Cytotoxic reactions of murine lymphoid cells studied with a tritiated proline microcytotoxicity test. A lymphocyte cytotoxicity (CTX) test with 3-H-proline-prelabeled target cells was used to detect the immune response of murine lymphoid cells to H-2 and tumor antigens. The specificity of the reaction was determined by simultaneous tests on unrelated target cells and, for reactions directed against H-2 antigens, by blocking experiments with alloantiserum directed against the H-2 antigens of the target cells. After a single intraperitoneal (ip) injection of allogeneic spleen cells, CTX of unfractionated peritoneal cellswas strong, with a sharp peak on day 5. Repeated ip immunization markedly increased the CTX of unfractionated peritoneal cells. The reaction was strongest when the test was done at 37 degrees C. Sometimes CTX should be detected after as little as 6 hours' incubation. CTX depended primarily on the absolute number of effector or target cells per area rather than on the ratio of effector to target cells. Both nonadherent and adherent peritoneal cells destroyed target cells specifically. The CTX of nonadherent peritoneal cells was increased by 2-mercaptoethanol. The CTX reaction depended on effector cells bearing Tyl-1. Destruction of "innocent bystander" target cells was seen with one of four combinations of unfractionated and nonadherent peritoneal cells from hyperimmune animals.


Hyperplastic and neoplastic lesions of the kidney in Buffalo rats of varying ages ingesting N-4-(4'-flurobiphenyl)acetamide. Inbred Buffalo male and female rats 4, 12, 24, and 52 weeks of age ingested 0.04% N-4(4'-fluorobiphenyl)acetamide in a semisynthetic diet for 36 weeks. Animals were killed 12 weeks later. Male rats 24 weeks old were more susceptible to the development of carcinomas of the kidney than were female rats of the same age or younger or older animals of both sexes. Rats with renal cell carcinomas either did not have hepatic carcinomas or had small ones.


Effect of dietary beef fat on intestinal tumor formation by azoxymethane in rats. Two groups of 20 male Sprague-Dawley rats each were given azoxymethane subcutaneously (8 mg/kg body wt) and fed a normal diet or one high in beef fat. Control groups were not given azoxymethane. The rats on the fat diet consumed less food and gained significantly more weight than the animals on the normal diet. Those given high fat and azoxymethane developed more intestinal tumors than did the dietary controls receiving the carcinogen. Furthermore, they had a greater number of larger tumors and more metastases than did the animals fed normally. No intestinal tumors were observed in control groups not receiving azoxymethane. The results show that the diet high in beef fat enhances the carcinogenic effect of azoxymethane in the rat.


Carcinogen chemistry. I. Reactions of protonated dialkylnitrosamines leading to alkylating and aminoalkylating agents of potential metabolic significance. Three distinct modes of protolytic dialkylnitrosamine fragmentation were observed when we followed the time dependence of the nuclear magnetic resonance (NMR) spectra of seven nitrosamines in superacid solution: 1) In equimolar HSO3F: SbF5 ("magic acid"), dimethylnitrosamine was cleaved to the protonated Schiff base of formaldehyde and methylamine, and diethylnitrosamine was similarly converted to the protonated acetaldehydeethylamine Schiff base.2) By contrast, of the five dipropyl-and dibutylnitrosamines were studied, all cleaved nonoxidatively under these conditions (with loss of nitrogen gas) to the corresponding propyl or butyl cations. The carbocations thus produced underwent condensation and fragmentation to form the tert-butyl cation as the principal product ultimately observable by NMR. 3) Thethird fragmentation mechanism, which involved denitrosation to the dialkylammonium ion, was observed only as a minor pathway in the sulfuric or fluorosulfuric acid protolysis of dimethylnitrosamine. The mechanisms that are postulated for these cleavage reactions, if functioning in vivo, could account for several metabolic observations that have proved difficult to reconcile with previous conceptions of nitrosamine metabolism.


Correlation between the carcinogenicities of nitrofuran derivatives and their destructive actions on sebaceous glands of mouse skin. The effects of six nitrofuran derivatives (including a formerly used food preservative) on mouse skin sebaceous glands were investigated. A close correlation was found between the carcinogenicities and destructive activities of nitrofuran derivatives on the sebaceous glands. 5-Nitro-2-furaldehyde semicarbazone and 4-methyl-1-[(5-nitrofurfurylidene)amino]-2-imidazolidinone, which are carcinogenic, caused marked destruction of the glands at a dose of 1-5 mg/mouse. 2-(5-Nitro-2-furfurylidene)-aminoethanol almost completely destroyed the glands at a dose of 5 mg/mouse; its carcinogenicity has not yet been investigated. 1-[(5-Nitrofurfurylidene)amino]-carcinogenic, did not affect the glands, even at a dose of 5 mg/mouse. 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide, which is a potent mutagen but not carcinogenic, had no effect on the glands at a dose of 5 mg/mouse. Under similar conditions, the potent carcinogen 7,12-dimethylbenz(alpha)athracene almost completely destroyed the sebaceous glands at a dose of 0.05 mg/mouse, but dimethyl sulfoxide (used as solvent for the test compounds) had no effect.


Tumor initiation by N-acyloxy derivatives of piperidine and N-arylacetamides. Four N-Acetoxy-N-arylacetamides previously found to be local sarcomagens in the rat have been found to be initiators of tumorigenesis in mouse skin. The order of activity was: N-acetoxy-2-acetamidophenanthrene greater than N-acetoxy-4-acetamino-stilbene similar to N-acetoxy-2-acetamido-fluorene greater than N-acetoxy-4-acetamidobiphenyl. Two substituted N-benzoyloxypiperidines previously shown to yield nitrenium ions on solvolysis in methanol also had initiating activity in mouse skin.


Tumor response in strain A mice exposed to silylating compounds used for gas-liquid chromatography. Six reagents used to silylate, alkylate, or acylate compounds for ease of identification on gas chromatographic columns significantly increased the frequency of lung tumors in A/He mice.


Failure to detect chromosome damage in vivo in Friend virus-infected leukemic mice. The cytogenetic activity of Friend virus (FV) was tested in vivo on spleen and bone marrow cells of FV-infected leukemic C3H/HeJ and STS mice. No specific chromosome rearrangements were detected in the infected animals. Some chromosome abnormalities were recorded in both normal and diseased animals; however, aberrations did not significantly increase in the leukemic groups.


Matrical inclusions induced by clofibrate in hepatic microbodies of rats fed 2-acetylaminofluorene. Abnormal inclusions in microbodies were induced by clofibrate in hepatocytes of hyperplastic liver nodules in rats fed 2-acetylaminofluorene. These were matrical tubules and plates, each with the same ultrastructural features as those reported previously by other investigators. A hyperplastic state of hepatocytes induced by hepatocarcinogens might be related to the formation of these inclusions in response to clofibrate.


"Pseudocardiogenic" pulmonary edema.

"Pseudocardiogenic" pulmonary edema. Fifteen postoperative surgical patients, in whom noncardiac pulmonary edema developed were studied. A presumptive diagnosis of left ventricle failure would have been based on historical evidence of heart disease (80%), electrocardiographic changes of ischemia or arrythmia (87%), or cardiogenic shock (20%). (see article) Fig. 6. PAEDP-PCW gradient. Note that arterial oxygen tension had an inverse relationship to this pressure differential. Roentgenographic findings included pulmonary edema (73%), pulmonary vascular congestion (60%), cardiomegaly or congestive heart failure (40%). Mean increase in A-aDO2 was 290 torr. Further cardiovascular investigation seemed to exclude left ventricular failure. Mean cardiac index was 4.1 plus or minus 1.3 L/min/m2; pulmonary capillary wedge pressure 4 plus or minus 2.7 torr, and stroke work was 87 plus or minus 8.7 gm-meters. Possible etiologic agents included elevated pulmonary artery pressure (67%), allergic reactions (27%), peritonitis or multiple system trauma (54%), or multiple transfusions (33%). Forty-seven per cent of the entire group survived. Therapy was directed toward the underlying noncardiogenic suspected etiology. Direct cardiovascular measurements were necessary to correct the erroneous though seemingly well founded suspected diagnosis of left ventricular failure in these patients.


Physiologic response to impact.

Physiologic response to impact. The football field, an ideal setting for research in trauma by radiotelemetry, has allowed collection of data on man's response to impact. The physiologic response adds a new dimension to the measurement of impact tolerance. The present study has demonstrated the protective response of the athlete and explains how he is able to dissipate forty times more kinetic energy than his helmet is capable of absorbing.


A fracture board to facilitate the management of supracondylar humeral fractures in children. A simple fracture board and its construction is described to facilitate the radiological and nursing management of children with supracondylar fractures of the humerus which are managed with lateral skeletal traction.


Multiple spine fractures in ankylosing spondylitis. 1. Concomitant cervical and thoracic spine fractures are reported in a patient with advanced ankylosing spondylitis (second reported case). 2. The thoracic T9-10 interspace fracture-dislocation was grossly unstable, as well as the C7-T1 fracture-dislocation. 3. The higher incidence of cord injury following spinal fracture-dislocations in these patients is discussed. 4. The dangers of inadequate postinjury immobilization in those patients fortunate enough to be neurologically intact following spinal fracture are stressed.


Widened interpedicular distance secondary to trauma. A case of increased interpedicular distance in a patient involved in an auto accident is presented. With a fracture of the vertebral body, this radiologic sign indicates an associated fracture through the posterior elements. The importance of this diagnosis is emphasized, in order to prevent serious neurologic sequelae.


Injury patterns in motorcycle collisions. This report describes the incidence, nature, and severity of trauma for injuried and medically treated motorcyclists in Sacramento County, California in 1970. Using official police reports, hospital admission, and emergency-room medical records, 1,273 persons with a confirmed medically treated motorcycle injury were identified. Since less than 39% of all injured motorcyclists were identified in this study by use of official police reports only, statistics which rely solely on these reports greatly underestimate the frequency of motorcycle collision injuries in the community. The annual injury incidence was 2.0 per 1,000 population, with peak incidence injury rate for male drivers 18 years of age. Slightly more than 4% of all registered motorcycles were involved in an injury-producing collision in a single year. Almost 45% of injured motorcyclists suffered a serious injury, with injuries to the musculoskeletal system in the form of fractures being the most common. The average length of hospital stay was 12 days, and three-fourths of those injured indicated one or more days of disability. Physicians should be alert to the fact that persons injured in motorcycle collisions commonly sustain multiple fractures and other serious injuries.


