["Locked-in" syndrome in intensive care patients (author's transl)].

The "locked-in" syndrome constitutes a potential source of diagnostic and prognostic errors, especially in intensive care patients. The pathologicoanatomical, pathophysiological and clinical features of the syndrome are described and differentiated from other syndromes. Means of establishing contact are reviewed which would allow simple wishes on the part of the patient to be satisfied and thus prevent the psychic isolation of the (conscious) patient.


[A case of severe multiple trauma (author's transl)].

A case of severe multiple trauma sustained in a road accident is reported. The aim of the report is to show the determing role played by diagnostic and surgical methods and therapeutic possibilities available in the intensive care unit (shock treatment, controlled respiration, parenteral feeding, haemodialysis) in winning the five-months' battle for the life of the patient. Early haemodyalisis as supporting therapy in respiratory failure and conservation treatment of intestinal fistulae are important. Post-traumatic pancreatitis which is a not infrequent complicating feature of severe multiple trauma may present diagnostic difficulties.


[EEG-spectrum analysis for documentation of depth of anaesthesia. Correlation with pharmacokinetic data of fentanyl (author's transl)].

The article reports on a study regarding the posibility of monitoring anaesthesia via EEG characteristics when using fentanyl-nitrous oxide. An alpha-delta index correlated sufficiently accurately with the plasma levels of fentanyl administered via continuous infusion.


[Physical basis and therapeutic range of application of ultrasonic aerosols (author's transl)].

An aerosol of an aqueous solution still changes its size from development up to alveoli; therefore only conclusions can be made about possible sizes of particle spectrum. Volatilisation, condensation, coagulation and sedimentation are the important interfering factors. To characterize an aerosol one should know the aerosolvolume, the quantity of nebulised substance and the relative size distribution. A method for measurement of size distribution -- a radioactive aerosol was deposited in a spiral centrifuge -- is described and the aerosol of two ultrasonic nebulizers were compared. Because of their physical properties aerosols of ultrasonic nebulizers play a main part in prophylaxis and therapy of functional lesion of bronchopulmonary affections.


[The treatment of haemorrhagic complications due to disturbance of platelet function after operations with extracorporal circulation (author's transl)].

The preoperative selective blood cell separation followed by the postoperative platelet autoransfusion could prevent the exhaustion of platelet function by operations with extracorporal circulation. The postoperative blood loss could be reduced by about 57%. This method can be recommended specially in cases of increased platelet traumatization after long time perfusion. Partial disturbances of platelet function after operations with ECC can also be favourably influenced by infusion of homologous phospholipid (Fibraccel). The postoperative blood loss could be reduced by about one third. This method is beneficial in open heart surgery with short perfusion times due to its little technical expenses.


[Skin emphysema caused by a sump tube (author's transl)].

A case of a transnasal, paraoesophageally placed sump tube is reported with consecutive skin emphysema. This complication was caused by certain circumstances: 1. unnoticed perforation of oesophagus, 2. open tube, 3. inspiration against resistance, 4. tube tip placed in slack connective tissue.


[Clinical diagnosis of allergy (author's transl)].

"Allergic" manifestations are not necessarily of allergic origin; they can also be produced by non-allergic factors and their true allergic nature must, therefore, be proved. A detailed personal history and the presence of eosinophilia (in the blood or secretions) are suggestive evidence which has to be confirmed by the identification of specific antibodies of the immunoglobulin-E type. Criteria for arriving at the diagnosis "allergy" are (a) demonstration of antibodies by skin and mucous membrane tests with allergen extracts; (b) demonstration of the activity of the identified allergen by challenge tests on the reacting organ (conjunctiva, nose, bronchi); (c) in-vitro demonstration of the allergen-specific immunoglobulin-E by means of the radio-allergo-sorbent test. Details for the performance of the various tests are given and the interpretation and significance of the findings are discussed.


[Extrinsic allergy in obstructive respiratory disease in childhood and adolescence (author's transl)].

The incidence of extrinsic allergy was studied in 1,246 children and adolescents with recurrent unspecific respiratory and allergic complaints. Special attention was paid to obstructive respiratory diseases, such as bronchial asthma and obstructive of asthmatic bronchitis. Skin tests and the radio-allergo-sorbent test (RAST) showed sensitization in 77% of the cases. Challenge tests and a detailed personal history, however, revealed clinically active sensitization in only 62%. The clinical and practical significance of the findings is discussed.


[The clinical significance of challenge tests (author's transl)].

108 pollen-sensitive persons (positive skin test, positive history) and 40 latent pollen-allergic persons (positive skin test, but no conjunctival or nasal manifestations during the flowering season) were given intranasally increasing concentrations of pollen extract until a reaction occurred (itching, sneezing, running and blocked nose). 7.4% of the patients reacted to 0.001% w/v of the pollen extract, 56.5% reacted to 0.01, and 36% to a dose of 0.1% w/v. The corresponding figures for persons with latent allergy were 0.7, 5 and 30%; 62.5% reacted to 1.0 or 2.5% w/v of the extract. There was a relatively sharp division between doses of 0.1 and 1.0% w/v: persons who responded only to 1% concentrations invariably belonged to the group of latent allergy. 35 persons with positive skin tests to dust mites were divided into 3 groups: those with either a positive or a negative history of dust allergy and those concentrations of dust mite extracts (0.012, 0.12 and 1.2% w/v). Patients were considered to have latent allergy if they were sensitive to dust mite but were free from symptoms; or if they were sensitive to dust mite and pollen, but were symptom-free outside the flowering season. Although the group reacted slightly more often only to concentrations of 1.2%, the nasal response occurred on the whole with the same frequency with all three concentrations. In contrast to pollen allergy a positive intranasal dust mite test is not necessarily clinically relevant. Provocation tests are, therefore, not an infallible means to ascertain the presence of clinically relevant allergy.


[Immunotherapy with BCG and mycobacterial fractions and its use in bronchogenic carcinoma (author's transl)].

Animal experiments at the Nat. Cancer Inst. have established that only intra-tumorous application of BCG vaccine has a lasting immunotherapeutic effect on transplantable tumours. However, clinical observations have proved that BCG immunotherapy by the intra-tumorous route increases the incidence of complications, such as allergic reactions and generalized spread of BCG, to an unacceptable level. Ribi has produced a vaccine from mycobacterial fractions which is low in protein and which, as proved in clinical pilot studies in cases of melanoma and cancer of the breast, is so well tolerated that it can be injected into the tumour. Since bronchogenic carcinoma is in the majority of cases inoperable, but, on the other hand, can be reached directly via the bronchoscope or the perthoracic route a pilot study with the Ribi vaccine was started in patients with lung cancer. The preliminary results are reported.


[Immunological studies and immunotherapeutic possibilities in inoperable bronchogenic carcinoma (author's transl)].

By establishing an immune profile combined with detailed clinical observation an attempt was made to assess the value of various therapeutic measures, especially immunological methods, in the treatment of inoperable bronchogenic carcinoma. The results indicated that in advanced cases specific immunological measures or stimulation of the immune mechanism only play a supportive role. Toxic side-effects or tumour enhancement were absent.


[Architectonics of the thorax (author's transl)].

Blunt traumata cause injury to the thorax and intrathoracic organs by deforming the chest wall and the enclosed structures. Neither examination of the dead person and re-enactment of the accident nor experimental studies on the living or dead person can fully elucidate the course of events. A more satisfactory approach is to use biomechanic models to simulate the structure of the thorax and the type of deformation it undergoes when subjected to various traumata. Such an elasto-static analysis presupposes knowledge of (1) the global geometry of the thorax; (2) the cross sectional geometry of the individual components; (3) the mechanical properties of the material; (4) the force of the impact; (5) concomitant conditions. The results obtained with the models are reviewed. They make it possible to predict the deformation of the thorax in response to the force of the impact, the location and type of fracture of the ribs and the deformation of the intrathoracic organs.


[The physiology of intrathoracic pressure changes (author's transl)].

The pleural cavity, because of the thin film of fluid between the pleural layers, acts like a capillary space within which capillary forces operate. It is due to these forces that the lungs follow the respiratory movements of the thoracic cage and diaphragm and are kept expanded within the thorax. "Subatmospheric" pressure in the pleural cavity develops only if the capillary space is opened by injury to one of the pleural layers, thus allowing the elastic pull of the thoracic cage and lungs to act on the pleural cavity. The subatmospheric pressure registered by the exploratory needle is, in fact, non-existent in the normal chest. It owes its existence to the introduction of the needle which causes separation of the pleural layers and the introduction of a small quantity of air. The pulling and stretching forces exerted by the thorax and lungs on the air bubble then become measurable as subatmospheric pressure. The same forces operate during the respiratory movements and induce changes in volume and pressure in all air or fluid containing spaces. The result is a delicately regulated consonance of aire movement and blood distribution. Simplified graphs illustrate the interconnections.


[Diagnostic problems in chest injuries (angiography) (author's transl)].

Roentgenography is the simplest and most reliable means to arrive at the diagnosis of chest injury. General roentgenograms are difficult to interpret as they tend to be technically imperfect. Fractures, emphysema, pneumothorax, accumulation of fluid can usually be ascertained directly; but the traumatic origin of changes in the pulmonary parenchyma or of an enlarged heart shadow cannot be reliably deduced from the X-ray appearance. It may provide some differential-diagnostic information but the correct interpretation of the findings depends on further observation. In 6-7% of severe chest trauma with vascular injuries and rupture of the diaphragm angiography is indicated. The evidence to be obtained from chest radiography should not be overestimated: fractures of ribs are sometimes overlocked, even by the expert; parenchymatous lesions may manifest themselves as shadows but their nature remains obscure until they have been related to the clinical and subsequent radiological findings. The same applies to rupture of the diaphragm, bronchi or vessels, if only the immediate posttraumatic roentgenographs are examined. A tent-shaped heart shadow is considered characteristic of the presence of fluid in the pericardium; this is valid only for chronic hydropericardium, but not for the potentially fatal cardiac tamponade; if the pericardium has lost its elasticity a haemorrhage of not more than 150 ml may prove fatal. Nor does the roentgenogram provide information about pulmonary function. Especially in cases of pulmonary shock minor changes in the chest roentgenogram may give a false sense of security when, in fact, blood gas analyses show that a life-endangering situation has developed. The radiologist who is aware of the limititations of the method will derive maximum diagnostic benefit from a chest angiography. No other method is capable of supplying information of such great importance in such a short time.


