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Biomedical subjects

N Colombo

Publications and source records attributed to N Colombo.

At least 37 records · Page 2Linked to original sources

Sentinel node biopsy in early vulvar cancer.

Lymph node pathologic status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Lymphoscintigraphy associated with gamma-probe guided surgery reliably detects sentinel nodes in melanoma and breast cancer patients. This study evaluates the feasibility of the surgical identification of sentinel groin nodes using lymphoscintigraphy and a gamma-detecting probe in patients with early vulvar cancer. Technetium-99m-labelled colloid human albumin was administered perilesionally in 37 patients with invasive epidermoid vulvar cancer (T1-T2) and lymphoscintigraphy performed the day before surgery. An intraoperative gamma-detecting probe was used to identify sentinel nodes during surgery. A complete inguinofemoral node dissection was then performed. Sentinel nodes were submitted separately to pathologic evaluation. A total of 55 groins were dissected in 37 patients. Localization of the SN was successful in all cases. Eight cases had positive nodes: in all the sentinel node was positive; the sentinel node was the only positive node in five cases. Twenty-nine patients showed negative sentinel nodes: all of them were negative for lymph node metastases. Lymphoscintigraphy and sentinel-node biopsy under gamma-detecting probe guidance proved to be an easy and reliable method for the detection of sentinel node in early vulvar cancer. This technique may represent a true advance in the direction of less aggressive treatments in patients with vulvar cancer.

Adult↗

Diagnosis of persistent ovarian carcinoma with three-step immunoscintigraphy.

The diagnosis of recurrent ovarian carcinoma is usually determined at surgical re-exploration since the main non-invasive diagnostic tests have low accuracy. It would be desirable to have a high accuracy non-invasive diagnostic procedure. With this aim, we have assessed the utility of three-step immunoscintigraphy. Thirty patients were intravenously injected with biotinylated monoclonal antibodies MOv18 and B72.3, followed by avidin-streptavidin injection and finally by 111In-biotin. Tumour recurrences were imaged 2 h post radioactivity injection. All patients underwent surgical re-exploration 3-4 days after immunoscintigraphy; the presence of tumour in the area of immunoscintigraphic uptake was evaluated in the biopsied material. Twenty-one patients studied were true-positive, five were true-negative, four were false-positive and none was false-negative. The diagnostic accuracy, positive predictive value and negative predictive value were 87%, 84% and 100% respectively. If these findings are confirmed in a larger number of patients, we expect immunoscintigraphy to be introduced as a cost-effective procedure in the follow-up of patients who have received surgery for ovarian carcinoma, since it promises to reliably identify patients who do not require surgical re-exploration, and guide biopsies when they are indicated.

Adult↗

Inhibitory circuits in human dysplastic tissue.

PURPOSE: Different types of epilepsies and seizures depend on the nature and location of the primary disturbance and are presumably mediated by different physiopathological mechanisms. We immunocytochemically investigated possible changes in the inhibitory-aminobutyric acid (GABA)ergic system in specimens taken from four patients who underwent surgery for intractable epilepsy and presented two different types of focal cortical dysplasia in the temporal lobe. METHODS: The patients were selected on the basis of electroclinical, imaging, and routine neuropathological data: two had Taylor focal dysplasia, and two had non-Taylor dysplasia (microdysgenesia). The study was performed using antibodies against parvalbumin (PV), glutamic acid decarboxylase (GAD), and GABA-transporter 1 (GAT1). RESULTS: In the patients with Taylor dysplasia, laminar disorganization of the cortex was associated with the presence of giant neurons and ballooned cells; there was a reduced number of PV-positive neurons and terminals, the giant neurons were surrounded by clusters of PV- and GAD-positive terminals, and there was an overall reduction in GAT1. Despite the presence of cortical laminar disorganization, no giant or ballooned cells were found in the patients with non-Taylor microdysgenesia; there was a marked decrease in PV and GAD immunoreactive elements, with a patchy distribution of GAD and GAT1 immunoreactivity but no clustering of PV and GAD terminals. CONCLUSIONS: These results suggest that the two forms of cortical dysplasia are characterized by different and selective morphofunctional alterations in the GABAergic system.

Adult↗

Clinical ictal symptomatology and anatomical lesions: their relationships in severe partial epilepsy.

