High reliability rates of spatial pattern analysis by vectorcardiogram in assessing the severity of eccentric left ventricular hypertrophy. In 33 patients, including 12 control subjects and 21 with eccentric LVH, LV mass determined by angiocardiogram was correlated to 26 VCG measurements (Frank system) calculated from the scalar X, Y, and Z leads. The results demonstrated that the most reliable indices of VCG in assessing the severity of eccentric LVH determined by angiocardiogram were the magnitude of the spatial mean QRS vector and the time of the spatial maximal QRS vector ("spatial VAT"), of which correlation coefficients were 0.93 and 0.93, respectively. Such high correlation coefficients have never been obtained with the usual ECG analysis. These findings strongly suggest that (1) increased QRS voltage and usual prolonged QRS duration in eccentric LVH are due to an increase in LV mass, and (2) prolonged VAT observed in eccentric LVH is closely related to an anatomic alteration, namely, the greater distance of intra-ventricular conducting pathways as the result of LV dilatation, as an increase in LV mass is usually paralleled by the grade of the chamber enlargement in this type of LVH. Regarding the T loop, correlations between the LV mass and the VCG measurements were less as compared to those of the QRS loop. In general, T changes in moderate or severe LVH may be also related to a certain altered cardiac muscle state, in addition to an increase in LV mass. Angiocardiographic and light microscopic findings of a patient with eccentric LVH in whom a widened QRS-T angle was demonstrated to an extent much more than that expected with an increase in LV mass are presented and discussed. The spatial pattern analysis by VCG is very useful and reliable in assessing the severity of eccentric LVH.


Echocardiographic diagnosis of tetralogy of Fallot. The echocardiographic features of tetralogy of Fallot were defined in 25 patients with this malformation proved by cardiac catheterization. The echocardiographic characteristic that was present in all patients and that was most sensitive was the abrupt ending of the interventricular septal echoes with the aorta overriding the ventricular septal defect. The following additional echocardiographic features were frequently demonstrated in these 25 patients: right ventricular enlargement (20 patients), hypertrophy of the interventricular septum (20 patients), diminution of the right ventricular outflow tract (21 patients) and widening of the aorta (24 patients). The suggestion is made that the most specific echocardiographic pattern of tetralogy of Fallot is the finding of several echocardiographic abnormalities rather than the single feature of aortic overriding. Recognition of the altered anatomic relation coupled with a complete echocardiographic evaluation of all cardiac structures is a reliable means of diagnosing tetralogy of Fallot.


Severe alcoholic cardiomyopathy reversed with abstention from alcohol. In a chronic alcoholic with a severe congestive cardiomyopathy the angiographic and hemodynamic evidence of left ventricular dysfunction was completely reversed after 1 year of abstinence. At the time of initial presentation two of the traditional hallmarks of a poor prognosis were present, namely, a long exposure to alcohol before the onset of symptoms and severe diffuse left ventricular dilation and hypokinesis (ejection fraction 14.9 percent). Yet, today, 18 months later he is asymptomatic, receiving no medications and has normal left ventricular function. A reexamination of prognostic factors in alcoholic cardiomyopathy may be indicated.


Clinical evaluation of a new measles-mumps-rubella trivalent vaccine. In a series of clinical studies of a combined measles (Schwarz strain), mumps (Jeryl Lynn strain), and rubella (Cendehill strain) vaccine, 1,481 children received the vaccine or a placebo. The vaccine did not cause any significant reactions. The frequencies of mild, transient fever or rash or both in triple-susceptible vaccinees were similar to those that follow use of Schwarz strain measles vaccine alone. Measles, mumps, and rubella seroconversion rates in triple-susceptible vaccinees ranged from 95% to 100%. Geometric mean antibody titers were as high as those that usually result from use of these same virus strains as monovalent vaccines.


Echocardiographic studies of left ventricular disease in Ullrich-Noonan syndrome. Echocardiography has been used for cardiovascular evaluation of individuals and families with Ullrich-Noonan syndrome. Previously undiagnosed left ventricular disease has been found as a discrete lesion or in association with other cardiac abnormalities. This raises the estimated frequency of heart disease in the Ullrich-Noonan syndrome to about 50%. Since left ventricular disease in this syndrome may not be entirely typical of asymmetric septal hypertrophy, caution should be exercised in the echocardiographic diagnosis. To date, one notable difference between the echocardiograms in these patients and other patients with asymmetric septal hypertrophy is the absence of systolic anterior motion of the mitral valve. Since the most common cardiac lesion the the Ullrich-Noonan syndrome is pulmonary stenosis, the potential for septal thickening produced by severe pulmonary stenosis must also be taken into account.


Paraprosthetic-enteric fistula. Role of Preoperative endoscopy. A case of paraprosthetic-enteric fistula occurring after aortic aneurysectomy and Dacron graft placement is reported. Two and one-half years after aneurysectomy, the patient presented with the problems of fever of obscure origin, arthralgias, and anemia. The diagnosis of paraprosthetic-enteric fistula was made preoperatively by endoscopy. The role of endoscopy in the evaluation of postaneurysectomy complications is emphasized.


The role of additives in allergic vasculitis during intravenous hyperalimentation. A 39-year-old woman who had previously undergone a jejunoileal bypass for morbid obesity was receiving intravenous hyperalimentation. The patient developed allergic vasculitis while receiving fluid which contained a multi-vitamin solution. Rechallenge with this preparation resulted in an exacerbation of her skin lesions. The possible role of such additives in the development of unusual hypersensitivity reactions is discussed.


Kniest syndrome with dominant inheritance and mucopolysacchariduria. A mother and daughter with clinical and radiographic findings typical of the Kniest syndrome are reported. It is apparent that this syndrome is dominantly inherited and that sporadic cases may represent fresh mutations. Abnormally high keratan sulfate excretion was found, indicating that the Kniest syndrome is a mucopolysacchariduria.


Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. II. Clinicopathologic study of seven patients. A variety of renal structural and functional abnormalities have been associated with sickle cell disease. To define the relationship between the hemoglobinopathy and glomerular disease, clinicopathologic correlations, renal morphologic, ultrastructural immunohistologic and functional studies were performed on seven patients with clinical and laboratory evidence of glomerular disease. In addition, immunologic studies including isolation and characterization of cryoprecipitable immune complexes, and determination of immunoglobulin, total complement and complement component levels, and antibody titers to several antigens were performed in an attempt to define the etiologic and pathogenic mechanisms of the renal disease and its relationship to sickle cell anemia. Proteinuria was presnet in all patients. The nephrotic syndrome, hypertension, hematuria and renal insufficiency were found in more than one half the patients. All patients had membranoproliferative glomerulonephritis of varying degree; glomerular basement membrane splitting, electron dense deposits in the glomerulus; interstitial fibrosis, tubular atrophy and hemosiderin deposits were frequent. Immunoglobulin complement components (classif complement pathway) and renal tubular epithelial antigen were distributed in a granular pattern along the glomerular basement membranes of all patients studied by these methods. Cyroprecipitable complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen as well as antibody to renal epithelial antigen were detected in the circulation of some patients. There was no serologic evidence of activation of the alternate complement pathway. These studies demonstrated an immune deposit normocomplementemic nephritis associated with sickle cell anemia; they further support our hypothesis that the relationship is more then coincidental, and is mediated by glomerular deposition of immune complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen, the antigen possibly released after tubular damage secondary to oxygenation and hemodynamic alterations related to sickle cell disease.


An inexpensive laparoscopy system for female sterilization. Laparoscopy has become an established procedure for female sterilization. The cost of the equipment remains excessively high, thereby reducing its availability to all physicians and patients who desire and need it. We have described an inexpensive--but highly effective--female sterilization system utilizing equipment that should cost in the range of $400.00.


Mechanism of ethacrynic acid-induced choleresis in the rat. Ethacrynic acid (EA) was injected to rats with functional nephrectomy after a control period of steady-state bile flow sustained by taurocholate infusion. Biliary clearance of [14C]mannitol was measured in order to estimate canalicular bile flow and bile salt-independent fraction (BSIF). After EA infusion, bile flow increased by 56%; bile salt excretion rate decreased by 10%; electrolyte excretion rates all increased, principally Na+ and K+. Mannitol clearance increased in parallel with bile flow. The BSIF increased. EA was excreted into bile as a metabolite identified as the cysteine adduct of EA; its excretion rate was linearly correlated with the increment in bile flow. The results are consistent with the hypothesis that the biliary excretion of an EA derivative results in an osmotic water flow increasing the canalicular BSIF. Since EA ia a Na+-K+-ATPase inhibitor, it is necessary to reconsider the relationship between secretion of canalicular BSIF and active Na+ transport mediated by the Na+-K+-ATPase system.


Vitamin D-dependent, particulate calcium-binding activity and intestinal calcium transport. A vitamin D-dependent calcium-binding activity of relatively high molecular weight has been identified in the particulate fraction of rat small intestinal mucosa. The Ca-binding activity is sedimented at 140,000 X g after treatment of the mucosal particulate fraction with Triton X-114. Intestinal brush-border suspensions can also be used as starting material. The Ca-binding component is inactivated by heat and repeated freeze-thawing and consists of one or more protein complexes in the range of 0.5-1.0 million mol wt as indicated by gel filtration. The Ca-binding activity correlates positively with known features of the intestinal Ca transport mechanism, as demonstrated by studies of the distribution in the small intestine and the effects of vitamin D, dietary Ca, cycloheximide treatment, and rat age. It is suggested that the component might function in the transit of Ca across the brush-border surface to the cytosol of intestinal mucosal cells.


A group experience with chronically disabled adolescents. The author describes his experiences as the leader of a therapy group for adolescents with muscular dystrophy. The group progressed through discernible stages of dependence-flight, independence, regression, interdependence, disenchantment, and resolution. By the end of the experience, the group had developed more meaningful communication and interrelationships than they had exhibited previously. The author suggests that such groups could be helpful for other chronically disabled adolescents.


Skeletal abnormalities in the Kniest syndrome with mucopolysacchariduria. The roentgenographic and clinical findings are described in a mother and daughter with the Kniest syndrome associated with urinary keratan sulfate excretion. Osteoporosis, kyphoscoliosis, vertebral irregularity, pelvic deformity, flat femoral heads and enlargement of the ends of the long bones were the main roentgen findings. Irregularity of ossification on both sides of the growth plate was observed in the daughter, and marked degenerative changes were superimposed on several of the mother's abnormal joints. Abnormal mucopolysacchariduria, observed in both patients, and cataracts, fusion of the symphysis pubis, and deficiency of carpal bones, seen in the mother, have not been described previously.


