Pathophysiologic significance of S-T and T wave abnormalities in patients with the intermediate coronary syndrome.

The frequent association of new ST-T wave changes without Q waves in the surface electrocardiogram of patients with the intermediate coronary syndrome necessitates a better understanding of the pathophysiologic significance of this finding. A previous study in patients with stable coronary artery disease indicated that the surface electrocardiogram is insensitive in detecting epicardial Q waves. This relation was evaluated in 21 patients with the intermediate syndrome, characterized by recurrent chest pain at rest associated with significant new S-T or T wave abnormalities, or both, and no new Q waves in the surface electrocardiogram at the time of open heart coronary bypass surgery. Unipolar electrograms were recorded from the epicardial surface of the left ventricle before the bypass procedure. In 19 patients, epicardial electrograms revealed initial R waves over areas of the left ventricle in which the acute S-T and T wave abnormalities were evident in the surface electrocardiogram. Two patients had epicardial Q waves (one laterally and one inferiorly). In seven patients, a transmural biopsy specimen was also obtained from the ischemic area. All showed histologically normal myocardium without evidence of early inflammatory or necrotic tissue. Of the 19 patients discharged, only one demonstrated new postoperative Q waves that had been detected by epicardial recordings before bypass. In summary, patients with the intermediate syndrome exhibiting S-T or T wave abnormalities, or both without new Q waves in the surface electrocardiogram generally do not have Q waves either in the intraoperative epicardial or postoperative surface electrocardiogram. In addition, no histopathologic abnormalities are apparent in biopsy specimens taken from the ischemic area.


Sleep disturbances after open heart surgery.

This study was designed to document quantitatively the sleep disturbances that occur after open heart surgery and to investigate a group of patients who underwent a thoracic surgical procedure not involving cardiopulmonary bypass. Nine patients were studied, six after open heart surgery and three after partial or complete pneumonectomy. In each patient, sleep patterns were recorded with use of all night polygraphy before and after operation and for up to 5 weeks on follow-up studies. After open heart surgery, patients manifested considerable suppression of both rapid eye movement and slow wave sleep patterns. In the three patients subjected to thoracotomy these sleep indexes returned to preoperative levels much earlier. Evidence of stage 2 sleep was present in one of the three patients with thoracotomy on the first postoperative night, and in two of the three both rapid eye movement and slow wave sleep returned to preoperative levels by the time of hospital discharge. It is concluded that patients undergoining open heart surgery experience both acute and chronic disruptions of sleep that last well beyond the hospital period of convalescence. These sleep disturbances have considerable relevance for postoperative management.


Fiberendoscopy of the gastrointestinal tract in children. A series of 100 examinations.

This article reports the results of our first 100 examinations of the upper gastrointestinal tract and the colon in children and infants, using standard fiberscopes and also pediatric models. The procedure could be performed under sedation in 80% of the cases and general anesthesia was required mainly with standard fiberscopes. Compared to roentgenographic findings, fiberendoscopy proved to be more reliable in superficial mucosal lesions and gastrointestinal bleeding. Colonoscopy though difficult, is valuable in diagnosing rectal bleeding lesions and as a follow-up technique in inflammatory bowel diseases.


Tuberculous otomastoiditis in children.

We report three cases of tuberculous otomastoiditis in children. Review of the literature, with particular emphasis on the ten other cases reported since 1960, discloses that this form of tuberculosis is most frequent in infants and young children. All too often, the diagnosis is made too late, with resulting complications such as irreversible hearing loss and facial nerve paralysis. Antituberculous medication and surgical drainage controlled the infection in all 13 cases diagnosed since 1960. Tests for tuberculosis in children with chronic ear infection should be mandatory, but periodic testing of all children is recommended.


Hypopyon and orbital cellulitis associated with Haemophilus influenzae type B meningitis. Diagnostic and therapeutic implications.

Three children, 8 months to 2 years of age, demonstrated unusual manifestations in association with Haemophilus influenzae septicemia and meningitis. After one child had been diagnosed as having orbital cellulitis in conjunction with H influenzae meningitis, a second child, with orbital cellulitis and no clinical evidence of meningitis, had a lumbar tap indicative of a meningitis. A third child developed a hypopyon in association with H influenzae meningitis and septic arthritis of several joints. We report the problem of diagnosis and treatment of orbital cellulitis in the context of our cases and those previously reported.


Noncirrhotic portal hypertension in Felty's syndrome.

A case of Felty's syndrome with nodular regenerative hyperplasia of the liver, presinusoidal portal hypertension, and bleeding esophageal varices is reported. Increased splenic blood flow may be a contributing factor to the development of the regenerative nodules. The portal hypertension is postulated to be a result of intrahepatic vascular compression.


Structure and Barr body formation of an Xp + chromosome with two inactivation centers.

A patients with seizures, Von Willebrand disease, and symptoms of Turner syndrome was a chromosomal mosaic. In blood culture (1974), 56% of the cells were 45, X 33% 46, XXp+ and 11% 47,XXp + Xp +; in the skin, no cells with 47 chromosomes were found. Presumably the Xp + chromosome arose through a break in the Q-banded dark region next to the centromere on Xp to which an Xq had been attached. The abnormal X was late-labeling and formed a larger than normal Barr body. Of the chromatin-positive fibroblasts, 18.2% showed bipartite Barr bodies, which agrees with the hypothesis that the X inactivation center lies on the proximal part of the Xq. On the basis of the structure and behavior of the bipartite bodies in the present patient, as compared to those formed by other chromosomes with two presumed inactivation centers, we propose that the dark region next to the centromere of Xp remains active in the inactive X. In cells with 45,X and 46,XY, this region has the same relative size, whereas it is significantly shorter in the active X of three females, including the present patient, with one abnormal X. We propose that this region on the active X reveals different states of activity, as reflected in its length, depending on how many other X chromosomes are in the cell.


Pulmonary function in nonsmoking subjects with alpha1 antitrypsin deficiency (MZ phenotype).

We measured pulmonary functions in 10 nonsmoking asymptomatic subjects, ages 40.5 years +/- 9.2 years, with alpha1 antitrypsin heterozygous deficiency (phenotype MZ). The subjects were longstanding residents of the greater Los Angeles area. The range of physiologic studies and per cent of normal predicted values were forced vital capacity (FVC), 2.8 to 7.0 liters (86 to 124 per cent predicted); ratio of the forced expiratory volume in 1 second to the FVC, 70 to 86 per cent (86 to 104 per cent predicted); the ratio of the residual volume to total lung capacity, 28 to 44 per cent (94 to 119 per cent predicted); total lung capacity, 4.8 to 9.8 liters (80 to 119 per cent predicted); flow at 50 per cent FVC, 3.1 to 7.8 liters per second (69 to 140 per cent); and volume of isoflow, 7.3 to 26 per cent of forced vital capacity (38 to 137 per cent predicted). In eight patients studied, static deflation pressure volume curves were normal, and at respiratory rate of 60 breaths/min the ratio of dynamic compliance to static compliance did not fall below 84 per cent. We have found that these nonsmoking heterozygotes with alpha1 antitrypsin deficiency have normal pulmonary functions (within 1.67 SD of predicted mean).


Wolff-Parkinson-White Syndrome--current views.

The Wolff-Parkinson-White (WPW) syndrome is an important clinical entity because of frequent recurrences of very rapid tachyarrhythmias. The electrocardiographic finding of the WPW syndrome often mimicks pseudo diaphragmatic (inferior) myocardial infarction which should not be misinterpreted. The most important diagnostic criterion is recognition of a delta wave; the short P-R interval or broad QRS complex may not be present in every case. The mechanism for the tachycardia is considered to be a reentry phenomenon via anomalous and normal atrioventricllar (A-V) pathways. The drug of choice for the treatment of regular supraventricular (reciprocating) tachycardia with narrow QRS complexes, which is the most common arrhythmia in the WPW syndrome, is propranolol. Digitalis is almost equally effective in this case. For tachyarrhythmias, particularly atrial fibrillation or flutter with anomalous conduction, intravenously-administered lidocaine is considered to be the drug of choice. Procainamide or quinidine is also frequently used under this circumstance with excellent therapeutic result. Many patients with the WPW syndrome require long-term maintenance drug therapy (propranolol, digitalis or quinidine in most cases). In urgent clinical situations, direct current (DC) shock should be applied immediately. In selected patients with refractory tachyarrhythmias, the use of an artificial pacemaker or surgical approach may be considered.


Fungal endophthalmitis following intraocular lens implantation.

Endophthalmitis developed in a 61-year-pld man after an intraocular lens implantation. A whitish opacity developed, visual acuity decreased to light perception, and we enucleated the eye. Paecilomyces lilacinus (Thom) Samson, a saphrophyte that has contaminated laboratory solutions, was cultured.


Keratitis and endophthalmitis caused by Petriellidium boydii.

A 26-year-old man sustained burns of the left eye and eyelids from molten aluminum. Antimicrobial and anti-inflammatory therapy was instituted. Cultures of conjunctival material collected 14 days after the burn grew abundant colonies of Petriellidium boydii. Because of severe pain and impending corneal perforation, the eye was enucleated.


Unusual superficial variant of granular dystrophy of the cornea.

Two patients with a superficial variant of granular dystrophy of the cornea occurring primarily in nongrafted eyes developed rapid progression of clinical manifestations and visual deterioration at an early age. No other members of their family were known to be affected. A clinical diagnosis of superficial corneal dystrophy, type undetermined, was made. The histopathologic features of the corneas resembled the findings seen in Reis-Bücklers dystrophy and led to some confusion in the differential diagnosis. Electron microscopic studies in both cases unequivocally established the diagnosis of granular dystrophy.


Pneumocystis carinii in vitro: A study by scanning electron microscopy.

Pneumocystis carinii is a parasitic microorganism which induces an often fatal pneumonitis in a variety of compromised patients (e.g., premature infants, those with congenital immune deficiency disorders, those therapeutically immune suppressed, etc.). Organisms derived from murine sources were cultivated in vitro on monolayers of primary embryonic chick epithelial lung cells. The infected cultures were then examined by scanning electron microscopy. An examination of the surface ultrastructure revealed pleomorphic organisms which were not only attached to host cells with anchoring fibers but also connected to other parasites via fine fibrils. Another type of fine fibril was observed which may play a role in the organism's nutrition.


