A prospective controlled trial of sclerotherapy in the long term management of patients after esophageal variceal bleeding.

The preliminary results of the first 25 months of a prospective randomized controlled clinical trial, designed to compare repeated injection sclerotherapy with conservative medical management in the long term treatment of all patients shown to have previously bled from esophageal varices, are presented in detail. To date, 31 patients have been randomized, 15 in the chronic injection group and 16 in the control medical management group. In addition, five patients excluded for geographic reasons have been injected out of trial. Ethanolamine oleate has been injected into the varices, using a modified rigid esophagoscope under general anesthesia. The preliminary results have been encouraging. It has been possible to eradicate esophageal varices in the chronic injection group and, once the varices had been eradicated, no patient had recurrence of variceal bleeding. On the other hand, recurrent variceal bleeds have remained a continuing problem in a number of the patients in the control study. A longer follow-up period will be required to assess both the quantitative and the qualitative aspects of survival and to determine how long esophageal varices will remain eradicated as well as how frequently repeated injections will be required.


Methylprednisolone in the prevention of cerebral hemodynamic and metabolic disorders during endotoxin shock in the dog.

These results provide evidence that steroid pretreatment and subsequent post-treatment prevent cerebral hemodynamic and metabolic alterations during four hours of Escherichia coli endotoxin shock in the dog. However, in this study, no data are provided on how the steroid prevents an increase in cerebral vascular resistance, and no clear answer is available in the literature. While active vasodilation or alpha-adrenergic blocking properties, or both, have been attributed to glucocorticoids, recent evidence does not support these findings during normal conditions or circulatory shock. If the increase in cerebral vascular resistance is passive, steroids may help by preventing platelet aggregation, cell disruption and subsequent microvascular plugging. Intravenously administered fluids, dextran-saline solution, while in themselves are probably not important to survival, may augment cerebral blood flow during shock through a blood dilutional effect. Finally, it is possible that steroids act to permit normal, long term cerebral auto-regulation, which is apparently impaired during endotoxin shock in the dog.


Antacid therapy and nutritional supplementation in the prevention of Curling's ulcer.

The incidence of clinically evident Curling's ulcer among 109 potentially salvageable severely burned patients was reviewed. These patients, who had greater than a 40 per cent body surface area burn, received one of these three treatment regimens: antacids hourly until autografting was complete, antacids hourly during the early postburn period followed by nutritional supplementation with Vivonex until autografting was complete or no antacids during the early postburn period but subsequent nutritional supplementation with Vivonex until autografting was complete. Clinically evident Curling's ulcer occurred in three patients. This incidence approximates the lowest reported among severely burned patients treated prophylactically with acid-reducing regimens to minimize clinically evident Curling's ulcer. In addition to its protective effect on Curling's ulcer, Vivonex, when used in combination with a high protein, high caloric diet, meets the caloric needs of the severely burned patient. Probably, Vivonex, which has a pH range of 4.5 to 5.4 protects against clinically evident Curling's ulcer by a dilutional alkalinization of gastric secretion.


Intraperitoneal irrigation with povidone-iodine solution for the prevention of intra-abdominal abscesses in the bacterially contaminated abdomen.

A prospective randomized investigation was undertaken, involving 168 consecutive patients undergoing laparotomy for conditions accompanying bacterially contaminated peritoneal cavities, to evaluate the effectiveness of povidone-iodine irrigation of the peritoneum in preventing the development of intra-abdominal abscesses. In the treatment group irrigated with povidone-iodine solution, 0.1 per cent available iodine, one of 80 patients had an abscess, 1.3 per cent, while, in the saline solution irrigated control group, nine of 88 patients had abscesses, 10.2 per cent, p less than 0.05. Although the serum iodine levels were elevated 24 hours after intraperitoneal irrigation with povidone-iodine solution, iodine levels returned to near normal by 72 hours. Thyroxine levels showed no major changes. No complications resulting from the use of povidone-iodine were recognized.


Recent advances in the treatment of systemic mycotic infections.

Serious therapeutic problems are posed by the increasing incidence of invasive fungal infections in transplant recipients as well as in patients with compromised immune defenses, prosthetic devices and grafts and several other predisposing factors. A number of new approaches, including combination drug treatment and the development of newer agents, may justify increased optimism in the management of these infections.


Stereotactic implantation of iridium192 into CNS neoplasms.

A new method of stereotactic implantation of Iridium192 into CNS neoplasms is presented along with a method for tumor localization by computerized axial tomography, stereotactic angiography and stereotactic serial biopsies. A case treated with this technique is presented with an encouraging short term result.


Segmental pancreatic transplantation in pigs.

Segmental pancreatic allotransplants were performed intraperitoneally in pigs with and without ligation of the duct. Exocrine pancreatic function was suppressed by the administration of glucagon. All recipients also received high doses of methylprednisolone for the first 10 days after transplant as well as cyclophosphamide until death or sacrifice. Some animals received antilymphocyte globulin (ALG) in addition. Diabetes was induced by total panreatectomy. Allotransplantation in pancreatectomized animals was successful in preventing hyperglycemia for up to 33 days of observation. ALG in the dosage used did not show any beneficial effects and varying degrees of rejection occurred in the majority of these unmatched animal pairs. Grafts without ligation of the duct seemed to show the best preservation of tissue because of absence of obstructive damage following duct ligation. Of significance is the fact that no intraperitoneal inflammatory or infectious complications occurred in recipients of either duct-ligated or unligated grafts, presumably because of suppression of exocrine function with glucagon and the reabsorptive capability of the peritoneal surface. We speculate that this is a satisfactory physiological model for continued trials in pancreatic transplantation, although antirejection therapy was far from satisfactory.


Simplified distal pancreatectomy with the Auto Suture stapler: preliminary clinical observations.

The most serious complication following distal pancreatectomy is the development of a pancreatic fistula or subphrenic abscess. These complications are particularly prone to occur following distal pancreatectomy for trauma. The injured pancreas is divided in a contaminated field, often in the presence of hemorrhage and partly devitalized tissues, in which identification and secure closure of the transected pancreatic duct may be difficult. A review of 12 surgical publications describing experience with 234 distal pancreatectomies performed for trauma found the average pancreatic fistula rate to be 13% an in some reports as high as 25% to 30%. In an attempt to decrease the high postoperative fistula rate after distal pancreatectomy, transection of the gland with the autosuture has been investigated. There are at least three theoretical advantages of this technique. The pancreas is transected through healthy tissue, the pancreatic duct is closed securely, and stainless steel sutures are used, which probably are more resistant to the development of infection than other suture material. This report describes a technique of distal pancreatectomy for both trauma surgery and elective surgery with the TA-55 Auto Suture stapler. TA-55 Auto Suture stapler, with 3.5 mm staples, is placed across the mobilized pancreas, and two rows of staggered stainless steel staples are laid down. The gland distal to the stapler then is amputated. At present this technique has been used in a total of 12 cases--four for trauma and eight during elective procedures. One fistula related to pancreatectomy performed with the Auto Suture stapler developed, for a complication rate of 8.3%. This preliminary experience indicates that a more widespread evaluation of this technique is indicated.


Expanded microporous polytetrafluoroethylene as a vascular substitute: a two year follow-up.

Since 1974, 131 femoropopliteal, distal popliteal, and tibial bypasses have been performed using expanded microporous polytetrafluoroethylene (PTFE). Forty patients were operated on for limb salvage, and 21 had had previous bypass procedures. The overall patency rate was 82%. Early occlusions possibly were related to technical error, but most probably were due to severity of disease and poor runoff. Late occlusions were related to progressive atherosclerosis in the proximal or distal arterial tree. A 75.7% cumulative patency rate was noted at 28 months. In man the PTFE prosthesis demonstrates a smooth intimal lining with fibroblastic ingrowth into the interstices of the graft. These results are considered to be excellent in this high-risk patient population. The patency rates achieved with PTFE are better than those accomplished with alternative conduits and approach the patency rates reported with autogenous saphenous vein. Expanded microporous polytetrafluoroethylene with its high patency, pliability, and tissue incorporation is an excellent arterial substitute. Only with continued use of this material and a more uniform patient selection can more equitable comparisons be made between expanded PTFE and the autogenous vein.


Amino acid metabolism in dogs with E. coli bacteremic shock.

In 10 fasting dogs receiving 10(9) viable E. coli bacteria per kilogram intravenously, mean systolic blood pressure decreased from 120.6 +/- 15.1 to 82.2 +/- 12.8 mm Hg. The association of hypoglycemia and increased arterial alanine and glycine with elevated plasma glucagon implied impaired gluconeogenesis. A rapid elevation of blood urea concentration, indicating increased ureagenesis, a fall of blood glucose, and an increase of net urea synthesis relative to that of glucose suggested that an increased proportion of the carbon residues derived from glucogenic amino acids is catabolized via pathways other than gluconeogenesis. In the bacteremic dogs the absolute net release from the leg of valine, isoleucine, and leucine and their net release relative to the net rate of proteolysis were decreased, suggesting increased oxidation of these amino acids in skeletal muscle. An increased net release of alanine relative to the net rate of protein catabolism in muscle was in agreement with this contention.


Food-borne parasitic infections--old stories and new facts.

A review is presented of food-borne parasitic infections. Parasitic infections with public health hazards both from conventional slaughter animals and from seafood (fish and shellfish) are discussed. The former category includes cysticercosis, echinococcosis, and trichinosis, the latter category covers various trematode, cestode, nematode, and possibly also protozoan infections. Examples of trematode infections are heterophyidiasis, transmitted to man by marine fish, and Paragonimus spp parasites, transmitted by crustaceans. Cestode infections include diphyllobothriasis transmitted by both fresh water fish and fish from brackish waters. Special attention is drawn to the condition known as sparganosis. Of the nematode infections, the eosinophilic granulomatous enteritis due to the genera Anisakis, Phocanema, and Contracaecum, transmitted to man by either marine fish or crustaceans, is mentioned. Two other nematode infections. Angiostrongylus cantonensis and Capillaria philippinensis, can also be transmitted to man by marine fish. Free living amoebae (a.o. Naegleria) may be transmitted to man via shellfish as vehicles. Apart from a possible direct effect of these parasites, chemical alterations in seafood resulting from the presence of parasites may also be deleterious to the consumer. Special attention is drawn to a newly developed serological detection method, the enzyme-linked immunosorbent assay, which makes detection of infection possible not only at the slaughterhouse but also at the farm or in large herds. Strategies to control parasitic infections both in conventional slaughter animals and in seafood are discussed.


