Incidence of oral candidiasis during therapy with triamcinolone acetonide aerosol.

During treatment of 63 asthmatic patients for up to 12 months with an investigational drug, triamcinolone acetonide aerosol, no clinically diagnosed oral candidiasis occurred. After 14 months of treatment one patient (1.6%) developed an oral fungal infection. This low incidence prompted a survey concerning the incidence of oral candidal infection in the patients who took part in the entire clinical trial program of triamcinolone acetonide aerosol. The survey revealed a 2.5% occurrence of oral candidiasis among 674 patients who completed at least four weeks of treatment. While direct comparisons were not available, the incidence of oral candidiasis during treatment with triamcinolone acetonide aerosol was lower than that reported for other similarly administered steroid drugs.


Leukocyte changes and interferon production in calves injected with hydrocortisone and infected with infectious bovine rhinotracheitis virus.

Correlations between leukocyte counts and serum interferon titers were determined in calves given hydrocortisone (HC) and infectious bovine rhinotracheitis (IBR) virus. Calves were injected with either 1 mg or 3 mg of HC/kg of body weight every 8 hours for a total of 9 injections each. Control calves were given placebo injections. Viral inoculation was given IV 10 hours after the 1st dose of HC or placebo was given. By the time of viral inoculation, all calves injected with HC had developed neutrophilia, and the calves injected with 3 mg of HC also developed leukocytosis, lymphopenia, and eosinopenia; total leukocyte counts in calves injected with 1 mg of HC were increased, but not as much as in other HC-treated calves. Leukocyte counts in calves given placebo remained essentially unchanged before viral inoculation. At 1 day after IBR virus was inoculated, the number of circulating lymphocytes in HC-treated calves and control calves was decreased by more than 50%, on the average, of the counts taken before the HC injections or inoculation of virus. A significant negative correlation existed between the numbers of circulating lymphocytes and serum interferon titers at 1, 2, and 3 days after inoculation with IBR virus. The interferon response of calves undergoing lymphocyte suppression due to HC was not impaired, but was enhanced.


Lactoperoxidase, thiocyanate, and free cystine in bovine mammary secretions in early dry period and at the start of lactation and their effect on Streptococcus agalactiae growth.

The concentrations of lactoperoxidase (LP) and thiocyanate (SCN-) in the mammary secretions of 4 dairy cows in the early dry period were similar to or higher than concentrations in the milk before drying off. The concentrations of free cystine progressively increased in the secretions beginning 3 to 5 days after the last milking; the mean concentrations were 0.66 mumoles/L before drying off and 6.66 mumoles/L after drying off. The mean concentrations of free cysteine were 0.28 mumoles/L before drying off and 1.4 mumoles/L after drying off. The secretions, when diluted in steamed milk, showed greater stimulation of Streptococcus agalactiae growth as the drying-off period progressed. This increase in stimulatory activity was attributed primarily to the increased concentrations of cystine because cystine counteracts the LP/SCN-/hydrogen peroxide inhibitory system for S agalactiae. This effect on the LP system may account for any increase in susceptibility to S agalactiae under infection during the dry period. In 3 other cows, the mammary secretions on the day of calving had lower mean concentrations of LP, SCN-, and free cystine and cysteine than those obtained 4 to 5 days before, and 7 to 8 days after calving.


Pancreatic duct ligation in the therapy of chronic pancreatitis.

Total ligation of the pancreatic ducts of a normal gland in dogs and man results in atrophy of the acinar cells with preservation of islet cell function. Theoretically, this might be applied in the therapy of chronic pancreatitis since, in effect, an exocrine pancreatectomy results. Sustained islet cell function, as evidenced by a normal glucose tolerance test, following pancreatic duct ligation, was demonstrated in dogs for periods of up to two years. Resection of the head of the pancreas and ligation of the distal gland in six patients with chronic pancreatitis and an abnormal glucose tolerance test resulted in the development of insulin-dependent diabetes in all instances. Insulin-dependent diabetes was also demonstrated in one patient with a normal preoperative glucose tolerance test. Recurrent pancreatitis developed in only one patient. The study suggests that pancreatic duct ligation is effective in treating chronic pancreatitis but casts considerable doubt on the effectiveness of this procedure in preventing the development of diabetes, if the glucose tolerance test is abnormal


[Anosmia and hypogonadism (Kallman's or Maestre de San Juan's syndrome (author's transl)].

A patient, aged 15 years and three months, with hypogonadism and anosmia (Kallman's syndrome or Maestre de San Juan's syndrome) is presented. It is an sporadic case, with no associated abnormalities, who had been seen due to a lack of sexual development. Basal levels of plasmatic LH and FSH were lower than the sensitivity threshold of the method: 1.5 mlU/ml. Administration of 100 ng of GnRH alone in one dose did not evoke any change of these levels; when the same dosage was given during five consecutive days, plasmatic levels of both gonadotropins increased. Initial treatment with HCG (5,000 IU, biweekly) evoked very favourable changes in somatic and genital development.


Physostigmine reversal of diazepam-induced hypnosis. A study in human volunteers.

Under randomized double-blind conditions, 1.00 to 1.67 mg of intravenous physostigmine (Antilirium) reversed sleep induced by administration of 0.102 to 0.238 mg/kg body weight of intravenous diazepam in eight healthy human volunteers. Awakening occurred 330 to 740s after initiation of the physostigmine infusion at a rate of 0.5 mg/min every 4 min. Diazepam plasma levels were not significantly different at the start of either the physostigmine or placebo infusion. Physostigmine did not effect plasma binding of diazepam. Six subjects experienced nausea, and one subject developed an arrhythmia. Physostigmine reverses diazepam-induced hypnosis but causes side-effects requiring cautious administration.


Patients who amplify bodily sensations.

Patients troubled by symptoms, regardless of the degree of demonstrable disease, are subject to fources that cause them to amplify, focus upon, and worry about these bodily perceptions. These forces are psychological, sociocultural, or part of the medical care process. Optimal management of the symptomatic and somatizing patient thus entails obtaining psychological information about emotional precipitants, relevant childhood experiences, psychiatric disorders, and the personal meaning of the symptom; searching for the somatizing personality themes of masochism and guilt, hostility, and dependence; understanding the patient's goals in obtaining medical care, such as information and explanation, psychological counseling, or social and administrative intervention; and assessing situational stress, secondary gain, and ethnic and cultural forces that foster the amplification of physical symptoms.


Eosinophils in the cerebrospinal fluid.

Eosinophils in the cerebrospinal fluid are an uncommon finding that is most often the result of a helminthic infection of the central nervous system. Information from the recorded literature suggests the differential diagnosis of this clinical observation is relatively limited. Therefore, in the appropriate clinical circumstances, cryptic cases of central nervous system disease might be resolved or the diagnostic possibilities at least narrowed by finding these cells in the cerebrospinal fluid.


Poststreptococcal acute glomerulonephritis: fact and controversy.

Poststreptococcal acute glomerulonephritis is prototypic of the immunologic glomerulonephritides. It most commonly follows streptococcal infection of the pharynx or skin. The diagnosis is usually not difficult when a nephritic clinical presentation (with such manifestations as hematuria, edema, and hypertension) is associated with serologic evidence of recent streptococcal infection and a depressed serum complement concentration. Currently, however, the nephritogenic antigen(s) has not been identified and has not been shown to be the same antigen for all nephritogenic streptococci; it may not even be a part of the infecting organism. The development of a vaccine to prevent this illness from occurring is therefore still not possible. Whether poststreptococcal acute glomerulonephritis progresses to chronic renal failure is still uncertain. Painstaking laboratory research together with careful, prospective long-term follow-up studies of patients with poststreptococcal acute glomerulonephritis may provide some of the answers to these critical questions.


Computed tomography in the diagnosis of intracranial disease.

The introduction of computed tomography has revolutionized neurodiagnosis. This diagnostic procedure makes it possible to define intracranial anatomy by visualizing structures of different radiodensities. Computed tomography may detect and define the underlying pathologic processes more directly than is possible with other diagnostic procedures and has reduced the need for invasive contrast procedures.


Infection due to Corynebacterium species in marrow transplant patients.

A Corynebacterium species consistently resistant to all antibiotic therapy except vancomycin caused bacteremia in 32 of 284 (11%) marrow transplant patients. Twenty-one patients had colonization or infection before bacteremia. Twenty-six of the 32 patients were males, and males older than 16 years were infected significantly more often than females over 16, or than all patient under 16. A case-control study showed that infected patients had greater exposure to antibiotics; more often had failure of engraftment and persistent granulocytopenia; were in laminar air-flow rooms less often; and had greater inhospital mortality. Cultural surveillance showed that 17 of 42 marrow transplant patients were colonized with Corynebacterium species. Likelihood of colonization appeared related to age, sex, and duration of hospitalization. Prevalence of colonization in other populations was 1% in nonhospitalized healthy adults and 13% in adults in a general hospital. Corynebacterium species infections occur primarily in adult males with granulocytopenia, mucocutaneous defects, and receiving intensive antibiotic therapy.


Campylobacter enteritis: clinical and epidemiologic features.

Campylobacter fetus subspecies (ssp.) jejuni has been recently recognized to cause diarrheal disease in man. To assess its importance as an enteric pathogen, we prospectively studied 514 patients with diarrhea. Campylobacter fetus ssp. jejuni was isolated from the feces of 26 patients (5%) and seven of 11 of their symptomatic household contacts. This organism was isolated from the feces of only one of 18 asymptomatic household contacts and not at all from 157 other healthy persons. Seventeen of 20 patients from whom C. fetus ssp. jejuni was isolated from fecal culture showed at least a fourfold rise in specific IgG titers. Review of 35 cases of campylobacter enteritis identified a typical clinical syndrome with acute onset of diarrhea, abdominal pain, fever, and constitutional symptoms. Stool examination revealed blood in 60% and polymorphonuclear leukocytes in 78% of patients. Epidemiologic investigation strongly suggested an external source for the infection in 22 of 35 patients.


Hemodialysis in the treatment of psoriasis. A controlled trial.

