Occlusion pressure responses in asthma and chronic obstructive pulmonary disease. During CO2 rebreathing we measured ventilation and the pressure generated during the first 0.1 sec of inspiratory effort against a closed airway (P 0.1) in 12 asthmatics during acute exacerbation, 10 normal subjects, and 10 patients with chronic obstructive pulmonary disease. In normal subjects, the ventilatory responst to CO2 correlated with the P 0.1 response measured as delta In P 0.1. Patients with chronic obstructive pulmonary disease showed depressed responses to CO2 in terms of both ventilation and deltaIn P0.1. However, P 0.1 values in the patients with chronic obstructive pulmonary disease were greater than those of the normal subjects when they were compared at an alveolar PCO2 of 60 mm Hg. Asthmatics' responses to CO2 were similar to those of patients with chronic obstructive pulmonary disease. When measured at an alveolar PCO2 of 60 mm Hg, asthmatics' P 0.1 values were greater than those of both normal subjects and patients with chronic obstructive pulmonary disease. As the asthmatics' airway obstruction decreased so did their P 0.1. The asthmatics, and to a lesser extent the patients with chronic obstructive pulmonary disease, demonstrated increased inspiratory muscle activity that could not be explained on the basis of chemical drive or alterations in functional residual capacity. In the case of the asthmatics it was possible that the increased inspiratory muscle activity was a response to airway obstruction.


Lung function among black and white children. Racial differences in ventilatory lung function were evaluated in a community study of 393 children (158 blacks, 235 whites). Mean forced vital capacity was 18 per cent larger in nonsmoking white males than in nonsmoking black males, and 11 per cent larger in nonsmoking white females than in nonsmoking black females. Similar differences were observed for the 1-sec forced expiratory volume and for the maximal expiratory flow at 50 per cent of the vital capacity. However, when adjusted for lung size (on the basis of forced vital capacity), 1-sec forced expiratory volume and maximal expiratory flow at 50 per cent of the forced vital capacity were larger in the black children compared to the white children. Lung function prediction equations based on race, sex, age, height and weight are presented for healthy nonsmoking children; these allow for an evaluation of normal lung function in both black and white children.


IgE-induced respiratory and circulatory changes during systemic anaphylaxis in the rabbit. We studied systemic anaphylaxis induced by the administration of 200 mug of horseradish peroxidase into 11 anesthetized rabbits known to be producing anti-horseradish peroxidase antibodies only of the IgE class. Ventilatory changes included a transient, abrupt decrease in breathing frequency followed by increased minute ventilation; lung mechanical changes included decreased dynamic lung compliance and increased total pulmonary resistance;  cardiovascular changes included pulmonary hypertension, systemic hypotension, and, frequently, a transient bradycardia. Recovery from these physiologic changes took place within 60 min. After recovery, the administration of 2 mg of horseradish peroxidase into 6 of the rabbits induced a second reaction indistinguishable from the first with respect to ventilatory and circulatory alterations; however, lung mechanical changes were less prominent. No histologic evidence of pulmonary edema or intraluminal plugging of the pulmonary edema or intraluminal plugging of the pulmonary circulation was observed by light microscopy. Although the first anaphylactic reaction was accompanied by disappearance of stainable basophils from the circulating blood, the second reaction occurred despite the absence of circulating basophils. These studies characterize further the effects of antigen challenge in rabbits producing detectable concentrations of IgE, but not other classes of antibody to the antigen.


Localization of nonpalpable breast lesions detected by xeromammography. A technique for localizing nonpalpable lesions of the breast using methylene blue dye is described. This technique is recommended for its accuracy, patient acceptance, and reduction in size of the biopsy specimen.


Occurrence of gastric ulcer after Nissen fundoplication. Of 160 patients who underwent Nissen fundoplication for treatment of symptomatic peptic reflux esophagitis, five patients (3.1%) developed gastric ulcers. Four of these five patients experienced the "gas-bloat" syndrome. All ulcers were located on the lesser curvature of the stomach. Analyses of our experience with use of various types of hiatal hernia repair suggests that creation of the valvuloplastic mechanism unique to the Nissen procedure may be of etiologic significance in the development of gastric ulcers following this procedure.


Transenteric rupture of pancreatic pseudocysts: management of pseudocystenteric fistulas. Among the protean presentations of pancreatic pseudocyst, spontaneous transenteric perforation is being reported with increasing frequency. Review of the literature revealed 37 cases in which the diagnosis of transenteric perforation of a pseudocyst could be substantiated, 21 reported since 1960. Five additional cases are described, including the first case of pseudocystesophageal fistulization. Of the 26 recent cases, chronic alcoholism was associated with fistulization in 73 per cent (19/26), males outnumbered females 2:1, and the age at diagnosis ranged from 23-74. No predilection for any particular segment of intestine was apparent. All the patients had symptomatology suggestive of pancreatic disease. In addition, 54 per cent (14/26) had intestinal hemorrhage. In that group of patients with a palpable abdominal mass, the sudden disappearance of the mass as transenteric decompression occurred was pathognomonic. Defivitive diagnosis was best established by a combination of ultrasound and barium intestinal studies. The overall mortality rate was 27 per cent (7/26), all of the deaths occurring in those patients with hemorrhage complicating the pseudocystenteric fistula. Since spontaneous closure of the fistula may be expected, surgery should be reserved for those patients with incomplete spontaneous drainage or uncontrollable hemorrhage.


Wound infection: a prospective study of 7519 operations. Wound infection was prospectively studied in 7,519 consecutive operations after preoperative classification as clean, clean-contaminated, and infected. The overall infection rate was 3.9 per cent. Clean, 3.2 per cent; clean-contaminated, 4.4 per cent; contaminated, 12.4 per cent; infected, 16.2 per cent. Wound infection was not seasonally related or dependent on changes in house staff. In clean cases, the predominant role of Staphylococcus aureus (37%) has been superceded by enterococci (44%). In clean-contaminated cases, enterococci (43.5%) were the most common, followed by Escherichia coli (40.0%). In contaminated wounds, E. coli was most common (40.0%). The infected case category grew mixed flora (E. coli, 82 per cent; enterococci, 54 per cent, and Pseudomonas aeruginosa, 43 per cent). Nosocomial organisms were important only in the contaminated (14%) and infected (43%) categories. Antibiotic therapy before cultures are available should include agents with activity against enterococci as well as S aureus, and E. coli in clean cases.


Ultrasound diagnosis of popliteal arterial aneurysms. "B" mode ultrasound scanning is useful in the diagnosis of popliteal arterial aneurysms. It offers advantages over physical examination and arteriography, since these aneurysms are sometimes difficult to palpate and may be partially filled with laminated clot. The technique is noninvasive and without known hazard in this location. "B" mode ultrasound scanning promises to be useful in the diagnosis of aneurysms of other extremity arteries. It has already been useful in confirming the presence of femoral false aneurysms. Greater familiarity with the technique and improvepd technology will result in even greater reliance on ultrasound diagnosis.


Complications and management of methods of dialysis access for renal failure. The management of dialysis access requires the awareness that any single access site is finite. A commitment to maintain access is reasonable with a planned approach. Dialysis for the end-stage renal disease patient must continue acutely during the management of access complications, and chronically. The goal of treatment is to return the patient to a routine dialysis regimen as soon as possible. Suspected infections should be treated immediately with systemic antibiotics specific for resistant Staphylococcus aureus. Systemic infection should be controlled before a new foreign body is implanted. My personal philosophy of access includes the following principles. (1) distal is good, (2) preserve all possible sites, (3) arm is better than leg, and (4) everything is relative.


Irrigation removal of retained gallstone following cholecystostomy. A case is presented in which a patient, treated for acute cholecystitis by cholesystostomy, has a retained gallbladder stone removed by saline irrigation. A brief discussion is given on the  indication for cholecystostomy and its use as definitive versus temporizing therapy. In performing cholecystostomy, a catheter of diameter equal to or greater than the diameter of any stone which may be left is recommended.


[Birth weight in twins (author's transl)]. Birth weight of 1,134 twin pairs have been studied in the Maternity "La Paz" (Madrid) along years 1969-74. Mean weight among twin pairs of the like sex is 2,493.78 +/- 20.89 for males and 2,425.16 +/- 19.16 for females. Among the unlike sexes the means were 2,631.07 +/- 28.38 for males and 2,488.16 +/- 26.05 for females. Differences among the means were all statistically significative. This results have been compared with those obtained in other populations. Variability of mean weights acording with gestational age has been studied also (from 28 to 43 weeks). Curves obtained in this way were supperposed to those of single birth; until the 37 week, twins are comprised between the means and on standard deviation corresponding to single birth distributions. Increment weight per week among twins is higher than those corbresponding to single births until the 34 week. From these week growth becames slow. From the 39 week twins lost weight in a fast way. Weights differences among twin pairs grow with gestational age, being very significant from the 36 week.


[Jaundice associated with congenital hypertrophic pyloric stenosis (author's transl)]. The clinical and biological findings in six infants with congenital hypertrophic pyloric stenosis with associated jaundice are described. Pathogenesis of this association is not known but current hypothesis are based on either a decrease in the activity of hepatic glucuronyl transferase or an increase in the activity of intestinal glucuronidase. Correction of dehydration and alkalosis does not modify the hyperbilirubinemia which only disappears after pyloromiotomy.


[Idiopathic primary pulmonary hemosiderosis. Report of three cases (author's transl)]. Three cases of idiopathic primary pulmonary hemosiderosis are reported. Hemosiderin was demonstrated in macrophages (siderophages) in all three cases. In one of them, isotopic examination with  radioiron and in an other one, a pulmonary biopsy were performed. All the patients received corticosteroids. The first case had a good evolution in spite of five years without therapy. The second case showed a bad therapeutic response and required immunosuppressive drugs. The third case with a short follow-up is doing well. Literature is reviewed, and considerations about etiopathogeny, clinical features, roentgenographic and therapeutic aspects of the disease are made.


Acute myocardial infarction: prognosis after recovery. A prognostic index for 2-year survival after recovery from acute myocardial infarction was constructed from variables obtained during its course. One hundred ten of 143 patients survived 2 years, and 27 of 33 patients died of cardiac-related causes. Univariate analysis showed that 12 variables were significantly different between the surviving and nonsurviving groups. Discriminant analysis indicated five variables with meaningful predictive value to be included in a prognostic index: admission systolic blood pressure; highest blood urea nitrogen level in the cardiac care unit: atrial arrhythmias in the cardiac care unit; angina pectoris for more than 3 months or a previous myocardial infarction; and more than one ventricular ectopic beat per hour recorded on a dynamic electrocardiogram during the 17th to 24th hospital day. The prognostic index emphasizes the importance of extensive myocardial impairment and provides a means for identifying patients at risk of early mortality.