Repair of massive septic abdominal wall defects with Marlex mesh. Marlex mesh was used to close the abdominal wall defect in six patients with septic wound dehiscence and intra-abdominal infection. The mesh was implanted under local anesthesia and served as a protective covering for the bowel and allowed early ambulation, including prone positioning of the patient for easier wound care. In four surviving patients, the Marlex mesh was covered by full thickness skin flaps after granulation tissue had covered the material. No patients had infected sinus tract formation or extrusion. Two patients had incisional hernias develop when the Marlex mesh was not sutured to the abdominal wall permanently. The use of Marlex mesh to cover infected defects in the abdominal wall when primary closure cannot be accomplished is suggested by our experience.


Peritoneoscopy: A valuable technic for surgeons. 1. Modern peritoneoscopy which uses advanced optics and instrumentation now available is a valuable technic that can and should be learned by surgeons. 2. Peritoneoscopy is a safe procedure with a high diagnostic yield and minimal discomfort and inconvenience to the patient. 3. Earlier and more frequent use of peritoneoscopy will enable the surgeon to give appropriate surgical treatment more promptly and avoid unnecessary exploratory celiotomy. 4. The value of this technic in seventy-five consecutive cases is reported. There was no mortality and negligible morbidity. The over-all diagnostic accuracy was 91 per cent. An accurate peritoneoscopic diagnosis avoided surgical exploration in forty-five patients, and in fifteen patients the peritoneoscopic diagnosis provided indications for prompt abdominal surgery.


Temperature dependence of brain ATPases in immature and adult rats. In immature rats the temperature dependence of Na+-K+ ATPase of a crude homogenate of brain shows a compex curve with two activity maxima. When EDTA was present in the homogenization medium the curve obtained was of simpler, curvilinear type showing an increased activity at temperatures above 20 degrees C. The Na+-K+ ATPase activity in similar preparation from adult brain were not complex but curvilinear whether EDTA was used or not; however, EDTA increased the activity at temperatures above 20 degrees C. When such chelating agents as EDTA or histidine were used in preparation of microsomes from immature rat brain, the temperature dependence curve of Na+-K+ ATPase in this membrane fraction was changed to a steeper and simpler curve with increased activity especially at temperatures above 20 degrees. These agents, however, did not eliminate totally the complex shape of curve found in microsomes prepared without the presence of any chelating agents. When microsomes were prepared by using NaI-technique the temperature dependence of this enzyme was linear between temperatures 15-14 degrees, the activity being 4-5-fold higher than in the ordinary microsomal preparation. A stimulation of the Mg2+ ATPase by Na+ ions (100mM) was found at temperatures below 30 degrees but an inhibition by the same concentration of Na+ at upper temperatures. This effect together with the lowered activity due to bivalent metal ions (e.g. Ca2+, Cu2+) in 'crude' preparations was thought to be reasons for the complex shape of temperature dependence curve of Na+-K+ ATPase activity.


Brain and spinal cord lesions in pigs inoculated with swine vesicular disease (UKG strain) virus and coxsackievirus B5. Pigs inoculated intravenously with swine vesicular disease virus (UKG strain), those inoculated with coxsackievirus B5, and other pigs exposed by pen contact to the same viruses developed diffuse encephalomyelitis. Perivascular cuffing, with lymphocytes and formation of neuroglia cell foci, were most prominent in telencephalon, diencephalon, and mesencephalon. Encephalitis was of mild to severe intensity. Severity of lesions was more extensive and severe in the pigs exposed to swine vesicular disease virus. Pen contact exposure to either of the 2 viruses caused a more severe central nervous system reaction than did intravenous inoculation. The type and the distribution of lesions produced by the 2 viruses indicate that they may be related.


Sch 1000: a new anticholinergic bronchodilator. Sch 1000 is a derivative of atropine with equivalent bronchodilator activity. A double blind controlled study of Sch 1000 administered to asthmatic subjects by inhalation in 4 doses from 10 mug to 80 mug was conducted. The onset of action was between 15 and 30 min, compared to 5 min for isoproterenol, but persisted for 4 hours compared to 1 hour for isoproterenol. The maximal level of bronchodilatation produced by Sch 1000 was comparable to but not as great as that after isoproterenol. Dose-response data suggested that maximal bronchodilatation may be achieved by 10 to 20 mug of Sch 1000; larger doses did not result in significantly greater increases in forced expiratory volume in 1 sec or maximal mid-expiratory flow. The Sch 1000-mediated increase in maximal mid-expiratory flow was significantly greater than that of forced expiratory volume in 1 sec. Fewer side effects were encountered after Sch 1000 than after isoproterenol and no atropine-like effects could be attributed to Sch 1000 in the doses studied.


Mithramycin in the treatment of systemic mastocytosis. A patient had systemic mastocytosis of 16 years' duration, with urticaria pigmentosa, osteopetrosis with severe bone pain, mastocytosis of the bone marrow with myeloid metaplasia, gastrointestinal malabsorption, and Cushingold features associated with prolonged usage of corticosteroids. Treatment with a single dose of mithramycin resulted in an abrupt disappearance of the patient's generalized bone pain, but it had little effect on his histamine release-type symptomatology.


Levodopa.

Levodopa. Levodopa administered alone or in combination with a peripheral decarboxylase inhibitor is at present the best means available for the control of Parkinson symptoms. It has proved particularly effective in Parkinson's disease and postencephalitic parkinsonism. In these disorders its continued administration for periods that now exceed five years has resulted in sustained therapeutic responses and a significant decrease in mortality rate. Levodopa has been shown to be a safe pharmacologic agent even after long-term usage. However, its potential for inducing side effects makes it essential that patients be carefully screened before use and monitored throughout the period of administration. Though not fully established and lacking FDA approval at this time, levodopa appears to be useful in reversing the symptoms of hepatic encephalopathy and as a diagnostic aid in assessing pituitary disorders as well as uncovering presymptomatic Huntington's chorea.


Essential fatty acid deficiency in human adults during total parenteral nutrition. Three patients undergoing prolonged total parenteral nutrition at home developed skin lesions, characterized by dryness and scaly appearance, initially confined to the folds but becoming subsequently generalized. Fatty acid measurements in plasma of these patients showed a markedly abnormal lipid pattern: accumulation of 5,8,11-eicosatrienoic acid (20:3omega9) and a high 20:3omega9-to-20:4omega6 ratio. When parenteral fat (Intralipid) was administered, 500 ml/day, serial measurements of fatty acids showed a progressive normalization of the abnormal pattern and a dramatic improvement in the skin lesions. It appears that the daily requirement for linoleic acid in the adult, particularly during the period of rapid anabolism, has not been clearly established. Because more and more patients are becoming partly or totally dependent on parenteral nutrition for prolonged periods of time, the availability of parenteral fat preparations is urgently needed.


Carbohydrate catabolism of selected strains in the genus Agrobacterium. Radiorespirometric and enzyme analyses were used to reveal the glucose-catabolizing mechanisms functioning in single strains of seven presumed Agrobacterium species. The Entner-Doudoroff and pentose cycle pathways functioned in A. radiobacter, A. tumefaciens, A. rubi, and A. rhizogenes. Whereas both catabolic pathways were utilized to an almost equal degree in the A. radiobacter and A. tumefaciens strains, use of the Entner-Doudoroff pathway predominated in the A. rubi and A. rhizogenes strains. A stellulatum catabolized glucose almost solely through the Entner-Doudoroff pathway. In A. pseudotsugae and A. gypsophilae, glucose was metabolized mainly through the Emden-Meyerhof-Parnas pathway; the pentose phosphate pathway was also utilized.


Quinidine photosensitivity.

Quinidine photosensitivity. Photodermatitis occurring in three patients taking oral quinidine sulfate cleared when the drug was discontinued and recurred when it was readministered. The dermatitis was experimentally reproduced with long-wave ultraviolet light (UV-A, 320-400 nm) in these three patients, who also exhibited a decreased minimal erythema dose (MED) to hot quartz irradiation. Patients taking quinidine who had no dermatitis exhibited normal MEDs and normal response to UV-A. Normal subjects injected intradermally with quinidine and irradiated with UV-A showed no reaction. These observations indicate that the photosensitive dermatitis to quinidine that occurred in the three patients is idiosyncratic and that the UV-A is at least partially responsible for the development of the dermatitis that correlates with the absorption of quinidine in the UV-A range. Quinidine must be considered among the drugs that can produce photosensitive dermatitis.


Chlorpromazine photoallergy. Coexistence of immediate and delayed type. A 54-year-old woman had a recurrent pruritic eruption in light-exposed areas. She had a combination of three types of hypersensitivity to chlorpromazine, ie, allergic contact dermatitis, photocontact dermatitis, and immediate allergic photosensitivity. Immediate wheal reactions were found after long-wave ultraviolet light irradiation at photopatch test and intradermal injection sites with chlorpromazine. These responses were differentiated from phototoxic reactions. A positive passive transfer reaction was also observed. To my knowledge, chlorpromazine photosensitivity of the immediate type has not been previously described.


Testosterone metabolism in the skin. A review of its function in androgenetic alopecia, acne vulgaris, and idiopathic hirsutism including recent studies with antiandrogens. Current concepts of testosterone metabolism in the human skin are reviewed, and the role of dihydrotestosterone in the pathophysiology of androgenetic alopecia, acne vulgaris, and idiopathic hirsutism is discussed. The hypothesis is submitted that a temporary, increased dihydrotestosterone formation at specific skin target sites at different ages causes the normal development of certain sexual characteristics, as well as the androgen-dependent skin disorders. Future treatment of these conditions is discussed in light of recent studies with antiandrogens.


Allergic contact dermatitis caused by idoxuridine. Patterns of cross reactivity with other pyrimidine analogues. Idoxuridine has been used for many years in the treatment of herpex simplex infections of the eye. Use of the drug for herpes simplex infection of the skin is increasing. Ophthalmologists have noted occasional conjunctival and corneal irritant reactions, but no true delayed cutaneous hypersensitivity has been verified. We report four cases of allergic contact dermatitis from idoxuridine, sensitized by both eye and skin applications. Cross reactivity to brominated and chlorinated, but not fluorinated, pyrimidine analogues is noted. Extensive patch testing indicates the general relationship between the structure of pyrimidine compounds and their antigenic cross reactivity.


(+)-catechin effects on x-rays irradiated skin of rats. The effect of (+)-catechin on the skin of rats previously irradiated was a net decrease of AMPS content and a partial recovery of the insoluble collagen-loss due to X-Rays.


[A contribution to the classification of seborrheic keratoses (author's transl)]. A clinico-statistical study is reported, basing on a material of 639 excised tumours which were defined histologically as seborrheic keratoses. All statements concerning clinical diagnoses and differential diagnoses, localization, development, age and sex of patients were transferred to punch cards. By means of a suitable EDA program, basic counts and a multidimensional analysis of conditioned frequencies [14] were performed. The results indicate, that the different clinical forms of seborrheic warts, often discriminated in the literature, are variants of the same entity.


