The dynamics of streptococcal infections in a defined population of children: serotypes associated with skin and respiratory infections. Serial observations including cultures of the upper respiratory tract and of infected skin lesions and streptococcal antibody determinations were made over a two-year period in a semi-closed population of children between 10 months and 15 years of age. There was a high prevalence of group A streptococci in nose and throat cultures and of skin lesions containing these organisms. Almost 90% of the study population developed streptococcal impetigo during the study period. A slightly higher proportion of males than females developed skin infection but there was no relationship to age. Impetigo was observed throughout the calendar year, exceeding 12% of child-visits in one winter month, but was generally more common in the summer and fall. Conversely, group A streptococci were more often isolated from nose and throat cultures in the winter months. The increase in recovery of streptococci from nose and throat cultures lagged behind the increase in streptococcal impetigo and continued into the winter months, when the prevalence of impetigo had declined. Calculation of ratios for individual streptococcal serotypes isolated from different body sites revealed a clear cut distinction between "respiratory" and "impetigo" serotypes, with respect to both prevalence and acquisition rates. Respiratory serotypes were more commonly isolated in the winter and impetigo serotypes in the summer and fall. Significant antibody responses to extracellular antigens of the streptococcus were documented for pharyngeal acquisitions of both impetigo and respiratory serotypes and for skin lesions associated with impetigo serotypes. Group A streptococcal serotypes may be divided into three categories on the basis of their human pathogenicity for body sites: some with the potential for respiratory infection, others with the potential for skin infection and a few unusual serotypes with the potential for infecting both sites.


Pathogenesis of polycythemia vera--new concepts. Data presently available suggest that polycythemia vera is an acquired clonal disorder of the pluripotent stem cell resulting in expansion of committed stem cell pools, most prominently in the erythroid line. In vitro and in vivo studies suggest that erythropoiesis in polycythemia vera is at least partially modulated by erythropoietin.


Titles in the medicolegal field: a proposal for reform. One of the most readily apparent weaknesses in the field of medicolegal studies has been our inability to develop consistent and lexicographically defensible descriptive titles for the field itself. In this Article, Professor William J. Curran offers an analysis of the historical roots of the terminology which has been applied in this field over the years, an examination of current confused usage, and a proposal for reform.


Pharmacist's effect on digoxin usage and toxicity. Digoxin usage and toxicity were compared in a prospective group of patients who were monitored by a pharmacist and a retrospective group for which there was no pharmacist consultation. For the prospective group, the pharmacist monitored patients and estimated the steady-state digoxin levels by the use of a nomographic method. Level greater than 2.2 ng/ml and concurrent ECG or physical signs of digoxin toxicity were communicated to the physician. For the retrospective group, digoxin levels were calculated based on data from the patients' charts. The 49 patients in the two study groups were categorized according to four levels of digoxin toxicity (ranging from "no evidence" to "probable"). The only characteristic that was significantly different between the two groups was the calculated creatinine clearance (lower for the retrospective group). The maintenance dose of digoxin and the incidence of digoxin toxicity were significantly lower in the prospective group. It is concluded that pharmacist intervention may have had an effect in reducing digoxin dosage and toxicity.


Aerobic and anaerobic flora of the cervix during pregnancy and the puerperium. Comparison of species of bacteria isolated from patients with endometritis with species isolated from normal pregnant and nonpregnant women suggests that bacteria causing infections are indigenous to the genital tract. However, complete studies of the flora of pregnant women, especially anaerobic flora, are lacking. Aerobic and anaerobic cultures of the endocervix were obtained from women in all trimesters of pregnancy and at three days and six weeks post partum. The incidence of occurrence of each species of bacteria and the average number of different species per culture were determined for each period. The most prevalent organisms in each period were aerobic gram-positive rods and cocci and anaerobic gram-positive cocci. The average number of species of aerobic bacteria per culture remained approximately the same in each culture period. The average number of anaerobic species per culture decreased as pregnancy progressed, peaked on the third postpartum day, and at six weeks post partum returned to a level similar to that of the first trimester.


The apparent paradox of the negative and positive feedback control system on gonadotropin secretion. The separate and interactive effects of estradiol (E2) and luteinizing hormone-releasing factor (LRF) on the dynamics of LH storage and release were studied. Measurements were made of the serum gonadotropin responses to submaximal doses of LRF, given as brief pulses or infused over an extended period to normal women at various stages of the follicular phase of their menstrual cycles and to hypogonadal women with and without estrogen treatment. The two-pool concept of pituitary gonadotropin was verified; the dynamic responses of the two pools to the inputs of LRF and E2 were investigated and related to pituitary properties of sensitivity and reserve. Our results indicate that LRF appears to serve as a primary drive on the gonadotrophs, stimulating gonadotropin synthesis and storage (second pool), as well as release (first). E2 for the most part, amplifies the action of LRF except that it impedes LRF-induced release of gonadotropin. E2 augments the second pool activity (reserve) preferentially, and the relative activity of the first pool appears to be influenced by the E2-dependent self-priming effect of LRF. The interactions of the various elements of the system, when combined, provide a U-shaped curve to describe the over-all capacity of the gonadotrophs as a function of a broad range of E2 inputs. Negative and possitive feedback of E2 are revealed to operate by different mechanisms and to represent different segments of a single U-shaped curve rather than paradoxically disparate actions.


Evaluation of emotional reactions to oral contraceptive use. A review of available clinical studies indicates that 10 to 40 per cent of oral contraceptive users may suffer mild to moderate depression syndromes. Clinical and animal data indicate that a variety of mechanisms may be involved, including alterations in folate, pyridoxine, and vitamine B12 metabolism, as well as related effects on biogenic amine metabolism. Interactive effects may result, such as impairment of usual coping mechnisms and psychological defenses by altered central nervous system function.


Pars plana vitrectomy in the management of endogenous Candida endophthalmitis. A 27-year-old white man had endogenous Candida endophthalmitis with fungi in the vitreous cavity, presumably caused by hematogenous spread related to drug abuse, and was treated by pars plana vitrectomy and antifungal medications administered systemically after surgery. There was no evidence of other systemic involvement, and excision of fungi from the vitreous cavity confirmed the clinical diagnosis and determined the sensitivity of this fungus to antifungal medications. The fungus was sensitive to flucytosine (5-FC), which the patient received orally since it was less toxic to body tissues than amphotericin B. The intraocular infection cleared rapidly after vitrectomy, and visual acuity returned to 6/5 (20/15).


Correction of upper eyelid retraction.

Correction of upper eyelid retraction. We used two surgical procedures to treat upper eyelid retraction in ten patients: either a posterior myectomy or the anterior levator muscle recession technique. Our choice was usually based on the amount of retraction. We used the posterior myectomy technique to treat up to 2 mm of retraction or localized retractions (five cases), particularly after blepharoptosis surgery. We used the anterior recession method to treat more than 2mm of retraction (five cases), particularly when associated with dysthyroid ocular disease. Complex eyelid contour abnormalities were treated with a combined recession-resection approach to the aponeurosis of the levator palpebrae superioris muscle (one case).


Transiridectomy suture technique for the Binkhorst iris-clip lens implant. A magnet facilitated placement of the transiridectomy suture used in conjunction with the Binkhorst iris-clip lens implant.


An artificial anterior chamber.

An artificial anterior chamber. Corneas for penetrating keratoplasty that have been excised from the globe for storage ordinarily require punching of the donor tissue from the posterior surface. They may be trephined from the anterior surface when they are mounted on an instrument that forms a seal around the scleral rim of the excised cornea, allowing the endothelium to be supported physically by the liquid storage medium. The artificial anterior chamber protected the endothelial cells from damage as if they were still in the intact globe. The instrument allowed trephination to any desired depth and facilitated the cutting of corneal buttons with a rim of Descemet's membrane and endothelium. Sutures may be preplaced in the donor button before the button is seperated completely from the rest of the cornea. Iris prolapse did not interfere with the procedure.


Autoimmune phenomenon in Mooren's ulcer. Direct immunofluorescent techniques demonstrated immunoglobulins localized to the conjunctival epithelium in three cases of Mooren's ulcer. In addition, complement was found in association with the immunoglobulins in the two active cases. Circulating antibodies to the conjunctival and corneal epithelium were demonstrated by indirect immunofluorescent techniques in all three patients. Further immunological examinations of the three cases failed to demonstrate other significant immune alterations.


Macrophage migration inhibition factor activity in the aqueous humor during experimental corneal xenograft and allograft rejection. Macrophage migration inhibition factor (MIF), a soluble mediator of delayed hypersensitivity, was assayed for in the aqueous humor of rabbits undergoing corneal graft rejection. Penetrating and interlamellar xenografts and interlamellar allografts were performed in rabbits, and aqueous humor early in the course of xenograft and allograft rejection, and MIF activity was present during the course of the active rejection. This activity returned to near normal after the active rejection resolved. No significant MIF activity could be measured during the nonspecific inflammations produced by alkali burns, multiple paracenteses, intracorneal clove oil, mechanical debriding of the endothelium.


Corticosteroid therapy for the reduction of postoperative inflammation after cataract extraction. In an random, double-masked multicentric clinical trial, topical betamethasone phosphate 0.1% or placebo eyedrops were used five times daily for the first two weeks after uncomplicated intracapsular cataract extraction in 107 patients who had moderate to severe postoperative inflammation on the first postoperative day. Topical corticosteroid solution was significantly more effective than placebo in the reduction of postoperative ocular inflammation. There were no ocular complications of corticosteroid treatment.


Arch expansion: an integral part of surgical orthodontics. Two cases of mandibular prognathism have been presented. In both cases expansion of the dental arches was performed prior to surgery for the achievement of good and stable interarch relationships postoperatively. In the first case maxillary arch was expanded with a rapid-expansion technique; in the second, expansion of the mandibular arch was performed with a modified removable Coffine appliance. Results at 15 months and 2 years after retention showed the expansion to be stable.


