Polycystic renal disease--occurrence of malignant change and role of nephrectomy in potential transplant recipients. 28 cases of malignant renal neoplasms in patients with polycystic kidneys are reviewed from the literature and 2 new cases are reported. The difficulty in diagnosing this malignant change together with the increased survival of patients with polycystic kidneys on dialysis and transplant programmes leads to the recommendation that all such patients should be considered for nephrectomies. The reasons for this recommendation and its advantages and disadvantages are discussed.


Late ureteric obstruction in renal transplantation. 5 cases of ureteric obstruction occurring in renal allotransplant recipients who had received their grafts more than 3 years prior to presentation are reviewed.


Wound infection following appendicectomy: the effect of extraperitoneal wound drainage and systemic antibiotic prophylaxis. The value of extraperitoneal wound drainage and a 3-day course of prophylactic systemic cephaloridine used both separately and together have been assessed in a prospective controlled randomized trial involving 246 patients undergoing appendicectomy at the Leicester Royal Infirmary. Extraperitoneal wound drainage was shown to reduce significantly the incidence of postoperative wound infection in patients with a gangrenous or perforated appendix (P less than 0-025). Prophylactic cephaloridine significantly reduced the overall incidence of wound infection (P less than 0-02) and was also effective when the appendix was gangrenous or perforated (P less than 0-01). A highly significant reduction in wound infection was achieved when the appendix was gangrenous or perforated by the addition of wound drainage to the antibiotic regimen (P less than 0-001).


Diagnosis of acute abdominal pain in the accident and emergency department. This paper reports the findings in a study involving 1537 patients with 'acute abdominal pain' presenting over a 13-month period to the Accident and Emergency Department of the General Infirmary at Leeds. Of these, 341 patients who proved to have pain of greater duration than a week, pain incidental to some other identifiable condition or no pain at the time of their attendance were excluded. The remaining 1196 were diagnosed clinically (using a structured case sheet) and subsequently by a Bayesian computer system. Feedback of the results of clinical and computer systems was given to clinicians at regular intervals. Clinical diagnostic accuracy in patients with surgical disorders rose from 40 per cent before the study to 61 per cent. Computer accuracy in these patients was 69-9 per cent. The proportion of patients sent home without ill effects rose from 20 per cent to 39 per cent. In other areas (e.g. gynaecology) the effects were less marked. It is suggested that the introduction of a simple postgraduate educational service, aided by a small computer, might prove of practical benefit in this clinical situation.


The treatment of acute superficial abscesses: a prospective clinical trial. A total of 219 acute superficial abscesses was treated. Patients were randomly allocated to one of four treatment groups--primary suture with or without antibiotics and free drainage with or without antibiotics. No difference could be detected between the groups in duration of healing time. Eleven per cent of all abscesses sutured recurred and antibiotics did not affect this rate. It is suggested that free drainage following incision and drainage is the safest treatment for the majority of abscesses. Antibiotics do not have any significant effect on healing time or recurrence and their routine use is not recommended.


Superficial sepsis: the antibiotic of choice for blind treatment. When all cases of superficial sepsis were considered together Staphylococcus aureus was the most frequently encountered organism. Various anatomical sites were considered separately and it was found that the axilla and breast were particularly prone to infection by Staph. aureus. The incidence of infection by coliform bacili in Bartholin's and anorectal abscesses was significantly higher than in abscesses elsewhere. The importance of these observations in relation to antibiotic therapy is discussed.


Proliferative diabetic retinopathy: treatment with xenon-arc photocoagulation. Interim report of multicentre randomised controlled trial. One hundred patients with symmetrical proliferative diabetic retinopathy had one eye randomly chosen for treatment with xenonarc photocoagulation while the other was left untreated as a control. Patients were subdivided into those with new vessels on both optic discs and those with only peripheral new vessels. In patients with new vessels on the optic discs the vision of the untreated eyes deteriorated more than that of the treated eyes and the difference in deterioration was significant after one, two, and three years. There was no such difference in patients who had only peripheral new vessels. Eighteen patients had become blind in one or both eyes by the last assessment, but only one patient became blind in the treated eye without concomitant blindness in the untreated eye. Thirteen were blind only in the untreated eye. Both photographic and ophthalmoscopic examinations showed that new vessels on the disc regressed more in the treated eyes than in the untreated ones. As some forms of diabetic retinopathy are now treatable, early diagnosis and evaluation is increasingly important.


Metergoline in the inhibition of puerperal lactation. Seventy-eight mothers who did not want to breast-feed their newborn infants took part in a trial to assess whether metergoline could effectively suppress puerperal lactation. Metergoline 8 mg/day was given to 69 women within 24 hours after delivery and continued for five days to prevent lactation. The remaining nine women were given a course of metergoline once lactation had started. The drug was effective in both preventing and suppressing lactation. Milk secretion, engorgement, and pain were significantly reduced in women taking metergoline. Metergoline has a similar effect to bromocriptine in suppressing lactation, but its mechanism of action remains unknown.


Maintenance digoxin after an episode of heart failure: placebo-controlled trial in outpatients. The need for maintenance digoxin treatment was assessed in a double-blind, variable-dose, crossover comparison with placebo. Forty-six outpatients who had been prescribed the drug for heart failure were studied; 33 were in sinus rhythm and the remainder in atrial fibrillation. Mean serum digoxin concentrations in those with sinus rhythm averaged 1-33 nmol/l, but a lower concentration, averaging 0-97 nmol/l, was accepted in those with atrial fibrillation as six of them developed bradycardia. Sixteen of the 46 patients deteriorated on placebo, and eight completely recovered when digoxin was reintroduced; in the remainder additional diuretics were required temporarily. Spirometric values deteriorated on changing to placebo whether or not the patient showed clinical evidence of recurrence of heart failure. In a separate study of nine patients who showed no clinical evidence of deterioration on placebo, reintroduction of digoxin caused a shortening of left ventricular ejection time, which persisted for at least a month. This suggests that the inotropic response to digoxin is sustained during maintenance treatment.


Cholestyramine in uraemic pruritus.

Cholestyramine in uraemic pruritus. In a patient with longstanding severe uraemic pruritus who was undergoing chronic haemodialysis cholestyramine caused the pruritus to disappear completely within a few days. A four-week randomised controlled double-blind study was therefore performed in 10 other patients with uraemic pruritus who were on chronic haemodialysis. The pruritus improved considerably in four of the five treated patients, whereas only one of those treated with placebo experienced relief. The patient who had no relief while on cholestyramine showed a considerable improvement when the dose subsequently doubled. One of the five patients receiving cholestyramine experienced mild and easily reversible constipation, and another suffered nausea. Neither of these complications prevented the patients from continuing treatment. Cholestyramine seems to be useful in treating uraemic pruritus, although it is not known how it acts.


Partial antibiotic decontamination.

Partial antibiotic decontamination. Partial antibiotic decontamination and reverse isolation were carried out in nine patients undergoing bone marrow transplantation. The aim of this approach was to eradicate the patient's endogenous potentially pathogenic bacteria while preserving the anaerobic flora of the gut, which help to prevent recolonisation. No exogenous infections developed, and only one patient developed an infection associated with endogenous recolonisation. Colonisation resistance seemed normal in patients during partial antibiotic decontamination. This form of decontamination deserves further study in patients with immunodepression.


Dietary recommendations for the community towards the postponement of coronary heart disease. The public has recently been confronted with many, often conflicting, recommendations about diet and reducing the risk of coronary heart disease (CHD). Dietary recommendations to the community designed to lower the risk of CHD should be specific, clear, and brief. People should be advised to reduce their intake of foods that are high in saturated fats and replace these partially with foods that are relatively high in polyunsaturated fats. This will lower both total fat and dietary cholesterol intakes and will also change the ratio of polyunsaturated to saturated fats.


New cause of penicillin treatment failure. A large empyema infected with a penicillin-sensitive haemolytic group B streptococcus failed to respond to high doses of penicillin. After two weeks' treatment the pus aspirated was found not only to contain no penicillin, but also to inactivate penicillin added to it. We believe that the inactivating agent is an enzyme that may destroy various penicillins and cephalosporins but has no effect on other common antibiotics. When treatment was changed to doxycycline the patient made a rapid recovery.


High TSH concentrations in "euthyroidism": explanation based on control-loop theory. High concentrations of thyroid-stimulating hormone (TSH) in the serum have often been reported in apparently euthyroid patients with damaged thyroids. We have confirmed this finding in 14 patients 18 months after subtotal thyroidectomy for Graves's disease (group 1) and in 14 patients with manic-depressive psychosis (group 2) receiving lithium carbonate, which reduces thyroid reserve. One factor common to groups 1 and 2 but not to the controls was reduced thyroid reserve or functioning capacity, and, using established physical principles of servo-control, we have tried to define the mechanism. A series of curves were projected to indicate how TSH might be expected to vary with functioning thyroid capacity.


"Methicillin-resistant" Staphylococcus aureus: reassessment by controlled trial in burns unit. A controlled trial of oral flucloxacillin (250 mg six-hourly for four days) was performed in 34 patients treated by the covered method whose burns had yielded a heavy or moderate growth of Staphylococcus aureus resistant to methicillin at 30 degrees C but moderately sensitive at 37 degrees C. Staph aureus was eliminated in nine of the 17 patients treated with flucloxacillin but in none of the 17 controls; the proportion of patients from whose burns sensitive Staph aureus was eliminated in an earlier trial of cloxacillin was greater than this. Strains of Staph aureus commonly described as methicillin-resistant and showing heterogeneous growth at 37 degrees C of many sensitive and very few resistant bacterial cells should, in the light of these findings, be called moderately sensitive to flucloxacillin. Such "heteroresistant" strains showed consistent moderate sensitivity in replicate diffusion sensitivity tests at 37 degrees C, but very inconsistent results in replicate dilution tests, especially with flucloxacillin. These studies showed that 18-hour diffusion sensitivity tests indicate the clinical value of treatment with flucloxacillin for staphylococcal infections of moderate severity more correctly at 37 degrees C than at 30 degrees C.


