. Thus, the midgut provides an alternative to the classical concept of animal plasma membrane energization by the Na(+)-motive force generated by the Na+/K(+)-ATPase.


Vacuolar ATPase of Neurospora crassa: electron microscopy, gene characterization and gene inactivation/mutation.

We are using three approaches to investigate the vacuolar ATPase, V-ATPase, from Neurospora crassa. (1) Examination in the electron microscope shows the enzyme has a 'ball and stalk' structure like the F-type ATPases. However, the vacuolar ATPase is significantly larger, has a prominent cleft in the head sector, and has extra components associated with the stalk and membrane sectors. (2) Genes encoding three of the major subunits of the vacuolar ATPase and the homologous subunits of the mitochondrial F-ATPase have been isolated. The exon/intron structures of the genes have been analyzed and the chromosomal locations have been determined. Two of the vacuolar ATPase genes map very close to each other, suggesting the possibility of a cluster of ATPase genes. (3) The function of the ATPase is being investigated by isolating strains with altered or inactivated ATPase. We are characterizing strains that are resistant to bafilomycin A1, a potent and specific inhibitor of the vacuolar ATPase. Initial attempts to inactivate a vacuolar ATPase gene indicate that the enzyme may be essential for growth.


Molecular genetics of the yeast vacuolar H(+)-ATPase.

The yeast vacuolar proton-translocating ATPase was discovered in 1981 as the first member of the V-ATPases, which are now known to be ubiquitously distributed in eukaryotic vacuo-lysosomal organelles and archaebacteria. Nine VMA genes that are indispensable for expression of vacuolar ATPase activity have been identified in the yeast Saccharomyces cerevisiae. VMA1, VMA2, VMA3, VMA5 and VMA6 were cloned and characterized on the basis of partial amino acid sequences determined with the purified subunits. Genetic and biochemical studies of the yeast Pet-cls mutants have demonstrated that they are related to vma defects. Based on this evidence, VMA11 (CLS9), VMA12 (CLS10) and VMA13 (CLS11) were isolated from a yeast genomic DNA library by complementation of the vma11, vma12 and vma13 mutations, respectively. This article summarizes currently available information on the VMA genes and the molecular biological functions of the VMA gene products.


Mutations in the yeast vacuolar ATPase result in the mislocalization of vacuolar proteins.

The vacuolar ATPase of the yeast Saccharomyces cerevisiae acidifies the vacuolar lumen and generates an electrochemical gradient across the vacuole membrane. We have investigated the role of compartment acidification of the vacuolar system in the sorting of vacuolar proteins. Strains with chromosomal disruptions of genes (delta vat) encoding the A (69 x 10(3) M(r)), B (57 x 10(3) M(r)) or c (16 x 10(3) M(r)) subunits of the vacuolar ATPase accumulate and secrete precursor forms of the soluble vacuolar hydrolases carboxypeptidase Y and proteinase A. A kinetic analysis suggests that these precursor proteins accumulate in, and are secreted from, the Golgi complex or post-Golgi vesicles. In addition, subcellular fractionation shows that vacuolar hydrolase-invertase hybrid proteins are inefficiently localized to the vacuole in delta vat strains. This result suggests that the vat mutations cause a steady-state defect in vacuolar protein sorting. The vat mutations also affect the sorting of vacuolar membrane proteins. Precursor forms of alkaline phosphatase are accumulated in vat mutant cells, but to a lesser extent than is seen for the soluble vacuolar hydrolases. This finding, coupled with the insensitivity of alkaline phosphatase to the ATPase inhibitor bafilomycin A1, suggests that vacuolar membrane protein sorting is less sensitive to changes in lumenal pH when compared with the targeting of soluble vacuolar proteins. These results indicate that acidification of the vacuolar system is important for efficient sorting of soluble proteins to the vacuole.


Biogenesis of the yeast vacuolar H(+)-ATPase.