We have treated seven patients with severe psoriasis with sham or true hemodialysis. Three patients received one 24-h course of true hemodialysis over 4 d followed by an identical 24-h course 4 weeks later. Four patients received one 24-h course of sham diaglysis over 4 d followed by a 24-h course of true dialysis 4 weeks later. Significant subjective improvement was noted by both groups after the first series of treatments but not after the second. No objective improvement in skin disease was found at any time. We were unable to confirm the many uncontrolled reports on the efficacy of dialysis in ameliorating severe psoriasis. Neither the heparin used for anticoagulation, the acetate present in the dialysis bath, nor the removal of a "psoriatic factor" seemed to affect the skin disease in these patients.


Bretylium tosylate: a newly available antiarrhythmic drug for ventricular arrhythmias.

Bretylium tosylate (Bretylol) has recently been approved for parenteral use against resistant ventricular arrhythmias. The pharmacologic action of bretylium is complex, and its antiarrhythmic action differs significantly from other drugs. Bretylium is an adrenergic neuronal blocking agent taken up selectively at peripheral adrenergic nerve terminals, where it initially releases norepinephrine (sympathomimetic effect) and then produces adrenergic neuronal blockade. It has direct cardiac membrane effect to prolong action potential duration and effective refractory period but, unlike other membrane active antiarrhythmic agents, does not depress conduction velocity or automaticity. Bretylium increases ventricular fibrillation threshold and prevents the decrease in ventricular fibrillation threshold associated with myocardial ischemia. It does not depress myocardial contractility. Clinical studies have shown parenteral bretylium to be effective in suppressing ventricular arrhythmias, particularly recurrent, drug resistant ventricular tachycardia or ventricular fibrillation.


Multimodal primary cancer treatment (adjuvant chemotherapy): current results and future prospects.

In the 1970s chemotherapy has been successfully incorporated into curative primary treatment programs for various adult malignancies so that it is no longer solely palliative treatment for advanced disease. For at least three malignancies and tentatively a fourth (breast and colon carcinoma, osteosarcoma, and melanoma), certain groups of patients have had longer disease-free survival produced by the use of chemotherapy after surgical removal of the primary lesion. The potential impact on cancer mortality from these treatment results is obvious. We review here the fundamental laboratory concepts that have led to human trial of multimodal primary therapy regimens. Data from numerous clinical trials are analyzed, with delineation of the problems encountered in the interpretation of their results.


Closed eye techniques of intracapsular cataract extraction with intraocular lens implantation.

The advantages of a corneal incision are discussed and the general trend toward closed eye surgery, as well as the reasons for the trend, are defined and reviewed. The mechanics involved in my method are presented as well as the theory and use of the lens glide. Finally, the Beale Continuous Corneal Closure method is discussed. Though this suture may take as long as 8 to 10 minutes to place properly, when it is completed it provides the patient with total mobility and the surgeon with total peace of mind.


Size of donor corneal button and outflow facility in aphakic eyes.

Outflow facility was measured in 6 human eye bank eyes following penetrating keratoplasty and cataract extraction. A 7.5 mm corneal button was removed and replaced by an 8 mm button using conventional mid-to-deep stromal sutures. Baseline outflow facility in the phakic eyes (0.28 +/- 0.12 microliter/min/mm Hg, mean +/- SD) was unchanged (0.29 +/- 0.12) following the cataract extraction and penetrating keratoplasty using the larger corneal button.


[Cutaneous manifestations of malabsorption diseases (author's transl)].

Malabsorption (M) is characterized by absorption defect of one or several nutriments in small bowel. Its clinical expression is rarely obvious and biological signs are: anaemia, low serum protein, albumin and lipid rates, low serum calcium, phosphorus and potassium level, and hypoprothrombinaemia. But only 4 simple and reliable tests are needed for diagnosis: i. e.: daily faecal fat amount measurement, daily faecal nitrogen excretion, the xylose test and the Schilling's test. This syndrome is related to many conditions which can be divided into 2 groups with and without intestinal abnormalities. The relationships between M and skin diseases belong to 4 types (J. Marks and S. Shuster): 1) M is responsible for the cutaneous signs, 2) M is caused by a skin disease, 3) both M and skin disease are the result of a same cause, 4) M and skin disease are associated in an indirect way. Only the two first types are dealt with in this report. Skin manifestations occur as a complication in 10 p. 100 to 20 p. 100 of cases of M. They are mostly polymorphous or non-specific, as they are related to multiple vitamin or essential amino acid deficiencies and heal with the treatment of M. The main conditions encountered are diffuse pigmentation, acquired ichthyosis, follicular keratosis, nail brittleness and hair loss. Mucous membrane lesions, purpura and eczematoid or psoriasis-like dermatitis have also been described. More uncommon are clubbing of fingers, finger print abnormalities, kwashiorkor or acrodermatitis enteropathica-like eruptions. The dermatogenic enteropathy, i. e. a M syndrome due to a skin disease, occurs as a result of widespread involvement of the body for instance in psoriasis or eczema; its clinical expression is rarely obvious, the histological record of gut biopsy usually normal and the results of biological tests often dissociated, but steatorrhoea is frequently found. The pathogenesis of the condition is still unknown but its importance is related to the extent of the skin disease and it only improves with the treatment of the latter. All these features and others are discussed in the report with a comprehensive review of the literature.


Antibody activity in otitis media with effusion.

Bacteria were isolated from a high percentage of the effusions from patients with otitis media with effusion (OME, serous otitis media). In an attempt to determine if the isolated bacteria were involved in the disease process, we analyzed the serum and effusion of 25 OME patients for the presence of antibacterial antibodies by the indirect immunofluorescence antibody method. Specific antibody activity was detected in 20 of 25 effusions (80%) and 19 of 22 sera (86%). IgG antibodies were the most frequently found class of antibodies in both sera and effusions, but IgA antibodies were detected more frequently in the effusions than in the sera. Hemophilus influenzae, Streptococcus pneumoniae, and diphtheroids were the most frequently isolated organisms, and antibody activity to all bacterial species isolated was detected. The results support the concept that the isolated bacteria are not contaminants but are actively involved in the disease process.


Tissue adhesion with highly concentrated human fibrinogen in otolaryngology.

This paper summarizes a tissue adhesive system consisting of highly concentrated human fibrinogen and thrombin. The addition of blood-clotting factor XIII stabilizes the adhesive system against fibrinolysis. Although the adhesion system cannot and should not replace surgical suture, it provides valuable assistance in tissue synthesis and in local hemostasis, particularly in cases where conventional suture methods are especially difficult to apply. In addition to good adhesion, an elastic consistency, and good tissue compatibility, the adhesive is completely absorbed and, therefore, preferable to conventional tissue adhesives based on cyanoacrylate. The system has been used successfully in split thickness skin graft application, myringoplasty, repair of dural defects, hemostasis after tonsillectomy, and achieving an airtight seal in tracheoplasty.


[Sensitivity to antibacterial preparations of the pseudotuberculosis bacteria isolated on the territory of the Ukraine].

Sensitivity of 92 strains of the causative agent of pseudotuberculosis isolated in the Ukraine was studied with respect to 26 antibacterial drugs. It was found that the strains of the pseudotuberculous bacteria were sensitive to 17 drugs, i.e. benzylpenicillin, ampicillin, carbenicillin, cephaloridin, chloramphenicol, tetracycline, streptomycin, neomycin, monomycin, kanamycin, gentamicin, polymyxin, colistin, furadontin, nalidixic acid, sulfisoxazol and septrin. No differences in the sensitivity of the strains isolated in various districts of the Ukraine and from various sources were found. By their antibiotic sensitivity the strains isolated in the Ukraine did not differ from the cultures isolated in other districts of the USSR and abroad.


[Change in the biological properties of salmonellae in acquiring resistance to chloramphenicol].

Mutants of Salmonella typhimurium and Salmonella abony resistant to 40 microgram/ml of chloramphenicol were obtained during selection according to the method of Szybalski on Hottinger broth with increasing concentrations of the antibiotic. By the colony morphology the mutants were divided into 4 groups. The study of the mutant biological properties revealed changes in the growth rate characterized by elongation of the lag-phase and exponential phase, changes in the biochemical activity evident from lower fermentation rate of some carbohydrates and production of hydrogen sulphide and changes in some amino acid dependence. Increased cross resistance to tetracycline and benzylpenicillin and decreased resistance to kanamycin were noted. The LD50 of most mutants was increased as compared to that of the initial strains. Combination of several types of the changes was observed in some mutants. It is supposed that resistance to chloramphenicol in the mutants is due to mutations in several genes. Some of such genes had pleuotropic effect because of the changes in the structure of the ribosome 50S subunits.


Diagnosis of early endometrial cancer and precancerous states.

After a brief epidemiologic survey of endometrial cancer, the subject of detection and diagnosis of early lesions is addressed. Emphasis is placed on major gaps that exist in the knowledge of natural history of the disease. Cytologic and histologic detection and diagnostic techniques are reviewed and their advantages and disadvantages discussed.


[Effect of low doses of chloramphenicol on ribosomal precursor formation in E. coli cells].

RNA synthesized in the cells of E. coli CP 78 (rel+) in the presence of chloramphenicol low concentrations (5 microgram/ml) was found in 30S and 50S subunits and monosomes. A significant part of it was alotted to ribonucleoproteid or chloramphenicol particles. The protein content of ribonucleoproteid amounted to 22-25% and the content of RNA in it was equal to 78-75%.


The endocrine thymus.

The mediastinal, lympho-epithelial organ was termed thymus to denote a ductless, gland-like body which has the appearance of a "warty excrescence" (Greek, thymos). Early investigators had ascribed a functional role to this gland including the production of humoral factors which modulated cell growth, maturation and exerted influence on the process of mineralization. Investigators of the past decade have vindicated these observations and identified that the thymus is, indeed, an organ which "sets in motion, and spurs on" (Gr. hormaein) target tissues.


Histochemistry of steroid receptors in breast cancer: an overview.

Immunofluorescence and a new histochemical technique were employed to assay 226 breast cancer specimens for estrogen receptor. Results showed an overall correlation of 91 percent when compared to those of biochemical assays. The histochemical technique is rapid, easy to perform and reveals the same parameters as does immunofluorescence without the need for antiserum. Tumor cell receptor heterogeneity and location of receptor in cytoplasm or nucleus is readily defined by both methods. These histologic tests should prove to be useful in extending the availability of estrogen receptor analysis to all patients with breast cancer.


[Immunodepressive action of carminomycin and rubomycin derivatives].

