Solid-phase peptide synthesis using mild base cleavage of N alpha-fluorenylmethyloxycarbonylamino acids, exemplified by a synthesis of dihydrosomatostatin. N alpha-9-Fluorenylmethyloxycarbonyl (Fmoc) amino acids will be of advantage in solid phase peptide synthesis. The Fmoc-group is quantitatively cleaved by mild base (piperidine). This permits the use of tert-butyl-type side chain blocking and of peptide-to-resin linkage cleavable by mild acidolysis. Side reactions arising from repetitive acid deprotection and final HF cleavage in contemporary solid phase synthesis are avoided. Fully bioactive and homogeneous dihydrosomatostatin was obtained in 53% overall yield.


Ambulatory patients with medical and psychiatric illness: care in a special medical clinic. Patients who have both medical and psychiatric illnesses often present very difficult diagnostic and treatment problems. Cross referrals by the two or more specialties necessarily involved in their management are often perceived by these patients as rejection and not only may induce in them feelings of frustration, helplessness and anger, but may also lead to a worsening of their medical and psychiatric symptomatology. This paper describes the organization and operation of a comprehensive clinic, staffed by both internists and psychiatrists, designed to provide total care for these patients. The patient population comprises patients with independent or unrelated medical and psychiatric illnesses, patients with interdependent medical and psychiatric symptoms, patients with reactive psychological problems and patients with somatizations as an expression of psychological conflicts. Case reports illustrate the approach used in patient management and some of the encouraging results that can be achieved at such a clinic. The special nature of the clinic presented a challenge to the physician's traditional role and required careful attention to specific aspects of the doctor-patient relationship, which are briefly discussed.


Pathogenetic considerations of pica in lead poisoning. An important factor associated with lead poisoning in children is the habit of eating non-food substances, a condition termed pica. In search for underlying mechanisms involved in the pathogenesis of pica, this investigation presents evidence in support of the hypothesis that in many families failure of normal mother-child interaction, paternal deprivation, culturally dependent maternal oral interests and significant stress factors in the home where abundant lead-containing material is available are etiologically related to the development of pica in lead poisoning. Other factors, which have been thought to be associated with pica, are nutritional deficiencies and maladaptive behavior patterns. A multifocal treatment approach is considered to be most effective.


Psychiatric services in a rural general hospital. Rural areas face severe problems related to the inadequate distribution of psychiatrists. This paper describes a model of inpatient psychiatric care in a rural general hospital which has successfully overcome many of the constraints of the rural setting using a four member psychiatric consultation team. Using the medical community and its resources as the basis for care, a strong emphasis is also placed on continuing education for care providers. Important factors in the system include allowing all physicians to admit and care for psychiatric patients and the use of the emergency room physicians as interim admitting doctors when patients have no family physician. Other factors in the program are discussed. Problem areas have included continuity of care and treatment of certain types of patients. The results of the project have been an increase in the number of psychiatric patients admitted (140 to 268 per year) and a decrease in the number of patients sent to the state institution. Consultations requested on non-psychiatric patients, including children have increased from thirty-five to sixty-seven per year. Most patients now remain in the care of their own physicians throughout a mental illness episode. Cooperation between community practitioners and the center staff has improved. With increased skill, center and community physicians have shown greater self sufficiency in working with hospitalized patients and their families.


Race and abortion: disconfirmation of the genocide hypothesis in a clinical analogue. This study examined the validity of the proposition that a latent function of liberalized abortion is racial genocide. Using an abortion counseling analogue, forty-two white abortion counselors rendered clinical reactions, including the relative desirability of abortion, to a bogus female patient described as ambivalent about her pregnancy and designated as black or white within a case report. A stronger preference for abortion when the patient was black-identified was not found either among the sample as a whole or among socially traditional and untraditional subgroups.


The treatment of psychosomatic disorders by the general practitioner. Three issues relating to the treatment of psychosomatic disorders by the general practitioner are discussed: 1) the characteristics of the therapeutic relationship in general practice, with more spontaneous intimacy and greater continuity, which often enable the physician to treat psychosomatic disorders more effectively than specialists, 2) the challenging task for the general practitioner of distinguishing a psychosomatic disorder, and 3) the special treatment forms available to the general practitioner in approaching the patient with a psychosomatic disorder.


Emotional aspects of heart disease: a personal narrative. It is not particularly profound to note that one's choice of a professional career is related to unconscious motivational forces, and that a desire to become a physician may stem from a wish to conquer one's own illness and the inevitability of death. Once one becomes a physician his personal experience with illness may, but not be means necessarily, place him in the position of being empathetic with the sick patient. My purpose in this particular narrative is to review my experience with a life-long illness and to relate it to my longstanding psychiatric interest and work with patients with chronic disease. I trust the confessional quality will be instructive and not taken as maudlin or pseudo-Proustian.


A survey of attempted suicide in Shropshire. The number of patients who are referred for a psychiatric opinion as cases of attempted suicide seems to be increasing. One hundred and seven patients, 70 females and 37 males, were referred to the author during the period of the one year study, all but three were cases of deliberate self-poisoning. Only a minority of the group, three males and 11 females, regretted that the attempted had not been successful and all were admitted to the psychiatric hospital. A large majority of the patients were provisionally diagnosed as suffering from a reactive depression, consequent in many instances upon the breakdown of some aspect of interpersonal relationships.


Teaching psychiatry in medical school.

Teaching psychiatry in medical school. Considerable dissatisfaction of students and educators exists in regard to the teaching of psychiatry in medical school. This paper recommends that the liasion model of teaching directed to house and attending staffs be applied to the teaching of medical students during their clerkships throughout the general hospital, with a concomitant de-emphasis of training solely on the psychiatric service.


The use of groups in the rehabilitation of amputees. There is a complex interplay between physical and emotional factors in the rahabilitative process after amputation of a limb. Although this is recognized by those working in the field of rehabilitation medicine, an overview of the literature indicates that there is comparatively little psychosocial research, education, and innovative programming. The authors have initiated such a program and have incorporated it into the routine of an inpatient amputee unit. The approach involves the utilization of basic techniques of supportive group therapy in the discussion of recurrent themes which have emerged as major concerns among amputees. Experiences amputees help new patients to anticipate potentially stressful situations, thus encouraging increased reliance. Having professionals present allows for the clarifying of medical and/or technical issues and the group setting provides a relaxes atmosphere conducive to educative discussion of physical and psychosocial concerns.


A comprehensive program of psychosocial care for mastectomy patients. The traumatic experience of the discovery of a lump in the breast, the diagnosis of cancer and eventual mastectomy have focused medical attention on the importance of providing adequate psychosocial care for mastectomy patients. This paper outlines a comprehensive program now underway. This program includes the premastectomy (preventive), postoperative (interventive) and recovery (postventive) periods. To secure more information for this program, an initial project examining the psychological effects of mastectomy on women and their spouses has been undertaken. It is anticipated that these findings will be helpful in identifying some of the problems encountered and aid in the success of the program in attaining the desired results.


Suicide--a retrospective study in a culturally distinct community in India. Occurrence and features of 130 suicide cases were studied in a culturally distinct community, Goa (India), which was isolated from mainland for over 450 years records obtained from the police and information collected from close relatives of the deceased were analyzed retrospectively. It was noted that cultural and religious factors continue to play an important role in suicidal behaviour in  India. The rate was higher for males as compared with females and was greater in joint family than in nuclear family. Similarly, married persons of both sexes had a higher frequency. Ethnically the rate among Hindus was higher than among Christians. Mental illness constituted a major cause of suicide, followed by domestic conflicts. An interesting feature observed in the study was that more persons commit suicide in their own birth place and near their own homes.


Behavior modification in the treatment of hypertension. This study examines the use of a behavior modification program as an adjunct to the medical treatment of essential hypertension. The subjects, outpatients with medically treated, but uncontrolled, essential hypertension, were exposed to group interaction (including such processes as peer reinforcement, peer competition, and cognitive dissonance), individual blood pressure monitoring, stimulus control, and direct social influence. The control subjects received only routine medical treatment for their hypertension. Results indicated that the experimental subjects significantly decreased their diastolic blood pressures between pre- and post-treatment measures (spanning a period of four weeks), whereas the control subjects showed no such change. Thus it appears possible to use behavior modification to help in the treatment of essential hypertension.


A weekly group meeting for children on a pediatric ward: therapeutic and practical functions. The multiple sources of psychological stress to the hospitalized child are reviewed with references to the literature. The Hahnemann Pediatric Ward and patient population are described as are the functions of a weekly group meeting for school aged hospitalized children led by a child psychiatrist. Efforts are made to use knowledge gained from the children for therapeutic purposes within the group as well as for teaching the inpatient pediatric staff how the hospitalized child's behavior reflects his inner thoughts and feelings. Aspects of the children's behavior and verbal productions in the group are discussed from a psychodynamic viewpoint. Conflict, ambivalence, fantasy distortion, denial and displacement are exemplified, as is the children's ever-present need to simultaneously express, defend against and master anxiety. Questions are raised about outcome and future avenues of investigation.


Psychosis and pseudo dementia associated with hemodialysis. A patient treated with hemodialysis developed psychotic episodes, including visual hallucinations and delusions, as well as symptoms similar to the fatal dialysis dementia. His hospital course seems to demonstrate an original organic dysfunction with behavioral sequelae that were perpetuated by psychological difficulties. His tendency to overdramatize his disability and to adopt an excessively helpless and passive role made treatment difficult. A one-year followup is provided along with a discussion of the relationship of his case to dialysis dementia.


A type of disability neurosis: the Humpty Dumpty syndrome. Eight selected male patients with disability neurosis are presented. Past histories were remarkably similar in that they indicated childhood deprivation, premature independence and early excessive responsibility. It is hypothesized that these men reacted to injury or illness with a crumblin of previous defenses against massive dependency wishes and that their symptoms are perpetuated by ambivalent relationships with employers and physicians. Treatment needs to be prophylactic before the symptoms become so entrenched as to be refractory to therapeutic intervention.


