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In order to gain additional information on the role played by the opioids in the control of the secretion of anterior pituitary gonadotropins, morphine (an opioid agonist) and naloxone (an opioid antagonist) have been injected intraventricularly (i.v.t.) into normal or castrated male rats. The animals were killed by decapitation at different time intervals after treatment and serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were measured by radioimmunoassay. Animals injected i.v.t. with 0.9% saline solution and sacrificed at the same time intervals served as controls. When morphine (at the dose of 200 and 400 micrograms/rat) and naloxone (at the dose of 7.5 and 15 micrograms/rat) were injected i.v.t. into normal male rats, a significant increase of serum levels of LH was observed 10 and 20 min after injection. There was no effect at 5, 40 and 60 min. Lower doses of morphine (6.25, 12.5, 25, 50 and 100 micrograms/rat) given i.v.t. were ineffective. When morphine (200 micrograms/rat) and naloxone (either in the dose of 7.5 micrograms/rat or of 15 micrograms/rat) were given simultaneously, serum LH was significantly higher than in the saline-treated controls both at 10 and 20 min. However, the increases of serum LH levels induced by the combined treatment were in both instances lower than those produced by the administration of either drug alone. Morphine (200 micrograms/rat) when administered i.v.t. to normal male rats significantly enhanced prolactin release at 10 and 20 min, and this effect of morphine was blunted by the concomitant i.v.t. administration of naloxone (7.5 and 15 micrograms/rat).(ABSTRACT TRUNCATED AT 250 WORDS)

Since the description of the association of HLA-B8 antigen with celiac disease, it has been confirmed by many authors. The incidence of HLA-B8 antigen is higher in adults and children when it is compared to apparently healthy controls. Some authors found a reduction on the incidence of HLA-B7 antigen and others suggested that a higher incidence of HLA-B12 antigen in patients HLA-B8 antigen negative, is associated with celiac disease. We studied 19 unrelated patients with celiac disease and 64 controls. Their ages range from 18 months to 18 years old, onset of the disease was during childhood. We determined twelve antigens of the HLA-A locus and thirteen antigens of the HLA-B locus. We used the NIH Microlymphocytotoxicity Technique. The degree of association was computed by the relative risk and the results were statistically evaluated by the X2. The statistically significant increase in frequency was shown only for HLA-A29 The results did not show neither the higher incidence for HLA-B8 found by other authors, nor the higher incidence for HLA-B12; however HLA-B7 was not detected in our patients. The final decision on the association of HLA-A29 antigen with celiac disease in our population will require examination of a broader panel of probands.

Twelve infants with protracted diarrhea, unmanageable by the usual procedures, were treated with Total Central Parenteral Nutrition. Eleven of them were less than six months old. Two infants died in the course of treatment; the other ten recovered. The authors discuss the indications of this procedure, the technique used and, the possibility of performing it in centers not specialized in Nutrition.

Experiments have been designed in order to analyze whether the binding capability of mu opioid receptors in the brain of the male rat is modified by age. In a first experiment, the number of receptors (Bmax) and the constant of affinity (Ka) for the mu ligand 3H-dihydromorphine (3H-DHM) have been measured in the whole brain of male rats of 2, 15 and 22 months of age. In a second experiment the Bmax and the Ka for 3H-DHM have been evaluated in the hypothalamus of male rats of 2 and 22 months of age. In this experiment it was also investigated whether the administration of exogenous testosterone modifies the number and/or the affinity of the hypothalamic mu receptors. Serum levels of LH, FSH, prolactin and testosterone have been measured by specific RIAs. The results obtained show that: serum testosterone levels are significantly decreased in aged rats, while serum LH and FSH show only a small decline; serum prolactin is higher in old than in young animals; the number of mu receptors in the whole brain of 15 and 22 month old animals and in the hypothalamus of 22 month old rats is significantly lower than in the same tissues of young animals; the administration to old animals of testosterone, in doses able to bring back towards normal serum levels of testosterone, induces a decrease of LH and FSH, but has no effect on serum prolactin titers. Testosterone administration does not modify the number of hypothalamic mu opioid receptors, indicating that the decline of brain mu receptors in old animals is not the consequence of the physiological decline of testosterone secretion; in no instance the Ka for the mu ligand is significantly affected.

