[Physical work capacity of the patient with myocardial infarction submitted to intensive rehabilitative training (author's transl)]. The Authors have examined two homogeneous groups of patients with myocardial infarction; one underwent (61 patient) to a rehabilitating training, the other underwent (42 patient) to a domiciliary physical program. Patients have been considered by means of bicycle ergometer test at 2, 4, 12 and 24 months from myocardial infarction. They have been taken into consideration clinical and Ecg factors and also, as an index of physical work capacity was considered the complete work developed, the VO2 max/Kg per min., the product B.P. x H. R. and the pulse O2. The average value of parameters have been statistically compared by means of the t of Student, analysis of variation x2, and the test of Kolmogorov-Smirnov; moreover the correlation with linear coefficient has been studied. Afterwards the many-varied discriminating analysis and the test F di Snedelor have been carried out just for the index of functionality. From the statistical analysis of the data considered it results an increase of the functional capacity and its maintenance long after in the group that underwent to the rehabilitating training. However, two years after, this increase of capacity did not result greater than that obtained, in the same period of time, by the group of patients who underwent to a domiciliary physical rehabilitating program. These considerations point out the necessity of keeping physical exercise indefinitely or at least of repeating it periodically. In that event they suggest the right time to programme further cycles of training.


[Autoptic findings and anatomo-clinical correlations in subjects who died after repair of tetralogy of Fallot (author's transl)]. The postoperative course and the post-mortem findings of a group of 30 patients who died after repair of tetralogy of Fallot were reviewed. A residual ventricular septal defect was the most common finding at the autopsy (13 patients = 43%) while a severe residual obstruction to the right ventricular outflow was found in 5 patients (17%), miscellaneous lesions in 3 (10%) and no intracardiac defects in 9 (30%). Since a residual anatomic defect is frequently responsible for the hospital mortality, prompts hemodynamic evaluation and reoperation is recommended when the postoperative course is deteriorating.


[Routine clinical use of a new disposable bubble oxygenator: a comparative study (author's transl)]. The new bubble Oxybel oxygenator (Bellco Laboratories) has been used for routine clinical perfusions in this Institution. A comparison has been made between two groups of 51 patients each, one group perfused with on Oxybel oxygenator (OXY) and the other with the Harvey H 1000 oxygenator (H-H). Among these patients a wide range of acquired and congenital cardiac lesions have been encountered. Both series were comparable for patients' age, sex distribution, body weight, procedures performed, perfusion time and preoperative values of hematocrit, serum creatinine, platelet count, plasma hemoglobin. The gas/blood flow ratio was 2.09 +/- 0.07 (+/- SE) for the H-H oxygenator and 1.38 +/- 0.06 for the OXY series (P < 0.001). Serum-creatinine 24-hrs postoperative values (mg/100 ml) were 1.58 +/- 0.17 for the H-H and 1.30 +/- 0.06 for the OXY series (NS); 48-hrs postoperative values were 1.28 +/- 0.11 for the H-H and 1.20 +/- 0.11 for the OXY (NS). The 60 minutes postoperative platelet count was 127.9 +/- 7 X 10(3) for the H-H and 120.9 +/- 6 X 10(3) for the OXY series (NS). Fourtyeight-hrs postoperative platelet count was 153.0 +/- 5 X 10(3) for the H-H and 151.8 +/- 6 X 10(3) for the OXY series (NS). Postoperative plasma hemoglobin values (mg/100 ml) were 91.55 +/- 7.18 for H-H and 117 +/- 17.8 for the OXY series (NS). Total postoperative bleeding was 1037.9 +/- 94 ml in the H-H and 1056.7 +/- 98.9 ml in the OXY series (NS). The more favorable gas/blood flow ratio observed with the Oxybel oxygenator did not affect clinical and haematologic results. These were comparable in both series.


[Short-term and average-term automatic control of re-entry arrhythmias]. The AA. described an external stimulator to be utilized instead of invasive pharmacological treatment, as a short and middle-time therapeutic approach to re-entry tachycardia, in Departments of cardiology. The device must be connected with an electrode placed in atrium or in coronary sinus or in ventricle, according to individual request. A frequency discriminant device recognizes tachycardia and activates automatic scanning stimulator, synchronized on R or P waves, with progressive 5 msec stop delay; tachycardia interruption zone is automatically individuated. Stimulation has an automatic stop when tachycardia is interrupted; in case of persistent tachycardia scanning-function cycle will star again automatically. The device, which can be programmed for a simple or a double impulse emission, is equipped with a demand stimulator working if post-tachycardia asystole is present. Frequency discriminant device activates the scanning function beyond a defined threshold which can be varied within a wide range of frequencies.


[Right ventricular infarction. Report of a case with chronic congestive failure (author's transl)]. A case of myocardial infarction with severe shock, marked systemic venous congestion and transient A-V block was observed in our Coronary Care Unit four years ago; signs of pulmonary venous congestion were absent. The patient, still alive, remains seriously incapacitated, with persistent signs of right ventricular failure. Recently, coronary angiography has shown total proximal obstruction of a "dominant" right coronary artery. The left coronary artery was free from significant obstructions. Right and left ventriculography have shown severe diffuse impairment of right ventricular contractility and akinesis of the left ventricular posterobasal segment. Echocardiography has demonstrated marked paradoxical movement of the interventricular septum. The scanty literature on this rare syndrome is reviewed; diagnostic criteria, therapeutic approaches and prognosis are briefly discussed.


[Familial long QT interval and sudden death (author's transl)]. A family in whom two brothers, a sister and the father presented a long QT interval is reported. The father died suddenly at the age of 37. The opportunity of a more careful research of the syndrome, now underdiagnosed, is underlined in view of the curability such disease.


[Removal of an endocavitary electrode with cardiopulmonary bypass for septicemia associated with right atrial thrombosis. Report of a case (author's transl)]. A case of staphylococcus epidermidis endocarditis associated with a right atrial thrombosis around a pacemaker electrode is presented. Stuce the antibiotic therapy had proved uneffective, the electrode had to be removed with cardiopulmonary bypass; the infection was subsequently eliminated. When a foreign body cannot be removed by closed techniques, open heart surgery with cardiopulmonary bypass may be necessary.


[Psychological and occupational repercussions of myocardial infarct]. The AA. studied the psychological and working consequences of the myocardial infarction in a group of 147 patients outlived more than two years. 50% of them showed mood disturbances, 40% did not restarted of work and 20 worked again moderately. The interruption of the work had psychological reason in 32% of cases and economic reasons in 26%. The 38% of the subjects was pensioned and the 25% received a pension through work foult. According to the INPS data, in Italy, every year, 1000,000 pension claims, for arteriosclerotic cardiopathy or myocardial infarct are made. Pensions are granted in 99% of cases. The pension claims diminish from the North to the South of Italy and are lower among traders and farmers. The importance of psychological rehabilitation is confirmed by the resumption of work in 92% of the cases among the railway workers, that have a good medical assistance.


[Critical findings of captitate osteotomy in the treatment of lunatomalacia]. Five patients with Kienböck's disease had been treated by an osteotomy of the capitate (GRANER) with three poor results. In two cases necrosis of the capitate bone and resorption of the cancellous bone graft were obvious, perhaps due to damage of important vascular structures. Anatomical studies which have been carried out, showed that the main vessel of the capitate arises from the deep palmar arch and joints the bone on its ulnar-palmar and distal aspect. In order to achieve more satisfactory results with this operative procedure, the authors feel that it is important to protect the above mentioned vessel and indicate a more proximal osteotomy-site of the capitate bone.


[Kessler arthroplasty of the carpometacarpal joint of the thumb in arthrosis and arthritis]. Early results of the KESSLER-Implant in 11 patients are presented. 7 patients suffered from rheumatoid arthritis, 1 from psoriatic arthropathy. For technical reasons this endoprosthesis seems to be especially suitable for patients with rheumatoid disease. By remodelling the articular surface of the trapezium corresponding to the implant, it is possible to reestablish stability even in cases with severe destruction and subluxation of the CM joint.


[Variant of the coracobrachialis muscle (accessory origin from the shoulder joint capsule)]. A description is presented of a supernumerary head of the coraco-brachialis muscle, which was found over the shoulder joint. Theanomalous muscle can be confused with the subscapularis muscle approaching from front to the shoulder.


[Misdiagnosis: Raynaud's disease].

[Misdiagnosis: Raynaud's disease]. Within a few hours a patient developed necrosis of two finger tips. A provisional diagnosis of Raynaud's disease was made and an arteriogram was performed. This showed considerable hypervascularisation of the affected fingers. After 48 hours, the typical clinical picture of an acute infection became evident. The differential diagnosis and pathogenesis are discussed.


[Results of 2-stage flexor tendon transplantation on zone 2]. For reconstruction of injuries of flexor tendons within zone 2, we used pedicled two-stage tendon grafts in about 50 cases. Proceeding from the concept that a pedicled tendon graft, at least partially vascularised, would tend less to adhesions, we combined the technique of PANEVA-HOLEVICH with the two-stage procedure. The results of 31 follow-up cases are reported and analysed by using the evaluation criteria of BUCK-GRAMCKO. Very good results were obtained in 17,4%, 30,4% were judged failures, good in 30,4% and satisfying results in 21,7%.


[Graphic demonstration of finger mobility in the grasping region]. To test the functional capacity of a finger, the documentation of its range of motion is of great importance. The capacity to grasp is determined by the flexion and extension ability of the finger joints. Dexterity is based on the mobility field of the finger end, within the grasping area. Both can be shown graphically. A table is described with which the mobility within the grasping area of each finger can be tested and documented without joint measuring. The advantage of this method is the easy handling and the graphic demonstration, allowing a very precise judgment of the functional capacity of a finger. The graphic demonstration is especially qualified for testing disabled fingers as well as showing progress during physiotherapy.


