RESUMEN
Four men and 4 women with active acromegaly were treated with bromocryptine for 4 to 5 weeks. Serum growth hormone levels response to a glucose load were measured before and in the last weed of treatment. In only 1 patient was the grwotoh hormone response rendered normal by the drug. This patient, but none of the others, also showed an improvement in glucose tolerance and a reductin of the raised serum insulin levels during the glucose load. In three of the 8 patients vomiting was troublesome side effect of treatment.
Asunto(s)
Acromegalia/tratamiento farmacológico , Bromocriptina/uso terapéutico , Ergolinas/uso terapéutico , Acromegalia/sangre , Adulto , Anciano , Glucemia/metabolismo , Ayuno , Femenino , Hormona del Crecimiento/sangre , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
The effects of human recombinant insulin-like growth factor 1 (IGF-1) on the secretion, viability, and proliferation of dispersed human anterior pituitary adenomas secreting FSH, LH, and alpha-subunit (alpha-su) were examined in vitro over 4 h and 4 days. The acute effect of IGF-1 on secretion over 4 h was examined in four tumors secreting FSH, LH, and alpha-su. IGF-1 (100 nmol/L) reduced LH compared to control (100%) in one tumor (61%, P < 0.01), and three tumors remained unaffected. FSH and alpha-su secretion were insufficient to measure over 4 h. Nine tumors were studied over 4 days; relative to control, IGF-1 (100 nmol/L) increased FSH secretion in all seven tumors secreting FSH (28-266%, P < 0.05) and increased alpha-su secretion in all four tumors studied (36%, 63%, 91%, and 121%, P < 0.05). IGF-1 reduced LH secretion in four/nine tumors (13%, 23%, 32%, and 50%, P < 0.05). Dose response curves (1-100 nmol/L IGF-1) were performed on three tumors cosecreting FSH and LH. Stimulation of FSH was achieved with either 1 or 10 nmol/L IGF-1, a single tumor in which alpha-su was measured showed maximal stimulation at 10 nmol/L IGF-1, and one of three tumors showed LH inhibition with 100 nmol/L IGF-1. In situ viability of attached cells was assessed with fluorescein and propidium iodide in seven tumors. After 4 days' exposure to 100 nmol/L IGF-1, in situ viability was increased in five tumors (range 12-19%, 15 +/- 1.3% SEM, P < 0.05). The effects of IGF-1 on the adenoma cell proliferative S-phase fraction was determined in six tumors after 4 days of treatment using double immunostaining with bromodeoxyuridine incorporation for 1 h. In four/six adenomas that stained positive for bromodeoxyuridine in the controls (1-5.6%), the S-phase fraction was increased by 100 nmol/L IGF-1 [(range 2.1-10.6%, increase 90-220%) (P < 0.05)]. These results show that IGF-1 has differential effects on gonadotropins from human pituitary adenomas, stimulating intact FSH and alpha-su, inhibiting or being without effect on intact LH in vitro, and increasing both viability and number of tumorous glycoprotein-secreting cells entering into the S-phase of proliferation.
Asunto(s)
Adenoma/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Hormonas Adenohipofisarias/metabolismo , Neoplasias Hipofisarias/metabolismo , Adenoma/patología , Anciano , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Hormona Folículo Estimulante/biosíntesis , Hormonas Glicoproteicas de Subunidad alfa/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/fisiología , Hormona Luteinizante/biosíntesis , Masculino , Persona de Mediana Edad , Adenohipófisis/efectos de los fármacos , Adenohipófisis/metabolismo , Adenohipófisis/patología , Neoplasias Hipofisarias/patología , Proteínas Recombinantes/farmacología , Células Tumorales CultivadasRESUMEN
The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion, viability, proliferation, attachment and morphology of ten dispersed human clinically non-functional (NF) adenomas were examined in vitro. Four clinically NF adenomas secreting FSH and/or LH in vitro were unaffected by 10 nM bFGF over a 4-h period. Over 4 days 10 nM bFGF stimulated LH secretion (66% and 72%, P < 0.01) from two out of seven clinically NF adenomas secreting LH, whilst FSH (three tumours) and alpha-subunit secretion (three tumours) were unaffected. One adenoma co-secreting LH and alpha-subunit and one secreting LH alone were studied over 21 days; LH secretion fell progressively, but the decline was significantly less (P < 0.05) with bFGF (10 nM) treatment after 14 and 21 days in both adenomas, whilst the fall in alpha-subunit secretion was unaffected by bFGF treatment. A 24-h GnRH test performed at the start and end of the 21-day period in one of these tumours showed an increase in both basal and stimulated LH secretion in the bFGF-treated group over control (124%, P < 0.001). There was no effect of bFGF (10 nM) on viability, S-phase proliferation, attachment or morphology of adenoma cells over a 4-day period. These results suggest that bFGF has a role in tumorous LH secretion from these adenomas, but is not mitogenic (at least over 4 days) and is without effect on other parameters of in vitro differentiated function.