[Infections with strains of Escherichia coli indistinguishable from non-pathogenic porcine coliform organisms in animals other than swine (author's transl)].

A report on sixty cases in which so-called porcine coliform organisms were isolated post-mortem from various species of animal. Clinically, these were cases of abortion (cattle, dogs) and enterotoxaemia (sheep, dogs, cats, rabbits, goats, guinea pigs, deer and birds).


[Studies on the bacterial causes of neonatal mortality in foals. Report on post-mortem findings (author's transl)].

The causes of neonatal mortality in foals were studied over a period of two years. The total number of foals studied was 121. Bacterial infection was found to be an important factor. Infection caused by A. equuli (1.6%) which previously was the most important one, has been superseded by E. coli infection (56%). E. coli infections particularly occur during the first weeks of life and, depending on the course of the disease, give rise to various pathological changes. Infections running an acute course are mainly marked by pathological changes of the lung and lymphoid organs. Infections running a subacute course are frequently associated with polyarthritis and polyserositis. Another important cause of infection during the first weeks of life is Klebsiella pneumonia (10%). The pathological changes occurring in this infection are markedly similar to those in subacute E. coli infection. Infections with Salmonella spp. (7%) mainly occur in the older foals (1-3 months) affected with polyarthritis. C. equi and streptococcal infections (11%) also mainly occur in the older foals (1-3 months). The pathological features are characterized by generalized purulent lesions in various organs. In spite of the fact that post-mortem findings suggested septicaemia, bacteriological examination was negative in 12% of the foals. The discussion is concerned with an assessment of the relationship between the pathomorphological findings and the pathogenesis of the various infections.


Nervous system responses to work - site chemicals - toxicological basis.

A number of materials which are applied in the chemical industry in the work environment are liable to produce injury to health, particularly neurotoxic disturbances, when absorbed by the organism. The effects exerted are determined by the anatomic-structural factors of the nervous system and the physico-chemical characteristics of a given neurotoxicant. Some of the materials to be considered exhibit pronounced affinities for certain structures and ganglion groups in the central or peripheral nervous system. This gives rise to specific patterns of morphologic or functional disturbances or lesions and ultimately leads to the development of different clinical symptoms which manifest themselves as distinct intoxication pictures characteristic of certain work-site chemicals. Currently available suggestions for a grouping of industrial neurotoxicants which is both systematic and convenient to handle for practical purposes take their bearing from the clinical and morphologic-structural features reported in the literature.


The interaction between alcohol, chlorpropamide and phenformin in a severe combined poisoning: case report.

A young non-diabetic woman ingested 2.5-3.7 g of chlorpropamide and 0.6-0.9 g of phenformin together with a large dose of alcohol, nitrofurantoin and promethazine in a suicidal attempt. She developed severe metabolic acidosis, hypokalemia, polyuria and prolonged hypoglycemia in the absence of typical hypoglycemic symptoms. These unusual clinical features were in part explained on the basis of the interactions between alcohol and the other drugs.


[Clinical and microbiological studies on the effect of locally applied aminofluorides on bacterial plaque and gingiva condition of Soviet school children].

In a short-term (over 4 weeks) clinico-microbiological study on 18 Soviet school children, 12 years of age, it was found that a supervised oral hygiene action with the amine fluoride-containing caries-preventing agents Silca and Elmex fluid (produced in the GDR) had resulted in a marked reduction in plaque formation, an improvement in gingival conditions and a reduction of the germ content in the plaques.


[Possibilities and significance of immunological diagnosis for the differential diagnosis of periodontal diseases].

A clearer understanding of the aetiology of periodontal diseases can only be gained by further studies on the effects of plaques on the organism. Furthermore, the pathogenic plaque components must be assessed. It seems worth while maintaining the working hypothesis that periodontal disease is a plaque-induced clinical picture and that its various types are due to variations in the power of resistance of the organism. The better understanding of this changed reactivity and of the pathogenic plaque components must be aimed at.


[Significance of microscopy preparations in periodontal diseases].

A simple microscopic method for the quantitative determination of bacteria, leucocytes and epithelial cells was tested on 24 healthy subjects and 75 patients with the diagnosis of periodontal disease. It was found that the microscopic picture is on principle, in correlation with exact clinical data, suited for detecting periodontal disease.


[Roentgenological evaluation of success of nonvital teeth following treatment with dental post and crown].

For the purpose of a comparative study on the occurrence of periapical changes in non-vital teeth after application of pin crowns, the authors examined radiologically 379 teeth, 175 of which had been apicectomized. The groups of teeth with pin crowns was compared with the group of apicectomized teeth with pin crowns and with a control group of 60 teeth which had only had endodontic treatment. The statistical analysis showed that the group of teeth with pin crowns did not differ significantly from the control group in the occurrence of periapical changes. On the contrary, there was a marked increase in periapical changes in the group of apicectomized teeth with pin crowns compared to the two other groups. This difference was statistically significant.


[Hospital and outpatient clinic for dentistry-past and future].

A short historical survey deals with the development of the Clinic and Policlinic of Stomatology of the Magdeburg Medical Academy. Apart from especially marked stages prior to the erection of the new building in 1958 and the appreciation of the merits of F. Meyer, founder of the Clinic, the present paper treats the interdisciplinary connexion of the Clinic with other institutions of the Magdeburg Medical Academy and indicates its tasks in the fields of medical care, of medical education, training and continuing education, and of research. From a discussion on its significance and importance in the framework of the health policy of the Socialist Health Service of the GDR, certain speculations on its prospects are deduced (with reference to certain facts), and the consequences necessary for the continuation of its present development are pointed to.


[Development of dentistry in the Magdeburg district].

The author outlines some important stages of the development of medicine and, by that, of dentistry--the historical data evince their close connexion--especially in the region of Magdeburg. In view of the particularities and difficulties mentioned, it is easy to understand that the targeted practice of dentistry has become possible only in the twenties of our century.


[Osteoplastic interlocking in recurrent temporomandibular joint dislocation].

A short survey of the problems encountered in the treatment of recurrent luxations of the temporomandibular joint is followed by the description of the method of osteoplastic interlocking according to Rehrmann. In accordance with favourable reports in the literature, the authors' experience also permits to recommend this method.


Comparative trial on the therapeutic effectiveness of the new anthelmintic drug: ciclobendazole.

In a double-blind study in Cameroon the vermicidal effect of Ciclobendazole, a new Benzimidazole derivative, was evaluated and compared to Mebendazole. Ciclobendazole and Mebendazole were equally effective in the treatment of Ascaris and Hookworm infestations. An increase in the dosis of Ciclobendazole from 600 mg to 1200 mg did not lead to an improvement in the effectiveness. When treating trichuriasis significantly better results were achieved with Mebendazole (p = 0.01). Both drugs were tolerated equally well. Side effects, such as vomiting and diarrhoea, only occurred in a small percentage of cases.


Current concepts of the aetiology, pathogenesis and pathology of bladder cancer.

Attention is directed to the information currently available on the pathogenesis of human bladder cancer. The continuum between carcinoma, carcinoma-in-situ and other epithelial abnormalities is noted. Pre-neoplastic lesions are defined as irreversible but not necessarily progressive, and a possible morphologic marker for pre-neoplasia seen with scanning electron microscopy is described.


Fc receptor-like structures on in vitro-cultured human ovarian tumor cells.

Four ovarian cystadenocarcinomas cultured in vitro were tested by a radioisotopic method with sera from cancer patients or healthy donors to search for a possible specific antitumor immune response of patients bearing ovarian tumors. However, the ovarian tumor cells were found to bear on their membrane surface structures able to bind immunoglobulins from any tested serum, thus making impossible the detection of a hypothetical specific antitumor antibody. These structures were demonstrated to bind the Fc portion of the Ig and were therefore similar to the Fc receptors described on various normal cells, particularly of the immunocompetent compartment.


Immunoperoxidase staining of carcinoembryonic antigen in urinary bladder cancer.

An immunoperoxidase study of the presence of carcinoembryonic antigen (CEA) in primary cancers of the urinary bladder, metastases to the bladder, non-malignant diseased bladder, and normal bladder tissues revealed that approximately 10 percent of the urothelial carcinomas (transitional cell and squamous cell types) contained detectable quantities of this antigen. The other tissues were devoid of stainable CEA. It thus appears that the incidence of positive CEA by immunoperoxidase staining of formalin-fixed, paraffin-embedded tumour tissue sections is much less than the frequency of blood or urinary CEA elevations in patients with urothelial cancer.


Malignant Brenner tumor of the ovary: case report with a review of the literature.

A case of malignant Brenner tumor of the ovary is reported. From a survey of the literature some anatomo-clinical considerations are drawn and the histopathologic criteria for diagnosis are discussed.


Carcinoembryonic antigen in serum, urine and cells of patients with bladder carcinoma.

A raised level of CEA-like substance has been demonstrated by radioimmunoassay in the urine of patients with bladder carcinoma, in concentrations which increase with a more advanced stage, and in serum of patients with advanced disease. In a 2-year follow-up of patients receiving chemotherapy, a correlation of raised urinary CEA to local recurrence was seen, as well as rising and high serum values with metastases. In the patients who responded to treatment, CEA values became normal. CEA was also located in carcinoma cells from bladder washings in 24--61% of the cases. Combined studies of CEA in serum, urine and cells may be used to study the biology of the tumour and perhpas also in the monitoring of patients with urothelial carcinoma.


Transplantation for polycystic kidney disease.

Twenty-four patients with end stage renal failure due to polycystic renal disease have been treated with hemodialysis and transplantation. While on dialysis, the incidence of complications did not differ from a similar group of patients with other causes of renal failure. Bilateral pretransplant nephrectomy is not mandatory except in cases of persistent infection or hemorrhage. A much higher incidence of HLA A3 and HLA B7 was noted in patients with polycystic disease when compared with the general population. Following cadaver renal transplantation, kidney function was significantly better in patients with polycystic disease when compared with those with other forms of renal failure. Patient survival was the same in both groups. We conclude that hemodialysis and transplantation are acceptable forms of treatment for a patient with end stage polycystic renal disease.


