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Biomedical subjects

A Carpi

Publications and source records attributed to A Carpi.

At least 19 recordsLinked to original sources

Low-dose aminoglutethimide with and without hydrocortisone replacement as a first-line endocrine treatment in advanced breast cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research.

PURPOSE: A randomized study comparing low-dose aminoglutethimide (AG) with and without hydrocortisone (HC) was performed to investigate whether corticosteroid replacement contributes to the therapeutic effects of the drug administered as a front-line endocrine therapy in postmenopausal advanced breast cancer. PATIENTS AND METHODS: Postmenopausal patients who had not had prior endocrine therapy for advanced disease and with estrogen receptor (ER) or progesterone receptor (PgR) status positive or unknown were eligible. AG was administered at a dose of 250 mg twice a day orally (125 mg twice a day during the first month) with or without HC (20 mg twice a day orally). Seventy-nine and 74 patients were assessable for response on the AG plus HC arm and on the AG arm, respectively. The two treatment groups were well balanced and patients were largely untreated. Approximately 60% had not received any adjuvant treatment, and approximately 75% had not received any medical treatment after relapse. RESULTS: The overall responses (complete response [CR] plus partial response [PR]) were 44% and 41% for the AG plus HC and the AG arm, respectively, showing no significant difference. Time to progression (median, 8.1 and 6.3 months), duration of response (median, 15.8 and 13.7 months), and duration of survival (median, 34.2 and 36.3 months) were not significantly different between the two treatment arms. Side effects were infrequent and mild in both arms, with no significant differences. CONCLUSION: We conclude that half of the conventional daily dose of AG has optimal therapeutic activity as a front-line endocrine treatment of postmenopausal advanced breast cancer and that HC does not significantly contribute to the therapeutic effects.

Adenocarcinoma

Effect of a single oral dose of L-thyroxine (150 micrograms) on serum thyroid hormone and TSH concentrations in clinically euthyroid goitrous patients.

Serum TT4, FT4, TT3, FT3 and TSH, concentrations were measured before and 0.5, 1, 2, 3, 4, 5 hours after a single oral dose of L-T4 (150 micrograms) in 21 clinically euthyroid goitrous patients on a long-term therapy program. The mean basal TT4 concentration, 8.85 +/- 0.52 micrograms/dl (mean +/- se), increased significantly at the second hour (10.04 +/- 0.52 micrograms/dl, p < 0.001) and reached the highest value at the third hour (10.35 +/- 0.55 microgram/dl, p < 0.001). Subsequently the mean serum TT4 concentration remained elevated until the fifth hour (10.20 + 0.60 microgram/dl, p < 0.001). The mean basal value of FT4 concentration, 8.66 +/- 0.40 pg/ml, increased significantly at 30 minutes (9.19 +/- 0.40 pg/ml, p < 0.01) and reached the highest value at the third hour (11.81 +/- 0.56 pg/ml, p < 0.001). The mean basal serum FT3 concentration, 3.56 +/- 0.10 pg/ml, increased significantly 30 minutes (3.72 +/- 0.11 pg/ml p < 0.05) after L-T4 administration; the mean serum FT3 concentration was significantly higher than the basal level and 1 and 2 hours as well, and reached the highest value at the third hour (3.86 +/- 0.09 pg/ml). The mean serum TT3 concentration did not show any significant change at any time. The mean basal TSH value (2.73 +/- 0.42 microUI/ml) declined progressively. At 30 minutes it decreased significantly (2.29 +/- 0.38 microUI/ml, p < 0.01) and reached the lowest value at the fifth hour (1.39 +/- 0.26 microUI/ml, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Long term therapy with a new liquid L-thyroxine preparation: bioequivalence with L-T4 tablets.