Achieving an understanding of the biosynthesis, assembly and intracellular targeting of the vacuolar H(+)-ATPase is critical for understanding the distribution of acidic compartments and the regulation of organelle acidification. The assembly of the yeast vacuolar H(+)-ATPase requires the attachment of several cytoplasmically oriented, peripheral subunits (the V1 sector) to a complex of integral membrane subunits (the Vo sector) and thus is not easily described by the established mechanisms for transport of soluble or vacuolar membrane proteins to the vacuole. In order to examine the assembly of the enzyme complex, yeast mutants lacking one of the subunit genes have been constructed and the synthesis and assembly of the other subunits have been examined. In mutants lacking one subunit, the remaining ATPase subunits seem to be synthesized, but in many cases are either not assembled or not targeted to the vacuole. Immunofluorescence and subcellular fractionation experiments have revealed that deletion of one peripheral subunit prevents the other peripheral subunits, but not the integral membrane subunits, from reaching the vacuole. In contrast, the absence of one of the integral membrane subunits appears to prevent both the peripheral subunits and another integral subunit from reaching the vacuole and also results in reduced cellular levels of the other integral membrane subunit. These data suggest that transport of integral and peripheral membrane subunits to the vacuole may employ somewhat independent mechanisms and that some assembly of the V1 and Vo sectors may occur before the two sectors are joined. Current models for the assembly process and the implications for organelle acidification are discussed.


Four triggering factors in loudness adaptation.

A factor analysis was used to determine whether induced loudness adaptation (Botte, Canevet, & Scharf, 1982; Scharf, 1983) and adaptation measured by Hood's (1950) classic Simultaneous Dichotic Loudness Balance technique (SDLB) would cluster on the same factors. The two phenomena did not cluster on the same factors; thus, induced adaptation cannot replace SDLB adaptation. Four independent factors that trigger auditory adaptation were identified in the factor analysis.


Individual differences in anxiety level and eyewitness memory.

The present study investigated the relationship between individual differences in anxiety and eyewitness performance. Instructions designed to produce evaluative threat were given to anxious and nonanxious subjects at encoding and/or at retrieval. The performance of those subjects who were given anxiety-arousing instructions at encoding and retrieval and who scored high on the Test Anxiety Scale (TAS; Sarason, 1972) was less accurate on an eyewitness task than was that of the subjects who scored low on the scale. This difference in performance was attributable to improvement in the performance of nonanxious subjects, rather than debilitation in the performance of anxious subjects. Faced with the threat of failure, low-anxious subjects appeared to have the potential for increased effort. High-anxious subjects seemed to perform at or near capacity under all the experimental conditions because of their predisposition for task-irrelevant worry, which limited the possibility of an increase in working memory capacity.


Verbal indicators of depression.

Speech content, voice quality, and temporal pacing of speech were evaluated for 11 well and 11 depressed women. Sadness was the dominant mood of the depressed women's speech, whereas happiness and mood neutrality characterized the well women's speech. The well women's tone of voice changed with the content of their speech. The well women spoke with a wide range of fundamental frequency, and the average fundamental frequency of their voices changed according to speech content. In contrast, the depressed women spoke with a narrow range of fundamental frequency, and the average fundamental frequency of their speech was unaffected by speech content. The depressed women spoke with longer pauses than the well women did. The results of this study contribute to the understanding of measures for assessing depression.


Some perceptual and cognitive factors in mirror tracing: their limits.

Three mirror tracing experiments were conducted to investigate the connection between perception and motor behavior. In the first experiment, some subjects traced a hex-maze, other subjects traced a hex-maze after observing a model trace, others traced a hex-maze after reading instructions on mirror images, and others traced a hex-maze after having observed a model and heard the instructions. There were no significant differences between the groups' error scores, but their time scores differed significantly, although not always in the predicted direction. In Experiment 2, the subjects were to trace selected letters of the alphabet. Error scores for the second experiment did not differ much from those for the first experiment. In Experiment 3, the experimenter gave each subject commands for the correct directions of movement, using the subject's body as a frame-of-reference. There was little improvement in motor performance. These results suggest that the visual information presented in the mirror captured the subjects' attention and blocked their motor tracing program.


Exposed eye area (EEA) in the expression of various emotions.

Exposed eye area (EEA) was measured in photographs of Indian adults who modeled six emotions--happiness, sadness, fear, anger, surprise, and disgust--as well as a neutral expression. The data were analyzed with a 2 x 6 (Eyes x Emotions) factorial analysis of covariance (ANCOVA). EEA for neutral expression was used as the covariate measure. The EEAs of the two eyes did not differ significantly during the expression of emotion. The EEAs for fear and surprise were significantly larger, and the EEA for disgust was significantly smaller than those for either other emotions or neutral expression.