[A new treatment method for hydrochloric acid burns of the hand]. The progression of hydrofluoric acid corrosion on the hands, which cannot be arrested by other means and leads to crippling or amputation, can be stopped by one single or several repeated intra-arterial perfusions of 10 ml 20% calcium-gluconate solution in 40 ml normal saline over 4 hours as close to the defect as possible via the brachial artery or one of the forearm arteries. In 4 patients, with corrosion of a severity judged to be between first and third degree, spontaneous healing resulted after this treatment. Based on our experience we advise the use of intra-arterial perfusion and show its advantages over subcutaneous injections or intravenous infusion of calcium.


[Functional improvement in the treatment of large soft tissue defects of the thumb by a free tissue transplant]. The advantages of free transplantation used to cover defects of the thumb are demonstrated with the aid of a clinical example. A 27 years old patient had lost large parts of the covering soft tissue as well as the nerves and vessels on the flexor side of the distal phalanx of his left thumb. After a single wound toilet the thumb could hardly be used because of the reduced mechanical resistance to stress, the missing sensibility and a severely disturbed circulation. This kind of large soft tissue defect at a functionally important location can now be covered with a free composite tissue transplantation. We took a neurovascular flap out of this patient's forefoot and anastomosed it with the vessels and nerves of the proximal phalanx of the thumb. After an uncomplicated healing the covering soft tissue could be mechanically stressed and was well supplied with blood. Three month later a beginning sensibility can be proved. After 2 years the fully rehabilitated patient shows a good functional result with a two-point discrimination of 10 millimeters.


A study on operative findings and pathogenic factors in ulnar neuropathy at the elbow. A study was made of operative findings obtained in 44 cases of ulnar nerve neuropathy at the elbow in an attempt to help elucidate the pathogenetic factors for the condition. Distinction must be made between Lig. epitrochleo-anconeum or a ligament-like thickening at the same site and the tendinous arch of M. flexor carpi ulnaris. These 2 sites constitute the entrapment points for the condition. A thick tendinous arch, Lig. epitrochleo-anconeum of M. anconeus epitrochlearis deters the ulnar nerve from being mobile, thereby contributing to the development of neuropathy with trauma acting as a precipitating factor. Dislocation of the ulnar nerve cannot be considered a factor of major etiologic significance. An important part is played by the tendinous arch in the pathogenesis of neuropathy, regardless of whether it is in association with ganglion, osteochondromatosis or osteoarthritis. In surgery for ulnar neuropathy decompression of the nerve is of primary necessity. Division of the tendinous arch is mandatory. Medial epicondylectomy may be added as required.


Arthroscopic examination of the posteromedial compartment of the knee joint. In a series of 356 arthroscopies of the knee joint 127 patients were explored by arthrotomy. A Storz arthroscope was introduced through the patellar tendon, and we alternated between the 30 degrees and 70 degrees optical systems in the same trocar sheath. The 30 degrees system was used for inspection of the superior, anterior, medial and lateral compartments, and to lead the tip of the instrument to the posterior part of the joint. The 70 degrees telescope was then used, providing a good view of the posterior cruciate ligament and the posterior horn of the menisci and their attachments. It also allowed direct inspection of the posterolateral and posteromedial compartments. No major diagnostic error was made by the arthroscopist in the 127 patients operated on as a result of the findings of endoscopic examination. Arthroscopy with the use of both 30 degrees and 70 degrees telescopes at the same session gives high diagnostic accuracy and detailed, exact pre-operative diagnosis.


Transcutaneous meniscectomy under arthroscopic control. A technique of arthroscopic excision of a torn meniscus has evolved during two years' experience of therapeutic arthroscopy of the knee joint. The same method is used for both medial and lateral meniscus lesions under full visual control throughout the procedure, with a standard arthroscope inserted centrally through the patellar tendon. The first 18 consecutive patients thus treated have been followed up. Endoscopic operation was complemented by arthrotomy in three; in 15 no other treatment was given. The time in hospital, convalescence, sick leave, and knee function at follow-up were compared in these 15 patients with matched controls treated in the ordinary way by arthrotomy. Knee function did not differ between the groups, whereas all other variables showed better results after arthroscopic excision.


[Rupture of the extensor apparatus of the knee; 45 cases]. The authors describe 45 cases of rupture of the extensor apparatus of the knee (excluding fracture of the patella). Some new ideas are put forward concerning the frequent cause by road accidents and the contribution of certain predisposing features which cause degenerative changes of the tendon. Operation was performed in all cases. The extensor apparatus was reconstructed by suture, cerclage or reinsertion, together with the use of procedures described by Mac Laughlin and Scuderi. The results are presented in detail. 90% are very good or good but complications during operation or in the post operative phase were frequent and occurred in 27% of the cases.


The effect of high tibial osteotomy on osteoarthritis of the knee. Clinical and histological observations. High tibial osteotomies were performed on 136 osteoarthritic knees for correction of varus deformity. Before osteotomy all patients experienced moderate or severe pain, and the knees showed lateral thrust on weight-bearing. The patients were followed up for one to five years. Marked relief of pain was obtained in 112 knees, and the patients were satisfied with the result of operation in 122. These painless knees showed no lateral thrust, and in the majority the deformity had been adequately corrected, with post-operative femoro-tibial angles (standing) ranging from 165 degrees to 174 degrees. Four of 28 knees with femoro-tibial angles of 175 degrees to 179 degrees, when measured one year after operation, showed recurrence of varus deformity three years after osteotomy. Preoperative ranges of knee motion were well maintained after osteotomy even when arthrotomy had also been undertaken. Intra-articular assessment in two patients, several years after operation, showed that the most degenerated portions of the articular surface were completely covered by a fibrocartilagenous layer, with no bare bone. High tibial osteotomy is most effective in osteoarthritic knees with varus deformity, when correction is made to a femoro-tibial angle (standing) of 170 degrees (10 degrees valgus).


Biochemical and structural abnormalities of the connective tissue in Larsen's syndrome. Skin, iliac crest cartilage and tendon of a patient affected with Larsen's syndrome were subjected to biochemical and ultrastructural investigation. A substantial increase in the ratio of glucosamine to galactosamine was found both in skin and cartilage. Ultrastructural abnormalities of collagen fibres and proteoglycan filaments were also found in Larsen's tissues. The significance of these findings are discussed.


[A case of melorheostosis. Clinical, radiological, pathological and biomechanical details]. A patient with melorheostosis of the right lower limb is described with the clinical findings and radiographic appearances which include angiographs and microradiographs. Tissue was taken from the knee joint at the time of arthrodesis and examined by histological, histochemical and biomechanical techniques. It is concluded that the bone in melorheostosis is not different from normal bone.


Primary treatment of comminuted intertrochanteric fractures of the hip with a Leinbach prosthesis. The authors present 43 cases of comminuted intertrochanteric fracture, treated by replacement with a Leinbach prosthesis. The average age of the patient was 81 years, the average time of operation was 70.8 min, and the average blood loss was 502 cc. 88% of the patients were walking within 4--10 days. One deep infection occurred requiring removal of the prosthesis five months later. Based on this experience, the authors recommend consideration of the use of a Leinbach prosthesis in the primary treatment of the elderly patient with a comminuted intertrochanteric fracture of the hip.


The role of embolic fat in post-traumatic pulmonary insufficiency. An evaluation of the pulmonary haemodynamics and blood gas levels. Pulmonary haemodynamic and arterial blood gas changes were measured in dogs subjected to either an intravenous injection of triolein or external trauma, which produced fractures of the ipsilateral femur, tibia and fibula. Musculoskeletal trauma resulted in pulmonary vasoconstriction followed by vasodilatation, arterial hypoxia with a pulmonary shunt of 30% and a 20% decrease in systemic oxygen delivery. Lipid injection produced an increased pulmonary vascular resistance, but no significant hypoxia, pulmonary shunting or inadequate tissue oxygenation. We therefore suggest that pulmonary fat embolism does not account for the pulmonary insufficiency following musculoskeletal trauma.


Complications of the treatment of congenital dislocation of the hip by the Pavlik harness. The results of the treatment of congenital dislocation of the hip using the Pavlik harness were satisfactory, but lateral displacement and deformity of the femoral head were sometimes observed after treatment. The causes of these complications are discussed and the measures taken to avoid them are discribed.


Replacement arthroplasty using the Charnley prosthesis in old tuberculosis of the hip. This report is based upon a retrospective study of a consecutive series of twenty patients who had tuberculosis of the hip in quiescent state. Two patients had only a short history but were included in this study. An interesting feature at the time of operation was that in many cases the bone showed old features of tuberculous disease despite the long history of quiescence. A modification of the Charnley technique is discussed. In addition, details of radiographic assessment before operation, antituberculous drug therapy and the use of Kanamycin in bone cement are given. The complications and results are recorded.


An experimental analysis of injuries to the menisci of the knee joint. Direct methods were used to determine the distribution of injuries to the menisci in formalin fixed knee joints, rotated under physiological pressures when extended and at different degrees of flexion. The position of the joint during rotation rather than the direction of rotation determined the distribution of injury between the menisci, whereas both direction of rotation and joint position determined the position of major types of lesion within the meniscus. Support is given for the view that the incidence of injury to the lateral meniscus is higher than generally accepted.


Solvent effects on the time-dependent photoisomerization of methyl retinoate. The photoisomerization of methyl all-trans-retinoate is dependent upon both solvent polarity and irradiation time. The all-trans-isomer isomerizes most rapidly in solvents of high polarity. Methyl 11-cis-retinoate is maximally produced after three hours in dimethyl sulfoxide, while it is not formed to an appreciable extent in heptane. Methyl 13-cis-retinoate forms maximally after two hours in heptane, then decrease in concentration by one-half to about the same level maximally formed in dimethyl sulfoxide. The solvent and time dependences of the other isomers are presented to allow selection of conditions for maximal production of desired isomers. The results for methyl retinoate appear applicable for retinoic acid.


Effect of lipid antioxidants on rat erythrocyte hemolysis. Lipid antioxidants, DPPD, DAH, BHT, SQ, retinol and alpha-tocopherol were studied for their effects on normal rat erythrocytes. Retinol, BHT and SQ were found to induce hemolysis while DPPD, DAH and alpha-tocopherol were non-hemolytic. Further more the three antioxidants BHT, SQ and retinol showed a synergistic effect on the lysis. Retinol, BHT or SQ alone, and BHT or SQ along with retinol when administered to rats produced a marked modification of the erythrocyte membrane integrity, simultaneously lowering the levels of membrane bound enzymes--acetyl choline esterase and ATPase. It is concluded that the lipid antioxidants may therefore be classified on the basis of their lytic action in vitro.