Seventy-four euthyroid patients with nodular goiter (55) or primary hypothyroidism (19) were selected for long term treatment with a new preparation containing L-T4 in solution (Tiroxen, Laboratori Baldacci, Pisa, Italy). Each patient underwent, before or after receiving the L-T4 in solution, long term treatment with L-T4 in tablet form at the same dose. The serum concentrations of TSH, TT4, TT3, FT4 and FT3 were measured basally and during therapy with each of the two L-T4 preparations (liquid and tablet). In the golter group, mean serum TSH concentration was 1.4 microUI/ml basally, while it was 0.47 microUI/ml following both L-T4 tablet therapy and L-T4 solution administration. Mean basal TSH value was significantly different from the two values on the therapy (p < 0.001 in each instance). Mean basal serum TT4 concentration was 8.2 +/- 0.25 microgram/dl basally while it was 9.9 +/- 0.28 microgram/dl (p < 0.001) on L-T4 tablet therapy and 9.7 +/- 0.26 (p < 0.001) on L-T4 solution administration. Mean basal serum concentration of TT3, FT4, FT3 was not significantly different from the value on the therapy, either with L-T4 tablet or with L-T4 solution. In the hypothyroid patients the high mean basal serum TSH concentration (23.6 microUI/ml) returned to normal similar values on L-T4 tablet therapy (0.96 microUI/ml; p < 0.01) and on L-T4 solution administration (1.24 microUI/ml; p < 0.01). The serum TSH concentration value during L-T4 therapy varied from unmeasurable level to 3.5 microUI/ml during the tablet administration and to 4.8 microUI/ml during the solution administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Evaluation of serum CA15-3 determination with CEA and TPA in the post-operative follow-up of breast cancer patients.

The usefulness of post-operatively serial serum CA15-3 determination with CEA and TPA was evaluated in a group of 285 breast cancer patients. In particular, the CA15-3 sensitivity to 'early' diagnosis and monitoring of the response to treatment of breast cancer relapses, was compared with those of the two other markers in order to define the most suitable association. Moreover, in a group of 169 non relapsed patients with a prolonged follow-up (40 +/- 8 months; mean +/- s.d.) CA15-3 specificity was investigated. During post-operative follow-up in 27 (10%) patients, distant metastases occurred. In most of them, elevated values of one or more tumour markers were the first pathological sign and CA15-3, CEA and TPA sensitivity to 'early' diagnosis of metastases were 46%, 7% and 63% respectively. When each tumour marker was considered in combination, CA15-3-CEA-TPA association showed a higher sensitivity (87%) than both CA15-3-TPA (83%) and the CEA-TPA (70%). Serum CA15-3 increase preceded the certain sign of metastases 2.7 +/- 2.6 months (mean +/- s.d.). Shortly before appearance and during treatment of distant metastases, constant elevation and/or progressive increase in serum CA15-3 values occurred in all evaluated patients except three in whom isolated elevated values were found as well. In 24 (14%) of 169 non relapsed patients with prolonged follow-up (40 +/- 8 months; mean +/- s.d.) high serum CA15-3 values occurred. In 16 of these 24 patients, an isolated elevated value was found, while four (2.3%) or the eight remaining ones with constant elevation and/or progressive increase were falsely suspected of metastases. In this group of non relapsed patients, chronic liver failure, diabetes and/or hepatic steatosis were the reasons more commonly responsible for the CA15-3 increase. In metastatic patients, no organ-specificity was shown either by CA15-3 or by CEA and TPA. In these patients serum TPA values showed the highest sensitivity and paralleled clinical and/or instrumental signs better than the CA15-3 and even more than CEA values. These data indicate that in the post-operative follow-up of breast cancer patients, TPA is the most useful tumour marker and TPA-CA15-3 the most suitable association. Contemporaneous measurement of serum CEA levels only slightly increases sensitivity and positive predictive value of TPA-CA15-3 combination.

Adult

The thyroid nodule: diagnostic strategy.

This paper comments on the principal techniques (nuclear imaging echography and needle aspiration) and the most widely used protocols available for preoperative selection of thyroid nodule patients. Successively, the authors report the principles to define a new appropriate protocol based on needle aspiration and hormone assays and evaluate their experience with this new simple protocol. Long term clinical practices shows that surgical excision can be avoided for more than 90% of the nodule patients and that thyroid scintigraphy can be avoided for most of these patients, without appreciable disadvantage.

Adult

The measurement of plasma D-dimer in the follow-up after thyroidectomy for cancer: preliminary data.

Plasma concentration of fibrinopeptide A (FpA) and D-dimer (DD), sensitive indicators of coagulation and fibrinolysis activation, were measured in 21 patients thyroidectomized for differentiated cancer (4 had distant metastases) and in 27 control subjects. Only two patients (one with distant metastases) presented elevated FpA values. All the four patients with distant metastases showed elevated DD levels. In three patients who developed distant metastases the time course of the circulating levels of plasma DD and serum thyroglobulin (Tg) was monitored. Monitoring of plasma DD concentration correctly indicated the time course of all the 3 metastatic patients while serum Tg levels failed to adequately describe the outcome of one metastatic patient. These data suggest that fibrinolysis is enhanced in thyroid cancer patients with distant metastases and that plasma DD levels are useful in the monitoring of this condition.

Adenocarcinoma

Enhancement of pharmacologically induced bronchoconstriction by Ro 5-4864.