Nicotine chewing gum as a substitute for smoking. The capacity of nicotine-containing chewing gum to produce plasma nicotine levels comparable to heavy cigarette smoking was tested in 21 subjects. On a fixed schedule of one piece of gum (4 mg nicotine) per hour, the average peak plasma nicotine concentration was 175-7 nmol/l (28-5 ng/ml) compared to 189-3 nmol/l (30-7 ng/ml) obtained from normal ad libitum smoking. Unpleasant side effects were common and in some cases plasma nicotine concentrations were two and even three times as high as with smoking; The chewing gum provided some satisfaction to all but four subjects, but its degree was not related to the concentration of plasma nicotine it produced, neither was there an inverse relation between the plasma nicotine concentration while taking the gum and the subjective sense of missing cigarettesmthis suggests that the capacity of the gum to act as a substitute for smoking is not necessarily related to its capacity to provide nicotine. Flexible dosage dictated by individual needs would probably lower the incidence of side effects and might secure closer approximation to smoking concentrations of plasma nicotine.


A double trial of amoxycillin in the treatment of gonorrhoea. A double blind comparison of two regimens of amoxycillin plus probenecid in the treatment of uncomplicated anogenital gonorrhoea is reported. Forty-three (86-0%) of 50 patients treated with 1 g amoxycillin plus 1 g probenecid and followed-up for 14 days were regarded as cured, and 51 (94-4%) of 54 patients treated with 3 g amoxycillin plus 1 g probenecid were regarded as cured. Fifty-nine per cent of 69 isolates of Neisseria gonorrhoeae were sensitive to amoxycillin (minimum inhibitory concentration less than or equal to 0-05 mg/ml). Although there was no statistical difference between the results of the two regimens it is concluded that the larger dose of amoxycillin plus probenecid is required where only 60% of gonococci are sensitive to amoxycillin.


Yeasts and circumcision in the male.

Yeasts and circumcision in the male. Sixty-six circumcised men and 69 uncircumcised men, both heterosexual and homosexual, had specimens taken from the coronal sulcus and meatus of the penis. Yeasts were isolated at similar rates in both the circumcised (14%) and uncircumcised (17%) men. The circumcised men had significantly fewer symptoms (P = 0-0058). Therefore the female partners of both circumcised and uncircumcised men are exposed to similar rates of yeast infection despite the absence of symptoms in circumcised men. Eighty per cent of the female contacts of yeast-positive men had yeast infection while 32% of the contacts of yeast-negative men were affected. This difference was statistically significant (0-05 greater than P greater than 0-025). Men with non-specific genital infection seemed more likely to carry yeasts than men with gonorrhoea or normal men.


First experiences with single-dose treatment of vaginal trichomoniasis with carnidazole (R 25831). This paper reports the results of treating 152 women with carnidazole, a new trichomonacidal drug. They were divided into two groups. The first comprised 91 patients who were treated with 2 g, while the second group comprised 61 patients who were treated with 1-5 g carnidazole in a single oral dose. Defaulter rates were 6-6% for the first group and 13-1% for the second. Of the remaining 85 patients in the first group, 76 (89-5%) were negative at the first follow-up one to three weeks after treatment, three (3-5%) were considered to be treatment failures, and six (7-0%) were considered to be reinfected. Of 53 women treated with 1-5 g, 39 (73-6%) were negative at first follow-up, eight (15-1%) were considered to be treatment failures, and six (11-3%) were considered to be reinfected. The difference between the number of patients cured in both groups is statistically significant. Fourteen patients experienced side-effects, but these were of little significance. Carnidazole given in a single oral dose of 2 g in 16 women did not cause consistent changes in any of the haematological and biochemical parameters studied.


The Ayerst Award Lecture 1976. Novel factors in protein biosynthesis. Comparison of nucleotide sequences surrounding the initiation sites of a number of mRNAs reveals few common features. These may be the presence of in- or out-of-phase nonsense codons and (or) polypurine bases complementary to the 16S RNA of the 30S subunit of ribosomes. Since the bases which precede or follow an initiation site vary in length and composition we have examined whether they play a role as spacers between cistrons or whether they have an active function in the termination and initiation of translation. In vitro we have observed that some sequences 5' terminal to AUG are preferred over others in forming an initiation complex. The same bases have much less effect when present at the 3' terminal end of an AUG codon. When the 5' terminal codon is the termination codon UAA, absolutely no initiation complex can be detected. This suggests that spacing may be needed between a stop and a start codon. Conversely, the hexamer AUGUAA failed to elicit chain termination. This was so in systems that terminated when free UAA was added or when a sense triplet was present between the initiation and termination triplets. These results suggest that ribosomes may recognize the stop triplet. Hence ribosomes may not obey simple A and P site models in the termination reaction.


An effect of enzyme and ligand concentration on the state of aggregation of aspartate transcarbamylase of E. coli: I. The binding of CTP and ATP to the enzyme. Detailed binding studies of the inhibitor, cytidine triphosphate (CTP), to native Escherichia coli aspartate transcarbamylase (EC 2.1.3.2) reveal significant changes in subunit interaction when enzyme concentration is altered. In contrast, similar binding studies of the activator, adenosine triphosphate (ATP), do not reveal such changes, but do indicate more complex subunit interactions than previously reported. Equilibrium dialysis studies of 4 degrees C are consistent with six binding sites for CTP and ATP per enzyme molecule of molecular weight 310 000, at all enzyme concentrations. CTP binding studies reveal a progressive change from apparent positive to negative cooperativity as the enzyme concentration is decreased. ATP binding studies reveal complex subunit interactions involving a mixture of apparent negative and positive cooperativity. Sucrose gradient studies indicate the presence of at least three enzymatically active polymeric forms of the enzyme. The preliminary sedimentation studies indicate possible ligand and enzyme concentration perturbations of a preexisting association equilibrium in the aspartate transcarbamylase system. The binding data are therefore interpreted in terms of an association model.


Small-scale trial of live-attenuated influenza vaccine (A/Hong Kong/68). Seventy-one men who were given live-attenuated A/Hong Kong/68 (H3N2) influenza vaccine during November 1973, and 34 men given placebo were examined for changes in antibody level. Overall, 12 of the 71 men (17%) given the vaccine showed a fourfold rise in haemagglutination-inhibition (HI) antibody titre after 14 days. No such rises were seen in the 34 men given placebo. However, 10 of the men showing a fourfold rise were from 19 who had no detectable HI antibody to this virus before vaccination, representing a conversion rate of 53%. The other two had a HI titre of 1/10 before vaccination. The absence of antibody response, at 14 days, in those with an HI titre of 1/20 or greater may indicated that this represents a protective level against infection. However, the vaccine virus was probably overattenuated and may have constituted a weaker challenge than might occur with a wild strain. No influenza virus was isolated from either group in the week after vaccination and no evidence of transmission to the placebo group was seen. Mild symptoms, chills, muscle pain, and stiffness were more frequently seen in the 12 persons showing a fourfold rise in antibody than in the rest of the volunteers.


A modified bioassay for heat-stable Escherichia coli enterotoxin1. Infant mice were injected orally with preparations containing Escherichia coli heat-stable enterotoxin (ST) and Evans blue dye, and incubated at 22 degrees C. With enterotoxin-positive samples, the stomach was distended and contained essentially all of the dye. With enterotoxin-negative samples, the stomach remained normal in size and the dye passed freely into the intestines. The time required to obtain the maximum ratio of gut weight to body weight varied from 30 to 90 min and was dependent upon the concentration of enterotoxin. Heat-labile enterotoxin (LT) had no effect during this period. Based on these findings, the mouse incubation time was reduced from 4 h to 90 min, and the heating of test samples was retained only for confirmation of ST. The location of the dye and stomach distention served as an indicator of positive responses to ST. Incubation of the mice at room temperature (22 degrees C) was found satisfactory.


Slow infections of the central nervous system. This review describes the recent advances in slow infections of the nervous system emphasizing the pathogenetic aspects of these diseases. A theoretical model for the pathogenesis of subacute sclerosing panencephalitis (SSPE) is proposed, illustrating the factors that may affect host response to the measles virus and allow it to persist and produce the panencephalitis. The isolation of an oncogenic virus from progressive multifocal leukoencephalopathy (PML) has implications in the consideration of a viral etiology for some brain tumors. The agent responsible for the transmissibility of kuru and Creutzfeldt-Jakob disease (CJD) remains uncharacterized despite recent interest in viroids and abnormalities in replication of cell membranes. The epidemiological data on multiple sclerosis suggests an exposure to an infectious agent at an early age of life modified by the host response. No specific agent has been consistently associated with multiple sclerosis. Amyotrophic lateral sclerosis (ALS), Parkinson's disease, Mollaret's meningitis and Behcet's disease are other examples where a virus is suspect but unproven. The ability of viruses to persist in the host for months to years has linked many chronic neurologic diseases to an infectious agent, enlarging the spectrum of disease caused by viruses.


Pepsin and acid secretions during and after gastric operations in patients with duodenal ulcer. Measurement of gastric pepsin and acid secretion was performed before, during and after selective vagotomy with antrectomy (SVA) and Billroth I gastrectomy (B-I) in 20 patients with a duodenal ulcer. Preoperative pepsin concentration increased during operation and decreased gradually 72 hours after SVA and 1 to 3 months after B-I. Although the pepsin concentration decreased substantially, it was never less than 70% of the preoperative level in both groups. Acid concentration decreased immediately after vagotomy in the SVA group and decreased gradually after 72 hours in the B-I group. Although there was a notable increase in the pH in both groups after operation, a pH of 5 was never reached. Decrease in gastric secretory volume (about 50%) was approximately equal in both groups. It appears that any increase in acid secretion occurring after vagotomy or gastrectomy may be sufficient to activate high-and low-pH-acting pepsins. Extravagal and extraantral stimulation of gastric pepsin secretion after operation should be considered an important etiologic factor in the pathogenesis of recurrent ulcer.


Exogenous bacterial contamination of donor blood. The Canadian Red Cross blood transfusion service has followed a set protocol for phlebotomy and collection of a unit of blood. Recent requirements for automated testing have necessitated that a second tube of blood be obtained from the blood line following collection of the unit. Evaluation of the techniques used, however, has indicated the possibility of bacterial contamination from the skin of donors, from insertion of the needle through an unsterile rubber stopper, and through backflow from a nonsterile vacuum tube. To test these possibilities swabs were taken from skin and stoppers of vacuum tubes. Further, vacuum tubes were deliberately contaminated with Escherichia coli. The normal sampling procedure, which involves stripping the donor line to refill and mix the blood, was then followed. This resulted in contamination of the segments and even the blood bag. These findings led to modification of the standard bleeding technique, whereby stripping was eliminated and sterile vacuum tubes were to be used at all times.