Airway disease caused by phenolic (phenol-formaldehyde) resin exposure. A standardized respiratory questionnaire and pulmonary function tests, including measurement of forced vital capacity (FVC), one-second forced expiratory volume (FEV1.0), and maximum expiratory flow rate at 50% FVC (MEF50%), were administered to five groups of employees in a filter-manufacturing plant to determine the acute and chronic effects of exposure to phenolic resin fumes. Employees exposed for more than five years had lower FEV1.0/FVC and MEF50%/FVC ratios than a group that had smoked more but that had never been consistently exposed to resin fumes. The existence of chronic airway obstruction was also evident by a slight excess of chronic cough and sputum production in the exposed groups. However, in spite of the high proportions of subjects reporting acute respiratory symptoms, we found only small decreased in pulmonary function during the workday and workweek.


[Hemodynamic aspect of infundibular hypertrophy of pulmonary valve stenosis]. Reactional infundibular hypertrophy in pulmonary valve stenosis is usually assessed on the catheterization curves obtained in the infundibulum and in the inflow tract of the right ventricle. It is usually indicated by a peculiar pattern of the infundibular curve: its descending branch is more rapid than in the inflow tract and is slightly curvilinear. This deformity is the more marked the more intense the hypertrophy. Simultaneously a mid-late systolic murmur is recorded into the infundibulum the more intense and high-pitched the more marked the hypertrophy. Comparison with the angiocardiographic data and the operative findings showed a good correlation.


[Rupture of the tricuspid cordae simulating a right intraventricular tumor]. Ruptured chordae tendinae of the tricuspid valve is exceptional. It results in an intense valvular incompetence through systolic eversion of one leaflet. In fact, this is not always the case, and in patient reported, the clinical picture suggested an obstacle to right ventricular ejection with paroxysmal phenomena of the faintness type, indicating the temporary obstruction of the pulmonary pathway. Right cine-angiocardiography demonstrated a mobile intraventricular neoformationreaching in systole the pulmonary sub-valvar area. No tumour was found on operation. The patient died in the post-operative period. On post-mortem examination there was a rupture of tricuspid chordae tendinae and a raise of the anterior leaflet of the tricuspid valve into the pulmonary infundibulum. Rupture could be related to a severe thoracic trauma which had occurred 17 years previously.


Effect of protective agent against lipid-solvent-induced damages. Ultrastructural and scanning electron microscopical study of human epidermis. The ultrastructural and relief (cyto-architectural) changes of human epidermis following exposure to a protective gel and acetone or kerosene were studied in healthy volunteers. Topical applications of acetone and kerosene on unprotected skin produced cell damage and a disorganized pattern in the upper layers of epidermis. The ultrastructural changes following acetone consisted of large paranuclear vacuoles, swollen mitochondria, and clumped tonofilaments. Severe disorganization with intense cytolysis and enlarged intercellular spaces occurred after exposure to kerosene. Scanning electron microscopy revealed edematous connified cells (corneocytes) following acetone exposure, whereas kerosene induced the occurrence of large lacunae in the swollen corneocytes. The application of a protective agent prior to solvent exposure substantially reduced the ultrastructural and relief changes of epidermal cells.


Evaluation of endarterectomy for aortoiliac and aortoiliofemoral occlusive disease. During the past 11 years, 180 patients with aortoiliac and aortoiliofemoral occlusive disease were treated exclusively by endarterectomy. There were 59 patients in the former group and 121 patients in the latter group. A standard method of aortoiliac endarterectomy was applied to all patients. However, when disease extended to the external iliac and common femoral arteries, the eversion endarterectomy proved to be an invaluable technical aid. Cumulative patency rates to 11 years for the aortoiliac group was 85.7%, and for the aortoiliofemoral group it was 90.6%. Our results suggest that endarterectomy is the procedure of choice for the management of obilterative disease in the aorta, iliac, and femoral arteries.


Host response to implanted dacron grafts. A comparison between mesh and velour. Segments of open Dacron mesh grafts were subcutaneously implanted in rats and harvested for a period of up to 12 weeks after operation at serial intervals. The gross and histologic events of the host response to the external surface were compared to that of segments of low-porosity Dacron velour implanted in a similar fashion. Mature collagen, generously vascularized with new capillaries, was noted throughout the mesh within three to four weeks, while a tightly bonded inner fibrous layer had formed from the surrounding tissues. Major segments of velour floated in amorphous caseous material for up to five weeks. These pools of debris with their concomitant inflammatory response slowly resolved during a ten-week period. This prolonged healing may contribute to eventual graft closure by progressive fibrosis and extrinsic contracture.


Injury to the ureter during laparoscopic tubal sterilization. As the use of laparoscopy and laparoscopic tubal sterilization has increased, a number of serious complications have been reported. A case is described in which the ureter was damaged during laparoscopic sterilization. The majority of serious complications associated with laparoscopic sterilization have been burn injuries resulting from the use of cautery instruments. Thermal injuries are likely to occur when the operator is inexperienced, and when cautery instruments of the high-energy type are used. Meticulous technique is required in the performance of laparoscopic sterilization and low-energy "cold cautery" units should be used in this procedure.


Using celioscopy to determine stages of intra-abdominal malignant neoplasms. From January 1973 through June 1974, 23 patients underwent celloscopy to assess the extent of intra-abdominal malignancy. Of the 23 patients in the study, eight were spared a needless exploratory procedure. Three patients had potentially curative surgery after intrahepatic neoplasm suggested by liver scintiscan was excluded by celloscopy. The therapies of eight patients were greatly altered after the extent of hepatic or peritoneal disease was de-ermined. Four patients had no change in treatment as a result of celloscopy. Three additional patients underwent celloscopy to determine the cause of an intra-abdominal mass. No complications occurred in these patients. We conclude that celloscopy prior to a major operative procedure may assist in determining the stage of intra-abdominal malignant disease and may lead to notable changes in patient management.


Filtration characteristics of polyester mesh (Pall) micropore blood transfusion filter. Stored human blood of varying age was passed through polyester mesh (Pall) micropore blood transfusion (pore size, 40 mu). Passage through the filter resulted in decreased screen filtration pressure (SFP) of the blood and increased filter weight. Mumerous microaggregates were removed, but SFP did not return to normal after filtration. On the basis of this research, we conclude that polyester mesh micropore blood transfusion filters are not as effective as Dacron wool (Swank) transfusion filters in removal of micro-aggregates from stored human blood. If a polyester mesh filter must be used, it is recommended that once occlusion of the filter has occurred, the filter should then be discarded and another inserted.


[Changes in the lungs and the mass of the right ventricle of the heart in chronic hypoxia (experimental-morphological study)]. In experiments on 105 white rats using histological, histochemical, and morphometric methods the state of the lungs following daily "rises" in a pressure chamber to the "hight" of 5000--9000 m at verious time intervals--from 1 day to 9 weeks was studied. In 18 animals "ascents" were preceded by sinistral pulmonectomy. In parallel, the heart was investigated by the method of separate weighing. At initial stages changes in the lungs were characterized predominantly by impairment of the blood- and lymphocirculation. Subsequently, disorders of the microcirculation were observed to diminish and compensatory-hypertrophic changes in the lung tissue and vessels were noted. As the effect of hypoxia continued, sclerotic processes appeared, and extensive focal emphysema developed. These changes were manifested in a greater degree and appeared sooner with an increase in the extent of rarification of the atmosphere. Possibilities for adaptation to hypoxia in animals with the one lung were considerably lower as compared with normal ones. Hypercapnia produced an effect similar to that of hypoxia, making its influence on the structural elements of the lungs graver. Prolonged hypoxia led to hypertrophy of the right ventricle of the heart; the main factor in development of which the authors considered the elevation of the tonus and subsequent structural rearrangement of small vessels in the form of myoelastosis and myoelastofibrosis of the walls with narrowing of the lumen.


Skin irritancy and sensitivity to laundry detergents containing proteolytic enzymes. Part II. The late type contact sensitizing effect of alkaline protease enzymes (PE) on the intact human skin has been investigated in the present study. The immune process of sensitisation was induced with "Tenzym prilled" (TP, Grindstedvoerket) and with "Maxatase" (M, Gist-Brocades) protease enzymes in the epicutaneous test (ET), using concentration series and various durations of application. The ETs were made on the intact (symptom-free) skin, as well as under conditions promoting the subcorneal penetration of PE. Challenge was carried out at 21 to 30 days following induction of 2092 subjects, and at 2 to 5 months on 1624 subjects. Despite the large number of subjects tested, contact sensitisation developed in none of the cases, although the inducing exposure took place under conditions promoting the immune process of sensitisation. In 60 individuals suffereing from occupational dermatitis on regular contact with PE and having no symptoms of early type inhalative allergy (mucous membrane changes, bronchial asthma-like symptoms) were challenged also by the intradermal test. No reaction was noted in any of them at 10 and 30 minutes, as well as at 24 and 48 hours following the test. Next the influence of PE is analysed in the induction or increased severity of the irritation caused by bioactive laundry detergents. The studies involved the use of serial dilutions of "Biopon" (Bn) laundry detergent containing TP or M, or not containing PE, respectively, by means of the ET. A total of 740 series (5220 tests) of the three variants were applied in dilution series to intact skin surface, as well as to pathologically and arteficially lsioned skin areas. The Bn variants containing and not containing PE increased the number of irratative reactions in essentially the same degree. This suggests that the irritative effect is not due to the presence of PE, but to the laundry-active detergents (WAS) of Bn in the first place, and to a lesser extent to its other ingredients.


Using the HmL1 strain of Histomonas meleagridis in evaluating chemotherapeutants in chicks. Ten-day-old White Leghorn cockerels were inoculated per cloaca with 500,000 culture forms of the HmL1 strain of Histomonas meleagridis. Birds dying on the 6th and 7th days and birds necropsied 7 days postinoculation had prominent cecal and liver lesions indicative of severe histomoniasis. Dose responses were obtained with three 1,2-disubstituted 5-nitroimidazoles blended into the feed at various concentrations, demonstrating the utility of this virulent strain in chemotherapy studies.