Spontaneous glomerular sclerosis in aging Sprague-Dawley rats. I. Lesions associated with mesangial IgM deposits. The present studies examined the pathogenesis of focal glomerular sclerosis in aging rats. A marked difference in development of the lesion was noted between males and females, and strain variability was an important factor. Increased glomerular basement membrane permeability with loss of selectivity unrelated to changes in glomerular sialoprotein occurred with aging and was accompanied by increasing proteinuria. Noncomplement-fixing mesangial deposits of rat IgM were present after 1 month of age and were also found in lesser amounts in germfree rats. Fluoresceinated eluates of rat kidneys did not have antibody activity against rat serum or tissue antigens. There was no evidence for a pathogenetic role of IgM deposits. Rat IgG, IgA, IgE, C3, and fibrin were occasionally found in sclerotic areas. Analysis of multiple histologic sections revealed a close correlation between aging and glomerular pathology, with a poor correlation between tubular damage and aging. Glomerular damage appeared to be the initial event leading to tubular damage. Indirect evidence suggests that a relative thymic deficiency may play an important role in the pathogenesis of the lesion.


Some interrelations of neutrophil chemotaxis, lysosomal enzyme secretion, and phagocytosis as revealed by synthetic peptides. Synthetic oligopeptides of appropriate structure stimulate neutrophil random locomotion, chemotaxis, lysosomal enzyme secretion, and phagocytosis. The structure-activity relationships found for enhanced migration and lysosomal enzyme secretion strongly suggest that the peptides bind to a structurally specific receptor on the neutrophil surface. It is further suggested that the binding of a peptide to the same receptor initiates all of these neutrophil functions. It is postulated that this is accomplished by the receptor-peptide combination initiating a series of parallel but coordinated and interdependent biochemical sequences leading to either microfilament or microtubule activation in addition to other processes. The various functions of the neutrophil differentially utilize the microfilament and microtubule systems.


Modulation of human eosinophil polymorphonuclear leukocyte migration and function. Eosinophil migration toward a concentration gradient of a chemotactic factor is regulated at four levels. Diverse immunologic pathways generate stimuli with eosinophil chemotactic activity, including the complement products C5a and a fragment of C3a and the peptide products of mast cells and basophils activated by IgE-mediated reactions, such as eosinophil chemotactic factor of anaphylaxis (ECF-A) and other oligopeptides. The intrinsic preferential leukocyte activity of the chemotactic stimuli represents the second level of modulation, with ECF-A and other mast cell-derived peptides exhibiting the most selective action on eosinophils. The third level of control of eosinophil chemotaxis is composed of inactivators and inhibitors of chemotactic stimuli and is exemplified by degradation of C5a by anaphylatoxin inactivator or chemotactic factor inactivator and of ECF-A by carboxypeptidase-A or aminopeptidases. The activity of ECF-A is uniquely suppressed by equimolar quantities of its NH2- terminal tripeptide substituent, presumably by eosinophil membrane receptor competition. Factors comprising the fourth level of regulation, which alter eosinophil responsiveness to chemotactic stimuli, include the chemotactic factors themselves, through deactivation; nonchemotactic inhibitors such as the COOH-terminal tripeptide substituent of ECF-A, the neutrophil-immobilizing factor (NIF), the phagocytosis-enhancing factor Thr-Lys-Pro-Arg, and histamine at concentrations greater than 400 ng/ml; and nonchemotactic enhancing principles represented by ascorbate and by histamine at concentrations of 30 ng/ml or less. Local concentrations of eosinophils called to and immobilized at the site of a hypersenitivity reaction may express their regulatory functions by degrading the chemical mediators elaborated including histamine, slow-reacting substance of anaphylaxis (SRS-A), and platelet-activating factor (PAF) by way of their content of histaminase, arylsulfatase B, and phospholipase D, respectively. Immunologic pathways may thus provide the capability for early and specific host defense reactions with a later influx of eosinophils preventing irreversible local tissue alterations or distant organ effects.


Feasibility of computer evaluation of the histopathologic findings in human skeletal muscle disease. Optical Fourier methods of image processing coupled with mutual information analysis were applied to the separation of human muscle specimens into four diagnostic classes. This process allowed rapid, relatively inexpensive data acquisition, reduction, and classification. The accuracy of the method when compared to that of experienced surgical pathologists is acceptable. Difficulties arise when material outside of the previous experience of the computer is presented.


From phrenology to psychosurgery and back again: biological studies of criminality. Characteristics of scientific research--careful definition of the problem, random sample selection, relevant control groups, careful measurement techniques, and caution in drawing conclusions from the data--are employed to evaluate the argument for constitutional, genetic, mental, endocrinal, and neurological theories of crime causation. A historical continuity in assumptions and methodological flaws is revealed between contemporary studies of the biological correlates of crime and their earlier counterparts. Social and political ramifications of biomedical research are considered.


The use of liver epithelial cultures for the study of chemical carcinogenesis. Liver cultures offer several special advantages for the study of chemical carcinogenesis in cell culture; these include the sensitivity of the cells to procarcinogens requiring enzymatic activation, the epithelial nature of the cells which qualifies them as a model for epithelial carcinogenesis, and the opportunity to compare culture findings with the extensive information available on the effects of carcinogens on liver. The actions of chemical carcinogens have been studied in primary and long-term rat liver cell cultures. A variety of procarcinogens induced DNA repair in primary cultures, indicating the usefulness of this system for studying carcinogen metabolism, the interaction of carcinogens with DNA, and the repair of carcinogen-induced DNA damage. In addition, this system may provide a screen for chemical carcinogens in which metabolic activation occurs in the target cell. Carcinogen treatment of long-term cultures initiated from the primary cultures resulted in morphologic transformation accompanied by an increased growth in soft agar and an increased frequency of 8-azaguanine-resistant mutants. Cultures with a high fraction of cells in S phase were found to be most sensitive to the induction of 8-azaguanine-resistant mutants.


The effect of practice orientations on clinical assessment. Increasing theoretical evidence suggests that assessment procedures in themselves may have deleterious effects on mental health intervention. This experimental study of assessment processes suggests that negative labeling is related to the main effects of practice orientations and status differential. Results are discussed in terms of the unexpected negative consequences of assessment.


Tumors in the remains of ancient Egyptians. A survey of the tumors found in the remains of the Ancient Egyptians shows the occurrence of all the kinds of tumors which would be expected to be preserved in the osteological evidence. On the other hand, findings of tumors in the soft tissues of mummies are only exceptional. The frequency of tumors seems to be lower than in recent years, probably because of the shorter mean duration of life. The pathological lesions preserved in bony sturcture reveal not only osseous tumors, but also the presence of some tumors of soft tissues eroding the bone. To the survey of cases described in the literature, original findings of a calcified myoma uteri and of a probably epipharyngeal carcinoma are added. Because our knowledge on the history of tumors is not yet comprehensive, much more attention should be devoted to the search for them, starting from the moment of excavation of any cemetary.


Aboriginal new world epidemiolgy and medical care, and the impact of Old World disease imports. Various workers, including T. D. Stewart, claim that the aboriginal Americas were relatively disease-free because of the bering Strait cold-screen, eliminating many pathogens, and the paucity of zoonotic infections because of few domestic animals. Evidence of varying validity suggests that precontact Americns had their own strains of treponemic infections, bacillary and amoebic dysenteries, influenza and viral penumonia and other respiratory diseases, salmonellosis and perhaps other food poisoning, various arthritides, some endoparasites such as the ascarids, and several geographically circumscribed diseases such as the rickettsial verruca (Carrion's disease) and New World leishmaniasis and trypanosomiasis. Questionably aboriginal are tuberculosis and typhus. Accordingly, virtually all the "crowd-type" ecopathogenic diseases such as smallpox, yellow fever, typhoid, malaria, measles, pertussis, polio, etc., appear to have been absent from the New World, and were only brought in by White conquerors and their Black slaves. My hypothesis is that native American medical care systems--especially in the more culturally advanced areas--were sufficiently sophisticated to deal with native disease entities with reasonable competence. But native medical systems could not cope with the "crowd-type" disease imports that struck Indian and Eskimos as "virgin-field" populations. Reanalysis of native population losses through a genocidal combination of diease, war, slavery and attendant cultural disruption by Dobyns, Cook and others strongly suggest that traditiona estimates underplayed the death toll by a factor of the general order of ten. This would make for an immediately pre-contact Indian population of some 90-111 million instead of the tradition 8-11 million. Evidence is growing that Indians may have been no more susceptible to new pathogens that are other "virgin soil" populations, and thus their immune systems need not be considered less effective than those in other people. Present-day high mortality rates in Indians of both continents from infectious disease imports may be more socioeconomic than anything else.


Colonial modern skeletal change in the U.S.A. Eighty-two people dating from 1975 to 1879 compared with 182 modern middle-class White and Black skeletons test the myths of radical changes produced by improved diet, less disease, and nineteenth century immigration. Longevity increases and health and growth improvement is clearest in reduced juvenile deaths (census data) and deepening of true pelvis. Stature increase is minimal (though seventeenth century Londoners and modern West Africans are shorter than Colonial to Modern Americans); teeth deteriorate and for cultural reasons fractures increase. Clavicles and forearms elongate. From Old to New World Colonial samples there is a noticeable skull change (and a greater Old World to Modern contrast) but White Colonial to Modern shows strong continuity surprisingly, the key changes being increasing head height, and retraction of face with increasing nose projection, and longer mastoids, resulting from selection and mixture. Blacks change more, possibly from Indian and White mixture. Variabilities are above average. Change is much less than expected, and apparently involves heterosis and selection as well as the obvious health advance and mixtures.


Kallikreinlike activity in perfusates and urine of isolated rat kidneys. In the perfusate and the urine produced during perfusion of isolated rat kidneys a kallikreinlike enzyme similar to that found in the kidney was detectable by bioassay 15-25 min after the beginning of the perfusion. The source of the kallikrein activity was the kidney itself, since before the perfusion was started the blood remaining in the kidneys was washed out and the perfusion medium was free of kallikrein and its precursors and substrates. The kallikreinlike activity of the perfusate was characterized by a) an oxytocic effect on isolated rat uterus, b) a kininogenase activity on kininogen II, c) an esterase activity on N-benozyl-L-arginine ethyl ester, and d) a hypotensive effect on anethetized rats. These properties were inhibited by diisopropyl activity in the perfused kidney was lower than that in the nonperfused organ, but the total amount of kallikrein activity released to the excreted urine and the perfusate was significantly greater than the corresponding activity that disappeared in the kidney. This result is in keeping with the concept that the renal tissue is able to synthesize kallikrein.


