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Biomedical subjects

R Colombo

Publications and source records attributed to R Colombo.

At least 37 records · Page 2Linked to original sources

Plasma mitomycin C concentrations determined by HPLC coupled to solid-phase extraction.

The aim of this study was to set up a method for quantification of plasma mitomycin C (MMC) concentrations during intravesical chemotherapy delivered in the presence of local bladder hyperthermia (HT). In comparison with existing methods, this assay, characterized by relative simplicity and efficiency, resulted in the facilitation of performance with nondedicated instrumentation or nonspecialized staff. Purification from plasma matrix was carried out by solid-phase extraction under vaccuum. The purified drug was then collected directly into the vials of the HPLC autosampler. Chromatographic analysis was performed on a reversed-phase C18 column with water:acetonitrile (85:15 by vol) as the mobile phase and the UV detector set at 365 nm. The use of porfiromycin as internal standard provided a method with good within-day precision (CV 6.0% at 5 micrograms/L, n = 6), linearity (0.5-50 micrograms/L), and specificity. The lower limit of detection (< or = 0.5 microgram/L) proved to be suitable for plasma pharmacokinetics monitoring in two tested patients treated with MMC + HT for superficial bladder cancer.

Antibiotics, Antineoplastic

[The effects of chronic beta-blocker administration on respiratory sinus arrhythmia].

The results of studies on the effect of beta-adrenergic blockade on respiratory sinus arrhythmia (RSA) are discordant. In some studies in which an increased RSA was reported, central vagotonic activity has been proposed. The aim of this study was to verify whether chronic beta-adrenergic blockade is capable of increasing RSA, and therefore vagal outflow, and to analyze whether the mechanism of action is central or peripheral. Twenty normal subjects (mean age 28 +/- 2 years) were randomized to receive a hydrophilic (nadolol, N), a lipophilic (metoprolol, M) beta-blocker and placebo (PL). After 1 week of therapy a spectral analysis was made of the variability in heart rate and systolic blood pressure (SBP) while they controlled their breathing at 16 breaths/min for a period of 5 min. The high frequency component was calculated for the RR interval (HF-RR, RSA measure) and SBP (HF-SBP), and the squared coherence (K2) and phase functions (phi HF) were assessed between RR and SBP fluctuations in the respiratory band (RR-SBP); a negative phi HF means that RR changes follow SBP changes. The alpha HF (an index of the baroreflex gain) was also calculated. Both beta-blockers increased the mean RR interval (PL 808 +/- 21, N 1054 +/- 30, M 1031 +/- 27 ms; p < 0.0001), HF-RR (PL 6.3 +/- 0.3, N 7.1 +/- 0.3, M 7.2 +/- 0.3 ln-ms2; p = 0.002) and alpha HF (PL 13.6 +/- 1.5, N 21.9 +/- 2.8, M 24.5 +/- 3.6 ms/mmHg; p < 0.002), and both modified phi HF (PL -0.23 +/- 0.05, N -0.02 +/- 0.05, M -0.03 +/- 0.04 s; p < 0.0001). No difference was found between N and M. Chronic beta-adrenergic blockade enhanced RSA and baroreflex gain and reduced the phase between the RR interval and SBP oscillations. Since no difference was found between the hydrophilic and the lipophilic beta-blockers, these changes seem to be due to a peripheral effect.

Administration, Oral

Effects of short-term treatment with the alpha 1-blocker alfuzosin on urodynamic pressure/flow parameters in patients with benign prostatic hyperplasia.

OBJECTIVE: The objective of this double-blind, placebo-controlled urodynamic pressure/flow study was to assess the efficacy of short-term treatment with the alpha 1-blocker alfuzosin in outflow obstruction of patients with symptomatic benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: Urodynamic pressure/flow parameters were assessed after 2 weeks of placebo run-in, 4 weeks of placebo (47 patients) or 2.5 mg t.i.d. alfuzosin treatment (47 patients), followed by an 8-week extension period with alfuzosin (single-blind). RESULTS AND CONCLUSION: Four weeks of alfuzosin treatment significantly increased maximum flow (+29.0%) and decreased detrusor pressure at maximum flow (-30.2%), detrusor opening pressure (-39.4%) and maximum detrusor pressure (-28.7%). Short-term alfuzosin treatment improved outflow conditions in BPH by reducing prostatic urethral obstruction.

