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Biomedical subjects

E Rossi

Publications and source records attributed to E Rossi.

At least 19 recordsLinked to original sources

Inhibition of human lymphocyte coproporphyrinogen oxidase activity by metals, bilirubin and haemin.

Coproporphyrinogen III oxidase activity in human lymphocytes was found to be inhibited by cadmium and mercury but not by lead. The organo-metal compounds tributyltin and methylmercury were effective inhibitors of this haem biosynthetic pathway enzyme. Haemin (the ultimate product of the pathway) and bilirubin (a product of haem catabolism) were also shown to be inhibitory. Kinetic studies performed under initial velocity conditions showed that bilirubin was a non-competitive inhibitor and that one bilirubin molecule was bound to both the enzyme and enzyme substrate complex. The analysis also showed haemin to be a non-competitive inhibitor in which two haemin molecules bind to the enzyme whereas the enzyme substrate complex accepts only one haemin molecule. The possible physiological significance of the inhibition of coproporphyrinogen III oxidase activity by haemin and bilirubin is discussed.

Bilirubin

Functional protein S in women with lupus anticoagulant inhibitor.

Protein C (PC) and protein S (PS) are components of a potent, natural anticoagulant system. A deficiency of one of these two inhibitors is associated with thrombotic events in young people. A significant reduction in functional PS activity has been observed during normal pregnancy, and recurrent fetal loss may occur in women with lupus anticoagulant (LA) inhibitor. We measured functional PS activity and free PS antigen in 16 non pregnant patients with LA inhibitor and in 17 normal women as controls. A significant difference was observed between patients and controls in functional PS activity (65 +/- 23% vs 87 +/- 15%, p = 0.02) but not in free PS antigen (88 +/- 17% vs 93 +/- 17%). Functional PS activity decreased only in six patients (37%). Removal of IgG from plasma reduced the difference in functional PS activity between patients and controls. Immunologic IgG levels did not correlate with anti-phospholipid antibodies (APA) activities, activated partial thromboplastin time/kaolin clotting time (aPTT/KCT) data or functional PS activity.

Abortion, Habitual

Abundance of the primary transcript and its processed product of growth-related genes in normal and leukemic cells during proliferation and differentiation.

The relative abundance of primary transcript and mature mRNA of the c-myc, calcyclin, S14 ribosomal protein, and rRNA genes was determined densitometrically after reverse transcriptase-polymerase chain reaction and Northern blotting analysis in resting and mitogen-stimulated lymphocytes, proliferating and terminally differentiated HL-60 cells, and leukemic blast cells. Transcription and processing of c-myc and rRNA gene transcripts increased proportionally after mitogen stimulation, whereas these processes were independent of cell cycling status in the case of the S14 gene. Normal lymphocytes showed an unexpectedly large amount of primary transcript of the calcyclin gene, whereas the corresponding mRNA was undetectable. The abundance of c-myc, calcyclin, and S14 mRNA in terminally differentiated HL-60 cells decreased sharply, compared to their proliferating counterparts. This decrease reflected post-transcriptional modulation, since the abundance of precursor remained essentially unchanged. After HL-60 differentiation, the 32S rRNA levels remained relatively high, whereas the 45S primary transcript almost disappeared. Leukemic blast cells displayed highly variable precursor/mRNA ratios of c-myc, calcyclin, and S14 genes but consistently high ratios of 32S to 45S RNA, suggesting that the cleavage rate of the 32S rRNA was sharply reduced in these cells, resulting in an accumulation of this molecule. These results suggest the importance of efficient processing of primary transcript to generate adequate functional mRNA, thus regulating gene expression. Furthermore, in terminally differentiated cells and leukemic blast cells a stabilization of the primary transcript without efficient processing can be observed. The role of the stabilization of the primary transcript in terminal differentiation is further supported by the results of run-off transcription, indicating a sharp decrease of c-myc and calcyclin transcription rate in retinoic acid/dimethyl sulfoxide-treated HL-60 cells.