Pretreatment with Ro 5-4864 enhanced the bronchoconstrictor responses to histamine or carbachol in the anaesthetized artificially ventilated guinea pig. This suggests the involvement of a peripheral-type benzodiazepine receptor as also indicated by the lack of effect of clonazepam. PK 11195 did not antagonize the Ro 5-4864-induced enhancement, but itself enhanced the bronchoconstrictor responses to histamine or carbachol. The data indicate that Ro 5-4864 and PK 11195 behave as metactoid sensitizers of histamine or carbachol.

Animals

A comparison of continuation versus late intensification followed by discontinuation of chemotherapy in advanced breast cancer. A prospective randomized trial of the Italian Oncology Group for Clinical Research (G.O.I.R.C.).

One hundred ninety-eight postmenopausal women with metastatic breast carcinoma were entered in this study. After six induction cycles with cyclophosphamide, methotrexate and 5-fluorouracil (CMF), patients with at least stable disease were randomized to the "continuation arm" (continuation of CMF until progression) (A, 49 evaluable patients) or to the "intensification-discontinuation arm" (addition of adriamycin and vincristine to two of the three drugs of CMF for six more cycles; i.e., CMAV, CFAV, MFAV, twice; discontinuation of chemotherapy; radiotherapy to pre-study sites of disease in patients prospectively considered as candidates to receive this treatment) (B, 46 evaluable patients). After randomization, escalation of response category occurred in five patients on A (10%) and in five on B (11%). Time to progression was transiently delayed in arm B within 6 months after randomization. There were no significant differences in the overall time to progression, duration of response or survival. On arm B, after discontinuation of chemotherapy, median time to relapse was 22 weeks. This time was significantly longer in patients who were candidates for radiation therapy (36 weeks, P = 0.005), or with a disease-free interval greater than 1 year (32 weeks, P = 0.004) or who achieved complete remission (60 weeks, P = 0.0001). On arm B, three patients (7%) are still alive in complete remission in excess of three, five and six years following discontinuation of therapy. This study indicates that late intensification of chemotherapy followed by discontinuation of treatment may maintain palliation, and allow a long treatment-free period in responding patients with advanced breast carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols

Low protein supplemented diet corrects altered serum thyroid hormone and TSH concentrations in patients with chronic nephrotic syndrome.

Creatinine clearance, daily urinary protein excretion, serum concentrations of thyroid hormones (TT4, TT3, fT4, fT3), TSH and parathyroid hormone (PTH), have been measured before and after 2 or 6 months of a low protein diet supplemented with aminoacids and ketoanalogues in 18 patients affected by chronic nephrotic syndrome without significant impairment of renal function. Mean creatinine clearance and mean serum protein concentration (79.5 +/- 13.8 ml/min and 5.4 +/- 0.6 g/dl, mean +/- S.D., respectively) did not significantly change (79.1 +/- 17.3 ml/min and 5.5 +/- 0.6 g/dl) after the diet. Mean daily urinary protein excretion (7.1 +/- 2.2 g/day basally) significantly decreased (5.5 +/- 1.9 g/day) after the diet (p less than 0.05). Mean serum TT4 concentration (5.6 +/- 1.8 micrograms/dl basally) significantly increased (6.7 +/- 2 micrograms/dl, p less than 0.05) after the diet. Mean serum TT3 concentration (106.7 +/- 28.5 ng/dl, basally) significantly increased (126.7 +/- 22.6 ng/dl) after the diet (p less than 0.01). Mean serum fT4 and fT3 concentrations (8.0 +/- 2.9 pg/ml and 4.5 +/- 1.6 pg/ml, respectively) did not significantly change (9.4 +/- 2.7 pg/ml, and 4.9 +/- 1.9 pg/ml, respectively) after the diet. In some patients low basal serum concentration values of TT4, TT3, fT4, fT3 became normal after the diet. Mean serum TSH concentration (3.1 +/- 2.3 microU/ml basally), significantly decreased (1.5 +/- 1.3 microU/ml) after the diet (p less than 0.05). Mean serum PTH concentration (0.7 +/- 0.3 ng/ml basally) significantly decreased (0.4 +/- 0.2 ng/ml) after the diet (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Sjögren's syndrome in childhood. Description of a clinical case].

A case is reported of Sjögren's syndrome in childhood. According to Fox's classification, this patient presented all four inclusion criteria for the diagnosis of the disease. The Authors report the satisfactory evolution of the disease using therapy with FANS and corticosteroids and immunosuppressors during acute exacerbations.

