[The therapy of non-Hodgkin's lymphomas in stage III and stage IV]. / La terapia dei linfomi non-Hodgkin in III e IV stadio.

The features that distinguish non-Hodgkin and Hodgkin forms of lymphoma are briefly described, together with the method employed in classifying 45 non-Hodgkin cases treated with polychemotherapy and cobalt. The results were satisfactory. Remission (complete or incomplete) was obtained in 75% and 73% of lymphocytic and histocytic forms respectively. Survival after 5 yr was 50% for cases in the 3rd stage and 11% for those in the 4th. It is felt that the 3rd stage should be regarded as a generalised form, requiring the intensive systematic management offered by combining polychemotherapy and radiotherapy.

[Salmon calcitonin nasal spray in the treatment of Paget's disease]. / La calcitonina di salmone spray nasale nella terapia del morbo di Paget.

Salmon calcitonin (sCT) is biologically effective when intranasally (i.n.) administered. CT is the treatment of choice for Paget's disease; however, the chronic nature of the disease makes parenteral administration uncomfortable due to the high incidence of adverse reactions occurring after CT injection. The aim of our study was to investigate the efficacy, safety and tolerability of a sCT i.n. spray in the long-term treatment of Paget's disease. Ten pts (4M,6F; age between 58-74 years) with radiological lesions characteristic of Paget's disease, serum alkaline phosphatase (sALP) levels at least 50% above the normal range and never treated for their disease before, were given 200 IU/day of sCT nasal spray for 6 months. sALP levels were measured at month 3 and 6 of therapy; clinical data were recorded every month. sALP levels significantly dropped after 3 months of treatment (72 +/- 6% of basal level, p less than 0.01). After 6 months of therapy sALP levels were similar to the 3 month levels. Pain and functional impairment self-evaluated by the patients decreased after 6 months of therapy: pain index from 5.5 +/- 2.2 to 2.1 +/- 1.1, p less than 0.01; functional impairment index from 2.2 +/- 0.5 to 0.7 +/- 0.5, p less than 0.01. Side-effects were not observed during the entire period of the study. In conclusion, the 200 IU daily regimen of the i.n. spray of sCT without absorption enhancer was, for our patients, effective, safe, and well tolerated in the long-term therapy of Paget's disease.

[Craniometric findings in sickle-cell anemia]. / Rilievi craniometrici nell'anemia drepanocitica e nella drepanocitosi.

Craniometric measurements have been taken on teleradiographs in lateral and antero-posterior projection of five patients suffering from sickle-cell anaemia. All were Sicilian. The investigations revealed a proportional dysharmony among the various segments of the face, the results of excessive development of the mandibular bone, particularly transversally. This characteristic would appear to be peculiar to patients with homo- and heterozygote haemoglobinopathy.

Effect of arginine on the GHRH-stimulated GH secretion in patients with hyperthyroidism.

Patients with hyperthyroidism have reduced GH responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of arginine on GH secretion has been suggested to depend on a decrease in hypothalamic somatostatin tone. The aim of our study was to evaluate the effects of arginine on the GH-releasing hormone (GHRH)-stimulated GH secretion in patients with hyperthyroidism. Six hyperthyroid patients with recent diagnosis of Graves' disease [mean age +/- SEM, 39.2 +/- 1.4 years; body mass index (BMI) 22 +/- 0.4 kg/m2] and 6 healthy nonobese volunteers (4 males, 2 females; mean age +/- SEM, 35 +/- 3.5 years) underwent two experimental trials at no less than 7-day intervals: GHRH (100 micrograms, i.v.)-induced GH secretion was evaluated after 30 min i.v. infusion of saline (100 ml) or arginine (30 g) in 100 ml of saline. Hyperthyroid patients showed blunted GH peaks after GHRH (13.2 +/- 2.9 micrograms/l) as compared with normal subjects (23.8 +/- 3.9 micrograms/l, p < 0.05). GH peaks after GHRH were only slightly enhanced by arginine in hyperthyroid subjects (17.6 +/- 2.9 micrograms/l), whereas, in normal subjects, the enhancement was clear cut (36.6 +/- 4.4 micrograms/l; p < 0.05). GH values after arginine + GHRH were still lower in hyperthyroid patients with respect to normal subjects. Our data demonstrate that arginine enhances but does not normalize the GH response to GHRH in patients with hyperthyroidism when compared with normal subjects. We hypothesize that hyperthyroxinemia may decrease GH secretion, both increasing somatostatin tone and acting directly at the pituitary level.

Comparative effect of galanin and pyridostigmine on the growth hormone response to growth hormone-releasing hormone in normal aged subjects.

The aim of our study was to investigate the effects of aging on the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) alone and in combination with either the neuropeptide galanin or the acetylcholinesterase inhibitor pyridostigmine (PD) in normal subjects. In protocol 1 (GHRH/galanin), 9 old healthy volunteers, ranging in age from 68 to 97 years, and 6 young subjects, ranging in age from 25 to 31 years, received: (a) human GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) porcine galanin, 500 micrograms in 100 ml saline, as an intravenous infusion from -10 to 30 min combined with GHRH, 100 micrograms i.v. at time 0. In protocol 2 (GHRH/PD), 14 old healthy volunteers, ranging in age from 65 to 91 years, and 11 young subjects, ranging in age from 19 to 34 years, received: (a) GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) PD, 120 mg administered per os 60 min before GHRH, 100 micrograms as an intravenous bolus. Blood samples for GH were drawn at -75, -60 (time of PD administration), -45, -30, -15, -10 (time of beginning of galanin infusion), 0 (time of GHRH injection), 15, 30, 45, 60, 90, and 120 min. The GH response to GHRH was significantly (< 0.05) enhanced either by galanin or PD pretreatment both in young and old subjects. However, the GH response to GHRH alone or combined with either galanin or PD was significantly greater in the young subjects as compared to the old subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Galanin does not affect the growth hormone-releasing hormone-stimulated growth hormone secretion in patients with hyperthyroidism.