Anaerobic bacteriuria in renal transplantation.

Renal allograft recipients were studied prospectively utilizing improved culture techniques to investigate anaerobic bacteriuria. The study population was compared with a population of patients with chronic renal insufficiency and end stage renal disease. The over-all incidence of anaerobic urinary tract infection was 7.5 per cent while the over-all incidence of aerobic urinary tract infection was 23.5  per cent. Patients with cadaver renal transplants during the early postoperative period had the highest incidnece of both anaerobic (42.9 per cent) and aerobic (71.4 per cent) urinary tract infection of all groups. The potential association between significant anaerobic bacteriuria during the first postoperative month and poor  prognosis for cadaver renal allografts merits further investigation.


Ureteral reconstruction in renal transplantation.

The complications associated with ureteral reconstruction in renal transplantation produce significant morbiditiy and mortality rates. We have evolved a combined intravesical-extravesical nonstented ureteroneocystostomy and have used it in 100 consecutive transplants, 50 of which were in high-risk diabetic recipients. No instances of urinary extravasation, fistula formation, disruption of the ureterovesical anastomosis, ureteral solughing, or ureterovesical obstruction have occurred in this series. The lack of urologic complications utilizing this technique offers reduced morbidity and mortality to transplant recipients.


Experience with the radioimmunoassay for parathyroid hormone in the diagnosis of primary hyperparathyroidism.

Our results with radioimmunoassay studies for parathyroid hormone performed during the last 6 years are compared retrospectively to results of the laboratory tests customarily secured when hyperparathyroidism is suspected. The results obtained in patients with known primary hyperparathyroidism and in patients with unconfirmed but presumptive hyperparathyroidism are compared to the results obtained from a group of normal controls. Despite the fact that certain discrepant results were noted in the earlier assay techniques the over-all results and, in particular, those of more recent years have been highly sensitive and reproducible corroboratives of the existence of primary hyperparathyroidism. About two-thirds of the patients with primary hyperparathyroidism will present to the urologist. All patients with calcium-containing stones should have at least 3 determinations of the serum calcium in screening for primary hyperparathyroidism. The radioimmunoassay for parathyroid hormone provides the most reliable confirmation. The patient with calculous disease, elevation of the immunoreactive parathyroid hormone level and hypercalcemia is virtually certain to have primary hyperparathyroidism.


Further studies of renal preservation: protection of the ischemic kidney with inosine.

Preliminary data are presented on additional means of renal preservation, particularly in the case of warm ischemic insult. We hypothesize that 1 factor responsible for the failure of kidneys to recover after ischemic insult may be depletion of energy sources during the warm ischemic period. Specifically, adenosine triphosphate in the kidney is the principal source of energy for metabolic activity and membrane stability. Inosine, an adenosine triphosphate precursor, was used in a canine model and preliminary work suggested that inosine, when coupled with mannitol, may provide enhanced protection. In vivo assay of kidney slices suggests that inosine may, indeed, tend to maintain adenosine triphosphate levels in the ischemic kidney in contrast to relative adenosine triphosphate depletion in the kidneys not protected with inosine. These data are in concert with the apparently favorable survival data in inosine and mannitol-treated animals.


A computer-assisted filing system for urologic information.

Our increasingly inefficient, cumbersome, often ineffective and time-consuming manual mental cataloguing and retrieving system indicated to us that there must be a better technique available. However, our search of existing systems failed to reveal any matching our needs. Therefore, we developed a 4-category system for cataloguing and retrieving urologic materials. Our program is divided into 3 sections: 1) index, 2) catalogued data and 3) computer programs. We have used this system for more than a year and believe that it has satisfied our original requirements. It is easily adaptable to changes of information, allows for identification of unlimited types of material, offers thorough and accurate data retrieval techniques and is economical now that the expense of organizing the system is behind.


Evaluation and treatment of patients with failed hypospadias repair.

Hypospadias repair is often accompanied by complications, some of which may be major. We herein analyze 70 patients whom we have seen and enumerate the defects, list the operative procedures that have been necessary to correct the lesions and illustrate the use of some of these techniques. Surgeons treating patients with hypospadias should have command of many techniques and use them aggressively with imagination and great care.


Reaction of the vesical wall to bacterial penetration: resistance to attachment, desquamation and leukocytic activity.

To determine the contribution of the bladder wall to defense against infection we designed a series of experiments wherein movement of introduced bacteria and inflammatory processes (cystitis) were observed by an autoradiographic technique. As a first defense line the bladder mucosal surface showed strong resistance against bacterial attachment and penetration. Moreover, epithelial cells gripped and penetrated by bacteria were desquamated and eliminated through voiding, thus arresting deeper invasion into the bladder wall. When organisms did penetrate the bladder wall they were phagocytized by polymorphonuclear leukocytes and macrophages in the submucosa and muscularis. In contrast, once leukocytes had migrated into the urine within the bladder they no longer participated in phagocytosis. Organisms also entered the veins, the lymphatics or both and disappeared rapidly from the local site through the action of the reticuloendothelial system. These observations indicate that in addition to mechanical emptying resistance to bacterial attachment, desquamation of invaded cells, activity of leukocytes and macrophages, and disappearance of bacteria from local site are 4 mechanisms whereby the bladder resists and fights infection.


Novel bacterial structures in human blood. II. Bacterial variants as etiologic agents in idiopathic hematuria.

Novel bacterial structures have been demonstrated in lysed blood filtrates placed in special culture media from patients with idiopathic hematuria. These structures converted rapidly to gram-positive coccal (streptococcal and staphylococcal-like) coccobacillary and filamentous, bacterial forms in vitro from 96 per cent of the patients studied. Blood cultured conventionally yielded negative findings. Although structures (dense bodies) were demonstrated in normal control blood specimens (albeit in lesser numbers) few converted to classical bacteria in vitro (7 per cent). Erythromycin therapy appeared to correlate with disappearance of hematuria and inability to revert rapidly the variant froms to classical bacteria in vitro. It is suggested that continual bombardment of the blood by bacteria entering from the mouth or other sites may lead to the development of variant bacterial parasitism. In an effort to survive the deleterious host effects the organisms may convert to persisting osmotically stable variant bacterial forms (dense bodies). Development of a disease state may be conditioned by some existing or developing abnormality in the host (immunologic, physiologic and/or biochemical). Furthermore, changes (genetic?) that might take place in the organisms per se during their transition to variant forms and adaptation to life in vivo may not allow certain host environments to adapt to these new forms, possibly leading to a pathogenetic role in renal diseases whose etiologies have long been enigmas.


[Reconstructive-restorative operations of the skin after amputation of the limbs].

Up to 70% of cases admitted for primary prosthetics after amputation of the extremities suffer from some defects aod diseases of the stumps requiring surgical treatment. The experience of the Leningrad Scientific Research Institute of Prosthetics with 593 reconstructive-restorative operations on the stumps of the extremities allows to define indications for skin plasty on the stumps and to assess the advantages and drawbacks of different methods.


[Papillosphincterotomy in lesions of terminal segment of the common bile duct].

The dissection of the papilla was carried out in 70 patients with pure stenosing papillitis and with papillitis combined with choledocholithiasis and cholangitis. The authors consider subtotal papillosphincterotomy with the length of incision of 1.5 cm to be an expedient means for the dissection of the papilla, which, in their opinion, allows to prevent developing of restenosis. The dissection of the papilla was carried out upon 35 patients with incarcerated stones and upon 8 patients with floating stones. Some practical and helpful recommendations are suggested.


[Production of live attenuated vaccine against colibacillosis in pigs].

Two strains of beta-hemolytic Escherichia coli, p-0141 and i-0149 were used to obtain mutant E. coli organisms with unchanged cultural, morphological, biochemical, and serological properties. The mutants proved apathogenic for albino mice at intravenous injection of a 6-hour broth culture at the rate of 0.3 cm3 or an endotoxin in the same dose. Neither were they enteropathogenic for pigs when inoculated into intestinal segments. They could be used as vaccinal strains.


[Fibrous suppurative arthritis in sheep].

Described are cases of fibrinous supprative arthritis in sheep characterized by thickenning of the joint, resulting from the involvement of the capsule (periarthritis). Histopathologically, there have been suppurative and necrotic processes combined with fibrinoid necrotizing of the collagen fibers and leukocyte infiltration of the joint capsule. Slight leukocyte infiltration has also been said to occur in the parenchymal organs. Microbiologic studies have revealed the presence of pyogenous bacteria (Corynebacterium pyogenes, Streptococcus pyogenes, Pasteurella multocida).


[Pathomorphological studies of spontaneous and experimental abortions in cows and guinea pigs].

The morphologic studies of aspergillosis abortions in cows and guinea pigs were carried out on 83 spontaneously affected aborted cattle fetuses, pregnant guinea pigs and their offsprings. Fifty-four fetuses were of spontaneously aborted cows from 12 farms along with 15 pregnant guinea pigs experimentally infected with Aspergillus fumigatus and a total of 14 fetuses of theirs. Microscopically, both in the cattle fetuses and in guinea pigs and their fetuses there were stasis, thrombosis, diapedetic hemorrhages, hyperplasia of the reticulohistiocytes, necrobiosis, and a good amount of polysaccharides in the investigated organs at the absence of hyalin in them. Special staining of cross sections of the studied viscera revealed hyphae of Aspergillus fumigatus--in the blood vessels and the tissue of the organs in spontaneously and experimentally infected, resp., aborted cattle fetuses as well as in guinea pigs but not in their fetuses.


[Contribution of the Moscow P.A. Gertsen Research Institute of Oncology to the development of oncological immunology in the USSR].

The main steps in the development of experimental and clinical oncoimmunology in Moscow Research Institute of Oncology named after P.A. Herzen for the period of 75 years of its existence are reported.


[Method of medical history taking and control group recruitment in oncoepidemiological studies].

