Mechanism and epidemiology of bone effects of cadmium. A slow epidemic of a combination of osteomalacia and kidney damage (itai-itai disease) was first noted in Japan in the late 1940s. During the same period reports of severe bone effects in cadmium-exposed workers in some European factories were published. Cadmium-induced kidney effects and their connection with bone effects were first reported in 1950. Epidemiological and clinical studies in Japan since 1962 have shown that the bone effects develop only at very high cadmium exposures and that persons with low intakes of calcium or vitamin D are particularly at risk. Animal experiments have confirmed that cadmium induces bone effects at high exposures. Six possible mechanisms may explain the cadmium-induced bone effects: (1) interference with parathyroid hormone (PTH) stimulation of vitamin D production in kidney cells; (2) reduced activity of kidney enzymes activating vitamin D; (3) increased excretion of calcium in urine; (4) reduced absorption of calcium from intestines; (5) direct interference with calcium incorporation into bone cells; and (6) direct interference with collagen production in bone cells. The high cadmium exposures needed to produce bone effects may still occur in developing countries, where many people have poor nutritional status and could be vulnerable to such effects.


Dose-response relationship for renal dysfunction in a population environmentally exposed to cadmium. Two epidemiological studies aimed at investigating the dose-response relationship of environmental cadmium exposure were performed in a population living in the Kakehashi River basin, a cadmium-polluted area in Japan. In the first, the average cadmium concentration in rice from each village was used as an indicator of exposure and metallothioneinuria or beta 2-microglobulinuria as an index of renal tubular dysfunction. Dose-related increases in both the latter indices were observed. The total cadmium intake resulting in both metallothioneinuria and beta 2-microglobulinuria was calculated to be approximately 2 g for both sexes. In the second study, the dose-response relationship between urinary cadmium and metallothioneinuria or beta 2-microglobulinuria was evaluated in the same population. Prevalence rates increased proportionally with increasing urinary cadmium (Cd-U). The values of Cd-U corresponding to the prevalence rates of metallothioneinuria in the non-exposed population were calculated to be 4.2 micrograms/g creatinine for men and 4.8 micrograms/g creatinine for women; for beta 2-microglobulinuria the corresponding figures were 3.8 micrograms/g creatinine for men and 4.1 micrograms/g creatinine for women.


Integrated index of occupational exposure to cadmium as a predictor of kidney dysfunction. In a study carried out in an alkaline battery factory, the study group consisted of 141 factory workers exposed to cadmium, while 206 workers in the textile industry constituted the control group. Cadmium in blood (Cd-B), cadmium in urine (Cd-U) as well as beta 2-microglobulin and retinol-binding protein (RBP) in urine were determined. Exposure to cadmium in the factory was high. In 1988, Cd-B concentrations in different departments averaged 11.2-29.9 micrograms/l. To evaluate the admissible period of occupational exposure to cadmium, an integrated exposure index [Cd-B (micrograms/l) x years of exposure] is proposed. According to the dose-response relationship, an increase in low molecular weight protein excretion in urine can be expected in 10% of subjects at an integrated exposure index of about 300 micrograms/l x years of exposure. The data obtained confirmed the validity of the recommended health-based limits for occupational exposure of 10 micrograms/l and 10 micrograms/g creatinine for Cd-B and Cd-U respectively.


Critical levels of blood and urinary cadmium, urinary beta 2-microglobulin and retinol-binding protein for monitoring cadmium health effects. The critical levels for monitoring cadmium health effects in 358 workers engaged in ore crushing/roasting (cadmium concentration in the workplace air 2.5-6.5 mg/m3), dry smelting (10.8-23.3 mg/m3), cadmium melting (0.01-0.16 mg/m3), and ingot making (2.8-4.7 mg/m3), were investigated. Exposure parameters such as blood and urinary cadmium were determined, together with biological parameters such as proteinuria, amino acids, glucose, beta 2-microglobulin, retinol-binding protein, albumin, plasma beta 2-microglobulin, creatinine clearance, tubular reabsorption of beta 2-microglobulin and phosphate, and blood and urinary levels of zinc, copper and lead. Factor analysis and stepwise regression analysis were then applied to the data to classify parameters and to find the main contributing parameter. Blood and urinary cadmium, urinary beta 2-microglobulin, retinol-binding protein and the ratio of urinary beta 2-microglobulin to albumin were also subjected to multiple correlation analysis, multiple regression analysis and the Chi-square test was applied to contingency tables. It is concluded, based on the data, that cadmium health effects may be assessed by using the following critical levels: blood cadmium: 10 micrograms/l, urinary cadmium: 10 micrograms/g creatinine; urinary beta 2-microglobulin: 2000 micrograms/g creatinine, urinary retinol-binding protein: 200 micrograms/g creatinine and a ratio of urinary beta 2-microglobulin to albumin of 0.001.


Assessment of the causality of the cadmium--protein relationships in the urine of the general population with reference to the Cadmibel study. The assessment of acceptable exposure levels to cadmium in the work or general environment frequently relies on the analysis of the relationships between urinary cadmium (an indicator of the body burden) and proteins used as markers of nephrotoxicity. A possibility which cannot be excluded a priori is that the relationships between cadmium and proteins in urine might sometimes result from renal dysfunction unrelated to cadmium toxicity. To test this hypothesis, we have measured cadmium in the urine of 114 pregnant women of whom about 20% had developed a reversible tubular proteinuria. Cadmium excretion was correlated significantly with age but not with duration of pregnancy nor with low molecular weight urinary proteins. This indicates that tubular dysfunction unrelated to cadmium exposure does not necessarily increase cadmium excretion. Hence, these data support the conclusion of the recent Cadmibel Study on the renal tubular effects of cadmium on the general population of Belgium.


The World Health Organization study on health effects of exposure to cadmium: morbidity studies. Studies according to the protocol of the WHO Regional Office for Europe were performed in Germany, the Netherlands and Belgium. Pilot studies were performed in Czechoslovakia, Hungary and Poland. The results of the Belgian study are described elsewhere; some striking results of the other studies are reported here. The highest levels of cadmium in blood (Cd-B) were reported in a cadmium-polluted area in Hungary, the lowest in a non-polluted urban area. In Poland, levels were enhanced in polluted and non-polluted areas. The highest levels of cadmium in urine (Cd-U) were found in Hungary, the lowest in the Netherlands. In nearly all the studies significant increases in both Cd-B and Cd-U were found in cadmium-polluted areas. The picture is less clear with regard to the biological effect parameters. The renal parameters were sometimes significantly enhanced for the polluted areas, but sometimes the opposite was reported. Because of the many confounding variables, stratification at least by smoking behaviour, sex and age is necessary if firm conclusions are to be reached. A better approach, however, is to use multivariate regression analysis. This technique allowed the calculation of the relation between Cd-U and age in the German and Dutch studies, and between Cd-U and age in the German and Dutch studies, and between Cd-U and NAG, AAP, Alb-U and Creat-S levels.


Health effects of cadmium with special reference to studies in Japan. This paper gives an overview of the health effects of cadmium with special emphasis on the natural history of cadmium poisoning. The following questions are discussed: (1) Do the renal changes caused by cadmium result in both glomerular and tubular dysfunction? (2) What is the fate of these renal changes? (3) What is the relationship between renal changes and osteomalacia? (4) Is there a dose-response relationship between cadmium exposure and renal dysfunction? (5) What is the solution to the enigma of cadmium and respiratory cancer? Although innumerable papers have been published, the above questions remain unanswered. The natural history of cadmium poisoning is ironically more complicated than that of communicable diseases in man despite the fact that the element is static and not propagated in living organisms.


Is cadmium genotoxic?

Is cadmium genotoxic? Previous evidence that cadmium(II) causes gene mutations in bacteria or mammalian cells was weak. However, alterations in protocol have recently led to better evidence for its mutagenicity, especially in bacteria. Mutagenicity results may be confounded by tolerance mechanisms. Exposure of DNA in vitro to Cd2+ or to Cd2+ hydrogen peroxide does not result in strand breaks or alkali-labile sites. The fact that bacterial and mammalian cells appear to sustain some type of repairable DNA damage after exposure to Cd2+ suggests that the damage must be caused in an indirect manner. Recently, the ability of cadmium-metallothionein complex to cause DNA strand breaks has been described. Cd2+ also induces a "pro-oxidant state" by causing a depletion of cellular glutathione. This finding is consistent with the role of Cd2+ as a clastogen and may explain its weak mutagenicity at loci which cannot detect complex mutations. Cd2+ can also inhibit DNA repair, and can therefore act synergistically with certain mutagens and, presumably, carcinogens.


Chromosomal effects of cadmium exposure in humans. Cytogenetic studies on subjects occupationally or environmentally exposed to cadmium are reviewed and discussed. After a first report of increased chromosome aberrations in lymphocytes of itai-itai patients from Japan, several studies on workers occupationally exposed to cadmium gave conflicting results. These differences may perhaps be explained by the action of co-factors (e.g., nutritional deficiencies in itai-itai patients; concomitant exposure to other metals in some occupational groups), or by different levels of exposure. In a study on cadmium workers with a wide range of cumulative exposure, as compared with matched controls, an increase in chromosome-type aberrations in lymphocytes, an indicator of cumulative damage, was found only because of the increased rates in the subgroup with the highest cumulative exposure and cadmium burden. As far as environmental exposure is concerned, of two recent reports, one from China is positive for chromosome aberrations and the other, from Japan, is negative for sister chromatid exchanges.


Immunotoxicology of cadmium.

Immunotoxicology of cadmium. A number of investigations have suggested that cadmium may exert immunosuppressive effects in animals even though conflicting findings, due mainly to varying conditions of exposure, have been reported. Overall, cadmium has been shown to enhance humoral immune responses at low levels of exposure, whereas higher ones may result in either no effect or decreased antibody production. By contrast, cell-mediated immunity was more consistently shown to be depressed. Similarly, phagocytosis, natural killer cell activity and host resistance toward experimental infections were markedly impaired in most instances. Very few data are available regarding cadmium immunotoxicity in humans. Hypersensitivity reactions have so far not been described. No immune alterations were found to be associated with "chronic cadmium disease", whereas a depressed phagocytosis, the clinical relevance of which remains to be established, was recently documented in cadmium-exposed workers. Further investigations are therefore needed to determine how immunotoxic cadmium actually is and what health consequences are to be expected in occupationally or environmentally exposed humans.