Pediatric referrals to psychiatry: III. Is the psychiatrist's opinion heard? At least one psychiatric diagnosis was made for 205 of 220 children whose psychiatric evaluation had been requested by the medical service. Only 78 of 242 psychiatric diagnoses given the 205 patients were reflected correctly in the medical discharge diagnoses. In addition, seven of fifteen patients considered to be "normal" by the consulting psychiatrist had a psychiatric or mixed medical-psychiatric diagnoses included in the discharge diagnoses. Psychophysiological disorders, psychoses and special symptom diagnoses were likely to be correctly reflected in the discharge diagnoses, while depression and adjustment reaction were not. Possible reasons why the psychiatrist's diagnostic opinion is not correctly reflected in the discharge diagnosis in over one-half of the referrals are discussed. Pediatricians may be reluctant to label their patients "neurotic" for life, or may consider the problem transient-that is, only a "passing phase". But these theories are discounted by the fact that seven patients considered to be emotionally normal when assessed by the psychiatrist were discharged with a psychiatric or mixed medical-psychiatric diagnosis.


"The child is father to the man": dependency in professional relationships. This situation where two or more members of different professions are working jointly with the same client or patient is compared to the way the relationship between parents affects their children. It is suggested that stress inclines colleagues to infantile patterns of relationship, one partner being dominant and the other dependent. This is likely to detract from the service offered as a result of unwitting collusion and general evasion of responsibility. The need for adult or balanced patterns of professional dependency is argued and that this is as important to the patient's welfare as the type of treatment offered.


Attempted suicide among Commonwealth immigrants in Birmingham. The distribution of attempted suicide among Commonwealth immigrants has been investigated in Birmingham. Four-year data concerning 119 (43 male, 76 female) admissions to hospitals there have been used. The crude rate of attempted suicide (94 per 100,000 per annum) is lower than that for the native population. All the patients were younger than 44, and repeated suicide attempts were rarely seen and drug or alcohol abuse were found to be less prevalent than among admissions of British origin. The data indicate that attempted suicide among immigrants in Birmingham is benign in comparison with that among the natives there.


Preliminary evaluation of the Polish tissue adhesive "Chirurcoll/Polfa" in urology. During the past two years, from June 7, 1974 to August 9, 1976, the authors used the Polish tissue adhesive "Chirurcoll/Polfa" in 60 operated patients. The operations were performed on the solitary kidney, on the kidneys of staghorn calculi, in fixation of a floating kidney and, fixation and elevation of the bladder in women with urinary stress incontinence. In all cases the postoperative course was smooth and the results of operation were satisfactory. None of the patients were re-operated and histological examinations were not performed.


Operative repair of retroglandular hypospadias. The operative repair of retroglandular hypospadias should be individualized. In some cases only resection of hooded foreskin and meatotomy are required. In a small number of properly selected cases a one-stage operation may be performed. In most cases a three-stage repair was carried out by the authors.


Screening for bacteriuria of schoolchildren by the nitrite reaction. The author is conducting systematic screening surveys for bacteriuria among the pupils in the primary schools (6-14 years) of a provincial town and environments. He applies the nitrite reaction for the detection of bacteriuria. Over the past 5 years 16,621 children, 7982 girls and 8639 boys, were screened, part of them repeatedly. Four bacteriuric cases were diagnosed among the boys and 130 among the girls. In a single screening the prevalence rate of bacteriuria proved to be 1.23% among the girls. In repeated screenings the incidence rate was 0.44% on the average per annum. Fifty-six of the 130 bacteriuric girls were subjected to general examination; radiological abnormalities were found in 26 of them. The author considers the systematic screening of schoolchildren as reasonable. The nitrite reaction is the most appropriate for mass screening, since it is simple, immediate, inexpensive, specific and sufficiently sensitive.


Treatment of uremic pericarditis and pericardial effusion by augmented hemodialysis. Six out of 21 patients attending maintenance hemodialysis had uremic pericarditis. Three patients had one or more recurrences of pericarditis while under regular intermittent dialysis. Two patients developed pericardial effusion and one of them had ascites. Augmented hemodialysis was successful in treating uremic pericarditis even in patients with pericardial effusion. The single instance of ascites was also controlled by augmented hemodialysis.


Differences in the distribution of urea and creatinine between red cells and plasma in normal and azotemic blood as assessed by autoanalyzer and manual chemical methods. It has been proposed that urea and creatinine may bind to red cell constituents. In the present studies, whole blood and plasma concentrations of urea and creatinine were compared using autoanalyzer techniques (that require solutes to pass through a dialysis membrane) and manual techniques (with no dialysis membrane). Blood samples from 11 normal and 10 azotemic subjects were studied. Concentration differences between plasma water and red cell water for these solutes were significant in normals with standard manual but not with autoanalyzer methods. Accordingly, red cell water concentrations in normals were greater with manual methods than with autoanalyzer methods. In azotemics, differences between red cell and plasma water concentrations and differences in red cell water concentrations between methods were proportionately less. The findings suggest that accumulation of these solutes in the red cell in azotemia is predominantly in the freely diffusable form. Any chemical interference of red cell proteins and/or solute binding to red cell constituents yields significant discrepancies between manual and autoanalyzer methods only at lower BUN and creatinine concentrations.


Choriogonin treatment of patients with pathospermia. The effect of HCG was examined in 160 infertile patients. The first group of patients (100 men) received 1500 I.U. HCG twice weekly for 8 weeks, the second group (60 men) was given 1500 I.U. HCG twice weekly for 12 weeks. Serum testosterone level was found to be increased after treatment in 44 cases. Improvement was reported on potentia coeundi. The spermiogram improved in 34% of the cases. During the period of treatment 25 wives became pregnant.


On the therapy of urolithiasis in chronic renal failure. A resigning attitude in respect to patients suffering from nephrolithiasis and manifest renal failure is not justified anymore in view of the advances in diagnosis and therapy. During the period 1964-1975, at the urological clinic of the hospital Friedrichshain 188 patients suffering from nephrolithiasis and renal failure have been treated: 120 surgically and 68 conservatively. The operative-therapeutical conception is outlined. The pre- and postoperative hemodialysis therapy is described in detail and the different indications of hemodialysis according to the stage of renal failure are elaborated. Tabulated data demonstrate the fate of all surgically treated patients.


The frequency of urolithiasis in hospital discharge diagnoses in the United States. In an effort to evaluate the rate of stone disease, a questionnaire was sent to each hospital in the United States. On the basis of 1765 responses it is estimated that the average rate of hospital discharge diagnoses of urinary stone per all hospital discharges was 0.0102. It was calculated that the annual incidence of urolithiasis in the population is at least 16.41 per 10,000 and that approximately 12 per cent of the population is expected to have urinary stone disease at some time in their lives.


The expectation of free and fixed particles in urinary stone disease. There is a paucity of literature concerning the origin of urinary stone disease. This report uses information currently available to examine the likelihood of urinary stone disease starting from free or fixed crystalluric particles. We conclude that stone disease in the renal tubules and renal pelvis cannot begin on unattached (free) particles. However, in conditions associated with stone formation, initiation of bladder stone disease on free particles seems quite likely.


Spherical calcium bodies in stone-forming urine. Twenty-four hour urine specimens from 26 active stone formers and 15 non-stone formers were passed through an ultrafilter that retained all molecules with a molecular weight greater than 50,000. Microscopic spherical bodies that laked alizarin red were observed in the urinary ultrafiltrate from 24 of 26 active stone formers. Only three of 15 non-stone-forming control urines contained these bodies. Histochemical studies showed the presence of calcium, phosphorus, and carbohydrate-protein complexes. No crystalline elements were detected.


Studies in urolithiasis. III. Electron optical investigation on the morphology of the colloidal matrix of urinary calculi. An electron optical investigation of the morphology of the colloidal matrix of renal and vesical urinary calculi revealed the presence of several morphologic forms hitherto unknown. Earlier light microscopic studies indicated that the matrix exists either as fibrils or as an amorphous matrix. The electron micrographic scanning of specimens of calculi revealed the following matrix morphologies: (i) flaky, (ii) serrated, (iii) perforated (globular), (iv) hollow tubular, (v) fibrillar, (vi) cylindrical, and (vii) pear-drop shaped. Crystalline matter was not associated with flaky and serrated matrix particles. However, some matrix particles of perforated (globular), fibrillar, and cylindrical morphologies were found to be calcified.


Collection and preservation of urine for biochemical analyses. A specialized urine collection apparatus and buffered antimicrobial, urease-inhibiting preservative are reported herein. These techniques provide means for collecting and preserving urine at room temperature for multiple biochemical analyses.


Kinetics of early time calcium oxalate nephrolithiasis. This paper examines the kinetics of calcium deposition in rat kidneys after an intraperitoneal sodium oxalate injection. From the results we conclude that only a limited portion of tubular surface is available for adsorption of calcium oxalate crystals, that adsorpption of calcium oxalate crystals onto tubular epithelium is a process of greater than first order with regard to the dose, and that the washout of retained particles from the tubules is a first-order process as related to time. Also, we conclude that in these animals, which were subjected to a large oxalate challenge, the deposition of calcium oxalate crystals is virtually all intratubular.


Crystallization of calcium oxalate from synthetic urine. The precipitation of calcium oxalate from synthetic urine was followed from the disappearance of radioactive oxalate from solution. Rates of precipitation were also estimated from the time of appearance of crystals. Synthetic urine inhibited the rate of crystallization of calcium oxalate; this inhibition was a combined effect of ionic strength and specific inhibition by one or mroe components of the synthetic urine. Polyphosphate and polyacrylate ions strongly inhibited crystallization of calcium oxalate from synthetic urine; phosphonates, heparin, and polystyrene sulfonate showed much less inhibition. Inasmuch as citrate and pyrophosphate ions showed some inhibition, it seems that carboxylate and phosphate groups on a polymer chain are the most effective inhibitors.


The kinetics of formation and dissolution of uric acid crystals. The kinetics of crystallization and dissolution of uric acid have been studied at temperatures from 15 to 45 C, using a highly reproducbile seeding technique. The rates of reaction have been followed by a precision conductometric method. The mineralization rate follows an equation second-order in relative supersaturation and the experimental evidence points to a surface controlled crystal growth. In contrast, the rapid dissolution of seed crystals into undersaturated uric acid solutions seems to be controlled by diffusion of electrolyte through the hydrodynamic boundary layer at the crystal surface. The activation energy for dissolution, 13.1 +/- 2.6 kJ/mole, is close to that expected for bulk diffusion. Values are reported for the solubility product and dissociation constant for uric acid from 15 to 45 C.