Some methodical aspects of using the questionnaire as one of the basic tests, employed in oncoepidemiological investigations, are analysed. Under discussion is the potentialities and limits of the questionnairing method; the rules and ways of the optimum application of the given test to obtain the most comprehensive and objective enough information are reported. Also, the principles and criteria of selecting control groups in oncoepidemiological investigations are considered. The factors and conditions which may cause significant differences between the control and "test" groups irrespective of the genesis of the affection under study are discussed. An analysis is made of a number of typical methodical errors in oncoepidemiological investigations.


[Development of combined methods of treatment of malignant tumors].

The term "combination treatment" should implicate various methods of treatment for malignant tumors scheduled beforehand. The combination treatment of malignant tumors is aimed at improving the immediate and late results. This is gained by means of reducing the biological activity of a tumor, both the effect of summation and potentiation of the action of different therapeutic measures being observed. The choice of methods and their sequence is determined by the prognosis factors, which incude the histological tumor structure, anatomical type of growth, the degree of its proliferation both within the range of proximate and remote zones of metastases spread, the general patient's state. At this stage it is difficult to elaborate the methods of combination treatment. The difficulties are conditioned by a variety of forms of many solid tumors, methodical difficulties and complexity of estimating an efficacy of different variants of treatment. Accumulating of knowledge should determine the a range of lesions subject to the combination treatment.


[History of the foundation of the Moscow P.A. Gertsen Research Institute of Oncology].

The Moscow Oncology Institute was opened on November 18 (December 1) 1903 and named "Institute for Treatment of Malignant Tumors at Moscow University". With the lapse of time this name was changed several times. In 1947 it was named after a prominent Soviet surgeon P.A. Herzen. It is the oldest in Russia  and one of the oldest in the world institutions for oncology researches.


[Prognostic value of cytological signs in breast cancer].

From a variety of cytological patterns of breast cancer the signs are singled out, which may be of a prognostic value for determining the degree of tumor malignancy prior to instituting any kind of therapy. The data on 59 patients, radically treated for breast cancer, stage IIIb, are reported: 17 patients died during a year period, 42 - survived for 5 years and longer. There were singled out 11 cytological signs among which are those available in the WHO classification for typing breast cancer malignancy. The most informational signs were as follows: the character of cell location, the content of "naked" nuclei and nuclear hyperchromia. It was found that for low malignancy cancer a combination of the following signs is typical: a predominance of cell aggregations, the content of "naked" nuclei not exceeding 20%, and the absence of nuclear hyperchromia. To determine the rate of breast cancer malignancy in a cytological investigation, it is recommended to take into account, in addition to the recommended by the WHO classification signs (hyperchromia, the number of mitoses, heterogenity of nuclei in size, form and character of staining), also such a sign as the content of "naked" nuclei.


[Development of a system for determining antibodies to the surface antigen of the virus of hepatitis B (HBsAb)].

A method for preparation of an immune diagnosticum using human erythrocytes of 0 (I) blood group sensitized with hepatitis B surface antigen in the presence of chromium chloride followed by the addition of formalin solution, for detection of antibody to the hepatitis B surface antigen is described. Using this immune diagnosticum, antibody to the surface antigen of hepatitis B virus was detected in 12-15% of the normal population in the Latvian SSR, and in 91% of patients with hepatitis B.


[Pharmacology of DTIC (author's transl)].

DTIC, a new cytostatic drug developed by the NCI-USA, is described and some relevant pharmacological characteristics are defined. This drug was proved to be the number one choice for the treatment of malignant melanoma and of sarcomas. It also appears to be of value in advanced cases of Hodgkins disease. DTIC represents a very valuable addition to the available drugs for chemotherapy of malignant tumours.


[Dacarbacine (DTIC) in the therapy of a malignant disease. A review (author's transl)].

Indications and results are reviewed with regard to recent data on the effect of DTIC in patients with malignant melanoma, soft tissue sarcomas, Hodgkin's disease, gastrointestinal carcinomas and oat cell cancer of the lung. Whilst this drug induced--mainly partial--remissions in 25% of the patients with melanomas, it is generally used in other malignant conditions in combination with other cytoxic agents. In soft tissue sarcomas adriamycin appeared as the principal additional drug. In patients with Hodgkin's disease resistant to MOPP treatment and requiring additional cytotoxic drugs, combination chemotherapy including DTIC may induce remissions in more than half of these patients. Other schedules were, however, also effective and results in this difficult group of patients are discussed and compared. In gastrointestinal and in oat cell carcinomas cytotoxic protocols including DTIC have shown some effect, perhaps comparable to other combinations usually employed in these conditions.


[DTIC in malignant melanoma: a perspective (author's transl)].

Effective therapy of malignant melanoma is still problematic. A variety of chemotherapeutic agents has proved to be ineffective in this tumour. The most extensively used chemotherapeutic agent for treatment of melanoma is DTIC (dimethyl-triaceno-imidazol-carboxamide). The objective response rate in monotherapy schedules has been reported to be up to 25%. Combination therapy with other cytostatic agents did not improve the results of DTIC alone. Experimental studies and clinical investigations have demonstrated that chemotherapy can be combined successfully with immunotherapy by potentiating the effect of tumour elimination. A review of the clinical studies with DTIC in malignant melanoma is presented.


[Significance of prostaglandins for fat and carbohydrate metabolism with special reference to pathogenesis of diabetes mellitus ].

A survey is given of the literature on the influence of prostaglandins on the lipid- and carbohydrate metabolism. Some common pathobiochemical features in the development of diabetes mellitus and the ischaemic heart disease are outlined, which became apparent by examinations of the fatty acid pattern in patients. Thus a biochemical basis for that epidemiologically well known fact is given, that diabetes represents a risk factor for the ischaemic heart disease. Some of the latest results from the experimental research suggest that the vascular complications occurring in chronic diabetes are caused by a decrease in the formation of prostacyclin and possibly by an increase in the thromboxane A2 production. Similar changes in the prostaglandin metabolism occur in the ischaemic heart disease and myocardial infarction, too, as experimental results have shown.


Liver transplantation.

The development of liver transplantation has been difficult. However, substantial advances have been made mostly because of better surgical techniques and because of better postoperative management. It has been necessary for surgeons to be more inquisitive about the reasons for post-transplantation liver dysfunction rather than to ascribe hepatic perturbations to rejection. With these nonspecific improvements, there has been movement of liver transplantation into the area of actual service. Before the next great step will be made, there must be an improvement in immunosuppression. The nature of such improvement is not yet clear.


Prostacyclin: a potent activator of human colonic adenylate cyclase activity.

Prostacyclin and its stable catabolite 6-keto-prostaglandin F1 alpha were tested on the human colonic mucosal adenylate cyclase which represents the key enzyme in the secretory process in this organ. Prostacyclin was able to activate dose-dependently the human cyclase system. Saturating concentrations of prostacyclin and 6-keto-prostaglandin F1 alpha (each 0.28 mM) increased the enzyme activity 2.5-fold and only 1.4-fold, respectively. The presence of prostacyclin receptor sites in human colonic mucosa suggests a physiological role of this novel prostaglandin in human colonic function.


[Histotopographic demonstration of hepatitis-B-surface-antigen (HBSAg) in liver-biopsies with the peroxidase-antiperoxidase (PAP)-method in symptomfree HBSAg-carriers].

In 241 paraffin-embedded liver-biopsies of HBSAg-positive, voluntary blood-donors hepacellular HBSAg was demonstrated with the immunomorphologic peroxidase-antiperoxidase (PAP)-method. In all sections, HBSAg-positive liver-cells were estimated, their distribution-pattern was assessed and different types of cytoplasmatic localisation of HBSAg were described. Despite high sensitivity of the PAP-method, 24% of seropostive cases were histologically negative. A correlation of HBSAg-content and histologic diagnosis was lacking. An association of high HBSAg-content with non-aggressive liver-disease and of low HBSAg-content with aggressive liver-disease in a single biopsy could not be found in our material in contrast to the literature. 34 patients were followed up through 4-6 years. Constant or improved liver-histology was associated with increased, deterioration with decreased HBSAg-tissue-content.


Babesia bovis (argentina): components of the cryofibrinogen complex and their contribution to pathophysiology of infection in splenectomized calves.

A cryofibrinogen complex, found in the plasma of cattle acutely infected with Babesia bovis (argentina), was characterized. The fibrinogen-like proteins of the complex were isolated and the structure of their polypeptide chains analysed. In general, the chain structure was similar to that of soluble non-crosslinked fibrin (fibrinogen) although chains indicating some degree of fibrin crosslinking were often detected. Only rarely did the chain structure suggest that fibrinolysis occurred. It was concluded that the complex was produced by activation of the coagulation system but that fibrinolysis did not occur to any marked degree. The complex was implicated in assistance to the sludging of erythrocytes in the internal organs which is a feature of the pathogenesis of the disease.


IgG antibody binding to the outer surface of infective larvae of Ancylostoma caninum.

Applying the indirect fluorescent antibody technique to the infective stages of the hookworm Ancylostoma caninum, it appeared that they do not show IgG antibody binding when serum from dogs infected with A. caninum was used in the test (antiserum). However, inhibiting these stages metabolically with azide or with low temperatures, IgG antibody binding to the outer surface was observed. When the inhibitory factors were removed, shedding of fluorescent substances was seen, which were obviously coming from the outer surface of the larvae. This suggests that shedding of the antigen might occur.


Experiences with our surgical technic of partial resection of the kidney.

On the basis of 305 partial resections of the kidneys is reported on experiences with an own operation technique. By applying a chromium cat-gut supporting suture a secure and pboblem-free care of the resection wound is possible, which guarantees an as far as possible uncomplicated postoperative course. The operation technique is described and in general the problems of postoperative early and late complications are discussed.


[Methods and value of an immunofluorescence-optical determination of IgM, IgG and IgA rheumatoid factors].

