A study of family practice in Wisconsin. Studies of family practice in Wisconsin and elsewhere show that the clinical content of family practice has about 20 to 45 patient contacts per day and about two to six diagnoses per patient contact. Seventy-five percent of patient contacts are in the office and on the telephone, 15 to 20 percent in the hospital, and 5 to 10 percent elsewhere. There is a broad array of patient problems. Special Conditions and Examinations Without Illness contain the largest number of patient problems. About 60 percent of patients are female and present more endocrine and genitourinary problems. Men present more trauma, circulatory, and respiratory problems, and less health maintenance care. Well-baby and well-child examinations stop at age 15 years. Pre and postnatal care decline sharply at age 35 years, at which time surgical care increases. Infectious disease and trauma, ranking high in the young, are low in the elderly. Circulatory problems, obesity, diabetes, and arthritis increase greatly with age. There is no major difference in type of patient problems related to town size (ie, population). However, comparative studies may uncover different disease occurrence rates between regions.


Patient expectation: what is comprehensive health care? A patient expectation survey was developed and implemented in order to define the spectrum of health care activities expected from the University of Nebraska Family Health Centers. The hypothesis underlying the survey is that patient expectations or opinions vary considerably among the members of any given population. High expectation is present for office visits, emergency services, yearly physical examination, and performance of chest x-ray, blood test, proctoscopy, and eye examination. Psychiatric services, marital counseling, youth counseling, nursing home care, and health education are indicated as not necessary by a plurality of the respondents. Examination of the responses by age, sex, and payment status through canonical correlation reveals a number of strong correlations of specific subgroups and expectations. Factor analysis revealed three independent factors or clusters representating health care issues as perceived by the patient. This study and further similar studies will be helpful in aiding the family physician's understanding of what patients expect. Through a better understanding of patient expectation, patient satisfaction and compliance may be improved.


Electrodesiccation and fulguration of lesions of the skin. Electrosurgery--electrodesiccation, fulguration, and electrocoagulation--is a simple and relatively inexpensive modality for treatment of small skin lesions, whether benign or malignant. The technique is easily mastered, and the results, with proper selection of patients, compare favorably with the results of scalpel-and-suture surgery. Electrosurgery does not mean "burning off" lesions and biopsy of the lesion is an integral part of the technique.


Ophthalmia neonatorum due to Chlamydia trachomatis: a family problem? The most frequently seen type of infectious ophthalmia neonatorum, inclusion conjunctivitis, is caused by the organism Chlamydia trachomatis. This agent is known to be transmitted sexually. Until recently, the infections produced by C trachomatis were though to be relatively benign. Recent evidence, however, suggests that the organism may produce urethritis and epididymitis in the male; cervicitis, cervical erosions, salpingitis, and puerperal infections in the female; and prematurity and pneumonitis in the infant. An infant who develops ophthalmia neonatorum should be thoroughly evaluated for the presence of a chlamydial infection. In many instances the first evidence of chlamydial infection within the parents will be the development of inclusion conjunctivitis in their newborn infant. Family members of infants with inclusion conjunctivitis who manifest any evidence of clinical disease should be evaluated and treated with appropriate antibiotics.


Complications associated with IUD use in a family practice setting. This study compares the complication rate of intrauterine contraceptive devices (IUD) with other contraceptive measures in a residency practice. The study population included 220 randomly selected women who had IUDs inserted by residents over a five-year period. One hundred similarly selected women started on birth control pills (BCP) were used as a control group. Of the IUD patients, 8.6 percent developed pelvic inflammatory disease vs 2 percent of the BCP patients. The incidence of gonorrhea was not significantly different between the two groups: 8.2 percent for the IUD groups vs 7 percent for the BCP group. Discontinuation of IUDs for reasons other than desiring pregnancy was significantly higher than discontinuation of BCPs: 41 percent vs 12 percent. Of the total IUD insertions, there were 21 expulsions (10 percent) and one uterine perforation (0.4 percent). Five pregnancies occurred in the IUD group, yielding a pregnancy rate of 1.7 per 100 women-years. There was a four percent rate of gynecologic hospitalizations in the IUD group as contrasted with one percent rate in BCP group. IUD use in the family practice setting under study is associated with comparatively poor long-term acceptance and a relatively high rate of complications.


An approach to the adolescent for the primary care clinician. The clinician should take into account all development aspects when evaluating the adolescent patient. Adolescents will frequently present underlying concerns in an indirect manner, as "functional" complaints, excessive concerns over minor ailments, or nonverbal cues. The clinician should relate to the adolescent patient in a direct, interested, and sincere manner aimed at developing mutual respect and trust. Confidentiality of visits should be extended. Physical examination of adolescents should be performed with sensitivity and awareness of areas of concern. The primary care clinician can provide comprehensive physical and emotional health care to most adolescents.


A model for communication skills development for family practice residents. The purpose of this paper is twofold: (1) to demonstrate the need for including interpersonal communication skills training in family practice residency programs, and (2) to present a communication model that can be used for such training. Interpersonal communication skills are important in almost all areas of contact with patients: history taking, physical examination, prescription writing and patient education, counseling, and psychotherapy. Presentation of the communication model includes definition of the interpersonal communication skills that would be stressed in family practice residency programs. These skills include empathy, respect, warmth, concreteness, genuineness, self-disclosure, confrontation, immediacy, and behavior modification. Examples of how a family physician may communicate each of these skills are also included. The implementation of the communication model in a department of family practice for training residents and faculty in the use of these communication skills is also described.


Geriatric training in family medicine: the natural history of a developing program. During the past three years, the Duke-Watts Family Medicine Program and the Duke University Center for the Study of Aging and Human Development have developed training in geriatric medicine as an integral part of the family medicine residency program. This paper traces the following steps in the development of this program: a survey of resident and faculty interest, institution of a conference series, identification of potential training sites, development of elective rotations, and use of consultants. Principles found helpful in establishing training in geriatrics for family medicine residents include the following: involve residents in planning, start with modest goals, make the program relevant and practical, build on local strengths, include other health care professional trainees, and use ambulatory, acute hospital, and long-term care sites in the training rpogram.


The effect of a course in family medicine on future career choice: a long-range follow-up of a controlled experiment in medical education. The career choices and professional behavior of three cohorts of students who participated in a family medicine program were studied by mail questionnaire. Cohort I (1957--1960), as part of an educational experiment, had been randomly assigned to the course; unselected classmates were used as controls. Cohort II (1961--1965) and Cohort III (1966--1970) were volunteers; alphabetically adjacent classmates were used as a comparison group. The results suggest that the impact of a given medical school course on future behavior must be evaluated in the context of general medical school orientation and societal trends extraneous to the school itself.