[Neonatal gastric perforation (author's transl)]. Three cases of neonatal gastric perforation of unknown etiology are presented. All three patients are female, one of them a second twin and two of them less than 2,000 g. in weight. All the patients were born under anoxic deliveries and needed resuscitative treatment. Digestive and respiratory symptoms started in all between the 2nd and the 4th days of life. Diagnosis, clinically suspected, is established radiologically. Perforations were surgically closed in all three patients. Two remain alive.


[Radiological and angiocardiographical aspects of primary endocardial fibroelastosis in children (author's transl)]. In this article we try to show the value of radiography and angiocardiography in primary endocardial fibroelastosis. The 20 CASEs studied in this report, were angiocardiographically and/or necropsically proved. In spite of different opinions, we think that it is possible to reach an approximate diagnosis of this condition if we use the clinical and angiohemodinamic examinations. On the other hand, it is necessary to point out that pathology is characteristic. The most important radiological signs were cardiomegaly, together with venocapilar congestion, both of variable magnitude, and dependent on the degree of cardiac insufficiency. By means of angiocardiography we could appreciate a great dilatation and hypertrophy of the left ventricle and a reduction of the mobility and distensibility of this cavity along the cardiac cycle.


Nosocomial viral hepatitis B. A cluster among staff with subsequent transmission to patients. In a 2-month period four cases of hepatitis B occurred in hospital staff. Three months later two patients, hospitalized  for open-heart surgery when the staff members had been infected, developed acute hepatitis B. Sera from all six ill individuals were subtype ayw and e-determinant positive. Epidemiologic investigation showed that the four staff had been exposed 3 months earlier to an asymptomatic hepatitis B surface antigen-positive (HBsAg) patient who was also e positive. To determine transmission from staff to patients study of 17 open-heart surgery patients was undertaken. Four of 17 were either HBsAg or anti-HBs positive. No correlation between infection and contact with three of four ill staff members or receipt of blood products was noted; however, 22 (46%) of 48 arterial blood gas specimens had been obtained from infected patients by one staff member, an inhalation therapist; this compared with seven (4%) of 157 specimens she obtained from control subjects (P less than 0.001). Furthermore, she handled indwelling arterial cannulae 25 (76%) of 33 times in infected patients compared with three (3%) of 95 times in control subjects (P less than 0.001). Transmission may have occurred via the arterial cannulae from a severe exudative dermatitis on the therapist's hands.


Complications with heparin-lock needles. A prospective evaluation. Because the frequency of complications related to heparin-lock needle usage is unknown, 221 heparin-lock needle insertions in 78 patients were observed for the development of complications. Upon removal of 119 heparin-lock needles from 42 patients, specimens were obtained for culture. Phlebitis was associated with 27 (12%) heparin-lock needle insertions. Only a positive flush culture of the heparin-lock needle system correlated with the development of phlebitis. Phlebitis developed during the first 4 days after heparin-lock needle insertion in two instances and later than 4 days after insertion in 25 instances. All positive flush cultures were obtained from heparin-lock needles in use for longer than 4 days. No patient developed clinically apparent systemic infection. These data suggest that heparin-lock needles should not be used for more than 4 days because, after 4 days of use, there is a significant risk of developing phlebitis, a lesser risk of developing contamination of the infusate in the heparin-lock needle system, and a potential risk of developing nosocomial infection.


[Long term evolution in Blackfan-Diamond hypoplastic anemia (author's transl)]. Six cases of Blackfan-Diamond hypoplastic anemia are reported. Five were initiated within six months of life. All cases showed intense anemia, severe reticulopenia and hypersideremia. Two of them had associated malformations. Treatment was established with Dexametasone at high doses, followed by a maintenance treatment at lower doses. A partial response was obtained in all cases. Treatment with deforroxiamine was used in order to paliate hemosiderosis. Two cases developped microangiopathic hemolitic anemia; relations with primary disease could not be determined.


[Epidemiologic comments on hypertonic dehydration in Madrid (author's transl)]. The epidemiologic factors are studied in 584 cases of Hypertonic Dehydration (H.D.) admitted to the Children's Clinic "La Paz" over a period of 5 years. The overall monthly mean (MMT) resulted in 9.75 children a month with a standard deviation of +/- 2.1. The overall monthly evolution is analysed according to the sex, the seasonal incidence, as well as the more relevant etiologic factors: Concentrated diet, diarrhoea, vomiting, respiratory pathology and fever. The epidemiologic peculiarities are discussed according to age.


Arizona hinshawii infections. New cases, antimicrobial sensitivities, and literature review. Although disease caused by Arizona hinshawii is known to resemble the spectrum of clinical syndromes seen with Salmonella infections, little is known of their sensitivity to antimicrobials. We present three cases that are illustrative of Arizona sepsis, localized infection, or both; review the literature; and report sensitivities to 12 antimicrobials for 32 human and animal isolates of Arizona hinshawii from various geographic areas. With the exception of erythromycin and streptomycin, most strains were sensitive to many of the commonly used antibiotics. As with Salmonella infections, ampicillin or chloramphenicol appear to be the initial antimicrobial agents of choice for severe infections with A. hinshawii. Definitive antimicrobial therapy must be individualized on the basis of sensitivity testing and with regard to host factors.


[Incomplete Digeorge syndrome (author's transl)]. A newborn with multiple malformations, recurrent infections and hypocalcemic tetany is presented. The malformations included: Facial asymmetry, micrognathia, epicantus, low set nose, peculiar ears, club-feet and heart disease. The immunologic work-up disclosed a cellular immunodeficiency, but normal humoral immunity, and a diagnosis of "incomplete DiGeorge syndrome" was made. No thymus, nor parathyroid glands were found at autopsy. The disagreement between the analytical data and the pathological findings of "complete DiGeorge syndrome" are discussed. The existence of vestigial ectopic thymus not found in the dissected organs is considered the most likely hypothesis. Finally some considerations are made about a possible role of the rubeola virus on its etiology and the actual therapeutic possibilities.


Gonadal function abnormalities in sickle cell anemia. Studies in adult male patients. Thirty-two adult patients with sickle cell anemia were evaluated endocrinologically. Secondary sex characteristics were abnormal in 29, and eunuchoidal skeletal proportions were present in all except one. The age at which different stages of pubic hair growth were attained in these patients was delayed in comparison to normals (P less than 0.005). Hormonal assays were carried out in 14 patients. Basal serum testosterone, dihydrotestosterone, and androstenedione values were lower (P less than 0.02) in patients than controls. Serum LH and FSH levels before and after stimulation with gonadotropin-releasing hormone were consistent with primary testicular failure. Erythrocyte and  hair zinc concentrations were significantly decreased, and there was positive correlation between erythrocyte zinc and serum testosterone (r = 0.61, P less than 0.01) in sickle cell anemia. Our study shows that androgen deficiency in this disease is a result of primary rather than secondary hypogondadism. Further studies are required to establish the role of zinc in the pathogenesis of testicular failure in sickle cell anemia.


Miliary tuberculosis and adult respiratory distress syndrome. Three patients with miliary tuberculosis developed the adult respiratory distress syndrome. In two patients this complication developed despite treatment with antituberculous drugs. The third patient developed the syndrome, but miliary tuberculosis was not suspected. The presence of disseminated intravascular coagulation in all three cases suggests a possible pathophysiologic relation. Miliary tuberculosis should be considered in patients presenting with adult respiratory distress syndrome of unknown cause.


[Remnants of the embryologic sinus venosus valves. "Cor triatriatum dexter" (author's transl)]. Remnants of the embryologic sinus venosus valves are not uncommon. However, persistent venous valves in the right atrium, which are large enough to obstruct the blood flow through the tricuspid valve (the so called cor triatriatum dexter) are very rare. There are 3 different types according to the location of the right atrial membrane. Right heart chambers hyoplasia is the most common association. Concurrent lesions of lesser degree have also been described. Although isolated cor triatriatum dexter could be symptomatic, both the clinical features and the prognosis usually are the consequence of the associated malformations. A review of the embryological aspects is offered.


[Lupus erithematosus and kidney disease in a three year old girl (author's transl)]. A case of systemic lupus erythematosus in a 3-year-old girl is presented. The diagnosis is based on the systemic involvement and repeated positivity for anti-DNA antibodies and L.E. phenomenon. A renal biopsy under optic and electron microscopy, disclosed diffuse glomerular cell proliferation and electron-dense deposits along the basal membrane. Increased basement membrane-like material is present between mesangial cells. Hematoxilinic bodies or virus-like inclusions were not found. Treatment with corticosteroids gave good results. A trial with antimalarial drugs had to be discontinued due to gastric intolerance and alopecia.


Immunization for the internist.

Immunization for the internist. The emphasis of immunization programs and schedules has traditionally been directed to infants and children, since most of the vaccine-preventable diseases are seen predominantly in these age groups. Immunization procedures in adults are less well defined but still of importance. Diseases for which immunizations are given before disease exposure include tetanus, diphtheria, influenza, rubella, and mumps; travelers to foreign countries may need immunizations against typhoid, cholera, yellow fever, typhus, poliomyelitis, plague, and viral hepatitis; other vaccines are available before disease exposure in unusual epidemiologic situations. After exposure to disease but before onset of symptoms, immunizations are available for rabies, viral hepatitis, and measles. After the onset of clinical illness, passive immunization should be given for tetanus, diphtheria, and botulism. This paper summarizes current practices for active and passive immunization against these diseases in adults.


Spironolactone and endocrine dysfunction. Therapy with spironolactone is often associated with estrogenlike side-effects, including impotence and gynecomastia in men and menstrual irregularity in women. Several possible mechanisms by which spironolactone could cause these side-effects have been identified. Spironolactone has been shown to affect both gonadal and adrenal steroidogenesis, to elevate plasma gonadotrophin levels in children, and to act as an antiandrogen at the target tissue level. This conference presents a discussion of how these effects might interact to produce the endocrine side effects associated with spironolactone therapy.


