Clinical aspects of anaerobic infections in the surgical patient. Oxygen-sensitive anaerobic bacteria comprise the largest group of organisms among the human endogenous microflora. The oral cavity, vagina and colon are the areas where obligate anaerobes are predominant and can be isolated in very high numbers. Sepsis following surgery of any of these organs is frequently due to the escape of endogenous bacteria during the course of the operative procedure. To isolate and successfully identify most of these anaerobic microorganisms from clinical exudate, special collection and bacteriologic techniques are necessary. The acceptable anaerobic collection techniques mentioned above minimize exposure of the clinical specimen to atmospheric oxygen during collection and transfer. Clinical clues indicating anaerobic sepsis include a putrid odor of the exudate and evidence of abscess, necrosis or associated gas formation. The importance and value of the Gram stain in early identification of surgical sepsis is stressed. Treatment of infectious complications includes surgical drainage and specific antibiotics.


Gonadotropin-releasing hormone radioimmunoassay and its measurement in normal human plasma, secondary amenorrhea, and postmenopausal syndrome. A sensitive and specific double antibody radioimmunoassay for gonadotropin-releasing hormone (GnRH) has been developed for measurement in ethanol extracts of human plasma. Iodinated hormone was prepared with the use of the chloramine-T method, and antibodies were developed in rabbits over a six-month period with a GnRH synthetic copolymer immunogen. A Scatchard plot revealed at least three species of antibody. The assay can measure conservatively at the 5 pg. per milliliter level and shows no cross-reactivity with other available hypothalamic and pituitary hormones. The releasing hormone was quantitatively recovered from human plasma with immunologic identity to native hormone. Unextracted plasma could not be used because of nonspecific displacement. The measurement of GnRH in individuals receiving 100 mug of intravenous bolus infusions of the synthetic decapeptide show extremely elevated values with two half-lives: one of two to four minutes and another of 35 to 40 minutes. In our experiments, we have found measurable GnRH in patients with secondary amenorrhea and at the midcycle in normal women. In the normal cycling woman during the follicular and luteal phases, GnRH was undetectable. In postmenopausal women with extreme hypoestrogenism and markedly elevated luteinizing hormone values, GnRH was also undetectable. No bursts of GnRH could be detected in normal men when sampled every ten minutes over a two-hour period and every two hours throughout the day.


Giant drusen (astrocytic hamartoma) of the optic nerve seen with computerized axial tomography. An EMI scan (computerized axial tomography) performed on a 75-year-old man with giant drusen (astrocytic hamartoma) of the left optic nerve clearly revealed a dense localized mass at the distal termination of the left optic nerve. The EMI scan proved to be an accurate, noninvasive technique for neuro-ophthalmologic diagnosis.


Superficial lines and associated disorders of the cornea. In a clinical classification of fine superficial corneal lines, we recognized five major types of line: mare's tail lines, fibrillary lines, fingerprint lines, lacunar dystrophy or map-like changes, and tram lines. The fingerprint lines were further classified into several subgroups. There was a relationship between certain lines, in particular, fingerprint lines and lacunar dystrophy or map-like change with the occurrence of Cogan's microcystic dystrophy and recurrent erosion.


A telemeter without refractive optics.

A telemeter without refractive optics. A conic tube may be adjusted by varying the distal diameter and by using binocular vision for measuring distances. This device appears to be the earliest telemeter in the world. It is mentioned in the Talmud as being used in the first century A.D.


Clinical immunology in ophthalmology. The 1975 Bedell lecture. Immunology has played a recognizable role in ophthalmology for many years. The old immunology concerned itself with antibodies, skin tests, complement, agglutinins, precipitants, and lysins. The old immunology was responsible for the remarkable development of vaccines, vaccinations, antisera, and the prophylactic use of toxins. The new immunology cannot display such achievements as yet. However, continued study in this area could lead to significant improvements in diagnosis, prognosis, and the development of effective immunoregulants in inflammatory and neoplastic disease.


Effect of drug vehicle on human ocular retention of topically applied tetracycline. Tetracycline hydrochloride--as a 1% suspension in oil, 1 and 2% suspension in ointment, and 1 and 2% solution in water or balanced salt solution USP--was applied once to the conjunctival cul-de-sacs of volunteers and patients before cataract extraction. The tear film concentrations of drug were maintained above a bacteriostatic level in excess of six hours for 1 and 2% tetracycline in ointment, less than two hours for 1% tetracycline in oil, and less than 30 minutes for 1 and 2% tetracycline in water or balanced salt solution. The 2% tetracycline in ointment produced the highest tear film levels of drug. The 1% tetracycline in oil induced excessive lacrimation and much of the drug was washed from the conjunctival surface. The tear film levels of the drug were mirrored by the maintenance of bacteriostatic levels of tetracycline in the aqueous humor for 1 1/2 hours with 2% tetracycline in ointment. Whereas 1% tetracycline in ointment produced drug levels approaching bacteriostasis in the aqueous humor, 1% tetracycline in oil produced only trace levels of the drug within the anterior chamber. The ointment acted as a depot for the suspended drug and most of the drug in the absence of excessive tearing was lost from the conjunctiva via the lacrimal system.


Intravitreal effects of pimaricin in experimental fungal endophthalmitis. Evaluation of 25, 50, and 100 mug of pimaricin given intravitreally to albino rabbits with Aspergillus endophthalmitis revealed that 25 mug of pimaricin, while nontoxic to the retina, was ineffective in inhibiting the fungal process. A dose of 50 mug was significantly more effective in inhibiting fungal disease but also caused significant retinal damage with loss of retinal function and iridoplegia. Dosages above this level resulted in vitreous retraction and degeneration, iridoplegia, and retinal detachment. Twenty-five micrograms of pimaricin given in three dosages spaced three days apart may be effective in inhibiting fungal endophthalmitis.


Marginal ulceration after intracapsular cataract extraction. In four cases of marginal corneal ulceration after uncomplicated intracapsular cataract extraction three of the ulcers appeared within three months after the surgery. In all patients the ulcers were located anteriorly to the site of limbal incision and were progressive. Conservative management was successful in three patients, including one after recurrence of the ulcer after surgery, and one patient resisted medical and surgical management.


Beta-ray treatment of malignant epithelial tumors of the conjunctiva. Fifteen patients with malignant epithelial tumors of the conjunctiva were treated with beta-ray ocular applicators filled with radioactive strontium and yttrium (90Sr/90Y). Histologic examination confirmed the diagnosis. There were ten squamous cell carcinomas, four carcinomas in situ, and one case of epidermidalization. In one patient,  who may have received an insufficient dose,  recurrence led to enucleation. Radiogenic complications-secondary glaucoma and corneal degeneration-caused visual loss in two other patients. All of the other tumors disappeared completely without seriously affecting the eyes. Beta-ray irradiation with 90Sr/90Y applicators was effective if a sufficient dose (15,000 to 18,000 rads) was applied to the tumor surface and if the height of the tumor did not exceed 5 mm.


Resection of both medial rectus muscles in organic convergence insufficiency. Six patients with a prolonged history of severe muscular asthenopia caused by persistent convergence insufficiency underwent resection of both medial rectus muscles. A temporary consecutive esotrapia occurred in each instance and was controlled with prisms. Five weeks after surgery the consecutive esotropia had disappeared in all but one patient who still required prismatic correction for distance fixation. All patients experienced relief from their symptoms. Whereas orthoptic training is useful in most cases of convergence insufficiency a resection of both medial rectus muscles should be considered in persistent cases especially with an associated weakness of accommodation.


Changes in nasal airway resistance associated with rapid maxillary expansion. Records consisting of nasal resistance measurements, postero-anterior radiographs, and dental casts were obtained on seventeen patients before they underwent rapid maxillary expansion. These records were retaken after maximum expansion of the appliance and after 3 months of retention. Measurements of nasal resistance, binasal cavity width, and maxillary first molar width were made for each subject at each stage of treatment. The following conclusions were derived: 1. Rapid maxillary expansion produced a significant reduction in nasal resistance measured at both 0.50 L. per second and 0.25 L. per second air flow. The reduction of nasal resistance by maxillary expansion was stable through a 3-month period of retention. 2. There was very low correlation between the amount of maxillary first molar expansion and change in nasal resistance. Also, changes in nasal resistance showed low correlation with the amount of nasal cavity widening which occurred during the expansion procedure. 3. Changes in nasal cavity width was not closely related to the amount of maxillary first molar expansion. 4. The patient's subjective opinion of changes in his ability to breathe through the nose was not closely related to the amount his nasal resistance was reduced. 5. The change in nasal resistance of subjects who noticed an improvement in their ability to breathe through the nose was not significantly different from nasal resistance change in children who did not notice any change in their breathing. 6. When subjects treated with an all-wire expansion appliance were compared to subjects treated with a wire-and-acrylic appliance, the two groups were not significantly different with respect to maxillary first molar expansion, nasal cavity widening, or changes in nasal resistance. Differences in amount of molar tipping or alveolar bending were not investigated. 7. Patients requiring rapid maxillary expansion treatment for constricted maxillary arches have significantly higher nasal resistance than other orthodontic patients and nonorthodontic subjects. The rapid maxillary expansion procedure reduced the nasal resistance of those treated to a level which was not significantly different from that of subjects with maxillary arches of normal dimensions. 8. The reduction in nasal resistance achieved with the expansion procedure was not lost after 3 months of retention. 9. Where indicated, rapid maxillary expansion is not only an effective method for increasing the width of narrow maxillary arches but also reduces nasal resistance from levels associated with mouth breathing to levels compatible with normal nasal respiration.


Cause and prevention of injuries to teeth and supporting structures during orthodontic treatment. The present investigations have shown that, although there are definite risks in undertaking orthodontic treatment with fixed appliances, such treatment need not cause any appreciable damage when accepted orthodontic principles are followed in cooperative patients with good oral hygiene and regular fluoride treatment. On the other hand, when these principles are neglected, the damage may be considerable and the benefits from orthodontic treatment questionable. Progressively increasing evidence from preventive dentistry that the bacterial plaque is the single most important causative factor in periodontal breakdown, and is important also in causing dental caries, opens unique possibilities for the orthodontist and his auxiliary personnel with simple means to increase their patient's oral hygiene awareness. This would not only reduce the prevalence and severity of iatrogenic damage, but would increase the long-term benefits of the orthodontic therapy. Orthodontists may thus provide young adults with an improved esthetic facial appearance, a perfectly functioning occlusion, and the desire, interest, and possibilities of maintaining the dentition in this condition for all or most of their lives (Figs. 3 to 5, 12, and 13).


