An alternative approach to lesions in the proximal segments of the brachiocephalic arterial system. Tolerance of a cerebral hemisphere to permanent interruption of the ipsilateral carotid artery or to prolonged operative clamping of this vessel, can be determined preoperatively by a noninvasive technique combining the use of the ocular pneumoplethysmograph with compression of the proximal part of the common carotid artery. This technique is essential for the management of proximal lesions of the brachiocephalic arterial system to avoid the use of bypass grafts and to permit a supraclavicular approach rather than thoracotomy or a median plane sternotomy.


A study of the critical bacterial inoculum to cause a stimulus to wound healing. Results of previous work have shown that wounds infected with gram-negative bacteria may be stronger than uninfected wounds. The inoculum in these studies was about 2 X 10(7) organisms. Laparotomy wounds were swabbed with inocula of from 10(2) to 10(9) organisms, Escherichia coli. Only with inocula of 10(6) or greater were all parts of all wounds infected by gross inspection. All wounds inoculated with 10(7) organisms, or more, were significantly stronger than the wounds of the control group on the 14th day. A smaller inoculum--10(3) to 10(6)--also resulted in stronger wounds, but not consistently so.


Evaluation of the painful hip by aspiration and arthrography. The preoperative or postoperative painful hip can present a difficult diagnostic problem. In a series of 46 aspirations on such hips, one instance of Staphylococcus aureus, three instances of Staphylococcus albus, one instance of Escherichia coli and one instance of tuberculous infections were diagnosed. In addition, in a series of 22 fluoroscopically controlled arthrograms performed on patients with painful total hip replacements, six instances of loose acetabular components and one instance of a broken femoral stem were found.


A technique for closure of the lesser curvature of the stomach used in the von Eiselberg-Hofmeister reconstruction after subtotal gastrectomy. A technique for closing the lesser curvature of the stomach after subtotal gastrectomy has been used in 847 subtotal gastrectomies. In this group, one patient had transient postoperative bleeding and none had anastomotic leakage. The technique is recommended as a simple method of obtaining a secure and hemostatic closure which can be accomplished rapidly and which does not require the use of special instruments or material.


Liver replacement for alpha1-antitrypsin deficiency. A 16-year-old girl with advanced cirrhosis and severe alpha 1-antitrypsin deficiency of the homozygous Pi ZZ phenotype was treated by orthotopic liver transplantation. After replacement of the liver with a homograft from a donor with the normal Pi MM phenotype, the alpha 1-antitrypsin concentration in the recipient's serum rose to normal; it had the Pi MM phenotype. Two and a third years later, chronic rejection necessitated retransplantation. Insertion of a homograft from a heterozygous Pi MZ donor was followed by the identification of that phenotype in the recipient's serum. Neither liver graft developed the alpha 1-antitrypsin glycoprotein deposits seen with the deficiency state. These observations confirm that this hepatic-based inborn error of metabolism is metabolically cured by liver replacement.


Tissue culture isolation and preservation of human cadaveric pancreatic islets. Six specimens of human cadaveric pancreas were collagenase-dispersed and placed in tissue culture. Media were changed at 2 day intervals and assayed for insulin and amylase. Experiments were terminated after 8 days, and phase-contrast and light microscopy were performed on cultured tissue. Insulin content in media remained high for 6 days in five cases and for 8 days in four experiments; this correlated directly with morphologic viability of cultured tissue. Media amylase fell to zero after 4 days in four cases and after 6 days in two cases. These data support the concept that tissue culture may be an efficient method for (1) islet cell purification, since acinar tissue and amylase activity disappear, and (2) islet preservation.


Long-term results with forty-five living related renal allograft recipients genotypically identical for HLA. During the past decade 45 living related renal allografts have been performed between siblings genotypically identical for HLA. In each case all available family members were serotyped and haplotype analysis was performed. Immunosuppressive therapy consisted of standard azathioprine and prednisone regimens. Only one instance of HLA-D incompatibility was documented. HLA-A, -B haplotypes were identical in each case. Histopathological evaluation by light, immunofluorescence, and electron microscopy was completed. Four patients experienced acute cellular rejection with mild long-term impaired renal function. Five patients had acute cellular rejection but subsequently experienced long-term normal renal function. Twenty-three patients had little or no rejection documented and half of these patients are being maintained without steroid therapy. Five patients had histologically proven acute humoral rejection and, of these, three subsequently lost their allografts whereas two regained relatively normal renal function. Recurrent glomerulonephritis was documented in six cases. One was lobular, one crescentic, and one dense-deposit membranoproliferative glomerulonephritis. Three cases of IgA nephropathy were diagnosed. In each case the recurrent glomerulonephritis reflected the same histopathology and clinical course as the disease realized in the host kidneys. Eighty-seven percent of the 40 surviving patients have been rehabilitated completely and are fully employed.


Harvey Cushing: "From tallow dip to television". Harvey Cushing was not only a leading founder of neurosurgery, but his work in general surgery provoked research which advanced medical knowledge, and he made substantial contributions to medical education and general literature. He discovered (with L.E. Livinggood) that the stomach and small intestine could be rendered sterile by fasting before operations; he successfully sutured the cervical thoracic duct without subsequent leakage; he suggested, after attempted repair of chronic valvular lesions in the dog, the possibility of surgery on cardiac valves in man; he demonstrated the relation of intracranial pressure to blood pressure; he devised one of the first charts for recording pulse and respiration and introduced routine blood pressure determinations during operation; and he stimulated continuing research by internists and endocrinologists through his work on the pituitary body and its disorders-work which was crowned by his discovery of pituitary basophilism. His unique course in operative surgery for medical students at the Johns Hopkins was adopted by other medical schools and he advanced other provocative theories concerning the organization and content of the medical curriculum. He provided elective clinics at Harvard Medical School for students and established postgraduate fellowships at the Hopkins, Harvard, and Yale schools of medicine. Cushing brought distinction upon himself and the medical profession through his books and essays of high literary quality and originality, most notably his biography of Sir William Osler, which was awarded a Pulitzer Prize in 1926.


Cholinomimetic teratogens. V. The effect of oximes and related cholinesterase reactivators. Pyridine-2-aldoxime methiodide and pyridine-2-aldoxime methyl methane sulfonate (P2S) used as supplements to carbachol or neostigmine, greatly lowered the incidence of chicken embryos of vertebral defects and muscular hypoplasia. With 4-pyridine aldoxime the effect of the teratogens was less reduced. Supplementation of carbachol or neostigmine with either ambenonium or toxogonin lessened the occurrence of muscular hypoplasia, but did little, if anything, to prevent malformation of the neck vertebrae. In tests with physostigmine P2S as supplement reduced or prevented cervical defects, but failed to protect the nicotinamide-sensitive parts of the embryo.


Time course of bronchoconstrictive response in asthmatic subjects to reduced temperature. Thirteen young adults with bronchial asthma and a like number of controls were subjected for 45 minutes to a temperature of 2 degrees C after leaving a temperature of 24 degrees C to which they subsequently returned. Pre-exposure examination included VC, FEV1, MMEF, FEV1/VC%, and urinary catecholamines. The pulmonary measurements were repeated at 15, 80, and 200 minutes after exposure. Catecholamines were measured from a second urine sample, the collection of which corresponded to the period during and after the stress. Controls showed no significant pulmonary changes throughout the time of study, but 15 minutes after exposure the asthmatic subjects showed a significant mean decrease of all pulmonary measurements from pre-exposure values. The controls showed a significant mean increase in urinary catecholamines after the stress, whereas those with asthma showed no significant increase.


Surgery of isolated patent ductus arteriosus: a new technique of suture and division. Since mid-1973 29 cases of isolated patent ductus arteriosus were treated in the Hong Kong University surgical unit with a new technique of suture and division. This technique has almost eliminated the problem of intraoperative haemorrhage and its consequences.


Morphology and pathogenesis of desquamative interstitial pneumonitis. Thirty human lung biopsy specimens have been diagnoses as desquamative interstitial pneumonitis. Six cases had intraalveolar lesions, believed to be early, while 20 had advanced disease characterised by intraalveolar cellular clumps, alveolar wall fibrosis, distortion, and loss of pulmonary parenchyma. Electron microscopy, high resolution light microscopy, and cytological examination have shown that the characteristic clumps in the alveolar air spaces are formed predominantly by enlarged and aggregated macrophages. Lymphocytes and eosinophils are also present in the intraalveolar clumps and in alveolar walls. Inflammation and immunological mechanisms are suggested as causes of the cellular clumping. Interstitial pneumonitis, alveolar wall fibrosis, changes in the alveolar epithelium, and loss of lung parenchyma are believed to be secondary events.


A comparison of coagulation factor replacement with and without prednisolone in the treatment of haematuria in haemophilia and Christmas disease. A double-blind controlled study was carried out to investigate the effectiveness of treatment with factor VIII or factor IX concentrate and a reducing dose of prednisolone in contolling haematuria in patients with haemophilia and Christmas disease.  41 episodes of haematuria were studied in 30 different patients. No appreciable benefit was observed in the treated, as compared with the control group and this is at variance with the results of the few studies reported elsewhere.


Heat illness. I. Epidemiology.

Heat illness. I. Epidemiology. Reliable information on the epidemiology of heat illness has come, until recently, mainly from the armed forces and, to a lesser extent, from some industries and civil communities. Data from the records of the British Army, Royal Navy, Royal Air Force, Indian Armed Forces, U.S. Army and forces engaged in the Arab-Israeli wars, from the South African gold mining corporations and Persian Gulf oil tankers, and from civilian communities, mainly in the U.S.A., are reviewed and discussed with particular reference to the classification of heat illness and definition of the terms used, and the effects on acclimatized and non-acclimatized personnel and on other sections of the civilian communities most at risk, i.e. the old and very young. This section concludes with an outline of the classification of acute heat illnesses from 1899 to the eighth revision of the WHO International Classification of Diseases in 1967.


Heat illness. II. Pathogenesis.