A geriatric medical residency program. A four-year experience. Geriatricians are needed to further improve the health care of elderly Americans. The first formalized geriatric residency program in the United States was developed at the Mount Sinai City Hospital Center in New York, and this has produced a second program at the Jewish Institute for Geriatric Care at Long Island Jewish-Hillside Medical Center, New Hyde Park, New York. The goals of this training are to develop special clinical skills to deal with the medical and psychosocial problems of the elderly, and to achieve the ability to develop health care systems for the elderly. Emphasis is on a multileveled system, including home, outpatient, acute hospital, convalescent unit, and long-term institution care. The training period is 12 to 24 months, after an initial 24 to 36 months of standard internal medicine, thus fulfilling the requirements for board eligibility in internal medicine.


Precursors of premature disease and death. The predictive potential of habits and family attitudes. The youthful habits and family attitudes of medical students who later developed or died from one of five disease states were different from those of healthy classmate controls to begin with. In medical school, the total disorder group had significantly more nervous tension, anxiety, and anger under stress, had more insomnia, smoked more cigarettes, and took alcoholic drinks more frequently. Individual disorder group means were significantly different from each other. The mental illness group showed the most nervous tension, depression, and anger under stress and the malignant tumor group the least. The malignant tumor group resembled the healthy control group in these respects. The suicide, mental illness, and malignant tumor groups had low mean scores for closeness to parents, while the hypertension and coronary occlusion group means were slightly higher than the control group mean. Thus psychologic differences in youth have predictive potential in regard to premature disease and death.


Human values in medical education.

Human values in medical education. Attitudes and values in medicine vary with the nature of the individual, his education and training, and the circumstances of his professional life. Comparisons are drawn between medical education in Britain 40 years ago and today. Though education has changed, British students are still mainly motivated by a desire to care for sick people. The impact of personal medicine on a country that has long accepted the need for some kind of national health service is described. It is postulated that as government and public become increasingly involved in health care, it is of paramount importance that medical education should provide a clear understanding of what a profession is and inculcate a determination to maintain true professional status. New responsibilities of the profession, to the public at large and to society, are suggested. The ability of medical education to exert a good influence on concern for human values in medicine depends in the final analysis on the ability to show excellence to medical students.


Medical oncology in journals of internal medicine. The coverage of medical oncology in internal medicine journals was evaluated by reviewing the contents of the 1974 and 1975 issues of three leading American internal medicine journals. The percentage of articles relevant to medical oncology compared favorably with figures for the other subspecialties of internal medicine. The subject matter of the medical oncology articles in the three journals was found to be complementary to the content spectrum of the subspecialty journal, Cancer. This distribution may be useful to the medical oncologist but may present a skewed view of recent developments in medical oncology to the nononcologist internist who relies largely on internal medicine journals for information regarding new trends in medical oncology. The implications of these findings are discussed, particularly with regard to the possibility that a similar situation exists for the other subspecialties of internal medicine.


The exfoliation syndrome.

The exfoliation syndrome. A clinical and ultramicroscopic review, including discussion of both scanning and transmission microscopy of the exfoliation syndrome, suggests that the term pseudoexfoliation be replaced by exfoliation syndrome. Involvement of the lens epithelium and, particularly, the pigment epithelium of the iris and the ciliary body epithelium are emphasized as being the likely sources of the exfoliative fibrils. A case of exfoliation syndrome in an eye with an eccentric pupil revealed that the granular material seen on the lens capsule occurs only where the iris is in contact with the lens surface and the process may even involve the central anterior capsule under proper conditions. This finding, together with the evidence of continuing deposits after intracapsular cataract extraction, suggests that the granular material is deposited from the iris and that the material formed by the lens epithelium remains within the lens capsule.


Ocular alkali burns in a large urban area. A retrospective study of 63 ocular alkali burn victims revealed that black males in the 30 to 49 year age group were at highest risk, and that the burns were most commonly sustained via assault. One hundred eyes were involved, and in 38 cases there was bilateral involvement. There were 116 hospital admissions and 125 surgical procedures, yet 58% of the injured eyes had a final visual acuity of less than 20/200. Other demographic and socioeconomic factors were characterized to identify this event as a public health problem with well-defined risk factors and unsatisfactory treatment. Primary preventive measures are, therefore, necessary.


Ganglionic neuroretinal aplasia and hypoplasia: aplasia and hypoplasia of optic nerve. A new clinical feature, DM/DD (distance between the centers of the disc and the macula/disc diameter) ratio, of the hypoplasia of the optic nerve is described. Two cases of hypoplasia, one unilateral and one bilateral, and one case of pseudohypoplasia or micropapilla (small discs with normal function) are reported. On the basis of the underlying defect (the failure of the development of the ganglion cells in the retina), it is suggested that this entity should be called ganglionic neuroretinal hypoplasia and aplasia (when all the ganglion cells are missing). For the same reason it is proposed that this entity should be included in the discussion of the retinal disorders. Also this entity should be differentiated from the small discs with normal function (pseudo-hypoplasia or micropapilla). A classification of ganglionic neuro-retinal hypoplasia is given and associated ocular anomalies are mentioned.


Traumatic hyphema.

Traumatic hyphema. This report contains a study in retrospect of 50 patients treated for traumatic hyphema between 1964 and 1974 at the Kern Medical Center, Bakersfield, California. The prognosis for visual acuity is summarized in 3 distinct groups. The 50 patients studied were all treated in a similar manner by conservative method of bed rest with elevation of the head from 20 to 30 degrees and binocular patching. A review of our statistics, we believe, warrants this conservative method of treatment.


Transposition of vertical recti for residual tropias. Transposition of vertical muscles for residual tropia was performed: nasal displacement for exotropia and temporal displacement for esotropia. Five millimeter equal displacement of superior and inferior recti corrected 10 to 14 prism diopter while equal displacement of 7 to 8 mm resulted in correction of 25 prism diopter. Special indications of this procedure may be: (1) residual tropia in cases with severe intractable ambylopia or pathology in one eye where patient and surgeon may be reluctant to operate on the sound eye, or (2) residual tropias of the alternating type in patients who underwent operations in all horizontal muscles of both eyes.


[An unusual and dangerous clinical form: chronic osteomatous otitis]. Some chronic otites result in local or diffuse attico-antral osseous outgrowths. These may complicate all sorts of chronic otites: cholesteatomatous or otherwise, suppurative or merely inflammatory, with the tympanum open or closed. They should be distinguisged from tympanosclerosis and condensation or osseous eburnation lesions. They seem to result from post-inflammatory irritation causing metaplastic bone growth or from an exostosis. The key to their diagnosis lies in radio-tomography. From the surgical point of view, diffuse attico-antral forms are particularly dangerous and deadly. It is essential that the kopho-surgeon should be aware of their existence which, as far as we know, does not seem to have been noted so far.


[Deafness in the Muckle-Wells syndrome]. Typical of the syndrome described by Muckle and Wells is a combination of progressive perceptive deafness appearing at various ages in a family, but usually at the same age in the same family, arthralgia, urticarious eruption and renal amyloidosis. The existence of incomplete forms, either without deafness or without renal amyloidosis should be known. This perceptive deafness is very probably due to lesion of the internal ear but the histological characteristics do not seem to be very clear at the present time. Finally, as certain of our observations show, in a few cases, conduction may be impaired, either in isolation, or associated with impairment of perception. Only an analysis of a large number of cases will enable the audiological characteristics of this curious syndrome to be defined.


Acute epiglottitis in infants and children. Sixty-one cases of acute epiglottitis at the Royal Alexandra Hospital for Children, Sydney, from July 1968 to December 1974 are reviewed. The average age of 2.7 years is lower than previously reported. The average time from the initial symptom to arrival at the hospital was 14 hours. The average time from arrival to performance of tracheotomy was two hours. The diagnosis was made when first seen and assessed in 50 of the 61 cases. There were eight respiratory arrests in the Casualty and five of these were successfully resuscitated. We believe that an artificial airway is necessary in most cases, and in this series, tracheotomy was performed, with minimal complications. Particular emphasis is given to diagnosis from the history, and a detailed description is given of physical examination of the oropharynx. Although x-ray examination is usually unnecessary when the diagnosis is in doubt, a plain lateral x-ray may be useful, with due precaution not to increase the respiratory obstruction. We consider that a patient with acute epiglottitis should be transferred immediately to a major pediatric hospital, and that in almost every case an artificial airway should be established.


Acquired and congenital subglottic stenosis in the infant. During the calendar year of 1974, the Intermountain Newborn Intensive Care Center at the University of Utah Medical Center had 603 admissions. A representative group of 293 charts were reviewed which indicated that 44% of these children were intubated from hours to weeks. The overall mortality rate for the 293 children was 29%. Eighteen of the 603 children were diagnosed as having subglottic stenosis. Fifteen of these children appeared to have acquired subglottic stenosis secondary to endotracheal intubation. Three children had congenital subglottic stenosis. Tracheostomy was necessary in the management of 15 patients. Ten of the 18 patients have survived and two of these patients still have tracheostomy tubes in place. The survival and thickness of the stenotic area are inversely proportional to the birth weight and the duration of intubation. Endoscopic excision, dilatation and stenting were techniques utilized in the treatment of these stenotic lesions. The extubation technique utilized is described. The factors involved in the production of acquired subglottic stenosis are presented along with suggestions to decrease the incidence of this problem in the intubated child.


Repair of laryngeal stenosis with nasal septal grafts. Autogenous nasal septal grafts were utilized in 18 dogs. The availability, method of transfer, placement, take, stability and long-term survival of these grafts are presented. Transfer of septal cartilage or composite grafts of nasal mucosa and cartilage to surgically created defects of cricoid and thyroid cartilage was performed on eight animals. Ten animals had composite grafts three months after stenosing procedures. Results were excellent in all grafts to the cricoid and subglottic areas. Grafts to the thyroid and glottic regions were characterized by severe resorption of cartilage and fibrosis. Composite grafts to the glottic area were successful in improving the airway. Results are documented by microlaryngeal photographs and histologic sections. A literature review accompanies the presentation with emphasis on clinical utilization of composite nasal septal grafts. Twelve previously reported cases of repair by this method for laryngeal and upper tracheal stenosis are discussed. A patient with severe traumatic laryngeal stenosis successfully rehabilitated is added to this list and details the clinical value of these grafts.