Genetic analysis of adenovirus type 2. I. Isolation and genetic characterization of temperature-sensitive mutants. Temperature-sensitive mutants which replicate normally at 33 C but poorly at 39 C were isolated from nitrosoguanidine- or nitrous acid-mutagenized adenovirus 2 by (i) testing the cytopathic effect or inclusion body-forming capacity of random plaque isolates, or (ii) reduced plaque enlargement upon shifting from 33 to 39 C. Thirty-six mutants were isolated with 33 C/39 C plaque ratios varying from 20 to 10-5. Some of these mutants could be arranged into 13 groups by the complementation test. By means of recombination analysis a provisional linear genetic map was constructed.


Sequence relationships between adenovirus 2 early RNA and viral RNA size classes synthesized at 18 hours after infection. Synthesis of cytoplasmic viral RNA was studied during infection of cultured human (KB) cells with adenovirus 2. At 6 h, before viral DNA synthesis began 5% of the poly(A)-containing RNA hybridized to viral DNA; by 12 h and at later times more than 80% was virus specified. At 18 h after infection, four major size classes of cytoplasmic viral RNA were identified among the poly(A)-containing molecules. These size classes migrated as 27S, 24S, 19S, and 12 to 15S in polyacrylamide gels. The three larger size classes could also be identified in denaturing formamide gels. Hybridization of the 27S, 24S, and 19S viral RNAs was not inhibited by RNA harvested from cells at early times in infection. Therefore, these three major RNAs must code for late viral proteins. Hybridization of the 12 to 15S RNA was partially inhibited by RNA from cultures harvested at early times, suggesting that in this size class some of the RNA labeled at 18 h codes for early viral proteins.


Comparative biophysical studies of hepatitis B antigen, subtypes adw and ayw. Comparative biophysical and biochemical analyses were performed on purified preparations of hepatitis B antigen (HBs Ag) subtypes adw and ayw, including isoelectric pH evaluations, analysis of the different morphological forms, molecular weight determinations, and analysis of the polypeptides by polyacrylamide gel electrophoresis, Both HBs Ag-positive plasma and purified HBs Ag were analyzed by electrofocusing in a sucrose ampholyte gradient. Four distinct populations of HBs Ag with a pH range of 4.5 plus or minus 0.1 to 5.4 plus or minus 0.1 for unfractionated plasma samples and 3.9 plus or minus 0.05 to 4.9 plus or minus 0.05 for purified samples were detected in both adw and ayw preparations. Electron microscopic studies of each population of purified HBs Ag revealed 19- to 27-nm spheres in each fraction. Purified material labeled with 125I by the chloramine-T method behaved as one major population with an isoelectric pH value of 3.9 plus or minus 0.1. Purified adw preparations revealed a major population with a molecular weight of 3.7 times 10-6 and a second one of 4.6 times 10-6. Purified preparations of ayw contained one population with a molecular weight of 4.6 times 10-6. Polyacrylamide gel electrophoretic analysis of purified HBs Ag revealed nine polypeptides for ayw and seven for adw particles. These studies indicate that purified preparations of HBs Ag are heterogeneous and that distinct differences can be detected between the two subtypes.


Characterization of type 5 adenovirus fiber protein. Type 5 adenovirus fiber protein was purified and subjected to chemical characterization. Equilibrium sedimentation ultracentrifugation analysis indicated that the intact fiber has a molecular weight of approximately 183,000. Denaturation and chemical analyses implied that the fiber consists of three polypeptide chains, each of about 61,000 mol wt. Mapping of tryptic peptides and electrophoretic separation of the constituent chains suggested that the intact fiber consists of two identical and one unique polypeptide chains.


The 3'-terminal nucleotide sequences of adenovirus types 2 and 5 DNA. Short nucleotide sequences at the 3'-termini of adenovirus types 2 and 5 DNA have been determined using T4 DNA polymerase as described by P. T. Englund (1972). The terminal sequences of both serotypes appear to be completely identical. Both molecular ends of type 2 as well as of type 5 DNA terminate with the sequence ...pCpC...pGpApTpG3', consistent with the presence of an inverted terminal repetition in adenovirus DNA.


T4 DNA polymerase (gene 43) is required in vivo for repair of gaps in recombinants. Experiments with a mutant of T4, tsL97, temperature sensitive for gene 43, showed that T4 DNA polymerase was necessary in vivo to repair gaps in recombinant molecules. CsCl density gradient experiments showed that molecular recombinants were not repaired when the T4tsL97-infected cells were shifted to 42 C after replication and recombination had taken place. Repair was almost complete when the same procedure was followed with the wild-type T4, or when the T4tsL97-infected cells were incubated at the permissive temperature, 36 C. Long-single-strand production was also affected similarly by the T4tsL97 mutation. All the results were consistent with the theory that gaps exist in many recombinant molecules at the recombinant joint, that T4 DNA polymerase is the enzyme that repairs these gaps in vivo, and that covalent repair of the recombinants leads to extensive long-single-strand production.


Host-phage interaction on Agrobacterium tumefaciens. IV. Phage-directed protein synthesis. Gel electrophoretic and autoradiographic techniques were used to detect the temporal sequence of protein synthesis after infection of the sensitive strain Agrobacterium tumefaciens with phage LV-1. Three classes of protein were detected: early proteins, class I, which include a protein capable of shutting off host protein synthesis; class II, proteins which are detected after 30 min; and late proteins, class III, which include the phage-directed endolysin and five additional proteins that appear 45 min after infection.


Method for determination of nucleotide sequence homology between viral genomes by DNA reassociation kinetics. A model and appropriate equations were derived for the quantitative estimation of nucleotide sequence homology between two partially related viral genomes by measurement of the initial rate of reassociation of one labeled DNA in the presence of a second unlabeled DNA. The validity and usefulness of this procedure were demonstrated by the analysis of the reassociation kinetics of labeled adenovirus 7 DNA in the presence of unlabeled adenovirus 2 DNA. Based on DNA reassociation, the extent of homology between adenovirus 2 and 7 genomes was found to be 10 to 12%. The duplex formed between adenovirus 2 and 7 DNA had the appropriate thermal stability for a well-matched DNA-DNA hybrid.


Template activity of complexes formed between bacteriophage f2 RNA and coat protein. Formation of complexes between f2 RNA polymerase cistron was partially inhibited, some RNA and coat protein was studied using salt conditions which are optimum for phage protein synthesis. In this ionic environment, coat protein precipitation can be prevented by sulfhydryl group-protecting agents. Complexes formed at different protein-RNA input molar ratios were isolated and tested for template activity in an in vitro protein synthesizing system. Simultaneously, the number of protein molecules bound per RNA strand in such complexes was measured by the membrane (Millipore) filtration technique. Under conditions in which translation of the RNA strands were complexed with six molecules of coat protein, whereas some remained unbound. Strong inhibition of the translation of the RNA polymerase cistron was observed when each of the RNA strands present in the mixture was associated with six molecules of coat protein.


Agglutination of Japanese encephalitis virus with concanavalin A. Results of experiments have indicated that reduction in biological activities at high concentrations of Japanese encephalitis virus is caused by aggregates of the virus by concanavalin A. The possibility exists that the concanavalin A binding site is different from hemagglutination and antireceptor sites of Japanese encephalitis virus.


Complementation of human adenovirus type 5 ts mutants by human adenovirus type 12. Temperature-sensitive mutants of type 5 adenovirus belonging to eight complementation groups were complemented in mixed infection by type 12 adenovirus, whereas mutants of 7 other groups were not enhanced. In some crosses, phenotypic mixing took place. No evidence of recombination between type 5 ts mutants and type 12 was found.


Anaphylaxis manifested by hypotension alone. Three instances of life-threating adverse reations to intravenous contrast media and penicillin have been presented. Hypotension was the major presenting sign, and was prolonged and relieved only by copious dluid therapy. In 1 case the onset of hypotension was delayed for an hour. Urologists should be aware of the variety and proper treatment of drug reactions.


Succinylcholine-induced ventricular fibrillation in the paralyzed urology patient. A myelotomy patient with succinylcholine-induced hyperkalemia and ventricular fibrillation was succesfully resusciated. The urologist and anesthetist can prevent this problem by using non-depolarizing muscle relaxants in patients with denervated skeletal muscle.


Transitional cell carcinoma of renal pelvis in an infant. A case of transitional cell carcinoma of the renal pelvis in a 4-month-old japanese boy is reported. This patient is the youngest one described in the literature with a tumor of this type. The differential points of Wilms tumor and other types of neonatal renal tumors are discussed.


Management of ureteral obstruction after an antireflux operation: triangular flap ureteroplasty. Pronounced ureteral obstruction following an antireflux operation is an uncommon but often difficult problem to manage. Based on a limited experience we have found that triangular flap ureteroplasty is a worthwhile means of repeat reimplantation of the obstructed ureter and perhaps provides a better alternative than transureteroureterostomy.


Use of ileocystoplasty in the hypertonic neurogenic bladder. An ileocystoplasty was used successfully in the management of incontinence secondary to a hypertonic neurogenic bladder. The indications for its use and possible benefits in patients with neurogenic bladder have been discussed.


Treatment with phenoxybenzamine of upper urinary tract complications caused by intravesical obstruction. Five children in whom reflux and progressive hydronephrosis persisted despite multiple surgical attempts or repair are described. In all cases cystomanometry displayed a marked elevation of the bladder outlet resistance combined with high intravesical pressure values. Therapy with phenoxybenzamine, an alpha-adrenergic blocker, was successful  in all cases, restoring a free urine passage of the upper urinary tract and unimpaired voiding preventing urinary diversion which has been considered in some of these children. Although there were no signs of bladder neuropathy, a hyperfunction of the sympathetic innervation as acause for bladder complications is discussed.


Congenital urethral fistula with chordee. The tenth reported case of congenital urethral fistula with chordee was repaired by  a 1-stage procedure. The ventral intact prepuce was used to form a tubular pedicle flap from which the distal portion of the new urethra was constructed. The proximal neourethra was fashioned from a tubular pedicle flap based at the proximal fistulous orifice. The prevailing hypothesis advanced for the etiology of hypospadias postulates a deficiency of testicular evocator substance prior to complete formation of the urethra. This theory inadequately explains the genesis of congenital urethral fistula as well as chordee without hypospadias. Congenital urethral fistula and congenital chordee without hypospadias are best explained by the theory of deficient urethral plate.


The insignificance of an elevated acid phosphatase in children. Acid phosphatase values in normal children were incorrectly assumed to be within the same range of adult levels. The enzyme was found to be elevated in 25 boys less than 14 years old and did not return to adult levels until after puberty. It is emphasized that extensive genitourinary investigation and prostatic biopsy are not indicated on the basis of elevated enzyme levels in the prepuberal age group.