Amino acid and glycosaminoglycan composition of epiphyseal cartilage of neonate and osteoporotic lambs. The epiphyseal plates of neonate and healthy or osteoporotic 60-day-old lambs were analyzed chemically. Uronic acid was higher in 60-day-old healthy lamb than in neonates but galactosamine was higher in neonates than in 60-day-old healthy lambs. Fourteen of the 17 amino acids identified in the epiphyseal cartilage were higher or had a tendency to be higher in 60-day-old healthy lambs than in neonates. Lower levels of uronic acid were noted in 60-day-old osteoportic lambs than in healthy lambs of the same age.


Transfer of alpha-tocopherol from plasma to erythrocytes in vitamin E-deficient rats. The transfer of alpha-tocopherol from plasma to erythrocytes was examined using labeled alpha-tocopherol in vitamin E-deficient rats and at the same time the appearance of resistance to dialuric acid-induced hemolysis in the erythrocytes was observed. It was noticed that the transfer took place in two sequential steps. The second step seemed to correlate the appearance of resistance to dialuric acid-induced hemolysis, d-alpha and d,l-alpha-Tocopherol were compared under the same in vitro experimental conditions and no difference between them was observed in the effect on the recovery of antihemolytic activity. The difference in physiological activity between d-alpha- and d,l-alpha-tocopherol may exist other than in the transfer step. The coexistence of alpha-tocopherol and alpha-tocopherol quinone did not show any inhibiton for transfer of alpha-tocopherol from plasma to erythrocytes in vitamin E-deficient rats.


Pyrithiamin shortens ethanol-induced narcosis and increases voluntary ethanol drinking in rats. To investigate the role of thiamin deficiency in increasing voluntary ethanol intake in rats the effect of ethanol on the central nervous system was studied by measuring the duration of ethanol narcosis in pyrithiamin-treated rats. The duration of ethanol-induced narcosis was significantly shorter and blood ethanol concentration at the moment of righting reflex recovery was higher in pyrithiamin-treated rats than in controls. Thus, the shorter ethanol narcosis of pyrithiamin-treated rats was not a result of a change in ethanol metabolism but rather suggests changes in the central effects of ethanol. Treatment with thiamin increased the duration of ethanol narcosis to the initial level in rats pretreated with pyrithiamin. During the same pyrithiamin treatment as used for the narcosis test voluntary ethanol intake of rats was higher than during optimal treatment by thiamin. The results suggest that there might be a decrease in central sensitivity to ethanol in pyrithiamin treated rats, which may have a role in increasing their voluntary ethanol drinking.


Studies on folate metabolism in folic acid-deficient rats. The distribution in liver of pteroylpolyglutamates and urinary excretion of folate metabolites was studied in folic acid deficient rats after injection of the vitamin, in order to evaluate the effect of folic acid deficiency on the conversion of the vitamin into actual coenzymic forms. Any significant difference neither in total activity nor in pteroylpolyglutamates of liver does not appear between deficient supplemented and unsupplemented animals. Also the urinary amounts of reduced metabolites in deficient rats do not increase after injection of folic acid. Therefore the inability of deficient rat liver to synthesize polyglutamates may be ascribed to the lower availability of tetrahydrofolates as they are the preferred substrates of pteroylpolyglutamate synthetase.


Influence of dietary ascorbic acid on plasma lipid levels in the rainbow trout. Rainbow trout maintained on ascorbic acid deficient and three grades of ascorbic acid supplemented diets (160--1280 mg ascorbic acid pr kg feed) for a period of 53 weeks, were studied for effects on plasma lipid levels. Fish fed the diet with no ascorbic acid manifested lethargy, lordosis, scoliosis, internal hemorrhages and low body weight. With regard to blood properties, ascorbic acid deficient fish had low hematocrit and high plasma levels of triglycerides and cholesterol but low level of free fatty acids. Plasma level of free fatty acids was low also in fish fed the diet containing the highest amount of ascorbic acid.


Is plasma zinc a useful investigation?

Is plasma zinc a useful investigation? Plasma zinc is totally protein bound and its concentration is markedly influenced by alteration in protein concentration. Venous occlusion such as is used prior to venepuncture causes a marked increase in plasma zinc concentration. The extent of this change exceeds the analytical variation for zinc determination and may cause difficulty in the interpretation of plasma values. Although in most individuals there is a close correlation between plasma zinc and total protein, collectively this is not so, thus adjusting zinc values for change in protein is inappropriate. For plasma zinc to be a useful investigation blood samples should be obtained without venous occlusion.


Organic solvent soluble lipofuscin pigment in brain tissues of mice fed large amounts of polyunsaturated fats in presence and absence of various antioxidants. The amount of lipid soluble fluorescent pigment is compared in brain tissues of mice fed a diet containing 10% safflower oil with and without a supplement of antioxidants as Vitamin E, Ascorbyl-Palmitate and Sodium-Selenite. Addition of 0.2 g/kg Vitamin E to the diet gives a high raise in the mortality. The addition of 0.2 g/kg Vitamin E and 0.5 g/kg Ascorbyl-Palmitate leads to higher values of extractable lipid soluble fluorescent pigment in mice brain tissues.


[Training of general surgeons as perceived from private practice]. A recent Swiss opinion poll has revealed that the medical profession is still enjoying a high prestige. The large majority of the surgeons in free practice has an optimistic view of the future of private medicine. Abdominal and peripheral vascular surgery as well as the surgery of the extremities belong also in smaller hospitals. About 75% of the surgeons feel that 10 years of postgraduate training is sufficient. A theoretical final examination is rejected. For further professional training, lectures, various courses and congresses are very popular. Compulsory examinations by the Swiss Medical Association (FMH) are undesirable.


[French Switzerland commentaries and reflections on the education and activities of surgeons working in private clinics]. This complementary report discusses different points of view of the surgical education. Is his actual concept up to date? with or without final examination? with or without regular control of the theoretical and practical knowledges? what represents "general surgery"? which is the education and the activity of a surgeon working in private clinics?


[Surgery in the regional and district hospitals of German Switzerland]. The Regional Hospital is the hub in the surgical service for the broad population. According to its importance, it has furthermore an eminent role in instruction and postgraduate teaching. The requirements and profile for such competent medical chiefs are delineated. The broad surgical requirements, the executive duties in hospital administration, which are shared with the nursing and administration services, and the permanent personal education make it mandatory, that the position of the head surgeon be partitioned by two equally competent and polyvalent general surgeons. The ultimate responsibility for such adequate positioning rests with the political authority.


[Activities of the general surgeon in a non-university hospital]. There is little difference between the work of the general surgeon as the head of a provincial hospital (B2) or in a central non-university one (A2). The operative statistics of such a service show that the type of operations is varied and requires broad polyvalence. Surgical services in provincial hospitals should not be subdivided into several specialised department. There is a real need for general surgeons in our country. Their quality depends on a broad and adequate training including the majority of surgical specialities. Such an activity requires constant postgraduate training, analysis of the results and ability to self criticism. Frequent contacts should be encouraged with other colleagues and university hospitals. The head surgeon in a provincial hospital should be able to evaluate the majority of the cases which are submitted to him and to decide whether the patient will be operated by him personnally or by a specialized consultant, or whenever he should be transferred to a specialized unit. This type of work has certain advantages: the possibility of independent decisions, a broad ability in the different surgical fields, allowing an easy adaptation when unexpected situations happen during operation.


[Training possibilities for surgical interns]. Two questionnaires were prepared and adressed to interns in all surgery clinics in Switzerland. They trend to determine opinions on the actual formation in surgery. The results appears that, if a good formation may be obtained, the "postgraduate" has to be considered nowadays as the forgotten child in the hospitals. Important effort must be envisaged, to ameliorate the structuration of the post-graduate teaching, between and in the hospitals, but also to determine ways to inspect his quality.


[Federation of Swiss Physicians and the training of general surgeons]. The author recommends the Residency Program of the Halsted type as developed by D.C. SABISTON in the Departement of Surgery at Duke University. A two-year training in the basic problems, knowledge, and attitudes, common to all surgical subspecialties, is of fundamental importance (Fig. 1). The goal of this type of training is the US-Board Certification.--The Swiss Medical Federation considers the following factors as essential in a surgical training programm: The training of the general surgeon should be geared to broad principles without early overspecialisation. The training should allow a certain flexibility for the teacher as well as the candidate. A sufficient operative experience is paramount as well as the habit of a continuous education all trough a life-long surgical career and an understanding for economy in surgical practice.--The training of an university--or a private--surgeon does not give rise to important problems, whereas the training of surgeons for the medium sized and small Swiss hospitals represents a difficult problem. A double training in "visceral" and "orthopaedic" surgery with an accent on one or the other seems necessary in order to have one chief surgeon take the place of another during vacation, week-ends and illness. Even if such a complete training seems desirable, it can be justly questioned if under the present circumstances (emergency transportation, regionalized hospital organization, specialized hospital consultants) it is still justified to aim at the training of a "complete" surgeon who elsewhere, in a university hospital or in private practice or for that matter in other countries, is no longer absolutely necessary.


[Dangers of thoracic drainage].

[Dangers of thoracic drainage]. Three case histories are presented in order to demonstrate the hazards of apparently well-placed pleural chest tubes. In one instance of ruptured diaphragm the dislocated and distended stomach imitated a pneumothorax, thus inviting thoracic drainage; in two other cases the drainage of a massive hematothorax accelerated the oncome of hemorrhagic shock.


[Drainage in surgery of the heart and great vessels]. Based upon some recent experience with pericardial drainage a comparison is established between the surgical procedure and the needle-punction; the best approach to the pericardium, depending on the nature of the effusion is described. In the second part, the value of various types of drainage used since 19 years in the cardiac surgery is reviewed on the basis of our own experience with more than 7000 cases.