ATP utilization associated with recovery metabolism in anaerobic frog muscle.

The ATP turnover during single isometric 0.5-, 1-, and 3-s tetani in anaerobic frog sartorii was measured at 20 degrees C. In parallel experiments, we measured the lactate production by sartorii during their metabolic recovery from such tetani. From these measurements, we obtained an experimental P/lactate ratio which was less than 1.5, the expected value for simple Embden-Meyerhof glycolysis when glycogen is metabolized to lactate. We interpreted these results as indicating a substantial amount of suprabasal ATP breakdown occurred during metabolic recovery. The operation of the fructose phosphate substrate cycle is suggested as a cause of this additional ATP breakdown.


Stratum corneum of frog skin: inferences for studies of Na entry and transport pool.

Pieces of isolated stratum corneum from frog skins were studied. Preliminary data showed that approximately 56% of the total sodium of split skins was associated with the stratum corneum. In more detailed studies, the sodium space estimated with 22Na and the volume of tissue water were identical, averaging 0.95 mul/cm2. Thus, the stratum corneum contained approximately 0.11 mueq Na+/cm2. Similar determinations of the sucrose, mannitol, and inulin spaces of the stratum corneum gave mean values of 0.84, 2.21, and 1.84 mul/cm2, respectively. Surprisingly, the mannitol and inulin spaces were observed to be at least twice as large as the space occupied by the tissue water, and this can be interpreted to mean that mannitol and inulin bind in appreciable amounts and thus are unsuitable markers of the sodium space. Whereas the kinetics of sodium uptake and washout  could be described simply, similar studies for sucrose, mannitol, and inulin were more complex and consistent with appreciable binding of the substances to the stratum corneum.


A hard look at colonoscopy.

The fiberoptic colonscope represents a significant diagnostic and therapeutic acheivement in the management of colonic disease. Despite some claims to the contrary, it is not universally simple, rapid, thorough, reliable, and inexpensive or without morbidity and mortality. Until these goals are achieved through future refinements, modifications, and new instrumentation, it is strongly recommended that the indications for colonscopy be sharply defined to include the following: (1) Investigation of colonic lesions seen on two successive or one air-contrast barium enema examination. Pedunculated polyps less than 1 cm in diameter can be observed. (2) Preoperative investigation of patients with demonstrable colorectal cancer (to rule out synchronous lesions). (3) Postoperative evaluation after colectomy for carcinoma where the anastomosis is above the reach of a sigmoidoscope. (4) Evaluation of patients with inflammatory bowel disease of the colon. (5) Investigation of persistent occult or gross rectal bleeding when anoscopy, sigmoidoscopy, and barium studies are negative. Patients who represent prohibitive surgical risks because of age or systemic disease should not be considered as candidates for colonoscopy without compelling indications. The decision to biopsy rather than remove or fulgerate a detected lesion must be left to the judgment and experience of the endoscopist. The morbidity that follows polypectomy or fulgeration of sessile lesions less than 0.5 cm in diameter probably exceeds the incidence of carcinoma.


Efficacy and risks of the distal splenorenal shunt in the treatment of bleeding esophageal varices.

Analysis of twenty-two patients who underwent distal splenorenal anastomosis shows that the operative mortality and morbidity are low if the indications for the procedure are strictly adhered to. The decompression of the esophageal varicosities is effective, even in the presence of persistent varicosities. This decompression is probably less important and perhaps slower than after portacaval shunting, so we now do not recommend distal splenorenal shunting as an emergency operation. Thrombosis of the shunt is rare and related especially to local anatomic conditions and operative technic. Shunt thrombosis is an early complication that we observed on two occasions manifested by recurrence of hemorrhage. There does not appear to be an appreciable difference between the terminoterminal and terminolateral distal splenorenal anastomoses. The effect of ligation of the splenic artery in the hypersplenism is doubtful. The frequency of postanastomotic encephalopathy is minimal with this type of shunt. Liver function tests were little changed during the period of postoperative observation, but our results do not permit us to conclude that the distal spleno-renal anastomosis less unfavorably affects liver function than do classic shunts.


Comparative group study between patients surviving five or more years after portacaval shunt procedure and those surviving less than one year.

The classic criteria utilizing preoperative clinical evaluations and laboratory tests for predicting risk and long-term survival in cirrhotic patients under-going portacaval shunting still appear to be the most useful. Analysis of the factors that could be determinant in separating patients who are going to survive a portacaval shunt for five or more years from the short-term survivors revealed the former group had a lesser incidence of preoperative encephalopathy, ascites, malnutrition, and hypoalbuminemia. None of the intraoperative factors were found to be decisive. However, the prompt and uncomplicated postshunt recovery was an accurate prediction for long-term survival. This could be explained by the assumption that these patients had a better hepatic functional reserve at the time of portal-systemic shunting. The early appearance in the postoperative period, of fluid retention, azotemia, oliguria, inability to eat, and the early appearance of the symptoms of portal encephalopathy were premonitory of short-term survival. Return to alcohol ingestion was also associated with short-term survival. The hepatorenal syndrome was usually the cause of death in the short-term survivors whereas nonhepatic disease was the cause of demise in the long-term survivors. The operative mortality for all patients undergoing portacaval shunting during an eight year period was 10.7 per cent. Of the patients who left the hospital alive, 16.1 per cent died within the subsequent twelve months, 53 per cent survived from thirteen to fifty-nine months after their operation, and 19.6 per cent survived sixty or more months.


Hemobilia from ruptured hepatic artery aneurysm. Report of a case and review of the literature.

Hepatic artery aneurysm is a rare vascular disease associated with high mortality caused by massive hemorrhage or by complications following surgical treatment. Over the past twenty-five years it has been managed surgically with increasing success. Eighty reported cases of hepatic artery aneurysms ruptured into the biliary tree were reviewed and the etiology, clinical signs, diagnosis, and treatment of such an aneurysm are discussed. A personal case with an aneurysm of the right hepatic artery ruptured into the common hepatic duct is reported. The diagnosis was made before surgery by arteriography and the aneurysm was successfully managed by ligation of the right hepatic artery both proximal and distal to the aneurysm, closure of the communication between the common hepatic duct and the aneurysm, and choledochal drainage. Hemobilia secondary to hepatic artery aneurysm must be considered in thedifferential diagnosis of unexplained gastrointestinal hemorrhage.


Management of upper gastrointestinal haemorrhage.

The results of emergency endoscopy in 61 patients with upper gastrointestinal haemorrhage are presented. The merits of urgent endoscopy in tha management of this condition are discussed and the results obtained compared with those of other methods of investigation.


Rapid method for determining the minimum inhibitory concentration of ampicillin for Haemophilus influenzae.

A rapid method for determining the minimal inhibition concentrations (MICs) of ampicillin using Haemophilus influenzae as the test organism is described. This semiautomated technique using the Autobac system was compared with the agar dilution MIC method. Fifty-seven isolates of both susceptible and resistant H. influenzae were tested. There was exact quantitative agreement with 65% of the isolates, and 91% of the isolates showed no more than a one-dilution-interval difference when MICs were determined by both methods. Total testing time was 3 to 4 h.


Eye-tracking and optokinetic nystagmus. Results of quantitative testing in patients with well-defined nervous system lesions.

Eye-tracking and optokinetic nystagmus (OKN) abmormalities in patients with focal lesions of the nervous system are reviewed. Patients with peripheral labyrinthine lesions can have deficits in smooth pursuit and OKN, but they are rapidly compensated after an acute lesion. By contrast, patients with large, cerebellopontine angle tumors have progressive impairment of pursuit and OKN as the tumor enlarges. Abnormalities of saccadic eye movements suggest intrinsic central nervous system (CNS) dysfunction. Saccade accuracy is severely impaired with cerebellar lesions, while brain stem disease frequently results in a slowing of saccade maximum velocity. Smooth pursuit and OKN abnormalities are common with all types of CNS lesions. The pattern of eye-tracking and OKN abnormality can be useful in anatomically localizing nervous system lesions.


Phagocyte function and cell-mediated immunity in systemic lupus erythematosus.

Lymphocyte, granulocyte, and macrophage function were studied simultaneously in 26 untreated patients with systemic lupus erythematosus (SLE) and 26 matched controls. The overall cellular response, as assessed in vivo by skin tests and sensitization to dinitrochlorobenzene, was diminished in the SLE group. Although T cells were reduced in number in patients with SLE, their function appeared unimpaired, as shown by normal lymphocyte transformation to phytohemagglutinin and bacterial and fungal antigens. The depressed cutaneous reactivity observed in vivo was explained by the finding of major deficits in the efferent limb of cellular immunity. Initial rate of phagocytosis of both polymorphonuclear neutrophils and macrophages was significantly reduced in patients with SLE as compared with normal persons. Because of cell interaction, the presence of an intrinsic macrophage defect in SLE may contribute to the alleged T- and B-cell dysfunction in that disease.


Antinuclear antibody studies in chronic cutaneous discoid lupus erythematosus.

The prevalence of antinuclar antibodies (ANA) in chronic cutaneous discoid lupus erythematosus (DLE) is influenced by both patient selection and test sensitivity. If one excludes serum samples from patients with DLE with a history suggesting extracutaneous disease and defines the significance of the ANA test by simultaneously testing serum samples from patients with well-characterized connective tissue diseases, then only a small percentage of the patients with DLE have ANA at significant titers. These patients with DLE do have a higher pervalence of positive ANA tests at low serum dilutions when compared with controls, but only a few have positive ANA tests at titers comparable to those seen in patients with active systemic connective tissue diseases.


Visual suppression test.

Visual suppression of caloric nystagmus was studied in normal adults and in 98 clinical cases in order to justify the application of the procedure as a clinical test. The maximum slow phase velocity during ten seconds in darkness and the slow phase velocity during ten seconds in light were taken from the recordings and measured. The mean values of these slow phase velocities were calculated and the mean slow phase velocity in darkness was assigned a value of 100%. The value which the slow phase velocity in light subtracts from the slow phase velocity in darkness, represents the visual suppression. It was determined that visual suppression of the slow phase velocity of caloric nystagmus was 48 +/- 10% in 22 normal adults. This was caused by the visual fixation mechanisms. Cases in which lesions were diagnosed in the cerebellum, such as spinocerebellar degeneration and cerebelitis, showed reduced or abolished visual suppression. The lesion side can be determined by this test. Compensation following unilateral sudden loss of inner ear function can be measured by the visual suppression test.