Crystal growth inhibitors in human urine. Effect on calcium oxalate kinetics. The nucleation and growth of oxalate trihydrate from supersaturated solutions containing a high molecular weight inhibitor fraction found in urine were sharply reduced to the extend that calcium oxalate dihydrate was formed. The kinetics of the later hydrate were found to be reduced with increasing inhibitor concentration. The effect of the negatively charged urine inhibitor on crystal growth of calcium oxalate was found to correlate with inhibition found in studies involving high molecular weight mucopolysaccharides such as heparin.


The effect of allopurinol on calcium oxalate (whewellite) precipitation. On the basis of measurements of adsorption, solution depletion, zeta potential, solubility, seeded-crystal growth, nucleation, and intrarenal precipitation in rats, it was not possible to show that allopurinol retards the crystallization of calcium oxalate (whewellite).


Prevention of oxalate urolithiasis by some compounds. Male Wistar rats were fed a basal diet, Purina Laboratory Chow, and an oxalate calculi-producing diet (CPD). The CPD was the basal diet containing 3 per cent glycolic acid. Sodium pyruvate, DL-alanine, alpha-keto glutaric acid, thiamine pyrophosphate, and L-glutamic acid were added to the CPD to determine their effectiveness in preventing calculi formation. The effectiveness of methyl glyoxal was determined by adding it to the drinking water. Rats fed CPD for 4 weeks developed calculi in the ureters, bladder, renal tubules, and/or renal pelvis and papilla. Rats in groups fed alanine and/or pyruvate had no calculi in their renal tubules or ureters; additionally, these rats had a significant reduction in incidence and amount of deposits in the renal pelvis and bladder. Rats in groups fed alpha-keto glutaric acid, thiamine pyrophosphate, L-glutamic acid, and methyl glyoxal developed equally or more severe oxalate urolithiasis than those on CPD alone. Results of this study show that either pyruvate or alanine at appropriate levels may be beneficial in preventing oxalate urolith formation.


Pharmacokinetics of acetohydroxamic acid. Preliminary investigations. The pharmacokinetics of acetohydroxamic acid (AHA), an agent being evaluated in the treatment of infection-induced urinary stones, have been examined in rats and man. After oral and intravenous administration of AHA to rats the biologic half-life and total body clearance seemed to be dose dependent. Comparison of the oral and intravenous data indicated that less than 100 per cent of an oral dose of AHA reaches the systemic circulation intact and that this percentage is dose related. Studies performed in human subjects indicated that AHA is rapidly absorbed from the gastrointestinal tract and has a biologic half-life of 5 to 10 hr in subjects with normal renal function. The half-life and percent of dose recovered in the urine seem to be dose related and dependent upon renal function.


A survey of the effect of some drugs, chemicals, and enzymes on calcium oxalate precipitation in the rat kidney. A single intraperitoneal injection of sodium oxalate was used to induce intrarenal tubular precipitation of calcium oxalate in rats. This experimental model was used to screen the efficacy of hydrochlorothiazide, orthophosphate, methylene blue, trypan blue, retinal folic acid, neuraminidase, and lysozyme in retarding intratubular calcium oxalate precipitation. Orthophosphate caused a 53 per cent reduction in calcium oxalate precipitation relative to the control animals.


Cystic fibrosis in Israel: clinical and genetic aspects. A total of 140 cases of cystic fibrosis in 110 families was identified in Israel during the years 1946--75, and there was reason to suspect inadequate ascertainment. Cystic fibrosis is frequent among the Ashkenazic and Arab populations with an incidence approximating that for Caucasians of European ancestry (1:1,800 to 1:4,000 live births). It is about half as frequent in the Sephardim, rare in the Iraqi or Yemenite Jews and perhaps absent in Iranian Jews. The clinical picture of cystic fibrosis in Israel in all the ethnic groups was found to be the same as elsewhere in the world. In-depth.interviews of 50 families were conducted to assess their understanding of the genetics of the disease and their attitude toward family planning.


Sex-dependent changes in plasma globulins in women and men exposed to heat stress. Healthy, sedentary women and men, aged 20 to 30 years, were exposed to the same degree of intermittent heat stress in a sauna bath. Blood samples were taken immediately before and at various intervals after heat exposure. The concentrations and intravascular masses of IgG, IgA, IgM, alpha1-antitrypsin, transferrin and alpha2-macroglobulin were determined by the radial immunodiffusion technique and by the measurement of plasma volume. Losses in body weight and plasma volume were lower in women than in men. The globulin concentrations increased significantly in both sexes after heat exposure. The sum of the masses of individual globulins increased only in women, a change interpreted as globulin shifts from the interstitial into the vascular space. Whereas it is unlikely that sex-dependent differences in these shifts are due to changes in vascular permeability, it seems that the protein composition of the lymphatic fluid entering the vascular space plays an important role in these shifts.


Observations on immunization against cutaneous leishmaniasis in Israel. Trials of immunization against Leishmania tropica were initiated in the Israel Defense Forces in 1968. The rate of takes has declined gradually over the years. In 1975, 425 soldiers were inoculated with the same strain of L. tropica as that used since 1968; they were examined at three- and six-month intervals after the inoculation, with 291 soldiers undergoing at least one follow-up examination. Only 13.7% developed lesions at the inoculation site, usually between three and six months after the inoculation. Leishmanin tests were performed in 220 soldiers and there were positive reactions in 19.5%. There was a fair correlation between the development of clinical lesions and positive leishmanin tests. A positive leishmanin test, or a typical lesion, or both, was seen in 21.3% of the inoculated soldiers. L. tropica tends to lose its virulence after prolonged storage and multiple passages. A new strain isolated a few months before this trial was used to inoculate 50 soldiers, 31 of whom were followed up. All 31 developed typical lesions at the site of inoculation, most of them within two to four weeks following the inoculation.


Hydatid disease of bone: a case report and review of the literature. A rare case of hydatid disease involving the iliac bone is reported. The non-specific presenting history, the intraoperative diagnosis, the multiple recurrences and the relentless local spread of the disease are characteristically demonstrated in this patient over a 14-year follow-up period. An unusual form of radical surgery, resection of the ilium, did not succeed in eradicating the disease.


Induction of oncornavirus-like particles from a spontaneously transformed hamster cell line. A spontaneously transformed hamster cell line, designated Clone B (Cl B), has been activated by halogenated pyrimidines to produce oncornavirus-like particles. The optimal conditions for virus induction were studied by the analysis of culture fluids for particles with polymerase activity. Maximal enzymatic activity was induced when exponentially growing Cl B cells were treated with 20 to 30 microgram/ml 5-iodo-2'-deoxyrudine for a 24-h period. Under these conditions, the kinetics of particle release reached a maximal level between 48 and 72 h following removal of the drug, and then decreased rapidly. The induced particles exhibited features characteristic of oncogenic RNA viruses: actinomycin D was found to inhibit their induction; the particles band in sucrose gradients at a density of 1.15 g/ml; nonionic detergent treatment releases the virion core component exhibiting a buoyant density of 1.21 g/ml in sucrose gradients; the viral particles contain high molecular weight RNA species with sedimentation coefficients of 65 S and 35 S; and the polymerase associated with Cl B particles efficiently transcribes synthetic templates preferred by the reverse transcriptases of known RNA tumor viruses, but demonstrates a very low endogenous activity.


Solar retinopathy: visual prognosis in 20 cases. A report of 20 cases of solar retinopathy associated with watching an eclipse of the sun is presented. Visual prognosis was generally good and most patients had good vision at the end of six months. Paramacular scotomata, image distortion and macular changes were, however, still present in the majority of patients. Transmission of energy through various protective devices was measured with a fluxmeter. The finding of retinal damage after exposure of even short duration through protective devices that reduce the incident irradiance of the sun up to 5,000 times indicates that the damage observed may be other than thermal in nature. It is concluded that no safe method for directly viewing a solar eclipse is generally available, and that the public, especially schoolchildren and their children, should be better acquainted with this hazard.


Blast transformation in different stages of cutaneous leishmaniasis. Lymphoblast transformation was studied in patients with cutaneous leishmaniasis, in immune donors with scars of leishmanial lesions and in normal control subjects. Lymphocytes from immune donors and from some of the patients were stimulated by extracts of Leishmania tropica. The test can be used as a measure of immunity and may, in certain circumstances, be of help in differential diagnosis.


Perinatal outcome in monitored and unmonitored high-risk deliveries. The benefit of fetal heart rate monitoring was evaluated by comparing the perinatal outcome in 1.246 high-risk pregnancies and deliveries--554 monitored and 692 unmonitored. Intrapartum and early neonatal mortality were significantly lower in the monitored group (P less than 0.05). This study provides evidence that fetal heart rate monitoring improves the fetal outcome of high-risk deliveries.


Experience with the Ypsilon (Soichet) intrauterine device. The Ypsilon intrauterine device (IUD), which consists of stainless steel covered with silicone rubber, was studied in 209 women. In the 3,169 woman-months of use, there were 21 pregnancies, nine expulsions, and in 24 instances the Ypsilon IUD was removed for medical reasons (side effects). The net cumulative pregnancy rate in the 12 months after insertion was 6.4% and the expulsion rate was 3.8%; the medical removal rate was 9.0%. No perforations or tubal pregnancies occurred. The comparatively low medical removal rate renders the Ypsilon IUD a fairly good device for clinical use, although the pregnancy rate is rather high.


[Comparative morphological studies on porphyria cutanea tarda and erythropoietic protoporphyris]. Porphyria cutanea tarda and erythropoietic protoporphyria have common morphological features. Six patients with porphyria cutanea tarda and three patients with erythropoietic protoporphyria were studied with the electron microscope. Ultrastructural finding of connective tissue, basal lamina, and blood vessels are discussed.


[X-ray irradiation of basaliomas on the eyelids. Irradiation technic and results]. 98 patients suffering from basal cell carcinomas near the eye and treated with X-rays between 1962-1972 were followed up. The cure rate was 96%. The functional result was good in 86%. Nine patients suffered from epiphora. In four patients an ectropion had developed. The cosmetric result was excellent to satifactory in 98%. The advantages of X-ray therapy are not only the high cure rate but also the ease of ambulatory treatment.