Direct bonding of orthodontic brackets.

Direct bonding of orthodontic brackets. The direct adhesive bonding of orthodontic brackets to enamel was investigated. For a number of resin systems, all based on a bisphenol-GMA type of resin, commercially available or synthesized, the adhesive bonding to the enamel as well as to the bracket was studied. The maximum average bond strength to enamel was 121 Kg. per square centimeter; the maximum adhesion to the bracket material was 53 Kg. per square centimeter. Consequently, the attachment of the adhesive to the bracket material is the bottleneck of the direct-bonding procedure. Special attention has been given to preconditioning procedures to enhance the bonding between adhesive and bracket. The best results were obtained when the bracket base was roughened by means of a small amount of resin powder. Because all adhesives studied show large standard deviations of the bond strength, criteria of reliability are discussed. They show that future approaches should aim not only for higher average bonds strengths but also for a smaller standard deviation. The setting process, one of the factors influencing reliability, has been considered in some detail. Results of different mixing ratios as well as the influence of the amount of catalyst are presented.


Changed cholinergic receptor characteristics after vagotomy in gastric fistula dogs. By the use of small doses of atropine (0.2-10 mug/kg-h) the kinetics of atropine antagonism to the gastric stimuli Urecholine and pentagastrin could be defined in intact dogs and in dogs after fundic vagotomy. Though pentagastrin was a much less effective stimulus after vagotomy, atropine had very similar effects on the pentagastrin response before and after vagotomy. Stimulation of both acid and pepsin by Urecholine remained unchanged by vagotomy but was uncompetitively inhibited by atropine in the intact dog, suggesting irreversible binding of atropine to gastric cholinergic receptors. After vagotomy, however, atropine inhibited Urecholine competitively, suggesting that atropine was now bound reversibly to cholinergic receptors. These changes are analogous to those occurring in muscle after denervation and suggest the growth of new cholinergic receptors with changed characteristics after denervation of the stomach.


Overview: Ethical issues in contemporary psychiatry. The authors survey the ethical problems confronting psychiatry today. They state that with rare exceptions psychiatric intervention can be morally justified only with the potential patient's informed consent. Within this framework, they discuss the fact that today nonpsychiatrists, particularly ethicists, lawyers, legislators, and social scientists, as well as psychiatrists are concerned about medical ethics, specifically regarding the right to be treated, the right not to be treated, the civil rights of psychiatric patients, the ethics of behavior control, the problem of conflicts of interest in therapeutic goals, privacy and confidentiality, the ethics of human experimentation, policy decisions, and psychiatry's relationship to the changing moral value structure of U.S. society.


The behavior therapies: therapeutic breakthrough or latest fad? The author critically examines the evidence for the effectiveness of the behavior therapies as described in the American Psychaitric Association's task force report on behavior therapy. He concludes that current attempts to evaluate behavior therapy suffer from inadequate methodology and that the claims for its therapeutic efficacy are excessive and unsupported by the controlled clinical evidence.


Current diagnostic concepts in schizophrenia. The diagnosis of psychiatric disorders currently relies primarily on clinical observation and evaluation of manifest psychopathology. Symptom-based diagnosis of schizophrenia defines a highly variable patient population and thus makes replication of research results difficult. However, this diagnostic approach is useful because it has established communicative value, encourages clinicians to rely on the diagnostic data most readily available (i.e., the patient's behavior), and relates directly to treatment plans. The author describes a 12-point symptom-based diagnostic system for schizophrenia that enhances the reliability and (presumably) validity of the diagnostic process. He then illustrates methods that can be used to select homogeneous schizophrenic populations for specialized research purposes.


Recent developments in the drug treatment of schizophrenia. The author reviews six topics relevant to the drug treatment of schizophrenia. The quantitative effectiveness of promazine is of interest with respect to the structural models of the phenothiazines and the dopamine theory of schizophrenia. The quantitative effectiveness of antipsychotic drugs is also important in evaluating new agents and therefore relevant to a discussion of two newly released neuroleptics, molindone and loxapine. The author's discussion of high-dose treatment of typical acute schizophrenics or treatment-resistant patients reviews the available data and calls attention to the fact that these areas of pharmacologic research have not received sufficient attention.


Visceral and parietal suture in abdominal surgery. The effect of various modifications in suture technic on the healing of intestinal and other alimentary anastomoses is reviewed in the light mainly of controlled clinical comparisons by the author and other workers. (a) In small bowel anastomoses and in colonic and colorectal anastomoses in which both participating stumps have a peritoneal coat an inverting technic of suture has been found to be much more secure than an everting technic, but no significant difference has been demonstrated between the classic two-layer inverting technic and a one-layer inverting technic. However, for low anterior resections in which the distal stump is devoid of a peritoneal coat, the one-layer end-on slightly inverting technic has been shown to be followed by significantly fewer anastomotic dehiscences than the two-layer technic. (b) No controlled clinical studies are available regarding anastomoses in the upper gastrointestinal tract, but for anastomoses between the stomach and the intestine, the weight of surgical experience seems to be heavily in favor of a two-layer technic, whereas for esophago-gastric, -jejunal, or -colonic anastomoses there is one body of authoritative opinion in favor of a one-layer inverting technic. (2) The method of determining the relative merits of some of the many different ways of closing parietal abdominal wounds, by means of controlled clinical trails, is discussed. By one such trial, continuous layer suture with chromic catgut has been shown to be significantly inferior to catgut layer suture combined with tension, sutures or to figure-of-eight (Tom Jones) sutures of wire, as judged by the incidence of wound dehiscence or of subsequent incisional herniation. Reference is made to other trials in progress for evaluation of Prolene, Dexon, and other suture materials and comparison of median and paramedian incisions.


Incidence of incisional hernai after dehiscence of the abdominal wound. The records of 103 patients whose abdominal wounds burst were studied in an attempt to assess the subsequent incidence of incidence of incisional hernia. Sufficient information about seventy patients was obtained. Forty-nine patients (47.6 per cent) had a hernia whereas twenty-one patients (20.4 per cent) definitely did not have a hernia. The incidence of hernia was associated wit- the age of the patient, the site of the wound, the day of resuture, an original diagnosis of malignancy, and the postoperative blood urea level but not with the technic employed in the resuture nor with infection. It is suggested that a blood-stained serous discharge and the "dip sign" should enable an early diagnosis of dehiscence to be made before the small bowel appears in the wound; after diagnosis, the wound should either be explored electively or the skin sutures left for at least three weeks until the skin heals.


Gunshot wounds of the colon. A review of 100 consecutive patients, with emphasis on complications and their causes. The cases of one hundred civilian patients with gunshot wounds of the colon treated at the Louisville General Hospital have been reviewed. Most injuries were in the transverse colon (44%), followed by the ascending colon (27%), rectosigmoid (19%), and descending colon (10%). Associated injuries occurred in 81 per cent of the patients; the small bowel was the most common structure injured. Primary closure was used in 52% of the patients, with a resultant 19% rate of wound infection and 14% rate of serious complication. When the extent of contamination or tissue destruction required resection, an attempted primary anastomosis was followed by a high rate of wound infection (57%) and serious complications (36%) as compared with end-colostomy and mucous fistula, which resulted in a 24% rate of wound infection and 24% rate of serious complication. The rate of wound infection between these groups is significant (p = 0.05). Results end-colostomy and mucous fistula were better than with attempted primary anastomosis.


Urologic complications in renal primary and retransplantation. Experience with 202 consecutive transplants. In a period of two years, 202 kidneys were transplanted in 162 patients at the Downstate Medical Center. On hundred twenty-nine patients had primary transplantations, twenty-nine second transplantations, and five third transplantations. Urologic complications occurred in twenty-four of the patients (12%). There were eight complications involving the urinary bladder and fifteen ureteric complications. In twenty-one patients the complications appeared within six weeks after surgery. Surgical correction immediately upon diagnosis of the urinary complications resulted in a high degree of early restoration of the urinary tract continuity and preservation of renal function. Leakage from the bladder was frequently associated with previous surgery. In five of eight patients, bladder leakage occurred after the second or third transplantations. Complications of the urinary bladder in general had a significantly favorable prognosis as compared with ureteric complications. Although all the patients with bladder complications fully recovered and maintained good renal function, four patients with ureteric complications either died or lost the graft.


Immunologic monitoring and aspergillosis in renal transplant patients. Three cases of pulmonary aspergillosis in a "high risk" population of renal transplant recipients are presented. The source of infection was traced to the forced air exhaust system of the Transplantation Unit. Early definitive diagnosis of the infection was very important for effective management. Immunologic monitoring was demonstrated to be instrumental in indicating the early presence of infection, and as a guideline to reduced immunosuppression during therapy. Bronchoscopy with brushings and endobronchial cavitary biopsy were valuable methods for obtaining the infected tissue. Amphotericin B was effective when therapy was started early. Adequate levels of the drug were obtained by varying the dose and frequency of administration according to serum inhibitory titers. Control of infection was aided by immunologic monitoring at regular intervals.


[Diagnosis of herpetic keratitis by immunofluorescence (author's transl)]. Between December 1973 and October 1974 scrapings of the corneal epithelium of 52 patients were examined by immunofluorescence. 41 of these corneal scrapings were suitable for examination. In 31 of 38 cases with the clinical diagnosis of a herpes simplex keratitis virus-specific antigen was found by means of immunofluorescence. The procedure takes only a few hours, and shows with 81,5% correct diagnoses a high reliability; scrapings of patients without herpetic affection never revealed a positive result. In 3 of 4 cases of deep herpetic keratitis, in which the herpetic etiology could only be supposed clinically, the diagnosis was proved by immunofluorescence.


[Controlled hyperventilation with dead space (author's transl)]. We report on a new kind of ventilation-hyperventilation, whereby dead space is added between the patient and the respirator. This kind of ventilation is compared with positive end expiratory pressure ventilation together with intermittent sighs on 10 dogs. Over a period of 80 hours no respiratory or circulatory differences were found in the two groups. There also was no difference in clinical or anatomic histologic findings. It was demonstrated that dogs can be artificially ventilated for a much longer period than estimated. The findings of "respirator lungs" were only shown in an emphysema of the lungs.