Patients with hyperthyroidism have reduced spontaneous and stimulated growth hormone (GH) secretion. The aim of our study was to evaluate the effects of galanin, a novel neuropeptide which stimulates GH secretion in man, on the GH response to GHRH in patients with hyperthyroidism. Eight untreated hyperthyroid patients with Graves' disease (6F, 2M, aged 25-50 years) and six healthy volunteers (3F, 3M, aged 27-76 years) underwent from -10 to 30 min in random order: (i) porcine galanin, iv, 500 micrograms in 100 ml saline; or (ii) saline, iv, 100 ml. A bolus of human GHRH(1-29)NH2, 100 micrograms, was injected iv at 0 min. Hyperthyroid patients showed blunted GH peaks after GHRH+saline (10.2 +/- 2.5 micrograms/l) compared to normal subjects (20.7 +/- 4.8 micrograms/l, p < 0.05). GH peaks after GHRH+galanin were also significantly lower in hyperthyroid subjects (12.5 +/- 3 micrograms/l) compared to normal subjects (43.8 +/- 6 micrograms/l, p < 0.05). That galanin is not able to reverse the blunted GH response to GHRH in hyperthyroidism suggests that hyperthyroxinemia may either increase the somatostatin release by the hypothalamus or directly affect the pituitary GH secretory capacity.

Lymphadenopathic and oropharyngeal Kaposi's sarcoma in a drug addict with acquired immunodeficiency syndrome. Immunological abnormalities in peripheral blood and lymphoid tissue.

Lymphocyte subsets were analyzed in peripheral blood and lymph nodes from a drug-addict with acquired immunodeficiency syndrome (AIDS) presenting with disseminated lymphadenopathic and oropharyngeal Kaposi's sarcoma. At the onset of disease, hypergammaglobulinemia, increase of OKT8+ T cell subset and reversal of OKT4/OKT8 ratio were found in the blood. At the same time, lymph nodes displayed, besides Kaposi's sarcoma, marked follicular hyperplasia, plasmocytosis and increase of OKT8+/Leu 2a+ T cells within follicular centers. These results are interpreted to indicate that at an early stage of disease the major tissue alterations took place within follicular centers and consisted of both B cell activation and T suppressor cell reaction. These changes correlated with immunological abnormalities observed in peripheral blood. Immunohistochemical investigation of lymphoid tissue may be useful to detect AIDS patients at an early stage.

Effects of methimazole treatment on growth hormone (GH) response to GH-releasing hormone in patients with hyperthyroidism.

In vitro studies have demonstrated that thyroid hormones can enhance basal and stimulated growth hormone secretion by cultured pituitary cells. However, both in man and in the rat the effects of high thyroid hormone levels on GH secretion are unclear. The aim of our study was to test the GH response to human GHRH in hyperthyroid patients and to evaluate the effects on GH secretion of short- and long-term pharmacological decrease of circulating thyroid hormones. We examined 10 hyperthyroid patients with recent diagnosis of Graves' disease. Twelve healthy volunteers served as controls. All subjects received a bolus iv injection of GHRH(1-29)NH2, 100 micrograms. Hyperthyroid patients underwent a GHRH test one and three months after starting antithyroid therapy with methimazole, 10 mg/day po. GH levels at 15, 30, 45, 60 min and GH peak after stimulus were significantly lower in hyperthyroid patients than in normal subjects. The GH peak was also delayed in hyperthyroid patients. After one month of methimazole therapy, most of the hyperthyroid patients had thyroid hormone levels in the normal range, but they did not show significant changes in GH levels after GHRH, and the GH peak was again delayed. After three months of therapy with methimazole, the hyperthyroid patients did not show a further significant decrease in serum thyroid hormone levels. However, mean GH levels from 15 to 60 min were significantly increased compared with the control study. The GH peak after GHRH was also earlier than in the pre-treatment study.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular structural changes and calcium antagonist therapy in patients with hypertension.

Regression of cardiovascular structural changes is a main goal of antihypertensive treatment. Two recent meta-analyses of relatively small noncomparative studies have suggested that angiotensin-converting enzyme (ACE) inhibitors may be more effective than other classes of drugs in inducing regression of left ventricular hypertrophy (LVH). The effect of different antihypertensive drugs on arteriolar structural changes has not yet been properly investigated. The aim of this study was to evaluate the effect of 6 months of treatment with amlodipine (5-10 mg o.d.) or enalapril (10-20 mg o.d.) on blood pressure (BP) (ambulatory monitoring), heart rate (HR), LV mass and function (M-mode echo, two-dimensionally guided), forearm minimal vascular resistance (min VR = BP/max blood flow-venous occlusion plethysmography, taken as an index of vascular structural changes) in 24 hypertensive patients in a comparative single-blind, randomized study, with blind reading of echocardiograms and plethysmographic tracings. After 6 months of treatment with amlodipine 5-10 mg o.d., significant reductions in LV mass index (p = 0.004) and forearm min VR (p = 0.02) were observed. Before and during treatment, LV systolic function, both at rest and during stress (handgrip test), evaluated by fractional shortening as related to end-systolic stress, was in every case within 95% confidence limits calculated in normal subjects. Similar results were observed with enalapril. No significant differences were observed for Doppler indices of diastolic filling after 6 months of treatment with either drug. These results indicate that a significant regression of structural changes in the heart and in the small resistance vessels can be observed after long-term treatment with amlodipine in essential hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)