High-resolution imaging techniques can demonstrate anatomic alterations in most patients identified as candidates for surgical treatment of their partial epilepsy. The demonstration of an anatomic lesion is only one step in the presurgical diagnostic procedure, which includes video-EEG and, when necessary, video-stereo-EEG recordings of seizures. A review of the literature shows that the simple removal of the magnetic resonance imaging (MRI)-evident lesion ("lesion-ectomy") reduces but does not completely suppress seizures in a large percentage of patients, especially those with neuronal migration disorders. This phenomenon could, at least in part, be explained by preliminary data (in 33 patients) showing that less than 20% of seizures correspond to a well-localized, intralesional discharge in about 40% of stereo-EEG-investigated patients with at least one intralesional electrode. The authors illustrate some anatomo-electroclinical examples of intraindividual variability of the ictal symptomatology, raising the problem of the decision about the extent of the surgical removal. Recent histologic and immunohistochemical studies have demonstrated several kinds of structural alterations in the stereo-EEG-defined epileptogenic zone, not always overlapping with the MRI-visible lesion. This aspect can further explain some failures of MRI-guided lesionectomies. That relationships between "lesions" and epileptogenic zones may be variable is also suggested by reports of patients who present with multiple lesions (i.e., cavernous angiomas, Bourneville syndrome) and are cured by removal of only one of them.

Adult↗

Chorea as a symptom of neuroborreliosis: a case study.

Borrelia burgdorferi (Bb) can cause a large number of neurological symptoms. Although extrapyramidal disturbances are rare (representing less than 2% of all neurological complications), diffuse choreic dyskinesias have been described during the course of mild encephalitis. The data published in the literature suggest that there are clinical and neurological analogies between neuroborreliosis and multiple sclerosis (MS). The presence of specific anti-Bb antibodies in cerebrospinal fluid is a discriminating factor that allows a diagnosis of neuroborreliosis to be made. We describe the case of a patient with Lyme disease, characterised by widespread chorea and behavioural disturbances. Emphasis is placed on the atypical onset and evolution, the difficulties encountered in formulating a diagnosis, and the uncertainties concerning the pathophysiology and clinical/neuroradiological correlations of the disease.

Brain↗

Intracranial hypotension syndrome: neuroimaging in five spontaneous cases and etiopathogenetic correlations.

Intracranial hypotension (IH) is essential or, more frequently, secondary. This syndrome is characterized by severe postural headache and low opening cerebrospinal fluid (CSF) pressure; although other symptoms may exist. In this study five patients are investigated. Neuroimaging showed: on computerized tomography scan (CT), poor visualization of the cerebral sulci with small ventricles; on magnetic resonance imaging (MRI), subdural fluid collections with enhancement on the convexity, along the tentorium and in the upper cervix after administration of contrast medium and downward displacement of the brain. Radionuclide cisternography was normal in the two patients who underwent this treatment as well as the meningeal biopsy in another patient. In all patients the opening CSF pressure was low or unmeasurable. The clinical syndrome spontaneously recovered contextually to normalization of neuroradiological findings. The possible pathogenesis (dural border cell layer tear) was discussed and the importance of diagnostic confirmation with MRI and measurement of CSF pressure when IH is thought to be present was underlined.

Adult↗

Neoadjuvant chemotherapy with cisplatin, ifosfamide and paclitaxel for locally advanced squamous-cell cervical cancer.

BACKGROUND: Neoadjuvant chemotherapy is increasingly being used for the treatment of bulky and locally-advanced cervical cancer. Cisplatin and ifosfamide are known to be effective in cervical cancer, while paclitaxel is one of the promising new drugs for the treatment of this neoplasm. OBJECTIVE: To assess the toxic effects and antitumor activity of a multidrug neoadjuvant regimen consisting of cisplatin, ifosfamide, and paclitaxel in bulky and locally advanced cervical cancer. PATIENTS AND METHODS: Thirty-eight patients with pathology-confirmed squamous-cell cervical cancer (27 IB2-IIA, two IIB, eight IIIB, one IVA) were prospectively enrolled in the study. Their treatment consisted of paclitaxel 175 mg/m2 given over three hours on day 1, cisplatin 50 mg/m2 (75 mg/m2 in 10 patients), ifosfamide 5 g/m2 in a 24-hour continuous infusion and mesna 5 g/m2 in a 24-hour continuous infusion on day 2, and mesna 3 g/m2 in a 24-hour continuous infusion on day 3. The course was repeated every three weeks for three courses and all of the patients, except those with disease progression or who were inoperable, were scheduled for radical hysterectomy and pelvic lymphadenectomy. RESULTS: All patients are evaluable for response. Eleven achieved clinical complete responses, 21 had partial responses, five had stable disease and one had progression of disease. Of 34 patients who underwent surgery, six (16%) had pathology-documented complete responses, seven (18%) had partial responses with only microscopic residual disease in the cervix, 19 had sub-optimal partial responses, and two had stable disease, for an overall response rate of 84% (95% confidence intervals (CI): 68.7%-94%). Grade 3-4 neutropenia was recorded for 27 (71%) patients, grade 3-4 thrombocytopenia for four (10.5%), and grade 2 peripheral neuropathy for two (2.5%). At a median follow-up of 16 months (range 7-22), 29 (76%) women are alive without recurrence, seven are alive with persistent/recurrent disease and two have died of their disease. CONCLUSIONS: According to pathology examination, this regimen yields a 34% complete and optimal partial response rate with acceptable toxicity, and it should be prospectively compared to other regimens.