[Drainage and lavage in abdominal surgery: bacteriologic aspects]. The efficiency of draining a purulent collection in the thoracic or abdominal cavity is well known. The actuel knowledge about opsonisation and phagocytosis of pathogenic bacterias offer a new and attractive explanation for this phenomenon. The prophylactic drainage of an uninfected cavity on the other hand has the advantage of eliminating blood and other materials promoting infection. However, the drainage has the inherent risk of a foreign body, obstruction and introduction of an artificial fistula. Therefore it should be inserted for a period as short as possible.


[Acute necrotizing pancreatitis and post-operative irrigation-lavage]. A series of 62 operated cases of acute necroto-hemorrhagic pancreatitis is presented along with discussion of the four principle objectives of surgical treatment: exposure, evaluation and selective resection of the lesions followed by close observation. Based on peroperative determination of anatomic site and macroscopic character, a double codification for each lesion is proposed. This codification provides the surgeon an objective basis for his choice of the type of procedure to be done. The surgery itself has a dual purpose: to eradicate frank necrosis and to protect the remaining tissue from autodigestion by installing one or more drains for irrigation and lavage of the lesion site. In the case of stage 3 necrosis, the procedure must include a left pancreatectomy of varying extent.


[Acute hemorrhagic pancreatitis--extended abdominal drainage and perirenal drainage links]. Acute haemorrhagic pancreatitis, when mainly situated in the body and tail of the pancreas, may be associated with abscess formation in the left perirenal region through the radix mesosoli transversi. Next to the extensive drainage of the abdomen and pancreas, we advise supplementary primary left perirenal-retroperitoneal drainage, considering how difficult it can be to loalize a secondary postoperative pancreatic abscess, especially when a computer-assisted tomography (CAT) is unavailable. In those cases in which the transverse colon had suffered circulatory damage from the acute pancreatitis, good results have been obtained with temporary coecostomy.


[Drainage following sigmoido-rectal surgery]. There is a great diversity of opinion concerning the management of wounds in rectal surgery. In resection of the rectum we recommend to use the soft Penrose drain, we put in several drains, if the operative field isn't completely clean, we rinse more thoroughly the wound per- and postoperatively in cases of massive bacterial and fecal contamination. Irrigation combined with suction drainage is only installed in presence of general peritonitis. In amputation of the rectum we have abandonned primary closure combined with suction drainage of the perineal wound, a loose bundle drainage neither delaying wound healing nor prolonging hospital stay. In cases of hemorrhage we plug the wound by a Mikulic tampon. If the pelvic floor cannot be closed, we place a plastic sheet on the abdominal side of the Mikulic tampon, this sheet serving as complementary draining system. The disadvantages of every draining system are overruled by their life saving capacities.


[Transvaginal drainage in rectum amputations]. In cases of abdomino-perineal excision of the rectum, a monobloc excision of the posterior vaginal wall and the rectum is performed. The flaps thus formed are rotated and sutured to the side-walls of the cavity. The perineal fat is approximated and the skin sutured. The "new vagina" is packed. The vaginal epithelium covers in less than three weeks the posterior raw area reconstituting a normal vagina. The packing is irrigated daily with an antiseptic. Postoperative cares are more easier.


[Peritoneal drainage in emergency surgery of the appendix, colon and small intestine]. Retrospective study of patients who underwent as an emergency, a peritoneal drainage during laparotomy for peritonitis with perforated appendix (147 cases), or operation for lage bowel (68 cases) or small bowel (46 cases) pathology. The technique of drainage number of drains, duration of drainage, and length of stay in hospital are examined, as well as antibiotherapy. The conclusions do not allow us to attribute a harmful influence to peritoneal drainage, except perhaps that the duration of stay in hospital can be longer. The absence of a comparison group does not allow us to prove the utility of peritoneal drainage. The literature at our disposal is discussed, the majority of which is opposed to peritoneal drainage.


[Should drainage be performed in perforated appendicitis?]. During a follow-up study we examined 85 patients (34 children) with perforated appendicitis. The operating procedure is shortly sketched. The very favourable early and late results of our patients confirm the findings of other authors [2, 4, 5] that an intraperitoneal drainage is unnecessary in patients with perforated appendicitis. We take a thick Penrose drain for any abscess within a capsule.


[Drainage following urological surgery]. Prolonged leakage of urine and infection are the most troublesome complications following surgical exposure of the lumen of the urinary tract. The available methods of wound and urinary drainage are discussed. Careful attention should be paid to the material from which the drain is manufactured, because of long periods of drainage in a closed system.


[Drainage and lavage in abdominal trauma]. Peritoneal lavage is a reliable procedure in diagnosis of posttraumatic intra-abdominal bleeding. The method is extremely sensitive. If the return is found weakly positive, the lavage catheter should be left in position until the situation is cleared. Insufflation of air through the catheter may be used in diagnosis of a ruptured diaphragm. In the first days after trauma, peritoneal lavage may as well be helpful to detect secondary bleeding (for example in delayed rupture of the spleen) in unconscious patients or during mechanical ventilation. Postoperative drainage of the abdomen, too, is of considerable diagnostic value: for assessment of postoperative bleeding and in diagnosis of delayed intestinal perforation or insufficiency of a sutured bowel lesion. In pancreatic trauma, adequate drainage of pancreatic secretions prevents arterial arrosion or the formation of a pseudocyst. Determination of amylase in the drained fluid guides the further therapy: duration of total parenteral nutrition, suppression of pancreatic activity by drugs, removal o the drains. Tactics in draining the abdominal cavity after trauma should take into consideration an optimal removal of blood and secretions as well as the mentioned diagnostic value. In specially indicated cases the drainage system also should allow to perform peritoneal dialysis.


[Indications and technic of subphrenic percutaneous drainage]. Introduction of percutaneous drainage (pcd) of subphrenic space in early subphrenic abscesses or fluid collections (e.g. bile) seems to be an alternative to common surgical treatment, if the indication is restricted to single contaminated abscesses. Septicemia, continued contamination, hematomas and multiple abscesses are contraindications. A modified angiocatheter is placed directly or by a Seldinger technique. Adjunct antibiotic treatment is important. The advantages of subphrenic pcd are: simple low risk procedure in local anesthesia, rapid improvement of associated respiratory symptoms, no further contamination of the abdomen. 4 of 6 patients were treated successfully by this procedure.


Perception of moving sounds: velocity discrimination. Two experiments investigated auditory velocity perception. Exper. I compared auditory to visual velocity estimates. Five adults judged, in miles/hr, the motion of a sound source (a small loudspeaker) moving on a 1.88-m boom around S's head at each of 7 velocities from 15 to 360 degrees/sec. The sound source was either visible or not visible. Velocity judgments were shown in both modalities to be a power function of source velocity, with a slope of approximately 0.90. No significant difference was found between the auditory and visual functions. A control Exper. II determined with 14 naive adults that the similarities between the functions in each modality could not be attributed to either previous visual experience or proprioceptive feedback. Ss estimated the velocity of the visible moving loudspeaker while tracking the source with their eyes (N: 7) or while fixating on a small stationary light (N: 7). Eye motion was recorded from electrodes on the canthi. No significant differences were found between these conditions. The estimates were again shown to be a power function of source velocity (though slightly higher slopes of 0.99 for visual pursuit and 1.0 for visual fixation were obtained than in Exper. I). These experiments suggest a surprising degree of similarity in the perception of velocity in auditory and visual spatial functions.


Sensitivity to the elements of pure-tone auditory dyads. Judgments of 15 college students for the presence of one or two tones in a dyad were obtained while both the distance between frequencies (from 129--258 to 488--976 c/s) and the musical interval (from Octaves to Major Thirds) were independently changed. When the critical bands of the constituent tones mainly overlapped, the percentage of correct responses was high and depended primarily upon the distance between frequencies as opposed to the musical interval. Percentage of correct responses decreased with the size of the interval when there was no encroachment of critical bands. It was concluded that critical-band theory could readily explain the data: when critical bands overlap, Ss used the presence of "roughness" to judge that the stimulus contained two tones; when there was no critical band overlap, there was no roughness and Ss had to analyze the tones separately. This was more difficult than simply listening for roughness, and the percentage of errors increased in consequence.


The effect of age in brief-tone audiometry. The influence of age and sex on temporal intergration as it might be measured clinically was assessed in 50 normal-hearing Ss aged 6--24 yrs. A threshold-tracking paradigm was employed. Age did not systematically influence temporal integration. Variability of integration values among Ss of 6--7 yrs indicates that such children are capable of tracking threshold successfully in a brief-tone paradigm. Significant sex differences in integration slope were obtained across test frequency and age group.


Congenital vs acquired deafness: differences in reading and mathematics levels. Measures of reading ability and math skills were taken in 22 adults who were either congenitally deaf or had acquired deafness in the second or third year of life. Both groups were equivalent with respect to I.Q., education level and degree of loss. The following tests were administered: (1) the performance scale of the Weschler Adult Intelligence Scale, (2) the math section of the Wide Range Achievement Test, (3) the Reading Comprehension subtest of the Peabody Individual Achievement Test, and (4) the Raven Test of Progressive Matrices. There were no significant differences between the two groups on reading level, but a significantly higher math level was found in the congenital group. It was suggested that the pathology in the acquired group may have affected other neural centers in addition to the auditory, or that the acquired group may have been handicapped by the possibility of switching from one coding system (auditory) to another (visual), while in the congenital group the coding remained confined to the visual mode.


A study of five parameters of calorically-induced nystagmus in the clinical situation. Latency, duration, and amplitude of response, frequency of nystagmic beats, and speed of the slow component of calorically-induced nystagmus were studied by ENG in 14 normal-hearing adults. Attention was directed toward differences as a function of stimulus temperature (30 degrees C vs 44 degrees C) and side of stimulation. Nystagmus amplitudes were significantly larger from R ear as compared to L ear irrigations, and from cool as compared to warm. Ssc's from cool irrigations were also significantly larger than from warm. A series of t-tests computed for correlated samples indicated that the R ear 30 degrees irrigation, which was the first stimulus for all Ss, was responsible for the significant differences. Implications of the need for research on caloric interstimulus intervals and vestibular response fatigue were presented, and a procedure outlined to avoid erroneous results in caloric testing.