Effects of ions on amylase release by dissociated pancreatic acinar cells. Dissociated acinar cells prepared from guinea pig and mouse pancreas were intact on the basis of structure, ion content, and their ability to increase release of amylase in response to bethanechol and the calcium ionophore A23187. Guinea pig but not mouse acinar cells increased amylase release in response to caerulein. An increase in the concentration of K+ in the medium, which increases amylase release from whole pancreas, did not increase release. The effect of varying the ionic content of the medium on basal and stimulated amylase release was studied. Bethanechol and caerulein were still able to stimulate amylase release when Ca2+ was omitted from the medium, whereas stimulation induced by A23187 was abolished. Elevation of the concentration of Mg2+ did not affect basal or stimulated amylase release. Removal of Na+ from the medium initially had no effect on amylase release although bethanechol-stimulated release by mouse cells was inion of the HCO3- or Cl- content of the medium did not affect cholinergic stimulation of secretion. It is concluded that stimulated amylase release by isolated acinar cells is relatively independent of the ionic constituency of the bathing medium.


Notes from "Pavlov's Wednesdays": Pavlov's law of effect. Pavlov's Wednesday seminars indicate that he adopted homeostatic balance as a law of effect in order to deal with Konorski's experiments on omission and avoidance training; he did not, as is often thought, completely assimilate instrumental conditioning into his classical framework. He saw the 'new' type of conditioning as the basis of voluntary behavior in higher animals and devoted considerable attention to it in 1930-1933.


Angiographic and ultrasonic findings in infected simple cysts of the kidney. This paper describes angiographic and ultrasonic findings in three patients with proven infected renal cyst. The clinical picture was that of inflammatory renal disease. B-mode ultrasonography showed the characteristic features of renal cyst; however, this technique cannot differentiate between infected and simple cysts. Selective renal angiography demonstrated the following, enabling differentiation from simple renal cyst; hypervascular rim, irregular inflammatory vessels, indistinct interface between cyst and adjacent parenchyma, and prominent capsular branches. Since percutaneous puncture of an infected renal cyst or abscess carries risk of infectious complications, angiography appears justified only for those patients with fever and flank pain who have cystic lesions in the kidney confirmed by echography.


Radiologic features of gram-negative pneumonias in the neutropenic patient. While gram-negative pneumonia is a frequent complication in immunosuppressed patients with malignant disease, the diagnosis is difficult to establish. Clinical and radiographic study of 195 episodes of pneumonia in 175 consecutive patients was undertaken. Chest radiographs were negative in 19% of the episodes, probably due to absence of alveolar inflammatory cell infiltrate. Radiographic patterns were classified as either alveolar or mixed alveolar and interstitial; no case of interstitial pattern alone was identified. A positive correlation was found between the neutrophil count and the presence of radiographic abnormalities. The different types of organisms could not be distinguished by the radiographic appearance. The importance of early diagnosis and prompt specific treatment is stressed.


Successful treatment of dendritic keratitis with human leukocyte interferon. A controlled clinical study. There were 40 virologically confirmed cases of dendritic keratitis treated in a randomized double-blind placebo-controlled study. After thermomechanical debridement of the corneal epithelium, the patients received two drops of human leukocyte interferon (HLI) twice daily. The activity was 3 X 10(-6) units/ml. HLI significantly accelerated healing and inhibited virus shedding. It remains to be studied whether HLI will be equally effective in the prophylaxis of late herpes recurrences.


Diabetic retinopathy study. Assessment and comparison of retinal lesions for computer analysis. A method of documentation of a diabetic retinopathy (dR) is described. Panorama fundus photographs (PPhs) of each eye are taken every 3-6 months. The retinopathy is classified according to qualitative, quantitative, and topographic criteria. The retinal lesions are assessed according to a subjective grading scale. Data of direct readings and of comparisons between two PPhs of one eye are transferred to punch cards for storage and computer processing. In a double evaluation of 200 PPhs, the overall reliability of readings was found to be approximately 95%.


[Dichlorphenamide treatment in acute glaucoma (author's transl)]. Dichlorphenamide as well as Diamox lowers intraocular pressure. For adequate treatment of acute glaucoma only 20% of commonly used Diamoxdosis is requested to reach comparable pressure release two hours later. After one hour control intraocular pressure of 60% from patients with Dichlorphenamide treatment was found below 40 mm Hg since in Diamoxgroup there were only 30% below 40 mm Hg. Different effects of Dichlorphenamide and Diamox after one hour use is demonstrated in respect of serum electrolytes and base excess as well. Essential side effects after a single dosis of 200 mg Dichlorphenamide or in combination with Diamox for acute glaucoma treatment could not be observed.


Distribution of growth hormone-release-inhibiting hormone (somatostatin) in the rat brain as observed with immunocytochemistry. The objective was to determine the distribution of growth hormone-release-inhibiting hormone (somatostatin) in the rat brain using the peroxidase-antiperoxidase immunocytochemical method with antisera prepared against unconjugated, synthetic somatostatin. Somatostatin occurred in low quantity in the organum vasculosum of the lamina terminalis. It was present throughout the full length of the median eminence and occupied the entire width between the tuberoinfundibular sulci. Most somatostatin was located in the dorsal portion of the external lamina, and the amount varied according to the mediolateral position. The bodies labeled for somatostatin were most often granules; occasionally they appeared as clusters of granules that seemed to be membrane-enclosed. Some of these bodies appeared to be portions of axons. Many of the larger bodies were arranged alongside tanycytes, but no label was distributed generally in tanycyte cytoplasm. Somatostatin was highly concentrated in the proximal one-quarter of the infundibular stem and appeared in lower concentration throughout the distal portion of the stem. It was absent from the pars nervosa and pars intermedia of the pituitary gland. The distribution of somatostatin in the median eminence differed considerably from that of gonadotropin-releasing hormone. Somatostatin was identified in the ventromedial and/or dorsomedial hypothalamic nuclei of only two animals. Here it was probably located in axons that terminated on neuronal cell bodies but also may have been present in a restricted portion of the perikaryonal cytoplasm.


The influence of pharmaceutical compounds on male fertility. 1. Steroid hormones can affect spermatogenesis and thereby fertility directly and/or indirectly. All antigonadotropically active steroids inhibit spermatogenesis via inhibition of gonadotropin secretion, mainly that of H. Androgens and steroids occurring in the biosynthetic chain of testosterone synthesis have a direct promoting effect on spermatogenesis if applied in high doses. It has not been possible as yet to make clinical use of this positive effect since it is obviously not possible to achieve the necessary intratesticular androgen concentrations. 2. As concerns the different androgens and the steroids in the androgen biosynthetic chain, and also all synthetic anabolics, there is no parallelism between the direct spermatogenic activity, the androgenic activity and the antigonadotropic activity. 3. Estrogens and synthetic gestagens do not inhibit spermatogenesis directly at the testicular level. All effects of estrogens can be abolished experimentally by adequate substitution with gonadotropins or androgens, or a combination of androgens and gonadotropins. 4. Only those antiandrogens inhibit spermatogenesis with additional antigonadotropic properties (e.g. cyproterone acetate). Pure antiandrogens, like flutamide or cyproterone, have a slight and transient influence on spermatogenesis at the most. If at all, they merely cause transient subfertility. 5. Beside steroids and several centrally active pharmaceutics (e.g. psychotropic drugs and several antihypertensive compounds), only siloxanes and methallibur seem to affect spermatogenesis via inhibition of gonadotropin secretion. Other antispermatogenic agents act by inhibition of mitosis (Colchicine, alkylating agents) or presumably via damage of the Sertoli cells. 6. Based on present knowledge, contraception in men could be principally managed by administration of a) androgens alone, b) gestagen/androgen combinations, c) estrogen/androgen combinations, d) certain antiandrogens. 7. The difficulties of contraception in men by steroid hormones or steroid hormone combinations have been pointed out. As regards the usefulness of antiandrogens for contraception, no definite conclusions can be drawn at the moment. All non-steroidal inhibitors of spermatogenesis which have been found up to the present are not suitable because of toxic effects.


Evaluation of the functional state of male accessory glands by the analysis of seminal plasma. In man, the seminal vesicles, together with the ampuls, constitutes the main source of seminal fructose. The human prostate produce citric acids, acid phosphatase and other enzymes. The exceeding high content of prostaglandins probably derives from the seminal vesicles. A combined analysis of fructose and citric acid in the ejaculate is desirable to state morphologic alterations or functional disturbances of the accessory glands. The well-known split ejaculate method enables to decide whether the ejaculatory process is normal, slight or heavily disturbed. Variations in the morphology and secretory function of the accessory glands in different mammalian species are pointed out. The influence of testosterone on the secretory function of the accessory glands is described and discussed in detail.


Type IV reactions in the skin.

Type IV reactions in the skin. Delayed type (Type IV) hypersensitivity is commonly manifested in clinical practice as allergic eczematous contact dermatitis (AECD). This reaction can be transferred by lymphoid cells but not serum and parallels other T lymphocyte immune responses. Recent evidence correlates the sensitization phase of AECD with in vitro lymphocyte transformation and the elicitation phase with lymphokine activity. Although a bewildering variety of haptens may be responsible for AECD, they have in common an ability to form co-valent bonds with proteins. Patch testing with the offending antigen will reproduce the disease. Therapy of choice remains topical or systemic corticosteroids.