Cadmium exposure in rats and tumours of the prostate. Recently, we completed three chronic studies in rats indicating that cadmium exposure can induce tumours of the prostate. In the first study, s.c. cadmium exposure increased prostatic tumour incidence only at doses below the threshold for cadmium induction of testicular dysfunction (5.0 mumol/kg). In a second study, prostatic tumours were elevated at higher doses of cadmium (30 mumol/kg, s.c.) if testicular dysfunction was prevented by zinc treatment. Finally, dietary cadmium (25-200 micrograms/g) increased prostatic neoplastic lesions. Thus it appears that cadmium produces prostatic tumours only if testicular function is maintained. Accumulation and retention of prostatic cadmium appears to be highly androgen-dependent. Furthermore, metallothionein, a protein associated with tolerance to cadmium, may be deficient in the rat prostate, and the prostatic metallothionein gene, at least in the ventral lobe, may be unresponsive to metal stimuli. The finding of prostatic cancer in cadmium-treated rats clearly supports a possible role for exposure to cadmium in human prostatic cancer.


Induction of tumours of the haematopoietic system by cadmium in rats. Several of our recent studies in rats indicate an association between exposure to cadmium and haematopoietic tumours. In the first study, male WF rats received dietary cadmium (0-200 micrograms/g cadmium as cadmium chloride) for up to 77 weeks. A dose-related increase in large granular lymphocyte (LGL) leukaemia was observed with a maximal incidence in rats fed 100 micrograms/g cadmium. In a second study, male F344 rats received a single high dose of cadmium chloride (30 mumol/kg, s.c.) and were observed for 90 weeks. The high natural incidence of leukaemia in these rats (24%) was markedly reduced (6%) by this dose of cadmium. The paradoxical effects of cadmium on haematopoietic tumours may be the result of a dose-related spectrum of lymphotoxicity ranging from cell-specific cytotoxicity and carcinogenicity to destruction of key progenitor cell populations.


Pulmonary carcinogenicity of cadmium by inhalation in animals. Although, the tumorigenic effect of cadmium after subcutaneous and intramuscular injection has been known since 1961, lung tumours after inhalation exposure were reported only more than 20 years later by Takenaka et al. (1983), using cadmium chloride aerosols. Based on these results, aerosols of cadmium sulfate, cadmium oxide and cadmium sulfide pigment were investigated for carcinogenic effects after inhalation exposure in rats, hamsters and mice. All the cadmium compounds tested appeared to have a very similar carcinogenic potency in the rat lung, whereas no exposure-related tumours occurred in hamsters and in mice only cadmium oxide seemed to increase the lung tumour rate. Subsequent analytical investigations of the aqueous suspension of cadmium sulfide used to generate the aerosol showed that it was soluble in water to some extent as a result of photo-oxidation. The exposure atmosphere therefore actually consisted of a mixture of sulfide and sulfate, and the observed lung tumour rate must be attributed to a combined action of the two compounds. For this reason, a clear-cut carcinogenic effect of cadmium sulfide could not be proved by this inhalation study, but because of the high carcinogenic potency of cadmium ions in the rat lung and because cadmium sulfide retained in the lung is bioavailable to a certain extent, aerosols of this compound should be regarded as a probable human carcinogen.


Validity and limitations of animal experiments in assessing lung carcinogenicity of cadmium. Several cadmium compounds have been observed to induce in rats, but in rats only, a dose-dependent increase in lung cancer. A similar sensitivity to lung cancer induction in both humans and rats can be deduced from a comparison of the histogenesis of tumours and the dose response to radiation, since similar numbers of DNA lesions are produced. Since the carcinogenic action of cadmium is limited to the site of deposition, the toxicokinetics of inhaled particles in human and rodents are discussed in relation to the exposure of the respective target cells in both species. It is stressed that the rat may be much more sensitive to the induction of cancer following the retention of poorly soluble compounds. A comparison of the possible dose-effect response in humans and the dose response in rats showed that the shape of the "dose" response cannot be extrapolated. Finally, clonogenicity and DNA repair of tracheal cells sublethally exposed in vitro to cadmium differ significantly in rats and hamsters. This may explain why hamsters exposed in vivo do not develop tumours.


Methodological aspects of the epidemiological association between cadmium and cancer in humans. The main epidemiological evidence of an association between cadmium exposure and human cancer comes from studies on occupational groups such as smelter and nickel-cadmium battery workers. Lung and prostate are the sites more frequently reported to be at increased risk of cancer, but the various epidemiological studies do not enable any definite conclusion to be reached. Methodological problems in the interpretation of these studies include: (i) the assessment of exposure to cadmium; (ii) the dose-response relationship between indicators of cadmium exposure and cancer risk; (iii) concomitant exposure to occupational carcinogens, mainly nickel and arsenic; (iv) confounding by non-occupational risk factors, such as smoking and diet; and (v) interaction between cadmium and other exposures. The confounding effect of smoking and diet is particularly interesting since they may act both as additional uncontrolled sources of cadmium and as independent cancer risk factors.


Is cadmium a human carcinogen?

Is cadmium a human carcinogen? Continuing observations on cadmium-exposed workers have failed to yield evidence of an increased mortality from prostatic cancer, as initially suspected. There is, however, evidence of an increased mortality from lung cancer and, in at least two of the studies, of a dose-response relationship, but interpretation of these studies with regard to the role of cadmium is complicated by concurrent exposure to other known or suspected carcinogens, including arsenic, nickel, beryllium, chromium and heated mineral oils. An update of a long-term cohort mortality study from 17 plants in England employing a wide range of cadmium processes, while confirming an increased lung cancer risk related to intensity of cadmium exposure, shows some evidence of this risk also being associated with exposure to arsenic. It is thus not possible at present to attribute the excess mortality from lung cancer to cadmium owing to the presence of multiple confounding factors in the populations studied. Their role in the 17-plant study is currently being further investigated.


A quantitative assessment of lung cancer risk and occupational cadmium exposure. We have performed a quantitative assessment of the risk of lung cancer from exposure to cadmium based on a retrospective cohort mortality study of cadmium-exposed workers. The findings were analysed using a life-table analysis to estimate standardized mortality ratios (SMRs), and various functional forms of Poisson and Cox proportionate hazards models to examine dose-response relationships. An excess mortality from lung cancer was observed for the entire cohort (SMR = 149,95% CI = 95-222). Lung cancer mortality was significantly elevated among non-hispanic workers, among those in the highest cadmium-exposure group, and among workers with 20 or more years since first exposure. A statistically significant dose-response relationship was evident in nearly all of the regression analyses. Based on our analyses, the lifetime excess lung cancer risk at the current OSHA standard for cadmium fumes of 100 micrograms/m3 is approximately 50-111 lung cancer deaths per 1000 workers exposed to cadmium for 45 years.


Biological monitoring in the occupational setting--relationship to cadmium exposure. Statutory health surveillance of occupational exposure to cadmium exists in most Western countries. For biological monitoring, both indicators of internal dose and indicators of effect are available. Cadmium in urine is an indicator of chronic exposure and essentially reflects the body burden under low-exposure conditions and in the absence of renal damage. Whole blood cadmium is primarily a useful indicator for use in evaluations of recent exposures. Biological threshold limit values for cadmium in urine and blood are based on the correlation of biological levels with thresholds for renal dysfunction. The use of markers of high and low molecular weight proteinuria should be integrated into the health surveillance of cadmium-exposed workers. Priority should be given to the determination of albumin and of proteins such as beta 2-microglobulin, retinol-binding protein and alpha 1-microglobulin. Interpretation of biological monitoring data in terms of the threshold values requires a programme of periodic biological, medical and environmental monitoring.


Biological monitoring of the general population for cadmium. Over 2000 blood samples and about 1000 24-h total food duplicates were collected in 49 non-polluted regions in Japan, and analysed for cadmium (Cd-B and Cd-F). Cd-B increased with age to reach a plateau at 40-59 years, where the geometric mean (GM) Cd-B was 3.2 ng/ml in men and 3.7 ng/ml in women. Smoking also increased Cd-B. The GMs of Cd-F were 43.9 and 37.0 micrograms/day for men and women, respectively, with boiled rice as a major source of cadmium (> 40%). Cd-B correlated significantly with Cd-F when compared on a regional mean basis. Similar Cd-B analyses among non-smoking women showed that Cd-B was lower in Korea (ca. 1.6 ng/ml) and in China (1.3 ng/ml) than in Japan. This observation is in accordance with the fact that rice in Korea (16.1 ng/g dry weight) and China (7.6 ng/g) contained less cadmium than that in Japan (52.5 ng/g). A preliminary follow-up in 1989 suggests a decrease in Cd-B (by ca. 30%) among the Japanese population, probably due to a reduction in cadmium in rice (ca. 14%) and a decreased rice intake.


Quantitative analyses of cadmium: quality assured? Legislation has been a powerful stimulus for measuring the concentrations of cadmium in many different matrices. Unfortunately, much of the quantitative data in the literature is flawed because of a paucity of information on the reliability of sampling and measurement. Non-specific analytical methods, inaccurate calibration, lack of matrix reference materials, poor laboratory technique in general, lack of statistical control, and ignorance of contamination all militate against gathering truly valid data. The implications for bioavailability of chemical and physical speciation also need to be considered, especially in the analysis of airborne particulates and foodstuffs. Effective quality assurance serves several distinct purposes: (1) to allay analysts' concern for the quality of their work; (2) to discharge management's responsibility for the cost and quality of the laboratory's output; (3) to inform users of the quality of the data sets; and (4) to provide archival data and documentation.


