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Biomedical subjects

C Boni

Publications and source records attributed to C Boni.

At least 37 records · Page 2Linked to original sources
PubMed1989

Exacerbation of metastatic disease shortly after administration of tamoxifen in ER negative advanced breast carcinoma. A case report.

In a patient with long untreated slow-growing osteoblastic bone metastases from an ER/PgR negative breast carcinoma, new metastatic sites in many lymphnodes pleura and massively in liver have been observed 4 weeks after receiving tamoxifen. Cause-effect relationship between administration of the drug and this unusually rapid spreading of the disease may be considered only as a hypothesis, as it is based wholly on clinical outcome. However, reporting of any exacerbation of breast cancer apparently induced by tamoxifen, even if only anecdotal, is advisable.

Breast Neoplasms↗
PubMed1989

Bone marrow biopsy in the staging of small cell lung cancer.

From April 1982 to December 1987, 71 patients with small cell lung cancer entered a randomized clinical trial, and underwent bone marrow biopsy (BMB) as part of staging procedures. We identified 8 patients (11%) with bone marrow metastases, 6 with extensive disease independently of BMB, and 2 with extensive disease on the basis of the BMB only. BMB determined a change in the stage in only 3% (2/71) of the cases. No differences were found in the hematological parameters of the patients with or without bone marrow metastases. The median survival of the patients with bone marrow involvement was the same (41 weeks) as those with extensive disease but without bone marrow involvement. We conclude that unilateral BMB without aspiration detects a substantial proportion of bone marrow metastases in patients with extensive disease. This fact does not worsen the prognosis. A small proportion of patients with apparently limited disease has bone marrow involvement. The technique therefore contributes, to a small extent, to the definition of the clinical stage of the disease. However, bone marrow involvement is an important data of natural history, and therefore new methods to better assess this peculiar site of the disease are needed.

Adult↗
PubMed1989

Cisplatin and etoposide (VP-16) as a single regimen for small cell lung cancer. A phase II trial.

Forty-seven consecutive patients with small cell lung cancer (SCLC) were treated with a combination chemotherapy program including 60 mg/m2 of cisplatin (P) on day 1 and 120 mg/m2 of etoposide (E) on day 4, 6, 8, every 21 days. Limited disease (LD) patients, achieving complete response (CR) or partial response (PR) after the three initial courses, received radiotherapy (RT) to the pretreatment primary tumor volume and, those achieving CR, additional RT to the brain. During RT, chemotherapy was administered with 50% dose reduction. Forty-three patients were evaluable for therapeutic response. In the 19 patients with LD, CR was achieved in 63% of patients and the PR rate was 32%. In 24 patients with extensive disease (ED), CR was 34% and PR rate was 54%. Median duration of survival was 66 weeks for LD and 48 weeks for ED. Six patients were disease-free after 2 years. Leucocyte count less than 2000/mm3 was seen in 26% of patients; platelet count less than 50000/mm3 was observed in 9%. Nonhematologic toxicity included universal nausea or vomiting and severe neurotoxicity in 7%. These data indicate that PE combination is a very active front-line regimen in SCLC and could be suggested as one of the reference treatments.

Adult↗
PubMed1989

Multiparametric approach to diagnosis of non-Q-wave acute myocardial infarction.

The present study investigated whether the lack of enzyme increase is reason enough to exclude necrosis in patients with ischemic heart disease who develop electrocardiographic sustained ST-T changes in the absence of Q waves. In 15 consecutive patients with angina who developed sustained ST-T changes during hospitalization, the presence of myocardial necrosis was investigated by a prospective multiparametric approach. Serum enzymes and myoglobin, pyrophosphate uptake, 2-dimensional echocardiography, perfusion scintigraphy, left ventriculography and coronary angiography were evaluated. According to creatine kinase and creatine kinase-MB peak at twice the upper normal value, the diagnosis of acute myocardial infarction applied only to 40% of patients. However, myoglobin was positive in 80% and a perfusion defect could be documented by an electrocardiographic gated microsphere technique in 100% of patients. The positivity of myoglobin increased to 100% and of creatine kinase and creatine kinase-MB to 87 and 60%, respectively, when a peak value twice the individual lowest value was considered for positivity. The 100% presence of perfusion defects associated with the high prevalence of both positive pyrophosphate uptake (87%) and regional dyssynergies (87 and 73%, respectively, by left ventriculography and echocardiography) strongly suggest that sustained (greater than or equal to 7 days) ST-T changes in this population were indicative of myocardial necrosis. Thus, by conventional enzymatic approach, diagnosis of non-Q-wave infarction can be missed in a sizable number of patients and present important clinical implications.