The bony tentorium of the cat: stereotaxic coordinates. The cat's tentorium cerebelli is an osseous structure which overlies much of the brain stem. None of the current brain atlases list the coordinates of this bony projection. With a stiff wire and a stereotaxic apparatus, the location of its free edge and dorsal surface was mapped in 1.0 mm steps in the skulls of 16 cats. In the midline the dorsal surface meets the calvaria at a point 7 mm posterior and 15 mm superior to the atlas zero (intra-aural plane + 10 mm horizontal). From this junction it slopes inferiorly and anteriorly between the cerebrum and cerebellum along a 50 degree slope to terminate along a curved line. In the midline this free edge is located 0.5 mm anterior, and 6.5 mm superior to the atlas zero. It recedes laterally along a curved line to a point 6 mm lateral, 6 mm superior and 3 mm posterior to the atlas zero. The free edge then curves forward and descends to pass through an imaginary line 3 mm anterior and 4.5 mm inferior to the altas zero. Statistical comparisons between measurements made in male and female cats revealed no significant differences.


Dental and skeletal relationships to attritional occlusion. Dental attrition has been investigated in depth. Besides alterations in arch length due to attrition, skeletal and intra-arch differences were discovered. It is felt that these findings do have value in helping us realize that present-day concepts of proper occlusion cannot necessarily be applied to dentitions that existed at another time. A more thorough knowledge of occlusions exhibiting dental attrition provides information that is helpful in understanding more fully the nature of tooth eruption and associated dental arch occlusion and the interrelationships of these factors with supporting skeletal structures.


Immediate skin-test reactivity in a general population sample. To assess the prevalence and distribution of allergic skin-test reactions in a general population sample, allergy prick tests were applied to 3101 subjects older than 2 years of age. Test materials included allergens common to the Tucson environment, and subjects were randomly stratified by age, sex, and socioeconomic status. No difference in the prevalence of measurable reactions was found among male subjects versus female subjects. A definite age relation was apparent, however, with the peak prevalence of reactivity (more than 40%) occurring during the third decade, and falling rapidly past age 50. When present, reactions tended to be multiple, highly reproducible, and more frequent among those in the higher socioeconomic strata. The prick test was judged to be a useful tool for the assessment of atopy.


Hereditary renal-retinal dysplasia and the medullary cystic disease-nephronophthisis complex. Nine of 81 members of two families were found to have renal problems. Three patients in one family had renal-retinal dysplasia with probable recessive inheritance. Of the 6 patients in the second family, one received a kidney transplant from his brother who initially had no detectable renal abnormality but later developed renal failure. In this family, the mode of inheritance seems to be dominant. Hereditary renal-retinal dysplasia differs from medullary cystic disease and nephronophthisis in its pattern of uniformly recessive inheritance and its accompaniment by retinitis pigmentosa. Because genetic considerations have important implications in selection of donors for renal transplant, these entities should be considered distinct despite the similarities in their clinical and pathologic features.


Penetration of clindamycin phosphate into the abnormal human biliary tract. Clindamycin phosphate, 600 mg, was given intravenously to 14 patients undergoing biliary tract surgery. Seven had complete obstruction of the common bile duct. Concentrations of total and active (nonesterified) antibiotic were measured in serum, gall bladder and common duct bile, gall bladder wall, and liver. Persons with patent common ducts had high levels of active drug at all hepatobiliary sites; concentrations were two and one half to three times higher in bile and liver than in serum. Persons with obstruction of the common duct had no measurable drug in bile and had reduced levels in gall bladder wall; however, concentrations in the liver were slightly higher than those in the group without obstruction. The results of this study suggest that, even in the presence of common duct obstruction, the concentrations of active clindamycin in the liver may be sufficient to limit the spread of intrahepatic infections due to susceptible organisms.


Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis. The clinical spectrum of isoniazid-induced liver injury seems to be clinically, biochemically, and histologically indistinguishable from viral hepatitis, except that the injury occurs primarily in persons older than 35 years. A possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug has been found. Examination of isoniazid metabolites showed that patients with rapid acetylator phenotype hydrolyze much more isoniazid to isonicotinic acid and the free hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazid is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. It seems likely that formation of chemically reactive metabolites is also the biochemical event initiating isoniazid liver injury in man. Recognition of the seriousness of isoniazid hepatic injury, not readily accepted at first, has led to revisions in the uses of isoniazid prophylaxis.


Toxoplasmosis in the compromised host.

Toxoplasmosis in the compromised host. In 81 cases of toxoplasmosis in patients with neoplasia, collagen-vascular disorders, and organ allografts, the clinical manifestations were highly variable but neurologic syndromes consistent with diffuse encephalopathy, meningoencephalitis, or cerebral mass lesions predominated. Many concomitant infections with DNA viruses were seen. The diagnosis of toxoplasmosis was not made until postmortem examination in most cases. Biopsy of lymph nodes or brain and serologic tests needed for definitive diagnosis were done infrequently. Twenty patients received antitoxoplasma chemotherapy (pyrimethamine and sulfonamide), 16 (80%) showing marked clinical improvement or complete remission. In immunosuppressed hosts disseminated toxoplasmosis appears to result from defects in cellular immunity that permit recrudescence of latent infection. Because cell-mediated immunity to Toxoplasma gondii can be enhanced in animals by administration of adjuvants, immunotherapy may become a useful adjunct to chemotherapy in immunoincompetent humans suffering potentially lethal infection.


Asparaginase activity of BCG and its phenotypes in relation to culture phases. The asparaginase activity of the Montreal strain of BCG and of 2 of its phenotypes varies with the age of the culture; it starts to increase at the midlog phase of growth, reaches a maximum value near the end of this phase and decreases during the stationary or autolytic phase. However, the variations in this enzyme activity are greater in 2 the phenotypes than in the parental BCG.


[Recent progress made in the classification of lymphoid and monocytoid leukemias and of lympho- and reticulo-sarcomas]. New methods helpful in the classification of lymphoid and monocytoid leukaemias and haematosarcomas have recently become available. Among the most valuable procedures have been those detecting immunological markers and the ultrastructural analysis permitted by convention and scanning electron microscopy. The results of these studies, taken together with a meticulous morphologic examination on Giemsa smears allow a more subtle classification on these neoplasias. Among the most interesting points, one can list: a) The description of macroglobulinemic proplasmocytic leukaemia; b) The observation that all the prognostic parameters in the four types of common acute lymphoid leukaemia (ALL) (prolymphocytic, microlymphocytic, macrolymphocytic, prolymphoblastic) such as age, tumour mass (or leucocytosis are related to the cytological type); T marker may be found in all these types, except for the prolymphoblastic one; c) T or B immunoblastic acute lymphoid leukaemias have been described as a fifth type of ALL; d) The lymphosarcomas which can be histologically nodular (composed of B cells) or diffuse (composed of cells presenting B, T or no markers) can be cytologically prolymphocytic or lymphoblastic (or lymphoblastoid) if they are nodular, prolymphocytic, lymphoblastic, or immunoblastic if they are diffuse; true (African) Burkitt's lymphosarcomas (BLS) must be distinguished from all the pseudo (non-African) Burkitt's lymphosarcomas which have been described elsewhere and which are either immunoblastic or lymphoblastic (oid) lymphosarcomas with a few macrophages; e) The diagnosis of reticulosarcoma which was in the past abusively carried out (because of confusion with immunoblastic lymphosarcoma) is based on the presence of many reticluins fibers at histological examination and on the cytological aspect of the cells on smears (the distinction of those cells with immunoblasts is easy).


[Chronic renal insufficiency in the terminal stage. Therapeutic possibilities offered by repeated dialysis and transplantation in the absence of selection. Apropos of 136 cases]. Repeated dialysis in hospital or at home, and renal transplantation, carried out mainly with cadaver kidney, should permit in France, in the near future, treatment of all patients with chronic terminal renal failure. This report shows the results obtained between the 1st of November 1972 and the 1st of January 1975 in 136 patients treated without any selection at the Nephrology Department and Renal Transplantation Unit of the Pitié-Salpĕtrière Hospital in Paris, in connection with 20 public and private dialysis centers. 66 patients, i.e. 45% of all, were "high risk" patients, mainly because of their age or cardiovascular condition. The overall percentage of survival rate at 2 years in dialysed patients was 81%. It was 67% in the high risk group and 94% in the others. About half of the deaths occured because of cardiovascular reasons. 82 patients were considered for transplantation. Owing to the lack of donors, the number of transplanted patients was only 21. 19 transplantations were carried out with cadaver kidneys. On the 31st of December 1974, 15 patients, i.e. 71% lived with a functioning transplant. In the reported series, complete rehabilitation was obtained in 30% of cases. The results obtained justify, in our opinion, the policy of non-selection of patients.


An accurate method for the determination of inorganic phosphate in serum. Cali's approach to accuracy is reviewed, and it is concluded that the main factor limiting its extension to analytes other than elements is the lack of suitable definitive methods of analysis.  The work published on calcium, andwork known to be under way on other elements, is based on the use of stable isotope dilution-mass spectrometry (I.D.M.S.) as the definitive technique.  This paper outliones the theorectical considerations involved in extending I.D.M.S. to the determinatioons of molecules; in particular, exact equations for the calibration graph obtained by I.D.M.S. are developed, and special cases of practical significance are defined.  It is concluded that in theory there is no reason why accurate resluts should not be realised.  Ther determination of isotope rations is central to the tecnique of I.D.M.S.  The means available for such measurments are discussed, and it is concluded that adequate precision cnan be achieved with standard equipment/  To illustrate the application for I.D.M.S. to molecules the steps involved in an assay for inorganic phosphate are defined, and the protocol this evolved is applied to specimens from the Wellcome Group Quality Control Programme.  Although good correlation was found between I.D.M.S. results and the participants' mean results, there was a substantial bias.  It is argued that this is a result of the difficulty of defining "inorganic phosphate" as a chemical entity.  Some requirements for...