Gene topography and function. I. Gene expression in germinating conidia of Neurospora crassa. In an attempt to find clues for the significance of the gene ordering along the eukaryotic chromosome, a system consisting of germinating conida of Neurospora crassa was studied. Thirteen enzyme activities corresponding to genes widely distributed on five chromosomes were determined in dormant and in germinating conidia. Ten of these enzymes showed lower activities in the resting state, and the time patterns of their increase were determined during germination. The results obtained do not support a scheme of sequential expression of genes during the emergence from dormancy as a counterpart of the sequence of the corresponding genes along the chromosome. Two of the loci studied were analyzed both in the normal (wild-type) ordering and in a translocated position in which the two genes are located in an inverted order respective to the centromere and farther apart from it. The altered order of the genes did not influence significantly the time and pattern of increase in the activities of the corresponding enzymes.


Mechanics of the isolated ventricular myocardium of rats conditioned by physical training. Force-velocity relations from after-loaded contractions, from isometric and isotonic QR experiments, resting-tension curves and biochemical analyses were conducted on sixteen trabecular muscles (SH) from hearts of rats conditioned by eight weeks of swimming training (increase in heart weight 8%), and compared to a control (CH) of eighteen trabecular muscles. (SH) showed increased tension development (p less than 0.01), whereas the diastolic properties remained almost unchanged. Analysis of the amount of hydroxyproline did not prove any variation. Vmax of (SH) was only slightly increase when there was a singificnat rise in actomyosin and myosin ATPase activity, while PO of the force-velocity relations of (SH) on the x axis (tension) shifted clearly to the right (p less than 0.01). Consequently, the maximum instantaneous power of (SH), expressed by the maximum rectangular plane under the force-velocity curve, increased considerably (p less than 0.01) in comparison with (CH). The experiments show that haemodynamic load induced by training does not alter the passive properties of the myocardium, but does bring about an increase in the contractile capabiltiy.


Editorial: Subunits of myosin. Relations to ATPase activity and mechanical function of muscle. Under certain conditions the specific ATPase activity of myosin of a given muscle can be altered. The cause of this alteration can only lie in the myosin molecule itself. To produce an enzymatic activity of myosin, an interaction between their light and heavy chains is necessary. However, the specific activity appears to be determined mainly by light chains. Hence, one ought also to look for a basis of the changed activity in changes of the subunits of myosin. There are strong indications that the alterations in specific activity are accompanied by changes in the relative stoichiometry of the essential light chains of the respective myosin preparation. They differ in their pattern of subunits. The specific activity of a given kind of myosin seems to be determined by the combination of their light chains. Thus, a close correlation exists between these two properties of myosin (ATPase activity and structure of its molecule). There are sufficient indications, that these two properties of myosin correlate also with the mechanical capabiltiy of the corresponding muscle. Particularly the results of cross innervation studies demonstrate a close correlation between these three properties in skeletal muscle. The single subunits of myosin are produced and degraded independently and at heterogenous rates. The synthetis of these subunits is significantly accelerated in response to work overload. Thus, it is quite likely that the individual chains are non-coordinately synthesized, giving rise to variations in the relationship of different molecule types of myosin with different specific ATPase activity. Hence, the control mechanism to synthesize the individual subunits could also be the regulative mechanism to produce a myosin of the specific ATPase activity appropriate to the activity pattern of tissue.


Quantitative measurement of local blood flow with heat clearance. Measurements of the local blood flow through organs by means of heated thermistor-probes enable one to perform continuous recordings of flow. The principle is based on the measurement between a heated and an unheated probe, both implanted in the tissue or placed on the superficial layer of the organ. The flow-measure for this type of blood flow recording is the heat transported from the heated site of the tissue. It is measured in cal-cm(-1)-sec(-1)-degree C(-1). This is the dimension of the heat conductance. Quantification of continuous blood flow measurements in ml flow/g tissue-min has been carried out with combinations of gas clearance and heat transport. It has now become possible to measure blood flow in ml blood-ml(-1) tissue-min(-1) solely with the aid implanted thermistors. Two types of local blood flow measurements are described. 1. Measurements with "slug heating" by which a thermistor is heated for a very short time and the temperature change is subsequently recorded. 2. The measurement of flow by sudden introduction of heat, if a heating coil around a micro-thermistor is switched on or off and the course of the tissue temperature is subsequently followed. It is proven, that the temperature of a point-shaped micro-thermistor in nonperfused tissue and in homogeneous perfused tissue differs only by an exponential factor (see article) where uslug is the temperature field after a slug injection of heat dependent on location, time, blood flow (phi) and partition coefficient for heat (lambda) and where index 0 = unperfused tissue. If the heater is not heated in the form of a delta function but is switched on and the temperature is subsequently recorded or if the heater, after a period of constant temperature, is switched off, the derivatives in respect to time differ only by an exponential factor and can be used as a measure of flow. The evaluation of blood flow is described in detail. The measurements show the following advantages, compared with former techniques: 1. Heat clearance and continuous blood flow measurements by means of heat transport measurements are both possible at the same site. 2. No other operation and procedures are necessary except implantation of the thermistor. 3. Turning on the heater does not affect the tissue and does not cause emotional reactions. As examples the measurements of local blood flow in brain tissue and in the myocardium of conscious animals are described.


The effects of inhibition of gluconeogenesis on ketogenesis in starved and diabetic rats. Experiments were performed in which the effects of inhibiting gluconeogenesis on ketone-body formation were examined in vivo in starved and severely streptozotocin-diabetic rats. The infusion of 3-mercaptopicolinate, an inhibitor of gluconeogenesis (DiTullio et al., 1974), caused decreases in blood [glucose] and increases in blood [lactate] and [pyruvate] in both normal and ketoacidotic rats. Patterns of liver gluconeogenic intermediates after 3-mercaptopicolinate infusion suggested inhibition at the level of phosphoenolpyruvate carboxykinase. This was confirmed by measurement of hepatic oxaloacetate concentrations which were increased 5-fold after 3-mercaptopicolinate administration. The infusion of 3-mercaptopicolinate caused a decrease in total ketone-body concentrations of 30% in starved rats and 73% in the diabetic animals. Blood glycerol and hepatic triglyceride concentrations remained unchanged. The decreases in ketone-body concentrations were associated with increases in the calculated hepatic cytosolic and mitochondrial [NADH]/[NAD+] ratios. The decrease in ketogenesis seen after inhibition of gluconeogenesis may have resulted from an inhibition of hepatic fatty acid oxidation by the more reduced mitochondrial redox state. It was concluded that gluconeogenesis may stimulate ketogenesis by as much as 30% in severe diabetic ketoacidosis.


The effect of butacaine on adenine nucleotide binding and translocation in rat liver mitochondria. The effect of the local anaesthetic, butacaine, on adenine nucleotide binding and translocation in rat liver mitochondria partially depleted of their adenine nucleotide content was investigated. The range of butacaine concentrations that inhibit adenine nucleotide translocation and the extent of the inhibition are similar to the values obtained for native mitochondria. Butacaine does not alter either the total number of atractyloside-sensitive binding sites of depleted mitochondria, or the affinity of these sites for ADP or ATP under conditions where a partial inhibition of the rate of adenine nucleotide translocation is observed. The data are consistent with an effect of butacaine on the process by which adenine nucleotides are transported across the mitochondrial inner membrane rather than on the binding of adenine nucleotides to sites on the adenine nucleotide carrier. The results are briefly discussed in relation to the use of local anaesthetics in investigations of the mechanism of adenine nucleotide translocation.


A simple and rapid method for the preparation of adenosine triphosphatase from submitochondrial particles. An almost pure form of the bovine heart mitochondrial adenosine triphosphatase (ATPase) is released from the membrane by shaking submitochondrial particles with chloroform. Analyses on polyacrylamide gels and by electron microscopy, and also sensitivity to inhibitors, show that the chloroform-released enzyme is similar to other ATPase preparations from bovine heart mitochondria.


Studies on the linkage between teichoic acid and peptidoglycan in a bacteriophage-resistant mutant of Staphylococcus aureus H. 1. In addition to poly(ribitol phosphate) the walls of a bacteriophage-resistant mutant of Staphylococcus aureus H contain glycerol phosphate residues that are not removed on digestion with trypsin or extraction with phenol. 2. The glycerol phosphate is present in a chain, containing three or four glycerol phosphate residues, which is covalently attached to the peptidoglycan through a phosphodiester linkage to muramic acid; this linkage is readily hydrolysed by dilute alkali. 3. The degradative studies described suggest that the poly(ribitol phosphate) chains of the wall teichoic acid may be attached to the wall by linkage to this glycerol phosphate oligomer.


The nature of the protein moieties of cartilage proteoglycans of pig and ox. Proteoglycans extracted with 4M-guanidinium chloride from pig laryngeal cartilage and bovine nasal septum were purified by density-gradient centrifugation in CsCl under 'associative' followed by 'dissociative' conditions [Hascall & Sajdera (1969) J. Biol. Chem. 244, 2384-2396]. Proteoglycans were then digested exhaustively with testicular hyaluronidase, which removed about 80% of the chondroitin sulphate. The hyaluronidase was purified until no proteolytic activity was detectable under the conditions used for digestion. The resulting 'core' proteins of both species were fractionated by a sequence of gel-chromatographic procedures which gave four major fractions of decreasing hydrodynamic size. Those that on electrophoresis penetrated 5.6% (w/v) polyacrylamide gels migrated as discrete bands whose mobility increased with decreasing hydrodynamic size. The unfractionated 'core' proteins had the same N-terminal amino acids as the intact proteoglycan, suggesting that no peptide bonds had been cleaved during hyaluronidase digestion. Alanine predominated as the N-terminal residue in all the fractions of both species. Fractions were analysed for amino acid, amino sugar, uronic acid and neutral sugar compositions. In pig 'core' proteins, the glutamic acid content increased significantly with hydrodynamic size, but in bovine 'core' proteins this trend was less marked. Significant differences in amino acid composition between fractions suggested that in each species there was more than one variety of proteoglycan. The molar proportions of xylose to serine destroyed on alkaline beta-elimination were equivalent in most fractions, indicating that the serine residues destroyed were attached to the terminal xylose of chondroitin sulphate chains. The ratio of serine residues to threonine residues destroyed on beta-elimination, was similar in all fractions of both species. Since the fractions of smallest hydrodynamic size contained less keratan sulphate than those of larger size, it implies that in the former the keratan sulphate chains were shorter than in the latter.