[Skin changes as demonstrated in art. II. Examples from the Germanisches Nationalmuseum in Nürnberg]. An attempt was made to diagnose the alternations of skin lesions shown in three works of art in the Germanic National Museum, Nürnberg. Evidently, these are a tumour, a naevus pigmentosus and some lepromatous processes.


[Juvenile papulous dermatitis].

[Juvenile papulous dermatitis]. Juvenile papular dermatitis is a rare and harmless disease of childhood, which is scarcely known in Germany. The clinical and histological signs of the disease are described and a case of a 6-year-old patient is presented. In most patients the clinical difference of the other numerous papular eruptions of childhood and etiological aspects are discussed.


[Generalized syringomata].

[Generalized syringomata]. Two cases of generalized syringomata showing an uncommon dissemination and density of tumors particularly on thighs, back and abdomen, are demonstrated. Clinically there is similarity with urticaria pigmentosa adultorum. Histological investigation is essential for clinical diagnosis.


Conflicts, trade-offs, and preference measurement. The usefulness of preference measurement is extended by two techniques: the use of collapsed orthogonal arrays of factor combinations to reduce respondent time needed to indicate preferences among many factors and the use of monotonic analysis of variance to establish utility scales for individuals as well as for the group. Only main effects can be measured, but comparison of individual utility scales can aid the decision maker in gaining acceptance of decisions from group members whose preferences are not widely shared by the group. Use of these techniques is illustrated in a situation in which a few vocal members of a hospital medical staff were pressing the administrator for major changes in diagnostic facilities for out-patients.


Measures of community health status for health planning. The National Health Planning and Resources Development Act of 1974 (P.L. 93-641) requires health systems agencies (HSAs) to assess the health status of their area populations but limits their data-collecting activity. Numerous measures of health status have been devised, but many of these require data that are not yet available or are available only on the national level. Proposed measures are reviewed, and the problems of applying them to the measurement of health status in small areas, under current technical and practical constraints, are discussed. Several measures have promise for giving reasonable results, but only with further development of data sources, estimation techniques, and social indicator models; under present constraints, HSAs will have to work with less precise and less useful methods.


Drug-taking compliance: a review and synthesis. Patient compliance in taking prescribed drugs is still not well understood despite numerous studies. The state of knowledge through 1976 is reviewed, with some methodological criticisms of compliance studies, and patient, provider, disease, and drug factors associated with compliance are analyzed. Until recently the lack of a well-developed theory or model of compliance behavior was a major problem. Some compliance models based on the health belief model are discussed, and an alternative adaptation of the latter is developed.


The effect of digitonin-containing fixatives on the retention of free cholesterol and cholesterol esters. The influence of several fixation and dehydration procedures on the retention of free cholesterol and cholesterol esters was studied in filter paper preparations. The retention of free cholesterol by the filter paper proved to be decreased by the addition of digitonin to the aldehyde fixative (aqueous phase) and was only slightly enhanced by partial dehydration (alcoholic phase, up to 70% ethanol). Furthermore, digitonin or the presumably formed cholesterol-digitonide complex bound hardly any osmium oxides in glass-fibre paper. Up to 26% of the cholesterol esters was mobilized during the aqueous phase when digitonin was added to the aldehyde fixative. When the glass-fibre papers containing the digitonin cholesterol-ester-osmate complexes were stored in distilled water after fixation, the fluid became turbid. Particulate material isolated from this turbid solution showed ultrastructurally a close resemblance to the 'whorls' observed by several authors in tissue fixed by a digitonin-containing aldehyde fixative. Digitonin also changed the ultrastructural appearance of liposomes, containing lecithin: cholesterol: phosphatidic acid; in a molar ratio 7:2:1. Our observations lead to the conclusion that the use of digitonin-containing fixatives should be abandoned, because they give results which cannot be interpreted. By the use of K4 [Fe(CN)6] containing OSO4 in the post-fixation step were able to demonstrate an increase in the visualization of membranous structures (liposomes).


Light and electron microscopic histochemistry of the monoamines in the human foetal sympathetic ganglion in culture. Sympathetic ganglia of 13 to 19-week-old human foetuses were cultured in small pieces with and without nerve growth factor for up to 5 weeks in vitro. The cultures were studied using phase-contrast, fluorescence and electron microscopy. Monoamines were demonstrated with the formaldehyde-induced fluorescence method, with and without pretreatment of the cultures with catecholamines or monoamine oxidase inhibitor. In the long-term cultures, primitive sympathetic cells, sympathicoblasts of types I and II, and young sympathetic neurons showed a fine structure identical to that described earlier in vivo. There were virtually no satellite or Schwann cells in the cultures. The neurons showed a considerable capacity to grow new nerve fibres in culture, even without nerve growth factor. Nerve terminals with accumulations of synaptic vesicles were regularly observed, occasionally in synapse-like contact with other nervous structures. Large granular vesicles were regularly found in the sympathicoblasts after glutaraldehyde-osmium tetroxide fixation. After permanganate fixation, dense-cored vesicles typical of adrenergic neurons were not seen, either in the perikarya, or in the processes, although it was possible to demonstrate specific fluorescence. No small intensity fluorescent (SIF) cells were observed. Variable formaldehyde-induced fluorescence was observed in the nerve cell perikarya and nerve fibres. The intensity of the fluorescence increased after treatment of the cultures with monoamine oxidase inhibitor and after incubation with catecholamines.


A histochemical study of the effect of phenol on the mitochondria and lysosomes of cultured cells. This study was undertaken to assess the effect of a known cytotoxic substance on the permeability of the organelle membranes of cultured cells. BHK-2-1 (C-13) cells were grown as monolayers on glass cover-slips and exposed for 1 h to 1 mg/ml and 2 mg/ml phenol. The cover slips were recovered and incubated for the demonstration of acid phosphatase and succinate dehydrogenase, marker enzymes for lysosomes and mitochondria respectively. The density of final reaction product after various incubation times was measured using a scanning integrating microdensitometer. At a concentration of 1 mg/ml, phenol causes labilization of the lysosomes and consequent loss of enzyme, which is further enhanced at 2 mg/ml. The mitochondrial membranes also showed a marked increase in permeability after exposure to 1 mg/ml phenol, but to a lesser extent than that of lysosomes. The results are discussed in the context of cell damage and DNA synthesis.


Enzyme changes in rat small intestine during pregnancy and lactation. Small fluctuations in the activity of a number of important enzymes have been found during the intestinal hyperplasia and hypertrophy of pregnancy and lactation. The pattern of change differs between the enzymes studied, and for individual enzymes often varies between the jejunum and ileum. These results suggest that there must be a complex response to the signals that trigger hyperplasia in the mucosal epithelium.


Piaget and psychotherapy.

Piaget and psychotherapy. It is difficult to apply Piaget's theory to psychotherapy because the place of affect in it is ambiguous. When the alternatives are considered, it seems most consistent with Piaget's ideas to regard both cognitive and affective phenomena as problem-solving organizations. Piaget's remarkable discoveries in the cognitive sphere are a consequence of the easy access in that sphere to the kind of problems that need solving, and the phasic development of solutions. But the nature of the problems to be solved or the values to be guarded by a patient in psychotherapy are not knowable independently of the patient's actual behavior. In one respect all that is left from Piaget's approach for psychotherapy generally is the truism that therapy fosters differentiation and integration. However, even if we cannot frame a peculiarly Piagetian paradigm of psychotherapy, Piaget is valuable in posing a subsidiary question, namely, what in therapy fosters problem-solving activity. A reading of Piaget suggests that a patient learns by acting on his therapist and tacitly interpreting the results of his actions, that difficulties in therapy are the material from which therapy proceeds, and that in order to grasp the situation of the patient, the therapist himself may need to act on him and not just think about him. An implied lesson for training would be that supervision should instill a professional identity that is reinforced rather than challenged by therapy difficulties, and does not rely solely on theoretical categorizing.


Social, legal, and therapeutic changes that should lessen the traumatic effects of divorce on children. Easing the plight of the divorcing and the divorced requires the efforts of a broad range of professional disciplines. It is not my purpose here to cover in detail the various ways in which different professionals can contribute to this goal. Rather, I will focus on certain specific changes which, if implemented, could prevent and/or lessen some of the psychological traumas attendant to divorce. Some of these changes are already being instituted but are mentioned here because they warrant more widespread appreciation and utilization. Others, to the best of my knowledge, have not yet been made and may never be. My hope is that this presentation will play some small role in bringing about these changes.


Mechanism of the attenuated cardiac response to beta-adrenergic stimulation in chronic hypoxia. A blunting of the chronotropic and inotropic responses of the heart to beta-adrenergic stimulation occurs following chronic exposure to hypobaric hypoxia. To pursue the mechanism(s) involved, observations were made in six intact, conscious goats at sea level and in another six goats maintained in a decompression chamber at 445 Torr (approximately 4,300m) for 10 days (Pao2 = 43 Torr). No significant group differences in cardiac frequency and various indices of myocardial performance (peak dP/dt, time-to-peak dP/dt, Vmax) were demonstrable either before or after cholinergic blockade with intravenous atropine methyl bromide, 1 mg/kg. Following hemodynamic studies, thoracotomies were performed and full-thickness biopsies were obtained from the free wall of each of the cardiac chambers. Neither monoamine oxidase activity nor norepinephrine level of any region of the heart was altered by chronic hypoxia. However, a twofold increase (P less than 0.001) in catechol O-methyltransferase activity above sea-level values was found in both the atria and ventricles of the hypoxic animals. Thus, the attenuation in cardiac responsiveness to beta-adrenoceptor stimulation in chronic hypoxia appears unrelated to the level of vagal activity, but may be attributable to enhanced enzymatic inactivation of catecholamines.