Asunto(s)
Factor 2 de Crecimiento de Fibroblastos/farmacología , Neoplasias Hipofisarias/metabolismo , Adenoma/metabolismo , Adulto , Anciano , Supervivencia Celular/efectos de los fármacos , Femenino , Hormona Folículo Estimulante/metabolismo , Hormonas Glicoproteicas de Subunidad alfa/metabolismo , Humanos , Hormona Luteinizante/metabolismo , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
Human anterior pituitary adenomas proliferate and express the p53 tumour suppressor gene protein, but it is not known if apoptosis (programmed cell death) occurs. Therefore, the detection of apoptosis was undertaken in tumorous human anterior pituitary tissue and compared with p53 protein expression, tumour type and tumour size. Apoptosis (detected by the in situ end labelling technique) and p53 suppressor gene protein (detected by DO.1-antibody immunocytochemistry) were determined in formalin-fixed and paraffin-embedded tissue from 37 human pituitary adenomas (2 macroprolactinomas, 9 somatotrophinomas and 26 non-functioning adenomas). Two normal anterior pituitaries were also included in this study. Pre-operative tumour size was scored 1 to 4 from magnetic resonance imaging radiology. Apoptosis was found in 7 of 29 tumours (24%), 11% of somatotrophinomas and 33% of non-functioning adenomas, although this difference was not significant. The p53 tumour suppressor protein was found in 7 of 31 tumours (23%), 33% of somatotrophinomas and 19% of non-functioning adenomas. Apoptosis and p53 protein expression were not found in normal anterior pituitary. In conclusion, apoptosis occurs in human anterior pituitary adenomas, but no significant association was found between apoptosis and p53 protein expression, tumour type or tumour size.
Asunto(s)
Adenoma/patología , Apoptosis/fisiología , Genes p53/genética , Neoplasias Hipofisarias/patología , Proteína p53 Supresora de Tumor/genética , Adenoma/química , Adenoma/genética , Adulto , Anciano , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/química , Neoplasias Hipofisarias/genética , Proteína p53 Supresora de Tumor/análisisRESUMEN
OBJECTIVES: To study the relationship between cervical mucus (CM) quality, postcoital test (PCT) results and plasma estradiol (E2) in clomiphene citrate (CC)-treated women. A subsidiary aim was to study the relationship between CM quality and plasma progesterone (P). DESIGN: Untreated women were compared with oligo-ovulatory patients given CC. SETTING: Infertility Clinic, Fazakerley Hospital, United Kingdom. PATIENTS, PARTICIPANTS: Fifty-one untreated patients and 31 women given CC. INTERVENTIONS: The treated women were given 50 mg/d CC from days 2 to 6 of their cycle. MAIN OUTCOME MEASURES: A CM assessment, a PCT, plasma E2, and P were performed at the anticipated time of ovulation based on at least two previous basal body temperature charts and menstrual patterns. RESULTS: In untreated women there was a very strong tendency for CM quality to improve with rising plasma E2 levels and to worsen with rising plasma P levels. There was a significant association between CM quality and PCT results. Similar results were found in CC-treated women, except that plasma E2 was very significantly higher and there was a significant inverse relationship between plasma E2 and CM quality. CONCLUSION: High plasma E2 in the periovulatory phase in CC-treated women is a marker for increased sensitivity to and continuing action of the antiestrogen. This impairs the quality of the CM.
Asunto(s)
Moco del Cuello Uterino/efectos de los fármacos , Clomifeno/farmacología , Estradiol/sangre , Progesterona/sangre , Clomifeno/uso terapéutico , Coito , Femenino , Humanos , Infertilidad Femenina/sangre , Infertilidad Femenina/tratamiento farmacológicoRESUMEN
Patients with gastrointestinal malignancy demonstrate impaired postoperative glucose disposal (17.5 +/- 1.4 mumol/kg min vs 28.9 +/- 2.5 mumol/kg min; P less than 0.001) and a reduced insulin response, during steady state hyperglycaemia, when compared with control. Analysis of glucose disposal when compared with insulin concentration suggested insulin resistance as a factor in the causation of impaired glucose disposal. In the control group both glucose disposal and insulin response demonstrated a negative correlation with malnutrition score (as assessed by a 13 factor, three grade scoring system), whereas in the cancer group only the insulin response was related to malnutrition score. However, the insulin response in the cancer group was quantitatively different from control subjects. The possible clinical implications of these findings are discussed.