Cancer control in xeroderma pigmentosum.

This study of identical twins affected with xeroderma pigmentosum, with follow-up and re-evaluation after a period of eight years, is unique in that it demonstrates clearly the value of cancer control methods, primarily the avoidance of solar radiation. The findings in the identical twins have been evaluated in context with their other affected siblings who also have shown a remarkable low rate of skin cancer upon initiation of cancer control (solar radiation avoidance).


Results of a modified distal spleno-renal shunt for portal hypertension.

Twenty-five patients were treated with a distal spleno-renal shunt modified after that of Warren. The operative mortality was 4/25. One patient had an early thrombosis. All post-operative angiography otherwise showed patent shunts. After a median observation time of 43 months, 10/20 patients included in the followup were dead. The chief cause of death was liver failure. Encephalopathy has been common although generally of minor degree. Hypersplenism, judged by thrombocyte count, was not significantly affected by the operation. Six of 21 patients have had gastrointestinal hemorrhage after the operation but no hemorrhage proved fatal. Postoperatively esophageal varices size was considerably diminished in most cases as judged by contrast x-ray. Ascites has not been a problem in this series. Postoperative angiography showed a marked and rapid reduction of portal blood flow to the liver with progressively more blood deviated through the coronary vein towards the shunt. This reduction in portal flow is a possible explanation of the high frequency of postoperative liver failure. This version of the distal spleno-renal shunt has probably no advantages over the portacaval shunt.


Sympathetic denervation in association with coronary artery grafting in patients with Prinzmetals' angina.

Myocardial revascularization in patients with Prinzmetal's angina has yielded variable results. Two patients are presented who underwent partial cardiac sympathectomy in combination with coronary artery grafting for typical variant angina associated with severe organic obstructive coronary artery disease. Late results 12 and 18 months postoperatively have been excellent in both instances as shown by clinical and angiographic evaluation. Although the exact mechanism responsible for Prinzmetal's angina is not known, it is believed that spasm through increased activity of vasomotor tone or of the autonomic nervous system plays a major role. Since this variant form of angina encompasses a whole spectrum at angiography, ranging from normal arteries to severely narrowed ones, including those with spasm, it is suggested that surgical treatment be planned accordingly. Thus, in patients who have organic stenoses with and without spasm, operative treatment may consist of removal of the preaortic or pretracheal plexus in association with conventional coronary artery grafting. In patients who have intractable episodes of ventricular arrhythmia or angina and who angiogram is normal or shows isolated spasm, coronary artery grafting should be abandoned, in view of the poor results reported in the literature in these circumstances, and cervicothoracic sympathectomy should be considered.


Selective intracavitary and coronary profound hypothermic cardioplegia for myocardial preservation: a new technique.

A technique is described for selective intracavitary and coronary hypothermic perfusion during cardiac bypass with cardioplegia to facilitate cardiac operations. A cold perfusate (Plasmalyte 148 and mannitol, 12.5 gm/L at 8 degrees to 10 degrees C) is administered with the aid of a low-flow perfusion pump into the left ventricular cavity and coronary circulation through an apical perfusion-venting (Per-Vent) catheter. This perfusate cools the myocardium rapidly and homogeneously to a temperature of 15 degrees to 20 degrees C. Within this temperature range, complete cardioplegia occurs and the safe ischemia period can be extended to 120 minutes. This method was applied in 50 unselected consecutive adult patients undergoing aortocoronary saphenous vein bypass grafting or aortic or mitral valve replacement. All patients survived and had excellent recovery of ventricular function.


A comment on aortic perfusion cannulas.

An improved aortic perfusion cannula is described. The portion that passes through the aortic pursestring suture is tapered. The cannula can thus adapt to any enlargement of the cannulation site and miminize annoying leakage of blood during cardiopulmonary bypass.


Early and long-term effects on direct myocardial revascularization on cardiac function: a prospective study using multivariable physiological analysis.

Perioperative and late follow-up hemodynamic cardiovascular studies to assess the effects of direct myocardial revascularization on cardiac function objectively have been completed on 51 patients. Analysis of the data delineated three distinct groups basedon the patterns of their early postoperative recovery. Group I patients (12) had a hyperdynamic cardiovascular response to operation and returned to a normal physiological range of cardiac function within 24 hours. Group II patients (24) initially had moderate to severe myocardial decompensation postoperatively but responded to inotropic support and moved into the normal physiological range within 24 to 48 hours. Group III patients (15) had severe, prolonged myocardial decompensation with little response to inotropic support. There were no early deaths in Group I, 1 early iatrogenic death in Group II, and 2 deaths from sepsis, 1 in Group I and 1 in Group II. All 7 cardiogenic deaths occurred in Group III patients. Late follow-up studies 4 to 23 months postoperatively have been completed on 29 patients. These showed cardiovascular stability in the mean values in Groups I and II. Significant improvement in mean cardiac function was seen in surviving Group III patients.


Management of anticoagulation in outpatients: experience with an anticoagulation service in a municipal hospital setting.

In 66 months, a general hospital's outpatient Anticoagulation Service (ACS) monitored 263 patients who received 280 courses of warfarin sodium totalling 254 patient treatment years. Major hemorrhagic morbidity was 4% of courses and there was no mortality attributable to warfarin therapy. Major hemorrhage occurred in patients with increased anatomic risk of bleeding (diverticulosis, hemorrhoids, cystitis), and was not a function of patient age, sex, anticoagulation control, or medications administered concurrently with warfarin. Control of anticoagulation was not correlated with age or other medications, but was worsened significantly by the presence of congestive heart failure. We attribute a favorable experience with outpatient ACS to careful patient selection, patient education and monitoring, attention to duration of anticoagulation, and continuing communication with primary physicians who retained responsibility for medical care. An ACS offers safety, consistency, efficiency, and a unified approach to outpatient anticoagulation in the general hospital setting.


Multiple myeloma and chronic lymphocytic leukemia in a single individual.

Chronic lymphocytic leukemia and multiple myeloma in a single individual is a rare occurrence; In previously reported cases, data relevant to the cional relationship between the two entities is not available. In this case, to our knowledge, the tenth reported, immunologic studies indicate that a chance association of two independent diseases has occurred rather than expansion of one single clone of Bcells at two morphological levels.


Kartagener syndrome: report of a case with mesangiocapillary glomerulonephritis.

The first known case of Kartagener syndrome associated with glomerulonephritis is reported. Mesangiocapillary glomerulonephritis was diagnosed in this patient several months before her death. This report also includes a review of the recent literature dealing with Kartagener syndrome and mesangiocapillary glomerulonephritis and a consideration of the possible relationship of infection to the cause of mesangiocapillary glomerulonephritis.


A survey of cohabitation on two college campuses.

Cohabitation emerged in the late 1960s because of relaxed housing rules, the availability of the "pill," a philosophy held by a plurality of students regarding the desirability of sex accompanying affection, and, perhaps, a need on the part of some students for a primary relationship. Some empirical data on the climate in which cohabitation emerged on two colleges are presented. A limited portrait of some of the characteristics of students who would cohabit or had cohabitated and the conditions under which they would consider entering into this arrangement is also provided. Data from this study revealed that a plurality of students on both campuses felt that cohabitation was acceptable when it was part of a relationship involving either planned marriage or affection. In addition, willingness to cohabit as well as cohabitation was more common among (1) males than females, (2) Jewish than Catholic and Protestant students, and (3) low church attendance students than high church attendance students. Between 10% and 15% of the students on the campuses were cohabiting.


Acquired cerebral dyschromatopsia.

Color blindness developed in five patients apparently because of lesions in the posterior portions of both cerebral hemispheres. Three of them also had symptoms of prosopagnosia. The lesions were neoplastic in two and vascular in three of the patients. It would appear that bilateral, inferior, occipital lobe lesions may be responsible both for acquired cerebral dyschromatopsia and prosopagnosia. Evidence from experimental investigations in primates suggests that the areas of the cerebral hemispheres analogous to those involved in these patients, may be specialized for the processing of colored stimuli.


The Davidson and Hemmendinger color rule as a color vision screening test.

The Davidson and Hemmendinger (DH) color rule was evaluated for color vision screening of normal and congenital color-defective subjects. Ninety-eight normal and 14 color-defective subjects were tested on the color rule under Macbeth illumination of 5,400 K. The color-defective subjects were also tested on the Nagel anomaloscope, the Farnsworth D-15, and the H-R-R pseudoisochromatic plates. The DH color rule performed as accurately as the anomaloscope and was superior to the other two tests in detecting anomalous trichromats and in discriminating protanomalous subjects. The color rule also discriminated dichromats from anomalous trichromats. For severe color-defective subjects (dichromats, achromats), the color rule was more time-consuming than the other tests and discrimination was less certain. Response patterns on the DH color rule and response variability of the different classifications are reported.


Intravitreal amphotericin B treatment of Candida endophthamitis.

A 43-year-old heroin addict with Candida albicans endophthalmitis was treated with a single 5-mug intravitreal injection of amphotericin B. The diagnosis was confirmed by smears and cultures of a vitrous aspiration. The patient's accidental death seven weeks after treatment enabled us to obtain histopathologic evidence that the infection had been cured and that the amphotericin B had had no toxic effect on the retina. Intravitral amphotericin B should be considered an important mode of treatment of Candida endophthalmitis.


Computer tomography of cerebellopontine angle lesions.

Computer tomography (CT) was used in 53 consecutive patients with a working diagnosis of cerebellopontine angle tumor. The CT was performed with the 160 X 160 matrix scanner, height of sections was 13 mm. Metrizoate sodium (1.5 ml/kg of body weight) was used for tumor enhancement. Seventeen CT scans revealed tumors; one patient proved at operation to be false-positive. Thirty-six CT scans revealed no tumors; two examinations may prove to be false-negative, but surgical verification has so far not been obtained. The smallest tumor demonstrated by CT extended 7 mm into the angle, while one of the possible false-negative CT scans after iophendylate injection cisternography showed a tumor extending 5 mm into the angle. It is concluded that CT is a harmless, noninvasive neuroradiological procedure, and should precede invasive procedures. It can be used safely in patients with increased intracranial pressure.