Twenty-seven patients with carcinoma of the fallopian tube were treated at the First Obstet. Gynecol. Clinic, University of Milan. Nineteen of them had the primary surgical procedure in our center and accounted for 2% of tubal and ovarian carcinomas. The others had been operated elsewhere. Another primary genital cancer occurred in 7 of these women and a breast carcinoma was recorded in the history of other 2. At laparotomy, 11 tumors were Stage I, 9 Stage II, and 7 Stage III. Postoperative adjuvant therapy was not homogenous, however chemotherapy was given to about 59% of patients. Five years survival rate was 65% for Stage I, 34% for Stage II and 17% for Stage III. The discussion deals with early diagnosis, prognostic and/or therapeutic role of pelvic and/or aortic lymphadenectomy and effectiveness of adjuvant therapy.

The aim of the present study was to evaluate whether arachidonic acid metabolism may play a role on luteinizing hormone (LH) and prolactin (PRL) release directly at the pituitary level. To this purpose, exogenous arachidonic acid, alone or in presence of inhibitors of cyclooxygenase (indomethacin:IND) and lipoxygenase pathways (nordihydroguaiaretic acid:NDGA), was added to perfused rat anterior pituitary cells. PGE, PGF alpha, LH and PRL levels present in the eluate were assayed with specific RIA methods. Both PGE and PGF alpha show a dose-related response after the addition of increasing doses of arachidonic acid. The addition of 0.05 mM arachidonic acid induces an increase of LH and PRL. The addition of IND to the perfusion medium highly potentiates the stimulatory effects induced by arachidonic acid on LH and PRL release. On the contrary, the addition to the medium of either NDGA or IND plus NDGA completely reverses the stimulatory action induced by arachidonic acid alone. The present results suggest that: adenohypophyseal cells are able to metabolize exogenous arachidonic acid; arachidonic acid induces an elevation in LH and PRL levels; lipoxygenase pathway metabolite(s) are likely involved in these activities, and the site of action of arachidonic acid is at the pituitary level.

Several experiments have been performed in order to clarify the mechanisms through which aging in male rats brings about profound modifications of the neuroendocrine system (reduced pulsatile secretion of LH and FSH, decreased serum levels of gonadotropins and testosterone, etc.). (1) It has been found that the number of mu opioid receptors decreases significantly in the hypothalami of old male rats; the substitution therapy with testosterone is ineffective in increasing the number of mu opioid receptors. These data suggest that the decrease of hypothalamic mu opioid receptors is not due to a decline of serum testosterone levels, but appears to be an independent phenomenon. (2) K opioid receptors increase significantly in the amygdala and in the thalamus of old male rats. These results show that aging, in addition to mu receptors, affects also the number of K receptors in selected areas of the brain. The increase of the number of K receptors in the amygdala might have some bearing on the decrease of serum gonadotropins observed in aged rats, since the amygdala is involved in the nervous circuitry influencing the hypothalamo-pituitary-gonadal axis. (3) The study of the release of LHRH from the hypothalamus of old male rats with an in vitro perfusion system shows that the release of the hormone is comparable in young and old animals, both in basal and in K+ stimulated conditions. These results indicate that the hypothalamus of old male rats retains the capacity of releasing LHRH both in basal and in stimulated conditions. (4) It has been observed that the number of LHRH receptors at the level of the anterior pituitary is significantly reduced in old male rats. This finding might explain the low serum levels of gonadotropins and testosterone in aged rats, due to a lack of an adequate response of the pituitary to hypothalamic LHRH.