Adrenergic alpha-Antagonists

Detection and significance of a discrete very low frequency rhythm in RR interval variability in chronic congestive heart failure.

Although in advanced chronic congestive heart failure (CHF) very low frequency (< 0.04 Hz, VLF) oscillations are prominent, the clinical importance and the physiologic basis of these rhythms have not been elucidated. To investigate the physiologic determinants of the VLF rhythms in RR interval variability, we studied 36 patients with stable, moderate to severe CHF (33 men, age: 58 +/- 8 years, ejection fraction 25 +/- 10%, peak oxygen consumption 18.1 +/- 4.6 ml/kg/min) and 12 age- and sex-matched controls using autoregressive spectral analysis of RR interval, blood pressure, and respiratory signals during controlled conditions. We quantified low frequency (LF) (0.04 to 0.15 Hz), high frequency (HF) (0.15 to 0.40 Hz), VLF, and total power (0 to 0.5 Hz), and calculated the coherence between systolic blood pressure and RR interval variability within each band. Peripheral chemosensitivity was assessed by the ventilatory response to hypoxia using transient inhalation of pure nitrogen. The influence of transient inactivation of peripheral chemoreceptors on the VLF rhythm was investigated by exposing 6 patients to hyperoxic (60% oxygen) conditions for 20 minutes. Twenty-three patients (64%) with CHF, but no controls, had a discrete VLF rhythm (0.019 +/- 0.008 Hz) in RR variability. The presence of VLF rhythm was not related to any difference in clinical parameters (etiology, New York Heart Association class, ejection fraction, oxygen uptake) but rather to a different pattern in RR interval and blood pressure variability: lower LF power (2.8 +/- 1.6 ms2 natural logarithm [ln]) compared either to patients without VLF (4.0 +/- 1.3 ms2 ln) or to controls (5.9 +/- 0.7 ms2 ln), higher percentage of power within VLF band (86.3 +/- 8.3% vs 77.5 +/- 7.9% and 61.5 +/- 14.1%) and a markedly impaired coherence between RR interval and systolic blood pressure variability within the LF band (0.26 +/- 0.10 vs 0.42 +/- 0.18 and 0.63 +/- 0.15, in patients with vs without VLF peak and controls, respectively). Patients with VLF had significantly increased hypoxic chemosensitivity, and hyperoxic conditions were able to decrease VLF power and abolish the VLF rhythm in 5 of 6 patients with CHF. Discrete VLF oscillations in RR variability are common in patients with advanced CHF and appear to be related to severely impaired autonomic regulation and suppression of baroreceptor function, with enhancement of hypoxic chemosensitivity. We hypothesize that this rhythm represents an enhanced chemoreflex harmonic oscillation in CHF patients, which may have application for arrhythmogenesis.

Autonomic Nervous System

Short- and long-term reproducibility of time and frequency domain heart rate variability measurements in normal subjects.

OBJECTIVE: To obtain data relating to the reproducibility of the time and frequency domain measurements obtained from 10-min ECG recordings. METHODS: Eighteen normal volunteers underwent evaluations of time and frequency domain heart rate variability 2 weeks and 7 months after baseline analysis. The time domain parameters were mean NN, the standard deviation of NN intervals, the percentage of successive NN intervals > 50 ms and the root mean square successive difference of NN intervals. The frequency domain evaluations (total power, low frequency, and high frequency) were made by means of both the Fast Fourier Transform algorithm (FFT) and the autoregressive method (AR) from 10-min ECG recordings made under three different conditions: rest, controlled respiration, and after a passive head-up tilt test. Reproducibility was evaluated by means of the interclass correlation coefficient (ICC), comparing baseline values with the results obtained at the second week and the seventh month. Time domain evaluation were also made from 10-min ECG. RESULTS: All of the time domain measurements had an ICC > or = 0.75, except for the standard deviation of NN intervals, which had an ICC of 0.57. The frequency domain parameters obtained by means of either FFT or AR showed similar reproducibility. Low frequency was reproducible under all three conditions, total power only at rest, and high frequency only during controlled respiration. CONCLUSION: The reproducibility of frequency domain parameters depends on the analysed condition. These results are of primary importance when the effects of drugs or other interventions on heart rate variability are under investigation.