Today the immuno-fluorescence technique is the simplest method to detect rheumatoid factors of all immuno-globulin classes. When applying sheep erythrocytes, standard sera may be used without exception. The airdried smear of the cells is to be incubated with rabbit anti-human-erythrocyte serum. The rheumatoid factors of the subsequently applied inactivated patients' sera localise above the amboceptor on the erythrocyte membrane. Only they bind FITC marked anti-human-gamma-globulin and cause a specific fluorescence. As a proof heteroagglutinines and crossreacting antibodies of the marked sera are first absorbed and corresponding controls are carried out. According to assessments of 101 sera approximately 20% of healthy people, approximately 50% of "definitely seronegative" patients with rheumatoid arthritis according to the agglutination method as well as 30% of other arthropathies had rheumatoid factors by these methods. A negative immunofluorescence optical test does not absolutely exclude the presence of rheumatoid factors in the serum. It is suggested that their occurrence are due to secondary reactions to the formation of immunogen antigen-antibody complexes.


[Prophylaxis of thromboembolism using low dosage heparin (author's transl)].

In establishing a surgery free from thromboembolism low dosage-Heparin is a promising line. Its efficacy, regulation, control and side effects are surveyed. The results achieved justify its indication on a large scale.


[Spermatozoa immunity].

A report is given on the spermatozoan and seminal plasma antigens and the possibilities of immunization of woman and man with these antigens. The occurence of sperm antibodies is demonstrable with more or less specific methods. The clinical importance of sperm antibodies for female fertility depends on quality of semen and many other factors. The local immune reactions to sperm and other reproductive antigens in the female genital tract has been inferred from the detection of higher titer of activity in tissue than was found in the circulation.


[Modern concept of the makeup of intestinal microflora in healthy adults].

Analysis of the literature data on the significance of normal intestinal microbial population in the vital activity of the organism, and also on the sequelae of unfavourable shifts in the intestinal microecology is presented. The results of personal studies on the composition of normal microbial population in healthy adults are discussed; criteria for the assessment of normal intestinal biocenosis are given. The importance of bifidum flora is emphasized, and the necessity of its correction in various pathological conditions is underlined.


[Transplantation and cellular reactions to tissue antigens in Streptococcus-immunized rabbits].

The immunization of rabbits with the cells and the disintegration products of fractions of the cytoplasmic membranes of group A streptococcus (type 1) in incomplete Freund adjuvant, introduced in a single injection into the pads of the paws, caused lesions in autoplastic skin grafts and accelerated the rejection of alloplastic skin grafts. The rabbits showed positive delayed-type skin reactions to streptococcus and homologous skin antigens, and lymphocytes specifically reacting with FITC-labeled homologous skin antigen were found in their blood. Prolonged intravenous immunization with streptococcus, which induced the formation of complement fixing antibodies to homologous skin antigens, did not influence the taking of autoplastic and alloplastic skin grafts. The injection of hyperimmune streptococcus rabbit antiserum containing antibodies to skin antigens to intact rabbits produced no lesions in the autoplastic skin grafts and prolonged the lift of the alloplastic skin grafts.


[Identification of the enterobacteria isolated from patients by using the Enterotube test system].

The Enterotube test system intended for the accelerated identification of enterobacteria was used to study 319 strains isolated from patients with suppurative complications after surgical operations and traumatic lesions.  The test system was found to allow a reliable identification of Enterobacteriaceae having characteristic biochemical properties. It was also found that the kit intended for 10 tests could prove insufficient for the identification of atypical bacteria. The Enterotube test system made it possible to differentiate 95% of enterobacterial strains; in the identification of bacteria by their genus and species and results obtained with the use of the Enterotube test system and common biochemical methods were found to be identical (in 96.4% of tests).


[Use of the passive hemagglutination test to diagnose toxoplasmosis].

The authors describe a method of obtaining toxoplasma erythrocytic diagnostic agent by sensitization of formalinized tannin-treated SRBC with purified toxoplasma antigen isolated by fractionation of complete toxoplasma antigen on Sephadex G-100. Comparative experiments with titration of sera of persons with suspected toxoplasmosis were conducted; the passive hemagglutination test with the antigen obtained proved to be highly sensitive in comparison with immunofluorescence and complement fixation tests.


[Gibb's free energy as a index of the assimilation of carbohydrate sources by bacteria].

The author presents substantiation of the use of thermodynamic function--of free Gibbs' energy (--deltaG) for energy characteristics of enterobacteria periodic cultures on synthetic media. Examination of strains of E. coli K12P4X Hfr, E. coli PA-309, and Sh. newcastle 762S showed the --detlaG = f (N) curves to characterise the energy value of various carbohydrate sources more completely, and also permitted the choice of their optimal concentrations in synthetic media for each of the enterobacteria strain.


[Study of the enterotoxic action of the neurotoxin of the Sonne dysentery microbe in a rabbit small intestine loop model].

The enterotoxic action of neurotoxin from Sonne dysentery microbes (obtained by the method of Mesrobeanu et al.), and also of the culture autolysates and homologous Boiven's endotoxin was studied on a model of the isolated loop of the rabbit small intestine. Neurotoxin preparations obtained from virulent strains as well as autolysates of these cultures possessed enterotoxic activity, whereas purifed endotoxin preparations in doses of 1--10 mg failed to cause any dilatation of the isolated intestinal segment. A significant individual rabbit sensitivity to the enterotoxic action of the neurotoxin preparation was revealed. Lyophilization of neurotoxin preparation did not influence its enterotoxicity. However dialysis against distilled water and boiling of the neurotoxin preparations led to the loss of enterotoxic activity.


The general pharmacology of prostacyclin PGI2, (PGX): a new prostaglandin especially active on the cardivascular system.

Prostacyclin is a new prostaglandin first demonstrated as a product of arterial microsomes and prostaglandin endoperoxide intermediates. The potential to form prostacyclin has now been demonstrated in many organs. It inhibits platelet aggregation, inhibits gastric acid secretion, stimulates the monkey but not the rat uterus in vivo, is a bronchodilator, is a vasodepressor on both systemic and pulmonary circulation, increases cardiac output and markedly decreases peripheral resistance. It reduced progesterone in pregnant hamsters but is not luteolytic in non-pregnant monkeys. In rats, i. v. infusion of 0.56 but not 1 mg/kg/day was tolerated without overt central nervous system depression. The depressor effect of i. v. infusions of prostacyclin in anesthetized rats was partially antagonized by a pressor reaction eliminated by nephrectomy, an effect not seen during infusions of prostaglandin.


A possible role of thromboxane A2 (TXA2) and prostacyclin (PGI2) in circulation.

Recently two local hormones, thromboxane A2 (TXA2) and prostacyclin (PGI2) have been discovered. These hormones are labile metabolites of arachidonic acid. TXA2 is generated by blood platelets, while PGI2 is produced by vascular endothelium. TXA2 is a potent vasoconstrictor. It also initiates the release reaction, followed by platelet aggregation. PGI2 is a vasodilator, especially potent in coronary circulation. It also inhibits platelet aggregation by virtue of stimulation of platelet adenyl cyclase. Common precursors for both hormones are cyclic endoperoxides PGG2 and PGH2, being formed by cyclooxygenation of arachidonic acid. This last enzymic reaction is more efficient in platelets than in vascular endothelium, and therefore the generation of PGI2 by vasuclar wall is accelerated by an interaction between platelets and endothelial cells. During this interaction platelets supply the endothelial PGI2 synthetase with their cyclic endoperoxides. The newly formed PGI2 repels the platelets from the intima. When PGI2 synthetase is irreversibly inactivated by low concentration of lipid peroxides, then the platelets are not rejected but stick to the endothelium, generate TXA2 and mature thrombi are formed. A balance between formation and release of PGI2, TXA2 and/or cyclic endoperoxides in circulation is of utmost importance for the control of intra-arterial thrombi formation and possibly plays a role in the pathogenesis of atherosclerosis.


Some actions of prostacyclin (PGI2) on the cardiovascular system and the gastric microcirculation.

Prostacyclin, generated by the vascular wall, is a potent vasodilator, reducing systemic blood pressure, increasing coronary blood flow and relaxing isolated vascular strips. Its vasoactive properties are little changed by passage through the lung. Prostacyclin, which is also formed by the gastric mucosa, increases gastric mucosal blood flow and inhibits gastric acid secretion and indomethacin-induced erosions. It is the most potent inhibitor of platelet aggregation in all species tested. It is suggested that prostacyclin and PGE1 act on similar sites on platelets distinct from those for PGD2.


Influence of coronary vasodilators on prostaglandin E, F2alpha, I2, and adenosine metabolism.

We investigated the influence of oxyfedrine, verapamil, prenylamine, sodium nitrite, nitroglycerin, papaverine and carbochromen on the release of prostaglandins (PG) and adenosine from Langendorff heart preparations of guinea pigs and rabbits and on the PG biosynthesis in the heart and renal medulla of rabbits, in the bovine seminal vesicle homogenate, and in the rat stomach fundus. Oxyfedrine stimulated the release of PGE and PGF2alpha from the Langendorff hearts and increased the PG biosynthesis in all organs investigated. Compared with the other drugs, oxyfedrine showed the strongest stimulation of PGI2-synthesis in the rat stomach fundus. Prenylamine depressed the PG biosynthesis in all organs investigated but increased the PGE release from Langendorff hearts. Nitroglycerin, verapamil and, to some degree, also carbochromen increased the PGI2 synthesis in rat stomach fundus. Sodium nitrite was without influence on the PG release from Langendorff hearts and on the PG biosynthesis. Papaverine did not influence the PGI2 synthesis. Independently of the PG release, oxyfedrine, prenylamine and sodium nitrite increased the adenosine efflux from the rabbit hearts.


The antiarrhythmic action of prostacyclin (PGI2) on aconitine induced arrhythmias in rats.

Prostacyclin (PGI2) produces an antiarrhythmic effect on aconitine induced arrhythmias in rats. The ED50 of PGI2 was 0.7 microgram/kg and the maximum antiarrhythmic effect 54 per cent. The equi-effective doses of PGE2 and PGF2alpha were higher (ED50 of PGF2alpha = 1.2 microgram/kg, ED50 of PGE2 = 2.7 microgram/kg). However, PGF2alpha and PGE2 had a maximum antiarrhythmic effect of 80 per cent in this model.


Development of polyploidy in B-cells of normal and diabetic mice.