Data collection forms of 50,165 routine smears were examined, and of these 47,577 were considered for this study. Viral cytological lesions (VL) were observed in 101 cases: of these, 19 were associated with cervical intraepithelial neoplasia. The total frequency of VL was 0.21%, with the peak in the teenager group (0.49%). The frequency of CIN among VL showed an overall frequency of 18.8%: this was null under 21 years of age and highest (50%) between 51 and 60 years of age. The frequency of VL in relation to clinical provenance of patients and the season of the year did not attain significance.

176 cases of cervical stump cancer have been reviewed. "Coincident cancer" and "True cancer" distinction has been made. Histological features, therapeutic plane and survival have been reported.

Thermal lesions were placed in the subcommissural organ (SCO) of female rats with normal cycles and long-term ovariectomized rats. In normal female rats SCO lesions disrupted the oestrous cycle in more than half of the animals, the majority of which entered a state of prolonged dioestrus. In these animals, serum gonadotrophin levels were similar to those of rats with regular cycles on day 2 of dioestrus. In animals in which the oestrous cycle was maintained, a delayed LH surge occurred on the day of pro-oestrus and the pro-oestrous FSH surge was absent. The usual increase in FSH on the day of oestrus was present. Lesions in the SCO did not change the high gonadotrophin levels typical of ovariectomized animals. These results suggested that the SCO may play a role in the control of the cyclic but not the tonic release of the gonadotrophins. In particular, it appears that the SCO might be involved in the regulation of the hypersecretion of FSH during the day of pro-oestrus.

A 29-year-old woman with tubal adenocarcinoma stage IA was treated only with bilateral salpingectomy, pelvic lymphadenectomy, and omentectomy. Two years later the patient successfully underwent in vitro fertilization and embryo transfer, and at 39 weeks gave birth to a healthy son by cesarean section. The result of oncologic follow-up 3 years after surgery is negative.

Several experiments have been performed in order to analyze whether physiological or experimental changes of the endocrine environment might modify the binding characteristics of brain mu and kappa opioid receptors in the brain of the female and male rat. (a) In a first series of experiments, it has been observed that in the whole brain of regularly cycling female rats the number of mu receptors shows variation during the different phases of the estrous cycle. In particular a significant increase of the number of mu receptors has been observed in the morning of proestrus and in the afternoon of estrus. (b) In a second series of experiments, it has been shown that the administration of estrogens brings about a significant increase in the number of mu receptors in the hippocampus and in the thalamus of ovariectomized rats, while the administration of a regime including estrogen and progesterone induces a significant decrease of the number of mu receptors in the hypothalamus and in the corpus striatum. These data seem to indicate that hypothalamic mu receptors may be involved in the positive but not in the negative feedback control of LH secretion. (c) In a third series of experiments, it has been found that the number of mu receptors in the whole brain of 15- and 22-month-old male rats and in the hypothalamus of 22-month-old male rats is significantly lower than in the same tissues of young animals; moreover, the administration to old animals of testosterone does not modify the number of hypothalamic mu opioid receptors, indicating that the decline of brain mu receptors in old animals is not the consequence of the physiological decline of testosterone secretion but probably represents an autonomous phenomenon. (d) In a fourth series of experiments, it was shown that, in young male rats, the concentration of kappa receptors is extremely variable in different regions of the brain. The highest concentrations have been found in the hypothalamus and in the striatum; also in the mesencephalon and in the amygdala kappa receptors are present in rather elevated quantities; lower concentrations have been found in the thalamus, the frontal poles, the hippocampus and in the anterior and posterior cerebral cortex. These experiments have shown in addition that the process of aging induces an increase of the number of kappa receptors in the amygdala and in the thalamus; no age-linked modifications were observed in the other structures examined.(ABSTRACT TRUNCATED AT 400 WORDS)