Family practice residents' perceptions of behavioral science training, relevance, and needs. Fifty-six family practice residents representing programs in 23 different states were surveyed concerning their training experience in behavioral science. Questions covered three basic areas of concern: experiential content, subsequent relevance to family practice, and suggestions for curriculum improvement at the residency level. The results point out definite knowledge of medical psychology, psychiatric consultation to medical patients, and practical intervention skills. Suggestions are made concerning curriculum development in behavioral science which (1) emphasize some new areas of concern raised by the residents, (2) recommend a more practical, integrated approach beginning in the medical school training, and (3) emphasize a dual approach requiring skills in medical psychology and skills more traditionally subsumed under the "mental health" field.


Antigenicity and polypeptide composition of native and heated echovirus type 7 procapsids. The native procapsid (naturally occurring empty capsid) of echovirus type 7 (E7) possesses N-antigenicity, which is as highly strain-specific as the native virion. When the native procapsid is heated, its antigenicity is converted to H-antigenicity which is common among strains of E7 and thus type-specific. However, no difference was detected in the sedimentation rate (80S) and polypeptide composition (VP0, 1 and 3) of the native and heated procapsids.


The matrix protein gene determines amantadine-sensitivity of influenza viruses. The genetic composition of several recombinant strains, produced by mixed infection with an amantadine-sensitive and an amantadine-resistant influenza virus, have been compared with their response to amantadine. It is concluded that transfer of resistance or sensitivity to amantadine is determined by a single gene, that coding for the matrix protein.


Further studies on rabies postexposure prophylaxis in mice: a comparison of vaccine with interferon and vaccine. Mice were inoculated in the left hind footpad with street rabies virus, and 24 h later various types of rabies vaccine were administered intramuscularly in the right leg. The vaccines alone were ineffective in reducing mortality, but when an interferon inducer, polyriboinosinic acid-polyribocytidylic acid complexed to poly-L-lysine (polyICLC), was given along with the vaccines, a marked reduction resulted. The polyICLC-vaccine combination was effective even when it was injected 5 days after infection, suggesting that effective postexposure treatment in man might be successful when given at a comparable late time.


De novo synthesis of two classes of DNA induced by vaccinia virus infection of HeLa cells. Equilibrium density gradient centrifugation in CsCl confirms that DNA synthesized after vaccinia virus infection of HeLa cells is homogeneous in buoyant density and thus in base composition and is similar in this respect to bulk HeLa cell DNA. In contrast, rate sedimentation in alkaline sucrose gradients distinguishes two main classes of virus-induced DNA, neither of which can be equated with cell DNA synthesized in the same cultures prior to infection. The slower sedimenting class of virus-induced DNA co-sediments with DNA from purified virus particles: the second class sediments faster than pre-labelled cell DNA. Heterogeneity of virus-induced DNA does not result from fragmentation of radioactively labelled DNA, virus-mediated breakdown of cell DNA or association with either proteins or polyamines. Both slow and fast sedimenting classes of virus-induced DNA contain sequences complementary to all restriction endonuclease Hind III-specific fragments of the virus genome. The multiple species of DNA synthesized after infection are distinguished further by the effect of ethidium bromide. At a concentration which prevents the formation of infectious progeny virus, this compound inhibits selectively the de novo synthesis of that class of virus-induced DNA which sediments faster in alkaline sucrose gradients.


Structural polypeptides of the murine coronavirus JHM. Analysis by SDS-polyacrylamide gel electrophoresis shows that the purified coronavirus JHM contains six polypeptides. The apparent mol. wt. of the polypeptides (GP1, GP2, GP3, VP4, GP5 and VP6) are 170000; 125000; 97500; 60800; 24800 and 22700, respectively. Four polypeptides are glycosylated (GP1, GP2, GP3 and GP5). The analysis of particles obtained after limited proteolysis with pronase suggests that GP2 and GP3 are protruding from the lipid envelope and, together with GP1, form the spike layer. Protein VP6 and a part of GP5 are located within the lipid bilayer. Protein VP4 is susceptible to digestion at a concentration of pronase which changes the morphology of the virus particles making the interior of the virus accessible. Subviral particles produced after treatment with the detergent Nonidet P40 banded at a higher density than the virus and contained only VP4, GP5 and VP6.


Biosynthesis of the influenza virus envelope in abortive infection. Synthesis and processing of the envelope proteins of influenza A virus (fowl plague virus) have been analysed in BHK, HeLa and L cells, in which the virus undergoes abortive replication and does not form virus particles, and in the productive chick embryo fibroblast system. In abortive infection, synthesis of the M protein is specifically inhibited. The extent of this defect varies depending on the host cell and the amount of virus particles formed closely reflects the amount of M synthesized. Cell fractionation experiments demonstrated that the haemagglutinin glycoprotein HA is synthesized in abortive as well as in productive cells at the rough endoplasmic reticulum, that it migrates via smooth internal membranes to the plasma membrane and that it is cleaved by proteolysis into fragments HA1 and HA2 in the course of migration. Immune electron  microscopy using monospecific antibodies against haemagglutinin and neuraminidase showed that both glycoproteins are exposed at the cell surface. Thus, synthesis and processing of the virus glycoproteins does not depend on the formation of the M protein. However, the M protein appears to be necessary for budding and thus for particle formation.


The effects of noise on telephone operators. 1. One hundred twenty-nine telephone operators were given audiograms before work and again after four hours of work exposure. Since these operators habitually use the same ear for their monaural headset, the non-listening ear served as a yoked control in examining work related effects on hearing. The hearing threshold measurements conducted on the operators in this study disclosed no statistically significant shifts in mean threshold indicating no population effect for either short-term or long-term work exposure. 2. Two thousand random hours of magnetic tape recordings of operator positions disclosed the occurrence of 36 spurious signals of 94 dB SPL or above lasting from 0.4 to 145 seconds. The maximum amplitude recorded was 109 dB SPL. These tones occurred at a rate of about one per week per operator position. 3. On 36 operators reporting 51 incidents of acoustic disturbance, audiograms were obtained about 15 minutes and again at least 16 hours following the acoustic disturbance. No significant objective effects on hearing thresholds were identified.


