The progestational activity of different gestagens used for human contraception in the beagle bitch

In long-term studies chlormadinone acetate (CMA) and cyproterone acetate (CPA) have much more pronounced mammotropic effects in dogs than norethisterone acetate (NA) or levonorgestrel (LN). To evaluate gestagenic potency of these compounds in dogs as a potential determinant of these substance differences, a quantitative canine gestagen bioassay was developed. Ovariectomized adult beagles were sequentially treated with 30 μg estradiol (E₂)/d s.c. for 15 days and gestagen (s.c., p.o.) + 3 μ g E₂/ d s.c. days 16–29. This regimen was found optimal for endometrial gestagen effects.

According to their s.c. transformatory potency in day 29 endometrial biopsies, the compounds could be ranked as follows; progesterone (P)

Related to p, LN and NA have a much lower gestagenic potency in dogs than in humans. The opposite is true for CMA and CPA. The low oral activity of NA and LN in dogs points to an important first liver passage metabolism of both compounds in this species. Serum determinations substantiate the very low or high oral. bioavailability in case of LN, NA and CPA.

Clinically, by the oral route of administration, there is no doubt of the fact that CMA is markedly less potent than NA which itself is less potent than LN whereas in the dogs, CMA is unequivocally the most potent of the progestagens under consideration. This implies that the dogs are overdosed with several human multiples when CMA is administered and probably underdosed with NA, at least on a comparative basis.

Our data are consistent with the view that the ability or inability of gestagens to induce mammary tumours in chronic toxicity studies might reflect a dog-specific high or low gestagenicity.     

Standardization of the indirect fluorescent antibody test for malaria.

Methods are described whereby results of malarial immunofluorescence tests can be evaluated objectively. The IFA test was quantitated by standardizing the physical system against a fluorescent standard and preparation of biological standards of malarial antisera and fluorescein labelled conjugates. Using these known standards the reactivity of antigens was characterized. It was found that antigen preparations are best when they include mature schizonts, and keep best when they are stored in a dry condition at or below -20 degree C. However, even under carefully controlled conditions of storage, antigens showed considerable variation of reactivity between individual batches.     

A comparison of enzyme-linked immunosorbent assay and indirect fluorescent antibody test in the sero-diagnosis of cutaneous and visceral leishmaniasis in Iran.

ELISA AND IFAT have been applied to the sero-diagnosis of cutaneous and visceral leishmaniasis and the levels of leishmanial antibody detected by Leishmania donovani antigens in both tests have been compared. From the results it appears that ELISA is a little more sensitive than IFAT, but IFAT seems to be more specific in detecting leishmanial antibodies. In both tests reactions between leishmanial antigen and some other infections, such as malaria and typhoid, were observed. These non-specific reactions reduce the validity of both tests, especially ELISA, in the sero-diagnosis of cutaneous leishmaniasis but, in visceral leishmaniasis, the leishmanial antibody levels were high enough to be unaffected by non-specific reactions. In general, ELISA is as good as IFAT and more practical in the sero-diagnosis and mass screening surveys for kala-azar.     

The dose-dependent effects of ingested chrysotile on DNA synthesis in the gastrointestinal tract, liver, and pancreas of the rat.

The effects of single oral administration of saline suspensions of chrysotile A to fasting male albino rats on DNA synthesis in the GI tract, pancreas, and liver were studied after a subsequent interval of 3 days. Incorporation of [³H]TdR was elevated in the whole stomach, duodenum, and jejunum following administration of chrysotile in the dose range of 5 to 100 mg/kg; incorporation in the liver was, however, reduced. There was no change in pancreatic and colonic [³H]TdR uptakes following administration of chrysotile. Preliminary data suggest that physicochemical alterations of chrysotile by gastric acid may influence its subsequent effects on DNA synthesis.     

A study on the contraceptive effectiveness of a newly designed IUD "FD-1" in Japan

A newly designed IUD, FD-1, was inserted in 671 women for a total of 9624.5 months of use. The IUD is ready-loaded in its insertion so no folding or loading of the IUD before insertion is necessary. The net cumulative termination rates at the end of 23 months using the life-table techniques are as follows: pregnancy 4.0, expulsion 2.1, removal due to bleeding and pain 2.7, other medical reason 0.8, planning pregnancy 1.0, and other personal reason 0.4, per 100 women. This clinical experience has demonstrated that this IUD has a high contraceptive effectiveness with a low expulsion rate and high acceptability.     