Clinical experience with the tracheoesophageal anastomosis for intractable aspiration. Clinical experience in six patients in whom the tracheoesophageal diversion procedure or a modification thereof has been performed is presented. Two of these patients have been reconstructed with resulting normal laryngeal and esophageal function. Three of the patients have successfully undergone tracheoesophageal anastomosis and are candidates for reconstruction. One patient in whom the tracheoesophageal anastomosis has been present for 2 1/2 years may never demonstrate neurological return sufficient for reversal of the procedure. On the basis of these six cases, we consider the tracheoesophageal anastomosis to be an effective, yet reversible, procedure for intractable aspiration.


Congenital tracheoesophageal fistulas in adults. Congenital tracheoesophageal fistula without esophageal atresia is commonly known as "H" type. This is an extremely rare anomaly in infants and accounts for approximately 1 1/2-4% of all congenital tracheoesophageal malformations. An anomaly should be described by its anatomical defect, not by a number or letter. There are five main anatomical categories with 85-95% being of the esophageal atresia and distal tracheoesophageal fistula type. About 1 1/2% are of the "H" type. Although today tracheoesophageal fistula is a well-recognized entity, a few of the "H" type have passed through the pediatric period without diagnosis. Those undetected fistulas have successfully masqueraded as chronic lung disease of unknown etiology. Congenital "H" type tracheoesophageal fistulas assume an oblique orientation with the growth of the host to adulthood. This helps to explain the difficulty in diagnosis plus the ability of the host to survive to adult life. Treatment is surgical, consisting of simple ligation via cervical or thoracic approach depending upon location. The 12 previously reported cases in the English literature are reviewed, and a 13th case has been added.


Tracheal resection and mucociliary clearance. Mucociliary transport following tracheal resection and end-to-end anastomosis was evaluated in beagle dogs, using the movement of 99MTC labeled sodium pertechnetate solution as a marker. Preoperatively, mucociliary clearance was stable, but a three-fold decrease in tracheal mucus movement was found three days postoperatively. Clearance rates had returned to normal by 31 days postoperatively and remained stable over a ten week period of observation. By histological examination, normal ciliated epithelium was seen within six months following resection and anastomosis. Since up to 25% (4 cm or seven tracheal rings) of tracheal length was removed, significant longitudinal loss can take place without functional impairment of mucociliary clearance. Circumferential narrowing, however, was associated with a significant decrease in clearance.


Flexible fiberoptic nasopharyngolaryngoscope. A new practical flexible fiberoptic nasopharyngolaryngoscope is introduced. This instrument allows for a completeness of examination heretofore not totally possible in all cases as an office or bedside procedure. The ease of examination and patient tolerance make for a superior new clinical tool.


Test-retest reliability in clinical electrocochleography. The intratest test-retest reliability in clinical electrocochleography was studied by measuring the difference between amplitude of the test and retest and latency of the test and retest. Eighty-four comparisons were made in 40 patients with different types of hearing losses. The type of hearing loss and whether test and retest were performed in sequence or not did not affect the variability of the amplitude. The test and retest correlation between amplitudes was good. Small amplitudes mainly found near the action potential (AP) "threshold" showed less absolute variability than larger amplitudes found at higher intensities. The correlation between the intratest latencies was excellent. The latency showed less variability at higher intensities than near AP "threshold".


Tracheal afferent nerves.

Tracheal afferent nerves. The individual fibers of the inferior laryngeal nerve and anastomosing branch of the superior laryngeal nerve arising from the upper five to six tracheal rings were studied. In 30 mongrel dogs using simple and multifiber nerve preparations, afferent nerve activity was studied both in the intact trachea and in an isolated segment of trachea with artificial stimuli of graded pressure and flow. The adaptation rate, threshold, spontaneous firing frequency, maximum firing frequency, and rate of change in afferent discharge were recorded. Subsequently, these fibers were electrically stimulated to determine what reflex effects could be produced. Afferent nerve activity recorded from the upper trachea was found to be sensitive to tracheal pressure changes of 0.5 to 12 mm Hg. Nerve activity paralleled the frequency of pressure changes. Electrical stimulation of these fibers demonstrated reflex bradycardia, bradypnea and alteration of blood pressure. These data and that of other investigators indicate that upper airway mechano-receptors may be significant, not only in the initiation of upper airway protective reflexes, but also in the regulation of normal respiration.


Survey of the development of laryngeal epithelium. An overview of the developing laryngeal epithelium has been presented to establish the norm. The sequential relationships of the formation of the protective laryngeal covering, cellular and glandular, have been reviewed. The topographical distribution of the epithelial elements in the human larynx are illustrated in the adult and contrasted in the child. Unique and previously undescribed cellular ultrastructure and transition areas have been identified. Biological integrationof form and function is again well illustrated in the epithelium of the human larynx.


[Embryonic development of 2 Phyllobothriidae (Cestoda: Tetraphyllidea)]. Caulobothrium longicolle (Linton, 1890) and Phyllobothrium gracile (Weld, 1855) (Cestoda: Tetraphyllidea, Phyllobothriidae) have the same embryonic development with the following characteristic data: --a small number of vitelline cells (2 or 3) pass with the zygote in the ootype;--a non operculate thin egg-shell;--the entire and equal zyhote cleavage following by unequal divisions leading to the formation of four blastomere types (Macromeres, secondary Macromere, Mesomeres and Micromeres);--the differentiation of two syncytial embryonic envelopes during the preoncospheral phase. The outer envelope encloses the vitelline material remnant and three Macromeres among which the secondary Macromere. The inner envelope or embryophore, originates from five or six Mesomeres;--the presence of the oncospheral membrane;--the Phyllobothriidae ontogenesis is similar to that of the Onchobothriidae. By their embryonic features, the Tetraphyllidea are close to the Cyclophyllidea. This similarity suggests a phylogenic relationship between those two Cestoda orders.


Fine structures of the normal mucosa in developing rat middle ear. Forty-two fetal and 90 developing young rats were studied electron microscopically to obtain a normal cellular distribution pattern of middle ear mucosa. The results showed that while ciliated columnar or cuboidal cells interspersed with secretory cells were predominantly distributed around the tympanic orifice and transitional zone, cuboidal or squamous nonciliated cells without secretory granules were numerous in the remaining part of the bulla. Development of ciliated cells started at the 17th or 18 th fetal day,paralleling that of secretory cells. The number of ciliated and secretory cells increased rapidly after birth. Glands were not found in the osseous tube, tympanic orifice, or other portions of the middle ear cavity in fetal, newborn, or suckling rats, while they are abundant in the cartilaginous portion of the tube. The findings of this study indicate that both secretory and ciliated cells are normal components of middle ear mucosa although these cells are restricted to the tympanic orifice and transitional zone, and that the mucociliary defense system starts to develop during the fetal stage.


[Description of the supposed adult of Bursotrema tetracotyloides Szidat, 1960, and of a new species of the genus Didelphodiplostomum Dubois, 1944, parasites from Didelphis azarae Temminck, 1825 (Trematoda: Alariinae) (author's transl]. The author describes two South American trematodes (Diplostomidae: Alariinae) collected by Dra Margarita O. de Núñez from a opossum, Didelphis azarae Temminick, 1825, in the vicinity of Buenos Aires. One of them permits to define the larval genus Bursotrema Szidat, 1960. The other one is a new species of the genus Didelphodiplostomum Dubois, 1944.


[The life cycle of Plagiorchis neomidis Brendow, 1970, digenean parasite of Neomys fodiens in the Pyrénées. Chronobiology of cercarial emergence (author's transl)]. The first host in the life cycle of Plagiorchis neomidis in the Pyrenees is the Mollusc Radix limosa var, glacialis. The cercariae encyst in the aquatic larvae of the Insect Sialis lutaria (Megaloptera). The adult parasite is found in the rectum of Neomys fodiens. The chetotaxy and the rhythm of cercarial emergence are described in detail as is the development of the metacercaria in its second intermediate host. Comparison of the life cycle of P. neomidis in the Pyrenees with that described in Germany demonstrates differences in the biology at both larval and adult stage.


[Coexistence of nematodes Trichostrongyloidea in marsupials from French Guyana (author's transl)]. Analysis of the helminthofauna of two Didelphis marsupialis, compared to that of a Metachirops opossum from the same area, studied by Durette-Desset, 1974. Except for their similarities in the general repartition of the species, the two Marsupials are easily differentiated: the dominant species is not the same. The location of common or "vicariant" species is stable. In opposition to former notions, the fauna appears to be composed of but one lineage, except for Moennigia, which would appear as captures from Xenarthes.


[Anomotaenia brevis (Clerc, 1902) Fuhrmann, 1908, Cestoda Cyclophyllidae, parasite of Leptothorax nylanderi (Forster), Hymenopterous, Formicidae (author's transl)]. Cysticercoids recovered from hemocoele of the ant Letothorax nylanderi are examinated by light and electron microscopy. This examination proves that the Cestode is a Dilepididae. The structure of the cysticercoids is the same that another Dilepididae, Anomotaenia constricta. The cysticercoids observed are those of A. brevis, parasite of three species of birds, Dendrocopos major, D. minor and Garrulus infaustus. The contamination of L. nylanderi by A. brevis occurs before metamorphosis of the Ant. The adults of L. nylanderi infested by A. brevis cysticercoids are morphologically different from the others; their physiology and behaviour are also different. The mechanisms of the parasitic action on the larval stages of L. nylanderi are discussed.


[The life cycle of Maritrema misenensis (A. Palombi, 1940), n. comb. (Trematoda: Microphallidae, Travassos, 1920) from French Mediterranean coast (author's transl)]. The life cycle of Maritrema misenensis (A. Palombi, 1940) n. comb. is described with illustrations. The sporocysts parasite the digestive gland of the Prosobranch snail Cerithium mediterraneum. The cercariae are the same as Cercaria misenensis, A. Palombi, 1940 described from Italian coast. The adults have been obtained by artificial infestations of Larus argentatus michaellis. Their morphological features are same as those of the caribbean species Maritrema patulus W.H. Coil, 1955. When the life cycle of the American species is pointed out, it will be possible to know whether there are two or only one species.


