Meningococcal sepsis with endophthalmitis. Endophthalmitis is a rare complication of meningococcemia. A child had endophthalmitis as the initially occurring complaint. Although both eyes appeared inflamed, the pupil in the right eye was fixed and dilated, the fundus could not be seen, and a hypopyon was seen in the right anterior chamber. There was gradual improvement when the child received antibiotic therapy. Since the introduction of antimicrobial drugs, endophthalmitis has rarely been observed as a complication of meningococcal disease. However, this report is evidence that meningococcemia may occur with unusual sites of local infection.


Risk factors and mortality in patients with cancer and hemorrhage from stress ulcer. Hemorrhagic gastritis is the most frequent cause of upper gastrointestinal bleeding in patients with cancer. A study was undertaken to evaluate the clinical course of 87 patients, in a cancer hospital setting, with hemorrhagic gastritis associated with stress, exogenous gastric irritants and the combination of the two. The average number of blood transfusions was four times higher and the average duration of bleeding was twice as long in stress patients as in patients without stress. Fifty-four per cent of stress patients died, whereas all patients survived in the group without stress. Although there were no statistically significant differences, patients with the combination of gastric irritants and stress tended to bleed longer and have a higher mortality than patients with stress alone. Over two-thirds of the deaths were ascribed to associated stress risk factors such as sepsis, multiple organ failure and advanced cancer and not to gastrointestinal hemorrhage.


An alpha 1-antitrypsin variant, Pi B Alhambra (Lys to Asp, Glu to Asp), with rapid anodal electrophoretic mobility. A variant of human alpha 1-antitrypsin (alpha 1 AT) was found by acid starch gel electrophoresis and by thin-layer electrofocusing. The variant has an anodal migration velocity almost identical to PiB. It is designated as Pi B Alhambra. Pi B Alhambra was purified to homogeneity from a heterozygous PiM1/PiB Alhambra subject. Specific trypsin inhibitory activity and composition of amino acids and carbohydrates were similar to those of normal PiM1. The structural difference between the normal and the variant inhibitors was elucidated by peptide mapping of their tryptic digests. Two amino acid substitutions, Lys to Asp and Glu to Asp, were found. The amino acid substitution, Gly to Asp, has been found in a common PiM2 variant [1]. The Pi B Alhambra variant presumably originated by two steps of mutation: generation of PiM2 from wild type PiM1 by the substitution Gly to Asp, and subsequent generation of Pi B Alhambra from PiM2 by another substitution, Lys to Asp.


Structural difference between the normal PiM1 and the common PiM2 variant of human alpha 1-antitrypsin. The common PiM2 variant of human alpha 1-antitrypsin (alpha 1-AT) which can be distinguished from the wild type PiM1 by isoelectric focusing (IEF) in a narrow pH gradient, was purified to homogeneity from plasma of a homozygous PiM2/PiM2 subject. The specific trypsin inhibitory activity and the amino acid and carbohydrate composition of the normal PiM1 and the variant PiM2 are very similar. The structural difference between the normal and the variant inhibitors was elucidated by peptide mapping of their tryptic digests. An amino acid substitution of glutamic acid in the normal inhibitor by aspartic acid in the variant inhibitor was found. The same amino acid substitution was found in PiMN, which was presumed to be identical to PiM2 based on their IEF patterns.


Effects of the converting enzyme inhibitor (SQ 20881) on the pulmonary circulation in man. The effects of the converting enzyme inhibitor (SQ 20881) on the pulmonary circulation were investigated in 13 patients in whom systemic hypertension developed following coronary artery bypass surgery. Pulmonary vascular resistance was decreased by the inhibitor, from 128 +/¿ 19 to 92 +/- 20 dynes sec cm-5 (or by 30 +/- 7 per cent; P less than 0.005), and this resulted in a decrease in mean pulmonary artery pressure from 17 +/- 1 to 13 +/- 1 mm Hg (or by 23 +/- 3 per cent, P less than 0.005). Consequently, right ventricular work was decreased by the inhibitor by 30 per cent (P less than 0.01), despite an increase in cardiac output (increase in stroke volume) by 16 +/- 6 per cent (P less than 01). This increase occurred despite a 13 +/- 3 per cent decrease in right ventricular filling pressure. The changes in pulmonary vascular resistance correlated with the pretreatment plasma renin activity (r = 0.74, P less than 0.01), as did the decrease in mean pulmonary artery pressure (R = 0.82, P less than 0.001), but neither change was related to the decrease in left ventricular fillling pressure nor to changes in cardiac output or mean arterial pressure. These results indicate that blockade of the formation of angiotensin II by the converting enzyme inhibitor results in reductions in pulmonary vascular resistance and pulmonary artery pressure which are unrelated to alterations in left ventricular function. Thus, angiotensin inhibition may have therapeutic value in various clinical states characterized by pulmonary hypertension--especially if renin levels are high.


A clinical study of the effects of galvanic vaginal muscle stimulation in urinary stress incontinence and sexual dysfunction. A preliminary study was designed to test the effect of pelvic for pelvic floor stimulation using the Vagette, a galvanic device, on the symptoms of urinary stress incontinence and pelvic relaxation. A significant improvement in pelvic muscle strength was observed as measured by the Kegel meter. This effect was seen within a short period of treatment. It is suggested from the study that the Vagette may be used for short-term therapeutic trial for urinary stress incontinence and pelvic relaxation before surgery is considered.


Value of immune monitoring in gynecologic cancer patients receiving immunotherapy. Immunotherapy with nonspecific immunopotentiators such as Corynebacterium parvum is under study in several areas of gynecologic oncology. The efficacy of this new modality awaits the results of carefully done clinical trials designed to measure an improved effect on survival when this and similar agents are added to conventional therapy. This report deals with an attempt to demonstrate enhancement of the cell-mediated immune response in a small number of patients with advanced ovarian (18 patients) and cervical (12 patients) cancer who were treated with intravenous C. parvum in addition to either chemotherapy (Alkeran) or pelvic radiotherapy. Monitoring of the immune response was accomplished by skin testing, T-lymphocyte rosettes, B-lymphocyte rosettes, simulation of lymphocytes with mitogens (PHA and Con-A) and total lymphocyte counts. No distinct improvement in these parameters could be demonstrated as a result of immunotherapy with C. parvum. These results and the value of immune monitoring as currently performed are discussed.


Fusarium solani endophthalmitis without primary corneal involvement. A 45-year-old woman developed a fungal endophthalmitis caused by Fusarium solani. No primary corneal lesion existed. Therefore, the focus of infection was considered endogenous. Although disseminated systemic infections with Fusarium species have been described in compromised hosts, including a patient with metastatic panophthalmitis, we believe this is the first report of an endogenous endophthalmitis caused by F. solani in a healthy individual.


A clinicopathologic study of autosomal dominant optic atrophy. Of a family with 40 members, 12 had autosomal dominant optic atrophy. The affected members were aware of reduced vision from the first decade. Visual loss was moderate to severe, 6/12 (20/40) to 3/60 (10/200). The affected members showed similar centrocecal scotomata. Most affected patients had severe unclassified color defects. Electroretinography measurements were normal in all but one patient who had a small reduction in the scotopic response. The pathologic changes in a patient with autosomal dominant optic atrophy showed diffuse atrophy of the ganglion cell layer of the retina with a loss of myelin and nerve tissue within the optic nerves. We suggest that autosomal dominant atrophy is a primary degeneration of retinal ganglion cells.


Serum and vitreous Toxocara antibody in nematode endophthalmitis. Five patients had a clinical diagnosis of nematode endophthalmitis and had both a serum and vitreous titer for Toxocara antibody. All five patients had a vitreous titer that was equal to or greater than the serum titer. Serum and vitreous obtained from ten other patients who had no evidence of endophthalmitis did not show this correlation. This study provides the clinician with a further understanding of the meaning of a positive enzyme-linked immunosorbent assay titer as well as an additional area for analysis in selected patients with ocular inflammation.


Bilateral endophthalmitis in acute bacterial endocarditis. A 53-year-old diabetic woman had ketoacidosis, urinary tract infection, and bilateral endophthalmitis. She subsequently developed a ruptured chorda tendineae of the mitral valve, and a diagnosis of acute bacterial endocarditis was made. No organisms were cultured during life or at autopsy. At autopsy, bilateral nongranulomatous panophthalmitis was found with perinephric, myocardial, intracranial, and mitral valve abscesses.


A survey of intraocular pressures with emphasis on patients under ten years of age. This paper presents the results of a cross-sectional survey of intraocular pressures in patients of the University Optometric Center, the clinical facility of the State College of Optometry, SUNY. The study consisted of two parts: a pilot study conducted by one of the authors and a survey of patient records that were reviewed at random with particular emphasis on patients under 10. The results indicate that the intraocular pressure norms used to evaluate the general population are also appropriate for evaluation of patients under 10 years of age.


Congenital cone dysfunction.

Congenital cone dysfunction. Three patients with congenital cone dysfunction are described with their clinical findings, including electrophysiologic and color vision evaluation, diagnostic criteria, and rehabilitative regimes. A classification system for this rare spectrum of disorders is presented.


Lysophosphatidic acids. II. Interaction of the effects of adenosine diphosphate and lysophosphatidic acids in dog, rabbit, and human platelets. In order to explore a possible relationship between platelet aggregation induced by lysophosphatidic acid (LPA) and that induced by adenosine diphosphate (ADP), we have studied the influence of palmitoyl-LPA (P-LPA) on platelets from dogs and rabbits and on human platelets made refractory to LPA. Dog platelets did not aggregate with P-LPA alone, but P-LPA enhanced ADP aggregation, and after a small dose of ADP, P-LPA was itself effective in causing aggregation and internal contraction in dog platelets. Rabbit platelets showed no response to P-LPA alone, but, as with dog platelets, P-LPA enhanced ADP aggregation. In addition, when P-LPA was added during or immediately after ADP aggregation, it caused a contraction within the platelets and a small wave of aggregation by itself. P-LPA added to human platelets caused aggregation without the need for ADP. However, when a small dose of P-LPA was added to human platelets and the wave of aggregation was allowed to reverse, these platelets subsequently were unresponsive to P-LPA, although they showed an enhanced response to ADP. The addition of a small dose of ADP to the P-LPA refractory platelets partially reversed the refractory state, and the platelets then showed aggregation with P-LPA. The results demonstrate that ADP and P-LPA have significant interactions in their effects on platelets. These interactions are discussed in terms of a two-component mechanism for the ADP-induced intracellular calcium flux, LPA, or possibly phosphatidic acid, being one component.