Microprocessor versus self-recording audiometry in industry. Auditory thresholds of 46 industrial workers tested on both a self-recording audiometer and a microprocessor audiometer showed significant differences at 2, 3, 6, and 8 kc/s with the self-recording instrument measuring lower thresholds by from 2.3 to 6.7 db. Differences appear to be the result of the psychophysical methods used and the use of pulsing versus steady tones. The differences, though significant, should be of little consequence in a carefully administered industrial hearing conservation program.


2AFC versus standard clinical measurement of high frequency auditory sensitivity (8--20 KC/S). A two-alternative forced choice (2AFC) psychophysical method of assessment was employed to judge the validity of using a standard clinical test procedure for obtaining thresholds in the frequency region 8--20 kc/s. Close agreement was demonstrated between "same-day" thresholds obtained with a standard clinical test procedure and the 2AFC method, for 6 well trained normal-hearing adults. In addition, close agreement was shown between the 2AFC sensitivity measure and the mean of thresholds obtained at 4 separate times during this investigation with the standard method. The standard clinical test method demonstrated good between-test reliability. It is concluded that a standard clinical test technique is a valid and feasible clinical measurement procedure for this high frequency region.


Preference for complexity in the auditory and visual modes. The contribution of sex and age was determined in comparisons of complexity preference in the auditory and visual modes. Six tonal passages and 22 random polygons of varying complexity constituted the auditory and visual stimuli, respectively. Preferences for complexity were elicited from 30 M and 30 F Ss, all of similar socio-economic status, in each of the age groups 5 and 17 yrs. Preference for complexity was not correlated across auditory and visual modes for any age or sex group. It was interesting, however, that although for 5-yr-old boys there was anon-significant inverse relationship between modes, and for 17-yr-old youths there was a non-significant direct relationship, the difference between these two correlations was significant. There was a significant (p less than .001) increase in visual complexity preference with age, although no such effect was found for auditory complexity; preference in the auditory mode remained at a moderate level for all groups.


Age and sex differences on preferred listening rates for speech. The preferred listening rate of speech was investigated in 30 men and 30 women aged 18--87 yrs. Ss were presented auditorially a reading of a standard prose passage and themselves adjusted a Varispeech I time compressor/expander to yield preferred listening rate. Differences in rate preference were significant for age but not for sex differences. Results support previous reports of auditory perceptual differences with increasing age and suggest that variability in previous reports of preferred listening rates may have been due in part to age differences of the Ss.


Influence of acoustic reflex on pure-tone thresholds in sensorineural patients. Discrete-frequency Bekesy HTLs (.25, .5, 1, and 2 kc/s) of 12 sensorineural impaired Ss (8 bilateral, 4 unilateral) were compared under 3 conditions to determine the influence of the acoustic reflex (AR). The conditions were (1) tones in quiet, (2) tones with contralateral noise 20 db below the AR threshold for noise, and (3) tones with contralateral noise 10 db above AR threshold. The results revealed statistically and clinically significant threshold shifts due to the AR. Clinical implications were discussed.


Reducing auditory feedback and the acquisition of motor response timing. Three groups of subjects (n=10) attempted to move a lever 50 cm along a track in 1.50 sec under one of three auditory feedback conditions: Fully augmented increasing auditory feedback (FAF) in which a constant level of velocity-related auditory feedback was provided for all 25 learning trials, reducing auditory feedback (FAF) in which the level of feedback was progressively reduced over the learning trials, and no auditory feedback (NAF). All subjects performed 10 trials with no auditory feedback after a 10-min rest interval. The hypothesis that acquisition of the criterion task would be facilitated under RAF compared to FAF derived partial support. It was concluded that there is sufficient evidence to justify further investigation of reducing auditory feedback as a technique of motor skill acquisition.


Prediction of serum testosterone before and after an exercise program using physiological and personality variables. This study investigated the relationships between serum testosterone level and selected physiological and personality variables in 58 males (21-61 years) before and after a four month physical fitness program consisting of jogging, calisthenics, and recreational activities. Physical fitness scores were obtained for each subject using a regression equation. Serum testosterone was determined using a radioimmunoassay technique. The multiple correlation was used to determine the relationship between serum testosterone and 19 independent variables consisting of age, height, and weight, and percent lean body weight, systolic and diastolic blood pressures, ten factors from the Cattell 16 PF and the three scales of the Eysenck Personality Inventory. A stepwise linear regression was used to identify the predictive power of each of the independent variables. The subjects improved significantly in physical fitness (p < 0.01). The multiple correlations both at the pre-test (R=0.77; R2=0.59) and post-test (R=0.67; R2=0.46) were significant at the 0.01 level. Neuroticism, factors dealing with emotional stability, aggression, and intelligence were powerful predictors initially. Similar results were obtained at the post-test except for the addition of percent lean as a powerful predictor and the absence of factors dealing with intelligence and aggression. The emergence of percent lean was seen to reflect changes in body composition associated with testosterone secretion. The absence of aggression at the post-test was interpreted in light of free catecholamine excretion associated with habitual exercise.


A predictive and descriptive model of interns' hospital selections. This paper examines the differences among medical students who have chosen different types of hospitals for internship training. The criterion variable of a medical student electing to take internship training in a government, private, public, or university hospital is analyzed using admissions, medical training, and practice data as independent variables. Multiple discriminant analysis is employed to evaluate the profiles of physicians who have taken internship training in the different types of hospitals. Classification rates were found to be somewhat accurate. Computer graph plots of discriminant analysis mappings are used to depict differences among the hospital-based internship groups. The results of applying these techniques and methods are of value for more efficient hospital administration.


On-line computer management of cardiac surgical data. The surgeon (or one of his assistants) enters, in a computer file, information on open-heart surgical procedures though a remote terminal located in the recovery room. Clinical and historical findings, complications occurring during the immediate postoperative period, and postmortem data when applicable are entered in the course of the hospital stay or after discharge. Relevant information entering the computer system in other hospital departments is automatically incorporated in the open-heart surgery file. A final multicopy operative report is printed in the recovery room shortly after the surgical procedure is completed. All information on patients in the file constitutes a permanent and dynamic data base that is accessible at any time from any remote terminal in the hospital computer system. This data base contains an average of 500 items of information per surgical procedure and is available via an on-line retrieval program for both quality control purposes and extrapolation of prognostic data on new patients.


A hospital medication monitoring system. Hospitals need to process large quantities of scattered information to properly screen medication orders. The data includes complex relationships involving drugs, diseases, and other drugs that determine whether a particular drug is contraindicated for a patient. Hospitals would therefore benefit from a flexible system for storing complex medical data relationships. We have used GPLAN, a CODASYL-like data management system, to construct a functioning model of a hospital pharmacy medication monitoring system. the patients' histories, drug-drug contraindications, disease-drug contraindications, and recommended dosages are stored in the data base in a network structure defined by the Data Description Language. Each drug order is checked for dose, allergies, current diseases, and current medications.


A note on computer graph plots of physician practice locations. This note examines the distribution of a medical school's physician graduates among states. Computer graphy plots of this distribution are shown to be an alternative way of providing information to health care administration decision-makers concerned with physician practice location.


Determining clinical significance in repeated laboratory measurements. The "Clinical Delta Range". A study of healthy subjects was conducted at the University of Florida wherein 52 routine clinical laboratory procedures were measured durng normal operation of the clinical laboratories. The goal of the study ws to quantify nonsignificant personal variation for a number of laboratory procedures referred to as a "Clinical Delta Range," which results from taking several samples per day, several days during the week. Results of the statistical test of hypotheses are given together with summary statistics for the 52 different laboratory procedures. A discussion of the model and testing methods are provided. Further, examples are given to illustrate the methodology and certain limitations associated with the concept of a Clinical Delta Range.


A proposal for laboratory data reporting. Changes are proposed regarding the presentation of laboratory information. More definitive statements are required for reference limits, sampling variance (the Clinical Delta Range), and multivariate group analysis of large test batteries. To make this transition possible, laboratory reports should be classed so that the practicing physician has some measure of confidence in the product and its compatability with other sources. The proposal extends to the range of financial reimbursement and suggests that class standing be issued by an accrediting agency and support a structured level of payment.


Uninterruptible power systems and other power protection equipment for electronic health care systems. The increasing usage of electronic instruments in health care systems invariably leads to some level of dependence on them. In order to maximize the utility of these tools a high degree of reliability is essential. Many of the failures being experienced in systems where electronic instruments are being utilized may be attributed not to a failure of the instrument itself but rather to the poor quality of the commercial power to which they are attached. In order to reduce the effects of power fluctuations and outages, some type of power protection equipment must be installed between the commercial power system and the instrument. This article discusses the types of "electronic noise" present on commercial power lines and the various types of equipment used to reduce its effect on electronic instrumentation. In general, the Uninterruptible Power System (UPS) is shown to be the most effective power buffering element for a health care environment. General terminology associated with specifications of a UPS is defined in the article and attached appendix.


[A study on the physiological basis of training effect--with special reference to myoglobin. I. Isolation and properties of myoglobin from dog skeletal muscle (author's transl)]. Myoglobin (Mb) was isolated from canine skeletal muscle by a novel heat denaturation-gel filtration-ion exchange chromatography procedure. The purified major Mb was homogeneous by gel electrophoretic and ultracentrifugal analysis, and the sedimentation coefficient at infinite dilution (S degrees 20, w) was 1.9 S. The molecular weight by sedimentation equilibrium was 1.72 X 10(4) and was essentially identical with the values by the iron analysis (1.80 X 10(4) and the amino acid composition (1.78 X 10(4). The spectroscopic properties of deoxy-, oxy-, carbonmonoxy- and met-derivatives of the Mb were determined in ultraviolet, Soret and visible regions. The pK' of acid-alkaline transition of the met-Mb was estimated as 8.80+/-0.04 (25 degrees) from the pH-dependent spectral change. The oxygen equilibrium studies revealed complete absence of such allosteric properties as heme-heme interaction, anion effect and the Bohr effect which were always present in normal mammalian hemoglobins. Oxygen tension for the half-oxygenation was 0.48 mmHg (20 degrees) and its temperature-dependent change gave the delta H degrees of -15.7 Kcal/mole.