The bronchodilator effects of terbutaline: route of administration and patterns of response. The effectiveness and clinical indications of Terbutaline as a bronchodilator were analyzed by the subcutaneous, oral and aerosol route in 56 patients. A significant improvement in air flow rates both in major and smaller airways was achieved by all routes of administration. The inhalation route offered the fastest onset of action, maximal response and longest duration. Similar trends, but of decreased magnitude, were seen following the subcutaneous and oral routes. Overall analysis of results did not indicate a definite dose-response dependency within the aerosol and oral routes at the tested dosages, whereas the incidence of side effects was clearly dose-dependent. On this basis it is recommended that for maintenance therapy treatment should begin with oral Terbutaline 2.5 mg every 6-8 hours and this dose be adjusted according to the clinical response. For the treatment of acute bronchospasm 0.50 mg or 0.25 mg subcutaneously, or a dose as low as 0.375 mg by aerosol, would be highly effective within five minutes. A combination of oral and aerosol administration represents a highly effective synergistic combination for most clinical situations requiring maintenance therapy.


Study of E rosettes, serum IgE and eosinophilia in asthmatic children. In this study active and total E rosettes in asthmatic children were comparable to those in healthy children and healthy adults. There were no interrelations among E rosettes, serum IgE levels and total eosinophil counts.


Intensification by glucocorticoids of induced acute leukocytic responses in the rabbit uterus. Sexually mature does were given cortisone acetate, hydrocortisone acetate, or 9 alpha-fluoroprednisolone by intramuscular injection for 3 days, then the uterine lumens were inoculated with Escherichia coli. The glucocorticoids doubled the number of leukocytes that migrated into the uterine lumen during the acute inflammatory response. The corticoids had similar effects in estrous, ovariectomized, and pseudopregnant rabbits. The administration of hydrocortisone acetate nearly doubled the number of polymorphonuclear (PMN) leukocytes in the circulation within 24 hours. The high numbers of circulating PMN leukocytes were maintained over the 3 days of treatment. The increased leukocytic response to induced uterine infection was similar in magnitude to the increase in numbers of circulating PMN leukocytes; the corticoid-induced neutrophilia was probably responsible for the intensified leukocytic response to uterine infection.


Serologic studies of naturally occurring feline infectious peritonitis. Serum antibodies to the feline infectious peritonitis (FIP) virus were measured in cats, using an indirect fluorescent antibody procedure. Antibody titers of 1:400 to 1:25,600 were seen in cats with both effusive and noneffusive forms of FIP. About 87% of the normal cats in FIP problem catteries and 20% of the cats in the Davis, Ca, area also had antibody titers to the FIP virus, ranging from 1:25 to 1:400. Although the infection rate is high among cats, relatively few of the cats infected with the FIP virus ever develop clinically apparent FIP.


Feline malignant lymphomas: comparison of morphologic and immunologic characteristics. Lymphoid cell populations from various hematopoietic tissues of normal cats (n = 22) and from cats with malignant lymphoma (n = 14 cats) were examined simultaneously for morphologic and immunologic features. Scanning electron microscopy and mitogen stimulation studies were not useful in identifying the B or T cell nature of malignant lymphomas. Cell markers successfully used to identify B cells were the presence of surface immunoglobulin by fluorescent-immunoglobulin staining procedures and the presence of complement receptors by EAC (erythrocyte, antibody, complement) rosette formation. The formation of rosettes with guinea pig erythrocytes was used to identify T cells. Using these cell surface markers, thymic lymphomas were found to be composed of T cells and alimentary lymphomas were found to be composed of B cells. The multicentric lymphomas lacked B or T cell surface markers. Classification by cytologic type of cell did not show any correlation with other values.


Bacteriologic cultural examination of the lower respiratory tract of laboratory dogs. During lung transplantation experiments, the lower respiratory tracts of dogs were examined by bacteriologic cultural technique pre- and postoperatively. Three methods were used to obtain culture material: transtracheal aspiration, lung puncture, and lung biopsy collection. Both before and after operation, infections were commonplace. Antibiotics given at the time of operation tended to suppress infection.


Interstitial pneumonia in angio-immunoblastic lymphadenopathy with dysproteinemia. A case report with special histopathologic studies. A patient presented with characteristic historical, physical, and laboratory findings of angio-immunoblastic lymphadenopathy with dysproteinemia. This newly described entity apparently represents a nonneoplastic proliferation of the B-lymphocyte system with immunoblastic transformation of many lymphocytes and excessive production of immunoglobulins. It is associated with fever, sweats, weight loss, skin rash, lymphadenopathy, splenomegaly, hepatomegaly, and characteristic histologic features of the involved lymph nodes. Noteworthy in the patient reported here are the extent and course of radiographically and clinically evident pulmonary involvement and the biopsy documentation of an interstitial pneumonia marked by histopathologic changes closely resembling those found in the lymph nodes, with immunohistologic demonstration of immunoglobulins in the alveolar walls.


[Meconium aspiration syndrome. Two cases treated with continuous positive airway pressure (author's transl)]. Two cases of Meconium Aspiration Syndrome successfully treated with CPAP are presented. In both patients the introduction CPAP enhanced arterial oxygenation. The A-a DO2 showed a decrease of 57 and 228 mm Hg respectively. After the introduction of CPAP it was possible to decrease the enviromental oxygen concentration and both patients survived. The possible mechanism by which CPAP improves hypoxia in MAS is discussed.


Idiopathic pulmonary fibrosis. Clinical, histologic, radiographic, physiologic, scintigraphic, cytologic, and biochemical aspects. Idiopathic pulmonary fibrosis is a fatal disorder that starts as an alveolitis and progresses to interstitial fibrosis. Correlative morphologic, physiologic, and biochemical studies in 29 patients have shown that the inflammatory process in best followed by serial bronchoalveolar lavage and 67 Ga citrate scanning, and the fibrotic process is best followed by quantitation of the exercise-induced drop in arterial oxygen tension per unit of oxygen consumed. Although biopsies in idiopathic pulmonary fibrosis seem to show increased amounts of fibrotic tissue, biochemical studies suggest that the disease is probably one of collagen rearrangement rather than collagen increase. Perhaps becasue of this, peripheral lymphocytes of these patients recognize collagen as "non-self" and, when exposed to it in vitro, produce lymphokines and cell lysis. The fibrotic process is probably irreversible, but the inflammatory and immune processes that cause it may be amenable to therapy if diagnosed early.


[The first spanish report of complex congenital heart defect (author's transl)]. The first spanish report of complex congenital heart defect with single ventricle and single arterial trunk is presented. The clinical and pathological description was made by G. Faraudo in 1866 in a 10 months-old infant.


The Jake Walk Blues. A toxicologic tragedy mirrored in American popular music. In 1930 thousands of cases of muscle pain, weakness of upper and lower extremities, and minimal sensory impairment occurred in the United States. The illness was caused by the consumption of an adulterated Jamaica ginger extract ("Jake"), an illicit beverage then popularly used in the southern and midwestern  United States to circumvent prohibition statutes. The additive tri-ortho-cresyl phosphate caused severe, only partially reversible damage to the spinal cord and peripheral nervous tissue. Victims with resultant gait impairment, sometimes permanent, were said to have the "Jake Leg" or "Jake Walk." Twelve commercial phonographic recordings made between 1928 and 1934 by southern rural artists, white and black, refer to Jake or Jake-induced infirmity. These reveal preepidemic cultural familiarity with Jake, and the later, postepidemic performances reflect a whimsical, even cynical, cultural attitude that those with "Jake Leg" were suffering the wages of sin and should not be regarded as objects of pity or sympathy.


Quality assurance today and tomorrow: forecast for the future. We review here the definition,  history, and current findings of quality assessment. Difficulties with quality assessment center principally on methods problems, including using the medical record as a source of information, using process versus outcome criteria, and ignoring decision analysis methods in establishing quality criteria. One overriding issue is placing a value on health and, by extension, on quality assurance and assessment efforts; another is the degree to which improvements in the quality of care can be achieved through changes in physician practices. Several sets of recommendations address these topics. With the assumption that such recommendations could be acted on in a transition period, a hypothetical quality assurance system is described for the 1980s and beyond. This system is based on preservation of the fee-for-service system, adoption of a national health insurance plan, and minimal federal involvement in quality of care decisions at the regional level.


[Evolution of pharmcopoeias and prospects for their future development]. The pharmacopoeias of today reflect out of date conditions; they address only the pharmacists, they do not take into considerations the industrial pharmaceutical production, they do not deal with quality control, nor do they give rules of good manufacture; they only relate a limited number of medical products. The future pharmacopoeias should contain the specifications of all base products and of all galenical forms; they should be the code of drugs production, quality and distribution.


[Pharmacopoeia and veterinary medicine]. The A recalls briefly the evolution of the veterinary pharmacopoeias. They were at first national and became later international. The A. describes the situation of the veterinary drugs and of their inclusion in the national pharmacopoeias, as far as the European countries are concerned. Are we supposed to assign to them, because of their specificity, a special section in the pharmacopoeia or should we set up a special pharmacopoeia for them? In view of the effects they have on public health should we incorporate them into the pharmacopoeia in the same forms as the human drugs? The A. relates the arguments in favor of each of these points of view. Whichever the decision will be taken to solve this problem, the A. emphasizes the usefulness of the insertion of veterinary drugs in a pharmacopoeia, because of the improper use that some countries make of this type of drugs and because of the consequences this use can possibily have on public health.


[Independence of plasmids harboured in the "Escherichia coli" of patients in hospital without antibiotics (author's transl)]. A study has been carried out of the faeces of nine patients in the same surgical ward. Viable counts and detection of drug resistance were effected by a replica plating method. Bacteria harbouring the drug resistance pattern (ST) were found in seven faeces. Among them, five R plasmids (ST) were transferred to Escherichia coli K12 and have been differentiated by incompatibility studies. As they didn't belong to the same incompatibility group it was concluded that they were not the same incompatibility group it was concluded that they were not the same plasmid acquired in the hospital. One of these R plasmids (ST) was unclassifiable into a known incompatibility group. So, a new incompatibility group, group 12, is proposed.


[Concentration of bacteria in water using the ultrafiltration method (author's transl)]. Four ultrafiltration units have been tested in order to concentrate bacteria in water. The experiments run with Escherichia coli allows the selection of an ultrafiltration apparatus which concentrates bacteria with high recovery efficiencies. The use of this concentrator is simple and fast. Its filtration power is very stable and its little capacity allows the continuous ultrafiltration of large volumes of water.