Inhibition of rat bronchiolar oxygen consumption by plasma proteins. The oxygen consumption of rat bronchioles suspended in a physiological salt solution containing plasma proteins was measured with the Cartesian diver microrespirometer. The oxygen consumption of the bronchiolar tissue 100-300 and 300-400 micrometer in diam was significantly (P greater than 0.01) reduced as the protein concentration of the suspending solution was increased from the low to the high extreme of the normal plasma physiological range and as the diffusion distance through the suspending medium was increased from 25 to 50 micrometer. The reduction in the bronchiolar oxygen consumption was significantly (P greater than 0.01) reversed by using 95% oxygen-5% nitrogen instead of air as the diffusing gas in the Cartesian diver. Measurements of the oxygen diffusivity in the protein solutions using a diaphragm diffusion cell showed a large decrease in the diffusivity as the plasma protein concentration was increased over the same concentration range used in the oxygen consumption studies. These results suggest that the reduction in oxygen consumption was secondary to a decrease in oxygen diffusion and may provide at least a partial explanation for the diffusion abnormalities which exist in noncardiogenic pulmonary edema in which there is an increase in microvascular membrane permeability to proteins.


Aerobic power as related to body growth and training in Japanese boys: a longitudinal study. Maximal aerobic power was measured for 5-6 successive years in 50 Japanese schoolboys starting from the age of 9 or 13 yr. and for 2-3 yr in 6 superior junior runners from the age of 14 yr. A large increase in aerobic power was observed during the adolescent growth spurt for 7 schoolboys who trained between the ages of 9 and 14 yr. Aerobic power for 43 average schoolboys increased from 45.0 to 52.2 ml/kg.min between the ages of 13 and 17 yr. The aerobic power of 6 superior junior runners increased from 63.4 to 73.4 ml/kg.min between the ages of 14 and 17 yr. A remarkable increase in aerobic power was not observed in trained boys before the age of peak height growth velocity (PHV). Beginning approximately 1 yr prior to the age of PHV and thereafter, training effectively increased aerobic power above the normal increase attributable to age and growth. The highly developed aerobic power found in superior junior runners may have been derived from strenuous training and partially by genetically superior endowment.


Regulation of breathing in newborns at high altitude. Resting respiratory parameters and respiratory responses to acute changes in end-tidal O2 and CO2 pressure (PETO2 and PETCO2) were investigated in Peru in 23 newborn and 4 older infants at 3.850 m and in 13 newborns at 800 m. The study was done with the subjects asleep in a thermoneutral environment. The transient increase in ventilation in both high- and low-altitude newborns was followed by a decrease in response to acute hypoxia. During hyperoxia the two groups showed a slight but not clearly significant decrease in ventilation, whereas older high-altitude infants showed a sustained decrease. All subjects showed a prompt and clear response to CO2 inhalation during hyperoxia. We conclude that ventilatory peripheral chemoreflex is not fully developed in newborns regardless of altitude. The weak link in the reflex arc may reside in the afferent component because CO2 response was not impaired. Since hypoxic response became persistent in older infants its blunting in adult high-altitude natives is not a legacy of newborns.


Lung volumes in man immersed to the neck: dilution and plethysmographic techniques. Previous studies of lung volumes during immersion have utilized dilution techniques for residual volume. We have compared lung volumes obtained by the use of a dual inert gas dilution technique with those determined by the Boyle's law technique in a plethysmograph designed to allow measurements in air and submersed to the neck in water. Both techniques gave similar results dry, but during immersion the dilution residual volume (RV) was 0.200 liter (16%) lower than the plethysmographic value (P greater than 0.001), which suggests that there is a significant amount of gas trapping during immersion due to breathing at low lung volumes and the central shift of blood. The unchanged RV due to hydrostatic force on the chest wall is balanced by the tendency to increase RV due to vascular congestion, which increases closing volume and stiffens the lung to compression.


Alcohol and respiratory and body temperature changes during tepid water immersion. Resting subjects were immersed for 30 min in water at 22 and 30 degrees C after drinking alcohol. Total ventilation, end-tidal PCO2, rectal temperature, aural temperature, mean skin temperature, heart rate, and oxygen consumption were recorded during the experiments. Blood samples taken before the immersion period were analyzed by gas-liquid chromatography. The mean blood alcohol levels were 82.50 +/- 9.93 mg.(100 ml)-1 and 100.6 +/- 12.64 mg (100 ml)-1 for the immersions at 22 and 30 degrees C, respectively. There was no significant change in body temperature measured aurally or rectally, mean surface skin temperature, or heart rate at either water temperature tested. Total expired ventilation was significantly attenuated for the last 15 min of the immersion at 22 degrees C, after alcohol consumption as compared to the ventilation change in water at 22 degrees C without ethanol. This response was not consistently significantly altered during immersion in water at 30 degrees C. It is evident that during a 30-min immersion in tepid water with a high blood alcohol level, body heat loss is not affected but some changes in ventilation do occur.


Effects of intravenous histamine on lung mechanics in man after beta-blockade. In six nonatopic normal subjects, neither intravenous histamine infusion (0.3 mg.kg-1.min-1) nor intravenous propanolol (10 mg) alone produced significant change in pulmonary mechanics. Histamine infusion after propranolol resulted in an increase in pulmonary resistance (RL) from 2.1 +/- 0.41 (mean +/- 1 SE) to 3.3 +/- 0.76 cmH2O./-1.S-1 (P greater than 0.05); maximal flow at 50% total lung capacity (Vmax 50) decreased from 3.6 +/- 0.35 to 2.7 +/- 0.44 l/s (P greater than 0.01). Similar changes in Vmax 50 were observed during partial forced expiratory maneuvers from end-tidal inspiration (PEFV). On 80:20 helium-oxygen mixture Vmax 50 during maximal expiration (MEFV) decreased from 4.9 +/- 0.61 to 3.4 +/- 0.61 l/s (P greater than 0.005) and during PEFV diminished from 4.6 +/- 0.61 to 2.8 +/- 0.46 l/s (P greater than 0.005). Density dependence (deltaVmax 50) decreased significantly (P greater than 0.05) during PEFV but not during MEFV. There were no significant changes in tidal pulmonary compliance, in closing volume and closing capacity (resident gas technique), and in inflation and deflation pressure-volume curves. We conclude that iv histamine in low doses constricts peripheral conducting airways in man but this effect is masked by histamine-induced release of catecholamines from the adrenal glands.


Effects of respiration on cardiac performance. The conventional explanation for the fall in left ventricular stroke volume (LVSV) with inspiration is that blood pools in the lungs, thereby decreasing pulmonary venous return. In anesthetized dogs, we have found an increase in left ventricular filling pressure (LVFP) with both constant and increasing lung volume during an inspiratory effort. Transmural aortic diastolic pressure rises as LVSV falls and LVFP rises consistent with the hypothesis that a fall in pleural pressure afterloads the left ventricle. Additionally the increase found in right ventricular filling pressure with inspiration may adversely affect LV performance by decreasing LV compliance and/or contractility. Our findings are incompatible with pooling of blood in the lungs being the primary determinant of the fall in LVSV with inspiration.


Response of the iron-deficient erythrocyte in the rat to hyperoxia. Normal and iron-deficient rats were exposed to 90% O2 at 760 Torr for 24 or 48 h. Erythrocyte response to hyperoxia was monitored by potassium (rubidium) influx studies, by storage stress, and by ultrastructural studies. Normal rat erythrocytes exhibited morphological changes and decrease of ouabain-sensitive potassium influx compared to unexposed controls. Both components of erythrocyte potassium influx were affected by iron deficiency. Erythrocytes from unexposed iron-deficient rats showed a 50% increase in ouabain-sensitive potassium influx compared to controls. Iron-deficient rats exposed to hyperoxia for 24 or 48 h, had erythrocytes with morphological changes. Erythrocytes of iron-deficient rats exposed for 24 h showed no influx change; those exposed for 48 h showed a decrease of ouabain-sensitive influx compared to erythrocytes of controls.


Urinary catecholamine excretion in temporary residents of high altitude. Urinary catecholamine excretion was estimated in 50 lowlanders temporarily staying at altitudes above 3,000 m. They were divided in subgroups according to the length of their continuous stay. For comparison, 25 highlanders who were born and brought up at high altitude and 50 lowlanders who had never been to altitudes of more than 1,000 m were also studied. High catecholamine excretion was noted in temporary residents staying at high altitude for up to 30 days as compared to that in lowlanders (P greater than 0.01). The excretion rate gradually returned to basal values thereafter. Catecholamines were essentially similar in lowlanders and highlanders. The significance of these findings is discussed regarding the possible pathogenetic role of the sympathoadrenal system in the development of ill effects in respone to high-altitude exposure.


Relationship of central and peripheral airway resistance to lung volume in dogs. We could not reconcile reported relationships between lung resistance measurements and lung volume with bronchographic and anatomic studies showing that airway diameters change monotonically with lung volume and that small airways change diameter proportionately at least as much as large ones. Accordingly we measured central and peripheral airways resistances with a new technique. The relevant pressures were measured with a tracheal cannula, a wedged retrograde catheter, and two parenchymal needles in seven open-chested dogs while pleural pressure was oscillated at 1 Hz. In contrast to previous studies, the volume dependency of peripheral resistance was at least as great as that of central resistance with vagi intact, the volume dependencies of central and peripheral resistances were not abolished by vagotomy, and neither resistance increased systematically at high volumes. Volume dependency of central resistance resembled predictions for isotropic expansion of airways with vagi cut but increased with bronchomotor tone. These results fit generally with bronchographic data. Previous studies may have been affected by volume dependency due to "tissue resistance" and catheter phase lags.


Distribution of pulmonary responsiveness to aerosol histamine in dogs. Dose-response curves to aerosol histamine in 102 anesthetized, intubated, spontaneously breathing dogs revealed a spectrum of airway responsiveness with a greater than 40-fold difference between the most and the least sensitive animals. The frequency distribution of responses fits a log normal distribution. No correlation was found between sex, age, or control values of dynamic compliance (Cdyn) and lung resistance (RL) and the dose of histamine required to cause a response. Repetitive studies in 17 dogs observed for up to 20 mo showed that the dose at which an individual dog would respond was reproducible within a narrow range and that the differences between dogs were highly significant (P greater than 0.001). The long-term reproducibility of the response to aerosol histamine in individual dogs suggests that short-term reversible airway insults are not responsible for the range in responses noted between animals.