[Emergency treatment in chest trauma (author's transl)].

The measures taken by the emergency physician can in many cases decisively affect the subsequent course of a chest trauma. In cases where the injured person has to be extricated from collapsed structures the medical officer has to decide on the mode and sequence of the rescue operation, prevent further damage and initiate shock therapy, intubation and artificial ventilation while the rescue operation is in progress. Emergency treatment also includes infusion therapy, if necessary via a central venous catheter; intubation, suction drainage and artificial ventilation; evacuation of fluid from the pleural cavity, mediastinum and pericardium combined with electrodiagnosis (ECG) and electrotherapy (defibrillation) if necessary. By closely observing the reaction and condition of the patient during transport to hospital he can provide important information regarding further treatment, especially in polytraumatized persons. Close collaboration between the trained rescue teams of the Fire Service, the emergency medical officer and the hospital staff has succeeded in reducing the mortality rate of combined chest injuries to 13%. 87% of cases who had received emergency treatment were subsequently admitted to hospital.


[Chest injuries (author's transl)].

The mortality rate of chest injuries sustained during work or in road accidents stands now at 15-20%. The considerable force of the impact in road accidents is, in 60-80% of the cases, responsible for chest injuries which involve not only the chest wall but also the lungs. The extent and course of the lung damage must be assessed by repeated X-ray examinations, blood gas analyses and clinical observations. The decision to intubate and apply artificial ventilation should be made at an early stage. Fracture of a single rib needs only pain killers. If a rib is broken in several places or if several ribs are fractured instability of the chest wall is apt to develop in 15-20% of the cases. It manifests itself in paradoxical breathing and ensuing increase in the dead space. These cases require prompt "internal pneumatic splinting" in the form of positive pressure respiration and intubation. In recent years surgical stabilization of the chest wall has regained favour. Plate osteosynthesis, screw-less rib plates, self-gripping steel plates and steel splints are being used (Brunner, Hofmeister, Koncz). Primary osteosynthetic stabilization of the chest wall is indicated only if artificial ventilation has proved inadequate and there are other reasons for performing a thoracotomy. In these circumstances surgical intervention ensures that prolonged artificial ventilation and its attendent risks and complications and the demands made on the nursing staff are reduced to a minimum.


[Open and closed chest trauma (author's transl)].

The observations made in 1,023 cases of chest trauma during 1947-1976 inclusive are analysed. According to the extent of the injuries they were classified as mild (group 1), moderate (group 2) and severe (group 3). The clinical picture was dominated by other than chest injuries in 45% of patients in group 1, in 66% in group 2 and in 51% in group 3. Injuries to the intrathoracic organs were seen in only 34 patients. Total mortality of all chest injuries was 12%; in group 3 it was 62%. Severe respiratory insufficiency was the direct cause of death in 25% of persons in group 3.


[Surgical aspects of open and closed chest injuries (author's transl)].

263 persons with chest injuries were treated over a period of 16 years. 47 had performating chest injuries, in the remaining cases it was a blunt trauma. Prompt recognition of a life-endangering situation (cardiac tamponade, tension pneumothorax, mediastinal emphysema, massive haemothorax) is essential; radiological and laboratory diagnostic methods play a secondary role. The most effective emergency treatment is intercostal continuous suction; in many cases it is the only one needed. A haemothorax must be evacuated completely because of the risk of complications and fibrin formation. Thoracotomy is rarely, and surgical removal of lung tissue hardly ever, indicated. 30 persons needed emergency thoracotomy. Accompanying intraabdominal injuries, mostly rupture of the diaphragm and spleen, were observed in 45 patients. Late sequels were lung abscesses, posttraumatic cysts, pleural empyema and adhesions, atelectases. Decortication, if indicated, should be performed at an early stage.


[Indications and methods for the surgical stabilization of an unstable thorax caused by multiple fractures of the ribs (author's transl)].

Every year 8,000 persons involved in road accidents die of irreversible respiratory insufficiency caused by chest injuries. Fractures of the ribs extendig over a number of ribs are present in 70% of the cases and in 15% of them they are accompanied by instability of the thorax and "paradoxical" respiration. Treatment of the instability by "internal pneumatic splinting" (Avery) and by surgical measures is reviewed. Indications for the latter are: (1) open fractures of the chest wall; (2) instability of the thorax combined with intrathoracic injuries; (3) instability of the chest wall with severe therapy-resistant respiratory insufficiency. In a series of animal experiments unilateral instability of the chest wall was induced by multiple rib fractures. By measuring oscillatory resistance before and after stabilization of chest wall the effects of the latter on the impaired lung function could be demonstrated. The results of the experiments indicate that with this type of surgical treatment mortality from combined thoracic injuries with paradoxical breathing can be reduced.


[Stabilization of the thoracic wall (author's transl)].

The improvement of mechanical respiration by surgical stabilization of the chest wall is an important measure to reduce disadvantages and complications of long time respiratory treatment. Indications are: (1) Chest wall instability with indication for emergency thoracotomy; (2) Respiratory insufficiency mainly caused by chest wall instability; (3) Respiratory insufficiency due to severe laceration of intrathoracical organs with additional chest wall instability as an obstacle for sufficient respirator treatment.


[Injury to the lung parenchyma (author's transl)].

Injuries involving only the lungs are relatively rare; generally they are a combination of thoracic and pulmonary trauma. As a result of the increased incidence of severe polytraumata combined injuries have become more frequent. Isolated thoraco-pulmonary injuries by stabbing or a bullet are comparatively rare. Various types of lung injuries are described. During 1970-1976 388 persons with various injuries involving the chest were admitted to the Surgical Unit of the University Hospital, Düsseldorf. In 155 of them (40%) the lungs were injured; in only 49 was the trauma confined to the thorax and lungs. Over-all mortality was 60%. The case material was classified as (1) isolated lung injuries without damage to the thorax; (2) combined injuries to the chest wall and lungs. Combined injuries predominated in the proportion of 136:19 cases. Polytraumatised persons predominated in both groups (71 and 98% respectively). The clinical features and treatment of the various types of injuries are reviewed.


[Clinical classification of the severity of lung injuries (author's transl)].

The observations made in 651 cases of traumatic lung injuries suggested the advisability of dividing these injuries into three groups according to the severity of the clinical picture. The criterion was the degree of impairment of respiratory function as assessed by repeated gas analyses. By relating function to severity of the clinical picture it was possible not only to institute the appropriate therapeutic measures but also to obtain information regarding the prognosis. Lung injuries in group 2 and 3 require prompt transfer to an intensive care unit with experience in chest surgery before irreversible damage has set in.


[Trachea and main bronchi in thoracal trauma (author's transl)].

On the whole, only few lesions of the trachea and main bronchi are amenable to treatment. The ideal treatment is that which is applied immediately in so far as successful management of the acute shock has been achieved. Reluctance to effect mechanical stabilisation of the thoracic wall by means of wires or metal plates, has been fortunately abandoned. The increased application of fibre bronchoscopy by surgical intensive-care units, or regular consultation of a bronchologist or thoracic surgeon, has improved chances of earlier detection of any serious lesion of the main respiratory tract. Lesions of the parenchyma are important and significant only to the extent as they can become serious or insurmountable obstacles during immediate dressing and final surgical treatment if they are present side by side with a lesion of the trachea or of the main bronchi.


[Tracheal and bronchial ruptures (author's transl)].

Rupture of the major airways is rare. Open injuries usually involve the trachea; injuries to the airways in closed chest trauma are in 80-90% of the cases located at the bifurcation or the main bronchus. Rupture of the bronchial system may cause an immediate threat to life, but may also produce few symptoms. The possibility of such an injury should always be taken into consideration, even if at first the clinical signs only point to damage of the lung parenchyma. Intubation and continuous suction drainage are life-saving emergency measures to be followed as soon as possible by bronchoscopy to establish the diagnosis. Treatment is by prompt suture or anastomosis. Failure to diagnose rupture of a bronchus results very soon in stenosis and, later on, in damage to the lungs and jeopardizes the success of subsequent reconstructive surgery. The repair of extended stenoses presents particularly difficult technical problems. Alloplastic grafts may be the answer. During 1961-1978 7 persons with injuries to the trachea and bronchi were treated at the Department of Surgery, Giessen. 3 persons were saved by immediately performing an anastomosis.


[Indications for the correction of tracheal stenosis caused by prolonged artificial ventilation of polytraumatized persons (author's transl)].

Pronounced, short-length narrowing of the trachea combined with dyspnoea at rest is an absolute indication for partial resection. For stenoses of moderate degree the indications for surgical intervention are as yet not clearly defined. They depend not only on the clinical, roentgenological and tracheobronchoscopic findings, but also on the results of lung function tests. Changes in respiratory function become noticeable at reduction of under 30% of the tracheal diameter. Experiments with artificially induced stenosis have shown an exponential rise in flow resistance when the diameter of the trachea was narrowed to below 8 millimetre. observations made in patients have proved that the experimental results also apply clinically. The indications for surgery of a tracheal stenosis should be made dependent on the results of the determinations of flow resistance, whole body plethysmography and expiratory and inspiratory volume/1 sec. Flow resistance exceeding 5 cm H2O/1 sec, equivalent to narrowing to under 8 mm in diameter, is considered to be an indication for partial resection.


[Diagnosis and treatment of tracheo-oesophageal fistula (author's transl)].

Three cases of tracheo-oesophageal fistula as an extremely rare complication of blunt chest trauma are described in detail. 32 similar cases reported in the medical literature are analysed and the pathogenesis of this type of injury is discussed.


[Injury to the diaphragm (author's transl)].