Heat illness. II. Pathogenesis. The effects of elevated temperatures and the time-temperature combinations for irreversible damage are outlined. Coagulation abnormalities and the effects on the kidney, liver, heart, brain and serum enzymes, the role of electrolytes and water, including salt deficiency and the controversial question of salt supplements, potassium deficiency, changes in other electrolytes and sweat solutes, and rhabdomyolysis (including a discussion of experimental work on dogs) are reviewed. The section ends with a discussion of the effects of drugs and an account of a recent fatal case of heat stroke which may have been triggered by chlorpromazine therapy.


Heat illness. III. Acclimatization.

Heat illness. III. Acclimatization. In this third paper on heat illness, the position of acclimatization in prevention of heat illness is reviewed. Both short and long-term acclimatization are considered, the former in more detail with discussion of present knowledge of the differences arising from artificial and natural acclimatization, the effects of training, water intake and increasing salt intake, and climatic chamber and vapour-barrier suit acclimatization. The possibility of the development of a safe drug to accelerate acclimatization is considered remote. The effects of age and acclimatization in the healthy and unhealthy elderly and the very young are reviewed briefly as is also the possibility that air conditioning may have an adverse effect on acclimatization.


A strain of Plasmodium vivax characterized by prolonged incubation: the effect of numbers of sporozoites on the length of the prepatent period. The North Korean strain of Plasmodium vivax was characterized by its extraordinarily prolonged incubation period in certain circumstances. It was clearly demonstrated by quantitative observations that the phenomenon may be elicited by the inoculation of small numbers of sporozoites. After the intradermal inoculation of 10 or 100 sporozoites, the incubation period was delayed for periods varying between 262 and 628 days; after u,000 sporozoites, with one exception, the same delay occurred; after 100,000 sporozoites, the incubation period was always of normal duration (13--16 days). Two laboratory-acquired infections in workers who had taken a prophylactic drug showed incubation periods of 315 and 329 days, respectively. Various theories for the phenomenon of prolonged prepatent periods are examined, and the most satisfactory one is based on the presumed existence of two populations of sporozoites in P. vivax. In temperate strains, sporozoites requiring long prepatent periods (LPP) for development are present in great excess over a much smaller proportion of sporozoites characterized by short prepatent periods (SPP); thus small doses will elicit the phenomenon, though doses of over 1,000 sporozoites will mask the effect as the few SPP sporozoites will produce an infection with a normal (i.e. short) prepatent period. In tropical strains, the relative proportions are different, perhaps in equal numbers, and even in small doses some SPP sporozoites will be present and normal prepatent periods should ensure whatever the dosage."


Prepatent periods of a tropical strain of Plasmodium vivax after inoculations of tenfold dilutions of sporozoites. Eleven patients requiring malaria therapy were inoculated intradermally with graded doses of sporozoites of the Chesson strain of Plasmodium vivax. Estimated doses of 10 sporozoites were given to four patients, of 100 to three patients, of 1,000 to two patients, and of 10,000 to two patients. Parasitaemia was detected in all patients 12 to 17 days after inoculation; fever began on the 14th to 19th days. The results of the trials are compared with earlier work on a temperate strain of P. vivax in which patients given small doses of sporozoites exhibited long prepatent periods of 257 days or more. It is concluded that the differences in the two strains can be explained by the assumption that, in varying proportions, all strains of P. vivax produce two types of sporozoites, one eliciting short prepatent periods (Type I), and the other lying dormant or developing slowly to give rise to long prepatent periods (Type II). The latter type greatly predominates in temperate strains, but not in tropical strains; at high dilutions, therefore, pure suspensions of Type II sporozoites of temperate strains can be prepared. It is thought that relapses of P. vivax are in reality a dalyed parasitaemia arising from Type II sporozoites.


Urinary infection in kidney transplantation. Urinary tract infection is the most frequent complication following renal transplantation and is important in the etiology of post-transplantation sepsis. The 87 renal homografts done in 1974 at The New York Hospital-Cornell Medical Center were reviewed retrospectively, with at least one year follow-up, in all cases, with particular attention to factors relating urinary tract infection to ultimate success or failure of the renal graft. The over-all incidence of urinary tract infection was 61%. Early infection was associated with a particularly poor prognosis for graft survival. Most patients with urinary infections after successful transplantation experience a combination of both early and late infections. Anatomic factors constitute a remediable cause of urinary infections after transplantation and should be searched for in cases of multiple, recurrent infections, de novo hypertension, or deterioration of previously stable graft function. There were significant differences in the bacteriologic spectrum of urinary tract infections associated with successful transplants as opposed to unsuccessful transplants.


Surgical treatment of male genital lymphedema. The etiologic classification and history of the surgical treatment of male genital lymphedema are presented. Two case reports and their results illustrate the surgical technique of skin flaps and split thickness skin grafting.


Avian botulism and the high prevalence of Clostridium botulinum in the Norflok Broads. An account is given of a severe outbreak of type C botulism in waterfowl that occurred on the Norfolk Broads during the exceptionally warm summer of 1975. Forty-five mud samples were collected from 22 well distributed aquatic sites representing a considerable proportion of the total number of Broads. All samples except one (ie, 97-8 per cent) were shown to contain Clostridium botulinum and 58 per cent contained more than one type of the organism. Types B, C and E were demonstrated in 62-2 per cent, 51-1 per cent and 60 per cent of samples respectively. Recent surveys, made by identical methods, of aquatic environments in the London area and the Camargue (France) showed prevalences of Cl botulinum of 72-5 per cent and 4-5 per cent respectively. It seems likely that the Norfolk Broads will continue to present a risk to waterfowl from botulism in future hot summers.


Immunological injury in "shipping fever" pneumonia of cattle. Electron opaque deposits were found on the alveolar capillary walls, luminia of alveolar capillaries, subendothelium and interstitium of four out of 10 Holstein dairy cattle with past shipping histories. The deposits were positive for anti-IgG bovine immunoglobulin by fluorescent antibody technique. Evidence is presented that antigen antibody complexes may play an important role in bovine respiratory diseases.


Volume limitations of plasmapheresis.

Volume limitations of plasmapheresis. The published specifications of the acceptable limits of the maximum plasma volume to be "harvested" by plasmapheresis from one individual per year vary from 10-15 liters in Europe to 50-60 liters in the United States. To answer the question which of these widely diverging precepts is appropriate, the effects of plasmapheresis on serum protein levels and their relationship to albumin metabolism, the accepted safeguards for the donation of whole blood, and the disease known as the nephrotic syndrome are considered. A living person who cosents to his bodily integrity being violated for the benefit of others must be protected not only against the generation of manifest illness by such violation, but also against any prolonged deviation from the normal state of his body. It is concluded that plasmapheresis donors should not deliver more than 10 to 15 liters of plasma per year, as now recommended by European authorities. Not more than 500 ml of plasma should be withdrawn per session, and the interval between two such sessions should not be less than 2 weeks.


Increase in strength of red cell Bga antigen following infectious mononucleosis. Following an attack of infectious mononucleosis, the red cells of HLA B7 patients may show a greatly increased reactivity with anti-Bga antibodies. This occurs from about the 3rd week of the disease, the reactivity then slowly decreasing over a period of months or years. Both specific and nonspecific reactions to other HLA antisera may also occur. Five patients were followed in detail and the reason for the increase in antigen strength was investigated without a conclusive result.


[Tubular involvement in glomerular diseases of the kidney (author's transl)]. An attempt is made in this study to provide an answer to the question whether glomerular diseases are accompanied by tubular disorders. The urinary lysozyme activity was determined by means of a turbidimetric assay method in 10 healthy children as controls, 10 patients with glomerulonephritis, 8 patients with Alport's syndrome (hereditary glomerulonephritis with deafness) and 12 children with idiopathic nephrotic syndrome. In most of the cases a significant increase in urinary lysozyme excretion, indicative of tubular damage, was found and this finding correlates well with the tubular morphology of the patients.


Fluoro-immuno-cytoadherence (FICA): A new method for the identification and enumeration of antigen-binding cells. Antigen-coated particles of cross-linked dextran may be used for affinity chromatography of antibodies and for the fractionation of lymphoid cells with appropriate surface receptors. Furthermore, such particles serve as convenient substrates for quantitative immunofluorescence tests. The fluoro-immuno-cyto-adherence (FICA) is a simple technique which combines affinity chromatography and immunofluorescence, provides durable antigen-coated substrates and allows the identification, enumeration and characterization of lymphoid cells capable of binding an antigen, covalently linked via a spacer onto the surface of dextran beads. In the present study chicken thyroglobulin (TG) or bovine serum albumin (BSA) were coupled onto fluorescein and rhodamin-labelled or unlabelled Sephadex G-25 beads by means of spacer molecules. The specificity and degree of antigen-coating were controlled by indirect immunoflourescence. For the study of antigen-binding cells the different antigen-coated beads were mixed with suspensions of peripheral blood lymphoid cells from Obese strain (OS) chickens with spontaneous hereditary autoimmune thyroiditis, or with cells from BSA-immunized or unimmunized normal White Leghron chickens. Specific adherence of OS lymphocytes to TG-coated beads and of lymphocytes from BSA-immunized chickens to BSA-beads was found. The test and control preparations are observed simultaneously under the fluorescence microscope where the distinction of beads coated with different antigens can be made on the basis of the color of their fluorescence. Results obtained with the FICA technique are in good agreement with those of conventional rosette tests.


Changes in peripheral blood lymphocyte nucleoli in a follow-up of renal allograft recipients. Correlation with the response to PHA. Changes in the morphology of nucleoli in peripheral blood lymphocytes and the reactivity to PHA were used in the immunological follow-up of renal allograft recipients. The increased numbers of "active" lymphocytes containing compact nucleoli or nucleoli with nucleolonemas, characteristic for cells actively synthesizing RNA, preceded 21 out of 28 rejection episodes. The results of the nucleolar test mathematically correlated with the results of the test of lymphocyte transformation to PHA. The described testing of lymphocyte activation according to the morphology of the nucleoli may serve as a rapid and economical method for the prediction of impending allograft rejection crises in the clinic.