Acute Disease

A follow-up and family study of DSM-III-R schizophreniform disorder with good prognostic features.

A follow-up and family study was carried out of 16 first episode, DSM-III-R schizophreniform disorder patients with good prognostic features. Mean length of follow-up was 52.3 months. It was found that 62.5% had affective episodes, 31.2% had schizophreniform episodes. No case of schizophrenia was observed. Outcome was good. Morbid risk for affective disorder among first degree relatives was 25%, morbid risk for schizophrenia was 0%. These findings suggest a link between DSM-III-R schizophreniform disorder with good prognostic features and affective disorder, and no relationship with schizophrenia.

Adolescent

Abnormal intraventricular flow patterns in left ventricular dysfunction determined by color Doppler study.

We examined the relation between left ventricular (LV) flow dynamics measured by color Doppler, and either global or regional LV function in 19 normal subjects (group 1), in 55 patients with old myocardial infarction (MI) (29 without [group 2] and 26 with LV aneurysm [group 3]), and in 16 with idiopathic dilated cardiomyopathy (group 4). We calculated by M-mode color Doppler a flow persistence index (FPI) (duration of flow directed in systole toward the apex/LV ejection time). Contrast echocardiography was performed as a control method in 14 patients of the four groups. In normal subjects, rapid systolic inversion of flow toward the aorta was evident (FPI: 0.11 +/- 0.16). In all but one patient in group 2, a similar LV flow pattern was observed, but FPI was greater (0.32 +/- 0.26). In groups 3 and 4, a paradoxical antegrade LV flow pattern was evident during the entire period of systole (FPI: 1.13 +/- 0.42 and 1.28 +/- 0.36, respectively). LV flow patterns were reproduced in echo-contrast studies. FPI was related to LV end-diastolic volume (r = 0.77), end-systolic volume (r = 0.82), and ejection fraction (r = -0.84). However, when data were analyzed separately in the different groups, these correlations were significant only in groups 2 and 3. Paradoxical flow pattern is not peculiar to regional LV dysfunction; it also occurs in global LV dysfunction. This LV flow abnormality may develop after MI even in the absence of severe LV dyssynergy or dilation, and is quantitatively related to the degree of LV dysfunction.

Adult

Family history, smoking habits, alcohol consumption and risk of psoriasis.

We have conducted a multicentre case-control study to assess the epidemiological importance of previously suggested risk factors for psoriasis, including family history of the disease, smoking and alcohol consumption. Newly diagnosed psoriatics, with a history of skin manifestations no longer than 2 years were eligible as cases; as controls we selected subjects with newly diagnosed dermatological conditions other than psoriasis. Interviews were performed by trained medical investigators using a structured questionnaire. Two-hundred and fifteen cases, aged 16-65 years (median age 38), and 267 controls, aged 15-65 years (median age 36), were interviewed and included in the analysis. Family history was a risk factor for psoriasis; the multiple logistic regression (MLR) adjusted-odds ratio was 18.8 (95% confidence interval 6.4-54.8) for a history in parents, and 3.2 (95% confidence interval 1.5-6.6) for a history in siblings. The risk of psoriasis was higher for current smokers than for those who had never smoked. The MLR adjusted odds ratio was 2.1 (95% confidence interval 1.1-4.0) for people smoking 15 cigarettes or more per day. The risk of psoriasis was higher for alcohol drinkers: compared with teetotallers the MLR adjusted-odds ratios were 1.3 (95% confidence interval 0.8-2.3) for subjects drinking one or two drinks/day and 1.6 (95% confidence interval 0.9 to 3.0) for those drinking three or more. However, the trend in risk was not statistically significant. Our study confirms the role of family history in psoriasis and provides some evidence of a dose-response relationship for an association between smoking habits and psoriasis.

Adolescent

Serum thyrotropin response to combined arginine and thyrotropin-releasing hormone administration provides evidence for an altered somatostatinergic tone in acromegaly.