Health costs of air pollution: a study of hospitalization costs. This study of the hospitalization costs of exposure to air pollution in Allegheny County, Pennsylvania was conducted to determine whether persons exposed to air pollution incurred higher hospital utilization rates and additional costs for treatment. A hospitalization data-base comprising 37,818 total admissions for respiratory, suspect circulatory diseases, and comparison circulatory diseases was tested in a cross-section type analysis for relationships between rates of hospitalization, length of stay, and levels of air quality in the neighborhoods of patients' residence. Air quality was identified using data from 49 monitoring stations. Corrections were made for race, age, sex, smoking habits, median income, and occupation. The results show that hospitalization rates, length of stay, and costs of respiratory and suspect circulatory system diseases were significantly greater among populations residing in the more polluted zones of the County. At average costs for hospitalization in this area in 1972, the total increased cost for the 1.6 million persons in the County was estimated at $9.8 million ($9.1 million for increased hospitalization rates and $0.7 million for increased length of stay). The total health costs resulting from air pollution exposure in this area would be much greater when non-hospitalization costs are also included.


Schistosomiasis japonica in Barrio San Antonio, Basey, Samar , The Philippines. I. Epidemiology and morbidity. Barrio San Antonio is a coastal settlement on the San Juanico straits in the municipality of Basey on the island of Samar, the Philippines. It has a population of approximately 1,900 in 320 households. Initially, 851 residents (45%) of 240 households participated in this survey to determine the prevalence and intensity of Schistosoma japonicum infection, and morbidity as indicated by associated hepatomegaly and splenomegaly. As a result of an initial single stool examination of 1 ml by a modified formalin concentration technique, 40% of this population was found to be infected. On subsequent examinations, with the addition of serologic techniques and recording the history of therapy, approximately 70% of this population was found to be infected with S. japonicum after the age of 10 years. If judged by the number of eggs produced per milliliter of feces, infection intensity in this population might be considered to be low. However, 25% (73 of 391 positives on single examination) exhibited schistosomal hepatomegaly or hepato-splenomegaly and had a mean egg count of 10.9. Those infected but without hepatomegaly had a slightly lower mean egg count of 8.4. Of the infected males with hepatomegaly, 75% were 19 years of age or less and 45% of these were producing less than 10 eggs/ml of stool. Of infected females with hepatomegaly, only 28% were 19 years of age or less, and 68% of these were producing less than 10 eggs/ml. Abdominal pain, distress, diarrhea, and dysentery were significantly more frequent in the infected than uninfected persons, and this frequency was related to egg output. The heights and weights of these infected individuals were less than those of the uninfected members of this population and significantly less than the Filipino norm. The small percentage of the infected population (6.6%) that were producing 51% of the eggs had a mean egg count of approximately 260 with a mean age of 33.7. In this group, 7 of the 22 individuals were in the age group 10--14 years and 15 were above 20 years of age. Although some individuals of Barrio San Antonio have sought therapy, this population and area have been largely unstudied and have not up to the present been involved in control or mass chemotherapy programs. The findings of this survey give an opportunity to determine the impact of such programs when they are instituted in this area.


Selective embolization for control of gastrointestinal hemorrhage. Transcatheter embolization using Gelfoam plugs or autologous clot is an alternative or adjunct to the conventional management of gastrointestinal hemorrhage. During a 12 month period we successfully treated 10 patients who had massive gastrointestinal hemorrhage with selective embolization; 6 patients had upper gastrointestinal hemorrhage and 4 had bleeding from the colon. Most of these patients were critically ill and were poor surgical candidates. Hemorrhage was controlled by selective catheterization of the bleeding vessel, followed by injection of Gelfoam pledgets. Since the procedure was accomplished with ease and prolonged hemostasis obtained, we recommend it for gastrointestinal hemorrhage, especially in patients who are poor surgical risks or are unresponsive to vasopressin infusion, or both. Operative intervention for the primary disease could subsequently be performed electively, if necessary, days or weeks after transcatheter embolization.


The effect of the epidermal growth factor (EGF) on the corneal epithelium in humans. Epidermal growth factor (EGF) is a polypeptide hormone present in mammalian organs. In vivo, it shortens the time course of the corneal reepithelialization by stimulating a marked cell proliferation of the corneal epithelium. A further direct effect in vivo has been confirmed on human corneal epithelium and epidermis in culture. Tests in several nondystrophic diseases of the corneal epithelium confirmed the observations previously made in the rabbit that EGF accelerates the process of epithelial healing. The integrity of the corneal stroma is prejudicial for the maximum effect of the EGF, in the sense that the deeper the stroma is damaged, the less EGF acts. In herpetic lesions EGF is effective within 48 h only when the virus-affected area of the corneal epithelium has been scraped off. EGF is proposed as a new and efficacious agent for increasing the restorative process of the corneal epithelium in many nondystrophic diseases.


Results of intraocular lens insertion for traumatic eyes and effects on binocular vision. Eighteen traumatic eyes were inserted with Medallion lenses in a very complex operation procedure. Eight patients were examined for binocular vision and compared with eight nonpseudophakic eyes. With the exception of tropic eyes, they regained binocular vision. We obtained very hopeful results for the management of seriously traumatic eyes through this study.


The effect of exposure to heat on intraocular pressure. During exposure to heat there is an increase of the intraocular pressure in nonacclimatized persons. This increase is not found after heat acclimatization has been carried out. The increase of the intraocular pressure in the nonacclimatized persons can be attributed to the increase of the body temperature due to insufficient sweating.


Determination of pseudofacility in man.

Determination of pseudofacility in man. Based on a new method of measuring episcleral venous pressure (EVP), i.e., using the 'air-jet principle' of Krakau et al. (1973), pseudofacility was determined in 20 human eyes. According to Bárány's formula, a mean value of 23.3% of the total facility was found, and a mean value of 16.9% according to Goldmann's formula.


[Morphological and metabolic findings in retinal detachment]. The authors investigated retinal structure and metabolism under normal conditions and after experimental detachment for 7--10 days and for 30--40 days in 80 experimental animals. Labeled protein predecessors were selected as indicators of retinal-cell element viability. Tey included the amino and 35S-methionine acids glycine (marked with 14C or 3H) and 35S-methionine. Metachromatic staining was employed to demonstrate retinal mucopolysaccharides. Histologic sections were analyzed in 15 patients with retinal detachment. Comparing the data obtained at early and developed stages of the process, they discovered the sequence of changes. Comparative analysis of the morphologic changes caused by retinal detachment in rabbits and human patients showed their similarity. The authors propose and substantiate the hypothesis that detachment extension into intact areas is caused by tension in the already detached retinal areas due to shrinkage of the tissues. It was established that labeled protein predecessors can penetrate into all layers of detached retina through the central artery. Hence it is possible to maintain retinal viability during the preoperative period by employing drugs.


[Malignant non-Hodgkin-lymphomas on lid, orbita and lacrimal sac (author's transl)]. Two personal observations on malignant non-Hodgkin lymphomas of the eye are presented, i.e., a lymphoplasmocytoid lymphoma (so-called immunocytoma) of the lid and orbita and a case of mixed centroblastic-centrocytic lymphoma of the lacrymal sac. The different histological findings are demonstrated. According to the lymphoma-classification by Lennert (Kiel), both the tumours belong to the group with a low degree of malignancy. No general synptoms could be found in the afflicted patients.


[On the distribution of fat in eyes and brain in experimental fat embolism (author's transl)]. In 18 rabbits a mixture of 131-J-labeled Triolein and purified olive oil was injected intravenously. Afterwards the radioactivity of the eyes and the brain was measured. The relation of distribution of fat between eye and brain differs markedly, even when the surface tension was controlledly altered by admission of essential phospholipids.


[Inhibition of secondary increase of intraocular pressure following cyclokryocoagulation (author's transl)]. Prostaglandin mediated transient increase in intraocular pressure following cryokoagulation of the ciliary body in rabbits was completely inhibited by preoperative administration of Aspisol (D, L-Lysin-mono-(acetylsalicylat)). To avoid additional increase in intraocular pressure in patients chosen for cyclocryotherapy, pretreatment with Aspisol could prove to be effective.


[Angiomatosis retinae (et papillae)].

[Angiomatosis retinae (et papillae)]. The ophthalmologic and histologic signs of an angiomatosis retinae (et papillae) are presented. Some capillaries are filled abundantly with blood while others appear completely empty. Reticular fibers, starting from the vessels, form dense networks. Large sinusoid venous connections exist between choroid and tumor.


Pulmonary function in heterozygotes for alpha,-antitrypsin deficiency: a case-control study. In this paper we present the initial cross-sectional data from a prospective study of lung aging in heterozygotes for alpha 1-antitrypsin deficiency. Using a case-control design, our cases included 37 heterozygotes for alpha 1-antitrypsin deficiency, protease inhibitor phenotypes MZ and MS, selected because they were parents of children with homozygous alpha 1-antitrypsin deficiency identified in a statewide newborn screening program between 1971 and 1974. All of the heterozygotes were less than 40 yr of age. Our control subjects were selected from a random sample of a working population participating in a longitudinal study of lung aging, using a 2:1 match of control subjects to cases, matching age, sex, ethnic origin, and smoking. Using a respiratory symptom questionnaire, spirometry, and the single-breath N2 test, we found no significant difference between heterozygotes and control subjects in terms of respiratory symptoms or pulmonary function data. We conclude that to 40 yr of age, the heterozygous phenotype (Pi MZ and MS) is not a risk factor for impairment of pulmonary function.


Alpha,-antitrypsin and leukocyte elastase in infected and noninfected sputum. Leukocyte elastase and alpha 1-antitrypsin have been implicated in the pathogenesis of pulmonary emphysema. The relationship between these proteins has been studied in sputum both qualitatively and quantitatively in bronchitic patients with and without chest infections. Leukocyte elastase was found in 75% of the noninfected samples but was enzymatically inactive, suggesting complete inhibition. During infection, leukocyte elastase and alpha 1-antitrypsin concentrations increased, although the enzyme was only partially inactivated. The proportion of alpha 1-antitrypsin present as "complex" was smaller in the presence of infection, suggesting damage of the protein by excess enzyme.