Rosette formation of pig peripheral blood lymphocytes with sheep red blood cells. Peripheral blood lymphocytes of normal young pigs formed spontaneous and EAC rosettes with sheep red blood cells. Pretreatment of the SRBC with a sulphydryl reagent increased the percentage of spontaneous rosettes and the number of SRBC bound by the lymphocytes. The influence of an incubation period prior to centrifugation and the duration and temperature of the following incubation were tested for spontaneous and EAC rosettes. The importance is stressed to define the number of bound SRBC to call a lymphocyte a "rosette-forming cell". Rosette formation is interpreted as a quantitative rather than a qualitative marker.


[Arthordesis of foot joints with the Cloward-technique (author's transl)]. The Cloward instruments can be used not only for the interbody cervical fusion, but also for the arthrodesis of the talo-crural and talo-navicular joints. By exact pinning with autolog spongiosa pins while the joints are distracted further internal is not necessary. In contrast to other methods the arthrodesis of the talo-crural joint is not accompanied by a shortening of the leg. Technical details of the method are described and the first results of 15 cases are reported.


[Spondylitis caused by Salmonella typhimurium (author's transl)]. Described is a case of spondylitis caused by Salmonella typhimurium. According to literature osteomyelitis and spondylitis are rare as local manifestation of a salmonella infection. Spondylitis caused by Salmonella typhimurium, the most common species, is almost unknown. The problems in diagnosis and therapy are discussed.


[Congenital rocker-bottom foot (author's transl)]. A report was made of 19 patients with rocker-bottom foot operated on during the last 10 years in the Orthopedic Hospital and Out-Patient Clinic of the University of Heidelberg. No additional bone anomalies were present in 6 cases. The remaining malformations occurred together with multiple contractures and in the context of spina bifida cystica. The various malformations of the foot were divided into three groups. This study is particularly concerned with therapy for rocker-bottom foot. Conservative measures are not suitable for types I and Ia while conservative therapy should be attempted in type II. The surgical procedure involves 4 steps: development of the calcancal part of the foot, repositioning of the navicular bone, new adjustment of the ankle and various stabilization measures including the Grice operation and transposition of various tendons. The surgical procedure and the results were discussed.


The management of gonorrhea in an emergency room. This study reviews the experience with gonorrhea and "pelvic inflammatory disease" in an emergency room of a university hospital. In spite of the large volume of critically ill patients seen in the emergency room, proper diagnostic methods and appropriate treatment for gonococcal disease were used by these physicians in over 90% of the cases. However, performance of serologic tests for detection of latent syphilis and the reporting of the disease to the Health Department were often overlooked. Two other problems in the management of these diseases were identified. One was the discovery of a low yield of organisms by culture, and the other was the failure of most patients to return for followup. This study indicates that periodic retrospective analysis is a useful method of ascertaining the effectiveness of diagnosis and management of gonococcal infections in a setting not specifically oriented to venereal disease. This analysis indicates that better mechanisms can be instituted in treating these infections to assure high quality care.


[Amniofetography in antenatal diagnosis of fetal abnormalities]. The authors report the application of the amniofetography in the field of the antenatal diagnostic of fetale deformities. All pregnant women were investigated by Ultrasonic-B-scan. In cases of unambiguous hydramnios and in cases of pathological findings or findings which are not clear in Ultrasonic-B-scan an amniofetography was made. This method was carried out in 14 patients between the 28th and 37th week of pregnancy. It was found changes in 8 cases which in control of pregnancy and delivery were important.


[Comparative studies on the antimicrobial activity of S-alkylthiuroniumhalides (author's transl)]. S-alkylthiuroniumhalides according to formula I (table 1) have been tested under standardized conditions with respect to their antimicrobial activity against bacteria, yeasts and fungi. In table 2 the bacteriostatic and fungistatic efficiency and in table 3 the microbicidal efficiency of 8 different S-alkylthiuronium compounds are compared with the efficiency of N,N-dimethyl-coconutoilalkyl-benzyl-ammonium-chloride. The germ inhibitory effect of the quaternary ammonium compound has been superior to the S-alkylthiuronium salts in almost all respects. The germicidal effect of the S-alkylthiuroniumhalides depends on the alkyl chain length bound to the S-atom and gets the optimum with S-dodecylthiuronium-chloride. Already a 0.0005% concentration is sufficient to kill all test germs within 30 minutes. S-dodecylthiuroniumchloride proved to be just as effective as the known well effective quaternary ammonium compounds. It seems to be possible to increase the microbicidal efficiency by additional alkylating - specially methylating - of both nitrogen atoms.


[Drug resistance of phage types of Salmonella typhimurium (author's transl)]. Antimicrobial susceptibility testing (disk diffusion test) and phage typing (method according to Anderson, performed by Prof. Brandis, Bonn) of 703 strains of Salmonella typhimurium from humans, isolated in Essen and surrounding during 1972 to 1975, was performed to dertermine whether characteristic patterns of drug resistance were associated with a single phage type or not. The most frequently isolated phage types are phage type 17 (12.2%), 12 (10.1%), 49 (8.1%), 15a (5.7%), 2 (3,3%) and the untypable phage type (46.7%). Resistance to tetracycline (45%) was most common, followed by resistance to sulfanilamide (19%), ampicillin (9%), and chloramphenicol (7%). Resistance to other antimicrobial agents (trimethoprim/sulfamethoxazol, gentamicin, colistin) was quite rare. Antibiograms of different phage types were found to be different, not only as far as the ratio of sensitive to resistant strains is concerned, but also for the ratio single-resistant to multiple-resistant strains. These differences were found to be statistically significant (chi-square-test, table 2). Comparison of antimicrobial resistance to tetracycline showed, that the portion of resistant strains was about 70% for the untypable phage types, 40% for phage type 17 and 7% for phage type 12. Among isolates of the phage type 49 multiple resistance was most common. The combination of resistance determinants is specified in figure 3. A possible interrelation between resistance pattern and the presence of R-plasmids in isolated strains is discussed.


[Epidemiologic relationship of infections with Salmonella typhimurium in Switzerland studied by phage typing (author's transl)]. In the area, controlled by the Institute of Microbiology of St. Gall, 262 S. typhi murium strains could be isolated during 1973. By means of phage typing, according to GUINEE, 20 different phage types as well as 6 additional atypically reacting strains, with characteristic atypical pattern, were recognized. The phage type 650 was most frequently encountered (37.0%) folowed by types 61 (20.2%) and 505 (10.3%). An intensive change in phage types was noted among 114 cases, observed over 7 months, in the region of Wil SG. In the beginning, 5 different phage types were determined, but in the following 2 months, they were replaced by the type 650, and, finally, by the type 61. Phage typing enabled the understanding of epidemiologic relationship of two outbreaks occurring in Kirchberg (type 650) and Bütschwil (type 61) by consumption of infected slaughtered beef. Also, an outbreak of the infection in Wil, transmitted by an infected butcher, could be cleared. Testing of the resistance against tetracycline, chloramphenicol, ampicillin and trimethoprim-sulphamethoxazol showed that 80.1% of the strains were sensitive and 18.3% were resistent against tetracycline; some phage types were sensitive (2, 3, 4, 61 etc.), predominantly sensitive (650) or resistent (330, 450, 504, 505 ARS-12). Four strains were resistent against one or more chemotherapeutic agents used.


[The occurrence of antibiotic-resistant microorganisms (Escherichia coli type I and coliforms) in some foods (author's transl)]. 96 specimens of minced beef, ice cream, soft ice and lettuce were tested for their contamination with E. coli and/or coliforms. Colonies of these contaminants were checked for their antibiotic resistance pattern and it was found that many of the E. coli and coliforms proved to be resistant to up to six different antibiotics. The possible public health consequences of this finding are discussed.


[Aspects of rudimentary psychology, psychopathyology and psychotherapy]. The critical study tries to show systematical conception of the psychic phenomena and abnormal manners described in the work of Seneca after having illustrated the principal terms within the framework of the stoic philosophy according to the imagination of the healthy soul including the demonstration of examples relating to the psychology of feelings. Among other things the study shows the annaeic opinions of the fear of death, the suicide and of getting old; furthermore, it points to the psychotherapeutic activity by laymen at that time.


[Relationship between the presence of K- and O-antigens and the behavior of salmonellae in a culture of macrophages]. It was shown on experimental models (mice and in kerato-conjunctival reaction) in comparative study of spontaneous stable salmonella mutants that disturbances in the process of synthesis of K- or O-antigens led to the weakening or the loss of the bacterial virulence. In the study of the behavior of the salmonella mutants it was revealed in the culture of phagocytizing macrophages that a reduction of the cytotoxic action of bacteria was connected with the changes of the somatic O-antigen, whereas the capacity of salmonella to reproduction inside the macrophages correlated with the presence of surface K-antigen.


[Psychoanalysis and suggestion].

[Psychoanalysis and suggestion]. In the history of psychoanalysis the problem of suggestion has been a central one. At first it involved the necessity to establish the psychoanalytic technique as independent scientific paradigm in contrast to persuasion and hypnosis. However, it was not only the symptom-oriented suggestion that had to be given up for scientific reasons and reasons of treatment technique. Since professional and human factors as well could have influenced the psychoanalytic situation to revert to the traditional "suggestion", Freud has given some technical considerations (e.g. the mirror-analogy), that were meant to counteract the confusion of the psychoanalytic technique with the persuasive one that had to come up to late. The discovery of the transference phenomena has further complicated the problem. It became obvious that the capacity of the analyst to exert an influence and to have impact, originated in very basic human categories and their specific psychogenetic developments and distortions. This understanding contributed to the development of psychoanalytic theories of suggestibility. Until the present day the discovery of the transference phenomena has determined the discussions of psychoanalytic technique in term of the relationship between the special and general therapeutic factors (i.e. interpretation versus relationship). The departure from the therapeutic mode of persuasive suggestion and the introduction of psychoanalytic technique signaled the revolutionary paradigm of Sigmund Freud, i.e. the active participation of the patient and the process of observation. Often scientific problems related to this pradigm and suggestion are discussed concurrently.