Enterobius vermicularis infestation and secondary enuresis. We recently saw 5 young girls with the sudden onset of frequency and enuresis secondary to enterobius vermicularis. All children had sterile urine and 4 had been unjustly considered neurotic. Anthelmintic therapy resulted in an immediate cure in all 5 cases. More frequent diagnosis and treatment of this common ailment would do a great service to affected girls and their families.


Chemotherapy of advanced renal cell carcinoma with vinblastine and CCNU. Forty-four patients with advanced renal cell carcinoma (stage IV) were divided into 3 groups. The 23 patients in group 1 received CCNU alone,the 6 patients in group 2 received CCNU and vinblastine and the 15 patients in group 3 received methyl CCNU and vinblastine. The over-all response, subjective and objective, was 30% in group 1, 60% in group 2 and 54% in group 3. These results are compared to other existing modalities of treatment and appear to be superior.


Ureteroarterial fistula.

Ureteroarterial fistula. Among the many complications of total pelvic exenteration is a fistulous communication between the iliac artery and ureter. We reported 1 such case complicated by near exsanguination and shock. Repair of the fistula was accomplished by closure of the iliac rent and cutaneous ureterostomy.


Urodynamic assessment of ureteral obstruction in retroperitoneal fibrosis,. A means of assessing the degree of obstruction of the ureter involved in retroperitoneal fibrosis by perfusion studies is described and the results in 3 patients are discussed. This type of urodynamic assessment is recommended when the extent of lysis of the ureter is in question.


External sphincterotomy in traumatic and non-traumatic neurogenic bladder dysfunction. Experience with external sphincterotomy in 40 patients with traumatic and non-traumatic neurogenic bladder is reviewed. The procedure is a safe, reliable technique designed to establish a balanced neurogenic bladder in patients with detrusorsphincter dyssynergia. Spincterotomy should be performed in most patients before consideration of supravesical diversion.


Nephrogenic adenoma of the bladder.

Nephrogenic adenoma of the bladder. Nephrongenic adenoma is a rare, apparently benign lesion of the bladder, occuring predominantly in young male subjects. Although it may occur spontaneously several cases have developed after trauma to the bladder. Histologically the lesion consists of tubules lined by a single layer of cuboidal or columnar epithelium resembling renal tissue and should be regarded as an unusual form of metaplasia of the bladder urothelium. Treatment by parenteral administration of broad-spectrum antibotics and diathermy excision has produced satisfactory results. Long-term followup is recommended.


Paraganglioma of the bladder: report of a case. A patient with a most unusual neoplasm of the bladder, a paraganglioma, is presented herein. A combination of episodes of hypertension during or immediately after micturition associated with hematuria is almost pathognomonic of this condition. The patient presented with hematuria only. Less than 7 per cent of all reported cases have a malignant course. The proper treatment appears to be partial cystectomy with wide margins of the affected area, being prepared for wide fluctuations in blood pressure in those patients who have elevated catecholamine levels preoperatively.


Urethral adenocarcinoma (possibly originating in the glands of Littre). Adenocarcinoma involving the bulbomenbranous urethra is a rare disease. This disease is describe in a 30-year-old man and the surgical management is detailed. The adenocarcinoma described seems to have arisen from the periurethral glands of littre. Despite the radical nature of the tumor excision, it was possible to spare the distal penis in order to achieve a more normal appearance of the external genitalia.


Testicular scanning: a new modality for the preoperative diagnosis of testicular torsion. A simple, safe and rapid scanning procedure using 99-m technetium is described for the diagnosis of torsion of testicles. The procedure is especially useful in the adult with an enlarged scrotum of recent origin in whom the surgeon cannot clinically differentiate torsion of the testicle from epididmitis. It is not suggested that this procedure replace immediate scrotal exploration in the acutely illpatient.


Torsion of the testis diagnosed by ultrasound. An ultrasonic method to diagnose acute testicular torsion is presented. With the doppler  principle the presence of absence of intratesticular arterial pulsation can be demonstrated. In 5 patients with acute testicular torsion and 10 patients with epididymitis a correct ultrasonic diagnosis was made. In long-standing torsions some arterial pulsation may be present.


The nitrofurans as sperm immobilizing agents. In certain critical concentrations nitrofurantoin sodium and nitrofurazone cause sperm immobilization. Intraoperative was irrigation with these solutions in 16 patients produced sterility in the immediate postoperative period. This procedure minimizes time-consuming postoperative sperm analyses. Moreover, in underdeveloped countries where postoperative followup is difficult to obtain, this procedure would provide an additional positive factor in an attempt to ensure sterility.


A clinical study of vasectomy failure and recanalization. An analysis was made of the 26 unsuccessful operations from the 2,197 vasectomies performed in a non-profit medical facility. Hhe operations were performed by 6 physicians and significant differences were found in the failure rates. In all instances the tissue removed proved to be vas deferens when examined histologically. Two factors seem to account for the differences of failure rates amoung the physicians; 1) the lenght of vas excised and 2) the character of thechnique. Phsicians with a high rate of success removed a significantly longer section of vas than physicians exhibiting higher failure rates. At least  15 mm. of vas should be excised to maximize the success of the procedure. Excised vas segments less than 15 mm. had up to a 25-fold greater incidence of failure. Although considered of secondary importance, good surgical technique subjectively  measured by the minimal amount of accessory tissue attached to the excised vasa was also considered to aid in reducing the number of vasectomy failures.


Bilateral renal aspergillosis.

Bilateral renal aspergillosis. The recent increased use of steriods, immunosuppressive agents and cytotoxic drugs has been associated with a rise in the incidence of significant fungal disease. The first case of bilateral renal aspergillosis without disseminated involvement is reported. A multitherapeutic approach, including surgical evacuation of masses of hyphae, parenteral antimycotic chemotherapy and topical instillations of amphotericin B, were necessary to clear the kidneys. Newer systemic agents such as 5-fluorocytosine and rifampicin were also used. Treatment of fungal infections of the urinary tract is discussed.


Angiographic management of bleeding secondary to genitourinary tract surgery. Angiographic methods were applied to control bleeding in 2 patients following genitourinary tract operations. In 1 patient hemorrhage into the prostatic bed after needle biopsy of the prostate was controlled with embolic occlusion of branches of the hypogastric arteries. In the second patient bleeding from the ileum following ileal loop cutaneous diversion was controlled with the infusion of vasopressin into the superior mesenteric artery. Therefore, angiography offers an attractive alternative to an operation in the management of postoperative hemmorrhage from the genitourinary tract.


Renal pelvic tumors.

Renal pelvic tumors. A study was made of 35 patients with tumors of the renal pelvis. Tumors were indipendently graded and staged by a newly proposed method. The method of staging correlated well with grading of renal pelvic tumors and bore a direct relationship with prognosis. The high incidence of associated urothelial tumors, especially on the involved side, mandated radical nephroureterectomy including a bladder cuff as the treatment of choice.


The removal of renal carcinoma thrombus extending into the right atrium. A relatively simple technique is described for removal of intra-atrial extension of renal cell carcinoma. A balloon catheter is inserted through an incision in the inferior vena cava and inflated in the atrium. Coupled with an elevation of venous pressure this procedure provides control beyond the tumor and a mechanism for withdrawal of the tumor to the abdominal venotomy for extraction. Radical nephrectomy and resection of directly invaded cava complete a definitive surgical procedure. The technique has proved satisfactory in 2 patients.


Retroperitoneal fibrosis with intrinsic ureteral involvement. Two cases of idiopathic retroperitoneal fibrosis are discribed. In both cases intrinsic involvement of the ureteral muscularis was found, which is in contradistinction to the classical description of ureteral encasement or compression by the process without actual invasion. Surgical procedures, in addition to ureterolysis, may be required.


Antireflux ureteroileal anastomoses in humans. It is now apparent that the standard total cystectomy and Bricker procedure, by eliminating the ureterovesical junction with its reliable antireflux mechanism, markedly reduces the protection of the upper urinary tracts. In an attempt to restore this protective principle, the subserosal ileoureteral antireflux procedure was devised and subsequently performed in 6 patients with infiltrating bladder carcinoma. The operation is technically easy to perform, it is not time consuming and has consistently prevented ileoureteral relux without causing obstruction. There have been no serious complications, no episodes of pyelonephritis or urinary leakage and no evidence of renal functional deterioration as measured by serum creatinine and IVP. Although it is still to early to predict the eventual long-term results our experience with the first 6 patients with the antireflux ileoureteral anastomosis suggests that this modification of the original Bricker procedure offers superior protection to the upper urinary tracts.


The effect of digitalis on the bladder in man. The effects of intravenous digitalis on the bladder were investigated in 36 patients. Digitalis consistently decreased the bladder capacity and in some it increased the intravesical pressure. The significance of these findings and its clinical applications are discussed.


Radical cystectomy for carcinoma of the bladder: 16 years of experience. The records of 141 consecutive patients who underwent simple or radical cystectomy between 1955 and 1971 were reviewed. Symptoms, interval before diagnosis, and stage and grade of lesion were analyzed and correlated with survival rates. Although stage was the most critical determinant of survival, grade, presence or absence of dysuria and delay in diagnosis were also important. Preoperative radiotherapy caused downstaging in 41.2 per cent of patients, with complete disappearance of tumor in some. Postoperative complications from cystectomy and from various forms of urinary diversion were correlated with the type of diversion, type of ureteral anastomosis, radiotherapy and stents. Improved operative techniques, method of fluid balance, and preoperative and postoperative care have led to a progressively decreased operative mortality in patients with carcinoma of the bladder.


Post-obstructive diuresis: a varied syndrome. A prospective study was undertaken to define the clinical features, natural history and etiology of post-obstructive diuresis. Studied in detail were 8 patients with a massive diuresis after relief of urinary tract obstruction. We found that urea mediated osmotic diuresis, natriuresis owing to elimination of retained sodium from the obstructed phase, tubular defects in sodium reabsorption, renal unresponsiveness to antidiuretic hormone and iatrogenic factors may play varying roles in each individual diuresis. Overzealous fluid replacement should be avoided.


The eradication of intraurethral condyloma acuminata with 5 per cent 5-fluorouracil cream. Twenty patients have had successful eradication of intraurethral condyloma acuminata by the intraurethral instillation of 5 per cent 5-fluorouracil cream. Avoidable complications are scrotal irritation and meatitis. Endoscopic examination is delayed until distal lesions have been eradicated. The method is safe, inexpensive, painless, and effective.