The immunodepressive effects of carminomycin and its 3 semi-synthetic derivatives, as well as rubomycin and its derivative R-103 were compared. It was found that 14-hydroxycarminomycin was much superior to the other substances in the experiments with synthesis induction suppression of antibodies against sheep red cells in mice. Suppression of the rejection of the skin allogenic grafts in the mice by carminomycin was higher as compared to that by the other substances. Probably different populations of the immune competent cells have selective sensitivity to separate anthracyclines.


[Clinical effectiveness of carbenicillin in suppurative inflammatory processes of varying localization].

The study on sensitivity of clinical strains of the causative agents of purulent infections to carbenicillin showed that 34.6% of the staphylococcal strains, 48.1% of the E. coli strains and 40.3% of the Proteus strains were sensitive to the antibiotic. The strains of Ps. aeruginosa were characterized by moderate sensitivity to carbenicillin. The MTC for most of the isolates ranged within 25-128 microgram/ml. High therapeutic efficacy of carbenicillin in treatment of cases with purulent inflammatory processes of various localization was shown. Positive results were obtained in 82.5% of the adults and 76.2% of the premature infants treated with carbenicillin. A satisfactory therapeutic effect was observed in the cases with sepsis, diffuse purulent peritonitis and abscessing pneumonia treated with carbenicillin in combination with gentamicin.


Histochemistry of steroid receptors in prostatic diseases.

Tissue obtained from 55 men with prostatic disease was assayed for estrogen and androgen receptors by a newly developed histochemical technique. The material studied consisted of 45 specimens of benign nodular prostatic hyperplasia and 10 specimens of prostatic adenocarcinoma. The results obtained were compared to those of parallel biochemical assays in 17 cases and successfully correlated in 85 percent. The new procedure is rapid, inexpensive and accurate, allowing for the detection of receptor in cytoplasm and/or nucleus and evaluation of receptor heterogeneity. The histochemical method may offer an alternate to biochemical assay of prostatic tissue as contamination with steroid binding globulins does not appear to be a problem at this time.


[Course of dysentery and the specific alteration of the neutrophils in children in the use of monomycin and a diet with an increased protein content].

Acute dysentery mainly due to Shigella sonnei and dynamics of the neutrophil damage index (NDI) of the blood were studied in 80 children at the age of 1 to 14. 20 children (group 1) were treated with monomycin under conditions of a diet with an excessive content of protein (by 25% higher than the physiological norm). 60 children or 3 groups of 20 children each were not subject to such conditions and were considered as control groups. Reduction in the time of recovery (by 4 days) and bacteriological sanation (by 6 days) of the convalescents in the 1st group decreased as compared to that in the control groups. The test for the NDI of the blood was close in all the groups. It was concluded that an excessive protein content in the diet increased the efficacy of monomycin therapy in dysentery children. It is recommended that the diet with an excessive protein content be used in monomycin treatment of dysentery children.


Inhibition of Escherichia coli K-12 by beta-lactam antibiotics with poor antibacterial activity: interaction of permeability and intrinsic activity against penicillin-binding proteins.

The effect of methicillin, cloxacillin, 1078/1/1, penicillin G, and cephaloridine upon the penicillin-binding proteins of a permeability mutant of Escherichia coli K-12 and its isogenic wild type have been investigated. Comparison of the 50% inhibition values for the antibiotics against the penicillin-binding proteins of the two strains with the minimal inhibitory concentrations for the same compounds indicates that methicillin, cloxacillin, 1078/1/1, and to a lesser extent penicillin G, owe their poor antibacterial activity to exclusion from the bacterial cell, whereas cephaloridine is not excluded and is equally active against both the mutant and its wild type. The results further suggest that the lesion in the permeability mutant E. coli DC2 allows free access of all the compounds tested to the inner membrane target proteins.


Cefamandole therapy in anaerobic infections.

Thirty-one adult patients with infections due to anaerobic bacteria were treated with cefamandole. Bacteroides fragilis group (17) and Bacteroides melaninogenicus (13) were the most frequent anaerobes isolated. Duration of therapy varied from 2 to 49 days. Results were judged satisfactory in 26 cases, and unsatisfactory in 1 case. Four cases could not be evaluated. Adverse reactions occurred in 16 patients and included positive direct Coombs' test without hemolysis, transient liver function abnormalities, phlebitis, reversible neutropenia, fever, eosinophilia, and toxic epidermal necrolysis. The more significant reactions were associated with prolonged therapy. None was lethal. These data suggest that cefamandole is effective in treatment of most anaerobic infections.


Clindamycin in treatment of aspiration pneumonia in children.

Twenty-eight patients with anaerobic pleuropulmonary infections were treated with clindamycin alone or clindamycin with gentamicin. Sixteen of the patients presented with pneumonitis, nine with necrotizing pneumonia, and three with lung abscesses. The average length of treatment was 13.8 days, and the duration of temperature after initiation of therapy was 3.1 days. The predominant isolates were anaerobic gram-positive cocci (23 isolates), Bacteroides melaninogenicus (14), Bacteroides fragilis (9), and Fusobacterium nucleatum (11). The most frequent aerobic isolates were alpha-hemolytic streptococci (12), Diplococcus pneumoniae (12), Pseudomonas aeruginosa (9), Klebsiella pneumoniae (7), group A beta-hemolytic streptococci (5), Staphylococcus aureus (9), and Escherichia coli (6). All patients responded to the therapy and were cured of the infection. There were no side effects observed from the administration of clindamycin. None of the patients developed any blood dyscrasia, liver damage, diarrhea, or colitis. Clindamycin appears to be effective in the treatment of mixed aerobic and anaerobic pleuropulmonary infections in children, alone or with an aminoglycoside when indicated.


Effect of a Salmonella group H1 R factor on virulence and response of infections to antimicrobial therapy.

A group H1 R factor encoding resistance to chloramphenicol, streptomycin, sulfonamide, and tetracycline was transferred into Salmonella typhimurium LT-2. The virulence of LT-2 for mice, as assessed by intraperitoneal 50% lethal dose and the number of organisms in the spleen, was not affected by the R factor. On the other hand, the R factor conferred resistance in mouse infections to therapy with chloramphenicol and trimethoprim plus sulfamethoxazole.


Synergistic effects of ampicillin-aminoglycoside combinations on group B streptococci.

The in vitro activity of gentamicin, tobramycin, kanamycin, and amikacin in combination with ampicillin was determined against aminoglycoside-resistant group B streptococci. Synergy in each combination was determined by quantitative kill curves and demonstrated in all the combinations tested.


Thienamycin: new beta-lactam antibiotic with potent broad-spectrum activity.

Thienamycin, a new beta-lactam antibiotic, exhibited potent, broad-spectrum activity in vitro against gram-negative bacilli and gram-positive cocci, including many isolates resistant to currently available antibiotics. All isolates were inhibited at concentrations less than or equal to 25 mug/ml, with the exception of 12% of isolates of Enterobacter spp. and 3% of isolates of Serratia marcescens. Its activity decreased with an increase in inoculum concentration of from 10(5) to 10(7) cells per ml.


Nosocomial multiply resistant Klebsiella pneumoniae: epidemiology of an outbreak of apparent index case origin.

A nosocomial epidemic of multiply resistant (MR) Klebsiella pneumoniae characterized by resistance to gentamicin, tobramycin, kanamycin, cephalothin, chloramphenicol, and ampicillin occurred in a Veterans Administration hospital from 1975 to 1977. A total of 66 infected or colonized patients were observed in a 2-year period; there were 43 urinary tract infections, 13 wound or soft tissue infections, 8 pneumonias, and 6 patients with only asymptomatic stool colonization. Four patients had both pneumonia and a urinary tract infection. There were five secondary bacteremias. The majority of MR K. pneumoniae strains were type 30, but types 17, 21, and 23 and nontypable organisms were also recovered. Other gram-negative bacilli with the same antibiotic resistance pattern were isolated from 14 patients. Seven MR K. pneumoniae and three resistant Escherichia coli isolates were shown to transfer resistance to E. coli K-12. MR K. pneumoniae-infected patients were seriously ill, had long hospitalization times (mean, 67 days), and were in close geographic proximity to other cases. Compared with controls, cases more frequently had prior antibiotic treatment and urinary catheters, but not respiratory instrumentation, nasogastric tubes, or antacid treatment. The apparent source of the outbreak was traced to an index case who entered the hospital with an MR K. pneumoniae urinary tract infection. Asymptomatic gastrointestinal carriage without infection elsewhere was infrequent (1.6% of cultured patients), but 78% of patients with MR K. pneumoniae infections at other sites also had the organism in their stools. Hospital antibiotic usage was unchanged before and during the outbreak. The identification of an index case and relative lack of asymptomatic stool carriers are unique features of this plasmid-mediated MR K. pneumoniae epidemic. Although this MR K. pneumoniae outbreak appeared to be controlled by the use of isolation techniques, a simultaneous increase in gentamicin resistance among other gram-negative organisms was observed.


Physical characterization of ten R plasmids obtained from an outbreak of nosocomial Klebsiella pneumoniae infections.

Gentamicin resistance in Klebsiella pneumoniae involved in an outbreak at the Minneapolis Veterans Administration Hospital was due to a transmissible R plasmid. In addition to gentamicin, this plasmid conferred resistance to tobramycin, kanamycin, ampicillin, carbenicillin, cephalothin, chloramphenicol, and sulfathiazole. R plasmids which transferred this complex antibiogram were identified in several clinical isolates, including four different serotypes of K. pneumoniae, Escherichia coli, Enterobacter cloacae, and Proteus morganii. The covalently closed circular form of all R plasmids isolated had a sedimentation coefficient of 76S to 77S, corresponding to a molecular weight of 58 x 10(6). The possibility that a single R plasmid was responsible for the dissemination of multiple drug resistance among all of these different clinical strains was examined by characterizing the plasmids by using EcoRI restriction endonuclease. The same 15 fragments were obtained from each of the 10 plasmids analyzed. Their molecular weights ranged from 4 x 10(5) to 11 x 10(6). Thus, we conclude that each of the 10 plasmids present in the various clinical strains isolated from the hospital over a 7-month period originated from a common source and that R plasmid transfer was important in their spread.


Effect of clavulanic acid on the in vitro synergism between carbenicillin and gentamicin against Serratia marcescens.