Rat as a model for humanlike ventilatory adaptation to chronic hypoxia. Oxygen uptake (VO2), expired volume (VE), and arterial blood gases were studied in awake, unrestrained rats over 14 days of hypobaric hypoxia (4,300 m altitude) and upon return to acute normoxia. Control data (at 250 m) showed (mean +/- 95% confidence limits (CL)) arterial oxygen pressure (Pao2) = 85.5 +/- 1.1; arterial carbon dioxide pressure (PaCO2) = 39.8 +/- 0.5; arterial pH pHa) = 7.430 +/- 0.009; VE = 78 +/- 3; VO2 = 2.36 +/- 0.09 ml.min-1.100 g-1; and dead space volumetidal volume ratio (VD/VT) = 0.37 +/- 0.04. During 14 days at 4.300 m the rat showed: a) a constant PaO2 (50-52 Torr); b) a time-dependent hyperventilation (e.g., PaCO2 = 30.2 +/- 1.1 at 1 h of hypoxia, 24.7 +/- 1.3 at day and 21.9 +/- 1.0 at 14 days); c) an increase in VE (85% of control) due to both frequency (33%) and VT (40%); d) a continued but reduced hyperventilation upon acute return to normoxia after 5 h to 14 days at 4,300 m; e) a 24% fall in VO2 after 1 h of hypoxia which returned to control by 4 days at 4,300 m; and f) a rise in pHa to 7.52 after 5 h of hypoxia, which fell to 7.45 by 14-day hypoxia. The rat's marked ventilatory response and changing VO2 during acute hypoxia clearly differs from the human response to sojourn at 4,300 m. However, the progressive and sustained hypocapnia during hypoxic exposure and the continued hyperventilation with acute normoxia in the rat provided essential, perhaps unique characteristics for an animal model of human ventilatory acclimatization.


Pulmonary tissue volume in dogs during pulmonary edema. Pulmonary tissue volume (Vt) and pulmonary capillary blood flow (Qc) were measured in anesthetized dogs by analyzing end-expiratory concentrations of dimethyl ether (DME), acetylene (C2H2), and sulfur hexafluoride during a 30-s rebreathing maneuver. Vt was compared to the postmortem lung weight of control dogs and dogs with hemodynamic and nonhemodynamic (alloxan) pulmonary edema. Qc was compared to the cardiac output measured by dye dilution. A 100-ml increase in alveolar volume (VA) in the range of 1-2 liters resulted in a 9 +/- 3 ml increase in Vt. Vt measured at a VA of 1.9 liters measures 114 +/- 18% of the postmortem lung weight in 20 control dogs and in 6 dogs with moderate edema (lung weight < 250% of predicted). Vt measured only 53 +/- 14% of the lung weight in 11 dogs with more severe edema. DME and C2H2 gave the smae mean values of Vt, but the reproducibility of a series of 3-7 measurements was greater with DME (coefficient of variation was 5% with DME and 8% C2H2). Qc measured 96 +/ 15% of the cardiac output during the rebreathing maneuver, but the maneuver caused a 4-40% fall in the cardiac output. These data show that Vt determined by rebreathing DME is between 86% and 135% of the lung weight in dogs with pulmonary edema until the lung weight is greater than 250% of the predicted value.


Aerosol transport in the human lung from analysis of single breaths. Experimental and theoretical results are presented for the single-breath inhalation of an aerosol with 0.5- and 1-micrometer particles of bis(2-ethylhexyl) sebacate droplets. Experimental results show that the recovery from the tidal volume decreases with increasing tidal volume and increases with increasing flow rate. The reserve volume recovery does not vary much with either flow rate or tidal volume. Experimental values for reserve volume recoveries for 1-micrometer particles were slightly larger than those for 0.5-micrometer particles, indicating intrinsic particle motion plays some role in the mixing process for larger particles. Calculated results from a convection-diffusion equation for the aerosol concentration are compared with the experimental results, with the aim of testing the hypotheses of the theoretical model. Detailed comparisons between theory and experiment for the exhalation profiles demonstrate that most of the mixing between the tidal and reserve volumes occurs in the alveolar region of the lung, as postulated in the model. Mechanical mixing in the upper airways plays a relatively minor role in the overall mixing process. Theoretical results for the recoveries show the same trends with tidal volume and flow rate as does experiment, and the agreement is good. Calculated values for the mixing of the tidal aerosol range from about 0.06 at a tidal volume of 400 cm3 to 0.23 at 2,000 cm3, and no variations with flow rate was found.


Effects of age, sex, and physical fitness on responses to local cooling. The response to local cooling was estimated by the cold hand test (5 degrees C for 2 min) and the cold face test (0 degrees C with 66 km.h-1 wind for 2 min). Heart rate, blood pressure, and skin temperature were measured before, during, and after the tests. The increase in blood pressure (cold hand test) and the fall in Tsk (cold face test) were reduced in trained subjects. Similarly older subjects (53-60 yr of age) responded less to a cold hand test than younger subjects aged 20-40. However, the bradycardia caused by the cold face test was more pronounced in the older subjects. The responses to the cold hand and cold face tests were the same for male and female subjects. During the 2 min after the test, blood pressure and heart rate fell below initial values in the female group but not in the male. It is concluded that, besides adaptation to cold, individual factors such as age, sex, and physical fitness also have a relative importance in the responses to local cooling.


Estimation of cardiac output by the CO2 rebreathing method during tethered swimming. The reproducibility of cardiac output (Q) estimated by the CO2 rebreathing method during tethered swimming was studied in five highly trained college swimmers. The reproducibility of the CO2 rebreathing method for estimations of Q during tethered swimming was similar to the reproducibility reported for the CO2 rebreathing method, direct Fick method, or dye-dilution method during either cycling or treadmill walking. All duplicate estimates of Q by the CO2 rebreathing method were within 15% of one another. A comparison was made between the Q's estimated by the CO2 rebreathing method during tethered swimming and previously published data on Q determined by the dye-dilution method during free swimming in a flune. At any given oxygen uptake, Q obtained by the CO2 rebreathing method during tethered swimming was not significantly different from the Q obtained by the dye-dilution method during flume swimming. Estimates of Q by the CO2 rebreathing method made during high intensities of tethered swimming were reproducible and appear to be valid.


Analysis of cerebrospinal fluid specific gravity. The specific gravity of 71 CSF samples from clinically normal dogs ranged from 1.004 to 1.006, with a mean of 1.005. A 3-year retrospective study of CSF samples obtained from 124 animals suspected of having neurologic disease revealed only 30 samples (24.2%) having a specific gravity greater than 1.006. Diagnostic or prognostic value from CSF specific gravity determination was not recognized.


Effects of atropine on cardiac rate and rhythm in dogs. Changes in cardiac rate and rhythm were determined in atropinized dogs prior to, during, and after anesthetic induction with thiamylal sodium and maintenance with 1% halothane in 50% nitrous oxide and 50% oxygen. The incidence of cardiac dysrhythmias and sinus tachycardia was significantly higher prior to and after anesthetic induction in dogs given atropine, compared with dogs not atropinized. Second-degree atrioventricular block was the most frequent dysrhythmia prior to anesthetic induction in atropinized dogs. Most cardiac dysrhythmias were detected during the anesthetic induction and early maintenance periods. The most common dysrhythmias during these periods were unifocal ventricular premature depolarizations and ventricular bigeminy.


Primary urethral tumors in dogs.

Primary urethral tumors in dogs. In a review of cases of neoplasia in dogs seen at The Animal Medical Center during a 6-year period, 20 cases of primary urethral tumors were found. The majority of these cases were in older dogs (av abe, 10.4 years) and females (18/20). The most common clinical signs were hematuria and stranguria. Nineteen of the 20 tumors were diagnosed clinically, and the most consistent and useful diagnostic method was pneumocystography-cystography, with voiding urethrography. Of the 5 tumor types (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma, hemangiosarcoma, and embryonic rhabdomyosarcoma), squamous cell carcinoma was the most common (12/20). Metastasis occurred in 6 of the 20 dogs. Because of metastasis to regional lymph nodes and diffuse extent of the tumor in the urethra in many of the dogs, a caudal abdominal approach for surgical excision is recommended if treatment is attempted.


Zygomatic salivary mucoceles in the dog. Zygomatic salivary mucoceles were diagnosed in 2 dogs. Ophthalmologic signs differed in both cases and reflected the position of the mucocele in relation to the orbit. Cytology of aspirated material and sialography were performed in both cases, but his enabled confirmation of the diagnosis in only one. Surgical excision of the zygomatic salivary gland, with drainage of the mucocele, was curative in both cases. Both dogs had a history of trauma to the head.


Osteomyelitis in the dog: a review of 67 cases. The clinicopathologic aspects of bacterial osteomyelitis in 67 dogs were compared. The femur, humerus, metacarpals, metatarsals, and phalanges were the bones most commonly affected. In most dogs, the infection was attributed to repair of fracture by open reduction. Staphylocuccus spp and Streptococcus spp were the organisms most frequently isolated. Most dogs had chronic osteomyelitis at the time of initial examination.


Development of the indusium griseum. III. An autoradiographic study of cell production. An autoradiographic study of neuronal and glial production was carried out in the indusium griseum of mice. Most neurons were produced between 13 and 15 days post-conception. One part of the glial population underwent its last or second-last divisions between 14 and 16 days post-conception, while the other continued to undergo a number of divisions into postnatal life. It is suggested the former were astrocytes and the latter oligodendrocytes.


The permeability of a keratinizing squamous epithelium in culture. Horseradish peroxidase or lanthanum was applied to the surface of keratinized oral epithelium growing in tissue culture and the extent of penetration of these substances examined with the electron microscope. Both tracer substances penetrated between the superficial keratinized squames of the tissue, the lanthanum reaching the basal cell layer and the peroxidase diffusing to within 3--8 cells of the basal layer. The permeability of the keratinized layer in this epithelium is in contrast to the situation in vivo where an intercellular barrier is found in the superficial layer. This difference might be related to the absence of membrane-coating granules from the tissue maintained in culture.