[The inhibition of post-exponential growth in "Saccharomyces cerevisiae" by L-lysine (author's transl)]. The inhibitory effect of L-lysine upon the post-exponential growth of Saccharomyces cerevisiae has been previously demonstrated and the present report extends the observation. During the post exponential phase, the cells do not divide but the cell mass normally increases two or three-fold; in the presence of exogenous lysine this increase is considerably reduced, bud growth is blocked and the cytological features of the post-exponential cells are considerably modified. The effect is apparent in liquid as well as on solid media. L-alpha-aminoadipate, being a precursor of L-lysine, exerts a similar effect since the exponential phase. Mutants resistant to the effect of lysine proved to be permeability mutants. The phenomenon is not restricted to any one strain of S. cerevisiae but characterized all strains of the species which are unable to catabolize lysine.


Chemoimmunotherapy of syngeneic mouse mammary carcinomas employing methanol extraction residue. Isografts of two mammary carcinomas, one spontaneously arising in a BALB/cfC3H female infected  with MTV and one free of MTV (tumor D7T4S), were removed surgically from Balb/c (MTV free) female hosts, and fragments of each tumor were immediately reimplanted in situ (simulated local recurrence challenge). The animals were then subjected to treatment with the MER fraction of tubercle bacilli, with one of three chemotherapeutic drugs (5-FU, cyclophosphamide, and methotrexate), or with both MER and one of the chemotherapeutic agents (chemoimmunotherapy). The incidence of progressively developing recurrence tumors and the longevity of the animals were determined. The therapeutic effects of treatment with MER alone were ascertained by comparing groups of mice that received the fraction by various schedules with saline-injected control groups; the efficacy of chemoimmunotherapy was assassed by comparing groups that received MER plus one of the drugs with groups subjected to drug intervention by itself. MER administered alone did not reduce the incidence of recurrent tumors but was consistently efficacious in prolonging the lives of animals challenged with the MTV (+) carcinoma, although considerably less so in animals tested with the weakly immunogenic tumor D7T4S. A negative effect by MER on tumor frequency did not occur and was seen only once with regard to host life duration. Combined intervention with MER and 5-FU proved to be significantly and consistently superior to similar treatment with only 5-FU in animals challenged with the MTV(+) carcinoma. No such additive action by MER plus 5-FU was seen in mice challenged with D7T4S, however, nor did the other two chemoimmunotherapeutic regimens differ significantly in therapeutic efficacy from the corresponding chemotherapy alone in most of the trials with both tumors.


Double-blind levamisole trial in resectable lung cancer. The third interim analysis of a prospective double-blind placebo-controlled trial with levamisole as an adjunct to surgery in resectable primary lung carcinoma is reported. The data show that a beneficial effect is clearly present in patients who weigh 70 kg or less but not in others; therefore, it would seem advisable to prescribe levamisole at a dosage of 2.5 mg/kg/day. In the adequately dosed patients, an almost complete elimination of distant metastases is found. The levamisole effect also seem more pronounced in patients who have a heavier tumor load at operation. The rationale for starting levamisole before surgery and for continuing thereafter is briefly discussed.


Dialyzable transfer factor in the treatment of human osteosarcoma: an analytic review. In conclusion, then, we would answer the seven questions raised earlier concerning transfer factor as follows: Certianly, as shown by clinical results, it does exist. It does have a definite immunologic effect in humans, boosting cell-mediated immunity, as shown by a rise in the level of active T cells. Its clinical effects have been demonstrated repeatedly, and it should become useful in still other clinical situations as further research provides more effective therapeutic modalities. Transfer factor from selected donors appears to provide prophylaxis against metastasis when administered to osteosarcoma patients with no clinically evident metastases at the time of surgical removal of the primary tumor; whether this treatment is superior to chemotherapeutic prophylaxis is conjectural and controversial. Its mechanism of action has not been demonstrated as yet, although many theories exist. The best evidence is that the effects are both specific and nonspecific. It appears to be produced by T lymphocytes. The exact nature of the substance we call "transfer factor" remains to be elucidated. Further research should provide more conclusive answers to these questions.


Vitreoretinal and anterior segment surgery through the pars plana: part I. Instrumentation and clinical experience dealing with intraocular surgery through a pars plana approach have advanced rapidly during the past 5 years. These techniques have been used to successfully treat a number of ocular disorders. Considerable experience with this form of surgery has accumulated, and the results and incidence of complications are similar among centers. Additional refinements in instrumentation and surgical techniques will probably expand the capabilities and further improve the results of pars plana surgery. However, we are rapidly approaching a point at which the primary limiting factor will be the pathophysiology of ocular diseases rather than instrumentation or surgical skill. The ability to improve vision by removing persistent opacities of the ocular media has been demonstrated, and follow-up of 2 more years has shown that the eye can continue to function well after excision of the formed vitreous. The indication for vitreous surgery which has proven to be the most difficult and hazardous is treatment of complicated rhegmatogenous retinal detachments in which elevated, mobile retina presents special problems. The role of vitrectomy in the management of proliferative diabetic retinopathy and early management of penetrating injuries involving the posterior segment are the primary clinical-research objectives for the immediate future. In these conditions vitrectomy may be useful to alter the course of progressive vitreoretinal pathology as well as being used to treat previously existing complications. Finally, our experience has shown that risk of significant complications is present in every case of surgery performed through a pars plana approach. The incidence of mechanical complications can be minimized by careful attention to detail during surgery, but complications cannot be eliminated. Retinal detachment is the most frequent potentially blinding complication, and the vitreous surgeon should be skilled in management of retinal breaks and retinal detachment. Also, there are biologic complications, including rubeosis iridis, which may occur following technically successful surgery in certain eyes. Rubeosis iridis is a major problem in diabetic eyes because it can destroy the functional results of an otherwise successful operation, and no effective treatment is now known. Hopefully, research efforts will improve our understanding of the pathogenesis of this disorder and permit us to develop effective means of prophylaxis or treatment.


Histological features of acute viral hepatitis. The constant and inconstant light microscopic changes in liver biopsies from patients with acute viral hepatitis are reviewed. The constant changes are essential for the diagnosis, and the distribution of ceroid (and often of haemosiderin) is important in the staging of the disease. Many and large piecemeal necroses in the acute stage are often followed by chronic aggressive hepatitis. A key to the understanding of the development of regeneration nodules - and thereby to posthepatitic cirrhosis - is portal-central bridging with subsequent formation of septa. Bridging and formation of septa is almost always preceded by piecemeal necroses in the acute stage and also by confluent necroses in 1/3 - 1/2 of the cases.


Clinical course and prognosis of acute hepatitis. The clinical course of acute viral hepatitis may vary from asymptomatic to fulminant, and the final outcome can be complete recovery, chronic hepatitis or cirrhosis. The two main challenges this generally benign, self limiting infection has presented for may years have been to understand 1) the progression to fulminant hepatitis, and 2) the progression to chronic hepatitis or cirrhosis. Fulminant hepatitis may appear infrequently (1-2 % of patients with clinical hepatitis) in both type A and type B infections. Nearly 10% of patients with acute viral hepatitis type B develop either chronic hepatitis or cirrhosis. The exact figures for progression to chronicity in patients with type A infections are probably less,but are still not fully known. During the acute phase of the disease, the patients with later progression to chronicity differ significantly from those with subsequent resolution in a number of serological, biochemical and morphological variables. Persistence of HBS antigenaemia for more than 13 weeks, a high concentration of circulating Dane particles, and the presence in the serum of the "e" antigenic determinant seem to be reliable prognostic markers for pregression to chronic hepatitis or cirrhosis. Such markers are prerequisites for therapeutic trials with potent drugs which are only justified for patients with fulminant hepatitis and patients with progression to chronicity. If the different outcome of viral hepatitis is a result of the individual T-cell function, these two categories of patients may represent the opposite extremes in lymphocytic function. Controlled clinical trials are required to evaluate the clinical effect of immunosuppression in fulminant hepatitis and immunostimulation in chronic hepatitis.


Bacterial, viral and auto antibodies in acute and chronic liver disease. There have been numerous reports of elevated antibody titres to a variety of bacteria and viruses in the sera of patients with acute and chronic liver disease. The results are reviewed in the light of the immunological function of the liver, notably its ability to sequester exogenous antigens and the loss of this property following liver damage. Non-organ specific auto-antibodies are also commonly found in most forms of acute and chronic liver disease, the pattern varying from one disorder to another. A possible hypothesis linking these phenomena is put forward.


Failure of customary treatment in chronic active liver disease: causes and management. Among 134 patients with chronic active liver disease, selected by identical clinical, biochemical and morphologic criteria, assigned to standard treatment programs and followed at regular intervals, 21 of 105 failed treatment with standard regimens containing steroids. Treatment failure was more common in patients whose serum contained hepatitis B surface antigen, those with more severe liver disease as judged by liver function tests (prothrombin time) and hepatic morphology (subacute hepatitis or cirrhosis). Early diagnosis of treatment failure, based on changes in liver function tests rather than on clinical features of deterioration, coupled with the immediate administration of higher doses of prednisone with or without higher doses of azathioprine, resulted in disappearance of clinical and biochemical features of disease activity in the majority of patients. These results were greatly superior to those earlier reported by us from patients chosen by identical criteria but treated by conventional measures. However, when endogenous encephalopathy developed the outlook was grave, regardless of previous or subsequent therapy. We recommend that patients at risk for failing conventional treatment be identified early, followed carefully with serial liver function tests, and be treated promptly with higher doses of medication when deterioration occurs.


Controlled clinical trial comparing the effect of betahistine hydrochloride and prochlorperazine maleate on patients with Meniére's disease. Therapeutic effects of prochlorperazine and betahistine on patients with confirmed Meniere's disease (range of duration 1-11 years) were compared in a double-blind cross-over trial. The two active treatment periods lasted 4 montsh each, separated by a single blind "wash-out" period of 1 month's duration. Out of 30 patients 23 completed the trial. The clinical status of the patients was followed by the investigator by regular control visits during the trial period. Upon completion of the study preference for the first or the second period was assessed. The therapeutic effect of betahistine was found to be superior to that of prochlorperazine (sign test a = 0.05). The number of vertigo attacks was calculated in 17 patients and on this basis the two drugs were of equal value (Pratt's test 2 a = 0.05). No side effects were observed.