Acute hypersensitivity pneumonitis: serial changes in lung lymphocyte subopulations after exposure to antigen. The earliest lesion in hypersensitivity penumonitis is an acute inflammatory alveolitis characterized by parenchymal hemorrhage and accumulations of polymorphonuclear leukocytes within the lung. In many instances, this initial lesion is replaced by a more chronic alveolitis, with development of mononuclear cell interstitial infiltrate, granuloma formation, and interstitial fibrosis. To help define the mechanisms by which the early polymorphonuclear leukocyte alveolitis of acute hypersensitivity pneumonitis evolves into a chronic mononuclear-cell process, an animal model of the disease was developed using guinea pigs sensitized by footpad injeection with either ovalbumin (OVA) in complete Freund's adjuvant (CFA), CFA alone, or phosphate-buffered saline. Ten days after sensitization, the animals were challenged by intratracheal injection of either particulate OVA, particulate human serum albumin, or phosphate-buffered saline alone, and their lungs were evaluated sequentially for changes in histologic appearance and lymphocyte subpopulations. After challenge, only animals sensitized with CFA plus OVA and challenged with particulate OVA developed pulmonary lesions consistent with acute hypersensitivity pneumonitis. Within 4 h after challenge, these animals developed an acute hemorrhagic alveolitis that persisted for more than 24 h. By 48 to 96 h, the alveolitis evolved into a predominantly mononuclear-cell infiltrate. This change in the histologic appearance of the lungs in these animals was preceded by a rapid increase in the proportions of T-lymphocytes within the lungs, noted by 24 h after intratracheal challenge with specific antigen. Before intratracheal challenge with antigen, lung lymphocytes from only the group of animals immunized with CFA plus OVA were capable of proliferating on exposure to OVA in vitro. In the same group, lymphocytes recovered from the lung after intratracheal particulate OVA demonstrated blast transformation in vivo, a phenomenon not found in any other group. These studies suggest that the alveolitis of acute hypersensitivity pneumonitis is rapidly associated with changes in populations of immune effector cells before development of the mononuclear cell alveolitis characteristic of the chronic disease.


Vascular complications as a result of intra-aortic balloon pumping. Intra-aortic balloon conterpulsation (IABP) was used to assist 109 patients with extensive myocardial infarcts, unstable angina, cardiogenic shock, and unstable cardiodynamic states after cardiopulmonary bypass over a six year period. Severe vascular occlusion occurred in three patients (3%) which required an above the knee amputation. Each patient had a long history of smoking. Obesity, atherosclerotic disease of the femoral vessels, and extensive coronary artery disease were additional contributing factors. Two of the three patients survived, but both survivors had extensive postoperative myocardial infarctions. A low flow cardiac state and the presence of atherosclerotic changes in the legs must be precipitating factors for the vascular complications. Several possible methods to minimize complications of this nature include 1) angiographic examination of the lower aorta and femoral arteries at the time of cardiac catheterization, 2) frequent monitoring with ultrasound equipment, and 3) use of anticoagulation during and after the period of counterpulsation.


Arteriovenous malformations of the cecum: operative localization by Doppler ultrasound. The Doppler ultrasonic flowmeter was used for operative localization of an arteriovenous malformation of the cecum in a patient with recurrent large intestinal bleeding. Application of the technique permitted operative confirmation of the diagnosis in an other wise normal appearing cecum.


[Vestibular meanifestations of multiple sclerosis. A new diagnostic element revealed by bithermic tests]. We studied 56 cases of disseminated sclerosis, all during an attack of the disease and all presenting with symptoms of incoordination. The diagnosis was certain both clinically and biochemically. Out of this population, 64% of the patients had unprovoked nystagmus; of these patients 48% had central type nystagmus (multiple, vertical superior or vertical inferior, or bilateral "gaze nystagmus"). We investigated particularly abnormalities in the bithermic tests (vestibular hypovalency, directional preponderance of nystagmus, thermic preponderance) and in particular we studied an index which to the best of our knowledge has never been seriously and statistically investigated. We called this the bithermic reflexogenic index or BRI. We express abnormalities in this index in terms of a disharmony in the bithermic response of one or both vestibules. This index is expressed by the formula o cold + o hot/o cold-o hot x 10 which is the relative difference in the cold and hot test for the same vestibule. The normal index based on research in 180 normal vestibules, is always less than 20. The response is measured in frequency. The results of this study on bithermic tests allowed us to divide our DS population into two main groups: -- the first group comprised 36% of our cases. All the parametric indices are normal (directional preponderance of the nystagmus, thermic preponderance and bithermic reflexogenic index) but the presence of unprovoked nystagmus (88% of the group) is always associated with bilateral vestibular hypereflectivity; -- the second group comprised 64% of the DS patients studied. Unprovoked nystagmus was seen in 50%. All had normal vestibular reflexes or subnormal reflexes without clear cut hypovalency, associated with an abnormality either of directional preponderance of the nystagmus (30%) or of thermic preponderance (25%), or both combined (22%). But in all cases there was an abnormality of the bithermic reflexogenic index greater than 20. This abnormality seems to us to be the most frequent and the most typical. The specificity of this index is under study at the present time. One or another of these syndromes appearing in a young subject who does not have a past medical history of head injury or vascular accidents is strongly in favour of an attack of disseminated sclerosis.


[Acoustic neuroma and others tumors of the angle, and internal auditory meatus. Surgical results and choice of the approach (126 cases) (author's transl)]. 126 tumors of the angle and I.A.C. (118 acoustic neuromas) have been operated by the author from 1966 to 1978. The surgery was done either by the middle fossa, or the translabyrinthine, or the retrosigmoid approach. The perservation of the Facial nerve is obtained in 93%, the facial function is normal in 70%. The hearing is preserved after removal of the tumor in 50% of the intracanalar neuromas, and in 35% after removal of tumors expanded in the angle.


Comparative activities of cefotaxime, a new cephalosporin derivative, and of selected beta-lactam antibiotics against Haemophilus species. The activity of cefotaxime (HR756), a new semi-synthetic cephalosporin, was compared with the activity of ampicillin, carbenicillin, cephalothin, cephaloridine, cefazolin, cefamandole and cefoxitin against 247 strains of Haemophilus sp.; 20 of these strains produce a beta-lactam inactivating enzyme. The minimal inhibitoring concentrations were determined by the agar plate dilution technique. Cefotaxime is not only more active than any other cephalosporin but also than ampicillin, generally estimated the most active drug against Haemophilus sp. Bacteriostatic concentrations of cefotaxime which inhibit 50 and 95% of the strains (BSC50 and BSC95) were 0,009 microgram/ml and 0,03 microgram/ml, respectively, showing an activity 20 times superior to that of ampicillin. Cefotaxime activity was unaffected by the production of beta-lactamase.


[Bactericidal activity of ampicillin, chloramphenicol and gentamicin, alone or in combinations against susceptible and resistant "Haemophilus influenzae" (author's transl)]. Bactericidal activity of three antibiotics, ampicillin, chloramphenicol and gentamicin, alone or in combinations, was determined against susceptible and resistant strains of Haemophilus influenzae. The various antibiotic combinations were studied for the determination of a synergistic or antagonistic effect. The study was done by the checkerboard method. A percentage of survivors inferior or equal to 0.01% of the inoculum represents the bactericidal activity. Ampicillin and chloramphenicol are bactericidal antibiotics against H. influenzae at concentrations of 1 microgram/ml and 4 microgram/ml, respectively. The combination of ampicillin and gentamicin exhibited a synergistic effect against strains sensitive and resistant to ampicillin. The combination of chloramphenicol and gentamicin was synergistic against all strains. Ampicillin and chloramphenicol, when combined, were antagonistic against two strains using a bacteriostatic concentration of chloramphenicol; and against the remaining strains the effects of the combination were indifferent.


[Stapedo-vestibular ankylosis associated with osteopathy of the promontory (author's transl)]. The authors present two unusual operative findings during surgery for stapedo-vestibular ankylosis, of which no similar cases would appear to be found in the literature. The first case posed the problem of stapedo-vestibular ankylosis as a sequel of clinically latent otitis, the only manifestations of which were radiological opacity of the mastoid and an area of osteitis of the promontory, still active, in the absence of any other progressive inflammatory phenomena or sequelae. Surgery required curettage and opening of the promontory, associated with total stapedectomy and a Teflon-inter-position. The functional result was very good. The second case of typical bilateral stapedo-vestibular ankylosis suggested the possibility of "malignant" otospongiosis, or at all events, markedly progressive. Surgery led to opening of the labyrinth. After platinectomy and excision of a bony sequestrum, there remained only a large fossa with an area equivalent to 3 times that of a usual fenestra ovale. A Teflon-interposition piston was performed with a good result. These rare forms lead to discussion of:--Lobstein's disease, Paget's disease and parathyroid osteosis. Finally, the authors approach the problem of the therapeutic attitude to be adopted in the presence of such rare conditions.


Ocular tilt reaction with peripheral vestibular lesion. Following inadvertent destruction of the left vestibular labyrinth during stapedectomy, a patient developed a transient abnormality of posture consisting of leftward ocular counterrolling, leftward had tilting, and a right-over-left skew deviation. This postural pattern, known as the "ocular tilt reaction," is the normal compensatory response of the dependent utricle to tilting. In this patient, the unopposed action of the intact right utricle was presumably responsible for the appearance of a normal leftward ocular tilt reaction.


LY-127935: a novel beta-lactam antibiotic with unusual antibacterial activity. The in vitro activity of LY-127935, a new beta-lactam antibiotic, was examined by using 370 clinical bacterial strains. In comparison with several other beta-lactam agents, LY-127935 was the most inhibitory against the Enterobacteriaceae. It was remarkably active against multi-drug-resistant strains of Enterobacter spp., Serratia spp., and Pseudomonas aeruginosa. LY-127935 had four- to eightfold greater activity than did cefoxitin against Bacteroides fragilis. Production of beta-lactamase by Enterobacteriaceae did not influence the minimal inhibitory concentration of LY-127935. However, the beta-lactamase-producing strains of B. fragilis and Haemophilus influenzae had generally higher minimal inhibitory concentrations. LY-127935 was the least active agent tested against gram-positive aerobic cocci. Variations in pH, salt content, protein content, or inocula size had little influence on susceptibility to LY-127935. Although combination studies with LY-127935 and gentamicin demonstrated synergy for P. aeruginosa, the rates of killing for the combination and for gentamicin alone were similar.