[Sound sensations produced by electric stimulation of the structures of the middle ear and the tympanic chord]. Certain facts must be clearly understood before any attempt is made to analyse the sensations produced by electrical stimulation of the structures of the middle ear. Firstly, when the current passes from an electrode to the skin or to any polarised structure whatsoever, the point at which the electrode is applied and the skin behave like the two plates of a condenser microphone. Electrical vibrations are transformed into ordinary acoustic resonances which can travel through air or bone. These acoustic resonances are fairly pure in comparison with electrical vibrations, judged by the standards under investigation. If a continuous polarisation potential, which gives better distribution of the electrical charges, is added, the capacity of the microphone is increased and greater purity obtained. Consequently, the quality of sound heard in this way depends not only on the quality of this electro-physiological microphone but also on the quality of the internal ear. The acoustic effect produced in this way is called an electrophonic effect. Stevens, Jones and Flottorp described this. Therefore an internal ear which has lost the ability to hear high-pitched sound cannot hear them by means of this electrophonic effect any more than it can by ordinary auditory stimulation. Stimulation of the skin of the mastoid and of the external auditory meatus can be sensed by means of this electrophonic effect. Next, sensations recorded by means of direct stimulation of the acoustic nerve (DJOURNO and EYRIES) or by implantation of intra-cochlear electrodes (SIMMONS, DOYLE, MICHELSON) were studied. Sounds heard through stimulation of the structures of the middle ear should be analysed in the light of these findings and bearing in mind that very strong stimulation of the promontory or of the auditory meatus always causes an auditory sensation without frequency awareness due to global stimulation of the acoustic nerve (faciaestations appeared when experiments, the results of which are described, were carried out, although there is a possibility of episode vestibular irritation. These stimulations were in fact always very weak. Our results were analysed in relation to the quality of the internal ear: completely deaf, serious condition, internal ear normal. The impulses were provided by a direct current battery: these were square with a frequency of between 50 and 900 Hertz, a tension of 0 to 8 volts per 1/10 volt. The electrode was bipolar. The experiments were monitored from time to time by oscilloscope. Mention should be made of the technical and psychological precautions to be observed when stimulation of this kind is carried out if results of any value are to be obtained: a relaxed, sensible patient with whom one can communicate easily. Not much can be gathered from a person deaf in both ears. With the ear opened, the posterior part of the tympanum pulled forward, stimulation of the round window always results in production of a sound at a threshold of 0.5 to 2.5 volts.


Clinical interpretations of the measurement of folic acid and vitamin B12 in neuromuscular disease. 56 patients were studied in an attempt to define neurologic complications associated with folic acid and vitamin B12 deficiency. 2 patients had abnormal levels of vitamin B12. 1 of these showed decreased vibRATORY SENSE IN THE LEGS. 10 of 15 patients with serum folate less than 4.0 ng per ml and 16 of 23 patients with serum folate less than 6.0 ng per ml by radioassay had neurologic abnormalities. The control group demonstrated 17/31 with neurologic abnormalities, a figure not significantly different from the deficient group. It is suggested that more patients with "pure folate deficiency" must be analyzed to eliminate the possible role of toxic effects of alcohol and other diseases of the nervous system in patients with low serum folate and neurologic problems.


[Male hypogonadotrophic hypogonadism: successful treatment of infertility with HMG + HCG (author's transl)]. Ten typical cases of male eunuchoidism (two with anosmia) are reported. After administration of clomifene citrate to five patients there was no change in blood levels of gonadotrophins in four cases; in the fifth, a small and transitory increase of LH was noted. The intravenous injection of LHRH (100 mcg) to five patients induced an increase of serum LH in all cases and serum FSH in three cases. The initial site of the dysfunction is possibly hypothalamic with secondary gonadotrophic pituitary insufficiency. Among six patients desiring paternity, prolonged treatment (for 36 to 98 weeks), with HCG(1700-7000 I.U. weekly) + HMG (450-825 I.U. FSG weekly) resulted in the appearance of spermatozoa in the seminal fluid in five cases and a pregnancy was obtained in four cases. Methods of treatment are discussed.


[An immunofluorescent study of circulating sperm antibodies in humans (author's transl)]. 1. By means of an indirect immunofluorescent technique with reference to Weller and Coons (1954), modified for spermatozoal immunofluorescence we found antibodies against spermatozoa in the sera of: 6 of 35 female partners of couples with unexplained infertility, 5 of 35 male partners of couples with unexplained infertility, 8 of 40 prostitutes, 8 of 18 men after orchitis and vasoresection. In contrast to these findings the sera of 20 fertile women, 25 fertile men, and 20 virgins showed negative results with the test mentioned above. 2. The site of the antigen-antibody reaction was mainly the spermatozoal tail and in the second place, the equatorial segment. 3. The immunoglobulins primarily belonged to the IgG and secondly to the IgA class. 4. Our results differ partly from the findings made by other authors perhaps on account of methodical differences. 5. The clinical relevance and associated problems are discussed.


[Free amino acids in human Eocrine sweat (author's transl)]. With the aid of ion exchange column chromatography we determined quantitatively the free amino acids in eccrine, thermal sweat. Sweat was collected (a) from the face of 27 healthy men and 26 healthy women (b) from the face, chest, armpits, shoulders, back, upper part of the abdomen, hypogastrium, forearms and thighs of the same individual and (c) from the face of the same individual at different times. Sweat was deproteinised by adding an equal volume of 5% sulphosalicylic acid. 1. The results showed not only a constant, qualitative amino acid pattern in sweat, but also a relative constancy among the individual amino acids. 2. The concentrations of the free amino acids in sweat showed significant, individual variations. Particularly high excretion rates were observed in the following amino acids: alanine, glycine, citrulline, histidine, ornithine, threonine and serine. 3. As compared to men, women had an increased excretion of all the examined amino acids in sweat from the face, except for cystine. Statistically significant higher excretion was seen within this sex-specific comparison for the following amino acids: alanine, citrulline, glycine, histidine, isoleucine, serine, taurine, threonine, tyrosine and valine. 4. Essential amino acids such as isoleucine, leucine, lysine, methionine, phenylalanine and valine and also cystine were always excreted only in small amounts. 5. Significant differences were also observed in the total amino acid excretion and in the individual amino acid excretions in sweat obtained from different parts of the body of the same person. 6. The amino acid concentrations determined in the sweat from the face of the same individual at different times showed a relative constancy as compared to the large differences of the amino acid concentrations determined in the sweat from the face of different individuals.


Immunofluorescent investigations in cutaneous vasculitis. II. Histotopical demonstration of IgD and fibrin. The histotopical distribution of IgD and fibrin was examined in skin lesions of 12 patients with cutaneous vasculitis, by means of the direct IF method. IgD was found in 9 cases mostly in a striking fixation to the PMN-leucocytic inflammation cells. Homogeneous depositions of IgD in cutaneous blood vessel walls were seen twice. In 3 cases with older, lympho-histiocytic infiltrations, IgD was lacking. Fibrin was constantly present in the blood vessel walls of fresh and older vasculitis lesions, and showed up in the regions of "fibrinoid necrosis" in form of distorted vascular rings. Although neither IgD nor fibrin appear in a disease-specific histotopical distribution, their simultaneous in vivo demonstration, connected with the result of vascular bound complement, is a good aid to substantiate the diagnosis of cutaneous vasculitis.


Promotion of sporulation by caffeine pretreatment in Saccharomyces cerevisiae. I. Metabolism of nucleic acids and protein during sporulation. Cells cultured in the presence of caffeine had high sporulation ability. The sporulation-promotive effect of caffeine was studied, special attention being paid upon changes in nucleic acid metabolism. When transferred to a sporulation medium, the breakdown of RNA, the synthesis of protein, RNA and DNA, commitment to sporulation and the appearance of mature asci took place in caffeine-treated cells significantly earlier than in control cells. Commitment to sporulation occurred before the completion of premeiotic DNA synthesis in both caffeine-treated and control cells.


[Metabolic products of microorganisms. 150. Ferricrocin, triacetylfusigen and other sideramines from fungi of the genus Aspergillus, group Fumigatus (author's transl)]. The sideramines of 14 species of the genus Aspergillus, group Fumigatus, were isolated and analyzed. Ferricrocin was identified in 11 extracts, ferrichrome in 2 others. A lipophilic sideramine produced by 4 species was identified as triacetylfusigen, another minor component as triacetylfusigen B. Six species produced an alanine-containing sideramine, which may be identical with ferrichrom C.


The regulation of carbohydrate metabolism in Klebsiella aerogenes NCTC 418 organisms, growing in chemostat culture. Klebsiella aerogenes NCTC 418 was grown in chemostat cultures (D = 0.17 hr-1; pH 6.8;35 degrees C) that were, successively, carbon-, sulphate-, ammonia-, and phosphate-limited, and which contained as the sole carbon-substrate first glucose, then glycerol, mannitol and lactate. Quantitative analyses of carbon-substrate used and products formed allowed carbon balances to be constructed and direct comparisons to be made of the efficiency of substrate utilzation. With all sixteen cultures, carbon recoveries of better than 90% were obtained. Optimum utilization of the carbon substrate was invariably found with the carbon-limited cultures, the sole products being organisms and carbon dioxide. But the extent to which excess substrate was over-utilized varied markedly with both the nature of the growth-limitation and the identity of the carbon-substrate. In general, sulphate-, ammonia-, and phosphate-limited cultures utilized glycerol more efficiently than mannitol, mannitol better than lactate, and glucose least efficiently. Glucose-containing cultures also synthesized some extracellular polysaccharide. When the carbon source was in excess, a range of acidic compounds generally were excreted. Sulphate-limited cultures, growing on glucose, excreted much pyruvate and acetate, whereas similarly-limited cultures growing on glycerol, mannitol or lactate produced only acetate. Ammonia-limited cultures invariably excreted 2-oxoglutarate and acetate, whereas phosphate-limited cultures produced gluconic acid, 2-ketogluconic acid and acetate, when growing on glucose, but only acetate when growing on mannitol or lactate. From the rates of substrate and oxygen consumption, and the rates of cell synthesis, yield values for both substrate and oxygen were calculated. These showed different trends, but were similar in being highest under carbon-limitation and substantially lower under all other limitations. The physiological significance of these findings, and the probable nature of the regulatory mechanisms underlying "overflow metabolism" are discussed.


Postpsychotic depression in schizophrenia. Several authors have described a severe depression in patients emerging from psychotic states. The clinical picture usually resembles that of a retarded depression with strong neurasthenic and schizoid components. It frequently emerges after a patient has been discharged from the hospital and may often go unnoticed. When manifest, the syndrome is usually stable phenomenologically, is often lengthy, and may be resistant to all modalities of treatment. Postpsychotic depression is a relatively neglected clinical area despite the risk of suicide and prolonged suffering. Therapeutic perseverence purportedly can improve the patient's long-term prognosis, and the phenomenon itself may be favorable prognostic sign. We present here a review and reformulation of this syndrome.