Occupational mental health: its monitoring, protection and promotion. Work should respect the worker's life and health, leave him free time for rest and leisure, and enable him to serve society and achieve self-fulfillment by developing his personal capacities. This is not what work looks like to hundreds of millions of workers all over the world. Occupational stress arises where discrepancies exist between occupational demands and opportunities on the one hand and the worker's capacities, needs and expectations on the other. Ill effects are mediated by three classes of mechanisms: (1) feelings of distress (e.g., anxiety, depression, alienation, etc); (2) behaviors (e.g., increase in alcohol and tobacco consumption, risk taking, self-destructive behavior, etc.); and (3) hyper-, hypo- and dysfunction in various organs and organ systems (e.g., physiological stress reactions as described by Selye; specific changes in endocrine and immunological function, etc.). These effects are common and they are a challenge to occupational medicine. Work environments are man-made and can be adapted by man for man. Local, national and international monitoring of occupational health should be aimed at making work man's servant and not his master.


Studies on occupational health problems during agricultural operation of Indian tobacco workers: a preliminary survey report. Occupational sickness among tobacco farmers due to the handling of green tobacco leaves is termed "green symptom." This symptom was investigated among 197 Indian tobacco workers and it was found that 88.83% of the workers were suffering from green symptom when exposed to green tobacco leaves during their occupational operation. Nicotine concentration of the urine was estimated only among male subjects who were smokers. During the exposure period (when subjects were suffering from green symptom), more than a three-fold increase in nicotine concentration in the urine was observed. Both cured and uncured leaves may cause such sickness.


The effect of phenobarbital pretreatment on the antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl-1-nitrosourea (PCNU), and on the plasma pharmacokinetics and biotransformation of BCNU. Many patients being treated for primary and secondary brain tumors receive phenobarbital as an anticonvulsant. The effects of chronic oral administration of phenobarbital on the antitumor activity of BCNU, CCNU and PCNU against the intracerebral 9L tumor in rats were determined. Phenobarbital pretreatment eliminated the antitumor activity of BCNU and reduced the activity of PCNU and CCNU. Pretreatment with phenytoin, sodium methylprednisolone succinate and dexamethasone had little or no effect. Pharmacokinetic data for i.v. BCNU in the plasma of rats showed an increase in drug clearance for phenobarbital pretreated animals, compared to a control group. Larger differences were observed when BCNU was given i.p. The half-life of BCNU in sera from pretreated and control group rats was similar. Finally, the in vitro rate of BCNU disappearance in 9000 X g supernatants and microsomes from the livers of pretreated rats was 5-fold faster than the rate of disappearance of BCNU in supernatants from normal animals. We conclude that the chronic oral administration of phenobarbital induces a change in liver enzymes, which accelerates the clearance of BCNU, thereby reducing the antitumor activity of BCNU and the other nitrosoureas. Phenobarbital pretreatment reduces systemic BCNU toxicity.


Methadone during pregnancy: assessment of behavioral effects in the rat offspring. Pregnant rats were administered methadone hydrochloride by gastric intubation. Beginning on day 8 of gestation, a drug group received 5 mg/kg/day; the daily maintenance dose was increased to 10 mg/kg after 4 days with the final dose given on day 22. An intubation control group received sterile water alone on the same gestation days and a nontreated control group was left undisturbed, All experimental and control litters were fostered at birth to untreated mothers, Body weights were low at birth among the methadone offspring but were similar to controls by weaning. During adulthood, offspring were tested on several operant tasks that included acquisition of a lever-pressing response, performance on a variable interval reinforcement schedule, acquisition and performance of an auditory-visual discrimination and response inhibition in a "punishment" paradigm. None of these measures revealed any learning or inhibitory impairments among the methadone-exposed offspring. The major behavioral effect produced by the treatment was a high response output which emerged for each sex in different phases of testing.


The selection and evaluation of new chelating agents for the treatment of iron overload. A large-scale systematic evaluation of potential iron chelators for the treatment of hemosiderosis was conducted. The compounds were identified and evaluated using a hypertransfused mouse screen in which deferrioxamine B was a standard. This screen was designed to measure iron depletion in the tissues as well as iron excretion. Groups of 10 previously hypertransfused BDF1 male mice received a single daily i.p. injection of either vehicle, standard, or test compound for 7 days. Iron in daily urine pools and individual spleen and liver homogenates was determined by atomic absorption. More than 70 chelators were evaluated, including natural and synthetic hydroxamic acids, phenols, catechols and tropolones known to have a high affinity for iron (III) in vitro. Ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid) was shown to be considerably more effective than deferrioxamine B (i.p.) and, in addition, was orally active. Factors determining the efficacy of this and other chelating agents are discussed.


Development of functional tolerance to pentobarbital in goldfish. The acute effects of pentobarbital were measured by the times required for the loss of righting reflex (overturn point) and the pentobarbital brain concentration associated with the overturn. The test consisted of immersing the fish in a 0.3 mg/ml sodium pentobarbital in 0.1 M Tris buffer challenge solution until the overturn point was reached. To examine the development of tolerance the fish were pre-exposed to 0.1 M Tris buffer solutions containing 0.0, 0.010, 0.015 and 0.025 mg/ml of sodium pentobarbital for 6, 24 or 48 hr at which time the overturn times and the pentobarbital brain concentrations at overturn in the challenge solution were determined. The mean pentobarbital content in the brain at overturn of fish pre-exposed to 0.015 or 0.025 mg/ml solution was significantly higher (P less than .01) than in control fish. The loss of tolerance was determined at 3 hr after termination of the pre-exposure of the fish to the various pentobarbital solutions; tolerance was measured only in the group of animals pre-exposed to the 0.025 solution by the significant increase (P less than .01) in the pentobarbital brain levels over control fish. The equilibration curve for fish swimming in 0.025 mg/ml of sodium pentobarbital was determined for 48 hr. A steady state was attained within 6 hr with brain levels that reached approximately 80% the concentration of the external solution.


Rapid development of tolerance to the hypothermic effect of ethanol in mice. The hypothermic response to i.p. injection of ethanol (2.0-4.0 g/kg) in mice was found to be attenuated by a single equivalent ethanol injection given 24 hr earlier. The diminished hypothermic response was not an artifact since it could not be attributed to changes in body weight and was independent of familiarity with test environment and procedures. A parallel shift in the dose-response curve was found. It appears, therefore, that the reduced change in body temperature is indicative of tolerance. If the second ethanol injection was given 48 or 72 hr later, tolerance could no longer be seen. With injections spaced 24 hr apart, a third administration of ethanol did not further increase the tolerance seen after the second injection. Since blood ethanol levels did not differ in tolerant and nontolerant mice, and since tolerance was already present 10 min after the second ethanol injection, a functional rather than a metabolic tolerance is likely.