The effects of ammonium, inorganic phosphate and potassium ions on the activity of phosphofructokinases from muscle and nervous tissues of vertebrates and invertebrates. 1. The effect of NH4+, Pi and K+ on phosphofructokinase from muscle and nervous tissues of a large number of animals was investigated. The activation of the enzyme from lobster abdominal muscle by NH4+ was increased synergistically by the presence of Pi or SO4(2-). In the absence of K+, NH4+ plus Pi markedly activated phosphofructokinase from all tissues studied. In the presence of 100 mM-K+, NH4+ plus Pi activated phosphofructokinase from nervous tissue and muscle of invertebrates and the enzyme from brain of vertebrates, but there was no effect of NH4+ plus Pi on the enzyme from the muscles of vertebrates. Nonetheless, NH4+ plus Pi increased the activity of vertebrate muscle phosphofructokinase in the presence of 50 mM-K+ at inhibitory concentrations of ATP, i.e. these ions de-inhibited the enzyme. In the absence of NH4+ plus Pi, K+ activated phosphofructokinase from vertebrate tissues at non-inhibitory ATP concentrations, but the effect was less marked with the enzyme from invertebrate tissues. Indeed, high concentrations of K+ (greater than 50 mM) caused inhibition of invertebrate tissue phosphofructokinase. Of the other alkali-metal ions tested, only Rb+ activated phosphofructokinase from lobster abdominal muscle and rat heart muscle. 2. The properties of lobster abdominal-muscle phosphofructokinase were studied in detail. This muscle was chosen as representative of invertebrate muscle because large quantities of tissue could be obtained from one animal and the enzyme was considerably more stable in tissue extracts than in extracts of insect flight muscle. In general, the properties of the enzyme from this tissue were similar to those of the enzyme from many other tissues: ATP concentrations above an optimum value inhibited the enzyme and this inhibition was decreased by raising the fructose 6-phosphate or the AMP concentration. In particular, NH4+ plus Pi activated the enzyme at noninhibitory concentrations of ATP and they also relieved ATP inhibition (see above). 3. It is suggested that increases in the concentration of NH4+ and Pi, under conditions of increased ATP utilization in certain muscles and/or nervous tissue, may play a part in the stimulation of glycolysis through the effects on phosphofructokinase (the effect may be a direct activation and/or a relief of ATP inhibition). Changes in the concentration of NH4+ and Pi are consistent with this theory in nervous tissue and the anaerobic type of muscles. The role of AMP deaminase in production of NH4+ from AMP in these tissues is discussed in relation to the control of glycolysis.


Salmonella typhimurium HfrA, a mutant in which adenosine triphosphate can drive amino acid transport but not energy-dependent nicotinamide nucleotide transhydrogenation. In contrast with wild-type Salmonella typhimurium LT2, strain HfrA did not have ATP-driven energy-dependent transhydrogenase activity, although ATP-dependent quenching of atebrin fluorescence was normal. Respiration-dependent and energy-independent transhydrogenase, and Ca2+-activated ATPase (adenosine triphosphatase) activities were similar in both strains. Purified ATPases from the two strains had similar specific activities, similar subunit polypeptides, and were equally effective in restoring energy-dependent transhydrogenase activities to membrane particles of strain LT2 from which the ATPase had been stripped. The purified ATPases from both strains could restore respiration-dependent but not ATP-dependent transhydrogenation to stripped particles of strain HfrA. Both strains grew aerobically equally well on salts media containing glucose, malate, succinate, citrate, acetate, pyruvate, fumarate, lactate or aspartate as substrates. Growth on glucose under anaerobic conditions was similar. Strains LT2 and HfrA were equally effective in the accumulation under both aerobic and anaerobic conditions of the amino acids proline, phenylalanine, histidine, lysine, isoleucine and aspartic acid. Inhibition of amino acid accumulation by KCN and dicyclohexylcarbodi-imide occurred to the same extent in both strains. The complete inhibition by dicyclohexylcarbodi-imide of amino acid uptake under anaerobic conditions suggested that ATP could drive amino acid uptake in both strains. The ability of strain HfrA to carry out ATP-dependent transport or quenching of atebrin fluorescence but not ATP-dependent transhydrogenation is different from the wild-type strain and from any previously described energy-coupling mutant. It is difficult to reconcile the properties of this mutant with the chemiosmotic hypothesis.


Fenfluramine and 5-hydroxytryptamine. Part 2: Involvement of brain 5-hydroxytryptamine in the anorectic activity of fenfluramine. As it is well-known, fenfluramine produces anorexia and decrease in brain 5-hydroxytryptamine (5-HT). As it has been suggested that the anorectic effect of fenfluramine may be due to a release of brain 5-HT, we have examined the influence of several drugs active on 5-HT mechanisms and metabolism, on the anorexigenic activity of fenfluramine. These studies were made in relationship with the depletion of 5-HT levels and the concentration of brain fenfluramine or m-trifluoromethyl-isopropylamine. The results have confirmed the involvement of a tryptaminergic mechanism in fenfluramine anorexia and suggest the hypothesis that fenfluramine itself can interfere with the serotoninergic system in the brain (stimulation of tryptaminergic neurons directly).


Relapsing polychondritis. Electron microscopic study of ear cartilage. Light microscopic and for the first time electron microscopic (EM) studies of involved elastic ear cartilage in a patient with relapsing polychondritis confirm the superficial location of the inflammatory reaction. EM studies of deep cartilage were identical to those on controls except for a rare necrotic cell. Superficial cartilage showed a finely granular electron-dense material. This material, which may be protein, possibly of enzyme or immunoglobulin origin, also surrounded some elastic fibrils. Findings of predominantly superficial changes and the multisystem disease in the present patient and in many others suggest that the cartilage destruction is part of a systemic inflammatory disease.


Predictive tests for malignant hyperpyrexia. Four carriers of the abnormal trait for malignant hyperpyrexia have been studied to determine the value of the various methods of carrier detection. Tests included enzyme estimations, histochemistry, electronmicroscopy, biochemistry and in vitro exposure of muscle strips to halothane. By combining these procedures it is possible to detect all the asymptomatic carriers of this disease.


Bronchial carcinoma with eosinophilia and cardiomegaly. A patient with a giant cell carcinoma of the bronchus presented with headache and flushing attacks and a blood eosinophilia. He developed a right bundle branch block and later congestive cardiac failure. At post mortem he was found to have the appearance of Loeffler's endocarditis. A tentative mechanism for these events is proposed.


Ascorbic acid and glycosaminoglycan and lipid metabolism in guinea pigs fed normal and atherogenic diets. The effect of low and high doses of ascorbic acid on glycosaminoglycan and lipid metabolism was studied in guinea pigs fed both normal and atherogenic diets. The high dose of ascorbic acid (25 mg/100 g body weight/day) decreased the cholesterol level in the liver and aorta but not in the serum in animals fed the normal diet in comparison with those fed the low dose of ascorbic acid (0.1 mg/100 g body weight/day). In animals fed the atherogenic diet, cholesterol decreased in the serum and liver, but not in the aorta. Serum triglycerides were not affected by the dose of ascorbic acid in the group on the normal diet, but in the animals receiving the atherogenic diet, the high dose of ascorbic acid caused serum triglycerides to decrease when compared with the low dose. Hepatic and aortic triglycerides decreased in groups on normal and atherogenic diets receiving the high dose of ascorbic acid. Lipoprotein lipase activity was not affected in the aorta by the dose of ascorbic acid either in the normal or atherogenic diet group. It was increased in the liver and heart in both the groups receiving the low dose of ascorbic acid but decreased in the high dose group. The concentration of all the glycosaminoglycans significantly increased in the aorta of animals on normal diet receiving the high dose of ascorbic acid when compared with the low dose group. In the group on the atherogenic diet, hyaluronic acid was not affected, but all the sulphated glycosaminoglycans increased in the animals receiving the high dose when compared with those receiving the low dose. In the liver all the sulphated glycosaminoglycans increased while hyaluronic acid decreased in both the normal and atherogenic diet groups receiving the high rather than the low dose of ascorbic acid. L-Glutamine:D-fructose-6-phosphate aminotransferase and UDPG dehydrogenase, two key enzymes in the biosynthesis of precursors of glycosaminoglycans, were studied in relation to the dose of ascorbic acid. Hepatic aminotransferase activity was higher both in the normal and atherogenic diet groups when receiving the high rather than the low dose of ascorbic acid. UDPG dehydrogenase was not affected by the dose of ascorbic acid. The activities of the degrading enzymes -- hyaluronidase, beta-glucuronidase, beta-hexosaminidase and aryl sulphatase -- significantly increased both in the normal and atherogenic diet groups when receiving the low rather than the high dose of ascorbic acid. The concentration of PAPS, sulphate activity and sulphotransferase activity were all increased in both the normal and atherogenic diet groups receiving the high dose of ascorbic acid.


Specific and nonspecific channels leading to proteolysis in antibody preparations. Current ways of fractionating immune sera give rise in the guinea-pig species to an active plasmin that contaminates antibody preparations. The enzyme appears as a free molecule separable from the immunoglobulin. In contrast, when a purified antibody has been obtained through the immunoabsorption process, plasmin activated during the contact between antibody and polymer binds firmly to the immunoglobulin. This phenomenon occurs separately and indistinctly with IgG1 and IgG2. Moreover, the alternate pathway of complement activation could be a tributary to the plasmin system.


A follow-up of tetracycline-treated rosacea. With special reference to rosacea keratitis. Seventy patients with rosacea were treated with systemic tetracycline for 6 months. Sixty-eight of them cleared with treatment. After withdrawal of the drug seventeen relapsed immediately and the overall relapse rate over 4 years was 69%. The serum tetracycline levels were not significantly different in two patients who failed to respond. Six patients had rosacea keratitis and responded dramatically within 1 month. Symptoms recurred as the drug was withdrawn. It is suggested that rosacea patients with keratitis should receive early and prolonged tetracycline medication.


Structural and enzymatic properties of adenine 1-oxide nucleotides. We decribed the preparation of adenine 1-oxide nucleotides by oxidation of the natural compounds with monopermaleic acid in aqueous solutions at neutral pH, with an overall yield after chromatographic purification between 75 and 80%. If irradiated, the adenine 1-oxide nucleotides undergo a photochemical rearrangement reaction, the main photoproducts in aqueous solution at alkaline pH being the corresponding isoguanine nucleotides. The modified ring vibration pattern of the 1-oxide analogues as well as the 13C chemical shift indicate a loss of aromaticity as compared to the natural compounds. Coupling constant measurements show that the dihedral angle between the 31POC and OC13C planes is around 180degree, i.e., trans, as in the natural adenine nucleotides. The modified adenine nucleotides were tested as potential substrates and/or inhibitors of mitochondrial processes, as substrates of varous phosphotransferases from mitochondria or cytosol, and as allosteric effectors in the reactions catalyzed by glutamate dehydrogenase and phosphofructokinase. Although the adenine 1-oxide nucleotides are not recognized by the translocase system of the inner mitochondrial membrane, they are good substrates for mitochondrial phosphotransferases located in the intermembrane space. Similarly, they participate in the phosphoryl group transfer reactions catalyzed by pyruvate kinase, phosphofructokinase, and hexokinase. As allosteric effectors, the modified nucleotides are less active than the natural compounds, probably because of a lower binding capacity to the allosteric sites of the regulatory enzymes.