Aminoglycosides, genes and regulation.

Aminoglycosides, genes and regulation. A major role has been played by aminoglycoside research in the development of fermentation science especially involving genetics and regulation. The first report of the use of an antibiotic to select high producers of that antibiotic was done with the streptomycin producer. Mutational biosynthesis of new antibiotics originated with studies on the neomycin producer. The first demonstration of the presence of genes coding for antibiotic inactivation in antibiotic producers was made with Streptomyces griseus, the producer of streptomycin. Induction of an enzyme involved in secondary metabolism was found first with mannosidostreptomycinase. The first example of a nonprecursor molecule which could induce an entire antibiotic biosynthetic pathway was A-Factor involved in streptomycin production. Glucose repression and amino acid repression of mannosidostreptomycinase were the first examples of carbon catabolite repression and nitrogen metabolite repression respectively of an enzyme involved in secondary metabolism. Data supporting the occurrence of nitrogen metabolite regulation of antibiotic biosynthesis were first gathered in the early days of development of the streptomycin fermentation when it was found that the slowly used soybean meal and proline were the best nitrogen sources for antibiotic production. Aminoglycoside research also provided the first explanation of a mechanism of phosphate control of antibiotic biosynthesis. The first indication that antibiotic formation is not obligatory for spore formation was provided by data on streptomycin production.


Isolation and characterization of human placental chorionic villar extracellular matrix. The cell-free extracellular matrix of human placental chorionic villi has been prepared by a procedure employing extraction of the terminal villar fragments with the detergents Triton X-100 and sodium deoxycholate. The isolated human placental extracellular matrix retains an intact, but collapsed, histoarchitecture, as observed by scanning and transmission electron microscopy. It remains intact, in large part because of the presence of continuous sheets of villar basement membranes and associated interstitial collagen fibers and scattered patches of fibrin. The staining charcteristics and chemical composition of the isolated human placental extracellular matrlix are similar to those reported for basement membranes in several tissues and indicate the presence of collagen-like and glycoprotein components in this preparation. Gel electrophoresis of urea-SDS-mercaptoethanol extracts of the matrix showed that it consists of several polypeptide components of various molecuar weights, some of which are associated into high molecular weight complexes by disulfide bonds.


Comparison of the structures of human fibronectin and plasma cold-insoluble globulin. Human amniotic fluid fibronectin and plasma fibronectin (cold-insoluble globulin) are indistinguishable both immunologically and by amino acid composition. Cyanogen bromide and tryptic peptides also suggest substantial structural homology. However, carbohydrate analysis has demonstrated additional saccharides in fibronectin and an overall increase in carbohydrate content relative to cold-insoluble globulin. Furthermore, limited proteolytic cleavage of the two proteins indicates differences in primary structure or in conformation. Using affinity-purified antibodies to cold-insoluble globulin, a glucosamine-labeled pronase-resistant component, probably proteoglycan, was found to coprecipitate with fibronectin, suggesting an association between these two macromolecules in the connective tissue matrix.


[Atypical adenomatous hyperplasia of the endometrium]. By women in climacterium and postmenopause the authors found 30 adenomatous atypical hyperplasias out of a total of 909 active hyperplasias. They also detected 68 endometrial carcinomas and 65 other changes. Out of 30 patients with adenomatous atypical hyperplasia, 23 had been subjected to curettage earlier but at that time had revealed only milder forms of hyperplasia. Surgery was performed in 21 patients: in 15 patients the diagnosis based on the operative preparation agreed with that based on curettage findings, in 2 patients endometrial carcinoma and in 2 patients glandular hyperplasia were detected, while in 2 patients there was no functional endometrium. Out of 9 patients who for various reasons were not surgically treated and represented an unintentional prospective study, 5 subsequently developed endometrial carcinoma, 3 mild forms of hyperplasia, and 1 atrophia cystica. In the authors' opinion, the histogenesis of endometrial carcinoma in late postmenopause is still an open question.


[Inversion of the uterus during cord traction]. Two cases of the uterine inversion during cord traction is described. Both women were primiparae, aged 26 and 19, respectively. Once there was a shorter umbilical cord and once the adherent placenta. In both cases the manual reposition of the uterus proved successful, but the patients were threatened by the shock, one of them even developed the heart arrest. The authors draw attention to the fact that the cord traction method in the third stage of labour could be exceptionally dangerous, in spite of its other advantages.


[Dehiscence in episiotomies].

[Dehiscence in episiotomies]. Among 3,977 episiotomies (51.80%) in 1977 there were 99 cases (2.48) of dehiscence and 21 of them (0.52%) had to be treated with secondary suture. Dehiscences were found to be more frequent in nulliparae than in multiparae. They were also more frequent in anaemic women. The labour lasted longer in the group of women where dehiscences had to be surgically treated than in the group where they were treated conservatively or where episiotomies were healed per primam. Vaginal examination were more frequent in the group of women where dehiscences in episiotomies were surgically treated than in other groups. A higher precentage of operative deliveries was found in the group of women with dehisced episiotomies. The author believes it possible to reduce the number of dehisced episiotomies using safer surgical methods (interrupted suture) and a better material (dexon) in treating episiotomies in primiparae, in cases of prolonged labour involving a great number of vaginal examinations, and in surgically completed deliveries. In the author's opinion, a strict prevention and treating of anaemia during pregnancy could also reduce the number of dehisced episiotomies.


[Histopathological diagnosis and clinical significance of endometrial hyperplasia]. Histological analysis of 266 hyperplastic endometria obtained by curettage revealed the following forms of hyperplasia: simplex 29.3%, cystic 50%, adenomatous 18.4, and atypical 2.2% (according to the classification accepted by the authors). Mild forms of endometrial hyperplasia (simple and cystic) recede in most cases spontaneously or after therapy and rarely turn into endometrial adenocarcinoma, whereas severe forms of hyperplasia (adenomatous and atypical), unless treated, often turn into endometrial carcinoma. The etiology, some clinical manifestations, and therapy of this condition of the endometrium are reviewed.


[Structure, treatment and success of treatment in invasive carcinomas of the uterine cervix]. At the University Hospital Gynecological Department in Zagreb 1666 cancers of the uterine cervix were treated in the period of 4 years [1969--1972]. Among them were only 309 carcinomas in situ, the remaining 1357 were invasive. The distribution by stages was as follows: IA--75, IB--223, II--326, III--611, IV--122. Such unfavourable groups of cervical cancers proceed from the fact that cancer in situ and the early cancer stage I are often treated in other institutions; only the patients with advanced cancer, a poor general condition and those with various accompanying diseases are concentrated in the above quoted institution where there are technical possibilities and a team of surgeons and radiotherapists well educated in the treatment of cervical cancer. The authors present a five-year survival achieved by surgical, radiological, as well as by a combined method of treatment. The total cure rate for stage I was 87.6%, for stage II 64,4%, for stage III 34.4% and for stage  IV 6.6%.


[The value of preoperative intracavitary radiation in uterine carcinoma]. The analysis comprised 240 uterine carcinomas: 145 carcinomas of the cervix and 95 carcinomas of the corpus uteri. Preoperatively 100 patients--57 with the carcinoma of the cervix and 43 with the carcinoma of the uterine body--were radiated with Co60 intracavitary. In the first stage of the carcinoma of the cervix a five-year survival in primarily operated patients amounted to 74.30% and in the group of preoperatively intracavitary radiated patients to 83%. In patients with the stage I carcinoma of the corpus uteri a five-year survival proved to be 69.57% if primarily operated and 93.75% if preoperatively radiated. Local relapses were recorded in 33 patients surgically treated for carcinoma of the uterine cervix and in 9 patients surgically treated for the carcinoma of the uterine body. In both these localizations the relapses were more frequent in the group primarily operated patients: in patients with the primarily operated carcinoma of the cervix the relapses occurred in 20.69% and in preoperatively radiated patients in 3.4% of cases. The same observations were recorded in the carcinoma of the corpus uteri (11.51% : 6.97%). This means that the relapses were six times as frequent in patients with the primarily operated carcinoma of the uterine cervix and about 1.65 times as frequent in those with the primarily operated carcinoma of the corpus uteri as in intracavitary radiated patients.


[Menstrual cycle after artificial abortion]. In 84 women the establishment of the menstrual cycle after artificial abortion was observed by measuring basal temperature, examining the cervical mucus, and by cytologically analysing smears from the lateral vaginal fornix. Out of 3 women with the cycle up to 24 days before abortion, none had a cycle after abortion lasting less than 25 days. Of 31 women with the cycle exceeding 45 days before abortion, only 25 had such a long cycle after abortion. In the subsequent three cycles the menstruation appeared regularly, at the interval of 25--32 days, in 67 women. Before abortion such a cycle existed in 36 women. In most patients (56) the luteinic phase in the first cycle was shorter, it lasted 10 to 12 days.


[Primary malignant melanoma of the uterine cervix]. A melanoma of the uterine cervix, 4 mm in diameter, considered primary, in a 44-year-old pluripara is described. She was subjected to hysterectomy coupled with adnexectomy and also to BCG immunotherapy. A year following the beginning of the therapy she is without any symptom of the disease. The rarity of the tumour in this localization is pointed out, and a short review is given of the cases reported in the literature, including those of benign melanosis and "blue nevus". The histogenesis and cytologic diagnosis are discussed, as well as therapeutic possibilities. Emphasis is laid on the varying biological behaviour of the tumour which prevents the assessment of the therapy with regard to the possibility of a very late development of metastases.


[Uterine leiomyosarcoma].

[Uterine leiomyosarcoma]. A case of leiomyosarcoma of the uterus in a 46-year-old patient is described. The sarcoma developed within a leiomyoma and reached the weight of 9,000 g. The preoperative diagnosis was uncertain. During the operation the case was suspected of malignancy only histologically proved malignant. The patient died of metastases 70 days after hysterectomy coupled with bilateral adnexectomy, in spite of cytostatic treatment.