The effect of depletion of brain dopamine by 6-hydroxydopamine on tolerance to the anorexic effect of d-amphetamine and fenfluramine in rats. The effects on food intake of repeated administration of d-amphetamine and fenfluramine were examined in rats adapted to a 4 hr/day feeding schedule. Control rats given daily injections of amphetamine before food access rapidly developed a partial tolerance to the food intake reducing effect of amphetamine. However, rats given a 6-hydroxydopamine (6-HDA) treatment which produced a large selective depletion of dopamine in brain failed to display tolerance to amphetamine-induced anorexia after either 10 or 23 days of amphetamine injections. Although higher than normal doses of amphetamine were required to reduce feeding in 6-HDA-treated rats, control rats displayed tolerance after repeated injections of drug doses which were either equianorexic or equivalent to doses used in rats given 6-HDA. Furthermore, 6-HDA-treated rats failed to display tolerance to the low amphetamine doses normally used in control rats. In contrast to the results with amphetamine, both control and 6-HDA-treated rats displayed tolerance to the anorexic effect of fenfluramine. These results suggest that central dopaminergic neurons are involved in the tolerance which normally develops to the anorexic effect of amphetamine.


Tubular secretion and metabolism of dopamine, norepinephrine, methoxytyramine and normetanephrine by the rat kidney. The fate of catecholamines released in rat kidneys was examined by microinjecting tritiated norepinephrine (NE), normetanephrine (NMN), dopamine (D) and 3-methoxytyramine (3MT) into proximal and distal tubule lumina and peritubular capillaries. [14C] Inulin included in the injectate served as a reference standard. After injection of NE, D, NMN and 3MT at 0.1 to 4.0 pg/min for 4 to 10 min into proximal tubules, 87 to 94% was recovered in the urine of the injected kidney. Less than 10% of the amines was chemically altered during passage through the nephron. After injection into capillaries, percentages secreted in the first passage through the kidney were: D, 25 +/- 5; 3MT, 47 +/- 3; NE, 13 +/- 2; and NMN, 4 +/- 3. After D capillary injections, excretion of 3MT and D from the microinjected was twice that from the contralateral kidney. Acidic metabolites, homovanillic acid and dihydroxyphenylacetic acid were excreted equally by both kidneys. There was no appreciable difference in the products excreted from left and right kidneys after NE injections. In summary, D released into the peritubular space is converted to 3MT and both compounds are secreted avidly. NE released into the peritubular circulation is converted to NMN and both compounds are secreted but to a much smaller extent than occurs with D and 3MT.


Diuretic and antihypertensive effects of 2-aminoethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride (MK-447). 2-Aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride or MK-447, is a chemically novel diuretic agent which produced diuretic and saluretic effects in rats, dogs and chimpanzees. At doses ranging from 0.1 to 10 mg/kg p.o. (0.32-32 mumol/kg) MK-447 was more effective then furosemide at the same or higher doses in increasing the excretion of Na+, K+ and Cl- in rats and dogs. At single oral doses, MK-447 had antihypertensive activity in spontaneously hypertensive rats and renal hypertensive dogs. Other diuretics are known to lower arterial pressure in these models only by repeated administration. The antihypertensive and diuretic effects of MK-447 in spontaneously hypertensive rats were reduced by indomethacin.


Differing actions of nitroprusside and D-600 on tension and 45Ca fluxes in canine renal arteries. Administration of nitroprusside (NP) subsequent to induction of contraction in canine renal arterial strips with norepinephrine (NE) yielded a dose-dependent relaxation and with 80 mM potassium (KCl) yielded only a small degree of relaxation. The effect elicited with 0.1 mM NP was significantly greater for responses obtained with NE (68%) than for those with KCl (12%). However, responses of muscles pretreated for 5 min with NP to NE to KCl were reduced by 23 and 31%, respectively. The relaxant effect of NP persisted after incubation with D-600 and/or 30 min of a 0-Ca plus 0.05 mM EDTA solution (low EDTA). Neither D-600 nor NP altered 45Ca uptake in the absence of stimulatory agents. Efflux of 45Ca (into low EDTA solution) was decreased by NP in a maintained manner but was unaffected by D-600. The NE-induced decrease in 45Ca efflux (but not that with KCl) was blocked by NP. However, changes in 45Ca efflux elicited with KCl or NE were not affected by D-600. In contrast to D-600 (which is known to inhibit increased Ca++ entry associated with some stimulatory conditions), NP acts in a manner that is relatively independent of uptake of extracellular Ca++. Thus, these two vasodilators appear to affect Ca++ utilization by different mechanisms and, presumably, in an additive manner.


Requirement of the pituitary gland for gonadal hormone effects on hepatic drug metabolism in rats. Previous studies have demonstrated an important role for the pituitary gland in the regulation of hepatic drug and steroid metabolism. The present studies were carried out to determine the relationship between the pituitary gland and the actions of gonadal hormones on hepatic drug metabolism in rats. Testosterone administration to castrated male rats increased hepatic microsomal cytochrome P-450 concentrations and enhanced the rates of ethylmorphine demethylation and benzo(a)pyrene hydroxylation. Estradiol treatment, on the other hand, lowered cytochrome P-450 levels and decreased the rates of aniline, ethylmorphine and benzo(a)pyrene metabolism in orchiectomized rats. However, when given to hypophysectomized male rats, neither testosterone nor estradiol affected cytochrome P-450 levels or enzyme activities. Similarly, 5alpha-dihydrotestosterone administration increased hepatic drug metabolism only in the presence of the pituitary gland. The effects of both testosterone and estradiol were fully demonstrable in the absence of the thyroid or adrenal glands, excluding the need for either organ. The results indicate an absolute dependence on the pituitary gland for gonadal hormone (testosterone and estradiol) actions on hepatic mixed-function oxidases.


