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Biomedical subjects

G Marotta

Publications and source records attributed to G Marotta.

At least 19 recordsLinked to original sources

Muscle damage induced by black cohosh (Cimicifuga racemosa).

Extracts of black cohosh (Cimicifuga racemosa) are commonly used for the treatment of symptoms associated with menopause. Adverse events with black cohosh are rare, mild and reversible. A few number of serious adverse events, including hepatic and circulatory conditions, have been also reported, but without a clear causality relationship. We report the case of a woman with severe asthenia and very high blood levels of creatine phosphokinase and lactate dehydrogenase. The patient referred to take a dietary supplement derived from black cohosh for ameliorating menopause vasomotor symptoms. To exclude a possible involvement of this product, the patient was suggested to discontinue this therapy. After suspicion the patient showed a progressive normalization of biochemical parameters and improvement of clinical symptoms. We can hypothesise a causative role for black cohosh in the muscle damage observed in this patient. Factors suggesting an association between black cohosh and the observed myopathy included the temporal relationship between use of herbal product and asthenia and the absence of other identified causative factors. Rechallenge with the suspected agent was inadvisable for ethic reasons because of the risk of a serious relapse. This is the first time that asthenia associated with high muscle enzymes serum levels by black cohosh has been reported. In our opinion, this report is of interest because of the widespread diffusion of use of black cohosh as an alternative medicine for relief from menopausal symptoms.

Asthenia↗

Brain SPECT imaging in multiple system atrophy.

Clinical diagnosis of multiple system atrophy (MSA) relays on signs and symptoms that are often difficult to identify particularly at early stage. Indeed neuropathological studies have demonstrated that MSA is the first cause of misdiagnosis in a cohort of patients presenting with parkinsonian features. Dopamine transporter imaging (DAT) shows striatal decrements in both MSA and Parkinson's disease (PD) making it not sensitive for differential diagnosis. Studies of dopamine D2 receptors with IBZM may help revealing striatal degeneration but a large overlap exist particularly if PD patients with advanced disease are included. We have measured brain flow with technetium-99m ethyl cysteinate dimer (ECD-SPECT) in 36 MSA patients and compared it with 43 PD and 39 age-matched controls. Using Statistical Parametric Mapping (SPM99) we found areas of significant reduced perfusion in the striatum, brain stem and cerebellum in MSA compared to the other groups. We believe that ECD-SPECT imaging may offer significant advantages compared to other imaging techniques in the assessment of neuronal degeneration in MSA and may help the clinician in the diagnostic characterization of patients presenting with atypical parkinsonism.

Animals↗

Role of extracorporeal photochemotherapy in patients with refractory chronic graft-versus-host disease.

Recent studies suggest that extracorporeal photochemotherapy (ECP) may be beneficial in patients with steroid-refractory chronic graft-versus-host disease (cGvHD). However, it is not yet clear whether certain conditions, such as age, mode of onset of cGvHD etc., influence clinical response and whether certain affected organs are more sensitive to ECP than others. We analysed the main clinical and laboratory parameters related to evolution of the disease in 32 steroid-refractory cGvHD patients, to identify any useful response predictors to ECP. ECP affected the course of the disease positively in 78% (25/32) of our cases.

Adult↗

Vardenafil-induced generalized urticaria.

Vardenafil is a potent selective and reversible inhibitor of the cGMP phosphodiesterase type 5 that has been shown to improve erectile function in men. Vardenafil is usually well tolerated; the most common adverse events are headache, flushing, rhinitis, sinusitis and dyspepsia. We report a case of a 48-year-old man with an acute episode of widespread urticaria following vardenafil consumption and in absence of other identifiable causative factors. The patient had no previous episodes of urticaria. This appears to be the first report of urticaria associated with vardenafil.

Erectile Dysfunction↗

Optimised nuclear medicine method for tumour marking and sentinel node detection in occult primary breast lesions.

