Total body potassium and long-term treatment with amiloride HCL and/or hydrochlorothiazide. The potassium sparing effect of 5 mg of amiloride (A) given either alone, or in combination with 50 mg of hydrochlorothiazide (HCTH) was evaluated in 23 patients with essential hypertension on a daily diet containing 70 mEq of K and 130 mEq of Na. Two studies were carried out. In the first, patients received HCTH alone (2 months) followed by A alone (2 months) and the two combined (6 months). The results of this study demonstrate that A is capable of correcting and preventing the loss of serum and total body potassium (TBK) and of reducing the increase of serum uric acid induced by HCTH. In the second study, each patient received from the beginning A + HCTH for 12 months; no statistically significant changes for serum and total body potassium and for serum uric acid appeared in any patient after six and twelve months. This study proves that A is capable of clinical potassium sparing effect in hypertensives and that this effect is a long lasting one.


Comparison of hemodynamic effects induced by pentaformilgitoxin and deslanoside in patients with heart failure. The effect of pentaformilgitoxin and deslanoside on heart rate, blood pressure and cardiac output was compared in six patients with heart failure. Pentaformilgitoxin caused an increase of cardiac output from 3361 ml/min to 4183 ml/min (p less than 0.01). Deslanoside induced a non significant increase of cardiac output from 3617 to 3848 ml/min. Heart rate decreased significantly by both drugs: the reduction was greater after deslanoside (from 93.7 to 77.5 beats/min) than after pentaformilgitoxin (from 92 to 85 beats/min). Both drugs caused a comparable increase in stroke volume.


Absorption of sustained-release and plain papaverine in man. The concentrations of papaverine in the plasma of healthy volunteers were determined by a GLC-method both after single and repeated oral doses of plain and sustained-release drug formulation. In both experiments the AUC-value after the sustained-release drug form was significantly lower than after the plain papaverine and no maintenance of plasma levels for 12 hours after the sustained-release drug form was observed. Our work demonstrates that the systemic availability or papaverine can be markedly affected by product formulation.


Effects of metoprolol and propranolol on lipid metabolism. Treatment of five hypertriglyceridemic and one normolipemic patients with propranolol, a non-selective beta-blocking agent, and metoprolol, which is generally considered to be a cardioselective beta-adrenoceptor antagonist, was observed to produce a further elevation in their triglyceride levels. The subjects were followed for 20 weeks, during which they received propranolol for eight weeks, a placebo for four weeks and metoprolol for eight weeks in a crossover design. The analysis suggested that the increase in triglyceride levels was less pronounced with the more cardioselective agent. Moreover, alpha-cholesterol decreased significantly after propranolol but remained constant while on metoprolol. Both drugs decreased beta-cholesterol whereas chylo- and pre- beta-cholesterol increased, particularly with propranolol. Considering the contradictory evidence regarding the clinical importance of chronic elevation of plasma triglyceride and decreased alpha- und beta-cholesterol concentrations, it is suggested that a cardioselective drug would be presently preferable in hyperlipidemic subjects.


Monitoring adverse drug reactions-the problem of integration of heterogeneous data. Effective systems for a meaningful integration and interpretation of data of heterogeneous origin are essential for successful monitoring of adverse drug reactions internationally or in multicenter programs. Particular difficulties are encountered in the area of suspected drug adverse reactions and in the area of drugs. Both problem areas are discussed in the paper.


The pharmacokinetics of the oral cephalosporins cefaclor, cephradine and cephalexin. The pharmacokinetics of the oral cephalosporins cefaclor, cephradine, and cephalexin were examined following single 500 mg oral doses to fasted, healthy volunteers. Absorption of the three compounds was rapid following a brief lag period and peak serum levels were obtained in 1-1.5 hours. Serum levels of cefaclor tended to be lower than those of cephradine and cephalexin during the 2-5 hour postdosing period and cefaclor was eliminated more rapidly than other cephalosporins from serum. No difference was observed in the overall bioavailability of the three antibiotics based on comparable FD/V values. Urine levels of the three cephalosporins greatly exceeded the minimum inhibitory concentrations of susceptible organisms during 0-6 hours postdosing, but were considerably reduced during the 6-12 hour collection period. Total urinary recovery of antibiotic activity accounted for almost 90 percent of dosed cephradine and cephalexin compared to 55 percent of dosed cefaclor. Lower serum levels and reduced urinary recovery of intact cefaclor are probably due primarily to its chemical instability. The reduced levels of cefaclor may be compensated for therapeutically by its greater in vitro antibacterial activity.


Spectrophotometric assay of antipyrine in plasma: a reevaluation. The linearity, sensitivity, and replicability of the spectrophotometric antipyrine assay were reevaluated. Standard curves are always linear through concentrations of at least 50 microgram/ml, whether prepared in water, dilute acid, or plasma. Sensitivity limits are 1 to 2 microgram of antipyrine per ml of plasma in healthy individuals. Within-day coefficients of variation for identical samples ranged from 12.3% at 2 microgram/ml to 1.2% at 50 microgram/ml. Identical samples assayed two years apart deviated by a mean of 3.8%, indicating high between-day replicability as well as stability during prolonged storage at -20 degrees C. Thus the spectrophotometric assay for antipyrine is suitable for most clinical pharmacokinetic studies.


Side effects of antihypertensive drugs. Incidence and methods of collection. A prospective study has been carried out in two groups of hypertensive patients (482 inpatients followed during 2-3 weeks; 120 outpatients followed for 18 months) to evaluate the prevalence of side effects (SE) induced by antihypertensive drugs in current use. Only SE of definite or probable type as operatively defined were taken into consideration. SE were collected in different ways for inpatients and outpatients. Among 120 outpatients, 30 patients were randomly selected for cross over of placebo and drugs. Definite or probable SE were recorded in 236 (48.9%) of 482 patients: the prevalence of SE was below 20% both in single and multiple drug therapy. A prevalence greater than 20% was recorded in the outpatients. The placebo treatment demonstrated that many SE are not related to drug administration.


Pharmacokinetics of cefamandole in patients undergoing hemodialysis. The pharmacokinetics of Cefamandole was studied in 17 patients with terminal renal impairment, 10 of which were undergoing sessions of hemodialysis while 7 were in the period between dialysis sessions. An open two-compartment kinetic model was used to describe the bi-phasic decrease of the plasma concentrations of Cefamandole thus establishing the amounts of the antibiotic in the peripheral and central compartments together with the amount eliminated. All patients received an i.v. bolus injections of 15 mg/kg body weight. During the hemodialysis sessions, the pharmacokinetic parameters of Cefamandole were the following: alpha = 5.006 hr-1 beta = 0.182 hr-1 K12 = 2.598 hr-1 K21 = 2.147 hr-1 K13 = 0.441 hr-1 Vc = 5.700 l Vp = 6.190 l Vdss = 11.94 l It may be seen that there is a decrease in the overall elimination constant compared with that obtained during the periods between the dialysis sessions. A dosage regimen of multiple doses is established as a function of the pharmacokinetic parameters of the antibiotic for patients with terminal renal impairment undergoing periodic sessions of hemodialysis.


Tricho-rhino-phalangeal syndrome.

Tricho-rhino-phalangeal syndrome. The major characteristics of tricho-rhino-phalangeal syndrome (TRPS) include shortened and deviated digits, a typical facies with a pear-shaped nose, a long philtrum and slow-growing, fine, sparse hair. Cone-shaped digital epiphyses are seen on x-ray. A few patients with TRPS are mentally retarded. Associated endocrine abnormalities have been reported. Autosomal dominant and recessive patterns of inheritance have been described with most cases showing a dominant mode of inheritance.


Effect of frequent sun exposure on bacterial colonization of skin. The bacteria colonizing the surface of the skin of a group of frequent sunbathers and a group of infrequent sunbathers were surveyed. Frequent sunbathing does not greatly affect the total number of organisms on the skin, but does tend to increase the proportion of bacteria containing carotenoid pigments.


The treatment of Darier's disease: a comparison of superficial x-ray and Grenz ray therapy. Radiation therapy of Darier's disease with both conventional x-rays and Grenz rays has been advocated in the past. A comparison of the effects of x-rays and Grenz rays in a typical case of Darier's disease showed some improvement with both qualities of ionizing radiation. The effects of x-rays were superior to those of Grenz rays with improvement of more rapid onset and longer duration. However, spontaneous improvement noted in both treated and untreated areas demonstrates the difficulty in evaluating the benefits of ionizing radiation on Darier's disease. The authors do not recommend the use of radiation therapy in Darier's disease except in cases where a temporary anti-inflammatory effect is desired.


Main puteri: an indigenous Kelantanese form of psychotherapy. The permainan puteri (usually abbreviated to main puteri) is an indigenous Kelantanese healing ceremony in which the bomoh (traditional medicine-man), the sick individual and other participants become spirit-medium through whom puteri (spirits) are able to enact a permainan ('play'). It has been successfully used as a psychotherapy for depression. The bomoh assisted by his minduk (master of spirits) and a troupe of musicians, is able to provide a conceptual framework around which the sick individual can organize his vague, mysterious and chaotic symptoms so that they become comprehensible and orderly. At the same time the bomoh is able to draw the sick individual out of his state of morbid self-absorption and heighten his feelings of self-worth. The involvement of his family, relatives and friends tends to enhance group solidarity and reintegrate the sick individual into his immediate social group.


Locus of control and symptoms of psychological distress among Chinese-Americans. A sample of Chinese-Americans in the District of Columbia was drawn to examine the relationship between the locus of control, the personality factor, and two indices of symptoms of psychological distress. The findings indicated that the externals scored higher on symptomatology than did the internals. A multivariate analysis further compared the predictive utility of locus of control with other determinants of psychiatric symptoms, i.e., sex, marital status, SES, kinship and friendship tie, and amount of life change. The evidence showed that locus of control is an important determinant of Chinese-Americans' symptomatology. It accounted for a greater proportion of the variance in the two indices of psychological distress than did the other independent variables.


Social attempted suicide: young women in two contrasting areas. The study compares attempted suicide data among young women of two ethnic groups resident in native West Indian and immigrant Birmingham environments. Although African rates were higher than East Indian ones, the three-fold increase in the immigrant population was unrelated to ethnic origin. This was also true regarding clinical data, patients using psychotropic tablets and giving similar reasons for attempting suicide. Formal psychiatric diagnoses were, however, less frequently made in Birmingham where patients preferred analgesic tablets to the domestic agents used instead by the West Indian population. The aetiological significant of sociocultural factors is discussed.