A distinction is made between acute injury to the diaphragm (18 cases) and late sequels of such lesions (enterothorax, 9 cases). The acute trauma is often not felt as such and it is only after some time that its consequences manifest themselves. The effect of a trauma on the diaphragm depends on whether the former acts on the abdomen or thorax. Surgical repair of the damaged diaphragm is nearly always feasible regardless of whether the operation is performed at an early or late stage of the injury. In only two cases (since 1963) was it necessary to resort to heteroplastic material, viz.: lyophilized dura mater. The possibility that viscera displaced into the thorax are also injured must be taken into consideration. Rupture of the diaphragm involved the left side in 95% and the right half in 5% of the cases (protection provided by the liver).


[Diagnosis and treatment of blunt injury to the diaphragm (author's transl)].

Blunt injuries to the diaphragm are rare. They usually occur in combination with injuries to other structures (craniocerebral trauma, fracture of the pelvis, rupture of the spleen or liver). Regarding the diagnosis, knowledge of the mechanism of the accident may point to the possibility of a ruptured diaphragm, and so may auscultation and percussion of the chest. Examination of the gastrointestinal tract and contrast enema may show up displacement of abdominal viscera into the left pleural cavity. In cases of rupture of the right diaphragm coeliacography and scintillation scanning are indicated. As regards treatment: every rupture of the diaphragm needs surgical repair. If prolapse of viscera has been established, prompt intervention is necessary because of the risk of acute incarceration. Asymptomatic prolapse causing only minor complaints should also be rectified to obviate complications. The best approach for both early and late repair of the diaphragm is via the thorax.


[Traumatic rupture of the diaphragm (author's transl)].

Traumatic rupture of the diaphragm is diagnosed during the acute stage in only 50% of the cases. The reasons for this failure are that in many of these cases clinical symptoms of damage to abdominal organs or of injuries to the limbs predominate. Traumatic rupture of the diaphragm is usually the result of an indirect trauma. Clinical signs of extensive prolapse of viscera into the thoracic cavity are: dyspnoea, tachycardia, cyanosis or intestinal sounds heard over the thorax during auscultation. Once the diagnosis has been established surgical repair should follow. During the acute stage laparotomy is preferable; thoracotomy is indicated during the chronic stage. Post-operative symptoms are: dyspnoea during exercise, pain in the affected half of the chest and roentgeno-kymographically demonstrable restrictions of movement in the ruptured side of the diaphragm.


[Unrecognized traumatic rupture of the diaphragm (author's transl)].

20 cases of rupture of the diaphragm (one due to direct trauma, the other 19 due to indirect trauma) which were not recognized at the time of the accident are described. The reasons for the delay in diagnosing the true nature of the condition and the misleading complaints caused by the unrecognized injury are reviewed. Essential diagnostic measures are discussed and guide-lines are suggested to ensure the early diagnosis of rupture of the diaphragm.


[Injuries to the diaphragm (author's transl)].

A traumatic rupture of the diaphragm is nearly always accompanied by injuries to the intrathoracic and abdominal structures. As the symptoms arising from these injured organs generally predominate, the presence of a ruptured diaphragm is apt to remain unrecognized or to be diagnosed at a very late stage. If the diagnosis is made immediately after the accident surgical repair should follow promptly; if the rupture is of long standing (traumatic hernia) surgery should preferably be performed during a symptom-free interval. An analysis of the case material showed that the left diaphragm was more often involved than the right one, an observation that tallies with the published reports. The transthoracic approach provides a clearer view of the operating area and was, therefore, chosen. The post-operative results were satisfactory; mortality rate was nil.


[Diagnosis and treatment of acute injuries to the heart and intrathoracic vessels (author's transl)].

The massive blood loss that accompanies penetrating chest wounds involving the heart or intrathoracic vessels generally leaves no option but to act immediately. Blunt chest trauma in combination with other injuries makes particularly stringent demands on diagnostic and therapeutic skills. Most injuries to the intrathoracic aorta are in the form of intiially closed tears of the descending part; but rupture is an ever-present threat. The symptoms are: enlargement of the mediastinum in the chest roentgenogram, differences in blood pressure between the upper and lower half of the body and haemothorax. Whenever possible aortography should be performed to locate the site of the rupture. The therapeutic measures are determined by the extent and severity of the various injuries.


[Diagnosis and treatment of post-traumatic aneurysm of the thoracic aorta (author's transl)].

A post-traumatic false aneurysm of the thoracic aorta is generally the result of a severe closed chest trauma in which deceleration and compression mechanisms operate on the aortic isthmus. Early diagnosis is difficult except where the lesion progresses to rupture. A not inconsiderable number of incomplete and initially closed tears in the wall of the aortic isthmus escape detection and in due course lead to dilatation of the vessel and false aneurysm. The condition is diagnosed, often accidentally, during aortography. The indications for surgical intervention are given by the aneurysm-specific complications, viz.: rupture penetration, embolization. The operation is performed with the aid of a temporary left-heart bypass; it carries a mortality of 5%.


[Post-traumatic aneurysm of the thoracic aorta; the results of surgical repair (author's transl)].

29 patients aged 11-55 years underwent surgery an aneurysm of the descending part of the thoracic aorta that had developed after a blunt chest trauma. In all patients continuity of the vessel was restored by interposition of a prosthesis. Surgery was performed during the acute stage in 5 patients, two of whom died postoperatively due to infection of the prosthesis and shock lung respectively. One of the 24 patients who were operated on during the chronic stage died on the 16th postoperative day of apoplexy. One of the 26 patients who were discharged from hospital after the operation died of a spurious aneurysm that had developed at the site of the prosthesis. Follow-up examinations of 21 patients showed normal postoperative function. In 5 cases there was an angiographically demonstrable slight narrowing at the site of the anastomosis; the pressure gradient, measured intravascularly, did not exceed 30 mm Hg.


[Injury to the mediastinal organs in chest trauma (author's transl)].

10% of chest traumata are accompanied by injuries to the mediastinal organs. Since rupture of a bronchus may be masked by additional intrathoracic injuries any suspicion of such lesion must be verified by bronchoscopy. Symptoms of a shock condition after traumatization of the precordial region point to damage to the heart the extent of which may range from a slight disturbance of cardiac function (commotio cordis) to laceration of cardiac tissue and rupture of the myocardium. Enlargement of the mediastinum after a sufficiently forceful chest trauma should be examined by visualization of the aortic arch to elucidate its aetiology and exclude an aortic aneurysm. The mortality of chest trauma involving the mediastinal structures is 35%. This fairly high figure is partly attributable to severe accompanying injuries.


[Intensive care in chest trauma (author's transl)].

A statistical analysis of the case material at the Intensive Care Unit, Freiburg, for the years 1975 and 1976 established that 40% and 39% respectively of patients with multiple injuries had also suffered a chest trauma and that the latter was the direct cause of respiratory insufficiency in 61% (1975) and 57% (1976) of patients in need of controlled respiration, i.e. respiratory insufficiency dominated the clinical and pathophysiological picture. The causes were: restricted respiratory movements due to pain, compression of the lungs or pathological changes in the injured lung, and they affected the normal gaseous exchange in a variety of ways. Alveolar hypoventilation with disturbance of ventilation-perfusion, increase in the functional shunt volume, rise in the functional dead space combined with reduced functional residual capacity and compliance result, if left uncorrected, in a drastic increase of resistance on the part of the pulmonary vessels and finally in, often fatal, hyoxaemia and hypercapnia. Regular estimations of the arterial blood gases in air and pure oxygen, of the arterio-alveolar difference in oxygen pressure, shunt volume, dead space and effective compliance of the chest wall and lungs are, therefore, essential. Treatment in an intensive care unit comprises the relief of any acute condition, such as tension pneumothorax, haemothorax, and general measures. Means to relieve pain in patients whose chest injuries are not sufficiently severe to require artificial ventilation are: intercostal blocking, acupuncture or peridural analgesia; efficient breathing exercises are important. The indications for artificial ventilation should be interpreted generously and the decision to perform it should be made at an early stage. The technique is determined by the type of pathological changes in the gaseous exchange and should aim at restoring normal conditions as far as possible.


[Surgical aspects during the intensive care of chest trauma (author's transl)].

A wide range of surgical methods is available in the intensive care of patients with a chest trauma. Discussions with the anaesthetist as to the planning and co-ordination of diagnosis and treatment must take into consideration a great number of factors. The indications for surgery in polytraumatized persons are different from those that apply to single injuries. Table 6 which lists the cause and time of death of 52 persons with multiple injuries provides evidence that during the first 7 days after a severe accident all surgical intervention that is not absolutely necessary should be avoided and attention focused on the problem of adequate ventilation and primary and secondary complications of shock.


[Pleural adhesions and deformation of the chest wall (author's transl)].

Deformation of the chest wall and pleural adhesions are some of the sequelae of chest trauma with fractures of ribs. If sufficiently extensive these lesions may result in restrictive disturbances of ventilation and partial respiratory insufficiency. In these cases marked improvement in function and perfusion can be obtained by decortication at an early stage. Follow-up examinations of 37 patients who had sustained fractures of more than 4 ribs revealed restrictive respiratory impairment in only three cases. Hypoxia was present in 11, but a causal connection with the trauma could be ascertained in only 4 persons. For assessing the extent of the lesions and the indications for decortication perfusion scanning is a "must", as it will show up pathological changes at a time when the gaseous exchange and lung function still appear normal. There seems to be no correlation between the radiological extent of the adhesions or the deformation of the thorax and the extent of changes in lung function and blood gases.


[Residual lesions after serial fracture of ribs (author's transl)].

Follow-up examinations at regular intervals to recognize trauma-induced lesions are as essential for persons who have suffered a chest trauma as they are for cases of injury to the limbs. A classification into three groups according to the number of broken ribs relates satisfactorily with thoraco-pulmonary complications and residual damage. Injuries in group 1 leave practically no permanent damage; in group 2 they are apt to be followed by residual respiratory impairment while in group 3 the likelihood of permanent impairment of lung function is very high. Spirometry, roentgenography and fluoroscopy, and lung scanning are of special diagnostic value in assessing late sequelae of multiple rib fractures. Gas analyses are of little value. They would provide more accurate information if performed during exercise under standard conditions.


