CARCINOMA OF THE BREAST—Possible Significance of Menstrual Cycle in Results of Operation

Among 55 patients upon whom mastectomy was done for cancer of the breast, survival without evidence of metastasis (after varying periods of follow-up) was significantly higher for those who were operated upon in the seven days preceding the beginning of menses than it was for those who underwent operation in any of the three other seven-day periods in the menstrual cycle. Moreover, in a comparison of results of operations done in each of the four seven-day periods, there was a graduating increase in mortality and metastasis from the first period (the seven days preceding menses) through the fourth period.The results of the study of this small series are considered not conclusive but indicative of possible profit in studies of larger and better controlled series.     

Impact of lactation upon fertility in the New World primate capuchin monkey (Cebus apella)

In the present paper, we have studied the impact of lactation upon fertility in the capuchin monkey, Cebus apella, under laboratory conditions. Nursing females (ten females, 12 postpartum periods) presented lactational amenorrhea (first menses at 159.2 +/- 9.0 vs 42.6 +/- 5.8 days postpartum in five non-nursing females, seven postpartum periods). Plasma estradiol and progesterone concentrations during lactational amenorrhea were lower than those during the follicular phase of the menstrual cycle. Prolactin was higher than in non-nursing females at 31-60 days postpartum. Interbirth interval, studied in three non-nursing (four intervals) and six nursing females (eight intervals) lasted for 349.5 +/- 11.8 and 613.4 +/- 30.8 days, respectively. In non-nursing females, early recovery of the menstrual cycle was followed by a residual infertility (mating but no pregnancy) lasting 152.8 +/- 7.9 days. In nursing females, recovery of the menstrual cycle was followed by an extended residual infertility of 301.5 +/- 22.7 days. Thus, in the capuchin monkey, nursing prolongs the interbirth interval by inducing lactational amenorrhea and extending the residual infertility period.     

Development of the mammary gland of rabbits

Mammogenesis of rabbits was studied in dynamics, including periods of sexual maturity (3-6 months old), pregnancy, lactation and involution. A characteristic of histological structure of mammary gland of rabbits in different physiological periods was done. Variation in maintenance of glandular tissue of mammary gland during mammogenesis was analyzed. It has been shown that the share of parenchyma tissue is increased with the pregnancy onset and achieves its maximum value by the 25-30 th days of pregnancy. The increase in densities of mammocyte nucleus in this period and also in the period preceding the sexual maturity was observed that is associated with the active proliferation of cells. It is shown that an in vitro cell culture, derived during the period preceding the sexual maturity, has a great grown potential, whereas a culture devired in the course of lactogenesis is characterized by the presence of highly specific lactocytes and has a low proliferative activity.     

Effects of profuse sweating induced by exercise on urinary uric acid excretion in a hot environment

In order to determine whether exercise-induced profuse sweating could reduce urinary uric acid excretion, we simulated badminton players training and measured their uric acid in urine, sweat and blood during the training period. Thirteen male volunteers who were well-trained badminton players were recruited in this study. On the first 2 days and the last 2 days of the study period none of the subjects engaged in any intense exercise- or activity-inducing profuse sweat, but they accepted routine training 2 h per day during the middle 3 days. The results show that mean serum urate levels of thirteen volunteers rose significantly on day 4, when the concentrations increased by 18.2% over day 2 (P < 0.05). The mean ten-hour urinary uric acid excretion of seven volunteers on the 3 training days was significantly less at 178.5 micromol/day and 118.3 micromol/day than those on the preceding and subsequent days of the training days, respectively (P < 0.05). Furthermore, for six volunteers, the mean ratio of clearance of uric acid to creatinine was 6.6% on day 2, which significantly decreased to 5.4% on day 4 (P < 0.05). It is concluded profuse sweating exercise results in a decrease of urinary uric acid excretion amounts and leads to increased serum uric acid after the exercise. We suggest that persons who take vigorous exercise or are exposed to hot environments need drinking enough fluids to prevent dehydration and maintain adequate urinary output. People with profuse sweat after rigorous exercise are recommended taking sports drinks containing abundant sodium in order to decrease serum uric acid.     

Developmental staging and thalidomide teratogenicity in the green monkey (Cercopithecus aethiops).