Plastic surgery in hydronephrosis (Indications and follow-up. Isotope nephrographic studies). Surgical interventions for the reconstruction of the renal pelvis were performed in 108 cases between 1962 and 1974. On follow-up, 3 to 6 months after operation the results were found good or satisfactory in 54 cases (50%). Isotope nephrography revealed a good or satisfactory fall of the curve in the excretion phase in 49 out of the 54 cases (94%), distinct retention curves having been found in the remaining 6%. In 35% of these cases isotope nephrography showed a far more complete urinary drainage than it had been assumed on the ground of radiography. In 63% of the cases the results of the two diagnostic methods were congruent.


Extraction of ureteral calculi with the Dormia basket. The Dormia basket was successfully used for stone extraction on 260 occasions, the original technique having been slightly modified and the indications for instrumental techniques substantially extended. The results are analysed primarily under the aspect of complications. These were of minor severity in 69 cases (26.4%) and of major severity in 14 cases (5.38%). Instrumental stone extraction offers the best chances if the stone is located in the distal third of the ureter and is not larger than 10 mm. The possible complications inherent even in this procedure emphasize the importance of a flexible therapy in renal calculosis in accordance with the individual situation.


Anatomical basis of radiodiagnosis of the adrenal gland. Studies on 220 human adrenal glands were carried out microscopically, microangiographically and by direct dissection following preliminary filling of the vessels with injection masses. The position, size and shape of the adrenals, as well as their intrinsic and extrinsic arterial and venous vasculature were assessed. In the present work attention was directed mainly to the venous architecture. The understanding of venous pattern is of considerable importance to those who perform and evaluate adrenophlebography. The latter examination represents the most useful method of radiological assessment of adrenal glands.


Blood coagulation and hereditary nephritis. Nineteen patients with hereditary nephritis - members of six families - were studied for haemostasis on 11 occasions by the use of four capillary tests, 14 different blood coagulation tests and two different platelet function tests. Systemic capillaropathy was demonstrable in 8 out of 15 cases of the non-uraemic, and in all the 5 cases of the uraemic group. No completely normal blood coagulation was found in any of the cases and the coagulation disorders were never of exclusively haemorrhagic pattern. On the evidence of the complex studies, hypercoagulability as well as hyper-hypocoagulability were found in the uraemic and non-uraemic groups alike. Reduction in plasma fibrinolytic activity, elevation of the fibrinogen level and a shift of the thrombelastogram in the direction of thrombosis were demonstrable in the majority of the cases.


Serum and ultradiafiltrate middle molecules in hemodialysed patients. The gel filtration technique was used for the fractionation of middle molecular substances (MMS) in plasma from conservatively treated patients, from dialysed patients with renal failure and in the ultradiafiltrate from dialysed ones. The following observations were made: 1. MMS accumulate in the plasma of conservatively treated patients in chronic renal failure. 2. The accumulation of MMS in dialysed patients is even higher. 3. The elimination of the most important MMS in the ultradiafiltrate is excellent. 4. It is concluded that hemofiltration and ultradiafiltration are indicated also for the removal of MMS, namely in the case of clinical complications which cause a further accumulation of MMS.


Home peritoneal dialysis (two year's experience). Twenty patients on home peritoneal dialysis were studied during two years. The patients dialysed 4--5 times a week, using an average of 78 l dialysis fluid. The dialysis equipment used was either a simplified delivery system or a fully automatic dialysis machine. Despite clinical improvement, serum urea and serum creatinine levels were the same after 12 months of therapy as before. The patients' weight and serum albumin levels remained constant. Only 1 patient developed hyperparathyroidism, otherwise serum calcium levels ranged from normal to subnormal. Fifteen patients did not require blood transfusions. Twenty episodes of peritonitis occurred, an incidence of 0.58%. All patients carried out dialysis themselves without assistance. Three were working full-time, and 5 were able to look after their homes. The rest were able to take care of themselves. Four patients died from causes unrelated to peritoneal dialysis. In selected patients this mode of treatment provides an acceptable alternative to haemodialysis.


Spinal epidural abscess in patients on maintenance haemodialysis (a presentation of two cases). Two cases of spinal epidural abscess in patients on maintenance haemodialysis, one of them secondary to infection in an arteriovenous fistula, are described. Both cases presented the typical symptoms known from the literature, but were diagnosed too late to prevent neurological sequelae. The condition is rare, but dialysis patients are to be considered a risk group because of their reduced immunocapacity and increased hazard of infection, especially fistula and shunt infections. Awareness of this, and knowledge of its early symptoms are required for timely neurosurgical intervention and thus prevention of irreversible spinal cord damage.


Observations with the "Bi-flo" cannula (continuous, single-needle haemodialysis). Observations with the double-lumen "Bi-flo" cannula in chronic intermittent haemodialysis are reported. On the evidence of urea and creatinine measurements, recirculation of blood corresponds to 7.9 and 6.1 per cent, respectively. In comparison with double-needle or single-needle dialysis, use of the double-lumen cannula does not affect the efficiency of dialysis to any notable degree. The advantages and shortcomings of the "Bi-flo" cannula with regard to the technique of dialysis are summed up.


Accelerated atherosclerosis during maintenance hemodialysis: detection from chest radiographs. Evidence of accelerated atherosclerosis was studied from chest radiographs of 26 patients on maintenance hemodialysis. The aortic knob was observed for presence of and increase in calcified plaques. At the initiation of hemodialysis, the degree of aortic calcification was no different from that seen in the control group. After periods ranging from one and a half to eight years, the patients on hemodialysis showed a significantly greater amount of aortic calcification and a significantly higher rate of calcification. The degree of calcification correlated with the severity of cardiovascular disease as determined clinically. For patients on maintenance hemodialysis, close scrutiny of serial chest-radiographs may help to identify those who are at greater risk for life-threatening cardiovascular disease.


1979 Memorial Award Paper. Comparison of exercise right ventricular performance in chronic obstructive pulmonary disease and coronary artery disease: noninvasive assessment by quantitative radionuclide angiocardiography. The right ventricular (RV) response to upright bicycle exercise was assessed in 16 patients with chronic obstructive pulmonary disease (COPD), in 23 patients with coronary artery disease (CAD), and in 19 normal control subjects. Right ventricular (RV) and left ventricular (LV) ejection fractions were determined noninvasively using first-pass quantitative radionuclide angiocardiography, a technique well suited for simultaneous assessment of RV and LV systolic performance. The factors limiting exercise in COPD and CAD are distinctly different, and therefore patients with COPD were studied by means of a single-stage submaximal exercise test, while patients with CAD were studied by means of a graded maximal test. The normal response to exercise, irrespective of exercise protocol, was at least a 5% increase in RV and LV ejection fractions. In 12 of 16 patients with COPD, RV ejection fraction either decreased or remained the same with exercise (abnormal exercise RV reserve). Left ventricular exercise reserve was abnormal only in five patients, probably due to occult CAD. Isolated abnormal exercise RV reserve was present in nine patients. The severity of ventilatory impairment and resting arterial hypoxemia were major determinants of abnormal exercise RV reserve in patients with COPD. In 12 or 23 patients with CAD, RV ejection fraction either decreased or remained the same with exercise (abnormal exercise RV reserve). Left ventricular reserve was abnormal in 18 of 23 patients; RV exercise reserve was abnormal only in CAD patients with concomitant abnormal LV reserve. The presence of proximal right coronary artery stenosis (the major blood supply to the RV) was not a significant determinant of the RV response to exercise in patients with CAD. These data suggest that abnormal exercise RV reserve occurs frequently both in COPD and CAD patients. In COPD the predominant hemodynamic abnormality involves performance of the RV, while in CAD the predominant abnormality involves the LV. The common factor modulating RV exercise performance in both diseases appears to be altered RV afterload.


Absence of a persistent nephrogram in experimental acute renal failure. Studies showing diminished cortical perfusion and reduced glomerular filtration in acute renal failure are apparently at odds with reports of a persistent nephrogram during urography in this disease. We followed the progression of nephrograms in eight dehydrated normal rats, in seven dehydrated rats treated with 12 mg/kg of mercuric chloride (nephrotoxic acute renal failure), and in nine dehydrated rats receiving 5 g/kg of IM-glycerol (myoglobinuric acute renal failure). To assess the capacity of our technique to identify a persistent, dense nephrogram, hemorrhagic hypotension (mean arterial pressure, 55-70 mm Hg) was induced in three rats. All rats showed nephrograms on magnification radiographs 1 minute following the injection of 1 cc/lb of sodium diatrizoate. Duplicate coded readings showed no prolongation of nephrograms in ARF-affected animals. Only the hypotensive rats manifested nephrograms on 2-hour radiographs. Some differing characteristics of nephrograms among the groups are explainable on the basis of differences in renal blood flow, as determined in separate experiments. Our findings would favor a preglomerular mechanism as the cause of oliguria in acute renal failure.


Direct and indirect effects of docosanol (IK.2), the active principle in Tadenan, on the rat prostate. To better understand the mode of action of Tadenan, a drug used in the treatment of benign prostatic hyperplasia, the effect of its active principle docosanol, IK.2, was investigated in rats. IK.2 had no effects on the weight and histologic appearance of the prostate in intact rats but increased the RNA/DNA quotient in the ventral prostate. The plasma concentrations of luteinizing hormone and testosterone were reduced. In orchiectomized animals IK.2 increased the weight of the prostate and the adrenals. In adrenalectomized, orchiectomized animals IK.2 did not increase prostatic weight but on the contrary caused a further weight reduction. IK.2 had a thymolytic effect in intact rats but not in adrenalectomized rats in which the thymus weight was increased. The results indicate that IK.2 increases adrenal steroid secretion. The supposedly higher concentration of adrenal androgens causes a stimulation of the prostate most easily discernible in orchiectomized animals. The further weight reduction of the ventral prostate in orchiectomized, adrenalectomized animals, and the increased thymus weight in adrenalectomized animals after IK.2 administration may suggest that IK.2 has effects other than the stimulatory effect on the adrenals.