[Mismanagement of chest trauma; sequels and the possibility of repair (author's transl)].

60 persons with a chest trauma were treated during the past years. In a number of cases the injuries and the resulting complications were of so serious a nature that their repair was attended by the greatest difficulties. The most serious and initially unrecognized complications comprised: 1) tracheo-bronchial defects, partly of traumatic origin and partly arising during intensive care; 2) failure to detect rupture of the diaphragm with displacement of visceral organs into the thoracic cavity; 3) insufficient evacuation of blood or fluid from the pleural cavity; 4) failure to diagnose irreparable damage to part of the lungs. Means to repair these lesions are reviewed; the necessity for long-term observation of these cases is emphasized.


[Assessment of residual lesions after a chest trauma (author's transl)].

The correct assessment of residual respiratory lesions after a chest injury requires clinical examination, roentgenographic examination in two planes, lung function tests including ergo-spirometry and blood gas analyses before and after exercise. Oxygen consumption during exercise should be one of the criteria whereby to judge any reduction in working capacity. Improvements in respiratory function have been observed as late as two years after the accident.


[Assessment of residual functional impairment after chest trauma (author's transl)].

Inadequate knowledge of the variety of residual functional lesions after a chest trauma accounts for the inconsistent assessment of these sequelae. An accurate analysis of the mode of the accident and the subsequent course greatly helps towards clarifying the situation. A final assessment should not be made until at least one year later, since improvement in respiratory function may still occur up to 12-18 months after the trauma. Tests of respiratory function should include all componente factors (ventilation, mechanics of breathing, diffusion, perfusion). An analysis of 41 cases submitted for assessment of residual respiratory lesions showed that lung scanning is the most sensitive method for detecting such damage. It revealed pathological changes in 94% of the cases, as compared with spirometric test (59%) and examination of the mechanics of breathing (33%). Whether and to what extent reduced perfusion without ergo-spirometric evidence of impairment should qualify as residual damage is a moot point.


[Chest trauma--a challenge to the general surgeon and chest surgeon for co-operation (author's transl)].

During 1968-1977 86 persons with chest trauma were treated at the Chest Clinic Heckeshorn. Until 1973 only a few cases of, mostly slight, chest injuries were admitted and treatment was mainly concerned with pneumothorax and haemothorax induced by fracture of ribs. Since 1974, however, cases of chest trauma have markedly increased in both number and seriousness of the injury. During the past years 50 patients with chest injuries were treated. They included 6 cases of stab wounds, 4 cases of bullet wounds and one case each of damage to the trachea and bronchial rupture respectively. Thoracotomy was performed in 11 of the 50 patients, in 3 cases to stabilize the chest wall. Willingness to cooperate on the part of the general surgeon has made it possible for the surgically trained lung specialist to participate in chest traumatology.


[A simple method for pleural drainage (author's transl)].

21 patients had pleural drainage with a rubber valve (Heimlich) on account of pneumothorax (15) and massive pleural effusion (6). The method succeeded in every case. It has the advantage that it dispenses with suction and bottles, that it needs no turning-off when the patient gets up, but maintains its draining action, and that in cases of persisting broncho-pleural fistula there is no additional suction. The technique represents a simplified alternative to the customy methods of pleural drainage.


[Treatment of complications of pulmonary anomalies in childhood (author's transl)].

Congenital anomalies of the lungs very often remain asymptomatic and are discovered accidentally during routine examinations. Only one-third of 24 patients with congenital pulmonary abnormalities showed acute symptoms; in a further one-third a chronic recurrent symptom complex required surgical intervention as the only possible mode of treatment. The complications arising from these anomalies varied considerably. The most serious was the "acute thorax" in newborns; in a number of cases it needed emergency thoracotomy. The various types and their symptoms are described and their treatment is reviewed.


[The tuberculosis situation in the German Federal Republic (author's transl)].

Based on a statistical anlaysis of the records the present tuberculosis situation in Germany and how it has developed during the past years are reviewed. The main means of control are: BCG vaccination, mass radiography and public health measures. Suggestions made by the Central Committee for the Control of Tuberculosis concerning surveillance and protection against occupational exposure to tuberculous infections are discussed. Recommendations regarding the assessment of incapacity for work and degree of disablement are evaluated. The aims and plans of the Committee for the next years, also in the international field, are reviewed.


[Tuberculosis in the developing countries and the work of the international Union for the control of tuberculosis (author's transl)].

In the developing countries tuberculosis is one of the most common diseases. According to estimates the number of cases of infectious tuberculosis is 3-4 millions. The guidelines for the effective control of the disease in the developing countries were laid down in a report by a Spezial Committee of the W.H.O. in 1974. The emphasis is 1) on protecting young people as far as possible by BCG vaccination, 2) on the early detection and treatment of as many cases of infectious tuberculosis as possible. The diagnosis does not depend on (expensive) radiographic equipment, as it can be made simply by microscopic examination of the sputum. For treating the infection various efficacious and not too expensive drugs are available which succeed within a few weeks in reducing the process to a non-infectious stage. Sanatorium or hospital treatment is generally not necessary.


[Death due to tuberculosis (author's transl)].

The records of autopsies performed during the last year were examined with the view of assessing the accuracy of the diagnosis: death from tuberculosis. The study showed that the infection was only rarely the cause of death. Subsequently, in collaboration with R. Gruber, the deaths reported by the Study Group, Bavaria, were analysed. Over a period of two years there were 302 deaths in which tuberculosis was either the primary or a complicating disease. The analysis shows how important it is to establish the correct diagnosis and to ensure that in deaths attributed to tuberculosis the infection is, in fact, the sole cause of death and not a complicating factor.


[Severe forms of tuberculosis observed during the past year (author's transl)].

A list of all cases of tuberculosis (pulmonary tuberculosis, cavitating processes, destroyed lung) observed during 1977 was compared with a list of cases seen during the past 10 years. The incidence of cavitating tuberculosis among foreigners was 11%; men and women were involved in the ratio 68:32. The incidence of tuberculosis was related to oeconomic status and occupation. The source of infection were compared with those of 1955 and 1963. The age distribution for the severe and very severe types of tuberculosis, the stage at which the infection was first diagnosed and the incidence of relapses are reviewed. The results are tabulated.


[The clinical picture of acute tuberculosis (author's transl)].

The clinical picture of acute tuberculosis infection is undergoing a change. The classic symptoms of pain in the chest and night sweats are giving way to general symptoms. In 50% of the cases the infection manifests itself as an acute disease. The observation that some cases of tuberculosis are not admitted to hospital until they are in a critical condition is ascribed to lack of "tuberculosis awareness".


[Tuberculosis in Romania (author's transl)].

The incidence of tuberculosis in Romania has decreased considerably over the past years, particularly since 1972 when the combined rifampicin-ethambutol-pyrazinamide therapy was introduced. During the period 1968-1977 it fell from 127.9 per 100,000 to 73.4 per 100,000. The incidence of relapses fell at a slower rate. The most endangered are the 20-24 years age-group and old people; but here again the number of cases tends to fall. Childhood tuberculosis showed a yearly decline by an average of 20%. Bacteriological examinations and diagnosis are assuming increased importance.


[Which type of tuberculosis predominates in cases newly diagnosed during mass radiography? (author's transl)].

12.8 millions roentgenograms, 288,000 of which showed suspicious lesions, were made during the past 25 years by the Tuberculosis Committee of Rheinland-Westfalen. They were analysed with the view of finding whether and to what extent the features of tuberculosis had changed during this period. Although severe tertiary forms of the disease had not entirely disappeared, minimal asymptomatic lesions now tended to predominate when first diagnosed--evidence of the valuable contribution made by mass radiography towards the eradication of tuberculosis. However, the picture changes somewhat if the extent of the tuberculous process is related to the number of patients in need of treatment including cases of re-activation. These figures have remained remarkably constant, viz.: the percentage of cases of unilateral tuberculosis localized to one lobe was 50-54%, of bilateral tuberculosis confined to one lobe was 22-25%; the figures for unilateral and bilateral tuberculosis involving more than one lobe were 10-13 and 10-14% respectively. The type of tuberculosis discovered during voluntary mass radiography in Rheinland-Westfalen do not yet signal an end to the proven methods of tuberculosis control.


[Liver function and anti-tuberculous drug therapy (author's transl)].

Every year since 1972 all records pertaining to an unselected group of tuberculous patients were collected on August 1st and analysed with the view of establishing trends and detecting special problems associated with anti-tuberculous chemotherapy. One of the subjects of the analysis was to find the effects of chemotherapy on the global transaminase levels. The case material was divided into two groups: in group 1 rifampicin had been included in the therapy, in group 2 it had been omitted. In approximately 20% of the patients treated during 1976, 1977 and 1978 transaminase levels were already increased when they were admitted to hospital; in about 15% transaminase levels rose during treatment. The personal history of the patients showed that in 31% of the cases the disturbed liver function was attributable to alcohol abuse and that in 22% manifest damage to the liver had been diagnosed prior to admission. Despite these "unfavourable pre-conditions" antituberculous drug therapy succeeded in 50% of the patients in normalizing the transaminase levels, even if the original values had been fairly high. Further controlled studies have confirmed these observations but an interpretation of the results is not yet possible. Antituberculous drug therapy induced a rise in transaminase levels less frequently than it caused a return to normal of initially raised levels. As so many factors are involved it is impossible to single out any particular causal factor.


[A comparative morphological and enzyme-histochemical study of experimental pneumoconiosis and experimental allergic-hyperergic pulmonary granuloma (author's transl)].

Six endotracheal applications of 15 milligrams of cadmium sulfide (CdS) given to rats at weekly intervals induce pneumoconiosis with massive adhesions. The same quantities of lead sulfide (PbS) given under the same conditions have much less effect, causing only the formation of fairly small fibrous nodules. The tissue reactions to CdS and PbS were studied morphologically (light and electron microscope) and enzyme-histochemically. The results were compared with those observed in experimental anthracosilicosis in rats and with those seen in allergic-hyperergic reactions of the lung in guinea pigs (induced by several applications of the complete Freund adjuvans). A considerable increase in macrophages in the alveoli and interstices of the lungs with increased activity of acid phosphatase and oxydoreductases had occurred in every animal. None showed primary damage to type 2 pneumocytes. The results indicate that the two toxic agents differ in their capacity to induce fibrosis not because they interfere to a different degree with the clearing function of the lung or surfactant production, but because they differ in their capacity to stimulate fibroblast formation.