Electron microscopic studies of macrophages in Wallerian degeneration of rat optic nerve after intravenous injection of colloidal carbon. The origin of macrophages in the degenerating optic nerve of rats after eye enucleation was investigated electron microscopically following intravenous labelling of mononuclear leucoytes with colloidal carbon. In the various post-operative periods studied carbon-labelled macrophages were seen at the site of lesion. At 4 and 7 days after enucleation carbon-labelled cells were seen at the site of Wallerian degeneration of the optic nerve over 4 mm distal to the site of the lesion. In the electron microscope these cells showed a flattened nucleus bearing coarse chromatin clumps, their cytoplasm contained a prominent Golgi complex and long isolate profiles of rough endoplasmic reticulum. Clusters of carbon particles in the cytoplasms were membrane-bound. Lysosomal bodies embedded with carbon particles were also observed. In relation to the blood vessels of the optic nerve, endothelial cells and pericytes with ingested carbon were seen. Macrophages in the meninges covering the optic nerve were also labelled. The results suggest that some macrophages in the region of Wallerian degeneration in the optic nerve, as well as those at the actual site of the lesion, were transformed blood leucocytes.


The epithelial innervation of the lower respiratory tract of the cat. A quantitative ultrastructural study of intra-epithelial axons in the lower respiratory tract of the cat has compared the innervation at four airway levels, two extra- and two intrapulmonary. The morphology of intra-epithelial axons has been described, and their association with different epithelial cell types recorded. Their morphology suggests that most are afferent in function.


Cell specialization in the epithelium of the small intestine of feeding Xenopus laevis tadpoles. The intestinal epithelium of feeding Xenopus laevis tadpoles was studied using light microscope, electron microscope and autoradiographic techniques. The wall of the small intestine differs from that of most other vertebrates studied in that it lacks villous-like folds. A single prominent longitudinal fold, the typhlosole, forms about stage 49, and a series of shallow longitudinal epithelial pleats is also present in some animals. The morphology of the epithelial cells indicates that there are no differences between the cells in their degree of specialization. Three epithelial cell types were recognized: principal cells, gland cells and endocrine cells, making up about 65%, 15% and 1%, respectively, of all cells present, while approximately 20% of the cells in the epithelium are lymphocytes, 1% appear to be discharged gland cells, and 2% degenerating cells. No Paneth, caveolated or undifferentiated cells were identified. The findings are discussed in relation to other studies on cell proliferation and on nuclear transplantation.


The thickness of the cartilage in the hip joint. The pattern of distribution of cartilage thickness in corresponding femoral heads and acetabula was ascertained in ten hip joints. The differences between individual acetabula and their corresponding heads were small enough for it to be admissible to calculate an average distribution pattern for head and socket. Comparison of these patterns showed that: (a) The maximum thickness is found at points in the ventrocranial area of the acetabulum and ventrolateral area of the head. (b) From these points the cartilage thickness decreases concentrically. (c) In the 'natural position' of the hip joint the points of maximum thickness of head and acetabular cartilage do not correspond. In relation to the line of the hip joint 'force resultant', the area with the thickest cartilage on the head is slightly shifted towards its medial side, and on the socket slightly to the lateral side. It is not possible fully to explain these results on the basis of existing conceptions about the functional stressing of the hip joint.


An autoradiographic study of the afferent innervation of the trachea, syrinx and extrapulmonary primary bronchus of Gallus gallus domesticus. A method for injecting a small quantity of tritiated leucine directly into the nodose ganglion of the adult hen is described. The presence of an inner and an outer nerve plexus in the trachea and extrapulmonary primary bronchus is confirmed. Structures in the luminal epithelium of the trachea, syrinx and extrapulmonary primary bronchus having an afferent innervation are described and their possible function is discussed. The question of positive chemography in autoradiographic studies is discussed.


Ultrastructure of parathyroid glands in triamcinolone-treated mice. 6 weeks old ICR strain mice were given 21 daily injections of the synthetic glucocorticoid, triamcinolone diacetate (8 mg/kg body weight) and their parathyroid glands were examined by light and electron microscopy and compared with untreated litter-mate controls. Parathyroid glands are composed of a single basic cell type, but some cells are electron-dense ('dark' cells) and some less dense ('light' cells). There is considerable variability in numbers of light and dark cells from gland to gland. Following triamcinolone treatment the cells are arranged more in whorls, and there is a relative increase in the numbers of 'light' cells, which become more elongated, with pronounced nucleoli, and develop in many cases marked cytoplamsic vacuolation. Some cells show accumulations of lipid droplets. Interdigitations between adjacent cells become more complex, and the numbers of atrophic cells increase. The significance of the various cell conditions is considered. The ultrastructural appearances suggest that parathyroid gland cellular activity is stimulated in response to the drug-induced hypercorticoidism, but no overall glandular hypertrophy is found.


Effects of dark rearing on dendritic spines in layer IV of the mouse visual cortex. A quantitative electron microscopical study. The effect of visual deprivation on dendritic spines in the visual cortex layer IV of 19 days old mice was studied with the electron microscopy. From the serial ultrathin sections of the selected dendrites bearing spines the author has calculated the volume and surface area of dendritic spines, and also the surface area of their synaptic zones. Employing statistical methods he has demonstrated that visual deprivation produced a retarded development of some dendritic spines in dark reared mice. The fact that the smallest dendritic spines cannot be seen with the light microscope while the number of such small spines is larger in the dark reared mice can well explain the apparent reduction in the number of dendritic spines in deprived animals studied in Golgi impregnated material.


On the calibre of the ureteric lumen.

On the calibre of the ureteric lumen. The cross sectional appearances of the lumen of rat ureter were compared in specimens fixed by perfusion and by immersion and processed for electron microscopy. After efficient perfusion fixation in untreated animals, and in animals previously injected with 6-hydroxydopamine, there was substantial dilatation of the ureter, and the lumen was approximately circular in section. In inadequately perfused and immersion-fixed material the lumen was usually narrowed, and was either slit-like or stellate in appearance. Ultrastructural examination indicated that closure of the lumen was accompanied by the development in the cells of the muscle coat of the features usually associated with contraction, and the possibility that the appearance of the ureter in well perfused specimens approximated to its state in vivo was discussed.


A collagen and elastic network in the wing of the bat. Bundles of collagen fibrils, elastic fibres and fibroblasts are organized into a network that lies in the plane of a large portion of the bat wing. By ultrastructural (TEM and SEM) and biochemical analyses it was found that individual bundles of the net are similar to elastic ligaments. Although elastic fibres predominate, they are integrated and aligned in parallel with small bundles of collagen. A reticulum of fibroblasts, joined by focal junctions, forms a cellular framework throughout each bundle. Because of the unique features of the fibre bundles of the bat's wing, in particular their accessibility, and the parallel alignment of the collagen fibrils and elastic fibres in each easily isolatable fibre bundle, they should prove a most valuable model for connective tissue studies, particularly for the study of collagen-elastin interactions.


The comparative anatomy of the blood supply of cardiac ventricles in the albino rat and guinea-pig. The hearts of 118 albino rats and 80 guinea-pigs were investigated by angiography. It was found that the blood supply to the cardiac ventricles of the rat is a coronary balanced circulation similar to that frequently met with in man. On the other hand, the distribution of the coronary arteries in the guinea-pig showed a definite left coronary preponderance to an extent never seen in man.


An electron microscopic study of the adductor externus superficialis muscle associated with the venom gland of the cobra (Naja naja). The adductor externus superficialis muscle closely envelops the venom gland in the cobra (Naja naja). Only twitch fibres are present in the muscle, supporting the view that the muscle is concerned with the rapid evacuation of venom. 'Satellite' cells are readily observed in relation to the muscle fibres.


A histological study of post mortem changes in the skeletal muscle of the fowl (Gallus domesticus). II. The cytoarchitecture. Changes in the histology of skeletal muscle at an ultrastructural level have been studied in the pectoralis thoracica and iliotibialis muscles of the fowl (Gallus domesticus). The carcasses were stored at 40 degrees C and samples removed at various times post mortem. The Z discs and I bands degenerate rapidly (less than 4 hours) but the thick filaments of the A band are remarkably resistant to change (greater than 24 hours). The sarcolemma, mitochondria, glycogen content, sarcotubular system and myonuclei also show marked changes in less than 4 hours. Myelin figures and autophagic vacuoles are among other features seen in post mortem tissue. There are more degenerate mitochondria and vesicular remnants of the sarcotubular system in the iliotibialis than in the pectoralis muscle, but this reflects a differing concentration of these organelles in vivo. No other consistent difference in the post mortem histology of these muscles has been observed.


The normal human appendix: a light and electron microscopic study. Human appendices from 3 to 12 years old children were studied by light and electron microscopy. Three morphological zones were determined: sub-epithelial (or lymphoid lamina propria), parafollicular, and follicular. The fine structure of these regions has been studied and discussed with regard to the thymus-dependent and thymus-independent regions of other lymphoid organs. Two types of lymphocytes, 'light' and 'dark', and intermediate forms, were also found. The light ones are the more abundant in the epithelium and within the parafollicular post-capillary venules; they form groups or clusters between epithelial cells, becoming like blast cells and possibly maturing into plasma cells in the sub-epithelial region. Whether light lymphocytes are T or B or both is discussed. The general conclusion is that the human appendix, at least in children, has the characteristics of a well-developed lymphoid organ, suggesting that it has important immunological functions.


Antimetabolites produced by microorganisms XVI. Synthesis of N5-hydroxy-2-methylarginine and N5-hydroxy-2-methylornithine. N5-Hydroxy-2-methylornithine and N5-hydroxy-2-methylarginine were synthesized. 2-Amino-5-hydroxy-2-methylpentanoic acid was prepared from 5-hydroxy-2-pentanone and converted to N-(tetrahydro-3-methyl-2-oxo-2H-pyran-3-yl) acetamide which was treated with hydrogen bromide affording 2-(acetylamino)-5-bromo-2-methylpentanoic acid. This acid was esterified with methanol and used to alkylate anti-benzaldoxime yielding methyl 2-(acetylamino)-2-methyl-5-[(phenylmethylene)amino]-pentanoate N5-oxide which, upon hydrolysis, yielded N5-hydroxy-2-methylornithine, and, upon aminolysis and short acid-treatment, gave N2-acetyl-N5-hydroxy-2-methylornithinamide. Carbamimidoylation and hydrolysis of the latter compound furnished N5-hydroxy-2-methylarginine.