Maprotiline-a double-blind study of a new tetracyclic antidepressant in severe depression. A double-blind study was carried out comparing the antidepressant properties of maptotiline (a new tetracyclic antidepressant) and amitriptyline. Twenty-one hospitalized severely depressed patients, selected on the basis of clinical and psychometric criteria, completed the trial period of 28 days. The new drug was found to have an order of effectiveness similar to that of amitriptyline and both drugs were effective in agitated as well as retarded forms of depression. For both, the "day of effect", intended as the timing of sharp clinical improvement, tended to occur during the second week of treatment. Both drugs were well tolerated by most patients but one of the maprotiline patients presented a generalized rash which resolved after discontinuation of the drug. In conclusion, maprotiline is seen as an interesting addition to the group of major antidepressant drugs.


Randomized clinical trial of cystosine arabinoside and 6-thioguanine in remission induction and consolidation of adult nonlymphocytic acute leukemia. One hundred and forty-seven adults with acute nonlymphocytic leukemia were randomized to one of two treatment regimens utilizing cytosine arabinoside and 6-thioguanine. In regimen A the drugs were administered every 12 hours until marrow cellularity was reduced by at least 50%. In regimen B the drugs were administered every 12 hours for 5 days with five to 7 days rest intervals between courses. Decisions to continue or reinstitute therapy were based solely on marrow cellularity and marrow ratings. The overall response in referee-verified cases in both groups was similar (41%); regimen B proved to be the easier protocol to administer but required greater support. Younger patients or those with an initial high hemoglobin count responded best to these drug regimens. Only 36% of our patients experienced severe marrow hypoplasia (i.e., a 75% or greater reduction in marrow cellularity) prior to complete remission, suggesting that cytosine arabinoside and 6-thioguanine in combination may selectively suppress leukemic cells while sparing normal hematopoietic elements.


Results of a randomized clinical trial of preoperative irradiation versus postoperative in treatment of tumors of the hypopharynx. Preoperative radiotherapy vs postoperative radiotherapy in the management of patients with primary tumors of the hypopharynx was evaluated by a prospective, randomized clinical trial. A statistically significant difference (p less than 1%) existed in favor of postoperative radiotherapy relative to survival rates, complications, and quality of survival. The postoperative radiotherapy group showed a 56% 5-year survival rate compared to 20% in the preoperative radiotherapy group. An analysis of the results is discussed.


Yolk sac carcinoma (endodermal sinus tumor): ultrastructure and histogenesis of gonadal and extragonadal tumors in comparison with normal human yolk sac. Human yolk sac carcinomas have been studied only twice with the electron microscope, and have never been compared at this level with normal human yolk sac. In the present study, the ultrastructural features of three primary ovarian yolk sac carcinomas, omental metastases from one of these, and a primary retroperitoneal yolk sac carcinoma in a male are reported, as are the ultrastructural findings in human yolk sac from normal 7- and 12-week gestations. The most prominent feature of the tumors is the presence of voluminous basement membrane material (the nature of which is confirmed by indirect enzyme-labeled antibody technique in one case) in both intra-and extracellular location, corresponding to the PAS-positive hyaline globules seen in these tumors by light microscopy. The tumor cells are also demonstrated to produce this material in tussue culture. Although basement membrane has not been described previously in normal human yolk sac at 8 and 10 weeks' gestation, it was present in the 7-week specimen which we studied, suggesting that its production may be a feature of only very young sac. Other ultrastructural findings are also similar in human yolk sac carcinoma, normal human yolk sac, and rodent yolk sac and yolk sac carcinomas. Thus, these studies confirm the suggested germ cell-derived yolk sac origin of the human tumor.


Malignant lymphomas of the thyroid: a clinical pathologic study of 35 patients including ultrastructural observations. The clinical and pathologic findings for 35 patients with malignant lymphoma presenting in the thyroid are reviewed. The lymphomas tended to occur in females with a median age of 65 years and clinically were manifested by a mass in the neck. The majority of patients were euthyroid and thyroid scans demonstrated cold nodules. In none of the patients was there clinical suspicion of lymphoma prior to surgery. Thirty-four of the cases were histiocytic lymphomas; the one exception; a patient with nodular poorly differentiated lymphocytic lymphoma, had histiocytic lymphoma in a subsequent biopsy of the soft tissues of the neck. Although classified as histiocytic, the lymphomas had the histologic and ultrastructural features of transformed lymphocytes or immunoblasts. Lending possible additional credence to the immunoblastic nature of these lymphomas was the histologic documentation of chronic lymphocytic thyroiditis in all 27 cases where residual thyroid parenchyma remained. This relationship suggests possible evolution of thyroid lymphomas from chronic lymphocytic thyroiditis and probably is analogous to the malignant lymphomas developing in other altered immune states, including Sjogren's syndrome. In the current study the overall 5-year survival was 54%. Patients under age 65, without local soft tissue extension or regional lymph node involvement, and with stage I disease survived the longest; a nodular histologic pattern also appeared to favorably influence the prognosis. Improved staging procedures and newer modes of therapy appear essential, particularly for those patients with clinical stage II disease and with local extension to soft tissues.


Factors in the prognosis of gastric lymphoma. The tumor-nodes-metastases (TNM) staging classification for gastric carcinoma was applied to 50 consecutive cases of primary gastric lymphoma. Survival statistics were obtained for each respective stage category and were remarkably similar to survival statistics for gastric carcinoma. Overall, patients with primary gastric lymphoma have a much better prognosis for survival than patients with gastric carcinoma since the latter present with far more frequent serosal penetration and nodal and distant metastases. Penetration of gastric lymphoma beyond the serosa is associated with a significantly decreased 5-year survival rate from 88 to 24%, and the presence of perigastric nodal involvement decreased the survival rate from 88 to 32%.


Primary adenocarcinoma of the duodenum.

Primary adenocarcinoma of the duodenum. Primary adenocarcinoma of the duodenum is rare. An extensive experience with fiberoptic esophagogastro-duodenoscopy in our institution has indicated that duodenal neoplasms may be more frequent than suspected and are readily diagnosed by this modality. With this mind, clinical, pathological, diagnostic and therapeutic aspects of the 71 patients with primary carcinoma of the duodenum reported in the literature in the last 10-year period, 1965-1974, were reviewed. It would appear that fiberoptic endoscopy of the upper gastro-intestinal tract should become the major diagnostic tool for this disease. It enables biopsies, brushings and washings to be taken. A preoperative histological diagnosis ensures that both patient and surgeon can be prepared for major abdominal surgery. It is imperatire that during the endoscopic examination, the entire duodenum be examined. Pancreatico-duodenectomy appears to offer the best chance of long term survival in patients whose lesion is resectable. The role and value of adjuvant chemo- and radiotherapy is still to be determined.


Epidemiologic methods in clinical trials. Epidemiologic methods developed to control confounding in non-experimental studies are equally applicable for experiments. In experiments, most confounding is usually controlled by random allocation of subjects to treatment groups, but randomization does not preclude confounding except for extremely large studies, the degree of confounding expected being inversely related to the size of the treatment groups. In experiments, as in non-experimental studies, the extent of confounding for each risk indicator should be assessed, and if sufficiently large, controlled. Confounding is properly assessed by comparing the unconfounded effect estimate to the crude effect estimate; a common error is to assess confounding by statistical tests of significance. Assessment of confounding involves its control as a prerequisite. Control is most readily and cogently achieved by stratification of the data, though with many factors to control simultaneously, multivariate analysis or a combination of multivariate analysis and stratification might be necessary.


Evaluation of cancer screening programs: parallels with clinical trials. The methodologic limitations of available observational evidence for the evaluation of ongoing cancer control programs is reviewed. The specific example of Control Programs for Cervical Cancer is chosen to illustrate these limitations. These limitations pertain to the special features of the natural history of this disease, to the types of data available as well as to problems in the interpretation of these data. Given the unacceptability of conducting a rigorous randomized clinical trial of an ongoing and accepted cancer control procedure, an alternative experimental approach is proposed. This approach consists in the random allocation of census tracts with a high risk population to either of two groups: 1) an experimental group in which active and repeated screening activities will attempt to reach virtually all susceptible women, 2) a comparable control group which will only benefit from regularly available services.


Cancer and occupation: status and needs of epidemiologic research. In the United States about 15% of cancer in men and 5% of cancer in women is probably due to occupational exposures. Yet, among the populations actually exposed, occupational cancer is a major health hazard. Further, occupational carcinogenesis should be studied because of it scientific interest and the likely generalizability of findings to non-occupational exposures. The alert clinician remains the most important source of leads to occupational cancer. When groups of cases occur, particularly cases of rare tumors among relatively young persons, an occupational exposure should be suspect. A reasonably detailed occupation history should be included in every medical record. Formal evaluation, measurement of risk and identification of specific hazards is usually done by epidemiologic methods. Several approaches to the improvement of these methods and, possibly, to disease control are presented.


Cancer following occupational exposure to asbestos and vinyl chloride. A review is presented of the various factors important in the identification of carcinogenic disease from occupational and environmental exposure to asbestos and vinyl chloride. The long lapsed period, usually of 20 or more years from first exposure to these materials, is discussed, as well as the requirement for sufficiently long observation periods in prospective epidemiological studies. The multiple-factor etiology of lung cancer involving cigarette smoking and asbestos exposure is illustrated. The risks of asbestos-related cancers to other than those directly working with the material are discussed in a variety of circumstances, and finally the effectiveness of control procedures for vinyl chloride and asbestos are compared.