Limited effect of trimethoprim-sulfamethoxazole prophylaxis on Pneumocystis carinii. Trimethoprim-sulfamethoxazole has been proven effective in the treatment and prevention of Pneumocystis carinii pneumonitis in lower animals and humans. How effective the drug combination is in eradicating P. carinii from the host is not known. The immunosuppressed rat model was used to determine whether or not trimethoprim-sulfamethoxazole effectively eradicated the organism. Animals treated with trimethoprim-sulfamethoxazole for as long as 6 weeks were then placed in individual isolator cages, immunosuppressed with prednisone for 12 weeks, and sacrificed. P. carinii was found in the lungs of at least 90% of the drug-treated as well as untreated control groups. The data indicate that trimethoprim-sulfamethoxazole has a limited rather than a lethal effect on P. carinii and that protection is afforded only during the period of trimethoprim-sulfamethoxazole administration.


Lymphocyte response after surgery in the neonate. Fourteen neonates born with congenital malformations were investigated for lymphocyte function before and after surgery. Total leucocyte and absolute lymphocyte counts were unaltered after surgery. The mean percentage of T-lymphocytes observed either pre- or postoperatively was considerably lower than that reported in older children and adults. While there was an increase in the percentage of B-lymphocytes after operation in the infants, the absolute number of B-cells remained unchanges. The preoperative transformation response of lymphocytes to PHA (mean 12.9 +/- 5.4 X 10(3) counts/min) was little different from the postoperative values (mean 12.4 +/- 4.4 X 10(3) counts/min). These results suggest that the neonate is immunologically different from older children and adults in its response to anaesthesia and surgery.


Surgical treatment of ascending aortic aneurysms associated with aortic valve insufficiency. From 1965 to 1978, 111 patients underwent combined operation for ascending aortic aneurysms and aortic valve insufficiency. Fifteen patients had direct coronary implantation (Group 1). In 25 patients operated on between 1972 and 1977, the aortic root was retained (Group 2). An additional 71 patients operated on between 1965 and 1972 were included (Group 3): 40 who had synthetic graft replacement and retention of the aortic root and 31 who had aortoplasty and associated aortic valve repair. In 8 patients in Group 3, recurrent aneurysms were detected an average of 6.5 years after operation. The mortality rate for repaiajor complication after incomplete resection of the aortic root. Total exclusion of the aneurysm should be considered.


The importance of monitoring intramyocardial temperature during hypothermic myocardial protection. In 50 patients undergoing cardiac operation, hypothermic cardioplegic solution was infused into the root of the aorta immediately after aortic cross-clamping. Cardiac standstill was achieved within 1 to 3 minutes. However, monitoring of intramyocardial temperature with a needle thermistor revealed that such core cooling is unpredictable (the intramyocardial temperature achieved ranged from 7 degrees to 33 degrees C), unstable (this temperature can rise at more than 0.5 degrees C per minute), and uneven (a difference of up to 17 degrees C was observed between the intramyocardial temperature of the anterior and posterior left ventricular sites). The area supplied by the stenotic coronary artery was least protected. Monitoring of intramyocardial temperature enables one to know when supplementary cooling is indicated. We conclude that widespread differences in this temperature during cardiac operation make monitoring advisable for optimal myocardial protection.


Left ventricular decompression by sump drainage. Decompression of the left ventricle during cardiopulmonary bypass is a useful adjunct to open-heart operation, primarily to preserve myocardial tissue and also to improve the exposure of the operative field. The addition of sump drainage to left ventricular decompression systems enhances the usefulness of this established technique. Technical aspects of this sump drainage are detailed.


Naloxone reversal of drug-induced diarrhea in mice. The potential role of endogenous opiates in the mediation of the diarrheal actions of prostaglandin-F2 alpha (PGF2 alpha), 5-hydroxytryptophan (5-HTP) and methacholine was investigated. The interaction of the antidiarrheal agents morphine, propantheline bromide and cyproheptadine on the course of PGF2 alpha-induced diarrhea in mice was studied, as were the effects of naloxone on PGF2 alpha-, methacholine-, and 5-hydroxytryptophan-induced diarrhea. The three diarrheal agents, administered intraperitoneally, showed dose-dependent and parallel dose-response curves with the following order of decreasing potency: PGF2 alpha, methacholine and 5-HTP. Naloxone significantly inhibited the diarrhea induced by these agents. The diarrheal action of PGF2 alpha was also significantly attenuated with morphine, propantheline and cyproheptadine. These results suggest that PGF2 alpha, methacholine and 5-HTP induce diarrhea via a common pharmacological mechanism(s) which may involve an interaction with endogenous opiate receptors. However, the antagonism of diarrhea with agents having diverse pharmacological actions would suggest that factors unrelated to an interaction with endogenous opiates may also be involved in the production of diarrhea by the diarrheagenic agents studied.


Hereditary multiple exostoses with myelopathy. A 58-year-old woman with hereditary multiple exostoses had slowly progressive myelopathy due to a vertebral exostosis that compressed the spinal cord at T1-2. She did not show skeletal deformities, but had numerous palpable long-bone exostoses. While CNS complications are rare in hereditary multiple exostosis, 17 other cases have been reported.


Frontal ventricular dimensions of the brain in infants and children. Four hundred computerized tomographic scans of the brain in infants and children from birth to 15 years of age were reviewed. Of these, 142 were judged to exhibit normal ventricular dimensions as determined by the biventricular (V/H) index, the length of a line drawn between the heads of the caudate nuclei (V) relative to the width of the cerebral hemispheres (H) at the same level. When all scans were analyzed collectively, the V/H index followed a Gaussian distribution (mean, .11 +/- .03) [SD]; range, .00 to .20). The index did not increase with advancing age within the pediatric population (0 to 15 years), as it does in adults.


Adrenergic innervation of blood vessels. A fluorescence microscopic study of the eighth nerve and inner ear structures in man. Fluorescence microscopy was used to examine the perivascular adrenergic innervation in the eighth nerve and vestibular end-organ specimens from 13 patients with otoneurological diseases. It was observed that all the blood vessels accompanying the cochlear and vestibular nerves from patients with acoustic neuroma or Meniere's disease were devoid of specifically fluorescent fibers, while several adrenergic fibers were seen around the arterioles accompanying the inferior vestibular nerve from the patient with sudden deafness.


Iron deficiency anaemia--a prospective study. A prospective study was performed over 15 months to determine the cause of iron deficiency in adult males and postmenopausal females attending a general hospital. The laboratory computer identified all subjects with a haemoglobin less than 10.6 g/dl and a mean corpuscular volume less than 86 fl. Patients becoming anaemic after trauma or recent surgery were excluded. The iron status of each patient was assessed by serum iron studies, serum ferritin or sternal marrow aspiration. Reduced red cell indices and blood film morphology were not diagnostic of iron deficiency. Of 215 patients assessed, about half (103) were found to be iron replete. This group had a variety of disorders--malignancy, chronic inflammation, chronic renal and non-malignant haematological diseases. The other group of 104 patients satisfied criteria for iron deficiency, and 100 of these were investigated further. The cause of iron deficiency was found in all but three subjects. Inadequate dietary intake was a contributing factor in over half of the patients and 40 regularly took salicylates. Investigation defined a source of chronic gastrointestinal blood loss in most instances.


Studies of the effects of sex hormones on autosomal and X-linked genetic control of induced and spontaneous antibody production. In these studies we investigated the modifying effect of sex hormones on both the levels of induced antibodies after immunization with single-stranded DNA (ssDNA) and the levels of spontaneously produced anti-T cell antibodies (NTA). To learn whether the responses were genetically determined or under hormonal regulation, we analyzed hybrids produced by crossing the autoimmune NZB strain with the nonautoimmune DBA/2 strain. For both anti-ssDNA and NTA, males usually had a lower response than females; this difference could largely be removed by castration of the males. Females given testosterone implants also had decreased antibody levels. The higher responses in females and suppression by testosterone were true for all mice studied except NZB mice. NZB mice appear to have an insensitivity to the suppressive effects of testosterone.


A Y chromosome associated factor in strain BXSB producing accelerated autoimmunity and lymphoproliferation. Strain BXSB/Mp mice develop a spontaneous lupus-like syndrome which is strikingly accelerated in males. The accelerated autoimmune disease occurs in male F1 hybrids with strains NZB/BINJ, SJL/J, and C57BL/6J when the male parent is BXSB but not in the reciprocal hybrid male nor in females. The pattern is similar in F2 hybrids with strains NZB and SJL. The accelerated disease in males occurs only when the Y chromosome is derived from recombinant inbred strain BXSB and ultimately from strain SB/Le.


[Factors influencing the changes in liver melanin content of amphibia. I. Effect of breeding temperature]. Frogs caught in winter and kept at summer temperatures, show an increase in the melanic content of the liver. Frogs caught in summer and kept at winter temperatures do not show variations in hepatic melanins with respect to the summer control specimes. This data does not correspond with the natural course of hepatic melanin fluctuations, therefore the causes of the variations are to be sought in factors other than the temperature, one of which could very probably be represented by alimentation.


[Study of factors influencing the changes in liver melanin content of amphibia. II. Effect of fasting]. Statistical examination of the data from experiments conducted on groups of Amphibians induces us to retain as plausible the hypothesis which indicates in fasting one of the preminent factors that cause an increase in the melanic content of their liver. The temperature does not act directly, but indirectly, on the process of melanosynthesis, by inducing or otherwise the semilethargous state on which alimentation depends.


[Statistical observations on the incidence of Trichomonas vaginalis in the female population of Terni from 1974 to 1978]. The casuistics refers to 1646 cases equal to 20,5% of vaginal trichomoniasis in a total of 7996 pap tests examined in the service of Anatomy and Histology Pathology in the hospital of Terni. The exams of the incidences of trichomoniasis in the various age classes, reveals that the main frequency is found in the 2nd., 3rd., 4th decades of life, that is in the period of maximum sexual attivity. Vaginal Trichomonas is rarer before puberty and after the menopause.


[Association between Trichomonas vaginalis and some types of lesions of the uterine neck based on data collected in the quinquennium of 1974--1978]. In our statistic the number of cases of vaginal trichomoniasi in which discariosi, displasie, metaplasie are found are represented in about 40%. While 37,5% of women affected with neoplastic lesions had Trichomonas vaginalis. It is certain that in the presence of flogosi from Trichomonas vaginalis we meet more frequently than normal, atipie cellulars and that often an exact valutation of this lesion is put back to an exam after the recovery of the Trichomonas vaginalis, because fortunately, more than often these disturbances disappear.


Reoperation for recurrent angina.