[Findings on the life cycle of Pseudoleucochloridium soricis (Soltys, 1952) in the Pyrenees (author's transl)]. Pseudoleucochloridium soricis develops to the sporocyst stage in the digestive gland of the terrestrial Pulmonate Cepaea hortensis. The cercaria, microcercous in type, is liberated and actively penetrates a second terrestrial pulmonate where development to the free metacercarial stage takes place in the pericardial cavity. Ecologically, the cycle of P. soricis in the Pyrenees, exhibits two characteristics which require particular attention: --the transmission of the parasite to the second host, which, although experimentally possible, and with equal success, in two species of Helicide (C. hortensis and Euomphalia strigella) occurs in the wild preferentially in E. strigella. The differing trophic behaviour of the two molluscs is thought to be the factor responsible for this selection;--the level of infection in shrews appears to be extremely low (never more than 1%) in all sampling areas, a character which contraste with the persistantly high level of infection in the second host (at least 50%). This epidemiological character points to the probable evolution of P. soricis in a definitive host (almost certainly a Bird) which has not yet been discovered.


[Massive presence of Schistosoma mansoni in the lungs of rats trapped in Guadeloupe (author's transl)]. Examination of rats (Rattus norvegicus) trapped in Guadeloupe and naturally infected by Schistosoma mansoni reveals the massive presence of these parasites (adults and eggs) in the lungs.


[Experimental trichinasis (IV), study of the action of cyclophosphamide on the transplantation of 18 days old adults of T. spiralis (author's transl)]. The survival and the transplantation of adult trichinae collected in cyclophosphamide treated and untreated mice were studied. 1) The worms'burden harbored by treated mice on the 18th day after the infestation is from 4 to 5 times higher than in untreated ones. The sex ratio is here around one instead of 1/2 in the control lot of mice. 2) The female worms parasitic in treated mice continue to lay larvae. When these adult are transplanted in the gut of treated mice they seem give a greater number of larvae than if they are put in the gut of normal mice.


[Study of free living amoebae in the waters of Strasbourg. Preliminary report (author's transl)]. 75 strains of free living amoebae were isolated from public drinking water supplies, swimming pools and official swimming ponds in Strasbourg. 42 strains were identified till now. No pathogenic strain of Naegleria fowleri was found.


[Further description of two African bovine's Onchocerca (author's transl)]. The synonymy of O. dermata with O. ochengi Bwangamoi, 1969, is established. Further description of O. ochengi and O. dukei Bain, Bussiéras and Amégée, 1974.


[Presence in a rodent of Chili of the nematode Inglamidinae (sub. fam. nov.) belonging to Amidostomatidae, a family known to be found in mammals of Australia]. The Inglamidinae n. sub-fam., a new sub-family of Amidostomatidae from chilean Cricetidae is described with Inglamidum akodon gen. et sp. n. as the type genus and species. Out of the 23 Akodon captured in the same area, three samples of this nematode have been collected from two different species. These findings confirm that we are dealing with a well-adapted parasite and exclude the possibility of a fortuitous catch or an accidental transfer. This family displays two significant groups of taxonomic characters, including archaic characters such as cephalic structures which unite them to the Amidostomatidae, and on the other hand some more recently elaborated characters such as monodelphism and shape of synlophe and spicules which relate them to the Heligmosoms and more significantly to the line Viannaia-Viannella parasite of South-American Marsupials. We interpret this species as a "parasite of capture" and we assume that very similar species might occur in other endemic Mammals, mostly Marsupials. On a paleobiogeographical point of view this interpretation would make due allowance for postulating that the Amidostomatidae from Mammals have originated during the Secondary concurrently with the Marsupial expansion. These ancestral Nematodes would have given birth to the other Trichostrongyloidea through reduction of buccal cavity, and to the Ancylostomatoidea by further elaboration of buccal apparatus. Contrary to Inglis's hypothesis we are in favour of the genera Globocephaloides and Hypodontus to be assigned to the Globocephalinae and Uncinariinae (Ancylostomatidae) respectively, rather than to the Amidostomatidae. The occurrence of an Amidostomatidae in a South American Cricetidae is somewhat quite unexpected, mostly because this family is known to occur from australian Mammals only and also because the parasited Mammals are the most primitive of the group (Monotremes and Marsupials).


[Presence of Haematomyzus hopkinsi Clay, 1963, in Ethiopia (author's transl)]. The author records the presence of H. hopkinsi Clay, 1963, parasitic of wart-hog (Phacochoerus aethiopicus) in South-Eastern Ethiopia (collected by E. Brumpt in 1901).


[Aedes (Ochlerotatus) surcoufi (Theobald, 1912). Restoration of the binomen; morphological analysis; position in the holarctic "excrucians" complex (author's transl)]. The study of the morphology of eggs, larvae, pupae and adults of Aedes excrucians from Germany, Italy and France has led the authors to rise again the binomen Aedes surcoufi (Theobald, 1912) to particularize the european populations. At the same time, the characteristics of the different species of the Aedes excrucians complex are discussed.


Long posterior flap amputation in geriatric patients with ischaemic disease. A series of 165 primary amputations performed on 148 patients at Queen Mary's Hospital, Roehampton, from 1967 to 1975 is reported. The average age of these patients was 70 years, the oldest being 95. Those aged 70 years and over are considered in special detail. The problems of management of these elderly patients are complex, involving medical, surgical, and social problems. The object of treatment is to restore these patients to their previous way of life with the shortest possible time in hospital. Every patient is assessed with a view to arterial surgery, and amputation is avoided where possible by a lumbar sympathetic block or direct arterial surgery. When amputation cannot be avoided a below-knee level is selected if possible. A long posterior flap technique is used which forms a myoplasty of the gastrocnemius muscle; thus the ischaemic anterior tibial skin is avoided. Before the operation the patient is assessed by a specialist team and the management is discussed in detail. Every patient is kept in hospital until rehabilitation is achieved to the point of independence inside the home. Of the 90 patients in the group aged 70 years and over, 22% had above-knee amputations and 75% had below-knee amputations, with the result that 69% of the latter were discharged home walking. This result is contrasted with the smaller number who had an above-knee amputation. Below-knee amputation gives the elderly patient a better chance of walking because of the use of the patellar tendon bearing prosthesis. When followed up 36% of those patients with below-knee amputation were fully independent for periods exceeding six months. The price of a below-knee level of amputation is a longer hospital stay, but the quality of function and mobility obtained by the patient makes this worth while.


Exploration of the abdomen.

Exploration of the abdomen. The findings at 1500 consecutive laparotomies are reported. The likelihood of finding an alternative condition to the preoperative diagnosis and of discovering important incidental findings is so high that complete abdominal exploration should be carried out whenever possible at routine abdominal operations. However, laparotomy is no substitute for careful preoperative investigation. Routine preoperative endoscopy is recommended before all operations on the upper gastrointestinal tract. If no cause for symptoms is found at operation no procedure should be carried out; the placebo effect of laparotomy and subsequent assurance often leads to alleviation of the symptoms.


The importance of plasma fibrinogen in vascular surgery. The plasma fibrinogen concentration is directly related to blood viscosity, which in turn is inversely related to blood flow. The way in which the plasma fibrinogen level affects the clinical status of patients with peripheral vascular disease is discussed with reference to both retrospective and prospective studies of patients undergoing major arterial surgery. Animal experiments are described in which the effect of reducing the plasma fibrinogen level with oral clofibrate and parenteral Arvin (ancrod) on the patency of Dacron arterial grafts was studied.


Sclerosing peritonitis and practolol therapy. The case is described of a patient who presented with the characteristic symptoms and signs of sclerosing peritonitis due to practolol therapy. The clinical features, operative findings, and management are discussed.


Traumatic haemobilia: value of ultrasonography. A case of post-traumatic haemobilia treated by right hepatic artery ligation is described. The role of 'B'-mode grey-scale ultrasonography in the investigation of hepatic trauma is discussed.


[Control of the efficiency of ligature of the pancreatic canal in rabbit (author's transl)]. The purpose of this work is to determine whether ligature of the pancreatic canal effectively stops exocrine secretion by the pancreas. Two methods of study were used: histology of the pancreatic gland and enzymology in the intestine. Optical microscope results, for rabbits with the pancreatic canal ligatured during 5, 10, 15, 20, 30 and 60 days, showed clearly pancreatic degeneration followed by regeneration phenomena. However search for trypsic activity in the intestine has given only negative results.


Partition and absorption of valatile fatty acids in the alimentary canal of the rat. The partition and absorption of volatile fatty acids (VFA) have been studied in the rat using a non purified diet comprising mainly a mixture of cereals and soya-bean meal. 2. The concentration of acetic and lactic acid was compared in non secretory (cul-de-sac) and secretory regions of the stomach. The greatest concentrations of both acids were found in the cul-de-sac region where the pH was highest (pH 5.0). 3. Concentration and absorption of VFA were negligible in the small intestine. 4. High VFA concentrations were found in the caecal contents, while lactic acid concentrations were lower. The volume and concentrations of the caecum contents varied little during the day and decreased rapidly during the first 24 h of fasting. 5. The concentrations of VFA, particularly that of butyric acid, were lower in the proximal colon than in the caecum. Caecumectomy caused a considerable decrease in VFA concentrations in the colon. 6. Arteriovenous differences in VFA and detone bodies were studied for the caecal and colon veins in rats. A close parallel between VFA concentration in the caecal contents and the arteriovenous differences was observed. In rat, ketogenesis was weak in the caecal wall (12 p. 100 of butyric acid absorption) and negligible in the colon wall. VFA are absorbed entirely in ionized form when caecal PH attains 7.5 in fasted rats. Special mechanism for caecal absorption should therefore be considered, perhaps linked with the large sodium transport in the caecum. 7. The relatively high VFA concentrations measured in the portal vein suggested that they are important in the digestive processes.


Sub-clinical swine fever: a survey of neutralizing antibodies in ther sera of pigs from herds having reproductive failures. Sera harvested from breeding farms where reproductive failures were observed but where swine fever vaccination was not carried out, where tested for the presence of neutralizing antibodies specific for swine fever virus. Neutralization tests were performed in tissue culture using two viruses strains: the american serological variant "331" strain isolated by MENGELING (1969) and the virulent "normal strain" Alfort. For comparison, sera harvested from healthy, vaccinated and unvaccinated breeding farms were also tested. Results show absence of antibodies against these two strains in healthy and unvaccinated animals. All sera harvested from healthy and vaccinated breeding farms have high levels of neutralizing activity against the two strains. From 1,251 harvested unvaccinated breeding farms have reproductive failures, 6.2 p. 100 had neutralizing antibodies against the "Alfort" strain and 17.1 p. 100 contained neutralizing antibodies against the "331" strain. In 87 out of these 189 breeding farms, positive serological reactions were observed. Considering the respective intensity of neutralizing activity against the two strains , the vaccination with live virus vaccines ("Chinese strain" or "Thiverval" strain) induces high levels of antibodies but a higher titer against "Alfort" strain. Inversely, low virulent strains responsible for sub-clinical swine fever induce low or moderate levels against the "331" strain and nil or low levels against the "Alfort" strain. These results suggest that low virulent strains having common antigenic properties with the serological variant "331" strain are circulating among pigs in unvaccinated breeding farms having reproductive failures. These features are important for future development and establishment of routine serological checking for diagnosis and herd testing.