This study was designed to clarify the relationship between pancreatic B-cell polyploidization and the progress of the diabetic syndrome in genetically diabetic (C57BL/Ks-db/db) and normal control mice (C57BL/KsJ) of matched age groups. Nuclear volume was confirmed to be a proper index of the polyploid class of the B-cell by correlation with Feulgen-DNA content as measured by microdensitometry. Nuclei of B-cells, identified by aldehyde fuchsin positive cytoplasmic granules, were traced by camera lucida and their volumes determined by semiautomatic particle size analysis. Six age groups were studied: 4.5, 7, 9.5, 12, 14.5 and 17 weeks. The major conclusions are: 1) The percentage of tetraploid nuclei in normal mice is consistently between 1.0 and 2.0% from 4.5 to 14.5 weeks of age and increases to approximately 3.0% at 17 weeks of age; however, further studies are required to determined the significance of this increase; 2) in all age groups studied, percentages of polyploid nuclei are significantly greater in diabetic than in control mice; 3) the percentage of tetraploid nuclei in diabetic animals is elevated 220% over controls at 4.5 weeks of age, remains constant until 12 weeks (while other parameters such as blood glucose level and body weight continue to rise) and increases significantly between 12 and 14.5 weeks of age. Implications of both the increased polyploidy observed at the onset of disease symptoms, and the dramatic increase occurring during the later stages of the disease, are discussed.


Immunohistochemical localization of adrenodoxin and adrenodoxin reductase in bovine adrenal cortex.

The zonal distribution of adrenodoxin and adrenodoxin reductase (EC 1.6.7.1) in the bovine adrenal cortex as well as their intracellular localization has been studied by the direct method of peroxidase-labelled antibody (Fab' or F(ab')2 fraction) technique. The results indicated that both proteins localized mainly in zonae fasciculata and reticularis whereas very few were present in the zona glomerulosa. Only parenchymal cells in the adrenal cortex were proved to contain both proteins. The intracellular localization of both adrenodoxin and the reductase was demonstrated to be exclusively on the inner membrane of mitochondria of these parenchymal cells by immunoelectron microscopy. The validity of the immunocytochemical method employed in this study to determine the fine localization of both proteins in the mitochondria as well as the significance of the zonal distribution in relation to the function of each individual zone is discussed.


[Cimetidine in the treatment of the active duodenal ulcer].

Thirty six patients with active duodenal ulcers were studied in this double blind work. 19 received placebo and 17 Cimetidine: 1 gr./day. The endoscopic control after 21 days, showed healing in 81,2% of the cases treated with Cimetidine and in 22,2% of those with placebo. After 42 days of continous treatment with Cimetidine the healing of duodenal ulcers was 82,3% against 50% with placebo; the difference being highly statestically significant; p less than 0.01. The symptoms improved with Cimetidine revealing less diurnal and nocturnal pain complete disappearance of nausea and vomit and a significant decreased ingestion of alkali tablets.


Spinous leafy nerve endings in the feline stomach wall.

The Champy-Maillet ZIO technique has been applied to the study of the muscular tunic of the stomach. In the corpus and antrum pyloricum some nerve fibres end in non-capsulated expansions owning thorn-like protrusions. Their morphology is studied and a possibly functional sensory significance is proposed, on the basis of previous experimental results.


Effect of a slow release preparation of levodopa on Parkinson's disease in combination with a peripheral decarboxylase inhibitor.

Plasma concentrations of levodopa were determined after therapeutic oral levodopa-carbidopa doses. The wide fluctuations observed in plasma levodopa levels could be considerably reduced by the addition of a slow release levodopa preparation. This kind of combination medication was given to 15 parkinsonian patients, whose earlier therapy had proved inadequate. With the combination medication, levodopa-carbidopa, on an average 420 mg/42 mg combined with 950 mg of levodopa in slow release form, a statistically significant improvement in parkinsonian signs could be achieved without any worsening of the side effects. The results suggest that parkinsonian patients may tolerate much higher daily levodopa doses if the fluctuations in plasma levels of the drug can be diminished.


Improvement of defective lactation by using oral metoclopramide.

An attempt has been made to pharmacologically enhance PRL secretion to improve lactation. Twenty-one puerperal women with past history of defective lactation and PRL levels under the normal range were studied for 4 weeks postpartum. Eleven patients who received orally 20 mg a day of metoclopramide showed persistently elevated basal levels of serum PRL during the four weeks' observation period. These women also had a good milk production and their infants did not need supplements. Ten women receiving placebo, however, showed an abrupt decrease in basal PRL levels, and this decrease persisted despite the continuation. Simultaneously a decline in the milk yield was observed and by the 14th postdelivery day milk production was minimal. The administration of metoclopramide at this moment to this group of poor lactating mothers produced an increase in serum PRL levels which presisted for the rest of the study. Metoclopramide also augmented the milk production so that these women were able to continue breast feeding their infants. Our preliminary results seem to prove that defective lactation associated with low prolactin levels (prolactipenia) can be treated by the manipulation of endogenous PRL secretion through the administration of metoclopramide or drugs which enhance PRL release.


Long-term prognosis of infants with idiopathic respiratory distress syndrome. Follow-up studies in infants surviving after the introduction of continuous positive airway pressure.

Fifty-one children surviving IRDS with CPAP alone or CPAP and IPPV were studied at the age of 2.5 to 4.0 years. One child had developed tetraplegia and mental retardation and 6 children were speech-retarded. Correlation with perinatal events showed that this group of children had a significantly lower gestational age and birth weight, a lower Apgar score and a higher PCO2 prior to ventilatory treatment than the remainder. Re-examination by age 4.0 to 5.0 years showed persistent handicaps in only four of the seven children.


Electron-microscopic demonstration of Streptococcus mutans in 5-day-old experimental dental plaque using immunohistochemistry.

The present work described the distribution of horseradish peroxidase reaction product obtained after immunohistochemical staining of consecutive ultra-thin sections of 5-day-old experimental dental plaques using differently absorbed anti-S.mutans sobrinus, anti-S.mutans mutans, and normal rabbit lambda-globulins. It was found that an in situ identification of S.mutans subspecies sobrinus could be obtained using thoroughly absorbed anti-S.mutans sobrinus gamma-globulins and consecutive sections. The anti-S.mutans mutans gamma-globulins were after tests on pure cultures of several oral bacteria found to cross-react with S.milleri. Furthermore, crude and absorbed normal rabbit gamma-globulins were observed to contain antibodies that cross-reacted with several plaque microorganisms.


Respiratory and circulatory responses to sustained positive-pressure breathing and exercise in man.

To investigate the effects of sustained positive-pressure breathing (PPB) on the adaptation of respiratory and circulatory functions to exercise, 8 healthy volunteers were exposed to PPB of air at 15 and 30 cm H2O in the supine position at rest and while performing leg exercise at 50% of individual maximal working capacity. PPB was both subjectively and objectively better tolerated when combined with exercise than it was at rest. PPB at 30 cm H2O resulted in marked hyperventilation with alkalosis in the resting condition, but did not significantly affect respiratory minute volume, blood gases or acid-base balance during exercise. Cardiac output and left ventricular work were reduced by about one fifth and one third, respectively, both at rest and during exercise. In contrast to the case at normal airway pressure, exercise-induced increase in cardiac output was accompanied by an increment in stroke volume during PPB. Although mean arterial pressure (relative to atmospheric) was elevated by PPB at rest and during exercise, the driving pressure in systemic circuits (arterial minus central venous pressure) was reduced in both conditions. It is concluded that dynamic exercise counteracts deleterious effects of PPB by normalizing respiratory function and by improving cardiac filling by activation of the leg muscle and the abdominal pumps.


A double-blind comparison of flupenthixol, nortriptyline and diazepam in neurotic depression.

A double-blind trial of flupenthixol, nortriptyline and diazepam in neurotic depression using flexible dose schedules suggested that each drug is an efficient treatment for this category of depression although the patterns of response and prevalence of side-effects varied. No differences reaching a level of significance could be shown on rating scales of depression or anxiety, but trends favoured flupenthixol. However, clinical evaluation suggested flupenthixol to be more effective than diazepam on mental state examination (P less than 0.05) and to have a greater overall therapeutic effect than nortriptyline (P less than 0.05). It also had fewer side-effects than nortriptyline (P less than 0.05).


Preliminary clinical test of zimelidine (H 102/09), a new 5-HT uptake inhibitor.

Zimelidine, a bicyclic compound, which in animal experiments causes specific inhibition of the uptake of 5-HT, was tried on 15 patients with depression of endogenous type. It produced considerable and highly significant 5-HT uptake inhibition in rat brain slices incubated in blood plasma from the patient under treatment, but no inhibition of NA uptake. Depressive symptoms were effectively relieved or entirely abolished in about two thirds of the patients. Only four patients did not react to the drug, and three of these were probably in need of NA uptake inhibitors, which on other occasions had worked well on their depressions. These three patients showed an extreme degree or retardation. During zimelidine treatment they were not just unaffected but showed signs of excitation, impatience and desperate feelings. These preliminary findings strongly indicate the true existence of depressive cases in need of an NA uptake inhibitor, but completely resistant to a specific 5-HT uptake inhibitor. The final dose of zimelidine was 75 mg b.i.d. This dose, although sufficient in most cases, was obviously somewhat low for a few of our patients. The concentration in blood plasma of zimelidine should probably reach a minimum level of 250 nmol/l and norzimelidine 500 nmol/l, and to achieve this a general dosage of 100 mg b.i.d. is recommended.


Changes in learning, memory, and mood during lithium treatment. Approach to a research strategy.

In a double-blind study the effects of a 14-day lithium medication (dosage: 24 mval/day to 36 mval/day) were investigated. The subjects were 24 healthy male volunteers. The effect of lithium on their mood, ability to learn nouns, and memory of the words learnt was measured after 2 hours and 14 days. In spite of a relatively low mean plasma lithium level on the 14th day (0.54 +/- 0.15 mmol/l), the lithium volunteers assessed themselves after 2 weeks of treatment as significantly less relaxed, less active, less socially involved, more bored, and more tired than the placebo group. As to learning, the lithium group showed only a slight impairment of performance compared with the placebo groups. As to memory, there was a significant difference in free recall over 2 weeks: the lithium group remembered fewer words than the placebo group. Additional motivation of free recall over 2 hours was ineffective. It is discussed whether lithium changes spontaneous initial action and thereby the will to act. This could be interpreted as a change in the production of the characteristics of experience and behaviour.