Immunochemical studies on the serotype of Shigella flexneri and its recombinant. Chemical and serologic analysis of polysaccharides of Shigella flexneri 2b and its recombinant revealed complete defect of the gene responsible for type II specificity as a result of recombination. At the same time, function of the gene in the same locus responsible for 7,8 group specificity was partially inhibited. Attenuation of group antigen 7,8, associated with partial uncovering of the structure of the basic chain, causes appearance of a distinct 3,4 group antigen. Changes of this type in Shigella flexneri have not been described hitherto.


Comparative serologic analysis of Lac+ recombinants of serotypes 2a, 2b, 5a and variant Y of Shigella flexneri. The serologic structure of Lac+ recombinants of 2a, 2b, 5a and var. Y serotypes of Sh. flexneri was compared. Rec. 2a Lac+, rec. 2b Lac+ and rec. Y Lac+ were shown to be identified, and rec. 5a Lac+ was found to differ from those mentioned in that it was deficient in determinants for 3,4 group antigen complex. Furthermore, the paper discusses the presumable genetic mechanisms of the described variability.


Cytophilic and cytotoxic antibodies in sera of rabbits after allogeneic skin grafts. The appearance, distribution in serum fractions, and specificity of cytophilic and cytotoxic antibodies in rabbits after skin allotransplantation were investigated. The sera were obtained from rabbits receiving three subsequent skin allografts across the RL-A barrier. The direct cytophilic test and the microcytotoxic test using the graft recipients sera and lymphocytes from the donor rabbits, as well as lymphocytes from other rabbits were performed. In all the sera under investigation both cytophilic and cytotoxic antibodies were found. The specificity of cytotoxic antibodies was directed against rabbit histocompatibility antigens (RL-A), in contrary to cytophilic antibodies, which were strongly active with the donor lymphocytes, and to a somewhat lesser degree with other lymphocytes, regardless their RL-A constitution. Posttransplantation cytophilic and cytotoxic antibodies were present in the gamma1 and gamma2 classes of immunoglobulins and absent from the IgM immunoglobulins. It is concluded, that allografted rabbits develop, besides the known cytotoxic antibodies, also cytophilic antibodies, not connected with the strong histocompatibility antigen system.


A double-blind clinical trial of laxogas evacuant suppositories. A double-blind study was carried out to evaluate Laxogas gas producing suppositories--in inpatients confined to bed for long periods, and in elderly outpatients with constipation. Laxogas was found to give positive results in 92 per cent of cases treated, the time for evacuation of the bowel ranging from 15--40 min. No side effects were noticed.


Early and late histologic effects of stereotactic neurosurgery. The histologic lesions produced in the brain by stereotactic chemosurgery and cryosurgery are reviewed in four patients who died from 25 days to 15 years postoperatively. Three of four patients had damage to the internal capsule and died of pulmonary emboli. The early lesions are histologically nonspecific, but the old lesions of chemopallidectomy and chemothalamectomy in one patient contained metaplastic bone. Lesions produced by freezing are more discrete than those made by chemical means.


The angiographic evaluation of human renal allotransplants. Functional graft deterioration and hypertension. The renal arteriogram is a highly reliable test in the differential diagnosis of early transplant anuria, graft rejection, and hypertension. The reliability of the renal arteriogram was 97.8% in either substantiating or disproving the presence of a suspected episode of graft rejection or renal artery stenosis. The earliest signs of acute humoral and acute rejection were a prolongation of arterial clearance time, diffuse edema with enlargement of the kidney, and progressive deterioration of the nephrogram. Renal artery stenosis may be a sharply localized septum or an elongated narrowing at or distal to the actual site of anastomosis. This was seen primarily in patients' arteriograms more than 60 days after transplantation, and it is important because it is a surgically correctable cause of hypertension.


Complete scalp avulsion.

Complete scalp avulsion. Complete scalp avulsion results in serious consequences, including hospitalization, economic loss, devasting disfigurement, and psychological effects on the patient. Three patients suffering complete scalp avulsion are discussed. Each case involved injury from farm tractors and occurred in young girls with long hair. In each of them we successfully employed split thickness skin graft for repair of the extensive scalp loss. Excellent aesthetic results were obtained with the use of a wig. Other reported experiences using replacement of the avulsed scalp have been almost uniformly unsuccessful. With recent advancements in microsurgery, the potential for replantation of a completely avulsed scalp has become a hope for the future.


Pneumonia in recipients of renal allografts. Pneumonia developed in 33 of 266 renal transplant recipients while they were receiving immunosuppressive therapy. Clinical factors were compared for patients with pneumonia and the control group of 220 transplant recipients without pneumonia. The diagnosis was usually established roentgenographically. Most cases of pneumonia were of bacterial origin and occurred within three months after transplantation. Pneumonia occurring during the first two postoperative weeks had no fatal outcomes. Patients with pneumonia occurring three to 12 weeks after transplantation had significantly greater leukopenia (P less than .05) and more therapy for allograft rejection (P less than .01) than  the control group. Cases of fungal pneumonia developed later, were preceded by rejection, and had a poor prognosis. The mortality was 51.5% for all cases of pneumonia. Early diagnosis, prompt administration of specific antimicrobial agents, and immediate cessation of immunosuppressive therapy should improve the survival rate.


Forty-eight-hour kidney preservation. A comparison of flushing and ice storage with perfusion. Cold nonperfusional (flushing and ice storage) with Collins or Sacks solution and perfusional preservation with cryoprecipitated plasma or albumin were compared in dog kidneys. All these methods were effective in achieving excellent 48-hour preservation of fresh kidneys. After exposure to 20 minutes of ischemia at 37 C, neither of the flushing solutions yielded kidneys that permitted survival of recipients after 48 hours of preservation, and flushed kidneys functioned poorly after 24 hours of preservation. In contrast, both plasma- and albumin-perfused kidneys exposed to ischemia supported life satisfactorily and with normal function. Therefore, simple and inexpensive flushing and ice storage techniques are entirely satisfactorily for the preservation of ideally harvested cadaver kidneys, while the more complex and expensive perfusional techniques must be employed in preserving ischemia-damaged organs.


Organophosphorus esters causing delayed neurotoxic effects: mechanism of action and structure activity studies. Evidence is reviewed that the initial biochemical event leading to delayed neurotoxicity is phosphorylation of the active site of a specific enzyme called Neurotoxic Esterase. This is followed by a bondcleavage (? hydrolytic) leading to formation of a mono-substituted phosphoric acid residue on the protein. The mechanism by which some phosphinates protect hens against neurotoxic compounds is explained. Screening Assay. Assay of effects of compounds on Neurotoxic Esterase activity of hen brain in vitro and in vivo provides a quick biochemical screen to supplement the 3-week clinical test. This test provides an estimate of safety margin for compounds which give negative results in the clinical test and are currently used as pesticides, plasticisers, etc. Simplified assay procedures are being developed. Structure/Activity Studies. Data is now available for the biochemical and neurotoxic activity of many compounds. This provides a basis for structure/activity predictions; neurotoxicity data published since 1930 has been assessed in this light.


[Connective tissue development in rats with implanted chambers for in vivo microscopy]. The Sandison and Clark method of intravital microscopy including the implantation of special chambers into different areas of the body in order to study tissues in vivo in the chambers in the passing light was modified and adapted for experiments in rats. With the help of microcinematography the velocity of movement of the regenerating connective tissue of the rat and the velocity of the shift of granulocytes were found to equal 0,3 mm/a day and 50-200 nm/an hour respectively. Functional and morphological distinctions between leucocytes, macrophages and fibroblasts were noticed. The formation of vascular branches of a "stretched" type, arteries, veins and anastomoses between them was studied. The details of intravital staining of different connective units with neutral dyes and bright cresyl blue were investigated.


Midbrain corectopia.

Midbrain corectopia. Intermittent corectopia was recently observed in a patient with bilateral, rostral midbrain infarction. Results from neuropathologic examination disclosed isolated but intact Edinger-Westphal nuclei. An explanation of midbrain corectopia centered on segmental innervation of the pupil by the Edinger-Westphal nucleus. In the presence of a paralyzed dilator muscle, select, central inhibition of sphincter tone resulted in an oval and eccentric pupil.


Cadaver storage time. An important factor in donor cornea survival. The effects of cadaver storage on endothelial survival are assessed by the temperature reversal effect in rabbit eyes. Eyes removed at death show little deterioration after one week of refrigerator storage. Eyes left in the cadaver from one to four hours after death show increasing deterioration with time in the body; the deterioration becomes more pronounced as the days of refrigerator storage increase. The sooner an eye is removed from the body, the more reliably it will survive refrigerator storage.


[The indication and technique of the arthrodesis by children and adolescents (author's transl)]. The indications and techniques of an arthrodesis procedure, in children and adolescents, differ greatly with that of adults. And this, on account of, the growth of the epiphysis and its circulation during that period, and also, due to the thick cartilage coating the joint's surface. And therefore, only for the rare exceptions, where there are strict indications that the procedure is weeded, should it be performed, and preferably, when possible in late adolescence. It is advised to perform the arthrodesis even earlier, when it will prevent an increase in the static's impairement especially that of the feet. In general, for the seldom splintplastics one should consider autologous material, as primary choice. To conclude, special arthrodesis will be mentioned later.


[The distribution of B-lymphocytes in lymphoepithelial tissues as well as in tumors of the neck-, nose-, and throat region derived from lymphoreticular and lymphoepithelial tissues (author's transl)]. B-Lymphocytes carrying IgG-, IgM,- and IgA-surface receptors were estimated by fluorescence microscopy in the palatine tonsil of 50 patients aged 3 to 18 years as well as in 44 patients with various types of malignant lymphoms and lymphoepithelial carcinomas. Hyperplastic tonsillartissue contains large numbers of B-cells with a marked variability in concentration (4-30% IgG-cells, medium 12,9%;6-36 IgM-cells, medium 23.4%;3-38% IgA cells, medium 20.8%). There appears to exist an age-dependent increase in IgM-cells and an increase in IgG-and IgA-cells in patients with numerous recurrent infections of the upper respiratory tract. Malignant lymphomas can be grouped into three main categories: Such with a predominance of one B-cell line (above 75-80% of one immunological cell type); these include primarily malignant lymphomas of the well differentiated lymphocytic type (IgM and IgA receptors). Secondly, such with a significant decrease in B-cells (below 10%) which include primarily malignant lymphomas of the poorly differentiated lymphocytic type. Thirdly, such with an increased B-cell content but with more than one cell line participating in cell proliferation. The latter ones comprise certain cases of Hodkin's lymphomas. Lymphoepithial carcinomas are charactersized by a significant decrease in total B-cell content, except for IgE- and IgD-cells which were not investigated. The results show that the immunologic classification of malignant lymphomas correlates only to a certain degree with the morphologic classification; i.e. the same morphologic type of tumor may possess different immunologic characteristics. Since the immunologic characteristics may reflect a certain functional potential of these tumors as well as probably a certain kind of immunologic incompetence prior to tumor development, it is suggested, that future morphologic investigations of malignant lymphomas and lymphoepithelial carcinomas are combined with immunologic classifications.