Granulomatous orchitis.

Granulomatous orchitis. Three cases of an uncommon but extremely interesting inflammatory process are reported. As our discussion indicates, many questions remain unanswered. It is important to recognize this condition because it is often initially thought to be neoplastic. The disease is characterized by acute recurring exacerbations over a long period and is often associated with urinary tract infections or trauma. The testis is almost always extremely firm and frequently enlarged and tender. We believe that orchiectomy is indicated in most instances, except in extremely young individuals and those in whom the only remaining testicle is involved. Biopsy is probably sufficient in the latter case unless symptoms persist. The final diagnosis must rest on the exclusion of other granulomatous diseases as well as the microscopic picture.


Hemangioendothelioma of the testis.

Hemangioendothelioma of the testis. A case of hemangioendothelioma of the testis is reported. Although the tumor has been reported in almost all organs and tissues, this is the first case involving the testis to be found in the literature. A distinction is made between the benign and the malignant form of the tumor. Hemangioendothelioma of the corpus cavernosum is discussed.


The surgical management of scrotal and penile lymphedema. Presented here are 3 cases of penile and scrotal lymphedema of different etiologies and the results of surgical treatment. Also presented is a brief discussion of the etiology, pathophysiology and surgical techniques useful in treating scrotal and penile lymphedema.


Preliminary evaluation of urinary polyamines in the diagnosis of genitourinary tract malignancy. Normal ranges for urinary polyamines have been obtained. Non-malignant genitourinary tract disease is not associated with elevated urinary polyamines. A high correlation exists between the presence of active urologic cancer and elevated urinary excretion of polyamines. Post-treatment polyamines correlate with the continued presence or absence of genitourinary tract malignancy.


Complications of megaureter repair in children. In the last 14 years 160 megaureters were repaired in 110 patients. Complications encountered are described as well as suggestions which can help prevent and correct them.


Fetal vesicoureteral reflux.

Fetal vesicoureteral reflux. Intrauterine fetal vesicoureteral reflux has been demonstrated in a 25-week fetus. A voiding cystourethrogram when the patient was 1 year old showed persistence of the bilateral reflux. No urinary tract infectious have been documented. A survey of other physicians performing fetal transfusions indicates that fetal cystograms are infrequently obtained and that vesicoureteral reflux has been observed by ourselves and one other contributing physician. The incidence of reflux in fetal cystograms reviewed appears to be higher than would be expected when compared to normal premature babies, newborns, infants and children. This procedure provides an unusual opportunity to document intrauterine fetal vesicoureteral reflux and later obtain followup cystourethrograms in these children to determine the resolution or progression of this urinary tract abormality.


Carcinoma of the bladder in children.

Carcinoma of the bladder in children. Apparently, epithelial bladder tumors in children differ markedly from their more malignant counterparts in adults. The childhood bladder epithelial tumors morphologically are of a lower grade malignancy, show no evidence of invasion and no tendency to recur. Therefore, all cases thus far reported have resulted in a benign clinical course with a 100 per cent survival rate. These childhood epithelial bladder tumors apparently do not recur, which is in sharp contrast to their adult counterparts. However, this should not lessen the urologist's obligation to provide routine cystoscopic re-evaluation.


Carcinoma of the bladder in young children: report of 2 cases. Papillary epithelial tumors in the bladders of a 2-year-old and a 3-year-old child are described because of the rarity of the condition in children and some unusual features.


A new dimension in the diagnosis of posterior urethral valves in children. Infants with posterior urethral valves may seem to have diverse and unrelated symptoms when, in fact, the clinical findings are all related to the primary effect of the valves during various stages of early growth. In some, prenatal urinary obstruction leads to such severe oligohydramnios that the fetus is stillborn. Others, somewhat less affected, are born alive but have severe respiratory distress from hypoplastic (stiff) lungs and die of respiratory problems. Still others can be associated with massive ascites and urinomas, and be stillborn or die soon after birth. In less severe cases the neonates may have unexplained respiratory distress with pneumomediastinum or pneumothorax as the only indication of obstructive urologic disease with deficient urinary output. Urinomas or ascites may later develop beyond the neonatal period as the post-natal obstructive effects of the valves accumulate and the urinary system ruptures and decompresses itself. Finally when the urinary system does not decompress itself, the back pressure can lead to rapid and progressive renal damage until the kidneys can no longer concentrate urine and lose water. The infant becomes dry, acidotic and paradoxically at this stage, puts out large quantities of dilute urine. Physicians caring for infants should be highly suspicious of posterior urethral valves in any male infant with unexplained respiratory distress or metabolic derangements, abdominal distension or flank masses.


A search for blood protozoans in the American woodcock. Smears were prepared from heart blood of 55 woodcock collected in central Maine between spring and fall, 1972 and 1973. Peripheral blood taken from the wings of 41 of these birds also was examined. Examination of stained films revealed no infected blood cells. Samples of heart blood from 35 of the 41 woodcock were injected into young ducks, quail, and a gull. Plasmodia were not seen in inoculated birds.


Cardiovascular calcification associated with nephritis in a badger. Calcification of the endocardium of the left artrium, and to a lesser extent the media of the pulmonary artery and aorta, was found associated with nephritis in a badger (Taxidea taxus).


Arthropathy in white-tailed deer and a moose. Degenerative lesions were found in the skeletal system of 20 to 128 white-tailed deer (Odocoileus virginianus) examined. Similar changes were found in an aged male moose (Alces alces). Arthropathy involving the stifle joint was present in 60% (15/25) of male deer 4 years of age or older, and in 16.7% (4/25) of females in the same age range. Vertebral osteophytes were not found in any of 62 female deer, nor in male deer less than 6 years of age, but were present in 50% (7/14) of males 6 year of age or older. The possible etiology and significance of the conditions are discussed.


Paragonimus kellicotti infection in wild carnivores in southwestern Ontario: I. Prevalence and gross pathologic features. Paragonimus kellicotti Ward, 1908 was recovered from 16 of 105 mink (Mustela vison), 14 of 244 striped skunks (Mephitis mephitis), 10 of 446 red foxes (Vulpes vulpes), 1 of 31 coyotes (Canis latrans), 0 of 326 raccoons (Procyon lotor) and 0 of 8 weasels (Mustela spp.) collected from southwestern Ontario. The majority of carnivores harboring P. kellicotti was collected from two counties (Huron and Bruce) bordering the east shore of Lake Huron where 6.0% of the animals (excluding raccoons) were infected . There were extensive adhesions between the lungs and parietal pleura and dorsal mediastinal pleura in 25 of 301 raccoons collected from these two counties. This lesion was thought to be associated with a reaction to migrating P. kellicotti. This is the first time P.kellicotti has been reported in the striped skunk and red fox from Ontario and apparently the first record of this parasite in the coyote.


Venezuelan equine encephalomyelitis in pheasants and chukars. Phesants (Phasianus colchicus) and chukars (Alectoris graeca) were inoculated with Venezuelian equine encephalitis virus. Antibody titers reached a peak 2 weeks postinoculation and the declined. Viremia was of short duration, clinical signs were not detected, and unionculated cage mates did not develop antibody titers.


Renal fibrosarcoma in the northern fur seal. A 2-week-old northern fur seal female pup (Callorhinus ursinus) found dead in the Pribilof Islands had an irregular mass at the anterior pole of the right kidney. Histopathological examination revealed a fibrosarcoma.


Contagious ecthyma in bighorn sheep and mountain goat in western Canada. Contagious ecthyma (CE) is reported in bighorn sheep (Ovis c. canadensis) from several national parks in western Canada and in moutain goat (Oreamnos americanus) from Kootenay National Park, British Columbia. (This is the first report of CE in mountain goat.) Diagnosis was based on clinical signs, histopathology, transmission experiments and the demonstration of a proxvirus with the electron microscope. The infection was transmitted from wild to domestic goat, but not to domestic sheep. Most infections, some of them severe, were found in lambs and kids. Clinical signs of disease were similar to those seen in domestic sheep and goats. General body condition was poor and animals had difficulty feeding normally. All infected herds had prolonged contact with areas where salt was provided artificially (i.e., salt blocks, highways and campgrounds). Fewer infected sheep were observed annually when salt blocks were removed from Jasper National Park.


Tuberculosis in lesser flamingoes in Kenya. Four cases of tuberculosis are recorded in lesser flamingoes (Phoeniconaias minor) from Lake Nakuru, Kenya. The clinical, pathological and microbiological findings are given and the possible significance of the infection in this species is discussed.


Further observations on rangiferine brucellosis in Alaskan carnivores. Antibodies against rangiferine brucellosis, Brucella suis type 4, are commonly found in the serum of various domestic and wild alaskian carnivores which feed on caribou, Rangifer tarandus granti, arctic Alaska. Sled dogs from five native villages on the range of the Artic caribou herd, but not from two villages on the the range of the Porcupine caribou herd, are commonly infected. Wolves (Canis lupus) and red foxes (Vulpes fulva) are less commonly infected. About 90% of the grizzly bears (Ursus arctos horribilis) associated with the Artic caribou herd and 30% of those associated with the porcupine caribou herd show serologic signs of exposure to Brucella, presumalby the enzootic strain present in Alaska caribou. This is the first evidence of natural Brucella infection in bears. It is concluded that infection of predators by enzootic strains of Brucella present in prey species (e.g., ruminants) is common to many areas of the world. Evidence from the literature and unpublished experimental data suggest that such infections may intefere with reproduction in wild species, but additional study is needed to clearly resolve this question.


Seasonal variations in total serum protein concentration in an estuarine raccoon population. Total serum protein (TSP) levels were recorded for the adult cohort in a population of southern Florida raccoons (Procyon lotor marinus) for a period of 1 year. TSP levels were found to fluctuate seasonally, with autumn levels being the highest and spring and summer levels the lowest. Values for males tended to be higher than those for females. There may be a correlation between mean TSP levels and mean body weight. In 10 male raccoons recaptured during the study period, the same pattern of fluctuation in TSP levels was observed.


Psoroptic mange in a Wapiti.

Psoroptic mange in a Wapiti. In northern Idaho, a 10-year old wapiti(Cervus canadensis nelsoni) died showing signs of ataxia and alopecia. Examination of dermis revealed infestation with Psoroptes equi var. cervinus.


A fourth pair of mandibular molars in a white-tailed deer. A fourth pair of mandibular molars in a white-tailed deer(Odocoileus virginianus) was located posterior to the third pair. There was a distinct gap between the third and fourth molars on both left and right sides.