Adult↗

Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.

Antineoplastic Agents↗

Human apolipoproteins A-I and A-II in cell cholesterol efflux: studies with transgenic mice.

The first step in reverse cholesterol transport is the movement of cholesterol out of cells onto lipoprotein acceptors in the interstitial fluid. The contribution of specific lipoprotein components to this process remains to be established. In this study, the role of human apolipoproteins (apo) A-I and A-II in the efflux of cellular cholesterol was investigated in transgenic mouse models in which the expression of murine apoA-I was abolished due to gene targeting (A-IKO). Serum from A-IKO mice and from mice expressing human apoA-I and/or human apoA-II was incubated with [3H]cholesterol-labeled Fu5AH rat hepatoma cells for 4 hours at 37 degrees C. The cholesterol efflux to the serum of A-IKO mice was markedly lower than that to the serum of mice transgenic for human apoA-I (5.0 +/- 1.5% versus 25.0 +/- 4.0%). Expression of human apoA-II alone did not modify the cholesterol efflux capacity of A-IKO mouse serum. Cholesterol efflux to serum of mice expressing human apoA-II together with human apoA-I was significantly lower than that to human apoA-I mouse serum (20.0 +/- 2.3% versus 25.0 +/- 4.0%). Regression analysis of cholesterol efflux versus the lipid/apolipoprotein concentrations of mouse serum suggested that 3 independent factors contribute to determine the cholesterol efflux potential of serum: the apolipoprotein composition of HDL, the serum concentration of HDL phospholipids, and the presence of a small fraction of particles containing apoA-I.

Animals↗

Iron-ovotransferrin preparation does not interfere with ciprofloxacin absorption.

Iron supplements can interfere with the bioavailability of a number of drugs, including thyroxine, tetracycline derivatives, penicillamine, methyldopa, levodopa, carbidopa, ciprofloxacin, and the newer fluoroquinolones. A new iron formulation was tested in which iron ions are bound to ovotransferrin, a protein that shares more than an 80% similarity with the sequence of human transferrin and apparently is less likely than the commonly used iron salts to reduce drug absorption. Ciprofloxacin was taken as a model drug, of wide use and restricted range of therapeutic levels, and its absorption was evaluated after the administration of the iron-ovotransferrin complex versus an iron-gluconate formulation in healthy volunteers. At variance with the iron gluconate formulation, which led to a reduction of about 50% of peak serum ciprofloxacin levels (Cmax; 1.0 +/- 0.2 versus 2.4 +/- 0.3 micrograms/ml; p < 0.01) and of the area under the serum concentration-time curve from time 0 to infinity [AUC(0 - infinity); 10.1 +/- 1.1 versus 18.3 +/- 1.0 mg.L-1.hr; p < 0.01], the iron-ovotransferrin complex caused only modest, non significant changes in absorption with a minimal reduction of the AUC[0 - infinity) (17.3 +/- 1.0 versus 18.3 +/- 1.0 mg.L-1.hr; difference not significant) and a nonsignificant decrease in the Cmax (2.2 +/- 0.3 versus 2.4 +/- 0.3 microgram/ml; difference not significant). Iron was also well absorbed from the formulation in the presence of a fatty meal. The very common drug interactions with oral iron preparations can be effectively prevented by the use of the iron-ovotransferrin complex interacting to a minimal extent with a sensitive drug with a reduced margin of efficacy, such as ciprofloxacin.

Adult↗

Vaginal cabergoline in the treatment of hyperprolactinemic patients intolerant to oral dopaminergics.

OBJECTIVE: To evaluate the effectiveness and tolerance of vaginal cabergoline in hyperprolactinemic patients intolerant to oral dopaminergics. DESIGN: Case reports. SETTING: University hospital endocrinological outpatient clinic. PATIENTS: A 35-year-old primipara woman with idiopathic hyperprolactinemia and a 22-year-old female with primary amenorrhea harboring macroprolactinoma. INTERVENTIONS: Treatment with vaginal cabergoline (0.5 mg two and five times a week). MAIN OUTCOME MEASURES: The serum PRL levels and side effects were assessed before and during treatment. RESULTS: A single vaginal dose of 0.5 mg cabergoline reduced serum PRL levels by approximately 50% to 85% of basal values over a period of 4 to 5 hours. In the patients with idiopathic hyperprolactinemia, serum PRL levels normalized during long-term treatment, whereas in the one with macroprolactinoma they remained above the normal values (79 ng/mL [conversion factor to SI unit, 3.180]) despite resumption of menses and marked tumor shrinkage (70% reduction). No side effects were reported. CONCLUSIONS: Vaginal cabergoline is a safe and effective method of therapy for hyperprolactinemia and it avoids the adverse events of oral administration.