Role of monoamine neural systems in L-dihydroxyphenylalanine-stimulated activity. The potentiation of the stimulatory response to L-dihydroxyphenylalanine (L-dopa) in 6-hydroxydopamine-treated rats given a peripheral decarboxylase inhibitor occurred only after treatments that destroyed dopamine-containing fibers, Destruction of serotonin- or norepinephrine-containing fibers did not potentiate the action of L-dopa. Furthermore, other data indicated thatL-dopa-induced activity could not be attributed to release of serotonin or to the formation of norepinephrine. That the L-dopa must be converted to catecholamines was demonstrated by antagonism of the activity responses to L-dopa with inhibition of decarboxylases in brain. After destruction of serotonin-containing fibers with 5,7-dihydroxytryptamine, L-dopa-induced activity in 6-hydroxydopamine-treated rats was significantly reduced, as was the accumulation of dopamine formed from L-dopa. These latter data provide direct evidence that serotonergic fibers contribute to the accumulation of dopamine in brain after L-dopa administration to 6-hydroxydopamine-treated rats.


Dose-dependent pharmacokinetics and hypnotic effects of sodium gamma-hydroxybutyrate in the rat. The pharmacokinetics of sodium-gamma-hydroxybutyrate (NaGHB) have been examined as functions of dose and route of administration. The elimination of NaGHB appeared to be controlled by a capacity-limited process which can be described by Michaelis-Menten kinetics. Oral absorption of NaGHB appeared to be fairly extensive in the dose range studied (200-1600 mg/kg), but the peak drug plasma concentrations achieved after oral dosing were relatively low and insensitive to changes in the magnitude of the dose, explaining the lack of pharmacological activity, viz., hypnosis, after oral NaGHB administration even at comparatively high doses. Plasma and brain concentrations were determined at the time when the animals recovered from the hypnotic effects of NaGHB. These concentrations also appeared to be dose-dependent, although the ratio of "waking" plasma to brain concentration was constant with respect to dose.


Relative potencies and durations of action with respect to respiratory depression of intravenous meperidine, fentanyl and alphaprodine in man. Fentanyl, 0.7 and 1.4 microgram/kg, alphaprodine, 0.135 and 0.270 mg/kg meperidine, 0.564 and 1.127 mg/kg, and placebo were administered intravenously over 2.6 min by infusion to five healthy adult males. The crossover study was of incomplete Latin square design with at least 1 week between administrations of each study drug. The subjects breathed from a mixing chamber the gas composition of which was servo-controlled so as to produce CO2 ramps in the end-tidal gases. Each experiment was composed of: 1) control CO2 ramps, 2) a 25-min isocarbic run during which the drug was infused and 3) CO2 ramps at half-hour intervals for 3 hr postinfusion. The 20-liter intercept (the PETCO2 at which ventilation was 20 liters/min) was used as the measure of respiratory drive; the change in 20-liter intercept measured drug effect. The potency ratios at peak effect were: fentanyl/meperidine, 679; alphaprodine/meperidine, 3.68; fentanyl/alphaprodine, 179. With the area under the time-effect curves, the potency ratios of mean effect were: fentanyl/meperidine, 45c; alphaprodine/meperidine, 3.00; fentanyl/alphaprodine, 141. Thus, both fentanyl and alphaprodine are shorter-acting than meperidine, and fentanyl is shorter-acting than alphaprodine. The time-effect curves were fitted to linear and mono- and bi-exponential models. The time constants were compatible with the above relative durations of action.


Morphine-induced mydriasis and fluctuation in the rat: time and dose relationships. The purpose of this investigation was to establish complete dose- and time-response relationships of morphine action on the rat pupil using serial observations. Adult male, albino rats of the Sprague-Dawley strain were used. Pupil size was measured by a series of photographs taken every 60 sec for at least 90 min under dim red illumination. The pupil began to dilate within 20 min after s.c. administration of doses of morphine sulfate as low as 1 mg/kg. The dose-related mydriasis reached a maximum with a dose of 32 mg/kg at 35 to 50 min after injection and lasted for 3 to 4 hr. The mydriasis was characterized by a rapid and marked fluctuation which was also dose-related and reached a peak with 32 mg/kg of morphine sulfate. Naloxone HCl (1 mg/kg) rapidly reversed both the mydriasis and the oscillation, thereby implicating an opiate receptor-mediated mechanism. In addition to providing a convenient measure of narcotic actions, the pupil may offer a particularly useful means for studying opiate receptor mechanisms since it is one of the few cases where, in many species, the anatomical pathways and neurochemical innervations are known.


The effect of morphine on the endogenous phosphorylation of synaptic plasma membrane proteins of rat striatum. The synaptic plasma membrane (SPM) fraction was prepared from rat striata and assayed for endogenous phosphorylation in vitro. After the separation of membrane proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the incorporation of phosphate into specific membrane proteins was analyzed by gel slicing and autoradiographic techniques. Phosphate was incorporated into several SPM protein bands, two of which were regulated by cyclic adenosine 3':5' monophosphate. As a consequence of the chronic (in vivo) administration of morphine, the phosphorylation of two protein bands, designated protein II (MW 48,000-52,000) and protein III (MW 11,000-18,000), was reduced by approximately 20 and 50%, respectively; the phosphorylation of the former proteins was regulated by cyclic adenosine monophosphate whereas the phosphorylation of the latter proteins was not. The incorporation of phosphate into these same two protein bands was similar to control values when the membranes were obtained from rats undergoing naloxone-precipitated withdrawal. Morphine, in vitro, did not alter the phosphorylation of any SPM proteins in the assay, although at a high concentration morphine did antagonize the calcium-stimulated phosphorylation of one or more proteins in band II. The development of tolerance to and dependence on opiates may include changes in the phosphorylation of specific SPM proteins.


Psychosocial measures and cardiovascular risk factors in children and adolescents. The objective of this study was to test four psychosocial measures (self-concept, locus of control, goal blockage, A-B Rating Scale) which are hypothesized to be correlates of cardiovascular risk factor variables in children and adolescents. The psychosocial questionnaire was administered to all eighth grade students in a biracial public school. The results, based on replies from 103 boys and girls, are reported for each measure, and, in addition, reliability correlation coefficients (six week test-retest) and intrachild correlation coefficients are reported for each of the four measures. It is concluded that the four psychosocial measures are suitable for future research and could be employed in association with risk factor studies. Finally, a theoretical model for psychosocially mediated disease is presented.