Studies on (Na+ plus K+)-activated ATPase. XXXVII. Stabilization by cations of the enzyme-ouabain complex formed with Mg1+ and inorganic phosphate. Dissociation of the (Na+ + K+)-ATPase ouabain complex, formed in the presence of Mg2+ and inorganic phosphate (Complex II), is inhibited by Mg2+ (21-45%) and the alkali cations Na+ (25-59%) and K+ (27-75%) when kidney cortex tissue (bovine, rabbit, guinea pig) is the enzyme source. Choline chloride at 200 mM, equivalent to the highest concentration of NaCl tested, does not inhibit. Dissociation of Complex II from brain cortex (bovine, rat, rabbit) or heart muscle (rabbit) is much less inhibited: 0-11% by Na+ and 11-19% by K+. The degree of inhibition is not directly related to the size of the dissociation rate constant (k-) of the various complexes, but rather to the extent of interaction between the cation and ouabain binding sites for these tissues. Inhibition curves for Na+ and K+ are sigmoidal. Half-maximal inhibition for rabbit brain and kidney cortex is at 30-40 mM Na+ and 6-10 mM K+, and the maximally inhibitory concentrations are 50-150 and 15-20 mM, respectively. Maximal inhibition by Na+ or K+ for these tissues is the same. For guinea pig kidney cortex Na+ and K+ are almost equally effective, but 150 mM K+ or 200 mM Na+ are still not saturating, and inhibition curves indicate high- and low-affinity binding sites for the alkali cations. The inhibition curve for Mg2+ is not sigmoidal. In the kidney preparations Mg2+ inhibits half-maximally at 0.4-0.5 mM, maximally at 1-3 mM. Maximal inhibition by Mg2+ is higher than by Na+ or K+ for rabbit kidney cortex and lower for guinea pig kidney cortex. There is no competition or additivity among the cations, indicating the existence of different binding sites for Mg2+ and the alkali cations. Complex II differs in stability in the extent of inhibition, in the dependence of inhibition on the cation concentration and in the absence of antagonism between Na+ and K+, from the ouabain complex formed via phosphorylation by ATP (Complex I). This indicates that the phosphorylation states for the complexes are clearly different.


Induction of the catalytic protein of (Na+ plus K+)-ATPase in the salt gland of the duck. The (Na+ plus K+)-ATPase activities in salt gland homogenates increased 3- to 4-fold after saline treatment of ducks for 3 weeks. The ATPase was purified to a specific activity of 460 and 1015 mumol Pi/mg protein per h, respectively, in control and saline-treated ducks. The catalytic protein was identified on polyacrylamide electrophoresis gels by phosphorylating the enzyme with (32P)ATP. The molecular weight of the protein was estimated to be 98 000. The amount of catalytic unit increased commensurately with the enzyme activity after saline treatment. It is therefore concluded that the increased enzyme activity is due to a de novo enzyme synthesis and is not an activation effect. Phospholipid concentration in the salt gland tissue increased 1.7-fold after the saline treatment. Significant increases occurred in the percentage of the total phospholipids as phosphatidylserine and sphingomyelin. In the partially purified (Na+ plus K+)-ATPase preparation, the percentage composition of phosphatidylserine and phosphatidylethanolamine increased after saline treatment.


Observations on the (Ca2+ plus Mg2+)-ATPase activator found in various mammalian erythrocytes. 1. A soluble activator of membrane (Ca2+ plus Mg2)-ATPase is present in hemolysates of the newborn calf and cow, the new born and adult pig as well as human erythrocytes. 2. The activator is also found in reticulocytes of the adult pig. 3. The activator obtained from any of the above species is capable of stimulating the membrane (Ca2+ plus Mg2+)-ATPases of the other species, regardless of the age of the animals. 4. The results obtained from density fractionation of human erythrocytes revealed that the soluble factor has little simulatory effect on membranes of young erythrocytes from which it is derived but caused a marked stimulation on (Ca2+ plus Mg2+)-ATPase activity of the intermediate aged and old erythrocyte membranes. 5. The above observations support the following conclusions: (a) the extremely low levels of (Ca2+ plus Mg2+)-ATPase in cow erythrocytes is not due to the lack of a (Ca2+ plus Mg2+)-ATPase activator; (b) the distribution of (Ca2+ plus Mg2+)-atpase activator is not species specific and the differences in the level of membrane (Ca2+ plus Mg2+)-ATPase activity in various species of cells is an inherent property of that particular membrane (c) the (Ca2+ plus Mg2+)-ATPase activator is present at least from the time of reticulocyte formation and remain during tthe life span of the erythrocyte.


Evidence for electronogenic sodium pumping in the ductal epithelium of rabbit salivary gland and its relationship with (Na+ plus K+)-ATPase. The temperature dependence of the transepithelial potential difference (PD) of the main duct of the submaxillary gland has been measured during in vitro perfusion studies. The magnitude of the PD depends strongly on the anion composition of the perfusing and bathing fluids. The following combinations of perfusion and bathing fluids respectively were used: (1) Na2SO4/NaCl, (2) Na2SO4, (3) NaCl/-NaCl, (4) NaCl/Na2SO4. The mean transepithelial potential differences at 35 degrees C with these four sets of conditions were respectively: 144, 148, 10 and - 15 mV, serosal side positive with respect to lumen. From the data obtained it was possible to construct Arrhenius plots of temperature dependence of the PD for the four sets of experimental conditions. They all show a breakpoint between 16 and 19 degrees C. The apparent activation energies in the four situations above the breakpoint are 4.2, 1.4, 12.0 and 10.6 kcal/mol, respectively. Below the breakpoint they are 29.9, 37.5, 29.0 and 31.3 kcal/mol, respectively. The rapid change in the PD as a function of temperature (which can also be achieved by the addition of ouabain), the effects of the removal of K+ on the  serosal side on the PD, the decrease in the PD after the addition of ouabain or CN-, and the activation energies and breakpoints all lead to the conclusion that a large part of the PD is caused by an electrogenic sodium pump which is very probably the enzyme (Na+ plus K+)-ATPase. When the duct is perfused with Na2SO4 we find, above the breakpoint in the Arrhenius plots, a lower activation energy than is found when perfusing with NaCl.


[Tryptophan fluorescence of Na+,K+-ATPase preparations]. On the strength of the study of tryptophan fluorescence of Na+, K+-ATPase preparation a conclusion about conformational changes of the enzume molecule at the level of its tertiary structure is made. The largest changes of intensity and position of fluorescence spectrum consequently the macromolecule structure are discovered at the formation of Mg-ATP-enzyme complex.


[Effect of hexammine cobaltchloride on the transport of bivalent cations in liver mitochondria]. It is found that hexammine cobaltichloride (HAC) which interacts with anionic groups of sulphate-containing glycosamine glycanes, is a specific inhibitor of mitochondrial transport of Ca2+ (semi-maximal inhibition in the presence of 6 nmoles HAC/mg of protein) and Sr2+ (semi-maximal inhibition in the presence of 30 nmoles HAC/mg of protein). Mn2+ translocation was inhibited by considerably higher HAC concentrations, 4-fold increase in the transport rate being observed in the presence of 15 nmoles/mg of protein. Inhibition of Ca2+ translocation is competitive, and its inhibition constant is 6-10(-6) M. HAC (3-120 muM) does not affect respiration, oxidative phosphorylation and DNP-stimulated ATPase activity of liver mitochondria, but at the concentration of 15 muM it decreases markedly the activity of "detergent" ATPase from liver mitochondria. It is suggested that the effect of HAC is due to its interaction with anionic groups of mitochondrial glycoproteins.


[Properties of artificial vesicles from biological membranes]. Ultrasonic treatment of microsome fraction or the preparation of partially purified Na+, K+-ATPase from cattle brain resulted in the formation of closed structures which immobilized rubidium and sodium ions and were easily discovered in electron microscope. Gradual release of bound rubidium ions was observed under the incubation of ultrasonic-treated membrane preparation in salt solutions. This process was activated by ATP. ATP-activated release of rubidium was observed only in the presence of sodium and was inhibited by ouabain. A hypothesis on the participation of sodium pump in the ion transport through membranes of artificial vesicles is discussed.


Absence of one component of spectrin adenosine triphosphatase in hereditary spherocytosis. The stimulation by calcium and magnesium of ATPase activity of isolated ghosts, of water-soluble protein (spectrin), and of residual vesicles, derived from normal erythrocytes and from hereditary spherocytes (H.S.), has been measured. The ATPase activity found in normal water-soluble protein (WSP) at low levels of calcium (0.1-2.0 mM) is essentially absent in H.S. water-soluble protein, but the ATPase activity with magnesium and with high levels of calcium (60-100 mM) is the same in H.S. and normal WSP. Compared to normal, H.S. ghosts have increased Mg2+-stimulated activity. This increased activity is retained by the sedimentable vesicles ("residue") after extraction of the ghosts with 0.025 mM EDTA. The Ca2+, Mg2+-ATPase associated with the calcium pump is not significantly different in H.S.


[HCO3-sensitive adenosinetriphosphatase from ascites tumour cells]. HCO3--sensitive ATPase was found in nuclear and plasma membrane fractions of Ehrlich ascites tumour cells and lymphoma NK cells. HCO3--ATPase was not sensitive to monovalent cations and to ouabain (10(-4) M). The 60 mM HCO3- is the concentration of maximal activation of the HCO3--sensitive ATPase. The HCO3--sensitive ATPase was inhibited by anions in the sequence: SCN- greater than F- greater than ClO4- greater J-. The anions Br-, NO3-, HSO3- were not effective.


[Distribution of Na+, K+-ATPase and Mg+-ATPase in different subfractions of rod outer segments]. Na+, K+-ATPase and Mg++-ATPase are shown to be distributed non-uniformely in different subfractions of the rod outer segments (ROS) of bovine retina. Distribution of the enzymes differs significantly from that of rhodopsin. Predominant portion of Na+, K+-ATPase and Mg++-ATPase is concentrated within the subfractions with the lowest rhodopsin content. The most purified subfractions ROS containing the main amount of rhodopsin lack Na+, K+-ATPase at all, the activity of Mg++-ATPase does not exceed 0,4 plus or minus 0,05 mumoles Pi/mg protein-hour. Distribution of the succinic dehydrogenase is similar to this Na+, K+-ATPase. The data show that Na+, K+-ATPase activity in the ROS fraction is due to the contamination by the inner segment membranes, and that this enzyme is absent in the photoreceptive membranes of ROS.