Clavulanic acid, a potent beta-lactamase inhibitor, reduced the minimum inhibitory concentrations of carbenicillin for 13 of 15 clinical isolates of Serratia marcescens by at least eightfold. The combination of clavulanic acid and carbenicillin also exhibited synergistic activity with gentamicin against 11 of 15 isolates tested, including 9 of 10 strains which were highly resistant to carbenicillin (minimum inhibitory concentration >/= 8,000 mug/ml) and had previously been found resistant to the synergistic activity between carbenicillin and gentamicin.


Effect of propanolol on monosynaptic reflex activity during a task.

20 normal healthy subjects in a double-blind crossover experiment were given a table of either 40 mg propranolol or placebo half an hour before the beginning of the experiment. At rest and during the performance of a task, hert rate, Achilles tendon (T) and Hoffmann (H) reflexes were recorded. No increase in heart rate occurred during the task in the propranolol session. The increase of T-reflex amplitude, a common finding during the task under consideration, was larger in the propranolol session. No difference with H reflexes was found. It is concluded that the increase of T-reflex amplitudes during the task is caused only by fusimotor and not by sympathetic activity. It is speculated that if the sympathetic system plays a role at all, the effect on the T reflex is depressive rather than facilitating.


The position and organization of motor fibers in the internal capsule found during stereotactic surgery.

Data gathered from exploratory stimulation of the diencephalon in 130 stereotactic operative procedures have been studied, with the aid of a computer graphic technique, to show the position and topography of motor responses in the internal capsule. The results obtained indicate that pyramidal fibers are organized into a rostral-caudal face-arm-leg sequence and occupy a short compact band in the caudal third of the posterior limb of the internal capsule. This is in contrast to previous concepts of the position of these fibers in the capsule.


Bullous pemphigoid. Occurrence in psoriasis treated with psoralens plus long-wave ultraviolet radiation.

The occurrence of bullous pemphigoid during treatment for psoriasis has been described in the literature. We saw a case of psoriasis that was complicated by bullous pemphigoid in a patient receiving orally administered psoralen followed by long-wave ultraviolet radiation (PUVA) therapy. In our patient the localization of bullous lesions to psoriatic plaques demonstrates that the PUVA-treated psoriatic skin may have a decreased threshold for the development of clinical bullous pemphigoid. This suggests factors other than simple coexistence of the two diseases. Therapy with PUVA might induce bullous pemphigoid in psoriasis, either primarily or by facilitating the expression of a previously existing subclinical form of the bullous disorder.


Serological diagnosis of Candida albicans-balanitis and -balanoposthitis.

The Candida hemagglutination test (Candida-HA-Test), the complement fixation, Candida immunofluorescent test (Candida-IF-Test) and the agglutination-test were performed in 34 patients suffering from genital candidosis and in 34 healthy controls. The results obtained were: Candida hemagglutination and complement fixation titers are raised to the same extent in patients suffering from Candida albicans-balanoposthitis when soluble polysaccharide antigens are used in both tests. The high titers indicate a great portion of mercaptoethanol susceptible antibodies in those subjects. When compared with controls, the hemagglutination titers are fourfold lower than those of the patients. There is a four-to-sixfold decrease of the hemagglutination titers performed after mercaptoethanol treatment of the sera in the patients. On the other hand, there is only a twofold decrease of hemagglutination titers in the controls. In chronically infected persons the hemagglutination titers are within the normal range or are raised insignificantly. There is only a twofold decrease in HA-titers after treatment of the sera with mercaptoethanol. On the other hand, the agglutination- and the Candida-IF-titers seem to be elevated as a rule in chronically infected. In those patients the gamma G- and the gamma A-titers are significantly raised, too. The results mentioned above are discussed with regard to their clinical significance.


Recent advances in epidermal cell cultures.

Among the many skin culture systems, three have been selected in this short review because of their specific potentials in dermatological research. H. Green cultures newborn human forsekin keratinocytes on a mouse 3T3 feeder layer. Keratinocytes grow and keratinize. The feeder cells release factor(a) which allows serial propagation of keratinocytes to be achieved. The cell yield is further increased by adding epidermal grohth factor. This system has already proved to be a potent tool for the study of keratinization at the molecular level. A. Freeman has described a system in which explants of adult human skin are cultured on the dermal aspect of dead split-thickness pig skin. Keratinocytes can be passaged several times. Their differentiation is remarkable: it includes the production of keratohyaline, membrane coating granules, pemphigus as well as pemphigoid antigens. This system is interesting in the study of epidermal morphogenesis and may be applicable to the treatment of burns. The culture of epidermal cells from adult guinea pig ear in comparison with that of dermal fibroblasts is being used to study the specificity of action of pharmacological compounds on growth and keratinization of epidermal cells. Furthermore, the isolation (and culture) of pure populations of basal cells appears as a promising approach to the study of the mechanisms which moderate epidermal cell proliferation.


Action of staphylococcal epidermolysin: further observations on its species specificity.

Sensitivity to epidermolysin was tested in a number of species of the families of mice (muridae) and hamsters (cricetidae) and in hedgehogs. None of the animals proved sensitive except mus musculus (house mouse) and mesocricetus auratus (golden hamster).


A semiquantitative measurement of anti-nuclear antibody using immuno-microfluorimetry.

1. Using microfluorimetry, the strength of fluorescence was measured on fluoresceinated anti-nuclear antibody of SLE sera. The indirect "Sandwich" method was applied using human peripheral lymphocytes as substrates tissue. 2. The results of using three FITC-labelled anti-human IgG conjugates of different types were compared with each other. 3. More specific and more consistent results were obtained with conjugates with a lower F/P ratio and lower antibody and protein concentration that those in the case of conjugates with a higher F/P molar ratio and higher antibody and protein concentration. 4. The immuno-microfluorimetric technique is very useful for the objective determination of the results of fluorescence microscopy and for the comparison of conjugates of different qualities.


[Characteristic of endotoxin (and haemolysin) for S-, R- and M-forms of the enteropathogenic "E. coli" (author's transl)].

Endotoxins of E. Coli O 149, IN S-, R- and M-forms, were examined in comparison. Gas chromatography showed only quantitative differences in the amount of volatile fatty acids. Electrophoresis of immunsera and bacteriostatic potency of sera, showed the immunogenicity of those 3 endotoxins, in sequence: S leads to R leads to M. Endotoxin of enteropathogenic E. coli O 149 provokes haemorrhagic effects in bones marrow of mice. Endotoxin influences the reticulo-endothelial system (mobilization of immunocytes). Endotoxin does not provoke any changes in "ligated loop tests'.


[Role of possible endotoxin contaminants present in some preparations of biological products and injectable drugs].

On the basis of personal contributions and of most recent data, the A. reports some observations and comments regarding the role of possible contaminating endotoxins demonstrated in some biological products and parenteral solutions used in clinical and experimental studies. Since endotoxins even in minute amounts have a variety of biological effects, the use of such contaminated preparations can lead to spurious results and erroneous conclusions. The Limulus assay appears to be a rapid, specific and sensitive method for detection and quantitation of endotoxin in various biological and pharmaceuticals products before they are used in clinical and experimental investigations.


An in vivo evaluation of microaggregate blood filtration during total hip replacement.

In order to evaluate the effect of microaggregate blood filtration on pulmonary status, hemostatic status, and incidence of infection, a prospective study was performed on patients undergoing elective total hip replacement for osteoarthritis. Forty patients were randomized to either a 260 micron standard filter group or a 20 micron microaggregate filter group. Patients were monitored pre- and postoperatively for changes in arterial blood gases and in vitro test of hemostasis. Postoperative measurements were also made of the total volume of blood collected from the operative wound drain and of the number of infections incurred by patients in the two filter groups. Average transfusion was 4.0 units for the standard filter group and 4.6 units for the microaggregate filter group. Results showed that postoperatively, either immediately or after 48 hours, there were no statistically significant differences (p greater than 0.05) between either filter group for any of the tests of pulmonary or hemostatic function evaluated. For infection no trends were found to suggest that microaggregate filters conveyed any protective effect. These data suggest that routine microaggregate blood filtration of up to 5 units of blood is not required.


A method for primary reconstruction following radical excision of sacrococcygeal pilonidal disease.

A great variety of procedures have been proposed for the cure of Sacrococcygeal pilonidal disease. Initial enthusiasm has usually given way to disappointment when it is realized that the treatment is painful, the hospitalization is prolonged, the aftercare is tedious or the original condition appears to have recurred. A technique is described which permits the total extirpation of cyst and sinus tracts while allowing for a tensionless wound closure by advancement of a buttock flap. Hospitalization is brief and the postoperative course is comfortable. Fifty such operations have been performed since November 1968. In the first group of thirty patients operated upon between three and ten years ago, a single bonafide failure occurred. An additional twenty patients have been successfully treated for an overall failure rate of 2%.


Conservative management of the prolapsed mitral valve.

Prolapsed leaflet is the result of ruptured chordae, elongated chordae, or ruptured papillary muscle. Various techniques adapted to each of these lesions were developed, and repair of 213 prolapsed mitral valves was performed between 1969 and 1977. There were 109 patients with ruptured chordae treated by quadrangular resection of the prolapsed leaflet; 103 patients with elongated chordae were treated by either a "sliding plasty" of the papillary muscle or a "shortening plasty" of the chordae; and 1 patient with ruptured papillary muscle was treated by reimplantation. The great majority of patients had an associated annular dilatation or deformation requiring the use of a Carpentier ring to remodel the annulus and reinforce the repair. The operative mortality was 4% and the late mortality, 3%. There were 6 reoperations, 3 of which occurred within 1 year. Thromboembolic complications occurred in only 1 patient (0.5%), even though the majority of patients received no anticoagulation treatment. Actuarial curves demonstrated a 91% survival at 8 years.


[Recent data about microorganisms of the genus Serratia (author's transl].

The Authors on the basis of most recent references, expose the epidemiological, cultural, biochemical and taxonomical characteristics of microorganisms of the genus Serratia. In addition the most recent data regarding the typing and the sensitivity to antibacterial agents are discussed.


[Research of the RNA-coliphages, in comparison with usual microbial and chemical indexes of biological pollution, for hygienic and sanitary evaluations of coast-waters (author's transl)].