Some hematological values of free-ranging African elephants. Blood samples were collected from 23 free-ranging African elephants(Loxodonta africana) in Tanzania. Red and white blood cell counts, white blood cell differential, hemoglobin, blood copper, and blood inorganic phosphate were determined. No correlation of any of these measurements with age and sex was discernible, except that the total white count was significantly higher in females than in males in all age groups. The findings are compared with those previously reported for captive and free-ranging African elephants.


Mortality factors in whistling swans at Lake St. Clair, Ontario. Post mortem examinations of 31 whistling swans (Olar columbianus) collected from the Lake St. Clair marshes in the spring of 1972 indicated that lead toxicosis and filariasis (Sarconema eurycerca) were the main causes of mortality.


Some hematologic and blood chemistry values in two herds of American bison in Kansas. The data presented are compiled from two herds of American bison (Bison bison) in Kansas. In this study there were differences in the mean values of white blood cell count, neutrophil percentage, lymphocyte percentage and cholestrol, alkaline phosphatase, specific glutamic-oxalacetic transaminase concentrations between the age groups of animals under 2 years of age and bison over 2 year old. Differences in the two age groups paralleled those found in Jersey and Hereford cattle. Packed cell volume and hemoglobin concentrations was considerably higher than found in domestic Bovidae. More data is needed from other bison herds in this country to better describe the range of normal variation in individuals, population and age groups of B. bison.


Echocardiographic diagnosis of endocardial cushion defects. Sixteen patients with endocardial cushion defects were studied by echocardiography and ultrasonocardiotomography. Three characteristic findings, common to both complete and partial forms, were observed. They were the ostium primum defect of the interatrial septum, the left ventricular outflow narrowing and the atrioventricular valve abnormalities which are the anatomic bases of endocardial cushion defects. Several additional findings were observed in patients with complete form. Most strikingly, the anterior leaflet echo locating in the left ventricle had the direct connection to that in the right ventricle without the interposition of the interventricular septum by echocardiogram. Ultrasonocardiotomogram, on the other hand, demonstrated beautifully the common anterior leaflet and the high inteventricular septal defect. There were, in addition, the absence of the paradoxical motion of the interventricular septum and the diffuculty in detecting the interatrial septum. The intact interatrial septum continuous with the anterior mitral leaflet was demonstrated in patients with the interventricularseptal defect of atrioventricular canal type, in which there were the typical abnormalities in the atrioventricular valves and the left ventricular outflow narrowing as well. This study indicates that ultrasonic examination may provide a direct, yet noninvasive method in the diagnosis of various types of endocardial cushion defects.


Renal hemodynamics and medullary osmolal gradient in ischemic acute renal failure in rabbits. The effects of 2 hours of renal artery occlusion were studied in previously uninephrectomized rabbits. Oliguric renal failure by arterial clamping was produced. Renal blood flow was maintained during observation periods, except for an early decrease in outer cortical blood flow without change elsewhere. During the oliguric stage medullary osmolality was markedly diminished, concomitantly with reduced (U/P)osm. Cin, EPAH and sodium reabsorption were decreased, accompanied by tubular necrosis and intratubular casts. During the early diuretic stage Cin, medullary osmolality and (U/P)osm were still reduced. Intratubular casts disappeared while regenerated tubular cells were focally observed. Two weeks after the occlusion, improved Cin, EPAH, sodium reabsorption, medullary osmolality and (U/P)osm, and regenerated tubular epithelium were found. In 7 weeks Cin and EPAH had returned to the preclamping values whereas medullary osmolality remained decreased with the appearance of medullary fibrosis. (U/P)osm was not completely restored. The findings indicate that during the oliguric stage of acute renal failure of rabbits  renal blood flow is maintained, except for a decrease in outer cortical flow, and urine concentrating ability is restored more slowly than other measured functions.


Effects of radiopaque material on coronary vascular reserve. The relationship between the increase in coronary blood flow (CBF) following contrast material injection and that following temporary occlusion was studied in the anesthetized dogs. The peak flow following a contrast injection was almost equivalent to the peak reactive hyperemia flow following a 10 sec occlusion (r equeals 0.86). An increase in coronary sinus blood oxygen pressure (Pcso2) occured in associated with an increase in CBF. Administration of dipyridamole diminished the increment of CBF following contrast injection with little changes in Pcso2. Thus, in the coronary system the increase in CBF after contrast injection, similar to that observed after temporary occlusion, is related to coronary vascular reserve and measurement of Pcso2 after coronary arteriography might be an aid to evaluate the coronary vascular reserve.


Aneurysmectomy for symptomatic supraventricular tachycardia associated with ventricular aneurysm. A case of left ventricular aneurysm associated with repeated supraventricular tachyarrhythmias was successfully treated by ventricular aneurysmectomy. Ventricular aneurysmectomy should be considered for supraventricular tachyarrhythmia as well as ventricular tachycardia, if they are symptomatic and refractory to medical therapy.


Factors influencing sodium and water excretion in uremic man. Urinary excretion of sodium and water was investigated in patients with chronic end-stage renal disease before and after three different experimental manipulations: reduction in urea solute load by dialysis while extracellular fluid volume (ECFV) was maintained, dialysis without alteration in urea solute load or ECFV and reduction in ECFV without alteration in urea solute load. Sodium and water excretion significantly declined in association with a reduction in both urea solute load and ECFV, but not during a dialysis when reduction on both of these indexes was prevented. The excretory changes occurred in the absence of any alteration in creatinine clearance. The studies suggest that both solute load and the degree of extracellular fluid volume expansion contribute independently to the rate of sodium and water excretion in chronic renal disease. It is concluded that in any given patient the overall excretion of sodium and water is directly influenced by a number of factors including the solute load, the degree of ECFV and the glomerular filtration rate.


Focal glomerular sclerosis in nephrotic patients: an electron microscopic study of glomerular podocytes. Renal biopsy specimens of 16 adult patients with nephrotic syndrome and focal glomerular sclerosis were examined by light and electron microscopy. Particular attention was paid to alterations of podocytes. Except for loss of foot processes, five patients had no podocyte changes, five had mild changes and six had severe changes. Of the last group (group III), four patients were heroin addicts, the fifth had infectious mononucleosis and the sixth, an apparent idiopathic disease; five patients were males, 16 to 25 yr old. Podocyte changes consisted of cytoplasmic degeneration, detachment of epithelial cells from basement membranes, with filling of resulting space by cell debris and new membranes. Underlying capillaries were often collapsed. Repeat biopsies in three patients in group III revealed progression of lesions, paralleling rapid clinical deterioration. It is concluded that some cases of focal glomerular sclerosis are associated with severe damage to podocytes which may be caused by drugs, infection or unknown factors and may contribute to the development and progression of the glomerular lesions.


Oxidative metabolism of the normal rat glomerulus. Glomeruli from adult normal male Wistar rats were obtained by teasing a cortex slice with stainless steel needles. The enzyme content and the morphologic aspect of these glomeruli were assessed as a preliminary step to further metabolic studies. Robinson's medium appeared to be the most suitable medium. There was no loss of glutamic dehydrogenase, glucose-6-phosphate dehydrogenase or acid phosphatase. Lactate dehydrogenase was lost to about 50%. Electron microscopy showed morphologic signs of damage in the podocytes. The glomerular oxygen uptake was measured with the help of the Cartesian diver technique, using approximately 20 glomeruli per assay. The endogenous respiratory rate was linear for at least three hours. The endogenous respiratory rate was linear for at least three hours. The mean dry wt of lyophilized glomeruli was determined for 13 rats for which the glomerular oxygen uptake had been measured, and these data showed a glomerular Q-02 of 4 mul/hr/mg of dry wt. The following substances were tested for their influence on the oxygen uptake: acetate, alpha-oxoglutarate, citrate, oxalacetate, glutamate, alanine, all 10 mM; succinate, 2.5, 5 and 10 mM; glucose, 5, 10 and 20 mM; fructose 10 and 20 mM; and palmitate. Citrate increases the O-2 uptake/hr/glomerulus by 30%; glucose, 20 mM, by 30%; and succinate, 2.5 mM by 50% and 10 mM by 190%. In a Robinson's medium containing 35 mg of albumin/ml, the endogenous respiration is not different from that obtained in the inorganic medium but the oxygen uptake is increased 26% by glucose, 10 mM. From these data, it can be concluded that the oxygen uptake of the glomerulus is small. This fact explains its resistance to anoxia. The systematic investigation of possible substrates indicate that glucose, citrate and succinate may play a role in supporting this small oxidative metabolism.


Lack of relationship of potential difference to fluid absorption in the proximal renal tubule. Fluid absorption by isolated perfused rabbit proximal convoluted tubules is accompanied by an electrical potential difference (PD), negative in the lumen, when the tubule is bathed by rabbit serum and perfused with an ultrafitrate of that serum. In contrast the PD is positive when the perfusate composition approximates that of fluid in the late proximal tubule in vivo, which lacks glucose, amino acids and bicarbonate. The principal purpose of the present studies was to investigate the characteristics of fluid absorption under these conditions. Proximal convoluted tubules were dissected from rabbit kidneys and perfused in vitro. When the PD was positive, the mean net fluid absorption was 81 nl mm minus 1 min minus 1. The positive PD is caused by a chloride concentration difference across the tubule epithelium (higher in the lumen than in the bath). Elimination of the chloride concentration difference by replacing the bicarbonate in the bath as well as in the perfusate with chloride caused the PD to fall to zero without a significant change in the rate of fluid absorption. Therefore, neither the positive PD nor the chloride concentration difference is significantly related to the fluid absorption. Ouabain inhibited fluid absorption under all of the above conditions, making it likely that the fluid absorption is due to active sodium transport. Although the results are consistent with the generally accepted view that active sodium transport is a major driving force for fluid absorption, the mechanism of anion (chloride) transport is uncertain owing to the lack of correlation between fluid absorption and the transepithelial PD.


[Physical work capacity and oxygen requirements of rats during physical exertion following prolonged hypokinesia]. The white rats exposed to 60 and 100 day hypokinesia showed a substantial and progressive decline in the tolerance to a maximum physical load. This was accompanied by disorders in the regulation of the oxygen balance: during load oxygen requirements were mainly met by the oxygen debt. The above changes that followed a 100 day hypokinesia returned to the normal two months later.