[Myelin sheets of spiral ganglion cells in rats and guinea pigs, an electronmicroscopical study (author's transl)]. Comparative studies of the spiral ganglion cells in guinea pigs and rats, subsequent to osmium and glutaraldehyde fixation were undertaken to demonstrate the structure of their myelin sheets. We believe that the myelin sheets consist only out of loose and compact myelin components, which can be seen using glutaraldehyde fixation. The so called semicompact myelin must be an artefact due to osmiumfixation followed by a slight shrinkage of the ganglion cells with tearing of the compact myelin.


Histological examination of the aldolase monomer composition of cells from human kidney and hypernephroid carcinoma. Aldolase was specifically fixed in tissue sections by the use of antibody prepared either against aldolase A or against aldolase B. The localization of the antigen was demonstrated with the immuno-histochemical method. Aldolase A was found to be the predominant constituent in the cytoplasm of the distal tubules, the large vessels and the glomerula of normal kidney, and aldolase B in the proximal tubules. The collecting tubules and the capillaries contained a mixture of the two types. In the hypernephroid carcinoma cells only aldolase A could be found, but the capillaries within the tumor tissue did contain some aldolase B. Confirmation of these results was obtained by analysis of homogenate prepared with carefully selected tissue parts.


[Embedding of undecalcified bone tissue for electron microscopic investigation (author's transl)]. The preparation of undecalcified bone tissue for electron microscopic investigation depends on the quality of the embedding medium. Penetration of bone tissue is improved by a low viscosity of the monomer plastic material. Hardness of polymerized embedding medium should be similar to bone tissue, but a good cutting quality must be maintained. A low viscosity resin proposed by Spurr (1969) proved to be in compliance with these conditions. The embedding medium is composed of four components: vinylcyclohexenedioxide (ERL, 4206), polyglycolepoxide (DER 736), nonenyl succinic anhydride (NAS) and dimethylaminoethanol (DMAE). The most favourable molar ratio between anhydride (NSA) and epoxide (ERL 4206 and DER 736) was A : E = 0.81 : I. Hardness and brittleness of polymerized epoxy resin can additionally be influenced by varying the amounts of both epoxy components in the final mixture. Human iliac crest trabecular bone as well as rat bone tissue were embedded to test the quality of the medium. Resutls: Ultra-thin sections were performed at low cutting speed (0.5 mm/sec) using diamond knives. Artificial alterations of bone surfaces did hardly occur due to a good penetration of the bone tissue. The special hardness of the embedding medium stabilized the tissue, thus chattering of the transition from osteoid to mineralized bone could be markedly reduced.


Evidence for an active dimer of Escherichia coli beta-galactosidase. BETA-Galactosidase (EC 3.2.1.23), prepared from strains ML 308 and K12 3300 of Escherichia coli, dissociated into an inactive monomer in the presence of Ag+. When such a monomer preparation is treated with excess of thiol an enzymically active dimer is formed in addition to an active tetramer. It is suggested that Ag+ may be of value in studies on other multimeric proteins as a mild dissociating agent.


A 30 S precursor of 30 S ribosomes in a mutant of Escherichia coli. Escherichia coli 15-28, a mutant with a defect in ribosome metabolism, accumulates a ribonucleoprotein particle that is indistinguishable from 30S subunits by sedimentation but contains the precursor form of 16S RNA. This particle is probably a precursor of 30 S ribosomes.


The distribution of different molecular species of collagen in fibrous, elastic and hyaline cartilages of the pig. The distribution of type II collagen, considered to be characteristic of cartilaginous tissues, was determined in various specialized cartilages of the mature pig. The tissues examined were: (1) fibrocartilage of the semilunar meniscus of the knee; (2) elastic cartilage of the external ear; (3) hyaline cartilage of (a) the synovial joint (b) the thyroid plate of the larynx, and (c) the nasal septum. The predominant species of collagen in each tissue, whether type I or type II, was appraised semi-quantitatively by analysis of purified collagen solubilized by pepsin and of peptide fragments produced by cyanogen bromide. Cyanogen bromide-derived peptides were characterized by column chromatography on CM-cellulose and by electrophoresis in sodium dodecyl sulphate-polyacrylamide gels. The proportion of each type of collagen was determined precisely by isolating the homologous small peptides alpha1(II)CB6 [nomenclature of Miller (1973) Clin. Orthop. 92, 260-280], by column chromatography on phosphocellulose and determining their relative proportions by amino acid analysis. Thus collagen of the fibrocartilage of the meniscus proved to be all type I; type II was not detected. In contrast, collagen of elastic cartilage of the outer ear, after rigorous exclusion of perichondrium, was type II. Similarly, type II was the only collagen detected in all the mature hyalline cartilages examined.


Interchain disulphide bridges of mouse immunoglobulin M. Mouse IgM (immunoglobulin M) was selectively and partially reduced and treated with iodo[2-14C]acetate to label the interchain disulphide bridges. The carboxymethylation was studied in some detail. The labelled peptides were purified, sequenced and positioned by homology with human IgM. Only peptides originating from three interchain disulphide bridges were labelled, in contrast with the four labelled bridges obtained in human IgM under the same conditions. These peptides are homologous to human bridge peptides forming the heavy-light bridge and two inter-heavy bridges, one present in the CMU2 region and the other in the C-terminal region. The inter-heavy bridge in the Cmu2 region was alone cleaved and radioactively labelled in selectively reduced IgM held together as a pentamer by non-covalen interactions. The same bridge was the only one to be totally cleaved in subunits released after more extensive, though still selective, reduction. In the light of these results a possible arrangement of the disulphide bridges of the mouse IgM.


Crystallization of one of the chicken pepinogens and its derived pepsin. Dodecahedral crystals of chicken pepsinogen have been prepared, one perfect cystal having the dimensions 0.090mm x 0.086mm x 0.009mm.  The derived pepsin crystakkized in the form of flat plates, often with one rounded end.  The dimensions of one such crystal wer 0.076mm x 0.043mm.  Both types of protein crystals showed full enzymic or potential enzymic activity.


[Are there pseudophototropic reactions in biology? Part 1: Some considerations on molecular repair (author's transl)]. The phenomenon of repair in light and darkness in biological systems is compared with the reactions of the pseudophototropy of synthetic macromolecules. The reactions of the pseudophototropy, that is the formation of terminal double bond sequences and their reactions which are effected through ultraviolet irradiation or oxidation, seem to be identical to the mechanism of DNA repair.


[Phalloidin antagonists 4th communication: Thioctic acid, SH-compounds, rifampicin, choleretics, dexamethasone, estradiol, unspecific inhibitors, and ineffective compounds (author's transl)]. 1. Thioctic acid used clinically in poisoning by A. phalloides, protected perfused livers and also isolated hepatocytes against phalloidin, when given in high concentrations. 2. Some SH-compounds like coenzyme A, dimercaprol, cysteine and cysteamine were found to be protective in different concentrations. 3. Rifampicin protects mice against lethal doses of phalloidin, and inhibits poisoning of isolated hepatocytes at low concentrations. 4. Some choleretic drugs like dehydrocholate, temoebilin (extr. cucumae xanth.), ethacrynic acid influenced phalloidin poisoning by inhibition of binding. 5. Doses of 0.2 to 4.0 mg dexamethasone added to 100 ml of perfusion medium did not protect perfused rat livers against 0.5 mg phalloidin. 6. Pretreatment of female rats with estrogens effected protection against phalloidin in vivo. The same procedure resulted in moderate decrease of phalloidin effects when the livers of pretreated animals were poisoned in vitro. In male rats estrogen pretreatment was less effective. Castration did not augment the protective effect. 7. Secophalloidin, a biologically inactive derivative, did not influence phalloidin poisoning in perfused livers, even when applied in excessive concentrations. 8. Concanavalin A, probably bound in the neighborhood of binding sites for phalloidin, did not protect perfused livers against phalloidin. 9 Diethyldithiocarbamate, a compound protecting livers against carbon tetrachloride and halothane, was ineffective in phalloidin poisoning. 10. Further protective actions of Evans blue, of some phenanthrolines and of EDTA are discussed. 11. Pretreatment of animals with hepatotoxic compounds (CCl4, CHCl3, cinchophen) decreased the toxicity of phalloidin in vivo. Possible mechanisms are discussed.


[Histometrical studies on induced paw inflammation by carrageenan and Freund's complete adjuvant in rats]. A group of male Wistar rats (strain AF/HAN) received carrageenin in a tragacanth suspension and saline solution by subplantar injection into the right and left hind paws, respectively. Another group was treated similarly with Mycobacterium butyricum in Freund's adjuvant given in the right hind paw while the left paw served as control. The experiments ran for 20 days. The paw volume was measured plethysmometrically and general histological examination was carried out on samples of the dorsal paw epidermis and dermis. The mast cell count and thickness of epidermis were also determined. Epidermal and dermal changes developed in distinct stages following carrageenin or adjuvant treatment. During the acute phase (from 0 to 12 h post-treatment) the paw volume as well as the thickness of the epidermis increased while the dermal mast cell count decreased. Furthermore, hyperemia, edema and leukocytic infiltration of the connective tissue was observed. Eosinophilia and focal necrosis appeared only in the adjuvant treated animals. In the subacute phase (from 1 to 3 days post-treatment) paw swelling and epidermal hyperplasia recessed slightly in the carrageenin treated group. On the other hand, paw volume of the adjuvant treated animals continued to rise. These changes were accompanied by proliferative and degenerative processes of the connective tissue (fibroplasia, histiolymphocytic infiltration, focal necrosis). A chronic phase of inflammation (from 4 to 20 days post-treatment) developed only in the adjuvant treated group. Epidermal hyperplasia reappeared and the paw volume increased significantly (secondary reaction). Also granulomatous chronic inflammation and foreign-body giant cells proliferated in the connective tissue.