[Phagedena due to leishmaniasis. Immunologic and experimental studies]. The author reports a rare case of phagedenisme due to leishmaniasis which was resistant to classical treatment for eight years. Immunological research led to the conclusion of a cellular immune deficiency. It seems that this immune deficiency is due specifically to an insensitivity of the organism to the Leishman body and not to other antigens.


[Collodion baby. Clinical course based on 29 cases]. Study of 29 cases of collodion baby and 169 cases previously published led to several conclusions. In the short-term, the child is threatened by pulmonary infections. The increased skin permeability may result in the loss of water or intoxication by cutaneous absorption of a substance applied to the skin. In the long-term the condition progresses to one of a congenital disturbances in keratinisation. In 2/3 of cases, the problem is that of congenital non-bullous ichthyosiform erythrodermia. Profression to lamellar ichthyosis, ichthyosis vulgaris, circumflex linear ichthyosos and Conradi's syndrome is established. Ichthyosis related to sex in our cases did not seem to be a feature of the collodion baby, the opinion in the literature being divergent. Congenital bullous ichthyosiform erythrodermia never begins as collodion baby syndrome.


[2 mechanisms of tetracycline resistance in bacteria]. Two mechanisms of resistance to chlortetracycline stipulated by retarded transport of the antibiotic or decreased sensitivity to it of the translation apparatus were studied using clinical bacterial strains and strains obtained under laboratory conditions. No strict proportion between the population resistance to the antibiotic and the level of a decrease in its absorption by the bacterial cells was observed in most of the clinical and laboratory strains of Staph. aureus. Apparently the resistance level observed in the bacteria cannot be entirely explained by the retarded transport of the antibiotic in these cases. Direct experiments showed that sensitivity to chlortetracycline in the protein-synthesizing apparatus of some resistant strains of Staph. aureus 209 was decreased 10 times. On the other hand correlation between the level of the decrease in the absorption of the antibiotic and the level of the bacteria resistance to it was observed in resistant strains of E. coli. The protein-synthesizing apparatus of the resistant strains in this case preserved its sensitivity to chlortetracycline. Sensitivity of the protein-synthesizing apparatus to the antibiotic did not change in the process of the resistance induction by incubation of the baceria in the presence of low concentrations of the antibiotic.


Toxic cardiomyopathies.

Toxic cardiomyopathies. Examples of toxic cardiomyopathies of various characteristics are presented. Daunomycin and doxorubicin, antineoplastic drugs, cause multifocal cardiomyopathies and intractable heart failure by cardiotoxic mechanisms; these effects are delayed and related to the cumulative dose. Cobalt caused diffuse vacuolar cardiomyopathy in chronic beer drinkers. The development of fulminant heart failure was the function of factors that increased the adsorption of cobalt or sensitized the myocardium to its cytotoxic effect. Beta-adrenergic receptor stimulant bronchodilators like isoproterenol or vasodilating antihypersensitive drugs like hydralazine are able to produce focal subendocardial necroses. This lesion is due to ischemia brought about by the acute exxagerated pharmacological effects of these compounds.


[Resistance of clinical strains of Proteus to various beta-lactam antibiotics]. Sensitivity of Proteus clinical strains to benzylpenicillin, ampicillin and ceporin, as well as the dynamics and stability of the drug resistance was studied. It was found that the beta-lactamides were active against Proteus, ceporin being the most effective antibiotic. Strains resistant simultaneously to 2 or 3 drugs were also resistant to higher concentrations of each of them. The Proteus cultures isolated from various pathological materials did not differ by their sensitivity to benzylpenicillin and ceporin, while the strains isolated from the patient urine were least sensitive to ampicillin. The cultures of Proteus vulgaris were more resistant to the beta-lactamides as compared tcal material were more resistant to benzylpenicillin and ceporin as compared to the cultures in the H-form. No increase in the number of the Proteus strains resistant to benzylpenicillin, ampicillin or ceporin was observed within 1968-1973. The Proteus resistance to ampicillin and ceporin was not stable and was lost on storage. Reversion to sensitivity depended on the individual properties, the period of storage and the resistance level. The studies showed that the clinical strains of Proteus preserved their sensitivity to the above beta-lactame antibiotics which provided their recommendation for therapy of Proteus infections.


Acute toxic nephropathies: clinical pathologic correlations. Man's ever increasing exposure to numerous drugs and chemicals, which are the results of medical and industrial progress, produces a by-product of acute toxic nephropathies. These include acute toxic renal failure, drug-induced acute oliguric renal failure, acute hemorrhagic glomerulonephritis, nephrotic syndrome, tubular disturbances and potassium deficiency. In depth information is provided for the previously mentioned disorders.


A rapid glutamic decarboxylase test for identification of bacteria. A simple rapid glutamic decarboxylase test is described. This test was found useful in the identification of Escherichia coli, Shigella sp., Providencia alcalifaciens, Clostridium perfringens and Bacteroides fragilis.


[Method for the quantitative determination of penicillin acylase activity by the formation of phenylacetic acid]. The quantitative method for determination of penicillinacylase activity is described. The method is based on detection of phenylacetic acid (PAA) formed during hydrolysis of benzylpenicillin. PAA is extracted with toluol and nitrated with potassium nitrate solution in concentrated sulphuric acid followed by reduction of nitrophenylacetic acid into aminophenylacetic acid with zinc powder. Aminophenylacetic acid interacts with p-dimethylaminobenzaldehyde in acid medium forming a coloured compound (Schiff base). The optic density of the latter was determined with spectrophotometer SF-16 at 430 nm. The method was used for determination of acylase in Yersinia species and some other bacteria.


[Study of penicillin amidase for E. coli. Kinetics of enzymatic hydrolysis of 7-phenylacetamidodeacetoxycephalosporanic acid]. Kinetics of hydrolysis of 7-henylacetamidodeacetoxycephalosporanic acid catalyzed by penicillin amidase as a result of which phenylacetic and 7-aminodeacetoxycephalosporanic acids are formed was studied. The kinetic parameters of the reaction were determined on the basis of both the dependence of the initial rate of enzymatic hydrolysis on the substrate concentration and the analysis of progress kinetic curves of the product accumulation. The values of Km determined by the two methods were equal to (10 +/- 1) muM and kcat (50 +/- 5) sec-1 and (50 +/- 10) sec-1 respectively. The study of the inhibition of the enzymatic hydrolysis by the reaction products showed that phenylacetic and 7-aminodeacetoxycephalosporanic acids were competitive and non-competitive inhibitors of the penicillin amidase activity respectively. The inhibition constants were (55 +/- 8) muM and (12 +/- 1) mM respectively. The physiological role of the enzyme and the effect of the structure of the substrate on the specificity of the enzyme are discussed.


[Distribution and properties of streptomycin-resistant clones in a population of freshly isolated Shigella sonnei strains]. It was found that the rate of emergence of streptomycin resistant clones in the populations of fresh isolates of Shigella Zonne amounted to 10(-6)--10(-4). Such streptomycin resistant clones masked streptomycin resistance of the initial Shigella population. The main biological properties of the streptomycin resistant clones were identical to those of the initial population.


[Free amino acid content in the blood and urine from the use of monomycin on children with dysentery]. The progress of acute dysentery in 73 children at the age of 1 to 14 years treated with monomycin and the levels of free amino acids in the blood and urine in dynamics were studied. It was found that the blood levels of 6 amino acids in the children treated with the antibiotics significantly decreased, while those of 3 amino acids increased as compared to the levels of the same amino acids in the children treated without the antibiotics. It was concluded that the diet of dysentery children treated with monomycin should contain stimulators of protein synthesis and increased amounts of protein.


[Intensification of the bactericidal action of mitomycin C and of UV irradiation with some anthracycline antibiotics]. Anthracycline antibiotics, such as rubomycin C (rubomycin, daunomycin), rubomycin B, carminomycin and tavromycetin (cinerubin) significantly increased the bactericidal effect of ultraviolet radiation and mitomycin C with respect to mutant 19-8 of E. coli with increased permeability of the cell membrane. This may be accounted for inhibition of DNA reparation. Beromycin, an antibiotic of the same group had no such capacity. With respect to their activity the antibiotics were arranged as follows: rubomycin C, rubomycin B, carminomycin, tavromycetin.


[Change in the sensitivity of dysentery bacteria to certain antibiotics, furazolidone and antifungal preparations when cultured together with Candida albicans]. The effect of Candida albicans (2 collection cultures and 1 freshly isolated culture) on sensitivity of dysentery bacteria (5 Zonne strains, 4 Flexner strains and 2 Newcastle strains) to antibiotics, furazolidone and their combinations with nystatin or decamine was studied by the method of serial dilutions. A total of 937 tests were performed with the use of 10 concentrations in each test. It was found that sensitivity of the Shigella to levomycetin succinate, monomycin and furazolidone decreased in the presence of Candida. Decamine increased the bactericidal effect of furazolidone on Shigella in pure cultures and in addition increased sensitivity of various Shigella species to the antibiotics tested and especially furazolidone when the cultures were grown together with Candida albicans. Nystatin combination with levomycetin succinate and especially with monomycin increased sensitivity of various Shigella species in the presence of Candida albicans. The data are useful in treatment of dysentery since Candida are often isolated from dysentery patients.


[Chemotherapeutic effectiveness of rifampicin in experimental infections]. Studies on the chemotherapeutic action of rifampicin in treatment of staphylococcal sepsis and sepsis caused by gramnegative organisms showed its high efficacy only in treatment of the staphylococcal infection. By the level of its efficacy rifampicin was much superior to benzylpenicillin and especially tetracycline. No difference in the activity level of the antibiotic in treatment of staphylococcal infections caused by sensitive and multiple resistant staphylococcal strains was found. In treatment of the infections caused by gramnegative organisms the drug activity was moderate.