Comparison of hepatic VX2-carcinomas after intra-arterial, intraportal and intraparenchymal tumor cell injection. An angiographic and computed tomographic study in the rabbit. Hepatic VX2-carcinomas were produced in 45 rabbits by injection of approximately 25 x 10(6) tumor cells into the proper hepatic artery, the superior mesenteric vein, or directly into the liver parenchyma. With the intra-arterial and intraportal approaches, survival times (12 +/- 4 and 13 +/- 5 days, respectively), radiographic and autopsy findings revealing a liver with diffuse tumor involvement were very similar. With intraparenchymal tumor cell injection, survival time was significantly longer (18 +/- 14 days) and the hepatic VX2-carcinoma always localized. The tumor appeared hypervascular on angiography and hypodense on computed tography (CT). After intravenous injection of diatrizoate, the attenuation in the tumor increased less than in the surrounding liver so the lesion became relatively less dense and more easily recognized on CT-scans. The apparent discrepancy between angiographic and contrast enhanced CT findings can be explained with the difference in blood supply of hepatic tumors and normal liver parenchyma.


A transplantable tumor of the urinary bladder in rabbits. The latency period for induction of urinary bladder carcinoma is at least 2 years in animals that can be followed endoscopically. We studied the possibility of producing a model of malignant urniary bladder tumor in rabbits in less time by transplanting tumor cells. Each of 80 male mixed bred rabbits received 1 ml of tumor cell suspension of Brown-Pearce carcinoma. Transplantation was done subcutaneously, intratesticularly, transurethrally, or aftet cystotomy via injection into the bladder submucosa. Within 2 to 3 weeks malignant tumor growth in the bladder could be shown. Superficial scarification of the mucosa, performed at the same time as transplantation, led to exulceration of the tumor into the bladder lumen. Tumor incidence reached a 80 to 95 per cent level. Metastases in these animals were analogous to human urothelial bladder carcinoma. This malignant tumor model seems especially suitable to study new methods of transurethral therapy for cancer of the urinary bladder.


Tunica vaginalis autografting for Peyronie's disease: an experimental study. Groups of dogs were studied at varied intervals after autografting of tunica vaginalis from the testes to cover excised patches of tunica albuginea of the penis. Postoperative cavernosography revealed neither ballooning nor chordee. Histologically, the grafts were well accepted and uniformly merged with the neighboring collagen tissues at 6 months. We propose that tunica vaginalis would be ideally suitable for autografting to the penis after excision of Peyronie's plaques.


Emptying the gallbladder prior to intravenous cholangiography: effect on gallbladder visualization. Experiments were done to test the hypothesis that emptying the gallbladder prior to intravenous cholangiography (IVC) would result in earler and better opacification of the gallbladder. Five dogs were studied on two separate days in a crossover experiment. Each dog had a standard IVC (15-minute infusion of meglumine iodipamide) 2.5 cc/kg of following a 14-16-hour fasting period. On one of the days, 0.3 mcg/kg of Ceruletide was intramuscularly administered to each dog 30 to 45 minutes prior to the iodipamide infusion. Films obtained at the end of infusion and at 20, 40, 60, and 90 minutes were evaluated independently by three radiologists. The results indicate that pretreatment with Ceruletide produces a significant (p less than 0.05) improvement in the quality of gallbladder opacification during the first 90 minutes following iodipamide infusion. We conclude that earlier and better opacification of the gallbladder during IVC can be obtained by prior emptying of the gallbladder with a cholecystokinetic agent.


Computed tomography of experimental acute renal ischemia. The potential role of computed tomography (CT) in the detection of acute renal ischemia was assessed in nine mongrel dogs. Ischemia was produced by inflation of a balloon catheter in the main renal artery, with scans performed before, during, and after a 60-minute period of ischemia. A small but consistent increase in the attenuation value of ischemic renal parenchyma was observed. When intravenous contrast material was given, the ischemic kidney was markedly less enhanced than the contralateral, nonischemic kidney. By using the contralateral kidney for comparison, the ischemic kidney could be identified with or without the use of a contrast agent. Although calculations of mean pixel values were necessary when a contrast agent was not injected, the abnormal kidney could be easily recognized from the CT images themselves when intravenous contrast material was given. Because of the consistency with which the abnormalities were observed, we recommend a clinical trial of CT in suspected acute renal ischemia.


Lymph node reactivity to experimental bladder tumor in preimmunized animals as measured by two parameter flow cytometry. Lymph node lymphocyte reaction to an explanted, transplantable mouse bladder tumor (MBT-2) was investigated by flow cytometry in animals previously immunized with irradiated tumor cells. Nodal lymphocytes in representative samples from four different lymph node sites were differentially stained for DNA and RNA with the fluorescent dye acridine orange; cell proliferation and the increase in RNA content were measured. Immunization abrogated tumor growth; one immunization reduced tumor take to 25 per cent of the animals, and two immunizations to 14 per cent. Lymphocyte reactivity to the tumor was reflected both by an increase of DNA synthesizing cells and by diploid cells with high RNA. The latter response was more pronounced and thus the more sensitive parameter for measuring immunologic lymph node reactivity. The juxtatumoral node displayed the most pronounced reactivity, but all node sites showed some degree of reaction.


Prostatic osteoblastic factor.

Prostatic osteoblastic factor. Cell cultures of fetal rat osteoblasts and organ cultures of fetal rat calvaria were used to study the effects of extracts of prostatic tissue on bone cell growth. Extracts of bening prostatic hyperplasia, but not an undifferentiated prostatic carcinoma, stimulated the incorporation of 3H-thymidine and 14C-proline into fetal rat osteoblasts, calvaria, and skin fibroblasts. Extracts of well-differentiated prostatic cancer and normal postpubertal prostate also stimulated 3H-thymidine incorporation by fibroblasts. These findings support the hypothesis that a potentially unique factor found in prostatic tissue induces the osteoblastic response of bone to metastatic prostatic cancer.


Histologic study of the early events in oxalate induced intranephronic calculosis. The early phases of calcium oxalate crystal formation in rat kidneys after intraperitoneal challenge with sodium oxalate were examined. From the results we conclude that the crystals are formed intraluminally in the proximal tubules of the renal cortex. The size, number, and distribution of calcium oxalate particles depend on the amount of sodium oxalate injected and the time interval after its injection. Tubular necrosis and dilation were evident after administration of higher doses of sodium oxalate. The papillary tip and corticomedullary junction were the preferential sites for crystal localization after longer periods of injections of higher doses of sodium oxalate.


Therapeutic manipulation of Nb rat prostatic adenocarcinomas: chemotherapeutic evaluation of autonomous tumors. Nb rat autonomous prostatic adenocarcinomas were transplanted into several groups of synergeneic Nb rats. Chemotherapy using 5-fluorouracil, methotrexate, Adriamycin, and cyclophosphamide was evaluated. Significance was seen with the use of these agents with varying doses. Cyclophosphamide and 5-fluorouracil treated animals had complete tumor regression whereas Adriamycin and methotrexate treated animals had cessation of tumor volume increase in some groups after chemotherapy; however, neither agent causes complete tumor regression.


Evidence for transventricular absorption in the hydrocephalic dog. Hydrocephalus was induced in 10 mongrel dogs by injection of a silastic mixture into the basal cisterns. The posterior part of the left lateral ventricle was isolated from the remainder of the ventricular system by introducing Pantopaque into both lateral ventricles and the third ventricle with the animals in prone positions. Labeled albumin injected into the posterior part of the left lateral ventricle was shown to enter the blood stream before it was shown in the fourth ventricle or vallecula. This provides qualitative evidence of transventricular absorption.


Entrance of water into the bladder during sitz bath in elderly catheterized and noncatheterized females. This study was conducted to determine if water enters the bladders of elderly catheterized and noncatheterized women during a sitz bath. Subjects were placed in a sitz bath containing fluorescein for 20 min. Serial urine specimens were collected at varying intervals up to 1 hr after the bath and compared to urine samples collected before the bath. No significant difference in fluorescence was found between the urine specimens in any subject which provides strong evidence that there is no detectable leakage in either group. Under the conditions of this experiment, the periurethral space was tightly sealed and did not permit passage of water.


The induction of urologic malformations. Understanding the relationship of renal ectopia and congenital scoliosis. The normally straight caudal trunk of the 3-day-old chick embryo was surgically deflected, constricted, or pierced using fine steel instruments. The delayed effects of these injuries were evaluated anatomically by performing microdissections of the genitourinary systems of the chicks surviving these operations. Eighty-six of 181 survivors of 347 operations showed malformations. Renal ectopia appeared with scoliosis 10 times more often than it appeared by itself (P less than 0.01). Eighty-six chicks survived 102 control operations; only two had a urinary anomaly (P less than 0.01). The paring of renal ectopia with scoliosis may be attributable to an isolated spinal defect that precludes complete renal ascent, an injury to the anlages of both the spine and kidney, or a genetic abnormality that affects both anlages.


Urinary ionic calcium and binding sites in normocalciuric idiopathic calcium urolithiasis. Total bindings sites, ionic calcium, and other crystalloids were measured in 41 normocalciuric patients with idopathic calcium urolithiasis and in 34 normocalciuric healthy subjects. Twenty-six stoneformers were treated with thiazide to determine the effect of the drug. The average total calcium excretion was higher in patients than in controls and patients receiving therapy. The fraction of total calcium ionized was higher in patients than in normal subjects; thiazide therapy did not seem to cause a decrease in this fraction in stoneformers. The 24-hr excretion of ionic calcium was equal in normal subjects and in patients receiving thiazide therapy, but was higher in patients without therapy. Normal subjects have a significantly higher concentration and total excretion of magnesium and citrate. Apparent binding constants for calcium were significantly different for all three groups. The concentration of total binding sites was lower in patients with and without therapy than in normal subjects; this was partly attributed to the higher urinary concentration of citrate in normal subjects. However, citrate accounted for less than 20 per cent of the total bindings sites in urine. There was no significant differential 24-hr excretion of binding sites. Measurement of the specific excreting pattern of binding sites on proteins, peptides, nucleotides, and amino acid may emerge with a characteristic pattern in patients with urolithiasis.


Obstruction induced changes in longitudinal force-length relations of rabbit ureter. The force-length relationships of rabbit ureters subjected to 2 weeks of obstruction were compared with those of normal rabbit ureters. After 2 weeks of ureteral obstruction, length increased by 24 per cent, diameter by 100 per cent, and cross-sectional muscle area by 248 per cent. At the in vivo length, the resting forces of the control and obstructed ureters were similar. With muscle lengthening, resting force increased. For the same per cent increase over in vivo length, both control and obstructed ureters exhibited the same resting forces. At the in vivo length, the obstructed ureter developed less active force and less stress in response to a suprathreshold electrical stimulus than did control ureters. At the length of maximum force development (1.4 times the in vivo length for both control and obstructed ureters), the force developed by the obstructed ureter was 3.5 times greater than that of the control, yielding a 250 per cent increase over control levels. Thus, active stress (force/unit area) was unchanged after 2 weeks of obstruction.