[Roentgenologically demonstrable changes in pneumoconiosis (author's transl)].

Based on the new international definition of pneumoconiosis the various types of this lesion and their roentgenological appearance are described. The lesions may arise from fibrosis-inducing dusts (silica, asbestos) and also from the deposition of dust particles especially those of high atomic weight. Pneumoconiosis in coal miners, the most common dust-induced lung disease in Germany, is reviewed in detail and the X-ray demonstration of dust in the lungs is discussed.


[Clinical aspects and prevention of pneumoconiosis caused by inorganic dusts (author's transl)].

Anthracosilicosis and asbestosis are the most important types of pneumoconioses induced by inorganic dust. They produce entirely different damage to the broncho-pulmonary system. Anthracosilicosis graded B or C roentgenographically is very often accompanied by obstructive respiratory disorders; in asbestosis restrictive disturbances predominate. The question whether obstructive lesions also tend to occur remains to be solved. Dyspnoea often accompanied by bronchitis is the main clinical feature. Anthrocosilicosis is amenable to therapeutic measures which have resulted in a considerable prolongation of the life span of these cases. Improved dust control is the most rational prophylactic measure. Abstention from smoking also plays a part.


[An anlysis of the post mortem material of a chest unit (author's transl)].

Tuberculous persons tend to live longer, i.e. death from tuberculosis has shifted to the older age groups. Cavitating processes frequently accompany intestinal tuberculosis, but not tuberculosis of the bones and joints. Fungus infections were found in 36 of 846 post mortem examinations, in 22 cases in association with tuberculosis.


[Early diagnosis of small airways disease in young smokers (author's transl)].

Investigations during the past years have established that determinations of closing volume, flow-volume curves and frequency-dependent compliance are capable of detecting pathological changes in the bronchial system at a time when the customary lung function tests (FEV1.0 resistance as measured by bodyplethysmography) are still normal. These observations have been made use of to diagnose incipient damage in persons exposed to bronchial noxae. In the present investigation the effect of smoking on the airways was studied in a group of 25 persons aged 20-25 years by determining the closing volume and differences in ventilatory distribution (Thews method). The results were compared with those obtained in a group of 27 non-smokers in the same age group.


[The value of lung biopsy in the radiological stage of bihilar adenopathy of sarcoidosis (author's transl)].

The classification of intrathoracic sarcoidosis into stages is based on radiological criteria. As pulmonary involvement is often considered to be an indication for corticosteroid therapy a comparison was made between the X-ray picture and lung biopsy in stage I sarcoidosis. Non-caseating epitheloid granulomas were found in 9 of 12 patients. The material was obtained by open biopsy in 8 patients and by the transbronchial approach in one case. Open and transbronchial biopsy failed in 3 patients to demonstrate sarcoid granulomas. The results suggest that the presence of mottling in the chest roentgenogram does not provide the rationale for treatment. Further studies will show whether irreversible damage to lung tissue could be prevented if lung biopsies were taken and, consequently, steroid therapy initiated, at an earlier stage of the disease.


[The value of measurements of oscillatory resistance in the evaluation of lung function. A comparative study in adults and children (author's transl)].

Measurements of total oscillatory impedance (ROS) together with spirometric and body plethysmographic determinations were made in adults and children and the results were compared. In adults (n = 260) correlation was less close (r = 0.53) than it was in 88 children (r = 0.82). Even if ROS was of similar magnitude the phase shift between pressure and flow tended to be more negative than it was in children. These differences are presumably due to anatomical differences between the adult and the growing lung. In interpretation of the results it is suggested that the differences in the ratio: airways compliance/airways resistance reflect changes arising from age and disease processes.


[Propagation of error, sensitivity and specificity of the CO gas transfer in various breath holding and steady state methods (author's transl)].

For determining DL/VA or the Krogh factor use of the breath-holding CO method only is recommended because it is relatively free from errors, independent of distribution and is relatively specific regarding diffusion. The steady state methods tend to be unspecific despite calculation of DL/VA and to be rather sensitive to uneven distribution of ventilation.


[The mixing index in the argon breath holding test for the demonstration of pharmacologically induced airways reactions. A comparison with other methods (author's transl)].

In 42 patients with obstructive airways diseases the behavior of the mixing index (delta argon %/1 during phase III of the argon-volume diagram) was studied after beta2 stimulation or after provocation by acetylcholine. Changes in airways resistance resp. conductance (GAW), FEV1.0 and residual volume (RV) were also determined for comparison. In an inhomogeneous subgroup with obstructive airways disease of various aetiology the mixing index (MI) and FEV1.0 indicated changes in the airways system with about equal frequency. Distinct discrepancies between the two tests, observed in a few cases, suggest that the two methods register different pathophysiological reactions. These differences could be confirmed statistically in a more homogeneous subgroup with extrinsic bronchial asthma. A correlation could be established between MI and RV on the one hand and between FEV1.0 or GAW and RV on the other hand. The results indicate that the mixing index as a test of distribution of ventilation reflects mainly the reactions of the small airways. Its use offers the possibility of a more differentiated pharmacodynamic evaluation.


[Long-term follow-up of lung function parameters in patients with idiopathic pulmonary fibrosis treated with prednisone and azathioprin or d-penicillamine (author's transl)].

The prognosis of idiopathic pulmonary fibrosis is poor, it amounts to 4-6 years (after beginning of the symptoms). Spontaneous remissions are very rare, the corticosteroid monotherapy shows a certain success in only 11-16-20% of the cases. Therefore, since 1970 we carry out a combined therapy (see above); the results, confirmed by pulmonary function tets (vital capacity, static compliance, pO2 at rest and after exercise) will be presented. In summary: (1) Azathioprin and Prednisone: After a treatment of 2 years: 6 patients improved, 2 deteriorated, 3 died; the corresponding figures after 4 years were 6/1/4, after 6 years 3/-/5, after 8 years 2/-/3; (2) D-Penicillamine and Prednisone: After 2 years 3/2/4, 1 unchanged; after 4 years 1/-/4, 1 unchanged. The results of the therapy are discussed especially regarding prognosis of the disease and used drugs.


[Bronchial asthma and auriculo-acupuncture (author's transl)].

The mode of action of acupuncture is briefly reviewed. The effect of auriculo-acupuncture is ascribed to a direct reflex action via the brain. Attempts are being made to employ auriculo-acupuncture in the treatment of acute and chronic bronchial asthma. The preliminary results are encouraging.


[Acupuncture and thoraco-pulmonary function (author's transl)].

Disturbances of thoraco-pulmonary function of reflex origin can be influenced by acupuncture; it primarily affects the movements of the thorax. The most important points are enumerated. During 1958-1972 1,421 persons with bronchial asthma had acupuncture. Subjective evaluation of the results by the patients was as follows: great improvement in 45% and satisfactory improvement in 38% of the cases; 17% of the patients were not satisfied. The study continues.


[Cortisol and adipocyte indicators in exogenous-constitutional obesity].

The authors examined 64 patients with exogenous-constitutional adiposity, aged from 17 to 61 years (27 men and 37 women). The indices of the cortisol content were compared, depending on the patients' age, the degree of adiposity, heredity, and duration of the disease; the dependence and the correlation between cortisol and adipocyte morphology were ascertained. The blood cortisol content proved to depend on the patient's age and the degree of adiposity. Thus, in young patients its content was elevated; with the advance of age and increase of body weight the mean cortisol indices decreased. There was found a direct relationship between the cell size and the adiposity degree. Simultaneously marked increase of the cortisol content and marked adipocyte hypertrophy were found in individual patients. There was no increase of the cortisol content in case of normal adipocyte size. However, there was no distinct correlation between the cortisol content, the size and number of adipocytes. As the doby weight decreased the adipocyte size reduction was recorded in obese patients; some of them developed activization of the glucocorticoid function of the adrenal glands.


[Blood lipid level in obesity associated with latent and manifest diabetes mellitus].

Free fatty acids (FFA), triglycerides, cholesterol, and blood FFA levels were studied in the glucose tolerance test (GTT) in 63 women with adiposity combined with normal and diabetic GTT, and in those suffering from manifest diabetes mellitus during reduction of body weight and normalization of carbohydrate metabolism. It appeared that normalization of body weight and of glycemia on fasting stomach and in the course of the day led to a significant normalization of the FFA, triglycerides, and cholesterol levels. Normalization of body weight alone with persisting GTT disturbances caused a significant normalization of the triglyceride and cholesterol levels; as to the FFA they remained significantly elevated. GTT normalization with persisting adiposity led to reduction of the triglycerides, cholesterol, and FFA levels, but they still significantly exceeded the parameters in healthy persons. The curve of the FFA reduction following glucose load became normal with the weight and GGT normalization, and remained delayed in cases with no loss of body weight. The data obtained permitted to draw a conclusion on the leading role of the body weight reduction in the normalization of lipid metabolism in these patients.


[Sex hormone regulation of progesterone and estradiol receptors in the cytosol of human endometrium in normal and pathologic pregnancy].

Hormonal control of progesterone and estradiol receptors was studied in the cytozol of short-lived culture of human endometrium in normal and undeveloping pregnancy. Endometrium was cultivated in the presence of estradiol or progesterone for 16 hours. In cultivation of normal endometrium with estradiol the content of estradiol receptors increased 4-fold in comparison with unstimulated tissue, and of progesteron receptors--3-fold. In cultivation of normal endometrium with progesterone the content of estradiol receptors rose 4--5-fold, and of progesterone receptors--3-fold. In cultivation of pathological endometrium with estradiol or progesterone the number of estradiol receptors was only doubled, and of progesterone receptors--increased only 1 1/2 times, this pointing to a diminished sensitivity of pathological endometrium to the regulating action of sex hormones.


[Role of serotonin receptors of the medial-basal hypothalamus in the mechanisms of negative feedback of the hypophyseal-testicular complex].