Adult↗
PubMed1989

Time dependence of the interaction between lipid and glucose in humans.

The time-dependent effect of Intralipid infusion on glucose metabolism was examined in seven healthy young subjects who participated in the following three experimental protocols: study I, a 4-h euglycemic insulin clamp (0-240 min) with [3-3H]glucose and indirect calorimetry; study II, a 4-h insulin clamp with Intralipid infusion started at time 0; and study III, a 4-h insulin clamp with Intralipid infusion started at 120 min. When Intralipid infusion was begun at the start of the insulin clamp, the increase in insulin-mediated glucose oxidation was completely inhibited, and the rise in nonoxidative glucose disposal was diminished by 22%. When Intralipid infusion was begun 120 min after the start of the insulin clamp, no inhibitory effect on either glucose oxidation or nonoxidative glucose disposal was observed. The change in lipid oxidation was closely and inversely correlated with the change in glucose oxidation (r = -0.826, P less than 0.001) during studies I-III; no correlation between the change in lipid oxidation and nonoxidative glucose disposal was observed. These results indicate that, in healthy subjects, the metabolic competition between lipid and glucose is very time dependent. Furthermore, mitochondrial oxidative processes are more sensitive and are affected earlier than the cytosolic metabolic pathways, i.e., nonoxidative glucose disposal.

3-Hydroxybutyric Acid↗
PubMed1989

Coronary hemodynamics and myocardial metabolism during and after pacing stress in normal humans.

We investigated coronary hemodynamics, myocardial utilization of circulating substrates (by coronary sinus catheterization), and overall use of oxidative fuels (by regional indirect calorimetry) in healthy adults during incremental atrial pacing (up to 159 +/- 9 beats/min), and during 25 min of recovery. Great cardiac vein flow (thermodilution) increased from 52 +/- 9 to 115 +/- 15 ml/min (P less than 0.001) with pacing; myocardial O2 uptake (301 +/- 53 to 593 +/- 71 mumol/min, P less than 0.001) and CO2 production (225 +/- 37 to 518 +/- 66 mumol/min, P less than 0.005) paralleled the pacing-induced rise in rate-pressure product (9.4 +/- 0.9 to 21.1 +/- 1.1 mmHg.beat. min-1.10(-3), P less than 0.001). During recovery, all the above variables returned to base line within 5 min, but myocardial O2 extraction remained depressed (67 +/- 2 vs. 71 +/- 3%, P less than 0.05). Circulating glucose uptake rose linearly with pacing (P less than 0.05) and remained above base line throughout recovery. By contrast, free fatty acid (FFA) uptake (10 mumol/min) did not increase with pacing and fell during recovery (P less than 0.01). Calorimetry, however, showed that net lipid oxidation exceeded FFA uptake throughout the study, whereas net carbohydrate oxidation was small at base line, rose significantly at maximal pacing (62% of myocardial energy output), and remained above base line during recovery (32% of energy output). In the basal state as well as during recovery, myocardial uptake of glucose equivalents (lactate plus glucose plus pyruvate) was in excess of carbohydrate oxidation, indicating nonoxidative disposal of these substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The value of bone marrow biopsy in breast cancer at the time of first relapse. A prospective study.