The aim of this study was to evaluate plasma thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) responses to the TSH-releasing hormone (TRH) test and to a combined arginine-TRH test (ATT-TRH) in 10 normal subjects and in 15 acromegalic patients. In controls, TSH responsiveness to TRH was enhanced by ATT (p less than 0.001). When considering the 15 acromegalic patients as a whole, no significant difference in TSH responses was detected during the two tests. However, patients without suppression of plasma GH levels after oral glucose load showed an increased TSH responsiveness to the ATT-TRH test if compared to TRH alone (p less than 0.025), while patients with partial suppression of plasma GH levels after glucose ingestion showed a decreased TSH responsiveness to ATT-TRH (p less than 0.05). No difference was recorded in PRL and GH responses, evaluated as area under the curve, during TRH or ATT-TRH tests in controls and in acromegalics. In conclusion, (1) normal subjects have an enhanced TSH response to the ATT-TRH test and (2) acromegalic patients without suppression of GH levels after oral glucose load show a TSH responsiveness to the ATT-TRH test similar to that of controls, while acromegalics with partial GH suppression after oral glucose load have a decreased TSH responsiveness to the ATT-TRH test. These data suggest that acromegaly is a heterogeneous disease as far as the somatostatinergic tone is concerned.

Acromegaly

Evaluation of GH paradoxical responses to TRH and LHRH in acromegalic patients during long-term treatment with octreotide.

In some acromegalics, GH release can be induced by TRH and/or LHRH administration. The pathogenesis of these GH paradoxical responses was supposed to be a somatotroph-reduced sensitivity to somatostatin, somatotrophin release-inhibiting factor (SRIF), or an hypothalamic derangement of the SRIF release. In this study, this hypothesis was investigated by means of GH suppression during chronic therapy with octreotide [Somatostatin analogue (SMS)] in order to evaluate the possible correlation between GH and insulin-like growth factor 1 (IGF-1) normalization and the disappearance of these paradoxical responses in 15 acromegalic patients: 15/15 with a paradoxical GH rise after TRH and 7/15 with a paradoxical GH rise after LHRH. SMS therapy was administered subcutaneously at the dose of 150-450 micrograms/day. During the treatment, GH and IGF-1 levels normalized in 12 patients and were reduced in the remaining 3 others. The GH response to TRH disappeared in 7 patients, while the GH response to LHRH disappeared in 4 patients. chi 2 analysis failed to show any significant correlation between GH and IGF-1 normalization and the disappearance of GH response to TRH and LHRH (chi 2 = 0.00686). No linear correlation existed between GH/IGF-1 decrease and GH peak or area under the curve at any time ('r' values: TRH test, GH -0.47, IGF-1 -0.48; LHRH test, GH -0.50, IGF-1 -0.49). The absence of any significant correlation between GH/IGF-1 normalization and the disappearance of GH paradoxical responses during chronic octreotide administration suggests that other factors apart from SRIF sensitivity are involved in the genesis of these responses.

Acromegaly

Further evaluation of IGF-I responsiveness to ACTH in children affected with IGHD.

In our previous studies we had demonstrated that, in children affected with isolated GH deficiency (IGHD), a short-term recombinant growth hormone (rGH) therapy increases the 11-deoxycortisol (S) secretion and induces an IGF-I responsiveness to the ACTH challenge. The aim of the present study was to further investigate the mechanisms by which IGF-I is secreted after ACTH challenge in children affected with IGHD by correlating IGF-I versus cortisol (F) time courses after ACTH administration. Ten children affected with IGHD were subjected to rGH therapy (4 IU/day subcutaneously) for 10 days. The responsiveness of IGF-I, F and S to the ACTH 1-17 test were evaluated before and at the end of the therapy. No IGF-I response to the ACTH test was recorded in the patients before the rGH treatment, whereas after rGH administration ACTH induced a significant IGF-I release (p < 0.001) which started at the 1st hour, reached a peak value between the 5th and 6th hours and disappeared at the 10th hour. In conclusion, our study confirms that a short-term rGH therapy induces an IGF-I responsiveness to ACTH and helps to better define the kinetics and the mechanism of this IGF-I response to ACTH.

