Sexual dysfunction in multiple sclerosis: The impact of different MSISQ-19 cut-offs on prevalence and associated risk factors.

BACKGROUND: Although multiple sclerosis (MS) Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a widely applied tool, no unique definition of sexual dysfunction (SD) based on its score exists. OBJECTIVE: To explore the impact of different MSISQ-19 cut-offs on SD prevalence and associated risk factors, providing relevant information for its application in research and clinical settings. METHODS: After defining SD according to two different MSISQ-19 cut-offs in 1155 people with MS (pwMS), we evaluated SD prevalence and association with sociodemographic and clinical features, mood status and disability via logistic regression. RESULTS: Depending on the chosen cut-off, 45% to 54% of pwMS reported SD. SD defined as MSISQ-19 score >30 was predicted by age (OR=1.01, p=0.047), cognition (OR=0.96, p=0.004) and anxiety (OR=1.03, p=0.019). SD defined as a score >3 on any MSISQ-19 item was predicted by motor disability (OR=1.12, p=0.003) and cognition (OR= 0.96, p=0.002). CONCLUSION: Applying different MSISQ-19 cut-offs influences both the estimated prevalence and the identification of risk factors for SD, a finding that should be considered during study planning and data interpretation. Preserved cognition exerts a protective effect towards SD regardless from the specific study setting, representing a key point for the implementation of preventive and therapeutic strategies.

Prognostic markers in AML: focus on CBFL.

Acute myeloid leukemia (AML) is a heterogeneous disease increasing in frequency owing to an aging population. Decisions on intensive induction treatments, intensification and allografting rely on the ability to divide an apparently homogeneous group according to risk. A wide range of clinical, cytogenetic and molecular variables may be used to inform this task; here we examine those variables useful in assessing prognosis for a patient with non-acute promyelocitic AML focusing on core binding factor leukemia. In clinical practice, when counseling an individual patient with AML, a range of well-known clinical variables (age, performance status and tumor burden) and genetic variables (cytogenetic and gene mutation) must be considered to better define the prognostic risk.

Long-term survival in metastatic melanoma patients treated with sequential biochemotherapy: report of a Phase II study.

The overall survival for patients with metastatic melanoma is very poor, with a median survival of 8.5 months. In this Phase II trial, we assessed the efficacy, safety, and tolerability of a sequential biochemotherapy schedule, using dacarbazine as antiblastic agent and immunomodulant doses of interleukin-2 and interferon-alfa. Thirty-one eligible patients with metastatic melanoma received dacarbazine IV as antiblastic therapy and interluekin-2, plus interferon-alfa SC as sequential immunotherapy, for 6 months. Responding and nonprogressing patients were subsequently maintained on immunotherapy treatment for further 6 months. Twenty-nine patients had an adequate trial, and were assessable for both response and toxicities, with a median follow-up of 49 months. The overall response rate was 52 percent (3 CR and 12 PR), SD was 8 (27 percent) and PD were achieved in 6 patients (21 percent). The median survival duration of responders was 28 months, significantly longer (p < 0.001) than the 16 months of nonresponders. Therapy was well tolerated and produced a significant improvement in progressive-free survival. Further studies, thus, are recommended for larger groups of patients not only to confirm these results, but also to apply this biochemotherapy regimen as adjuvant postsurgical treatment in early stages of malignant melanoma.

Weekly paclitaxel and epirubicin in the treatment of symptomatic hormone-refractory advanced prostate carcinoma: report of a phase II trial.