The developmental stages of 11 Cercopithecus aethiops embryos, 24 to 45 days post-mating, are described. The onset of organogenesis in this species is approximately five to seven days later than that reported for macaques and baboons. This temporal difference in the embryonic period is an important factor in the analysis of the subsequent teratogenic study. Oral administration of thalidomide in single or multiple (3-day) treatment periods to pregnant green monkeys between days 28 and 33 resulted in defects of the limbs which resemble those observed in macaques and baboons. However, the sensitive period occurs approximately four days later than that reported for another nonhuman primates. These results indicate that the sensitive period of the limbs to thalidomide coincides with their earliest development.     

Continuous-flow plasmapheresis in management of severe rhesus disease.

Eight patients with severe rhesus disease and expected fetal loss were treated by intensive plasmapheresis using a continuous-flow cell separator. Plasmapheresis was started at 16-27 weeks'' gestation, and continued until planned intrauterine transfusion or until the infant was delivered or the rhesus disease became uncontrolled again. Altogether 24 to 2371 of plasma was exchanged over periods ranging from seven to 16 weeks. In seven of the eight patients the anti-D concentration fell during the period of plasmapheresis. Amniotic fluid spectrophotometry values remained below those recorded in the preceding pregnancy in six out of seven women. In five patients an attempt was made to control the rhesus disease by plasmapheresis alone, and two of these women delivered infants who survived. In the other three cases the infants died, one from the idiopathic respiratory distress syndrome and the other two in utero. These preliminary findings suggest that intensive plasmapheresis with a cell separator may reduce fetal haemolysis is delivered. Nevertheless, plasmapheresis may best be used to reduce haemolysis until intrauterine transfusions may be given more safely after 30 weeks'' gestation.     

The importance of farrowing to service interval in sows served during lactation or after shorter lactation than 28 days

In a retrospective study, based on data from the national litter recording system, farrowing rate and litter size of sows served (inseminated or mated) during the lactation period (n = 574) or after a lactation period shorter than 28 days (n = 14,219) were analysed. The results were compared with the corresponding figures for sows with lactation length between 28 and 35 days and weaning to first service interval of 4 or 5 days (reference group; n = 41,741). The farrowing rate of the reference group was 80.9% and subsequent litter size was 13.7 total piglets born. Among sows served prior to weaning, the farrowing rates and litter sizes were significantly lower for those served earlier than 22 days post-farrowing compared to those served later (P < 0.05). Shorter lactations than 28 days and service within 10 days post-weaning led to lower farrowing rates than in the reference group (P < 0.01). Significant differences were seen after different lactation lengths. After correction for weaning to service interval, preceding litter size weaned, parity, breed and the interaction between parity and breed, litter size was significantly and positively associated with the preceding lactation length. The study shows that service within the first 3 weeks post-farrowing results in reduced reproductive performance.     

Ultrasonography for detection of pregnancy and study of embryonic development in heifers

Real-time B-mode ultrasonography was used to evaluate uterine changes associated with the estrous cycle in 22 ovulatory periods in 12 nulliparous heifers. Irregular, nonechogenic (black) areas were seen on the images of uterine horns during the periovulatory period. These nonechogenic areas were presumably due to intraluminal fluids since they coincided with the discharge of clear, viscous mucus preceding ovulation and blood-tinged mucus after ovulation. Eight heifers were bred until five pregnant heifers were obtained for study of the ultrasonic morphology of the conceptus. Ultrasound examinations were done daily to day 50 of pregnancy. Discrete, nonechogenic areas were first visible within the uterus between days 12 and 14, when they were approximately 2 mm in diameter. These discrete nonechogenic structures were identified as the embryonic vesicle, since they were observed only in heifers later confirmed to be pregnant and were always in the uterine horn ipsilateral to the corpus luteum. The presence of an embryo within the embryonic vesicle was confirmed by observing an echogenic (white) area with rhythmic pulsations (heartbeat). The embryonic vesicle gradually increased in length from the day of first observation until day 26 when it extended past the curvature of the horn and began to encroach into the contralateral horn. In all heifers, by day 32 the vesicle extended to the tip of the contralateral horn. The embryo was first visible between days 26 and 29 when the mean length was 10 mm. The embryo increased in length an average of 1.1 mm per day. A heartbeat was detectable in the embryo on the first day observed. In one superovulated heifer, five vesicles were visible in the uterine horns by day 14 and by day 33 seven embryos were observed; two of the seven embryos apparently resorbed by day 43.     