Chromium complexes with proteins and mucopolysaccharides and their relationship to chromium allergy in sensitized guinea pigs

Theoretical considerations and equilibrium dialysis are utilized to refute previous reports on the amounts of chromium that can be complexed to proteins and mucopolysaccharides. Purified chromium complexes containing no free chromium were then used to test chromium-sensitized guinea pigs. The chromium-albumin complex is the only one of those studied found to reproducibly elicit.     

Development of the serological response in rabbits infected with Toxocara canis and Toxascaris leonina

The indirect fluorescent antibody test using frozen sections of infective Toxocara canis and Toxascaris leonina eggs, and the enzyme linked immunosorbent assay using homogenized Toxocara canis embryonated egg extract and T canis excretory-secretory products as adsorbed antigens were used to determine the specificity and development of circulating antibodies in rabbits. Frozen sections were subdivided into four morphologically distinct compartments for analysis of the development of the circulating antibody response. The fluid surrounding the larva was the most reactive up to 21 days after infection, and this material was found to be predominantly excretory-secretory in nature. As the infection progressed antibodies directed against ‘somatic’ tissue materials increased. Cross reactions between sera from rabbits infected with T. canis eggs and Toxascaris leonina frozen sections, and rabbits infected with T. leonina eggs and Toxocara canis frozen sections occurred between both the excretory-secretory fluid and somatic components of the infective eggs. These results were substantiated using the enzyme linked immunosorbent assay. When T. canis excretory-secretory antigen was used, an earlier response (peak day 21) was detected than when using T. canis embryonated egg extract (peak day 35). However, cross reactions between T. canis excretory-secretory antigen and sera from rabbits infected with Toxascaris leonina occurred, indicating that the serodiagnosis of visceral larva migrans using Toxocara canis excretory-secretory antigen may still prove unsatisfactory when considering the role of Toxascaris as a possible causative agent.     

Evaluation of polymer flock and metal alloy intra-tubal device in pigtail monkeys.

Two intratubal devices, one covered with a flock made from ethylene vinyl acetate and the other constructed of titanium-aluminum-vanadium alloy with an etched surface were evaluated after being placed in the Fallopian tubes of pigtail monkeys. In some instances, the devices were medicated with 10% silver nitrate or 50% quinacrine hydrochloride. The microflock device anchored in the tube mechanically, but there is no evidence that either the polymeric or metal alloy device formed an actual attachment with Fallopian tube epithelium. It is suggested that a mechanical design approach to ITDs might be more productive than one which assumes a tissue-device bond.     

A specific S-antigen of Plasmodium falciparum is expressed in a proportion of primary isolates in Brazil, Thailand and Papua New Guinea

The expression by Plasmodium falciparum of a specific S-antigen has been examined in primary isolates in different regions of the world using a monoclonal antibody that recognizes an epitope within a known repeated amino acid sequence. The epitope was expressed by a small proportion of primary isolates in each of Brazil, Thailand and Papua New Guinea, demonstrating that this S-antigen gene is widespread. The data are consistent with the possibility that the occurrence of P. falciparum strains expressing a particular S-antigen is periodic, related to the duration of immunity against that antigen in a given human population.     

Information control and the exercise of power in the obstetrical encounter

Interactions between doctor and patient involve participants with unequal power and possibly different interests. While a number of studies have focused upon the doctor/patient relationship, few have examined the utility of the concept of power and its capacity to help us understand the outcome of these interactions. The information sought by pregnant women from their obstetricians is used to provide a case study of one conceptualization and test of the utility of the concept of power. Pregnant women and their obstetricians are found to have different perceptions of the information that should be exchanged during their interactions. Women generally fail to obtain the information they want. Lower social class patients desire more and obtain less information than their higher status counterparts.     