Effect of oxipurinol and allopurinol riboside on whewellite crystallization: in vitro and in vivo observations. Solubility measurements, seeded crystal growth kinetics, solution depletion adsorption studies, nucleation observations, zeta potential measurements, and measurements of in vivo intrarenal crystallization all failed to show that either oxipurinol or allopurinol riboside interacts with calcium, oxalate, or whewellite (CaC2O4.H2O) at concentrations expected in therapeutic situations. We conclude that at therapeutically expected concentrations, oxipurinol and allopurinol riboside do not affect crystallization of calcium oxalate.


Experimental model of calcium-containing renal stone formation in a rabbit. An experimental method of calcium-containing renal stone formation was devised using a rabbit on normal diet. The stone formation was induced unilaterally, massively, and rapidly in an extremely high incidence by temporary obstruction of the upper urinary tract, but not by permanent obstruction. The contralateral kidney was used as a control. The initial stone formation was not solid but muddy and seemed to occur through massive crystal aggregation, resulting in concretion within a few weeks. We strongly suspect that the mechanism of this stone formation is crystal aggregation induced by temporary obstruction of the kidney. This animal model should contribute to the investigation of the process of crystal aggregation which is considered to be the most important factor in idiopathic calcium stone formation in man.


Reticuloendothelial phagocytosis in patients with chronic renal failure. Using the clearance of microaggregated iodinated human serum albumin, the phagocytic function of the reticuloendothelial system was tested in 73 patients with chronic renal failure and in 30 normal subjects. Of the patients with chronic renal failure 26 were undergoing hemodialysis. Increased reticuloendothelial phagocytosis was shown in all patients with chronic renal failure. No correlation was shown between hematocrit-creatinine and T 1/2 (min) in patients with chronic renal failure.


Release of prostaglandins into the pelvic venous blood of dogs in response to vesical distension and pelvic nerve stimulation. Prostaglandin release into the pelvic venous blood in response to vesical distension and pelvic nerve stimulation was studied in anesthetized female nonpregnant dogs. The change in the prostaglandin content of the plasma at sequential physiologic points in the voiding cycle and with pelvic nerve stimulation was measured using a radioimmunoassay technique. A significant liberation of PGE and PGF2 alpha was observed during maximal bladder distension and after micturition. The increased levels returned to near control levels when measured 5 min after bladder evacuation. After pelvic nerve stimulation, PGF2 alpha was also significantly released. The source, mechanism, and functional significance of prostaglandin release during bladder activity are discussed.


Ultrastructural surface alterations of guinea pig seminal vesicle epithelium during postnatal development and after castration. We have designed a topographic anatomic study using scanning electron microscopy to define surface changes in seminal vesicle epithelium during normal development and after bilateral orchiectomy. Scanning electron microscopy of seminal vesicles from 1-day, 4-week, and 3-month-old intact animals revealed a microvilli-studded luminal epithelial surface with high polyhedral cell profiles extending into the luminal area. Deep furrows outlined all intercellular junctions. Microvilli profiles ranged from short knob-like projections located preferentially along cell margins in 1-day-old animals to 1 mu-long microvilli wih random distribution in mature animals. The most striking finding was that the seminal vesicle epithelium in castrated animals did not revert to the prepubertal state. Rather, cell apices receded from the luminal surface to a level below that of the cell borders and microvilli generally remained somewhat longer in the castrate than in the prepubertal animal. These morphologic findings suggest that the seminal vesicle epithelium in the prepubertal animal and the long-term castrate are quite different.


Crystallization studies in a urothelial-lined living test tube (the catheterized female rat bladder). I. Calcium oxalate crystal adhesion to the chemically injured rat bladder. We developed an in vivo technique to study crystallization in a urothelial-lined "living test tube" by employing the catheterized female rat bladder. Calcium oxalate crystals adherent to the bladder urothelium were distinguished from free or intraluminal crystals. Chemical injuries of the urothelium induced by either 0.1 N HCL or 5 per cent Triton X 100 in saline resulted in marked calcium oxalate crystal adhesion to the injured urothelium. Control bladders without urothelial injury remained free of adherent crystals but formed large numbers of small free crystals relatively uniform in size. Histologic and fresh microscopic evaluations of urothelial injury and crystal adhesion are presented.


An entomopoxvirus from Oncopera alboguttata (Lepidoptera: Hepialidae) in Australia. A new entomopoxvirus has been isolated from field-collected larvae of Oncopera alboguttata at Ebor, New South Wales, Australia. The ovoid proteinaceous virus-containing bodies measured about 8 x 6 microns and contained up to about 17 centrally-embedded virus-free spindles and up to about 180 occluded virus particles. The virus particle had a beaded outer membrane and measured about 390 x 270 x 230 nm. The particle contained a single lateral body and a unilaterally concave core which in longitudinal section measured 320 x 80 nm. Dissolution of inclusion body and spindle protein to release virus particles occurred in carbonate/thioglycollate buffer at pH greater than 12.0. It is postulated that this virus has recently evolved from similar viruses in soil inhabiting coleopteran larvae.


Rhabdoviridae. Report of the Rhabdovirus Study Group, International Committee on Taxonomy of Viruses. The family Rhabdoviridae comprises approximately 75 viruses infecting vertebrates, invertebrates and plants. The main characteristics of the member viruses are: (i) the viruses infecting vertebrates and invertebrates are bullet-shaped and the viruses infecting plants are usually bacilliform; (ii) the viruses have particle lengths varying from 130 to 380 nm and widths varying from 60 to 95 nm; (iii) the viruses possess unit-membrane envelopes from which protrude spikes 5 to 10 nm long; (iv) the viruses have precisely coiled helical nuecleocapsids with a diameter of approx. 50 nm; (v) most of the viruses which have been studied contain 5 proteins; the prototype, vesicular stomatitis virus, contains proteins designated L (large), G (glycoprotein), N (nucleoprotein), NS (nonstructural) and M (matrix); N or NS is phosphorylated in most members which have been studied; (vi) the viruses contain single-stranded RNA which is transcribed into several messenger RNA species with sizes corresponding to the structural proteins; (vii) the nucleocapsid contains the RNA-dependent RNA polymerase and is infectious; and (viii) many of the viruses produce morphologically distinct defective-interfering (T) particles.


The effect of membrane-active agents on Sindbis virus morphogenesis. In chicken cells infected by Sindbis virus and exposed to a variety of membrane-active compounds, virus release was inhibited. In infected cells exposed to antiserum directed against the virion glycoproteins E1 or E2, retinol, cortisone, Pb++ or insulin, the processing of two Sindbis virus precursor polypeptides which lead to the formation of virion polypeptides was inhibited. The B-protein, which is the precursor to both envelope proteins, accumulated in cells treated by these compounds. This precursor is generally not detected in chicken cells, presumably because it is processed rapidly. The cleavage of the precursor PE2 to the envelope glycoprotein E2 was also inhibited. E2 was also absent in cells exposed to menadione or to antiserum prepared against uninfected chicken cells. Since each of the compounds tested interfered with Sindbis virus polypeptide cleavage, despite their diverse mechanisms of action, it suggests that perturbation of normal membrane fluidity can interfere with Sindbis virus budding.


A microprocessor-based aid for training autistic children. This paper describes a unique application of microprocessor technology to training autistic children. Such training presents problems in data collection and reduction. The system described is a training session monitor which accumulates data from a session. The system also generates prompt data and controls the end of a session based on five possible criteria. The accumulated data are then automatically reduced and printed. The evolution of this training session monitor and recorder is reviewed. A description of the hardware and software realization of the final system is presented. The tools and techniques used in the development of the system are discussed. Possibilities for future additional training aids are explored, and improved development tools and techniques are suggested.


Crash test dummy lower leg instrumentation for axial force and bending moment. Instrumented anthropomorphic dummy surrogates of humans have been used in automobile occupant crash protection research and development programs for many years. Lower leg instrumentation provides the safety engineer with a valuable tool for gaining otherwise unavailable insights into occupant restraint system performance. Instrumentation described in this paper constitutes an advancement of the state of the art of dummy test technology. A more comprehensive study of crash victim leg loadings is possible with only the traditional femur (upper leg) axial force transducer. Each lower leg has five electrical resistance strain gage circuits to monitor orthogonal bending moments and axial force. Stress analysis and Wheatstone bridge theories are combined in the paper to define strain gage locations and predict transducer sensitivities. Transducer fabrication and calibration precedures are also discussed.


New control algorithms via brain theory. New concepts and viewpoints are needed to develop control algorithms for large scale systems. It is hypothesized that brain functions in human beings clearly demonstrates the existence of superior techniques for controlling complex systems with multiple objectives. The theory of compacta is investigated as a basis for learning, memory, and perception.


A mathematical model of the human body in health, disease, and during treatment. This paper presents a preliminary description of a mathematical model of the human body and some details of the computer software and hardware used to study the model. The model includes many organ systems of the body and the interplay among systems. In addition to this physiological framework, a variety of diseases and therapeutic measures can be simulated. The model can be used in two different ways. In one mode, hypothetical experiments can be conducted that focus on the underlying physiological mechanisms and the complex interaction among organ systems that are essential to the maintenance of life. In a second mode, clinical encounters can be simulated in which hypothetical patients are seen, diagnosed and treated.


Control sensors for biomedical systems.

Control sensors for biomedical systems. In biomedical systems, sensors play roles ranging from off-line diagnosis to prosthetic support in continuous real-time control. This diversity is illustrated with examples from mechanical limb prostheses, fluid (bladder) control, and chemical sensing. The chemical field, least advanced but under active development, offers special promise toward future automation of the classical diagnosis-therapy control loop.