[Glycemic indices in animals at different stages of hypokinesia and with administration of glucose, adrenaline and insulin]. The sugar content in the blood was measured (and sugar curves were plotted) in healthy rats and in rats during the 15, 30, 60 and 90th hypokinetic days after they were injected with glucose at a dose of 4 g/kg, epinephrine at a dose of 150 mg/kg and insulin at a dose of 0.5 u/kg. The three glycemic parameters were determined: 1) the coefficient of maximum hyper- and hypoglycemia; 2) the intensity of hyper- and hypoglycemia and 3) the hyper- and hypoglycemic limit. An analysis of the sugar plots and the above coefficients showed an increased sensitivity to insulin, an elevated tolerance to glucose and a less distinct response to epinephrine.


[Physiologo-hygienic basis for the construction of individual equipment for preventing the adverse effects of weightlessness]. In order to prevent the unfavourable effect of weightlessness, it is recommended to use individual suits for long wear. These include a preventive pressure suit which provides an axial pressure on the skeleton and moments of forces during movement, and a preventive vacuum suit which provides lower body decompression. The suits ensures the conditions for the function of the musculoskeletal apparatus and the cardiovascular system which are close to those on the Earth.


[Effect of hypokinesia on the development of osteoporosis]. The skeletal changes in the rabbits exposed to a 90-day hypokineisa have been examined. Osteoporosis has been diagnosed using an X-ray investigation which included rentgen-densitometry and rentgen-grammetry. The process involved the thinning of the cortical layer and a decrease of the bone density. The importance of the above methods for an objective evaluatuon of osteoporosis is discussed.


[Energy expenditures of the "Soiuz-9" space crew during an 18-day flight]. The paper presents a method for studying metabolism on the basis of the changes in the partial pressure of CO2 in the space cabin which takes into account the performance of absorbers--superoxides of alkali metals. With the aid of this method the oxygen consumption by the crew was measured during the flight. The average energy expenditure by crew members was 2300 kCal per day with variations from 2020 to 3050 kCal per day and the average oxygen consumption was 22.0 nl per hour with variations from 17.6 to 26.6 nl per hour. The level of oxygen consumption by the crew showed a certain periodicity which was attributed to the energy expenditures during physical exercises. The oxygen consumption during the weightlessness adaptation (during the first 6 to 7 days) was reduced to 20 nl per hour on the average. No significant changes in the basal metabolism were found in the crew members throughout the flight.


[Nature of self-regulation of the blood circulation as a criterion of body tolerance to external factors]. With respect to the proportion of the theoretical and actual values of the cardiac output and the peripheral resistance 98 young healthy men were divided into three groups: 42 with the mixed type, 31 with the cardiac type and 25 with the vascular type of the circulation regulation. The environmental factors of a small size chamber gave rise to the changes that were the greatest in the subjects with the cardiac regulation and the least in the subjects with the mixed regulation. The subjects with the vascular type of regulation were those who showed varying tolerance to the environmental effects. It is suggested that the type of circulation regulation in the occupational selection as an indicator of the body tolerance to the environmental effects should be suggested.


[Perception of 2-dimensional space coordinates during prolonged experimental hypokinesia]. The effect of a 30-day hypokinesia on the perception of the subjective optic vertical (SOV) was studied. The test subjects who were in the antiorthostatic position (at an angle of 96 degrees to the vertical) showed the greatest changes in the SOV perception and illusive perception of the spatial position of the body. During the first two days of the experiment and ten days after it they displayed a 1.5-fold increase in the error of the SOV perception. In addition, they exhibited an asymmetrical perception of the SOV on the right and left side. In all cases the direction of the SOV displacement from the true line coincided with the body position. The test subjects who were kept at an angle of 84 degrees to the vertical (orthostatic hypokinesia) demonstrated only illusions of the body position during the first hypokinetic day and a unilateral increase in the error of the SOV perception after the experiment. The test subjects who underwent preventive treatment following antiorthostatic hypokinesia (at an angle of 94 degrees to the vertical) exhibited no asymmetry and an insignificant error in the SOV perception. These findings are discussed with regards to the changes in the function of pressuretension receptors and disorders in the skeletal tone during hypokinesia.


[Effect of hypokinesia and lowered barometric pressure on the tolerance of animals to the action of ethyl acetate]. Experiments were carried out to study the resistance of rats to an acute effect of ethylacetate vapors at concentrations of 25 to 69 g/m-3 after their 20-day exposure to hypokinesia and 20-day exposure to altitudes of 3200 and 5000 m. The effect of ethylacetate at concentrations of 47 and 10 mg/m-3 on the rats in a chronic 90-day experiments was also investigated. After an exposure to hypokinesia and hypoxia the sensitivity of the rats to an acute effect of ethylacetate vapors increased 2- or 3-fold. The chronic inhalation of the substance by the hypokinetic animals brought about disorders in the brain microstructure and renal pathology. The poisoned animals that retained normal motor activity displayed serious pathological changes in the thyroid gland. It is concluded that changes in the reactivity of the animal and human body to chemical agents must be taken into consideration when developing standards for the space cabin atmosphere.


The use of cation-bound microsomes for studies of protein synthesis. Low speed microsomes prepared by centrifuging at 30 times g for 10 minutes after interaction with Ca-2plus or Mg-2plus are comparable to high speed microsomes (105,000 times g) with respect to incorporation of 3-H-leucine in vivo, protein-synthesizing ability in vitro, and the pattern of ribosomal profiles on a linear sucrose density gradient. Low and high speed polyribosomes, i.e., those isolated with and without Ca-2plus or Mg-2plus from a postmitochondrial supernatant, also displayed similar protein-synthesizing capability in vitro and identical profiles on a linear sucrose density gradient. Other divalent cations, such as Ba-2plus, Ni-2plus, Co-2plus, Cu-2plus, Fe-2plus, Hg-2plus, Zn-2plus, and Sr-2plus, inhibited enzyme activities and depressed protein synthesis. Low speed microsomes may now be deemed suitable for all studies of microsomal function.


[Informativeness of pulse bloodfilling of auricular helical vessels for evaluation of human tolerance to plusGz acceleration]. The possiblity of using photoelectric plethysmography as an objective method to assess the human tolerance to accelerations was examined. The tolerance of 40 young healthy male test subjects to plus GZ accelerations of 3, 5, 6 and 7 g with an increase gradient of 0.4 g/sec and a plateau time of 30 sec was measured. The test subjects induced an arbitrary tension of the abdominal and leg muscles in order to better tolerate accelerations. When the tolerance reached its limit (as judging by optic disorders), the auricular pulse amplitude decreased 4-fold in 84% test subjects. The threshold value of the amplitude can be used as an informative indicator of a group and individual tolerance to plus GZ accelerations. A portable photoelectric plethysmograph has been designed for operational medical control of the health state of pilots inflight.


[Effect of intellectual evaluation of the situation on emotional reactions in pilots]. Emotional reactions of pilots to a real emergency were studied during simulations of critical and dangerous situations. The vague information on the situation was shown to be the most important emotional factor in such a case. The data have been obtained indicating that with lacking information the level of emotional stress depends on the mental assessment of the signals based on the previous experience and training.


Age-dependent changes on the state of aggregation of cartilage matrix. The state of aggregation of cartilage matrix and its variations with age have been studied by biochemical, cytochemical, and ultrastructural methods. Determination of proteoglycans and collagen in costal cartilage from newborn, 4-week-, and 4-year-old rabbits showed that marked changes occurred during the first 4 weeks, i.e., a 30 percent decrease in proteoglycan content and a 3-fold increase in collagen. No significant changes were observed thereafter. The extractability of the proteoglycans after treatment with 4 M guanidinium chloride varied drastically, depending upon the age of the animal. Whereas 73 per cent of the proteoglycans was extracted from the neonatal tissue, the yield from old tissue was only 10 per cent. It is suggested that the decrease in extractability with age is related to the increase in collagen content. Cytochemical observations demonstrated that, in the neonatal tissue, metachromatic staining of the matrix was lost after guanidinium chloride treatment, with the exception of chromotropic granules still present in the lacunae. In the 1-month-old animals, a general decrease in the staining reaction ensued, except in the perilacunar areas. In the extracted tissues, instead, the picture changed drastically in that metachromasia was decreased in the interterritory but was not modified, as in the neonatal tissue, in the areas adjacent to the cell nests. In the old tissue, the patchy and irregular staining, typical of the cartilage of this age, was not modified by extraction with the guanidium salt. At the ultrastructural level, the proteoglycans in the neonatal tissue appeared as granules of different size, the largest having dimensions of about 900 A, In the 1-month-old animals, degenerative changes were already observed in the chondrocytes, including loss of the perilacunar space, reduction of the endoplasmic reticulum, and an increase of intracellular glycogen and lipids. The proteoglycan droplets, so prominent at the neonatal stage, were no longer evident. In the older animals, apart from the many foci of mineralization, the chondrocytes were almost all degenerated and showed signs of extensive vacuolation and lipid infiltration.


[Dynamics of temperature rhythm phases in the course of rhythm inversion]. The process of inversion of the diurnal rhythm of the body temperature was studied on two test subjects during an altered work-rest cycle. The temperature changes during individual phases were investigated. With respect to certain phases it is concluded that the rate of rearrangement depended on the relationship between these phases and the level of the physical and mental activity of the body. The inversion of the temperature rhythm induced changes in those phases of the temperature curve in which the temperature should not have changed due to an altered work-rest cycle. When evaluating the completeness of the rearrangement of the diurnal rhythm of the body temperature brought about by an altered work-rest cycle, it is important to pay particular attention to the body temperature in the minimum phase and in the adjacent phases, since the rate of the rearrangement of the temperature rhythm in these phases can be the lowest.


Formation of anomalous lysosomes in monocytes, neutrophils, and eosinophils from bone marrow of mice with Chédiak-Higashi syndrome. Chédiak-Higashi syndrome, a rare autosomal recessive disorder occurring in man, beige mice, and other homologues, is characterized by abnormally large lysosomes in many cell types. The formation of these anomalous lysosomes in developing monocytes, neutrophils, and eosinophils in beige mouse bone marrow, as well as lysosomal formation in the corresponding normal cells from C57 Black mice, was investigated by electron microscopy, together with a method for the demonstration of peroxidase activity. Localization of peroxidase reaction product was the same in both C57BL and beige mice. In promonocytes and in neutrophilic and eosinophilic proganulocytes, peroxidase reaction product was localized in lysosomes, in the perinuclear cisternae, all cisternae of the endoplasmic reticulum, and the Golgi succules. In the later stages of development, reaction product was localized only in the lysosomes. In promonocytes and progranulocytes from the C57BL mice, lysosomes apparently form from the inner Golgi succule. Fusion of newly formed lysosomes was occasionally seen. Lysosomal fusion was never observed in the more mature monocytes and eosinophils and was only rarely seen in mature neutrophils. In the beige mouse, lysosomes were formed as in the C57BL mice. However, in the beige mouse, fusion of newly formed lysosomes occurred frequently in promonocytes and neutrophilic progranulocytes. Lysosomal fusion was also frequently observed in the more mature cells. As a result of the continued lysosomal fusion, the mature monocytes, neutrophils, and eosinophils from the beige mouse contained fewer but often greatly enlarged lysosomes.