The aim of this study was to evaluate the feasibility of sentinel node (SN) biopsy in occult breast lesions with different radiopharmaceuticals and to establish the optimal lymphoscintigraphic method to detect both occult lesions and SNs (SNOLL: sentinel node and occult lesion localisation). Two hundred and twenty-seven consecutive patients suspected to have clinically occult breast carcinoma were enrolled in the study. In addition to the radioguided occult lesion localisation (ROLL) procedure, using macroaggregates of technetium-99m labelled human serum albumin (MAA) injected directly into the lesion, lymphoscintigraphy was performed with nanocolloids (NC) injected in a peritumoral (group I) or a subdermal site (group II). In group III, a sole injection of NC was done into the lesion in order to perform both ROLL and SNOLL. Overall, axillary SNs were identified in 205 of the 227 patients (90.3%). In 12/62 (19.4%) patients of group I and 9/79 (11.4%) patients of group III, radioactive nodes were not visualised, whereas SNs were successfully localised in 85 of 86 patients of group II ( P<0.001). Pathological findings revealed breast carcinoma in 148/227 patients (65.2%) and benign lesions in 79 (34.8%). A total of 131 axillary SNs were removed in 118 patients with breast carcinoma; intraoperative examination of the SNs revealed metastatic involvement in 16 out of 96 cases of invasive carcinoma (16.7%). It is concluded that the combination of the ROLL procedure with direct injection of MAA into the lesion and lymphoscintigraphy performed with subdermal injection of radiocolloids represents the method of choice for accurate localisation of both non-palpable lesions and SNs.

Adult↗

Brain flow changes before and after deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) markedly improves motor symptoms and reduces medication needs in Parkinson's disease (PD) patients. However, its effect on brain function has remained unclear. We used SPECT and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the STN in 22 PD patients and 13 healthy controls. PD patients were divided into good and poor responders to DBS, if changes in "off" UPDRS motor scores after surgery were >60% or <40%, respectively. Statistical analysis was performed using the SPM99 software. At baseline, all PD patients showed significant perfusion reductions in cortical areas (premotor frontal, parietal, and occipital). After DBS, changes were normalized only in the good responders, while cortical defects in the poor responders were unchanged. No flow decrements were detected in basal ganglia and thalamus in both groups, suggesting that DBS does not have a "lesion-like" effect. We conclude that good surgery outcome is associated with normalization of cortical flow abnormalities in PD.

Case-Control Studies↗

Functional neuroimaging (PET and SPECT) in the selection and assessment of patients with Parkinson's disease undergoing deep brain stimulation.

Deep brain Stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor complications who can no longer be improved by adjustment of medical therapy. Selection of surgery candidates and follow-up after surgery are critical for good outcome. Functional neuroimaging can help in the clinical assessment of these patients. We have used single photon emission computed tomography (SPECT) and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the subthalamic nucleus (STN) in 20 patients with advanced PD. We found a significant increase in the anterior cingulate/supplementary motor cortex in the 12 good responders (change in off unified UPDRS >50%). Conversely, patients with poor response (n=8; change in off UPDRS-III <50% following DBS) revealed a significant worsening of cortical hypoperfusion particularly in the prefrontal areas. No flow decrements were detected in the basal ganglia and in the thalamus in both groups during DBS stimulation suggesting that DBS does not have a "lesion like" effect. If DBS stimulates and does not inactivate STN projection neurons, flow reduction in the poor responders may be secondary to increased inhibitory basal ganglia output.

Cerebrovascular Circulation↗

Maternally inherited deafness associated with a T1095C mutation in the mDNA.

Hearing loss is a relatively frequent defect in children with a genetic or predisposition basis in about 50% of cases. Mitochondrial DNA (mtDNA)-associated disorder often present with sensorineural hearing loss (SNHL) either in isolation or as a part of a multisystem disorder in adults but the frequency in pediatric cases is unknown. We analysed deafness-related mtDNA mutations in 80 deaf children to assess the relative frequency of alterations in childhood-onset SNHL. In 16 patients in whom maternal inheritance was possible, we screened for new mutations likely to affect mitochondrial protein synthesis. In one child we detected a novel mutation (T1095C) in the 12S rRNA gene. This mutation fulfils the suggested criteria for definition of a disease-related nucleotide variant. No mutations were found in other patients. Although we cannot exclude the presence of still undefined new mtDNA mutations, our data suggest that mtDNA defect are not common in childhood-onset SNHL.

Base Sequence↗

Role of Tc-99m sestamibi scintigraphy in the diagnosis and surgical decision-making process in primary hyperparathyroid disease.