Analytical quality control of cadmium and lead in blood and cadmium in urine: results of its implementation during a five-year epidemiological study. Quality-control programmes are very important in assessing the reliability of biological analyses. Such programmes are essential if misleading results in epidemiological studies dealing with low levels of exposure to heavy metals present in the general environment (e.g., cadmium, lead) are to be avoided. Internal and external quality-control programmes for the measurement of cadmium and lead in blood and of cadmium in urine were implemented from 1985 to 1989 in support of a national epidemiological study, Cadmibel (2327 participants), conducted in Belgium to assess the effects of environmental exposure to cadmium and lead on the general population. Apart from these programmes, inter-comparisons between the two participating laboratories were carried out on 10% of the samples. The results of these quality-control programmes met external acceptability criteria, emphasizing the analytical proficiency of these measurements at the relatively low concentrations in the Cadmibel study.


Definition of reference values for Cd-B and Cd-U: methodological aspects and preliminary results. In the present study, a definition of the reference values of blood cadmium (Cd-B) and urinary cadmium (Cd-U) was attempted, adopting the same methodology as that used for Hg-B by ICOH and IUPAC. Papers published from 1976 onwards were reviewed. The majority of the studies were concerned with the formation of control groups for toxicological and epidemiological investigations rather than with the definition of reference values. Since the number of subjects for whom data on cadmium were available was small, only the data on Cd-B were considered. After evaluation, only four studies were found to be suitable for the establishment of tentative reference values for Cd-B. It is essential in all such studies to check the statistical and analytical methods for correctness, and the case-list must be selected taking smoking into account as the main interfering factor. It was found that Cd-B values show less dispersion when geometric means and standard geometric deviations are used instead of arithmetic means and standard deviations.


MCH record maintenance at primary health centre level. Scrutiny of MCH records of 1977-78 and 1988 at PHC level revealed glaring deficiencies in their maintenance e.g. missing of entries., duplicate entries etc. Extent of supervision of service records was extremely low. Record linkages could be poorly established and thus present mechanism of health care delivery could not ensure continuity of care. The level of record maintenance has almost remained same over a decade period. This can be avoided by modifying the information system, making records at the PHC level simple, action oriented with built in system of evaluation and involving community in its maintenance and utilisation.


An enquiry into work environmental status and health of workers involved in production of incense sticks in city of Bangalore. This preliminary study represents 10% of the workers in this occupation in Bangalore. The industry is highly commercial in nature and the city of Bangalore; has the largest number of units in Karnataka State. The study provides base line data relating to some morbidity conditions for future comparisons. Low back ache, tiredness, head ache, irritation in the eyes, sleeplessness, joint pains, chest pain, postural giddiness, persistent running nose, abdominal pain, cough and tremors of hands, were some of the common conditions elicited among the workers. Some of the conditions were identified to be possibly related to various processes within the industry. Particularly low back ache and irritation in the eyes (rolling and dipping), tremors of hands (packing). It is very likely that in the final stages when certain chemical ingredients are added which finally give the scent, the chances of pollutants entering either through skin or inhalation is possible. Environmental monitoring has not shown any appreciable dust hazard. The study has helped in identifying some of the areas in the work environment which required improvement. There is a need for social workers, medical personnel and industrial hygienists to explore the possibilities of minimizing possible hazards. A national sampling survey in other parts of the country might also be beneficial.


Respiratory illness and tuberculin sensitivity among children below 15 years of age in a rural community. The incidence of respiratory illness and tuberculin sensitivity of children below 15 years were studied among 245 families in village Chinimore and the observations were compared between two groups families keeping livestock and families non-keeping livestock. There were 135 (out of 446) children with respiratory illness with 30.2% incidence and 45 (out of 187 tuberculin tested) children were positive to Mantoux test. Families keeping livestock had statistically significantly more (P 25.18 of 0.1% level) tuberculin sensitive children.


Attitude of Indian urban adults towards mental illnesses. In an urban area of Jhansi 238 adults were interviewed to asses their views regarding mental illnesses. Mental illness was not perceived as a serious disease. Cancer was perceived as the most serious disease. Worries, faulty upbringing, overwork were perceived as a cause of mental illness by majority. Early identification sings of mental illness described by them were difficulty in sleeping, changes in facial expression and feeling of impending mental imbalance. Marital alliance with them was not favoured. However, a sympathetic attitude towards mental patients was favoured. Avoiding tension, adapting oneself to circumstances, a consulting elders were considered as preventive measures against mental illness by majority.


Distribution and trends of HIV infection in blood donors of four metropolitan cities. Screening for HIV infection has been made mandatory for every unit of blood collected for transfusion in major cities of the country, having facilities for such screening. Results of HIV screening among blood donors received from the 4 Metropolitan cities of Delhi, Bombay, Calcutta and Madras have been analysed year wise from 1989 to 1991 to determine the magnitude and trends of HIV infection in different categories of blood donors and the seropositivity rates seems to be increasing over time. Universal coverage of HIV screening for donated blood has not been fully achieved and the justification and urgency for achieving complete coverage is highlighted.


Awareness about sore-throat, rheumatic fever and rheumatic heart disease in a rural community. This I.C.M.R. study was conducted in 74 villages of Chiraigaon block, Varanasi, U.P., during the period March 1983 and December 1986. Before and after health education awareness survey about sore throat, rheumatic fever and rheumatic heart disease was carried out by interviewing 315 persons by stratified random sampling. The study shows that there is significant increase in the knowledge about most of the symptoms, causes, consequences and preventive measures of sore throat, rheumatic fever and rheumatic heart disease. This paper highlights the importance of health education as a vital component of rheumatic heart disease control programme.


Study of leprosy among slum dwellers in Pune. Part-I. Prevalence. While conducting a point prevalence total population survey in Ghorpuri slum in Pune, the overall prevalence or leprosy was 9.16 per thousand. The prevalence rate varied in different bastis with Madari basti having a very high prevalence rate of 17.31 per thousand and showing clustering. Prevalence was highest in age group 31-40 years, females, Muslims, Widower/widow, skilled workers, illiterates and primary school educated and the lower socio-economic groups. Joint families had the highest prevalence of leprosy (20.83/1,000) and also higher prevalence was seen in families with more than 7 members.


Salmonella in foods of animal origin: enterotoxigenicity and antibiogram. A total of 82 strains of Salmonella belonging to 17 different serotypes recovered from foods of animal origin were in this study. Out of 39 cell free culture supernatants (CFCS), tested for enterotoxigenicity, 26 (66.67%) were positive in rabbit ileal loops. None were found positive for enterotoxigenicity in infant mouse model. According to the disc diffusion methods of testing, gentamycin, nalidixic acid and chloramphenicol were found to be most effective against Salmonella organism. Erythromycin and oxytetracycline were least effective.


Relations among verbal and nonverbal cognitive skills in normal language and specifically language-impaired children. This study tested the hypothesis that specifically language-impaired (SLI) children have a qualitatively different cognitive system from that of normal language (NL) children. Twenty NL and 20 SLI children between the ages of 4:2 (years:months) and 5:11 were presented with experimental language-learning measures, experimental nonverbal measures, and verbal and nonverbal norm-referenced tests. A confirmatory analysis of the covariance matrix structures of the two subject groups indicated that relations among cognitive skills differed between NL and SLI children. In addition, a planned comparison indicated that the relation between nonverbal rule-induction and novel bound-morpheme learning differed significantly between groups. The findings indicate that a "qualitative-differences" model of specific language impairment better accounts for the co-occurrence of poor verbal and poor nonverbal cognitive skills in SLI children than a "low-normal" model.


Use of the Clark-Madison Test of Oral Language with the hearing-impaired: a content validity and comparative study. This study examined the content validity of the Clark-Madison Test of Oral Language (CMTOL) as a measure of nonwritten expressive language with hearing-impaired children. Twenty severely hearing-impaired children were administered the CMTOL using total communication. All test administrations were considered valid. The content of the test was generally found to be valid. The content validity of selected items is discussed. A comparison of the performance of the hearing-impaired to a group of normal-hearing respondents revealed a different profile of strengths and weaknesses than did intragroup analysis.


Voice therapy practices and techniques: a survey of voice clinicians. Members of the American Speech-Language-Hearing Association Special Interest Division on Voice were asked to rate statements which emanated from a previously conducted national survey regarding the practice of voice therapy (Larson and Mueller, 1991). Respondents rated eight data-based statements on a five-point scale as to agreement/disagreement. Results indicated strong agreement with previous findings with the exception of the item addressing treatment time. Implications of these results are discussed.


Study of leprosy among slum dwellers in Pune. Part II--Disabilities. While conducting a leprosy survey in an urban slum in Pune 45 cases of leprosy were detected in a population of 4915 and only 7 of these cases had some disability. Disability rate in the leprosy cases was 15.56 percent, and maximum number had Grade 2 disability of hands or feet. Disability was higher in the higher age groups, males, Hindus, widower/widows, unemployed and lower socio-economic classes. Majority of the cases had a very low Disability Index DI (2) between 0.10 to 0.69 which is heartening and proves the successful implementation of the National Leprosy Eradication Programme.


Prevalence of diarrhoeal diseases amongst tribals of Car Nicobar Island, India. In a cross sectional study of total 14514 tribal Nicobarese people of Car Nicobar Island, an union territory of India, situated in Bay of Bengal, morbidity, mortality and treatment practices of diarrhoeal diseases of under-five children were surveyed. The incidence of diarrhoea (0.2 episode/ch.year), Crude death rate (3.6/1000) and IMR (31/1000 live births) were exceedingly low as compared to SouthEast Asian Countries including mainland of India. ORS utilisation rate was high (41%) as compared to the National figure (12.0%). This is the first study of it's kind carried out in this island and amongst the Nicobarese tribe in India. A preliminary study carried out among the mothers of the hospitalised children indicated that protective behaviours like breast feeding, hand washing, use of chlorinated water and proper disposal of stool were regularly being practiced by the community traditionally. An in-depth study on risk factors of diarrhoea in this island can yield useful clue for describing the same.