Scrapie infections initiated at varying doses: an analysis of 117 titration experiments

An analysis of 117 titration experiments in the murine scrapie model is presented. The experiments encompass 30 years' work and a wide range of experimental conditions. To check that the experimental designs were reasonably consistent over time, comparisons were made of size, duration, source of inoculum, etc., in each experiment. These comparisons revealed no systematic trends that would render invalid comparisons across experiments. For 114 of the experiments it was possible to calculate the dose at which half of the challenged animals were infected (the ID50). These 114 experiments were then combined on the basis of relative dose (i.e. tenfold dilution relative to the ID50). This created a data set in which over 4000 animals were challenged with doses of scrapie ranging from four orders of magnitude below to five orders of magnitude above the ID50. Analysis of this data reveals that mean incubation periods rise linearly with logarithmic decreases in dose. A one unit increase in relative dose (i.e. a tenfold increase in actual dose) will, on average, decrease the incubation period by 25 days. At ID50 the average incubation period in this data set is 300 days. Within a single dose, in a single experimental model, incubation periods have a distribution close to normal. Variability in incubation period also rises linearly as dose decreases. There is no age or sex effect upon the probability of infection, but female mice have incubation periods that are, on average, nine days shorter than their male counterparts and young mice have incubation periods that are longer by seven days. Although many of these patterns are apparent in the results of single titration curves, they can be more rigorously investigated by considering the outcome for thousands of mice.     

Is routine episiotomy necessary?

One hundred and eighty one primigravid women delivering vaginally in July and August 1982 in the Rotunda Hospital, Dublin, were randomly allocated to one of two groups. Patients in one group were to undergo episiotomy. Those in the other group were not to undergo episiotomy unless it was considered to be essential. The outcome was compared with that of the clinical practice over the previous six months at the hospital. Of the 92 patients allocated not to undergo episiotomy, seven (8%) had one done for medical reasons compared with 507 (89%) in the previous six months. First degree tears occurred in 23 (25%) and second degree tears in 43 (47%). Nineteen (21%), however, retained an intact perineum compared with only 35 (6%) of the women who had delivered in the preceding six months. Assessments of perineal pain, bruising, swelling, and healing and records of ingestion of analgesics were made for the first four days after delivery, and again at a check up six weeks after delivery, in patients who had had spontaneous vertex deliveries. Forty patients who underwent episiotomy and 37 who sustained a second degree tear formed two comparable groups. There was no difference in outcome between them. Data were also evaluated for 19 women who retained an intact perineum, 22 who sustained a first degree tear, and 11 who underwent episiotomy and epidural anaesthesia; all 52 of these women had spontaneous vertex deliveries. Despite severe soft tissue injury in two patients those who fared best were those who retained an intact perineum. First degree tears were associated with symptoms similar to those associated with second degree tears. Those who fared worst were women who underwent episiotomy after epidural anaesthesia. The value of routine episiotomy in primigravid patients is questioned, but the final decision can be made only by the accoucheur at the time of imminent delivery.     

Autoimmune progesterone dermatitis in a patient with endometriosis: case report and review of the literature

Autoimmune progesterone dermatitis (APD) is a condition in which the menstrual cycle is associated with a number of skin findings such as urticaria, eczema, angioedema, and others. In affected women, it occurs 3-10 days prior to the onset of menstrual flow, and resolves 2 days into menses. Women with irregular menses may not have this clear correlation, and therefore may be missed. We present a case of APD in a woman with irregular menses and urticaria/angioedema for over 20 years, who had not been diagnosed or correctly treated due to the variable timing of skin manifestations and menses. In addition, we review the medical literature in regards to clinical features, pathogenesis, diagnosis, and treatment options.     

Hematopoietic reconstitution of CD34+ cells derived from short-term cultured cord blood mononuclear cells

Ex vivo expansion of hematopoietic stem cells (HSCs) is very important for clinical applications of cord blood (CB). With the aim to find proper culture duration for ex vivo expansion, mononuclear cells (MNC) was applied as starting culture cells to expand HSCs and the repopulating potential of seven-day and fourteen-day cultured CD34⁺ cells were compared. The average expansion of total cells and CD34⁺ cells cultured for 7 days were higher than those cultured for 14 days. The results of phenotypic analysis of fresh and cultured cells showed that the percentage of CD3⁺ cells declined and the percentage of CD33⁺ cells increased during culture. The engraftment levels of fourteen-day cultured CD34⁺ cells were higher than those of fresh and seven-day cultured CD34⁺ cells. Fourteen-day cultured CD34⁺ cells also showed better multilineage reconstitution ability than fresh and seven-day cultured CD34⁺ cells. The results of the present study demonstrated that prolonged culture could preserve the hematopoietic reconstitution ability of ex vivo cultured CB cells and improve the engraftment level in NOD/SCID mice.     