[Is it necessary to limit the use of the Copper-T-200 IUD to 3 years?]. The authors put forward their experience in the use of the intrauterine contraceptive device Copper-T-2--in 2026 women over a period of nine semesters. In that period, during a total exposure of 32519 months, 39 normal and 2 extrauterine pregnancies were recorded. What is to be pointed out is that in the first five semesters of the use of the device 35 pregnancies (85.36%) occurred, while in the last two semesters not a single pregnancy was recorded. According to their own indicators, the authors did not find any statistically significant advantages of the Copper-T-200 IUD in the prevention of pregnancy in relation to the behaviour and safety of the inert uterine device of the Beospir type. In view of these data and other positive properties of the Copper-T-200 IUD, they are inclined to think that the inserted Copper-T-200 IUD should be left in situ as long as its presence does not in any way disturb the health and general condition of the woman.


[Uterine perforation in a legal abortion]. In the General Hospital Osijek, from 1974 to 1977, out of 15,716 legal abortions and 2323 abortions completed in the hospital, there were 16 perforations (0.08%) of most serious kind, two of them including injured intestines. The most serious complications followed abortions made in pregnancies exceeding 10 weeks.


[A successfully completed abdominal pregnancy]. The first pregnancy of a 22-year-old woman with somewhat more pronounced and prolonged symptoms of emersis gravidarum was followed up in the outpatient unit and was considered normal. The woman was admitted to the maternity ward 38 days before the term of labour because of painful abdominal cramps, vomiting and weakness. In the course of the first 17 days in hospital, the pregnancy was maintained by the use of spasmolytics but at that time it became clear on the basis of the symptoms, gynecological findings, and the gravidogram, that the case related to abdominal pregnancy. On the 18th day of hospitalization, laparotomy ws performed and a live, female, prematurely born baby, 2,450 g/45 cm, without any deformity, was delivered. The pregnancy was abdominal, with the nidation of the placenta at the right uterine horn. The placenta was completely removed. The girl is now 6 years old and her psychophysical development is normal, corresponding to her age.


[Obstetrical prospects of women with stillborn children]. The analysis of 59 women with still-born children in their case history has shown that in a woman with a still-born child the risk of the second still-born is three times higher and in the woman with two still-borns four times higher than in women having had no still-born child.


[Determination of trace elements in dietary fats and emulsifiers by non-flame atomic absorption spectrometry (AAS). 2. Determination of mercury in dietary fats and emulsifiers]. Of the trace elements, mercury holds an exceptional position as to its chemico-physical and toxic properties. In the light of the special analytical problem, the methods used (cold-steam AAS in combination with the addition method) are discussed. The experimental conditions required for the digestion and the cold-steam AAS of samples of emulsifiers and dietary fats are indicated. The accuracy and the reproducibility of the procedure are dealt with, and the amounts of mercury found in products of the oil and margarine industries are reported.


[Methodological bases of the nutritional-physiological assessment of the per capita consumption of foods. 2. Nutritional-physiological assessment of the per capita consumption]. The different items of the per caput consumption (cf. Part I) are evaluated from the viewpoint of nutritional physiology, and the average energy and nutrient supply of the total population is calculated and compared with the recommended dietary allowances. The nutritional status of the population is globally assessed. A reduction in calorie and fat consumption seems desirable, which will be promoted by a better supply of calorie-reduced products. Further food modifications, e.g., in the form of protein, vitamin and mineral fortifications, are not necessary for the average population.


[Analytical methods for nitrate and nitrite determination in foods. 3. Spectrophotometric determination of nitrate and nitrite using sulphanilic acid/1-naphylamine, and of nitrite using resorcinol/zirconium (IV) oxychloride]. The Nitrate content of foods may be determined by means of azo-dye coupling after reduction of the nitrate with the aid of active cadmium produced in the sample solution. An easy method for determining nitrite consists in the colorimetric estimation of a coloured chelate formed from nitrite, resorcinol and zirconium(IV) oxychloride.


Congenital cerebellar hypoplasia in newborn calves. A sporadic outbreak of congential cerebellar ataxia (CCA) was seen in calves. The abnormality of this disorder of the central nervous system characteristic was cerebellar hypoplasia, which was observed in eight calves. The cerebellum was almost completely absent in some of these calves and approximately one-fifth of the normal size in some others. Six of the eight calves were also affected with hydrocephaly. The significant changes of the cerebellum were complete or partial destruction of the cortex, deficiency of granules and/or Purkinje cells, clumping of the remaining granule cells, and an irregular cavity formation in the terminal portion of the folium. The clinicopathological changes of CCA quite closely resembled those of the bovine viral diarrhea-mucosal disease virus infection.


Mouse strain identification by means of discriminant analysis using mandible measurements. Mouse strains were identified by the aid of discriminant functions obtained from discriminant analysis of values measured at 13 sites of the mandible. They consisted of nine inbred strains of mice, AA, DDD, DDK, DDY, DSD, KK, NC, RR, and SS, and one mutant strain, NC-brp, maintained exactly in the National Institute of Animal Health, Minstry of Agriculture, Forestry and Fisheries. As a result, the probability of erroneous discrimination was 1 head/246 head, or 0.41%, for the males and 2 head/238 head, or 0.84%, for the females. Therefore, almost all the mouse strains were identified correctly. These results seemed to indicate that the strains of mice would be identified more correctly than before, if the present method by the aid of discriminant functions was applied in addition to the methods of identification based on the coat color, biochemical marker-genes, and histocompatibility genes.


[Entrapment neuropathies of the posterior interosseous nerve. Clinical findings and surgical treatment (author's transl)]. Radial nerve compression palsies at the elbow and forearm result in a lower radial nerve palsy whose clinical data are generally a hardly diagnosed dissociated radial palsy, or a rough paresis in the range of epicondylalgia. Apparently spontaneous non traumatic compressions are rare. They are essentially due to lipomas, to fibromas, or sometimes to synovial cysts of the elbow. In the course of rheumatoid arthritis, palsies must be isolated. Besides, there is an actual inflammatory canal syndrome of epicondylalgias range, in which radial nerve paresis must be investigated. Traumatic compressions are essentially due to Mongeggia fractures. Radial nerve injury at the elbow is explained by a real radial canal being, in which the nerve is entrapped and where it is especially fixed on a level of its entering the supinator brevis. Any addition of a pathological element in that area (traumatic or not, tumoral or inflammatory) will be able to involve a compression and a nerve stretching, on a level of the arch of Frohse, essentially. Surgical treatment in non traumatic compressions enables to give the etiological diagnosis and to warrant healing by opening the radial canal excising the added pathological element. To achieve a total surgical operation, in epicondylalgias, the surgeons will have to open this radial canal, as well. Traumatic compressions will be explored only in cases of non spontaneous recovery, after treating the osteoarticular injury.


[Pre-operative non-shaving for neurosurgical operations (author's transl)]. The authors report their pre-operative technique for scalp attendance according to which they operated on more than 1000 cranial neurosurgical patients in three years without the classical complete hair shave. Major psychological advantages are obvious. Principle technical details are: as complete cleaning of scalp-grease as possible by repeated shampoos; in the operating room: shaving only a thin pathway along the skin incision drawn by the surgeon himself, and disinfection with tincture of iodine exclusively. During the same time, they observed a fall to 0,6% of surgical infections needing bone flap removal because of osteitis. Secondary but always transitory partial alopecia has been observed in three patients.


[Gaseous myelography. Accidents and complications. Case reports]. Attention is called to the risks of gas myelography and two cases of complications are described. One of these, observed personally, was fatal and its possible pathogenetic mechanisms are illustrated. Stress is laid on certain rules and precautions that should be respected in radiological and anaesthesiological practice. Insufflation pressure and volumes of injected air deserve particular attention and scrupulous intraoperative control cut of vital parameters must be carried and appropriate attention paid to patient hydration during the postoperative period.


[Ketamine and analgesia during labor].

[Ketamine and analgesia during labor]. Ketamine, owing to the numerous contraindications in pregnant women, gives selective childbirth analgesis. The results obtained in 80 cases of analgesia (60 treated in dilatation period and 20 during expulsion) are reported. The drug's absolute non-toxicity (as observed in quoted experimental studies) together with the labour response and effects on the foetus and mother (tested in most cases with cardiotocography and haemogasanalysis) suggest that ketamine is useful in obstetric analgesia.


[Measurement of compliance and resistance to respiratory airflow in the course of mechanical ventilation]. The importance in resuscitation treatment of the measurement of air ways flow resistance and compliance is stressed. In this regard, attention is paid to the possibility of utilizing the automatic respiratory (recording the mouth pressure curve) as an authentic measuring apparatus for these factors. Research into mechanical models and real patients also points to the possibility (seemingly not reported up to now) of measuring expiratory resistance independently and of highlighting air-trapping phenomena.


[Paraquat poisoning. Clinical and anatomo-pathological aspects]. Two cases of Paraquat poisoning of anticonservative origin are described. A brief account of the chemical composition and mechanism of action of Paraquat is followed by a discussion of the clinical and therapeutic features of the two cases. The anatomopathological findings obtained from lung specimens examined during necropsy are also described. Personal experience and the literature data are cited in an explanation of what is currently regarded as the most effective treatment protocol.


[Problems in emergency surgery: rupture of the spleen in 2 stages. Apropos of 4 cases]. Six cases of delayed rupture of the spleen in two stages are described. One case of occult rupture is also presented. A picture of acute anaemia was observed in the five two-stage cases, whereas the occult rupture was diagnosed as organised splenic haematoma following computerised scintiscanning, arteriography and tomography. Splenectomy was performed in all cases, under emergency conditions in the first five, and of choice in the sixth. No post-operative complications were noted.