Quantitative morphometry of glomerulonephritis with crescents. Diagnostic and predictive value. Histologic patterns in the glomerular tufts in "Glomerulonephritis with many crescents" take three main forms: (1) compression and sclerosis of glomeruli, (2) necrotizing glomerulitis, and (3) proliferation with or without exudation. In the third group, histologic differentiation between patients with poststreptococcal glomerulonephritis with many crescents (AGN) and those with nonstreptococcal rapidly progressive glomerulonephritis (RPGN) may be impossible. In a retrospective study, quantitative morphometry of glomeruli effectively separated three patients with AGN from two patients with RPGN after the usual histologic and electron microscopic observations had failed. Parameters studied were areas of tufts and crescents and total number of cells and granulocytes in tufts and crescents. Surface areas of tufts and crescents were separately determined by photographing glomeruli, projecting and tracing outlines of tufts and crescents, and cutting out and weighing the tracings. The cell density of glomerular tufts (cell per 1000-sq. mum. area) was significantly greater in AGN than in RPGN when either total cell densities (17.64 plus or minus 0.41 versus 13.63 plus or minus 0.30) or total cells minus granulocytes (16.39 plus or minus 0.50 versus 12.99 plus or minus 0.52) were compared. The cell density in the tufts was 120 and 70 per cent greater than controls in AGN and RPGN, respectively. Exudation of inflammatory cells is contributory but not the major cause of hypercellularity in AGN. Follow-up studies with biopsies showed marked resolution in two of three patients with AGN, with normal blood urea nitrogen levels and focal scarring in the third, whereas the two patients with RPGN had either extensive scarring and reduced renal function or required chronic hemodialysis.


Influence of quantity of diet on protein synthesis of rats force-fed a threonine-devoid diet. The influence of the quantity of diet on protein synthesis of rats force-fed a complete diet or one free of threonine for 3 days. Protein synthesis was studied. The results revealed that rats force-fed an adequate amount (6.5 gm. per day) of threonine-devoid diet demonstrated increased hepatic and cardiac protein synthesis and decreased skeletal muscle and splenic protein synthesis in comparison to the results with rats force-fed the complete diet. In contrast, rats force-fed one-half the quantity (3.25 gm. per day) of the diets revealed no or small differences in protein synthesis of the liver, heart, gastrocnemius muscle, and spleen between the rats force-fed the complete and the threonine-devoid diets, although both of the one-half quantity groups had values which were decreased in comparison to those of rats force-fed the adequate quantity of complete diet. The tube feeding of L-threonine (60 mg.) to rats force-fed one-half the quantity of the complete or threonine-devoid diet on the 4th morning 2 hours before killing did not influence the results of organ protein synthesis. Protein synthesis was studied in vivo by measuring  14C-leucine incorporation into organ proteins and in vitro by measuring 14C-leucine incorporation into proteins by using postmitochondrial supernatants or microsomes of livers. Sucrose density gradients of hepatic polyribosomes were studied and revealed that there were more aggregated polyribosomes in rats force-fed adequate quantities of the experimental diets than in those force-fed the control diets. Rats force-fed one-half quantity of the complete and threonine-devoid diets revealed similar polyribosomal patterns which revealed more disaggregation than those in rats ofrce-fed the adequate quantity of complete diet.


Scanning electron microscopy of mast cell degranulation. Scanning and transmission electron microscopy were used to study the morphologic changes occurring in isolated mast cells after stimulation by compound 48/80. Two approaches were used to obtain cells for scanning electron microscopy. Cells incubated in suspension were collected on Millipore filters and air-dried from isopropyl alcohol. Other cells were allowed to attach to cover slips, stimulated, fix in situ, and dried from Freon at its critical point. Resting mast cells prepared by the latter method were covered by a tracery of shelflike ridges, whereas cells prepared by the first method had no ridges but presented a bumpy surface disclosing the underlying granules. Stimulation by compound 48/80 caused marked changes in the surface configuration of the cells, with loss of the regular pattern of ridges, extrusion of granules, and the appearance of openings leading to the interior of the cell. Correlation with transmission electron microscopy indicates that these openings lead to channels containing granules and lined by an intact membrane. These openings give extracellular cations access to granules within the confines of the cell, where the cations may exchange for histamine.


Virus-initiated septic shock. Acute death of Venezuelan encephalitis virus-infected hamsters. Hamster hematopoietic and lymphatic organs were studied sequentially by light and electron microscopy following Venezuelan encephalitis virus inoculation. In addition to extensive marrow and splenic necrosis nearly transmural necrosis of the ileum in Peyer's patch areas, with concomitant bacterial overgrowth, was noted. Viruses were observed ultrastructurally in reticular cells of Peyer's patches. In addition, bacterial blood cultures, consistent with an enteric origin, were generally positive in late stages of the infection. Reticuloendothelial function, measured by clearance of colloidal carbon, was significantly depressed in Venezuelan encephalitis virus-infected hamsters. It is proposed that the acute death of hamsters infected with Venezuelan encephalitis virus may be determined by the development of an endotoxic shock syndrome mediated by the extensive ileal lesions, coupled with impaired reticuloendothelial detoxifying function.


Pancreatic necrosis and regeneration induced by 4-hydroxyaminoquinoline-1-oxide in the guinea pig. A single intravenous injection of 4-hydroxyaminoquinoline-1-oxide, in a dose of 22.5 mg. per kg., induced marked necrosis of exocrine pancreas in inbred strain 13 guinea pigs within 48 hours. The pancreatic acinar cell necrosis was dose-dependent and was associated with a significantly elevated serum amylase level and reduction in amylase activity in the pancreatic tissue. The maximal necrotic changes in the exocrine pancreas were observed at 48 hours. After the necrotic phase, a striking regenerative response of pancreatic acinar tissue ensued. 3-H-thymidine autoradiographic studies revealed a labeling index of 28 per cent cells in several pancreatic lobules 66 hours after 4-hydroxyaminoquinoline-1-oxide injection. The acinar cell repair, as well as formation of the new acini in many pancreatic lobules, was complete by 84 hours. In some pancreatic lobules, pseudoacinar or ductular transformation was noted. The regenerative response in pancreatic acinar tissue and ductal epithelium induced by 4-hydroxyaminoquinolone-1-oxide in the guinea pig appeared to be severalfold higher than that noted during ethionine regeneration.


Scanning electron microscopy of the heart after coronary occlusion. The scanning electron microscope was used to study the ultrastructural alterations which occur following periods of myocardial ischemia of 30 minutes and 1, 2, 5, 10, and 24 hours. The alterations were compared with those seen with the transmission electron microscope. The early changes consist of swelling of organelles and clumping of nuclear chromatin. After 5 hours, disintegration of the transverse tubular system becomes apparent, and breakdown of the connections between the nucleus and the sarcoplasmic reticulum is seen coincident with distortion of the shape of the nucleus. It is suggested that the sarcoplasmic reticulum may be a part of the "endoskeleton" of the cell and may play a role in maintaining the shape and location of the nucleus. After 10 hours, extensive membrane alterations have occurred in many of the intracellular organelles. It is concluded that the changes seen with scanning electron microscopy are consistent with those seen with transmission electron microscopy.


Studies on the pathogenesis of cell injury: effects of inhibitors of metabolism and membrane function on the mitochondria of Ehrlich ascites tumor cells. The effects of cell injury on Ehrlich ascites tumor cell mitochondria were studied using two model injuries: (1) interference with cell membrane function and (2) inhibition of ATP synthesis with specific mitochondrial inhibitors. These studies indicate a good correlation between level of ATP and number of swollen mitochondria and between swollen mitochondria and occurrence of flocculent densities. No correlation existed between total ADP level and percentage of condensed mitochondria if all ADP values were considered, although a biphasic relationship appeared to exist between the number of condensed mitochondria and the levels of ATP. The study suggests a reproducible sequence of mitochondrial events following either inhibition of ATP synthesis or induction of cell membrane permeability with the nonpenetrating, membrane-damaging agent p-chloromercuribenzene sulfonic acid. These include the rapid appearance of condensed mitochondria, the reinflation of these to resemble orthodox mitochondria, and the occurrence of high amplitude swelling followed by flocculent densities or calcification, or both. Calcification did not occur when ATP synthesis was inhibited but did occur when the cell membrane was damaged with p-chloromercuribenzene sulfonic acid. It is suggested that the early mitochondrial condensation is related to loss of ions and water from the mitochondrial inner compartment following inhibition of active accumulation systems. It is furthermore suggested that the appearance of the condensed mitochondrial state can be taken as evidence of the intactness of the mitochondrial respiratory chain. The occurrence of swelling indicates structural changes in the mitochondrial inner membrane which occur following loss of ability for ATP synthesis.


Subcellular mechanisms of parathyroid hormone secretion: ultrastructural changes in response to calcium, vitamin A, vinblastine, and cytochalasin B. The effects of various agents on the in vitro secretion of parathyroid hormone (PTH) were studied previously, using bovine glands. Low calcium, (0.75 mM), vitamin A (vit A), and cytochalasin B stimulated secretion, and high calcium (3.0 mM) and vinblastine (VB) inhibited secretion, whereas hydrocortisone and VB inhibited the vit A-induced PTH secretion. In order to define subcellular mechanisms of PTH release at the morphologic level, a semiquantitative analysis of ultrastructural characteristics has been made on the same tissue with the same agents. Low calcium increased convolutions of the intercellular membrane, the number of large type I secretory granules, phagolysosomes, lipoid vacuoles, and lamellae of endoplasmic reticulum. Vit A and cytochalasin B widened intercellular spaces and increased intercellular membranous interdigitations, the number of type I secretory granules, and phagolysosomes. Vit A also dilated Golgi membranes, and cytochalasin B also increased the number of small type II secretory granules and the margination of granules along the cell membrane. High calcium increased the number of phagolysosomes and crinophagic and lipoid vacuoles. VB decreased the number of microtubules and caused stacking of endoplasmic reticulum lamellae. VB or hydrocortisone diminished some of the ultrastructural effects of vit A. The common ultrastructural findings in response to stimulation of PTH secretion by low calcium, vit A, and cytochalasin B raise the possibility that these agents may facilitate PTH secretion through a common messenger or may directly interact with the cell membrane or with the secretion granule for phagolysosome (or both). Our findings are consistent with the role of VB as a microtubule disrupter, but also suggest that VB inhibits PTH secretion through other mechanisms involving the cell membrane and endoplasmic reticulum. Microtubules may facilitate basal PTH secretion and vit A-induced secretion; however, since VB does not inhibit low calcium-stimulated PTH secretion and, ultrastructurally, microtubules were not increased in the presence of low calcium, low calcium-stimulated secretion is not dependent upon microtubular function.