Adult

Quantitative evaluation of normal muscle tone.

Forty-eight normal subjects were evaluated for the purpose of objectively quantifying muscle tone. Flexor carpi radialis and extensor digitorum communis electromyographic (EMG) activity was simultaneously recorded during wrist movements imposed by a torque motor. Each session was subdivided into three steps: (1) measurement of the 'intrinsic stiffness index' (ISI) at 10 degrees/s; (2) measurement of the 'total stiffness index' (TSI) at 500 degrees/s; (3) evaluation of the stretch reflex threshold speed (SRTS). No stretch reflex (SR) was found in about half of the subjects, even at the highest speed. ISI was higher in males (p < 0.001); significant differences in TSI were found between subjects with SR and those without (p < 0.02); no statistical differences in SRTS were found for either age or gender. ISI, TSI and SRTS, appear to be reliable indices of the range of normal muscle tone for its quantitative assessment.

Adult

Reproducibility of heart rate variability measures in patients with chronic heart failure.

1. In patients with chronic heart failure, heart rate variability is reduced with relative preservation of very-low-frequency power (< 0.04 Hz). Heart rate variability has been measured without acceptable information on its stability and the optimal recording periods for enhancing this reproducibility. 2. To this aim and to establish the optimal length of recording for the evaluation of the very-low-frequency power, we analysed 40, 20, 10 and 5 min ECG recordings obtained on two separate occasions in 16 patients with chronic heart failure. The repeatability coefficient and the variation coefficient were calculated for the heart rate variability parameters, in the time-domain (mean RR, SDRR and pNN50), and in the frequency-domain: very low frequency (< 0.04 Hz), low frequency (0.04-0.15 Hz), high frequency (0.15-0.40 Hz), total power (0-0.5 Hz). 3. Mean RR remained virtually identical over time (variation coefficient 8%). The reproducibility of time-domain (variation coefficient 25-139%) and of spectral measures (variation coefficient 45-111%) was very low. The stability of the heart rate variability parameters was only apparently improved after square root and after log transformation. 4. Very-low-frequency values derived from 5 and 10 min intervals were significantly lower than those calculated from 40 and 20 min intervals (P < 0.005). Discrete very-low-frequency peaks were detected in 11 out of 16 patients on the first 40, 20 and 10 min recording, but only in seven out of 16 when 5 min segments were analysed. 5. The reproducibility of both time or frequency-domain measures of heart rate variability in patients with chronic heart failure may vary significantly. Square root or log-transformed parameters may be considered rather than absolute units in studies assessing the influence of management on heart rate variability profile. Recordings of at least 20 min in stable, controlled conditions are to be recommended to optimize signal acquisition in patients with chronic heart failure, if very-low-frequency power in particular is to be studied.

Chronic Disease

Dynamic gadolinium-enhanced magnetic resonance imaging in staging of superficial bladder cancer.