The history of drugs for the treatment of Parkinson's disease.

In 1817, the English physician, James Parkinson, described the classical symptoms of a disease that was characterized by tremor, rigidity and akinesia. In 1861, the first autopsy of a patient with Parkinson's disease was carried out. Although Ordenstein, a pupil of Charcot, introduced treatment with belladonna in 1867, this later fell into disuse. In 1875, Brissaud determined that the lesion responsible for Parkinson's disease must be locatec the subthalamic regions of the brain. He was also the first to discuss arteriosclerosis-induced forms of Parkinson's disease. In 1919 Tretiakoff discovered cellular damage in the substantia nigra of patients with the encephalitic form of Parkinson's disease. In the 1920s, C. and O. Vogt discovered the basic histological conditions underlying the function of the corpus striatum; later Hassler significantly expanded and completed this work. The following chronology of dates and events is aimed at creating an understanding of the historical aspects of this diseases and consists of milestones in the development of antiparkinsonian treatment.


Early diagnosis in Parkinson's disease.

In early stages of Parkinson's disease (PD) clinical symptoms are often very subtle. Therefore additional instrumental and biochemical methods could be useful to confirm the diagnosis. Firstly, clinical signs could be detected in a more sensitive way by using kinesiologic methods e.g. the Motor Performance Test. Secondly, imaging techniques like Positron Emission Tomography are valuable tools. Up to now, specific biochemical markers for early PD are not available. Field studies are needed to validate the sensitivity of different instrumental and biochemical methods for early diagnosis in PD.


Mental disorders in Parkinson's disease.

Certain psychiatric complications are associated with various stages of PD. The possible causes known to date are analysed. Depression, isolated cognitive impairments, pharmacotoxic psychosis and dementia-related changes are the predominant mental disorders in PD. PD and depression syndrome occur very frequently in old age. Behaviour and mimicry of patients with progressive PD and of patients with depression syndrome are sometimes so similar that the two conditions can be differentiated only by long-term monitoring. In addition, PD and depression may occur simultaneously. However, frequency and intensity of depressive phases do not differ in PD patients and aged-matched depressed patients without PD. About one third of patients hospitalized at the neurological department of the Geriatric Hospital Lainz require antidepressant drug treatment. Similar percentages were found for other chronic cerebral and extracerebral diseases in the aged. Major depressions are independent of the parkinsonian disability and can be successfully managed only by antidepressant medication. Pharmacotoxic psychoses are not only serious conditions, they also reveal the limitations of therapeutic options. The unusual frequency of such acute psychoses, i.e. 30 to 60% in the terminal stages of the disease, indicates a special relation between antiparkinson medication and increasing neurotransmitter disturbances. Permanent pronounced depression in the sense of DSM III is not one of the symptoms of typical PD. States of dementia occur only in connection with a second or third cerebral pathology, mostly in combination with SDAT and MID.


Modern therapy of Parkinson's disease.

The article summarizes historical aspects and current concepts of the treatment of Parkinson's disease. Antiparkinsonian therapy varies with the progression of the disease, age and clinical subtypes. Levodopa, anticholinergic substances, direct dopamine agonists, amantadine, L-deprenyl are used to treat motor symptoms of Parkinson's disease. Novel substances and therapeutic concepts are currently investigated. Treatment of non-motor symptoms of Parkinson's disease and supportive therapies are discussed in the article.


Trichloroharmanes as potential endogenously formed inducers of Morbus Parkinson: synthesis, analytics, and first in vivo-investigations.

The hypnotic chloral reacts chemically with tryptamine and tryptophan under physiological conditions to give novel trichloro-tetrahydroharmanes ("TTHs"). These are structurally similar to the classical neurotoxin MPTP. Moreover, the TTH-precursor chloral is also a metabolite of the frequently used solvent trichloroethylene (Tri). These properties and first hints at a neuropharmacological potential of this class of substances warrent investigations whether TTHs and other chloral-derived harmanes are formed endogenously and possibly have to do with the pathogenesis of Morbus Parkinson (MP). For an investigation of these problems, some fundamental methods and results had to be elaborated first: the synthesis of several representatives of this novel class of trichloroharmanes, sensitive analytical methods for the detection of these compounds even in biological matrices, and studies concerning their biological "fate".