Locus of control and anxiety as mediating variables of locus of conflict in disadvantaged youth. A measure of trait anxiety and locus of control was administered to 134 fourth-grade children who attended a low-socioeconomic-district school. Ratings of locus of conflict were also obtained from the parents of the children. As hypothesized, external locus of control scores correlated significantly with the locus of conflict scores, although this varied for both the sex of the children and the type of behavior problems exhibited. Further analyses revealed that children with medium locus of control scores had more externalization behavior scores than children with either internal or external locus of control scores. The hypothesized relationship between anxiety and locus of conflict was not supported.


Fears of institutionalized mentally retarded adults. The patterns of fears of institutionalized mentally retarded adults were studied in a sample of i2 moderately retarded men and women between the ages of 21-49. The direct questioning method was employed. Two interviews were held, two weeks apart; the first interview elicited the Ss' fears, while the second concerned the fears of their friends. A total of 146 responses were obtained, and these were categorized according to the types of fears: supernatural-natural events, animals, physical injury, psychological stress, egocentric responses, and no fears. The Ss displayed a higher percentage of fears in the preoperational stage than in the concrete operational stage. In a comparison of male to female fears, only one category, that of fears of animals, reached significance. The study suggested that the same developmental trend of fears that appears in normal children appears in the retarded as well, and these fears follow Piaget's level of cognitive development, proceeding from egocentric perceptions of causality to realistic cause and effect thinking.


Self-esteem, locus of control, and adolescent contraception. The relationships between locus of control, self-esteem, and attitudes to contraception and contraceptive behaviors were assessed for 486 single women of ages 13 to 20, attending 10 birth control centers in Southern Ontario, Canada. The Ss voluntarily filled out a questionnaire, and the data were measured with the Fatalism scale of Reid and Ware's I-E scale, a Likert-type self-esteem scale, and a semantic differential birth control pill scale. There were no significant relationships between locus of control and any of the contraception variables. Ss with high self-esteem were found to have positive attitudes toward using birth control pills, to be less embarrassed about obtaining contraception, and to be more effective and consistent contraceptive users.


Sex differences in mental health.

Sex differences in mental health. The purpose of this study was to investigate the relationship between sex and mental illness. A sample of male and female adult psychiatric outpatients (n = 44) completed the Denver Community Mental Health Questionnaire (DCMHQ), the Taylor Manifest Anxiety Scale, an abbreviated version of the Minnesota Multiphasic Personality Inventory (the Mini-Mult), and the Social Readjustment Rating Scale. Differences in life event experiences, as well as differences on measures of anxiety, depression, psychological distress, and social functioning, were explored and identified by means of Pearson product-moment correlations. The strongest correlations were found between sex and four of the subscales of the DCMHQ: women tended to be less productive and evidenced more psychological distress than men; men had more legal difficulties and were more likely to use soft drugs. A modest correlation was found on the Taylor Manifest Anxiety Scale, with women showing higher scores.


Vesicoureteral reflux in end stage renal disease. Of 85 adults with end stage renal disease examined consecutively for renal transplantation 25 (29.4 per cent) had vesicoureteral reflux. Of these 25 patients 11 had a nephropathy as the cause of renal failure that was unrelated to reflux (for example glomerulonephritis) and 12 had, in addition to vesicoureteral reflux, a history of urinary tract infections and chronic pyelonephritis, which seems to be significant in the etiology of terminal renal failure in our patients (14 per cent). Only 2 of the 25 patients had severe, sterile reflux: 1 had bilateral megaureter with reflux into 1 side after ureteroneocystostomy and 1 had bilateral grade IV sterile reflux complicated by megacystitis. We had no case of uncomplicated, sterile reflux, which, in our experience, seems to be a rare cause of renal failure.


Bilateral complete ureteral obstruction secondary to an abdominal aortic aneurysm with perianeurysmal fibrosis: diagnosis by computed tomography. The sixteenth case of bilateral ureteral obstruction with anuria secondary to an abdominal aortic aneurysm with perianeurysmal fibrosis is presented. The details of this case clearly indicate the need for a combined vascular and urologic approach to patients with this disorder. A complete preoperative evaluation, including excretory urography, retrograde pyeloureterography, aortography and, when indicated, venacavography, may determine renal and vascular abnormalities that will allow a more definitive and successful management of this difficult problem. Furthermore, we believe that the use of computed tomography is an invaluable tool to define this retroperitoneal disease process and its precise relationship to the ureters.


Combined retrocaval ureter and retroperitoneal fibrosis: report of a case. The first case of a simultaneous retrocaval ureter and retroperitoneal fibrosis of the right ureter is presented. The diagnosis was made roentgenographically on the basis of the S-shaped course of the proximal right ureter and medial deviation of the tapered and obstructed mid ureteral segment. This was confirmed by exploration of the right ureter and retroperitoneal biopsy. The surgical treatment of this unusual entity is described.


Steroids in the treatment of retroperitoneal fibrosis. Two cases of retroperitoneal fibrosis with asynchronous bilateral hydronephrosis are reported. One case was managed initially by unilateral ureterolysis. Subsequent contralateral disease was treated with a 6-week course of oral steroids alone with resolution of the bilateral hydronephrosis for 10 years. The other case was treated with unilateral renal exploration. Subsequent contralateral and residual ipsilateral disease was treated similarly with steroids and 7 months later there was resolution of bilateral hydronephrosis.


Resection of the suprarenal inferior vena cava for retroperitoneal malignant disease. Minimal renal dysfunction was noted in 4 of 5 patients undergoing right nephrectomy with resection of the inferior vena cava and ligation of the left renal vein. However, the results of this series confirm previous reports that patients with locally advanced right renal carcinoma requiring vena caval resection are cured rarely by an operation alone. In the absence of effective adjunctive therapy for renal cell carcinoma this procedure will most likely benefit patients with neoplasms responsive to either chemotherapy or radiation therapy.


Ultrasound evaluation of bladder calculi. A case is presented in which the identification of intravesical calculi by ultrasound was an aid in management. Bladder stones appear as high intensity echoes within the bladder, have an associated acoustic shadow and shift to the dependent portion of the bladder with alterations in position. Ultrasound provides a rapid, safe imaging technique to diagnose or verify the presence of bladder calculi.


Use of penile corporeal injection to assess coronal hypospadias. Coronal hypospadias is a frequent abnormality of the genitalia. It is recommended that patients with coronal hypospadias be assessed with the technique of penile corporeal injection during anesthesia and any patient with coronal hypospadias should be circumcised with the utmost caution and surgical discretion.


Intermittent erection in spinal canal stenosis. A case of intermittent erection in a patient with spinal canal stenosis is reported. The symptoms disappeared after lumbar laminectomy. The mechanism of erection remains speculative.