Temporal relationships among LH, estradiol, and follicle vascularization preceding the first compared with later ovulations during the year in mares

Diameter of the preovulatory follicle, plasma concentrations of LH and estradiol, and vascularization of the follicle wall, based on color-Doppler signals, were characterized in 40 pony mares for 6 days preceding ovulation (Days -6 to -1; preovulatory period). Comparisons between the preovulatory periods preceding the first compared with a later ovulation during the year were used to study the relationships between LH and estradiol and between vascularization and estradiol. Diameter of the preovulatory follicle was greater (P<0.02) and concentration of LH was less (P<0.02) during the first preovulatory period, whereas concentration of estradiol was not different between the first and second preovulatory periods. Vascularized area (cm(2)) of the follicle wall increased at a reduced rate during the first preovulatory period, as indicated by an interaction (P<0.03) between day and group. Vascularized area was similar between the preovulatory groups on Day -6, and a reduced rate of increase resulted in a lesser (P<0.001) area on Day -1 before the first ovulation (1.4+/-0.1cm(2)) than before a later ovulation (2.2+/-0.2 cm(2)). Results demonstrated that follicle vascularization and the LH surge were attenuated preceding the first ovulation of the year with no indication that estradiol was involved in the differences between the first and later ovulations.     

Changes in glycosylated haemoglobin after poor control in insulin-dependent diabetics.

Glycosylated haemoglobin (HbA1) was measured in seven insulin-dependent diabetic patients before, during, and after a seven-day period of monitored poor control. There was considerable individual variation in the pattern and degree of change in HbA1 concentration induced by poor control and the time when it occurred. Greater increases in HbA1 were seen during the period of metabolic derangement than in the subsequent two months. More information is required before HbA1 estimations are widely used clinically to monitor control in individual diabetics.     

Response of the Sleep-Wake Rhythm to an 8-Hour Advance of the Light-Dark Cycle in the Rat

We have studied the effects of an 8-h advance of the environmental light-dark (LD) cycle on the sleep-wake rhythm in the rat. Electroencephalograms and electromyograms were recorded simultaneously on chart paper through a two-channel telemetry system for 3 days before phase shift (baseline) and 8 days during and after phase shift. Phase advance of the LD cycle led to an increase in both non-rapid eye movement (NREM) and REM sleep. The amount of NREM sleep in the light period correlated positively with that in the preceding dark period for 4 days after phase advance. The duration of REM sleep in the light period correlated negatively with that in the preceding dark period. The results suggest that homeostatic control of the amount of NREM sleep between the preceding dark period and the following light period is disturbed by phase advance of the LD cycle.     

One man, 73 years, and 25 species. Evaluating phenological responses using a lifelong study of first flowering dates

Phenological shifts linked to global warming reflect the ability of organisms to track changing climatic conditions. However, different organisms track global warming differently and there is an increasing interest in the link between phenological traits and plant abundance and distribution. Long-term data sets are often used to estimate phenological traits to climate change, but so far little has been done to evaluate the quality of these estimates. Here, we use a 73-year long data series of first flowering dates for 25 species from north-temperate Sweden to evaluate (i) correlations between first flowering dates and year for different time periods and (ii) linear regression models between first flowering date and mean monthly temperatures in preceding months. Furthermore, we evaluate the potential of this kind of data to estimate the phenological temperature sensitivities (i.e. number of days phenological change per degree temperature change, β₆₀) in such models. The sign of the correlations between first flowering dates and year were highly inconsistent among different time periods, highlighting that estimates of phenological change are sensitive to the specific time period used. The first flowering dates of all species were correlated with temperature, but with large differences in both the strength of the response and the period(s) of the year that were most strongly associated with phenological variation. Finally, our analyses indicated that legacy data sets need to be relatively long-term to be useful for estimating phenological temperature sensitivities (β₆₀) for inter-specific comparisons. In 10-year long observation series only one out of 24 species reached ≥80 % probability of estimating temperature sensitivity (β₆₀) within a ±1 range, and 17 out of 24 species reached ≥80 % probability when observation series were 20 years or shorter. The standard error for β₆₀ ranged from 0.6 to 2.0 for 10-year long observation series, and 19 out of 24 species reached SE < 1 after 15 years. In general, late flowering species will require longer time series than early flowering species.     