Asunto(s)
Glucemia/metabolismo , Neoplasias Gastrointestinales/sangre , Adulto , Anciano , Femenino , Neoplasias Gastrointestinales/fisiopatología , Técnica de Clampeo de la Glucosa , Humanos , Insulina/sangre , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Estado Nutricional , Periodo PosoperatorioRESUMEN
Patients with gastrointestinal malignancy demonstrate impaired glucose disposal during steady state hyperglycaemia, 20.5 +/- 1.4 mumol/kg min when compared with controls 28.2 +/- 2.2 mumol/kg min. This appears to be unrelated to antecedent weight loss, but is related to the presence of metastatic spread (P less than 0.05). Insulin response to hyperglycaemia is normal, but analysis of glucose disposal with time suggests insulin resistance as a factor in the causation of impaired glucose disposal. Free fatty acid levels fail to suppress in cancer patients but their role in the causation of insulin resistance remains unclear.
Asunto(s)
Adenocarcinoma/sangre , Glucemia/metabolismo , Peso Corporal , Neoplasias Gastrointestinales/sangre , Adulto , Anciano , Anciano de 80 o más Años , Caquexia/sangre , Femenino , Glucosa/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
The authors compared detection methods for cell proliferation in human anterior pituitary adenomas using histological sections and dispersed cell culture. After tumor cells had been grown for 4 days in dispersed culture, bromodeoxyuridine (BUdR), proliferating cell nuclear antigen (PCNA), and Ki-67 were compared by double immunostaining and contrasted with single staining of PCNA and Ki-67 indices in the corresponding histological sections from 12 human pituitary adenomas. In vitro, the BUdR labeling index was positive in six of 12 tumors (range < 0.1-5.1%), 10 of 12 tumors were PCNA-positive (range < 0.1-100%), and Ki-67 was positive in 10 of 12 adenomas (range < 0.1-8%). In vitro, BUdR and Ki-67 gave similar proliferative indices for 10 of 12 adenomas. In vivo, the PCNA labeling index was positive in 12 of 12 adenomas (range 0.9-95%) and Ki-67 was positive in 11 of 12 adenomas (range < 0.1-2%). Tumors with a labeling index less than 0.1% were considered to be negative for proliferation. High PCNA values were found in vitro and in vivo, whereas Ki-67 labeling indices were similar in vitro and in vivo for nine of 12 adenomas. It is concluded that Ki-67 proliferative indices in vivo reflect those found in vitro, at least after 4 days in dispersed culture, but that PCNA overestimates pituitary adenoma proliferation in histological sections as well as in dispersed culture.
Asunto(s)
Adenoma/patología , Adenohipófisis , Neoplasias Hipofisarias/patología , Bromodesoxiuridina/metabolismo , División Celular , Células Cultivadas , Fijadores , Formaldehído , Humanos , Técnicas Inmunológicas , Antígeno Ki-67/metabolismo , Neoplasias Hipofisarias/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Coloración y EtiquetadoRESUMEN
A method to determine whether dispersed human anterior pituitary adenoma cells proliferate in mixed culture was developed. Fifteen pituitary adenomas were dispersed enzymatically to single cells, following which twelve were double immunostained after eight days. Proliferating cells were identified immunologically following one hour of bromo-deoxyuridine incorporation. Adenoma cells were subsequently identified with an anti-neuron-specific enolase antibody system. A time course of bromo-deoxyuridine labelling was performed on three nonfunctional adenomas over a four day period, with bromo-deoxyuridine being added to cultures at one hour, 24 hours and four days prior to immunostaining. Double immunolabelled cells were unambiguously identified by a dark brown nucleus surrounded by red cytoplasm. Eight out of 12 pituitary adenomas (two prolactinomas, three nonfunctional, three growth hormone secreting) showed an increased bromo-deoxyuridine labelling index (range 0.1%-1.4%). Bromo-deoxyuridine incorporation over four days showed an increase in bromo-deoxyuridine from 0.02%, 0.03% and 3.3% at one hour to 10.1%, 1.3% and 5.0% at four days, respectively, but evidence of mitosis was scant. This study shows that pituitary adenomas may proliferate in vitro and that this double immunostaining method may be used as an in vitro proliferation assay in a mixed cell population.