PURPOSE: Ultrasound (US) and scintigraphy are used most frequently of all the available imaging techniques for the preoperative evaluation of patients with possible primary hyperparathyroid disease. The aim of this study was to assess the value of dual-phase Tc-99m MIBI scintigraphy compared with US in the detection of adenomatous or hyperplastic glands and in the surgical decision-making process for patients with a biochemical diagnosis of primary hyperparathyroid disease. METHODS: Ninety-seven patients with increased levels of parathyroid hormone and calcium, and at least 6 months' follow-up after US and scintigraphy, were examined retrospectively to assess the influence of the diagnostic work-up on the therapeutic decision of the referring clinicians and to evaluate the sensitivity of these diagnostic tools in the surgically treated patients. Forty-eight patients underwent surgery. RESULTS: Parathyroid adenomas were found in 43 patients and hyperplasia in 1, whereas 4 patients had no evidence at surgery. The sensitivity and specificity rates were 84.4% and 95.9% for scintigraphy, and 66.6% and 98.6% for US, respectively. Of the 49 nonsurgically treated patients, 35 had negative results with both MIBI and US; only 3 had positive findings with both imaging methods. Patients treated conservatively had significantly lower parathyroid hormone and serum calcium levels than did the patients who had surgery. CONCLUSIONS: The data suggest that the high sensitivity of dual-phase MIBI scintigraphy can improve the detection of hyperfunctioning parathyroid glands. Furthermore, despite the controversy surrounding the use of imaging methods in the preoperative assessment of primary hyperparathyroid disease, these data suggest that the decision of the clinician to order surgery for a patient with a moderate increase of serum PTH level may be influenced by the results of the imaging methods.

Adenoma↗

Efficacy of anti-CD20 monoclonal antibodies (Mabthera) in patients with progressed hairy cell leukemia.

BACKGROUND AND OBJECTIVES: Recently, a chimeric monoclonal antibody (MoAb) directed against the CD20 antigen (rituximab) has been successfully introduced in the treatment of several CD20-positive B-cell neoplasias and particularly of follicular lymphomas. Based on these premises we evaluated the efficacy and the toxicity of chimeric anti-CD20 monoclonal antibody (MoAb) in relapsed/progressed hairy cell leukemia (HCL). DESIGN AND METHODS: Ten patients with relapsed/progressed HCL entered the study. Eight patients were males and two females with a median age of 55 years (range 41-78) and all of them had been previously treated with 2-chlorodeoxyadenosine and/or deoxycoformycin and a-interferon. Two out of 10 patients were anemic (Hb < 10 g/dL), 4 thrombocytopenic (Plt < 100 x 10(9)/L), 3 had fewer than 1.0 x 10(9)/L neutrophils and 3 had circulating hairy cells (HC). All patients received 375 mg/m2 i.v. of anti-CD20 MoAb once a week for 4 doses. RESULTS: All patients were evaluable for response, one patient showing a complete remission and 4 a partial response. Adverse reactions, such as fever, chills, bone pain, hypotension and thrombocytopenia, were transient and mild (grade 1-2) and occurred only during the first course of treatment. One month after the last infusion, patients who had had anemia, neutropenia or thrombocytopenia, recovered normal peripheral blood values. Circulating HC also disappeared within one month. Immunostained bone marrow biopsies were checked 1, 3 and 6 months after the end of therapy and in 5 out of 10 patients a >50% reduction of bone marrow HC infiltration was recorded. INTERPRETATION AND CONCLUSIONS: On the basis of these preliminary results observed in 10 patients with progressed HCL, it appears that treatment with anti-CD20 MoAb is safe and effective in at least 50% of patients, particularly in those with a less evident bone marrow infiltration (50%) and in those previously splenectomized.

Adult↗

Expression of the CD11c antigen in B-cell chronic lymphoproliferative disorders.

This study analyzed the expression of the beta2 integrin CD11c in 155 patients with well-characterized B-cell chronic lymphoproliferative disorders: 106 B-cell chronic lymphocytic leukemias (B-CLL), 21 hairy cell leukemias (HCL), 9 B-cell prolymphocytic leukemias (PLL) and 19 low grade non-Hodgkin's lymphomas (NHL) in leukemic phase. CD11c was expressed in 100% of patients with HCL and B-PLL, while in B-CLL and NHL it was expressed in only 49 and 57%, respectively. Furthermore, in B-CLL the expression of CD11c was found mainly in patients with early stage of disease. In addition, when the fluorescence intensity of CD11c, calculated by MFI, was evaluated, it proved significantly higher in HCL and B-PLL compared to the values recorded in B-CLL and NHL (325 and 387 vs 34 and 56, respectively) (p < 0.05). Our results demonstrate that the evaluation of CD11c, both in terms of overall positivity and of fluorescence intensity, represents an additional useful parameter for a more precise differential diagnosis within the spectrum of B-cell chronic lymphoproliferative disorders.

Chronic Disease↗

Fludarabine containing-regimens may adversely affect peripheral blood stem cell collection in low-grade non Hodgkin lymphoma patients.