Reoperation for recurrent angina. Forty patients with persistent or recurrent angina after an aortocoronary bypass procedure underwent a second operation. The cause of recurrent angina, defined by angiography, was thought to be isolated graft failure in 13 patients, progression of disease in ungrafted vessels in 4, incomplete revascularisation in 2, and stenoses distal to patent grafts in 1. More than one factor was responsible in 20 patients. There was 1 early postoperative death and 3 perioperative myocardial infarctions. Thirty-four patients have been followed for more than 3 months (4 to 63 months). Of these, 17 had previously bypassed vessels regrafted and 5 are sympton free, 4 have mild angina, and 8 have severe angina. Ten patients had previously ungrafted vessels grafted and 4 are sympton free, 3 have mild angina, 2 have severe angina, and 1 is limited by breathlessness. Seven patients had a combined procedure and 4 are sympton free, 1 has mild angina, and 2 have severe angina. Reoperation can be carried out safely but the results are less satisfactory than for a primary procedure.


Thallium-201 myocardial imaging in assessment of results of aortocoronary bypass surgery. Thirty-six patients were assessed by thallium-201 myocardial imaging before and after aortocoronary bypass operations and the results were compared with evaluation based on symptomatic assessment, exercise testing, and electrocardiography. After operation, the majority of patients were free from symptoms or symptomatically improved with increased exercise duration. Perioperative myocardial damage was shown in eight patients and myocardial ischaemia in 15 patients when assessed by thallium imaging during exercise. Thallium imaging proved more sensitive than electrocardiography in the demonstration of perioperative infarction and in the detection of postoperative ischaemia. Exercise electrocardiography may be misleading after aortocoronary bypass operations. Thallium imaging offers a simple, objective evaluation of the results of revascularisation procedures, throws light on the mechanisms of relief of angina by operation, and helps in the assessment of the patient whose progress is unsatisfactory after operation.


Association of host immunoglobulins with solid tumours in vivo. Using a direct radioimmune antiglobulin technique and a competitive double-antibody radioimmune assay, we have demonstrated the presence of appreciable amounts of host immunoglobulins on the surface and in extracts of cell suspensions from freshly excised solid tumours. IgA appeared to have the greatest concentrations from freshly excised solid tumours. IgA appeared to have the greatest concentration, followed in turn by IgM congruent to IgG2a greater than IgG1 congruent to IgG2b greater than IgG3. The amount of immunoglobulin appeared to be influenced by the tumour under investigation and its mode of maintenance. It could also be increased by the administration of C. parvum but was not significantly influenced by the T-cell status of the host.


Transient impairment of peripheral blood lymphocyte function during PUVA therapy. Three parameters of immune function--enumeration of circulating T and B lymphocytes and response of lymphocytes to graduated doses of phytohaemagglutinin (PHA)--were examined serially in eleven patients with psoriasis before, during, and after an intensive course of PUVA therapy. A trend was detected for the lymphocyte response to PHA to fall during the first week of treatment and then rise back towards the pre-treatment level. No alteration was found in the percentage or absolute numbers of circulating T and B lymphocytes. This study shows that routine PUVA therapy can induce an alteration in immune function but that this alteration is slight and short-lived.


Immune pancytopenia.

Immune pancytopenia. Circulating T-lymphocytes from a 13-year-old boy with autoimmune anaemia, severe neutropenia and thrombocytopenia inhibited autologous and normal homologous bone marrow myeloid colony formation in vitro. This inhibition was abolished when the patient's antithymocyte globulin and complement-treated T-lymphocytes were used. T-lymphocytes from normal individuals did not cause such an inhibition. The patient's lymphocytes showed no inhibitory effect on erythroid colony formation. Investigation of the patient's serum failed to disclose any leucoagglutinin, lymphocytotoxin or humoral factor against myeloid colony formation. These findings indicate that T-lymphocytes may play a role in the pathogenesis of neutropenia in immune pancytopenia.


Generation of factor VIII coagulant activity by isolated, perfused neonatal pig livers and adult rat livers. Isolated, normal, neonatal pig livers released VIII:C into perfusates of porcine von Willebrand blood lacking VIIIR:AG and VIII:RWF. Neonatal von Willebrand livers released VIII:C only when partially purified VIIIR:AG was added to the von Willbrand blood. Adult rat livers, perfused with frozen-thawed erythrocytes suspended in Tyrode's solution containing 6% bovine serum albumin and hence no VIIIR:AG released VIII:C only when serum, adsorbed serum or cryoprecipitate from rat plasma was added to the perfusate. Cycloheximide blocked the release of VIII:C from rat liver.


Maternal hormone profile in oxytocin induced labour. Serial blood samples were collected from ten patients at between 40 and 42 weeks gestation, who were having labour induced by amniotomy and intravenous oxytocin. The plasma levels of human placental lactogen and pregnancy-specific beta 1 glycoprotein showed no more than their normal late pregnancy variability during labour; oestradiol-17 beta showed a small rise in early labour followed by a fall in the second stage of labour; unconjugated oestriol and 11-hydroxycorticosteroids showed a progressive rise throughout labour and progesterone a progressive fall. The ratio of progesterone to oestradiol-17 beta fell throughout labour. The significance of these changes in our understanding of the control of placental hormone secretion and of the hormone profile of spontaneous labour is discussed.


Polyamine oxidase activity in human pregnancy serum. The existence of a spermine oxidizing enzyme was established in human pregnancy serum by a radiochemical method, and a cross-sectional study of its quantitative profile between 10 and 40 weeks gestation was undertaken. Though there was a wide scatter of values, the rise in the average activity was continuous and highly significant. The flavoprotein inhibitor, quinacrin, inhibited the enzyme activity, while the pyridoxal phosphate inhibitor, isoniazid, had no significant inhibitory effect suggesting that the enzyme is of tissue origin. The possible role of polyamines and their oxidation in physiological immunoregulation is discussed.


Circulating levels of pregnancy proteins in early and late pregnancy in relation to placental tissue concentration. The concentrations of human chorionic gonadotrophin (hCG), human placental lactogen (hPL), pregnancy specific beta 1 glycoprotein (SP1), ferritin (PP2) and placental protein 5 (PP5) were examined in maternal serum and placental tissue in early and late pregnancy. The circulating concentration of hPL, SP1, and PP5 were higher during late pregnancy than early pregnancy, that of hCG lower, and ferritin (PP2) levels showed no difference. Placental tissue levels of hPL and SP1 were higher in late pregnancy, hCG levels lower, and ferritin (PP2) and PP5 showed no change. The ratio of the concentration in maternal serum to that in placental tissue increased during pregnancy for all proteins with the exception of ferritin. It is proposed that the mechanism of secretion of trophoblast specific proteins varies widely and that this should be taken into account in the clinical interpretation of circulating levels in the mother.


Disappearance of pregnancy-specific beta 1 glycoprotein from the maternal circulation after delivery. It is likely that there are systematic differences between circulating pregnancy-specific beta 1 glycoprotein (SP1) levels measured by radioimmunoassay and immunoprecipitation systems. We have re-investigated the decline in circulating levels of SP1 following delivery of the placenta. Serial blood samples were collected for 120 hours from 10 women following Caesarean section or vaginal delivery at term. The apparent half-life of SP1 after delivery ranged between 17 and 45 hours.


Management of subluxated and dislocated lenses with the vitrophage. Thirty-two eyes with subluxated and disclosed lenses were surgically managed by means of the vitrophage. The best results were obtained for those cases in which subluxation or dislocation of lenses into the vitreous was not associated with other complications such as glaucoma, perforating injuries, and retinal detachment. No major intraoperative or postoperative problems were seen in uncomplicated cases during a follow-up period ranging from 5 to 45 months.


Membranes of Rhodopseudomonas sphaeroides. VII. Photochemical properties of a fraction enriched in newly synthesized bacteriochlorophyll a-protein complexes. Previous pulse-chase studies have shown that bacteriochlorophyll a-protein complexes destined eventually for the photosynthetic (chromatophore) membrane of Rhodopseudomonas sphaeroides appear first in a distinct pigmented fraction. This rapidly labeled material forms an upper band when extracts of phototrophically grown cells are subjected directly to rate-zone sedimentation. In the present investigation, flash-induced absorbance changes at 605 nm have demonstrated that the upper fraction is enriched two-fold in photochemical reaction center activity when compared to chromotophores; a similar enrichment in the reaction center-associated B-875 antenna bacteriochlorophyll complex was also observed. Although b- and c-type cytochromes were present in the upper pigmented band, no photoreduction of the b-type components could be demonstrated. The endogenous c-type cytochrome (Em = +345 mV) was photooxidized slowly upon flash illumination. The extent of the reaction was increased markedly with excess exogenous ferrocytochrome c but only slightly in chromatophores. Only a small light-induced carotenoid band shift was observed. These results indicate that the rapidly labeled fraction contains photochemically competent reaction centers associated loosely with c-type and unconnected to b-type cytochrome. It is suggested that this fraction arises from new sites of cytoplasmic membrane invagination which fragment to form leaky vesicles upon cell disruption.


Structural studies on reconstituted reaction center-phosphatidylcholine membranes. Reaction center protein, isolated from the photosynthetic bacterium Rhodopseudomonas sphaeroides R26 mutant, was incorporated into phosphatidylcholine bilayers forming a homogeneous population of unilamellar vesicles. Cytochrome c, added to preformed reaction center-phosphatidylcholine vesicles, rapidly reduced up to 90% of the laser-generated (BChl)2+ of the reaction center (with kinetics of electron transfer similar to those in the chromatophore membrane) which suggests that the portion of the reaction center which accommodates functional cytochrome c binding sites is exposed predominantly on the exterior of the vesicles. Unit cell electron density profiles were derived from lamellar X-ray diffraction from oriented reaction center-phosphatidylcholine membrane multilayers at varying lipid/protein ratios. The analysis of these profiles showed that the reaction center protein incorporates into the phosphatidylcholine membrane with unique sidedness and that the profile of the reaction center protein itself is asymmetric and spans the membrane.