Electron microscopy in the diagnosis of head and neck tumors. Six patients with malignant head and neck tumors are shown to have required electron microscopy for accurate diagnosis. In all of these tumors, there were ultrastructural features of cytodifferentiation that were not discernible by light microscopy, such as neurosecretory granules, desmosomes, cytoplasmic processes, tonofibrils, and myofilaments. Electron microscopy is helpful in the differential diagnosis of tumors in general, but its effectiveness is particularly apparent in small-cell "undifferentiated" tumors such as neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma, undifferentiated squamous-cell carcinoma of the lymphoepithelioma type, and malignant lymphoma. It has also been helpful in the identification of amelanotic melanoma and spindle-cell carcinoma.


Wegener's granulomatosis and midline (nonhealing) "granuloma". There has been considerable controversy over the years regarding the distinctions between various disorders characterized by a necrotizing and granulomatous inflammation of the tissues of the upper respiratory tract and oral cavity. It now seems clear that if infections and other known agents can be excluded, three clinicopathologic entities remain: Wegener's granulomatosis (a systemic disease), idiopathic midline (nonhealing) granuloma, and premalignant or malignant lymphoreticular lesions. The antigenic stimulus for all three may be related but remains unidentified.


Repair of the bilateral cleft lip: a personal approach. The author presents his personal method of repairing a bilateral cleft lip, focusing on both the embryogenic factors of this condition and its anatomic-functional abnormalities. The surgical technique used enables correction in a single operation through suture of the lateral portions at the midline and elevation of the bifurcated flap of the prolabium to form the columella and the nasal floor. The deep psychological, social, and economic impact of the pathology is discussed, and the importance of a one-step surgical correction of the defect for the particular patient population at question is stressed.


Reinnervation of the paralyzed larynx: a review. Our high-speed and increasingly aggressive society, coupled with a continuing rise in necessary surgery of the neck and adjacent areas, accounts for the current increase in patients affilicted with vocal-cord paralysis. Such patients may sustain relatively little persistent loss of function (e.g., when only one cord is involved, which then regains function or becomes compensated) or considerable loss (as in cases of bilateral vocal-cord paralysis). To improve on existing methods of dealing with these problems, the author has developed and refined the nerve-muscle-pedicle technique for reinnervating paralyzed muscles. A nerve-muscle pedicle obtained from the ansa hypoglossi branch to the omohyoid muscle or another strap muscle can be used to selectively reinnervate the posterior cricoarytenoid muscle in cases of bilateral-cord paralysis, or for selective reinnervation of the lateral thyroarytenoid muscle in cases of unilateral-cord paralysis. The bilateral reinnervation technique showed a 90% success rate in 90 patients, as demonstrated by their ability to sustain reasonable day-to-day activity without needing a tracheotomy tube and without manifesting further loss of voice. The unilateral technique has yielded promising results in a limited number of carefully selected patients.


Jaw cysts: diagnosis and treatment.

Jaw cysts: diagnosis and treatment. The classification, embryology, histopathology, clinical features, and treatment of benign jaw cysts are presented. Emphasis is placed on the differentiation of benign cysts from malignant radiolucent lesions of the jaws. Preservation of adjacent teeth and over vital structures is of paramount importance in the management of jaw cysts.


The synthesis of fetal hemoglobin types in red blood cells and in BFU-E derived colonies from peripheral blood of patients with sickle cell anemia, beta+ - and delta beta-thalassemia, various forms of hereditary persistence of fetal hemoglobin, normal adults and newborn. The biosynthesis of two types of human fetal hemoglobin (Hb F), namely Hb F with G gamma chains having glycine in position 136 and Hb F with A gamma chains having alanine in position 136, was studied in blood samples and in cultures of erythroid precursors from blood of patients with different hemoglobinopathies. High pressure liquid chromatography (HPLC) was adapted to allow the separation of the methionyl-containing tryptic peptides G gamma T-15 and A gamma T-15 (which include the Gly leads to Ala polymorphism at position 136) from a digest of microquantitites of 35S-methionyl labelled Hb F. This method was sensitive enough to quantitate the relative production of the G ygamma and A gamma chains by erythroid colonies derived from cloned Burst Forming Units (bfu-e) which were cultured for 16 days on methylcellulose. The production of Hb F in these colonies was generally higher than the level of Hb F in blood except for subjects with the G gamma A gamma-HPFH heterozygosity. The G gamma to A gamma ratio in the Nb F produced in cultures of cells from G gamma delta beta-thalassemia or G gamma-HPFH heterozygotes was lower and that from A gamma-HPFH heterosygotes was higher than the ratios in the Hb F of the corresponding peripheral blood cells. Mixtures of G gamma and A gamma chains were present in cell cultures of SS patients, beta+-thalassemia homozygotes and G gamma A gamma-HPFH heterozygotes in a ratio similar to that in the Hb F of mature red cells. These data suggest that erythroblasts in BFU-E derived colonies reactivate all available gamma chain structural genes, both in cis and in trans to the abnormal determinant. Hb F biosynthesis by adult blood samples concerns primarily the G gamma chains. This was particularly striking for blood samples in which erythroblasts were absent and the biosynthesis took place in fetal reticulocytes. Thus, the F-retuculocytes in blood of A gamma-HPFH heterozygotes with about 5% Hb F of the A gamma type produced primarily Hb F with G gamma chains. Similar differences were observed for G gamma A gamma-HPFH heterozygotes and, less strinkingly, for SS patients. A satisfactory explanation for this observation has not yet been obtained.


Hemoglobin Bougardirey-Mali beta 119 (GH2) Gly replaced by Val. An electrophoretically silent variant migrating in isoelectrofocusing as Hb F. Hemoglobin Bougardirey-Mali was detected by isoelectrofocusing during a screening in a 32 years old African, a native of Mali. This abnormal Hb, representing 35% of the total, exhibited the same pI as that of Hb F. In contrast, it was indistinguishable from Hb A in all the electrophoretic systems tested, and equally by its resistance to alkaline denaturation. Structural studies have shown that the abnormality was localized on the beta chain. A fingerprint of the tryptic digest of the aminoethylated beta chain indicated the absence of the beta T12 b. The presence of an abnormal beta T12 b was suspected in the T14-15 spot, as indicated by the intensity of staining and its amino acid composition. beta T12 b was isolated by chromatography on PA 35. Its sequential analysis by manual Edman-dansyl degradation showed that glycine 119 was replaced by a valine residue. This mutation is localized in a alpha 1 beta 1 contact, which makes the molecules slightly unstable. The clinical consequences of this mutation seem to be minor; similar observations have been reported for the other Hb mutated at the same locus, i.e. Hb Fannin-Lubbock beta 119 Gly leads to Asp.


Globin chain synthesis in beta-thalassemia with normal hemoglobins A2 and F. Biosynthetic studies were performed in a patient with beta-thalassemia intermedia heterozygous for both beta-thalassemia with normal hemoglobins A2 and F and beta-thalassemia with increased Hb A2, in his both parents, one sister and one brother. In propositus the alpha/beta ratio was 1.68. In his mother with normal Hb A2, this value was 1.21. In contrast, in his father who had increased Hb A2, the alpha/beta ratio was 1.07, possibly due to combination of alpha- and beta-thalassemia. In his sister who had increased Hb A2, alpha/beta ratio was 1.57. In his brother with normal Hb A2 (2.5%) ratio was 0.6 indicating the presence of an alpha-thalassemia gene. Similar beta-thalassemic syndromes found in other countries are discussed.


The pectoralis major myocutaneous island flap for reconstruction of the head and neck. The anatomy, design, and blood supply of the pectoralis major myocutaneous island flap are described. This versatile, nondelayed flap has, for the most part, replaced the usual cutaneous flaps. Clinical examples of its use in head and neck reconstructive surgery are presented.


Radiation therapy of the oral cavity: sequelae and management, part 1. This is the first article in a two-part series dealing with the effects and manifestations in the oral cavity of radiation therapy of head and neck tumors. In this section, oral mucous membranes, taste buds, edema and trismus, diet, salivary glands, bone, periodontium, teeth, and composition of oral flora are discussed. Dental management of the dentulous patient is then approached; criteria for preradiation extraction are delineated. In the next issue of Head & Neck Surgery, the final article in this series will discuss preradiation and postradiation extractions and will elaborate on the dental management (fluoride treatments, follow-up, and restorative care) of the dentulous patient. Dental management of the edentulous patient will also be presented.


Tyrptic peptide compositions of hemoglobins from mink (Mustela vison) and hyena (Hyaenae hyaenae) and the alpha-chain of coatimundi (Nasua nasua). The amino acid composition of the tryptic peptides from hyena hemoglobin, two hemoglobins of the mink and the alpha-chain of coatimundi have been determined, allowing comparison with data previously obtained from other carnivores. The two hemoglobins of mink differ at only one amino acid residue, alpha 15, which is glycyl in one hemoblobin and aspartyl in the other.


The suboccipital approach to removal of acoustic neuromas. This article reviews the author's technique for removing acoustic neuromas by the suboccipital approach. Also discussed are various considerations regarding the selection and use of instruments for this operation. The anatomy of the internal acoustic meatus and the principles involved in facial- and cochlear-nerve preservation are described. A guide is provided for stepwise dissection of the internal acoustic meatus in the laboratory.


Rhabdomyosarcoma of the head and neck: diagnosis and management. Rhabdomyosarcoma represents the most common soft-tissue neoplasm of the head and neck found in children. The tumor is most commonly seen in Caucasian children under the age of 12, usually presenting as a painless mass. Distant metastases are frequently present, especially in regional lymph nodes, lung, and bone marrow. All patients suspected of having this disorder should have a thorough examination of the head and neck, as well as a complete radiographic evaluation of the primary region. Histologic disagnosis should be made as rapidly as possible. Once this has been accomplished, a thorough search for metastatic disease can be undertaken. Therapy must be individualized, and a team approach is advocated. The roles of surgery, radiation therapy, and chemotherapy are discussed. A staging system and a treatment-therapy plan are outlined.


Studies on a family with Hb J Calabria (alpha 2 beta 2 64 (E8) Gly replaced by Asp). Hb J Calabria is a fast moving hemoglobin variant which was found in an Italian family by Vecchio et al (1), and in a French family by Blouquit et al. who studied its functional properties (2). The original family described by Vecchio et al. in which both Hb J Calabria and beta-thalassemia were present has been reexamined and is the subject of the present study. Hematological and clinical features of the carriers are described. The heterozygous carriers of Hb J Calabria showed only mild variable subclinical anemia and levels of the abnormal hemoglobin ranging from about 33 to 42%. The Hb J Calabria/beta-thalassemia double heterozygote showed a moderate chronic hemolytic anemia with alterations of the RBC indices and morphology in addition to splenomegaly. The relationship between structural abnormality, functional properties and clinical expression of Hb J Calabria is discussed.