PURPOSE: We evaluated the usefulness of dynamic enhanced magnetic resonance imaging (MRI) in the staging of superficial tumors following a bolus administration of gadopentetate dimeglumine. MATERIALS AND METHODS: In 48 patients with proved bladder tummors the results of preoperative plain spin echo T1 (repetition time/echo time 500/20 msec.) and T2 (repetition time/echo time 2,000/40 to 100 msec.)-weighted MRI, dynamic gadolinium-enhanced MRI (repetition time/echo time 200/15 msec.) and late gadolinium-enhanced MRI (repetition time/echo time 500/20 msec.) were compared and correlated with the histopathological findings. RESULTS: Unenhanced spin echo T1 and T2-weighted MRI sequences were able to stage correctly 14 (56%) and 17 (68%) of 25 superficial bladder cancers, respectively. Muscular infiltration (stages pT2 and pT3a) was correctly depicted in 3 (27%) and 6 (54%) of 11 cases respectively, with over staging being the most frequent error. On the basis of the dynamic gadolinium-enhanced T1-weighted MRI appearance, superficial involvement of the bladder wall was correctly assessed in 21 of 25 cases (84%) and muscular infiltration (stages pT2 to pT3a) in 7 of 11 (63%). Delayed enhanced T1-weighted sequences showed a low accuracy rate in staging superficial tumors (44%). The overall accuracy of T1 and T2-weighted, dynamic T1-weighted and delayed T1-weighted MRI in staging bladder cancer was 58, 71, 81 and 56% respectively. CONCLUSIONS: The use of gadolinium improved the accuracy of dynamic enhanced MRI in staging superficial bladder cancer. On the contrary, delayed enhanced MRI was not useful for staging superficial bladder cancer. The degree of bladder distension was a determinant factor in staging superficial tumors.

Adult

Neoadjuvant combined microwave induced local hyperthermia and topical chemotherapy versus chemotherapy alone for superficial bladder cancer.

PURPOSE: We evaluated the effectiveness of local bladder hyperthermia and intravesical chemotherapy compared to intravesical chemotherapy alone in the treatment of superficial transitional cell carcinoma. MATERIALS AND METHODS: A new system designed to deliver simultaneously local bladder hyperthermia and intravesical chemotherapy has been developed at our institute. The system consists of a computerized 915 MHz. microwave source that directly heats the bladder walls (within a temperature range of 42.5 to 45.5C) using a transurethral catheter. From February 1989 to December 1993, 52 patients 44 to 81 years old (mean age 64.3) with superficial stages Ta to T1, grades 1 to 3 transitional cell carcinoma of the bladder were selected for neoadjuvant intracavitary treatment. Tumors were left intact as marker lesions. Of the patients 29 were randomly assigned to receive combined neoadjuvant intravesical chemotherapy and local hyperthermia (group 1), while 23 received intravesical chemotherapy alone (group 2). The treatment protocol included multiple sessions performed on an outpatient basis. Mitomycin C (40 mg. in 50 cc distilled water) was used for intravesical chemotherapy in both groups. All patients underwent transurethral resection of residual tumors and of all suspicious areas 7 to 10 days after completion of treatment. Only a complete response was considered for statistical analysis. RESULTS: A pathological complete response was documented in 19 cases (66%) in group 1 and 5 (22%) in group 2 (chi-square p< 0.01). CONCLUSIONS: According to these preliminary data, microwave induced hyperthermia combined with local intravesical chemotherapy seems to be a feasible, safe and promising approach for neoadjuvant and minimally invasive treatment of superficial bladder cancer.

Adult

Decreased heart rate variability in amyotrophic lateral sclerosis.

Autoregressive spectral analysis of heart rate variability (HRV) was performed in 29 patients with amyotrophic lateral sclerosis (ALS) and 33 age-matched healthy subjects to evaluate the involvement of the autonomic nervous system. HRV analysis provides a means to recognize low (LF) and high (HF) frequency components, respectively mediated by sympathetic and parasympathetic heart control. An increase in the mean heart rate at rest (P < 0.001), a decrease in standard deviation of R-R interval as well as in PNN50 (P < 0.001), and an increase in the LF/HF component ratio (P < 0.01) were found in the ALS patients, indicating a vagal-sympathetic imbalance. These alterations were not related to the clinical features and to the duration of the disease. Our results suggest a subclinical involvement of the autonomic nervous system in ALS, particularly affecting parasympathetic cardiovascular control.

Adult

H2O2-treated actin: assembly and polymer interactions with cross-linking proteins.