[Experimental study of the chemotherapeutic activity of gentamicin sulfate]. Antibacterial activity of gentamycin sulfate was studied in vitro and in treatment of albino mice with experimental infections. Gentamycin was superior to kanamycin with respect to its antibacterial effect against clinical strains of Staphylococcus, Coli bacteria, Proteus and Ps. aeruginosa. High efficiency of gentamycin was found with respect to acute and chronic staphylococcal infection, acute Proteus and Coli sepsis. The antibiotic was characterized by low LD50, high chemotherapeutic index, rapid decrease in isolation of the causative agent from the animal organs. The activity of gentamycin against infections caused by Ps. aeruginosa was the main advantage of gentamycin in comparison to kanamycin.


Chilling cells enhances the bactericidal action of fatty acids on Escherichia coli. Preincubation at 0 C considerably increased the bactericidal action of 0.4% nonanoic and decanoic acids on Escherichia coli K-12 154. This lethal effect seemed to be dependent on the media used to grow the bacteria. Stationary-phase cells were more sensitive than those from exponential cultures. A mutant (FA31) resistant to the bactericidal action of "cold shock" and 0.4% deconoic acid was isolated from E. coli FA23 (AN E. coli 154 derivative able to grow on 0.1% decanoic acid) by a recycling selection procedure. Other E. coli strains tested showed behavior similar to that of strain K-12 154. The chilling of cells as a tool to improve the bactericidal action of fatty acids in foods is discussed.


Influence of the rate of ethanol production and accumulation on the viability of Saccharomyces cerevisiae in "rapid fermentation". Whereas "rapid fermentation" of diluted clover honey (25 degrees Brix) fortified with yeast nutrients using 8 X 10(8) brewers' yeast cells per ml resulted in an ethanol content of 9.5% (wt/vol; 12% vol/vol) in 3 h at 30 C, death rate of the yeast cells during this period was essentially logarithmic. Whereas 6 h was required to reach the same ethanol content at 15 C, the yeast cells retained their viability. Using a lower cell population (6 X 10(7) cells/ml), a level at which the fermentation was no longer "rapid," the yeast cells also retained their viability at 30 C. Ethanol added to the medium was much less lethal than the same or less quantities of ethanol produced by the cell in "rapid fermentation." It was considered possible that ethanol was produced so rapidly at 30 C that it could not diffuse out of the cell as rapidly as it was formed. The hypothesis was postulated that ethanol accumulating in the cell was contributing to the high death rate at 30 C. It was found that the intracellular ethanol concentration reached a level of approximately 2 X 10(11) ethanol molecules/cell in the first 30 min of fermentation at 30 C. At 15 C, with the same cell count, intracellular ethanol concentration reached a level of approximately 4 X 10(10) ethanol molecules/cell and viability remained high. Also, at 30 C with a lower cell population (6 X 10(7) cells/ml), under which conditions fermentation was no longer "rapid," intracellular ethanol concentration reached a similar level (4 X 10(10) molecules ethanol/cell) and the cells retained their viability. Alcohol dehydrogenase (ADH) lost its activity in brewers' yeast under conditions of "rapid fermentation" at 30 C but retained its activity in cells under similar conditions at 15 C. ADH activity was also retained in fermentations at 30 C with cell populations of 6 X 10(7)/ml. It would appear that an intracellular level of about 5 X 10(10) ethanol molecules/cell is normal and that this level does not damage either cell viability or ADH activity. Higher intracellular ethanol concentrations, such as 2 X 10(11) molecules ethanol/cell (a fourfold increase in intracellular ethanol concentration), are accompanied by inactivation of ADH and loss of cell viability.


Evaluation of double violet agar in the isolation of Klebsiella pneumoniae from river water. A field evaluation of double violet agar for the isolation and presumptive identification of Klebsiella pneumoniae from water has been performed. Water from the North Oconee River, Clarke County, Ga., was cultured for presence of klebsiellae using the membrane filter technique. Colonies were presumptively identified as K. pneumoniae in the basis of their appearance on double violet agar. Such identifications were evaluated using appropriate biochemical tests. Once investigators have become familiar with cultural reactions on the medium, double violet agar can be used to indicate presence of K. pneumoniae in water with greater than 80% accuracy.


Starvation effects on Escherichia coli and aquatic bacterial responses to nutrient addition and secondary warming stresses. A gram-negative polar flagellated rod, isolated from a Colorado mountain stream and considered to be an Aeromonas sp., a mixed aquatic microbial population, and a culture of Escherichia coli were starved to determine their responses to the short-term presence of nutrients and mild warming stress (49.5 C for 2 min) in relation to starvation time. At the beginning of the starvation period, the Aeromonas isolate was extremely sensitive to the secondary warming stress. This response was markedly diminished after a 3-week starvation period. The mixed aquatic microbial population showed a similar trend in becoming less sensitive to stress with increased starvation. E coli under similar conditions, became more sensitive to the secondary stress after exposure to glucose. Respiration measurements after glucose additions also indicated that E. coli responded in a different manner to starvation stress and glucose presence than the Aeromonas isolate. The increased sensitivity of E. coli to secondary stress and short-term nutrient availability after starvation may contribute to the exclusion of this organism from aquatic environments.


Toxoid of Clostridium botulinum type F: purification and immunogenicity studies. Toxin from Clostridium botulinum type F was recovered from dialysis cultures and partially purifed by: (i) ammonium sulfate and ethanol precipitation; (ii) O-(diethylaminoethyl)-cellulose chromatography; or (iii) diethylaminoethyl-cellulose chromatography followed by O-(carboxymethyl)-cellulose chromatography. Toxin purities as reflected by specific activity were 1.83 X 10(6), 9.8 X 10(6), and 2.0 X 10(7) mouse 50% lethal doses (LD50)/mg of N, respectively, for toxins purified by the three methods. The toxins were converted to toxoids by incubation at 35 C in the presence of 0.3 to 0.45% formalin for 21 to 35 days. Toxoids were immunogenic in guinea pigs, as demonstrated by serum antitoxin response and the immunized animals' resistance to challenge by type F botulinal toxin. The immune response to type F toxoids was lower when toxoids of serotypes A, B, C, D, and E were combined with the type F toxoid than when the type F toxoid only was administered. The toxoid prepared from the most highly purified toxin (method [iii]) conferred the highest immunity in guinea pigs at a given dose level. A relation between serum antitoxin level and resistance to challenge was observed. At least 50% of the groups of guinea pigs with 0.015 antitoxin units or more per ml survived challenge by 10(5) mouse LD50 of type F botulinal toxin. A dose of 3.75 mug of N of the most highly purified type F toxoid in combination with the other five serotypes of botulinal toxoid invoked an immune response in guinea pigs comparable to that considered adequate for the other toxoids.


Characteristics of bacteria isolated by the anaerobic roll-tube method from cheeses and ground beef. In this study the methods of Hungate were used to quantitate the anaerobic bacteria present in commercially available ground beef, cheddar cheese, and German hand cheese. Of 235 anaerobic roll-tube isolates from ground beef and German hand cheese, all were facultative anaerobes. Of 213 anaerobic roll-tube isolates from cheddar cheese, 91% were facultative anaerobes and 9% were obligate anaerobes. Using results of biochemical tests, 14 or the 17 obligately anaerobic isolates from cheddar cheese were Propionibacterium acnes, two were strains of Propionibacterium that could not be speciated, and one was tentatively identified as a strain of Streptococcus evolutus. Obligate anaerobes were estimated to be present in the cheddar cheese at a level of about 10(6)/g. The possible significance of these levels of P. acnes in nonsterile foods is discussed.


Ultraviolet light and tar in the Goeckerman treatment of psoriasis. In an attempt to evaluate and improve the Goeckerman treatment of psoriasis, combinations of tar and ultraviolet (UV) light were studied. The effects of UV irradiation alone, of curde coal tar (CCT) ointment alone, and of UV irradiation with 1% CCT ointment and with 6% CCT ointment on psoriatic lesions were compared. The combinations of 1% CCT ointment with UV irradiation and of 6% CCT ointment with UV irradiation were found to be equally effective. The combination of UV irradiation with ointment had little effect on psoriatic lesions. In most cases, the combination of 1% CCT ointment and UV irradiation was superior to high-concentration (6%) tar ointment without UV irradiation. This study suggests that UV light is an important component of the Goeckerman treatment ant that tar and UV irradiation are superior to tar alone.


Role of chronic hepatitis in development of thalassaemic liver disease. Liver function and the presence of HBsAg and anti-HBsAg were studied in 90 hypertransfused thalassaemic children. Increased serum transaminases were found in 62 patients, and persisted from more than 6 months in 45 cases. Liver biopsy in this latter group led to a diagnosis of 14 cases of chronic persistent hepatitis, 9 cases of aggressive hepatitis, and 3 cases of hepatic fibrosis. In Italy thalassaemic children undergoing hypertransfusion therapy frequently encounter SH virus infection, with a consequent hepatitis that is generally anicteric and unrecognized unless systematically sought. In a liver already stressed by the concomitant iron overload, hepatitis infection might thus play a key role in the evolution of cirrhosis which frequently affects thalassaemics.


Differential protein clearances and response to treatment in Nigerian nephrotic children. Remission followed prednisolone therapy in 9 out of 21 Nigerian children with the nephrotic syndrome who had highly selective proteinuria (CG/CA less than 15%). Of these, 5 patients have remained well off all treatment during a follow-up of nearly 5 years, 4 have relapsed more than once but have responded to further courses of prednisolone. 3 of 21 with less selective proteinuria also remitted but all relapsed and only one of these has responded again. The other two have relapsed and further courses of prednisolone have not totally abolished their proteinuria though they are asymptomatic and in good health. Toxicity (hypertension, sometimes with encephalopathy and infection) was commoner in the patients with less selective proteinuria treated with steroids than in those with highly selective proteinuria. 3 steroid-sensitive patients who had had repeated relapses became free from relapse off all treatment after a course of cyclophosphamide, given during steroid-maintained remission. All but 2 of the renal biopsies taken were regarded as abnormal. The lesions were less severe in those who responded than in those who did not. There is some evidence to suggest that Plasmodium malariae may be a cause of some of the steroid-sensitive disease, as well as the steroid-resistant.