Fructose in wild-caught Phlebotomus ariasi and the possible relevance of sugars taken by sandflies to the transmission of leishmaniasis

Cold, acidified anthrone was used to test 200 wild-caught sandflies (Phlebotomus ariasi ♀♀) for the presence of fructose. This sugar, or others with a fructose moiety, were demonstrable in 157 (79%) of the flies; proportions of flies positive in different tests ranged from 44 to 91%. Higher proportions of flies gave positive results when tested less than one hour after capture than when kept in the laboratory for more than 12 hours before testing. Similarly high percentages of flies were positive in samples collected coming to engorge on dogs and in those caught in CDC miniature light traps. These results, together with published reports of the demonstration of sugars in 25 individually tested sandflies of other species, confirm that, like other biting flies, sugar is an important part of the diet of sandflies. Natural sugars may influence the development of leishmaniae in sandflies and their subsequent transmission. The anthrone test was found to be simple, rapid and suitable for field use; it is a valuable addition to indirect techniques for the study of the behaviour of sandflies.     

Surveys of haemagglutination-inhibiting antibody to arboviruses in Aborigines and other population groups in Northern and Eastern Australia, 1966-1971

Surveys of Aboriginal settlements by haemagglutination-inhibition tests against arboviruses of Groups A and B showed very low prevalence of antibody in eastern Queensland, very high prevalence in north-west Queensland and some settlements in the Northern Territory, and intermediate prevalence at other settlements in the Northern Territory. Sera from about 1500 patients received from the general community of east coastal Queensland for diagnostic serological tests, but with no evidence of current arbovirus infection, showed some differences in age distribution of antibody between Ross River virus of Group A (with prevalence rising to a plateau level of 50% from age 30) and Group B (with few reactions in younger age groups and steady rise in prevalence from age 20 to almost 90% beyond age 60).Sets of sera reactive to one Group B arbovirus were titrated by haemagglutination-inhibition test to 8 members of the Group; mean titres to each virus were computed and compared. 2 distinct patterns of response were defined, reacting significantly to both dengue and Murray Valley encephalitis subgroups (east coastal Queensland), or only to the Murray Valley encephalitis subgroup (north-west Queensland and Northern Territory). These findings, the history of extensive epidemics of dengue in eastern Queensland, and other laboratory studies described in this and previous papers, suggest that the broadly-reactive antibody is due to dengue infection. The long persistence of high-titre, broadly reactive antibody after dengue infection in Queensland and elsewhere is seen as an interesting phenomenon worthy of further study.Most of the many reactions to Group A viruses detected in the study were clearly to Ross River virus, but 15 patients gave serological results suggesting past infection with Sindbis virus. One of the 15 had rising titres following a mild febrile illness with lymphadenopathy and rash, suggesting that Sindbis virus may have caused the illness.     

The effects of an lh-rh antagonist ([N-Ac-D-Trp1,3,D-p-Cl-Phe2,D-Phe6,D-Ala10]-LH-RH) during the preovulatory period of the rhesus monkey

Seven regularly cycling rhesus monkeys ($\text{Macaca mulatta}$) were used in this experiment. The animals were followed during two consecutive cycles. During the first cycle (control), the animals did not receive any treatment and the date of ovulation was determined by using daily total serum estrogens and serial laparoscopies. In the second cycle, the animals received 1 mg daily of [N-Ac-D-Trp^1,3, D-p-Cl-Phe²,D-Phe⁶,D-Ala¹⁰]-LH-RH by intramuscular injection from days 10 to 14. The date of ovulation was determined by using the same methodology as the control cycle. Blood samples were drawn daily from day 8 of the cycle until the onset of menses, and the serum was used to measure total estrogens, progesterone and LH. A significant delay of the preovulatory LH peak and ovulation occurred in 5 of the 7 animals resulting in a proportional increase in cycle length as compared to the control cycle. No changes in cycle length or date of LH peak occurred in the other 2 animals. One of them did not present signs of ovulation as determined by laparoscopy (no recognizable stigma or corpus luteum). Progesterone production and length of the luteal phase were not affected by the treatment.     