During inflammation, hydrogen peroxide, produced by polymorphonuclear leukocytes, provokes cell death mainly by disarranging filamentous (polymerized) actin (F-actin). To show the molecular mechanism(s) by which hydrogen peroxide could alter actin dynamics, we analyzed the ability of H2O2-treated actin samples to polymerize as well as the suitability of actin polymers (from oxidized monomers) to interact with cross-linking proteins. H2O2-treated monomeric (globular) actin (G-actin) shows an altered time course of polymerization. The increase in the lag phase and the lowering in both the polymerization rate and the polymerization extent have been evidenced. Furthermore, steady-state actin polymers, from oxidized monomers, are more fragmented than control polymers. This seems to be ascribable to the enhanced fragility of oxidized filaments rather than to the increase in the nucleation activity, which markedly falls. These facts; along with the unsuitability of actin polymers from oxidized monomers to interact with both filamin and alpha-actinin, suggest that hydrogen peroxide influences actin dynamics mainly by changing the F-actin structure. H2O2, via the oxidation of actin thiols (in particular, the sulfhydryl group of Cys-374), likely alters the actin C-terminus, influencing both subunit/subunit interactions and the spatial structure of the binding sites for cross-linking proteins in F-actin. We suggest that most of the effects of hydrogen peroxide on actin could be explained in the light of the "structural connectivity," demonstrated previously in actin.

Actinin

An original balloon-expanding urethral suture guide for radical prostatectomy.

Between August 1991 and July 1994, an original balloon-expanding urethral suture guide (24 F) was used in 157 consecutive cases of radical retropubic prostatectomy. Both the instrument and its clinical use are described. This guide guarantees good intraoperative exposure of the sectioned urethral stump during vesical reanastomosis, thus improving the technical feasibility of radical prostatectomy.

Equipment Design

Lactate versus bicarbonate on-line hemofiltration: a comparative study.

In this study, 6 chronic anuric uremic patients underwent lactate hemofiltration (HF) with a substitution fluid, prepared in bags, for 3 months and bicarbonate HF, with continuous on-line preparation of the substitution fluid, for 3 months. We determined Na+, Cl-, K+, total calcium (Ca), ionized calcium (Ca2+), phosphate, intact parathormone (I-PTH), pH, PCO2, PO2, and HCO3- in plasma before, during, and after the treatment, as well as Ca, Ca2+, phosphate, and I-PTH in the ultrafiltrate. Moreover, heart rate (HR) and mean arterial pressure (MAP) were continually recorded during the procedure. Furthermore, the patients underwent echocardiographic study before and after the session. In comparison with lactate, bicarbonate HF caused a significant increase in HCO3- and a decrease in K+ plasma concentrations. This was detectable, with lower significance, even 44 h after the end of the treatment. At the end of the long interdialytic period (68 h after the end of the treatment), no significant difference was detectable. pH and PCO2 showed a significant but transient increase during HF. The other parameters investigated did not differ significantly between the two methods.

Adult

Imaging of renal cell carcinoma with gadolinium-enhanced magnetic resonance: radiological and pathological study.

The use of gadolinium-DTPA enhanced MR imaging (Gd-MR) in detecting and staging of large and small renal neoplasm was investigated in 61 patients with 66 renal cell carcinoma confirmed at surgery. The purpose of the study was also to evaluate the signal intensity of the lesions and to correlate the contrast-enhanced pattern to the pathological components and architecture of the surgical specimens. Forty-four tumors were larger than 3 cm and 22 lesions were smaller than 3 cm. Unenhanced MRI detected all large lesions (44/44) and 63% (14/22) of small lesions, while Gd-MRI detected all large and small neoplasms (100%). The overall staging accuracy was 79 and 87% for plain MRI and Gd-MRI, respectively, but both modalities led to an overstaging of the disease. Enhanced MRI was an excellent staging modality for the evaluation of tumor vascular extension and tumor spread to adjacent structures. The most frequent Gd-MRI pattern of small RCC was hyperintensity, while large lesions were mostly hypointense. The presence of fibrohyaline components seemed responsible for the hyperintense pattern. No specific contrast-enhanced MRI pattern was observed according to the tumor architecture (alveolar, tubular or papillar) of noncystic lesions. On the contrary, cystic lesion appeared as an area of low signal intensity and the use of contrast media improved detection and characterization. The inhomogeneous signal intensity increased the detectability of the lesion.