Administration of serotonin into the lateral ventricle of the brain of male rats, against the background of complete isolation of the medial-basal hypothalamus was accompanied by the block of the compensatory elevation of the blood testosterone level following unilateral castration. Experiments with local serotonin administration into the hypophysial region of the hypothalamus of hemicastrated rats indicated that the inhibitory effect produced by the excitation of the serotonin receptors of this region on the mechanism of the negative feedback of the hypophysis-testicular system was realized at the arcuate nuclei level.


[Interaction of insulin and its receptors in the muscles: specific I125 binding with plasma membranes of the skeletal muscle of rat].

A preparation of plasmatic membranes of the rat skeletal muscle was obtained which was used to characterize the interaction of insulin with its receptors in the myocyte. It was shown that insulin-125I binding by the membranes depended on the incubation time and temperature; the maximum binding occurred at 4 degrees, although the binding rate was low at this temperature. The degrading of labeled insulin at 4 degrees C did not exceed 1% in the course of 24 hours of incubation with the membranes. Crude pig insulin inhibited the binding by 50% in a dose of 2.7 nMol; fish insulin (biologically less active) in a dose which was 25 times greater, the other hormones studied were completely ineffective in this respect. A curve with a bend obtained by the treatment of these data after Sketchard indicated the heterogeneity of the receptors under study or their interaction of the "negative cooperation" type. A conclusion was drawn on the absence of any significant differences between the insulin receptors in the muscles in comparison with its receptors in other target cells.


[Somatotropin control of glucose transport and glycogen biosynthesis in the incubated diaphragm of hypophysectomized rats and rats with alloxan diabetes].

A study was made of the influence of somatotropic hormone of the hypophysis (STH) on the C14-glucose transport and on the C14-glucose incorporation into the glycogen of the incubated diaphragm of intact rats (group 1), hypophysectomized rats (group 2), rats with alloxan diabetes (group 3), and rats with combined exclusion of the hypophysis and the pancreas functions (group 4). The diaphragm of hypophysectomized rats had an increased capacity to the C14-glucose uptake from the medium and of incorporating it into glycogen, apparently on account of exclusion of the hormones group depending on the hypophysis, with the contrainsular action (STH, ACTH, TTH). On the contrary, the basal rate of the processes studied in the muscles of insulin-deficient rats (group 3) displayed a significant reduction. Alloxan exclusion of the B-cell function in the hypophysectomized rats (group 4) diminished the accelerated glucose transport and glycogen synthesis in the muscle. STH added to the incubation medium stimulated the glucose transport and the glycogen synthesis in the diaphragms of animals with altered endocrine homeostasis (groups 2, 3, 4). Muscles obtained from intact animals were refractory to the STH action. The most STH-sensitive were muscles of hypophysectomized animals (an increase of glucose absorption by 32%, and of C14-glucose incorporation--by 77%). Incubation of the muscles of rats suffering from alloxan diabetes with STH was also accompanied by increased rate of glucose transport and glycogen synthesis; this effect was less pronounced, however. The data obtained indicated that the regulation of carbohydrate metabolism in the muscle tissue with STH was individual, not mediated through any other hormone.


[Glycogen content in the placenta of rats in experimental diabetes].

Glycogen was determined histochemically and biochemically in the placenta of female rats with alloxan diabetes induced in sexually immature animals, including the placenta of rats treated with sulfamides before the occurrence of pregnancy. Histochemical studies were carried out on 18, and biochemical on 38 Wistar rats. Glycogen content in the mature placenta before labour was greater in animals with manifest alloxan diabetes than in healthy rats. This increase of glycogen granules took place on account of their increase both in the glycogen cells, and, extracellularly, in the spongious zone. A significant increase of glycogen content in the placenta in manifest and latent diabetes was also demonstrated by biochemical methods; as to "prediabetic" rats--elevation of glycogen content in their placenta was insignificant in comparison with control. In diabetes compensated with sulfamides glycogen content in glycogen cells changed differently: there was a disappearance of extracellular glycogen from the spongious zone, and numerous glycogen granules (determined in healthy rats and in those with alloxan diabetes in insignificant amount) appeared in the labyrinth.


[Hygienic effect of landscaping in urban areas].

The atmospheric environment in two blocks of flats with different degree of gardens and parks lain out and in a town park in Sofia was studied by the basic physical, chemical and physiologic parameters. The results give grounds to admit that laying out gardens and parks in urban zones contributes to the creation of definite, qualitatively and quantitatively different housing environment: a more favourable temperature-and-moisture, radiation - thermal and biologicaly active regime. The physiologic state of residents, looking for recreation in these places, was better in an environment of ample verdure. Laying out gardens and parks should gain wider acceptance in the urbanization of bloks of flats, since it is an effective means of improving the hygienic merits of housing environment.


[Age characteristics and circadian biorhythm of the leukocytes in schoolchildren].

The leucocyte counts were determined three times daily at 6 hours' interval in 480 children from 7 to 14 years of age (30 boys and 30 girls of each age group). The results showed that there exist no age or sex differences in the leucocyte counts in school-children. There was essential increase in the leucocyte counts in boys and girls from morning to evening. These data should be taken into consideration, when results of repeated determinations throughout the the day in clinical practice, sport medicine and research work are to be interpretted.


[Effect of physical exertion on the adrenal gland function and cardiovascular system in diabetes mellitus].

The response of the adrenal glands and the cardiovascular system to dosaged cycloergometric exercises was studied in 35 young patients with diabetes, depending on the state of carbohydrate metabolism, in  comparison with control healthy individuals. In diabetic patients physical load proved to induce an insignificant activation of the adrenal glucocorticoid function with a marked response of the sympathicoadrenal system. Physical exercises permitted to detect reduction of myocardial reserves and disturbance of vascular reactivity in the majority of diabetic patients. The detected changes in the adrenal gland response could serve as one of the causes of inadequate response of the cardiovascular system to physical load, and of reduced tolerance to it in diabetic patients.


[Degree of sexual maturation as an index of biological age].

Attempt was made to establish some characteristics of sexual maturation, depending upon chronologic and biologic age. A total of 1277 girls from 8 to 17 years of age in the city of Sofia are included in the study. There were no cases of precocious of considerably delayed pubertal development. Essential differences were found in the body dimensions, in connection with the increase in the degree of sexual maturation in one and the same chronologic age. The importance of biologic age for the individual approach to teen-agers girls and boys is emphasized.


[Reading and writing disorders in elementary school students with varying achievment].

In a group of 391 first and second year pupils, of whom 191 with low and 200 with excellent marks at school the author promoted studies, aimed at establishing reading and writing disorders of the so called dyslexia and dysgraphia type. Serious reading and writing disorders were detected in 14.8 per cent of all pupils in this study, disregarding their marks at school. These disorders were encountered however in 29.3 per cent of the children with low marks and in only 1 per cent of those with excellent marks. The incidence of some morbid states and functional disorders, including disorders of lateralization, was significantly higher in pupils with low marks at school. It is concluded that dyslexia and dysgraphia-type of reading and writing disorders in primary school children are factors exerting unfavourable effect on the marks at school and are likely to be etiologically related to some disturbances of health and disorders of lateralization. This prompts their early detection, with a diligent study of the causative factors and early promotion of adequate therapy and corrective measures.


[Effect of the protein intake on the rhythm of assimilation in white rats with proportioned feeding].

Experimental data on the influence of separate protein feeding by giving milk cassein at different hours of the day and night, apart from the energy-supplying food, to young rats, showed that protein is best utilized by the organism when given durins the dark period of the day. The results obtained are discussed in relation to the coefficients of protein and caloric effectiveness in the different hours of the day and night, with regulation of the light and dark period for 24 hours.


[Mutagenic activity of basfungin in its combined action with sodium nitrite].

The mutagenic activity of basfungin, when acting in combination with sodium nitrite, was studied in a subacute experiment, using the method of bone marrow cytogenetic analysis. The results were compared with those in groups in which basfungin and sodium nitrite were applied separately, as well as with the results of the parallel control. The mutagenic effect in the combined action group did not essentially differ from the effect of application of basfungin alone, both qualitatively and diaulitatively. Interesting results were obtained in the group receiving sodium nitrite alone - the percentage of cells with chromosomal aberrations was significantly than the control values.


[Potential teratogenic action of the mycelium of the higher fungus, Polyporellus squamosus].

The influence on the embryonic development of food with only source of protein derived from the mycelium of the higher fungus Polyporellus squamosus, was studied in a group of 90 pregnant rats. Animals fed caseine and standard food pressed into briquettes as source of protein served as controls. On the 17-th and 18-th gestation day 8 animals were examined and the number of of lutein bodies and fetuses was checked up. Anomalies were serched in the fetuses, by use of the method of Dawson and Wilson. The progeny of rats treated during gestation was examined on the 21-st day of life, by using a number of blood, integral and biochemical parameters (GOT, GPT, AP, SDH, catalase, sulfhydryl groups, soluble, protein). Proceeding from the results obtained, the authors rule out any teratogenic and embryotoxic activity of the mycelium of Polyporellus squamosus, under the aforegoing experimental conditions.


[General toxicity and specific action of the herbicide balagrin].

The influence of the herbicide balagrin on the maternal organism and fetus was experimentally studied on 60 pregnant albino rats of Wistar line. The preparation was given orally throughout the entire gestation period in daily doses of 1/1o - 110 mg/kg, 1/20 - 55 mg/kg and 1/50 - 22 mg/kg of LD50 - 1100 mg/kg. The detoxifying function was studied by the duration of hexabarbital sleep, the excretory function - by the cholic acid content in the bile, and the enzymatic function - by the dehydrogenase activities: LDH, MDH, LDH, GL-6-PDH in the liver of pregnant animals and the fetus, Marked toxic effect on the maternal and fetal organism was demonstrable at all balagrin application levels by the liver function disturbances.


[Morphological and histochemical changes in rabbits living for various times in the vicinity of cement factories in the villages of Beli Izvor and Zlatna Panega].