Adrenocorticotropic Hormone

The fibrinolytic system in the newborn: role of histidine-rich glycoprotein.

The fibrinolytic system controls fibrin deposition and its clearance. The efficacy of this system can be evaluated by plasminogen concentration determinations and by the behavior of factors such as histidine-rich glycoprotein (HRG) which controls plasminogen activation and alpha 2-antiplasmin which controls plasmin activity. Circulating plasminogen levels are decreased in the neonatal period. We studied factors affecting fibrinolysis in neonates and observed that an important reduction in HRG accompanied the reduced circulating plasminogen levels, with the result that 85% of circulating plasminogen was not bound to HRG and was thus free for binding to fibrin and for activation to plasmin. This condition is consistent with the increased fibrinolytic activity secondary to the "clotting activation' observed in the neonatal period particularly on the 1st day of life.

Fibrinolysin

Effect of a short-term treatment with recombinant growth hormone (GH) on adrenal responsiveness to corticotrophin stimulation in children affected by isolated GH deficiency.

Recent evidence suggests that GH and insulin growth factor-I (IGF-I) play a role in adrenal steroidogenesis. On the other hand, it has been shown that ACTH stimulates IGF-I secretion by cultured fasciculata adrenal cells. Aim of the present study was to investigate the influence of GH administration on adrenal steroids and IGF-I responsiveness to ACTH in children affected with isolated GH deficiency. Ten children (seven males and three females, 5-10 yr old) affected with isolated GH deficiency underwent a synthetic ACTH 1-17 test before and after administration of human recombinant GH at a dose of 4 IU/day sc for 10 days. After the therapy, no significant differences were detected in the responses of cortisol, dehydroepiandrosterone-sulfate, androstenedione, and 17-hydroxyprogesterone to ACTH 1-17, whereas an increased 11-deoxycortisol responsiveness to ACTH 1-17 was noted (P less than 0.005). Surprisingly, IGF-I significantly increased in response to ACTH 1-17 after short-term rGH administration (P less than 0.006). In conclusion, our data indicate that in isolated GH deficiency a short-term GH therapy does not substantially modify the adrenal responsiveness to exogenous ACTH, even if an increased 11-deoxycortisol and an induced IGF-I responsiveness to ACTH were observed.

Adrenal Glands

Acromegalic cardiomyopathy. Left ventricular filling and hypertrophy in active and surgically treated disease.

Myocardial hypertrophy and interstitial fibrosis are common in acromegalic hearts and may induce left ventricular (LV) dysfunction. The transmitral flow pattern was examined by pulsed-wave Doppler in 20 patients with active acromegaly and nine with acromegaly cured by pituitary microsurgery. Control groups consisted of 25 normal subjects and 13 patients with systemic hypertension. We related Doppler indices of LV filling (E and A peak velocities and E/A ratio) to the duration of acromegalic disease, the GH plasma levels and LV mass. The LV mass/BSA was significantly greater in active acromegaly (187 +/- 53 g/sq m) and systemic hypertension groups (161 +/- 48 g/sq m) than in cured acromegaly (125 +/- 35 g/sq m) and the normal control group (109 +/- 36 g/sq m) (p < 0.01 for both). No differences were found in the E peak velocity, A peak velocity, and E/A ratio in the groups with active acromegaly (E/A: 0.9 +/- 0.2), cured acromegaly (E/A: 0.9 +/- 0.3), and systemic hypertension (E/A: 0.8 +/- 0.5). An E/A ratio < 1 was found in 13 patients with active and four with cured acromegaly; (p = NS). In the active acromegaly group, the E/A ratio was related to either LV mass or the duration of disease (r:-0.45 and -0.47, respectively; p < 0.05). In the cured acromegaly group, the E/A ratio was related to the duration of disease before surgery (r:-0.70; p < 0.05) and not to LV mass (r:0.12). In conclusion, an impairment in LV filling may be present not only in the patients with active acromegaly but also in those successfully treated by surgery after a long duration of the disease, despite normal LV mass. These LV filling abnormalities may be in part determined by nonreversible myocardial changes, such as interstitial tissue fibrosis.