Treatment of psoriatic arthritis with azaribine. Thirty-two patients with psoriatic arthritis unresponsive to conventional therapy were treated wtih the antipyrimidine azaribine. For the group, improvement was highly significant (P less than 0.01) when average painful joint count, ring size, grip strength, pain, and morning gel were compared with baseline measurements. The spectrum of response of individual patients varied from total remission or arthritis in 5 patients to no improvement in 7. Dermatitis improved more than 50% in 26 patients. Reduction in hematocrit, gastrointestinal irritation, and occasional central nervous system toxicity were readily reversed by decreasing or discontinuing dosage. Azaribine appears to be a useful agent for trial in the treatment of refractory psoriatic arthritis.


Diagnostic parameters in experimental renal infection. Urinary tract infections are commonly encountered in medical practice but their laboratory diagnosis presents many difficulties. In this study we have used experimental models to assess the value of serum antibody, urinary antibody, rheumatoid factor, and the histochemical examination of renal tissue as diagnostic parameters. Under the conditions of the experiment the analyses did provide useful diagnostic information and may prove to be of value in the management of urinary tract infection in man.


Recent studies on the role of the thymus in early stages of lymphopoiesis and immune differentiation. The influence of thymus deprivation and thymus restoration was studied: a) on the cycling capacity of colony forming cells (CFU-S) in the bone marrow and b) on the establishment of tolerance in liver radiation chimeras. After neonatal thymectomy a reduction in the number of CFU-S in the bone marrow was observed. This reduction was accompanied by a striking decrease in the proportion of cycling cells in the bone marrow of thymus deprived mice. On the other hand, restoration of thymus function by thymic hormone (THF), by implantation of thymus in semi-impermeable cellophane bags, or by pregnancy, raised the number of cycling cells in the bone marrow to that of normal controls. Parental embryonic liver cells reconstitute lethally irradiated mice, and permit establishment of tolerance to further challenges of immunocompetent cells syngeneic to liver donors. We found here that adult thymectomy prevents the establishment of permanent tolerance in liver chimeras. Again, restoration of thymic function by THF permitted liver chimeric mice to resist the immunologic attack of parental spleen lymphocytes syngeneic to donor liver cells.


Blood-gas changes during induced hypotension with sodium nitroprusside. A blood-gas study of the respiratory effects of sodium nitroprusside during anaesthesia has shown a marked reduction in PaO2 when the drug was administered. After nitroprusside PaO2 returned to the previous values. It is suggested that the reduction in PaO2 is a result of an increased scatter of ventilation/perfusion relationships in the lung. The reduction in PaO2 was evident during both spontaneous and artificial ventilation. Nitroprusside was associated with a small decrease in actual bicarbonate.


Cardiovascular effects of extradural analgesia in labour: comparison of bupivacaine with lignocaine. Two groups of patients who requested extradural analgesia were studied in a within-patient controlled trial and received either 0.5% bupivacaine with adrenaline 5 mug/ml or 0.5% bupivacaine plain as the analgesic agent (first group) or 0.5% bupivacaine or 2% lignocaine both with adrenaline 5 mug/ml (second group). Arterial pressure, central venous pressure (CVP), maternal and foetal heart rate and uterine contractions  were monitored continuously. There was no significant difference in any of the cardiovascular measurements when solutions of 0.5% bupivacaine (with or without adrenaline 5 mug/ml) were used. The second group had a statistically significant increase in CVP during the study period in which 2% lignocaine was used. The position of the patient did not affect the cardiovascular measurements in either group. Since the addition of adrenaline 5 mug/ml to bupivacaine solutions did not confer any apparent advantages, it is concluded that plain solutions of 0.5% bupivacaine should be used except in the longest labours.


A study of inflatable cuffs on endotracheal tubes. Pressures exerted on the trachea. A simple method of measuring the pressure exerted by the cuff of an endotracheal tube on the trachea is described and has been used to measure the pressures exerted by 16 commercially available cuffs on the wall of a model trachea. The Shiley, Portex soft-seal, Kamen-Wilkinson (Bivona Fome) tubes had the lowest tracheal wall pressures. Using this method in vivo the changes in tracheal wall pressure exerted by a low-pressure cuff during percussion and vibration physiotherapy, and when the patient "fights the ventilator", were recorded.


A fluidically controlled ventilator for bronchoscopy. A simple time-cycled device uses an oscillating, fluidic, bistable element to control the high-pressure oxygen, supply to the ejector of a ventilating bronchoscope. Both manual and automatic modes of function are available, and inflation pressure and respiratory rate are controlled. Its construction is simple, the cost is low and the number of components is small.


A double-blind clinical trial of the analgesic effects of R & S 218-M, a new potent analgesic for the relief or pain following abdominal surgery: comparison with morphine sulphate. The analgesic effects of R & S 218-M, administered in doses of 0.56 mg/70 kg and 0.35 mg/70 kg, were compared with those of morphine sulphate 10.5 mg/70 kg for the relief of abdominal pain following surgery in healthy adults. The drugs were given as the first potent analgesic after operation and the subjects were interviewed at 30-min intervals until the pain became severe again. All the interviews were conducted by the one observer. R & S 218-M 0.56 mg/70 kg was as effective as morphine sulfate 10.5 mg/70 kg, while R & S 218-M 0.35 mg/70 kg was inferior. No evidence was found to support the claim that R & S 218-M causes less respiratory depression when compared with morphine sulphate.


Chemotherapy of advanced breast cancer: a controlled randomized trial of cyclophosphamide versus a four-drug combination. Ninety-nine patients with advanced breast cancer were randomized to receive either cyclophosphamide continuously or a combination of cyclophosphamide, methotrexate, 5-fluorouracil and vinblastine given intermittently. The number and duration of objective responses were greater in patients receiving the combination but the differences between the two treatments did not achieve formal significance. The combination was logistically easier to manage and produced less toxicity.


Serum lysozyme as a marker of host resistance. I. Production by macrophages resident in rat sarcomata. With progressive growth of syngeneic sarcomata in rats there was a rise in serum levels of lysozyme which correlated with their immunogenicity and their macrophage content. By an examination of lymph/blood differences in normal and in tumour bearing rats and of the production of lysozyme by cells obtained from the tumours and maintained in vitro, it is apparent that the macrophages resident in a tumour mass make a massive contribution to the elevation in serum lysozyme concentrations. Tumour cells did not release detectable lysozyme activity. Tumour amputation led to a rapid fall in lysozyme levels. Irradiation of the host rats abolished the lysozyme response and the subsequent development of metastases in these rats was associated with a rise in serum lysozyme. The serum concentration of this enzyme reflects the macrophage content of a tumour mass and the draining lymph nodes. We conclude that under well defined conditions serum lysozyme activity may be a useful marker of macrophage mediated host responses to a tumour.


Centrofacial lentiginosis. A survey of 40 cases. Forty patients with centrofacial lentiginosis have been studied. A greater than normal number of bone abnormalities, malformations due to dysraphia, endocrine dysfunctions, and neurological diseases, but not psychiatric impairment, were found.


Specific cell-mediated immunity in the laboratory diagnosis of dermatophytic infections. The leukocyte adherence inhibition test was used to detect cell-mediated immunity against antigens of the infecting fungi in patients with dermatophytosis. The species-specific diagnosis thus obtained was in all cases consistent with the eventual results of mycological examination. Most of the patients also produced a specific circulating blocking factor, the detection of which may be a useful guide to the success of treatment. Immunological reactivity against Candida albicans was also observed.


International mortality from bullous diseases since 1950. National mortality figures hold information about our overall success in treating bullous disorders which cannot be found elsewhere. The official data, since 1950, for England and Wales, the Unites States, France, Japan, Scotland, Ireland and Denmark have been analysed after corrections for changes in the population structure and in the International Classification of Disease. A steep fall in deaths occurred in England and Wales between 1952 (121 deaths) and 1955 (55 deaths). The low rate persisted from 1955 to 1962 (40 deaths) when it fell to a steady even lower level lasting until the present. The United States figures showed a sharp drop in mortality starting about 2 years earlier (from 283 deaths in 1950 to 150 deaths in 1954), followed by a gradual fall to the present. Mortality in Scotland, Ireland and Denmark has followed the same general pattern but the figures from France, after a steady fall between 1951 (68 deaths) and 1965 (29 deaths), have risen again until 1971 (62 deaths). The number of deaths has not fallen in Japan but the data are difficult to interpret. The timing of the improvement in mortality in England and Wales, and in the United States, fits well with the introduction of systemic steroids into general use. A fall to about one-third of the presteroid level is in general agreement with the improvement recorded in smaller personal series from several centres.


Cutaneous alternariosis.

Cutaneous alternariosis. Two patients with cutaneous alternaria infection are presented. In both patients the skin lesions were characterized by multiple non-healing ulcers covered with dry crusts. Although the skin changes were macroscopically alike in the two patients, differences in the histology were seen. Both patients had primary debilitating diseases. A review of the literature is presented and revealed an additional ten cases of cutaneous alternariosis. Methods for the isolation of Alternaria and the susceptibility of the fungus to antimycotic drugs are presented.


The relationship of platelet coagulant activities to venous thrombosis following hip surgery. Platelets have recently been shown to trigger intrinsic coagulation by two alternative pathways, protect active clotting factors from inactivation by plasma inhibitors and catalyse intrinsic coagulation reactions on the platelet surface to form fibrin. To determine whether these platelet coagulant activities (PCA) might have a role in the pathogenesis of DVT, 29 patients have been studied before and after arthroplasty or other surgery for fractured hip or degenerative hip disease. The occurrence of DVT was detected by [125I]fibrinogen uptake in the legs and confirmed by venography. In patients who developed DVT, all PCA increased progressively and significantly on day 1 (mean rise, 146% of baseline), day 3 (228%) and day 5 (298%) after surgery before isotopic evidence of DVT appeared (mean 3.27 days postoperatively). In patients without DVT no changes in PCA were observed. Plasma coagulation factor assays were no different in patients with a without DVT. Platelet counts and total platelet antiheparin activity increased during the early postoperative period in DVT patients but not in patients without DVT. It is suggested that progressive increases in PCA concerned with triggering and catalysing intrinsic coagulation reactions may play a pathogenetic role in DVT after hip surgery.