[Infra-red spectra and ATPase activity of cardiac sarcoplasmatic reticulum under extreme conditions]. The study of infra-red spectra of cardiac microsomal fraction revealed the changes in the membrane structure, induced by acute hypoxia and hypothermia in one's lifetime. These changes affect alpha- and beta-conformations of protein, phospholipid part of sarcoplasmic reticulum and are accompanied by the change in the activity of membrane-bound ATPases.


Laparoscopy and laparotomy combined with bone marrow biopsy in staging Hodgkin's disease. The relative merits of laparoscopy with liver and spleen biopsy and staging laparotomy were studied in 91 unselected patients with Hodgkin's disease. Laparoscopy with liver and spleen biopsy were combined with needle biopsy of the bone marrow and laparotomy was combined with open bone marrow biopsy. In 65 untreated patients six out of seven with liver or marrow disease, or both, were shown to have extranodal lymphomas in these sites by laparoscopy plus needle marrow biopsy. Among 26 patients who had been treated this finding occurred in six out of 10 patients. Spleen biopsies during laparoscopy detected infiltration by lymphoma in 14 out of 37 (38%) patients with diseases spleens. Morbidity was higher after laparotomy than after laparoscopy. Laparoscopy produced abdominal bleeding secondary to splenic biopsy in two patients. All patients with Hodgkin's disease should be subjected to laparoscopy plus needle marrow biopsy before undergoing laparotomy.


Drug-induced rhythmical activity in the inferior olivary complex of the rat. Experiments have been performed on pentobarbitone anesthetized or decerebrated rats. The nature of the synchronous rhythmical activity which occurs in the inferior olive following the electrophoretic or systemic administration of harmaline, harmine, dihydro-beta-erythroidine and various other compounds, is described. Harmine was shown to reduce the late phase of biphasic unitary action potentials and to evoke massed synchronous rhythmical activity on which the units were superimposed. The beta-carboline was more effective than ACh or DL-homocysteate (DLH) in increasing cell discharge rates. Synchronized rhythmical activity was recorded more than 500 mum from the site of ejection of the rhythm-inducing drugs. Developed rhythmical activity reduced the size of antidromic field potentials, but antidromic invasion could reset the rhythm of submaximal rhythmical activity. The effects of ACh and DLH, glycine, GABA, NA, DA and 5-HT were tested on established rhythmical activity. Of these, 5-HT was the only compound which almost invariably antagonized the rhythm. A number of tryptamine derivatives and reported 5-HT antagonists, as well as parachlorophenylalanine, have been tested, but the results were largely inconclusive. The hypothesis is advanced that the drug-induced rhythm results from the inhibition of a tonic inhibitory serotonergic input. This antagonism releases an innate tendency of olivary cells to discharge both rhythmically and synchronously.


Chondrocyte metabolism as affected by vitamin A. Chondrocytes from 13-day-old embryonic chick sterna were cultured for 6 days in the presence of vitamin A (10 I.U./ml). Vitamin A treated chondrocytes became flattened and stellate within the first 24 hours of culture. After 6 days of culture, the treated cells contained 59% less DNA than the untreated controls. Sulfated glycosaminoglycan synthesis was inhibited 84%, and a greater percentage of GAG was secreted into the medium (90%) than in control cultures (78%). Vitamin A inhibited cell proliferation, and to varying degrees, RNA and protein synthesis, and these effects are dose dependent.


Escape from mating-type incompatibility in bisexual (A + a) Neurospora heterokaryons. In Neurospora crassa, strains of opposite mating type generally do not form stable heterokaryons because the mating type locus acts as a heterokaryon incompatibility locus. However, when one A and one a strain, having complementing auxotrophic mutants, are placed together on minimal medium, growth may occur, although the growth is generally slow. In this study, escape from such slow growth to that at a wild type or near-wild type rate was observed. The escape cultures are stable heterokaryons, mostly having lost the mating type allele function from one component nucleus, so that the nuclear types are heterokaryon compatible. Either A or a mating type can be lost. This loss of function has been attributed to deletion since only one nuclear type could be recovered in all heterokaryons except one, but deletion spanning adjacent loci has been directly demonstrated in a minority of cases. Alternatively when one component strain is tol and the other tol+ (tol being a recessive mutant suppressing the heterokaryon incompatibility associated with mating type), escape may occur by the deletion or mutation of tol+, also resulting in heterokaryon compatibility. An induction mechanism for escape is speculated upon.


High dose cyclophosphamide therapy in solid tumors. Therapeutic, toxic, and immunosuppressive effects. Cyclophosphamide (CY) in a total dose of 120 mg/kg was given over 2 days on one to three occasions to 12 patients with a variety of nonlymphoid solid tumors. Two of 10 patients with measurable disease had a partial response. One had embryonal rhabdomyosarcoma and the other had ovarian carcinoma. In the 20 treatment courses, the mean leukocyte count was less than 1,000/mm for 7 days. Thrombocytopenia was variable with a mean nadir of 87,000/mm on day 12. There were four instances of local infection, one of bacteremia, and 11 of fever of undetermined origin. Weight gain of 2 or more kg occurred after 12, and EKG changes compatible with cardiotoxicity after six courses of CY. Serial skin testing with recall antigens revealed a frequent transient loss, and in three patients a later overall gain, in responsiveness. All patients were immunized with Vi antigen before CY, and with Vi and sheep red blood cells (SRBC) after CY. Specific immune tolerance to Vi, with a satisfactory response to SRBC, was found in six of 12 patients. Patients' responses to the lymphocytes of 2 ABO compatible normal subjects were measured in mixed lymphocyte culture (MLC) before and after CY. Patients were given 500 ml of whole blood from one of the subjects prior to CY. Following CY, the patients' responses to the blood donors' cells were not significantly lower than their responses to non-donor cells. Thus, tolerance to HL-A antigens was not demonstrable in MLC. Three patients had an increase from subnormal to normal reactivity to non-donor cells in MLC.


Effect of levamisole (NSC-177023) on DNA synthesis by lymphocytes from immunosuppressed C57BL mice. The effect of in vivo treatment of C57BL mice with BCNU and/or levamisole on the in vitro DNA synthetic capacity of their spleen cells was studied as a measure of cell-mediated immune function. BCNU treatment was suppressive to spleen cell DNA synthesis; conversely, treatment with levamisole was stimulatory. Levamisole treatment 5-8 days after BCNU treatment resulted in significant recovery of DNA synthetic capacity. Multiple doses of levamisole were not more effective than single doses. Allogeneic stimulation of BCNU-suppressed lymphocytes was not consistently increased by levamisole treatment.


Fate of streptozotocin (NSC-85998)in patients with advanced cancer. We have investigated the distribution, biotranformation, and excretion of streptozotocin and its 14C- and 3H-labeled metabolities in 15 patients with advanced cancer. Streptozotocin was detected in the plasma during the first 3 hours after administration while radioactive products were present for longer than 24 hours. No unchanged streptozotocin was detected in the cerebrospinal fluid (CSF); however, 14C-labeled metabolites were detected in the 2-hour CSF sample in a concentration equivalent to the 2-hour plasma level. H activity is the CSF was not detected at this time period. Radioactivity measured in biopsied tissues indicated that streptozotocin labeled with 14C and 3H or its metabolites penetrated tumor tissue. 14C tissue levels were found to approximate plasma levels; however, 3H levels were found to be greater than the corresponding plasma levels. Fifteen percent of the total dose of streptozotocin administered was recovered in the urine. 3H-labeled metabolites were recovered in excess of 60% in the urine, and approximately 30% of the 14C-labeled metabolites were recovered in the urine during a similar interval. Less than 1% of the administered 14C and 3H was recovered in the feces. 14C-labeled CO2 was also recovered, although quantitative recovery was not attained. At least three major metabolites of streptozotocin were detected in the urine by radiochromatography. Two metabolites contained only 3H and one metabolite contained both 14C and 3H in the same ratio as administered.


Quantitation of isoprenaline-induced changes in the ventricular myocardium. Small doses of isoprenaline sulphate given intermittently produce a characteristic cardiopathy consisting of subendocardial scarring and myocardial hypertrophy. A morphometric technique was successfully applied to the quantitation of these changes. This technique improves the use of the isoprenaline model for the study of cardiac necrosis as statistical analysis can be applied and objective comparisons made. No hypertrophy was seen in the absence of myocardial necrosis which suggests that it is at least in part compensatory.


Phase I study of thalicarpine (NAC-68075), a plant alkaloid of noval structure. An initial clinical trial of daily and weekly X 6 ihtravenous infusions of thalicarpine, a plant alkaloid of novel structure, was carried out in 36 patients. Twenty-eight patients received 33 courses of single-dose administration at doses of 200-1900 mg/m2. At the maximum tolerable dose of 1400 mg/m2, toxic effects included arm pain (nine or ten), central nervous system depression (seven of ten), nausea and vomiting (two of ten), hypotension (two of ten), hypertension (two of ten), arrhythmia (premature ventricular contractions) (one of ten), and electrocardiographic changes (mainly T-wave flattening) (five of ten). At the maximum tolerable dose for weekly administration, 1100 mg/m2/week X 6, arm pain was seen in seven of eight, central nervous system depression in three of eight, hypotension in one of eight, and electrocardiographic changes in three of eight. The recommended dose for phase II trials is 1100 mg/m2/week by a 2-hour intravenous infusion.


5-HT nerve terminals in the fourth ventricle of the rat brain: their identification and distribution studied by fluorescence histochemistry and electron microscopy. The occurrence and distribution of supra-ependymal nerve terminals storing serotonin (5-HT) are described for the fourth ventricle of the rat brain. The nerve terminals were identified as monoaminergic 1) fluorescence-histochemically, by the presence of a varicose, formaldehyde-induced  fluorescence (FIF) on the free surface of the ependyma, 2) electron microscopically, by the presence of electron dense (chromaffin) cores in small (50nm) and large (100 nm) vesicles found within the varicose regions of supra-ependymal nerve fibres, and 3) by the absence of both the FIF and chromaffin dense cores after treatment with reserpine. Moreover, the serotonergic nature of these nerve fibres could be concluded from 1) the yellow colour of the FIF, 2) the increased FIF after treatment with nialamide or reserpine+nialamide, 3) the diminished FIF and absence of chromaffin dense cores after treatment with p-CPA, and finally 4) the persistence of the FIF anc chromafin dense cores after treatment with alpha-MPT. A high density of 5-HT nerve terminals occurred throughout the floor of the fourth ventricle and on the floor and roof of the lateral recess. Few 5-HT nerve terminals occurred only on the roof of the fourth ventricle (velum medullare, lamina epithelialis of the tela chorioidea), and the surface of the choroid plexus epithelia was devoid of such nerves. Virtually all nerve terminals in the fourth ventricle appear to be serotonergic.