Acromegaly

Hormonal gradients between inferior petrosal sinuses in various pituitary diseases.

The aim of this retrospective study was to evaluate the existence of a multihormonal gradient between the inferior petrosal sinuses in various pituitary diseases: Cushing's disease (8 cases), acromegaly (4 cases), prolactinomas (7 cases), GH, PRL-secreting adenoma (1 case), functionless adenoma (2 cases), empty sella (3 cases) and in non-tumoral hyperprolactinemia (5 cases). A significant intersinus gradient (more than 1.4:1) was recorded for GH, ACTH and PRL in 16 patients (80%), but in only 9 patients (45%) out of the 20 with hormone-secreting tumors for TSH, FSH and LH. Moreover, of the 10 patients in the remaining groups, only in two cases was a significant intersinus gradient present: one for GH and one for LH. In conclusion, the finding of a multihormonal release in the inferior petrosal sinus ipsilateral to the adenoma is reported, for the first time, in patients with GH- and PRL-secreting adenomas. The possible explanation for such a finding may be either an increased blood flow in this site of sampling or a pituitary multihormone release through a paracrine mechanism primed by the tumoral hypersecreted hormone. In addition, the pulsatile secretory pattern and the short half-life of polypeptide hormones may contribute to better demonstrate this phenomenon in respect to glycoprotein hormones.

Adenoma

Renal function at hospital admission as a prognostic factor in adult hemolytic uremic syndrome. The Italian Registry of Haemolytic Uremic Syndrome.

The clinical records of adult patients with a diagnosis of hemolytic uremic syndrome were retrospectively reviewed with the aim of evaluating the long-term outcome of renal function. The setting is the Italian Registry of Haemolytic Uraemic Syndrome, with which 13 Nephrology Centers have participated. Clinical and laboratory data of 43 patients with hemolytic uremic syndrome were evaluated. The mean age at onset was 34.3 +/- 18.3 yr. Men and women were equally affected. No seasonal trend in presentation was observed. In 20 patients, hemolytic uremic syndrome was primitive, whereas in 23, it was associated with another disease (cancer, preeclampsia, malignant hypertension, vasculitides). Gastrointestinal symptoms were the most frequently observed prodromes. Thirty (70%) patients required dialysis during the acute phase of the disease. Six patients died during the acute phase of the disease, and one died later after discharge (overall mortality, 16%). After 1 yr of follow-up, 11 (26%) patients had recovered a normal renal function, 14 (33%) had hypertension and/or renal insufficiency, and 11 (26%) were on regular dialysis. When prognostic factors of survival and recovery of renal function were considered, it was found that older age was associated with higher mortality in the acute phase, whereas severe renal involvement at the onset of the disease (as expressed by elevated serum creatinine) was associated with a long-term unfavorable prognosis.

Adolescent

Effects of sodium meclofenamate on postoperative pain following periodontal surgery.

The analgesic activity of single doses of meclofenamate (100 mg) was compared to aspirin (500 mg) and to placebo on 99 outpatients with moderate to severe pain following periodontal surgery under double-blind conditions. Pain intensity differences scores (PID) at the first, second, and third hour after the ingestion of the first capsule of each medication were used to determine the analgesic efficacy of the studied drugs. Kruskal Wallis test followed by the Mann-Whitney rank sum test were used in the statistical analysis of results. Meclofenamate was statistically superior to placebo and superior to aspirin in the second hour of evaluation, while aspirin was not superior to placebo during the 3-hour period of pain evaluation. It is concluded that meclofenamate is a non-steroidal antiinflammatory drug with interesting analgesic properties which can be used as directed as an alternative to aspirin or acetaminophen for the control of postoperative pain following periodontal surgery.

Adult