Cerebral amino acids and energy metabolites in the growth retarded rat fetus under normoxia and hypoxia. The effect of intrauterine growth retardation (IUGR) on striatal energy metabolites and amino acid concentrations was studied in the fetuses of eight nulliparous rat dams after uterine artery ligation on day 18 of gestation. On day 22 (term = 23), four dams were subjected to normoxia and four to hypoxia (10% oxygen) for 58 min, while monitoring hemodynamics and blood gases. After decapitation of the dam, fetuses were delivered by sectio and decapitated. The measured parameters in the dams were stable under normoxia but exhibited decreased oxygen availability under hypoxia. Striatal energy balance was preserved in IUGRs, both under maternal normoxic and hypoxic conditions, compared to appropriately grown (AGA) littermates. Under maternal normoxia, the striatal concentration of aspartate was reduced (P < 0.01) in IUGRs and the level of alanine was increased (P < 0.01) as compared to AGAs. Under hypoxia, the level of GABA was higher in IUGRs (P < 0.01). Lactate was increased in all fetuses under hypoxia. It is concluded that striatal energy metabolism is preserved in IUGR rat fetuses in late gestation under both maternal normoxia and hypoxia. Amino acid metabolism, however, is disturbed and depends on the degree of growth retardation and on the severity of perinatal stress.


Effects of alveolar hypoxia on the pulmonary circulation and lung mechanics after cromolyn sodium and U-60,257 in lambs. Because alveolar hypoxia (HYP) triggers pulmonary mast cell degranulation with elaboration of vasoactive mediators such as leukotrienes, we investigated the effects of aerosolized cromolyn sodium (CS), a mast cell stabilizing agent, and U-60,257(U) (a leukotriene blocker) on the circulation, lung mechanics and thromboxane (TXB2) levels in 11 lambs during acute exposure to HYP. Studies were performed in awake, chronically instrumented animals, once after placebo (saline) and again after CS (100 mg; n = 5) or U (90 mg; n = 6). Pulmonary arterial pressure increased 42% during HYP after saline, and 32% and 19% after CS and U, respectively. Pulmonary vascular resistance did not change during HYP after CS or U. Systemic arterial pressure was unchanged after saline and CS but decreased after U; systemic vascular resistance dropped after both CS and U. No changes were seen in tidal volume, lung compliance or airway resistance during HYP after saline or either drug, but minute ventilation increased during HYP in all studies. TXB2 increased during HYP after saline in both studies and was not altered by CS. In contrast, after U, TXB2 decreased. Thus, U more effectively blunted the pulmonary vascular response to HYP than CS and resulted in mild systemic hypotension. The drop in TXB2 after U suggests leukotriene-induced thromboxane synthesis contributes to regulation of pulmonary, and possibly, systemic vasoactivity.


Corticotropin releasing hormone concentrations in umbilical cord blood of preterm fetuses. Corticotrophin releasing hormone (CRH), dehydroepiandrosterone sulfate (DHEAS) and cortisol were measured in umbilical cord plasma obtained from 90 preterm and 98 term fetuses. Maternal plasma was obtained from 23 women who delivered preterm and from 23 women matched for gestational age who ultimately delivered term infants. Mean umbilical cord plasma CRH concentration was significantly higher in the preterm fetuses (n = 69, 538 +/- 63 pg/ml) compared to the term fetuses (n = 98, 280 +/- 22 pg/ml, P < 0.01). Mean DHEAS level in the preterm fetuses was 208 +/- 22 mg/dl (n = 56), cortisol level was 7 +/- 1 mg/dl (n = 58). Umbilical plasma CRH concentrations (808 +/- 170 pg/ml) were significantly higher at 24-27 weeks than at 28-31 or 31-34 weeks gestation. Cortisol levels (12 +/- 3 micrograms/dl) were highest at 24-27 weeks. Mode of delivery and the presence of labor did not affect fetal CRH levels. The highest fetal CRH levels were measured in the pregnancies complicated by hypertension as well as prematurity; however, fetal CRH levels remained higher in the preterm group compared to the term group when hypertensive pregnancies were excluded. Maternal plasma CRH levels were significantly higher in the group that delivered preterm compared to women who delivered at term matched for gestational age (1058 +/- 184 pg/ml compared to 456 +/- 71 pg/ml, P < 0.00).(ABSTRACT TRUNCATED AT 250 WORDS)


Maternal fever at parturition and its effects on the newborn rabbit. The febrile response to administration of endotoxin has been reported to be suppressed in both pregnant animals at term and in their newborn. In a previous study we found that newborn rabbits under appropriate conditions to develop a febrile reaction to injected endotoxin. In this investigation we sought to discover whether pregnant rabbits at term had a febrile response to endotoxin, and if so, its effect on thermoregulation in their newborn. Endotoxin (E. Coli LPS) was injected into 19 pregnant rabbits at term. Six delivered spontaneously within an hour. At one hour, 13 were given oxytocin, and a further 8 delivered within five minutes. The colonic temperature (Tc) of the mothers before endotoxin administration and at delivery, and of their young, was measured. The results were compared with those of 10 pregnant rabbits not given endotoxin, and their young. Within 15 min of delivery newborn rabbits from each litter were placed on a thermal gradient to assess their thermoregulatory responses. Pregnant rabbits at term developed an impressive febrile response to injected endotoxin and their young were born with high colonic temperatures. Newborn rabbits from febrile mothers selected higher thermal environments and maintained a higher colonic temperature than the newborn of non-febrile mothers. We conclude that fever is sustained in the first hours of life in the newborn of mothers injected with endotoxin. The possible mechanisms are of considerable interest. None of the pregnant rabbits died after endotoxin administration, but the stillbirth rate was 50% compared with 10% in non-febrile does.


The effects of gestational age and labour on the breathing and behaviour response to oxygen and umbilical cord occlusion in the fetal sheep. We tested the hypothesis that the continuous breathing response to oxygen or oxygen plus umbilical cord occlusion, in the fetal sheep, could be modified by gestational age or labour. We studied 35 chronically instrumented fetal sheep on 84 occasions during late gestation (124 to 141 days), using our window model (Rigatto, 1984). After a resting cycle (1 low-voltage followed by 1 high-voltage electrocortical activity epoch), the fetal lung was distended via an endotracheal tube using mean airway pressure of about 30 cm H2O. Inspired nitrogen, and 100% O2 were given to the fetus during one cycle each. While on 100% O2 the umbilical cord was occluded using a balloon cuff. We found that: (1) the continuous breathing response to 100% O2 occurring in 8% of the experiments at a gestational age less than 130 days, in 25% from 130 to 134 days and in 45% at gestational ages greater than 134 days (P < 0.01); (2) at similar gestational age intervals the breathing responses to umbilical cord occlusion were 67%, 84%, and 100% (P < 0.01); and (3) in the presence of labour, 45% of the experiments responded to O2 with continuous breathing as compared to 23% in the absence of labour (P < 0.01). Cord occlusion did not affect these values. Because the highest PaO2 achieved increased significantly to 128 days but not thereafter it is unlikely that these results can be explained on the basis of an increase in PaO2 alone. We speculate that there is an age related maturation of the inhibition of breathing normally present in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of admission weight on neonatal mortality amongst hospitalised neonates in Calcutta. The study was conducted on 785 neonates aged up to 28 days to evaluate the influence of admission weight on mortality. It was observed that there were 200 (25.5%) cases of septicaemia, 134(17.1%) of diarrhoea, 120(15.3%) each of prematurity related conditions and neonatal jaundice, 117(14.9%) of respiratory diseases and 94 (11.9%) cases of convulsion. There were total 182(23.18%) deaths comprising 70(38.5%) from prematurity related conditions, 40(22%) from diarrhoea, 35(19.2%) from respiratory diseases, 26(14.3%) from septicaemia, 8(4.4%) from neonatal jaundice and 3(1.6%) deaths from convulsion. The incidence of deaths among neonates weighing less than 2500 g on admission was 59.2% in diarrhoeal diseases, 53.4% in respiratory diseases and 44.6% in other conditions compared to those of 10%, 8.2% and 7.1% respectively in neonates having admission weight more than 2500 g. The findings are statistically significant. The results of the study indicate that low admission weight should be considered as a predictor of mortality among neonates.


Epidemiological study of the victims of vehicular accidents in Delhi. The mortality and morbidity connected with road traffic accidents are increasing at an alarming rate throughout the world as a direct result of the rapid industrialization and increase of fast moving vehicles combined with lack of traffic sense of road users of this country. Epidemiological aspects manifested in vehicular accidents in New Delhi during the year 1983-84 are illustrated here.


Results of delayed operations for ruptured supratentorial aneurysms in 22 consecutive patients. Twenty-two patients with surgically treated ruptured aneurysms were reviewed retrospectively regarding age, sex, aneurysm site distribution, clinical grading, rebleeding, timing of surgery and long term results. The most common aneurysm site was in the Anterior Communicating artery (44%). The mean time between aneurysmal subarachnoid hemorrhage and surgery was 20 days. There were 4 cases with intraoperative rupture. The outcome was favorable in 63.6 per cent after a mean follow-up of 21 months. The overall mortality rate was 22.7 per cent. The results may be improved by an early, well planned operation.


Osseous adenocarcinoma of unknown primary site: study of survival and prognostic factors. A prospective study of 149 patients suffering from adenocarcinoma of unknown primary site (ACUPS) of bone was carried out. The tumors are classified as 63 extraspinal, 67 spinal and 19 mixed involvement. Upon meticulous physical examination, Virchow's node was detected in 15 cases, rectal shelf in 11 cases and hepatomegaly in 44 cases. Blood chemistry showed elevation of alkaline phosphatase (> 3 sigma units) in 98 cases and chest roentgenogram showed pulmonary lesions in 23 cases. Treatment was surgery and radiotherapy in 64 and two cases respectively. In all of these patients histological findings of the biopsy or resection specimen had confirmed the diagnosis of adenocarcinoma. Among 124 evaluable patients, overall survival was analysed using Kaplan-Meier life table analysis. Survival rates at one, two and four months after diagnosis were 80.7, 60.5 and 25 per cent with a mean and median survival times of 90 and 77 days respectively. Statistical analysis was also performed to ascertain the prognostic importance of the following variables: age, gender, Virchow's node, rectal shelf, hepatomegaly, serum alkaline phosphatase, pulmonary lesion, and multiplicity and site of the osseous lesions. The presence of pulmonary lesion or hepatomegaly significantly produced unfavorable impact on the duration of survival (p = 0.0004 and 0.0150, respectively) while other remaining factors had not.