The experiments to be described have been designed in order to: (a) provide new information on the concentrations of opioid kappa receptors in different regions of the brain of the male rats; and (b) to analyze whether the density of brain kappa receptors might be modified by the process of aging. The concentration of kappa receptors was investigated in the hypothalamus, amygdala, mesencephalon, corpus striatum, hippocampus, thalamus, frontal poles, anterior and posterior cortex collected from male rats of 2 and 19 months of age. 3H-bremazocine (BRZ) was used as the ligand of kappa receptors, after protection of mu and delta receptors respectively with dihydromorphine and d-ala-d-leu-enkephalin. The results obtained show that: (1) in young male rats, the number of kappa opioid receptors is different in the various brain areas examined: the hypothalamus and the striatum have a concentration of kappa binding sites which is significantly higher than that found in the mesencephalon and in the amygdala; much lower concentrations of kappa binding sites have been found in the thalamus, the frontal poles, the hippocampus, the anterior and posterior cerebral cortex. (2) Aging exerts little influence on the number of kappa receptors in the majority of the brain structures considered. However in the amygdala and in the thalamus the number of kappa receptors was increased in old animals. To the authors' knowledge, the data here presented are the first ones which suggest that age may increase rather than decrease the number of neurotransmitter receptors in the brain.

Morphine (200 micrograms/rat) was injected intraventricularly (i.v.t.) into normal and into long-term castrated (4 weeks) adult male rats. Animals were killed 10, 20, 40 and 60 min after treatment. In normal animals, the treatment with morphine resulted in a significant increase of serum prolactin concentrations at all time intervals considered. However, the i.v.t. injection of 200 micrograms morphine/rat into castrated rats did not exert any significant effect on prolactin release at any time interval considered. When morphine (200 micrograms/rat) was administered i.v.t. together with the specific opioid receptor blocker naloxone (7.5 or 15 micrograms/rat) the stimulatory effect of morphine on prolactin release was diminished at 10 min, and totally blocked at 20 min. Naloxone given alone did not influence serum prolactin concentrations. The results suggest that the presence of endogenous androgens is essential to permit the stimulatory effect of morphine on prolactin release.

It is becoming increasingly clear that the effects of the opioids and their synthetic analogs on anterior pituitary function largely depend on the steroid milieu present in the animal at time of drug administration. However, it is still unclear whether gonadal steroids regulate the opioid-modulated mechanisms by affecting the number of opiate receptors in the brain. To further investigate these issues, the effects of opiate agonists and antagonists on LH, FSH and prolactin (Prl) secretion have been studied in: (a) normal and castrated male rats, and (b) normally cycling female rats. The binding characteristics of the brain subclass of mu opiate receptors have been analyzed in the same group of experimental animals; this type of receptors seems to be particularly involved in the control of gonadotropin and Prl release. When injected intraventricularly into normal male rats, morphine (200 micrograms/rat) induced in a significant elevation of serum LH levels at 10 and 20 min. In long-term castrated animals the administration of the drug significantly reduced LH secretion at 40 and 60 min after the injection, the inhibition lasted up to 180 min. Morphine, when given intraventricularly to normal males, induced a conspicuous and significant elevation of serum Prl levels at 10, 20, 40 and 60 min after treatment. However, when the drug was administered to castrated rats, it did not significantly affect Prl release at any time interval considered. Morphine intraventricular injections did not modify serum FSH levels either in normal or in castrated male rats. The concentration of mu opiate receptors was found to be similar when measured in the whole brain of normal and orchidectomized rats. In adult cycling female rats, s.c. injections of naloxone (2.5 mg/kg) stimulated LH release in every phase of the estrous cycle; the magnitude of the responses was highly variable, being particularly elevated at 16.00 h of the day of proestrous and at 10.00, 12.00 and 14.00 h of the day of estrous. Conversely, LH response to naloxone was totally obliterated at 18.00 and 20.00 h of the day of proestrous, when the preovulatory LH surge was found to occur. The concentration of brain opiate receptors of the mu type showed significant variations during the different phases of the estrous cycle, with higher levels at 12.00 h of the day of proestrous and at 18.00 h of the day of estrous.(ABSTRACT TRUNCATED AT 400 WORDS)