Microchromatographic quantitation of fetal hemoglobin in patients with sickle cell disease. A microchromatographic procedure (Isolab Fast Hb Test System) which was developed for the quantitation of Hb AI (10) has been found useful for the quantitation of Hb F in samples that contain Hb S and/or Hb C but no Hb A (% Fmicro). This method has been evaluated through analyses of known mixtures of Hb F and Hb S. The Hb Fmicro levels in patients with sickle cell anemia and related conditions were compared with results obtained by alkali denaturation (% FAD) and conventional DEAE-cellulose chromatography (% FDE). This microchromatographic technique is a fast, simple, and sensitive method for Hb F quantitation in patients with Sickle cell disease.


Increased risk of diabetes mellitus in beta- thalassemia major due to iron overload. Frequent transfusions improve the general well being in patients with beta-thalassemia major but carry the risk of iron intoxication including the development of diabetes mellitus. Of 22 patients with beta-thalassemia major (age 3-17 years) only 3 had a normal oral glucose tolerance. The remainder had either borderline or moderately pathological glucose curves. The mean glucose concentration was increased, and the mean insulin concentration and insulin/glucose ratio were diminished. In contrast to the oral test, the i.v. glucose tolerance test gave pathological results in only 2 of 16 patients tested. The i.v. glucose test thus may be less selective than the oral test. The mean insulin concentration was lower also after intravenous glucose, but the early insulin peak was preserved. Arginine infusion led to a normal insulin and growth hormone release. This moderate impairment of insulin release found in most of the patients leaves the hope that an efficient chelating therapy scheme might reverse beta-cell dysfunction.


Contribution to the study of craniostenosis: disturbance of the cerebrospinal fluid flow in oxycephaly. In 6 cases of oxycephaly, isotope (RIHSA) cisternography showed an altered CSF circulation with ventricular reflux or cisternal block and accumulation of the contrast at lumbosacral level. These changes express increased absorption of the CSF by the spinal arachnoid villi to compensate for reduced or nonexistent absorption by the subarachnoid villi of the vault, obstructed by chronic intracranial hypertension secondary to craniosynostosis. The possible clinical implications are outlined.


[Primary testicular tumors in childhood. Observations in 21 cases and a discussion of the necessity of metastasis prevention]. A retrospective analysis of 21 primary testicular tumors in childhood is presented. Histologic review revealed 4 differentiated teratomas, 14 yolk sac tumors, 1 rhabdomyosarcoma of testicular envelopes and 1 paratesticular sarcoma. One tumor could not be classified. Two patients with yolk sac tumor and the patient with the paratesticular sarcoma died. In 4 of the 14 patients with yolk sac tumor iliac and/or paraaortic lymphnodes were removed 8-15 days after hemicastration but no tumor cells were found. Of 3 children with yolk sac tumor who developed metastases, one had had prophylactic resection and another one prophylactic irradiation of the draining lymphnodes. 8 patients with yolk sac tumor received prophylactic chemotherapy, and none developed metastases. For patients with yolk sac tumor prophylactic chemotherapy is indicated, particularly if more than 2 months have elapsed between the first detection of a testicular mass and operation. In prepubertal boys with testicular teratoma no prophylactic therapy to prevent dissemination is necessary. Patients with yolk sac tumor have an age distribution comparable to that of patients with an embryonal tumor.


Pulmonary alveolar microlithiasis. A case report with a discussion of differential diagnosis. The rare disease of pulmonary alveolar microlithiasis is characterized by innumerable microscopic stones, mainly of tribasic calcium phosphate, within the pulmonary alveoli. In a 13-year-old boy an earlier radiological examination showed diffuse lung opacity. The main differential diagnoses taken into consideration were sarcoidosis, idiopathic hemosiderosis, diffuse interstitial fibrosis and alveolar proteinosis. The correct diagnosis was made after a lung biopsy which showed intra-alveolar microliths. The radiological findings are in agreement with the reports in the literature. The specific X-ray features of pulmonary alveolar microlithiasis are calcified opacities, nodules, hilifugal trabeculations and pleural striae. These radiological signs are sufficiently diagnostic to restrict lung biopsy to particularly difficult cases. The disease is resistant to all therapeutic measures.


Idiopathic hypercalciuria with bilateral macular colobomata: a new variant of oculo-renal syndrome. Two siblings from a consanguineous family, suffering from nephrocalcinosis and nephrolithiasis caused by idiopathic hypercalciuria are described. The condition is associated with bilateral macular colobomata and tapeto-retinal degeneration. It is known that the latter can occur together with different nephropathies; however, until now it has never been described in combination with idiopathic hypercalciuria. Blood calcium levels were found to be normal, calcium excretion rates were, with one exception, more than 6 mg/kg/24 h corrected for 100 ml GFR. Hypomagnesemia of 1.5 and 1.2 mg/dl and hyermagnesuria of 1.9 and 2.5 mg/kg/24 h corrected for 100 ml GFR were found in both patients. Tubular phosphate reabsorption reached 87% and 84% at serum parathormone levels of 0.34 microgram/l and 0.31 microgram/l in the two patients, respectively. Under calcium and magnesium loading the clearance rates of calcium and magnesium were raised whilst there was only a small insignificant increase in the blood levels of these cations. Acid-base titrations showed normal excretion rates of acid and base in one patient and a mild proximal tubular acidosis in the other. Quantitative investigation of the renal concentrating and diluting capacity established a decrease in the formation of the medullary concentrating gradient in both patients.


Ferrocyanide enhancement of concanavalin A-ferritin and cationized ferritin staining blood cell surface glycoconjugates. Ferrocyanide was used to enhance cationized ferritin and concanavalin A-ferritin (Con A-ferritin) staining of surface glycoconjugates of peripheral blood and bone marrow cells from rabbits and humans. The glutaraldehyde-fixed cells were stained with Con A-ferritin or cationized ferritin and then exposed to a ferrocyanide solution. The resulting cuboidal and irregular stain deposits averaged 50 nm in diameter when viewed with the transmission (TEM) and scanning electron microscope (SEM). Rabbit blood cells demonstrated more Con A binding sites than human blood cells and the decrease in binding sites observed with maturation of human granulocytic and erythrocytic cells was not evident in rabbit cells. Differences in binding of cationized ferritin to rabbit and human cell surfaces were less prominent than that observed for Con A. These results extend previous studies of blood cell surface glycoconjugates and demonstrate that ferrocyanide enhancement significantly facilitates SEM evaluation of Con A-ferritin and cationized ferritin bound to cell surfaces.


Different aspects of membrane differentiation at the inner side (GERL) of the Golgi apparatus in rabbit luteal cells. After luteinization, during the growth phase, rabbit luteal cells showed a well-developed Golgi apparatus, which was clearly reduced at the end of pseudo-pregnancy. During this whole period, acid phosphatase was demonstrated in the saccules (g) of the Golgi stack and in the innermost Golgi element (G2), which may be part of GERL. Between both acid phosphatase-positive compartments, a negative or slightly positive element (G1) was present paralleling the saccules of the Golgi stack. This element was composed of cisternal (G1 c) and perforated portions (G1 p) and directly bordered the thiamine pyrophosphatase-positive saccules of the Golgi stack (g1 -g2). Arylsulphatase activity was present in two saccules in the middle of the stack (g3 -g4) and in the innermost Golgi element (G2). In the acid phosphatase and arylsulphatase reactions the limiting membrane of the lysosomes was more reactive than the matrix. After phosphotungstic acid staining at a low pH, the inner elements of the Golgi apparatus (G1 and G2) and the border of the lysosomes were heavily contrasted. The lysosomal matrix and the other Golgi stack saccules were either almost unstained or displayed a clearly lower contrast. It is concluded that the cytochemical difference between Golgi (g) and GERL (G) membranes is most probably the result of a specific process of membrane differentiation, which takes place at G1. There is also evidence that the lysosomal matrix hydrolases may be formed in the saccules of the Golgi stack. The strongly phosphotungstic acid-positive inner elements are, although more extended, comparable in large part with the GERL elements as described in neurons (Novikoff et al., 1971).


A unique acid phosphatase location: the transverse tubule of avian fast muscle. Acid phosphatase activity was localized cytochemically in the posterior latissimus dorsi muscle of the chicken. Reaction product was observed in three distinct structures: T-tubules, sarcoplasmic reticulum and dense bodies. Examination of cross- and longitudinal sections confirmed that the reaction product was membrane-limited. Acid phosphatase activity was observed in sarcoplasmic reticulum adjacent to the A-I junction and the A-band, in termyofibrillar dense bodies located along the length of the fibre and in the T-tubules but not in the surface caveolae or in the lateral sacs of the sarcoplasmic reticulum. The uniqueness of the T-tubular localization with respect to cytochemical localizations in other muscles is discussed.


Heterogeneity in distribution of cardiac glycogen following isoproterenol infusions in the dog. A combined biochemical, histochemical and cytochemical study was made of cardiac glycogen distribution following intravenous infusions of varying doses of isoproterenol in anaesthetized, open-chested dogs. There was a dose-dependent decrease in glycogen levels in biopsies of the posterolateral wall of the left ventricle which also exhibited a transmural gradient with the endocardial third the most severely affected. Periodic acid-Schiff (PAS) histochemical studies also suggested a transmural gradient. There was, however, a marked variability within each layer, particularly the large amounts in the conduction system fibres. The ultrastructural studies exhibited a marked variation in glycogen content from one cell to the next. This was particularly evident in the complete absence of absence of granules in the contraction band lesions of isoproterenol cardiotoxicity yet substantial amounts were retained in neighbouring cells. Isoproterenol, therefore, produces a heterogenous depletion of cardiac glycogen related to the scattered catecholamine-induced myocardial cellular lesions. These relations have not previously been documented or emphasized.