The value of bone marrow biopsy (BMB) in advanced breast cancer at the time of first relapse was studied in a prospective manner. Bone marrow biopsy was performed in 142 consecutive unselected metastatic patients: 129 at the time of first recurrence, and 13 in patients with metastases at the time of first diagnosis. Overall, BMB was positive in 32 patients (23%). In the group with negative bone x-ray, it was positive in two patients of 84 (2%); both of them had doubtful scan. In the group with positive x-ray, BMB resulted positive in 30 of 58 (52%). There was a significant correlation between number of bone segments radiologically involved and BMB positivity rate, ranging from 15% in the patients with only one, to 68% in those with more than three sites involved (P = 0.02). Patients with x-ray evidence of metastases in the pelvis had significantly higher rate of BMB positivity (67% versus 32%; P = 0.02). The median survival time from the first relapse was 153 weeks in BMB-negative cases and 149 in positive ones. Considering only the patients with demonstration of bone invasion obtained with either or both x-ray and BMB, 34/62 patients had positive BMB (55%). In these cases BMB was found more often positive in patients 50 years or younger than in patients older than 50 years (80% versus 47%; P = 0.05); the median survival time was longer, but not significantly, in BMB-positive patients than in negative ones (149 weeks versus 119; P = 0.3). The authors conclude that BMB is not required in common restaging procedure when both bone survey and scan are negative. Bone marrow biopsy results are more often positive in younger patients and survival is not negatively affected by bone marrow invasion as diagnosed by BMB.

Biopsy↗
PubMed1988

The value of bone marrow biopsy in breast cancer at time of diagnosis. A prospective study.

Bone marrow biopsies (BMB) were performed in 173 consecutive unselected breast cancer patients at the time of diagnosis to define the value of this diagnostic tool in the initial staging of mammary carcinoma. In a group of 160 patients with a negative standard staging work-up, BMB was positive in two (1%). Both of them had negative x-ray but bone scan was positive in one and doubtful in the other. Bone marrow biopsy was positive in 31% of 13 additional patients with metastatic disease and in 44% of the nine among them with radiologically involved skeleton. These results exclude that BMB is able to discover micrometastatic foci of neoplastic disease. Its positivity appears strictly correlated with that of bone x-ray and scan. Based on the results of this prospective study, BMB is not required when both bone survey and scan are negative, but could be useful in clarifying diagnostic doubts of skeletal involvement.

Adult↗
PubMed1988

Analysis of the 5' region of the human tyrosine hydroxylase gene: combinatorial patterns of exon splicing generate multiple regulated tyrosine hydroxylase isoforms.

A single human gene has been described to encode multiple tyrosine hydroxylase (TH) mRNAs. The study of this variation has been extended by S1 mapping experiments and by analysis of the 5' region of the TH gene. Four different mRNAs were found to originate solely from alternative splicing of two exons. Comparison of the 5' flanking regions of human and rat genes discloses several highly conserved segments, likely to play an important role in the regulation of TH gene expression.

Base Sequence↗
PubMed1988

Interaction of carnitine with insulin-stimulated glucose metabolism in humans.

To characterize the interactions of carnitine with glucose metabolism, we administered L-carnitine as a primed (3 mmol) constant (17 mumol/min) intravenous infusion to healthy young volunteers during short-term (2 h) euglycemic hyperinsulinemia. In comparison with a control (saline) infusion, exogenous carnitine administration resulted in a stable, fourfold increase in basal serum carnitine levels (160 +/- 14 vs. 36 +/- 2 microM, P less than 0.001). At similar steady-state plasma insulin levels (75 microU/ml), carnitine infusion was associated with a 17 +/- 3% stimulation of whole body glucose utilization (6.56 +/- 0.60 vs. 5.57 +/- 0.44 mg.min-1.kg-1, P less than 0.001). This effect was more pronounced in the subjects with higher rates of glucose disposal (r = 0.65, P less than 0.05). Net rates of insulin-induced glucose oxidation (measured by continuous, computerized indirect calorimetry) were similar with or without carnitine (1.67 +/- 0.23 vs. 1.65 +/- 0.10 mg.min-1.kg-1, respectively). As a consequence, the carnitine-induced enhancement of total glucose metabolism was quantitatively accounted for by a 50% increase in nonoxidative glucose disposal (2.89 +/- 0.81 vs. 1.92 +/- 0.51 mg.min-1.kg-1, P less than 0.05). The inhibitory effect of insulin on net lipid oxidation was not altered by carnitine (-0.67 +/- 0.09 vs. -0.62 +/- 0.06 mg.min-1.kg-1). Circulating levels of free fatty acids (FFA), glycerol, and beta-hydroxybutyrate fell in parallel during insulin infusion in the test and control study, and blood lactate concentrations rose by similar amounts (approximately 0.35 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Independent stimulation of glucose metabolism and Na+-K+ exchange by insulin in the human forearm.