The effect of 5-bromodeoxyuridine on chick embryo limb bud mesenchyme in organ culture. The thymidine analogue 5-bromodeoxyuridine (BrdU) prevents chondrogenesis in organ cultures of limb bud mesenchyme of 3 1/2 day chick embryos. The biologically active levels of BrdU inhibit both DNA and RNA synthesis, but the synthesis of methylated RNA is inhibited less than that of unmethylated RNA. If cell division is partially synchronized the ratio of incorporation of BrdU to thymidine is greater during the first few minutes of the S period than for unsynchronized cells. The results suggest that BrdU may be preferntially incorporated into the starting points of replicons and that this may affect subsequent transcription necessary for chondrogenesis.


Evaluation of vectorcardiographic criteria for the diagnosis of myocardial infarction in the presence of left ventricular hypertrophy. Vectorcardiograms (VCG) from a consecutive group of 77 patients with significant aortic valve disease were analyzed. All of the patients had complete left and right heart catheterization with normal coronary arteriograms and normal left ventricular contraction. Thirty-five (46%) patients met VCG criteria for anterior myocardial infarction (AMI-35%) and/or inferior myocardial infarction (IMI-14%). This was a significant increase in false positive diagnosis for both criteria compared to a group of 200 normal volunteers under age 30 and 100 patients with normal hearts by cardiac catheterization (P less than 0.01). It was found that if the VCG diagnosis of myocardial infarction was deferred when the maximal transverse plane magnitude was greater than 1.9 mV, the incidence of AMI false positive diagnosis decreased to 3% and the incidence of IMI false positive diagnosis decreased to 1%. The same rule was applied to the aortic valve disease cohort, a group of 124 patients with documented AMI and a group of 158 patients with IMI. This decreased the sensitivity of the AMI criteria from 93 to 83% and of the IMI criteria from 85 to 77%. The increase in average performance was statistically significant fro the AMI criteria (P less than 0.05) but not for the IMI criteria.


Relation between echocardiographically determined left atrial size and atrial fibrillation. In an attempt to define quantitatively the relation between left atrial size and atrial fibrillation, echocardiography was used to study 85 patients with isolated mitral valve disease, 50 patients with isolated aortic valve disease, and 130 patients with asymmetric septal hypertrophy. In all three groups of patients, atrial fibrillation was rare when left atrial dimension was below 44 mm (3 of 117 or 3%) but common when this dimension exceeded 40 mm (80 of 148 or 54%). In addition, when left atrial dimension exceeds 45 mm, cardioversion, while initially successful, is unlikely to produce sinus rhythm that can be maintained at least six months. These data suggest that left atrial size is an important factor in the development of atrial fibrillation and in determining the long term result of cardioversion. The pathophysiologic mechansim most consistent with this is that a chronic hemodynamic burden initially produces left atrial enlargement which in turn predisposes to atrial fibrillation. Only prospective studies will determine definitively whether these observations will be useful in decisions concerning prophylactic anticoagulation and elective cardioversion.


Noninvasive evaluation of ventricular hypertrophy in professional athletes. Athletes often exhibit ECG findings which are considered to be abnormal. Therefore, we used noninvasive graphic methods to study 42 active professional male basketball players, ranging in age from 21 to 31 years, without clinically evident heart disease. Of the 42, 11 (25%) met the Romhilt-Estes ECG voltage criteria for left ventricular hypertrophy, and 12 (29%) satisfied VCG criteria for left ventricular enlargement; nine (21%) had left ventricular hypertrophy by both methods. In 33 subjects (79%) the 0.04 sec vector in the horizontal plane was anterior, and 29 of these exhibited one or more standard criteria for right ventricular enlargement; the ECG and VCG were concordant for right ventricular hypertrophy in 16 subjects (38%). Submaximal treadmill exercise tests (Bruce protocol) were normal in eight athletes, while in one subject ventricular premature beats occurred during the test. In 24 of 25 athletes (96%) from whom phonocardiograms were obtained a third heart sound was recorded, while in 14 (56%), a fourth heart sound was present. Of the 14 athletes who had a fourth heart sound, 12 (86%) had either ECG or VCG evidence of ventricular hypertrophy. Only four of 23 athletes had an increased cardiothoracic ratio (greater than .50) on routine chest X-ray. Ten athletes and ten control subjects matched for height, weight and body surface area had echocardiograms satisfactory for analysis. The left ventricular end-diastolic dimension in the athletes averaged 53.7 +/- 1.3 (SE) mm compared with a value of 49.9 +/- 0.7 mm in the control subjects (P less than 0.02), and was increased (greater than or equal to 56 mm) in four. Left ventricular posterior wall thickness averaged 11.1 +/- 0.6 mm, compared with a value of 9.8 +/- 0.5 mm in the control subjects (P less than 0.05), and was increased (greater than or equal to 11 mm) in six athletes. The right ventricular end-diastolic dimension averaged 20.8 +/- 1.1 mm compared with a value of 12.9 +/- 2.2 mm in the controls (P less than 0.004), and was increased (greater than or equal to 23 mm) in four athletes. No athlete or control subject exhibited paradoxical septal motion. In the athletes, ejection fraction (cube method) averaged 79 +/- 2.0% and mean Vcf averaged 1.13 +/- 0.04 circ/sec; these values did not differ from those of the control subjects. Thus, both right and left ventricular enlargement ("physiological hypertrophy") are often present in the well-trained athlete, but left ventricular performance remains normal in the basal state in such individuals. We condlude that these individuals represent a selected subgroup of subjects who are variants of normal.


Satellite association: Giemsa banding studies in parents of Down's syndrome patients. Association patterns of acrocentric chromosomes in 3032 cells from chromosomally normal parents of regular mongols (nondisjunctional trisomy 21) and normal controls were studied by the Giemsa banding technique. In each group, chromosome No. 21 was found to be involved in satellite association more frequently than other acrocentric chromosomes. The most frequently seen association was between No. 21 and 22. However, no difference was shown between the parental test group and the normal controls in regard to these frequencies. These results render less tenable the proposed linkage between satellite association and the etiology of mongolism.


Mixed lymphocyte culture stimulatory and responding capacity of lymphocytes from patients with lymphoproliferative diseases. Lymphocyte reactivity in vitro was studied in patients with Hodgkin's disease, chronic lymphocytic leukaemia and lymphosarcoma. The responding capacity to phytohaemagglutinin (PHA) was markedly depressed and delayed in all three groups of patients  compared with the PHA response observed in lymphocyte cultures from normal individuals. In one-way mixed lymphocyte culture experiments a significant decrease in responding capacity of the patients' lymphocytes to lymphocytes from normal donors could be demonstrated. In contrast, the stimulatory capacity of the patients' lymphocytes was found to be intact, or only slightly reduced.


The role of vitamin B 12 and its transport globulins in the production of antibodies. Immunological functions were repeatedly tested in a patient with hereditary deficiency of transcobalamin II (TC II): he was unable to synthesize immunoglobulins and specific antibodies, but was able to do so normally after injection of high doses of vitamin B 12 (1000 mug per week). Lymphocytes (B and T) were present in normal numbers prior to therapy, thus indicating normal differentiation of stem cells. In contrast, clonal expansion, necessary for immunoglobulin production, was possible only after vitamin B 12 administration. These observations, as well as the well known disturbances in haemopoiesis, indicate that vitamin B 12 is indispensable to rapidly replicating tissues, and that a severe deficiency of this vitamin in the cells can result from the absence of TC II.


Cell-mediated lympholysis in vitro. Independence of mixed lymphocyte reactions and T-cell mitogen responses from the in vitro generation of cytotoxic effectors in primary immunodeficiency diseases. Cell-mediated lympholysis (CML) in eighteen patients suffering from primary immune deficiencies was studied. Fourteen of these patients had the variable type. Mixed lymphocyte response (MLR) and CML were clearly found to be independent: as well as two groups of patients in whom the two functions were either both normal or both deficient, two other groups were found in whom they were definitely separate. In one group MLR and T-cell mitogen responses were normal but no CML occurred against allogenic lymphocytes, and in the other cytotoxic effectors were generated normally but MLR and T-cell mitogen responses were very much lower than normal. These results show that the functions are independent, and are compatible with the theory that more than one subpopulation of T cells is involved. Neither the MLR or T-cell mitogen responses of these patients can predict their ability to generate cytotoxic effectors.


Immunological responsiveness of frozen-thawed human lymphocytes. Mononuclear cells (10--20 X 10(6)) obtained from human peripheral blood by a standard Ficoll-Hypaque technique were suspended in RPMI 1640 media at 4 degrees C containing 10% foetal calf serum and 7-5% dimethyl sulphoxide (DMSO). Two-millilitre aliquots were cooled at -1 degree C/min in a Cryoson BV-4 programmed freezing system to -30 degrees C, then -5 degrees C/min to -80 degrees C and stored in liquid nitrogen vapor. On the day of testing, cell suspensions were thawed rapidly in a 37 degree C water bath. DMSO was diluted slowly out of the sample and cells resuspended in fresh RPMI 1640. It was found that frozen stored human lymphocytes (FSHL) demonstrated all the characteristics of fresh unfrozen cells. These included their ability to form spontaneous rosettes with sheep erythrocytes ('E' rosettes) and sheep erythrocyte--antibody--complement rosettes ('EAC' rosettes). The presence of surface immunoglobulins and Fc receptors were shown by membrane immunofluorescence to be comparable. In addition, the results show that FSHL respond to mitogens, specific antigens; act as both stimulators and responders in the mixed lymphocyte culture reaction; and exhibit cell-mediated lymphocytotoxicity following in vitro sensitization, or against antibody-coated target cells.


Mechanism of cardiotonic action of monoethanolamine and its activity in experimental myocardial hypertrophy. The authors investigated the cardiotonic effect of monoethanolamine (MEA) and its influence on experimental cardiac hypertrophy in albino rats. In isolated hearts, myocardial cells, and glycerinized fibres as well as in the whole organism of the animals, a distinct cardiotonic effect on MEA was observed, which was most marked in pathological states of the organism. In rats with experimental coarctation of the aorta, MEA dosed 10 mg/kg stimulated, and dosed 60 mg/kg, inhibited the development of myocardial hypertrophy, while the myocardial contractility remained sufficiently preserved. The mechanism of cardiotonic action and the inhibitory effect on the development of myocardial hypertrophy at the dosage of 60 mg/kg are apparently connected with the participation of MEA in tissue metabolic processes contributing to a normalization of tissue respiration, oxidative phosphorylation, and activation of phosphatide-generating reactions, especially to the formation of phospholipids containing ethanolamine, which represent one of the most important membrane formations and components of numerous enzymic systems.