[Formation of the dysentery epidemic process in three small towns]. Data are presented concerning the epidemiological analysis of Sonnei dysentery outbreaks in three towns connected by common nutrition and water supply. The epidemic processes in these populated localites were strongly interrelated. Possibilities of the effect of the water factor on the extent of Sonnei dysentery incidence were studied as well. The results of studies led to the conclusion on the presence of numerous action forms of the water factor which should be taken into consideration in carrying out prophylactic and antiepidemic measures in Sonnei dysentery.


[Preliminary results of a bacteriologic study of the blood and urine of children with nephritis]. Single examination of the urine and blood by the method described in this paper was carried out in 14 children suffering from glomerulonephritis. L-form cultures were isolated in 11 cases. The cultures were isolated both at the active phase and during the remission. Three L-form cultures reverted into streptococci spontaneously. The revertants showed a sharp difference from the L-forms by the cell morphology and also by the colour and morphology of the colonies.


[Test of the safety, reactogeneity and immunogeneity of live Flexner 2a and Sonne dysentery vaccine from spontaneous mutants, prepared in dragee form, in a controlled experiment on adults]. Controlled experiment was conducted on 428 adult persons. A study was made of the reaktogenic properties and the immunological activity of live enteral dysentery vaccine Flexner 2a and Sonne from the spontaneous mutants developed at the N.F. Gamaleya Institute of Epidemiology and Microbiology. The vaccine is prepared in the form of sugar-coated pills covered with an acid-fast substance protecting from the gastric juice action. A single administration of the vaccine in a dose of up to 4 pills (6 to 8 X 10(9) live microbial cells) induced no general or local reactions. At the same time enteral administration of such low vaccine doses of the vaccine caused a significant accretion of specific hemagglutinins, including IgA, IgG, IgM antibodies in the serum, this pointing to the marked general and local immunological activity of the vaccine. Vaccine strains Flexner 2a and Sonne were isolated from 16 to 40% of the persons vaccinated, for the maximum period of 5 to 8 days. The isolated strains were avirulent when checked by the keratoconjuctival test.


[Determination of the concentration of antibody reactive centers using a standard antigen and erythrocytic antigen]. The concentration of the reactive centres of the antibodies in the preparation under study can be determined with the aid of an antibody erythrocytic diagnostic agent. A mathematical substantiation of the suggested method and definite examples of its use are presented. The sensitivity of the serological method of determination of the concentration of the reactive centres of the antibodies largely depended on the valency of the antibody erythrocytes and the heterogeneity of the antibodies. This method permits to determine the sum of the reactive antibody centres equivalent to the definite concentration of the molecules of the standard antigen whose valency remains unknown.


[Ultrastructure of LLR-mutants of E. coli K12]. The author studied the ultrastructure of two spherical E. coli K12 mutants (llr) obtained under the effect of N-nitroso-N-methylurea. Seven morphological types of cells differing from one another by shape, size and cytoarchitectonics were distinguished. Superficial structures of the majority of the cells were represented by the membranes of the cell wall and the cytoplasmic membrane of common structure. Some of the cells had only one membrane coat and a high electron optic density of the cytoplasm. Transitional forms of cells were also encountered. The ultrastructure of each morphological type in the population of the llr-mutants was described in detail. The capacity of the mutants to vacuolization, to the intra- and extracellular budding, and also the ability to form multiple membrane structures resembled analogous structures of stable L-forms of the Gram-negative microbes. The problems of morphological differentiation of the L-forms and of the llr-mutants, and also problems connected with the formation of the multiple membrane structures and small elemental bodies in the cells of the llr-mutants are discussed.


[Entobacterial transformation by R6K plasmid DNA]. Preparations of DNA of R6K plasmide obtained by various methods on the basis of the "clarified" lysate: by gel filtration on sepharose 4B, centrifugation in cesium chloride with ethidium bromide gradient, were analysed in the E. coli C600. S. typhimurium AG37, Pr. vulgaris 4636, S. marcescens 20-10 transformation. The frequency of transformation proved to depend on the extent of DNA purification. Factors influencing the E. coli C600 competence and the transformation efficacy (the phase of the culture growth, the concentration of cells in the mixture with DNA, theCaCl2 concentration, the time of the cell incubation at 42 degrees C) were studied. Kinetics of the phenotypical expression of the plasmide signs of ampicillin and streptomycin resistance in transformation was also studied in this work.


Glucose tolerance and insulin secretion in hyperthyroidism. To evaluate the glucose tolerance and insulin secretion in hyperthyroidism patients were examined in the toxic state and after they had been made euthyroid. Fasting values: In 42 untreated patients the glucose- and insulin concentrations in serum were significantly elevated. In 24 treated patients the glucose concentrations became normal, while the insulin concentrations remained elevated. Oral-glucose-tolerance test: In 20 untreated patients the glucose- and insulin responses were significantly increased. In 8 treated patients the glucose response became normal, while the insulin response remained unchanged. Intravenous-glucose-tolerance test: In 28 untreated patients the K-values were significantly decreased and the insulin response increased. In 23 treated patients the K-values rose significantly, but the insulin response remained unchanged. Intravenous-tolbutamide test: In 41 untreated patients the glucose concentration decreased significantly compared with the controls, and the insulin responses were significantly increased. In 23 treated patients the glucose concentrations decreased even more, while the insulin response remained unchanged. The results indicate enhanced sensitivity or an increase in the mass of beta-cells in hyperthyroidism. The glucose tolerance tests point to an increased peripheral insulin resistance. The normalized glucose tolerance and still enhanced insulin secretion during treatment support the assumption, that hyperthyroidism causes an increase in the beta-cell mass.


Inhibition of leukocyte migration by the agarose plate technique. Application to antigen from Candida albicans and Fusobacterium nucleatum. Leukocyte migration inhibition by antigen from Candida albicans and Fusobacterium nucleatum was studied in man by means of the direct leukocyte migration agarose technique (LMAT). Antigens were prepared by prolonged ultrasonication and were added to the leukocyte cultures in the original as well as in the concentrated solutions. Significant inhibition of migration with a 10-fold concentrated solution of candida antigen was demonstrated in subjects showing apositive intracutaneous reaction to candida. With the fusobacterial antigen, inhibition of migration or stimulation of migration were demonstrated in subjects with slight peridontal inflammation. A 5-fold increase in the concentration of fusobacterial antigen resulted in increased stimulation of migration or inhibition of migration. Preincubation of the leukocytes with puromycin abolished both inhibition and  stimulation of migration by candidal or fusobacterial antigen. The study confirms that it is important to study dose-related effects when applying the LMAT to test cell-mediated immunity. The study is in support of stimulation of migration being an immunologic reaction.


Anti-asthmatic properties of a new peroral drug (HC 20-5II). A clinical trial was performed with a new substance (HC 20-511) derived from the cycloheptothiophene group used in the management of asthma. Twenty-four asthma patients were treated at random, with HC 20-511 or placebo or the antihistaminic substance, clemastin (Tavegyl). A statistical evaluation of the results unequivocally demonstrates good protection with a single dose of 2.0 mg or two times 1.0 mg for 3 days against a challenging antigen, compared with the placebo or the antihistaminic agent. Tolerance was excellent.


Lack of impairment in skills related to driving after intramuscular administration of prilocaine or mepivacaine. A saline placebo, 3 mg/kg of 2% plain prilocaine, and 3 mg/kg of 2% plain mepivacaine were injected into the deltoid muscles of 10 healthy subjects in a doubleblind, cross-over trial. Before and at 0.5, 1.5 and 3 h after injection, psychomotor skills related to driving were measured. When compared to the saline placebo, neither prilocaine nor mepivacaine impaired the parameters of psychomotor function measured. Blood concentrations of prilocaine were significantly (P less than 0.001) lower than those of mepivacaine during the whole observation period. It was concluded that in comparison to lidocaine, bupivacaine, or etidocaine, which have been tested previously and found to impair psychomotor performance, mepivacaine and, especially, prilocaine are the anaesthetic agents to be preferred when effects on central nervous system should be avoided, e.g. in outpatient practice.


Ketamine and diazepam as anaesthesia for forceps delivery. A comparative study. In a clinically controlled trial in forceps delivery, a comparison was made between the general anaesthesia induced by ketamine and that by a combination of diazepam and N2O. Local anaesthesia was added in the diazepam group for episiotomy and suturation. The indication for operative delivery was in all cases a prolonged second stage of labour. In the katamine group, awareness was noted in four cases out of 13, even if the analgesic effect was found to be good. Four patients showed marked, short-lasting elevation of blood pressure and seven had unpleasant dreams. All thirteen mothers in the diazepam group found the anesthesia effective and the recovery pleasant. The blood pressure was stable. One mother in each group required ventilation with oxygen due to respiratory depression of short duration. Three of the children in the ketamine group and two in the diazepam group had subnormal Apgar score with slight acidosis. This was probably not attributable to the anaesthesia.


Clinical effects of carticaine, a new local anesthetic. A survey and a double-blind investigation comparing carticaine with lidocaine in epidural analgesia. Carticaine, a new local anesthetic of the amide type, differs from those previously known in that it contains a thiophene ring. The physico-chemical properties of the compound, its pharmacology and its toxicology are reviewed from the litererture. A controlled, double-blind investigation in which carticaine was compared with lidocaine for the purpose of throwing light on the effect of the new local anesthetic in epidural analgesia is presented. Carticaine and lidocaine 2% with adrenaline 1:200 000 were used in the investigation. It was not possible to show any stastically significant difference as regards latency, spread, duration, or motor blockade obtained with the two substances. Marked differences in the type of side effects or their frequency were not noted. From this investigation and a scrutiny of the published clinical studies on the effect of carticaine, it is concluded that its clinical properties are comparable to those of lidocaine.