The efficacy of weekly paclitaxel in androgen-independent prostate cancer and its addictive cytotoxicity with anthracycline derivatives led us to determine the safety and efficacy of a weekly schedule of paclitaxel and epirubicin. Between October 2000 and November 2002, 32 patients were enrolled in this study. Patients characteristics included a median age of 72 years (range 68-77), adequate hepatic, cardiac, renal and bone marrow functions, ECOG performance status of 1-2, and no prior chemotherapy. All patients had received hormonal manipulation and seven patients (22%) had received prior palliative radiation therapy. The regimen consisted of paclitaxel 70 mg/m2 i.v. infusion for 2 h and epirubicin 30 mg/m2 in bolus every week. Treatment was continued for 3 months or until disease progression or unacceptable toxicity were observed. During the study, prostate-specific antigen (PSA) was monitored and response was defined as a 50% reduction in PSA levels, to be confirmed 4 weeks later. Thirty-one patients were evaluable for toxicity and 21 for objective response. Seventeen patients (57%) had a decline above 50% in PSA level that lasted more than 4 weeks with a median time to PSA progression and a median duration of PSA response of approximately 5.5 months. Ten of the 21 patients with measurable disease (47%) had a confirmed objective response (one complete response and 20 partial responses). Thirteen of 25 symptomatic patients (56 %) had improvement in pain. The median time to disease progression was 7.6 months and the median survival was 12.9. The most prominent grade 3 toxicities were reversible myelosuppression and fatigue. Nausea, vomiting, diarrhea and peripheral edema were minimal. No evidence of cardiac toxicity was recorded. Alopecia was frequent, but reversible, in all patients. We conclude that despite the small sample size, this study demonstrates that the combination of weekly paclitaxel and epirubicin is a well-tolerated regimen for androgen-independent prostate cancer. The results imply that a combination of these agents in a weekly schedule may have clinical potential in prostate cancer treatment.

Phase II trial of weekly intravenous gemcitabine administration with interferon and interleukin-2 immunotherapy for metastatic renal cell cancer.

PURPOSE: Since metastatic renal cell carcinoma has a poor prognosis and treatment strategies, including hormone therapy, chemotherapy and immunotherapy, have little impact on the quality of life and global survival statistics, new interest has recently focused on the combination of immuno-chemotherapy using pyrimidine analogues, such as gemcitabine. MATERIALS AND METHODS: In a phase II study 16 patients with metastatic renal cell carcinoma were treated with 1,000 mg./m. gemcitabine intravenously on days 1, 8, 15 and 28 for 6 months, 3 MU (1 MU = 1 x 10(6) IU) interferon (IFN)-alpha intramuscularly 3 times a week and 4.5 million IU interleukin (IL)-2 subcutaneously daily for 5 days a week for 2 consecutive weeks every month for 6 months. Responding and nonprogressing cases were maintained on immunotherapy consisting of IFN-alpha and IL-2 for further 6 months. RESULTS: In 15 evaluable patients overall response rate (1 complete response plus 3 partial response) was 28% while stable disease was achieved in 7 (47%). Median survival duration was 20 months (range, 9 to 26+) and median time to tumor progression was 14 months (6 to 26+). The complete response lasted 24+ months and partial response lasted 16 months. The regimen was well tolerated with only 1 case of neutropenia (WHO grade 3), while anorexia, fatigue and flu-like symptoms were the most common toxicity problems but were never greater than grade 2. CONCLUSIONS: Despite the small sample size, this study demonstrates that gemcitabine combined with standard doses of IFN-alpha and low doses of IL-2 is effective treatment for metastatic renal cell carcinoma. This biotherapy was well tolerated and resulted in an optimum objective response and relatively long-term survival.

Raltitrexed plus oxaliplatin as first-line chemotherapy in metastatic colorectal carcinoma: a multicentric phase II trial.

For advanced colorectal carcinoma, two new drugs, raltitrexed (TOM) and oxaliplatin (L-OHP), have recently shown interesting results. Preclinical and clinical studies suggest that this combination, because of its favorable toxicity profile, high response rate and convenient schedule of administration, can be administered successfully in this disease. In our phase II study, 37 non pre-treated patients with metastatic colorectal carcinoma were treated with TOM (3 mg/m(2)) and L-OHP (130 mg/m(2)) every 3 weeks. In total, 222 cycles were administered; all patients received at least 2 cycles (median 6, range 2-8). There were two complete and 14 partial responses for an overall response rate of 43% (95% CI 27-69%). The median time to response was 2.5 months (range 2-4) and the median duration was 10.3 months (range 5-18). Twelve of the 23 (52%) patients with symptomatic colorectal cancer were classified as clinical benefit responders for at least 4 weeks during the study period. Treatment was well tolerated, and both acute, essentially hematologic, and cumulative hepatic and neurologic toxicities were manageable and reversible. Response rate and toxic effects observed during this study warrant additional studies comparing this TOM-L-OHP regimen with CPT-11 and/or capacitebine-containing regimens in metastatic colorectal carcinoma.