Ultrastructural localization of acid phosphatase activity in the small intestinal absorptive cells of adult rats. Ultrastructural localization of acid phosphatase activity was investigated in ultrathin (0.05 micron) and semithin (0.5 and 0.75 micron) sections of the small intestinal epithelial cells of adult rats. The results showed that the enzyme activity was localized on the membrane of microvilli, lateral cell membranes, lysosomes, the Golgi complex, and the GERL of Novikoff (a part of the smooth-surfaced endoplasmic reticulum located in close proximity to the inner Golgi saccules) of duodenal absorptive cells. The lysosomes contained within the duodenal and jejunal absorptive cells appeared to be mainly heterolysosomes rather than autolysosomes. The enzyme activity of absorptive cells was lower in the jejunum than in the duodenum, and was barely detectable except in the GERL and lysosomes of the ileum. The average numbers of lysosomes having a diameter of 0.2 approximately 1.0 microns, per cell profile in sections of 214 duodenal, 226 jejunal and 318 ileal epithelial cells were 8.9 +/- 0.189, 6.4 +/- 0.155 and 3.5 +/- 0.027 (mean +/- SE), respectively. From these results, it was assumed that both the Golgi apparatus and GERL produce some lysosomes in the duodenal and jejunal absorptive cells, but only GERL does so in the ileum. It was considered also that because of an unexpectedly high number of lysosomes containes within the epithelial absorptive cells of the proximal intestine of adult rats, these cells may possess the strong heterophagic, as well as absorptive capacity.


Cryo-ultramicrotomy after coating of the cut surface of the tissue block with carbon and metals before sectioning. Working under improvised conditions it is shown that coating of the cut surface of a frozen tissue block with metal and carbon improves, when applied prior to each cutting, the sectioning properties and the handling of the subsequent ultrathin cryosection.


Fluorescence microscopy of viable mast cells stained with different concentrations of acridine orange. Freshly harvested rat peritoneal mast cells were stained with different concentrations of acridine orange, a metachromatic fluorochrome known to form complexes with chromatin and muscopolysaccharides. Fluorescence metachromasia was observed in cytoplasmic granules in cell populations with intracelluar dye contents as low as 5 X 10(-16) mole per cell, one-half decade lower than required to produce metachromatic staining of the nucleus. Cytoplasmic granules did not stain uniformly throughout the cell; some granules exhibited red fluorescence and others green. As the amount of acridine orange uptake per cell was increased, cytoplasmic fluorescence became uniformly red and nuclear fluorescence gradually changed from green to yellow.


[On the cytochemical demonstration of glycogen in neutrophil granulocytes: periodic acid-Schiff reaction and diastase (amylase) digestion test (author's transl)]. The results of the present investigation indicate clearly that treatment of blood smears with diastase resp. amylase is unsuitable to identify glycogen in neutrophil granulocytes. This may be attributed to the contamination with proteases of commonly used preparations of diastase resp. amylase. Thus strong PAS-reactive material which presents most probably not glycogen but PAS-positive glycoproteins may be eliminated by the proteolytic activity of the contaminants. - In detail it has been shown that susceptibility resp. resistance of the PAS-positive material against treatment with diastase resp. amylase is highly dependent on both type of fixation and fixation time: Fixation with formol free absolute alcohol (ethanol, methanol), leads also after prolonged fixation time to a complete loss of PAS-staining after preliminary treatment with diastase resp. amylase. On the other side after fixation with formol containing fixatives (for example formol/ethanol and acetic acid/formol/ethanol) only after short term fixation practically a complete loss of PAS-staining material is observed. However, after long term fixation more or less complete resistance of the PAS-stainable material against treatment with diastase resp. amylase has been found.


Reflection versus fluorescence: a note on the physical backgrounds of two types of light microscopy. Bright microscopic images against a dark background can be originating not only from fluorescence, but also from selective reflection. Selective reflection or scattering of visible light in microscopic preparations can be used for the visualization of sometimes otherwise barely distinguishable material. The images obtained superficially resemble those from fluorescence microscopy. They do not, however, result from huminescence but from selectively reflected light with wavelengths in the region of the absorbance peak of the chromophore present in the stained biological material. The respective backgrounds of the underlying physical phenomena and the conditions under which selective reflection can occur are discussed.


Protein content, dry mass and chemical composition of individual mast cells related to body growth. Recently developed quantitative microscopical techniques were used to study relations between body growth and protein content as well as dry mass of individual mast cells. Since previous studies had shown an age-related increase of mast cell content of 5-hydroxytryptamine (5-HT) and heparin, these mast cell components were also included in the present study. The cells were obtained from the peritoneal cavity of rats aged 44--269 days (body weights 189--610 g). All studied mast cell parameters showed an increase that was related to the growth of the animals. The dry mass increased 60%, protein 50%, heparin 50% but 5-HT increased as much as 260% during the studied growth period. There was a mutual and linear correlation between all studied mast cell parameters. Population studies, based on large scale measurements of individual mast cells from young and adult rats, were made. These studies showed that histograms of 5-HT content, protein content and dry mass of individual mast cells were skewed with a tail towards higher values and approximately lognormal. On the other hand, the frequency distribution of heparin content of individual mast cells was approximately normal.


Ultrastructural demonstration of glucose-6-phosphate dehydrogenase activity in steroid-secreting cells. The ultrastructural localization of glucose-6-phosphate dehydrogenase (NADP-linked) has been attempted in steroid-secreting cells. Rat adrenocortical cells and newt testicular glandular cells were fixed in an ice-cold mixture of 1% methanol-free formaldehyde and 0.25% glutaraldehyde. Potassium ferricyanide was used as the final electron acceptor. After incubation, the final copper ferrocyanide precipitate is exclusively observed in the hyaloplasm of these cells, provided that an electron carrier (1.0 mM PMS) has been added to the medium in order to by-pass the tissue "diaphorase" (NADPH-ferricyanide reductase) reaction. No precipitate appears in the absence of glucose-6-phosphate (substrate). Incubation in a medium devoid of PMS results in an exclusively mitochondrial reaction; the latter is that of the "diaphorase", which in these cells is mitochondrial. These results prove the importance of utilizing exogenous electron carriers (such as PMS) in coenzyme-linked dehydrogenase cytochemistry. Although polyvinyl alcohol was included in the washing and incubation media, in order to increase their viscosity, problems still exist concerning ultracytochemical localization of this "soluble" enzyme; these problems are discussed in the paper.


"Blind focusing": an objective method for avoiding errors of focus at the television texture analysis system (TAS). The amount of light energy a particle absorbs does not depend upon correct focus. The change in the path of light rays brought about by defocusing causes absorbing areas to be registered as areas of higher transmittance than when in focus. Already wellknown in photometry, this effect is put to use by the "blind focus" method at the television texture analysis system (TAS, Leitz). Some chromophores within the object to be measured are compared to a preset value of transmittance, for example T = 0.40. Only the area representing the structures as dense or denser than the preset density are registered. If the structures are out of focus the size of the registered area is too low, since by defocusing, structures to be measured become pale and diffuse, the correct focus corresponds to the largest area to a preset value of transmittance.


Histochemical study on the localization of glucose-6-phosphate dehydrogenase induced by androgen or thyroxine in the convoluted tubules of mouse submandibular gland. The effects of 5 alpha-dihydrotestosterone (DHT) and thyroxine (T4) on glucose-6-phosphate dehydrogenase (G-6-PDH) activity in mouse submandibular gland were investigated histochemically. A strong positive histochemical reaction for G-6-PDH was observed in the excretory ducts of untreated male and female mice, with a slight reaction in the basal portion of the convoluted tubules (striated ducts) of males. Administration of DHT to female mice increased G-6-PDH activity specifically in the convoluted tubules. T4 increased the enzyme activity in the tubules more than DHT. The induction of G-6-PDH activity by T4 in adrenalectomized mice suggests that T4 has a direct effect on the submandibular gland.


Quantitative distribution of lysosomal hydrolases in the rat nephron. The activities of N-acetyl-beta, D-glucosaminidase (NAG, EC 3.2.1.30), beta, D-galactosidase (beta-gal, EC 3.2.1.23) and acid phosphatase (ac-Pase, EC 3.1.3.2) were measured in the glomeruli, five segments of the proximal and four segments of the distal tubule of normal male Wistar rats. The activities of NAG and beta-gal are 3- to 5-fold higher in the first part of the proximal tubule than in other segments and very low in glomeruli. We propose that the distribution of these two glycosidases reflects the contribution of the different tubular segments to the reabsorption of glycoproteins. The maximal activity of ac-Pase was found in the straight part of the proximal tubule. It was only 1.5-fold higher than in the distal tubule. Moreover, the activity in glomeruli is rather high. We conclude that ac-Pase is not primarily involved in the handling of reabsorbed molecules.


Surgical manipulation of portosystemic shunts in dogs. Surgical manipulation to achieve stenosis or occlusion of portocaval shunts in 7 dogs resulted in disappearance of signs of central nervous, gastrointestinal, or urinary dysfunction. Results of blood chemical analyses and hepatic function studies as well as hepatic cellular architecture returned to normal or near normal within several months. Cranial mesenteric angiography was done on 4 dogs following corrective surgery; there was evidence of improved hepatic-portal circulation in 3 of the dogs and complete shunt obstruction in 1 dog.


Nephrogenic diabetes insipidus in a dog with renal medullary lesions. Antidiuretic hormone (ADH) administration to a polyuric Miniature Poodle did not alter diuresis. Plasma ADH concentrations were high, and urine osmolality remained low during water deprivation. From these findings, it was concluded that the polyuria was of renal origin. In addition, the glomerular filtration rate was found to be high. Electron microscopic examination of the renal medulla revealed vacuoles containing myelinic figures and fingerprint structures in the cells of the Henle loops, blood vessels, and interstitium, similar to those in lysosomal lipid storage disease. Their absence in collecting duct epithelium indicated that the defect in concentrating ability was due to a disturbance of the counter-current multiplier mechanism rather than to a defect in ADH receptors.


Fenbendazole for treatment of Paragonimus kellicotti infection in dogs. The effect of fenbendazole therapy was studied in 9 dogs with pulmonary paragonimiasis induced by inoculation of metacercariae (25/dog) of Paragonimus kellicotti. At 42 to 47 days after 6 dogs were inoculated, they were given fenbendazole in 2 divided doses totaling 50 mg (4 dogs) or 100 mg (2 dogs)/kg of body weight each day for 10 to 14 days. Three dogs were not treated. The passage of Paragonimus eggs in the feces ceased after 3 days at the high dosage and after 3 to 8 days at the low dosage. All dogs were euthanatized and necropsied on day 14. Live flukes were not recovered from the lungs of any treated dog, but 15, 19, and 23 live flukes were recovered from the untreated dogs.