Fludarabine (FLUDA) based chemotherapy has shown promise in both initial and salvage treatment of low-grade non Hodgkin's lymphomas (LG-NHL). Recently, more aggressive therapies followed by autologous hemopoietic progenitor cell rescue, have also been successfully employed in these patients. However, this procedure, due to several factors including previous therapeutic regimens, is often limited by an inadequate collection of peripheral blood stem cell (PBSC). At present, very little data is available on the effect of FLUDA containing regimens in PBSC collection. We report our preliminary experience showing a possible correlation between FLUDA based chemotherapy regimens employed before mobilization and inability to collect an adequate number of blood derived hematopoietic progenitors for autologous PBSC transplantation in LG-NHL patients.

Adult↗

Low-dose fludarabine and cyclophosphamide in elderly patients with B-cell chronic lymphocytic leukemia refractory to conventional therapy.

BACKGROUND AND OBJECTIVES: In recent years fludarabine alone or in combination with other drugs has been reported to be effective in the treatment of B-cell chronic lymphocytic leukemia (B-CLL), both as first line and salvage therapy. Among the different combination regimens, the association of fludarabine and cyclophosphamide has shown a considerable therapeutic efficacy, although a relevant number of infectious complications have been described, particularly in elderly patients. The aim of this work was to evaluate the efficacy, the toxicity, and the incidence of infectious episodes of a regimen combining lower doses of fludarabine and cyclophosphamide in elderly patients with B-CLL refractory to conventional therapy. DESIGN AND METHODS: Twenty patients with progressive B-CLL with a median age of 75 years (4 in stage B and 16 in stage C) and refractory to conventional therapy were enrolled in this study. The combination regimen was as follows: fludarabine 15 mg/m2/day i.v. [max 25 mg] and cyclophosphamide 200 mg/m2/day i.v. for four days. RESULTS: All patients enrolled were evaluable for response. Three out of 20 (15%) patients achieved a complete remission (CR), 14/20 (70%) a partial response (PR) with an overall response rate (CR+PR) of 85%, according to National Cancer Institute-Working Group response criteria. Three patients were considered resistant. In four out of 20 patients (20%), a severe neutropenia (neutrophils < 0.5x10(9)/L) occurred and one of them developed an infectious complication which required treatment with systemic antibiotics and granulocyte colony- stimulating factor (G-CSF). Non-hematologic toxicity was negligible in all patients but one, who despite a adequate therapy with allopurinol and hydration, experienced a tumor lysis syndrome with transient but severe renal impairment. INTERPRETATION AND CONCLUSIONS: The association of low-dose fludarabine and cyclophosphamide appeared to be effective in this subset of B-CLL patients, reproducing a similar overall response rate obtained with other fludarabine-based combination therapies. In addition, in this group of elderly patients, toxic side effects were negligible and infectious complications remarkably low.

Aged↗

Cardiovascular responses in humans to experimental chewing of gums of different consistencies.

Although the cardiovascular effects of exercise have been extensively investigated in man, little attention has been paid to such responses to jaw muscle activity. The aim here was to investigate the general cardiovascular effects of chewing activity in a single-blind, cross-over design. Ten healthy individuals performed one of the following chewing tasks in four separate sessions: chewing a very hard gum, chewing a moderately hard gum, chewing a soft gum, and "empty chewing" without a bolus. Unilateral chewing of gum or empty chewing was performed for 20 min on the participant's most convenient chewing side at a constant rate of 80 cycles/min. In each session, heart rate and arterial blood pressure were recorded together with electromyographic activity in the masseter and anterior temporalis muscles on the chewing side. Ratings of perceived masticatory fatigue were recorded with visual analogue scales. The heart rate and blood pressure were significantly increased (ANOVA; p < or= 0.01) during the chewing tasks and the increases were, in parallel with the muscle activity, more pronounced the harder the gum. With the very hard gum, heart rate increased by up to 11 beats/min, the systolic blood pressure was 14 mmHg (1.9kPa) higher, and the diastolic blood pressure was 11 mmHg (1.5kPa) higher. The perceived fatigue was proportional to the level of muscle activity. After 10 min of recovery from exercise, heart rate and arterial blood pressures were slightly but still significantly elevated. The results demonstrate that chewing is associated with general circulatory effects proportional to the bolus resistance.

Adult↗

Long-lasting decrease of CD4+/CD45RA+ T cells in HCL patients after 2-chlorodeoxyadenosine (2-CdA) treatment.