Weekly gemcitabine plus Epirubicin as effective chemotherapy for advanced pancreatic cancer: a multicenter phase II study.

The current role of chemotherapy in pancreatic carcinoma is limited, and progress in the treatment of this disease represents a significant challenge to medical oncology. The most promising drug under study is gemcitabine, a relatively new antimetabolite that represents an attractive candidate for combination chemotherapy because of its excellent side-effect profile and the absence of overlapping toxicities with other chemotherapeutic agents. Combined administration of gemcitabine and anthracyclines could result in the induction of DNA breaks that are not easily repaired by the cell's machinery, thus enhancing the apoptotic signals triggered by these lesions. Forty-four patients with locally advanced and/or metastatic pancreatic adenocarcinoma were enrolled in this multicenter study. Patients received Epirubicin 20 mg m(-2) for 3 weeks followed by 1 week of rest (1 cycle) and gemcitabine 1000 mg m(-2) after Epirubicin on the same day. All were assessable for toxicity and response, 11 patients responded to treatment with one complete response and 10 partial responses, for an overall response rate of 25%. Median survival was 10.9 months (range, 2-26 months). Therapy was well tolerated, with a low incidence of haematologic grade >2 toxicity. A total of 12 of 27 (44.4%) eligible patients attained a clinical benefit response. Our findings suggest that the gemcitabine-epirubicin schedule is active and well tolerated in patients with advanced pancreatic cancer.

Gemcitabine plus Epi-doxorubicin as first-line chemotherapy for bladder cancer in advanced or metastatic stage: a phase II.

Combination chemotherapy with newer, more active drugs in patients with advanced and/or metastatic bladder cancer might show improved response rate and survival. Gemcitabine (GEM) and Epidoxorubicin (EPI) have demonstrated activity in this disease. In addition, experimental studies in vitro have shown that the two agents have additive-synergistic effects when used in combination. Our prior phase I dose-finding study in previously untreated patients with advanced or metastatic bladder cancer defined recommended doses for further trials of GEM 1000 mg/m2 and EPI 25 mg/m2 on days 1, 8 and 15 every 28 days. A phase II trial at this dose level was initiated in previously untreated patients to assess efficacy and toxicity. Eligible patients had measurable disease; Karnofsky performance status (PS) of > 40; no prior chemotherapy; and adequate bone marrow reserve, cardiac, hepatic and renal function. Thirty- one patients (22 males, 9 females) with median age of 64 (range 44-75) and median PS of 80 were accrued, and all were eligible. Twelve patients had T4N1-2 M0, 8 had lymph node only metastases, while 11 had visceral metastases (liver, bone, lung). A total of 181 cycles was administered (range 3-7 per patient). Major toxicities (WHO grade > or = 3) were: neutropenia in 5 patients, thrombocytopenia in 2 patients, and anemia in 2 patients. Three patients had febrile neutropenic episodes and only 3 patients required dose reduction. Grade 1-2 non-hematological toxicities included nausea/vomiting, stomatitis and alopecia. No cardiac toxicity was observed. Of the 30 response evaluable patients, 17 (57%) demonstrated a major response (3 complete and 14 partial) (95% CI: 39%-75%), 7 had stable disease (23%) and 6 progressed (20%). These preliminary results confirm the phase I observation that the combination of GEM--EPI is highly active in the treatment of advanced and metastatic bladder cancer with a favourable toxicity profile.

Hearing threshold assessment with auditory brainstem response (ABR) and ElectroCochleoGraphy (ECochG) in uncooperative children.

Two-hundred-and-sixty uncooperative children (442 ears) performed auditory brainstem response (ABR) and Electrocochleography (ECochG) in the same diagnostic session under general anaesthesia, and the results obtained with the two different methods were compared. A difference > or = 20 dB between the two methods was found in 134 ears (30.3%). The presence of middle ear effusion and symptoms of a possible central nervous system pathology were considered in order to verify the evidence of a correlation between the difference in ABR-ECochG results and these clinical parameters. The presence of middle ear effusion was not significantly correlated with differences > or = 20 dB (p = 0.1347). On the contrary, the presence of symptoms indicative of a possible central nervous system (CNS) involvement was significantly correlated with differences > or = 20 dB (p = 0.0000). ABR has to be considered the first choice in hearing assessment strategy, either for screening or diagnosis. However, the diagnosis of hearing loss only on the basis of the presence or absence of wave V requires some care in case of suspected central auditory pathway lesions. In these cases, ECochG may be the only reliable diagnostic tool for hearing assessment in uncooperative subjects.