Hygienic significance of the usual microbial (E. coli, Enterococci, Clostridia) and chemical (COD, NH3, NO2) indexes of sea-water biological pollution was investigated, in comparison with RNA-coliphages assay. E. coli was confirmed as an easily measurable and significant index of biological pollution (at least for routinary investigations), while the other microbial and chemical parameters do not significantly increase the hygienic selectivity of the E. coli assay. RNA-coliphages assay, on the contrary, is able to increase the hygienic selectivity of sanitary investigations, particularly in lowly polluted coast-water. This behaviour of RNA-coliphages is in accordance with their great persistance in sea-water, due to their survival-time, closely comparable with human viruses. RNA-coliphages assay is therefore proposed as a simple and useful index of "viral pollution" for a complete hygienic evaluation of sea-water environment in addition to routinary E. coli assay.


Median sternotomy dehiscence.

Sternal dehiscence requiring reoperation occurred in 36 out of 4,531 patients who had a sternotomy incison within an eight-year period. Twisted sternal wire sutures were used for the first four years and a crimped steel plate fixation was used during the second four years with a marked and significant decrease in the incidence of dehiscence from 17 out of 1,000 patients to 3 out of 1,000 patients. Thirty-five of the 36 patients were men, and 4 required reoperation for bleeding. Other factors such as mammary artery dissection, tracheostomy, and body weight of more than 82 kg were not significant. Although infection was noted in 20 patients, it was thought to be secondary. Early reoperation with antibiotic irrigation achieved wound stability in the 34 survivors with only 3 patients requiring additional procedures for chronic osteomyelitis of the sternum.


[Report on Citrobacter strains having antigenic relationship with "E. coli", and their characteristics (author's transl)].

During a research done on the diffusion of enteropathogenic E. coli in a children's community, 24 strains of Citrobacter have been isolated. By agglutination and agar-gel diffusion techniques, they looked to have some somatic antigens in common with those serogroups of enteropathogenic E. coli. The results were as follows: 14 strains were correlated with the serogroup O111; 9 strains with the serogroup O125 and 1 strain with the serogroup O55. The isolation of these strains has been made at the same period when we have found out the E. coli of homologous serogroups, even if they didn't belong to the same subjects. The colicine typing and sensibility to antibiotics tests made both on Citrobacter strains and on E. coli ones of homologous serogroups haven't pointed out other characteristics of identity. Furthermore, antigenic relationships between the 24 strains of Citrobacter and different serogroups of Salmonella have been demonstrated, that is: the strains containing the somatic antigen O111 were correlated with the serogroup O35; the strains having the somatic antigen O125, with the serogroup O6, 14, 24 and the strain containing the somatic antigen O55, with the serogroup O50. The presence of these strains in normal subjects only, gives a further witness that their role in enteric infections remains to be demonstrated.


[Filaments of the "Candida albicans" in human serum (author's transl)].

A study on human serum activity on Candida albicans cells has been carried out. In smear microcultures the microcolonies morphogenesis and the thread formation in the presence of serum, as well as the reappearance of normal yeast cells after re-growth in normal nutrient agar has been assessed. The serum globulin-fraction appeared to have the greatest germ-tube inducing activity: an heat-sensitive quality that went lost after 30 minutes at 100 degrees C. The multiplying activity of the Candida cells was almost completely abolished in the presence of serum. Realying on these experimental findings the AA. suggest that a demaging factor may be present in sera, linked to the globulin protein fraction, that hinders the Candida cell-wall normal synthesis: hence follows the appearance of threads, mostly deprived of multiplying activity. A condition in some way akin to the well known filament inducing activity of penicillin on Gram-negative bacteria.


Early and late results with the Mustard operation in infancy.

Eighty-one patients, ranging in age from 36 hours to 24 months and in weight from 2.5 to 12 kg had a Mustard operation for D-transposition of the great arteries (D-TGA) (20 with complex D-TGA) using either deep hypothermic circulatory arrest (68 patients) or conventional cardiopulmonary bypass (13 patients). A Dacron patch was used for the intraatrial baffle and pericardium for augmentation of the pulmonary atrium. Ten patients died following operation. Thirty-two patients had cardiac catheterization 1 year after operation. Of 24 patients with D-TGA and intact ventricular septum, 23 had normal pulmonary artery pressures. In 20 patients left ventricular outflow tract gradients decreased from a mean of 32 mm Hg to a mean of 18 mm Hg after operation. Five patients who had D-TGA and ventricular septal defect and systemic pressures in the left ventricle before operation, had a notable decrease in left ventricular pressures after the procedure. Seven patients required reoperation for baffle obstruction. Mortality following Mustard repair was primarily related to the complexity of the lesion, maturity of the infant, and degree of pulmonary vascular changes. Caval obstruction was related to the configuration of the baffle used in the early part of this series.


Is histidine essential for the adult man? A review.

Recent experimental observations as well as theoretical considerations suggest that histidine may be an essential amino acid for the adult man. In this paper, an up-to-date review of the literature on the essentiality of histidine is presented. Some practical implications of the indispensability of this amino acid in the human diet are also discussed.


Metabolic products of microorganisms. 181. Chitin synthase from fungi, a test model for substances with insecticidal properties.

Chitin synthase from Coprinus cinereus (Schaeff. ex Fr.) S. F. Gray (= C. lagopus sensu Buller) was used as a model for chitin synthase from insects. The effect of dimilin (difluorobenzuron), captan (trichloromethylsulfonyl fungicide), kitazin P (organophosphorus ester fungicide) and parathion (organophosphorus insecticide) on the fungal enzyme was compared with the effect of nikkomycin (nucleosidepeptide antibiotic).


Effects of dopamine agonists and antagonists in Tourette's disease.

The actions of haloperidol, dextroamphetamine sulfate, levamfetamine succinate, apomorphine, and piribedil were studied in two patients with Giles de la Tourette's disease in an attempt to clarify the catecholamine mechanisms involved in this condition. Both dextroamphetamine and levamfetamine increased the severity of the symptoms; dextroamphetamine was more potent. Haloperidol controlled the symptoms and also antagonized the effect of dextroamphetamine. Apomorphine injections reduced the severity of symptoms, even in the presence of dextroamphetamine. We conclude that dopamine rather than norepinephrine is the principal catecholamine responsible for the symptoms. The effect of apomorphine may be understood through its action on postulated presynaptic inhibitory dopamine receptors, or other presynaptic mechanisms of action.


Immunocytochemical identification of human chorionic gonadotropin. Comparative study of diaminobenzidine and 3-amino, 9-ethylcarbazole, a nonhazardous chromogen.

An immunomicroscopic study evaluated 55 fixed, paraffin-embedded tissues from surgical and necropsy-accessioned material reflecting a variety of physiologic and pathologic disorders. The sensitive unlabeled (peroxidase-antiperoxidase) immunoperoxidase technique was used. Cytoplasmic human chorionic gonadotropin (CHCG) was readily identified in syncytial trophoblastic cells. The only tissue sections that did not demonstrate CHCG activity were primary and secondary testicular teratocarcinomas without choriocarcinoma components. When the technique was reevaluated for the non-hazardous chromogen 3-amino, 9-ethylcarbazole, excellent results were achieved with equivalent staining distribution and intensity. The unlabeled immunoperoxidase method for the identification of CHCG is a sensitive, reliable, confirmatory immunohistochemical stain. A relatively safe chromogen can be substituted for the benzidine derivatives in the procedure with equivalent results.


Rapid slide agglutination test for Lancefield grouping of streptococci.

A rapid slide agglutination test (the Phadebact [PB] Streptococcus test) was compared with the standard autoclave extraction method of Lancefield and presumptive clinical laboratory tests for grouping of streptococci (bacitracin disk sensitivity for group A and sodium hippurate hydrolysis for group B). Identification of group A streptococci by the PB kit was statistically as accurate as by the Lancefield method, whereas bacitracin grouping was significantly less accurate than the Lancefield method (P = less than .02). With regard to group B, there was no statistically significant difference between the PB test and the sodium hippurate test. The PB test correctly identified all group C and G streptococci. The PB kit provides a rapid and reliable method for Lancefield grouping of streptococci.


Immunofluorescence study of skin rash in patients with dengue hemorrhagic fever.

Fifty-three skin biopsy specimens obtained from the cutaneous rashes of patients who had dengue hemorrhagic fever (DHF) were studied by immunofluorescence technique. Six specimens showed deposits of IgM, beta 1 C-globulin, dengue antigen, and fibrinogen during the first week of fever. Some but not all of these components (IgM, beta 1 C, dengue antigen) were demonstrated in 29 specimens. Twenty-three of them yielded negative results. Granular deposits of IgM and beta 1 C appeared in the blood vessel walls of dermal papillae. Dengue antigen was seen in mononuclear cells that were closely infiltrated around the blood vessel wall in dermal papillae. Fibrinogen was located within or about the blood vessels. The findings suggest that the cutaneous rashes occurring in DHF are caused by an immunopathologic process.


Hypertrophy and hyperplasia of islets of Langerhans associated with androgen therapy.

Hypertrophy and hyperplasia of the islets of Langerhans were observed in three patients treated with androgen-anabolic steroids for aplastic anemia. These patients formed a unique subset of patients with aplastic anemia in that they all had Fanconi's anemia, all demonstrated glucose intolerance following institution of androgen therapy, all had received androgen for at least 42 months prior to death, and all had coexistent benign liver cell tumors. Androgen-induced glucose intolerance may play a major role in the pathogenesis of both the pancreatic and hepatic abnormalities.


The use of free microvascular flaps in the leg. Their value in orthopaedic surgery.

After discussing the conventional techniques available for covering skin defects in the leg with associated complex orthopaedic problems the value of the free flap is empahsised. The technique is discussed briefly and six cases are presented. The advantages of this method are outlined and the improvement in healing afforded by the extra blood supply in cases where there is infection and exposure of bone or plate is stressed. Where large complicated skin defects can be predicted, early co-operation between orthopaedic and plastic surgeons is advised.


[Tissue compatibility of gentamycin PMMA beads and chains (author's transl)].

In chronic bone tissue infections a very effective local antibiotic therapy can be achieved by temporary implantation of Gentamycin-PMMA beads. Eight weeks later the chains were removed and the surrounding specimens of bone were subjected to histological examination. On the basis of the results, it was established that the beads were encapsulated in neutrophile granulocytes, collagen fibers and foreign giant cells.


Fresh immature articular cartilage allografts. A study on the integration of chondral and osteochondral grafts both in normal and in papain-treated knee joints of rabbits.