Effect of exogenous estrogens on LH and FSH secretion in women with hypothalamic amenorrhea. The effect of estradiol on FSH and LH secretion in 5 women with hypothalamic amenorrhea are presented. The functional capacity of the pituitary to secrete FSH and LH had been proved by testing with synthetic luteinizing hormone-releasing hormone (LH-RH) 100 mug i.m. The thyroid and adrenal functions were normal. In 3 patients estrogens were low-normal and in the other 2 extreme hypoestrogenism was found. Twelve days after the appearance of withdrawal bleeding each patient was given 10 mg estradiol benzoat (EB) i.m. In 3 patients a significant increase in the LH and a slightly smaller increase in the FSH concentration were noted, with an LH peak 60 to 84 hours after injection of EB. The first of these 3 patients became pregnant, in the second the biphasic BBT curve, urine pregnanediol excretion above 2.5 mg/24 hr and the histological finding of secretory endometrium indicated that ovulation had been successfully induced, while in the third patient, despite a satisfactory increase in the LH and FSH concentration, ovulation could not be induced. In the remaining 2 patients no increase in the LH and FSH concentrations was noted even as late as 96 hours after the injection of EB. In these women bleeding began on the 18th and 22nd day of the cycle, respectively, when histological examination revealed proliferative endometrium. The first 3 cases are classified as hypothalamic amenorrhea with dysfunction of the cyclic centre and the other 2 as hypothalamic amenorrhea with dysnfunction of the tonic centre. The effect of exogenous estrogens in patients with hypothalamic amenorrhea depends both on the functional capacity of the hypophysis and the capacity and condition of the tonic and cyclic centres in the hypothalamus.


A simple apparatus for controlled rate corneal freezing. The construction and operation of an apparatus for controlled rate corneal freezing is described. The cooling is obtained by close thermal contact between a vial holding the cornea and a metal core. A predetermined cooling rate is achieved by partial immersion of the core in a fixed amount of liquid nitrogen. In a preliminary series greater than or equal to 95% endothelial survival was obtained.


Transfer factor in chronic and recurrent respiratory tract infections in children. Five cases with abnormal sensitivity to respiratory tract infections are described. The cases showed a marked impairment in their cell mediated immunity state. Administration of a chromatographically purified transfer factor component increased the skin test sensitivity to common recall antigens. Interestingly, a similar effect in skin reactivity was observed with repeated skin tests alone, when antigen concentrations, initially high enough to cause a positive reaction, were used. Neither the administration of transfer factor nor skin testing with high antigen concentrations had an effect on blast transformation percentages. The therapy with chromatographically purified transfer factor appeared promising on the clinical condition of the patients.


Transfer factor and cellular immune response in urinary tract infections in children. Cellular immune responses in vivo and in vitro were studied in 20 children with chronic or relapsing urinary tract infections. Skin tests revealed decreased immune responses to PPD in cases with chronic or recurrent pyelonephritis and to OM, in these cases and in cases of lower urinary tract infections. Blast transformation responses to PPD, OM and PHA were at least as high as in controls. Administration of chromatographically purified fraction from human leucocyte transfer factor resulted in a positive skin reaction with antigen concentration, which before TF administration had caused a negative reaction. The results suggest that the action of the transfer factor component used in this study is based on an immunologically nonspecific stimulation of the cellular immune response.


Development of germfree animal characteristics in conventional rats in antibiotics. Conventional (CONV) rats were fed by stomach tube for five days with either benzylpenicillin, ampicillin, tetracykline, oxitetracykline, neomycin, bacitracin + neomycin, kanamycin or colistin. On the 2nd-3rd day all the animals developed one or several of the following symptoms or characteristics typical for germfree (GF) rats: no coprostanol formation, no stercobilin production, a GF pattern after gel electrophoresis of fecal supernatant and proteolytic activity in the feces. Under the same conditions succinylsulfathiazole or metronidazole had much less pronounced effects than the antibiotics. When clofibrate, acetylsalicylic acid or ferrous sulphate were administered the effects were none or negligible. The GF characteristics persisted for several weeks after the end of the administration of the drugs. In some instances this was the case up to 7 weeks, when the animals were contaminated by anal route with a suspension of the cecum contents from intact CONV animals. On the 2nd day after this treatment the GF characteristics had disappeared.


[Clinical and experimental use of ATP in internal ear diseases]. Intra-arterial ATP infusions with glucose and hyaluronidase were successful in 267 patients suffering from various inner ear disturbances but particularly in sudden deafness. Good clinical results were noted not only in early-treated but also in later cases. Recently, we have also used ATP with hyperbaric oxygen, being successful in cases which were previously treated without improvement. Investigations in guinea-pigs, using artificial hypoxia as a model for human sudden deafness failed because the patterns are not the same. So long as an increase of ATP in the cochlear cells cannot be demonstrated after the i.a. infusions, only an unspecific mechanism can be held responsible for the undoubted clinical successes.


Characterization of Enterobacter agglomerans (Erwinia spp.) from clinical specimens. The biochemical reactions of 18 anaerogenic and 45 aerogenic isolates of Enterobacter agglomerans are described and used for subdivision in the biogroups suggested by Ewing & Fife. The presence of special cultural characteristics (symplasmata and biconvex bodies) was also recorded and was found to be unrelated to formation of gas from glucose. Previous authors have reported such structures in anaerogenic cultures only. The amount of gas produced varied to a great extent between strains and also proved to be dependent on incubation temperature. The results do not support the division of E. agglomerans into one anaerogenic and one aerogenic major subgroup. The value of the gelatin liquefaction test for characterization of the species is emphasized.


A new rapid method for the in vitro demonstration of tonsillar lymphocyte activation. A simple method is presented suitable for the demonstration of the initial stage of lymphocyte activation. The method is based on the evaluation of the intranuclear birefringence of lymphocytes. With this technique, the activation of the cells is detectable after 30 minutes' in vitro activation. Tonsillar lymphocyte activation was demonstrated after phytohemagglutinin, antigen, or anti-mu antibody stimulation. This activation causes an increase in the intranuclear birefringence. A small group of rabbit tonsillar lymphocytes showed an increased birefringence without in vitro stimulation, thus indicating a continuous in vivo activation of the tonsils.


A simple procedure for determination of bacteriolytic activity in biological fluids. A new procedure for spectrophotometric determination of bacteriolytic activity in biological fluids is described. The method uses Micrococcus lysodeikticus cells as substrate. By inactivation of the sample through pre-incubation in ice-water, a large number of samples can be prepared and analysed simultaneously. The necessity of performing the whole analysis in the photometer for one sample at the time is thus eliminated. By measuring the increase in transmission at 570 nm after incubation of the samples at 37 degrees C a relatively long reaction time and wide concentration range is obtained. This makes the results quite precise and reproducible. The method has been used to determine the bacteriolytic activity in serum of healthy adults. Men have significantly higher levels than women.


Circulating T and B lymphocytes and immunoglobulin containing cells in the liver in chronic active liver disease. The number of circulating T and B lymphocytes was estimated in 25 patients with biopsy-verified chronic non alcoholic liver disease. Fifteen of these had circulating HBSAg and/or anti-HBSAg and 10 were without these markers of HB virus infection. In both groups of patients a significant decrease of T cells and a parallel significant increase in null cells was found, but any difference with respect to T and null cells in patients in the two groups was not observed. Liver biopsies from five of the patients with and four without HBSAg and/or anti-HBSAg were studied for the presence of immunoglobulin bearing cells. In three out of five liver biopsies from the HBSAg and/or Ab positive patients and in two out of the four liver biopsies from the HBSAg and anti-HBSAg negative patients, a heavy periportal infiltration with plasma cells was found. However, the number and classes of the immunoglobulin containing cells could not be correlated either to the histological evaluation of the stage of activity of the liver disease or to the markers for HB virus infection. The immunological findings in the two groups of patients with chronic liver disease seem to be of the same nature and are most likely a consequence of the liver disease and not the cause of it.


Immune response in mice to hapten conjugated sepharose. Mice were injected intraperitoneally with Sepharose 4B beads coupled with hapten NIP, and their anti-NIP response was studied by counting antibody forming cells and determining serum titers. Mice responded well to doses of 0.7 ml of packed beads but 0.3 and 1.2 doses induced much weaker responses. Anti-NIP titers in recipients of 0.7 ml of the antigen lasted nearly constant for at least 7 weeks. Both T cell status of the recipient and use of adjuvant had an effect on the response. Antigen without adjuvant induced primarily IgM antibodies in normal mice, but IgM and IgG in nude mice. When Hemophilus pertussis or polyacrylic acid was used as adjuvant both normal and nude mice produced IgM and IgG antibodies, and normal mice produced in addittion IgA antibodies.


Lymphocyte subpopulations in Crohn's disease and chronic ulcerative colitis. Lymphocyte subpopulations in peripheral blood were studied by the sheep red blood cell rosette technique for the identification of T-lymphocytes, and immunofluorescence staining with rabbit anti-human immunoglobulin sera for the identification of B-lymphocytes. In Crohn's disease, the total number of lymphocytes was found to be reduced and an almost equal reduction in all the lymphocyte subpopulations studied was found. In ulcerative colitis neither the number of T-lymphocytes nor of B-lymphocytes were found to differ significantly from normal values and the same was true of all B-lymphocyte subpopulations. However, the number of lymphocytes carrying neither surface immunoglobulin nor sheep red blood cell receptors was found to be significantly increased. The results were correlated to clinical data.


Unchanged protein binding and the increase of serum diazepam levels after food intake. Seven subjects received diazepam 0.3 mg/kg intravenously twice with a 2-week interval between the doses. The subjects ingested a fatty or carbohydrate meal in a cross-over fashion 4 hours after the injection on both experimental days. Venous blood samples were drawn 2, 3, 4, 5 and 6 hours after the injection of diazepam for measurement of the serum levels of total and free (unbound) diazepam, N-desmethyldiazepam, and free fatty acids. Serum levels of diazepam decreased progressively with time until the food intake, after which a significant (P less than 0.01) postprandial increase (average 23%) occurred with both diets as compared to the preprandial levels at 4 hours (average 240 ng/ml). Serum levels of free fatty acids decreased significantly both after a fatty (P less than 0.01) and a carbohydrate (P less than 0.05) meal. Diazepam was extensively (96 to 98%) bound to proteins and no changes in its protein binding was found. It is concluded that the late impairment of psychomotor skills that occurs with an increase in the diazepam serum level after its intravenous administration is due rather to its re-mobilization from a storage site than to variations in its protein binding.