Results are reported of morphologic and histochemical studies on 60 rabbits, exposed for scattered times to the noxious effects of neighbouring cement works (gr.I - more than one year, gr.II - up to one year, and gr.III - up to 6 months - progeny of gr.I). Experiment No 1 was carried out near the village of Beli Izvor, experiment No 2 - near the village of Zlatna Panega. The results were compared with those obtained in a group of 10 normal control animals at the breeding station in Russe. The degree of morphologic changes in the organs was in direct proportion to the duration of exposure. Comparative assessment of the morphologic findings in rabbits dwelling near Beli Izvor and near Zlatna Panega showed a milder degree of organ damage in rabbits of experiment No 2 (cement works near Zlatna Penga). Inhibition of the T - and B-zones in the lymph follicles of the spleen was observed, indicating injury to the lymph (immunogenic) tissues, which are essential for the normal existence of these animals.


[Occupational risk in asbestos textile manufacture].

Detailed investigations of the environment in asbestostextile industry ("Asbestos produce" plant in the town of Sevlievo) were carried out. The parameters determined were: overall dusting, amount of asbestos in aerosol, its mineral and disperse composition. Data on the degree of dusting in the plant for the period 1960--1976 were analyzed and summarized. Professiograms were elaborated, with chronometry and appraisal of the burden of the work operations. All workers were tested clinically and roentgenologically. The data obtained on the degree of dusting in the different departments were re-calculated as amount of inhaled asbestos, depending on how hard the work is, resp. the pulmonary ventilation. The actual risk of asbestos injury was highest in the carding department, followed by the preparatory and the spinning departments. A distinct correlation exists between the degree of professional risk, determined by the asbestos contaminations, and the clinical and laboratory findings.


[New data on the presence of submicroscopic crystalline particles in lung dusts].

Investigation of dusts, isolated from the lungs of decreased miners, has contributed much to the elucidation of the pathogenesis of dust-induced. Numerous theoretical and experimental investigations have been carried out in this field, but there are problems, which are still far from being well understood. One of these is the implication of particles less than 0,5 micron, reckoned by many authors among the air contaminators. In this report data are given on the cristal structure of particles, for which electron difraction and X-ray microanalysis have shown that they have the mineral composition of the bed, where the miner has worked.


[Atomic absorption determination of mercury vapors in the air of the work environment].

The concentration of mercury vapors in air samples obtained from work-environment may be determined by atom-adsorption technique. To this end, the most appropriate air absorption speed proved to be 0,3 dm2/min through sulphuric acid solution of potassium pemanganate. Additional oxdation of samples was performed with a mixture of sulphuric acid and nitric acid in proportion 2:1. a 24 per cent rise in the height of the adsorption peaks was thus achieved, because of reduced losses.


[New sorbents for industrial gas marks with a visual reading of their depletion].

The current status of problems, referrable to the use of industrial gas masks, is reviewed, with special reference to the type of sorbent to be used, the pathways of gas mask modernization in respect of the sorbents used, and the modern trends in adsorption cartridge manufacturing; decrease of weight, alleviated construction, adjustment to serve definite toxico-chemical agent, use of ion-exchange resins and hemosorbents. Aspects are discussed for producing sorbents, permitting visual registration of filter mass exhaustion, i.e. sorbents wtih alternating color in the process of sorption, with the purpose of increasing gas mask security and efficiency. The physico-chemical parameters of reference hemosorbent samples with alternating color in the process of sorption were compared with those of widely used sorbents - active carbon (specially processed and crude) and ion-exchange resins: relative dynamics, aktivity protection time, weight, mass activity, etc. Inferences are drawn from which one may see, that these new hemosorbents are highly perspektive, and their industrial acceptance is justifiable.


[Noise characteristics of the basic types of housing construction].

The noise regime in houses, depending on the type of buildings - brick, panel and "creeping shuttering" type is considered. Investigations, carried out under natural conditions, showed that the type of building correlates with the noise-isolation capacity of the construction elements, in relation to the stroke noise. Poorest noise-isolation properties are to be expected from the "creeping shuttering" type of buildings. The characteristics of generation and spreading of noise from baths and toilets is discussed. Some tangible technical noise-protecting devices are suggested.


[Changes in lipid metabolism in pregnant white rats and their fetuses in inhalational exposure to carbon disulfide].

It is known from the literature that carbon bisulphide affects lipid metabolism, but observations in this field are quite controversial. In the present work the authors studied the influence of carbon bisulphide on some parameters of lipid metabolism in pregnant albino rats, following inhalatory exposure to carbon bisulphide concentrations of 50, 100 and 200 mg/m3, 8 hours daily throughout the whole gestation period. The lipid metabolism changes were followed up both in two subsequent generations. The offsprings were examined at birth and after they had reached sexual maturity, at the end of gestation. Part of the animals of the basic generation were subjected to repeated carbon bisulphide treatment in the same concentrations. The following parameters were studied: total lipids, triglycerides, phospholipids, cholesterol and free fatty acids in the liver. Correlation dependencies were found between exposure carbon bisulphide concentrations and the parameters of lipid metabolism. The degree and nature of the changes depended on the concentration and type of exposure (antenatal, postnatal and combined). A distinct rise in free fatty acid levels was associated with a mild decrease in the triglyceride and phospholipid content.


The nutritional toxicity of Phaseolus vulgaris lectins.

In rats fed on beans (Phaseolus vulgaris) the poorly digestible lectins were shown to react with intestinal cells in vivo and to cause a disruption of many of the brush borders of duodenal and jejunal enterocytes. Although depressed to a certain extent, absorption still occurred, probably through the non-disrupted cells of the small intestine. In addition, abnormal absorption of potentially harmful substances, lectin-related or of bacterial origin, could also occur, possibly as a direct effect of the disruption caused by the lectins on the enterocytes. It is suggested that toxicity was the result of ensuing systemic effects, such as for example the observed high N excretion possibly through increased tissue catabolism.


Malnutrition and the family: deprivation in kwashiorkor.

The background to social and emotional deprivation is discussed and applied to a study of kwashiorkor in East African children. A group of 107 children with kwashiorkor was compared with  111 controls. Age, sex and tribe were all found to have significances of their own: fifty of each group were therefore matched for these three factors. Ten other factors were found to be significant in the background of children with kwashiorkor, all of which could be associated with social or emotional deprivation or both (see Table 14). It is concluded that, in childhood, sustained personal care and affection are essential to normal growth.


Schedule-induced drinking and thirst: a pharmacological analysis.

Similar levels of water consumption were induced in two groups of rats by means either of prior fluid deprivation or a schedule of food pellet delivery. Injections of d-amphetamine (0.25, 0.5, 1.0 and 2.0 mg/kg) had similar attenuating effects of drinking induced by both procedures. Chlordiazepoxide (2.5, 5.0, 10 and 20 mg/kg), however, exerted differential actions on schedule-induced and deprivation-induced drinking. Drinking induced by deprivation was facilitated by all doses of this drug while the higher doses decreased levels of schedule-induced drinking. This result emphasises the difficulties involved in using the concept of thirst in explanations of behavior and of drug action.


Exposure to a nonfunctional hot plate as a factor in the assessment of morphine-induced analgesia and analgesic tolerance in rats.

Rats not exposed to a hot plate with or without morphine and later tested on the functional hot plate with or without morphine, displayed increased paw lick latency relative to same-injected rats given pretest hot plate exposure. This analgesic effect, was termed behavioral analgesia since it, unlike morphine-induced analgesia, was not reversed by naloxone (Experiment 2). Behavioral tolerance was evident in animals exposed to the nonfunctional hot plate regardless of drug treatment and was dissociated from pharmacological tolerance. Behavioral analgesia and tolerance reported here may involve habituation to novel distractive stimuli associated with the hot plate test environment.


Effects of cerebral intraventricular magnesium injections and a low magnesium diet on nonspecific excitability level, audiogenic seizure susceptibility and serotonin.

Cerebral intraventricular injections of 17 and 50 microgram magnesium in artificial cerebrospinal fluid progressively depressed the Non-specific Excitability Level of permanently cannulated 150--200 g rats fed a low magnesium diet for 21 days. Compared with control diet, a low Mg diet caused an increase in brain serotonin. Weanling rats fed a low Mg diet for 2 weeks, then injected with 25 microgram Mg via acute cannulations, displayed reduced audiogenic seizure susceptibility compared with sham-injected controls.


Evidence supporting lack of discriminative stimulus properties of a combination of naltrexone and morphine.

The aim of the present experiment was to study the potentially discriminable effects of combinations of morphine and naltrexone during long-term treatment. Three groups of gerbils had to discriminate the effects of morphine (12 mg/kg) and those of either saline (4 ml/kg), naltrexone (2 mg/kg), or a combination of this dose of morphine plus naltrexone injected IP 60 min prior to the start of the discriminative training in a T-shaped maze. Rapid development of drug discriminative control of choice behavior (left or right turn in the maze) was evident in these 3 groups which is in marked contrast to the performance of gerbils trained with morphine-naltrexone combination vs. saline or gerbils trained with naltrexone only vs. saline. Neither of these latter groups reached the criterion of performing 8 correct first-trial choices in 10 consecutive training sessions during the 60 training sessions allowed, while the 3 other groups began their criterion performance after only 7--8 training sessions. Thus the discriminative properties of certain combinations of morphine and naltrexone are weak and therfore are not easily discriminable from the effects induced by saline.


Behavioral effects of aluminum ingestion on animal and human subjects.

Abnormally high brain aluminum concentrations have been detected in hemodialysis patients who died of an unexplained encephalopathy. As a result, this study was undertaken to examine whether the ingestion of aluminum produces behavioral aberrations in non-dialysed human subjects and rats with ostensibly normal renal function. Rats were fed AlCl3 by intubation in varying doses, and tests measuring learning ability, visual temporal acuity, motor coordination and activity were administered. It was found that orally ingested aluminum is absorbed by rats and deposited in the brain. High brain aluminum levels are associated with rapid general activity, decreased ability to maintain roto-rod activity, and increased sensitivity to flicker. Behavioral tests were also given to elderly human subjects and performance correlated with serum aluminum level. High serum levels of aluminum in elderly humans are associated with impaired visuo-motor coordination, poor long-term memory, and increased sensitivity to flicker.