The reconstitution of energy transfer in membranes from a bacteriochlorophyll-less mutant of Rhodopseudomonas sphaeroides by addition of light-harvesting and reaction centre pigment-protein complexes. Antenna and reaction centre complexes purified from photosynthetically-grown cells of Rhodopseudomonas sphaeroides have been mixed with cytoplasmic membranes prepared from an aerobically-grown bacteriochlorophyll-less mutant of Rp. sphaeroides (designated 01) in the presence of 1% sodium cholate. After removal of the cholate by dislysis, the dislysate was subjected to isopycnic centrifugation. Reconstituted cytochrome c2 photooxidation and cytochrome b photoreduction was demonstrated in a pigmented fraction recovered from the sucrose gradient, suggesting that the pigment-proteins were incorporated into the 01 membrane. The fluorescence properties of the system were examined. The appearance of a variable component after the initial fast fluorescence rise indicated that energy transfer occurred between the antenna and reaction centre proteins in the presence of 01 membrane. The order in which the system was assembled was important. Reconstituted energy transfer with a pre-dialysed reaction centre-antenna complex was more effective than when all the components were mixed at once. Energy transfer was also reconstituted between added reaction centre protein and the endogenous antenna present in membranes from the pigmented, but aerobically-grown reaction centre-less mutant PM8dp of Rp. sphaeroides. Preparations of 01 membranes reconstituted with reaction centre exhibited a light intensity dependent cytochrome c2 photooxidation. At low exciting light intensities, preparations containing reconstituted antenna protein in addition to reaction centres showed greated membrane cytochrome c2 photooxidation than preparations with the antenna omitted; this improvement was maximal when a pre-dialysed antenna-reaction centre complex was used.


Early changes in ornithine decarboxylase activity during Friend leukemia cell differentiation. Agents such as dimethylsulfoxide, N,N'-dimethylformamide and bisacetyldiaminopentane that induce erythroid differentiation of Friend leukemia cells, cause a rapid increase in ornithine decarboxylase (EC 4.1.1.17) activity in intact cells during the 'latent' period preceding the accumulation of hemoglobin-containing cells. Blockage of erythroid differentiation with 5-bromo-2'-deoxyuridine did not prevent these alterations in enzyme activity. Addition of each chemical inducer in the extracts of these cells stimulate the basal levels of ornithine decarboxylase activity. These data indicate that the chemical inducers of differentiation modify the normal pattern of ornithine decarboxylase activity in this system.


[Properties of membrane-bound sialyltransferase from rana temporaria liver]. It was demonstrated that microsomal membranes from frog liver contain at least two different sialyltransferases involved in the synthesis of alpha 2 leads to 3 and alpha 2 leads to 6 oligosaccharide isomers. Studies on acceptor specificity of the sialyltransferase system with respect to low molecular acceptors revealed its similarity to the mammalian sialyltransferase system. However, sharp distinctions were observed in sialylation of mammalian glycoproteins. It was assumed that that the disaccharide unit of the acceptor oligosaccharide chain is a structural element, which in necessary but not sufficient for glycoprotein recognition by sialyltransferases.


Partial characterization of colony stimulating activity from human leucocyte conditioned medium tested on human marrow cells. Conditioned medium from normal human leucocytes was fractionated by gel filtration (Sephadex G 150) and affinity chromatography (Con A-Sepharose). On gel filtration, all colony stimulating activity (CSA) was eluted as a single peak with a molecular weight of 33.000 -- 41.000. Affinity chromatography revealed two separate peaks of colony stimulating activity, one lacking and the other having concanavalin A affinity (MW congruent to 44.000 -- 58.000). The properties of these two fractions are under investigation.


Willebrand factor in hemostasis in the in vitro bleeding time. Heparinized porcine blood and plasma, at constant hydrostatic pressure, was allowed to flow through a 5-mm incision in a small piece of porcine skin. Changes in the exuded blood volume were measured, and the incision site was examined microscopically. When normal blood flowed through either normal or von Willebrand skin, the exuded blood volume decreased gradually and eventually stopped. Microscopic examination revealed a platelet plug in the incision site. This plug was positive for Willebrand factor when examined by immunofluorescence. In contrast, the blood from von Willebrand pigs continued to flow constantly, and a platelet plug was not seen. The delayed in vitro hemostasis in von Willebrand blood was corrected to the normal range by the addition of either normal plasma or partially purified Willebrand factor. Normal blood, in which the Willebrand factor was immunologically inhibited, showed delayed hemostasis. For this in vitro system, it appeared that plasmatic Willebrand factor played an essential role in hemostasis.


Incidence and patterns of bone marrow and blood involvement by lymphoma in relationship to the Lukes-Collins classification. Pretreatment lymph nodes, bone marrow, and blood were examined in 176 cases of non-Hodgkin's lymphoma. By the criteria of the Lukes and Collins functional--morphological classification, 158 (90%) were B-cell lymphomas and 17 (10%) were T-cell lymphomas. Bone marrow involvement was present in 53% of cases: 51% of B-cell types and 65% of T-cell types. Marrow involvement was most frequent in small lymphocyte (B) (89%), convoluted lymphocyte (60%), and small cleaved follicular center cell (FCC) lymphomas (55%). The pattern of bone marrow involvement was most frequently focal paratrabecular in B-cell lymphomas and diffuse in T-cell lymphomas. Blood involvement was present in 50% of cases with bone marrow lymphoma and generally reflected extensive bone marrow disease. There was a higher incidence of both bone marrow and blood involvement in pediatric patients than in adults.


Human leukocyte interferon preparation blocks granulopoietic differentiation. Since interferon administration in the treatment of some malignant conditions has been reported to cause leukopenia, we studied the effects of human leukocyte interferon preparation (HLIF) on myelopoiesis in vitro. The continual presence of HLIF in semisolid agar cultures caused a progressive decline in colony and a rise in cluster incidence with increasing concentrations of interferon. The total plating efficiency, however, remained nearly constant, regardless of the HLIF doses used. Morphological examination of the clusters demonstrated a progressively increasing percentage of immature granulocytic precursors with increasing HLIF concentrations. This suggests that HLIF causes leukopenia by blocking differentiation of marrow myeloid precursors.


Detection of primitive macrophage progenitor cells in mouse bone marrow. A previously undetected population of macrophage progenitor cells with high proliferative potential (HPP-CFC; an average of 5 x 10(4) cells/colony) in nutrient agar cultures has been demonstrated in post-fluorouracil (FU) and fluorouracil plus endotoxin (FUEt) treated and normal mouse bone marrow, using a combination of colony-stimulating factors, pregnant uterus extract (PMUE) plus human spleen-conditioned medium (HUSPCM). Neither PMUE nor HUSPCM alone stimulated colony formation by the HPP-CFC. The incidences of HPP-CFC were 1 in 2380 nucleated cells in normal marrow, 1 in 380 for 10-day post-FU, and 1 in 118 in 8-day post-FUEt marrow cells. HPP-CFC were only depleted to 57% of normal at 2 days after FU treatment, whereas the cells responsive to PMUE alone (low proliferative potential, LPP-CFC) were depleted to 1.2%, indicating a marked difference in cycling status of the respective types of progenitor cells.


Circulating breast tumour antigen-sensitive T lymphocytes in early breast cancer and high risk benign breast disease. Levels of circulating T lymphocytes sensitized to breast tumour associated antigens (BTA) were correlated with pathological tumour stage or benign histopathology in preoperative studies of 180 patients by the antigen-stimulated active rosette-forming T cell (AgARFC) assay. Incubation of lymphocytes with allogeneic BTA extracts produced increased AgARFC compared with incubation without BTA. Significant levels of BTA-sensitive T cells were found in 78 per cent of breast cancer patients compared with 23 per cent of patients with benign disease (P less than 0.0005, by X2). Over 93 per cent of stage I cancer patients responded to BTA, compared with 69 per  cent of stage II patients (P less than 0.025) and 59 per cent of stages III-IV patients (P less than 0.005). Twenty-nine per cent of 42 patients with fibrocystic disease were positive to BTA in contrast to 8 per cent of 25 patients with fibroadenomas. This  was a 3.6-fold higher incidence of BTA-sensitive T cells associated with fibrocystic disease than with fibroadenomas, which was in agreement with the increased breast cancer risk rate associated with fibrocystic disease. These findings suggest that the AgARFC assay may detect early malignant change in fibrocystic disease. The AgARFC assay was found to reliably detect early invasive carcinoma.


Overprescribing iron tablets to elderly people in Sweden. Iron should not be prescribed to middle-aged men or older women with anaemia unless the possibility that the iron deficiency is caused by a gastrointestinal tumour has been considered. Thus the prescribing of iron to elderly people was investigated by studying four different prescription statistics and by reviewing records. Over one in 10 women aged over 65 were prescribed iron tablets. Men and women in the oldest age groups were prescribed iron most frequently. The reasons for prescribing iron were examined at a rural health centre. Out of 327 records of patients who were prescribed iron during 1975, 157 were randomly selected and reviewed. Only 18 out of 48 (38%) patients aged 45-75 (men) and 55-75 (women) and 29 out of 109 (27%) aged over 75 years had probable or possible iron-deficiency anaemia as established from the records. Only nine (19%) of the younger patients had a plausible reason for the anaemia other than a bleeding tumour. Ten (9%) of the older patients were considered to be inoperable cases. Thus, according to the records, only 18 (17%) of the patients over 75 years and nine (19%) of those in the younger age group have been prescribed iron. About 70% of all the patients were considered not to have iron deficiency; 7% had had iron deficiency previously, and 20% probably had anaemia as a result of chronic disease; for 43% no real reason for the iron prescription could be found in the record. Thus it is concluded that iron is overprescribed in Sweden, particularly for elderly people. It should not be prescribed until the possibility of a bleeding gastrointestinal tumour has been excluded.


Metronidazole-resistant Trichomonas vaginalis. A 36-year-old woman with symptomatic metronidazole-resistant trichomonal vaginitis for 10 years had a total of 22 courses of treatment with either metronidazole or tinidazole according to different schedules. The minimum trichomonicidal concentration of metronidazole for the strain of Trichomonas vaginalis isolated from the patient was 160 microgram/ml compared with 1.25-10 microgram/ml for other freshly isolated strains. The former strain also showed a definitely decreased sensitivity to ornidazole and tinidazole (80 microgram/ml). The mechanisms behind the appearance of resistance in this clinical isolate are at present unknown and require further study from the theoretical as well as the therapeutic viewpoint.


Constant error of visual egocentric orientation in patients with acute vestibular disorder. Errors of visual egocentric localization are well-known in patients with paresis of ocular muscles or paresis of conjugate gaze. In the present paper a series of patients with unilateral vestibular disorder disclosed a constant lateralization of the visual agocentre in the absence of any ocular paresis. The perceptual illusion is associated with an altered resting position of the eyes caused by the vestibular imbalance. The disturbance of visual, egocentric localization was revealed only after elimination of the visual frame of reference and the extent of lateralization of the visual egocentre was proportional to the degree of resting deviation of the eyes. Although the findings are of limited clinical importance they have a considerable theoretical interest. From the clinical point of view they may provide a basis for further understnading of the complex-perceptual illusions which may accompany disorders affecting central vestibulo-ocular connections. The results indicate that the perceptual effects are related to an altered central evaluation of the oculomotor programme and thus depend upon the operation of an 'efference copy'. This hypothesis is discussed with reference to earlier and current theories of visual localization.