Round window ultrasonic treatment of Meniere disease.

The neurosensory structures within the vestibular labyrinth of the inner ear are selectively irradiated with ultrasonic energy to alleviate the vertiginous symptoms of Meniere disease. However, correct application and coupling of the ultrasonic transducer to the inner ear is essential for maximum transmission of energy into the vestibule. The importance of assessing the results of long-term postoperative treatment is demonstrated by a change in the success rate that decreased by approximately 10% when the results obtained within the first 12 months of treatment were compared with those after four years. In this investigation, 32 patients were treated by the round window approach between 1970 and 1972, and after four years it was found that 72% of these were successful in relieving the giddiness symptoms.


A human haemic cell line capable of cellular and humoral killing of normal and malignant cells.

A line of human leukaemia-derived cells is described that kills a wide range of human and animal cell lines, whether normal or malignant, even at a ratio of 1:1. During exposure to the target cells, the killer cells released a factor into the culture medium which destroyed target cells in the absence of the killer cells. This phenomenon occurs without exogenous complement and requires no pre-treatment of target or killer cells. The humoral factor is a protein precipitable by 60% saturation of ammonium sulphate and has a mol. wt. of approximately 70,000; It prevented the growth of a fibrosarcoma in mice.


Systemic lupus erythematosus associated with klinefelter's syndrome.

Studies in estrogen metabolism were carried out in 2 males with systemic lupus erythematosus (SLE) who also had Klinefelter's syndrome. Although these studies revealed elevated levels of urinary estrogens in 1 patient, abnormalities of estradiol metabolism suggesting persistent estrogen stimulation were detected in both. This report notes an association between SLE and Klinefelter's syndrome and suggests that chronic estrogenic stimulation may be significant in the development of SLE in these 2 patients.


Description of the cells from the lymph nodes of patients with non-Hodgkin's lymphoma according to some B- and T-cell characteristics.

The lymph node cell populations from 24 patients with non-Hodgkin's lymphoma were investigated for some of the surface characteristics which are used as T- and B-lymphocyte markers. Nineteen of the patients had had no treatment of any kind while the other 5 had had either recent radiotherapy or chemotherapy. Seven lymph nodes from patients without malignant disease and 7 others with reactive changes were also studied. It was found that lymphocytic lymphomas, nodular or diffuse, well or poorly differentiated, had a high proportion of cells which were positive for B-cell markers. Other non-lymphocytic lymphomas had a higher proportion of cells positive for T-cell markers, and were similar to the cells from non-malignant lymph nodes.


Effect of sodium salicylate on human and mouse granulopoiesis in vitro.

Sodium salicylate inhibited generation of granulocyte and macrophage colonies when added to soft agar cultures of mouse or human bone marrow cells (CFUc) containing colony-stimulating factor (CSF). This effect was dose-dependent with over 90% inhibition at 48 mg%. The salicylate effect was not decreased with increasing concentrations of CSF, but inhibition was reversed when salicylate-treated CFUc were washed with drug-free medium before plating. CSF production was not inhibited by salicylate.


HLA antigens and antinuclear antibody titres in juvenile chronic iridocyclitis.

HLA antigen frequencies and antinuclear antibody titres were studied in 43 patients with juvenile chronic iridocyclitis. We did not detect an increased incidence of HLA-B27 in patients having chronic iridocyclitis associated with juvenile rheumatoid arthritis or in patients with "chronic iridocyclitis in young girls". Both groups of patients had a statistically significant increased incidence of antinuclear antibodies. However, these antibodies were detected more frequently in patients with chronic iridocyclitis associated with JRA than in patients with "chronic iridocyclitis in young girls".


Bleb dystrophy of the cornea: histochemistry and ultrastructure.

Corneal epithelial biopsies from two patients affected with asymptomatic bleb dystrophy were examined by light and electron microscopy. The basis of this disorder appears to be the deposition of a neutral mucopolysaccharide-protein complex as a continuous layer between the basement membrane and Bowman's layer. This material, although homogeneous in light microscopy, has a fine granular ultrastructure. It is friable, and in view of the apparent integrity of the basement membrane/hemidesmosome system it is suggested that the recurrent epithelial erosions which can occur in this disorder result from shearing of this layer. Fissures in the bleb material contain cells which may play a role in its degradation.


[Pleuropulmonary lesions due to Haemophilus influenzae].

Empyema due to Hemophilus influenzae has been reported only rarely. This report describes the cases of ten children with empyema due to this organism. Diagnosis was made through growth of the organism in pure culture from pleural effusion. H. influenzae empyema may occur in older children as well as in infants and, in contrast to certain other infections with this organism, empyema due to H. influenzae may be more common than is generally suspected.


A new solid-state microelectrode for measuring intracellular chloride activities.

Solid-state microelectrodes from measuring intracellular Cl activity (alphaiCl) were made by sealing the tips of tapered glass capillaries (tip diameter 0.3 mum), coating them under vacuum with a 0.2-0.3 mum thick layer of spectrscopic grade silver, and sealing them (except for the terminal 2-5 mum of the tip) inside tapered glass shields. 106 microelectrodes had an average slope of 55.0+/- 0.6 m V (S,E,) per decade c  hange in alphaCl. Tip resistance was (77.1+/- 3.1) x 10(9) omega(n=30). Electrode response was rapid (10-20 s), was unaffected by HCO3, H2PO4, HPO42 or protein, and remained essentially unchanged over a 24-h period. AlphaiCl in frog sartorius muscle fibers and epithelial cells of bullfrog small intestine was measured in vitro. In both tissues, alphaiCl significantly exceeded the value corresponding to equlibrium ditribution of Cl across the cell membrane.


Intracellular distribution of lipophilic fluorescent probes in mammalian cells.

The intracellular distribution of several hydrophobic fluorescent probes (1,6-diphenyl-1,3,5-hexatriene (DPH), perylene, and 2-p-toluidinyl-6-naphthalene sulfonate (TNS) in mouse lymphocytes and a fibroblast cell line was examined using radiolabeled fluorescent probes and the technique of high resolution EM autoradiography. Following a short term incubation, DPH and perylene were found largely internalized in cells, while TNS was localized predominantly at the cell surface. These findings suggest that fluorescence polarization studies using such probes with intact cells do not necessarily monitor only the cell surface membrane and must be interpreted with caution.


Chromatography of human urinary erythropoietin and granulocyte colony-stimulating factor on insolubilized phytohaemagglutinin.

Human urinary erythropoetin was absorbed to phytohaemagglutinin coupled to agarose or porous glass and quatitatively eluted by a saturated solution of MgCl2. This method provides a means of separating erythropoietin from several of its contaminants, presumably on the basis of its carbohydrate side chains. Erythropoietin which had been purified by chromatography on insolubilized phytohaemagglutinin was sufficiently free of toxicity to be assayable in tissue culture even when crude urine was used as a starting material.


The Harold E. Himwich Memorial Lecture. Significance of biochemical parameters in the diagnosis, treatment, and prevention of depressive disorders.

There is  a suggestive evidence for a relationship between central 5-HT and the occurrence of certain types of depressions. This evidence is derived from three sources: postmortem studies; measurement of CSF 5-HIAA; accumulation of CSF 5-HIAA after transport blockade by probenecid. Disturbances of central 5-HT metabolism are not typical for any depression but for certain types of vital (endogenous) depression. This implies that the group of vital depression, though tending towards homogeneity in terms of symptomatology, is heterogenous in biochemical terms and comprises patients with and without disorders in central 5-HT metabolism. It is plausible that disorders of the 5-HT metabolism play a role in the pathogenesis of depression, instead of resulting from them. This statement is based on the following findings: (i) 5-HTP can abolish or alleviate the depressive syndrome or some of its elements. (ii) This 5-HTP effect can be potentiated by clomipramine (Anafranil), a relative selective inhibitor of 5-HT reuptake. (iii) There exists a negative correlation between 5-HT turnover in the CNS and the therapeutic effect of clomipramine. The alleged distrurbances in central 5-HT are more likely to be predisposing than of direct causative significance. This assumption is based on two observations: (i) In more that 50% of cases, the 5-HT turnover remains low after clinical recovery, the patient being drug-free. (ii) There is suggestive evidence that abolition of the 5-HT deficit (by means of 5-HTP) exerts a prophylactic effect in uni-and bipolar depression.


Brain polarization: behavioral and therapeutic effects.

Polarization is the passage of small constant direct currents through the brain. During the last 12 years some authors have investigated its therapeutic effectiveness in psychiatric patients with different and sometimes contradictory results. Although there seems to be a "fairly consistent body of evidence concerned with the effects of direct currents applied to the head in psychiatric patients" (Nias, 1976), only the procedure involving pulsating low-level currents (electrosleep) has received increasingly more attention in recent years, while polarization (constant d-c currents) is not even mentioned in most standard textbooks. This review concentrates on work dealing with behavioral and therapeutic effects of polarization. The procedure involves the continuous flow of low-level current (up to 1 ma) between cephalic and noncephalic electrodes during prolonged periods of time (usually hours), without inducing convulsions (as in electroconvulsive therapy) or sleep, the subject being almost unaware of the treatment. Because of its implications for research, attention is also devoted to some representative work on physiological effects of polarizing currents.


Granulopoietic studies in acute lymphocytic leukemia of children.

Studies have been carried out on the levels of serum and urine colony stimulating activity (CSA) and peripheral blood and bone marrow colony forming cell numbers in children with acute lymphocytic leukemia (ALL) during various phases of their disease. These studies have suggested that serum and urine levels of colony stimulating factor are reduced during the inital or relapse phase of the disease compared to levels found during remission. It has also been found that the number of bone marrow colony forming cells is reduced in relapse or before treatment and elevated during remission while the number of peripheral blood colony forming cells is increased during relapse or before treatment and normal during remission. It has also been shown that mixing of serum or leukemic cells with normal human bone marrow cells inhibits colony formation.


Effect of harmaline on sodium transport in Rana esculenta skin.

1 Harmaline, together with certain hallucinogenic alkaloids of the same group (harmine, 2 methyl harmin) stimulates sodium transport across the in vitro skin of Rana esculenta when it is added to the external medium at a low concentration (0.1 mM). This effect is due to an increase of the sodium influx, and is reversed by washing. It is suggested that harmaline intervenes at the sodium penetration sites at the external face of the transport compartment. 2 At a higher concentration (5 mM) added to the internal medium harmaline inhibits sodium net absorption. The inhibition is due mainly to an increase of the efflux, while the influx may be either inhibited or increased. Under these conditions the influx becomes insensitive to amiloride. It is suggested that the inhibition of sodium transport is the result of harmaline interfering with a transport ATPase, and also that harmaline induces new sites for the passage of sodium.


Cataleptic effect of 61-91 beta-lipotropic hormone in rat.

Intraventricular administration of a peptide from ovine pituitaries whose structure is identical to the 61-91 C-terminal portion of beta-lipotropic hormone (61-91 beta-LPH) induced catalepsy, muscular hypertonus and analgesia in rats. Naloxone inhibited both the analgesic and cataleptic effects. 1-dihydroxyphenylalanine (1-DOPA) completely prevented the cataleptic effect. The cataleptic effect of 61-91 beta-LPH was potentiated by 1-5-hydroxytryptophan (5-HTP).


Thymosin reconstitution of T cell deficits in vitro in cancer patients.

Thymosin, a soluble extract of fetal calf thymus, has increased cellular immunity in children with thymic deficiency. Prior to therapy, an increase in thymus-dependent lymphocyte (T cell) levels in vitro after incubation with thymosin correlated with a rise in peripheral blood T cell levels and improvement in other parameters of cellular immunity. These correlations constituted the basis for a study of the effects of thymosin on T cell levels in vitro in cancer patients. Groups studied were 350 untreated patients with local-regional solid malignancies, 157 patients cured of these tumors, 340 patients studied at 523 intervals during radiation therapy, 80 patients receiving chemotherapy for disseminated solid malignancies, and 427 normal volunteers. Although there were significant differences among the groups in mean leukocyte, lymphocyte and T cell levels, among those with low T cell levels in each group there was a significant inverse relation between T cell levels after incubation with thymosin in vitro and initial T cell levels, with the exception of patients receiving chemotherapy. In patients receiving chemotherapy, T cell levels increased independently of initial T cell levels. These in vitro observations are consistent with evidence that a major effect of thymosin is maturation of T cell precursors; however, the effect is that of reconstitution at low T cell levels, and not of elevation to levels significantly above normal. The results provide a rationale for clinical trials with thymosin to maintain immune competence during radiation therapy and chemotherapy, and for a two-phase approach to immunotherapy of cancer utilizing thymosin for reconstitution of cellular defects followed by administration of agents that potentiate cellular immunity.


The effects of therapeutic irradiation on lymphocytes and immunity.

The lymphocytotoxic effect of therapeutic irradiation may lead to immune depression. The significance of such effects is yet to be determined in many malignancies, especially in light of the persistant immune depression in many "cured" patients. The present review examines the effects of age, type of cancer, and stage of disease as well as the results of immune parameters following radiation therapy. Factors to be considered in both the analysis of present day data and in future studies are also reviewed.


Chromatin phospholipids in normal and chronic lymphocytic leukemia lymphocytes.

Certain phospholipids are associated with the nonhistone chromosomal proteins extracted from normal B- and chronic lymphocytic leukemia lymphocytes. The ratio of phospholipids to nonhistone chromosomal proteins was constant with the different methods used for isolating nuclei and extracting the chromatin, although the various methods allowed a different recovery of total lipids from chromatin. Three phospholipids were extractable from the nonhistone protein fraction, but their respective ratios varied in chronic lymphocytic leukemia compared to normal B-lymphocytes. The most significant variation concerns the reduction of sphingomyelin content in leukemic lymphocytes, since this prospholipid in vitro affects both DNA stability and transcription.


The susceptibility of guinea pig cells to the colony-inhibitory activity of lymphotoxin during carcinogenesis.

The time of susceptibility of cells to lymphotoxin during carcinogenesis was determined. At different stages of in vitro chemical carcinogen-induced neoplastic transformation, colony formation of guinea pig cells was evaluated with lymphotoxin obtained from syngeneic nonimmune leukocytes. Cells exhibiting sequential morphological alteration, morphological transformation, and neoplastic transformation had been preserved in liquid nitrogen and, after reintroduction in culture, were analyzed simultaneously for their susceptibility to lymphotoxin. Morphologically altered and morphologically transformed cells at subcultures prior to neoplastic transformation were resistant to lymphotoxin inhibition of colony formation. Cells neoplastically transformed by N-methyl-N'-nitro-N-nitrosoguanidine in vitro or by N-methyl-N'-nitro-N-nitrosoguanidine or diethylnitrosamine with the host-mediated, in vivo-in vitro method were susceptible and exhibited a quantitatively culture-specific degree of colony inhibition. The parental noncloned and cloned neoplastically transformed cells in each series, furthermore, exhibited similar degrees of colony inhibition, which indicates that lymphotoxin susceptibility developed concomitant with, or close to, the time of neoplastic transformation and remained stable during subsequent cell generations.


The interpeduncular nucleus (ITP). Ultrastructure data indicative of a possible neurosecretory activity.

Special types of cells of the interpeduncular nucleus (ITP) in the fog, Rana esculenta, are described after three typed of fixation: osmium tetroxide, aldehydes and potassium permanganate. Large granules with a sub-unit structure occurring together with bundles of filaments and elongated mitochondria are illustrated in the processes of cells, the perikarya of which lie distant from the ependymal lining of the aqueduct of Sylvius. Such processes cross the ITP in a dorso-ventral direction perpendicular to the fibers which traverse the nucleus in a horizontal and frontal plane. They reach the subpial ventral surface of the nucleus ending in foot-like expansions where granules and mitochondria are assembled. The secretory nature of the granules is assumed. The release of possible peptide hormones into the interpeduncular cistern, where a pool of cerebrospinal fluid and large blood vessels occur, cannot be excluded.


Ventricular apical vents and postoperative focal contraction abnormalities in patients undergoing coronary artery bypass surgery.

Ventriculograms made 9-15 months after surgery in 48 patients with normal preoperative apical contraction were reviewed to determine the influence of apical venting on apical wall motion in patients undergoing coronary bypass surgery. After interpretation of postoperative apical wall motion, the patients were subdivided into two groups. One group consisted of 34 patients who were vented by inserting a catheter through the apex of the left ventricle and the second group included 14 patients in whom no transventricular vent was made. The two groups were similar clinically and hemodynamically before surgery, and the surgical procedures were similar with the exception of vent site. Following surgery, incidences of graft patency and antegrade flow to the apex were also similar. Nineteen (56%) patients in the apically vented group had apical dyskinesia or akinesia observed on the postoperative ventriculogram while none of the patients who were not apically vented had these findings. None of the patients with apical dyskinesia or akinesia had congestive heart failure following surgery. The postoperative ventriculograms of 12 patients with mitral stenosis who underwent valvulotomy by inserting a Tubbs dilator through the apex were also analyzed. Only one patient (8.5%) had apical dyskinesia or akinesia. Since the patients with mitral stenosis probably did not have significant coronary artery disease, it is possible that the combination of the apical vent and ischemic heart disease was responsible for the focal contraction abnormalities observed.


Familial occurrence of histiocytosis.

The clinical and histological findings of four children with lethal histiocytosis are reported. The children belonged to two sibships and originated from a Swedish geographical isolate. Consanguinity between the parents was established for one of the sibships, belonging to a pedigree in which malignant disease occurred in two generations. The observations indicate that the type of histiocytosis investigated is caused by homozygosity for a single recessive gene. The association between histiocytosis and malignancy is discussed.


The disposition of sulindac.

The disposition of sulindac, a new nonsteroid anti-inflammatory drug, has been studied in normal volunteers in five separate clinical studies. Based upon material balance considerations, a minimum of approximately 88% of an oral dose is absorbed. The major biotransformations involve irreversible oxidation of the sulfinyl group of sulindac to sulfone and reduction to the corresponding sulfide. The latter, which all available evidence indicates to be the pharmacologically active form of sulindac, is not excreted in urine, and has an apparent terminal half-life of 18.2 hr, well suited to twice daily dosage of its pro-drug. Following twice daily dosage of sulindac for 5 days, plasma levels of sulfide approach an apparent steady state with concentrations varying only within a twofold range over each dosage interval. The reversible biotransformation between sulindac and its active sulfide metabolite provides the basis for two therapeutic advantages relating to the gastrointestinal intolerance usually associated with anti-inflammatory drugs: (1) circumvention of initial exposure of gastric and small intestinal mucosa to the active form of the drug and (2) maintenance of systemic levels of active drug by means of enterohepatic recycling, principally of inactive pro-drug.


The changing status of ejection fraction as a predictor of early mortality following surgery for acquired heart disease.

Several reports in the literature and our experience prior to 1974 support the thesis that operative risk in patients with acquired heart disease and poor ventricular function (as assessed by a biplane ejection fraction [EF] less than or equal to 0.40) was very significantly increased over the risk in patients with normal ventricular function. These results led to disagreement in the literature regarding the advisability of surgery in patients with poor ventricular function. Various EFs from less than 0.31 to less than 0.50 were suggested as contradicting elective surgery, while more aggressive groups recommended surgery in all patients with angina. Precise comparison of the results reported by different groups was not always possible because of the common reliance on single-plane right anterior oblique ventriculograms, which tend to underestimate EF and overestimate operative risk. Using biplane ventribulograms for accurate estimation of EF, we have demonstrated a significant reduction in 30-day operative risk to a clinically acceptable 3 percent (1/32) for single valve replacement and aortocoronary surgery patients with poor ventricular function (EF less than or equal to 0.40) during 1974. Considering the high risk of medically treated patients with reduced ventricular function, these results support further evaluation of surgical palliation for patients with valvular or coronary heart disease and reduced ventricular function.


Morphometric studies in triacetyloleandomycin-induced ultrastructural modifications of rat hepatocyte mitochondria.

Morphometric parameters of mitochondria such as volumetric density, surface density of envelopes and cristae and numerical density were calculated for control untreated and triacetyloleandomycin (TAO)-treated rat hepatocytes using a point-counting technique. Moreover, morphometric parameters calculated experimentally and those computed on the basis of the least square interpolation and the agreement with the chi2 test, were compared. The equations modelling each main morphometric parameter of experimental motochondria were also computed. Morphometric study revealed that TAO produces a highly reproducible pattern of morphological alterations in the mitochondrial population of rat hepatocytes, and a good agreement between experimental and theoretical data was found. The response of hepatocyte mitochondria to TAO may be modelled by parabolic functions described by equations of the second degree. During the whole experimental period, the number of mitochondria decreases, but the specific volume of mitochondria increases. The area of the cristae surface per mitochondrion does not change substantially during the whole experimental period but since the quantity of internal mitochondrial membranes per hepatocyte is less in the later experimental period than in control material, it can be assumed that the oxidizing capacity per hepatocyte has diminished. The morphometric model based on TAO-treated hepatocyte mitochondria is different from those so far described in the literature for rat liver.


[Emergency treatment of haemophilia A with factor VIII inhibitors using activated prothrombin complex concentrates (author's transl)].

Severe rectal bleeding in a 6-year-old boy with haemophilia A and factor VIII inhibitors could not be stopped with factor VIII concentrates. But a good effect was achieved with activated prothrombin complex concentrates (fraction FEIBA), given over eight days. Amaurosis occurred as a complication after injection of the first dose, but disappeared completely within several minutes. Tests revealed accelerated intravascular coagulation with increased fibrin monomers and fibrin/fibrinogen degradation products.


Effects of fibroblast and epidermal growth factors on ovarian cell proliferation in vitro. I. Characterization of the response of granulosa cells to FGF and EGF.

Despite numerous studies on the effects of gonadotropins on ovarian cells in tissue culture, the factors controlling the proliferation of granulosa cells in vitro remain unknown. We have examined the effect of fibroblast growth factor (FGF) and epidermal growth factor (EGF) on granulosa cell proliferation in vitro in an attempt to clarify their possible roles in the control of ovarian development. FGF and EGF both stimulate DNA synthesis in resting populations of granulosa cells. The half-maximal response forthis effect with FGF was observed at 4 X 10(-11)M and with EGF at 1.5 X 10(-13)M. Autoradiography demonstrated that the whole cell population initiated DNA synthesis in the presence of either EGF or FGF, thus precluding an additive effect of the two mitogens. When cells were maintained at low density (100 cells/cm2) in the presence of low serum (1%) they divided with a doubling time of 48-72 h, but addition of either EGF or FGF accelerated their proliferation. The doubling time observed in the presence of FGF was 16 h versus 20 h with EGF and the final cell density reached in the presence of EGF or FGF was 20 times that of cells maintained in the presence of 1% calf serum alone. In the presence of 10% serum, granulosa cells had a doubling time of 24 h and the final density reached was similar to that observed in 1% serum with EGF and FGF. Addition of EGF or FGF to 10% serum resulted in a final density 3 to 4-fold higher than that observed with 10% serum alone. The ultrastructure of the granulosa cells grown in the presence of EGF or FGF was similar to that of cells maintained in the absence of added mitogens. The only marked difference was that cells grown in the presence of FGF or EGF had a high lipid granule content while cells grown in their absence had a low lipid granule content. The effect of various concentrations of FGF and EGF on the proliferation of granulosa cells has been analyzed. The minimal effective dose of EGF was 3 X 10(-14)M and saturation was observed at 3 X 10(-11)M, with a half-maximal response at 6 X 10(-13)M. With FGF the minimal dose stimulating proliferation was 1.5 X 10(-12)M and saturation was achieved at 1.5 X 10(-10)M, with a half-maximal response at 3 X 10(-11)M. Our results show that EGF and FGF are the most potent mitogens ever observed and are mitogenic for granulosa cells at 300 to 3000-fold lower concentrations than for other cell types which have been studied, such as fibroblasts or lens epithelial cells.


Effects of fibroblast and epidermal growth factors on ovarian cell proliferation in vitro. II. Proliferative response of luteal cells to FGF but not EGF.

The effect of fibroblast growth factor (FGF) and epidermal growth factor (EGF) on luteal cell proliferation in vitro has been examined. Luteal cells maintained in the presence of low serum (1%) go through a doubling after 7 days. Addition of EGF induced one more doubling of the cells, after which the cells became resting. In contrast, FGF induced the cells to divide logarithmically with a cell cycle of 48 h. The effect of FGF was dependent on the serum and FGF concentrations. It has been obtained with serum concentrations ranging from 0.1% to 10% and with FGF concentrations ranging from 0.1 ng to 10 ng/ml. The half-maximal FGF response was observed at 1.5 x 10(-11)M. In contrast, EGF has no effect besides causing an initial cell doubline within the same range of serum or FGF concentrations. Since granulosa cells have been shown to be highly sensitive to EGF as well as FGF, it can be concluded that during the luteinization process that sensitivity of the cells to EGF is lost, while the sensitivity of FGF is retained. This demonstrates that although luteal cells and granulosa cells are interrelated cell types their sensitivity to growth factors such as EGF is quite different.


A superfusion system technique for the study of the sites of action of glucocorticoids in the rat hypothalamus-pituitary-adrenal system in vitro. II. Hypothalamus-pituitary cell-adrenal cell superfusion.

Basal and stimulated CRF release by hypothalamic blocks was studied by coupling the effluent of superfused hypothalamus tissue to a joint pituitary cell-adrenal cell superfusion system and measuring corticosterone production. Log dose-response curves of the adrenal cells for ACTH and of the pituitary cell-adrenal cell system for CRF were linear over the ranges used. Ca++-independent basal CRF release by the hypothalamus could be blocked in vitro by 0.2 mug/ml dexamethasone in the medium, or in vivo by treating the hypothalamus donor rats with corticosterone, 1 mg/rat ip 30 min before decapitation. These treatments did not impair CRF release caused by Veratridine (5 x 10(-6)M or by electrical stimulation. Adrenalectomy increased only basal but not stimulated CRF release. These results indicate that glucocorticoids have a hypothalamic site of action.


Immunodeficiency with lymphoid hyperplasia.

A 2 1/2-year-old boy presented with recurrent respiratory tract infections, generalized lymphadenopathy and hepatosplenomegaly. Immunologic evaluation revealed a deficiency of humoral immunity. Repeated lymph node biopsies during a 10-year follow-up constantly showed excessive follicular hyperplasia with huge germinal centers consisting of germinoblasts, but lacking plasma cells. The disease can be interpreted as a subtype of the common variable immunodeficiency in which the commutation of germinoblasts to plasma cells in the evolution of B cells is blocked.


Immunological studies in childhood scleroderma.

The results of immunological studies on 13 children suffering from scleroderma are reported. Antinuclear antibodies with speckled pattern of fluorescence could be found in systemic sclerosis and in 3 patients with scleroderma en bandes. The same patients (except but one with PSS) demonstrated high levels of DNA antibodies. The 2 patients with PSS were found to have a very low percentage of T cells, whereas the percentage of B cells was increased. The results demonstrate the significance of autoimmunity not only in systemic sclerosis but also in focal scleroderma. Beyond this it can be presumed that immune deficiency (with a defect in cellular immunity) may be the predisposing cause of at least progressive systemic sclerosis.


Response characteristics and vestibular receptor convergence of frog cerebellar purkinje cells. A natural stimulation study.

1. The horizontal sinusoidal frequency response and the problem of vestibular receptor convergence in Purkinje cells (P-cells) of the auriculum, dorsal rim and corpus cerebelli were studied in curarized frogs with natural stimulation. 2. Primarily "simple" but also "complex" spikes were evoked by sinusoidal stimulation of the horizontal canals. P-cell "simple" spike activity could be grouped into types I-IV. Type I and II responses were directionally sensitive and thus were evoked at the stimulus frequency. Type III (and IV) cells, on the other hand, had response waveforms double that of the input frequency, with peak increases (or decreases) in discharge inphase with head velocity in the mid-frequency range. Except in the cerebellar midline regions where type III response waveforms were symmetrical, ipsilateral sinusoidal responses were larger in magnitude than those evoked during contralateral rotation. Despite the differences in magnitudes, ipsi- and contralateral response phase angles for one cell were approximately equal. "Complex" spikes were evoked with ipsi (type I) or contralateral (type II) horizontal rotation. Generally only 1-2 spikes were evoked per cycle with short (0-60 degrees) or long (120-150 degrees) phase-lags following acceleration. 3. A Bode analysis of type I "simple" spike activity in yaw indicates a slightly greater phase-lag and a 10-15 fold smaller P-cell gain in the range 0.05-0.5 Hz when compared to peripheral horizontal canal neurons. 4. Stimulation of the vertical canals and otolith organs also evoked "simple" and, to a lesser extent, "complex" P-cell spikes. "Simple" spikes were in most cases (85%) evoked by stimulation of several canal and/or otolithic receptors thus demonstrating a high degree of receptor convergence. "Complex" spikes, however, were only evoked by stimulation of one canal or otolith receptor. 5. Otolithic input to P-cells, examined statically and with low level constant velocity rolls, was mainly phasic or phasic-tonic in nature.


Relation of a cross-reactive idiotype to genetic control of the immune response.

Antibodies elicited in strain A mice by immunization with keyhole limpet hemocyanin-p-azophenylarsonate (KLH-Ar) produce anti-Ar antibodies, some of which share a cross-reactive idiotype (CRI); in general, 20 to 70% of the antihapten antibody population carries the idiotype. Large amounts of antibody can be produced by the induction of ascitic fluids, using a 9:1 ratio of complete Freund's adjuvant (CFA) to antigen. Antibodies with the CRI can be isolated by isoelectric focusing from selected mice that have produced a high concentration of the CRI. The H chains exhibit a single homogeneous sequence through the first hypervariable region and, when isolated from a large number of individual mice, appear to be invariant in the first framework region. These findings indicate that somatic mutation is not a significant factor in the determination of framework sequences. Appearance of the CRI can be suppressed in adult A/J mice by administration of rabbit anti-idiotypic antiserum prior to immunization. Such suppressed mice produce normal concentrations of anti-Ar antibodies lacking the CRI. Anti-idiotypic antibodies produced against such antibodies failed to show cross-reactivity with anti-Ar antibodies arising in idiotypically suppressed or nonsuppressed A/J mice. The great sensitivity of the assay indicates that the number of such "private" idiotypes, all present on anti-Ar antibodies of a single strain, must be extremely large; this supports a somatic mechanism for the generation of diversity. The "private" idiotypes arising in suppressed, hyperimmunized mice can be adoptively transferred into multiple, irradiated (200 R) recipients by injections of spleen cells or of cells from ascitic fluids. The use of ascitic fluids permits the rapid production of a colony of mice bearing the idiotype. This should facilitate structural studies of a variety of idiotypically different molecules sharing the same (anti-Ar) specificity, as well as studies of the mechanism of suppression.


Action of the triglycyl hormonogen of vasopressin (glypressin) in patients with liver cirrhosis and bleeding esophageal varices.

Seven patients with compensated liver cirrhosis and esophageal varices, all with a base line wedge hepatic vein pressure greater than 20 cm H2O, received 1-mg doses of vasopressin hormonogen (tGLVP) intravenously. There was a significant mean decrease in wedge pressure of 32%, which lasted for at least 20 min (the duration of measurement), with no change in cardiac output measured. The only cardiac response was a 10 to 20% bradycardia at the height of the moderate pressor response-otherwise the ECG was without change. In 5 patients who received the same tGLVP dose during surgery, direct measurements of portal venous pressure showed the same degree of decrease within 10 min of intravenous injection. Fifteen patients with liver cirrhosis and severe bleeding from esophageal varices were treated conservatively with blood transfusion and tGLVP as the only major drug aside from antibiotics. A nonrandomized control group of 13 patients with the same age distribution, stage of disease, number of previous bleeds, etc., was treated conservatively in the same manner, except that they received either no hemodynamically active drugs or short acting neurohypophysial peptide preparations such as Pitressin. In the control group there was a 61.5% total mortality, a 53.8% mortality directly related to uncontrollable bleeding, and a mean duration of the bleeding episode of 11 days. In the tGLVP-treated group total mortality was 20%, mortality directly related to uncontrollable bleeding was 13.3%, and mean duration of the bleeding episode was 2.9 days. These results appear to justify a large scale clinical trial of the vasopressin hormonogen in this disease.


On the nature and etiology of vascular ectasias of the colon. Degenerative lesions of aging.

Vascular lesions of the right colon are being diagnosed increasingly as a cause of lower intestinal bleeding, but their nature and occurrence, primarily in the elderly, remains unexplained. Colons from patients with clinical and angiographic diagnoses of cecal vascular lesions were studied by injection and clearing, and by histological sections. In all injected specimens one or more mucosal vascular ectasias were identified. The mucosal lesions appeared to be secondary to dilated tortuous submucosal veins which were the more prominent feature and were often present without the mucosal ectasia. This suggests that ectasias are caused by chronic, intermittent, low grade obstruction to submucosal veins with dilation and tortuosity initially  of submucosal veins, then of venules, capillaries, and arteries of the mucosal vascular unit. Ultimately, precapillary sphincters lose their competency, producing small arteriovenous communications. The concept that ectasias are degenerative lesions was evaluated by studying 15 right colons resected for carcinoma with no history of bleeding. Mucosal ectasias were identified in four colons and submucosal ectasias in eight. These investigations suggested that these lesions: (1) are vascular ectasias developing as a degenerative process of aging, (2) are present with or without bleeding in a significant portion of the population over 60 years of age, (3) are multiple more often than single, and (4) may represent the commonest cause of major lower intestinal bleeding in the elderly.


Elastases from human and canine granulocytes, II. Interaction with protease inhibitors of animal, plant, and microbial origin.

Inhibitors of animal, plant, and microbial origin were tested against human and canine granulocytic elastases. The trypsin-chymotrypsin inhibitors from dog submandibular glands, from soybeans (Bowman-Birk) and from chickpeas show strong interaction with these proteases (Ki = 10(-8) - 10(-9)M). The trypsin-kallikrein inactivator of bovine organs (Trasylol) is not active against granulocytic elastases or against human granulocytic cathepsin G. Elastatinal, a specific inhibitor of elastases, isolated from actinomycetes (Streptomyces griseoruber), forms stable complexes with elastase from human (Ki = 6.2 X 10(-6)M) and canine granulocytes (Ki = 1.1 X 10(-6)M). A possible therapeutic application of these inhibitors for the inactivation of granulocytic proteases, which are able to degrade connective tissue in different pathological states, is discussed.


Genetic controls and cellular interactions in antibody formation.

Both thymus-derived lymphocytes (T cells) and bone marrow--derived lymphocytes (B cells) play critical roles in specific antibody responses to antigens. Genetic controls of the antibody response in mammals have been found to reside largely within the major histocompatibility complex where different genes appear to code for immune response (Ir), immune suppression (Is), and cell interaction (CI) molecules.


Brain-associated thymic antigen in chickens.

Sera were produced in rabbits against a saline extract of chicken embryo brain (CBE). The rabbit anti-chicken brain (RACB) sera revealed, in micro-Ouchterlony studies, brain-associated antigens in extracts from the thymus, bursa, spleen and kidney. Absorption of the sera with normal serum (ns) and kidney (K), (RACBns, K), removed all reactivity with tissues other than brain. However, cytotoxic studies demonstrated that the kidney-absorbed serum was toxic to lymphocytes from thymus, bursa and spleen. Proper dilution of the RACBns, K produced a serum which was more cytotoxic for thymic lymphocytes than bursal lymphocytes. This study indicates the presence of brain-associated thymic antigens in the chicken.


Role of T lymphocytes in the humoral immune response III. Lack of influence of antigen charge on the isotype and charge of antibody.

The influence of antigen charge on the anti-hapten antibody response and antigen-stimulated blastogenic response in vitro was measured in guinea pigs. The animals were immunized with dinitrophenylated bovine albumin (DNP-BSA; pl 4.9), methylated DNP-BSA (DNP-MBSA; pl greater than 10), and DNP-lysozyme (pl greater than 10). While the lymph node lymphocytes clearly distinguished between DNP-BSa and DNP-MBSA in terms of the magnitude of the antigen-stimulated 3H-thymidine incorporation, no differences were seen with respect to the characteristics of the antibody response. Thus, IgG1-to-IgG2 ratios, DEAE cellulose fractions and isoelectric focus profiles of anti-DNP sera from animals immunized with DNP-BSA, DNP-MBSA and DNP-lysozymes were indistinguishable.


Characterization of macrophage cytotoxicity factor (MCF).

Allogenetically sensitized T lymphocytes secrete in the presence of the specific antigen a factor which renders macrophages cytotoxic to target cells in vitro, macrophage cytotoxicity factor. Cytotoxicity is expressed as 51Cr release from labeled target cells. Experiments are described to characterize chemically nonspecific MCF activity. After purification on a DEAE-cellulose column, active material elutes from Sephadex G-100 in a single peak. Assaying individual fractions of this peak shows that nonspecific MCF activity is found at a mol. wt. of 28,000+/-5,000. This material is stable at -70 degrees C several months.


Murine sarcoma virus (MSV)-induced tumors in mice. I. Distribution of MSV-immune cytolytic T lymphocytes in vivo.

Quantitative studies using a 51Cr release assay were performed to analyse the time-course of appearance and specificity of cytolytic cells in C57Bl/6 mice inoculated with Moloney murine sarcoma virus (MSV). Various lymphoid organs were studied including spleen, mesenteric lymph nodes (MLN), lymph nodes regional to the MSV-induced tumor (RLN), and peripheral blood. Furthermore, the kinetics of appearance of cytolytic cells within the MSV-induced tumor was determined. In agreement with previous studied, it was found that cytolytic T lymphocytes (CTL) specific for MSV-associated antigens were present among the cells extracted from the tumor and from the lymphoid organs. However, differences in the kinetics of CTL activity could be documented: lymphoid cells from spleen, RLN and peripheral blood showed peak activity at the time of maximum tumor diameter, while intratumoral cells showed peak activity at the onset of tumor regression. MLN cells showed cytolytic activity only when tumor regression had begun. Naturally cytotoxic cell populations of thymus-independent origin, present in normal control mice, were also detected in MSV-infected mice.


Gross-virus-induced lymphoma in the rat. V. Natural cytotoxic cells are non-T cells.

The cytotoxic cells from the spleens of normal rats, which lyse Gross-virus-induced lymphoma target cells in a short-term 51Cr release test, are predominantly small to medium-sized cells sedimenting at 4-5 mm/h as shown by velocity sedimentation analysis. Their cytotoxic activity is relatively resistant to gamma-radiation, 50% surviving 1,000 rads and 30% remaining after 5,000 rads, and to heat, since 20 min incubation at 48-51 degrees C is required for its abolition. In these properties the natural killer (NK) cells are very similar to the cytotoxic T cells from tumour-immune rats, and they share in addition a requirement for Ca++ ions for cytolysis. They differ in that they are non-T cells as defined by their resistance to anti-T-cell antiserum and complement, and by their presence in T-cell-deprived rats. They lack detectable surface Ig, Fc receptors and phagocytic or adherence properties and belong therefore to that small proportion of lymphoid cells lacking the surface markers of T or B lymphocytes, as do the comparable NK cells of mice. Cytotoxicity appears to involve an autonomous, papain-sensitive recognition structure on the surface of NK cells, rather than acquired cytophilic antibody operating through an antibody-dependent mechanism.


Natural anti-tumor serum reactivity in BALB/c mice. I. Characterization and interference with tumor growth.

A natural cytotoxic reactivity directed against syngeneic or allogeneic tumor cells was demonstrated in serum of BALB/c mice by an in vitro cytotoxicity test using rabbit serum as the source of complement. The reactivity, studied on syngeneic fibrosarcoma cells, was found to be minimal in mice less than 10 weeks old and to increase progressively with age. T-deprivation determined an increase of reactivity in young mice to levels reached spontaneously only by the serum of 40-week-old mice. The BALB/c serum also revealed natural anti-thymus antibodies. Non-identity between anti-tumor and anti-thymus antibodies was demonstrated by direct cytotoxicity and absorption tests. An inoculum of syngeneic fibrosarcoma cells increased the level of anti-tumor serum reactivity in both normal and T-deprived young mice. The natural anti-tumor cytotoxicity revelaed in vitro seemed to exert a specific in vivo protection as suggested by the indirect correlation found between the level of the natural anti-tumor reactivity and the grwoth of a transplanted fibrosarcoma.


Natural anti-tumor serum reactivity in BALB/c mice. II. Control by regulator T-cells.

By a complement-dependent cytotoxicity test, 37 sera from 1- to 18-month-old BALB/c mice were tested for natural anti-tumor and anti-thymus immune reactivity. The level of anti-tumor and anti-thymus antibodies increased with age, and a high individual variability, particularly evident in the older animals, was found. The appearance of the spontaneous antibodies was correlated to the T-cell status of mice. Animals with the higher spleen T-cell content were those with the higher anti-thymus and the lower anti-tumor natural antibody level, and vice versa. In T-deprived mice the anti-tumor response increased, whereas the anti-thymus response was not influenced. An inoculum of T cells from young to older syngeneic mice yielded a decrease of the anti-tumor response and an increase of the anti-thymus response. Homeostatic immunologic mechanisms, in which the cellular and the humoral system alternate in the tumor cell control, are suggested.


The primary structure of human urogastrone.

Urogastrone is a potent inhibitor of gastric acid secretion which is present in human urine. Its existence has been known for over 30 years but it has only recently been isolated in a sufficiently pure form for detailed structural studies to be undertaken. Two separate polypeptides beta- and gamma-urogastrone were isolated. The structures were established by carrying out enzymic degradations of S-carboxymethyl and S-carboxamidomethyl derivatives with trypsin, chymotrypsin, thermolysin and a protease derived from the fungus Armillaria mellea. Sequences of the smaller peptides thus obtained were determined by the dansyl Edman method. Partial acid hydrolysis of urogastrone itself gave fragments containing single intact disulphide bonds, and oxidation then allowed the direction of individual bonds to be established. Beta-Urogastrone was shown to be a 53-amino acid residue polypeptide containing three disulphide bonds, and gamma-urogastrone had an identical sequence but lacked the C-terminal arginine residue. Urogastrone was subsequently found to be structurally related to mouse epidermal growth factor in that 37 of the 53 residues were commonly located in each polypeptide. Furthermore, as both peptides has similar effects upon gastric acid secretion and upon epidermal growth, urogastrone was also a human epidermal growth factor. The 16 variable residues were spread across the molecule, all apart from two were compatible with single base changes in the triplet condons, and the overall effect was to make uorgastrone more acidic than EGF. The smallest biologically active unit has not been defined but at least six residues can be removed from the C-terminus without causing a reduction in potency.


Angiography in gastointestinal bleeding.

Over a four-year period, eight patients with documented gastrointestinal bleeding had angiography as a part of their investigation and treatment at the Department of Radiology, Victoria General Hospital, Halifax, Nova Scotia. A review of these eighty cases has been carried out and angiography has been found to be both safe and reliable in the diagnosis of gastrointestinal bleeding. Cautiously administered intra-arterial pitressin infusion therapy will arrest bleeding in about one-third of cases and in most others will reduce blood loss so that a critically ill patient may be made more fit for subsequent surgery. Patients who have recently received intravenous pitressin should not be given intra-arterial pitressin.


Effects of selective forebrain noradrenaline loss on behavioral inhibition in the rat.

Virtually total depletion of cortical and hippocampal noradrenaline by stereotaxic injection of 6-hydroxydopamine into the fibers of the dorsal noradrenergic bundle produced no impairment in acquisition learning of a runway response for food reward. Extinction of this response, once learned, was markedly slower in the treated group than in controls, the treated animals perseverating in rapid running to the goal box even with no food present there. Similarly, no impairment was found on acquisition of a continuously reinforced lever-pressing response for food. Extinction of this response, however, was again slower in the treated group. Subsequent acquisition of a successive light-dark discrimination task was also slower in the treated group, with these animals perseverating in responding to the negative stimulus. Although selective forebrain noradrenaline loss does not impair the acquisition of appetitive responses, the suppression of responses in the absence of reward is impeded. A parallel is drawn with those effects found classically after surgical lesion to the hippocampus.


Inhibition of theophylline clearance by troleandomycin.

The effect of troleandomycin, a macrolide antibiotic, on theophylline elimination was examined in eight patients with chronic asthma. Clearance from serum was reduced by 50 +/- 6% (mean +/- SD) during administration of 250 mg troleandomycin four times daily. Reduction of clearance persisted to a lesser degree in one of these patients examined while receiving 250 mg troleandomycin daily. An increase in serum theophylline concentration can thus result from initiating troleandomycin in asthmatic patients receiving continuous treatment with theophylline. This may be at least a partial explanation for the apparent benefit of troleandomycin in chronic asthma and also suggests that possibility of inducing theophylline toxicity, including seizures, as was observed in one of the patients in this study.


Histamine receptor--bearing peripheral T lymphocytes in patients with allergies.

The effect of histamine on the capacity of T lymphocytes to form E rosettes was tested in 10 healthy subjects and in 13 patients with allergies. Histamine had no effect on the capacity of T lymphocytes to form E rosettes in healthy subjects, but significantly inhibited the E rosette formation of T lymphocytes in patients with allergies.


5'-Nucleotidase in different populations of mouse lymphocytes.

The activity of 5'-nucleotidase in different populations of intact lymphocytes was studied using biochemical, cytochemical and radioautographic methods. In some strains of mice the results showed a consistent difference in 5'-nucleotidase (AMPase) content between intact thymic and splenic lymphocytes. In the R III, C 57, BALB/c, CBA and Cd-1 strains AMPase activity in the isolated splenic cells was foru to 10 times the activity of intact thymocytes. In highly enriched populations of splenic T and B cells the average AMPase activity was about the same. From separate assays it was seen that the AMPase activity in highly enriched populations of lymphoctes was variable so that within one experiment the T cells seemed to have the higher AMPase activity while in other experiments B cells shown to be more active than T cells. Ultrastructural radioautography was done to count AMPase positive cells within T and B cell populations, the latter identified b  binding of I125-labelled anti-immunoglobulin. It was seen that about 50% of B cells, but only about 10% of T cells, were positive for AMPase. It is suggested that there is a subpopulation within B and T cell populations with a high membrane AMPase activity and another subpopulation with less or no enzyme activity. It is also suggested that the activity and/or the proportion of  these positive cells is changing within the splenic cell population. By using cortisone to deplete the immature cells from the thymus it was seen that the remaining mature cells have about the same AMPase activity as did the immaturecells, and thus mature T cells must gain their high acitivity after leaving the thymus. By incubating splenic lymphocytes with Concanavalin A it was also seen that the immature transformed cells had the same amount of enzyme as did untransformed cells.


Histochemical demonstration of unsaturated hydrophilic lipids with palladium chloride.

Compounds in which olefinic linkages are accessible to aqueous reagents reduce the chloropalladite ion [PdCl4]2-, to metallic palladium. This reaction is used in a histochemical method whereby hydrophilic unsaturated lipids are stained dark brown or black. The specificity of the new method has been confirmed by means of solvent-extraction and chemical blocking procedures and by comparison with other histochemical techniques. Yellow staining of collagen, keratin and cytoplasm is probably due to attachment of the chloropalladite anion to proteins. The yellow background can be largely decolorized by treating the sections with aqueous pyridine, which forms colorless complexes with divalent palladium. A standard technique for staining with palladium is presented and the method is discussed in relation to other histochemical procedures that demonstrate unsaturated lipids.


Histocompatibility requirements for cellular cooperation in the chicken: generation of germinal centers.

Cyclophosphamide-treated newly hatched chicks were transplanted with histocompatible, semiallogeneic and allogeneic combinations of B (bursa) and T (thymus) cells from newly hatched donors. At the age of 5 weeks the birds were studied for an anti-SRBC response and for the generation of germinal centers in the spleen. The results of these experiments are summarized as follows. i) Allogeneic bursal stem cells have the capacity to restore the bursal structures of CY-treated recipients, but not the germinal center or anti-SRBC formation. ii) When allogeneic B cells are combined with T cells histocompatible or semiallogeneic with them, a restoration of the germinal center formation is achieved, but not to the same level as observed in normal birds or in CY-treated birds transplanted with histocompatible or semiallogeneic B cells. iii) Allogeneic B cells, even when complemented with T cells histocompatible with them, fail to restore the antibody production against SRBC; this is achieved only after transplantation of B cells histocompatible or semiallogeneic with the recipient. These findings indicate that germinal center formation is dependent on cooperation of histocompatible or semiallogeneic B and T cells, and furthermore, that an additional factor provided by the host is involved. Studies with transplantation of histocompatible and histoincompatible 'empty' splenic stromata revealed that the additional factor is not related to the splenic stroma.


Suppression of IgE antibody production in SJL mice. II. Expression of Ly-1 antigen on helper and nonspecific suppressor T cells.

Under appropriate conditions of immunization combined with irradiation, SJL/J mice show a high and persistent anti-DNP IgE antibody response. Spleen cells transferred from normal untreated SJL mice suppress this response. Elimination of Ly-1+ cells, but not of Ly-2+ cells, abolished the capacity of spleen cells to suppress the IgE response. Thus of the three T cell Ly subclasses presently identified, Ly-1, Ly-2,3, and Ly-1,2,3, the normal SJL spleen cell which suppresses the IgE response of irradiated-immunized SJL mice belongs to the Ly-1 set. It is not known whether this Ly-1 cell suppresses the IgE response directly or by helping another cell in the recipient. The carrier-specific helper cell activity for IgE and probably IgG1 antibody response belongs to Ly-1 subclass in the SJL strain also.


Enhancement by irradiated T cells of human plasma cell production: dissection of helper and suppressor functions in vitro.

The addition of irradiated T-enriched lymphocytes to B cell-enriched fractions of human peripheral blood or to unseparated mononuclear cells stimulated the differentiation of plasmacytoid cells in culture with pokeweek mitogen beyond the synergy obtained by the addition of unirradiated T cells. This stimulation was observed in both the proportion and absolute number of plasmacytoid cells recovered from the cultures, and in the amount of IgM detected in culture supernatants by a hemagglutination inhibition assay. Irradiation-induced enhancement was observed with normal and hypogammaglobulinmic T cells, but not with monoclonal T cells from two patients. Inactivation of T cells by heating or by repeated freezing and thawing did not produce the same effects as did irradiation. These data suggest that cell-mediated suppressor function in man is selectively radiosensitive, while helper activity is not. Irradiation may be a useful method for the functional isolation of helper cells and for the manipulation of the balance between suppressor and helper cell activities.