Vaccination against bovine brucellosis with a low dose of strain 19 administered by the conjunctival route. III. -- Serological response and immunity in the pregnant cow. Seventy-four heifers, 7 to 12 months old, were randomized in four groups: group A, 8 heifers as controls; group B, 19 heifers vaccinated subcutaneously with 9 X 10(10) Brucella abortus strain B 19; group C, 19 heifers vaccinated as in group B, then revaccinated by the conjunctival route 6 to 8 months later with 5 X 10(9) bacteria; group D, 28 heifers vaccinated twice by the conjunctival route with the same dose and time intervals as in group C. Serological responses in agglutination, complement fixation and Rose Bengal tests were typical of those following standard vaccination with Strain B 19 in group B. Iu group C after the booster vaccination, there was a transient rise in titers which lasted about 3 months. Iu group D, titers were infrequent, low, and lasted no more than 8 weeks, after both primary and secondary vaccination. Fifty of the heifers, when 4 1/2 to 6 1/2 months pregnant, were challenged by the conjunctival route, with 16 X 10(6) B. abortus strain 544. Calves were born at full term (greater than or equal to 264 days) to 1/7 heifers in group A, 6/12 in group B, 8/II in group C and 14/19 in group D. Serological tests every two weeks after challenge; bacteriological examination of vaginal mucus, colostrum, foetuses and dead calves; bacterial enumeration of ten mixed samples of lymph nodes and organs taken at slaughter about 6 weeks after parturition, were made to determine the infection status of the heifers. Brucella was isolated at some time from 7/7 heifers in group A, II/I2 in group B, 6/I2 in group C and I4/I9 in group D. Five heifers (2 in B, I in C, 2 in D) cleared themselves of infection between parturition and slaughter, The average degree of infection per group at slaughter, expressed as a logarithmic index of the number of Brucella isolated from the ten samples, was significantly lower in the three vaccinated groups than in the controls, and in groups C and D than in groups B, and it was not significantly different in group C and D. For field vaccination, a booster vaccination by the conjunctival route, as in group C, would provide more protection than the standard vaccination without serious interference in routine diagnostic tests. Two vaccinations by the conjunctival route, as in group D, would be simpler, more economical and at least as effective as the standard system of vaccination, and would have the advantage that vaccination could be done at nay age without risk of serological response.


In vitro transformation of ochratoxin A by animal microbioal floras. Ochratoxin A is hydrolysed to ochratoxin alpha by the centrifugal pellet of rat caecal contents containing the microbial flora. The supernatant liquid is however, completely lacking in detoxifying enzymatic activity. The large proportion of toxin lost suggest that degradation of the active principe to non-fluorescent metabolites occurs. The rumen fluid of cows and sheep obtained at a slaughterhouse can hydrolyse the toxin and also, in certain cases, esterifies it to the equally toxic ochratoxin C. Cow rumen fluid obtained by oesophageal sounding does not have the latter activity but hydrolyses more intensively ochratoxin A. In this case the fraction responsible for this transformation contains mainly protozoa.


New systems for dental maturity based on seven and four teeth. An updated system for estimating dental maturity is presented. It extends the original system (Demirjian et al., 1973) based on radiographs of 7 teeth by including two extra stages, and by enlarging the standardizing sample to include 2407 boys and 2349 girls. Percentile standards from ages 2-5 to 17-0 years are presented separately for boys and girls. Scoring systems and percentile standards are presented for two different sets of 4 teeth and a comparison of all three systems is made. It is suggested that these systems may measure somewhat different aspects of dental maturity.


Effect of family size and mother's longevity. A prospective study of the mother's longevity and of her completed family size has been conducted on the basis of historical demographic records. We show that 1 to 5 pregnancies is associated with the greatest longevity in weakly inbred women and 11 pregnancies is associated with greatest longevity in more inbred women. Taking into account maternal inbreeding, completely sterile women and those who had a large number of pregnancies have an equal mean longevity. It is suggested that repeated pregnancies produce a cumulative hormonal effect, the distribution of which, following family size, should be bell-shaped.


Androgyny of physique in female track and field athletes. Androgyny scores (3 x biacromial breadth - bicristal breadth) were calculated for 66 female track and field five event categories and 76 female non-athletes. Runners (distance and sprinters) did not differ significantly from the non-athletes in androgyny. However, jumpers, discus/javelin throwers, and shotputters were significantly more androgynous in physique. Androgyny scores for participants in jumping and throwing events overlapped considerably those for college-age males.


An assessment of a stereophotogrammetric technique for the study of facial morphology in the child. An assessment has been made of a stereophotogrammetric technique (Beard and Burke, 1967) for measuring and contouring the face. Its contouring capabilities depend on the skin surface texture of the subject. Adults have good skin texture and accurate contours can be drawn. Young children cannot be contoured satisfactorily because they lack adequate skin texture, and only linear measurements can be obtained with precision. The disadvantage of incomplete facial coverage was eliminated by using a pair of oblique exposures instead of the conventional frontal exposure. The need for mechanical head positioning was avoided by use of a sighting device incorporated in the system to orientate each exposure to a common datum.


[Lymphocytes HLA antigens expressivity after neuraminidase treatment (author's transl)]. Neuraminidase treatment of lymphoid cells increases the cytotoxic action of antibodies and complement on these cells. We have studied the action of 25 human alloantisera on lymphocytes of 26 healthy subjects by the Trypan blue lymphocytotoxicity technic, before and after neuraminidase treatment of cells. The results show, as a rule, an increased cytotoxicity of sera, with a higher titer and/or a more important number of positive cells. In some sera a specific cytotoxic activity is found only with neuraminidase treated cells. The antibodies often reveal an anti-HLA specificity: that specificity was previously known in the serum or, in several cases, has been found only with neuraminidase treated cells. But in some cases the new specificity does not seem to be related to the HLA system. Different hypotheses are discussed in order to explain these results and the action of neuraminidase on membranes; lastly, applications of our neuraminidase treatment method to practical problems are presented.


[Relationship between temperatures behavior following short-term exposure of fingers to heat and cold and various anthropometric index values. Contribution on the problem of temperature regulation in man]. On a sample of n=201 male students between 18 and 30 years cold resp. heat tolerance tests were carried out in order to examine, how far correlations to anthropometric traits are present. No correlation between body height and heat resp. cold tolerance were found. Against that body weight, ROHRER-Index, subcutaneous fat tissue, weight/surface-ratio and surface/weight-ratio showed marked correlations with variations in body temperature. Particularly in the cold tolerance test more heavy and fatty individuals were characterist by a greater ability to store body heat as the decrease of temperature in them was obviously lower. The anthropological significance of these observations is discussed.


The complete sequence of the murine monoclonal immunoglobulin MOPC 173 (IgG2a): genetic implications. The complete amino acid sequence of the murine monoclonal immunoglobulin MOPC 173 (IgG2a, kappa) is reported. The heavy chain contains 447 amino-acid residues, and one carbohydrate prosthetic group attached to the ASX residue 299. The kappa light chain is composed of 214 residues. The H chains are covalently linked by 3 interchain disulfide bridges. The H-L bond-forming cysteine of the H chain is between the VH and the CH1 domain. Intrachain bridges are disposed linearly, according to the classical model. There is no simple relationship between the primary structure and any given function of a particular domain. This is presumably due to the fact that the selection pressure exerts itself on the three-dimensional structure which may retain a conserved general organization as a result of balanced multiple mutations. Selection seems to act in two ways: --horizontally, in a multigene system such as the immunoglobulin classes (C domains of the heavy chains), leading to interclass homologies which are particularly marked for all the COOH-terminal domains of H and L chains which have, in addition a fair degree of homology with human beta2 microglobulin (about 30% identities); --vertically, in which case strictly homologous domains appear extremely conserved between distinct animal species. Conservation of the VH domains seems just as high as conservation of the CH domains. The VH region contains 3 types of positions: invariant and subgroup characteristic ("framework") which may be accounted for by a rather small number of germ-line genes, and hypervariable for which the origin of diversity, somatic or germinal, cannot be decided from sequence data alone. Murine VK domains, although basically built according to the same pattern, show a much more marked polymorphism of the framework, which might necessitate a higher number of basic germ-line genes. Finally, a hypothetical model of the switch mechanism is proposed. Rotational symmetry regions can be deduced at the DNA level from the known amino acid sequences of the switch peptides for the three translocational systems: H, kappa and lambda. These would provide recognition signals for restriction-like enzymes such as those which operate in prokaryotes. An implication of this model is the definition of an exact limit between the V and the C regions of all immunoglobulin chains.


A selective theory for the epigenetic specification of the monospecific antibody production in single cell lines. A new selective theory for the specification of the antibody production is presented. It is grounded on the following postulates: (a) the antigen stimulus triggers the synthesis of antibodies having a wide variety of specificities in a given immunocompetent cell and its progeny; (b) only these antibodies having affinity for the antigen have their synthesis stabilized, and competition between the diverse syntheses will favor the antibodies having the highest affinity; (c) there existes a threshold synthesis such that when the production of an antibody becomes lower than the threshold, it will go to zero. As a consequence, one should observe, immediately after the antigen stimulus, the transient appearance of a large number of seemingly unspecific immunoglobulins, followed by specific antibodies. The apparent binding constant of these antibodies should also increase during the specification period. Besides, one should observe a small, but detectable amount of self antibodies during the early period of specification. Finally, in the presence of several antigens, one should find cells which appear to produce antibodies against several antigens during a transient period.