Sensorimotor deficits produced by phenytoin and chlorpromazine in unanesthetized cats.

Unanesthetized adult cats were evaluated for suprasegmental reflex activity and motor skills before and after administration of chlorpromazine (0.0625--0.5 mg/kg) alone and in combination with phenytoin (20 mg/kg). The greatest deficits were seen in the tests of balance and corrdination in which half the animals failed to match their control responses after administration of chlorpromazine and phenytoin. The impairment was most noticeable with the most stringent test (walking a 4 cm wide beam), and the effects of the two drugs were additive. Although there was no effect of either drug on muscle strength, the two drugs in combination depressed the animals' motivational state, making them less willing to work against imposed loads. Neither drug, alone or in combination, altered responses to the flexor reflex, blind placing, the hopping response or visually aided placing. It is concluded that the effects of chlorpromazine and phenytoin on motor control are selective for the CNS loci which control balance and coordination. Although the two drugs produce additive responses, the deficits occur only at doses which are well above those needed for clinical efficacy and thus may not pose a problem in their long term clinical use.


Puromycin: two distinct behavioral effects with different temporal parameters in the pigeon.

Pigeons were injected intracerebrally with either puromycin (PM) or control saline solution following training for one 12-min session on a visual discrimination. Injections were made either immediately following training, 1 hr later or 24 hr later. Retention testing 3 days after training showed that PM produced marked amnesia in the first two groups, but had no effect in the 24 hr condition. However, all PM groups were retarded subsequently in the number of days required to reach a 90% discimination criterion. This differentiation of two separate behavioral effects with different temporal gradients suggests that PM may be working through two distinct physiological mechanisms.


Imparied thermal regulation in juvenile rats following perinatal methadone exposure.

Offspring of female rats injected daily with methadone (5 mg/kg) or saline were cross-fostered at birth to form groups exposed to methadone during gestation (G), lactation (L), or gestation and lactation (G-L); controls (C) were exposed only to saline. Rectal temperature, body weight and food consumption were measured from postnatal Days 36-51. Ambient temperature was maintained at 21 degrees C except for Days 42--45, when the temperature was 10 degrees C. Group G rats never differed from controls, but offspring in Groups L and G-L were hypothermic at room temperature; Group G-L rats exhibited a further temperature loss during the cold stress. There were no group differences in food consumption after Day 39, and all groups increased food intake while in the cold. Group differences in body weight were not reliable but Group G-L rats gained less weight than the rest during the experiment, whereas Group L rats gained more. These results indicate that, depending upon treatment schedule, perinatal methadone exposure is associated with hypothermia during the postweaning period. A prolonged withdrawal reaction from methadone may account for the impaired thermal regulation.


Discriminative stimulus properties of levo-alpha-acetylmethadol and its metabolites.

The discriminative stimulus properties of l-alpha-acetylmethadol (LAAM), its metabolities 1-alpha-acetyl-N-normethadol (NorLaam) and l-alpha-acetyl-N,N-dinormethadol (DiNorLAAM), and methadone were evaluated in rats trained to discriminate between saline and morphine in a two-choice discrete-trial avoidance paradigm. All four compounds produced dose-related increases in the number of trials completed on the morphine-appropriate choice lever after either SC or oral administration indicating that the discriminative stimulus properties of the four compounds and morphine are qualitatively similar. LAAM and DiNorLAAM had a slow onset and long duration of action, and an oral: parenteral potency ratio of 1:3. NorLaam had a more rapid onset and shorter duration of action and was more potent following SC administration than either LAAM or DiNorLAAM; its oral: parenteral potency ratio was 1:10. These results are consistent with evidence from other studies that the pharmacologic activity of LAAM is dependent upon the conversion of LAAM to an active metabolite, probably NorLAAM. The similarities between DiNorLAAM and LAAM suggest that the discriminative stimulus effects of the former compound are also attributable to a metabolite.


Facilitation by opiate antagonists of sexual performance in the male rat.

Intraperitoneal administration of increasing doses (5 mg/kg or 20 mg/kg) of the opiate antagonists naloxone hydrochloride or naltrexone hydrochloride to sexually experienced male rats caused a significant reduction in the number of intromissions prior to ejaculation and ejaculation latency. Mount and intromission latencies were significantly reduced following treatment with only the lower dose of each antagonist. Ways are suggested whereby endorphins may modulate masculine sexual performance and thereby contribute to successful fertilization of female conspecifics.


Detection of antagonist activity for narcotic analgesics in mouse hot-plate test.

On the assumption that by the use of the hot-plate procedure the antagonist properties of narcotic analgesics could be detected, the effect of morphine, pentazocine, nalorphine and naloxone were investigated. The latency of paw-licking and jumping-off were determined and compared. The agonist, morphine, at doses of 0.025, 0.05 and 0.1 mmole/kg injected IP significantly increased paw-lick and jump-off latency above that seen in saline controls. The mixed agonist-antagonist, pentazocine, at doses of 0.048, 0.096 and 0.192 mmole/kg and nalorphine, an antagonist with some agonist activity, at doses of 0.032, 0.064 and 0.128 mmole/kg significantly increased the latency of paw-licking, but did not significantly change the jump-off latency. At a dose of 0.016 mmole/kg naloxone treated mice jumped from the hot-plate significantly sooner than controls but no effects of naloxone on paw-licking latency were observed. These results suggest that agonist properties are involved in the paw-lick response and that antagonistic properties determine jumping-off behavior.


Acute effects of parathyroid extract on renal vitamin D hydroxylases in Japanese quail.

The dose- and the time-response relationships of parathyroid hormone's modulation of in vitro 1,25-(OH)2D3 and 24,25-(OH)2D3 production in Japanese quail were investigated. 4-week-old female Japanese quail were injected intramuscularly with three different doses (30, 90 and 270 USP units/kg) of parathyroid extract (PTH). 4, 12 and 24 h after the in vivo administration of PTH, kidney homogenates were incubated with tritiated 25-(OH)D3. All three doses of PTH stimulated 1,25-(OH)2D3 and inhibited 24,25-(OH)2D3 production at 12 h relative to the vehicle-treated control group. The responses of the vitamin D hydroxylases were not detectable at 4 h and had returned to control levels by 24 h. Plasma calcium rose significantly at 4 h with the two higher doese of PTH (90 and 270 USP units/mg) but not with the lowest dose. By 12 h the plasma calcium had returned to control levels except at the highest dose of PTH. By 24 h all of the plasma calcium levels had returned to control values. Plasma inorganic phosphate levels were depressed at 4 h by all three PTH doses; they remained depressed at 12 h and returned to control levels by 24 h. It is concluded that the pharmacological effects of PTH on the renal vitamin D hydroxylases are slower in onset and shorter in duration when compared with those of estradiol.


Dose-dependent biliary and renal excretion of paracetamol in the rat.

In rats, the biliary and renal excretion of paracetamol changed in a dose-dependent manner. After an oral nonhepatotoxic dose of 200 mg/kg paractamol, the drug excreted in the bile amonted to only 5.5% within 24 h, whereas 72% of the dose were excreted into the urine. Following an oral hepatoxic dose (1,000 mg/kg), the biliary excretion of thotal paracetamol was enhanced to 13.5% whereas the renal elimination was reduced to 51% of the dose. After a nontoxic intravenous treatment with paracetamol (25-100-400 mg/kg), both the excretion of paracetamol conjugates into the bile and the elimination of free paracetamol into the urine were augmented in a dose-dependent manner. Hepatic damage due to carbon tetrachloride pretreatment (0.5 ml/kg i.p. 24 h before 100 mg/kg paracetamol i.v.) diminished both the bile flow and the biliary excretion of paracetamol conjugates, whereas the renal elimination was not affected.


Effect of steroid hormones and diethylstilbestrol on adrenomedullary catecholamine secretion.

Acetylcholine-induced catecholamine secretion from isolated, perfused bovine adrenal medulla was strongly inhibited by hydrocortisone (30 micro M), estradiol (30 micro M), and estriol (30 micro M). Diethylistilbestrol (DES) (10 and 30 micro M) inhibited acetylcholine-induced secretion, and the effect of the higher dose was prolonged. Inhibition of high potassium-induced secretion by DES (30 micro M) indicated that hormonal inhibition of evoked secretion was not by competition for acetylcholine-sensitive receptor sites. Dehydrotestosterone (30 micro M) was ineffective in inhibiting acetylcholine-induced secrection. Hydrocortisone, estradiol, and estriol treatments enhanced nonstimulated release. It is suggested that incorporation of certain steroid into plasma and granule membranes, thereby modifying membrane function, enhances nonstimulated release and may also block evoked release of secretoy material.


Assay of antipyrine and its primary metabolites in plasma, saliva and urine by high-performance liquid chromatography and some preliminary results in man.

A reversed phase system for the HPLC separation of antipyrine and its primary metabolites is described. Based on this system an assay procedure for antipyrine in plasma and saliva was developed with a lowest measurable concentration of 25 ng/ml and precision of +/- 3.6 and +/- 4.5%, respectively. Furthermore, assays for the parent compound, 3-hydroxymethyl-antipyrine, norantipyrine and 4-hydroxy-antipyrine in urine were developed. The lowest measurable concentration for these compounds is about 100 ng/ml except for 3-hydroxymethyl-antipyrine with a lowest measurable concentration of about 200 ng/ml. The precision was established at +/- 3.6 and +/- 5.0% for 3-hydroxymethyl-antipyrine, and antipyrine, respectively, and +/- 7.0 and +/- 3.6% for norantipyrine and 4-hydroxy-antipyrine, respectively. The method was applied to studies on antipyrine metabolism in humans. Following administration of a single dose of 500 mg antipyrine to 5 healthy volunteers, 3.3 +/- 1.2% of the dose was recovered from 48-hour hydrolyzed urine as unchanged drug, 39.7+/- 8.7% as 3-hydroxymethyl-antipyrine, 14.5 +/- 6.8% as norantipyrine and 28.5 +/- 2.2% as 4-hydroxy-antipyrine.