Epididymitis in infancy.

Epididymitis in infancy. The occurrence of epididymitis in infants suggests the presence of urinary infection and the likelihood of an associated structural genitourinary abnormality, requiring complete urologic investigation. The advent of testicular scanning and the ultrasonic stethoscope, coupled with an increased index of suspicion, makes possible the non-operative diagnosis and management of a condition usually made by surgical exploration.


Coccidioidomycosis of the prostate gland and its therapy. A case of disseminated coccidioidomycosis was diagnosed from a prostatic biopsy. Patients with sterile pyuria, prostatic nodules or symptoms of prostatitis who have lived in or traveled through an endemic area need careful evaluation of the lower genitourinary tract. Immunological treatment with a transfer factor currently is under investigation. Miconazole may offer a promise for future treatment of this fungal infection and, particularly, for patients with impaired renal function.


Early observations on 31 adults with non-refluxing colon conduits. A colonic segment with tunneled ureterocolic anastomoses was used for non-refluxing urinary diversion in 31 adults during the last 3 1/2 years. Half of the patients had undergone diversions previously. These pre-existing diversions had been associated with significant urologic complications. The remainder of the patients had a variety of benign and malignant diseases. After the non-refluxing colonic diversion all upper tracts remained stable or improved except in 3 patients in whom 4 ureterocolic anastomoses developed silent stenosis. Of 10 patients who had pre-existing refluxing diversion and episodic acute pyelonephritis 7 had no recurrences. No patient with sterile urine became infected and 18 of 24 patients with persistently infected urine improved. The anatomic versatility of the colon that allows the benefits of a low pressure system and unidirectional urine flow makes the non-refluxing colon conduit an advantageous alternative in adults requiring urinary diversion.


Uterus didelphys with unilateral imperforate vagina: a rare cause of acute urinary retention. The first case is reported of acute urinary retention caused by hematocolpos owing to uterus didelphys with a unilateral imperforate vagina. A brief description of this rare anomaly and its usual presenting signs and symptoms is presented. Finally, a synopsis of the embryologic defects responsible for the development of the anomaly and the recommended management of the disorder are outlined.


The bowel as substitute for the bladder. The long-term results with 16 patients who underwent uretero-intestino-urethral urinary diversion are presented. We believe that with meticulous attention to the operative technique and the criteria for the operation this is a reasonable procedure for a patient undergoing cystectomy as an alternative to cutaneous or large bowel diversion of the urinary stream.


Vesicovaginal fistulas on one urological service. Of 92 vesicovaginal fistulas 57 (62 per cent) were closed, at least temporarily, with 1 or more operations. Functional closure was not attempted in 23 per cent of the cases and failed in 15 per cent. Various techniques were used in these cases. The favorite method involved a combination of colpocleisis, splitting the posterior wall of the bladder suprapubically and a temporary cystostomy on low pressure suction. Five patients (5.4 per cent) died postoperatively.


Correlation of the cell surface antigens with stage and grade in cancer of the bladder. We examined 76 bladder tumors of various stages and grades for the presence of the ABO (H) cell surface antigen, using the specific red cell adherence technique. Of the grade I lesions studied 70 per cent were positive for the cell surface antigen and none of the 26 grade III tumors retained the antigens. When correlated with clinical stage the tumors showed no antigens for those of stages B1 to D, while 12 of 16 stage A lesions were positive for the antigen. When stage A lesions were studied and the findings were correlated with recurrence and metastasis/invasion rates the cell surface antigen was present on the initial tumor in only 1 lesion that recurred at an invasive stage. The findings of this study show that the specific red cell adherence technique may be valuable for predicting malignant potential in low grade, low stage cancer of the bladder. If supported by further investigation this technique may offer the capability of selecting low grade, low stage bladder tumors that are destined to invade or metastasize while they are at curable stages.


Prophylaxis of indwelling urethral catheter infection: clinical experience with a modified Foley catheter and drainage system. With the application of the oligodynamic bactericidal property of silver ions, modification of the urinary catheter and drainage system has been found effective in the prevention of urinary tract infections owing to prolonged bladder catheterization. The newly devised catheter and open drainage system were used in 102 patients for bladder catheterization postoperatively or in those with urinary retention for periods ranging from 4 to 77 days. During the period of indwelling catheterization usually no antibiotics were administered and no patient had overt bacteriuria (more than 10(5) bacteria per ml.) or symptoms of urethritis. In contrast, all 20 patients in the control group who had the conventional type of indwelling catheters had bacteriuria within 4 days of catheterization. The data obtained indicate that effective prevention of urinary tract infection, which frequently is associated with indwelling urethral catheterization, can be achieved by the use of the modified catheter and drainage system.


Diagnostic fine needle aspiration of soft tissue metastases from cancer of the prostate. Pathologic confirmation of soft tissue metastases is necessary for staging and followup of patients with cancer of the prostate. Fine needle aspiration with cytologic evaluation is recommended over other biopsy procedures because it is safe, accurate and applicable to deep and superficial lesions. Small metastases, such as lymph nodes or skin nodules, remain in situ as useful markers to follow the course of the disease and response to treatment.


Winter sports-related urologic trauma.

Winter sports-related urologic trauma. There is no characteristic pattern of ski-related urologic injuries except those associated with major blunt abdominal trauma. Isolated urologic injuries and injuries of the lower urinary tract are relatively uncommon.


Cath-A-Cyst: a new urinary catheter.

Cath-A-Cyst: a new urinary catheter. A new disposable catheter assembly using the advantages of the Foley catheter, filiform and followers is presented. This new system obviates emergency urologic consultation or further trauma to a patient with a difficult urethra to catheterize.


Evaluation of importance of cystoscopy in staging gynecologic carcinomas. Of 265 patients with gynecologic carcinoma undergoing initial evaluation during a 5-year period 238 were staged prospectively with procedures that included cystoscopy. Endometrial carcinoma was noted in 98 patients, none of whom had evidence of bladder extension nor did the clinical stage of disease change after cystoscopy. Of 120 patients with carcinoma of the cervix 7 were found to have extension of tumor to the bladder. The clinical stage was elevated in 3 of these cases but remained unchanged in 4 because of the cytoscopic findings. Of all 238 patients with gynecologic carcinoma 3 (1 per cent) also were found to have unsuspected low grade transitional cell carcinoma of the bladder.