Agranulocytosis and aplastic anemia among Ramathibodi Hospital patients. A one-year prospective prevalence study on aplastic anemia and agranulocytosis was performed in Ramathibodi Medical School. A total of 91,581 complete blood counts were screened for potential cases of aplastic anemia and agranulocytosis according to defined criteria. Nineteen cases of aplastic anemia and five cases of agranulocytosis were found. The prevalence of the two conditions was discussed.


Comparative efficacy of spiramycin and erythromycin in acute exudative tonsillitis in adults: a randomized controlled trial. A randomized control trial was designed to compare the efficacies of spiramycin given one gram twice daily and erythromycin given 500 mg thrice or four times daily in the treatment of acute exudative tonsillitis in adults whose ages were over 13 years old from January 1989 to January 1991 at a community clinic. A total of 120 cases were enrolled in the study. Fifty-three patients received spiramycin while 67 received erythromycin. Group A beta-hemolytic streptococci (GABHS), S. aureus, and positive titer of Mycoplasma pneumoniae were detected in 19, 47 and 8 per cent in spiramycin group and 21, 36 and 11 per cent in erythromycin group respectively. GABHS were totally eradicated on day 3 of treatment in both groups through eradication of S. aureus was slightly slower initially in the spiramycin group. Marked improvement was similarly achieved in both groups after 3 days of therapy. Dyspepsia was felt in 34.4 and 8.2 per cent of erythromycin and spiramycin groups respectively but was tolerable by most patients. We concluded that spiramycin given twice daily was as effectively as conventional erythromycin but spiramycin is more convenient to administer and causes much less gastro-intestinal side-effect.


Endoscopic removal of stone in patients with retained common bile duct stone and T-tube after cholecystectomy. Is it justified? Fifteen patients with retained common bile duct (CBD) stones and T-tube and twenty patients with CBD stones without T-tube had stones removed by endoscopic method. The result of endoscopic sphincterotomy, stone extraction, stone clearance and complication in patients with T-tube was similar to the results in patients without T-tube. The presence of T-tube did not create much difficulty in stone removal and the successful rate of 86.6 per cent (13/15) was satisfactory. Endoscopic removal of retained stones in patients with T-tube is recommended when retrieval via T-tube is not available since the later has fewer reported complications with very low mortality compared to the endoscopic technique.


Abnormal glucose tolerance and blood pressure in Khon Kaen. To quantify the association of abnormal glucose tolerance with hypertension, a population based study was carried out in subjects aged 30-65 years with oral glucose tolerance and blood pressure measurement compared with clinic based known diabetics. In males, subjects with diabetes (newly diagnosed and clinic based) had increased systolic and diastolic blood pressure with clinical significance compared to normal. The diastolic blood pressure in diabetic males was higher than normal but was not different from IGT. In females, the differences were observed between normal vs IGT, and diabetes. The differences were independent of age and obesity. The prevalence of hypertension also increased in diabetic patients, especially for systolic hypertension.


Inflammatory aortic aneurysm: a case report and review of literatures. A case of an uncommon variant of aortic aneurysm, inflammatory type, is reported. A 51-year-old Thai male presented with a pulsatile abdominal mass associated with pain. Ultrasonography demonstrated infrarenal abdominal aortic aneurysm preoperatively and operative findings revealed dense fibrous tissue around the lesion. Serological tests for syphilis and bacteriological studies of aneurysm contents were all negative. Aneurysmorrhaphy was done, using Dacron straight graft, and two serious complications developed at six and two months interval: aortocolonic and aortoduodenal fistulae. However, the patient survived the three operations. Definite diagnosis of inflammatory aortic aneurysm was confirmed by typical pathological findings. Clinical presentations, operative and pathological findings were compared to previous literature.


Nutritional and lactational regulation of fertility in sows. Two major conclusions were drawn from early studies on lactating sows. First, gonadotrophin secretion is suppressed during lactation and this constitutes the primary block to ovarian function and lactational oestrus. Second, in addition to the suckling stimulus per se, nutrition and changes in body condition during lactation have critical effects on post-weaning fertility of sows. Considerable progress has been made in defining the mechanisms that mediate the inhibitory effects of lactation on ovarian development. In sows, active secretion of luteinizing hormone (LH) constitutes an important luteotrophic signal throughout pregnancy. LH secretion may therefore increase in the immediate postpartum period in the suckled sow. In the absence of suckling, this high rate of LH secretion can result in the development of highly oestrogenic but often cystic follicles in the immediate postpartum period. Together with data from studies involving treatment with exogenous gonadotrophins or luteinizing-hormone-releasing hormone (LHRH), this indicates that ovarian sensitivity is not compromised during lactation in sows. The inhibitory effects of suckling on LH secretion, typical of established lactation, are imposed during the first 72 h post partum and from this time the inhibitory mechanism is at least partly opioid dependent. In two recently completed studies, however, it has not been possible to block the development of the suckling-induced suppression of LH by treatment with the opiate antagonist, naloxone, suggesting that other inhibitory mechanisms are involved. Differential regulation of LH and follicle-stimulating hormone (FSH) secretion is evident during lactation, probably as a consequence of ovarian inhibitory, inhibin-mediated control of FSH but not of LH secretion. There is still very little direct evidence for the mechanisms by which the metabolic state of lactating sows affect fertility after weaning. Low plasma insulin, glucose and insulin-like growth factor 1 (IGF-1), and high growth hormone (GH) and cortisol concentrations in sows in a catabolic state are all potentially involved. In lactating sows with a reasonable energy balance, the inhibitory neural effects of suckling are probably more potent inhibitors of LH secretion than are the metabolic demands of milk production.


Manipulation of reproduction in sheep.

Manipulation of reproduction in sheep. Active immunization of cyclic ewes against androstenedione (using melatonin, Fecundin) has been shown to increase reproductive output by about 30 extra lambs per 100 ewes put to the ram in UK sheep flocks. However, this technique has not been widely adopted within the industry. One possible reason for this is that it results in an unacceptable incidence of triplet births, even though the litter size distribution is similar to that obtained for untreated flocks with the same overall mean lambing percentage. The use of progestagen sponges plus pregnant mares' serum gonadotrophin (PMSG) for the induction of out-of-season breeding in ewes is associated with a number of recognized shortcomings. A possible reason for the variability in conception rates is the high incidence of complete embryo loss or fertilization failure in ewes that are induced to superovulate after treatment with the doses of PMSG required to promote a high oestrous response. Recent studies have indicated that slow release implants of melatonin (Regulin) can advance the onset of the breeding season of commercial sheep flocks, but only by about 4 weeks. This means that the optimum treatment window varies according to the natural breeding season characteristics for the breed. Nevertheless, this treatment appears to overcome a number of the shortcomings of progestagen sponges plus PMSG. It also produces a modest increase in litter size per ewe pregnant (about 15 extra lambs per 100 ewes) without the wide variation in birth types and birth weights associated with PMSG. The development of a laparoscopic procedure that improves conception rates after intrauterine insemination of frozen semen allows comparisons of genetic merit across flocks. This should promote far greater rates of genetic improvement for traits of high economic importance than those achieved by within-flock selection and in the last two years has allowed the development of sire-referencing schemes within the major terminal sire breeds. Laparoscopic procedures for the collection and transfer of embryos in sheep now have the potential to overcome many of the limitations of more invasive surgical approaches, although the unpredictability of superovulatory responses remains a particular obstacle to full exploitation of multiple ovulation embryo transfer (MOET) for genetic improvement through the female line.


Control of ovarian function in cattle.

Control of ovarian function in cattle. In cattle, ovarian function is controlled by complex local and systemic feedback mechanisms involving gonadotrophins from the pituitary gland and steroids and proteins from the ovaries. This control system ensures that in more than 96% of females, only one follicle will ovulate per oestrous cycle. Follicular growth and development in cattle occurs in a wave-like pattern, with two or three waves of follicles growing and regressing per oestrous cycle. Each wave is characterized by the emergence, from a pool of growing follicles, of a large dominant follicle which reaches a mature stage of development and may be induced to ovulate and form a functional corpus luteum with a single treatment of either human chorionic gonadotrophin (hCG) or gonadotrophin-releasing hormone (GnRH). The growth of this dominant follicle is associated with a marked reduction in both the number and growth of subordinate follicles in both ipsi- and contralateral ovaries, suggesting a systemic exertion of 'dominance'. The dominance concept is further supported by the observation that the subsequent wave of follicular growth cannot be detected until after the start of the regression of the previous dominant follicle. Furthermore, the dominance mechanism does not involve an action of inhibin, as previously proposed. In addition, in cattle, inhibin may not have a primary role in the control of follicle-stimulating hormone (FSH) release, unlike its role in other species such as sheep. Gonadotrophins provide the primary endocrine drive for the growth of follicles > 2 mm in diameter, but it is now becoming evident that other systemic and locally produced factors profoundly influence ovarian function. For example, short-term treatment of cattle with recombinant bovine somatotropin (BST) can double the number of small (< 5 mm) antral follicles without altering the pattern of circulating gonadotrophin concentrations. These follicles appear to be fully functional since they can be stimulated to develop further and ovulate with superovulatory treatment regimens. Dominance also appears to be exerted via a different pathway from that involved in the BST-induced recruitment of small follicles. The identification of the factor responsible for dominance, together with the elucidation of the mechanisms controlling follicular recruitment and growth should ensure that the full benefits ensuing from the precise control of ovarian function in cattle are achieved.


The potential role of molecular genetic manipulation in the improvement of reproductive performance. Revolutionary opportunities for the modification of animal performance are being created by the development of new methods for embryo manipulation and the application of molecular biology. This paper reviews the potential application of these procedures for the improvement of reproductive performance in livestock. There are three sections: a consideration of the methods of molecular manipulation that are available at present and those that seem likely to become available, a discussion of the modifications to hormonal systems and, finally, an analysis of candidate genes for manipulation of seasonality, number of ovulations, sex ratio and prenatal survival. The analysis points to a number of ways forward. Many of the most promising opportunities will depend upon the isolation of embryonic stem cells or the establishment of alternative methods of site-directed mutation. In most cases, the genes of interest have not yet been cloned and much remains to be learned about the molecular regulation of reproduction. A greater understanding seems likely to reveal the inadequacies of some of the present suggestions, but it is also certain to reveal further opportunities. However, in the longer term, there seems to be a real prospect of modification of at least some of these aspects of reproductive performance by molecular means.


Human contraception: development of new scientific opportunities. Our current methods of contraception were largely developed in the 1950s and 1960s. Collectively these methods can limit population growth, although their acceptability at a personal level remains marginal. The number of abortions in the UK has risen progressively, from < 130,000 in 1980 to > 170,000 in 1990, and more people have sought sterilization. In global terms, population continues to increase on a scale unrecorded in human history. More than 800 million people, equal to the current population of North America, Europe and Japan, will be added to the world population of 5400 million by the year 2000, with 95% of the increase located in the economically and environmentally fragile regions of the South. Worldwide, in these 8 years, about 500 million abortions will be performed (> 40% by unsafe methods), about 80 million children under 1 year of age will die, and about 5 million women with be lost from pregnancy-related causes. Over 100 million people, most in Africa, Latin America, India and South-east Asia, will have become infected with human immunodeficiency virus. Religious, commercial and political pressures continue to constrain the development and distribution of contraceptive products, though some changes are in sight. Contraception is now being advanced in the broader context of neonatal and maternal health care. New scientific opportunities are also evident, with the potential to advance contraception in a quantal step. Third generation contraceptive steroids, anti-steroids, steroid-releasing vaginal rings, and injectable steroid preparations for men are all under clinical trial. Developments in the longer term, however, could hinge upon the greater specificity afforded by the manipulation of regulatory peptides. Agonists, antagonists and binding proteins for GnRH and the gonadotrophins are being investigated in an attempt to regulate the pituitary-gonadal axis more precisely. Inhibition of this axis may require the provision of low level steroid replacement, appropriately titrated to provide positive health care in the context of menstrual cyclicity, well-being, breast cancer and osteoporosis. Attempts are being made to identify and intercept the highly specific signals involved in fertilization and the maternal recognition of pregnancy, with the current clinical focus on the immunoneutralization of beta human chorionic gonadotrophin (beta hCG). More specific and more acceptable targets might include peptides involved in sperm-zona adhesion and sperm activation, sperm-oocyte fusion, and sperm-activated oocyte cleavage. The interception of these signals would prevent fertilization, implantation or both, and yet leave the hormonal profile of the menstrual cycle unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)


Endocrine manipulation--toxicological frontiers. A variety of hormonal products has been developed for use in food animal production. Applications include therapy, particularly for fertility problems, zootechnical purposes comprising mainly the management of reproduction, for example the synchronization of oestrus, and the improvement of performance such as increased growth rate or increased milk yield. Although there is well established legislation both domestically and internationally for the registration of veterinary pharmaceutical products, hormones have become a special case at least to the public. This is particularly true when hormones are used to improve animal performance. The two notable issues to date have been the use of anabolic steroids as growth promoters and of bovine somatotrophin (BST) to increase milk yield in dairy cows. The high public profiles of these two issues have separately forced the introduction of new legislation in the EC, which will continue to have far-reaching implications for research and development in animal health and production for many years. This paper interprets recent developments in legislation concerning veterinary products and hormonal products in particular, giving examples of the toxicological assessment of four specific molecules and speculating upon the likely implications for the future practical exploitation of endocrine mechanisms in food animal production.


Current concepts of folliculogenesis in monovular and polyovular farm species. Follicular growth in sheep and pigs is under both endocrine and paracrine control, and the local factors involved include steroids, growth factors and other regulatory peptides such as the putative follicle regulatory protein. These factors can act either directly on ovarian cells, or by modulating the response to circulating gonadotrophins. It is suggested that during the early stages of development in sheep and pigs, follicles pass through a stage at which they are modulated by growth factors, after which endocrine control mechanisms become more important. There is evidence that interactions between follicle-stimulating hormone, insulin-like growth factor-1 and oestradiol further enhance development and steroidogenesis. Interfollicular relationships in polyovular pigs may differ from those in sheep, in that the more mature follicles may act to enhance development of the less mature in the selected population. Although it is unclear whether similar mechanisms operate in both hyperprolific pigs and prolific breeds of sheep, Meishan pigs and Booroola ewes do exhibit similar follicular characteristics compared with those of nonprolific breeds. The significance of this in relation to prolificacy requires further investigation.


Control of synthesis and secretion of ovarian oxytocin in ruminants. Increased expression of the oxytocin gene of ruminants is associated with the process of luteinization both in vivo and in vitro. Cell culture studies and measurements of mRNA in luteal extracts have confirmed that the gene is switched on in the preovulatory follicle about 24 h before ovulation, at the time of the gonadotrophin surge. It is downregulated again equally rapidly after ovulation, so that by day 2 of the cycle the capacity of the luteal cells to make oxytocin has already been greatly reduced. A number of factors can increase oxytocin production by luteinizing granulosa cells. They include oestradiol and compounds such as gonadotrophins and catecholamines which are known to act by increasing intracellular concentrations of adenylyl cyclase. However, all of these factors are ineffective if the follicle is collected too early, suggesting that an initial maturation step is necessary to develop responsiveness. Analysis of the promoter region of the bovine oxytocin gene has indicated that neither oestradiol nor cAMP can directly initiate activation; instead regulation appears to occur via a COUP factor binding site. Additional transacting nuclear proteins may therefore be required to act as intermediaries. The same factors that initially stimulate oxytocin production switch to inhibiting production shortly after ovulation, leading to downregulation of the gene. After translation of oxytocin mRNA during the luteal phase, oxytocin precursor is packaged into secretory granules in the large luteal cells. Processing involves a series of enzymatic steps, culminating in amidation to produce oxytocin. Cultured cells may secrete intermediate forms of partially processed peptide, but it is not known if this also occurs in vivo. Oxytocin release from the cell involves granule exocytosis which is probably triggered by an increase in intracellular calcium. During luteolysis this is regulated by the release of prostaglandin F2 alpha (PGF2 alpha) from the uterus, although additional factors may also contribute. Neither PGF2 alpha nor catecholamines appear to be prime regulators of luteal oxytocin release during the early and mid-luteal phases of the cycle and it remains to be determined how secretion is controlled at this time.


Luteinizing hormone pulses, follicle-stimulating hormone and control of follicle selection in sheep. The growth of large oestrogenic follicles that have the potential to ovulate if given an appropriate luteinizing hormone (LH) signal is dictated by the plasma concentration of follicle-stimulating hormone (FSH). Basal amounts of LH are essential for this FSH-induced follicle growth, but pulses of LH do not appear to be essential. The fall in FSH concentration during the follicular phase of the oestrous cycle in sheep, and the subsequent withdrawal of FSH from other developing follicles may not be sufficient to explain follicle selection. There is little evidence to support an active suppression of the growth of other follicles by a factor(s) produced by the dominant, or selected follicle. It is possible that LH pulses cause active atresia of non-selected follicles. The selected follicle is the one that can survive the fall in plasma FSH and the large increase in LH pulses during the follicular phase and selection may simply be a case of being the follicle(s) that is present at the correct time to receive adequate FSH and develop sufficiently to survive the inhibitory effects of LH pulses. Several mechanisms whereby LH pulses may inhibit follicle growth are suggested, and avenues for future research, particularly related to the expression of the LH receptor on granulosa cells of the developing follicle, are outlined.


Oxytocin and prostaglandin interactions in pregnancy and at parturition. The demise of the corpus luteum is brought about by an interaction between ovarian oxytocin and uterine prostaglandin F2 alpha (PGF2 alpha) release in sheep. Indirect evidence suggests that a similar, but intra-ovarian, mechanism may also be involved in luteal regression in primates. During early pregnancy, a specific class of interferon (omega interferon) is released from the developing embryo in sheep and this interferon inhibits pulsatile release of uterine PGF2 alpha. Studies in ovariectomized, steroid-treated ewes indicate that conceptus secretory proteins inhibit pulsatile secretion of PGF2 alpha directly via an effect on prostaglandin synthesis and indirectly by maintaining plasma progesterone concentrations that inhibit the development of endometrial oxytocin receptors which normally occurs at the time of luteolysis. As pregnancy progresses, there is an increase in basal secretion of PGF2 alpha and PGE2 from the uterus into the fetal and maternal circulation. The release of maternal PGF2 alpha, but not PGE2, in response to oxytocin is also increased in late pregnancy. Endometrial oxytocin receptor concentrations follow a similar pattern, except at parturition where there appears to be downregulation of receptors. However, the release of PGF2 alpha in response to oxytocin remains high at this time and is further increased if the progesterone receptors are blocked with the anti-progestin RU486. The dissociation between oxytocin receptor numbers and release of prostaglandins in response to oxytocin is also observed under other physiological situations, such as during seasonal anoestrus and after long-term ovariectomy, and requires further investigation. The role of oxytocin in the initiation of labour remains controversial. Although oxytocin concentrations in maternal and fetal plasma are not increased until parturition, uterine oxytocin receptor concentrations, uterine activity and maternal PGF2 alpha release in response to oxytocin are high in late pregnancy. Uterine activity and PG release is not altered by oxytocin in the fetal circulation at any stage of late gestation. We have used the oxytocin analogue CAP to investigate further the possible role of oxytocin in the initiation of labour. CAP can inhibit oxytocin-induced PGF2 alpha release in cyclic sheep, at luteolysis, and in late pregnant sheep by binding to, and blocking, uterine oxytocin receptors. CAP does not inhibit basal fetal or maternal PGF2 alpha or PGE2 concentrations in late pregnancy or at parturition. CAP inhibits oxytocin-induced uterine activity and delays, but does not prevent, the increase in uterine activity associated with labour in this species.(ABSTRACT TRUNCATED AT 400 WORDS)


The effects of luminance on FPL and VEP acuity in human infants. Grating acuity was measured in 16-week-old human infants. Three measurement techniques were used: forced-choice preferential-looking (FPL), and two visual-evoked-potential (VEP) techniques. The stimuli were counterphase flickering sinewave gratings with a space-average luminance of -1.0 or 2.0 log cd/m2. Slightly different luminance-dependent changes occur between FPL and VEP acuities, suggesting that some factor influences the two methods differently as stimulus luminance varies. A comparison between FPL acuities and VEP acuities within infants suggests a quantitative relationship between techniques. Infant's acuity for sinewave gratings with a space-average luminance of -2.0, -1.0, 0.0, 1.0 and 2.0 log cd/m2 was also measured using a single VEP paradigm. The results are compared to the same measurements in adults and to infant and adult ideal observers. VEP acuity in this group of infants improves by about 0.5 log units between -2.0 and 0.0 log cd/m2 and remains asymptotic between 0.0 and 2.0 log cd/m2. This result suggests that luminance-dependent changes in infant acuity cannot be fully accounted for by immaturities in the optics and photoreceptor spacing and efficiency.