A simple method for the determination of section thickness with high accuracy.

Using the partial carbon-coating of histological sections their thickness was determined by a relatively simple and accurate method. Calculations were based on the instrumental recording of the distance of focus change between the upper and lower section-surfaces. Determination of tissue refractive index was not required. Results compared favourably with those of more complicated techniques.


Elimination of Escherichia coli K88 adhesion determinant by antibody in porcine gut and mammary secretions following oral immunization.

1) Although virulence of enteropathogenic E. coli in the pig is essentially associated with the K88 adhesion determinant, protection of the neonate and weanling is not necessarily dependent upon antibodies to this surface antigen. 2) Modification of the surface antigenic characteristics of enteropathogens occurs in the presence of antibody, suggesting an immune mechanism of induced loss of the genetic elements responsible for the synthesis of K88. 3) Antibodies directed against the K88 antigen do not seem to participate in the elimination of the K88 antigen. These observations provide a new concept that antibody mediated mechanisms of host defense include elimination of virulence determinants, a feature vital to maintaining the balance of the host pathogen relationship favorable to the host.


Secretory IgA antibodies to enterobacterial virulence antigens: their induction and possible relevance.

1) Milk and salivary s-IgA antibodies are via the homing of IgA producing cells from the Peyer's patches closely connected with antigenic stimuli in the intestine. This explains the presence in human milk of s-IgA antibodies against E. coli O and K antigens, V. cholerae and Shigella O antigens, E. coli and V. cholerae enterotoxins. These secretory antibodies can be induced by intestinal exposure and boosted by parenteral vaccination. 2) Preliminary data suggest that the IgA response in the urinary tract and possibly in the lung may be involved in the homing mechanism as well. 3) The protective role of the milk s-IgA antibodies to enterobacterial virulence antigens is strongly suggested, as is the protection mediated by urinary antibodies against urinary tract infections.


Adhesion and chemotaxis as determinants of bacterial association with mucosal surfaces.

1) Chemotaxis of cholera vibrios facilitates the association of these bacteria with the mucosal surface. 2) Mucosal extracts can block the chemotactic receptors on the bacterial surface and thereby retard the association of chemotactic bacteria with the mucosal surface. 3) Chemotactic cholera vibrios grow more efficiently than non-chemotactic mutants in germfree mice and in isolated intestinal loops of rabbits. Conversely, non-chemotactic mutants grow more efficiently in infant mice. 4) Chemotaxis is therefore of considerable importance to the in vivo growth of cholera vibrios. The various mechanisms, including those of local immunity, by which bacterial chemotaxis can be exploited for the benefit of the host deserve further exploration.


Prevention of bacterial infections of mucosal surfaces by immune secretory IgA.

1) Colonization and diarrhea in the rabbit due to RDEC-1 strain E. coli elicits an immune response that prevents subsequent infection with the same bacterium. 2) RDEC-1 and InvEC strain colonization of the gut of pregnant rabbits is followed by the appearance, post-delivery, of anti-InvEC or RDEC-1 strain s-IgA in the milk, some of which was able to agglutinate as many as 3.4 X 10(11) bacteria per mg of s-IgA. 3) Immune s-IgA, given by the orogastric route to rabbits, is able to survive the digestive enzymes of the gastrointestinal tract to prevent the colonization and diarrhea that follows the inoculation of InvEC and RDEC-1 strains. One possible explanation for the protective effect of s-IgA is the in vivo agglutination of bacteria in the lumen of the gastrointestinal tract.


Studies on oral adjuvants against murine salmonellosis.

1) Attempts were made to develop oral adjuvants against murine salmonellosis. 2) Streptomycin, levamisole and PHA show potential immunoenhancing properties against salmonella infection. 3) The mode of action of these agents remain to be elucidated. Observed results of PHA enhancement may be related to its blastogenic effects in the splenic T-cells. 4) Decrease in certain bacterial flora resulting in less antigenic competition may be the mode of action of streptomycin as adjuvant when added to oral salmonella vaccine.


Epidemiology of Guillain-Barré syndrome.

The only measures of morbidity for Guillain-Barré syndrome in well-defined populations in the continental United States come from Olmsted County, Minnesota, and San Joaquin County, California. The estimated incidence rates are between 1 and 2 cases per 100,000 population per year. Despite the hazards of generalizing from such small samples, these are the only estimates available. Large case series have suggested that the syndrome is more common in males, that it may occur at any age, and that it is frequently associated with some antecedent infection. Only two case-control comparisons have been carried out which reveal an association between Guillain-Barré syndrome and an infection 1 month prior to onset of neurological symptoms. A recent survey of four states in the United States revealed that the risk of Guillain-Barré syndrome among individuals receiving immunization against influenza A/New Jersey is 7.3 times the risk among the nonvaccinated. Aside from these investigations and one study linking Guillian-Barré syndrome and high antibody titers to cytomegalovirus, adequate epidemiologic studies to test suggested etiologic hypotheses have not yet been carried out. The rarity of the condition and the variations in its clinical presentation and course pose certain problems for epidemiologic investigations. Strategies for overcoming these difficulties are discussed.


Epidemiology of radiculopathies.

Many diseases affecting the peripheral nervous system or the spinal canal may be associated with pathology in the nerve roots, but the most common sources of radiculopathy are conditions that cause direct compression of nerve roots, including prolapsed intervertebral disks, disk degeneration, and osteoarthrosis of the apophyseal joints. The risk for prolapsed lumbar disk is highest in the group 20 to 39 years of age, and it is probably increased by the driving of motor vehicles, full-term pregnancies, and sedentary occupations. Cervical disk prolapses tend to occur in a slightly older age group, but very little is known of specific etiologic agents. Both lumbar and cervical prolapses usually occur in a posterior-lateral direction, and thus they are generally associated with nerve root impingement. Both osteoarthrosis of the apophyseal joints and disk degeneration sometimes progress to nerve root involvement. Although the shape and position of the involved structures undoubtedly influence the likelihood of radiculopathy, it is unclear what other factors cause some individuals to progress to the stage of nerve root involvement and not others. Prevalence rates for osteoarthrosis of the lumbar and cervical spines increase markedly with age, and both are sometimes associated with generalized osteoarthrosis. Mechanical stresses from heavy occupations such as mining and from certain structural abnormalities of the spine such as spondylolisthesis predispose to osteoarthrosis of the lumbar spine. However, little is known about factors associated with osteoarthrosis of the cervical spine. The nature of the stress related to development of osteoarthrosis in the lumbar spine is not known. Disk degeneration is also strongly related to age, with preliminary degenerative changes occurring as early as 20 to 29 years of age and osteophyte formation tending to occur from the fifth decade on. Mechanical stress from heavy occupations is associated with lumbar disk degeneration, but, again, little is known about etiologic factors in cervical disk degeneration. It is apparent that much remains to be learned about the etiology and natural history of these conditions, and it is clear that the gaps in knowledge are even greater for the cervical region than for the lumbar spine. In view of the relatively high frequency of occurrence of these conditions and the amount of pain and disability they cause, epidemiologic studies of etiology and natural history are urgently needed.


Prostaglandins: physiological and clinical correlations.

This review has necessarily been incomplete. We have not considered the potentially important interplay between PGs and male and female reproductive functions or the well-documented relationships between PGs and inflammation. We have examined the evidence for the influence of PGs on the pulmonary and peripheral vascular circulations and the interaction between PGs and the kidney and the autonomic nervous system. Emphasis has been placed on the role of PGs in the control of the circulation of the ductus arteriosus, and our recent experiences with indomethacin in sick, preterm infants with large left-to-right ductal shunting have been outlined. Existing information has been reviewed concerning PGs and the fetal-placental and fetal-maternal units. It should be clear that a host of proposed functions exists for PGs; many remain tentative in light of the conflicting and often bewildering results of animal experimentation.


Environmental causes of cancer in childhood.

Although it is commonly said that only a small proportion of childhood cancers are caused by environmental exposures, much has been learned about exogenous carcinogens through study of their effects or noneffects in children: 1. Ionizing radiation poses some risk no matter how small the dose. 2. Concepts about the viral etiology of cancer have had to be adapted to fit observations in children concerning candidate viruses. 3. Transplacental chemical carcinogenesis has become a reality and poses an increasing threat as chemical pollution worsens. 4. Questions have been raised about the risk of breast feeding in (at present) rare instances when the mother has been heavily exposed to chemicals that are excreted in the fat of breast milk. 5. A few drugs administered to children induce cancers within the pediatric age-span. The pediatrician must take action not only against exogenous agents that induce cancer while the patient is under his care, but also against exposures that begin in utero and lie latent or accumulate throughout life to give rise to cancers in the years or decades ahead. There is much more to carcinogenesis than the effects of the environment. Important information has been gained about the origins of cancer and about human biology in general through studies of children who are unusually susceptible to certain forms of neoplasia. Knowing the mechanisms involved may lead to new modes of treatment, to screening tests for environmental carcinogens or to methods for detecting cancer early enough for treatment to be life-saving.


Coal gasification and occupational health.

Identification and prevention of health effects due to occupational exposures in coal gasification processes requires a basic knowledge of the technological process by which gasification proceeds. This paper presents an overview of the technology and a rational approach to health hazard identification based upon the concept of the unit operation specific micro environment. A final section is devoted to summarizing current research efforts being carried out under the aegis of the National Institute for Occupational Safety and Health.


Incidence of new pulmonary perfusion defects after routine cardiac catheterization.

The incidence of pulmonary perfusion defects after routine cardiac catheterization was assessed in 57 patients by comparing ventilation-perfusion lung scans obtained before and 1 day after catheterization. Patients were prospectively randomized to two groups, one in which right heart catheterization was performed using an antecubital venous cutdown procedure and one in which the percutaneous femoral vein approach was used. Seven patients (12 percent) had new postcatheterization perfusion defects consistent with pulmonary emboli. These patients did not differ significantly from patients without new defects in clinical characteristics, duration of catheterization, hemodynamic variables or route of right heart catheterization. The data suggest that pulmonary embolism may be a more common complication of routine cardiac catheterization than previously appreciated.