The integration of immature cartilage allografts to knee joints of both normal rabbits and those submitted to arthritis through papain was studied for a period of up to 9 months. Two types of grafts were compared: chondral--constituted only by cartilage, and osteochondral--cartilage plus a thin layer of subchondral bone. The integration of the grafts was analyzed through inspection of the articular surface and histologic sections. The viability of the grafts was checked through the incorporation of 35SO4 on the chondral matrix. The following conclusions were drawn: (1) A large member of the grafted cartilages were well accepted without histological evidence of immunological rejection, and metabolically active 9 months after transplantation. (2) The chondral graft was found to be superior to the osteochondral one regarding the integration, but both showed tendency to degeneration with time. (3) The presence of arthritis previously induced by papain affected the integration of the grafts causing a higher precentage of degeneration on the grafts causing a higher precentage of degeneration on the grafted cartilage.


Rapid arthrodesis of the ankle joint via verticalisation of the joint space.

A technique of arthrodesis of the ankle joint under television control and with the aid of a special milling-cutter is presented. A bone graft is obtained from the ankle and turned in two planes, so that the joint space becomes vertical. The operation time is shortened to 8--10 min. After two weeks the patient can walk, in a walking-cast, weight-bearing. Bone fusion is obtained in 3--4 months. Thirty-two cases were operated on, and in 30 a painless osseous fusion of the ankle, in a functional position was obtained. The technique is indicated only in cases in which, operatively, the foot can manually be reduced to a functional position.


[Critical study on the operative treatment of scaphoidpseudarthrosis (author's transl)].

At first causes for the emergence of os naviculare non-union and therapeutical principles are discussed. The Matti-Russe operative procedure, after a thorough evaluation of all available possibilities, seems to be the method most preferable. Seemingly bad results most of the time occur due to technical errors and mistakes in selection of the transplant. Furthermore sources of error in placing the skin incision, in extirpation of the pseudarthrosis gap, in preparation of the graft bed and in styloidectomy are explained in detail. Recommendations for the post-operative management are presented.


Renal transplantation for end-stage myeloma kidney: report of a patient with long-term survival.

A patient had prolonged survival after renal transplantation was performed for myeloma kidney. Continued function of the allograft without evidence of recurrent myelomatous involvement suggests that transplantation be considered for patients with multiple myeloma in whom renal failure constitutes the major problem.


Evaluation of effects of sexual steroids on the hypothalamic-pituitary system of animals and man.

Specific neuroendocrine regulatory mechanisms in rats and mice are known to be involved in the development of pituitary tumours (prolactinomas) in systemic tolerance and carcinogenicity studies of oestrogens, certain progestagens and their combinations. However, the susceptibility of the strain used seems to be of decisive importance. High doses of oestrogens may also, in special cases, stimulate development of PRL cell hyperplasia and tumours in humans. In other species such as the hamster long-term treatment with oestrogens results in hyperplastic and neoplastic changes in MSH-producing cells of the pars intermedia of the pituitary gland. On the other hand, in the dog and monkey, steroid-related pituitary tumours were not observed, in spite of long-term treatment with high doses of oestrogens, progestagens and their combinations. The capability of certain progestagens to stimulate canine GH secretion seems to play a major role as mediator of the species-specific progestagen-induced changes (mammary tumours, diabetes- and acromegalic-like syndrome) in the beagle dog. These progestagens also seem to have, in addition to their antigonadotrophic properties, an inhibitory effect on CRH-ACTH and TRH-TSH activity in the beagle bitch. These effects can be demonstrated in both the hypothalamic-pituitary system and in the corresponding peripheral target organs. These findings in the dog were not comparable to the situation in other species including man. The extent to which all these results in different species are applicable to other species depends on whether their neuroendocrine control systems are qualitatively and/or quantitatively similar. The physiological significance of the different pituitary hormones, sensitivity of target organs as well as a certain genetic disposition in the different species should also be considered. All these factors can vary from species to species. From these facts, it can be easily appreciated that results of experiments on different species with a substance possessing the same quality of biological effect in these species (e.g., oestrogen, progestagen, etc.) can only be compared when the experimental procedure takes account of the effect of this substance on the neuroendocrine system of the different species, and when dosage, mode of administration and period of treatment are correspondingly matched to the physiological conditions of each species.


Physiological mechanisms of diethylstilbestrol organotropic carcinogenesis.

Treatment of pregnant women with diethylstilbestrol (DES) during pregnancy has been demonstrated to be associated with an increased risk in the female offspring for development of an otherwise very rare type of malignancy: clear-cell adenocarcinoma of the vagina and cervix. The present knowledge about this association is reviewed. In experimental animals, many different types of malignancy can be induced by DES administered in large doses and during long periods. For the human situation there are as yet no indications that exposure to DES during fetal life has resulted in any generally increased incidence of malignant tumors. By injecting neonatal mice with DES for the first five days after birth, histologically malignant changes develope in the uterine cervix of the animals when more than one year old. A comparison is made between this animal model and development of tumors in the human female offspring of DES treated mothers. In the female mice, neonatal DES treatment results in a disturbed epithelial differentiation process in the upper part of the vagina and the uterine cervix, a disturbed development of the hypothalamic-pituitary gland control system as well as a disturbance in the normal development of the lymphoid system. The abnormal epithelial differentiation process results in development of adenosis and within these areas the malignant changes later appear. We do no know whether adenosis is a pre-cancerous condition or not, in the meaning that it contains dormant malignant cells. Other factors could act upon adenosis to result in cancer. The reasons for DES being called a "carcinogen" are reviewed. The possibility for factors in the environment acting as potential transplacental carcinogens in the human fetus should not be excluded.


Diethylstilbestrol metabolic transformation in relation to organ specific tumor manifestation.

Oxidative biotransformation of the synthetic estrogen diethylstilbestrol (DES) gives rise to several reactive compounds. Two mechanisms are proposed concerning the possible involvement of reactive metabolites in the organotropic tumorigenesis of DES. The first mechanism suggests an affinity of the metabolite to the estradiol receptor present in estrogen target organs. This has been shown for the olefinic epoxide of DES. The second mechanism is based on the organ specific oxidation of DES by peroxidase. The intermediates of this reaction were found to bind to nucleic acid and protein in a manner characteristic of chemical carcinogens.


[Oral contraception and multiple sclerosis].

The uncertain question of the use of oral contraceptives by women with multiple sclerosis is discussed. Reference is made to results observed in animals with experimentally induced allergic encephalitis subjected to oestroprogestin management. The course of M.S. during pregnancy is examined and the effects of blood lipid changes produced by oestrogens and progesterone, on the assumption that M.S. is due to a deficiency of unsaturated fatty acids. Lastly, attention is directed to interference with immunity, clotting, and platelet changes, these being factors in the spread off the disease. The data point to a protective rôle on the part of oestrogens, while the picture for progesterone is less conclusive. It would seem that these biological and immunological findings justify the use of oral contraceptives in subjects with M.S., though due caution is imposed by the absence of clinical and epidemiological data.


[Production of injection replicas of microvessels for scanning electron microscopy using resin "PN-8"].

A method for obtaining injection replications of microvessels for scanning electron microscopy using nonsaturated polyether resin PH-8 is described. Possible applications of the method in question to study microcirculatory bed are discussed. With resine PH-8 it is possible to obtain complete and detailed replications which give information on three-dimensional organization both of the microcirculatory bed and of the vascular microrelief peculiarities.


[Simple method of demonstrating adrenergic nerve structures in human and animal tissues using a glyoxylic acid solution].


[Cryptococcosis of the central nervous system: evaluation of amphotericin-B, 5-fluorocytosine and miconazole therapy in 18 cases].

Results obtained in the treatment of cryptococcosis of the central nervous system with amphotericin-B, 5-fluorocytosine and miconazole are evaluated. The evaluation is based upon 18 cases. Emphasis is given to data pertinent to aspects proper to 7 of them, submitted to chronic immunosuppressive treatment due to previous kidney transplantation. Side effects varied from case to case in the patients submitted to amphotericin-B and 5-fluorocytosine treatment. The intrathecal and the intraventricular administration of amphotericin-B was followed by complications of several types. Miconazole was used in one case. Its intravenous and its intrathecal administration did not provoke remarkable side effects.


Clinical specular microscopy and intraocular surgery.

Seventy patients were studied prospectively, using the clinical specular microscope, to compare and evaluate the effects on the corneal endothelium of routine intracapsular cataract extraction (ICCE), ICCE with intraocular lens (IOL) implantation, phacoemulsification, and penetrating keratoplasty. Results showed a 6% cell loss after ICCE, 12% loss after IOL insertion, 14% after phacoemulsification, and 21% loss after penetrating keratoplasty. Both phakic and aphakic grafts had 21% cell loss. Within the aphakic keratoplasty group, there was a 10% cell loss in patients who maintained an intact vitreous face compared with a 26% cell loss in patients who underwent an anterior vitrectomy (P less than .1).


Refractive variation and donor tissue size in aphakic keratoplasty. A prospective randomized study.

Forty-six patients were examined in a prospective, randomized clinical study to compare the use of the same size trephine on both donor and recipient with the use of a 0.5-mm larger trephine on the donor in aphakic keratoplasty and in keratoplasty combined with lens extraction. The results showed no statistically significant difference in refractive error, either in spherical equivalents or in astigmatism. The larger donor tissue may have some value in reducing high plus-refractive error and in reducing intraocular pressure after surgery.


Malignant lymphoma of the retina and brain. Initial diagnosis by cytologic examination of vitreous aspirate.

A case of malignant lymphoma reticulum cell sarcoma in a 42-year-old woman who had bilateral uveitis and vitreitis and neurologic manifestations is reported. The diagnosis was first established by cytologic examination of vitreous aspirate, which showed neoplastic cells consistent with malignant lymphoma and led to cancellation of a planned craniotomy for suspected intracranial tumor. The diagnosis was later confirmed postmortem by histopathologic examination of the eyes and brain. The role of cytologic examination of the vitreous in the diagnosis of malignant lymphoma is discussed briefly.


Identification of CSF leakage by immunofixation.

The use of immunofixation for identification of the presence of CSF by demonstrating its two electrophoretically separate bands of transferrin has proved to be a valid and rather simple method, particularly when the samples obtained from the nose or ear are very small and contaminated.


An evaluation of BIS-GMA resin pit and fissure coatings.