Occupational exposure to radiation as a cancer hazard. There is much experimental data which indicates that ionizing radiation is a very potent carcinogenic agent. Most types of carcinoma can be produced by radiation. Carcinoma is apparently induced through a single or a series of mutations in somatic cells. Radiologists have excess leukemia and other malignancy from external x-ray; uranium and other miners have excess lung cancer from internal alpha radiation; luminous dial painters have excess osteogenic sarcomas; and uranium mill workers appear to have excess lymphomas. A large number of persons are now exposed occupationally to radiation from nuclear reactors, and from various uses of radioisotopes. For the induction of most types of cancers from radiation it appears that the risk is between 0.5 and 2 cancers per rem per million person years. Epidemiological techniques are essential in determining risks of this low magnitude. Other agents may inhibit or enhance the carcinogenicity of radiation.


Clustering and aggregation of exposures in Hodgkin's disease. The epidemiologic evidence regarding case clustering and aggregation of etiologic exposures among patients with Hodgkin's disease (HD) is reviewed. In contrast to the literature on leukemia, there are few reported HD clusters. Statistical studies searching for time-space clustering in HD have been negative or inconclusive. The innovative Long Island school study of Vianna and Polan suggests that there is aggregation of etiologic exposures in HD. However, this study has been criticized and further confirmation is required. Additional support for the aggregation of exposures hypothesis is found in studies of familial aggregation of HD. On the other hand, teachers and physicians, groups suggested as having high exposure to HD patients, have been shown to be at no increased risk for HD. Available evidence would suggest that if HD is communicable, it is probably so only prior to manifestation of the disease and exposure must occur in childhood or adolescence. Although most studies have focused on the compatibility of their findings with interpersonal transmission of an etiologic agent, these data are equally compatible with an hypothesis of common source exposure to non-infectious etiologic agents.


Review of local soft tissue recurrence of breast cancer irradiated with and without actinomycin-D. Between 1962 and 1973, regionally recurrent breast cancer was treated in 156 patients by irradiation alone or irradiation with concurrent actinomycin-D. Thirty-two patients were entered into a randomized trial, and 124 patients were retrospectively reviewed. Local control with irradiation alone was achieved in 48 of 80 patients (60%) and in 60 of 76 patients (79%) treated with irradiation and actinomycin-D (p less than .05). Results were remarkably similar in the randomized and retrospective series.


Histiocytic lymphoma in the brain as the only manifestation of relapse following remission maintainance with BCG immunotherapy. This report describes an unusual case of lymphoma which, after 54 months of complete remission induced with chemotherapy and maintained with BCG immunotherapy, relapsed in the brain alone. It is possible that the immunotherapy led to this pattern of relapse: this is supported by several other studies. The difficulty in diagnosing brain lymphoma is emphasized.


Multiple granulocytic tumors of the skin: report of six cases of myelogenous leukemia with initial manifestations in the skin. The clinical and pathologic findings in six patients with myelogenous leukemia presenting initially as multiple granulocytic tumors of the skin were reviewed. The skin of the trunk was most commonly involved with multiple, confluent erythematous plaques and soft, tender, non-ulcerated, violaceous nodules. Two patients had been treated for malignant lymphoma eight and nine years prior to the onset of skin lesions (Hodgkin's disease and nodular lymphocytic lymphoma, respectively), and cutaneous granulocytic leukemia developed in sites of irradiated skin. The skin biopsies in all cases were originally misinterpreted by the pathologist as malignant lymphoma and the correct diagnosis of granulocytic leukemia was not established in any of the cases until overt extracutaneous involvement was detected. The interval in the six patients from skin biopsy to definite involvement of blood and bone marrow by acute granulocytic leukemia ranged from three weeks to six months with a mean interval of 3.8 months. The mean duration of survival from the diagnosis of extracutaneous dissemination was 12.7 months (range of three months to two and one-half years). Poorly differentiated myelogenous leukemia was demonstrated at postmortem examination in all cases. Cytochemical stains of formalin-fixed, paraffin-embedded tissues confirmed the granulocytic origin of the neoplasm: leukemic cells in skin biopsies, bone marrow aspirates, and autopsy specimens contained abundant naphthol AS-D chloracetate esterase. The findings indicate that granulocytic leukemia may rarely present with skin tumors as the original manifestation of the disease. Recognition of the distinctive clinical, histopathologic, and enzyme histochemical features of the lesion provide a basis for distinguishing granulocytic sarcoma of the skin from mycosis fungoides and other cutaneous malignant lymphomas.


Primary lymphoma of the breast: ultrastructural study of two cases. Two cases of primary non-Hodgkin's lymphomas of the breast were studied with light and electron microscopy. By light microscopy, according to Rappaport's classification, one was a poorly differentiated lymphocytic lymphoma, the other a diffuse histiocytic lymphoma. However, the ultrastructural features of the latter were more consistent with transformed lymphocytes. The differential diagnosis with medullary and poorly differentiated carcinomas of the breast is discussed. The first case had rapid dissemination as did most of the cases reported in the literature.


Primary malignant lymphomas of the breast. Fourteen cases of primary malignant lymphomas of the breast were found in the pathology files of the M. D. Anderson Hospital and Tumor Institute from 1944 to 1975. The lymphomas represented only 0.12% of 11,277 primary malignant breast tumors seen during the same period. There were no definite clinical features to distinguish the patients with lymphoma from those with breast carcinoma. All of the lymphomas had a diffuse pattern. Eight cases were classified as undifferentiated lymphoma, five as histiocytic, and one as poorly differentiated lymphocytic, convoluted cell type. Four patients had mastectomies and the remainder biopsies as their sole surgical procedure. Eight patients received post-surgical radiotherapy and all eventually had chemotherapy. The five-year survival rate for the 13 patients with follow-up was 49%. Patients with histiocytic lymphoma appeared to have a more favorable prognosis than those with the undifferentiated type. Six of the latter patients are dead with a median survival of seven months, comparable to the reported survival of patients with American Burkitt's lymphoma. The patient with the convoluted cell type has developed acute blastic leukemia and is currently under therapy.


Spontaneous rosette formation and rosette inhibition assays in patients with squamous cell carcinoma of the head and neck. Peripheral blood lymphocytes from patients with squamous cell carcinoma (SCC) of the head and neck were studied by spontaneous lymphocyte rosette and rosette inhibition (RI) assays prior to treatment. The patients were clinically staged and the results of the assays compared with the clinical stage of the disease. The percentage of T-lymphocytes as determined by the spontaneous lymphocyte rosette test was significantly lower (p less than .01) for the patient group when compared with a normal population. Patients with stage I and II disease did not differ significantly from controls. Individuals with stage III or IV disease, however, had significantly lower T-lymphocyte counts. The tumors were histologically graded as well, moderately well, or poorly differentiated SCC. Patients with poorly differentiated neoplasms had significantly lower T-cell counts. The RI assay (using horse anti-human thymocyte globulin to inhibit rosette formation) was abnormal in many of the patients but did not appear to be a more sensitive in vitro measure of cell mediated immunity in these patients. Performing both tests detected more patients with cellular immunologic incompetence than either one alone.


Complement receptor B lymphocytes in nodular sclerosing Hodgkin's disease. Infiltrated tissues from nine cases of nodular sclerosing Hodgkin's disease (NSHD) were examined for immunologic cell surface markers. In all nine cases a large population of complement receptor B-lymphocytes were present within the nodular infiltrates. B-lymphocytes were identified in frozen sections by adherence of sheep red blood cells (E) coated with IgM antibody (A) and complement (C) IgMEAC). IgMEAC attached to both small lymphocytes and to Reed-Sternberg cells and their variants. Red cells coated with IgG (IgGEA) attached to histiocytes associated with the internodular fibrous bands and only sparsely with the nodular infiltrates. The population of complement receptor lymphocytes appears to be an integral component of NSHD.


Cryptococcosis in a cancer hospital: clinical and pathological correlates in forty-six patients. The clinical and pathological findings in 46 patients with cryptococcosis at Memorial Sloan-Kettering Cancer Center from 1956 to 1972 are reported. The striking predilection for cryptococcal infection in patients with leukemias and lymphomas is again confirmed. Of 41 patients with neoplastic disease, those with chronic lymphatic leukemia (CLL), Hodgkin's Disease, chronic myelogenous leukemia (CML), myeloma and lymphosarcoma had the highest incidence of cryptococcosis. In all cases, neoplastic disease was widespread when infection occurred. All of these patients had leukopenia and absolute lymphopenia at the time of infection. Thirty-nine were on steroids. Thirty-one patients with neoplastic disease had disseminated infection. Review of pathology revealed a spectrum of inflammatory lesions. Histiocytic-lymphocytic infiltrates occurred in the central nervous system in 10 patients. In six cases, reaction was granulomatous. There were single instances of suppurative and fibrotic reactions. Mortality from infection was high in patients with neoplastic disease. Twenty-four of 28 deaths occurred within 60 days as a result of infection. Within one year, 10 more patients died, nine of cryptococcosis. Only three survived more than one year, and all patients died within 600 days. Twenty-nine patients with neoplastic disease received amphotericin B. Only nine survived more than 60 days.


Bronchogenic carcinoma presenting as spontaneous pneumothorax: case reports with review of literature. Six months after right-sided spontaneous pneumothorax developed in a 56-year-old man, squamous cell carcinoma was discovered in the ipsilateral lung. Fifteen cases of bronchogenic carcinoma presenting as spontaneous pneumothorax have been reported in the English language literature. Possible pathogenetic mechanisms include: direct tumor invasion of pleura; rupture of a subpleural bleb (in an area of obstructive emphysema) or an emphysematous bulla (in an overexpanded portion of the lung associated with lobar or segmental collapse); or unknown. Patients with spontaneous pneumothorax who fail to achieve complete expansion after three weeks of therapy or who have persistent roentgenographic pulmonary infiltration should undergo further investigation for bronchogenic carcinoma.