Teichomycins, new antibiotics from Actinoplanes teichomyceticus nov. sp. II. Extraction and chemical characterization. The teichomycins are new antibiotics produced by Actinoplanes teichomyceticus nov. sp. Teichomycin A1 is a phosphorus-containing antibiotic, active in vitro and in vivo against gram-positive bacteria, and active only in vitro against gram-negative bacteria. Teichomycin A2 is a chlorine-containing antibiotic, active in vitro and in vivo against gram-positive bacteria. Isolation, purification and physical and chemical properties of the two antibiotics are reported. Teichomycin A1 is a member of the phosphoglycolipid class of antibiotics while teichomycin A2 is related to the group of the glycopeptide antibiotics.


Preparation and biological evaluation of 4-O-demethyldaunorubicin (carminomycin I) and of its 13-dihydro derivative. A mutant strain of Streptomyces peucetius produced an anthracycline antibiotic whose structure has been established to be 4-O-demethyl-13-dihydrodaunorubicin (4), by application of spectroscopic methods and chemical degradation. A new synthesis of 4-O-demethyl-daunorubicin (carminomycin I, 2) starting from daunomycinone, together with the comparison of the antitumor activity of the anthracycline glycosides 2 and 4 are also reported.


Incorporation of 14C-labeled compounds into sinefungin (A9145), a nucleoside antifungal antibiotic. Streptomyces griseolus produces a complex of antifungal nucleoside antibiotics that contain an ornithine residue linked to the ribose moiety of adenosine. 14C-Labeled compounds were added to cultures of S. griseolus (approximately 0.5 muCi/ml culture broth) and the amount of label incorporated into the two major antifungal components (sinefungin and factor C) was measured. Substantial incorporation (16 approximately 52%) was obtained with adenosine [8-14C], ATP [14C(u)], adenine [8-14C], L-ornithine [14C(u)], and DL-citrulline [5-14C]. Glycine glucose L-arginine, and acetate were incorporated to the extent of 1.7 approximately 4.7%. Studies were conducted on the fermentation time course and on the time dependence of label incorporation in order to optimize the incorporation of labeled adenine into sinefungin. Adenine [8-14C] incorporation and sinefungin specific activity were highest 48 hours after label addition and both declined during subsequent incubation. As much as 43% of the labeled adenine was incorporated into the antibiotic and sinefungin was produced with a specific activity of 24.8 muCi/mg. The labeling experiments suggest that a performed adenine derivative (e.g., an adenine nucleotide) and ornithine (or a closely related metabolite) are direct biosynthetic precursors of sinefungin.


A genetic approach to the biosynthesis of the rifamycin-chromophore in Nocardia mediterranei. I. Isolation and characterization of a pentose-excreting auxotrophic mutant of Nocardia mediterranei with drastically reduced rifamycin production. The mutant under study, designated A8, is derived from a Nocardia mediterranei strain, N813, which is a high rifamycin B producer. A8 is auxotrophic for aromatic amino acids and produces much less rifamycin B than the parent. A mixture of pentoses with D (--) ribulose as the main product is accumulated in the fermentation broth of this mutant. It was shown to be affected in its transketolase activity as no formation of D-sedoheptulose -7P from pentose-phosphates could be detected in vitro using crude extracts. The only pathway so far known which is derived from D-sedoheptulose-7P is the shikimate pathway leading to aromatic amino acids and vitamins. Biochemical and genetic investigations with mutant A8, which is defective in both the biosynthesis of rifamycins and the biosynthesis of shikimate pathway products, show that the seven-carbon amino unit of the rifamycin-chromophore must be derived from an intermediate of the shikimate pathway.


A genetic approach to the biosynthesis of the rifamycin-chromophore in Nocardia mediterranei. II. Isolation and characterization of a shikimate excreting auxotrophic mutant of Nocardia mediterranei with normal rifamycin-production. The mutant under study, designated A10, is derived from a Nocardia mediterranei strain, N813, which is a high rifamycin B producer. A10 is auxotrophic for aromatic amino acids but unlike A8 (see preceding paper) produces the same amount of rifamycin B as the parent. Shikimic acid and 3-dehydroshikimic acid are accumulated in the fermentation broth of this mutant. It was shown to be blocked in one of the enzymes leading from shikimate to chorismate. No formation of shikimate-3-phosphate from shikimate and ATP could be detected in vitro using crude extracts of this mutant and of the parent. As mutant A10 is only defective in the biosynthesis of aromatic amino acids and not in the biosynthesis of rifamycins it would appear that the seven-carbon amino unit of the rifamycin-chromophore must be derived from an intermediate of the shikimate pathway not behind shikimate. By referring to the results of the preceding paper it can be seen that the origin of this moiety can definitely be localized between 3-deoxy-D-arabinoheptulosonic acid-7-phosphate and shikimate.


Behavioral control of medicine compliance. This study examined the effectiveness of several behavioral techniques on compliance of college students taking vitamin C on q.i.d. regimen. Compliance was assessed by a new technique using a variation of the urine tracer procedure designed specifically for this study. Subjects were provided vitamin C tablets, with three tablets per week containing phenazopyridine, a drug that produces a bright red-orange urine discoloration. Subjects were requested to indicate when urine discolorations occurred, and compliance was assessed by comparing the time of their report to the time predicted on the basis of the scheduled sequence of vitamin C and phenazopyridine tablets. Baseline compliance was assessed for 72 subjects over a three-week period, with the 40 most noncompliant subjects randomly assigned to four groups for Treatment I. The groups were: self-monitoring, taste, taste and self-monitoring, and a no-treatment control group. The self-monitoring procedure involved recording the time medicine was taken; the taste procedure involved providing the subjects with flavored tablets to increase the saliency of tablet taking; and the self-monitoring and taste procedure involved providing subjects with flavored tablets and asking them to record the flavor of each tablet they ingested. At the end of six weeks, half the subjects in each of these groups participated in response-cost procedures while the remaining subjects continued with their previous procedures. Response-cost procedures were implemented by returning a portion of the subjects' deposit only if a preset compliance criterion was met. Treatment II procedures were implemented for an additional three weeks. Results indicated the self-monitoring and taste plus self-monitoring procedures were superior during Treatment I. The implementation of response cost during Treatment II was associated with a marked improvement in compliance, independent of the history of noncompliance. The effects of the taste plus self-monitoring procedure were maintained during Treatment II and results obtained by this procedure were not significantly different from effects of response cost.


The timeout ribbon: a nonexclusionary timeout procedure. Recently, the use of timeout rooms has been questioned by various agencies, and some have adopted policies that prohibit or greatly restrict exclusionary timeout. The present study developed a timeout procedure that did not require removal of the misbehaver from the learning environment. The procedure was applied to the disruptive behaviors of five severely retarded children in an institutional special-education classroom. An observer prompted all teacher behaviors related to the procedures to assure their precise implementation. After baseline, a reinforcement-only condition was implemented. Each child was given a different colored ribbon to wear as a tie and received edibles and praise every few minutes for good behavior and for wearing the ribbon. When timeout was added, a child's ribbon was removed for any instance of misbehavior and teacher attention and participation in activities ceased for three minutes or until the misbehavior stopped. Reinforcement continued at other times for appropriate behavior. An ABCBC reversal design was used to demonstrate control of the behavior by the conditions applied. On average, the children misbehaved 42% and 32% of the time during the baseline and reinforcement conditions respectively but only 6% of the time during the timeout conditions. A followup probe during the new school year revealed that the teacher was able to conduct the procedure independently and that the children's disruptive behaviors were maintained at low levels. The practicality and acceptability of the procedure were supported further by the successful implementation of the procedure by a teacher in another state and by responses to a questionnaire given to 40 mental health professionals. The ribbon procedure appears to be a viable form of timeout, provided that disruptive behaviors during timeout can be tolerated within the setting, or a backup procedure such as exclusionary timeout can be tolerated within the setting, or a backup procedure such as exclusionary timeout is available when needed.


Modification of activity level through biofeedback and operant conditioning. The biomotometer, an electronic device that simultaneously measures activity and provides auditory feedback to the subject, was used in combination with material reinforcers in two experiments attempting to modify activity level in children. In the first study the activity level of an 11-year-old highly active boy was decreased below mean baseline during conditioning in a classroom setting. His level of activity returned to baseline when feedback was withdrawn. In the second study, activity level of a 10-year-old hypoactive boy was increased over mean baseline level during conditioning in a free-play setting, and returned to slightly below baseline during five extinction trials. Results of these studies indicate that the biomotometer is a useful instrument for modification of activity level.


The validation of procedures to assess prevocational task preferences in retarded adults. Three severely retarded young adults between the ages of 19 and 21 years participated in a prevocational training program, and worked regularly on six different tasks during the scheduled six-hour day. The study attempted to assess each subject's preferences for the six tasks: collating, stuffing, sorting, pulley assembly, flour-sifter assembly, and circuit-board stuffing. In Phase I, the procedure consisted of randomly pairing each task with all other tasks in a two-choice situation that required the subjects to select one task from each pair combination to work for a seven-minute period. The selection procedure consisted of presenting two representative task objects on a tray and requesting the subject to pick up one object and place it on the work table. The object selected represented the task worked for that period. The 15 possible pair combinations were presented randomly every two days for a period of 34 days to determine the preferences. During the validation phase (Phase II), each subject's least- and most-preferred tasks were paired separately with moderately-preferred tasks. As expected, these manipulations confirmed the baseline data, as choices for the moderately-preferred tasks decreased when consistently paired with the preferred tasks and increased when consistently paired with the least-preferred tasks.


Behaviorism: part of the problem or part of the solution. The form frequently taken by behavior-modification programs is analyzed in terms of the parent science, Behaviorism. Whereas Behaviorism assumes that behavior is the result of contingencies, and that lasting behavior change involves changing the contingencies that give rise to and support the behavior, most behavior-modification programs merely arrange special contingencies in a special environment to eliminate the "problem" behavior. Even when the problem behavior is as widespread as alcoholism and crime, behavior modifiers focus on "fixing" the alcoholic and the criminal, not on changing the societal contingencies that prevail outside the therapeutic environment and continue to produce alcoholics and criminals. The contingencies that shape this method of dealing with behavioral problems are also analyzed, and this analysis leads to a criticism of the current social structure as a behavior control system. Although applied behaviorists have frequently focused on fixing individuals, the science of Behaviorism provides the means to analyze the structures, the system, and the forms of societal control that produce the "problems".