A review of studies on the microleakage retention, durability, and cariostatic efficacy of BIS-MGA resin fissure sealants suggests that newly-erupted permanent molars benefit least but the benefit for premolars is consistently high. Problems arising in the assessment of the sealants in clinical trials are discussed.


Extending the range of composite resin in everyday practice.

Composite resins, coupled with an acid-etch technique, can provide simple solutions to otherwise complex restorative problems. A catalogue of these possibilities is presented.


The incidence of osteo-arthritis of the temporomandibular joint in various cultures.

Three hundred and forty-eight cranial remains from Bronze and Iron Age British, Romano-British, Anglo-Saxon, Eastern Coast Australian aborigines, Medieval Christian Norse, Medieval Scarborough, 17--20th century British and German cultures, were examined for the presence of osteoarthritis in the temporomandibular joints. Cultures exposed to more stringent living conditions and with well-worn teeth had about twice the incidence of osteo-arthritis as the more sophisticated cultures. In general, loss of either molar support or occlusal imbalance were potent aetiological factors in this disease.


Pregnancy and childbirth: is the doctor necessary?

The changing fashions in childbirth over the past 200 years are related to the present demand by women and their partners for "participatory" childbirth, including homebirth. The argument is advanced that doctors must be responsive to these changes. The opinion is made that home birth is currently inappropriate, but that hospitals should provide "birth centres"; and that obstetrics should be conducted by a "team", in which nurse-midwives and family doctors play as important a role as specialist obstetricians.


A technique of anastomosing bowel ends with discrepancy in size.

There have been only a few methods devised to solve the problem of discrepancy in size of the bowel ends for anastomosis. We describe another method to overcome this problem by using a one-layer open technique. For the posterior wall the anastomosis consists of a horizontal mattress suture on the larger end and a vertical mattress suture on the smaller end. For the anterior wall the Gambee suture is used.


The use of methylmethacrylate in the treatment of giant cell tumours of the proximal tibia.

Two cases of giant cell tumour of the proximal tibia are presented where the defect remaining after curettage has been filled with methylmethacrylate bone cement. The problems associated with the present management of giant cell tumours and the potential advantages of using methylmethacrylate are discussed.


The colonial career of James Patrick Murray.

This paper is a biographical sketch of Dr. Murray during the years 1860 to 1873 when he lived in Victoria, New Zealand and the Pacific Islands. It records details of his career from his residency at the Melbourne Hospital followed by his exemplary conduct in the Howitt expedition to recover the remains of Burke and Wills. It traces his progress of degradation unhampered by constituted authority and concludes with his magnum opus--the greatest massacre of South Sea Islanders in the annals of the South Sea slave trade. He departed from the colonies still registered to practise medicine and without penalty or probation. This paper concludes with a brief summary of his personal qualities and asserts that it was these qualities, together perhaps with the discordance between the colonies, which allowed this knave to escape the penalty which he appeared amply to deserve.


Low anterior resection.

A personal series of 93 patients treated by low anterior resection for carcinoma (87) and benign disease (6) is reviewed to highlight the technical problems and complications of the operation. The series comprises two groups for comparison of (i) technique of anstomosis; (ii) the use of protective stoma; and (iii) methods of drainage.


Orthopaedic problems of renal transplantation.

One in six patients receiving renal transplants has orthopaedic problems. Osteoporosis with accompanying fractures is common, as is avascular necrosis of the hips, knees, and other bones. Immunosuppressive therapy with steroids is implicated and its mode of action discussed. No means of prophylasix is known. If treated conservatively, aseptic necrosis of bone is much more disabling than is commonly believed as judged by the critical assessment technique of Charnley. The authors therefore recommend that a surgical approach should be adopted whenever possible.


Chronic mucosal ulcerative colitis with malignant lymphoma: report of a case.

A CASE OF NON-Hodgkin's lymphoma arising in association with longstanding mucosal ulcerative colitis is reported. The clinical course of the patient is described, and a review of previously reported patients is made.


Inflammation in schistosomiasis.

The inflammatory reactions that occur in schistosomiasis are reviewed. The inlammation is due to the migration of worms and eggs through the host's tissues via the vascular system. The greatest damage to the host is produced by the eggs which induce an extensive granulomatous inflammation in the intestine and liver. While the host modulates the course of the disease by developing a cell mediated immunity, ultimately the inflammation in the liver interferes with portal blood flow that may lead to portal hypertension, portal-systemic shunts and fatal hematemesis.


The inflammatory response to endotoxins.

1. Endotoxins are very potent and widely spread inflammation-inducing substances. 2. In the course of local infections endotoxins represent one of the main principles of the pathogenicity of gram-negative bacteria by inducing acute nonspecific inflammation. 3. The pharmacological activities of endotoxins consist primarily in generating and liberating the classic mediators of acute nonspecific inflammation. 4. Endotoxins are able to enter into the circulation through their capicity to activate pharmacological mediators. 5. The endotoxic mediators which increase the permeability of the microcirculation of the intestinum enable endotoxins as components of the physiological intestinal flora to enter into the circulation; these induce systemic disease or shock depending on their concentration in the circulation. 6. In the course of chronic inflammation recidivism or recrudescence as trasient acute inflammatory outburst can be caused by local effects of endotoxins. 7. According to some recent observations the inflammation inducing capacity of endotoxins may promote the entry of aerobic bacteria into the blood stream which can result in mixed septicemia.


[Ethical and legal problems in first clinical trials of psychotropic drugs (author's transl)].

Starting with the relevant national and international guidelines and legal regulations for clinical trials and with the distinction of therapeutical experimentation, therapeutical trial ("Heilversuch") and standard therapy the following points are discussed: a) informed consent in psychically ill patients with restricted capacity for stress and for insight and consent, b) consequences for insurances, c) advice and control for the researcher regarding the design, the performance and the judgment of the results of clinical trials of psychotropic drugs.


[Principles and regulations for clinical pilot studies on psycholeptic drugs (author's transl)].

Some difficulties concerning the patient selection for psychopharmacological trials are described. Problems, decisive factors and methodological principles are discussed, especially the duration of clinical trials and the placebo problem.


[Problems in clinical testing of a psychotropic substance examplified by L-5-HTP-ester (author's transl)].

An i.v. injectable form of the serotonin-precursor L-5-hydroxytyptophan (Ro 3-5940) was investigated for its acute psychotropic effect. The difficulties are presented which had to be overcome as it was not known which effects could be expected. It was shown that for the intensive psychotropic effect found, it was not possible to use a long and detailed self-rating scale. The problem of informed consent is discussed.


[DL-phenylalanine as an antidepressant. Open study (author's transl)].

In an open study dl-phenylalanine in doses from 75--200 mg/day was administered to 20 depressed patients for 20 days. At the end of the trial 12 patients (8 with complete, 4 with good response) could be discharged without any further treatment. 4 patients with partially untypical depressions experienced mild to moderate responses, whereas 4 patients did not respond at all to the phenylalanine administration. Depressive "core symptoms" as depressed mood, retardation and/or agitation were preferentially, anxiety and sleep disturbances moderately and hypochondriasis and compulsiveness were not influenced. It is concluded that dl-phenylalanine might have substantial antidepressant properties and that further controlled investigations are justified.


[The use of TV-technique for a quantitative evaluation of the longitudinal psychopathological profile (author's transl)].

19 depressed patients were treated with viloxazine (n = 9) or amitriptyline (n = 10) in a double-blind trial. TV-tapes produced for each patient on day 0, 10 and 20 were analyzed with respect to the global intensity of depression and to 4 other verbal or averbal psychopathological parameters by 4 independent raters under the condition of a time-blind analysis. Global intensity of depression, prosodic, depressive contents of experience, and psychomotoric inhibition were found decreased between day 0 and day 10 for the viloxazine group, and between day 10 and day 20 for the amitriptyline-group. The accuracy of judgement of agitation was the lowest one.


[Synopsis of psychopathological, electroencephalographical, and pharmacokinetic variables during antidepressive treatment with viloxazine (author's transl)].

In order to achieve a more differentiated assessment of the profile and time course of treatment with a new antidepressant drug, several psychiatric, neurophysiological, and biochemical parameters were examined in a double-blind study (viloxazine versus amitriptyline). Special attention was directed to the use of a time-blind audiovisual technique. The TV technique allowed to demonstrate an earlier onset of the therapeutic effect under viloxazine, which is in good agreement with the cross-sectional and longitudinal profile of viloxazine as regards pharmacokinetics and EEG.


[Multivariate investigation of reactions to tranquilizers dependent on personality variables (author's transl)].

5 mg of diazepam as well as 2.5, 5, and 10 mg of a substance from the thienodiazepine series (Bay g 5653) were compared with a placebo, following a double-blind procedure. The 149 male student volunteers were classified into introverts and extraverts. For 17 test variables including subjective and physiological measures, as well as psychomotoric and cognitive achievement variables, a 2 x 5-factorial MANOVA was computed. Effects of medication and of interactions between introversion/extraversion and medication were highly significant. Correlations of test variables with composite scores indicated that medication effects could be shown best with objective tests, while the interactions between introversion/extraversion and medication could be shown better with subjective variables. Results were discussed together with those of an earlier univariate analysis of the data using emotional stability/lability as a personality variable.


Pharmacological investigation on asclepin--a new cardenolide from Asclepias curassavica. Part II. Comparative studies on the inotropic and toxic effects of asclepin, g-strophantin, digoxin and digitoxin).

The cardiac effects of asclepin, a new glycoside from the plant Asclepias curassavica, were studies in vitro (isolated atrium and heart of guineapig) and in vivo (anaesthetized cat) and were compared with g-strophanthin, digoxin, digitoxin, or digitoxigenin, resp. Asclepin showed a marked positive inotropic effect as evidenced by the increase in the force of contraction, measured by (dp/dt)max and (formula: see text). It was found to be more active than the other glycosides.


Effects of warfarin administration on the immune response of mice.

Administration of warfarin to mice is shown to have little effect on the humoral immune response of these animals to sheep red blood cells (a thymus dependent antigen) or the trinitrophenyl hapten coupled to E. coli lipopolysaccharide (a thymus independent antigen). The ability of low doses of sheep red blood cells to prime T-cells in vivo for helper activity in the in vitro antibody-forming response to trinitrophenyl coupled to sheep red blood cells is also apparently unaffected. By contrast, delayed hypersensitivity responses, measured by foot pad swelling, are significantly stimulated by administration of the drug.