Permeability properties of the postcapillary high-endothelial venules in lymph nodes of the mouse. The permeability of the postcapillary high-endothelial venules in mice was investigated by light and electron microscopy. Experiments with intravenously injected horseradish peroxidase demonstrated a pronounced intercellular passage of this tracer. Vesicular transport was not observed. Additional experiments with lanthanum and tannic acid showed that no continous tight junctions sealed the intercellular spaces. However, some focal membrane appositions were observed.


Free and membrane-bound ribosomes in normal and methylcholanthrene-treated mouse epidermis. Total and free ribosomes were isolated from postnuclear supernatants of trypsinized normal and 3-methylcholanthrene-treated epidermis from female CD-1 mice. Membrane-bound ribosomes were determined as the calculated difference between total and free ribosomes. The value for total ribosomes from normal epidermis in the resting phase of the hair growth cycle was 0.32 mg. of ribosomal RNA per gm. of epidermis, or 0.07 mg. of ribosomal RNA per mg. of homogenate DNA. About 96 per cent of the ribosomes were free and 4 per cent were membrane-bound. Five days after a single application of 2 mu moles of 3-methylcholanthrene to the dorsal skin in the resting phase of the hair growth cycle, there was epidermal hyperplasia and cellular hypertrophy. Total ribosomes increased 2- to 3-fold, to 0.80 mg. of ribosomal RNA per gm. of epidermis, or 0.21 mg. of ribosomal RNA per mg. of homogenate DNA. This increase was further characterized as proportionate increases of both free and membrane-bound ribosomes.


The resistance of certain tissues to invasion. II. Evidence for extractable factors in cartilage which inhibit invasion by vascularized mesenchyme. If hyaline cartilage is explanted to the chick chorioallantoic membrane, it resists invasion by vascularized mesenchyme of the host. This resistance is diminished if the tissue is extracted with relatively low concentrations (1.0 M) of guanidine HCl. The extracts contain antiproteolytic activity. This molarity of guanidine HCl extracts only small amounts of the major structural components of cartilage extracellular matrix. It, therefore, seems reasonable to suggest that hyaline cartilage is both avascular and resistant to invasion because it contains extractable inhibitors of invasion, perhaps in the form of proteinase inhibitors.


Experimental glomerulonephritis in the rat induced by antibodies directed against tubular antigens. I. The natural history: a histologic and immunohistologic study at the light microscopic and the ultrastructural level. A new form of experimental immune complex glomerulonephritis is described which is induced by one single injection of heterologous antibody directed against antigens present in the brush border of the proximal tubules of the rat kidney. In this model, antigen-antibody complexes are deposited as early as 3 hours after injection of the heterologous antiserum. The first localization of these complexes is seen in the dense layer of the glomerular basement membrane. Later, they move up to the lamina rara externa and stay there for at least 3 months. This model is easily reproducible and offers possibilities for studying the effects of medication on the deposition of immune complexes.


The mechanism of myocardial protection from ischemic arrest by intracoronary tetrodotoxin administration. Intracoronary injection of 14 mcg. of tetrodotoxin into the ischemic isolated rat heart resulted in immediate cessation of mechanical activity. Upon reperfusion with oxygenated, modified Krebs-Henseleit bicarbonate buffer in a modified Langendorff apparatus, all hearts recovered normal rate, rtythm, and contractile vigor after up to 60 minutes of ischemia. In contrast, all hearts not administered tetrodotoxin showed bradycardia, irregular rhythm, and weak contraction upon reperfusion after 30 and 45 minutes of ischemia; after 60 minutes, no mechanical activity was evident. The improved cardiac function following ischemia in the tetrodotoxin-treated hearts was associated with persistence of normal adenosine triphosphate (ATP) levels after up to 30 minutes of ischemia and normal or elevated creatine phosphate (CP) levels after up to 60 minutes of ischemia. On the other hand, ATP and CP levels progressively declined to reach 50 per cent of normal values after 30 minutes in the ischemic hearts without tetrodotoxin. These findings indicate that postarrest ATP and CP levels play an important role in myocardial recovery after ischemic arrest.


An experimental model for studying myocardial ischemia. Correlation of hemodynamic performance and metabolism in the working swine heart. An intact, working swine heart preparation with controlled coronary perfusion is described. In this model, hemodynamic and metabolic functions were correlated in control and ischemic myocardium. A closed-loop, extracorporeal coronary perfusion circuit in series with a perfusion pump and oxygenator was designed to return reoxygenated coronary venous blood at controlled flow rates to the left and right coronary arteries. In 9 swine at normal flows (232 plus or minus 17 ml. per minute), the preparation maintained stable hemodynamic performance and oxygen consumption for a 1 hour period, after which ischemia was induced by reducing coronary flow by 50 per cent. As a result, left ventricular end-diastolic pressure (LVEDP) rose by 227 per cent, whereas heart rate (-17 per cent), aortic pressure (-9 per cent), pressure time/minute (PTM) (-28 per cent), left ventricular work (-47 per cent), and oxygen consumption (-39 per cent) all decreased. The ischemic myocardium shifted from lactate extraction to production. With this model, we can define, over a period of time, several mechanical and metabolic collations as a function of total coronary blood flow in an intact, large animal. We can also test interventions during the acute phases of ischemia in an effort to reduce myocardial damage.


Hemodynamic characteristics of critical stenosis in canine coronary arteries. To determine the hemodynamic characteristics of critical stenosis of coronary arteries, mean left circumflex coronary artery (LCCA) flow, myocardial peak reactive hyperemic response (PRHR), myocardial PO2 and PCO2 electrocardiograms, and aortic pressure were monitored at precise degrees of LCCA stenosis in 18 dogs. Stepwise LCCA constriction by a specially designed occluder resulted in a gradual drop in PRHR but little change in other variables. When PRHR was reduced 96 per cent, critical stenosis was achieved, and further constriction caused pronounced and sudden changes in all parameters. When critical stenosis occurred, LCCA diameter had been reduced by 74 plus or minus 2 per cent. Mean LCCA flow was reduced from a base-line level of 42 plus or minus 2 to 34 plus or minus 2 c.c. per minute. PO2 in the myocardium was reduced from 24 plus or minus 1.5 to 16 plus or minus 1.6 mm. Hg. PCO2 increased from 43 plus or minus 5 to 55 plus or minus mm. Hg. T waves in Lead II because isoelectric. The myocardium was well perfused and able to regulate flow through an artery narrowed up to 74 per cent. Beyond this point of critical stenosis, the vascular bed was maximally dilated and further narrowing caused ischemia. These findings indicate that PRHR may be useful at operation to determiine whether all significant lesions are bypassed and whether graft flow is adequate.


Surgical treatment of chronic constrictive pericarditis using cardiopulmonary bypass. The results of operative treatment of 11 patients with chronic constrictive pericarditis with the aid of cardiopulmonary bypass are described. Ten of the 11 patients had Functional Class III or IV disability preoperatively, and all had evidence of severe constrictive disease on physical examination and cardiac catheterization. Pericardiectomy, performed on cardiopulmonary bypass through a median sternotomy incision, required an average total perfusion time of 80 minutes. There were no intraoperative or hospital deaths, and none of the patients required prolonged postoperative hospitalization, All patients except 1, who died 4 weeks postoperatively of pulmonary embolism, have enjoyed marked functional improvement. The technical advantages of pericardiectomy performed on cardiopulmonary bypass are presented.


Surgical management of anomalous left pulmonary artery causing tracheobronchial obstruction. Pulmonary artery sling. An anomalous left pulmonary artery causing tracheobronchial obstruction is a rare malformation seen in infancy. Sixty-four cases have been described in the literature, with 17 survivors with or without surgical therapy. We reviewed the literature and the 5 cases seen at The Children's Memorial Hospital during the past 20 years. Three of these patients survived, 2 of whom have not been previously reported. The main clinical features are progressive respiratory distress, cyanosis, and apneic episodes resulting from obstruction of the lower trachea and bronchi by an anomalous left pulmonary artery. Obstructive emphysema with or without atelectasis is very common in this condition and should suggest to the clinician the possiblity of this anomaly. The important diagnostic clues are an anterior indentation of the esophagus on esophagography, narrowing of the lower end of the trachea and right bronchus on bronchography, and anomalous origin of the left pulmonary artery from the right on angiography. We prefer to approach this anomaly by a left anterolateral thoracotomy with transection and end-to-end anastomosis of the anomalous left pulmonary artery in front of the trachea. Respiratory complications due to residual tracheomalacia are common after the operation.


Mitral valve replacement with the Smeloff-Cutter prosthesis. Experience with 154 patients and comparison with results of replacement with a Starr-Edwards prosthesis. Mitral valve replacement with the Smeloff-Cutter (S-C) prothesis was performed in 154 patients between September, 1965, and January, 1970. In 84, only the mitral valve was replaced; in the remainder, other valves were reconstructed or replaced. The hospital and late mortality rates for isolated replacement were 6 and 25 per cent, respectively. Comparable figures for the Starr-Edwards (S-E) (Models 6000 and 6120) prosthesis during this period were 11 and 23 per cent. Similar rates of thromboembolism were associated with the use of either prosthesis in surviving patients (27 per cent for the S-C valve and 30 per cent for the S-E valve). In spite of the acceptable hospital mortality rate for the S-C valve, it is not now considered suitable for clinical use because of the high late mortality rate and the high risk of thromboembolism that accompany its use.


Rupture of the posterior wall of the left ventricle after mitral valve replacement. Rupture of the posterior wall of the left ventricle is an unusual but often lethal complication following mitral valve replacement (MVR). We have encountered it six times with a 100 per cent mortality rate in a series of 1,154 operations for MVR. Sites of rupture were located at the base of the resected papilary muscle or close to the artioventricular groove in the area adjacent to the resected posterior mitral leaflet. T stongly indicates the overzealous resection of the mitral leaflets and papillary muscle as an important eitiologic factor. Other possible etiologic factors are discussed and important pitfalls to be avoided during MVR are stressed.