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Biomedical subjects

F Carle

Publications and source records attributed to F Carle.

At least 19 recordsLinked to original sources

What do Italians at high risk of stroke know about ischaemic stroke? A survey among a group of subjects undergoing neuro-sonographic examination.

The objective was to assess the knowledge about ischaemic stroke among selected groups of persons at high risk for stroke. Outpatients referred to 3 hospital ultrasound departments in the Marche Region (Italy) were asked to answer a questionnaire. Data were collected on: (1) demographic characteristics; (2) risk profile determined using Coppola et al.'s scoring system; (3) knowledge about symptoms, risk factors, part of the body injured and best referral option for stroke. Of the 352 respondents, around 52% were unable to report even one warning symptom of stroke, while 58.4% of participants at increased risk did not know any risk factors. Only 64.5% identified the brain as the part of the body injured by stroke. Only 59.4% considered the Emergency Department as the best referral option in the event of stroke. This study confirms poor knowledge about stroke in our study population, particularly in subjects with increased stroke risk.

Aged↗

Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site.

The aim of this study was to assess the activity and toxicity of a platinum-based treatment on a group of patients with unknown primary tumours (UPTs). Patients with a diagnosis of UPT underwent a standard diagnostic procedure. Treatment was started within 2 weeks from diagnosis and consisted of carboplatin 400 mg m(-2) day 1, doxorubicin 50 mg m(-2) day 1, etoposide 100 mg m(-2) days 1-3, every 21 days. Response was evaluated after three courses and treatment continued in case of objective response (OR) or symptom control. A total of 102 patients were eligible. The median age was 59 years, sex male/female 54/48, histology was mainly adenocarcinoma or poorly differentiated carcinoma. Nodes, bone, liver and lung were the most frequently involved sites. In all, 79 patients received at least three courses of treatment; 26 patients received six courses or more. Six complete responses and 21 partial responses were observed, for a total of 27 of 102 ORs or 26.5% (95% confidence interval 18.2-36.1%). The median survival was 9 months and median progression-free survival was 4 months. Toxicity was moderate to severe, with 57.8% of patients experiencing grade III-IV haematological toxicity, mainly leucopenia. The regimen employed has shown activity in tumours of unknown primary site, but was associated with significant toxicity. Such toxicity may be considered unjustified, given the large proportion of patients with tumours not likely to respond. Efforts should therefore be addressed to identify predictors of response to chemotherapy, thus limiting aggressive treatment to those patients who could benefit from it.

Adult↗

Microalbuminuria, brain vasomotor reactivity, carotid and kidney arterial flow in Type 2 diabetes mellitus.

Diabetic microangiopathy produces widespread small vessel impairment which particularly affects renal glomeruli functions. Microalbuminuria is the earliest marker of microangiopathic kidney disease and has also recently been recognised as a marker of macroangiopathic cardiovascular involvement. To determine correlations between daily microalbuminuria, local microangiopathic kidney damage, systemic macroangiopathic involvement and functional brain microcirculation, 70 Type 2 diabetic subjects who were diagnosed more than 5 years ago underwent carotid (to determine index of macro- and microangiopathy) and interlobar kidney artery color Doppler (to determine microangiopathic involvement), transcranial Doppler (to determine alterations in brain vasomotor reserve), and evaluation of daily albumin excretion rate. All the indices of microcirculatory involvement in the kidney, brain and small vessels downstream-from the carotid arteries were closely related (for all p<0.001) but never correlated with the macroangiopathy index. Daily microalbuminuria correlated with all the micro- (p<0.0001) and macroangiopathic (p<0.005) Doppler indices. These findings confirm that microangiopathy is the main cause of the diabetic increase in the albumin excretion rate and support the view that microalbuminuria can be considered a powerful biomarker of widespread macroangiopathy. Our results suggest microalbuminuria may also identify cerebrovascular diabetic involvement, as it predicts both macroangiopathic carotid alteration and microvascular brain impairment.