The CD45RA and CD45RO isoforms of the leukocyte common antigen identify functionally distinct CD4+ T cell subsets: CD4+/CD45RA+ cells which represent a more 'naive' stage of T cell compartment and CD4+/CD45RO+ 'memory' cells. Phenotypic and functional abnormalities in T cell compartment have been frequently reported in patients with hairy cell leukemia (HCL) and, in more recent studies, a significant reduction in the absolute number of CD4+ lymphocytes bearing the CD45RO antigen has also been recorded. In our study we evaluated the CD45RA and CD45RO expression on CD4+ T cells by three-color staining in flow cytometry in 38 HCL patients, 19 untreated and 19 previously treated with 2-chlorodeoxyadenosine (2-CdA), administered at a daily dose of 0.1 mg/kg c.i. for 7 days. In HCL untreated patients, the proportion and the absolute number of CD4+/CD45RA+ and of CD4+/CD45RO+ T cell subsets were similar to normal controls. In contrast, HCL patients at 3-5 years by the end of treatment with 2-CdA, together with a reduction in the absolute number of CD4+ T cells, showed a persistent and significant decrease in the proportion and absolute number of CD4+/CD45RA+ cells as compared with both untreated HCL patients and normal controls (41 +/- 16% vs 57 +/- 14% and vs 65 +/- 7%) (P = 0.01 and 0.0001) and (0.201 +/- 0.137 x 10(9)/l vs 0.549 +/- 0.238 x 10(9)/l and vs 0.696 +/- 0.078 x 10(9)/l) (P = 0.00009 and P = 0.00001). In addition, together with the reduction of CD4+/CD45RA+ cells, we recorded a concomitant increase in the proportion of the CD4+/CD45RO+ cells as compared to untreated HCL patients and normal controls (62 +/- 16% vs 47 +/- 15% and vs 42 +/- 12%) (P = 0.08 and 0.02). These findings may suggest that CD4+/CD45RA+ cells are more sensitive than CD4+/CD45RO+ to the toxic effect of 2-CdA.

Adult↗

Weekly administration of 2-chlorodeoxyadenosine in patients with hairy-cell leukemia is effective and reduces infectious complications.

BACKGROUND AND OBJECTIVE: It has been widely demonstrated that one single 7-day course continuous infusion (c.i.) 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg daily is dramatically effective in inducing high and prolonged complete remission (CR) rates in patients with hairy-cell leukemia (HCL). However, 2-CdA administration often results in severe neutropenia and lymphocytopenia both responsible for the infectious complications observed in these patients. We previously reported preliminary data regarding the effectiveness and toxicity of a modified protocol of 2-CdA administration (0.15 mg/kg 2 hours infusion once a week for 6 courses) in 25 HCL patients. This treatment schedule produced a similar overall response rate compared to standard 2-CdA regimen and appeared to be followed by a lower incidence of infectious episodes. In the present study we report response rate and toxicity of weekly 2CdA administration in a larger cohort of patients and with a longer follow-up. DESIGN AND METHODS: In a group of HCL patients with a pronounced decrease in neutrophils count (< 1 x 10(9)/L), we modified the standard protocol (0.1 mg/kg daily x 7 days c.i.) by administering 2-CdA at a dose of 0.15 mg/kg 2 hours infusion once a week for 6 courses. Thirty HCL patients, 24 males and 6 females with a median age of 56 years (range 37-76), entered into this protocol. Seventeen out of 30 patients were at diagnosis while the remaining 13 had been previously treated with alpha-interferon (alpha-IFN) (7), or 2-CdA (4) or deoxycoformycin (DCF) (2). RESULTS: Overall, 22/30 (73%) patients achieved CR and 8 (27%) partial remission (PR) with a median duration of response at the time of writing of 35 months, ranging from 6 to 58 months. Five patients (1 CR and 4 PR) have so far progressed. The treatment was very well tolerated. Five out of 30 patients (16%) developed severe neutropenia (neutrophils < 0.5 x 10(9)/L) and only in two of them we did register an infectious complication which required treatment with systemic antibiotics and granulocyte colony-stimulating factor (G-CSF). INTERPRETATION AND CONCLUSIONS: In conclusion, we confirm that weekly administration of 2-CdA at a dose of 0.15 mg/kg for 6 courses appears to be very effective in HCL inducing a high CR rate, similar to that observed with daily c.i. administration. CR durability and relapse/progression rates are also comparable to standard 2-CdA schedule. Moreover this new regimen seems to be safer in pancytopenic patients, markedly reducing life-threatening infectious complications.

Adult↗