[Chickenpox, burns and grafts].

An outbreak of chickenpox that occurred at the Burns Repair Surgery Unit, Department of Children's Surgery, Hospital R. del Río, between June and November, 1975, is reported. 27 cases of burned children were studied, including analysis of correlations of the stages and outcome of the disease (varicela), the trauma (burns) and the graft (repair surgery). As a result, the authors emphasize the following findings: 1. Burns and their repair are not aggravating factors for varicella. In a small number of cases the exanthema looked more confluent in the graft surgical areas and in the first degree burns healing spontaneously. 2. Usually there was an uneventful outcome of graft repair surgery on a varicella patient, either during the incubation period, the acme or the convalescence. 3. The fact that the outmost intensity of secondary viremia of varicella occurs before the onset of exanthemia, that is, during the late incubation period, is confirmed.


[Treatment of typhoid fever with chloramphenicol or ampicillin combined with oxyphenbutazone].

Ninety-four patients with typhoid fever were treated, at random, with three therapeutic regimens: chloramphenicol alone, chloramphenicol plus oxyphenbutazone, and ampicillin plus oxyphenbutazone. The results are evaluated analyzing the body temperature graph and by serial blood had bone marrow cultures taken at intervals until they became negative. Bacteriologic diagnosis was confirmed by blood culture (39.3%) and/or bone marrow culture (77%). The mean duration of fever was 3.3 days for the group treated with chloramphenicol-oxyphenbutazone, 4.3 for those with chloramphenicol alone and 5 days for the group ampicillin-oxyphenbutazone; at the same time, blood cultures became negative at 4.4, 5.5 and 4.4 days respectively. Negativization of bone marrow cultures was not influenced by the addition of oxyphenbutazone. It is concluded that the influence of oxyphenbutazone in shortening the febrile period or in the negativization of blood cultures is not significant. It is considered that oxyphenbutazone is not an important therapeutic tool in this group of diseases.


[Treatment of true precocious puberty with medroxyprogesterone acetate].

The authors analyze the treatment of 16 female infants with true precocious puberty, ages ranging from 12 months to 9.5 years at the time of diagnosis, based on clinical and laboratory findings. All patients were treated with 150 to 300 mg. every 15 to 20 days of injectable medroxyprogesterone acetate (MPA) for periods from 5 months to 6 years. The prognosis of the adult height was evaluated before and during MPA treatment using the following parameters: height velocity as a function of bone age (good response of 15 patients); height as a function of bone age (good response of 13 patients); developmental quotient (good response of 14 patients), and adult height prognosis by the use of the tables of Bayley & Pinneau (good response of 8 out of 10 patients). The authors conclude that MPA treatment was effective in improving the prognosis of adult height in 14 out of 16 patients of true precocious puberty.


Coronary artery vasospasm: the likely immediated cause of acute myocardial infarction.

Features of infarction can be divided into two types--the spasmodic and the mechanical. The former (pre-infarct angina and emotional factors in infarction) seem readily explainable by spasm, and are similar to the findings in angina which prompted Heberden to consider angina as spasmodic. The mechanical features of infarction (association with thrombosis and arteriosclerosis, and severe and unremitting chest pain) seem to be the antithesis of spasm and probably account for the reluctance to consider spasm seriously in infarction. The injury-vasospasm hypothesis of acute myocardial infarction explains both spasmodic and mechanical features. Spasm represents a dominance of vasoconstricting over vasodilating forces. Coronary sclerosis can result in both ischaemia (vasodilating) and ischaemic injury-spasm (vasoconstricting). The fight-flight component of the autonomic nervous system is considered to be vasodilating, and the conservation-withdrawal portion to be vasoconstricting. Once spasm occurs, a new balance of forces obtains which can lead either to vasodilatation and relief of symptoms or to infarction.


[Subdural empyema due to Salmonella typhimurium. Analysis of a case].

The case was that of an infant with congenital hydrocephalus who developed subdural empyema. The most outstanding items were, the age of the patient (18 months), the identification of Salmonella typhimurium, a germ rarely described responsible for this pathology, the absence of anacrobe germs and the possible hematogenous dissemination from the digestive tract when the port of entry usually associated is the infection of the paranasal sinuses. The most useful method for study was the computerized axial tomography.


QT time in patients treated with alprenolol or placebo after myocardial infarction.

Studies were made on the effects of long-term beta-blockade on the QT interval in patients discharged alive from hospital after myocardial infarction. The patients (n = 230) in this study constituted all those who participated in the alprenolol study on postmyocardial patients in Göteborg, Sweden. The study was double-blind (alprenolol 200 mg b.i.d. or placebo) and randomised. The patients were divided into 4 risk groups (1-4) with different predicted mortality. The electrocardiograms before and after 8 weeks of treatment were analysed with respect to heart rate and QT time. There was a decrease in heart rate of about 10% in the alprenolol treated patients. The QT time was not significantly influenced by alprenolol. The rate corrected QT time (QTc) decreased in the subgroup of the most severely diseased patients (subgroup 4) treated with alprenolol.


Studies of drugs given before anaesthesia. XVII: anticholinergic premedicants.

The effects of premedication with the anticholinergic drugs atropine, hyoscine and glycopyrronium when administered by oral and i.m. routes have been evaluated in patients undergoing minor surgery and compared with a placebo using a double-dummy double-blind technique. Although the mouths of those patients who received adequate doses of anticholinergic drugs were dry, subjectively and observed, as compared with those who received a placebo, the overall course of anaesthesia did not appear to be different. Of the three drugs atropine seemed to be absorbed best following oral administration. Equally effective oral and i.m. doses of atropine were considered to be 2.0 and 1.0 mg respectively; of hyoscine 1.0 and 0.25--0.5 mg. The appropriate dose of glycopyrronium was 0.2 mg i.m. The routine use of anticholinergic drugs in preanaesthetic medication in minor surgery appears to be unnecessary.


Pharmacokinetic and clinical pharmacological studies with mepivacaine and prilocaine.

The tolerance and pharmacokinetic properties of mepivacaine and prilocaine were compared following i.v. infusion of 250 mg (0.88 and 0.97 mmol respectively) of each drug in five healthy volunteers. Side-effects were minor and occurred in only two subjects during the infusion of mepivacaine. Plasma concentrations of mepivacaine were greater in each subject than the corresponding values for prilocaine. The elimination half-life of mepivacaine was generally longer than that for prilocaine, whereas the total body clearance of prilocaine was consistently greater than the corresponding value for mepivacaine. For each subject the clearance of prilocaine substantially exceeded normal heptic blood flow and therefore an extra-hepatic site of metabolism of prilocaine has been postulated.


A comparison of the respiratory effects of meptazinol, pentazocine and morphine.

The respiratory effects of a new strong analgesic, meptazinol, were compared with a placebo and with equianalgesic doses of morphine and pentazocine in a double-blind crossover trial in seven healthy volunteers. No significant change in the ventilatory response to rebreathing carbon dioxide was observed after meptazinol 100 mg/70 kg or placebo. However, both morphine 10 mg/70 kg and pentazocine 60 mg/70 kg depresesd the slope of the ventilatory response (-30.0% and -31.6% respectively, P less than 0.02, averaged over the first 3.5-h period). End-tidal carbon dioxide tension (PE'CO2) while breathing room air increased significantly following all three drugs. However, the increase in PE'CO2 after meptazinol (0.22 kPa averaged over 3.5 h) was significantly less than that following morphine (0.40 kPa, P less than 0.05) and pentazocine (0.59 kPa, P less than 0.01). While breathing room air with a resistive inspiratory load of 8 kPa litre-1 s, PE'CO2 again increased significantly (P less than 0.05) following all three drugs. The increase in PE'CO2 after meptazinol was then the same as that after morphine (0.51 kPa averaged over 3.5 h). The increase following pentazocine (0.80 kPa) was significantly greater than that after both morphine and meptazinol (P less than 0.02).


Operative blood loss and the frequency of haemorrhage associated with adenotonsillectomy in children: a double-blind trial of ethamsylate.

One hundred children were allocated randomly to receive either ethamsylate (Dicynene) or a placebo before undergoing adenotonsillectomy. Blood loss at operation was estimated from the haemoglobin content of swabs and aspirated fluid. Mean blood loss in the ethamsylate-treated group was not significantly less than in the controls. The frequency of secondary haemorrhage was significantly less in children treated with ethamsylate (P less than 0.01). No side-effects were reported in either group.


Clofibrate and diabetes control in patients treated with oral hypoglycaemic agents.

1. Twenty-two maturity-onset type diabetics treated with oral hypoglycaemic agents entered a single-blind crossover study using placebo (periods A and C, 2 months each) and clofibrate (2 g/day; period B; 2 months). 2. In thirteen patients, under reasonably good control, clofibrate did not reduce fasting or post-prandial blood glucose, nor 24 h glycosuria; no improvement was noted in the M-value, an index of diabetes control. 3. In contrast, in nine patients, with poor diabetes control, clofibrate reduced 24 h glycosuria and significantly improved the M-value. 4. In all patients, clofibrate therapy was associated with a significant 19-23% reduction in plasma fibrinogen. 5. It is suggested that addition of clofibrate may be useful in maturity-onset diabetics not adequately controlled by diet combined with oral hypoglycaemic agents.


A comparison of the clinical and psychological effects of diazepam and amylobarbitone in anxious patients.

1. Twenty-four anxious inpatients were treated with diazepam, amylobarbitone sodium and placebo in flexible dosage for 1 week. They each received all three treatments according to a fully-balanced design, using double-blind procedures. 2. The clinical and the psychological effects of the drugs were assessed by the comprehensive battery of psychiatrist's ratings, subjective and psychological tests before treatment and at the end of each week of treatment. The tests included self-rating of anxiolytic and hypnotic effects, reaction-time, card sorting, coding and cancellation tasks, arithmetic and tappin. 3. Diazepam improved significantly subjective anxiety and insomnia, while amylobarbitone improved only the self-rated quality of sleep. Occasion effects were absent on clinical measures, indicating that the patients did not respond to non-specific temporal factors. Performance on motor tasks improved over time because of the expected practice effect, but an impairment relative to placebo was detected on two motor tests after the barbiturate and on four other tests with a cognitive component after the benzodiazepine.