Adrenal Cortex Hormones

A rational postoperative follow-up with carcinoembryonic antigen, tissue polypeptide antigen, and urinary hydroxyproline in breast cancer patients.

Breast cancer patients (n = 224) aged 28 to 81 were postoperatively followed up with serial determinations of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and urinary hydroxyproline (OHP). The clinical usefulness of these tumor markers to diagnose and monitor distant metastases was compared with that of the imaging techniques commonly used to monitor breast cancer patients (bone scanning [BS], liver echography [LE], chest radiograph, and skeletal radiograph). So far, 23 patients withdrew from the study, and distant metastases occurred in 33 patients. In 91% of the metastatic patients, constant elevation or progressive increase in serum CEA and/or TPA levels were the first pathologic findings of the relapse. Of the remaining 168 nonrelapsed patients, 122 were followed up longer than 24 months (43 +/- 17 months; mean +/- SD). In these 122 patients the false-positive results of CEA, TPA, and OHP were 0.8%, 2.4%, and 0%, respectively, when used simultaneously with clinical examination and the common laboratory examinations. BS and LE are the only imaging techniques that showed such a high sensitivity to be suitable in the postoperative follow-up of breast cancer patients. Nevertheless, because BS has a low specificity and is not harmless, it should be performed at longer intervals than tumor markers. Eventually, in the relapsed patients, TPA and OHP well reflected the response to treatment better than CEA and prevented useless radiologic examinations.

Adult

Clinical use of a new pharmaceutical preparation containing L-thyroxine in solution. Preliminary report.

A pharmacological preparation containing L-thyroxine in solution has been tested in man for thyroid substitution or suppression. Twenty-two women and 2 men, aged from 30 to 82 years, with primary hypothyroidism (10) or nodular goiter (14) were treated. Serial clinical and laboratory follow-up evaluations were performed, varying from 1 to 18 months. Five hypothyroid patients and 12 with goiter had not received any previous thyroid hormone medication. Clinical and laboratory euthyroidism was achieved in all 5 hypothyroid patients by a mean weekly L-T4 dose of 580 micrograms. Inhibited or blunted TSH response to TRH was obtained in the subjects with goiter by a mean weekly L-T4 dose of 683 micrograms. The remaining 7 patients (5 hypothyroid and 2 with nodular goiter) received first L-T4 in tablet and then L-T4 in solution. Four of these 7 patients (2 hypothyroid and 2 with nodular goiter), treated with equal doses of the two L-T4 preparations, showed lower basal and stimulated serum TSH concentration during administration of L-T4 in solution. No signs of hyperthyrodism were observed during the treatment. These data indicate that the tested preparation containing L-T4 in solution can be used for thyroid substitution or suppression, and agree with our previous determination of L-T4 content in the preparations indicating an excess of L-T4 in the solution.

Adult

Cisplatin (P) versus cyclophosphamide, adriamycin and cisplatin (CAP) for stage III-IV epithelial ovarian carcinoma: a prospective randomized trial.

In 1982 a randomized trial was started to compare a cisplatin-containing polychemotherapy (CAP: cyclophosphamide - CPA 750 mg/m2, adriamycin - ADM 50 mg/m2, cisplatin - P 50 mg/m2 on day 1 every 21 days) with full-dose cisplatin as single agent (P 60 mg/m2/day on days 1 and 2 every 28 days) in 44 patients undergoing exploratory laparotomy or debulking surgery for stage III-IV epithelial ovarian carcinoma with residual disease greater than 5 cm. The response was evaluated at second-look surgery with random biopsies and peritoneal washing. On the basis of the final results the authors underline some data which, although merely indicative (because of the small number of patients) appear to be worth considering since they are in accordance with the latest reports: a) similar response rate (CR + PR = 47%) to first-line treatment in the two groups; b) the CAP treatment may achieve a longer median duration of CRs than the P treatment (20 versus 11 months); c) overall survival seems similar in the two groups of patients (19 versus 18 months), whereas the survival of CRs seems longer in the CAP treated patients (greater than 32 versus 25 months). The authors also discuss some observations on a possible salvage therapy.

Adult

Needle aspiration of thyroid nodule: long-term control of its efficiency in preoperative selection.