Secretion of human growth hormone and insulin in levodopa test during carbamazepine therapy. The effect of oral administration of carbamazepine for a period of three weeks on serum growth hormone, serum immunoreactive insulin, and blood glucose was studied in healthy volunteers using a levodopa stimulation test. Serum growth hormone rose significantly from 1.3 +/- 0.3 ng/ml to 16.3 +/- 3.4 ng/ml in 60 minutes after levodopa administration (1000 mg orally) before carbamazepine, and almost similarly from 2.3 +/- 0.5 ng/ml to 15.1 +/- 4.0 ng/ml after carbamazepine during the test. No consistent changes were found in blood glucose concentrations in the levodopa test before or after carbamazepine. Levels of serum IRI were also normal throughout the test and no impairment in insulin secretion was seen during carbamazepine treatment. It is suggested that carbamazepine does not lead to an altered anterior pituitary function or to an impairment in insulin secretion. This is of advantage when growing children or subjects with a risk factor for diabetes are treated.


Comparative clinical evaluation of lofepramine and imipramine. Psychiatric aspects. Lofepramine, an imipramine analogue, was compared with imipramine in a multicentre, double-blind clinical trial. The 62 patients (31 in each of two treatment groups) had a depressive syndrome that normally would have been treated with a tricyclic antidepressant. These patients had not received any adequate treatment for this present depressive episode. After a wash-out period and once a week during treatment (up to 5 weeks), routine laboratory tests and electrocardiograms was done. The dosage was 50 mg t.i.d. for imipramine and 70 mg t.i.d. for lofepramine. Depression ratings with the Cronholm-Ottosson depression rating scale were performed before treatment and once weekly for 3 weeks and then in the 5th week. The last four ratings were combined with rating of side-effects. In the 5th week of treatment 15 out of 31 in the lofepramine group and 18 out of 31 in the imipramine group had recovered. This difference was not significant, nor did the median values of individual symptoms differ between the groups. The side-effects were moderate and the two groups only differed significantly in the items "dry mouth" and accommodation disturbances in favour of lofepramine. The drug compliance was checked by plasma levels of desmethylimipramine in the imipramine group, parent compound, and "apparent" desmethylimipramine in the lofepramine group. The relationship between plasma drug levels, the effect on noradrenaline uptake in vitro and amelioration  discussed in Siwers et al. (1977) in this issue. The clinical outcome in the two groups did not differ significantly; interpretation of this result is discussed in relation to the reliability and selection of patients.


Comparative clinical evaluation of lofepramine and imipramine. Pharmacological aspects. A multicentre comparative clinical evaluation of lofepramine, an imipramine analogue, and imipramine has been made with double-blind technique and fixed dosage (lofepramine 70 mg t.i.d., imipramine 50 mg t.i.d.). Plasma was drawn after 3 weeks for determination of noradrenaline-uptake inhibitory capacity of the parent compound and/or its active metabolites. Plasma concentrations of lofepramine and desmethylimipramine (DMI) were determined in the same samples. The concentrations of lofepramine in the whole material were low (5-27 ng/ml) except for one patient who had a level of 53 ng/ml. In both groups of patients there was an almost 40-fold range in the plasma levels of DMI or apparent DMI. The patients were rated for severity of depression before treatment, then once weekly for 3 weeks and finally during the fifth week. For further information concerning the psychiatric aspects, see d'Elia et al. in this issue (1977). A significant correlation was found between the concentrations of DMI and the noradrenaline-uptake inhibitory capacity in the plasma samples. No correlations were found between uptake inhibitory capacity of plasma samples and the amelioration scores.


Gangliosides in the treatment of mental deterioration. A double-blind comparison with placebo. Thirty patients showing signs of mental deterioration were submitted to a neuropsychological battery before and after treatment with gangliosides. Their performances were compared, in a double-blind study, with those obtained on the same tests by 30 patients affected by similar degrees of dementia and treated with placebo. The improvement shown on Raven's Coloured Progressive Matrices and on Immediate Visual Memory by the active group was significantly higher than that shown by the placebo group. Furthermore, an evaluation of the overall effect of gangliosides therapy showed a highly significant difference between the active and placebo group, still in favour of the subjects treated with gangliosides. It is concluded that gangliosides may exert a positive effect in the treatment of demential syndromes.


Sleep disorders in patients with severe mental depression: double-blind placebo-controlled evaluation of the value of pipamperone (Dipiperon). Pipamperone was compared double-blindly with placebo to evaluate its capacity to relieve sleep disorders in 40 depressive inpatients. At the end of the 1-week trial, most of the items relating to sleep disturbances had improved significantly in the 24 patients of the pipamperone group whereas only a few items showed such a change in the control group. On the Hamilton depression scale, improvement in the pipamperone patients was also superior to that in the placebo group as regards the items "depressed mood" and "insight". The adequate median daily dose of pipamperone appeared to be 80 mg (2 tablets).


Comparison of plasma lithium levels and their interindividual variations with coated lithium carbonate tablets and a medium-slow-release lithium sulphate preparation (Lithionit Duretter). In a cross-over study in 10 subjects, rapidly dissolving coated lithium carbonate tablets and medium-slow-release lithium sulphate tablets were compared. Both preparations were administered twice a day. They gave similar post-absorptive concentrations of lithium in plasma and similar standard deviations of these concentrations. The medium-slow-release tablets gave smaller increases of lithium in plasma, and postponed the absorption peaks. They also gave less interindividual variation of lithium in plasma during the first few hours after administration.


Comparison of side effects with coated lithium carbonate tablets and lithium sulphate preparations giving medium-slow and slow-release. Side effects with coated, rapidly dissolving lithium carbonate tablets, medium-slow-release and slow release lithium sulphate tablets, all administered twice a day, were compared in a double-blind, cross-over study in 27 patients who had only used lithium carbonate tablets. The relation between medication and meals was not standardized. The repidly dissolving tablets and the medium-slow-release tablets had a similar tendency to produce side effects, while slow-release tablets more often produced purgative side effects than the other two preparations did.


Detection of bacterial metabolites in spent culture media and body fluids by electron capture gas-liquid chromatography. Electron capture gas-liquid chromatography, when used to analyze derivatized extracts of spent culture media and body fluids under specified conditions, holds promise as a tool for use by physicians, hospitals, and clinical laboratories in identifying certain diseases and disease-producing organisms. The detection of certain disease processes and the identification of disease-producing organisms are based on qualitative or large quantitative differences in EC-GLC profiles or a combination of both. Various practical procedures are given for extracting and derivatizing compounds, such as carboxylic acids, hydroxy acids, alcohols, amines, and nitrosamines. The characteristics of the parameters essential for successful analysis are discussed. Species and, in some cases, strains have been differentiated by comparing EC-GLC profiles. Metabolic products are affected by change in substrate. Media that can be reproduced from lot to lot are essential in some studies. The volatile components detected by EC-GLC in spent culture media consist mostly of bacterial metabolites, but the volatile compounds detected in body fluids may be bacterial metabolites, volatile components produced by the host in response to an infection, metabolites of cells associated with host defense, or a combination of two or more of these groups of compounds. The EC-GLC profiles obtained by analysis of synovial and cerebrospinal fluids appear to have good potential for use in diagnosing certain forms of arthritis and meningitis. Well-documented samples are essential to establishing EC-GLC profiles representative of a particular disease. A moderately priced computer would greatly aid in data processing and could be especially useful in compensating for minor changes in the retention times of peaks, which can occur as a result of column aging or when columns are renewed. An approach to the identification of components detected by EC-GLC, which makes use of electron capture gas chromatography-mass spectrometry, is presented.


The determination of anticonvulsants in biological samples by use of high-pressure liquid chromatography. The procedure for anticonvulsant analysis represent use of a relatively new technology. The procedures compare favorably in accuracy and precision with accepted methodology using gas chromatography [14]. It is possible to determine a greater number of anticonvulsants simultaneously with liquid chromatography than with reported gas-chromatographic procedures. This is because gas chromatography necessitates manipulation of the sample to be analyzed, the various components of which may have completely different manipulation requirements. Liquid chromatography is able to effect the analysis without extensive manipulation of the sample. The columns recommended in Sect. III are currently available standard columns. Column technology is developing at an accelerating rate. It is now anticipated that new developments in microparticulate packings and improvements in packing techniques will give the analyst greater column efficiency. This may be used either to shorten overall analysis time or to include more drugs in a simultaneous analysis. There is not yet available to the analyst a variety of different detectors suitable for routine use. This situation will change. In the case of the successful use of ultraviolet spectrophotometric detectors, the technique is not being fully exploited. Ultraviolet spectrophotometry is firmly established in practice, but as yet it is not routine to apply dual-wavelength spectroscopy to the column effluent. Application of this technique may be expected to improve selectivity and quantitation besides permitting optical resolution of some components that are not separated by the column. In the procedures given in this chapter there was no detailed discussion on gradient elution. This technique is potentially of great utility for simultaneous analyses of many compounds. It should be used only where isocratic elution is out of the question because it calls for somewhat stricter requirements of equipment in control of chromatography conditions. An additional time for equilibration between analyses may be considered too high a price to pay for any advantage gradient elution may give the analyst. The problem of fully automatic operation of liquid chromatographs for the type of analysis discussed here remains to be solved. Automatic operation would advance the use of liquid chromatography in the clinical laboratory probably more than any other single improvement. However, regardless of refinements of this type, liquid chromatography in its modern manifestation has versatility and sensitivity in abundance for analyzing compounds of toxicological and clinical interest. It will therefore assume greater importance in these areas.


Some clinical and pharmacological applications of high-speed liquid chromatography. Through specific examples, the versatility of HSLC in clinical and pharmacological studies has been demonstrated. These examples are not intended to restrict the vision of the reader, like that of the author, but on the contrary, it is hoped that those not yet familiar with the usefulness of HSLC will gain perspective concerning this technique in their own fields of interest. The virtually unlimited ability to separate cellular metabolites (or other organic compounds for that matter) by HSLC is a reality at this time; however, development of more selective, sensitive means of detection and positive identification of eluting components is needed, similar to that gained by coupling mass spectrometry with gas chromatography.