Response of the Sleep-Wake Rhythm to an 8-Hour Advance of the Light-Dark Cycle in the Rat

We have studied the effects of an 8-h advance of the environmental light-dark (LD) cycle on the sleep-wake rhythm in the rat. Electroencephalograms and electromyograms were recorded simultaneously on chart paper through a two-channel telemetry system for 3 days before phase shift (baseline) and 8 days during and after phase shift. Phase advance of the LD cycle led to an increase in both non-rapid eye movement (NREM) and REM sleep. The amount of NREM sleep in the light period correlated positively with that in the preceding dark period for 4 days after phase advance. The duration of REM sleep in the light period correlated negatively with that in the preceding dark period. The results suggest that homeostatic control of the amount of NREM sleep between the preceding dark period and the following light period is disturbed by phase advance of the LD cycle.     

Breast-feeding and post-partum amenorrhoea in Indonesia

The association between breast-feeding patterns and resumption of menses post-partum was examined in a prospective study in Indonesia. In order to examine these relationships directly in a longitudinal study, it was first necessary to distinguish among women who experienced infant mortality before menses resumed, women who weaned before menses resumed, and women who had return to menses while breast-feeding. Information on suckling patterns and menstrual status was collected by recall for 444 women at monthly visits for 2 years. Three main breast-feeding variables, minutes per episode, number of episodes per day, number of episodes per night, and other breast-feeding variables were derived for each woman, to give the average nursing pattern up to menses or the end of the study, which-ever came first. While high levels of nursing for each of these three main variables were found to be significantly related to delay in return of menses post-partum, the interactions between more minutes per episode, and more frequent day- and night-time feeds, were found to be the most important factors in the delay in onset of post-partum menstruation in those women whose menses resumed while still nursing or who remained amenorrhoeic and nursing at the end of the study.     

Seasonal Variation of Suicide in Brazil

Most of what is known about the seasonal variation in suicide rate originates from studies conducted in the northern hemisphere; very few studies have been done in the southern hemisphere. The purpose of the present study was to explore the possibility that in Brazil, the seasonal variation of suicides is a function of photoperiod. This was accomplished by analyzing monthly suicide data for a 12 yr period (1979 to 1990), within latitudes ranging from 2°N to 33°S. Single cosinor analyses with periods of 12 or 6 months were applied to time series of monthly total and suicidal deaths, separated by gender and state. Significant spring or early summer peaks of suicide were found only in the south of Brazil for both men and women, except for the latter in one state. These peaks did not coincide with those found for total deaths, which occurred in the autumn or winter in all areas. No significant six‐month period was found. In the present study, the chance of a suicide was typically 10–17% higher during the peak period than during the other months of the year. Although this moderate seasonal effect might not be sufficient to justify planning large scale prophylactic interventions, those dealing with patients who have suicide ideation should be aware of this high risk time.     

Seasonal variation of suicide in Brazil

Most of what is known about the seasonal variation in suicide rate originates from studies conducted in the northern hemisphere; very few studies have been done in the southern hemisphere. The purpose of the present study was to explore the possibility that in Brazil, the seasonal variation of suicides is a function of photoperiod. This was accomplished by analyzing monthly suicide data for a 12 yr period (1979 to 1990), within latitudes ranging from 2°N to 33°S. Single cosinor analyses with periods of 12 or 6 months were applied to time series of monthly total and suicidal deaths, separated by gender and state. Significant spring or early summer peaks of suicide were found only in the south of Brazil for both men and women, except for the latter in one state. These peaks did not coincide with those found for total deaths, which occurred in the autumn or winter in all areas. No significant six-month period was found. In the present study, the chance of a suicide was typically 10-17% higher during the peak period than during the other months of the year. Although this moderate seasonal effect might not be sufficient to justify planning large scale prophylactic interventions, those dealing with patients who have suicide ideation should be aware of this high risk time.