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Biomedical subjects

C Boni

Publications and source records attributed to C Boni.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1985

Macro serum CK-BB in a woman with severe primary hypothyroidism.

We report the case of a woman with severe hypothyroidism and without concomitant myocardial damage, in whom elevated CK-MB values were measured by radioimmunological and enzymatic methods before and after thyroid replacement therapy. The patient's CK-MB activity was shown to be actually due to an atypical CK band between CK-MM and CK-MB (also termed "macro CK" or "idiopathic serum CK-BB").

Aged↗
PubMed1984

Effects of dilazep on coronary and systemic hemodynamics in humans.

The cardiovascular effects of dilazep, a new antianginal drug, were investigated in 18 patients, who underwent cardiac catheterization and coronary angiography for the evaluation of chest pain. Dilazep, 0.2 mg/kg, was injected intravenously over 1 to 2 minutes. The changes induced by dilazep in coronary tone were assessed by quantitative angiography in four patients, changes in systemic and coronary hemodynamics and blood gases in eight patients, and changes in systemic and pulmonary hemodynamics and blood gases in six. In 6 of the 18 patients the effects on hemoglobin-O2 oxygen binding were also investigated. Following dilazep administration, we observed a marked reduction of coronary resistance (six patients) (0.5 vs 1.0 mm Hg X min X ml-1, p less than 0.01) and of aortic-coronary sinus oxygen difference (seven patients) (4.6 vs 12.3 vol%, p less than 0.01), and a 23% increase in coronary diameter (four patients) (p less than 0.001). Total systemic resistance was also reduced by dilazep (six patients). Conversely, only minimal or insignificant changes were observed in heart rate (14 patients), aortic pressure (14 patients), total pulmonary resistance (six patients), myocardial oxygen consumption (six patients), double product (14 patients), blood gases (seven patients), and hemoglobin-oxygen affinity (six patients). We conclude that dilazep exerts a powerful dilating action on coronary vasculature without appreciable increase of myocardial oxygen consumption and cardiac work simultaneously with a reduction of peripheral resistance.

Adult↗
PubMed1984

Expression of cloned vaccinia virus DNA sequences introduced into animal cells.

Individual cloned HindIII fragments of vaccinia virus DNA were introduced into cells by DNA-mediated gene transfer. The presence of individual fragments in the different transformants was confirmed by Southern blot hybridization analysis. Several of the transformants were found to express viral sequences at various levels. The sizes of the transcripts containing vaccinia virus sequences were highly heterogeneous, with no discrete species of RNA. Positive clones contained vaccinia virus sequences in both the poly(A)+ and poly(A)- RNA fractions, although the prevalence of these sequences was variable in the two fractions. The S1 nuclease map of the 5' end of the transcripts from transformants containing the HindIII-J fragment revealed a unique 5' end, similar to RNA from virus-infected cells. In contrast, analysis of the 3' end of RNAs from these transformants showed a high degree of heterogeneity, which might explain the heterogeneity found in Northern blot patterns. In this report, it is shown for the first time that in cells transformed with vaccinia virus DNA there is proper initiation for, at least, the viral thymidine kinase gene.

Cells, Cultured↗
PubMed1984

Detection of hypothyroid myopathy by measurement of various serum muscle markers--myoglobin, creatine kinase, lactate dehydrogenase and their isoenzymes. Correlations with thyroid hormone levels (free and total) and clinical usefulness.

An accurate and close follow-up of serum levels of thyroid hormones and various muscle markers (myoglobin, creatine kinase and its isoenzymes CK-MB and CK-BB, lactic dehydrogenase, alpha-hydroxybutyric dehydrogenase, etc.) was carried out in 10 hypothyroid patients on replacement therapy. The main muscle markers, creatine kinase and myoglobin, were elevated respectively in 9 and 6 subjects. In 1 male significant CK-MB traces were measured, while in 1 woman significant CK-BB amounts were assayed. Significant correlations between patients' thyroid hormones and the levels of the muscle parameters were found. The rate of normalization of thyroid hormones and muscle markers in relation to replacement therapy was also studied. Myoglobin and creatine kinase have proved to be the best indicators of the hypothyroid myopathy, since they are sensitive for the early detection of muscle involvement due to the metabolic disorder and are closely correlated to the metabolic conditions of patients.

Adolescent↗
PubMed1983

Chemotherapy versus combination of chemotherapy and endocrine therapy in advanced breast cancer. A prospective randomized study.

One hundred-forty-five postmenopausal women with metastatic breast cancer entered a prospective randomized trial comparing treatment A (cyclophosphamide, methotrexate, and 5-fluorouracil; CMF) with treatment B (the same chemotherapy plus tamoxifen; CMF plus T). Patients on treatment A had T added to CMF at the time of progression or relapse (second-line CMF plus T). One hundred thirty-three cases were evaluable. Considering response rate to first-line treatment, CMF plus T appeared to be significantly superior to CMF alone (74 versus 51%, respectively; P less than 0.01). Median time to failure to first-line treatments, considering all patients, was longer in CMF plus T than in CMF arm (48 and 24 weeks, respectively; P = 0.06). Considering patients showing objective remission, median duration of response to CMF was similar to that of CMF plus T (47 and 51 weeks, respectively). Twelve of 39 evaluable women treated with second-line CMF plus T showed objective responses (31%). Median time to failure to treatment procedures scheduled in arm A (CMF leads to CMF + T) was longer than that to treatment in arm B (CMF plus T) (56 and 48 weeks, respectively; P = 0.08). Median survival was longer in patients randomized to treatment A (111 weeks) than in patients randomized to treatment B (78 weeks), but this difference was not statistically significant (P = 0.25). It can be concluded from this study that a combination of endocrine therapy and chemotherapy is significantly more active than chemotherapy alone in inducing an objective remission. This strategy of treatment is advisable in situations urgently requiring a clinical response. However, as a sequence of chemical and endocrine therapy induced a longer time to development of progressive disease and a better survival, sequential therapy is advisable for common clinical use.

Adult↗