Adult↗

Salvage therapy with ifosfamide and mitoxantrone in advanced ovarian cancer.

OBJECTIVE: To evaluate the anti-tumour activity and toxicity of ifosfamide (5 g/m2 continuous infusion) and mitoxantrone (10 mg/m2) given in combination every 3 weeks in patients with ovarian cancer resistant to at least two previous regimens which included platinum. PATIENTS AND METHODS: Additional eligibility criteria were an ECOG performance status < or = 2 and measurable disease. Of 47 patients entered in the study, 8 were defined as platinum-resistant and 39 as potentially sensitive according to Markman's criteria. Thirty-five patients had also received paclitaxel as last treatment before entering this study. Tumour response was evaluated every three cycles. RESULTS: One complete and 11 partial responses were reported, for an overall response rate of 25% (95% CI: 14%-40%). Three of the partial responders were resistant to platinum. None of the 7 partial responders pretreated with taxol had responded to it. The overall median survival was 11 months. Neutropenia G4 was reported in 18 patients (42%) with hospitalisation because of febrile neutropenia in 3 of them. CONCLUSIONS: In patients with ovarian cancer failing at least 2 previous therapies including platinum, the combination of ifosfamide and mitoxantrone has shown an antitumour activity comparable to that of paclitaxel, with acceptable toxicity. Objective responses were reported also in patients failing paclitaxel, suggesting a lack of cross resistance.

Adolescent↗

Propofol anaesthesia in spontaneously breathing paediatric patients during magnetic resonance imaging.

BACKGROUND: The aim of this study was to evaluate the use of propofol to induce and maintain anaesthesia in spontaneously breathing paediatric patients (age 2 weeks-11 years) during Magnetic Resonance Imaging (MRI) of the CNS. METHODS: All patients were spontaneously breathing, without intubation, and received supplemental O2. Pulse rate, blood pressure (BP), electrocardiogram and EtCO2 were recorded in all patients, and in 38 subjects SpO2 was also monitored. Patients were divided in 2 groups according to their body weights: Group A (n = 34, bwt < or = 10 kg), and Group B (n = 48, bwt > 10 kg). RESULTS: Dosage of propofol during the time of induction (from insertion of the i.v. cannula to positioning on the MRI table) was significantly higher in smaller children (Group A; 5.4 +/- 2.2 (SD) mg/kg) as compared to children with bwt above 10 kg (Group B; 3.7 +/- 1.6 mg/kg). Propofol dosage for maintenance of anaesthesia was significantly higher in smaller children (Group A: 10.1 +/- 5.7 vs Group B: 7.1 +/- 3.0 mgkg-1 h-1, P = 0.003). During the time of induction, transient episodes of reduced BP (< or = 20%) occurred in 6 patients in Group A and 2 patients in Group B. During anaesthesia in Group B there was 1 episode of oxygen desaturation (95%), and 3 episodes of short and mild increases of EtCO2(< or = 52 mmHg). No other side effects occurred in any patient. MRI studies were successfully completed, only 3 sequences (Group A) had to be restarted. CONCLUSION: Propofol can be safely used for total intravenous anaesthesia in children undergoing MRI.

Anesthesia Recovery Period↗

Intraperitoneal recombinant interferon gamma in ovarian cancer patients with residual disease at second-look laparotomy.

PURPOSE: The purpose of this study was to evaluate the efficacy and tolerance of recombinant human interferon gamma (rIFN-gamma) as second-line treatment in patients with persistent disease at second-look laparotomy. PATIENTS AND METHODS: One hundred eight patients with residual disease at second-look laparotomy were treated with rIFN-gamma (20 x 10(6) IU/m2) administered intraperitoneally (IP) twice a week for 3 to 4 months. In the absence of clinically assessable disease, response to rIFN-gamma was assessed with a third-look laparotomy. RESULTS: Of 98 assessable patients, 31 (32%) achieved a surgically documented response, including 23 patients (23%) with a complete response (CR). The age and size of residual tumor were significant prognostic factors for the response to rIFN-gamma. A 41% CR rate was observed in 41 patients younger than 60 years and with residual tumor less than 2 cm. The probability of response was independent of previous response to first-line chemotherapy. The median duration of response was 20 months and the 3-year survival rate in responders was 62%. Response to rIFN-gamma was the most significant prognostic factor for survival of patients with residual disease. Adverse events included fever, flu-like syndrome, neutropenia, and liver enzyme disturbances. No significant peritoneal fibrosis was noted. CONCLUSION: These results support the potential interest of IP rIFN-gamma as adjuvant treatment in ovarian cancer. Controlled prospective trials are required to determine its place in the therapeutic strategy of this malignancy.

Adult↗