Aged↗

Aldosterone synthase alleles and cardiovascular phenotype in young adults.

The C(-344)T promoter polymorphism of the human aldosterone synthase (CYP11B2) gene has been associated with hypertension and cardiac hypertrophy, but there were contrasting data. We analysed the genotype/phenotype associations between this polymorphism and cardiovascular variables in a young adult population, where interactions among genes, gene-environment, and acquired ageing-related organ damage are reduced. Anthropometric measurements, blood pressure, heart rate, left ventricular variables (by echocardiography), and carotid artery wall intimal-media thickness (by high-resolution sonography and digitalized morphometry) were taken in 420 white Caucasian students (mean age 23.5 years, s.d. 2.5 years). CYP11B2 alleles were detected by genomic polymerase chain reaction followed by digestion. Taking into account the three possible models of inheritance, we found no differences in the considered variables, except for an independent effect of the C(-344) allele on SBP in males (TT 125.6 (1.6), TC 128.4 (1.2) and CC 130.5 (2.2), mmHg, media (ES), P=0.03), and on interventricular septum thickness in diastole in females (CC 6.98 (0.12) vs TT 6.87 (0.09) and TC 6.87 (0.07), mmHg, P<0.01), in the codominant model. In conclusion, the CYP11B2 C(-344)T polymorphism appears to have a slight role in the cardiovascular phenotype of young healthy adults, even if these genotype/phenotype relationships might change with ageing.

Adult↗

Elderly patients with advanced non-small cell lung cancer. A pase II study with weekly cisplatin and gemcitabine.

OBJECTIVES: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly. We studied the toxicity and efficacy of a weekly schedule of gemcitabine and cisplatin in elderly patients with advanced NSCLC. METHODS: Patients aged 70 years or above with advanced NSCLC were treated in a phase II prospective trial with gemcitabine 1,000 mg/m(2) and cisplatin 35 mg/m(2) on days 1, 8 and 15 every 28 days. RESULTS: Forty-eight patients with a median age of 74 years (range 70-78) participated in the study. We observed 14 cases with partial response, 14 with stable disease and 16 with progressive disease, whilst 4 patients were not evaluable. By intention-to-treat analysis, partial response rate was 31.8% whilst progressive disease was 33.3%. Median survival was 9 months; 1-year survival probability was 34.4% and median time to progression was 4 months. Grade III-IV leukopenia was observed in 5/48 patients (10.4%), 20/48 patients (41.7%) had grade III-IV thrombocytopenia and 7/48 patients (14.6%) had grade III-IV anemia. One patient experienced grade III emesis and 2 patients had grade III-IV fatigue. CONCLUSIONS: At this dose and schedule the combination of gemcitabine and cisplatin appears to be an active and well-tolerated regimen for elderly patients with advanced NSCLC.

Adenocarcinoma↗

Diabetes and non-traumatic lower extremity amputation in a region of central Italy.

As stated in the St. Vincent Declaration, the reduction of the number of lower extremity amputations (LEA) is one of the major targets in diabetes care. Little information on the prevalence of this complication is available in Italy at present. The aim of this study was to evaluate the impact of diabetes on LEA in a region of central Italy. The regional database of hospital discharge records was used to identify all the cases of non-traumatic LEA (Nt-LEA) that had occurred in 1997 and 1998. Diagnosis of diabetes and the type of surgical intervention were defined on the basis of the medical records. Amputations were categorised as minor or major according to the level of the surgical procedure. The duration of hospitalisation was used to analyse the impact of diabetes on the health care system. Prevalence of diabetes in people who underwent Nt-LEA was 55.9% and it was similar in patients who underwent minor or major amputation (58.7 and 55.0%, respectively). No difference between diabetic and non-diabetic patients was observed as regards sex, level of amputation and duration of hospitalisation. Age was the only predictor of diabetes in amputees. The lack of specific protocols for diabetes foot care or a non-homogeneous application of these protocols in the health care service could account for a similar prevalence of diabetes among patients who underwent minor or major amputation.

Aged↗

Internal comparative audit in a thoracic surgery unit using the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM).

OBJECTIVE: The aim of the study was to use the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) to assess the performance of our thoracic surgery unit during two successive periods of activity. METHODS: From 1992 through 1997, 801 candidates for thoracic procedures at our institution were considered for the study. After validation of the logistic regression model, including the POSSUM score, observed and POSSUM-predicted morbidities were compared within two groups of patients divided by year of operation (group 1: 1992-1994, n=362; group 2: 1995-1997, n=439) by means of the z-test for the comparison of a proportion with an expected value. RESULTS: The POSSUM-predicted morbidity was significantly lower than the observed one in the first period of activity of our unit (19.6 vs. 24.3%, respectively; z-test for the comparison of a proportion with an expected value, 2.25; P=0.01), whereas no difference was found in the second period (20.5 vs. 19.1%, respectively; z-test for the comparison of a proportion with an expected value, -0.71; P=0.76). CONCLUSIONS: The result suggests a worse-than-expected performance of our unit in the first period of activity, showing that POSSUM can be reliably applied as an instrument of internal comparative audit in a thoracic surgery unit.

Hospital Units↗

Cardiovascular phenotype of young adults and angiotensinogen alleles.

OBJECTIVES AND DESIGN: Angiotensinogen (AGT) gene variants influence angiotensinogen plasma levels in children and young adults. The angiotensinogen promoter (-6)A variant facilitates gene transcription in human tissues and it has been associated with high blood pressure in older adults. A young adult population can be used as a model to study genotype/phenotype associations between AGT (-6) variants and cardiovascular variables. METHODS AND RESULTS: Anthropometric measurements, blood pressure and heart rate were taken in 422 white Caucasian students (mean age 23.5 years, SD 2.5 years). Family history for hypertension, physical activity and smoking history were evaluated. Left ventricular variables were measured by echocardiography. Carotid artery wall intimal-media thickness (IMT) was measured by high resolution sonography and digitalized morphometry. The AGT G(-6)A alleles were evaluated by mutagenically separated polymerase chain reaction controlled by direct sequencing. No significant associations were found between angiotensinogen genotype and blood pressure, cardiac variables [except for deceleration time in females which increased with the number of (-6)A alleles] and IMT. Allele frequencies were similar between the first and third tertile of blood pressure and left ventricular mass, and were also similar between negative or positive family history for hypertension (the last group having significantly higher systolic blood pressure in males, P = 0.04 and diastolic blood pressure in females, P < 0.01). Moreover, no relevant interaction on the cardiovascular variables was found between AGT genotype and body mass index. CONCLUSIONS: The angiotensinogen G(-6)A variants do not affect cardiovascular parameters in young adults, but an effect of this polymorphism on cardiovascular phenotype (and hypertension) in older adults cannot be excluded. Additional factors, associated with ageing, should be present to unleash the supposed unfavourable potential of the (-6)A angiotensinogen variant.

Adult↗

Interactions of posaconazole and flucytosine against Cryptococcus neoformans.

A checkerboard methodology, based on standardized methods proposed by the National Committee for Clinical Laboratory Standards for broth microdilution antifungal susceptibility testing, was applied to study the in vitro interactions of flucytosine (FC) and posaconazole (SCH 56592) (FC-SCH) against 15 isolates of Cryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of <0.50, was observed for 33% of the isolates tested. When synergy was not achieved, there was still a decrease in the MIC of one or both drugs when they were used in combination. Antagonism, defined as a FIC of >4.0, was not observed. The in vitro efficacy of combined therapy was confirmed by quantitative determination of the CFU of C. neoformans 486, an isolate against which the FC-SCH association yielded a synergistic interaction. To investigate the potential beneficial effects of this combination therapy in vivo, we established two experimental murine models of cryptococcosis by intracranial or intravenous injection of cells of C. neoformans 486. At 1 day postinfection, the mice were randomized into different treatment groups. One group each received each drug alone, and one group received the drugs in combination. While combination therapy was not found to be significantly more effective than each single drug in terms of survival, tissue burden experiments confirmed the potentiation of antifungal activity with the combination. Our study demonstrates that SCH and FC combined are significantly more active than either drug alone against C. neoformans in vitro as well in vivo. These findings suggest that this therapeutic approach could be useful in the treatment of cryptococcal infections.

Animals↗

Interactions between triazoles and amphotericin B against Cryptococcus neoformans.

The interaction of amphotericin B (AmB) and azole antifungal agents in the treatment of fungal infections is still a controversial issue. A checkerboard titration broth microdilution-based method that adhered to the recommendations of the National Committee for Clinical Laboratory Standards was applied to study the in vitro interactions of AmB with fluconazole (FLC), itraconazole (ITC), and the new investigational triazole SCH 56592 (SCH) against 15 clinical isolates of Cryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or =0.50, was observed for 7% of the isolates in studies of the interactions of both FLC-AmB and ITC-AmB and for 33% of the isolates in studies of the SCH-AmB interactions; additivism (FICs, >0.50 to 1.0) was observed for 67, 73, and 53% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively; indifference (FICs, >1.0 to < or =2.0) was observed for 26, 20, and 14% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively. Antagonism (FIC >2.0) was not observed. When synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when they were used in combination. To investigate the effects of FLC-AmB combination therapy in vivo, we established an experimental model of systemic cryptococcosis in BALB/c mice by intravenous injection of cells of C. neoformans 2337, a clinical isolate belonging to serotype D against which the combination of FLC and AmB yielded an additive interaction in vitro. Both survival and tissue burden studies showed that combination therapy was more effective than FLC alone and that combination therapy was at least as effective as AmB given as a single drug. On the other hand, when cells of C. neoformans 2337 were grown in FLC-containing medium, a pronounced increase in resistance to subsequent exposures to AmB was observed. In particular, killing experiments conducted with nonreplicating cells showed that preexposure to FLC abolished the fungicidal activity of the polyene. However, this apparent antagonism was not observed in vivo. Rather, when the two drugs were used sequentially for the treatment of systemic murine cryptococcosis, a reciprocal potentiation was often observed. Our study shows that (i) the combination of triazoles and AmB is significantly more active than either drug alone against C. neoformans in vitro and (ii) the concomitant or sequential use of FLC and AmB for the treatment of systemic murine cryptococcosis results in a positive interaction.

Amphotericin B↗

Calcium metabolism in adolescents and young adults with type 1 diabetes mellitus without and with persistent microalbuminuria.

Alterations in calcium metabolism can be demonstrated in the course of insulin-dependent diabetes mellitus. In order to clarify if the presence of persistent microalbuminuria (MA) can affect the main parameters of calcium metabolism, we studied 22 diabetic adolescents and young adults with persistent MA and compared them with 24 patients without MA and 24 healthy controls. Mean values of serum calcium, phosphorus and magnesium were similar in diabetic children and young adults without persistent MA and in controls. In addition, the mean values of PTH and 25-OHD, 1,25 (OH)2D3 and OC did not differ between these diabetics and controls. Diabetics with persistent MA showed no significant difference from the values of either controls or the group of diabetics without persistent MA for the mean values of serum calcium, phosphorus and magnesium and PTH. In contrast, diabetics with persistent MA had significantly (p<0.01) lower 25-OHD (26.5+/-5.2 ng/ml) and 1,25 (OH)2D3 (24.7+/-5.6 pg/ml) as well as OC levels (9.8+/-2.5 ng/ml; p<0.001) than controls (38.1+/-4.9 ng/ml, 40.7+/-6.4 pg/ml and 16.5+/-5.8 ng/ml, respectively) and subjects with normoalbuminuria (36.0+/-4.5 ng/ml, 38.8+/-8.9 pg/ml and 14.5+/-3.2 ng/ml). In conclusion, our study suggests that abnormalities in 25-OHD, 1,25(OH)2D3 and OC can be present in diabetic adolescents and young adults with incipient nephropathy.

Adolescent↗

Large incidence variation of Type I diabetes in central-southern Italy 1990-1995: lower risk in rural areas.

AIMS/HYPOTHESIS: To evaluate the relation between the incidence of childhood Type I (insulin-dependent) diabetes mellitus and the degree of urbanization in the central-southern part of Italy. METHODS: The incidence was determined in two areas: area A encompasses 3 regions of central-eastern Italy (Marche, Abruzzo, Umbria), whereas area B encompasses one southern region (Campania). During 1990-1995, 706 children aged 14 or under with insulin-dependent diabetes mellitus of recent onset were registered. The completeness of the case ascertainment in the registries analysed separately for each region was high, ranging from 96.3 % to 99%. RESULTS: The age-standardized incidence was higher in area A (9.6 per 100000 person per year; 95 % confidence interval: 8.5-10.8) than in area B (5.4 per 100000 person per year; 95% confidence interval: 4.9-6.0). In both areas the standardized incidence ratios increased with the degree of urbanization (chi-squared for trend: area A= 140, p < 0.0001; area B = 79, p < 0.0001). The highest standardized incidence ratios were in the most urban communities. CONCLUSION/INTERPRETATION: This study showed a statistically significant difference in incidence of childhood insulin-dependent diabetes mellitus among different areas of the continental peninsula of Italy. People living in the rural communities appear to have a lower risk.

Adolescent↗

POSSUM scoring system as an instrument of audit in lung resection surgery. Physiological and operative severity score for the enumeration of mortality and morbidity.

BACKGROUND: The physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) is a scoring system that was validated in general surgery with the aim of being used as an instrument to evaluate surgical outcome. We applied POSSUM to a population of lung resection candidates to assess its capability to predict postoperative complications. METHODS: Two hundred fifty lung resection candidates were prospectively evaluated from 1993 through 1996. The POSSUM value was entered along with other variables (sex, smoking history, type of resection, pulmonary function tests, arterial carbon dioxide, serum albumin level, total lymphocyte count, neoadjuvant chemotherapy and radiotherapy, and diabetes) in a multivariate analysis to identify independent predictors of postoperative morbidity. RESULTS: Logistic regression analysis showed POSSUM was predictive of postoperative complications, showing no significant difference between predicted and observed morbidity (chi2 test, p > 0.05). CONCLUSIONS: We think POSSUM can be appropriately used as a tool of surgical audit in lung resection operations.

Humans↗

Predictors of change in alcohol consumption among Frenchmen of the GAZEL study cohort.

AIMS: To identify the predictors of changes in alcohol intake among French men. DESIGN: Longitudinal study over a 2-year period. SETTING: The GAZEL volunteer cohort comprising workers employed by Electricité de France-Gaz de France. PARTICIPANTS: The study included 11,613 men aged 40-50 years who had answered a self-administered questionnaire in 1989 and 1991. MEASUREMENTS: Subjects were defined according to initial levels of alcohol intake and changes in that intake (cessation, decrease and increase) and compared with subjects with corresponding levels but unchanged intake by logistic regression. The effects of individual characteristics and of occupational and health conditions were investigated. FINDINGS: Different variables measured in 1989 were predictive of changes in alcohol consumption in 1991, depending on the change. Self-perception of bad health, consumption of sleeping pills and unmarried status were predictive of the cessation of alcohol consumption. Working under favourable conditions (with no specific occupational risks) and being a non-smoker tended to be associated with reduced consumption. Increased consumption was associated with the number of reported disease and the smoking status. Among abstainers or light daily drinkers, being exposed to more than one constraint enlarged the risk of increased consumption. For moderate drinkers, the risk of increased consumption was higher, irrespective of the number of physical constraints. CONCLUSIONS: These results highlight the fact that many inter-related factors help to determine changes in drinking habits.