Adult

[Transurethral needle ablation (TUNA) of the prostate: preliminary results].

A multicentric prospective study was designed in Italy to verify the efficacy and the safety of TUNA-BPH patients treatment. The study is co-ordinate by Progress in Urology Association was started in January 1994. Thirty five patients were treated (Mean age 68.4 +/- 4.1 aa). All patients were selected and evaluated to respect the recommendations of the International Consensus Committee (Paris 1993). The procedure was performed with lidocaine 2.5% urethral gel, oral intake of 10 mg of diazepam and steroidal antiphlogistic drugs 1 hour before treatment. Maximal number of prostatic lesions were 6; in 2 BPH initial cases were done 2 lesions alone. The treatment was interrupted at the third lesion in 2 patients because uncomfortable. Hematuria was observed in all patients, but it was resolved within 12 hours. Irritative symptoms were referred by 10 patients (28.6%) and they spontaneously were insignificant within 24 hours. One patient had an acute prostatitis. In 15 patients (42.6%) was necessary to put a suprapubic cystostomy, but all except one voided within 36 hours. We noted narrow connection between prostatic lesions number and urinary acute retention after TUNA. The average follow-up is 3.2 months (range 0.5-6). At the follow-up urine culture was always negative and PSA values increased in the first month. The value of PSA was always higher than pre-treatment, but from 1 month to 3 months progressively reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

A new approach using local combined microwave hyperthermia and chemotherapy in superficial transitional bladder carcinoma treatment.

For some time hyperthermia, alone or in combination with radiotherapy or chemotherapy, has proved to be a promising method for treating several kinds of solid tumors. After intensive laboratory investigations a new device, based on a microwave source delivering local bladder hyperthermia together with intravesical mitomycin C chemotherapy has been clinically tested as a neoadjuvant approach in 44 patients suffering from superficial cancer of the bladder. The combined approach was administered on an outpatient basis without major complications and with acceptable local toxicity. Endoscopic and histological evaluations proved that combined local hyperthermia and chemotherapy can induce necrosis of transitional tumors. The overall response rate was 90.8%, with 70.4% complete and 20.4% partial, leaving 4 patients (9.2%) nonrespondent. Clinical and histological evaluations have confirmed the feasibility and safety of this combined treatment. Further multicentric studies have been initiated.

Adult

Interactions of microtubule-associated protein MAP2 with unpolymerized and polymerized tubulin and actin using a 96-well microtiter plate solid-phase immunoassay.

A solid-phase immunoassay is used to study the protein-protein interactions between microtubule-associated protein MAP2 and the cytoskeletal proteins tubulin and actin. The assay can be performed on 96-well microtiter plates and can be used to study the interactions with both subunit proteins and their respective polymers, microtubules and microfilaments. The microtiter format allows a large number of samples to be processed, and a number of conditions can be varied. In this solid-phase immunoassay MAP2 bound to microtubules/microfilaments and tubulin dimers/G-actin in a concentration-dependent manner. However, the bound MAP2 was not dissociated from the filaments even at high NaCl concentrations, while simultaneous addition of NaCl diminished MAP2 binding to these proteins. MgCl2 was 1 order of magnitude more efficient in decreasing MAP2 binding compared with NaCl, suggesting that MAP2 may act by "screening" the electrostatic repulsion between tubulin dimers. The role of MAP2 in cross-linking microfilaments and microtubules was also examined. Microtubule/tubulin-bound MAP2 showed a diminished ability to bind to both microfilaments and G-actin, while microfilament/G-actin-bound MAP2 was able to bind efficiently to both microtubules and tubulin dimers.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton