Cobalt(III) complexes of bidentate azotyrosine analogs. As analogs for cobalt(III) complexes of bidentate azotyrosine in proteins, several cobalt(III) complexes of bidentate azophenols have been prepared and characterized. Tris(2-phenylazo-p-cresolato)cobalt(III) was shown to be a poor model complex for this purpose; while cobalt(III) complexes of either 2-phenylazo-p-cresol or 2-(4-carboxyphenylazo)-4,5-dimethylphenol with the linear tetradentate ligand ethylenediamine-N,N'-diacetic acid are very useful as model complexes. The complexes were characterized by magnetic susceptibility, visible spectra and 1H NMR. In the case of one of the mixed ligand complexes, a detailed description of the stereochemistry was possible. Comparisons of the spectral characteristics of metal complexes with bidentate and tridentate azophenols are made. These model studies are essential to a program involving the site specific modification of proteins with substitution inert metal ions.


Inhibition of L-alanine aminotransferase by lithium salts. Pharmacologic concentrations of either LiCl, LiN03 and LiF or the lithium salts of pyruvic or glutamic acids inhibit the formation of alanine arising from the transamination of glutamate in the presence of pyruvate. Lithium pyruvate is the most effective inhibitor, while the addition of K+ to the incubation reaction can effectively reduce this inhibition. Some possible modes of action of the lithium ion is presented.


Coordination of biogenic amines with synaptosomal and vesicular metal ions: equilibrium and spectral studies in model systems. Thermodynamic equilibrium studies using model systems were carried out on the nature and extent of coordination of twelve different biogenic amines and adenosine-5'-triphosphate (ATP) with the bivalent metal ions, viz., Ca2+ and Zn2+, which occur in the subcellular fractions of the brain, at 25.0 +/- 0.1 degrees C and at an ionic strength of 1.0 (KNO3). In the combined presence of the individual monoamines and ATP the metal ions were predominantly coordinated by ATP in the pH range 3.0 to 6.5 with binding constants (log KML) of 2.84 +/- 0.06 and 3.19 +/- 0.39 for the Ca2+ and Zn2+ chelates, respectively. Each of the monoamines coordinated with the metal-ATP chelate above pH 6. The stabilities of the chelates of some of the amines with Ca2+ -ATP (1:1) system were NE, 2.33 +/- 0.33; AA, 2.24 +/- 0.19; OA, 1.94 +/- 0.29; NMeN, 1.60 +/- 0.22; DA, 2.14 +/- 0.09. Values for the Zn2+-ATP-amine systems were: NE, 8.35 +/- 0.26; OA, 4.53 +/- 0.07; DA, 10.05 +/- 0.39. Absorption spectral studies were carried out in order to examine the nature of coordination of NE, DA, TA, and AA with Cu2+, Fe2+, and Mg2+ ions in the combined presence of ATP. Results of the spectral studies taken together with the (thermodynamic) equilibrium data have indicated that in the pH range of biological interest, the catechol amines (NE and DA) and ATP are both coordinated to the "synaptosomal and vesicular" metal ions. The results further indicated that both the pyrocatechol and the ethanolamine groups of NE might be involved in the coordination of Cu2+. However, the interaction of the ethanolamine group of the NE molecule with the rest of the metal ions was not indicated.


Methylation of chloroplatinate by methylcobalamin. Incubation of microM levels of K2PtCl6 and methylcobalamin (MeB-12) results in the complete conversion of MeB-12 to aquoB-12. Demethylation is optimal at pH 2.0 and is accelerated by the addition of K2PtCl4. The reaction is stoichiometric between MeB-12 and K2PtCl6 (1:1). Incubation of 40 microM K2PtCl6 with either 40 microM [Me-14C]MeB-12 or [Me-3H]MeB-12 followed by lyophilization converts 70% of the label to a stable form which is associated with Pt upon subsequent paper chromatography and electrophoresis. There is no preferential loss of 3H relative to 14C in the reaction product. When 50 mumoles each of [Me-14C]MeB-12 and K2PtCl6 were reacted and subjected to column chromatography, a labeled UV-absorbing product was separated with a 14C/Pt ratio of 0.9-1.2. The 14C-Pt product has absorption maxima at 260 nm and 208 nm with a minimum at 240 nm (A240 nm/A260 nm = 0.5). Proton NMR spectroscopy confirmed the presence of an H-C-Pt covalent bonding pattern (J for 1H, 195Pt = 78.2 Hz; tau for 194Pt-Me + 196Pt-Me = 6.956).


Cyclization of the phosphorus chain of the methylene-bridged analogs of adenosine triphosphate. The phosphorus-containing side chains of two methylene-bridged analogs of adenosine triphosphate have been cyclized to produce the corresponding analogs of monoadenosine-5'-trimetaphosphate. (The structures are given in the journal.) The molecules, which were generated in anhydrous media through a carbodimide-mediated condensation, were characterized by 31P nuclear-magnetic resonance, and the white-noise 1H decoupled spectra were simulated. These molecules are quite reactive and readily converted to their corresponding linear forms upon hydrolysis. The second structure contains an asymmetric phosphorus atom, and both of the possible cyclic molecules have been observed and the diasteroisomeric mixture has been isolated.


Binders of intravenously administered 65-zinc in rat liver cytoplasm. The fate of an i.v. injected trace dose of 65Zn2+ in the rat, was studied over a period of 10 days after injection. Tissue distributions were determined and a special study was made of 65Zn binders in liver cytoplasm. A total of 6 65Zn-binding fractions were observed in liver cytoplasm with apparent molecular weights of about 113,000, 66,400, 47,400, 29,000, 23,000 and 11,400. A time study showed that 4 hours after the injection the most prominent cytoplasmatic 65Zn binders are the 113,000, 66,400 and 23,000 molecular weight fractions. A tentative identification of the main Zn binders in the six 65Zn fractions is given, using the collected data regarding their apparent molecular weight, time dependent prominence and content of stable Zn.


Conformational properties of the osmium tetraoxide bispyridine ester of 1-methylthymine and a comment on the linearity of the trans O=Os=O group. The preparation and crystal and molecular structure of the osmium tetraoxide bispyridine ester of 1-methylthymine are reported. The complex crystallizes in the triclinic system, space group P1, with a = 11.493(6)A, b = 16.655(7)A, c = 6.082(2)A, alpha = 92.07(3) degrees, beta = 90.58(3) degrees, gamma = 71.36(4) degrees, V = 1102.4 A3, Dm = 1.85(1) g cm-3, DC = 1.84 g cm-3. The unit cell contains 2 osmium tetraoxide bispyridine esters of 1-methylthymine, 2 waters of crystallization and 1 disordered pyridine of solvation. Intensities for 3814 independent reflections were collected by counter methods. The structure was solved by standard heavy-atom techniques and has been refined by full-matrix least squares, based on F, to a final R value of 0.065. The osmium complex binds as a cis osmate ester to the C(5)-C(6) bond of the methylated pyrimidine in a fashion which is expected to be similar to the binding of the complex to thymidine residues in nucleic acids. The conformation of the 1-methylthymine ester is that of a half chair with C(6) showing a substantial deviation, 0.55 A, from the best mean plane of the thymine moiety. The primary coordination sphere about the Os(VI) atom is completed by 2 axial Os=O bonds and the binding of the 2 pyridine ligands in cis positions in the equatorial plane containing the ester linkages. The O=Os=O group is substantially nonlinear, 164.0(5) degrees, and this nonlinearity is attributed to intracomplex electronic effects.


A combined ultrasonic and biochemical study of fetal renal function in the term fetus. The fetal glomerular filtration rate of plasma (GFR) and the percentage of fetal tubular reabsorption of water were measured by means of combined ultrasonic and biochemical methods in 20 normal and 10 complicated pregnancies. The duration of pregnancy varied from 35 to 42 wk. In normal pregnancy GFR of plasma varied from 2.0 to 7.1 ml/min (mean = 4.1) and tubular reabsorption of water ranged from 84.1 to 93.0% (mean = 89.8). There was no relationship with gestational age. In the group of complicated pregnancies - apart from one anencephalic case - no apparent difference in GFR and percentage tubular reabsorption between the group of normal (greater than or equal to 10th percentile) and reduced fetal birth weight (less than 10th percentile) was observed.


Chemical and biological characterization of an active substance of the human placenta. Acetic acid extracts of human term placenta have been fractionated by pH and salt precipitations and by exclusion chromatography on a Sephadex G-75 column. A partially purified fraction (F-II) possessing uterotropic activity in immature and young mice was obtained. This active fraction was submitted to the action of protein denaturating agents (heat, 8 M urea) and of specific proteolytic enzymes (trypsin, alpha-chymotrypsin and pronase). These treatments completely destroy the uterotropic activity showing that the active substance is of protein nature. The administration of F-II to spayed mice did not produce any increase in their uterine weight suggesting that the uterotropic activity would be due to stimulation of the female gonad.


Biological and immunological studies of a placental gonadotropic protein. Precocious sexual maturity, ovarian weight increase and stimulation of the sex accessory organs in impuber female mice, was induced by a partially purified protein fraction obtained from human placenta. The relationship between this biologically active protein and HCG was studied by a comparative immuno-double diffusion technique (Ouchterlony) and two agglutination inhibition tests. Results showed that this protein with gonadotropic activity is neither immunologically related to HCG nor contaminated with this hormone.


Fetal growth retardation in the second trimester. Growth of the fetal head was assessed by serial ultrasonic measurements in a prospective study of a randomly selected group of 126 mothers. Three cases exhibiting second trimester fetal head growth retardation with varying degrees of catch-up growth before term are illustrated.


Massive feto-maternal hemorrhage as a cause of perinatal mortality and morbidity. 11 cases of massive feto-maternal hemorrhage (FMH) detected at the Leuven Blood Transfusion Center are described. Based on these case reports, a review is given of the various theoretical and practical problems related to this complication, e.g. the relative frequency of perinatal mortality and morbidity due to massive FMH, the causes and pathogenesis, the symptoms and diagnosis, the clinical varieties, and the pathophysiology as seen in the fetus and newborn. Finally, the indications for looking for large FMHs are described, and the therapeutic implications when this complication is discovered.


Tubal and uterine motility in vivo in the rhesus monkey. Previous data indicate that there are definite qualitative and quantitative patterns of tubal activity during the various phases of the menstrual cycle. In the present investigation, the simultaneous activity of the uterus and Fallopian tube was recorded in vivo in mature rhesus monkeys throughout the menstrual cycle. The observations indicate that there are characteristic patterns of both tubal and uterine activity, depending on the various phases of the menstrual cycle. The simultaneous recordings of tubal and uterine activity show that the tubal and uterine contractions are not synchronous or even have a similar pattern. The presence of a transmetrial catheter for recording of uterine activity seems to modify the patterns of tubal activity, particularly during the ovulatory phase. It seems possible that the transmetrial catheter has a similar effect as an intrauterine contraceptive device in this species.


Hemodynamic changes associated with angina pectoris induced by maximal treadmill exercise: effect of sublingual isosorbide dinitrate on systolic time intervals. A technique for the study of patients with angina pectoris has been described, in which systolic time interval (STI) measurements are obtained at intervals after the onset of stress-induced angina. The technique is uniquely suited to the evaluation of anti-anginal drugs. Sublingual isosorbide dinitrate (SISD) was randomly alternated with a placebo (P) tablet in a double-blind study of 20 patients with stable angina pectoris. After SISD, compared to placebo, a highly significant shortening of Q-S2 and LVET occurred (p less than 0.001) which lasted throughout the entire 120 minute study period. The hemodynamic basis for these differences was felt to be improved myocardial contractility secondary to a reduction in systemic vascular resistance and reduced venous return induced by the SISD. A significant prolongation of PEP occurred at 60 minutes post-SISD (p less than 0.01). This was attributed to an increase in the gradient between LVEDP and aortic diastolic pressure resulting from reduced venous return after SISD. The PEP/LVET ratio was significantly increased up to 60 minutes after SISD (P less than 0.05). Heart rate was uniformly higher post-SISD, compared to post-placebo values; the differences were highly significant up to 60 minutes (P less than 0.001) and remained significant at 120 minutes (p less than 0.05). The time to angina was significantly longer (immediately post SISD, p less than 0.05; 30 min, p less than 0.001; 60 mins, p less than 0.05; 120 mins, p less than 0.05); and the work load greater, for 120 minutes following SISD: the increase in the latter was highly significant for 30 minutes after SISD (p less than 0.001) and remained significant up to 120 minutes (60 mins, p less than 0.05; 120 mins, p less than 0.05). These observations were attributed to an improvement in myocardial function due to the sublingual isosorbide dinitrate. A high degree of correlation was found to exist between heart rate and the STI. This correlation was negative for the QS2 interval (-0.996) and LVET (-0.993) and positive for PEP (+0.817) and the PEP/LVET ratio (+0.950).


When does a fourth sound become an atrial gallop? A study of the fourth sound was conducted on 100 normal subjects (ages 1-88 years) and 42 clinical cases with either aortic stenosis, systemic hypertension or coronary heart disease. This study was based on the graphic recognition of a presystolic sound when the tracing was taken with the use of one or more of 5 different high pass filters. Attention was paid to the existence of the fourth sound, its magnitude, and its vibrational frequency. In general it was accepted that a magnitude of 1/2 of the first heart sound or a frequency of 30 Hz denoted a pathologic fourth sound. However, exceptions were found among normal subjects, so that only the combination of the two criteria could be considered highly significant for a pathologic phenomenon (gallop). Patients with aortic stenosis presented an increase in magnitude of the fourth sound but incidence and vibrational frequency were similar to those of controls. Patients with hypertension had a greater incidence of fourth sounds, especially in middle age (100%); middle age patients usually had a greater magnitude while older patients had more often an increase in vibrational frequency. Patients with coronary heart disease (evidence of old infarcts) had an increase in the incidence, magnitude, and vibrational frequency in comparison with controls. These data and the cause of the fourth sound are discussed. The fourth sound has been repeatedly studied in the past, both as an auscultatory finding and a graphic phenomenon. Attempts were made for separating the normal fourth sound from that denoting a pathological phenomenon but, so far, no clear cut criteria for the differentiation have been obtained. We thought, therefore, that a new study was indicated.


Daily tobacco consumption and electrocardiography [P1 and T1]. The unfavorable electrocardiographic effect of cigarette consumption in a large sample of health professionals [doctors and their wives] confirms earlier such reports in smaller groups.


Incidence of venous thromboembolic disease in nonpregnant women of childbearing age. Data from 12 Cincinnati hospitals were examined to determine the incidence of venous thromboembolic disease in nonpregnant women of reproductive age. The incidence of superficial and deep vein thromboembolic disease in women age 15 to 44 was 1.09 cases per 1,000 women per year; for women age 20 to 44 the incidence was 1.3 cases for 1,000 women per year. These figures include idiopathic and non-idiopathic cases and thus are representative of the general population of nonpregnant women of reproductive age. The incidence of pulmonary embolism was approximately 1 case per 5,000 women age 20 to 44. There were two deaths from pulmonary embolism, giving a mortality rate of 11.3 deaths per million women age 15 to 44.


Role of surgery in the treatment of pulmonary tuberculosis. The records of 9939 patients hospitalized for tuberculosis between 1963 and 1972 inclusive were reviewed with respect to patients who were treated surgically. During this period there was a steady decline in the number of patients thus treated; the success of antimicrobial drug therapy has altered the frequency of various surgical procedures, and pulmonary resection is now the procedure of choice, with a growing reluctance to perform segmental resection. Morbidity and complications among the patients in this series have been within acceptable limits. The problem of residual space has been minimal. Bronchopleural fistula with empyema (incidence, 3.1%) has been the most serious complication, accounting for the largest proportion of deaths. The mortality of 2.8% is comparable to that reported in the literature. Though mild to moderate respiratory insufficiency developed in some patients, none was seriously incapacitated. The majority of surviving patients have remained well, with their disease under control. In a number of patients reactivation of the disease occurred, probably because of conservative resection and discontinuance of drug therapy due to misunderstanding between patient and physician.


Experience with surgical salvage in pulmonary tuberculosis: application to general thoracic surgery. The diminishing incidence of pulmonary tuberculosis and the increasing effectiveness of drug therapy have resulted in an almost complete disappearance of surgical problems in the management of patients with this disease. However, the lessons learned from the management of such problems should not be forgotten, for they are equally applicable to the management of disabling and life-endangering problems in general thoracic surgical practice. "Salvage" situations develop when therapeutic requirements for control of disease are combined with factors affecting a patient's health so as to increase the surgical risk beyond the range usually considered acceptable. Attempts to salvage patients are indicated when treatment has failed to arrest disease, when life expectancy is threatened, or when return to normal activity is imperiled. Risk may be increased because of age, inadequate cardiopulmonary reserve, or chronic toxemia; in tuberculosis, risk may be increased because of positive sputum culture or resistance of organisms. Experience with 146 tuberculous patients has provided a basis for evaluation of the indications for resection, prophylactic and therapeutic thoracoplasty, and closure of bronchopleural fistulas in general thoracic surgical salvage. Both infection in residual spaces and bronchopleural fistulas are serious complications that can be controlled by thoracoplasty and pedicled muscle grafts. Prophylactic use of osteoplastic thoracoplasty and intercostal muscle grafts warrant more serious consideration. In established complications a "tailored" thoracoplasty can also be combined with an intercostal muscle graft.


Angiofollicular lymph node hyperplasia of the lung simulating carcinoma: pseudolymphoma with inflammatory changes. Angiofollicular lymph node hyperplasia of the lung developed in a 45-year-old man who was a heavy smoker. Slow growth of the lesion 3 years after biopsy and the finding of atypical cells in the sputum and bronchial washings strongly suggested a malignant lesion. There were no systemic manifestations other than dyspnea, which may have been related to allergy. The lesion was angiofollicular lymph node hyperplasia of the hyaline-vascular type. Invasion by lymphoid cells of both blood vessels and bronchioles suggested that the pathogenesis was probably infectious or inflammatory; also, the nature of the infiltrate indicated an immune mechanism. The course of the disease, as in other cases reported, has been benign, though a patchy density has developed in contralateral lung 4 years after lobectomy.


The Farfan back operation: technique and results. A total of 94 Farfan back operations were performed on 82 patients. As a group these patients were typical of those undergoing discoidectomy, with or without fusion. The follow-up period was from 3 to 5 years. Overall, the results were excellent, good or satisfactory in 85% of the patients; with one-level fusions the proportion of such results was 93%. The commonest cause of failure was extrusion of the bone graft.


Electromyographic and nerve conduction studies in idiopathic ischemic necrosis of the femoral head. Clinical features and results of nerve conduction and electromyographic investigations were studied in 13 consecutive patients with idiopathic ischemic necrosis of the femoral head. Of these patients, one was a diabetic, one had received steroids and six gave a history of high alcohol intake. Neurologic abnormalities were present in 9 of the 13 cases. Specimens were available for examination in the nine patients who underwent operation. This study suggests that disturbance in the neuromuscular system at a clinical or subclinical level could be common to idiopathic ischemic necrosis of the femoral head and its various associated disorders and might be a pathogenetic factor.


Photographic maps for coronary artery operations: how to make them easily. A modification of the Tagarno 35-mm ciné-film projector has been devised primarily for the cardiac surgeon, to produce excellent pictures of opacified coronary arteries. A combined screen and photographic holder allows the surgeon to view an image 10.2 X 12.7 cm and to make positive prints of selected frames in a matter of seconds. No photographic experience is needed.


The Warren (distal splenorenal) shunt for portal hypertension. The Warren distal splenorenal shunt, designed to decompress esophagogastric varices selectively while preserving portal venous inflow to the liver, was performed in 18 patients who had bled from esophageal varices. In 14 cirrhosis was micronodular, in 3 it was macronodular, and in 1 primary biliary. Two patients died within 1 month of surgery (operative mortality, 11%). Three patients died between 2 and 12 months after operation (1-year mortality, 28%). All five patients who died within 1 year had severe liver disease at the time of operation. None sustained further hemorrhage. Only one survivor requires protein restriction and none have fluid retention.


Anorectal and perianal complications of hematologic malignant neoplasms. Among 17 adults with hematologic malignant neoplasms in whom anorectal complications developed, the overall mortality was 53%; for those in whom the disease was not in remission the mortality was 69%, compared with zero for patients who were in remission. All but one of the deaths were directly attributable to septicemia secondary to the anorectal lesion. Over half of the patients had a history of previous anorectal problems or disordered bowel pattern preceding the anorectal complication. The anorectal lesions affecting these 17 patients included prolapsed hemorrhoids (in 5); discrete ulcers in the anal canal and surrounding cellulitis (8); necrosis of the anus and perianal area (2); and perirectal abscesses (2). Only the abscesses responded to surgical drainage. Treatment of the other lesions was conservative: bowel function was maintained as normal as possible, good perineal hygiene was practised and stool softeners were used, while efforts were directed towards achieving remission of the hematologic neoplastic disease.


Tension pneumoperitoneum: case report and review of the literature. Tension pneumoperitoneum in an 81-year-old man resulted from the perforation of an ulcer on the posterior aspect of the first stage of the duodenum into the lesser sac. This condition, though rare, should be considered in the differential diagnosis of the massively distended abdomen. A number of different causes of this condition have been reported, most of which are associated with various diagnostic and therapeutic procedures. Treatment is early laparotomy.


Maternal blood supply to the coneptus.

Maternal blood supply to the coneptus. This presentation gives an unorthodox account of the relationship of uteroplacental vessels to the structural units of the placenta, the lobules, and its development. Contrary to current opinion, neither the villous stems nor the ostia of maternal arteries have a one-to-one relation to placental lobules. Both are interlobular, and thus supply portions of adjacent lobules. The involvement of whole lobules, usually multiple, in degenerative processes such as infarction as is seen particularly in the placentas of stillborn infants, may indicate a general lowering of perfusion pressure in the intervillous space rather than occlusion of one artery. Just how maternal blood circulates within a lobule, is not known. In visualizing the development of the lobule it is only necessary to realize the commonly observed fact that anchoring points of large villi coming down along the sides of the lobules, are frequently if not regularly associated with the convolutes and ostia of maternal arteries. The areas containing both, form a network; how the intervening areas are formed into lobules is unknown.


Buerger's syndrome.

Buerger's syndrome. All cases diagnosed as Buerger's disease at The Mount Sinai Hospital from 1933-1963 have been reviewed. A large majority were found to have well-known vascular problems other than what we now consider as Buerger's disease. Only two specimens from 33 amputations had the characteristic histologic findings that Buerger described. It is suggested that the terminology Buerger's disease be replaced by Buerger's syndrome. In 1908, while at The Mount Sinai Hospital, Dr. Leo Buerger described a clinical entity with its histologic counterpart that soon became known as "Buerger's disease." The clinical picture was essentially that of arterial insufficiency, mainly in the lower extremities, in a young, Jewish, adult male who smoked. It was frequently associated with a migrating thrombophlebitis. The histologic picture was not as clearly defined but was stated to differ from arteriosclerosis in that normal vessel was found proximal and distal to the lesion, canalization of the occlusive lesion occurred, capillary ingrowth was present in the media, and there was an absence of elastic tissue in the organizing process. It should be noted that most of Buerger's specimens consisted of veins removed during an episode of acute thrombophlebitis. He specifically stated that only in the early stages of the disease, when phlebitis was the main finding, could the lesion be separated from the various stages of arteriosclerosis. In recent years, doubt has been cast on the existence of the clinical or pathological picture described by Buerger. Accordingly, it was thought advisable to review the case records and pathologic specimens of patients discharged from The Mount Sinai Hospital with the diagnosis of Buerger's disease over a recent 30-year period.(ABSTRACT TRUNCATED AT 250 WORDS)


Cerebral angioma and aneurysm of the cervical internal carotid artery. A case of internal carotid artery aneurysm in association with a congenital cerebral arterio-venous malformation is described. The carotid artery aneurysm was resected with primary anastomosis of the redundant artery, with satisfactory recovery.


Massive calcification of the myocardium. A case of dystrophic calcification of the myocardium is reported. The clinical, fluoroscopic, hemodynamic and angiographic findings are described, and correlate well with the lesions discovered at surgery. In this case, the diagnosis was originally suspected because of the calcification noted during fluoroscopy.


Cardiac effects of insulin, glucose, and potassium. Glucose-insulin-potassium (G.I.P.) infusions have been recommended as a useful adjunct to the management of severe congestive heart failure. Ten patients with cardiac disease underwent a diagnostic cardiac catheterization. Pressures and cardiac output were obtained prior to and immediately after the 10 minute infusion of a mixture containing 50 grams of glucose, 10 mEq of potassium and 20 units of insulin. (Table: see text). G.I.P. infusions can increase the cardiac index. This is due to a combined effect of volume expansion and catecholamine stimulation.


The cervical aortic arch anomaly.

The cervical aortic arch anomaly. Although the cervical aortic arch anomaly occurs rarely, it should always be considered in the differential diagnosis of pulsatile masses in the neck. The eighteenth case of this anomaly is presented herein. Review of the previous literature demonstrates the consistent pattern of branching anomalies associated with the cervical aortic arch and indicates the complex nature of this anomaly. Studies of these patients in biplane (frontal and lateral), as well as the right posterior oblique projection in order to precisely define the order of branching, is recommended, particularly when surgical intervention is indicated.


Exertion and acute coronary artery injury. Twelve cases of myocardial infarction as related to strenuous exertion are presented with the pathological findings in several of these cases. Three cases with coronary arteriography are also presented. The pathology of coronary arteriosclerotic plaques and the vulnerability to acute injury is reviewed and discussed. It is concluded that strenuous exertion can cause acute injury to coronary artery plaques due to the unusual stressful whip-like action to which coronary arteries are subject. These injuries may initiate as cracks in the plaques or subintimal hemorrhages and proceed to coronary occlusion and ultimate myocardial infarction. With this concept in mind we use the term of "crack in the plaque" (Black's Crack in the Plaque) to account for the sudden appearance of clinical coronary artery disease appearing during or shortly after exertion, or other stressful situations in patients without previous existing evidence of clinical coronary artery disease. This could also account for exacerbation of symptoms or death occurring after exertion in previously quiescent asymptomatic known coronary artery disease subjects. This concept may explain some of the puzzling features of coronary disease.


Termination of atrial flutter and atrial tachycardia with rapid atrial stimulation. The results in this series of fifty-seven patients confirms the safety and reliability of rapid atrial stimulation to terminate atrial flutter and atrial tachycardia. Transthoracic wires implanted at thoracotomy or transvenously placed atrial electrodes can be used for the confident intracardiac electrocardiographic diagnosis of tachyarrhythmias and for atrial stimulation. Our experience represents the second largest reported series of patients to undergo cardioversion by this method. In all but five of fifty-seven patients either the atrial tachyarrhythmia was converted to normal sinus rhythm or the flutter-tachycardia was terminated with resultant atrial fibrillation. In forty-three patients sinus rhythm was eventually re-established after atrial stimulation. Various aspects of rapid atrial stimulation, including it's preference over precordial shock, have been discussed. We feel particular consideration should be given cardioversion by rapid atrial stimulation in patients with possible digitalis toxicity and in all patients who have atrial flutter, atrial tachycardia, or junctional tachycardia after open heart surgery.


The effect of phentolamine on conduction in the bundle of His. A His bundle electrogram was obtained in a 65 year old male with syncopal episodes. A split bundle of His deflection was recorded. After the intravenous administration of phentolamine, a marked shortening of the H-H' interval was observed. This signifies an improvement in conduction at the bundle of His level.


Changes in enzyme levels in human skeletal muscle during obstructive arteriopathy of the lower limbs. Some enzymatic activities have been assayed in the gastrocnemius muscle of patients with obstructive arteriopathy of the lower limbs. The specific activities of all the examined glycolytic enzymes, of malate dehydrogenase and of glycerol-3-phosphate dehydrogenase are significantly decreased while the specific activities of two lysosomal enzymes, beta-glucuronidase and cathepsin A, are significantly higher than in the controls. Therefore it may be inferred that the metabolic capacity of glycolysis and of Krebs cycle are lowered. On the other hand the increased specific activity of lysosomal enzymes suggests the hypothesis that the above mentioned modifications and the morphologic alterations of the muscle and of the small blood vessels might be ascribed, at least partly, to a release of lysosomal hydrolases in active form.


Thrombolytic treatment with i.v. brinase of advanced arterial obliterative disease of the limbs. The material includes 17 patients suffering from different degrees of chronic peripheral arterial disease (11 chronic patients stage III and IV, two patients with acute arterial occlusion, and four patients stage II). Presence and extent of arterial occlusion was ascertained by initial arteriography. In twelve of the patients amputation had been considered. The patients were treated by a series of i.v. infusions of brinase, a proteolytic enzyme from Aspergillus oryzae. The brinase inhibitor capacity in plasma was determined by the azocollagen technique. Dosage of brinase was calculated to retain a rest-inhibitor capacity in order to avoid free proteolytic activity. In five patients the enzyme was also given preoperatively by intra-arterial instillation prior to a series of i.v. brinase infusions. Thirteen patients showed clinical improvement after brinase treatment. The condition of two patients remained unchanged, and in two patients amputation could not be avoided. In fourteen patients the treatment results were followed by measurement of peripheral systolic blood pressure. In ten patients obvious increase of the peripheral systolic blood pressure was observed. Cutaneous microcirculation was studied in seven patients by i.v. sequential fluorescein angiography and signs of improved microcirculation (appearance time, intensity and/or extent of fluorescence) were found in all examined patients. One patient with acute arterial occlusion of the right leg with obstruction of blood flow from the external iliac artery showed complete disobliteration after a series of i.v. brinase infusions. Bleeding complications associated with brinase treatment were not observed in the material. In three patients brinase treatment was discontinued because of complications (2 brinase, 1 heparin).


Dosage of i.v. brinase in man based on brinase inhibitor capacity and coagulation studies. In 17 patients a total of 148 brinase infusions were given. All patients but two had anticoagulant treatment (dicoumarol or heparin) during the brinase series. Dosage of brinase was based on determination of brinase inhibitor capacity in plasma (azocollagen technique) prior to infusion of the enzyme. Iv infusion of brinase lowered inhibitors in plasma. Good correlation was found between expected lowering and measured inhibitor values after brinase infusion. The stipulated safety margin for brinase inhibitor capacity could be maintained. alpha 1-antitrypsin showed irregular changes and alpha 2-macroglobulin values were decreased by iv infusions of brinase. Fibrinogen values were somewhat lowered after iv brinase infusion. Values for fibrinogen degradation products increased and the ethanol gelation test became positive. Thrombotest values were lowered and the activated partial thromboplastin time was prolonged in patients receiving dicoumarol and iv heparin respectively. Changes in other coagulation parameters were insignificant. In two patients transient renal failure was recorded, laboratory data indicated intravascular coagulation as a possible cause. None of these two patients were on anticoagulant treatment. One patient developed a haematoma of the forefoot during massive iv heparin treatment during a series of iv infusions of brinase. Bleeding complications due to brinase treatment were not observed.


Combined thoracic aorta and right carotid artery angiography in trauma. In the critically injured patient, time is of the essence; a method is described for performing a thoracic aortogram for possible ruptured aorta, followed by a right carotid cerebral angiogram as a screening procedure to rule out cerebral vascular shift, using the pigtail catheter.


The role of angiography in the management of intestinal carcinoid. Carcinoid tumors of the intestine may present with bowel obstruction or with the carcinoid syndrome. Confirmation of the diagnosis by biochemical means is easy. Management is often surgical and a number of different procedures have been advocated, e.g. resection of the primary, hemicolectomy and lately, partial hepatectomy. The angiographic features of two cases are presented and discussed; the usefulness of the information so gleaned in the choice of management is stressed.


Arteriointestinal fistula: report of a case following surgery for trauma. A case of an arteriointestinal fistula following surgery for trauma is reported. In prevention of this complication, it is suggested that temporary ileostomy and mucous fistula be considered in cases of combined right colon and intra-abdominal vascular injuries to eliminate a leaking bowel anastomosis as a source of contamination of the vascular repair.


Effect of papaverine hydrochloride on cerebral blood flow as measured by forehead thermograms. Using the atraumatic diagnostic technique of forehead thermography to indirectly evaluate cerebral arterial circulation, nine patients with vascular disease in the extracranial or intracranial carotid arterial system were given 300 mg. papaverine hydrochloride. All patients demonstrated some degree of improvement after the drug was administered as determined by comparing control thermograms to thermograms obtained 1, 4 and 8 hours after administration of the drug. Improvement was attributed to increased cerebral blood flow due to the direct vasodilating effect of papaverine hydrochloride. In conclusion, this study suggests that if potential stroke victims can be detected at an early stage with thermography (and/or with other atraumatic diagnostic techniques), drug therapy may prove to be of immediate therapeutic value. The response of any given patient to drug therapy may be determined simply and atraumatically by thermographic examinations in which each patient is used as his own control.


The effect of propranolol and verapamil on atrial and atrioventricular refractory periods in man. The atrial effective (ERP) and relative (RRP) refractory periods were examined at high atrial pacing rates in 12 patients before and after intravenous injection of propranolol, and in 5 patients before and after injection of verapamil, using the technique of paired pacing. Seven of the patients had A-V block grade II-III and 10 patients had sinus rhythm. The range of atrial ERP in all patients was found to be 200 to 270 msec. and the range of atrial RRP was 230 to 330 msec. The atrial ERP and RRP were longer at a pacing rate of 160 per minute than at a pacing rate of 240 per minute. The conduction delay between the second impulse and the atrial depolarization was found to be due to increased interval between the stimulus and the start of the depolarization wave. The atrial ERP increased after injection of propranolol in 8 of 12 patients, decreased in 3 patients and was unchanged in one patient. The atrial RRP increased in 7 patients, decreased in one patient and was unchanged in 4 patients. In all patients the changes were of moderate degree. The conduction delay between the stimulating impulse and the atrial response was shorter after propranolol in 7 patients, longer in one patient and unchanged in 4 patients. The ERP of the atrioventricular conducting tissue was 220 to more than 380 millisec. After injection of propranolol it increased in all of 3 patients in whom it could be measured. After injection of verapamil no significant effects on the atrial ERP and RRP were found. ERP of the atrioventricular conducting tissue was lengthened in 4 of 5 patients, and the degree of A-V block during rapid atrial pacing increased after injection of verapamil. It is suggested that the effect of propranolol on atrial arrhythmias is due to its effect on ectopic pacemaker activity rather than any effect on the refractory period of the atrium. The effects of verapamil on the atrioventricular conducting tissue may explain some of the antiarrhythmic effects of this drug.


Dosage titration with furosemide in congestive heart failure patients. Clinical status and diuretic requirements of a group of congestive heart failure patients were re-evaluated. A group of 115 congestive heart failure patients were hospitalized, given a comprehensive medical examination and treated with placebo for four weeks. Thirteen patients did not exhibit signs and symptoms of congestive heart failure during this phase. The remaining 102 patients were treated with 40 mg furosemide per day for a second 4-week period. Fifty-three required 80-120 mg furosemide per day and 49 were successfully controlled at 40 mg per day. Ten patients dropped out voluntarily and 39 were controlled for an additional four weeks at a dose of 20 mg bid furosemide. In the final phase, dosage was lowered to 20 mg per day and 24 of the 39 patients, (62%), were successfully controlled for four weeks, while 14, (36%), were controlled for eight weeks. Results of this study suggest that a number of congestive heart failure patients can be controlled with relatively low doses of furosemide and that there is a need for periodic re-evaluation of the clinical status and diuretic requirements of patients on maintenance therapy.


The single dose method of administering cholestyramine. A new and simplified method for the administration of cholestyramine is presented. It has been our finding that the total daily dose of the resin (as indicated below) may be administered once a day in a single dose at any time during the waking hours, without reference to meals, and the resulting degree of cholesterol lowering is as great or greater than that obtained by the same dose with the traditional method of t.i.d. administration of cholestyramine. Doses of 12 or 16 gm per day, have been administered as a single dose to adult patients. We have not encountered side effects from the administration of this resin as a single dose, however an occasional patient has objected to the volume involved, and has preferred to take a smaller volume 2 or 3 times daily. Because of the bulk involved in the administration of larger doses, we have found it expedient to give doses of 24 gms per day by dividing the dose in half and administering it twice daily without reference to meals. The 21 patients in our study who received cholestyramine in the single daily dose obtained an average reduction of their serum cholesterol of 21.58% over baseline values. Twenty patients receiving a somewhat larger dose, administered twice daily (b.i.d. dose), obtained a 27.57% reduction in the serum cholesterol, and out of this entire series there were 22 patients who had at other times received the cholestyramine by the t.i.d. regimen. They had obtained a 25.61% reduction of their serum cholesterol (by the t.i.d. regimen). All 3 average percent reductions compared to 0 are highly significant (p is less than 0.0001). One hundred forty out-patients treated by the conventional t.i.d. program of administration obtained a 16.8% reduction in the serum cholesterol. This includes some patients taking relatively small and less effective doses. Our entire series of 238 patients (to be reported subsequently) treated as out-patients have obtained an average reduction of 22% of their serum cholesterols. There has been no statistically significant influence on the levels of the serum triglycerides during cholestyramine therapy in this series (results on 69 patients showed an average rise of 5.9 mg per 100 ml in the serum triglycerides). See discussion in text. Some studies have indicated a rise of serum triglycerides during cholestyramine therapy. It is recommended that triglycerides be monitored periodically during the course of cholestyramine treatment.(ABSTRACT TRUNCATED AT 400 WORDS)


Traumatic subclavian arteriovenous fistulae. Arteriovenous (A-V) fistulae can be congenital or acquired. Acquired arteriovenous fistulae are met with during war as well as civilian practice as a result of penetrating injuries causing perforation in an artery and a vein which are surrounded usually by a firm sheath like the femoral, carotid or subclavian sheath, resulting in a communication between the artery and the vein. In the past, these fistulae were treated either by ligation of the feeding artery or by quadruple ligation after waiting for the collateral circulation to develop and feed the affected limb. The goal of the modern vascular surgeon, however, is to resume vascular continuity of both artery and vein. We were recently faced with a subclavian arteriovenous fistula and aneurysm caused by a gunshot wound of many years' duration. Searching the literature on a detailed technique for complete repair of such a fistula proved fruitless. Hence, we were thrown upon our own resources. We planned this operation which proved safe and successful. Repair of a subclavian arteriovenous fistula is a challenging piece of surgery. The location of this fistula under the clavical and its proximity and connection to important structures in the neck and the thoracic outlet makes its correction difficult and hazardous. The purpose of this paper is to present this method of safe repair and discuss the pitfalls and safeguards.


Dental auxiliaries, universities, and academic freedom. The practicing dental profession lately has asked questions regarding the propriety of research programs designed to investigate the use of expanded duty dental auxiliaries. The dental schools see paraprofessional research as socially responsive. Dental societies recognize the usefulness of auxiliaries but feel their responsibilities should be limited. This paper examines the status of dental auxiliaries, universities, and academic freedom.


Use of acid cleanser in endodontic therapy. The use of a 50percent citric acid cleanser in root canals after pulpectomy produced well-cleaned surfaces as shown by scanning electron microscopy. Compared with other cleaning agents, this cleanser provided improved penetration of rosin into the dentinal tubules and better wall adaptation of gutta-percha. No contraindication has been encountered in clinical practice. Application of the cleanser directly to the exposed pulp resulted in satisfactory destruction similar to the results obtained with strong acids.


Close-up photography in the dental office. Photographs taken by the dentist can be used in his professional contacts, in office administration, and for patient education and motivation. The parts of a camera including viewing systems, lenses, shutters, diaphragm, and film are described. The technique for close-up, intraoral photography requires special lens systems and proper lighting. The correct method for focusing is described.


Nonfatal anaphylaxis caused by oral penicillin: report of case. Severe allergic reactions may occur after the ingestion of oral penicillin. It is essential that the dentist who prescribes the drug is familiar with the rationale for therapy and is equipped to initiate urgently needed treatment.


An esthetic transitional treatment for amelogenesis imperfecta: report of two cases. The literature pertaining to amelogenesis imperfecta is reviewed as it applies specificity to two reports of cases. Psychologic, mechanical, or economic factors may warrant a transitional treatment of the teeth. Treatment with the use of an etchant and composite material and glaze is described.


Duration of amnesia during sedation with diazepam and pentazocine: preliminary report. Fifteen student volunteers participated in a study to determine the duration of amnesia obtained with diazepam and with pentazocine. The group that received pentazocine experienced only slight sedation and no amnesia. There was extreme variance in the level of sedation and in the incidence and duration of amnesia in the group that received diazepam. When amnesia occurred, it lasted for an average of 24 minutes. All students in the group that received a combination of diazepam and pentazocine were well sedated; the average duration of amnesia was 25 minutes.


Fenestrated palatal mucosal grafts for vestibuloplasty. Vestibuloplasties with fenestrated palatal mucosal grafts were successful in eight patients. The fenestrated palatal mucosa provides a tough, full-thickness, resilient mucosal graft from a limited donor site. The operating time is decreased, bleeding is minimized, and healing time of the donor site is shortened. Fenestration allows seepage of blood and tissue fluids from beneath the graft. The fenestrated grafts are readily adaptable to any irregularities of the edentulous mandibular ridge.


Complex odontoma of the maxillary sinus: report of case. During a screening examination for orthodontic evaluation and for possible partial anodontia, a large radiopaque mass was found in the right maxillary sinus of a 12-year-old boy. Further radiographic views were used to locate and establish a working diagnosis. The mass was removed with use of a standard Caldwell-Luc approach. It was diagnosed histologically as a complex odontoma.


Malignant hyperthermia.

Malignant hyperthermia. Malignant hyperthermia is a genetic disease that may become apparent after exposure to drugs; some of these drugs are commonly used by the oral surgeon. One in 14,000 young, apparently health individuals may be affected; mortality is 64 percent. Many cases of malignant hyperthermia can be prevented if an adequate history is obtained. Oral surgeons should be familiar with the prevention, diagnosis, and initial treatment of malignant hyperthermia.


Simplified technique to reduce perioral edema in intraoral sagittal split osteotomies. A simplified technique has been developed for the prevention of the severe perioral edema that is routinely associated with intraoral sagittal split osteotomies of the ascending ramus of the mandible. By the use of gauze sutured through the cheeks in the region of the oral commissures, trauma caused by retraction of instruments is significantly diminished.


Periadenitis mucosa necrotica recurrens. A review of the literature and a case report of PMNR that lasted more than 20 years is presented. The previously unreported use of large doses of erythromycin taken orally as a treatment alternative is offered.


Long-term effect of benzene in C57BL/6N mice. Weaning male C57BL/6N mice received repeated subcutaneous injections of benzene in corn oil for 54 weeks. These mice and surviving controls were killed 104 weeks after the first injection. There was no evidence of carcinogenic activity in benzene-injected mice. A high incidence of amyloidosis developed in  mice of all treated and untreated groups. Butyinitrosourea, used as a positive control, induced lymphomas or leukemias (in most exposed mice) and intestinal tumors in a few.


Primary malignant hemangioendothelioma of the gingiva. Report of a case and review of the literature. Primary malignant tumors of vascular origin are exceedingly rare in the oral cavity. Consequently, knowledge of their clinical and pathologic features is scanty. The varied array of terms applied to malignant vascular tumors has only further confused the issue. This article presents a review of twenty examples of oral malignant vascular tumors, with a report of a single personally studied case. Specifically, this case presented as a soft-tissue gingival lesion which subsequently invaded bone and represents a malignant hemangioendothelioma.


Migratory glossitis. A clinical-histologic review of seventy cases. The observations on seventy patients with migratory glossitis and follow-up experiences over a period of 10 years are recorded. Women represented 65.7 per cent of the total, and most cases occurred in patients over 40 years of age. In 20 per cent of the patients other anomalies of the tongue were associated, and in 20 per cent subjective complaints were associated with psychic stress. Histologic investigations showed an inflammatory reaction of the epithelium and of the underlying connective tissue. The patient must be reassured of the benign nature of the tongue lesion. At follow-up examination, the lesions were present but no malignant change was observed.


Studies on oral lichen planus. III. Clinical and histologic correlations in 213 patients. Two hundred thirteen adults in whom oral lichen planus had been diagnosed were studied in order to compare clinical and microscopic findings. In spite of considerable variabilities in both aspects, there was clinical and histologic agreement in 96 per cent. Alertness on the part of the clinician and pathologist is essential for diagnosis of atypical cases.


Dental pulp histology observed by scanning electron microscopy. This article describes the appearance of routine decalcified and paraffin-embedded histologic sections of the human dental pulp as observed with the scanning electron microscope (SEM). The tissue sections were cut at 12 mum in order to increase the three-dimensional effect. The technique was particularly successful in revealing the three-dimensional structure of pulpal blood vessels and nervous tissue. Possible interodontoblastic attachments were revealed at x10,000.


Developmental submandibular gland defect of the mandible. Review of the literature and report of a case. The literature relative to developmental submandibular gland defect of the mandible is reviewed, and an interesting case is presented. Evaluation for more serious systemic disease which may manifest radiolucencies in the region of the angle of the mandible is made.


Conservation of human research teeth by controlling cavity depth. In order for the dental profession to obtain reliable data as to whether new or experimental restorative materials and adjunct agents are more or less irritating to pulp tissues than dental products currently in use, pulp studies at the national and international level are being standardized to enhance corroboration. The purpose of this study was to reduce the number of human teeth required in any experimental pulp toxicity study by controlling the problem of cavity depth. Many valuable teeth are wasted by making cavity preparations that are either too shallow or too deep, with consequent pulp exposures. This needs to be corrected.


Compact foreign-made dental x-ray generators: an evaluation of their acceptability for effective dental radiography. II. Image characteristics and observer performance. Imported generators, while inexpensive and compact, feature fixed peak kilovoltage and fixed milliamperage levels. These generators, because of the relative inflexibility of their operating characteristics, cannot be modified to produce radiographic image characteristics of equal diagnostic value to the domestic generators without compromises which are unacceptable.


Application of a lateral compression clamp in the management of mandibular fractures. A lateral compression clamp system has been used in the treatment of fractures of the mandible. It provides rigid fixation and promotes earlier osteogenesis at the fracture site. Intermaxillary fixation can often be eliminated in edentulous persons and greatly reduced in duration when necessary as an adjunct to fixation in patients with teeth. These significant qualities make the compression clamp quite beneficial in the treatment plan and postoperative management of many otherwise difficult cases. Having evaluated our experiences with compression clamps, we believe that this approach deserves further attention and may contribute to a solution of the controversy that often exists regarding the management of mandibular fractures in both edentulous patients and those with a compromised complement of teeth.


The storage of teeth before reimplantation in monkeys. A histologic study. This study is a histologic comparison of twenty teeth which were extracted, endodontically treated, stored for 7 days at +4 degrees C. and at -10 degrees C., and subsequently reimplanted in ten monkeys. In these monkeys, as controls, ten more teeth were extracted, endodontically treated, and immediately reimplanted. Up to 1 year, 100 per cent success was obtained in those teeth stored at +4 degrees C. before reimplantation, and only 50 per cent success was obtained in those teeth stored at -10 degrees C. before reimplantation.


Metastatic renal adenocarcinoma presenting as periapical pathosis in the maxilla. A case is reported because of the infrequency with which tumors metastasize from the kidney to the maxilla. It is of special interest because it presented as a periapical pathosis associated with a nonvital tooth and emphasizes the value of routine histopathologic examination of tissue.


Congenital midline fistula of the tongue. A possibly unknown entity of congenital midline fistula of the tongue, hitherto not mentioned in the literature, is reported. The embryologic basis of it is explained and the role of the tuberculum impar in the development of the anterior two thirds of the tongue is discussed.


Lingual osseous choristoma. Report of two cases. The lingual osseous choristoma is a rare benign lesion of the tongue, and it is difficult to make a correct preoperative diagnosis of these lesions. Two cases are presented in this article.


Temporomandibular joint arthroplasty with fascia lata. Two patients with temporomandibular joint arthralgia and ankylosis were managed with arthroplasty and insertion of fascia lata. The role of physiotherapy, chances of facial nerve damage, role of steroids, and advantages of fascia lata are discussed.


An experimental study of intraoral carcinogenesis in rats. A new method has been devised for preparing artificial cecal pouches lined with mucous epithelium in the lower lips of Wistar and Sprague-Dawley rats in order to make carcinogens act continuously for a long time in the oral mucosa. When a 0.5 per cent mineral oil solution of DMBA, a crystal of MC, and a crystal of NG were administered, squamous-cell carcinoma, carcinoma in situ, papilloma, adenoma sebaceum. neurofibroma, fibroma, hemangiosarcoma, hemangiosarcoma, hemangioma, and lymphangioma were successfully produced in the oral mucosa of rats. In addition, interesting findings were obtained concerning tissue changes in the process of carcinogensis in the mucous epithelium.


The effect of high cervical cordotomy on portal vein plasma serotonin and 5-hydroxyindoleacetic acid levels in dogs with and without superior mesenteric artery occlusion. In ten dogs undergoing high cervical cardotomy, there was a statistically significant fall in plasma serotonin (5-HT) levels in portal vein blood; no further change in plasma 5-HT occurred after superior mesenteric artery (SMA) occlusion, which is an effective stimulus for 5-HT release. In five dogs undergoing high cervical corotomy with no SMA occlusion, there was a comparable fall in portal vein plasma 5-HT levels. The 5-hydroxyindoleacetic acid (5-HIAA) values in portal vein blood in the two groups of dogs above fell to comparable levels. These findings  indicate (1) that maintenance of the normal plasma 5-HT level in portal vein blood in this experimental model is dependent on the integrity of the spinal cord and (2) that SMA occlusion in animals with a high cervical cordotomy does not result in further changes in the plasma 5-HT level in portal vein blood.


Purinylhydantoins. Facile conversion of the naturally occurring N-(purin-6-ylcarbamoyl)-L-amino acids into 3-pruin-6-ylhydantoins and 3-cyclohexyl-1-(purin-6-ylcarbamoyl)hydantoins. The naturally occurring N-(purin-6-ylcarbamoyl)-L-threonine (PCT, 1b), N-(purin-6-ylcarbamoyl)glycine (PCG, 1a), and some of their analogs were converted into novel purine derivatives, the purinylhydantoins. The PCT and PCG underwent intramolecular cyclization in the presence of N,N-dicyclohexylcarbodiimide (CDD) to give the 3-purin-6-ylhydantoins (2a-c). The same hydantoins were also obtained when the PCT and PCG were allowed to react through the mixed anhydride formed from cyclohexyl isocyanate or ethyl chloroformate. 1,3-Dicyclohexyl-1-(N-(purin-6-ylcarbamoyl)aminoacyl)ureas 3a and 3c, by-products obtained from the DCC reaction, were rapidly converted in aqueous NaOH to another type of purinylhydantoins, the 3-cyclohexyl-1-(purin-6-ylcarbamoyl)hydantoins 4a and 4b. Compound 4a when heated in base underwent hydrolysis of the hydantoin ring giving biuret N-(cyclohexylcarbamoyl)-N-(purin-6-ylcarbamoyl)glycine (5a) and N-(purin-6-ylcarbamoyl)glycine cyclohexylamide (6a). The characterization of these hydantoins was carried out by uv, nmr, and mass spectrometry. The 3-purin-6-ylhydantoins and 3-cyclohexyl-1-(purin-6-ylcarbamoyl)hydantoins showed growth inhibitory activity in the cultured leukemic cells, while the parent amino acid compounds were inactive.


Hypofibrinogenemia associated with vincristine and prednisone therapy in lymphoblastic leukemia. Three patients with acute lymphoblastic leukemia and one with lymphosarcoma cell leukemia developed transient hypofibrinogenemia during a course of treatment with vincristine and prednisone. There was no evidence of overt, disseminated intravascular coagulation or significant liver impairment. Fibrinogen survival using homologous-125-I-labelled fibrinogen was measured in two patients; it was moderately shortened in both, perhaps indicating subclinical intravascular coagulation. Rapid lysis of leukemic cells might have been responsible for activating coagulation and fibrinolysis in vivo. These four patients, however, were not different in any clinical or laboratory parameter from nine others with lymphoblastic leukemia similarly treated and investigated without observing any defect in their fibrinogen. There were no bleeding complications and the fibrinogen level became normal within 13 to 30 days.


Total body irradiation (TBI) as primary therapy for advanced lymphosarcoma. The natural history of lymphocytic lymphomas is such that diffuse involvement usually is present at diagnosis. Extensive lymphatic irradiation with tumoricidal doses is seldom an appropriate form of treatment, as most patients require systemic therapy. We have investigated total body irradiation (TBI) as an alternative to chemotherapy. A series of 39 consecutive untreated patients with generalized disease is reviewed. Actuarial 5-year survival rates for the well-differentiated, poorly differentiated nodular, and poorly differentiated diffuse histologic types are 100%, 78%, and 56% respectively. The single major complication, acute myelocytic leukemia, has developed in 2 of the 8 patients given extensive nodal irradiation as a supplement to TBI. None of the 31 patients receiving only TBI as initial therapy has shown evidence of a myeloproliferative disorder to date.


Combined modality therapy of acute lymphocytic leukemia. The progressive improvement in the prognosis of acute lymphocytic leukemia has been a result of two major developments: 1) the more efficient use of chemotherapeutic agents, particularly the use of combinations of agents and the discovery that agents effective at one stage of disease may be inappropriate at another stage, and 2) the prevention with irradiation of central nervous system relapse. As many as one-half of children with this disease may enjoy long-term leukemia-free survival. However, further studies are needed to improve the efficacy and reduce the toxicity of therapy. This paper reviews the evolution of some of these studies.


Cell density-dependent growth in agar of bone marrow cells from tumor-bearing BALB/c mice in the absence of a colony-stimulating factor. Bone marrow cells from BALB/c mice with myeloid leukemia, lymphosarcoma, erythroblastosis, or mammary tumor produce small clusters in semisolid agar cultures in the absence of specific colony-stimulating factor. This spontaneous growth is observed only when high cell numbers (5 x 10 5 cells/ml) are plated. The phenomenon was encountered only when mice had an elevated number of mature or immature granulocytes in the peripheral blood. Removal of the adherent cells from the bone marrow did not abolish spontaneous growth, indicating that this colony-stimulating factor independency is not due to a high number of colony-stimulating cells in the bone marrow cells. This excluded the possibility that the spontaneous growth was due to a high endogenous stimulating activity of the bone marrow from tumor-bearing mice.


Decreased lymphocyte adenosine deaminase activity in acute lymphocytic leukemia children and their parents. Adenosine deaminase has been measured in the lymphocytes of children with acute lymphocytic leukemia and in those of their parents. The activity was found to be significantly lower in both acute lymphocytic leukemia children in remission and relapse and in the parents of acute lymphocytic leukemia children when compared with normal adults and children of similar ages.


Inhibition by 4'-demethyl-epipodophyllotoxin 9-(4,6-O-2-thenylidene-beta-D-glucopyranoside) of human lymphoblast cultures in G2 phase of the cell cycle. 4'-Demethyl-epipodophyllotoxin 9-(4,6-0-2-thenylidene-beta-D-glucopyranoside) is a semisynthetic derivative of podophyllotoxin with oncolytic activity against a variety of neoplasms, Unlike the parent compound and other derivatives, which cause methaphase arrest, 4'-Demethyl-epipodophyllotoxin 9-(4,6-0-2-thenylidene-beta-D-glucopyranoside) apparently blocks the entry of CCRF-CEM cells into mitosis by inhibiting cells in the G2 phase of the cell cycle. The inhibition of precursor incorporation into DNA, RNA, and the protein, if observed, was delayed and probably secondary to inhibition of cells in the G2 phase of the cell cycle.


Alterations in ribonuclease activities in the plasma, spleen, and thymus of tumor-bearing mice. Six transplantable murine tumor models were evaluated for changes in RNase activity. This study was conducted with spleen and thymus homogenates, as well as with plasma collected from tumor-bearing mice. Nuclease activity directed against the synthetic substrates, polyadenylic acid, polyuridylic acid, and polycytidylic acid, was measured and the data obtained for tumor-bearing animals were compared to their normal counterparts. Elevated activity against polyuridylic acid was observed in the plasma of all tumor-bearing mice. Although not as all inclusive, RNase levels in both the spleen and thymus were generally altered as well. The observance of unilateral changes in nuclease activity directed against the synthetic substrates demonstrated that, in most cases, two or more enzymes were being detected. The assay may have some eventual value in the monitoring of cancer


Genetic effects of radiation.

Genetic effects of radiation. The effects of radiation on biologic systems as manifested through genetic changes have been reviewed. The use of x-radiation by the health professions represents the largest contribution of radiation dose to the people of the United States. It is apparent that the genetic effect of radiation results in the production of chromosomal aberrations and gene mutations. Recognizing this, it becomes mandatory that appropriate measures are instituted to reduce to an absolute minimum the total amount of radiation that patients receive. Strict utilization of all known protective measures and adherence to protective guidelines promulgated by the ICRP and NCRP IS IMPERATIVE. Every attempt must be made to obtain maximal diagnostic yield from all radiation exposures used for diagnostic purposes, thereby assuring maximal benefit for our patients with minimal risk to our ancestors.


Dental variation among populations. An anthropologic view. There is considerable variation between and within populations with regard to tooth size, age of eruption, congenitally missing teeth, and crown morphology. These differences are a reflection of the ongoing process of evolution. The genetic basis for this variation is best explained by a polygenic model of inheritance. Even though tooth morpholoyg and agenesis have discontinuous distributions - usually evidence of single gene transmission - they are also  polygenic traits and are examples of "quasi-continuous" characteristics. These are traits which exhibit phenotypic discontinuity at the end of a continuous distribution. Postnatal conditions such as nutrition, disease, or climate seem to have little influence on normal dental variation. Most of the environmental factors which affect the dentition occur during the prenatal period. In particular the quality of the intrauterine environment appears to be most important. This suggests that good prenatal nutrition and medical care are needed for a normal and healthy dentition.


Gene-environment interactions during tooth development. The nature of the interaction between the environment and the genetic information of the organism has been examined vis-a-vis the local tissue environments in which the teeth are initiated. The directive role of the dental connective tissue, the papilla, and sac in initiating the tooth bud, controlling its shape, and maintaining its differentiation emphasize the importance of the mesenchymal connective tissue elements of tooth buds. The molecular character of this tissue interaction was described and the role of collagen as a mediator of developmental information was stressed. Finally these data from experimental studies suggest that the etiology of ectodermal dysplasia and inherited diseases involving the dentition may involve the function of the connective tissue of the dintition.


Effects of cement bases on the stresses in amalgam restorations. A computerized dental model was used to study the stress induced in a Class 1 amalgam restoration when supported by bases of varying materials and thickness. Under the same load, the maximum tensile stresses and deflections in the amalgam restoration increased at least threefold with a zinc oxide-eugenol base as compared with a ZnPO4 cement base.


Dentinoenamel junction area of a resorbing permanent incisor studied by means of scanning electron microscopy. The surfaces of enamel and dentin that had become separated from each other presumably in the region of the dentinoenamel junction were examined. The enamel surface at the junction was scalloped; the scallops were made of enamel rods. The dentinal surface showed a mirror image picture, tubular in nature. Both surfaces were granulated, which may indicate that apatite crystals from the two tissues intermingle there.


In vivo occlusal forces and moments: I. Forces measured in terminal hinge position and associated moments. Microducers and modified cephalometric roentgenogram techniques were used to study maximum biting forces and moments in an adult male. The force at the second molar was approximately 10% greater than that at the first molar. At the second molar, the moment of force was approximately 15% less than its value at the first molar.


In vivo occlusal forces and moments: II. Mathematical analysis and recommendations for instrumentation specifications. Mathematical models are derived to describe in vivo maximum occlusal force and moment data generated during mandibular terminal hinge closure for the molars and premolars and for the mandibular central incisors in the straight protrusive position. Recommendations for biting force instrumentation specifications are presented.


Electron microscopic study of the cytotoxicity of cadmium and mercury in vitro. The cells treated with cadmium chloride showed severe changes: ribosomes disappeared, mitochondria showed various degrees of destruction, and the endoplasmic reticulum had a swollen and beadlike appearance. In cells treated with mercuric chloride, ribosomes increased in their density and rosette-like polysomes were predominantly observed. The effects of these two metallic ions were discussed.


Inhibitory spectrum of a bacteriocinlike substance (mutacin) produced by some strains of Streptococcus mutans. Streptococcus mutans strains were surveyed to determine their lysogenicity. Growth inhibition of the indicator strains around the inoculum of stab culture of some S mutans strains was demonstrated. Many gram-positive bacteria, including mycobacteria and streptomycetes, were sensitive to the antibacterial activity.


Hypodontia: a polygenic trait--a family study among Israeli Jews. A high prevalence of hypodontia was detected among 820 first degree relatives of 305 probands and there was an increased risk if a second family member was affected. Hypodontia is a common trait in the population, and a deviation from normal sex ratio was observed in those affected. These results suggest a polygenic mode of inheritance.


Effect of exogenous lipid on lipid synthesis by bone and bone cell cultures. Newborn rat calvaria and isolated calvaria cells are capable of de novo lipid synthesis when grown in the presence or absence of exogenous lipid sources. Synthesis decreases when exogenous lipids are supplied. Several cholesterol precursors were found in these tissues and the presence of dihydrocholesterol was established for the first time.


Effect of topical applications of neutral sodium fluoride on dental careis in the rat. A study on various regimens by which the same total amount of neutral sodium fluoride is applied to the teeth of rats showed that greater effects were observed after frequent application of 0.2% solutions than after less frequent application of more concentrated solutions.


Objective quantification method for measuring in vivo accumulated dental plaque. Dental plaque was collected, dried, and weighed on a gold insert that fit into the buccal aspect of a posterior crown. The plaque weight was determined by calculating the difference between the postcollection insert weight and the precollection insert weight. This system for measurement of the dry weight of in vivo accumulated dental plaque was found to be a practical means of plaque quantification.


Elasticity of impression materials: IV. Permanent deformation as a function of time. The permanent deformation-time relationship under constant load, of 15 elastomer impression materials were studied. All materials showed a greater permanent deformation under constant load than with tensile load, except the polyether material. Silicone and polyether materials exhibited perceptibly less permanent deformation than mercaptan materials ten minutes after mixing.


Assessment of microleakage using a conductimetric technique. A new method enables the dimensional changes of a range of anterior restorative materials to be demonstrated in an artificial cavity. The cavity wall-restoration interspace was incorporated into an electrochemical cell and the changes in the current passing through this cell reflected changes in the dimensions of the interspace.


Surface-chemical studies on chlorhexidine and related compounds: I. Effects at air-water, n-hexane-water, and hydroxyapatite-water interfaces. The comparative ability of chlorhexidine diacetate and structurally related compounds to generate surface pressure at air-water and n-hexane-water interfaces, and to adsorb to hydroxyapatite, was determined. The order of effectiveness generally evident was 1-(p-chlorophenyl)-5-n-octylbiguanide acetate is greater than chlorhexidine diacetate 1-(p-chlorophenyl)-5-n-hexylbiguanide acetate is greater than 1-(p-chlorophenyl)-5-n-propylbiguanide acetate is greater than p-chlorophenylbiguanide acetate p-chlorophenylguanidine acetate.


Dentifrice detergent: its effect on human enamel. A scanning and transmission electron microscope study has shown that human enamel specimens treated with a mild detergent solution exhibit etching of the enamel surface. The tooth surfaces subsequently show a greater susceptibility to the acid attack than samples treated with mineral acid alone. The evidence suggests that reevaluation of sodium dodecyl sulfate and similar detergents as components of commercially available dentifrice products may be necessary.


Surface-chemical studies on chlorhexidine and related compounds: II. Interactions with monomolecular-film systems. Interactions of chlorhexidine and structurally related biguanides with selected monomolecular-film systems (that is, stearic acid, stearyl alcohol, and N-octadecylacetamide) were explored. The data reflected the significance of ionic associations between the compounds and stearic acid films and, in the instance of the biguanide analogs, indicated that the length of the alkyl chain was an important factor in the penetration process.


Role of afferent sensors in the initiation of swallowing in man. Chewing and swallowing sounds that were recorded on magnetic tape by means of a paralaryngeally placed contact microphone were used to evaluate temporal relationships of the events of the swallowing cycle in young women. Temporal inter-event parameters indicate a reflex nature for the initiation of swallowing, and the effects of topical anesthesia suggest a triggering mechanism for swallowing similar to the gating theory for pain proposed by Melzack and Wall.


Extractions in the presence of acute infections. Of 1,376 extractions performed in the presence of acute infection, 327 were performed in the presence of a coexisting fascial space abscess. No serious complications were observed. It seems that the relation of dental operations to the intracranial infections has been overestimated. The extraction of teeth in cases of acute suppurative infection treats the primary dentoalveolar infection and prevents the development of fascial space abscesses.


Potential applications of certain nickel-titanium (nitinol) alloys. The mechanical behavior ("shape memory") associated with martensitic solid-state transformation in nearly equiatomic Ni-Ti alloy (55-Nitinol) has been studied. Potential dental and medical applications for 55-Nitinol (55% Ni, 1.5% Co, balance Ti, by weight) and for 60-Nitinol (60% Ni, by weight) have been suggested.


Clinical correlation of hepatic flow studies. In 100 consecutive hepatic flow studies, 84 were read as negative. Of these, 73 (87%) also had negative static images. Knowing the nature of the primary tumor did not definitively aid in predicting whether hepatic meastases would have detectable early flow. Five cases showed early flow without defects seen in the static images. Three of these were probably related to lymphomas or allied disorders with altered flow. Two cases were in individuals with gastric carcinoma who had abdoninal radiation. One extrahepatic tumor was detected in the series.


An inhibitory principle in the matrix of periodontally diseased roots. The inhibitory influence shown by the periodontally diseased root resides in its organic component. Its nature is uncertain and it may be an etiologic factor in periodontal destruction. The apatite structures of healthy and diseased roots are alike in being more receptive to the growth of bone and marrow than are their respective matrices.


Histological evaluation of effects produced in alveolar bone following gingival incision with an electrosurgical scalpel. Gingival incisions were performed distal to each of the two lower incisors on 25 adult male guinea pigs. For every animal, electrosection with an electrosurgical scalpel was used on one side, and a conventional scalpel was used on the other. The surgical instruments in all cases were brought into direct contact with periosteum. Five animals were sacrificed at each postoperative period (12, 24, 48, 72, and 96 hours), and sections of the areas of surgery were prepared by standard laboratory procedures. At 12 hours postoperatively there were far more soft tissue necrosis, a more extensive inflammatory reaction, and greater destruction of periosteum after electrosurgery. No significant changes in osteocyte viability were seen after either technique. However, by 24 hours, many empty lacunae were observed in the bone associated with electrosurgery, such necrosis being even more extensive by 48 hours. In contrast, only very minor, localised areas devoid of some osteocytes were seen after use of the conventional scalpel. By 96 hours the electrosurgical connective tissue wounds were still lined by coagulum, but repair of the scalpel wounds had begun. The periosteum and bone had the same features that were seen at 48 hours. Throughout the study, no increase in osteoclasts was seen in any section, nor were significant changes in adjacent bone marrow observed.


The effects of age and fluoride exposure on fluoride, citrate and carbonate content of human cementum. A study was conducted to determine the values of several chemical components of dental cementum. Extracted teeth from continuous residents of low, optimal, and high natural fluoride areas were selected to determine the effects of fluoride exposure and age on the fluoride, citrate and carbonate content of cervical and apical areas of sound and periodontally diseased human cementum. 1. For normal cementum the mean fluoride content of all 18 groups was 0.443 plus or minus 0.04%on an ash basis and 0.253 plus or minus 0.02% on a dry weight basis; the mean citrate content was 1.52 plus or minus 0.10% on an ash basis and 0.86 plus or minus 0.06% on a dry weight basis; the mean carbonate content was 4.95 plus or minus 0.39% on an ash basis and 2.79 plus or minus 0.22% on a dry weight basis. 2. For diseased cementum the mean fluoride content of all 12 groups was 0.575 plus or minus 0.03% on an ash basis and 0.342 plus or minus 0.02% on a dry weight basis; the mean citrate content was 1.19 plus or minus 0.07% on an ash basis and 0.71 plus or minus 0.05% on a dry weight basis; the mean carbonate content was 5.95 plus or minus 0.47% on an ash basis and 3.50 plus or minus 0.28% on a dry weight basis. 3. There is a general increment in fluoride content of normal cervical and apical cementum, both with age and fluoride exposure. For diseased cementum this held true for fluoride exposure but not age. 4. The mean fluoride content of cervical cementum is greater than that of apical cementum for both normal and diseased groups. For citrate and carbonate no definite statistical differences were noted between cervical and apical areas. 5. The diseased cementum has a significantly higher mean fluoride content, a significantly lower citrate content, and a slightly, but not statistically significant, higher carbonate content than normal cementum. 6. Unlike bone, no inverse fluoride/citrate or fluoride/carbonate relationship was observed. 7. For both normal and diseased groups the carbonate content of cementum of individuals over age 40 tended to be lower than for individuals 20-40 years of age.


Observation of the mitochondria of the sulcular epithelium of clinically inflamed and clinically healthy gingiva. Ten human males with an average age of 22 years, free from any known systemic disease, were selected for this study. Each subject had a mild gingivitis around at least one lower incisor tooth. This was confirmed by the color, contour, and consistency of the tissue. The area was probed for gingival sulcus depth and a radiograph confirmed that there was no interproximal bone involvement. A specimen was excised from the inflamed area and examined histologically for inflammatory cell density and an inflammatory index number was assigned to the tissue. The gingivitis was treated and personal oral hygiene instructions were explained to the subjects. Healing continued uneventfully for ten to twelve weeks. A second specimen was excised from near the original area, examined histologically, and an inflammatory index number was assigned to the tissue. The ultrastructure of the sulcular epithelium and the connective tissue adjacent to the sulcular epithelium of all specimens was examined at powers varying from 3,500 to 70,000. The sulcular epithelium showed no positively recognizable mitochondria. Mitochondria in the connective tissue adjacent to the basal layer of the sulcular epithelium were abundant and well formed. There was no correlation between the number and morphology of mitochondria in the treated and untreated specimens.


Interproximal contact and marginal ridge relationships in periodontally healthy young males classified as to orthodontic status. Three groups of periodontally healthy young males, classified as to orthodontic status, were evaluated for proximal contact and marginal ridge relationships in the maxillary left quadrant. The majority of anterior teeth did not have satisfactory proximal contacts on both the mesial and distal aspects. Open or defective proximal contact relationships were common in all three orthodontic groupings. In posterior areas, the orthodontically treated group had the highest percentage of open contacts. The orthodontically treated group had a significantly higher percentage of even marginal ridges in the teeth that are customarily banded.


Acute lymphoblastic leukemia terminating as histiocytic medullary reticulosis. A young man with acute lymphoblastic leukemia was treated with vincristine sulfate, prednisone, and intrathecally injected methotrexate sodium for central nervous system involvement. A good remission was induced, but three months later he had hepatosplenomegaly, an enlarging mediastinal mass, and progressive anemia. Histiocytic medullary reticulosis was confirmed by a bone marrow biopsy specimen. The patient died of respiratory failure because of infiltration of the lungs by malignant histiocytes.


Extreme elevation of serum transcobalamin I in patients with metastatic cancer. Elevation of transcobalamin I and serum vitamin B12 levels has usually been associated with increased granulocytic proliferation, such as occurs in chronic myelogenous leukemia. Two patients with metastatic cancer had extremely high serum vitamin B12 and transcobalamin I levels--greater than those seen in even the most intense granulocytic proliferation--that were not explainable by leukocytosis. The subjects' serum vitamin B12 levels were 18,750 and 21,221 pg per milliliter (normal, 471 plus or minus 174 pg per milliliter, mean plus or minus S.D.) and unsaturated vitamin B12 binding capacity 158,750 and 5,400 pg per milliliter (normal, 1153 plus or minus 313 pg per milliliter) respectively. The abnormally elevated serum binder was shown to be identical with transcobalamin balamin I in every respect. Levels of transcobalamin II and serum third binder were normal. The cause of the binder abnormality is unknown, but factors other than granulocyte proliferation may control or contribute to the production or accumulation of transcobalamin I.


Neisseria catarrhalis septicaemia in acute lymphoblastic leukaemia. A case of septicaemia due to Neisseria catarrhalis occurring in an immunosuppressed individual is described. The clinical syndrome closely resembled that of N. meningitidis septicaemia. The potential pathogenicity in the immunosuppressed patient, of organisms usually considered harmless is stressed.


Aneurysmal bone cyst secondary to other osseous lesions. Report of 57 cases. Fifty-seven aneurysmal bone cysts which were associated with or secondary to other lesions of bone are reported. The most common associations were with solitary or unicameral bone cyst, and with osteoclastoma. Other associated lesions included osteosarcoma, nonosteogenic fibroma, osteoblastoma, hemangioendothelioma, and hemangioma of bone. Five aneurysmal bone cysts were secondary to fracture or other bone trauma.


Delivery of health care in hemophilia.

Delivery of health care in hemophilia. Data on 56 severe and 16 moderate hemophiliacs who were intensively trained in self-therapy and have completed one to five years on this program reveal several principles not emphasized by prior reports. (1) The immediate application of therapy for suspected hemarthrosis, before the appearance of physical signs, leads not only to a striking decrease in morbidity but to a slight decrease in the quantity of plasma products required. (2) Dollar costs of this method of health care delivery are considerably lower than other effective methods and now average $3500 per patient per year, in our hands. (3) Intensive education and training of patients and family members makes lay persons extremely valuable members of the health care team and produces occasional dramatic health benefits. (4) Progression of long-term problems such as hemarthrosis, formerly found in 90% of our group, still exists for 19%. (5) The failure rate is highest in the older hemophiliacs. (6) Periods of several months of prophylactic therapy have a limited but valuable role in selected cases. (7) Mechanisms for mandatory periodic comprehensive health evaluation mjst be a part of every home infusion program, in order that the inevitable failures can be detected and appropriate corrective measures instituted.


A boarding school for hemophiliacs: a model for the comprehensive care of hemophilic children. Ten years' experience with boarding schools as comprehensive-care centers for hemophiliacs created by the French Red Cross has documented their effectiveness. Far from implying that hemophilic patients should be permanently isolated from society, we think that a temporary stay in a boarding school provides a model for the comprehensive care of hemophilic children. These schools have become hemophilia care centers where, on a temporary basis, patients can receive proper instruction concerning the medical, psychological, and educational problems they will encounter in society at large. At the present time, most hemophiliacs are properly treated at home, but selected cases of patients with specific problems can certainly benefit from a stay in a boarding school. Psychological studies presented here emphasized the high frequency of disturbances in patients coming from a low economic lass. One of the most important factors determining the psychological adjustment of hemophilic children seems to be understanding of the disease by the family. The cultural level of the family also influences the education and the medical care of these children. A temporary stay in a boarding school permits at least partial resolution of such problems both on a short-term and a long-term basis. During the stay, a great effort must be made to improve the local medical situation and the involvement of the parents in the problems of hemophilia. It has been shown that adolescents have greatly benefited from a self-infusion training program from both a medical and a psychological point of view. The boarding school seems to be the best means of organizing a program that requires a solid framework, psychological support, and a great amount of time. This training may be achieved in a three- to six-month period, depending on the motivations and the psychological ability of the hemophiliac. Self-infusion is a powerful tool able to transform the situation of these adolescents from one of dependence to one of autonomy and to enable them to adjust to society.


Multiple myeloma and acute leukemia associated with alkylating agents. Rapidly fatal acute myelomonocytic leukemia developed in five patients with multiple myeloma who were treated with melphalan for 28 to 54 months. In each patient, multiple myeloma responded to therapy and progress was satisfactory until the development of acute leukemia. At postmortem examination, leukemic infiltration of organs was seen, and there was little or no evidence of myeloma. Consideration of these cases and a review of the literature suggest that these circumstances represent the development of acute myelomonocytic leukemia rather than plasma cell leukemia; there also appears to be an increased incidence of acute leukemia in multiple myeloma, probably related to the alkylating agent.


Surgical sterilization by vasectomy and its effects on the structure and function of the testis in man. The early and late effects of vasectomy have been investigated in 40 men. Besides histopathological examination, the volume of the testis and its total content of testosterone-screting Leydig cells have been measured. The volume of the testis showed a wide normal variation (5-3-23-3 ml) but was not significantly changed by vasectomy. One month after vasectomy widespread degeneration of the germinal epithelium, thickening of the basement membrane and some intertubular fibrosis were observed. Spermatogenesis had ceased. However, cases examined 2-31/2 years later showed an essentially normal structure with active spermatogenesis. This indicates that regeneration does occur spontaneously, even without recanalization. Whether the sperms formed are functionally normal remains uncertain. The normal total Leydig cell volume was 2-2 plus or minus 0-4 ml/testis in young adults and showed a modest increase after vasectomy, rising to 2-5 plus or minus 0-5 ml after 1 month and 2-6 plus or minus 0-5 ml after 2-31/2 years. The findings have been discussed in the light of Steinach's (1927) original hypothesis that vasectomy can rejuvenate ageing males by improving the endocrine function of the testis.


In vitro colony-forming characteristics of chronic granulocytic leukemia in childhood. Peripheral blood from a child with adult-type (Philadelphia chromosome positive) chronic granulocytic leukemia was found to contain large numbers of cells capable of colony formation in tissue culture. The majority of the colonies contained granulocytic cells. The source of these granulocytic colonies was found in a population of myeloblasts, promyelocytes, and myelocytes which could be separated from the more mature granulocytic cells of the peripheral blood by sedimentation of the buffy coat on Ficoll-Hypaque. The predominance of granulocytic colonies is in contrast to our observations previously made on the peripheral blood of children with "juvenile" type(Ph1 chromosome negative)CGL in which large numbers of exclusively monocytic colonies were produced in tissue culture. These current studies, when interpreted in light of relevant clinical data, suggest that the "juvenile" and "adult" types of CGL represent two very different forms of chronic leukemia in childhood. The Ph1 chromosome negative form may be classified as a monocytic leukemia with a granulocytic component but the Ph1 chromosome positive adult form, even when it occurs in a child, appears to be a true granulocytic leukemia.


Chronic granulocytic leukaemia: effect of elective splenectomy on the course of disease. Conventional treatment by drugs or irradiation produces little prolongation of life in patients with chronic granulocytic leukaemia (C.G.L.) because the onset of metamorphosis of the disease from a chronic to an acute or subacute leukaemic process is not substantially postponed. Isolated clinical observations as well as both cytogenetic and cytokinetic evidence suggest that the spleen may play a special though not exclusive role in the development of undifferentiated cell clones which lead to metamorphosis of C.G.L. The results of a study of elective splenectomy during the chronic phase of the disease are reported. Twenty-six patients with C.G.L. underwent splenectomy during clinical remission of their disease, and there were no deaths after the operation. Twenty-one patients were alive at the time of writing, two of them eight years after splenectomy. Five cases of metamorphosis of C.G.L. to a refractory phase occurred whereas 10 would have been expected, a significant difference. After the onset of metamorphosis the quality of life was better in splenectomized than in non-splenectomized patients. These results show that splenectomy is a reasonable and safe procedure in C.G.L., and its apparently beneficial effects on prognosis justify a larger controlled clinical trial.


Serum ferritin in acute leukaemia at presentation and during remission. In patients with acute myeloblastic leukaemia the mean serum ferritin concentration showed a twenty-five-fold increase compared with normal people, and in children with acute lymphoblastic leukaemia (A.L.L.) there was a thirteen-fold increase. The high concentration of circulating ferritin seemed to be related to increased synthesis by leukaemic cells. The return of serum concentrations to normal in A.L.L. patients after successful chemotherapy suggested that ferritin concentration may be a useful index of active disease and may help in prognosis.