Refractive state, corneal curvature, accommodative range and ocular anatomy of the Asian elephant (Elephas maximus). The resting refractive state of six mature, female, Asian elephants (Elephas maximus) was determined using streak retinoscopy and neutralizing video retinoscopy. The amplitude of accommodation was also measured by neutralizing video retinoscopy of two animals and the corneal curvatures of three animals was measured by photokeratoscopy. The net spherical refraction was found to be +0.23 D. No difference was observed between cyclopleged and non-cyclopleged eyes (data from three animals), nor was there any difference between right and left eyes. Nine of the twelve eyes refracted had > or = 0.5 D astigmatism. The mean corneal power, as measured by photokeratometry was 21.3 D (SD = 1.8 D). There was a tendency towards with-the-rule corneal astigmatism in our sample (mean value: 1.2 D), though it did not reach statistical significance (P = 0.06). Two elephants were examined using neutralizing video photoretinoscopy. They were able to accommodate through 3 D. Three fixed eyes from three different elephants were obtained for gross and microscopic examination. The mean axial length of the eye was 38.75 mm and the lens had an axial diameter of approx. 10 mm. The posterior sclera was thick (8.0-8.5 mm). Histologically, the cornea was comprised of five distinct layers. A thin, meridionally oriented smooth ciliary muscle was identified. Individual muscle fibers were also observed associated with the posterior trabeculae of the uveal meshwork.


Neurons immunoreactive to choline acetyltransferase in the turtle retina. Light microscopic immunocytochemistry using anti-choline acetyltransferase (ChAT) was performed to stain putative cholinergic amacrine cells in turtle retina. ChAT-immunoreactive somata lie in the inner nuclear (INL) and ganglion cell (GCL) layers. Three types of amacrine cells were found according to the location of their somata and their dendritic stratification pattern in the inner plexiform layer (IPL). Type I amacrines lie in the row of cells closest to the INL/IPL limits and they branch along the s1/s2 border of the IPL. Type II amacrines are displaced to the GCL and they ramify along the s3/s4 border of the IPL. Type III amacrines lie in the middle of the INL, 2-3 rows away from the IPL limits and their dendrites appear to be bi- or tri-stratified in s1 and s3-s4 of the IPL. The turtle ChAT-IR amacrines are thus similar to the types described in chicken retina. A regular, non-random mosaic formed by stained type II amacrine cells was observed in the GCL. Their density in mid-central retina was 750 cells/mm2, tapering off to 393 cells/mm2 in peripheral retina. Our study indicates that a pair of cholinergic amacrine cell types in turtle retina is arranged in mirror-image symmetry contributing to sublamina "a" and sublamina "b" of the IPL, like in other vertebrate retinas.


Opponent-processing effects on the field spectral sensitivity of pattern-elicited electroretinograms. Field spectral sensitivities of the pattern-elicited electroretinogram (PERG) were obtained from two subjects using a modified version of Stiles' two-color increment threshold procedure. A 540 nm checkerboard test pattern of 38 degrees dia was alternated at 8 Hz on a uniform adapting field of the same size. Test intensity, field wavelength and field intensity were varied parametrically. The derived field spectral sensitivity does not resemble that of any individual class of cones; it roughly approximates the photopic luminosity function V lambda, but with sensitivity dips at 540 and 600 nm, which may be associated with an adaptation of the red/green (R/G) opponent site. Thus, it is proposed that the PERG reflect activities in both the luminance and the R/G opponent channels.


Temporal frequency dependent adaptation at the level of the outer retina in humans. The focal electroretinogram (FERG) was used to examine temporal frequency tuning at the outer retinal level in humans by measuring temporal modulation thresholds. Changes in FERG thresholds as a function of ambient light level were compared to temporal modulation thresholds obtained psychophysically using the same stimuli. At lower temporal frequencies, both FERG and psychophysical thresholds changed sensitivity proportional to the mean illuminance level. At higher illuminance levels, both threshold measures were relatively independent of illuminance. The comparison of the FERG to the behavioral data suggest that most of the adaptation-dependent changes in temporal sensitivity in humans occur at the level of the photoreceptor complex.


Rapid and slow changes in the human cone electroretinogram during light and dark adaptation. Changes in the response characteristics of the human cone electroretinogram (ERG) during light and dark adaptation were studied in two visually normal subjects. Cone ERG responses were isolated under all adaptation conditions through the use of 31 Hz flicker. To determine the time-course of changes in the cone ERG during adaptation, responses to stimuli of constant luminance were measured repeatedly during 15 min of exposure to an adapting field of 2.0 log cd/m2 and during 30 min of dark adaptation following adapting field termination. In addition, luminance-response functions were obtained before and immediately after adapting field onset, as well as before and immediately after adapting field termination. The results indicate that the human cone ERG is influenced by two major processes. One process has a relatively rapid time-course and serves to reposition the luminance-response function along the luminance axis following changes in ambient light levels. The second process, which has a slow time-course, scales response amplitudes during light and dark adaptation by the same proportion at all stimulus luminances. The results provide a framework for predicting the manner in which the cone ERG will change with alterations in the state of retinal adaptation.


Rotation of Listing's plane during vergence. When visually fixating targets on an isovergence surface, the position of each eye was constrained to a plane. Thus, Listing's law holds during vergence. The planes were, however, rotated temporally with respect to those when viewing distant targets. The effect of this rotation was to produce a torsion which depended on eye elevation; extorsion of the two eyes for downward gaze and intorsion for upward gaze. The saccadic velocity command was relatively unaffected during vergence. Computer simulations suggest that the saccadic tonic command and the vergence command interact multiplicatively in three dimensions.


The effects of prolonged temporal modulation on the differential response of color mechanisms. The identification of three independent cardinal directions in color space suggests the existence of three independent post-receptoral mechanisms that can be desensitized by habituation to a temporally modulated light. In this paper, the differential response of each cardinal mechanism is estimated over a range of inputs before and after habituation. Simple mathematical considerations show that the threshold elevations following temporal modulation are not consistent with multiplicative gain changes; rather, these elevations require a change in the shape of each cardinal mechanism's response function. With this method, the effects of habituation can also be differentiated from the effects of a change in the steady adapting light.


Chromatic adaptation to natural and incandescent illuminants. A color CRT image display system was used to present adapting backgrounds that were spatially and temporally varied. Three observers adjusted the chromaticity of test stimuli to produce an achromatic appearance under a variety of adapting conditions. The achromatic-appearing chromaticities were used as measures of the observers' states of chromatic adaptation. The spatial configuration of the adapting background was varied to measure the spatial extent of the mechanisms responsible for chromatic adaptation. The temporal configuration of the adapting background was varied to measure the time-course of these mechanisms. The results show that chromatic adaptation is spatially localized with a time-course on the order of 10 sec. Since the mechanisms were shown to be spatially localized, the observed temporal integration across eye movements is required to allow these mechanisms to adjust to the spatially integrated scene chromaticity.


Reaction time distributions and their relationship to the transient/sustained nature of the neural discharge. Reaction time distributions (RTDs) were determined in response to near-threshold increments of long duration. Stimulus parameters were selected to isolate the chromatic and achromatic systems. The RTDs for the achromatic system peak sooner and are more narrow than those obtained for the chromatic system. These results are analyzed in terms of the neural discharge pattern of parvo and magno pathways.


Visual resolution of motion ambiguity with periodic luminance- and contrast-domain stimuli. Visual motion processes were studied with luminance- and contrast-modulated gratings. A sine-wave luminance grating was displaced abruptly back and forth by 3/16 cycle. The display sequence is ambiguous in that each 3/16-cycle phase shift (short-path motion) could just as readily be seen as a 13/16-cycle shift (long-path motion) in the opposite direction. By varying the duration of the interval (IFI) between the two phase positions, the luminance of the IFI, or the spatial frequency of the grating, it was possible to bias the ambiguous percept in favor of short-path motions or long-path motions. A contrast-modulated grating displaced through 3/16 cycle always appeared t undergo short-path motion. Current motion models which incorporate Reichardt-type/energy mechanisms and certain types of auxiliary signal transformations which precede those mechanisms do not adequately explain the effects of IFI intensity on the perceived motion of a sinusoidal grating or the effect of IFI duration on the perceived motion of a contrast-modulated grating.


A bidimensional theory of achromatic color vision. The theory is based on a perceptive color system where the achromatic colors are specified by their degree of similarity to the three qualities white, black and luminous. Black and luminous are treated as opponent variables. It is assumed that white and luminous/black are determined by different kinds of visual processes termed the w- and the b-process. The relationship between these processes and luminance parameters in a simple disc/ring configuration is derived from available data. The b-process is related to stimulus contrast in a simple manner. It is assumed to involve cells with antagonistic center/surround organization of the receptive field. The w-process is primarily determined by the local luminance, and it is assumed to involve cells that lack a center/surround organization of the receptive field. The w-process has properties similar to the processes involved in chromatic color vision. The theory can account for different kinds of psychophysical data on achromatic colors like data on simultaneous contrast, color scaling, and color constancy.