[Pilometric methods-contributions and critical aspects]. On the basis of 13,000 single-hair-measurements and their statistical data a sample-size of 100 hair-measurements could be proved as an absolute minimum for the determination of the individual hair-thickness. If the standard deviation of a hair sample exceeds 15 mu its size should be increased accordingly. All the individual determinations of hair-thickness basing on samples consisting of less than 100 single hairs will lead to false results. In order to test if the measurements of hair-cross-section and of longitudinal top plan view result in approximately equal, constant, individual means, one part of the hairs of each of the samples was measured according to the cross-section, the other part according to the longitudinal method; into more than 10,000 single hairs thus have been studied. The means of the corresponding samples are within the expected confidence intervals. There exists consequently no difference between the results of the two measuring methods. Nevertheless both procedures require at least measurements of 100 unselected single hairs per sample in order to obtain individual representative means. Practicability of direct square-measurements and indirect calculation methods are shown, their advantages as well as their disadvantages discussed. Attention is drawn to much more correct calculation formula.


Beta-lactamase activity in anaerobic bacteria. A diverse group of anaerobic bacteria representing a spectrum of resistance to beta-lactam antibiotics was studied to characterize their beta-lactamase activity and relate it to resistance. The Bacteroides fragilis organisms had moderate resistance and produced a cephalosporinase with low activity. The Clostridium ramosum was intermediate in resistance and had intermediate, inducible beta-lactamase activity. The B. clostridiiformis organism was highly resistant, produced a potent inducible penicillinase, and had a barrier to the penicillin substrates. Only the beta-lactamase of C. ramosum fit Richmond's classification (class IV). Although there was a rough correlation between beta-lactamase activity and antibiotic resistance, other mechanisms are undoubtedly involved in determining resistance levels.


Susceptibility testing of anaerobic bacteria with 100-microg carbenicillin disks. A total of 245 strains of anaerobic bacteria were examined for their susceptibility to carbenicillin by the disk test method and by minimum inhibitory concentration (MIC) determinations. Standard-curve studies with a strain of Bacteroides fragilis subsp. fragilis that was minimally susceptible to carbenicillin and Escherichia coli (ATCC 25922) demonstrated that a disk containing 100 mug of carbenicillin was suitable for testing susceptibility of anaerobes to carbenicillin. Thus, the diameter of zones around the 100-mug carbenicillin disks and MIC values were determined under the following test conditions: Mueller-Hinton agar supplemented with sheep blood, vitamin K(1), and hemin; an incubation temperature of 35 C; and an atmosphere of 80% N(2), 10% H(2), and 10% CO(2). The strains were separated into two populations by correlating zone diameters and geometric mean MICs. The disk test more clearly separated the resistant and susceptible populations and was more reproducible than the MIC test. Thus, a statistical analysis based on the distribution of zone diameters of susceptible and resistant strains was used to derive an interpretive scheme for anaerobic bacteria tested with 100-mug carbenicillin disks. The following interpretive scheme is recommended for testing anaerobes with 100-mug disks of carbenicillin: resistant, 8 mm or less; indeterminate, 9 to 12 mm; and susceptible, 13 mm or greater.


Antimicrobial susceptibility of group B streptococci isolated from a variety of clinical sources. The minimal inhibitory concentration of 10 antibiotics for 244 isolates of group B streptococci was determined. Susceptibility to penicillin G, ampicillin, cephalothin, chloramphenicol, and carbenicillin was uniform. Tetracycline and bacitracin resistance among these isolates was frequent (87.5 and 97.9%, respectively). Three strains (1.2%) failed to be inhibited by 100 mug of lincomycin or clindamycin per ml. Susceptibility of these 244 strains to the agents tested was unrelated to source of the isolate, year of isolation, or strain serotype. No apparent change in the suceptibility of group B streptococci to penicillin G has occurred during the past 2 decades.


Laboratory evaluation of 3-(5-tetrazolyl) penam, a new semisynthetic beta-lactam antibacterial agent with extended broad-spectrum activity. In the new agent 3-(5-tetrazolyl)penam, hereafter referred to as CP-35,587, the carboxyl function at C3 in the penicillin nucleus has been replaced with the 5-tetrazolyl moiety. Marked changes in spectrum and resistance to gram-negative beta-lactamases, particularly with regard to Klebsiella pneumoniae isolates, were conferred by this modification. The anti-Klebsiella activity clearly distinguishes the antibacterial spectrum of CP-35,587 from any known broad-spectrum penicillin. Compared to orally active cephalosporins, the spectrum advantage of CP-35,587 encompasses Enterobacter, Serratia marcescens, Citrobacter, Providencia, Haemophilus influenzae, and Streptococcus faecalis, both in vitro and in murine infections produced by many of the above-named microorganisms. Thus, CP-35,587 combines and extends the antibacterial activity of broad-spectrum penicillins and orally active cephalosporins.


Antiviral and interferon-inducing activity of a new glutarimide antibiotic, 9-methylstreptimidone. The antiviral effect of 9-methylstreptimidone (9-MS) was examined in mice infected with mouse-adapted influenza A(2) (H(2)N(2)) virus. Both a single and continuous prophylactic administration of 9-MS protected mice from virus infection, and comparison between the minimal effective and the 50% lethal dose gave a therapeutic index of 60. When the treatment was started after infection, however, no antiviral effect was demonstrated. After a single intraperitoneal administration of 9-MS, a highly potent virus-inhibitory factor was detected in the lungs (10 h later) and the sera (16 h later) of uninfected mice, which was assumed to be an interferon on the basis of the biological characteristics. These results suggest that the protective activity of the antibiotic is due to interferon induction in mice.


In vitro antimicrobial activity of cinoxacin against 2,968 clinical bacterial isolates. Cinoxacin demonstrated effective in vitro antimicrobial activity against the Enterobacteriaceae, but negligible activity against Pseudomonas aeruginosa and gram-positive cocci. The activity of cinoxacin was slightly greater than that of nalidixic acid.


Acute diffuse interstitial nephritis related to chemotherapy of tuberculosis. Acute renal insufficiency developed in three patients receiving chemotherapy for tuberculosis. It is proposed that acute diffuse interstitial nephritis related to the drugs was responsible for the renal injury. Recovery of renal function was slow and incomplete. Physicians administering chemotherapy to patients with tuberculosis must be aware of the potential nephrotoxicity of the common treatment regimens.


Triple crossover study on absorption and excretion of ampicillin, talampicillin, and amoxycillin. Talampicillin and amoxycillin were shown to be absorbed twice as well as ampicillin in a triple crossover experiment.


Photoinactivation of Venezuelan equine encephalitis virus mediated by tetracyclines. Demethylchlortetracycline and, to a lesser extent, chlortetracycline were found to mediate the in vitro photoinactivation of Venezuelan equine encephalitis virus.


Inhibition of L5178Y cells in culture by methotrexate and antibiotics. Methotrexate, tetracycline, gentamicin, streptomycin, and penicillin inhibited the growth of L5178Y murine leukemia cells in culture with I(50) (concentration of drug that caused a 50% inhibition of growth at 72 h) values of 0.0028 mug/ml (6.2 x 10(-9) M), 7.9 mug/ml, 200 mug/ml, 1,700 mug/ml, and 3,000 mug/ml (5,000 U/ml), respectively. At concentrations achieved clinically or utilized in the laboratory, the antibiotics did not alter the I(50) of methotrexate.


In vitro activity of josamycin and rosamicin against Bacteroides fragilis compared with clindamycin, erythromycin, and metronidazole. The inhibitory and bactericidal activities of josamycin and rosamicin against 29 clinical isolates of Bacteroides fragilis were compared with those of clindamycin, erythromycin, and metronidazole by a broth dilution technique. Josamycin and rosamicin had similar inhibitory activity to metronidazole and clindamycin. Rosamicin had similar bactericidal activity to clindamycin but was less bactericidal than metronidazole (the most bactericidal agent tested). Josamycin was slightly more bactericidal than erythromycin (the least bactericidal agent tested), but less so than rosamicin and clindamycin.


Bioevaluation of the antibacterial flumequine for urinary tract use. The antimicrobial activity of flumequine (R-802) was characterized by in vitro and in vivo procedures. Assay of the minimal inhibitory concentrations for 321 recent clinical isolates revealed that 88% of the gram-negative bacteria were inhibited by an R-802 concentration of 6.2 mug/ml or less. Cross-resistance in laboratory-derived mutants of Proteus vulgaris was essentially complete for R-802, nalidixic acid, and oxolinic acid, although quantitative differences were evident. R-802 was more effective than either of these quinolone antibacterials in preventing the development of experimental murine pyelonephritis (P. vulgaris). R-802 and trimethoprim/sulfamethoxazole (1:5) were equally effective in resolving a P. mirabilis-induced prostatitis of rats.


Pharmacokinetic parameters of sisomicin. Sisomicin in doses of 1 mg/kg was administered intramuscularly to 10 healthy volunteers, and 1 week later the same volunteers received sisomicin at the same dose intravenously. A peak serum concentration of sisomicin of 3.08 mug/ml was obtained 1 h after intramuscular injection, and a peak serum concentration of 7.12 mug/ml was achieved 30 min after a 30-min intravenous infusion. The sisomicin elimination data were analyzed according to a two-compartment model. Pharmacokinetic parameters derived from the intramuscular and intravenous studies were quite similar.


In vitro activity of gentamicin and minocycline alone and in combination against bacteria associated with intra-abdominal sepsis. The minimal inhibitory concentrations of gentamicin and minocycline alone and in combination were determined by a broth microdilution method for 100 aerobic, facultative, and anaerobic isolates representative of pathogens recovered from patients with intra-abdominal sepsis. Gentamicin inhibited all strains of Klebsiella, Enterobacter, and Pseudomonas aeruginosa in concentrations of 0.4 to 3.1 mug/ml and all strains of Escherichia coli and Proteus mirabilis in concentrations of 0.8 to 12.5 mug/ml. Whereas minocycline did not consistently inhibit these organisms in concentrations of 1.6 mug or less/ml, it did act synergistically with gentamicin against 43% of the Enterobacteriaceae tested in clinically achievable concentrations; significant synergy was most common with E. coli (60%). Minocycline inhibited 62% of Bacteroides fragilis, 71% of Clostridium, 40% of anaerobic cocci, and 40% of enterococci tested in concentrations of 1.6 mug or less/ml. Whereas gentamicin rarely inhibited these organisms in concentrations of 6.2 mug or less/ml, it did act synergistically with minocycline against 20% of B. fragilis, 67% of Clostridium, 22% of anaerobic cocci, and 22% of enterococci (which had minimal inhibitory concentrations of minocycline within the range tested) at clinically achievable concentrations. Although only four (13%) of the 30 isolates resistant to both gentamicin and minocycline alone were inhibited by clinically achievable concentrations of the combination, the observed synergy, particularly against strains of E. coli, was considered to be of potential clinical usefulness. Antagonism between gentamicin and minocycline was not observed at the concentrations tested.


