Twinning rate in a sample from a Brazilian hospital with a high standard of reproductive care.

CONTEXT: Epidemiological studies on twin births have been motivated mostly by the positive correlation between twinning rate and human fertility, prematurity, low birth weight, increased risk of infant death and long term risk for morbidity. OBJECTIVE: This paper intends to estimate the incidence of multiple births in a private hospital in Brazil with a high standard of reproductive care, and to evaluate the effects of maternal age, gestation order and assisted fertilization on twinning rate. DESIGN: Retrospective analysis. SETTING: First-class tertiary private hospital, São Paulo, Brazil. PARTICIPANTS: The multiple birth rate was investigated among 7,997 deliveries from 1995 to 1998, including 7,786 singletons, 193 twins, 17 triplets and one quadruplet. RESULTS: The rates per 1,000 dizygotic and monozygotic pairs and for triplets were estimated as 19.51, 4.50 and 2.13, respectively. The dizygotic and triplet rates were the highest observed in Brazil up to the present day. The twinning rate among primigravidae older than 30 years was very high (45.02 per 1,000) and was due to a disproportionately high frequency of dizygotic pairs. The triplet rate was also very high among the mothers of this age group (5.71 per 1,000). These facts are strong indicators that these women were the ones most frequently submitted to assisted reproductive techniques. The mean maternal age of the studied population was about six years higher than that estimated for mothers in the general population of southeastern Brazil. Primigravidae aged under 30 years as well as multigravidae showed similar twinning rates, which were almost 20 per 1,000. Among the deliveries of multigravidae older than 30 years, an unusually high frequency of monozygotic twins was observed (7.04 per 1,000), probably as a consequence of the residual effect of long-term use of oral contraceptives. CONCLUSIONS: The dizygotic twinning rate increased from 13.51 to 28.98 per 1,000 over the four years studied, with the twinning rate for primigravidae over 30 years old in 1998 being twice that observed in 1995. The mean maternal age was also high during this period, but the extremely high increase in twinning rate observed cannot be attributed solely to this variable. Assisted fertilization seems to be the most probable cause of this unusually high twinning rate.

[Primary lactose malabsorption in healthy Brazilian adult caucasoid, negroid and mongoloid subjects]. / Mabsorção primária de lactose em brasileiros adultos caucasóides, negróides e mongolóides sadios.

A lactose tolerance test consisting of the administration of 50 g lactose as a 10% aqueous solution was applied to 80 healthy adult individuals from Campinas, SP., Brazil (40 caucasoids, 20 negroids and 20 mongoloids of Japanese ancestry) with no secondary lactase deficiency. Lactose malabsorption was manifested by 45% caucasoids, 85% negroids and 100% mongoloids. The lactose malabsorption as assessed by the lactose loading test was more closely associated with symptoms of lactose intolerance (cramps, meteorism and diarrhea) than with fecal alterations (acid pH, as well as detectable glucose and reducing substances in the feces).

Leprosy and genetics. A review of past research with remarks concerning future investigations.

The few geneticists who are interested in leprosy have been working in this field only since 1962, and have made little progress in solving the problems presented by susceptibility to this disease.This paper reviews the research that has been conducted, with particular reference to the search for associations between leprosy and certain genetic markers. In each area, the advantages and limitations of different techniques are described, and attention is drawn to sources of bias that may invalidate many of the results that have been published. Of particular interest is the discussion of a new technique for evaluating resistance to-leprosy. The proposed technique is based upon the in vitro transformation of blood monocytes into macrophages, and the observation of their behaviour against Mycobacterium leprae.

Chromosomal aberrations in cultures of skin fibroblasts of leprosy patients.

A search for structural and numerical chromosomal aberrations was made on metaphases obtained by culturing in vitro skin fibroblasts of 16 leprosy patients (10 lepromatous, 2 borderline, and 4 tuberculoid cases) and 2 healthy individuals used as controls. The data were analyzed taking into account sex, age, race, form of leprosy, bacterial index, type of therapy, and age of the fibroblast cultures. Structural chromosomal aberrations are the only type of chromosomal abnormality that may be accepted as significantly increased in the skin fibroblasts of leprosy patients who are under treatment with dapsone alone or with combined therapy.

Effect of DDS on phytohemagglutinin-induced lymphocyte transformation.

The influence of DDS on PHA-induced lymphocyte transformation was investigated in leukocyte cultures from two samples of healthy Caucasoid individuals. In one sample the sulfone-treated cultures differed from the controls in that they contained 0.4 mug/ml of other sample, the treated cultures contained DDS in concentrations of 4 mug/ml, 8 mug/ml and 16 mug/ml. The frequency of lymphocyte transformation induced by PHA was significantly reduced by DDS in all concentrations used. The data obtained are a strong indication that the plasma levels of dapsone among leprosy patients may contribute to the depression of the blastogenic capacity of their lymphocytes when stimulated by PHA.

NADH-methemoglobin reductase and methemoglobinemia among leprosy patients.