Insulin promotes potassium uptake into skeletal muscle by stimulating the activity of the Na+-K+ pump. To test whether insulin-induced glucose and potassium uptake are linked processes in vivo, we used the perfused forearm technique in healthy volunteers. Local hyperinsulinemia (125 +/- 11 microU/ml for 100 min) induced a net uptake of glucose and potassium (4.79 +/- 0.61 and 0.76 +/- 0.22 mumol.min-1.100 ml-1 of forearm volume, respectively). When an intra-arterial ouabain infusion (0.72 microgram.min-1.100 ml-1, producing local levels of approximately 0.5 mM) was superimposed on the insulin infusion, potassium uptake was blocked (0.026 +/- 0.190 ml.min-1.100 ml-1, P less than 0.02), and glucose uptake was decreased (to 3.31 +/- 0.34 mumol.min-1.100 ml-1, P less than 0.03). The latter change was explained by a 30% fall in forearm blood flow (from 2.95 +/- 0.10 to 2.01 +/- 0.18 ml.min-1.100 ml-1, P less than 0.001). To separate out the effect of blood flow, in another series of studies forearm blood flow was clamped by co-infusing propranolol and phentolamine (7 and 8 micrograms.min-1.100 ml-1, respectively). Under these conditions of fixed flow (7.0 +/- 0.8 ml.min-1.100 ml-1), ouabain still abolished the stimulatory effect of insulin on potassium uptake but had only a small (and statistically insignificant) effect on forearm glucose extraction (from 20 +/- 2 to 16 +/- 2%, P = N>). We conclude that in human forearm muscle ouabain inhibits Na+-K+ exchange and depresses insulin-induced glucose uptake via an adrenergic-mediated limitation of blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Molecular genetics of catecholamines as an approach to the biochemistry of manic-depression.

Manic depressive illness has been clearly established to exhibit a strong genetic component and is therefore amenable to linkage analysis using random DNA markers. In view of the catecholamine hypothesis of this disorder, the gene encoding tyrosine hydroxylase (TH) the limiting enzyme in catecholamines is a good candidate to investigate. This gene has been localized to chromosome 11 in close linkage with Harvey-ras-1. The various transcriptional and post-transcriptional mechanisms that modulate short and long-term TH activity are discussed. Human tyrosine hydroxylase is coded by at least three distinct mRNAs derived from a single gene. This variation has clear functional consequences and could represent a novel mode of regulating catecholamines levels in normal and pathological neurons.

Bipolar Disorder↗
PubMed1987

Acute elevation of free fatty acid levels leads to hepatic insulin resistance in obese subjects.