Reoperation for dysfunction of the Björk-Shiley mitral disc prosthesis: report of eight cases. Of 193 patients with Björk-Shiley mitral valve prostheses, replacement was necessary in 8 (4.1%). The reasons for reoperation were: detachment (4), thrombosis (1), technical error (1), and late disc entrapment (2). Five of these patients died (62.5%), the death being directly related to the need for urgent operation because of low cardiac output. We recommend avoiding the use of the larger sized Björk-Shiley prostheses, since striking of the disc against the ventricle wall, probably consequent to postoperative decrease in heart size, may appear even 1 year after implantation of the prosthesis. An early diagnosis and early reoperation offer these patients a much more favorable prognosis.


Quantitative evaluation of vitamin E in the treatment of angina pectoris. Because of previous reports of the beneficial effect of vitamin E in angina pectoris patients, 48 patients, with both stable angina and positive (chest pain plus ishemic ST depression) maximal exercise treadmill tests, participated in a double-blind cross-over study of 6 months of vitamin E and 6 months of placebo therapy, separated by a 2 month no treatment period. All 48 patients had positive selective coronary arteriograms (75 per cent obstruction of at least a major coronary artery) and/or Q wave ECG evidence of previous myocardial infarction (Minnesota criteria). Evaluation of drug effectiveness was based on performance of serial maximal exercise treadmill tests, serial systolic time interval measurements, and daily angina diaries. No statistically significant differences between the two treatment studied. It is concluded that a large dose of vitamin E (1,600 I.U. of d-alpha-tocopherol succinate daily) for 6 months in patients with stable angina pectoris fails to increase the exercise capacity, improve left ventricular function, or reduce the frequency of chest pain.


New approach to interpretation of technetium-99m pyrophosphate scintigraphy in detection of acute myocardial infarction: clinical assessment of diagnostic accuracy. A modified classification for interpreting technetium-99m pyrophosphate scintigrams defines the 2+ diffuse pattern of tracer uptake as equlvocal rather than positive for acute myocardial infarction. Results of scintigraphy using this classification were compared with results of standard diagnostic tests for myocardial infarction in 235 patients admitted to a coronary care unit with acute chest pain. Of 81 patients with acute transmural infarction by standard clinical, electrocardiographic and serum enzyme criteria, 76 had a positive, 5 an equivocal and none a negative scintigram. Of 18 with acute nontransmural infarction by standard criteria, 7 had a positive, 9 an equivocal and 2 a negative scintigram. This it was uncommon for a patient with acute myocardial infarction, transmural or nontransmural, to have a definitely negative technetium-99m pyrophosphate study. Ten patients had equivocal evidence of infarction by standard criteria. Of the remaining 126 patients with no evidence of acute myocardial infarction by standard criteria, 87 had a negative, 35 an equivocal and 4 a definitely positive scintigram. Thus the definitely positive scintigraphic pattern was relatively highly specific for acute myocardial infarction. If the 2+ pattern had been considered positive, the specificity of the technique would have been greatly decreased. Computer processing strengthened observer certainty of the visual impression but changed the scintigraphic evaluation in only eight cases. Thus, use of an equivocal pattern renders technetium-99m pyrophosphate imaging both an extremely sensitive and specific method for detecting acute myocardial infarction.


Engelmann and his laddergram.

Engelmann and his laddergram. Thomas Lewis is alliteratively credited with devising the laddergram. Engelmann, or perhaps Chauveau, truly deserves the honor. Mackenzie and Wenckebach popularized the schema in their books.


Identification of challenged subarachnoid free cells. Three distinct types of free cell contours are recognizable in scanning electron microscopy (SEM) on the leptomeningeal sheaths of dogs twelve days after an intrathecal injection of bacillus of dogs twelve days after an intrathecal injection of bacillus Calmette-Guerin (BCG). Macrophages posses abundant plasmalemnal blebs which are shown in transmission electron microscopy (TEM) to be composed of large membrane-bound vacuoles. Smooth surfaced lymphoblasts exhibit many basal microvilli that rest upon and often indent the plasmalemma of an underlying pial cell. Neutrophils display many microvilli over their rounded, chrysanthemum-like surfaces. The consistency with which these external features are expressed suggests that each cell type possesses characteristic surface topography, at least under these conditions of challenge.


The effects of tissue processing on markers for T and B cells from solid tissues. Suspensions of lymphoid cells from tissues have been used for the determination of the quantitative relationship between the T and B cell populations. The distribution of the lymphocytes within a given tissue, however, cannot be demonstrated once such a suspension has been prepared. Various methods of characterizing lymphocytes within tissues were evaluated. The method of tissue preparation can alter the capability of detecting the lymphocyte markers. Fluorescein-labeled anti-immunoglobulin sera reacted equally well with lymphocytes in tissue regardless of the method of tissue preparation. Complement-coated sheep erythrocytes were less effective in detecting lymphocyte markers in tissue sections than in cell suspensions. Quantitative assays of lymphocytes could be done in suspensions only. Unaltered sheep erythrocytes did not bind to T lymphocytes in tissue. T lymphocytes could be identified in tissue sections, however, by the use of anti-human T cell serum.


Interaction of blood with enterobacteriaceae: hemolysis, hemagglutination, fibrinolysis. One thousand eighty enterobacteriaceae, isolated during a period of three months, were tested for the presence of hemolysis, hemagglutination and fibrinolysis on human erythrocytes and plasma. The fibrinolysis on human erythrocytes and plasma. The Escherichia coli have the greatest diversity of action on the blood. Of 481 strains, 32.9% were hemolytic, 21.9% fibrinolytic, and 10.5% hemagglutinating. Of 190 strains of Klebsiella, 95.2% were fibrinolytic. Of 53 strains of Enterobacter, 90.6% were fibrinolytic, and of 53 strains of Enterobacter hafniae, 66% were fibrinolytic. Of seven strains of Serratia, 28.5% were hemolytic and 14.3% fibrinolytic. The Proteae were mostly fibrinolytic: 60.5% of 141 strains, with three strains being hemolytic and fibrinolytic. Of 19 strains of Citrobacter, 52.6% were fibrinolytic only. Providenica, Salmonella and Shigella did not interact with human blood. The patterns of blood interactions with the different species of Enterobacteriaceae are of value in the evaluation of the pathogenesis of the infections and septicemias they cause. Their study is an essential step in the understanding of the sequence of events leading to severe disturbances of the blood-clotting mechanism.


Choriocarcinoma in mother and child, identified by immunoenzyme histochemistry. A case of metastic choriocarcinoma after term pregnancy, with tumor localization in the kidney of a hydropic stillborn infant, is presented. The primary tumor was found in a scraping four weeks after delivery. The identity and nature of the malignant growth in mother and child were substantiated by identical immunohistochemical patterns for gonadotropin activity. Because of a positive Kleihauer test it was assumed that massive feto-maternal transfusion had caused the hydrops and intrauterine death. Now, four and a half months after starting methotrexate therapy, the mother seems to be free of tumor. Plasma human chorionic gonadotropin titers have decreased to normal.


IgA-IgG nephropathy: a clinicopathologic entity with slow evolution and favorable prognosis. Renal biopsy specimens were obtained from nine patients with proteinuria and persistent macroscopic or microscopic hematuria. Histologic examination either disclosed no abnormality or showed moderate mesangial thickening and occasionally, evidence of focal segmental glomerulonephritis. Immunofluorescent studies revealed diffuse generalized mesangial deposits of IgA, IgG and betalc in all specimens. Fibrinogen deposits were present in the mesangial space in four specimens only, while IgM was uniformly absent. Serial sections of identical glomeruli allowed the localization of betalc within both IgA and IgG deposits. Ultrastructural studies of the renal biopsy specimens showed accumulation of electron-dense material in the subendothelial region of the capillary loops and the mesangium, with thickening of its matrix. Follow-up data indicated a generally good prognosis.


Individual sensitivity to lactose in lactose malabsorption. The clinical significance of lactose malabsorption and the individual sensitivity to lactose were investigated in 20 patients with verified lactose malabsorption. Thirteen patients were relieved of all symptoms while seven improved only on a lactose-free dth lactose-free milk but following provocation with increasing amounts of lactose, the tendency to diarrhea and abdominal discomfort increased considerably. Three patients experienced discomfort after provocation with only 5 gl lactose. On provocation with increasing amounts of lactose the seven patients who had not recovered also developed increased abdominal discomfort but none of them developed increased tendency to diarrhea. It is concluded that, in addition to lactose malabsorption, these patients must suffer from ittitable colon with tendency to constipation.


Pseudo-obstruction of the bowel. Therapeutic trial of metoclopramide. A patient with chronic idiopathic pseudo-obstruction is reported and the results of a double blind therapeutic trial of metoclopramide are described. Within the limits of this trial metoclopramide was ineffective by all clinical criteria.


Pharmacology and clinical use of drugs in hypertensive emergencies. The clinical pharmacology and appropriate choice of antihypertensive agents useful in the treatment of hypertensive emergencies are reviewed. The antihypertensive agents discussed are diazoxide, sodium nitroprusside, hydralazine hydrochloride, trimethaphan camsylate, methyldopa, reserpine and phentolamine mesylate.


Disseminated Nocardia caviae infection.

Disseminated Nocardia caviae infection. Disseminated Nocardia caviae infection occurs only rarely. To date, two cases have been recorded in the literature. We describe a third case of systemic N. caviae infection in a compromised host and compare it with the first two cases. Postmortem, microbiologic and antibiotic sensitivity data are included.


Lipids, 1973-1976.

Lipids, 1973-1976. More and more data are being accumulated on the relationship between triglycerides and cholesterol and atherosclerotic heart disease. Not all of it is positive. Several authors have come out against lipoprotein electrophoresis in the routine laboratory.


Histochemical studies relating the activation of macrophages to the intracellular destruction of tubercle bacilli. Dermal tuberculous lesions, both primary and those of reinfection, were produced in rabbits with 14C-labeled BCG and biopsied once at various times. Macrophage activation was evaluated by the indolyl histochemical test for beta-galatosidase, the number of bacilli in macrophages by acid-fast staining, and the breakdown of bacilli by autoradiography. After the rabbits became tuberculin positive, the stongly activated macrophage population contained a) fewer parasitized cell, b) fewer bacilli in each parasitized cell, and c) more "free" 14C-label (not associated with intact bacilli) than the weakly activated macrophage population. These results suggest that the more highly activated macrophages had destroyed many of the bacilli that they once contained and that their power to do so was enhanced by immunologic mechanisms.