The NADH-methemoglobin reductase activity as well as hemoglobin and methemoglobin levels were investigated in blood samples of 182 adult leprosy patients and 137 Brazilian army enlisted men. The level of sulfones in the blood samples of the leprosy patients, all of them ingesting a daily dose of 100 mg dapsone, was also investigated. The mean value of NADH-methemoglobin reductase activity exhibited by the leprosy patients did not differ from that observed among the healthy individuals. However, the variance of the former group was significantly higher than that observed among the healthy subjects. As a consequence, the proportion of individuals showing a partial deficiency of NADH-methemoglobin reductase was significantly higher among the leprosy patients (22.5%) than among the healthy individuals (2.9%). The activity of this enzyme among the leprosy patients was negatively correlated to the hemoglobin level and slightly positively correlated to age. The concentration of methemoglobin among the leprosy patients was slightly but significantly higher as compared to the healthy individuals. The increase of the methemoglobin level among the leprosy patients was influenced by the amount of sulfones in the blood. However, no case in which dapsone was ingested in a daily dose of 100 mg presented the signs or symptoms of toxic methemoglobinemia.

In vitro effect of dapsone on human chromosomes.

The proportion of accumulated metaphases, as well as the frequency of aneuploidies and structural chromosome aberrations were investigated in DDS-treated and untreated (controls) leukocyte cultures from two samples of healthy adult Caucasoid individuals. In one sample, the sulfone-treated cultures differed from the controls in that they contained 0.4 mug of DDS per ml of tissue culture medium plus phytohemagglutinin. In the other sample, these cultures differed from the controls in that they contained a tenfold higher concentration of DDS. The two concentrations of DDS used have not significantly affected the rate of metaphases, while 0.4 mug/ml DDS did not increase the frequency of chromosome aberrations. The same was not true for the cultures treated with 4 mug/ml DDS in which the proportion of aneuploides and achromatic gaps increased significantly.

Decline of the twinning rate in Brazil.

The twinning rate during a twenty-year period (1965-1985) was investigated at five-year intervals in four Brazilian hospitals. During this period the twinning rate has decreased significantly (from 10.68% to 8.11%), being highly negatively correlated with the five-year intervals (r = -0.97). This change was due mainly to the decline in dizygotic twinning, since the incidence of DZ twins has fallen from around 7% in 1965 to around 3.6% in 1985. The detected decline in DZ twinning seems to be due to the remotion of the fertility advantage of the more fecundable DZ twin-prone women by the introduction of effective birth control at the present, while some other mechanisms are causing the decline irrespective of the type of twinning.

Histology of the Mitsuda reaction of healthy adults with no known contacts with leprosy patients.

Mitsuda tests were performed on 100 healthy adult Brazilian males unrelated consanguineously to leprosy patients and with no known contacts with this disease. Three lepromatous patients served as negative Mitsuda controls. The lepromin employed was from Mycobacterium leprae-infected armadillo tissue prepared according to WHO standards. Clinical response to the lepromin inoculation was graded according to the recommendations of the VI International Leprosy Congress held in Madrid (1953). The histological reaction was graded according to the authors' criteria based on the intensity of the granulomatous response. The clinically positive (77), the doubtful (19), and 1 out of 4 clinically negative Mitsuda reactors disclosed histologically positive reactions of different degrees of intensity. A significant association between the clinical and histological readings of the Mitsuda reaction was demonstrated when the results of both readings were grouped in two classes: negative and non-negative. However, the different degrees of the histologically positive lepromin reactions were distributed at random among the clinically positive Mitsuda reactors. The frequency of histologically negative Mitsuda reactors observed among the healthy subjects who had no known contacts with leprosy patients (3%) was significantly low when compared to the frequencies reported in the pertinent literature concerning healthy contacts of patients with Hansen's disease.

The genetic epidemiology of leprosy in a Brazilian population.

Data on leprosy patients have been obtained from the Dispensary of Leprosy of Campinas, São Paulo, where records on practically all cases of leprosy in the Campinas area during the period 1960-70 are filed. The whole sample comprises 10,886 individuals, distributed among 1,568 families. Complex segregation analysis was utilized to determine the nature of the genetic factors that may operate on leprosy and its subtypes. The results suggest the presence of a recessive major gene controlling susceptibility to leprosy per se, with frequency of approximately .05, although there are deviations from the expected Mendelian segregation proportions. Possible etiologic heterogeneity was examined by considering two subtypes separately: for lepromatous leprosy and tuberculoid leprosy there are suggestions for a segregating major effect; however, Mendelian transmission could not be demonstrated in either case. Therefore, there is no evidence to suggest unique genetic determinants for leprosy subtypes.

Heritability of quantitative orbital traits.

We conducted a study of 63 couples and their 242 normal children from northeastern Brazil (no facial malformations or deformities) to evaluate the heritability of 4 quantitative traits of the orbital region adjusted by covariance for sex, age, (age)2, sex x age, and sex x (age)2. The heritability is estimated as 0.514 for the mean horizontal diameter of the palpebral fissures, 0.454 for the interpupillary distance, 0.390 for the internal intercanthal distance, and 0.337 for the external intercanthal distance. The heritability of the first principal component of the orbital region is estimated as 0.418.

Annual variation of sex ratio in twin births and in singletons in Brazil.