Comparative electrophilicity, mutagenicity, DNA repair induction activity, and carcinogenicity of some N- and O-acyl derivatives of N-hydroxy-2-aminoflourene. N-Myristoyloxy-N-acetyl-2-aminofluorene, N-acetoxy-N-myristoyl-2-aminofluorene, N-myristoyloxy-N-myristoyl-2-aminofluorene, and N-hydroxy-N-myristoyl-2-aminofluorene each yielded a high incidence of sarcomas in male rats within 5 to 7 months after s.c. injection of 64 micronmoles in divided doses. N-Acetoxy-N-acetyl-2-aminofluorene and N-hydroxy-2-acetylaminofluorene, although potent carcinogens at the s.c. site, were less active than the above derivatives with a myristoyl substituent. N-Sulfonoxy-N-acety--2-aminofluorene (purity larger than or equal to 70%) had little or no carcinogenic activity when administered in large amounts by s.c. injection to rats. The low incidence of tumors could have resulted from N-hydroxy-2-acetylaminofluorene or other decompostion products of the N-sulfonozy derivative. Each of the N-acetoxy and N-myristoyloxy derivatives of N-acetyl-2-aminofluorene and of N-myristoyl-2-aminofluorene showed electrophilic activity toward methionine; N-acetoxy-N-acetyl-2-aminofluorene was the most reactive and N-myristoyloxy-N-myristoyl-2-aminofluorine was the least reactive. Each of these esters also induced unscheduled tritiated thymidine incorportation in nondividing cultured human fibroblasts and thus appeared to induce lesions in DNA that lead to repair synthesis. EACH OF THE N-acetoxy derivatives was highly mutagenic for Salmonella typhimurium strains TA98 and TA1538 without tissue activation; neither N-myristoyloxy derivative was mutagenic under these conditions. While there was a qualitative correspondence between several of the above activities of these 2-aminofluorene derivatives, the quantitative differences and the lack of detectable mutagenicity of the 2N-myristoyloxy derivatives for S. typhimurium indicate the need for multiple short-term tests in the qualitative prediction of potential carcinogenic activity.


Immunofluorescent characterization of rat kidney tumors according to the distribution of actin as revealed by specific antiactin antibody. A series of 15 mesenchymal and 10 cortical epithelial tumors induced in the rat kidney by dimethylnitrosamine was investigated for immunofluorescent reactivity with a human antiactin antibody. Cells of epithelial tumors showed staining restricted to peripheral sites, corresponding to the brush border region. All various neoplastic cells forms comprising renal mesenchymal tumor were characterized by cytoplasmic staining in pattersn that varied with cell type. Epithelial profiles in the form of tubules and islands of epithelium showed staining patterns, or absence of them, consistent with their identity as sequestered segments of preexisting nephrons. It is suggested that the difference in actin distribution within the cytoplasm of cells of the two types of renal neoplasm, mesenchymal and epithelial, might reflect their difference in local invasive growth.


Fecal bile acids and cholesterol metabolites of patients with ulcerative colitis, a high-risk group for development of colon cancer. Patients with chronic ulcerative colitis are at increased risk of developing carcinoma of the colon. It has been shown that the concentration of fecal bile acids and neutral sterols was higher in cancer patients than in the comparable healthy controls. Fecal neutral steroids and bile acids were measured in patients with ulcerative colitis, family controls who were immediate relatives of patients, patients with other digestive diseases, and healthy unrelated controls. The fecal excretion of cholesterol, coprostanol, and cholestane-3beta, 5alpha, 6beta-triol was higher in patients with ulcerative colitis than in other groups. Patients with other diseases, family controls, and unrelated controls excreted comparable levels of neutral sterols. Patients with ulcerative colitis excreted levels of bile acids in their feces comparable to those excreted by other groups. These findings suggest that possible interactions between cholesterol metabolites and colonic epithelial cells may be relevant in colon carcinogenesis.


A cytokinetic analysis of bacillus calmette-guérin-induced growth control of a murine leukemia. The cytokinetics of an isogeneic, transplantable, lymphoid leukemia, growing as an ascitic tumor in the C57BL/6 mouse, has been investigated during normal growth and during regression induced by weekly injections i.v. of 1.0 mg Bacillus Calmette-Guérin (BCG). Survival was significantly prolonged in the BCG-treated group, and 27% of the mice were apparently cured. The tumor growth curves showed, furthermore, that BCG-rreated mice could be divided into two groups according to whether the ascitic tumor cell number was at control level or below that of the controls. By methods such as stathmokinetics, tritiated thymidine autoradiography, and cytophotometry, it was demonstrated that the proliferative activity was higher in BCG mice with a low tumor mass as compared to controls and BCG mice with a tumor mass similar to that of controls. The cytokinetic characteristics of BCG mice with a low ascitic tumor cell number were especially expressed by high mitotic activity, high initial labeling indices, short potential tumor doubling time, and a low number of G0-G1 cells. Furthermore the ascitic tumor cell loss rate was increased in these mice during the whole experimental period. It was deduced from the various parameters and especially from the cytophotometric and autoradiographic results that BCG induces a preferential kill of tumor cells in G0-G1 and the first part of the S phase. In addition, the cytological aspects of the ascitic tumor were found to be related to the cell kinetic pattern as the amount of small and large tumor cells increased and decreased, respectively, with accumulation of tumor cells in G0-G1.


Isolation of the glucuronic acid conjugate of n-hydroxy-4-aminobiphenyl from dog urine and its mutagenic activity. The glucuronic acid conjugate of N-hydroxy-4-aminobiphenyl (NOH-4-ABP) has been isolated in relatively pure form from the urine of dogs given 4-aminobiphenyl, utilizing molecular size, ion exchange, adsorption, and partition chromatography. This conjugate is an active mutagen in Salmonella typhimurium strains TA1538 and TA98 but not in TA1535 or TA1537. NOH-4-ABP and 4-nitrosobiphenyl are also highly active in TA1538 and TA98 and inactive in TA1535 and TA1537. These observations support the concept that this conjugate is the water-soluble carrier that delivers the active metabolite to the bladder. A substance of identical chromatographic and spectral properties to the conjugate isolated from dog urine has been synthesized in low yield by the direct condensation of NOH-4-ABP with glucuronic acid. This substance yields NOH-4-ABP on dilute acid hydrolysis. Sodium (N-4-biphenylhydroxylamino-beta-D-glucopyranosid) uronate, the N-O-C isomer, was also synthesized. It was found to have differing chromatographic and chemical properties to the natural conjugate. This evidence suggests that the urinary conjugate is the compound in which conjugation has occurred with the nitrogen atom of the hydroxylamine group rather than the oxygen atom.


Mutagenicity of pesticides containing 1,3-dichloropropene. In a systematic study of the mutagenic effect of chemical compounds used as pesticides, we found that D. D. soil fumigant and Telone are mutagenic. The test was performed using the bacterial tester strains following the procedure developed by Ames. The active principle of D. D. soil fumigant and Telone is a mixture of the cis and trans isomers of 1,3-dichloropropene. Both isomers are mutagenic in Salmonella strains TA 1535 and TA 100. 2,3-Dichloro-1-propene, a minor component (5%) of the commercial preparation Telone, was also found to be mutagenic in strains TA 1535 and TA 100. Mutagenesis of these tester strains is an indication of a base-pair substitution event causing a missense mutation. 1,3-Dichloropropene is widely used in agriculture all over the world. In Italy 2,187,100 kg were produced in 1972. In California over 1,000,000 kg of 1,3-dichloropropene-containing pesticides were used in 1971.


Polysaccharides immobilized in polyacrylamide gel as high-capacity adsorbents for Bandeiraea simplicifolia lectin and concanavalin A. A high-capacity adsorbent for lectins was easily prepared by immobilization of polysaccharides in a polyacrylamide gel. The properties of granulated guaran gel, used to purify by affinity chromatography the alpha-D-galactose-binding lectin from the seeds of Bandeiraea simplicifolia, were studied, as well as the binding of Concanavalin A (tetrameric) and succinylated Concanavalin A (dimeric) to a yeast mannan gel.


Effects of pre-irradiation on isogeneic and semi-isogeneic CFU growth: a study on genetic resistance. The genetic resistance to a parental bone marrow transplant as demonstrated, when transplantation was performed early after irradiation, failed to occur if the interval between irradiation and transplantation was increased to 4 days. A similar radiation induced weakening of genetic resistance to a parental bone marrow graft in spleen and bone marrow could be demonstrated in mice, which had been irradiated with a sublethal dose at 7 days prior to the lethal irradiation and transplantation. The pre-irradiation of the recipient with a sublethal dose induced an enhancement of the growth in spleen and bone marrow of isogeneic transplanted CFU. The pre-irradiation of a single tibia also resulted in a significant weakening of the resistance in the spleen. The experiments with partial body pre-irradiation suggested a local effect of the pre-irradiation, but it could be shown that the enhanced CFU growth is not caused by an enhanced seeding of CFU in pre-irradiated bone marrow. The role of microenvironment in the phenomenon of genetic resistance is discussed.


Rapid cell cycle analysis by measurement of the radioactivity per cell in a narrow window in S phase (RCSi). A new rapid method for the cell cycle analysis of asynchronously growing cells is presented. The new method is an alternative to the more time consuming and subjective fraction of labeled mitoses (FLM) method. Like the FLM method, all cells in the S phase of the cell cycle are marked by pulse labeling with a radioactive DNA precursor. The subsequent progress of the cohort of cells thus labeled is monitored through a narrow window in the cell cycle. The window is defined by a narrow range of DNA contents corresponding to cells in mid-S phase and is designated Si. The cellular DNA content is measured by flow cytometry and the cells in the window Si are selected by electronic cell sorting. The radioactivity per cell in Si (RCSi) is determined by liquid scintillation counting. The duration of S phase and of the total cycle and the dispersions therein are determined from the oscillation of the RCSi values with time. The complete cell cycle analysis can be accomplished in as little as 1 day following the collection of samples. Exponentially growing Chinese hamster ovary (CHO) cells were analyzed according to the RCSi method and the FLM method. It is demonstrated that the two techniques give essentially the same results.


Studies on the interactions between nerve fibres from para- and orthosympathetic ganglia and adreno-cortical and -medullary cells in joint culture. The interactions between nerve fibres from para- and orthosympathetic ganglia and adreno-cortical and -medullary cells were studied in joint cultures using explanted guinea-pig ciliary and sympathetic chain ganglia and enzyme-dispersed rat adrenal gland cells. Nerve fibres from both para- and orthosympathetic ganglia made only transitory contact with cortical cells, but consistently formed associations with isolated chromaffin cells which lasted for up to 10 days. Contacts between axons and chromaffin cells often showed particularly large varicosities and frequently withstood severe tests of durability from pulls of the fibre or the cell or both. By correlating phase contrast and catecholamine histochemistry (Falck-Hillarp method) it was shown that sympathetic fibres forming long-lasting contacts with chromaffin cells were adrenergic. The functional implications of the ability of autonomic nerves to distinguish between adreno-cortical and -medullary cells and the lack of specificity shown by the para- and orthosympathetic neurons during formation of long-lasting associations with chromaffin cells are discussed.