Adult↗

Poorly controlled elderly Type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin.

AIMS: To assess the effects and safety of increasing sulphonylurea dosages or adding metformin in poorly controlled elderly Type 2 diabetic patients. METHODS: A 18-month multicentre clinical study was performed on sulphonylurea-treated diabetic patients over 70 years of age with well-preserved renal function, steady fasting blood glucose > or = 200 mg/dl and HbA1c > or = 9%. Patients were randomly assigned to sulphonylurea increased up to its maximum dosage (1st group) or to addition of metformin (2nd group). Glycaemic control, lipid pattern, haemostatic status and safety were monitored during run-in, at baseline and at scheduled intervals for 18 months. Results refer to 85 patients in the 1st group and 89 patients in the 2nd with complete data. RESULTS: Similar improvements in glycaemic levels were observed with both treatments within the first month and a similar decrease in HbA1c within the third month. No further changes occurred in glycaemic control. In the 1st group, fasting glucose (mmol/l, mean +/- SE) decreased from 14.21 +/- 0.49 to 9.88 +/- 0.21, average day-long glucose from 14.87 +/- 0.27 to 10.69 +/- 0.19 and HbAt1c(%) from 10.32 +/- 0.13 to 8.66 +/- 0.13. In the 2nd treatment group fasting glucose decreased from 14.59 +/- 0.61 to 9.05 +/- 37.28, average day-long glucose from 15.09 +/- 0.29 to 10.32 +/- 0.21 and HbA1c from 10.33 +/- 0.13 to 8.77+/-0.12 (for all P<0.0005). In this 2nd group, a decrease in LDL-cholesterol (P < 0.05) and an increase in HDL-cholesterol levels (P < 0.02) were also observed. In the 1st group, anthrombin III activity increased significantly (P<0.01). In the 2nd group, significant reductions in markers of platelet function (FP4 and betaTG, P < 0.01), thrombin generation (FPA, F1 + 2 and D-D, P<0.01), and fibrinolysis inhibition (PAI-1 activity, PAI-1 antigen, P< 0.001) were observed. Increases in some fibrinolytic activation markers (t-PA activity, and AT-III activity, P<0.01) occurred. Fasting lactate concentrations were unchanged in the metformin-treated group. No serious adverse effects were observed in either group. CONCLUSIONS: These results suggest that either high sulphonylurea dosages or a therapy combining lower sulphonylurea dosages with metformin are effective and safe in an aged but healthy population. Metformin provides additional benefits counteracting several cardiovascular risk factors but must be administered with caution, bearing in mind the general contra-indications for the drug but not age alone.

Aged↗

Preoperative APACHE II and ASA scores in patients having major general surgical operations: prognostic value and potential clinical applications.

OBJECTIVE: To assess the prognostic value of the APACHE II score and the American Society of Anesthesiologists (ASA) classification system in preoperative evaluation of patients. DESIGN: Prospective study. SETTING: University hospital, Italy. SUBJECTS: 187 consecutive patients undergoing elective or emergency major general surgical operations. INTERVENTIONS: Patients were evaluated preoperatively using both indices. MAIN OUTCOME MEASURES: Morbidity and mortality within 30 days. RESULTS: Logistic regression and ROC curve analyses showed that the APACHE II score predicted morbidity and mortality well; it was superior to the ASA system in predicting outcome (area under the curve 0.894 for the APACHE II index, 0.777 for the ASA system; p < 0.001). The APACHE II score without its age points (area 0.888) had the same prognostic value as the complete score (area 0.894; p = 0.55). CONCLUSIONS: The APACHE II score may help clinicians to evaluate preoperatively the risk of postoperative morbidity and death after major general surgical operations. Age does not seem to have a specific weight.

APACHE↗