The annual variation of the sex ratio (SR) of 1385 twin births was analyzed and compared to that of 85909 singletons. These births referred not only to live births but also to stillbirths in two southeastern Brazilian maternity hospitals from 1984 to 1993. While the annual variation of the SR of singletons was very small, that of twin births was extremely high, due to the significant heterogeneity of the annual data. It is suggested that the large SR annual variation of the twin birth might be a consequence of the variation of male or female monozygotic twins. The hypothesis that twin births show a lower sex ratio than singletons could be supported by the present data.

PIP: This article presents the findings of a study of the annual variation of the sex ratio among twin births compared to singleton births among a maternity population in two urban hospitals in Brazil. Data are obtained from hospital records from a maternity hospital in Campinas and Sao Paulo, Brazil, during 1984-93. There were 1385 twin births and 85,909 singleton births delivered during 1984-93 in these maternity hospitals in Sao Paulo state. Deliveries included stillbirths weighing 500 g or more. Findings indicate that the sex ratio of singletons was 104.6 males per 100 females. The sex ratio of the 763 twins born in Campinas and the 622 twins born in Sao Paulo showed considerable variation from the mean sex ratio of singleton births. The mean sex ratio among twins in Campinas was 107.1 males per 100 females, with a standard deviation of 20.4 in Campinas and 29.7 in Sao Paulo. There were significant differences from the mean sex ratio among twin births in Campinas in 1984 and 1989 and in Sao Paulo in 1984, 1985, 1988, and 1989. There was significant heterogeneity of sex ratios among twin births even with pooled data. The mean of pooled data on twin births was 102.9 males per 100 females, with significant differences from the mean in 1984, 1985, and 1987. The application of Woolf's test indicated heterogeneity in the data and no effect on the sex ratio from twin births. Maternal age was negatively correlated with the sex ratio of twin births. It is argued that monozygotic twins were not primarily females and that twin births did not have a lower sex ratio than singleton births.

Investigation on seasonality of twin births in Brazil.

The hypothesis of seasonality of twin births was investigated in two important maternity hospitals in the State of São Paulo, Brazil. The study included 1,386 twin births that occurred among 154,699 deliveries from 1984 to 1993. No evidence of seasonality has been detected either for the twin birth rate considered as a whole or for dizygotic twinning rate. The distributions of these rates fitted well sinusoidal regression curves but the cyclic trend did not correspond to any specific season.

Genetic epidemiology of the Mitsuda reaction in leprosy.

This study comprised 544 nuclear families with 2,925 individuals tested for the Mitsuda reaction, from the Campinas region in Brazil. Segregation analyses suggest the segregation of a major gene (chi 2(1) = 0.07 - 0.07 = 0, p = 1), by failing to reject the hypothesis of Mendelian transmission and by rejecting the hypothesis of nontransmission of a major gene (chi 2(3) = 0.07 - 0.0 = 0.07, p > 0.99; chi 2(2) = 198.28 - 0.0 = 198.28, p < 0.0001).

[Thalassemia and Hansen's disease]. / Talassemia e hanseníase.

The beta-thalassemia trait was investigated among 165 Brazilians who were unmixed Italian descendants (80 Virchowian patients and 85 normal controls, composed of universitary students). The frequency of the beta-thalassemia trait was 6.25% among the Virchowian patients and 5.88% in the control group. In spite of the similar geographical distribution of both hanseniasis and the gene for beta-thalassemia in Asia, the present data does not support the hypothesis that hanseniasis might have contributed to maintain high prevalence of this allele by selection favouring beta-thalassemia trait.

Factors influencing the level of dapsone in blood.

The level of dapsone in the blood 4 and 6 h after the ingestion of the 7th daily dose of 100 mg of the drug was investigated in 36 adult males with leprosy who had normal renal function and were free of diarrhoea and emesis. The bimodal distribution of the dapsone levels at 6 h was shown by multiple regression analysis to be due to a negative correlation between this trait and the haematocrit value. Among the patients with high dapsone blood levels, 81.8% presented haematocrit values under 36%, whereas only 20% of those with low levels showed low haematocrit values. Partial regression coefficients, calculated for the dapsone level on the age, weight of the patient, estimated number of years since the onset of leprosy, number of years under sulfone treatment, and blood levels of haemoglobin, albumin, and globulins, did not show statistical significance.

Twinning rate in a southeastern Brazilian population.

The twinning incidence from 1984 to 1993 was investigated in Campinas, State of São Paulo, Brazil and the analyzed data were combined with previous series from the same population. This study has shown that the mean annual incidences and the standard deviations for DZ, MZ and DZ plus MZ twins for the period of 1984 to 1993 are estimated respectively as 4.7 +/- 0.92, 4.1 +/- 1.11, and 8.8 +/- 0.87 per 1,000. In the same period the mean annual incidence of triplets was 0.15 +/- 0.16. It was also shown that the incidence of DZ twins is steadily decreasing since 1925, while the incidence of MZ pairs, after a period of decline is increasing since the sixties, due perhaps to the widespread use of oral contraceptives. Concerning the twinning rate as a whole, it has been shown that its declining trend has disappeared over the last few years.