Electrophysiologic approach to therapy of recurrent sustained ventricular tachycardia.

The refinement of the techniques of programmed stimulation and intracardiac recording has led to understanding of the mechanism of ventricular tachycardia and these techniques can be applied clinically to the development of therapeutic regimens. The efficacy of drug therapy can be assessed in sequential studies evaluating the ability of drugs to prevent initiation of the arrhythmia by electrical stimulation. The efficacy of pacemaker therapy can be evaluated by assessing the effects of stimulation during the tachycardia. The recent development of endocardial mapping provides the surgeon with a tool to guide therapeutic surgical ablation of the site of origin of the tachycardia. Such an electrophysiologic approach to recurrent ventricular tachycardia can lead to the rapid development of successful therapy under controlled conditions.


The concept of trifascicular intraventricular conduction: historical aspects and influence on contemporary cardiology.

The efforts of Mauricio Rosenbaum and his co-workers in putting together the anatomic and electrocardiographic correlations that led to the development of the concept of trifascicular intraventricular conduction have had a major impact on electrocardiography. Perhaps the greatest testimony to their contributions is the large number of related publications by many authors since the printing of Los Hemibloqueos more than 10 years ago.


Nutritional anemia: its understanding and control with special reference to the work of the World Health Organization.

Since 1949, the World Health Organization, recognizing the public health importance of nutritional anemia, has sponsored efforts directed towards its understanding and control. During this period, often as a result of the work of the Organization, advances have been made in many areas. Basic understanding of iron, folate and vitamin B12 nutrition, and the various factors which may influence the availability and requirements of these factors, has greatly increased. Surveys in a number of countries have highlighted the widespread prevalence of nutritional anemia, particularly in developing countries. The major factor responsible is a deficiency of iron, whith folate deficiency also playing a role in some population groups, especially in preganant women. There is increasing evidence that anemia adversely affects the health of individuals and may have profound socioeconomic consequences. Control of nutritional anemia is possible by providing the deficient nutrient(s) either as therapeutic supplements or by fortification of commonly used foodstuffs. Some control programs are reviewed and suggestions for further action outlined. The Organization still has an important role to play in this field, encouraging the development of control programs and providing advice and technical assistance ot member countries.


Medical parasitology in China: an historical perspective.

Traditional Chinese anthelmintics prove to be interesting because social, political, cultural, psychological and philosophical factors could affect them. A review of the ideas on the origin of parasitic infection and the historical development of medical parasitology in China is attempted to aid in the elucidation of the rationale of traditional Chinese anthelminthic treatment.


Alcoholic hepatic disease. Specificity of IgA deposits in liver.

The extent to which the immunofluorescent phenomenon of homogeneous deposition of IgA in the hepatic sinusoids (so-called continuous pattern) was specific for alcoholic hepatic disease was investigated. In 66 of 320 liver biopsy specimens a continuous IgA pattern was observed. Alcoholism was mentioned in the cases of 50 of the 66 patients (76%). The biopsy specimens in the remaining 254 cases continued scanty detectable IgA (discontinuous pattern) or none. In the latter group only eight patients (3%) had histories of alcoholism. A direct correlation between a continuous IgA pattern in the hepatic sinusoids and alcohol abuse is thus inferred (P less than 0.001). Additional findings of the concomitant occurrence of IgA in the perisinusoidal linings of the liver, the wall of superficial cutaneous capillaries, capillaries of the gut, and the glomerular mesangium in association with alcoholic hepatic disease further substantiates the concept of the existence of an IgA-associated disease.


Characterization of a polyvalent conjugate of Bacterroides fragilis by fluorescent antibody staining.

A polyvalent conjugate (fluorescein-isothiocyanate-labeled antibody reagent) prepared for Bacteroides fragilis contained conjugates prepared against three strains of B. fragilis. This conjugate stained 93% of the 111 B. fragilis test strains; the other 7% of B. fragilis stained at certain times but not others. The conjugate was specific for B. fragilis, 91 strains of anaerobes other than B. fragilis and aerobes failed to give a positive fluorescence. The advantage of this conjugate is that it provides a quicker and less expensive identification of B. fragilis than the use of pre-reduced biochemical media and gas chromatography.


Annotated bibliography of health care books for children.

We present a comprehensive bibliography of books aimed to help physicians, other health care providers, and parents prepare children for medical contacts. Publications have been annotated and rated on the basis of use and cost. We propose that this will be a useful reference for those responsible for the health care of the pediatric population.


Effect of cimetidine on stimulated gastric secretion and serum gastrin in the dog.

The histamine H-2 receptor antagonist cimetidine was given for 90 minutes to four fistula dogs during a steady dose 270-minute infusion of histamine (50 microgram. base/kg.hr.), urecholine (80 microgram./kg.hr.) or pentagastrin (1.5 microgram./kg.hr). In each case there was gradual but marked (75-95%) inhibition of acid secretion with maximal effects after 60-90 minutes while pepsin secretion was also suppressed but to a lesser extent. These effects persisted for at least the 90 minutes after the end of cimetidine infusion. Serum gastrin was not significantly changed by cimetidine. Kinetics of effect of cimetidine were derived from stepdose responses to histamine (2-150 microgram./kg.hr.), pentagastrin (0.1 to 10 microgram.kg.hr.) and urecholine 20-160 microgram./kg.hr.) which were made alone and with background infusions of cimetidine. Cimetidine acted competitively for acid output with histamine as the stimulus and noncompetitively for pentagastrin or urecholine. With histamine or pentagastrin pepsin was less inhibited than H+ and in the case of urecholine, pepsin secretion was not inhibited by cimetidine.


Carcinoma of the small intestine in regional enteritis: presentation of a case and review of the literature.

A case of carcinoma of the jejunum occurring in a patient with Crohn's disease of 30-years' duration is presented. Forty-seven previously reported small bowel carcinomas in Crohn's disease patients are reviewed. The incidence of small bowel carcinomas in patients with Crohn's disease has been cited as being as low as 0.08%, a figure which is still higher than the 1 in 10(9) population which would be predicted if the two diseases were independent of one another. The average age of incidence of the Crohn's carcinomas was 46.5 years while that for the de novo group was 55 years. The sexual ratios were 2.46:1 and 2:1, males to females, for the respective groups. The de novo carcinomas had a slight predilection for the duodenum at 40.7% while the latter group had a heavy predilection for the ileum at 70.8% and contained no duodenal carcinomas. The prognosis of the Crohn's group appeared to be much worse than that of the de novo group with five-year survivals of 3.7% and 20-22% respectively. Late diagnosis in the enteritis group was felt to be the major reason for this. Finally, several pathological differences between the lesions in both groups are presented.


Comparison of the effects of glucagon and atropine sulfate on gastric emptying.

Six asymptomatic adult males cooperated in a study of gastric emptying. Each subject was given a test meal of 500 ml. of 3.5% glucose on a fasting stomach. Ten minutes prior to the meal each was given either 1 mg atropine sulfate, placebo, or 2 mg. glucagon, double-blind and crossover. Each drug was given twice, intravenously, in a random order. The meal was removed by a Salem sump tube half an hour after ingestion. When compared to placebo, the active drugs significantly (P less than 0.05) slowed gastric emptying; atropine sulfate was more effective (P less than 0.05) than glucagon. The active drugs significantly (P 0.05) decreased total gastric acid secretion and total gastric chloride as compared to placebo. Glucagon significantly (P 0.05) increased the blood glucose concentration as compared to placebo. These results indicate that both glucagon and atropine sulfate slow the gastric emptying of a liquid sugar meal from the stomach.


Alcohol-induced gastric and duodenal lesions in man.

To determine the effect of an acute dose of ethanol on the stomach and duodenum, seven alcoholic subjects with previously normal upper gastrointestinal endoscopy were reevaluated with endoscopy and directed biopsy three hours after the oral ingestion of ethanol (1 gm./kg. body weight) as a 35 gm./100 ml. solution. After ingestion of alcohol, all seven subjects had moderate to severe antral erythema and friability and two had patchy erosions and hemorrhage in the antrum and fundus of the stomach. Five of seven subjects had changes in the duodenal bulb consisting of erythema similar to that in the antrum of the stomach. Microscopically after alcohol, four of seven demonstrated focal subepithelial hemorrhage and another had frank mucosal hemorrhage in the antrum. In the duodenal bulb, four of seven subjects demonstrated focal subepithelial hemorrhage in the tips of bulbar villi and four of seven had striking infiltration of eosinophils in the subepithelial stroma. These histologic alterations were not present in prealcohol biopsies or in biopsies in two additional subjects given club soda alone or beef bouillon, or in repeat biopsies in two subjects re-endoscoped three days after the ingestion of alcohol when the endoscopic findings were again normal. It is concluded that a single dose of alcohol consistently causes macroscopic and microscopic antral and duodenal alterations.


Empiric therapy of febrile granulocytopenic patients.

Antibiotic therapy in granulocytopenic cancer patients, the risk factors predisposing these patients to infection, and the signs, symptoms and types of infections occurring in these patients are reviewed. The four most commonly isolated organism at most cancer treatment centers are Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa and Staphylococcus aureus. Early antimicrobial therapy with broad-spectrum antibiotics before culture results are known produces cure rates of approximately 70%, regardless of the combination used. The most important predictor of response to any antibacterial regimen is a rise in the absolute granulocyte count. The current recommended fever regimen would be carbenicillin (or ticarcillin) with an aminoglycoside. The choice of an aminoglycoside depends on the prevailing organism sensitivities at a particular institution; in many cases, gentamicin sulfate is suitable. Addition of a cephalosporin to the two-drug regimen offers little increase in cure rates, except whem aminoglycoside-resistant Enterobacteriaceae are prevalent. Because of nephrotoxicity produced with combinations of cephalothin sodium and the aminoglycosides, cefazolin sodium would be the current cephalosporin of choice. An alternate third drug to be considered is co-trimoxazole, a broad-spectrum antimicrobial not yet commercially available in parenteral form. In the absence of a clinical response to appropriate antimicrobial therapy in documented infections, granulocyte transfusions may be indicated.