Neurotoxicity and neuroprotection in Parkinson's disease.

Recent findings of impaired mitochondrial function, altered iron metabolism and increased lipid peroxidation in the substantia nigra in Parkinson's disease emphasize the significance of oxidative stress and free radical formation in the pathogenesis of the disease. Future research will focus on improvements in neuroprotective therapy to prevent or slow the rate of progression of Parkinson's disease. Possible neuroprotective strategies include free radical scavengers, monoamine oxidase-B inhibitors, iron chelators and glutamate antagonists.


Synergism of NBQX with dopamine agonists in the 6-OHDA rat model of Parkinson's disease.

Advance in understanding of the anatomy, physiology and pharmacology of basal ganglia organisation over the past decade revealed a functional relation between excitatory glutamatergic and the degenerated dopaminergic nigrostriatal transmitter systems which could serve as targets for pharmacological interventions in Parkinson's disease. The selective AMPA-antagonist NBQX is not effective in animal models of Parkinson's disease when given alone but ameliorates parkinsonian symptomatology and enhances the locomotor response of a threshold dose of L-DOPA. These synergistic effects are seen in the MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmoset and the rat with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Here we report that, in the latter model, such synergism of NBQX is also seen with the direct dopamine agonists lisuride and apomorphine, indicating the potential usefulness of AMPA antagonists for the symptomatic treatment of Parkinson's disease.


Behavioural pharmacology of glutamate in the basal ganglia.

In Parkinson's disease the dopaminergic inhibition--mediated by DA2 receptors in the striatum--is reduced. Therefore glutamatergic excitation predominates in the antero-dorsal striatum. In turn the glutamatergic neurons of the subthalamic nucleus become disinhibited. Antagonists of the NMDA-subtype of glutamate receptors injected locally into the glutamatergically innervated nuclei or competitive and non-competitive NMDA-antagonists administered systemically, counteract parkinsonian symptoms in animals.


In vitro and in vivo experiments--what is more informative?

In-vitro experiments offer a lot of informations but if in-vitro technics would be used exclusively for drug research and screening of new substances the complete pharmacological profile would be unknown. It is always necessary to integrate knowledge of basic research into living and active animals. The fruitful co-operation between theoretical and clinical disciplines--as demonstrated by the L-DOPA story here--demonstrates how to achieve real progress in medical research and the question which type of experiments is more informative is not relevant.


Dystonia--a clinical, neuropathological and therapeutic review.

Dystonia is a syndrome characterized by sustained muscle contractions frequently causing twisting and repetitive movements or abnormal posture. For diagnosis, prognosis and therapy, it is useful to classify dystonia with regard to types of abnormal movements present, their mode of activation and topographical distribution taking into account age of onset, and etiology. The majority of cases are idiopathic, or primary dystonias, while in a minority environmental, structural, or metabolic causes can be identified. Primary dystonias can be familial or sporadic. The most important neurophysiological phenomenon in dystonia is pathological cocontraction of antagonistic muscles, while there is no consistent neuropathological abnormality in idiopathic dystonia. Causal therapies for dystonia are only possible in a few symptomatic forms (M. Wilson, Segawa-syndrome). As a rule, treatment has to be symptomatic but results of systemic pharmacotherapies remain disappointing. For adult onset focal dystonias, a breakthrough in symptomatic therapy has been achieved with local "chemical" denervation by means of botulinum toxin type A injections.


Activity of monkey frontal eye field neurons projecting to oculomotor regions of the pons.