Interaction of membrane aminophospholipids of E. coli with fluorodinitrobenzene and trinitrobenzenesulfonate. E. coli cells were reacted with TNBS in bicarbonate-NaCl buffer, pH 8.5 (buffer A) and in phosphate-NaCl buffer, pH 7.0 (buffer B). In buffer A, DNP-GPE is the major product when FDNB is used. DNP-PE and DNP-LPE are formed in lesser amounts. Phospholipase A activity is high in buffer A. When TNBS is used, the labeling of the lipid components is less than with FDNB and more TNP-PE is formed relative to TNP-GPE. This data suggests that the phospholipases which are located primarily on the outer L-membrane of the cell wall act to a lesser extent on TNP-PE than on DNP-PE. E. coli cells were prelabeled with TNBS and FDNB in buffer A, washed and incubated in buffer A. The endogenous labeled DNP-PE gradually decreased with time with a concomitant increase in DNP-LPE and DNP-GPE due to phospholipase A activity. In contrast, the endogenous labeled TNP-PE also decreased with time as did the endogenous labeled TNP-LPE but a new orange lipid was produced. This lipid is believed to be a derivative of TNP-PE in which one of the nitro groups has been reduced to an amino group by nitroreductase. E. coli cells were prelabeled with TNBS and FDNB in buffer A, washed and incubated in buffer B. Under these conditions with both TNBS and FDNB there is an increase in TNP-PE and DNP-PE with a concomitant decrease in TNP-LPE, TNP-GPE, DNP-LPE and DNP-GPE. These results show that at neutral pH acylation occurs to regenerate TNP-PE and DNP-PE. E. coli cells were incubated with exogenous DNP-GPE or TNP-GPE in buffer A. The DNP-GPE and TNP-GPE were rapidly hydrolyzed by a phosphodiesterase to DNP-ethanolamine and TNP-ethanolamine. An orange derivative was formed which was provisionally identified as a derivative of DNP-ethanolamine or TNP-ethanolamine in which a nitro group has been reduced to an amino group by nitroreductase. The phospholipases and acylating enzymes present in the cell wall of E. coli are active on the dinitrophenyl and trinitrophenyl derivatives of PE and LPE and may act in concert to model and repair the plasma membrane.


A clinical survey of removable partial dentures. --Analysis of follow-up examinations over a sixteen-year period--. In order to carry out the proper prosthetic treatment, it is necessary to select the method of treatment on the basis of accurate information concerning the prognosis of the prosthetic appliance. The oral structures are particularly proved to change when partial dentures are being used because the structures of the partial dentures are quite complex and they are easily broken. Therefore, in an attempt to analyze the changes that occur in the oral structures and partial dentures after insertion of the partial dentures, we conducted 3 series of follow-up examinations. The author sent out questionnaires and also conducted follow-up examinations of the patients. A summary of the major findings is as follows: 1) The percentage of those patients who came for their follow-up examinations, using metal based dentures, rose sharply over time. There were only 11.99% of the patients using the metal based dentures at the time the first study was conducted, but this rose to 58.13% at the time of the second study and 73.73% at the time of the third study. 2) The proportion of the patients who had anterior partial dentures declined over time from 9.36% at the time of the first study to 8.74% at the time of the second study and finally to 5.61% at the time of the third study. 3) The proportion of the partial dentures that had fractured was 23.15% at the time of the first study and 16.37% at the time of the second study and 16.67% at the time of the third study. 4) There was a striking difference in the fracture frequency of the acrylic resin based partial dentures and that of the metal based partial dentures. The denture bases of the acrylic resin-based partial dentures fractured about four times as often as those of the metal based partial dentures. 5) In all three studies it was found that about 60% of the caries occuring on the abutment tooth occurred on the edentulous proximal side. 6) Changes in the mucous membrane, such as inflammation or development of ulcers, had occurred in 48.86% of the cases at the time of the first study. This proportion declined to approximately 47% at the time of the second and finally to 43% at the time of the third study. 7) In examining the changes in the mobility of the abutment teeth, it was found that in all three studies approximately 20 to 30% of the abutment teeth demonstrated increased mobility, and about 10 to 20% showed decreased mobility while 55 to 65% showed no change.


Evaluation of the radioimmunoassay for benzoylecgonine (a cocaine metabolite) in human urine. The 125I-radioimmunoassay (RIA) for benzylecgonine (cocaine metabolite) in urine was evaluated by comparison with gas-liquid chromatography (GLC) and thin-layer chromatography (TLC) and the Enzyme-Multiplied Immunoassay Technique (EMIT). By RIA, a statistically significant concentration, 2 microng/liter, was observed for urinary benzoylecgonine. The coefficient of variation for the RIA was 2.58+/-0.38% inter-assay and 2.20+/-0.14% intraassay. There was cross-reactivity with cocaine (more reactive than benzoylecgonine) and other members of the tropane family of alkaloids. There was agreement between results by RIA and GLC in 95.5% of the samples, between RIA and TLC in 87.0%, and between RIA and EMIT in 84.5%. The percentage of true false-positives was 3.5% for the RIA in comparison to GLC, 8.8% in comparison to TLC, and 9.1% in comparison to EMIT. True false-negatives were insignificant (0 to 1.0%). GLC and RIA results correlated highly (phi=0.908). GLC, therefore, was the best comparison method for this evaluation study. RIA for benzoylecgonine is sensitive, reproducible, and reliable for the detection of cocaine in urine.


Combination shower toilet.

Combination shower toilet. This paper argues the need for special toilet equipment for some children with spina bifida and hydrocephalus and describes the design of a special shower/toilet for an individual child.


Solid-phase enzyme immunoassay for hepatitis B surface antigen. A solid-phase enzyme immunoassay is described for measuring hepatitis  B surface antigen in human serum or plasma. Immunologically purified antibody labeled with horseradish peroxidase was used as the indicator. In the assay system, antibody-coated controlled-pore glass is used as a solid support and there are three sequential incubations, totaling 2 h, at room temperature. Results for serially diluted positive and reference sera compare favorably to radioimmunoassay in sensitivity and specificity.


Adaptation of the EMIT serum digoxin assay to a mini-disc centrifugal analyzer. We have modified the EMIT (Syva) serum digoxin assay for use with a mini-disc centrifugal analyzer. A minicomputer is used to control data acquisition, calculations, and readout for 14 cuvettes simultaneously. Thus, it is not necessary for time each individual assay manually or to plot calibration curves on graph paper. We use incubation times and dilutions similar to those used for the manual procedure, but we have changed the buffer solution, decreased the measurment time, and decreased the required serum volume per assay fivefold. We evaluated day-to-day and within-run precision, using Syva calibrators and control sera. EMIT assay values for radioimmunoassay control sera correlate well with the supplier's stated values.


Reduced 'gonadotrophin response to releasing hormone' after chronic administration to impotent men. Ten endocrinologically normal men with secondary sexual impotence were given 500 microng LHRH subcutaneously every 8 h. After 4 weeks treatment the LH response to 500 microng LHRH was reduced from a peak of 35.7+/-5.2 to 16.8+/-3.5 mu/ml (P less than 0.01) and the FSH response from 4.2+/-0.93 to 2.39+/-0.4 mu/ml (P greater than 0.01). Circulating total testosterone, oestradiol, prolactin and sex hormone binding globulin showed no significant changes. Whether this inability of the pituitary to maintain it s response to LHRH is peculiar to impotent men requires further study.


The development of equipment by the RCA. This paper describes the continuation of the work of the Royal College of Art team outlined in the preceding paper, and illustrates the development of some standard items of equipment to suit children with spina bifida. The standard items consist of a combined w.c. and shower seat and a height adjustable dressing/treatment bench. A situation in which items have been used is described and future developments are outlined.


Review: battered children, their parents, treatment and prevention. This paper reviews the literature on battered children, their parents, management, treatment and prevention. The work suggests that socioeconomic factors are less important than the psychology of the parent, who has often been a battered child himself. Management and treatment of the syndrome in the UK and the USA are indicated. The paper concludes with an outline of the preventive and research projects in the field.


The action of thyroid hormone.

The action of thyroid hormone. Thyroid hormone affects both developmental and metabolic processes. It has a relatively specific effect on the synthesis of a number of enzymes and other proteins. The fundamental cellular mechanism of action seems to be at the level of genetic regulation. It involves interaction with nuclear receptors, leading to an activation of the protein synthesizing machinery. How binding to receptors is coupled to genetic activation is completely unknown. At least part of the metabolic effects of thyroid hormone could be mediated through an interaction with mitochondria and cell membrane, and with some enzymatic systems such as adenylcyclase.


'Hyperacute rejection' due to perfusion injury. Two kidneys were harvested from a cadaver donor and subjected to pulsatile perfusion in an identical fashion with a perfusate which was free of cytotoxic antibody. Classical 'hyperacute rejection' occurred in the right kidney when transplanted into a male patient with no previous blood transfusion or transplants, and repeatedly negative tests for cytotoxic antibody. The left kidney was not transplanted and was examined by light, electron, and immunofluorescence microscopy as was the immediately removed, transplanted kidney. Despite the absence of any immunological pathogenetic mechanism in the non-transplanted kidney, virtually identical changes of 'hyperacute rejection' were seen in both kidneys. Thus,even technically satisfactory perfusion may cause a syndrome of 'hyperacute graft failure' secondary to non-immunologically mediated perfusion injury.


Disorders of hypo- and hyperkalemia.

Disorders of hypo- and hyperkalemia. Hypokalemia or  hyperkalemia may be present as an important feature of a large number of clinical entities. To understand the means by which a hypokalemia or hyperkalemic state may be generated, it is necessary to appreciate those factors which influence the external balance of potassium and the entities which effect its transcellular distribution. In this review the role of the kidney and the gastrointestinal tract in the regulation of the external balance of potassium is briefly discussed. This is followed by a description of the clinical disorders associated with hypokalemia and hyperkalemia.