Paratuberculosis in cattle and free-living exotic deer. Paratuberculosis was studied among dairy cows and exotic deer that shared grazing areas at Point Reyes National Seashore, California. Of the 10 dairy herds tested, 5 (50%) were infected with Mycobacterium paratuberculosis (based on results of fecal culture). Mycobacterium paratuberculosis was cultured from 9 (8.7%) of the 103 bovine fecal samples and from 4 (3.9%) of the 103 bovine rectal mucosa scapings tested. Of 89 fecal samples from 52 axis deer (Axis axis) and 37 fallow deer (Dama dama), 5 (9.6%) and 3 (8.1%), respectively, contained M paratuberculosis. Culture of intestinal necropsy samples from the same deer indicated that 3 (5.8%) of the axis deer and 2 (5.4%) of the fallow deer were infected with M paratuberculosis. The cows were tested for serum antibodies by the complement-fixation test and by radioimmunoassay. Of 95 sera tested by complement fixation, 15 (15.8%) were positive, as were 15 (14.7%) of 102 sera tested by radioimmunoassay. Culture results and serologic test results were compared on a herd basis.


Seasonal transmission of bovine gastrointestinal nematodes in the Texas Gulf Coast. Sentinel calves were placed in pastures for 1 month in two environmentally dissimilar areas of the Texas Gulf Coast to determine the seasonal transmission of various gastrointestinal nematodes. Transmission was determined for Cooperia spp, Haemonchus placei, Ostertagia ostertagi, and Trichostrongylus axei. Large numbers of Cooperia spp were acquired from May through November, with the peak of transmission occurring in July and August. Haemonchus placei was encountered on both field sites but was transmitted in large numbers only at one site, during August. Ostertagia ostertagi was acquired primarily from November through May, with the peak of transmission occurring in January and February. January through March was the period when the greatest numbers of Ostertagia larvae undergoing arrested development were acquired. Trichostrongylus axei was abundance in December and January at one field site. In general, trends of transmission were the same in both areas, indicating that weather conditions were most important than vegetation type in larval transmission.


Interaction of phenytoin with chloramphenicol or pentobarbital in the dog. Two dogs that had been given phenytoin for control of seizures for approximately 1 year developed signs of phenytoin toxicosis (postural ataxia an d a hypermetric gait) when chloramphenicol was added to the therapeutic regimen. The signs of toxicosis disappeared within 24 hours after cessation of chloramphenicol treatment. Oral treatment of laboratory dogs with chloramphenicol (50 mg/kg, TID for 3 days) prior to intravenous injection of phenytoin increased the half-life of phenytoin from 3 hours to 15 hours. Dogs infused with phenytoin during pentobarbital anesthesia had little or no change in serum phenytoin concentration during a 2-hour postinfusion observation period, which was unexpected for the intravenous route of administration.


Inappropriate secretion of antidiuretic hormone in a dog. Hyponatremia with simultaneous renal sodium loss was associated with the inappropriate secretion of antidiuretic hormone in a dog with heartworm disease. Antidiuresis caused expansion of extracellular fluid volume, which induced renal salt wasting and a negative sodium balance. The combination of water retention, salt wasting, and inactivation of intracellular solute contributes to the decrease in serum sodium concentration. Water intoxication due to hypotonicity of body gluids induced anorexia, depression, weakness, and incoordination.


Orbital chondroma rodens in a dog.

Orbital chondroma rodens in a dog. A chondroma rodens involving the superficial medial aspect of the right orbit was diagnosed in a 9-year-old dog referred because of chronic unilateral epiphora. Examination revealed several ophthalmic abnormalities attributable to a space-occupying mass in the superficial medial aspect of the orbit. The mass was excised; however, regrowths at the primary site necessitated additional surgical interventions. The dog was given radiation therapy, which provided encouraging results. Subtle histologic differences as well as differing epidemiologic features suggest that chondroma rodens is not analogous to the human entity of juvenile aponeurotic fibroma, to which it has been compared in the past.


Clinical evaluation of metrizamide as a myelographic agent in the dog. Metrizamide, a new, water-soluble contrast agent, was clinically evaluated as a myelographic agent in 17 dogs. Nine dogs were given lumbar subarachnoid injections and six were given cisternal injections. Two dogs were given cisternal and lumbar injections; in one dog, both injections were given on the same day. The dosage ranged from 0.3 to 0.57 ml/kg of body weight, using an isotonic solution of metrizamide. Of eight dogs given cisternal injections, two experienced convulsive activity requiring diazepam treatment during the anesthetic recovery period. The lumbar injections did not cause convulsions. Satisfactory radiographic density persisted up to 45 minutes after injection, allowing time for several views to be obtained. In general, metrizamide appeared to be an adequate myelographic agent in the dog.


Clinical, clinicopathologic, and electroencephalographic features of lead poisoning in dogs. Eleven dogs with signs of lead poisoning were examined. The principal clinical signs were neurologic and included ataxia, tremors, clonic-tonic seizures, amaurosis, and deafness. Basophilic stippling and circulating nucleated red cells were not common findings in blood films. Blood lead values varied from 0.22 ppm to 0.63 ppm before treatment. Electroencephalographic changes in nonsedated dogs were marked by intermittent high-amplitude slow wave activity.


Disseminated sporotrichosis in a cat.

Disseminated sporotrichosis in a cat. Sporothrix (Sporotrichum) schenckii was identified as the causative agent of a large pyogranulomatous lesion on the right forepaw of a cat. Organisms also were observed in axillary lymph nodes of the affected forelimb and in the lungs and liver of the cat. The agent was transmitted to another domestic cat and to mice.


Comparative approach to health maintenance: definition, need, and rationale. A comparative approach has been employed in many phases of medicine, eg, epidemiology, surgery, nutrition, cancer. It has been used widely in teaching, research, and surveillance, but little attention has been paid to its application in delivery systems. Geographic and financial circumstances often create situations in which it is extremely difficult to enter the health care system or even to know when such entry is indicated. Because the comparative approach has been successful in other phases of medicine, it deserves consideration in the health maintenance phase. The comparative approach has three major components: (1) Reliance on broad principles of health maintenance, not on specifics; (2) emphasis on health maintenance, not on curative medicine; and (3) utilization of health care systems designed for nonhuman beings to bring man into the human health care system. The ways to utilize ethically and legally the expertise of other health professionals in providing entry to the health care system and in facilitating transfer of our technical knowledge to more of the general public should be explored.


Comparative approach to health maintenance: how will it work? A prototype for the implementation of a comprehensive health maintenance program is described in which the expertise of veterinary medicine is brought to bear on preventive medicine and on special generic environmental disease factors as they impact on human health. For the sake of organization and the ease of presentation, certain specific activities have been divided into two overlapping categories: environmental health and health education. The implementation of a comprehensive health care delivery system will become a reality only when the full array of health resources is matched with health needs. It cannot be overemphasized that the delivery of health care services is not exclusively within the purview of any one profession; rather, interdependence and sharing of responsibilities and activities in a team approach are characteristics of the human health system.


Interfacing professional training in health maintenance and preventive medicine. Because of emerging economic realities of the latter half of this century, the practice of preventive medicine, as opposed to curative medicine, is becoming essential in developed and developing countries. This holds true in veterinary medicine as well as in human medicine, and as we become increasingly aware of this fact, we also recognize the increasing interdependence of both fields. To determine the extent to which veterinarians are prepared to deal with this change in emphasis, two surveys have been prepared; one directed to various specialty groups within the profession and the other directed to schools of veterinary medicine. The first survey was designed to identify areas in which veterinarians felt their training had been deficient relative to decision making in applied preventive medicine. The second survey queried the schools to determine what changes had been made in their curricula to remedy these inadequacies.


Clinical, morphologic, and chemical studies on copper toxicosis of Bedlington Terriers. In a study of 90 Bedlington Terriers, 68 had a defect that resulted in the accumulation of toxic excesses of copper in the liver. Concentrations of copper were 5 to 50 times that of clinically normal mongrel dogs. The bulk of this excess copper was sequestered in lysosomes. When copper concentrations exceeded 2,000 micrograms/g dry liver, progressive signs of functional and morphologic disturbance appeared as focal hepatitis, chronic active hepatitis, and ultimately cirrhosis. The disorder, which appears to be inherited, could only be diagnosed by liver biopsy. It was latent for many years in some dogs but led early in life to acute or chronic hepatic disease and death in others.


Agglutinins to Brucella canis in stray dogs from certain counties in Illinois and Wisconsin. In a serologic and blood culture survey for Brucella canis in 2,572 pound dogs from eight Illinois and Wisconsin counties, 173 (6.7%) were reactive in a presumptive slide test, 41 (1.5%) were reactive in a tube agglutination test, and 6 (0.2%) were positive in blood culture.


Treatment of cervical vertebral instability in the dog. In a retrospective study, common neurologic signs and results of treatment of cervical vertebral instabilities were reviewed. In 16 large dogs, vertebrae C5 and C6 were most frequently malformed and unstable. Treatment was conservative in 3 dogs, 1 dog was not treated, and 12 dogs were treated surgically (dorsal decompressive laminectomy and wire stabilization of the articular facets in most cases). The 3 conservative treatments and 8 of the 12 surgical treatments were considered beneficial.


Polycystic renal disease in related cats. Six kittens from four litters of related cats had greatly enlarged abdomens and died before they were 7 weeks old. Kittens from two litters were necropsied and found to have bilateral polycystic renal disease and cystic bile ducts.


Trombiculosis in a cat.

Trombiculosis in a cat. Trombiculosis (dermatitis caused by trombiculid mites) in a Domestic Shorthair cat was characterized by diffuse thickening and crusting of the skin of the abdomen and limbs and by multiple papules on the face, ears, and sides of the trunk. Skin biopsy revealed acanthosis and hyperkeratosis involving the epidermis and hair follicles, mites in epidermal tunnels, and edema of the dermis, with infiltration of eosinophils and mast cells. Mites from skin scrapings were identified as Walchia americana. The cat was treated systemically with a broad-spectrum antibiotic and topically with a carbaryl and pyrethrin powder preparation. The lesions were resolved within 2 months.


Acquired torticollis in eleven horses.

Acquired torticollis in eleven horses. Case records of 11 horses with acquired torticollis during a 15-year period were reviewed. The cause was established in seven of eight cases and included cervical intervertebral disk protrusion, skull fracture, neurogenic atrophy, and dystrophic myodegeneration. The latter condition was considered to be the most likely cause in the three horses that recovered.