Asunto(s)
Biomarcadores de Tumor , Fosfopiruvato Hidratasa/análisis , Neoplasias Hipofisarias/química , Prolactinoma/química , Adulto , Anciano , Bromodesoxiuridina , División Celular/fisiología , Endotelio/química , Femenino , Fibroblastos/química , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Fase S , Células Tumorales Cultivadas/química , Células Tumorales Cultivadas/citologíaRESUMEN
Concentrations of 14 commonly-requested plasma hormones were measured in octuplicate in each of six subjects to determine their stability when unseparated from red cells for periods up to 1 week. Most of the analytes were stable when stored in this way and although statistically significant changes were recorded, in the great majority of cases the changes seen would have no bearing on the clinical interpretation of the result. In the light of these findings, we would confidently report results of analyses for these hormones in plasma that had remained in contact with red cells at ambient temperature for long periods of time.
Asunto(s)
Hormonas/sangre , 17-alfa-Hidroxiprogesterona , Hormona Adrenocorticotrópica/sangre , Análisis de Varianza , Androstenodiona/sangre , Análisis Químico de la Sangre , Conservación de la Sangre , Deshidroepiandrosterona/análogos & derivados , Deshidroepiandrosterona/sangre , Sulfato de Deshidroepiandrosterona , Eritrocitos/metabolismo , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/sangre , Hidroxiprogesteronas/sangre , Hormona Luteinizante/sangre , Masculino , Progesterona/sangre , Prolactina/sangre , Testosterona/sangre , Tirotropina/sangre , Tiroxina/sangreRESUMEN
Eleven patients were investigated for pituitary function after the injection of alcohol into the pituitary fossa; all had persistent pain and 8 had carcinoma of the breast. Most of the patients showed varying degrees of reduction of pituitary activity; 8 patients obtained significant pain relief and 3 patients exhibited polyuria. These 3 observations could not be completely correlated; the possible mechanisms which may lead to pain suppression by this method are discussed.
Asunto(s)
Etanol/uso terapéutico , Cuidados Paliativos , Hipófisis/efectos de los fármacos , Adulto , Anciano , Neoplasias de la Mama/complicaciones , Etanol/administración & dosificación , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Pruebas de Función Hipofisaria , Hormonas Adenohipofisarias/sangreRESUMEN
A survey has shown that many women favour eliminating menstruation and it has been suggested that therapeutic induction of amenorrhoea might be an advantage in female personnel mobilised for war. The traditional method has been to take the oral contraceptive pill continuously. This produces weight gain and other side-effects; spotting and breakthrough bleeding can be a problem initially. The method is however cheap. The Gonadotrophin Releasing Hormone (GnRH) analogue, goserelin, is extremely effective, produces less side-effects, but it is very expensive. Two synthetic steroids, danazol and gestrinone, are moderately effective, have a variety of prominent side-effects and are also quite expensive. With all these drugs normal menstruation resumes in the cycle after they are discontinued. Although goserelin has many advantages over the continuously taken contraceptive pill, its cost precludes it from consideration as a means of eliminating menstruation.
PIP: The Royal Army Medical Corps (RAMC) of the UK is considering offering women in the Army the option of inducing amenorrhea especially those in war. Logistics problems of supplying sufficient sanitary protection makes inducing amenorrhea in these women an advantage. It is important that the Royal Army not force servicewomen ready for war to agree to chemical induction of amenorrhea, however. A survey of civilian women shows that 80% liked the notion of eliminating menstruation. continuous combined oral contraceptive (COC) therapy induces amenorrhea, but it poses some side effects including bleeding and spotting, 2 kg weight gain, breast tenderness, depression, and headaches. 12 weeks of COC therapy costs range form 2 to 6 pounds. The synthetic androgen used to treat endometriosis, danazol, may also induce amenorrhea at daily doses of 800 mg. It causes various side effects including reduced breast size, flushing, sweating, loss of libido, acne, weight gain, edema, hirsutism, and voice change. 12-week danazol therapy costs about 200 pounds. Another drug with androgenic, antigonadotrophic, antiestrogenic, and antiprogestogenic properties which is also used to treat endometriosis, gestrinone, in another possible amenorrhea inducer at 2 doses of 2.5-5 mg/week. Side effects are similar to those of danazol. In 1 study, all 20 patients developed acne and seborrhea. Its 12 week costs are considerably more than danazol and COC therapy (450 pounds). Intermittent administration of 2 gonadotropin releasing hormone (GnRH) analogues, buserelin and goserelin, suppresses production of gonadotropins. Health workers need to inject 3.6 mg goserelin every 28 days while they administer buserelin subcutaneously or intranasally. the leading side effect on both GnRH analogues is not flushes. 12-week therapy is about 375 pounds. Fertility is restored after discontinuation of all the aforementioned therapies. The GnRH analogue goserelin is the most effective therapy, but the cost factor causes the Royal Army to favor COCs.