Eight years extensive use of surgery for detecting thyroid cancer in euthyroid patients with palpable nodule was compared to 8 years preoperative selection by needle aspiration techniques to the same purpose. One thousand one hundred and forty operations were performed from 1972 to 1979; 3079 patients were examined by needle aspiration from 1980 to 1987. The female to male and single to multiple palpable nodule ratios were 5.2, 2.5 in the former and 6.8, 2.7 in the latter group respectively. Postoperative histology showed that nodules were malignant in 35 subjects and benign in 1105 patients of the first group. Two hundred thirty eight patients of the 3079 patients of the second group were operated upon mainly following aspiration findings. Postoperative histology showed primary malignant tumors in 88 patients. Therefore, introduction of needle aspiration techniques reduced the number of operations from 143 per year to 30 per year and increased from 4 to 11 per year the number of malignant nodules detected without any change of the incidence of cancer (about 3% in each group).

Biopsy, Needle

Effects of carotid compression, as assessed by near infrared spectroscopy, upon cerebral blood volume and hemoglobin oxygen saturation.

Near infrared spectroscopy, a recently developed optoelectronic technique, has been studied as a possible method of monitoring the adequacy of cerebral perfusion in 22 patients who were candidates for carotid endarterectomy. Using this technique, changes in haemoglobin volume, haemoglobin oxygen saturation and redox level of cytochrome-c-oxidase were recorded from the frontoparietal region during routine carotid compression tests performed under continuous electroencephalographic (EEG) monitoring. A highly significant association was found between EEG slowing, indicating impaired cerebral function, and a fall in haemoglobin volume and oxygen saturation, indicating a reduced blood and oxygen supply to the brain (Fisher exact test, P less than 10(-5]. In a few tests haemoglobin volume and oxygen saturation were reduced without changes in the EEG recording. This study raises new issues concerning the compensatory mechanisms taking place during carotid occlusion and suggests that near infrared spectroscopy might be useful in monitoring the blood and oxygen supply to the brain during carotid endarterectomy.

Aged

Arachidonic acid and pulmonary function in heart-lung-preparation of guinea-pig: modulation by PCO2.

In normocapnic and deeply hypocapnic guinea-pig heart-lung-preparations (HLPs), dose-response relationships were estimated for the bronchoconstrictor and pulmonary hypertensive responses to histamine (H), 5 hydroxytryptamine (5HT), arachidonic acid (AA) and U-46619, a prostaglandin endoperoxide analogue acting on thromboxane (TXA2) receptors. Hypocapnia potentiated in a different way the bronchoconstrictor effects of AA (increased slope of dose-response curve) and of U-46619 (shift to the left of the curve). The pulmonary vascular effects of U-46619 were unaffected by CO2 tension, whereas a linear log dose-dependence of the pulmonary hypertensive responses to AA was present only in hypocapnic HLPs. The amount of TXA2-like material released in normocapnic HLPs was compatible with the AA/U-46619 potency ratio calculated for the bronchoconstrictor responses in normocapnic HLPs and for the pulmonary vascular responses in hypocapnic HLPs. The above described effects of hypocapnia were different from those produced on the bronchial and pulmonary vascular reactivity to H and 5HT, suggesting that specific mechanisms are involved in the modulating effect of PCO2. The inhibition by indomethacin of AA-induced pulmonary vasoconstriction was unaffected by changes in CO2 tension; conversely, the bronchoconstrictor effects of AA were more substantially reduced by indomethacin in normocapnic HLPs. It is concluded that: the relative contribution of different AA metabolites to the final response of the airway system to the precursor is affected by changes in CO2 tension; different receptorial or prereceptorial mechanisms are involved in the CO2-AA interaction taking place in the two components of the lung parenchyma; the pulmonary outflow of AA metabolites provides only circumstantial evidence of the functional meaning of this release.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

Calcium entry blockers and cardioplegia: interaction between nifedipine, potassium, and hypothermia.

The potential additive protective effect provided by nifedipine to the University of Alabama Hospitals cardioplegia solution (ACS) was assessed with the use of a guinea pig heart-lung model of cardiopulmonary bypass and ischemic arrest. The addition of nifedipine consistently enhanced the protective properties of ACS infused at 37 degrees C; functional recovery was similar to that observed with cold ACS. Despite the additional protection under normothermic conditions, nifedipine did not improve recovery after infusion at 4 degrees C. The abolition by hypothermia of the protective effects of nifedipine suggests a similarity in action between nifedipine and hypothermic protection. The interaction between ACS and nifedipine was studied on bovine coronary arteries in vitro. Nifedipine caused a marked reduction in the coronary vasoconstricting effect of ACS, both under normothermic and hypothermic conditions. The use of nifedipine in cardioplegia may provide additional protection when uneven distribution of the cardioplegic solution is expected and hypothermic protection is unreliable.

Animals