Raised levels of free fatty acids (FFA) compete with glucose for utilization by insulin-sensitive tissues, and, therefore, they may induce insulin resistance in the normal subject. The influence of experimental elevations in FFA levels on glucose metabolism in native insulin-resistant states is not known. We studied seven women with moderate obesity (63% above their ideal body weight) but normal glucose tolerance with the use of the insulin clamp technique with or without an infusion of Intralipid + heparin. Upon raising plasma insulin levels to approximately 60 microU/mL while maintaining euglycemia, whole body glucose utilization (3H-3-glucose) rose similarly without (from 66 +/- 7 to 113 +/- 11 mg/min m2, P less than .02) or with (from 70 +/- 7 to 137 +/- 19 mg/min m2, P less than .02) concomitant lipid infusion. In contrast, endogenous glucose production was considerably (73%) suppressed (from 66 +/- 7 to 15 +/- 8 mg/min m2, P less than .001) during the clamp without lipid, but declined only marginally (from 70 +/- 7 to 48 +/- 7 mg/min m2, NS) with lipid administration. The difference between the control and the lipid study was highly significant (P less than .02), and amounted to an average of 3.8 g of relative glucose overproduction during the second hour of the clamp. Blood levels of lactate rose by 34 +/- 15% (.1 greater than P greater than .05) in the control study but only by 17 +/- 10% (NS) during lipid infusion. Blood pyruvate concentrations fell in both sets of experiments (by approximately 45% at the end of the study) with similar time courses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Plasma biguanide levels are correlated with metabolic effects in diabetic patients.

Metabolic abnormalities occur in biguanide-treated diabetic patients. We investigated the relationship between plasma metformin and phenformin concentrations and metabolic effects. Drug levels were measured in 37 type II diabetic patients by HPLC. The method was sensitive, specific, and linear over a wide range of drug concentrations. Metformin and phenformin values ranged from 236 to 718 ng/ml and from 28 to 114 ng/ml, respectively. The plasma metformin level was correlated with triglycerides (r = -0.55; P less than 0.05) but not with drug dosage, plasma glucose, HbA1, creatinine, creatinine clearance, lactate, pyruvate, lipid, and clinical parameters. Plasma phenformin concentrations correlated with lactate (r = 0.49; P less than 0.05) and HbA1 (r = 0.50; P less than 0.05) but not with drug dosage, parameters of diabetes control, creatinine, creatinine clearance, pyruvate, and clinical parameters. The clinical usefulness of this HPLC method, the evidence that the increase of lactate is related to the circulating phenformin levels, and the demonstration that the metformin effect on triglyceride metabolism is correlated to plasma drug levels are the positive findings of this work.

Aged↗
PubMed1987

[Ambulatory ECG in the peroperative period].

The clinical recognition of perioperative myocardial necrosis represents one of the clue factors in the management of cardiac surgical patients (pts). This study was performed to determine whether there is any relationship between reperfusion ventricular fibrillation and/or ST-segment elevation and postoperative enzymatic release. Serum enzyme levels and ECG were monitored during and after cardiac operations in 23 pts (15 for valvular replacement and 8 for aortocoronary bypass graft). After aortic unclamping only 6 pts showed stable rhythm. Of the 17 pts who developed ventricular fibrillation 10 showed ST-segment elevation (83% of the 12 pts with ST-segment elevation). Although no significant difference was observed, pts with ST-segment elevation showed higher average enzyme (CK, CKMB) levels. Pts who had valvular replacement showed significantly higher serum CK and CKMB levels. Of the 4 pts who showed a second enzymatic peak, one died and another one presented complex ventricular arrhythmias. No correlation was observed between electrocardiographic data and post-operative enzymatic release. New theories concerning oxygen free radical generation during and after cardiopulmonary by-pass, with the related therapeutic perspectives, are discussed.

Cardiac Surgical Procedures↗
PubMed1986

Linkage of tyrosine hydroxylase to four other markers on the short arm of chromosome 11.

Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine synthesis; the gene has previously been cloned and localised to the short arm of chromosome 11. Because of the interest in tyrosine hydroxylase as a candidate gene for manic-depressive psychosis and other affective disorders, we carried out family studies to determine the linkage of tyrosine hydroxylase with insulin, beta-globin, D11S12 and Harvey-ras 1, members of a linkage group which has previously been localised to 11p. Using DNA from the Centre d'Etude du Polymorphisme Humain (CEPH) and from two large British pedigrees, we show that tyrosine hydroxylase is closely linked to these four loci (z = 7.36, theta = 0.04 for linkage to insulin) and suggest a gene order based on multipoint mapping.

Alleles↗