Oestrogen therapy and the menopausal syndrome. Sixty-four patients with severe menopausal symptoms completed a four month double-blind placebo trial with conjugated equine oestrogens (premarin). Using a graphic rating scale system of assessment, a statistically significant improvement with premarin was observed in 12 psychological and symptomatic scores (Table 3). From a comparison between these results and the results of the 20 patients without vasomotor symptoms it would appear that many of these symptomatic improvements result from the relief of hot flushes (i.e. a domino effect). However, the improvement in memory and reduction of anxiety in these 20 patients suggest that oestrogens have a direct tonic effect on the mental state which is independent of vasomotor symptoms. Sixty-one patients with less severe menopausal symptoms completed the second twelve month double-blind placebo trial and, as assessed by graphic rating scales, a significant improvement with premarin was observed in five psychological and symptomatic scores (Table 3). In both the twelve and four month studies the marked placebo effect of "youthful skin appearance", and on skin greasiness in the twelve month study, indicate that no reliance can be placed on patient judgement of skin texture and appearance. Despite the lessening of the domino effect there was a slight improvement with premarin over placebo in 15 of the remaining 16 symptoms and it is likely that the cumulative effect of these small improvements results in an overall enhancement of well-being. The relief of atrophic vaginitis by premarin did not result in an improvement in libido and this suggests that the ability and the desire to have sexual intercourse are not related. The strength and duration of the placebo effect were well demonstrated in the three standard psychiatric scoring systems, the Beck score (for depression), the General Health Questionnaire and the Eysenck Personality Index (formula: see text) (for neuroticism). We observed a highly significant placebo effect extending for six months in all three, the improvement with premarin over placebo being non-significant. We must conclude that these tests are not sufficiently sensitive to assess psychological or symptomatic changes in menopausal women and that these changes are best assessed by the graphic rating scales. The number of side-effects and complications was assessed in the 61 patients in the long study. A higher incidence of minor side-effects was observed during premarin therapy; this was most marked in relation to leg cramps but radio-isotope scanning revealed no evidence of leg vein thrombosis in these patients or indeed in any patient in the study. Premarin caused no elevation of systolic or diastolic blood pressure; indeed there was a progressive fall in blood pressure throughout the study with no significant difference between premarin and placebo...


Phemister bone graft for osteonecrosis post renal transplant. Avascular necrosis of the femoral head is an unfortunate sequela of renal transplantation. The necessary exogenous steroids are felt to be the cause of the necrosis. The case histories of three patients with bilateral disease are presented. All 6 hips were initially treated with a Phemister bone graft. According to the classification of Marcus, et al., one hip was Stage 3, three hips were Stage 4, and two hips were Stage 5 at the time of grafting. Four of these hips have had minimal further collapse and have been functionally satisfactory for the patients. One femoral head has had marked collapse but is pain free. One femoral head has had marked collapse with pain sufficient to necessitate a total hip replacement. The two heads with marked collapse were both Stage 5 at the time of surgery. The Phemister bone graft is presented as a possible treatment for this problem, especially when the disease is treated before femoral head collapse occurs.


Iliac crest reconstruction following full-thickness graft: a preliminary note. Pain, pressure areas and even visceral herniation may accompany taking large full-thickness iliac crest grafts. Reconstruction of the defect with a rib graft was performed in 8 cases. These patients had little pain in the donor site, could be rolled on that side comfortably and completely incorporated the rib graft in twelve weeks radiographically.


Clinical pharmacokinetics of digoxin.

Clinical pharmacokinetics of digoxin. About 70 to 80% of an oral dose of digoxin is absorbed, mainly in the proximal part of the small intestine. The  degree of binding to serum albumin is 20 to 30%. Digoxin is extensively distributed in the tissues, as reflected by the large volume of distribution. High concentrations are found in the heart and kidneys, but the skeletal muscles form the largest digoxin storage. The half-life of elimination in healthy persons varies between 26 and 45 hours. The main route of elimination is renal excretion of digoxin, which is closely correlated with the glomerular filtration rate. In addition, some tubular secretion and perhaps tubular reabsorption occurs. Nearly all of the digoxin in the urine is excreted unchanged, with a small part as active metabolites. The clinical significance of dihydrodigoxin as a metabolite remains to be resolved. About 25 to 28% of digoxin is eliminated by nonrenal routes. Biliary excretion may rise up to 30% of a given dose, but the enterohepatic cycle seems to be of minor importance. The pharmacodynamic effects of digoxin, including toxic symptoms, are correlated with the uptake of digoxin in the heart after a single dose and with the steady state serum digoxin concentration during maintenance therapy. Impaired kidney function is the most important condition with an influence on the pharmacokinetics of digoxin. In addition to the renal clearance of creatinine, the biovailability of the digoxin formulation used, the volume of distribution, the amount of extrarenal clearance, body weight and serum albumin concentration, are other factors which may modify the serum level of digoxin. Certain drug interactions may also occur during the absorptive phase. Exact prediction of serum digoxin concentrations by various dosage calculations has not succeeded. Since many factors may influence the sensitivity of the myocardium to digoxin, measurement of serum digoxin levels in only one, but a useful criterion, when making clinical decisions about adjustment of digoxin dosage.


Clinical pharmacokinetics of digoxin in infants. Based on clinical experience, infants with congestive heart failure are given larger doses of digoxin than adults, whether calculated on the basis of body weight or surface area. The reasons for this difference in dosage are not clear. The myocardium of the infants might be more resistant to the effects of digoxin than that of adults, and/or differences might exist between infants and adults concerning the absorption, distribution and elimination of the glycoside. Infants have been found to absorb digoxin in solution at the same rate and to the same extent as adults. The relative distribution of the glycoside to different tissues is also similar in the two age-groups. However, the binding of digoxin to several tissues seems to be more extensive in infants than in adults. In agreement with this, the apparent volume of distribution of the glycoside is larger in infants than in adults. As no enhanced urinary excretion has been found in infants there might be a non-renal elimination of the glycoside. With most prevailing dose schedules for digoxin, serum concentrations higher than those considered optimum for adults are often obtained in infants. It is known that infants tolerate higher serum digoxin concentrations than adults without developing signs of toxicity. However, it is not known whether such high concentrations are necessary for obtaining an  adequate inotropic effect on the myocardium of the infants. If the relation between serum concentration and effect is the same in infants and adults, the loading (digitalising) dose generally given to infants is unnecessarily high.


Protein binding and kinetics of drugs in liver diseases. Although the liver is the major site for drug biotransformation, the effect of hepatic dysfunction on drug disposition has not been consistent or predictable. Most early studies of drug kinetics in liver disease measured only half-life. Only in the past few years has it been realised that liver diseases can affect drug absorption, hepatic metabolism, tissue distribution, and protein binding, which complicate interpretation of any change, or lack of change in drug half-life. Furthermore, it is now apparent that the efficiency with which a drug is metabolised by the liver, the extent of binding to blood constituents, and the aetiology and stage of the hepatic disorder are each important in determining whether significant alterations in drug disposition will occur. A pharmacokinetic perfusion model which takes into account many of the above factors has been proposed, and appears to be useful for predicting changes in the disposition of rapidly metabolised compounds. Nevertheless, the state of knowledge about those factors which limit the rate of metabolism of individual drugs or classes of drugs in inadequate, and no general  model or guidelines which are useful clinically have been developed. Patients with hepatic disorders may show increases or decreases in sensitivity independent of alterations in drug disposition. The clinician caring for such patients must be cautious about the use of any drugs, and rely heavily on careful patient observation to determine efficacy or toxicity.


Neurological evaluation of the newborn.

Neurological evaluation of the newborn. The neurological examination is an integral part of the evaluation of the newborn infant. In too many instances the infant is dismissed from the nursery as 'normal' when,in fact, little or no effort has been expended to determine the body's neurological status. The neurological deficits overlooked often do not become overt until a much later age. Early detection can prevent the mental anguish that plagues the parents who must be told that their 'normal' infant has significant neurological problems. In some instances early diagnosis may lead to a better ultimate prognosis. We have presented a simple scheme for the neurological evaluation of the full-term infant and hope that it will be useful in encouraging pediatricians to assess neurological status.


Drug absorption in gastrointestinal disease with particular reference to malabsorption syndromes. There is a considerable range in the dose of many drugs that is required to produce a given pharmacological effect in an individual patient. This individual variation in dose requirement is sometimes reflected in the wide scatter in the steady state plasma concentration that follows the same oral dose of a drug given to any group of subjects. Such individual differences are largely due to variation in the rate of elimination of drugs. Gastrointestinal disease may also alter oral dose requirements by producing variation in both the amount and rate of drug absorption. These changes may be reflected in the plasma concentration/time curve that follows an oral dose. The amount of drug abosorbed is simultaneously affected by many factors. These include the physicochemical properties of the drug and the physiological factors that operate within the gut, as well as the presence of other substances such as food, or interaction with other drugs in the gut. The availability of the drug within the intestinal lumen is largely governed by its dissolution characteristics, particularly  factors which can interfere with dissolution of the drug product in the gut. Physiological  factors within the gut that affect oral drug absorption include gastric emptying rate and intestinal motility, the pH of the gastrointestinal fluids, the activity of gastrointestinal drug metabolising enzymes (e.g. monoamine oxidase and dopa decarboxylase) or drug metabolising bacteria and the surface area of the gut. Many factors affect gastric emptying. These include disease, surgery and other drugs. A change in the rate of gastric emptying alters the rate of drug delivery from the stomach to the duodenum and upper small intestine. This may profoundly alter the plasma concentration/time curve that follows oral administration of many drugs. For some drugs, proximal jejunal disease may reduce, delay or increase the apparent amount of drug absorbed. Reduced absorption of an antibiotic leads to a fall in the peak plasma concentration. If the peak falls below the minimum inhibitory concentration for a particular organism then therapeutic failure may occur, if it is assumed that the peak plasma concentration is all important for antimicrobial activity. Excessive drug absorption may lead to drug toxicity. Abnormal drug absorption is a feature of lower small intestinal conditions such as Crohn's disease. This suggests that drug absorption is not confined to the jejunum but continues throughout the small intestine. It is not always possible to predict the pattern of drug malabsorption from a knowledge of the physicochemical and pharmacokinetic properties of the drug and the pathophysiology of the disease. The rate and amount of drug absorbed be one patient may differ from that in another patient with the same condtion. Although these differences reflect normal individual variation, they are also related to the extent and activity of disease at the time of study...