1. This study identified neurons in the rhesus monkey's frontal eye field that projected to oculomotor regions of the pons and characterized the signals sent by these neurons from frontal eye field to pons. 2. In two behaving rhesus monkeys, frontal eye field neurons projecting to the pons were identified via antidromic excitation by a stimulating microelectrode whose tip was centered in or near the omnipause region of the pontine raphe. This stimulation site corresponded to the nucleus raphe interpositus (RIP). In addition, electrical stimulation of the frontal eye field was used to demonstrate the effects of frontal eye field input on neurons in the omnipause region and surrounding paramedian pontine reticular formation (PPRF). 3. Twenty-five corticopontine neurons were identified and characterized. Most frontal eye field neurons projecting to the pons were either movement neurons, firing in association with saccadic eye movements (48%), or foveal neurons responsive to visual stimulation of the fovea combined with activity related to fixation (28%). Corticopontine movement neurons fired before, during, and after saccades made within a restricted movement field. 4. The activity of identified corticopontine neurons was very similar to the activity of neurons antidromically excited from the superior colliculus where 59% had movement related activity, and 22% had foveal and fixation related activity. 5. High-intensity, short-duration electrical stimulation of the frontal eye field caused omnipause neurons to stop firing. The cessation in firing appeared to be immediate, within < or = 5 ms. The time that the omnipause neuron remained quiet depended on the intensity of the cortical stimulus and lasted up to 30 ms after a train of three stimulus pulses lasting a total of 6 ms at an intensity of 1,000 microA. Low-intensity, longer duration electrical stimuli (24 pulses, 75 microA, 70 ms) traditionally used to evoke saccades from the frontal eye field were also followed by a cessation in omnipause neuron firing, but only after a delay of approximately 30 ms. For these stimuli, the omnipause neuron resumed firing when the stimulus was turned off. 6. The same stimuli that caused omnipause neurons to stop firing excited burst neurons in the PPRF. The latency to excitation ranged from 4.2 to 9.8 ms, suggesting that there is at least one additional neuron between frontal eye field neurons and burst neurons in the PPRF. 7. The present study confirms and extends the results of previous work, with the use of retrograde and anterograde tracers, demonstrating direct projections from the frontal eye field to the pons.(ABSTRACT TRUNCATED AT 400 WORDS)


Coding of odor molecules by mitral/tufted cells in rabbit olfactory bulb. I. Aliphatic compounds.

1. Recordings of extracellular spike responses were made from single mitral/tufted cells in the main olfactory bulb of urethan-anesthetized rabbits. Olfactory epithelium ipsilateral to the recorded olfactory bulb was stimulated with homologous series of aliphatic compounds using periodic artificial inhalations. 2. In the dorsomedial part of the main olfactory bulb, single mitral/tufted cells were activated by subsets of n-fatty acids with similar hydrocarbon chain lengths. Response selectivities of single mitral/tufted cells were examined in detail using a series of n-fatty acids at five different concentrations. The results indicate that although the range of effective fatty acids is broader at the higher concentrations, the best response at higher concentrations was similar to that determined at lower concentrations. 3. Analysis of single-unit responses to the panel of fatty acids, including those with branched hydrocarbon chains, suggested that the determinants for the response specificities of individual mitral/tufted cells in the dorsomedial region include the overall size of hydrocarbon chains of the odor ligand molecules. 4. Single mitral/tufted cells in the dorsomedial region tended to be activated not only by fatty acids but also by n-aliphatic aldehydes. For a panel of a homologous series of n-aldehydes at five different concentrations, individual mitral/tufted cells showed response selectivity to subsets of aldehydes with similar hydrocarbon chain lengths. 5. In most cases, normal aliphatic alcohols and alkanes were ineffective in activating mitral/tufted cells in the dorsomedial region. This suggests that carbonyl group (--C = O) in the odor molecules plays an important role in determining response specificity of these neurons. 6. Examination with an expanded panel of stimulus odor molecules that included ketones and esters indicated that single mitral/tufted cells sensitive to subsets of fatty acids and n-aliphatic aldehydes were also responsive to subsets of ketones and/or esters having hydrocarbon chain lengths similar to those of the effective fatty acids and aldehydes. 7. The present results show a clear correlation between the tuning specificity of individual mitral/tufted cells and the stereochemical structure of the odor molecules, with respect to 1) length and/or structure of hydrocarbon chain, 2) difference in functional group, and 3) position of the functional group within the molecule. 8. A hypothetical diagram suggesting functional convergence of olfactory nerve input to individual glomeruli is proposed to explain the mechanism for selective activation of individual mitral/tufted cells by a range of odor molecules with similar stereochemical structures.