The effect of pupil size on chromostereopsis and chromatic diplopia: interaction between the Stiles-Crawford effect and chromatic aberrations. Several studies have reported that the magnitude of chromostereopsis changes as the pupil size changes. Einthoven's theory, that chromostereopsis is determined by interocular differences of monocular transverse chromatic aberration, can not easily explain this change. Therefore, several alternative hypotheses have been introduced, most notably by Vos [(1960) Vision Research, 6, 105-107], who argues that shifts in chromostereopsis with pupil size are due to decentration of the peak of the Stiles-Crawford effect (SCE) with respect to the pupil. We tested this hypothesis by measuring chromostereopsis under both scotopic (no SCE) and photopic conditions with centered and decentered artificial pupils. The results show that the SCE plays an important role in the effect of pupil size on chromostereopsis. Similar changes were also measured in monocular chromatic diplopia which supports the hypothesis that the effect of pupil size on chromostereopsis is due to monocular mechanisms.


Changes in pattern induced flicker colors are mediated by the blue-yellow opponent process. The colors of Benham's Top [pattern induced flicker colors (PIFCs)] were matched with color stimuli provided by a computer aided color mixer. Subjects viewed a series of specifically modified black and white disks and matched the resulting subjective color with a comparison field containing the color generated by additive mixing. Different phase relations between the apparently colored ring and the surround were tested. The color loci of all PIFCs were found to lie on a plane in receptor three-space which is given by the axis of the shortwave receptor excitation and a vector given by combining the middle and long wave receptor excitation directions in a fixed ratio of nearly 1:1. From the orientation of this plane it can be deduced that the blue-yellow opponent process (the blue-on-center cells) alone accounts for the different PIFCs.


Binocular integration of contrast information in amblyopia. We asked whether suppression in amblyopia could be accounted for by dichoptic masking as described in normals, operating in the presence of a contrast threshold difference between the two eyes. A dichoptic masking paradigm was employed to investigate binocular interaction in a mixed group of amblyopic subjects. Normal dichoptic masking was not seen after threshold differences between the two eyes were accounted for in the majority of subjects studied. We found that the binocular dysfunction did not merely follow as a consequence of the known monocular loss and that it depended upon the aetiology of the amblyopia and the spatial frequency of the stimulus.


The role of saccades in the perception of texture patterns. We studied the perception of texture patterns when observers used saccadic eye movements to scan the display and when the line of sight was maintained in the display center without saccades. Saccades improved the discrimination of the size and the shape of a central randomly-shaped polygon for display durations > 1 sec. Saccades were more important with textures that did not readily segregate into target and background regions than with those that did. Directing saccades to the curvature extrema of the central target figure was more useful than directing them elsewhere. Saccades did not enhance texture segregation, but rather improved the discriminability of individual target and background elements by overcoming lateral interference. To the extent that strong lateral interference is inevitable with poorly-segregating textures, our results show that serial inspection is best carried out by sequences of saccades, not by sequences of attention shifts.


Color discrimination and adaptation.

Color discrimination and adaptation. We have measured color discrimination in the isoluminant plane under rigorously controlled adaptation conditions. Two regimes were studied. Under the first regime the observer was adapted to the region of color space in which the discriminations were made. Thresholds for detecting changes along the S-(L + M) axis are a linearly increasing function of the excitation of the S cones. Thresholds for detecting changes along the L-M axis are independent of the locus of adaptation along this axis. The straightness of these functions is inconsistent with the theory that second stage mechanisms are more sensitive in the middle of their operating ranges. No convincing evidence of interactions in the effects of adaptation locus or test stimuli was observed. Under the second regime the observer was adapted to one point in color space and the stimuli to be discriminated were located in other places in color space. Discrimination seems to be limited primarily by mechanisms maximally sensitive to modulation along the isoluminant cardinal axes but evidence suggestive of the operation of higher order mechanisms was also found.


Extrapolation of linear motion.

Extrapolation of linear motion. We investigated observers' ability to extrapolate a linear trajectory of a moving point, in order to determine how effectively the visual system can combine orientation and position information for moving stimuli. Observers saw a probe dot moving along a straight line toward a stationary target dot. The probe dot extinguished before reaching the target, and the observers' task was to judge whether an extrapolation of the trajectory of the probe would pass to the left or right of the target. Performance was measured as a function of probe velocity, length of the visible trajectory, and location of the target. The empirical results indicated that over a range of conditions, performance on this task is qualitatively similar to, but somewhat less accurate than, that on an analogous task with static stimuli. A four-component model is presented to account for the results. The model specifies an accurate extraction of probe motion parameters, extrapolation of the motion by an ideal observer, and limitations on the input to these processes in the form of visual field spatial inhomogeneity and temporal decay of position information.


Two movement aftereffects: evidence for luminance- and color-movement pathways. Two movement aftereffects (MAEs) that bear closely on the issue of visual processing of color and movement have been isolated. Following adaptation with a vertical luminance stimulus a strong MAE occurred with the same stationary test stimulus oriented horizontally and also in a perfectly uniform field. Neither effect occurred following adaptation with a color equiluminance stimulus. These aftereffects have not been reported before. It is concluded that there are at least three pathways for movement, a color, a color-plus-luminance, and a luminance pathway.


Ambiguous motion in a two-frame sequence. We measured the ability of ten different observers to identify the direction of motion displacement of a 1.77 c/deg grating in a two-frame sequence. One subject showed virtually errorless performance, in agreement with Derrington and Cox [(1992) Vision Research, 32, 2191-2193], but most subjects found the task difficult and made many errors. One subject saw motion in the reverse of the actual direction of displacement. We conclude that the two-frame sequence contains motion signals in both directions, and that selective attention to the forward direction is necessary for errorless performance.


[Nasal and sinusal polyposis. Semiology and values of magnetic resonance imaging]. Twelve patients with nasal polyposis were examined with magnetic resonance imaging (MRI) prior to surgical ethmoidectomies (20 ethmoidectomies). MRI signal was analyzed in correlation with surgical findings in order to define the semiology of nasal and sinuses polyps. One of the most important point of this semiology is based on the analysis of sequences after administration of gadolinium. MRI seems an interesting method for analysing the extension of nasal polyposis and could be useful for ENT surgeons before an endoscopic nasal surgery.


[Brush technique in cytological analysis of the nasal mucosa. A critical and comparative analysis]. The cytological study of the nasal mucosa is one the essential steps toward a better understanding of the physicopathological mechanisms involved in chronic affections of the nose. The development of a reliable, reproducible noninvasive technique to obtain cells in the prerequisite for this analysis. The brush technique is based on the use of a small cylindric nylon brush which is rotated as it is moved back and forth across the nasal mucosa to harvest the various cell types present on the surface of the mucosa. The specimen obtained is centrifuged and examined under an optical microscope. A semi-quantitative analysis is carried out to determine the relative richness of the specimen in epithelial cells (ciliated, qoblet and basal cells) and in inflammatory cells (neutrophils, basophils, eosinophils, lymphocytes, and monocytes). A precise differential cell count is then performed. According to the results obtained, an immunologic marker study of lymphocyte subsets may also be done using the same specimen. This technique may be used in both children and adults and permits cell harvest from various sites within the nasal fossa. Already tested in the study of the activity of cilia, this method is promising for the cytological study of the nasal mucosa. The brush method and other techniques of cell harvest are described and compared.


[Inverted papilloma of the nose and paranasal sinuses. Retrospective study of 18 cases]. The authors report about 18 cases of inverted papillomas treated between 1981 and 1991. The average age of the patients is 51 years, with a marked male predominance. The average follow-up is of 4 years. The most often noted revealing sign is unilateral nasal obstruction. A history of polypectomy and nasosinual surgery is found in 45% of the cases in our series. The treatment was surgical in all cases, including 4 De Lima's procedures, 11 procedures through a paralateronasal approach, 2 ethmoidectomies through an endonasal approach, and 1 degloving for a septal lesion. Endonasal surgery was performed for two limited tumors, for which the diagnosis of inverted papilloma never could be made preoperatively. The recurrence rate observed in our series is 5%. Out of 18 patients, 4 presented with a malignant change, either at once (2 cases) or some time after the primary exeresis of the inverted papilloma (2 cases). In the light of the results, and after analyzing the literature, the authors reassert the necessity of radical exeresis for inverted papilloma. Rhinosinual endoscopy must remain a diagnostic means and never is an indication of exeresis of inverted papilloma. The authors emphasize the difficulty of the histological diagnosis and set forth the various problems arising from the malignant degeneration of inverted papillomas. Recent discoveries on viral etiopathogenesis and on the oncogenic potential of the type-16 papilloma virus may allow characterizing the evolutive and prognostic features of inverted papillomas in the future.


[Retrospective study of 139 cases of epidermoid carcinoma of the upper respiratory and digestive tracts treated by induction chemotherapy with cisplatin-5FU. Influence of the result on the therapeutic protocol]. A retrospective study of 139 untreated staged III and IV epidermoid carcinomas of the upper aero digestive tract is reported concerning oropharynx, oral cavity, hypopharynx and larynx, all of them received as a first treatment, chemotherapy using a five days course of Cisplatinium (20 mg/m2/D) and 5FU (1,000 mg/m2/D). The aim of the trial was to determine: a) a free of disease survival and a global survival rate's increase, b) a more conservative treatment. The results of chemotherapy were clinically evaluated in two groups: Responders (a total or a more than 50% response), and no responders. The results were: on the tumor site: 64% responders (25% total response)--more in smaller lesion; on the lymphatic nodes: 54% responders (more in N1-N2). The results vary in inverse ratio to the stage of the lesion; usually, 2 cycles of chemotherapy are used but in case of efficiency: 2 to 6 cycles are provided increasing to 20% the rate of the total responders; toxicity of the drugs was neligible: 6 cases, 3 of them were renal insufficiency. The global survival rate at 3 months reaches 56.7%. The median line of survival reaches 32 months in responders reverse 15 months (NR); but there are no significant difference between the two groups concerning the recurrences, or the metastasis. The local treatment (after chemotherapy) decided in the 137 patients was surgery, in 40 cases and radiotherapy, in 97 cases (conservative treatment; 80%).(ABSTRACT TRUNCATED AT 250 WORDS)