Aetiology of emphysema.

Aetiology of emphysema. There is now overwhelming evidence that lung destruction resulting in emphysema is largely due to enzymatic action on pulmonary connective tissues, mainly elastin. These enzymes are probably derived from neutrophil polymorphonuclear leucocytes and alveolar macrophages. Arguments are advanced to show that release of these enzymes is related to cigarette smoking. This explanation for the pathogenesis of emphysema is compatible with the distribution of the disease within the lung noted in epidemiological studies. If this conclusion with regard to the role of cigarette smoking is correct it must follow that, apart from patients with alpha 1-antitrypsin deficiency, emphysems is a disease which could be almost entirely eliminated if the smoking habit was abandoned.


Vestibular suppression in peripheral and central vestibular disorders. Caloric tests have been carried out both in the presence of optic fixation and in total darkness upon normal subjects, patients with peripheral vestibular disorders and patients with central vestibular lesions. Nystagmic responses were recorded electronystagmographically and measurements made of latency and duration of response, maximum slow component velocity and beat frequency. The relative enhancement of the response in darkness is expressed as a fixation index: maximum slow component velocity in darkness maximum slow component velocity with fixation. Compared to the normal group the peripheral group were found to have abnormally high fixation indices, the central group abnormally low. A hypothesis has been developed of the nervous mechanisms underlying the suppressive effects of optic fixation in both peripheral and central lesions which accords well with the available clinical, anatomical and physiological data. The clinical implications of the findings are discussed both in respect of their localizing value and relevance to current innovations in the design of caloric tests.


Initiation and time course of mitosis of non-neuronal cells after spinal motoneuron axotomy. The mitotic response of non-neuronal cells following motor axon transection was measured after in vitro incorporation of [3H]thymidine in frog spinal cord. This predominantly ipsilateral response occurs more rapidly and is of greater magnitude when motor axons are unilaterally transected at the ventral root than after sciatic nerve transection. No increase in incorporation occurred when regenerating fibers were transected a second time before reinnervation, but an increase was observed when the second operation was performed after the formation of functional neuromuscular connections had taken place. Autoradiographic studies after dorsal or ventral root transection showed that the distribution of labeled cells approximated the anatomical extent of the injured cellular elements within the spinal cord. These data are discussed in relation to the characteristics of the dividing cells and the nature of the events eliciting mitosis.


Identification of lymphoblastic lymphoma cells using a dual assay for T cell differentiation markers. An assay that simultaneously detects two differentiation markers found in thymocytes is described. There markers include the membrane receptor for sheep erythrocytes (E) and the nuclear enzyme, terminal deoxynucleotidyl transferase (TdT). Cells are incubated with E, pelleted onto slides and then stained for TdT by an indirect immunofluorescence technique. The E-positive, TdT-positive phenotype is characteristic of the tumor cells in many cases of lymphoblastic lymphoma. Cells of this dual phenotype were not found in the peripheral blood or bone marrow of individuals without neoplastic disease. An 8-year-old-girl with lymphoblastic lymphoma is described whose peripheral blood and bone marrow smears were thought to be morphologically normal at the time of diagnosis. However, 3% of her peripheral blood and about 1% or her bone marrow mononuclear leukocytes were identified as E-positive, TdT-positive. These cells disappeared from both sites five weeks after institution of therapy, and her peripheral blood remains free of such cells nine months after diagnosis. This dual assay for E-rosette formation and TdT is a more sensitive technique than conventional morphology for the detection of tumor cells of this type. The assay may be useful in monitoring the therapy of patients with this tumor.


Terminal deoxynucleotidyl transferase positive lymphoblastic lymphoma: a study of 15 cases. The investigation was undertaken to define the features of lymphoblastic lymphoma. Fifteen lymph node biopsies from a group of 82 specimens studied for the enzyme terminal deoxynucleotidyl transferase (TdT) fulfilled morphological criteria for this diagnosis. These criteria required a diffuse infiltrate of relatively uniform, immature lymphoid cells with basophilic cytoplasm; round, oval or lobulated nuclei with evenly dispersed chromatin; rare or inconspicuous nucleoli; and numerous mitotic figures. Examination of 1-micron thick, plastic-embedded, Giemsa-stained tissue sections revealed convoluted nuclei in more than 50% of neoplastic cells in four cases: in six specimens there was an admixture of cells with grooved, hyperlobulated, and round nuclei, and in five the round or oval nuclei were non-convoluted. Specimens from all 15 patients were positive for TdT by fluorescent antibody and biochemical assays. The percentage of cells from involved nodes reacting by indirect immunofluorescence with an antiserum against bovine TdT ranged from 4 to 90% (mean of 52%), and the mean level of biochemically measured enzyme activity was 8.7 units/g of tissue (range of 1.9 to 27.5). Cytochemical stains for acid phosphatase were positive in 13 of the 15 cases. In eight samples more than 50% of cells formed rosettes with sheep erythrocytes, while the E rosettes varied from 14 to 38% in the other seven. The percentage of cells with complement receptors varied widely (range of 6 to 80), but cells bearing surface immunoglobulin or IgGfc receptors were not increased. All patients presented with supradiaphragmatic lymphaedenopathy, eight with an anterior mediastinal mass. Two-thirds of the patients were male, and the mean age was 20 years (range 4 to 46 years). None were leukemic at the time of diagnosis, but eight patients subsequently developed acute lymphoblastic leukemia. Involvement of the central nervous system was observed in four of the 15, and of the testes in two. Ten patients have died of their disease with a median survival of 8 months (range 4 to 20), and five are alive 3--8 months after diagnosis. We observed no differences in clinical findings at presentation, incidence of mediastinal involvement or leukemic dissemination, content of TdT, acid phosphatase staining, or immunologic cell surface characteristics between the convoluted and non-convoluted types of lymphoblastic lymphoma. Distinctive morphologic, cell surface, biochemical, and clinical features of lymphoblastic lymphoma can be identified irrespective of the presence or absence of convoluted nuclei.


Buoyant density analysis of myeloid colony-forming cells in germfree and conventional mice. Granulocyte-macrophage colony-forming cells (CFUc), in the bone marrow of germfree and conventioal CBA mice, were compared quantitatively and qualitatively. Cells were separated on the basis of their buoyant density by equilibrium centrifugation in continuous albumin density gradients. CFUc in the density subpopulations were detected by culture in agar containing three different types of colony stimulating factor (CSF). The sources of the CSF were post-endotoxin mouse serum (CSFES), mouse lung conditioned medium (CSFMLCM) and human urine (CSFHU). Mice were removed from the germfree environment and the buoyant density status of their CFUc was examined 1, 4 and 8 weeks later. No difference was found between germfree and conventional mice in the number of nucleated cells per femur or in their modal density. Neither was the number of CFUc per femur different. The cell cycle status of CFUc, as determined by the thymidine suicide technique was not significantly different. Functional heterogeneity was found among the density subpopulations for both groups of mice. This depended on the type of CSF. The density distribution of CFUc was significantly different in germfree mice. There were proportionately more low density CFUc. The mean modal density of CFUc under CSFES stimulation was less by 0.0045 g/cm3 in germfree mice. The removal of mice from the germfree environment resulted in a shift of the distribution to higher densities. The trend was towards the conventional situation. The significance of the buoyant density status of CFUc is discussed.


Mesothelial stomata overlying omental milky spots: scanning electron microscopic study. The presence in the rat omentum of intercellular pores (the classical stomata of von Recklinghausen) between the mesothelial cells overlying aggregates of lymphoreticular cells (the classical milky spots of Ranvier) and the apparent migration of lymphocytes through these stomata were recorded for the first time by scanning electron microscopy. Previous studies on passage of cells across the peritoneum and omentum used experimentally administered cells, while in the present study no cells were administered to the rats and their own lymphocytes were observed in situ. The possible role of lymphocytes in the peritoneal cavity is also briefly discussed.


Fine structural distribution of the surface-connected canalicular system in frog thrombocytes. The existence of the surface-connected canalicular system (SCCS) has been demonstrated in semithick sections of the frog thrombocytes by the use of a high voltage electron microscope. The SCCS of the thrombocytes in Rana catesbeiana and Rana nigromaculata consists of numerous canaliculi and vesicles with a diameter of 250 nm, which join with one another to make a complex network throughout the cytoplasm. Although the SCCS of Xenopus laevis fits well into the pattern described in Rana catebeiana, the diameter of the canaliculi of the SCCS is about 500 nm. The results of this study suggest that the SCCS is a specific organelle of the thrombocyte system common to submammals and mammals.


Scanning electron microscopy of the wall of the third ventricle in the brain of Rana temporaria. Part IV. The surface specializations of the wall of the third cerebral ventricle of Rana temporaria were investigated with the scanning electron microscope. These specializations can be divided into three types: cilia, large bulbous protrusions, and microvillus-like protrusions. Most parts of the ventricular surface are densely ciliated. In contrast, other regions are either scantily ciliated or devoid of cilia. Four areas of the ventricular surface are studded with numerous large bulbous protrusions. These large protrusions can be divided into two types: One type consists of intraventricular end bulbs of dendrites of secretory neurons. The other type is represented by large cytoplasmic extensions of ependymal cells. In the third ventricle of Rana, microvillus-like surface specializations of ependymal cells are ubiquitous structures. Generally, filiform protrusions of varying length are the predominant type. The microvillus-like specializations are transient structures, the number of which varies according to different physiological states of the ependymal cells.


Kinetic immunoturbidimetry: the measurement of pregnancy specific beta 1 glycoprotein. The extension of kinetic immunoturbidimetry to the measurement of low concentration proteins has been described using the protein pregnancy-specific beta 1 glycoprotein. The technique has a precision superior to that of all other methods currently available. The assay is rapid, cheap and compares well with other published methods. The assay further emphasises the usefulness of the technique of kinetic immunoturbidimetry.