The present experiments have been performed in order to analyse whether the binding characteristics of brain opioid receptors of the mu type vary during the different phases of the oestrous cycle in the female rat. To this purpose different groups of females with a regular 4-day oestrous cycle were killed by decapitation in different phases of their oestrous cycle, i.e. at 10.00 and 16.00 h of the first and second day of dioestrus, at 10.00, 12.00, 14.00, 16.00 18.00 and 20.00 of the day of pro-oestrus, and at 10.00, 12.00 14.00, 16.00 and 18.00 of the day of oestrus. The total brains, after discarding the cerebellum, were homogenized and crude membrane preparations were obtained. On these preparations the maximal binding capacity (Bmax, index of the number of receptors) and the constant of affinity (Ka) for dihydromorphine, a typical ligand of mu opioid receptors were evaluated. Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were measured by specific radioimmunoassays in order to exactly ascertain the different phases of the oestrous cycle. The results obtained show that the number of mu opioid receptors in the whole brain presents significant changes during the different phases of the oestrous cycle. In particular, an increase in the concentration of these receptors was observed at 12.00 h of the day of pro-oestrus and at 18.00 h of the day of oestrus; these fluctuations of the number of mu receptors were not accompanied by any change of their affinity for the ligand.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging exerts profound influences on the function of the hypothalamic-pituitary-testicular-axis. This work has been performed in order to verify whether, in male rats, the decreased secretion of LH and testosterone (T) occurring in old animals is reflected by modifications of luteinizing hormone-releasing hormone (LHRH) receptors at the level of the anterior pituitary and of the testes. To this purpose, the affinity constant (Ka) and the maximal binding capacity (Bmax) for the LHRH analog [D-Ser(tBu)6]des-Gly10-LHRH-N-ethylamide were evaluated, by means of a receptor binding assay, in membrane preparations derived from the anterior pituitary and testicular Leydig cells of male rats of 3 and 19 months of age. Serum levels of LH and T were measured by specific RIAs. The results obtained show that, in aged male rats, the concentration of pituitary LHRH receptors is significantly lower than that found in young animals. On the other hand, the concentration of LHRH binding sites is significantly increased on the membranes of Leydig cells of old rats. In no instance the Ka for the LHRH analog is significantly affected. Serum levels of LH and T are significantly lower in old than in young male rats. In conclusion, these results suggest that the reduced secretion of LH in old male rats may be linked, at least partially, to a decrease of the number of pituitary LHRH receptors. The impaired production of testosterone occurring in aged rats is accompanied by a significant increase of the number of testicular LHRH receptors, indicating that also the intratesticular mechanisms controlling testosterone release undergo significant alterations with aging.

It is known that the neural mechanisms which control PRL and gonadotropin secretion are different in male and female rats. The present experiments have been designed in order to analyze: 1) whether sexual differences exist in the responses of PRL and LH to the opioid antagonist naloxone; and 2) the mechanisms underlying these possible differences. To this purpose the responses of PRL and LH to the sc injection of either saline (0.5 ml) or naloxone (2.5 mg/kg) have been tested in the following four groups of animals: 1) normal male rats; 2) normal female rats; 3) female rats treated on the second day of life with 1.25 mg testosterone (androgenized female rats); and 4) male rats orchidectomized 2 days postnatally (demasculinized male rats). The naloxone challenge has been provided when the animals were 16, 26, and 60 days old; the animals were killed in the afternoon 20 min after treatment. The results obtained have shown that the acute injection of naloxone significantly decreases serum levels of PRL in normal males and in androgenized females at all ages considered. On the contrary, the opioid antagonist was always ineffective in normal females and in neonatally castrated males. The treatment of male rats with naloxone was without any effect on LH release before puberty (at 16 and 26 days of age), but induced a significant increase of serum LH titers after sexual maturation (60 days). In normal females, naloxone brought about a significant increase of serum LH only at 16 and 60 days (animals in estrus), but not at 26 days. Treatment with naloxone did not exert any significant effect on LH release in androgenized females and in deandrogenized males of any age. The present data suggest that, in the rat a sexual difference exists in the opiatergic control of PRL secretion; apparently, the central opioid systems which regulate PRL secretion develop towards a male pattern because of the presence of androgens in the neonatal period. On the contrary neonatal androgens do not seem to exert any important effect in directing the organization of the opiatergic mechanisms controlling LH release.