Glucose and lactate kinetics after endotoxin administration in dogs. We studied the effects of E. coli endotoxin on the glucose and lactate kinetics in dogs by means of the primed constant infusion of [6(-3)H] glucose and Na-L-(+)-[U-14C] lactate. The infusion of endotoxin induced a transient hyperglycemic level, followed by a steady fall in plasma glucose to hypoglycemic levels. The rate of appearance (Ra) and the rate of disappearance (Rd) of glucose were both significantly elevated (P less than .05) for 150 min after endotoxin, after which neither differed from the preinfusion value. The metabolic clearance rate of glucose was significantly elevated at all times 30 min postendotoxin. By 30 min postendotoxin, Ra and Rd of lactate, plasma lactate concentration, and the percent of glucose turnover originating from lactate were significantly elevated and remained so for the duration of the experiment. We concluded that after endotoxin hypoglycemia developed because of an enhanced peripheral uptake of glucose and a failure of the liver to maintain an increased Ra of glucose. We also concluded that lactate became an important precursor for gluconeogenesis and an important metabolic substrate.


Stimulation of insulin and glucagon secretion by vasoactive intestinal peptide. In vivo, vasoactive intestinal peptide (VIP) produces simultaneous increases in blood glucose and insulin levels. In order to determine whether VIP, like its homologues, also stimulates insulin secretion directly, studies were made in controlled glucose media employing the vascularly perfused cat pancreas. VIP stimulated insulin secretion significantly in the presence of constant physiological concentrations of glucose. The highest insulin response to VIP (100.3+/-8.1 muU/min) approached the highest insulin response to glucose (119.9 +/- 12.0 muU/min). In the absence of glucose, the insulin response to VIP was insignificant. Unexpectedly, VIP was found to be a more effective stimulant of glucagon than of insulin secretion. The highest glucagon response to VIP (327+/-51% of control levels) was attained in the presence of physiological concentrations of glucose and equalled the glucagon response obtained upon withdrawal of glucose from the perfusate. The glucagon response to VIP was blocked by increasing the glucose in the perfusate. These studies indicate the VIP present in pancreatic islets might play a role in the local control of pancreatic endocrine function.


Freeze-fracture electron microscopy: relationship of membrane structural features to transport physiology. Recent observations utilizing freeze-fracturing electron microscopy are discussed which indicate that the membrane structural features visualized by this technique may in some instances be related to specialized membrane transport properties. The occurrence of organized aggregates of intramembrane particles observed in vasopressin or cAMP-treated toad urinary bladder has been found to be closely correlated with induced changes in the permeability of the luminal membrane. Although a cautious interpretation is considered appropriate, these observations raise the possibility that some aspects of hormone action may be restricted to limited regions of membrane. Difficulties in interpretation and some serious limitations of the freeze-fracture technique are discussed.


A reinvestigation of the function of the mammalian urinary bladder. The function of adult mammalian urinary bladder is evaluated in light of recent in vitro experiments. The discrepancy between in vivo and in vitro experimental results is examined and a possible solution proposed. Techniques for eliminating edge damage and measuring apical membrane surface area are described. A new chamber design for microelectrode studies is illustrated. The possibility of apical cell membrane damage caused by microelectrodes is critically examined and tested using the polyene antibiotic Nystatin. Using data from transepithelial and microelectrode experiments, a model for net Na+ transport across the bladder is proposed and then critically analyzed. The possible clinical implications of the in vitro experiments are briefly discussed.


An analysis of interstitial fluid pressure in the web of the bat wing. A mathematical theory of interstitial fluid motion and capillary exchange is developed in order to understand and explain measurements of capillary and interstitial fluid pressure in the bat wing, in which a high degree of vasomotor activity occurs. As a result of precapillary sphincter activity, fluid is alternately filtered and reabsorbed from the capillary, and previous studies of related steady problems by the author suggest that the interstitial fluid pressure should oscillate with time. Wiederhielm and Weston did not observe such fluctuations when they measured tissue pressures near the capillaries. This apparent paradox is resolved in the present paper by including unsteady effects. It is shown that pressure oscillations are predicted, but because of the very high vasomotor frequency they die out within a very short distance from the capillary wall. The capillary pressure measurements of Wiederhielm and Weston are also explained in terms of precapillary sphincter activity.


Psychosomatic medicine in the seventies: an overview. The author discusses the theoretical, investigative, clinical, and teaching aspects of psychosomatic medicine in the seventies. Major research and clinical developments are discussed in relation to key theoretical postulates and concepts. The rapidly expanding field of psychosomatic medicine is far more divant than ever before. Its hallmarks include a multifactorial approach to the study of health and disease, formulation of testable hypotheses and their careful validation, concern with the clinical applicability of research, and development of integrative theories. Current advances in the field have far-reaching inplications for medicine, psychiatry, and the behavioral sciences.


Ten years of change in alcoholism treatment and delivery systems. The author reviews the major advances in concepts and methods that have been made in the treatment of alcoholism over the past decade but finds little change in the everyday operation of treatment programs. He examines the ideological differences between professionals and paraprofessionals in the field, the changes in treatment goals that have been made, the different types of alcoholic patients and their different needs and responses to treatment, the uses and misuses of drug therapies, the relatively unexamined values of psychotherapy, the recently successful behavioral therapies, and treatment delivery systems and their evaluation.


Moral therapy and the problem of morale. The author reviews the history of moral therapy and the lessons and warnings it holds for modern psychiatry. Custodial management replaced moral therapy in this country in the late 1800s because of inadequate manpower and fiscal resources, a lack of charismatic leaders, the increasing lack of control over admissions and discharge, and other factors. One "solution" to the unacceptable conditions of custodial care was an increased faith in science and technology; humanistic medical science became scientism, and patients suffered. Morale is essential to the provision of moral therapy, and the increasing emphasis on somatic therapies has strained the union of morale and moral treatment. The author believes that the profession can reaffirm its identity and distinguish itself through the appropriate provision of humane, psychosocial care--the essence of moral therapy.


The offspring of alcoholics: a critical review. In their review of the literature on the effects of parental alcoholism on the offspring of alcoholics, the authors focus on sample collection, criteria used for the diagnosis of parental alcoholism, and definitions of "emotional disturbances." Studies are grouped according to age of offspring; within each age group, the various approaches to the issue are described. The authors suggest a need for more carefully controlled studies using blind data collection and clear operational definitions. In addition, the "risk" status of offspring of alcoholics should be compared to that of children whose parents have other types of serious psychiatric disturbance. Although the literature has focused on the "casualties," the authors note that much could be learned from studies of the "successes"--those children who do not seem to be at increased risk for pychosocial illness despite the alcoholism of their parents.


L-tryptophan: a rational hypnotic with clinical potential. The author states that the use of the amino acid L-tryptophan as a hypnotic might avoid the problems of nonspecificity in the currently used CNS depressants because L-tryptophan is chosen on the basis of the chemistry of normal sleep rather than on a purely empirical basis. He reviews nine studies from his laboratory dealing with the effects of L-tryptophan on sleep. Studies in rats, normal human subjects, and subjects with mild insomnia all demonstrate that L-tryptophan reduces sleep latency. Polygraphic studies demonstrate that L-tryptophan, unlike hypnotics, does not produce distortions of sleep physiology when first administered, on long-term administration, or after withdrawal.


The psychiatrist: in the mainstream or on the banks of medicine? The author discusses psychiatry's historical estrangement from general medicine, beginning with its isolation in mental hospitals, aggravated by a deterioration in medical school teaching of clinical psychiatry and by limited psychiatric training programs, and further alienated by much of psychosomatic theory and practice. He sees hope for reconciliation, however, in the recent progress of psychopharmacology and liaison psychiatry within the general hospital.


An outbreak of introduced malaria in California possibly involving secondary transmission. During 1974, 12 cases of Plasmodium vivax malaria were reported from an agricultural area in California's Sacramento Valley. At least three of these cases resulted from local mosquito transmission. The imported cases were in Punjabi immigrants except for one in an American-born visitor to the Punjab. This is the 11th reported outbreak of introduced malaria in the United States since 1952, and the first in California since 1957. A unique aspect of this outbreak is the likelihood that secondary transmission occurred. Extensive surveillance activities, including a house-to-house case-finding survey in a 15-square-kilometer area of suspected transmission, yielded no new malaria cases, but the activities may have increased awareness of malaria among both the medical community and the public, and thus facilitated the detection of later cases. The occurrence of local malaria transmission coincided with unusually high numbers of Anopheles freeborni. The increase in imported malaria cases probably reflects a resurgence of malaria in Punjab State, India.


Feeding preferences of Triatoma dimidiata maculipennis in Yucatan, Mexico. To determine whether a low preference for human blood by Triatoma dimidiata maculipennis Stal, 1859, the only known vector of Chagas' disease in Yucatan, Mexico, would account for the low prevalence of antibodies to Trypanosoma cruzi in man in the area, the intestinal contents of 924 bugs were tested against antisera to blood antigens of chicken, opossum, dog, bat, monkey, pig, goat, rabbit, horse, human, rat, ox, cat, and armadillo. Although the chicken was the primary host, man was fed upon frequently; thus, the hypothesis was rejected. Other explanations must be found for the relative lack of antibodies against T. cruzi in humans in Yucatan.


Malarial lung: report of a case from Africa successfully treated with intermittent positive pressure ventilation. We describe the first recorded case from Africa of malarial lung, acute pulmonary insufficiency in Plasmodium falciparum malaria. The patient was successfully treated with intermittent positive pressure ventilation (IPPV). There was heavy parasitemia, preceding cerebral complications and rapid onset of pulmonary edema in the absence of fluid overload or cardiac failure. A further complication of polyuria from tubular dysfunction developed whilst the patient was being ventilated. IPPV may have an important place in the management of this rare and usually fatal complication of falciparum malaria.