Circulating immune complexes in patients with cryptogenic fibrosing alveolitis. Increased Clq binding levels have been obtained in serum from twenty-one (50%) of forty-two patients with cryptogenic fibrosing alveolitis (CFA) suggesting the presence of circulating immune complexes. There was a low frequency of positive results using a number of other tests for circulating immune complexes. The increased Clq binding levels were observed in six (35%) out of seventeen patients with lone lung involvement and in fifteen (60%) out of twenty-five patients with extrapulmonary connective tissue disorders. There was an especially close correlation between arthritis and elevated Clq binding. A strong correlation between Clq binding levels and levels of circulating rheumatoid factor (RF) and IgG, and enhancement in macrophage radiobioassay tests using RF-containing sera, suggested that RF might be involved in the circulating immune complexes in these patients. DNAase pre-treatment of sera did not influence the findings, and there was no correlation between Clq binding and levels of immunofluorescent ANA, C-reactive protein levels, or platelet counts. A weak correlation between Clq binding and erythrocyte sedimentation rates, and slightly lower binding levels in treated than untreated patients with 'lone' CFA suggested that binding levels may give some indication of disease activity and may in some instances be influenced by treatment.


Quantitation and characterization of soluble immune complexes precipitated from sera by polyethylene glycol (PEG). Polyethylene glycol (PEG) was used to isolate immune complexes from sera. Complexes were then quantified and partially characterized by a variety of immunological techniques. Complexes were detected in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Felty's syndrome and vasculitis, but not in polymyositis, scleroderma or Behçets syndrome. The level of immune complexes correlated with disease activity in SLE and RA patients. Rheumatoid factors and anti-DNA antibodies were enriched by PEG precipitation of RA and SLE sera, respectively, thus these antibodies appeared to be present in the form of soluble immune complexes. Immune complexes usually contained all three immunoglobulin classes, IgG, IgM and IgA. Complexes from RA patients were generally larger and often contained Clq, while C3 was found almost exclusively in SLE complexes which also tended to be smaller. Such compositional differences may one day explain the differences in clinical manifestations of various immune complex-mediated diseases.


The clearance of pre-formed immune complexes in rats with Heymann's nephritis. Previous studies have indicated the presence of reticuloendothelial system (RES) depression in chronic immune complex nephritis in rabbits. To determine whether RES immune complex clearance was abnormal in Heymann's nephritis in rats, radiolabelled pre-formed immune complexes were infused into rats with membranous nephropathy. There was augmented clearance of complexes from the peripheral circulation in animals with membranous nephropathy relative to controls, indicating the absence of RES saturation.


T and B lymphocytes in myasthenia gravis. Peripheral blood lymphocytes from seventeen non-thymectomized and nine thymectomized patients with myasthenia gravis (MG) and thirteen healthy controls were examined for the presence of surface markers characteristic of T and B lymphocytes by rosette formation with sheep red blood cells (SRBC). T cells were identified by their capacity to spontaneously form rosettes with SRBCs. The percentage of B lymphocytes was determined by the erythrocyte antibody complement (EAC) rosette-forming test. The EAC complex was prepared with either whole rabbit anti-SRBC serum or with the IgM fraction of rabbit anti-SRBC serum. The two kind of erythrocyte complement rosette-forming cells (EAC-RFC) are designated erythrocyte-haemolysin-complement RFC (EA(H)C-RFC), and erythrocyte-IgM-complement RFC (EA(M)C-RFC). The percentage of total lymphocytes and T cells was not altered in MG patients. The percentage of 'active' T cells, which have been considered to be more actively involved in cellular immunity, was also similar in MG patients and controls. A significant increase in EA(H)C-RFC occurred in both thymectomized and non-thymectomized MG patients, while in B cells detected by EA(M)C-RFC no alterations were found. The increase in EA(H)C-RFC in lymphocytes from MG patients may be due to an increase in the 19S antibody-forming B lymphocytes or to an increase in T cells which have Fc receptors on their surface.


Receptors for IgM on human lymphocytes. II. Mitogen-induced modulation of receptor expression. Human peripheral lymphocytes undergoing blastogenesis induced by phytohaemagglutinin (PHA) or concanavalin A did not express receptors for the Fc portion of IgM (RFcmu). Furthermore, treatment of lymphocytes with PHA produced a dose-dependent loss of RFcmu which began as early as 5 hr after exposure to the mitogen. Within 24 hr after the addition of PHA, the percentage of lymphocytes expressing RFcmu had decreased from 65% to 4%. Under the same conditions of treatment, the expression of the receptor for sheep erythrocytes (E) was unchanged. These findings seemed inconsistent with a direct blocking effect of PHA but suggested that PHA induced a time-dependent modulation (switch off) of expression of RFcmu. Pronase cleavage of surface proteins on cells incubated with PHA for 24 hr followed by overnight incubation showed an almost complete irreversibility of RFcmu modulation up to 72 hr later. Studies using T cells isolated by E-rosetting showed that RFcmu modulation predominantly occurred on T cells. The modulation of RFcmu expression is discussed in terms of its possible role in the immune response.


Subpopulations of lymphocytes in human thymomas. Lymphocyte populations in six normal thymuses and ten thymomas were examined. The majority of lymphocytes from both thymus and thymoma differ from peripheral T lymphocytes in their capacity to form E-rosettes resistant to incubation at 37 degrees C. Low percentages of T lymphocytes bearing receptors for the Fc portion of IgG (TG) and IgM (TM) were found in normal thymus. In contrast, lymphocytes from five out of nine thymomas showed remarkable percentages of TM cells. Compared with normal thymocytes, lymphocytes from seven out of ten thymomas responded vigorously to mitogens. The possible origin and nature of thymoma lymphocytes are discussed.


PHA-induced soluble factor(s) can activate B-cells from patients with chronic lymphatic leukaemia. Blood lymphocytes from eight patients with chronic lymphatic leukaemia (CLL) were stimulated by phytohaemagglutinin (PHA). The effect was defined as a pronounced increase of 3H-thymidine incorporation, and a concomitant blast transformation of a large portion of surface Ig-positive, E-rosette-forming (E-RFC) negative cells. E-RFC depletion reduced these effects to nearly background levels, and the pooled data strongly suggest that malignant B-lymphocytes in CLL are capable of responding to a PHA-induced T cell factor. A possible use for this factor in characterizing different subpopulations of CLL cells is discussed.


Characterization of the role of mononuclear cell subpopulations in the in vitro lymphocyte proliferation assay. Purified human mononuclear cell subpopulations have been evaluated in the in vitro lymphocyte proliferation assay. Monocyte-depleted mononuclear cells had reduced or absent responses to mitogens and antigens which could be restored to the original mononuclear cell response by addition of purified plastic adherent cells. Purified T lymphocytes obtained by density gradient centrifugation of E-rosette-forming cells demonstrated low but significant proliferative responses to mitogens, but no significant response to antigens. The addition of monocytes potentiated the response of purified T cells to mitogens and antigens, but did not fully reconstitute the original mononuclear cell response unless non-T lymphocytes were also present. It is concluded that mononuclear cell proliferation represents a complex mechanism of cellular interaction involving multiple subpopulations of cells.


The significance of serial measurements of serum complement C3 and C4 components and DNA binding capacity in patients with lupus nephritis. Eighteen patients with systemic lupus erythematosus (SLE) and proliferative glomerulonephritis, underwent serial serum determinations of C3, C4, and native DNA binding capacity, as well as repeat renal biopsy 7 to 48 months (median 25 months) following initial biopsy. Highly significant correlations were found between serum C3 levels and renal histologic changes (P less than 0.0001), and between serum C3 levels and DNA binding capacity (P less than 0.03). Histologic deterioration correlated with depressed C3 levels, while improvement was associated with normalization of C3 levels. No correlation between renal histologic changes and either serum C4 levels or DNA binding capacity was found. The data suggest that the serum level of C3 is the best index of activity of lupus nephritis.


Acute coronary occlusion with impending infarction as an angiographic complication relieved by a guide-wire recanalization. In a 45 year old male patient with a history of previous inferior myocardial infarction and unstable angina pectoris, coronary angiography revealed two-vessel disease: a 60-70% lesion in the middle third of the LAD, and a 90% lesion in the middle third of the very large RCA. There was only a small akinetic segment in the posterobasal region of the left ventricle. During angiography total occlusion of the RCA occurred followed the clinical and electrocardiographic signs of impending inferior reinfarction. Recanalization of the occluded vessel was accomplished by using a guide-wire, which was passed through a Sones catheter, placed in the RCA. The patient's symptoms subsided and the electrocardiographic signs of acute ischemia reverted within eight minutes. Aortocoronary bypass surgery with revascularization of the LAD and RCA was performed within 3 hours after recanalization. Postoperatively there was no evidence of major tissue loss by enzyme or electrocardiographic criteria. Control angiography, performed on the ninth day postoperatively, revealed the graft to the RCA to be widely patent. Left ventricular function was unchanged. It is concluded, that the combined approach of early transluminal recanalization of the acutely occluded RCA followed by successful construction of a graft to this vessel, has averted necrosis of a major portion of the left ventricle. However, general use of this technique does not seem advisable at the present time.


Cardiac emission tomography in patients using 201thallium. A new technique for perfusion scintigraphy. The distribution of 201thallium (Tl) in the myocardium has been studied by the new technique of emission tomography, and compared with standard gamma camera images in 5 patients. Tomographic imaging was carried out using a dual-detector scanner operated under the single-photon technique. Initial results have been promising, with visualisation of resting perfusion defects in patients with recent infarction and those with ventricular aneurysms. Emission tomography has also been performed at exercise, and has shown tracer deficits in the distribution of significant coronary stenoses. This new approach to myocardial perfusion scintigraphy may lead to improved sensitivity for detecting apical and inferior wall abnormalities by providing depth information not available from a conventional two-dimensional image.


Myocardial imaging with 134mCesium. Comparison of scintigraphic and cineradiographic results. Thirty-four patients had noninvasive myocardial perfusion imaging at rest using 134mCs. The results were compared with the results of coronary cineangiography and left ventriculography. All 21 patients who had abnormal left ventriculograms had corresponding myocardial imaging defects. This group included 14 patients with electrocardiographic evidence of either an old inferior, anteroseptal, anterior, or anterolateral myocardial infarction. Thirteen patients had normal left ventriculograms: this group included 6 patients with 75% or greater obstruction of one or more coronary arteries and 7 patients with normal or insignificantly diseased vessels. Only 2 of these patients had abnormal myocardial images: both had severe obstruction of the proximal left anterior descending artery without collateral filling of this vessel. In the resting patient who has 134mCs myocardial imaging, we concluded that we primarily are visualizing varying degrees of scarred myocardium rather than reversibly ischemic myocardium.


Scintigraphic findings of uncommon focal manifestations of Haemophilus influenzae septicemia. Haemophilus influenzae septicemia is usually associated with a clinical focus of infection. The investigators describe early scintigraphic findings in some uncommon manifestations of H. influenzae septicemia.