[Traumatic lesions of the liver. Our experience of 12 years. Clinical statistics of 118 cases]. 118 cases of traumatic lesions of the liver have been reviewed. The patients were admitted to the First Aid and Emergency Surgery Division of Niguarda General Hospital between 1965 and 1976. The statistico-clinical data were elaborated in accordance with classical subdivisions of each disease form and compared and discussed, as far as possible, with similar data provided by the recent literature. Stress is laid on the increase in the number and gravity of cases in recent years, the prevalent localization of lesions in the right lobe, the importance of trauma pathogenesis for diagnostic and therapeutic purposes, and diagnostic difficulties. The importance of peritoneal probing and dialysis and of the examination for bile salts in the urine are underlined. As for treatment, the various surgical techniques are mentioned and discussed in relation to the characteristics of the traumatic lesion; the commonest technique was simple suture of the break in the liver parenchyma. Mortality was 33.05%. The cause of death in the 39 cases is mentioned.


The effect of Schistosoma mansoni infection, and of oxamniquine, a new antischistosomal drug on some vitamins in the livers of hamsters. The hepatic levels of thiamine, pantothenic acid and niacin in hamsters infected with S. mansoni were depressed, while the levels of riboflavin and pyridoxine remained unchanged. A single dose of oxamniquine, 10-50 mg/kg, brought the levels of thiamine, pantothenic acid and niacin to values not significantly different from those in non-infected controls, but lowered the concentrations of riboflavin and pyridoxine in infected hamsters.


1,5-benzodiazepine derivatives with expected psychotropic activity. By sulfuration of 4-methyl-1H-tetrahydro-1,5-benzodiazepinone-2 (1) its 2-thione 2 was synthesized. From this compound 2-hydrazone 3 and s-triazole derivatives 4 and 5 were obtained. Screening revealed that only compound 2 showed strong inhibitory activity in the spontaneous motility test, weak synergism with hexobarbital, weak antinflammatory activity in the carrageenin test and strong analgesic activity in the hot plate test.


Biotransformation of some pyrazole derivatives to glutathione conjugates in rat liver subcellular fractions. During incubation of antipyrine, but not amidopyrine, 4-aminoantipyrine and 4-leucylaminoantipyrine, with rat liver microsomaland cytosol fractions in the presence of NADPH-generating system a reactive metabolite, which binds with glutathione is formed. The chemical nature of the metabolically activated intermediate is not known; it is suggested that the putative reactive metabolite responsible for this binding could be an epoxide.


Synthesis of alpha-[7-methyl-9-methoxy-5-oxo-furo-[3,2-g] [1]-benzopyranoxy-4]-butyric and valeric acids and their aminoesters. In the reaction of 4-desmethylkhelline with ethyl alpha-bromobutyrate or alpha-bromovalerate we obtained alpha-[7-methyl-9-methoxy-5-oxo-furo[3,2-g] [1] benzopyranoxy-4]-butyric 2 and valeric 3 acids and later their dialkylaminoethylesters as hydrochlorides (2b--2, 3b--3e). Compounds 2c, 2e, 2f (Table 1) and 3e (Table 2) show a weak hypotensic activity. Moreover compound 2f possesses an antriarrhythmic activity.


Testing of chemicals for carcinogenic activities and some problems related to the assessment of carcinogenic risks to men. It is recognized that many human cancers are influenced by environmental factors. Therefore, testing of chemicals for carcinogenic activities represents an important part of comprehensive toxicological examinations. Procedures to be employed in bioassays for carcinogenicity will be discussed. Short-term tests should be utilized as screening methods to select suspected chemicals which should or must be further tested in long-term animal experiments. Animal tests can predict carcinogenicity in man. Any substance which is shown conclusively to cause tumors in animals should be considered carcinogenic and therefore a potential hazard for man, but tests on experimental animals cannot provide irrefutable proof of the safety or carcinogenicity of a substance for the human species. Therefore, some of the problems related to the assessment of carcinogenic risks by chemicals will be discussed.


In vivo and in vitro inhibition of 3-methylcholanthrene-induced aryl hydrocarbon hydroxylase activity in rat liver by actinomycin D and 7,8-benzoflavone. Using the very well investigated and sensitive microsomal monooxynogenase aryl hydrocarbon hydrolase (AHH), we investigated the dose-response relations between an inducer, 3-methylcholanthrene (3-MC), and an inhibitor of transcription, actinomycin D (ACT D), in 10 days old rats. An optimum pretreatment schedule proved to be a single dose of 1 to 40 mg/kg 3-MC ip combined with two administrations of 200 to 600 microgram/kg ACT D within 16 hr. With increasing doses of ACT D the inhibition of 3-MC-mediated AHH induction increased up to 88%. With 7,8-benzoflavone (ANF) as a relatively specific in vitro inhibitor of the cytochrome P-448 species no distinct influence on the constitutive AHH activity could be observed up to the 30th days of age. In 60 and 200 days old rats the inhibition reached a significant level of about 50%. After 3-MC induction a nearly uniform ANF-mediated inhibition by about 50% of the hepactic AHH activity was observed: in older animals the percentage became slightly higher. The investigation appears to confirm the change in cytochrome pattern,--especially as for the participation of cytochrome P-448,--according to the age and induction stimulus by 3-MC.


Neoplastic transformation in vitro.

Neoplastic transformation in vitro. Oncogenic transformation of cultured cells is considered to be analogous to the induction of tumors in animals. Two properties of transformed cells: the capacity to grow in soft agar and morphological alterations were used as a basis for quantitative studies on the transforming properties of chemicals. The majority of experiments on chemical carcinogenesis were so far performed on murine, hamster and rat cell systems. The most pertinent questions to be resolved now are connected with malignant transformation of human cells.


Mutagenic activity of isoniazid in the mouse. Isoniazid was tested for genetic activity in the mammalian spot test by treating in utero mouse embryos, derived from the crosses C57 B1/6J X T-stock and NMRI X DBA/2, heterozygous for various loci affecting coat color. Induction of genetic changes is seen by expression of recessive alleles in colored spots within the fur of the adult animal in a non-agouti background. Injecting mothers with isoniazid (100 mg/kg ip), an expression of recessive loci was found in 7.41% of the F1 animals in the cross C57 B1/6J X T-stock, while in the NMRI X DBA/2 cross 2.92% animals with recessive spots were detected. The control frequencies were respectively 0 and 0.78% animals with recessive spots. The positive control substance, ethyl methanesulfonate (100 mg/kg ip), yielded 5.97% and 4.71% animals carrying a recessive spot in the fur, respectively. These studies clearly demonstrate for the first time the induction of genetic damage other than cytological damage in somatic cells of mice by isoniazid.


[Measurement of cardiac output by thermodilution with a diode as a temperature sensor]. An area integrator for the thermodilution curve in cardiac output measurement is described. A new temperature sensor is used, a diode with some advantages over the thermistor normally used. The main advantages are: easy calibration and replacement, and broad range of linearity. The cardiac output values obtained in dog with the integrator follow a linear relationship with those of the flowmeter. In simultaneous measurements the correlation is R = 0.96. Using a diode as temperature sensor a modification of the Steward Hamilton equation (used for thermistor) is necessary. With this new equation a monogram is performed to calculate the cardiac output from the area given by the numerical integrator.


Methadone exposure in utero: developmental status at one and two years of age. The developmental status of infants exposed to methadone in utero and non-drug exposed infants was assessed at one and two years of age. Fifty-three 12-month old infants (26 drug exposed and 27 controls) and forty-one 24-month old infants (17 drug exposed and 24 controls) were assessed with the Bayley Scale of Mental Development and a neurological exam. Neurologicals for all infants were normal. At twelve months of age the Mental Developmental Index (MDI) was within the normal range for both groups although the scores for the drug exposed group were significantly lower. There was no difference in the MDI between Family Center and control infants at 24-months of age. Differences were found, however, in the failure rates of specific items. The implications of these findings for delineating the effects of methadone exposure in utero are discussed.


Protracted behavioral effects of neonatal morphine-pellet implantation in male rats. Male rat pups (Charles Rivers CD albino strain) were implanted subcutaneously with a morphine (M), placebo (P), or no pellet (NP) on Day 5 or 11 of postnatal life. Body weights of both Day 5 and 11 drug-treated males were depressed below those of controls through Day 63 (p < 0.01). On Day 72, compared to P and NP controls, M-treated males showed impaired learning in a Lashley III maze. Day 5, but not Day 11 drug-treated animals showed greater activity-wheel behavior (p < 0.01) than controls on Days 85--86, and less suppression (p < 0.025) of a conditioned emotional response on Day 145. On Day 150, Day 5 M-treated animals showed a reduced steroid response (p < 0.05) to a challenge dose of M (18 mg/kg), suggesting protracted tolerance to the pituitary-adrenal activating effects of M. Members of each treatment group were successfully bred with females on Day 90; no group differences were found in litter size, sex ratios, or birth weights of the offspring. The results of this study indicate that early exposure to M causes long-term impairment of several behaviors in male rats.


Children of methadone-treated women at five years of age. Infants of methadone-treated and matched non-drug dependent women were found to differ in psychomotor development at one year of age. A follow-up of these groups at age five revealed no differences in cognitive or perceptual performance as assessed by the McCarthy Scales, although both groups performed below normative expectations. Groups did not differ in observed characteristics of home environments or patterns of child or caregiver behavior in a playroom observation, although children who had been transplacentally exposed to narcotics behaved less maturely and were more inappropriately active during psychological testing.


Offspring open field performance following maternal lead exposure: a question of dosage and nutritional status. Although a number of experiments has revealed offspring hyperactivity following maternal lead (Pb) exposure, a consistent correlate has been reduced pup size. The present study was designed to measure exploratory behavior employing a range of Pb dosages that allowed for the comparison between Pb and control offspring both in the presence and the absence of weight differences. Female rats were exposed to one of four dosages (0, 400, 750 or 1000 mg/kg) of Pb acetate from 21--90 days of age, mated and then continued on treatment throughout gestation and nursing. Treatment was administered via a restricted water schedule. Open field testing began on Day 22 with the pups receiving 3 min trials for 10 consecutive nights. At 120 days of age, all pups were retested. Analysis indicated that only in the presence of reduced birth and/or weaning weights (Groups 750 and 1000) did offspring exhibit exploratory patterns that were significantly different from controls. These differences were absent at retest.