Free-living volunteer's motivations and attitudes toward pharmacologic studies in man. Two groups of volunteers who had participated in pharmacologic studies were interviewed about their impressions of such studies. One group was from a university community, the other from the pharmaceutical industry. The differences between the two groups were correlated with their respective backgrounds. Both groups had favorable impressions about drug studies and investigators. Most were satisfied with the information given them about the nature and risks of the studies, but some believed that a written description of the study that they could consult at home would improve their understanding of the information. Financial reward was the primary reason given by both groups for volunteering, but the perceived risk of the study was the ultimate deciding factor. The volunteers disliked having their mobility restricted and for this reason might not be willing to participate in long-term studies, such as those formerly carried out in prisons. Alternative sources of volunteers for long-term studies will have to be found.


Clinical and cardiovascular effects of alpha methyldopa in combination with decarboxylase inhibitors. The peripheral decarboxylase inhibitor carbidopa, given (100 mg/day) for 6 wk in a double-blind trial, lowered supine diastolic pressure of 10 patients with essential hypertension treated with alpha methyldopa by a small (6 mm Hg) but significant (p less than 0.05) amount. Large doses of benserazide (1.5 gm) did not modify the hypotensive effect of 1.0 gm of alpha methyldopa in untreated hypertension but significantly reduced the central nervous side effects of sedation and dry mouth. These studies indicate that extensive peripheral decarboxylation is not necessary for alpha methyldopa to lower blood pressure and would be compatible with the central nervous site of hypotensive action of this drug.


Dose-ranging trial of N-acetylprocainamide in patients with premature ventricular contractions. Ten patients with chronic premature ventricular contractions (PVCs) received short-term oral therapy with N-acetylprocainamide (NAPA) to determine its antiarrhythmic efficacy and side effects under the conditions of a placebo-controlled, dose-ranging trial. NAPA was effective in suppressing PVCs in 8 patients but caused a paradoxical increase in PVC frequency in one. Results were equivocal in the remaining patient because PVCs did not recur when NAPA therapy was withdrawn. Mean NAPA plasma levels as high as 41.1 microng/ml did not have untoward hypotensive or myocardial depressant effects, as judged by electrocardiographic and systolic time intervals. There was, in fact, a consistent reduction in PEP/LVET ratio, indicating that NAPA increases the force of myocardial contraction. The mean NAPA elimination half-life of 10.9 hr was longer than the 6.2 hr half-life reported for normal subjects, but its prolongation was predictably correlated with reductions in creatinine clearance. Gastrointestinal side effects experienced by 3 patients and insomnia noted by 2 patients are similar to known adverse reactions to procainamide.


Once-a-day pindolol in hypertension.

Once-a-day pindolol in hypertension. The possibility of using pindolol on a once-a-day schedule was investigated in the treatment of mild to moderate hypertension. Eighteen patients whose blood pressure responded satisfactorily to thrice-daily administration has a similar response to the single daily dose (p greater than 0.05). The advantages of once-daily pindolol therapy as well as some of the biochemical changes produced by the drug are commented upon.


Management of soft tissue injury.

Management of soft tissue injury. The fate of a surgical wound is held in a delicate balance between the host's resistance to infection and the causal factors of infection. Considerable insight into this relationship between the host and pathogen can be gained from the results of quantitative bacteriologic measurements. Newer rapid slide techniques have been developed which provide the surgeon with this information within 20 minutes. In most soft tissue injuries, the wound bacterial count gives an accurate prediction of subsequent infection. Wounds combining greater than 10(5) bacteria per gram of tissue are destined to develop infection. When the bacterial count is below that level, the wounds will usually heal per primam without infection. This large number of bacteria required to elicit infection reflects the remarkable ability of soft tissues to resist infection. This state of high resistance to infection can be reduced by several factors which include circulatory embarrassment, tissue injury, dead space, and the presence of foreign bodies (dirt, sutures, drains, etc.). When treating soft tissue injuries, the surgeon must employ specific therapeutic modalities that allow the wound to heal per primam without infection. On the basis of experimental studies supported by clinical experience, the following treatment protocol for soft tissue injuries is recommended. Using strict aseptic technique, the wound must be first anesthetized with 1 per cent Xylocaine to permit painless sound cleansing. All wounds should be subjected to high pressure syringe irrigation to remove bacteria, foreign bodies, and blood clots. When necessary, debridement of all devitalized tissue should be performed with a stainless steel scalpel. Many wounds caused by sharp wounding agents contain no foreign bodies and few bacteria and exhibit considerable resistance to infection. In these wounds, primary closure can be initiated after irrigation without the development of infection. Wounds resulting from impact forces have a diminished resistance to infection and are susceptible to infection by low level of bacterial contamination. Immediate antibiotic treatment of patients with impact injuries subjected to meticulous debridement and cleansing will permit a safe primary closure. In wounds contacted by pus or feces, open wound management followed by delayed primary closure is usually indicated. Antimicrobial prophylaxis is also recommended for patients with such wounds. Ideal postoperative care of all traumatic wounds includes a surgical dressing and immobilization and elevation of the site of injury.


Veterinary toxicology: the epidemiology of poisonings in domestic animals. Animals are constantly exposed to a wide variety of foreign chemicals, many of which are potentially toxic and some of which result in the clinical poisonings. Pesticides are applied on or around animals for the control of insects and rodents. These chemicals may be placed in areas without regard for accessibility to household pets and domestic livestock. Insecticides, herbicides, and fungicides are routinely and haphazardly applied to animal and  environmental surfaces alike with apparent disregard for differences in absorptive capability. Fortunately, newer herbicides and fungicides are relatively nonhazardous. Drugs are considered to have therapeutic effects, but the lay and professional person's disregard for species differences and variations in recommended dosages can result in poisonings. Adverse reactions may be misnomers for errors in judgment. Failure to provide satisfactory storage facilities for animal feeds and the improper preservation and handling of feedstuffs allow the growth and development of a variety of mycotoxins. Ignorance on the part of animal owners and livestockmen can result in a number of unusual and sometimes fatal clinical syndromes. The dependence of domestic animals and livestock upon their owners for the total environment makes these animals extremely susceptible to environmental pollutants. Exposure to noxious gases, irritating and hazardous industrial materials and wastes, water contaminants, and casually discarded compounds of our own use can and frequently do result in animal illnesses and death. Persons responsible for animals may be unaware of the potential hazard or lack good judgment in the use of these chemicals. Forceful and continuing education for the safe and sensible use of all foreign compounds on and around domestic animals and livestock is needed. Persons handling and applying these materials must recognize their responsibility, not only to themselves but also to their neighbors and the animals in their care.


Laboratory support of drug abuse control programs: an overview. Labeling an individual a drug abuser has serious sociologic and legal implications that only laboratory testing can effectively allay. A proper specimen (both qualitatively and quantitatively) must be obtained for analysis. Positive identification of specimen with subject is of paramount importance. The problems of specimen substitution--other people's urine, tap water, apple juice--directly impinge here, as does the possibility of drug degradation by heat, light, and microbial attack and of drug adsorption by the container and urinary sediment. Confirmation of postives indicated by screening tests (thin layer chromatography and immunoassays) by gas chromatography and/or ultraviolet spectrophotometry is, in most situations, mandatory. An effective quality control program is an absolute requirement. Even under ideal circumstances, laboratory results can sometimes wrongly indicate the abuse of drugs; and conversely, drug abuse can take place without detection by the laboratory. As in any clinical situation, laboratory tests are only a part (albeit an important one) of the entire evaluation of the individual involved.


Drugs and children: methods for therapeutic monitoring. In this era of polypharmacy, the incidence of adverse reactions due to drug therapy has increased alarmingly since the precise effects on the metabolism of a drug given in combination with other drugs can never be predicted with certainty. Inadequate therapy due to insufficient medication or to factors which diminish absorption or enhance metabolism may be equally undesirable. The consequences to patients in terms of increased morbidity and financial cost of prolonged hospitalization may be considerable. For pediatric patients, particularly in the newborn period, these hazards may be much more dangerous. There is a need for more investigation into the validity of procedures in current use for the determination of drug levels in biologic fluids and into the interpretation of the values they produce. In addition clinical chemists and clinical pharmacologists are faced with the challenge of defining those drugs for which blood level information would be advantageous and developing rapid, sensitive, and accurate assays which can be performed by the routine clinical laboratory. The day may be not too far away when a major proportion of the workload of the clinical laboratory consists of assays primarily designed as an aid to therapy rather than diagnosis.


Hypertensive changes in experimental nephritis combined with experimental hypertension. The role of hypertension in chronic glomerulonephritis was studied in rats with experimental hypertension and nephrotoxic serum nephritis. Nephrotoxic serum nephritis accelerated the hypertensive course of Godblatt's type of experimental hypertension both in the acute and chronic phases. Malignant hypertension was found to be caused in some rats by the nephrotoxic serum injection in the chronic phase of experimental hypertension. Nephrotoxic serum nephritis was more protracted in SHR than in control rats. These results suggest that hypertensive changes might aggravate glomerulitis, and that nephritic processes also facilitate the hypertensive changes.


On the age-associated presence of immunoglobulin and complement in the renal glomeruli of mice. Immunofluorescence studies revealed the age-associated presence of mouse IgG, with or without beta1 C in renal glomeruli of various strains of laboratory mice. These were classified into two types: (1) IgG demonstrated without beta1 C and the fluorescence of which was easily decreased by prewashing with PBS. (2) IgG demonstrated almost always with beta1 C and the fluorescence of which remained unchanged by prewashing with PBS. The deposition of immunoglobulin seems to be closely connected with the immune state of animals including the phagocytic function of the mesangium.


Swimming and the skin.

Swimming and the skin. Most skin diseases associated with swimming are relatively minor and either heal spontaneously or respond quickly to treatment. Exceptions are those diseases made worse by sunlight such as lupus erythematosus, skin cancer, or prematurely aged skin. With the use of better sunscreens in the future, that problem will be solved.