Comparison of filtration staining (Bell) and thick smear (Kato) for the detection and quantitation of Schistosoma mansoni eggs in faeces

We compare results of one Bell and one Kato-Katz examination performed on each of 315 stool specimens from residents in an area in north-eastern Brazil endemic for schistosomiasis mansoni. The prevalence of schistosome infection detected by the Bell technique was 76% and by the Kato-Katz technique was 63%. 81% ($\text{44}\text{54}$) of the infections missed by a Kato-Katz smear were light infections (one to 50 epg range by Bell examination). Over-all, 55% ($\text{44}\text{80}$) of stools in this egg count range by the Bell technique were negative on a single Kato-Katz smear. This implies that five Kato-Katz smears per stool would ensure a 95% probability (0·55⁵ × 100) of detecting such light infections. However, a single Kato-Katz smear detected eggs in 97% ($\text{124}\text{128}$) of stools with a Bell count > 100 epg. For stools positive by both methods the egg counts per gram of stool were higher (p < 0·001) by Kato-Katz examination. Geometric mean egg counts for the infected population were 199 epg by the Kato-Katz and 92 epg by the Bell methods. 64% (59 v. 36) more persons were classified as heavily infected (> 400epg) by the Kato-Katz method than by the Bell method. The differing measurements of schistosome infection obtained with the Bell and Kato-Katz methods must be considered when comparing data on morbidity-infection relationships.     

The maximum density of anopheline mosquitoes that can be permitted in the absence of continuing transmission of filariasis

Using two years of mosquito collections from two fixed stations on Guadalcanal it was possible to compare the average man-biting rate with the prevalence of microfilaraemia. One area was found to be free of infection while the other still had one positive case. The DDT residual spraying had caused a change in biting habits of A. farauti No. 1 allowing a greater density of mosquitoes to bite man at times when they had lower microfilaria densities. This difference was compared with the pre-spray density so that the maximum permissible number of mosquitoes biting man without transmission of filariasis taking place, could be calculated.A theoretical value for m of 19.84 had been worked out previously, this study gave a corrected observed value of m of approximately 20, very close to the calculated theoretical value. The situation studied here probably showed incomplete interruption of transmission, so it was considered preferable to recommend a figure of 0.66 average vector man-biting rate per hour indoors for the critical value.     

Hunger and palatability: tracking ratings of subjective experience before, during and after the consumption of preferred and less preferred food

This study investigated the effects of palatability on ratings of hunger and other states, food preferences, bodily sensations, feelings and moods. Assessments of these were made before, during and after 12 healthy female subjects ate small equicaloric meals of either highly preferred of less preferred food. The sight of highly preferred food markedly increased subjects' rated desire to eat and this elevation was maintained during consumption. Hunger ratings were also elevated but only during consumption of the highly preferred food and to a smaller extent. There was no effect of the palatability of the food on rated feelings of fullness. Two hours after the meal, ratings of desire to eat and hunger were significantly higher after consumption of highly preferred food. This effect did not occur after eating less preferred food. Feelings of general positive affect, which followed the highly preferred meal, did not occur with the less preferred food. These findings throw light on the nature of the rated expression of hunger and on other terms used in describing dispositions to eat.     

Effect of specific and non-specific prior sensitization on the outcome of amoebic infection

Guinea-pigs were sensitized with monoaxenic amoebic antigen (Group I), bacterial associate antigen (Group II) and axenic amoebic antigen (Group III). All animals in Group I, 95% in Group II and 70% in group III, developed caecal lesions on intra-caecal inoculation of Entamoeba histolytica trophozoites; 92·8% of control (unsensistized) animals developed lesions in their caeca. Lesions were more severe in sensitized animals than in controls. Hepatic abscesses were found in 7·6% of group I, 11·1% of group II and 7·1% of group III. No animal from the untreated but infected group developed hepatic abscess. It thus appears that specific (amoebic) and non-specific (bacterial) prior sensitization may render the host more susceptible to hepatic amoebic infection.     

Perceived influence of different information sources on the decision-making of internal medicine house staff and faculty

To determine the extent to which different sources of information are perceived to influence common medical decisions, 10 interns, 22 senior residents and 9 faculty general internists rated the degree of influence of house staff, general internists, subspecialists, conferences, journal reading and past experience on their decisions concerning primary prevention (vaccination), secondary prevention (screening) and drug therapy. Analysis of variance of their questionnaire data supports the following conclusions: physicians at different stages of training rely on different sources of information; as physicians advance in training the influence of generalists wanes while that of subspecialists increases; subspecialists and past experience are perceived as primarily affecting therapeutic decisions; primary prevention appears least subject to influence by prevailing information sources; and the preference for reading begins early and increases as physicians advance in training. These data suggest that designing effective medical education requires considering the level of the physician's training and the nature of the medical decision.