Stomal obstruction of ileal conduits in children: a urodynamic study. In an attempt to diagnose stomal obstruction before radiological evidence is present, urodynamic perfusion studies were done on 40 children with ileal conduit diversion. Residual urine, capacity, resting pressure and mean emptying pressure were recorded after perfusion of the conduit with normal saline at 10 ml. per minute. Emptying pressure appeared to be the most sensitive parameter of obstruction. Residual urine may be normal in early obstruction and may be increased in the presence of normal emptying pressures in atonic conduits.


The artificial bladder sphincter AS-721 for the treatment of incontinence in patients with neurogenic bladder. An artificial sphincter was placed at the bladder neck in 9 male and 3 female patients with urinary incontinence and neurovesical dysfunction. Criteria for selection of patients included complete bladder emptying, absence of vesicoureteral reflux and normal upper urinary tracts. Of the 9 male patients 6 became continent, with an average followup of 25 months, and only 1 mechanical failure occurred. The results were less satisfactory in the 3 female patients, 2 of whom eventually required supravesical diversion. Artificial sphincters are valuable in the treatment of certain children and adults who are incontinent because the pelvic floor is damaged or denervated, even if they have neurovesical dysfunction.


Sodium-losing nephropathy.

Sodium-losing nephropathy. We studied prospectively 18 patients with sodium-losing nephropathy. In 12 patients (66.7 per cent) the sodium-losing nephropathy was owing to obstructions, challenging the hitherto existing concept that the most common cause of the condition is pyelonephritis. The diagnosis of sodium-losing nephropathy is important in urological practice since sodium repletion in these cases shortens significantly the hospitalization and preoperative waiting time.


Lymphomatoid tumor infiltration of renal veins. A case of bilateral renal vein infiltration and thrombosis secondary to malignant lymphoma is presented. Although the kidney frequently is known to be involved by metastatic lymphoma, uremia is a rare terminal complication. The etiology and diagnosis of this disorder are discussed. We believe that it is important to recognize renal vein thrombosis in such patients so that treatment with radiation and/or chemotherapy may restore renal function.


Esophageal carcinoma presenting as a primary renal tumor. A patient with esophageal carcinoma presenting with hematuria is described. Initial studies confirmed the presence of a renal mass that was thought to be a primary renal neoplasm. Further studies to evaluate anemia before a renal operation led to the discovery of an unsuspected esophageal carcinoma. Although metastases to the kidneys are relatively common it is uncommon for these lesions to be clinically apparent or responsible for producing initial symptomatology. Only after discovery of the esophageal lesion was the possibility of a secondary renal neoplasm considered. Intractable hematuria was treated successfully by embolizing the renal artery of the bleeding kidney with gelatin sponge fragments.


Renal carcinoma in adolescents.

Renal carcinoma in adolescents. Renal adenocarcinoma is an infrequent tumor in children. The clinical and radiographic findings in 4 adolescents with such tumors are described. The surgical therapies of these patients and the possible role of adjunctive chemotherapy and radiotherapy are discussed.


Solitary vaginal metastasis from unsuspected renal cell carcinoma. Four cases of solitary vaginal metastasis from previously unsuspected renal cell carcinoma are presented. Vaginal bleeding, the presenting symptom in each patient, led to the finding of the metastatic vaginal lesion and to the urological evaluation, which revealed the occult primary renal cell carcinoma. With surgical treatment 2 of the 4 patients have remained well for more than 5 years.


Excision of duplicated ectopic ureter: re-emphasis on technique. Excision of the residual duplicated ectopic ureter after partial nephrectomy is an uncommon but often difficult surgical procedure. The awareness of the benefits of the transvesical approach should be part of every urologist's surgical knowledge.


Accuracy of cord blood screening for sickle hemoglobinopathies. Three- to five-year follow-up. The strategic advantages of neonatal diagnosis of sickle hemoglobinopathies depend on an accurate cord blood screening procedure. One hundred thirty-eight black children in whom a range of normal and abnormal hemoglobin genotypes was identified by agar gel and cellulose acetate hemoglobin electrophoresis at birth were retested by cellulose acetate three to five years later. The original cord blood diagnoses were verified in all 138, including all 26 with major sickle syndromes (SS, S-beta thalassemia, and SC). Cord blood hemoglobin electrophoresis using these techniques permits accurate neonatal diagnosis of major and minor sickle hemoglobinopathies.


Bacteriology of chronic otitis media.

Bacteriology of chronic otitis media. Tympanocentesis was performed in 50 patients with chronic otitis media; pus was cultured aerobically and anaerobically. Only aerobes were isolated from 21 patients (42%), three patients had only anaerobes (Peptococcus sp), and 25 patients (50%) had both aerobes and anaerobes. Only one specimen had no growth. There were 68 aerobic isolates. Pseudomonas aeruginosa was recovered in 36 patients (72%); other aerobes commonly recovered included Proteus sp and Staphylococcus aureus. There were 48 anaerobes isolated. Anaerobic Gram-positive cocci were isolated in 24 instances (21 Peptococcus sp and three Peptostreptococcus sp). Sixteen Bacteroides sp were recovered, including seven B fragilis group and six B melaninogenicus.


On the diagnosis and treatment of breast cancer. Randomized trials comparing surgical treatments of breast cancer show that radical mastectomy offers no greater benefit than simple mastectomy followed by radiotherapy. Furthermore, in terms of survival, radical mastectomy seems to be no better than wide excision followed by radiotherapy when the disease is clinically diagnosed as stage 1. The incidence of diagnosed breast cancer showed an 18% increase between 1935 and 1965 and a 50% increase between 1965 and 1975. However, breast cancer mortality has remained unchanged for at least the past 40 years. Analysis of survival curves of women with breast cancer suggests that two or more populations exist, with about 40% suffering fatal outcome unaffected by treatment. The remaining 60% exhibit a relative mortality only modestly different from that of women of similar ages without evidence of disease. Increasing detection of an entity that is histologically defined as malignant but biologically relatively benign could account for the observed increase in incidence.


Allergic reaction to transfused cephalothin antibody. Antibodies to cephalothin sodium (Keflin) can be transferred passively via whole blood transfusion. In one case a mild allergic-type reaction was initiated in a patient who was receiving cephalothin therapy. This case is differentiated from a penicillin-caused allergic reaction. All patients that demonstrate allergic-type transfusion reactions should give drug histories. Investigation of passive transfer of antibodies to these drugs might be of benefit in any evaluation made.