It is becoming increasingly clear that the effects exerted by opioid agonists and antagonists on the release of gonadotropins and of PRL may vary according to the endocrine milieu. To investigate this issue further, female rats with a regular 4-day estrous cycle have been injected sc with the opioid antagonist naloxone at different hours of the day, during each of the various days of the estrous cycle. The animals were killed 20 min after the sc administration of naloxone (2.5 mg/kg dissolved in 0.9% saline solution) at 1000 and 1600 h on the first and second day of diestrus and at 1000, 1200, 1400, 1600, 1800, and 2000 h on proestrus and estrus. Animals were killed by decapitation, and trunk blood was collected and assayed for LH, FSH, and PRL. The data obtained from naloxone-treated animals were compared to those derived from controls injected sc with 0.9% saline solution and killed at the same time intervals. The sc injections of naloxone stimulated LH release in every phase of the estrous cycle; however the magnitude of the responses was highly variable. Increases of the order of 700-1.000% were observed during the 2 days of diestrus, at 1000 and 1400 h of the day of proestrus, and at 1600, 1800, and 2000 h of the day of estrus. Much higher responses (of the order of 2.700-3.300%) were observed at 1600 h of the day of proestrus and at 1000, 1200, and 1400 h of the day of estrus. The LH response to naloxone appeared to be obliterated at 1800 and 2000 h of the day of proestrus. Serum levels of FSH and PRL were not affected by the treatment at any of the time intervals considered. These findings suggest that, in normally cycling adult female rats, naloxone exerts a stimulatory effect on LH release during each day of the estrous cycle; that the stimulatory effect of naloxone is minimal at the time of the spontaneous proestrous LH surge; and that the effect of naloxone on LH release is, on the contrary, maximal just before the spontaneous proestrous LH surge and up to 1400 h of the day of estrus. The observation that naloxone does not affect FSH and PRL release underlines once more that the central mechanisms controlling LH, FSH, and PRL secretion are different.

This study of 200 Uruguayans between 0 and 86 years old was designed to determine the prevalence of lactose malabsorption. Lactose intolerance is defined as a clinical syndrome of abdominal pain, diarrhea, flatulence, and bloating after the ingestion of a standard lactose tolerance test dose (2 g of lactose per kilogram of body weight or 50 g/m2 of body surface area, maximum 50 g in a 20% water solution). Lactose malabsorption refers to the state in which dietary lactose remains unhydrolyzed and subsequently unabsorbed from the gastrointestinal tract; symptoms may or may not result from lactose malabsorption. The technique of breath hydrogen (H2) was used after ingestion of 2 g/kg body weight to a maximum of 50 g in a 20% solution. There was no lactose malabsorption in children younger than 5 years old. The prevalence increases progressively after the age of 5, and in adolescence the percentage of malabsorption is similar to that in adults, who show 65% lactose malabsorption, with 25% asymptomatic and 40% intolerant. In 109 white adults, the prevalence of lactose malabsorption is 63%, with 24% asymptomatic and 39% intolerant. In 11 black adults, lactose malabsorption is 82%, with 27% asymptomatic and 55% intolerant. The difference between white and black adults is statistically significant (p less than 0.05). The H2 test is simple, reliable, noninvasive, and appropriate to study large populations.