Characterization and quantitation of experimental surgical-wound infections used to evaluate topical antibacterial agents. Reproducible experimental surgical-wound infections in mice for use in the evaluation of topical antibacterial agents are described. The experimental would was created on the backs of mice by means of a midline incision and was infected by means of cotton sutures monocontaminated with Staphylococcus aureus or Pseudomonas aeruginosa. The course of these wound infections was followed by quantitation of surface bacteria through use of a surface rinse technique. Surface wound counts of the infecting organisms thus obtained appeared to reflect the dynamics of the total wound count, as determined by homogenization of biopsied tissue. Treatment of infected wounds with a placebo cream had only a slight effect on surface wound counts and on mortality in the case of the S. aureus infection but enhanced markedly the lethality of the P. aeruginosa infection.


Responsiveness of experimental surgical-wound infections to topical chemotherapy. Topical agents freshly formulated in a cream base vehicle as well as commercial topical preparations were used to evaluate in mice the responsiveness of experimental surgical wounds infected with Staphylococcus aureus or Pseudomonas aeruginosa to chemotherapy. The responsiveness of the infections to therapy or the efficacy of a topical agent was assessed primarily by means of wound counts of the infecting organism before and after the employment of an immediate (prophylactic) or delayed (therapeutic) treatment regimen. From tests of several concentrations of an agent formulated in the vehicle, a median effective dose could be determined. In the case of the lethal P. aeruginosa infection, a median protective dose could be determined. Both infections were found to be quite susceptible to treatment with those topical agents that demonstrated good activity in vitro against the test organisms. The results of the investigation indicated that the model infections were suitable for the screening of potential topical agents in vivo.


Susceptibility of Prototheca species to antifungal agents. Twenty isolates of Prototheca filamenta, Prototheca moriformis, Prototheca stagnora, Prototheca wickerhamii, and Prototheca zopfii were tested for in vitro susceptibility to five commonly used antifungal agents: amphotericin B, 5-fluorocytosine, griseofulvin, miconazole, and nystatin. The results revealed resistance to griseofulvin of all the Prototheca isolates tested and an inhibitory effect on P. filamenta by high 5-fluorocytosine concentrations (minimal inhibitory concentration [MIC] = 12.5 to 100 mug/ml; minimal fungicidal or algacidal concentration [MFC/MAC] = 50 to 100 mug/ml). P. filamenta isolates were also susceptible to miconazole (MIC = 0.1 to 0.5 mug/ml, MFC/MAC = 0.5 to 1 mug/ml); isolates of the other Prototheca species varied in regard to miconazole activity from susceptible to resistant (MIC = 1 - >100 mug/ml, MFC/MAC = 5 - >100 mug/ml). The Prototheca isolates revealed an in vitro susceptibility to the polyene antifungal agents, amphotericin B, and nystatin (MIC = 0.09 to 3.12 mug/ml and 0.19 to 12.5 mug/ml, respectively; MFC/MAC = 0.19 to 25 mug/ml and 0.75 to 25 mug/ml, respectively).


Gentamicin- and cephalothin-associated rises in blood urea nitrogen. Standardized rates of drug-attributed rises in blood urea nitrogen were 8.6%, 2.9%, and 9.3%, respectively, in patients receiving gentamicin alone, cephalothin alone, and both drugs together. These results provide evidence against a substantial synergism between the two drugs in the production of impaired renal function.


Inactivation of the enveloped bacteriophage phi6 by butylated hydroxytoluene and butylated hydroxyanisole. Butylated hydroxytoluene (BHT) is a potent inactivator of the enveloped bacterial virus ø6 at concentrations as low as 3 x 10(-5) M. The viral envelope is not removed by BHT treatment, in contrast to the effects of exposure to the detergent Triton X-100. BHT-treated viruses are morphologically indistinguishable from controls but are defective in their ability to attach to the host cell. Temperature at the time of exposure was found to be a crucial factor in the effectiveness of BHT against ø6. A precipitous drop in the degree of inactivation by 3 x 10(-5) M BHT occurred when the temperature was lowered from 20 to 15 C. Calcium ions were found to potentiate the effect of BHT, particularly at lower temperatures where BHT alone was relatively ineffective. Barium and strontium, but not magnesium, were also effective in enhancing the activity of BHT. A structurally related molecule, butylated hydroxyanisole (BHA), was also found to inactivate ø6 virus, but higher concentrations were required than with BHT. Both BHT and BHA are commonly used as food additives, have apparent low toxicity to humans and other animals, and are potentially useful as antiviral agents.


Effect of long-term therapies with penicillin and sulfadiazine on Streptococcus mutans and lactobaccilli in dental plaque. Plaque samples were obtained from 13 children receiving long-term therapy with benzathine penicillin for the prevention of rheumatic fever recurrences, 31 children receiving oral sulfadiazine for the same purpose, and 29 untreated siblings. The therapies were found to have no effect upon the proportions of Streptococcus mutans or lactobacilli in dental plaque, upon the percentage of children harboring the organisms, nor upon the susceptibility of the organisms to penicillin and sulfadiazine. Of the S. mutans strains tested, 97% had a minimal inhibitory concentration of penicillin G of less than 48 ng/ml and, of the lactobacillus strains tested, 96.8% had a minimal inhibitory concentration of less than 1,600 ng/ml. All strains of both organisms were profoundly resistant to sulfadiazine.


Amikacin in newborn infants: comparative pharmacology with kanamycin and clinical efficacy in 45 neonates with bacterial diseases. The pharmacokinetic properties of amikacin (BBK8) were similar to those of kanamycin in newborn infants. Peak serum concentrations of both drugs were in the range of 15 to 25 mug/ml with the exception of kanamycin in babies weighing greater than 2,000 g at birth where peak levels were 12.5 to 15 mug/ml. Volumes of distribution, plasma clearances, and serum half-life values were comparable for the two drugs. The clinical and bacteriological responses to amikacin therapy were assessed in 45 neonates with bacterial diseases. A case fatality rate of 26% was observed in infants with septicemia and/or meningitis, whereas no deaths occurred among 22 infants with urinary tract and mucocutaneous infections. Cultures from infected sites were sterile within 72 h of initiating amikacin therapy in 47% of the infants, continued positive for greater than 72 h in 31%, and were not reevaluated during therapy in 22%. The clinical response was judged to be satisfactory in 92% of the surviving infants. The efficacy of amikacin was comparable to that of kanamycin or gentamicin in neonatal bacterial diseases.


Comparison of direct and standardized antimicrobial susceptibility testing of positive blood cultures. In an effort to determine the feasibility and accuracy of performing direct susceptibility tests from positive blood cultures, minimal inhibitory concentrations (MICs), determined by the agar dilution method, of direct and standardized tests with seven antibiotics were compared. Results were analyzed as to the number of very major (change in MIC from susceptible in preliminary direct testing to resistant in final standardized testing), major (change in MIC from resistant to susceptible), and minor (change in MIC without change in interpretation) discrepancies. The results for gram-positive cocci and for gram-negative bacilli were 5, 6, and 82 of 162 strains tested and 3, 12, and 79 of 90 strains tested, respectively. Of the total number of susceptibility tests compared, major and very major discrepancies occurred in only 1 and 2.4% of instances with gram-positive and -negative isolates, respectively. The majority of discrepancies were noted with Staphylococcus epidermidis (four very major, five major), Klebsiella (two very major, four major), and Alcaligenes (five major). The antibiotics most often exhibiting discrepancies were penicillin, ampicillin, and cephalothin. The results indicate that preliminary susceptibility testing directly from positive blood culture bottles is generally both feasible and accurate.


Comparative activity in vitro of ticarcillin, BL-P1654, and carbenicillin. The activity of ticarcillin, BL-P1654, and carbenicillin was compared in vitro using a microtiter tube dilution test in Mueller-Hinton broth against 50 recent clinical isolates each of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella species, Enterobacter species, Proteus species, and Pseudomonas aeruginosa. Bactericidal end points were determined using a modified Steers replicator. Ticarcillin was generally two to four times more active against all organisms tested except S. epidermidis against which BL-P1654 was most active. Median minimum inhibitory concentrations in micrograms per milliliter were for S. aureus: ticarcillin (6.2), carbenicillin (12.5), BL-P1654 (25); for S. epidermidis: BL-P1654 (1.6), ticarcillin (3.2), carbenicillin (3.2); for E. coli: ticarcillin (3.2), BL-P1654 (6.2), carbenicillin (6.2); for Klebsiella sp.: >100 for all three drugs; for Enterobacter sp.: ticarcillin (3.2), carbenicillin (6.2), BL-P1654 (12.5); for Proteus sp.: ticarcillin (1.6), carbenicillin (1.6), BL-P1654 (3.2); for P. aeruginosa: ticarcillin (31), BL-P1654 (62), carbenicillin (125). Bactericidal end points were dependent on both the drug and the species but were in general no more than twofold more than the minimum inhibitory concentration with the exception of BL-P1654 against P. aeruginosa. BL-P1654 was bactericidal for only 60% of the strains tested at a concentration of 500 mug/ml.


A new cephalosporin with a dual mode of action. A cephalosporin, (6R,7R)-7-[(2R)-2-hydroxy-2-phenylacetamido]-3-(pyrid-2-yl-N-oxide) thiomethylceph-3-em-4-carboxylic acid (MCO), that could lead to a novel approach to the problem of beta-lactamase destruction is described. The compound is slightly more resistant to some beta-lactamases than is cephalothin, but it is still hydrolyzed by many to a varying degree. Hydrolysis of the beta-lactam bond of a cephalosporin releases the 3-substituent, which in MCO is itself an antibacterial agent, 2-mercaptopyridine-N-oxide. Thus, MCO has a dual mode of action, and bacteria that do not produce an effective amount of a beta-lactamase are inhibited by the intact cephalosporin, whereas those that do hydrolyze it are inhibited by the released antibacterial compound.