A new method for estimation of fetal weight in late pregnancy by ultrasonic scanning. The biparietal diameter and are of the fetal skull, and the area of the fetal thorax, were measured by ultrasonic scanning in 68 patients in the seven days prior to delivery. These parameters and various expressions based on the skull and thoracic areas were related to birth weight. It was concluded that the skull and thoracic areas multiple (STAM) index was a more efficient predictor of birth weight than the biparietal diameter.


The failure of pyridoxine in suppression of puerperal lactation. The benefits of pyridoxine in the suppression of lactation were assessed in a double blind controlled trial on 175 puerperal women. No significant differences were demonstrated between pyridoxine and the placebo whether assessed by subjective discomfort or by the persistence of lactation.


Neonatal hyperbilirubinaemia following the use of prostaglandin E2 in labour. A prospective study of 447 labours and the resulting newborn failed to reveal any significant difference between the incidence of neonatal hyperbilirubinaemia, defined as a level of at least 205 mumol/l (12 mg/100 ml), following spontaneous labour and after labour induced or accelerated with prostaglandin E2 (PGE2). The incidence of unexplained neonatal hyperbilirubinaemia after spontaneous labour was 4-5 per cent. There was no significant association between the incidence of neonatal hyperbilirubinaemia and the total dose of PGE2 used for induction. None of the babies of the six mothers who required more than 1-5 mg of PGE2 to induce labour developed hyperbilirubinaemia. No association was demonstrated between neonatal hyperbilirubinaemia and birth weight or the duration of labour. The implications of these findings are discussed.


Precision of ultrasonic fetal cephalometry. Ultrasonic measurement of the biparietal diameter is a frequently used technique in the assessment of fetal maturity. The popularity of this technique is based partly upon the claim that it can be performed with considerable presicion, but recently published work has not supported this claim. This paper  describes a blind clinical trial in which the precision of a single biparietal measurement was determined under normal clinical conditions. The results show that this measurement can be determined with a precision better than +/- 1.6 mm (+/- 2 standard deviations). The clinical significance of this result is discussed.


Eye signs in craniopharyngioma.

Eye signs in craniopharyngioma. A total of 45 patients with craniopharyngioma are reviewed, with particular reference to the presenting clinical features and neuro-ophthalmological findings. Of these 50 per cent had been referred in the first instance to an eye clinic. More than half the children presented with the clinical picture of raised intracranial pressure, although one-third of these had optic atrophy rather than papilloedema. One-third of the children had a history of concomitant strabismus, and only one patient had a paretic squint. The majority of the adults presented with visual failure and optic atrophy. Bitemporal hemianopia was fairly frequently found (27 per cent of our patients at the time of diagnosis) but was asymmetrical and unpredictable in its evolution. Homonymous hemianopia was relatively common, a presenting feature in II per cent of patients in this study. Full fields were found initially in nine patients (20 per cent), a high incidence compared with pituitary adenomas or suprasellar meningiomas. We consider pleomorphism, that is a distinct change from one type of field defect to another with progress of the disease, to be a characteristic feature of the tumour (as indeed are fluctuations in the clinical state and visual acuity); it was detected in 22 per cent of our patients. Endocrine disorders were common, especially in adults, and mental deterioration was a frequent presenting feature in patients over 30 years of age. Straight x rays of the skull are practically diagnostic of craniopharyngioma in children, but in adults a normal x ray does not exclude the diagnosis.


Comparative trial of Dexon (polyglycolic acid), collagen, and silk sutures in ophthalmic surgery. The tissue reaction, absorption, and handling properties of Dexon synthetic absorbable sutures, which are made from polymerized hydroxyacetic acid, were compared with those of silk and collagen in 51 eye operations, consisting mainly of cataract extractions and squint corrections. There was no significant difference between the sutures as regards degree of tissue reaction. The Dexon sutures were very strong and the knots held well. The sizes used in this series were found to be a little too thick and stiff for use in micro-surgery; smaller sizes would be easier to use and still remain strong enough. The Dexon was reliably absorbed in 5 weeks on average. No serious adverse reactions were seen with any of the sutures. Dexon was as well tolerated as the control sutures but had the advantage over silk of being absorbed and over collagen of containing no foreign protein.


Manganese(II) and substrate interaction with unadenylylated glutamine synthetase (Escherichia coli w). I. Temperature and frequency dependent nuclear magnetic resonance studies. A comprehensive study of solvent interaction with unadenylylated glutamine synthetase (E1.7) has been conducted using the enzyme isolated from Escherichia coli W. The longitudinal, (1/T1p)b, and transverse, (1/T2p)b, proton relaxation rates were measured with various enzyme samples as a function of frequency (6-48 MHZ) and temperature (1-40 degrees C). With Mn(II) bound at the "tight" metal ion site approximately two water molecules are rapidly exchanging with bulk solvent. This number is reduced to approximately one in the presence of glutamine. All data were successfully analyzed according to the Solomon-Bloembergen-Morgan (SBM) scheme for dipolar relaxation of water protons interacting with enzyme-bound Mn(II). The correlation time for this process varies from 1 to 3 X 10(-9) for the complexes described above. Significant contributions to the correlation time arise from both 1/taum, the exchange rate for water molecules bound at the metal site, and from 1/taus, the electron spin relaxation rate for Mn(II) with the latter rate showing a frequency dependence at the magnetic field strengths used in this study. A study of Mn(II) binding to E1.7 at 25 degrees C revealed two classes of metal ion sites, a "tight" set of one per subunit with KD=5.0 X 10(-7) M and a "weak" set of one per subunit with KD=4.5 X10(-5)M. In the presence of glutamine the affinity of the first site for Mn(II) was unchanged but the KD value for the weak site changed to 3 X 10(-6)M. In E1.7 samples with Mn(II) bound at both the tight and weak metal ion sites the data are interpretable with two rapidly exchanging water molecules interacting with each bound Mn(II)ion. With saturating amounts of glutamine or of ADP or of glutamine plus ADP plus arsenate, the proton relaxation rates progressively decreased suggesting that the substrates or inhibitors used were interacting with the bound Mn(II) ions resulting in diminished solvent accessibility to these bound ions. These results are interpretable in terms of ligand substitution into the coordination sphere of the bound Mn(II) ions. Indeed this is probably the case for Mn(II) at the weak metal ion site since Hunt et al. ((1975), Arch. Biochem. Biophys. 166, 102) showed that Mn(II) can bind as the Mn(II)-ADP complex to the second metal ion site. Results of proton relaxation rate data on E1.7 with Mn(II) bound at both the tight and weak metal ion sites led to the conclusion that these metal ion sites are greater than 6 A apart. In comparison with proton relaxation rate data on fully adenylylated glutamine synthetase (E11.8) as studied by Villafranca and Wedler ((1974), Biochemistry 13, 3286), the first "tight" metal ion site in E11.8 has three rapidly exchanging water molecules. Mn(II) has a weaker binding constant to E11.8 (KD approximately 5 X 10(-6)M) at the pH value used in both studies and a suggestion is made that an additional protein ligand is binding to Mn(II) in glutamine synthetase when the subunits are not adenylylated.


Borate inhibition of yeast alcohol dehydrogenase. Yeast alcohol dehydrogenase is inhibited competitively by borate with respect to NAD+. An unusual mechanism of competitive inhibition prevails: the competition for the substrate NAD+ by borate and enzyme. The following evidence supports this conclusion. (1) Much greater inhibition is observed with respect to NAD+ as compared with NADH as substrates. (2) Borate decreases the equilibrium constant of the overall reaction in the direction of ethanol oxidation, therefore, borate enters directly into the overall reaction rather than merely decreases the effectiveness of the catalyst. (3) The Ki values for unrelated enzyme reactions are identical for NAD+. (4) Stopped-flow experiments show burst kinetics only when NAD+ and borate are not premixed. (5) The Ki value is identical with the inverse of the borate-NAD+ complexation constant. (6) The pH dependence of the inhibitor demonstrates that only the B(OH)4-species is inhibiting. These results are consistent with the preferable binding of borate to NAD+ as compared with NADH. These two binding constants were found to be equal to 2000 +/- 60 and 130 +/- 8 M-1, respectively. In contrast to the liver enzyme, the yeast enzyme does not show pre-steady-state burst reactions in the reduction of NAD+. This would indicate that the interconversion of ternary complexes is at least partially rate limiting for the yeast enzyme.


Nepsilon-acetyllysine transfer ribonucleic acid: a biologically active analogue of aminoacyl transfer ribonucleic acids. Unfractionated Escherichia coli tRNA has been aminoacylated with lysine and preferentially acetylated at the epsilon-amino nitrogen of lysine by reaction with N-acetoxysuccinimide. After treatment with peptidyl-tRNA hydrolase, 90% of the aminoacylated tRNA molecules were Nepsilon-acetyl-Lys-tRNA. Post-ribosomal supernatant enzymes would not deacylate Nepsilon-acetyl-Lys-tRNA in the presence of AMP and PPi, even though such mixed enzymes could acylate, with lysine, tRNA which had been exposed to the acetylation reaction conditions. Poly(rA) stimulated the binding of Nepsilon-acetyl-Lys-tRNA to E. coli ribosomes. At the ribosome and tRNA concentrations used, Nepsilon-acetyl-Lys-tRNA was bound nearly as well as Lys-tRNA at 30 mM Mg2+; at 10 mM Mg2+, the analogue was bound one-half as well as Lys-tRNA. Both Lys-tRNA and Nepsilon-acetyl-Lys-tRNA reacted only slightly with puromycin at either 10 or 30 mM Mg2+. When Lys-tRNAE. coli or Nepsilon-acetyl-Lys-tRNAE. coli were added to rabbit reticulocyte cell-free protein synthesizing incubations, the incorporation of either amino acid into protein was complete within 5 min. The final incorporation level of the analogue was 82% that of the unmodified lysine. After protein synthesized in the presence of Nepsilon-acetyl-[14C]Lys-tRNA had been digested enzymatically to single amino acids, ion-exchange chromatography and paper electrophoresis showed that nearly all of the radioactivity was present as Nepsilon-acetyllysine. Gel filtration of the post-ribosomal supernatant revealed that most of the Nepsilon-acetyllysine radioactivity cochromatographed with tetrameric hemoglobin.