Consumptive opsoninopathy: possible pathogenesis in lethal and opportunistic infections. Serum levels of properdin, Factor B and C3 and the ability of these sera to opsonize E. coli 075 were measured in 17 patients with surgical infections ranging in severity from mild to fatal. There was good direct correlation between severity of infection, serum levels of properdin and C3, and the ability of the serum to support opsonization. The levels of Factor B were not significantly reduced when measured by radial immunodiffusion, but immunoelectrophoresis showed conversion. Restoration of full opsonic activity was accomplished only by the addition of a combination of C3, Factor B, and properdin in excess. The findings provide evidence that severe bacterial infection causes a consumption of opsonic proteins which may result in a reduced ability of the patient's serum to opsonize bacteria and thereby further increase susceptibility to infection.


Calyceal-cutaneous fistulae in renal transplant patients. Calyceal-cutaneous fistula is a serious sequela of renal transplantation occurring in approximately 3% of allografts. This complication occurred in 12% of allografts with multiple renal arteries. A localized area of poor parenchymal perfusion involving less than one-eighth of the kidney was noted at the time of transplantation in only one-third of the kidneys developing fistulae. Attempts of surgical correction of the fistulae in the presence of serious wound and urinary tract sepsis were usually unsuccessful, with the ultimate loss of 7 of 8 kidneys and the death of 3 patients from sepsis. One individual underwent successful partial resection and closure of the fistula with a muscular graft and survives with adequate function. This experience would suggest that if an initial aggressive surgical attempt at repairing a calyceal-cutaneous fistula fails, transplant nephrectomy should be performed.


Microcrystalline collagen hemostat (MCCH) and wound healing. The effect of MCCH on wound healing was studied in animals and patients. A full thickness dorsal skin defect was made in mice and standard amounts of MCCH applied immediately to the wound in half the mice. There were no significant differences in wound closure rates between control and MCCH treated mice. A standard dorsal skin incision was made in rats. In half the rats, MCCH was put into the incision just before suturing with fine stainless steel sutures. There were no statistically significant differences in breaking strengths between control and MCCH treated rats when tested on the 8th, 20th and 40th days postoperatively. Histologic examination of the wounds showed mild inflammatory reaction surrounding the MCCH-fiber fragments, but no giant cells. Small amounts of MCCH were demonstrable at 40 days. Full thickness skin burns in pigs were excised one day after burning. MCCH was applied immediately in some pigs; excess MCCH was removed by saline irrigation. Split thickness skin autografts were applied. MCCH was applied to donor sites. The "takes" of the grafts were excellent and not affected by the use of MCCH and the donor sites healed uneventfully. MCCH was used in four patients with burns, three of whom underwent early excision of full thickness skin burns and immediate autografting. The fourth underwent skin grafting to the granulating areas 3 months after injury. The MCCH was applied to some donor sites and to some areas of excision. In one patient with severe burns, wound sepsis developed equally in areas with and without MCCH and the grafts were lost. In the other three patients, there were excellent takes of the grafts at all sites. All donor sites, treated and untreated, healed normally in all patients.


Problems in differentiating between pancreatic lymphoma and anaplastic carcinoma and their management. A group of 6 patients with malignancies involving the pancreas is presented, with a range of diagnosis from primary reticulum cell sarcoma to probable anaplastic carcinoma. Even with adequate biopsy and autopsy material, it may be difficult to provide a definitive tissue diagnosis in these patients. Although this entire spectrum of tumors is uncommon, it is important to try to establish a diagnosis whenever possible. Biopsy of the tumor should be performed, even from the pancreas itself, if necessary, particularly when the initial presentation of the disease is unusual or if the pattern of metastasis is different from that usually seen with carcinoma of the pancreas. It is suggested that a therapeutic trial of appropriate radiotherapy and chemotherapy be instituted in patients of this type even if a diagnosis of lymphoma is not firmly established. The possibility exists of survival of some of these patients for periods of one year or more as a result of successive therapy.


A marked reduction in the incidence of cold haemagglutinin in Plasmodium falciparum malaria. A survey of cold haemagglutinin using the normal and tyrpsinized group O red blood cells was performed in 101 normal individuals, 139 individuals with Plasmodium falciparum malaria, 115 individuals with various infections other than malaria and 46 cases of auto-immune haemolytic anaemia. A marked reduction in the incidence of cold haemagglutinin reacting with the normal group O red blood cell was observed in cases of P. falciparum with parasitaemia higher than 100 000/mm3. Although this was also found in other infections, the proposed mechanism seems to be different. Neither remarkable changes in the incidence of cold haemagglutinin reacting with trypsinized red blood cell not the rise of the titres of agglutination in both types of the red blood cells could be detected in P. falciparum malarial cases. The findings are somewhat unexpected and the possible causes are discussed.


Patterns of development of Trypanosoma cruzi in the embryonated chicken egg. Blood forms of four strains of Trypanosoma cruzi were inoculated on the chorioallantois or intra-yolk sac in seven to nine day embryonated chicken eggs which were reincubated thereafter at 37-5-39-0 degrees C or at 32-34 degrees C. There were no significant differences between strains when total rates of infected eggs were compared. However, the highest proportions of positives, for every strain, were found among eggs inoculated into the yolk sac and reincubated in the lower temperature range. The most striking observations were: (a) independently of the route of inoculation, all strains developed through all stages of the invertebrate cycle within the embryonic cavities of eggs reincubated at 32-34 degrees C; (b) in a high proportion of these same eggs, all stages of the vertebrate cycle could be also found in the tissues of the embryo itself and its membranes; (c) no stages other than those characteristic of the vertebrate cycle could be found in the tissues of the embryo and its membranes among eggs maintained above 37 degrees C. It is thought that temperature is important in the transformation phases of the protozoon and that above 37 degrees C there was no conversion from the blood trypomastigotes to culture forms. Other transformation phases are probably also temperature-dependent, and strain differences in sensitivity to this factor are suggested. It is suggested that the embryonated chicken egg offers a suitable means for the study of the determinism of transformation in the cycles of T. cruzi and, possibly, also for helping in strain characterization.


Surgical versus medical treatment for stable angina pectoris: prospective randomized study with 1- to 4-year follow-up. A prospective randomized study to evaluate aortocoronary bypass was done on 116 patients (56 surgical, 60 medical) who had documented coronary artery disease (70% luminal obstruction in a major artery). The two groups were similar in age and risk factors. All patients have been followed for a mean of 34 months, and recatheterization has been done in 106 of the survivors. Important results show that although most patients in both groups are improved, more surgical patients are asymptomatic (68 vs 8%). Exercise tolerance was better in the surgical group (+94% vs +43%). There was significantly greater evidence of preinfarction angina in the medical group (p less than 0.02), but survival was similar.


Should the pericardium be closed after an open-heart operation? A controlled clinical study was carried out to decide whether the pericardium should be left open or closed after open-heart operations. One hundred patients had the pericardium closed with interrupted silk, another 100 had the pericardium left open. Complications were alike except for the more frequent occurrence of a pericardial rub in the closed group (14 vs 3 patients), though the incidence of post-pericardiotomy syndrome was equal. There was no late tamponade. Two early reexplorations for bleeding were done in the open group, none in the closed. There were no postoperative deaths. In the patients who consented to postoperative angiography following revascularization procedures, the incidence of graft failure was equal in both groups. The pericardium should be closed after an open-heart operation. Morbidity and mortality are unchanged, and repeat cardiac exploration is safer.


Gallium citrate Ga 67 scanning: clinical usefulness in lymphoma patients. Gallium citrate Ga 67 (67Ga) scans were performed in 50 consecutive lymphoma patients who underwent routine staging. The overall accuracy of 67Ga scans was greater than 80% for all nodal sites except the spleen (68%). Sensitivity was greater than 88% in the neck and mediastinum, 67% in the abdomen-pelvis, and 33% for the spleen. Specificity was greater than 85% for all nodal sites except for the mediastinum (67%). The accuracy of pedal lymphangiograms was 75%, sensitivity 87%, and specificity 68%. Gallium 67 scans complemented the lymphogram in the abdomen-pelvis but, due to limited sensitivity and high number of equivocal studies (16%), did not replace it. Infraclavicular, pectoral, and mediastinal lesions were detected by 67Ga scans when missed by other means. In 20% to 25% of patients, 67Ga scans provided information not afforded by other diagnostic studies and are therefore considered an important staging procedure for lymphoma patients.


Immunotherapy in the management of myelogenous leukemia. Now that it has been clearly established that tumor-associated antigens exist in acute leukemia in man, as in animals, the possibility of stimulating the patient's immune system to react against them arises. In animal experiments the most effective method of influencing the progress of leukemia after the implantation of living malignant cells has been a combination of nonspecific stimulation of the reticuloendothelial system, with agents such as BCG or Corynebacterium parvum, either with chemotherapy or with specific immunization with irradiated leukemic cells. However, such treatment is only effective if the number of living malignant cells is small as it takes a powerful immune response to overcome even a small number of malignant cells. It is for these reasons that most of the studies in man have been on patients with acute leukemia in remission. Mathé, in 1969, produced evidence that BCG and irradiated allogenic leukemia cells could lengthen the duration of remission in ALL in children. However, later results of intensive combination chemotherapy, together with prophylactic treatment of the central nervous system by Pinkel and his colleagues, were so encouraging that immunotherapy is not felt to be needed and therefore is not being extensively used in this form of leukemia at the moment. The situation in AML, particularly in adults, is completely different. The maintenance of remission with chemotherapy in this type of leukemia is difficult and relapses occur quite rapidly. Various centers have now shown that both remission lengths and overall survival are significantly prolonged by using BCG with or without irradiated allogenic leukemia cells.


[Results of television microscopy utilization in spermatology]. The use of television microscopy in insemination laboratories was tested by VEB Studio-technik on two insemination stations of the GDR. A transistorised remote-observation system is described as a tool providing a universal range of applications for long-time no-maintenance operation of selected microscopes. The system was found to add to the accuracy and objective value of optical microscopy for spermatological studies. TV microscopy also will improve job conditions for the personnel involved.