Cochlear implantation in a bilateral Mondini dysplasia.

We report the speech perception progress and programming procedures of a case of congenital profound deafness and bilateral Mondini dysplasia implanted with a Nucleus 20 + 2 cochlear implant at the age of six. Unclear relations between electrodes array and cochlear partition made implant programming difficult and non-standard procedures were set. Cochlear implantation may give excellent rehabilitative results also in cochleae with malformation.

[Speech perception test in Italian language for profoundly deaf children]. / Test di misura della percezione verbale nei bambini sordi profondi.

Speech perception tests are an important part of procedures for diagnosing pre-verbal hearing loss. Merely establishing a child's hearing threshold with and without a hearing aid is not sufficient to ensure an adequate evaluation with a view to selecting cases suitable for cochlear implants because it fails to indicate the real benefit obtained from using a conventional hearing aid reliably. Speech perception tests have proved useful not only for patient selection, but also for subsequent evaluation of the efficacy of new hearing aids, such as tactile devices and cochlear implants. In clinical practice, the tests most commonly adopted with small children are: The Auditory Comprehension Test (ACT), Discrimination after Training (DAT), Monosyllable, Trochee, Spondee tests (MTS), Glendonald Auditory Screening Priocedure (GASP), Early Speech Perception Test (ESP), Rather than considering specific results achieved in individual cases, reference is generally made to the four speech perception classes proposed by Moog and Geers of the CID of St. Louis. The purpose of this classification, made on the results obtained with suitably differentiated tests according to the child's age and language ability, is to detect differences in perception of a spoken message in ideal listening conditions. To date, no italian language speech perception test has been designed to establish the assessment of speech perception level in children with profound hearing impairment. We attempted, therefore, to adapt the existing English tests to the Italian language taking into consideration the differences between the two languages. Our attention focused on the ESP test since it can be applied to even very small children (2 years old). The ESP is proposed in a standard version for hearing-impaired children over the age of 6 years and in a simplified version for younger children. The rationale we used for selecting Italian words reflect the rationale established for the original version, but the choice of single words follows different criteria from the original version. In fact, the two languages differ in important linguistic features so that the test can not be not adapted to the Italian language by simply translating the words involved. As currently there is no children's language dictionary in Italian arranged according to age bracket, we chose words used in children and in pre-school reading material.

[Bisyllabic words for speech audiometry: a new italian material]. / Nuove parole bisillabiche per audiometria vocale in lingua Italiana.

Bisyllabic words are the most frequently used italian speech material in evaluating intelligibility function. The italian words presently used are those proposed by Bocca and Pellegrini in 1950. The Lists of these words do, however, present some problems with regard to phonemic balance and word familiarity. In speech audiometry testing, Lists are considered interchangeable if each individual List has the same phonemic balance. So as to avoid incorrect identification due to incomprehension of infrequently used words, we chose 200 of the most familiar bisyllabic words from the most recent, widely used occurrence vocabulary of the Italian Language. Secondly, we proceeded with phonemic balance of the speech material. The selected words were divided into ten lists of 20 words each, arranged in order to obtain the best phonemic balance within each individual List and among different Lists. The differences between the new and old speech material are presented and discussed.

Cochlear and neural dysfunction in acoustic neuroma: can they be separately revealed by auditory brain-stem wave V latency?

Cochlear and retrocochlear lesions may be differentiated by a diagnostic index (D5), which is derived from the patient's auditory brain-stem wave V latency and pure-tone hearing threshold at 2 to 4 kHz. The D5 values obtained from 49 cases of acoustic neuroma (AN) have been shown to share some properties with D5 values of patients with cochlear hearing loss (280 cases), indicating a lesser prolongation of wave V latency in cases with pronounced hearing loss. Assuming this finding is indicative of some degree of cochlear impairment concomitant to the neural dysfunction, AN data were corrected in an attempt to remove the effects of cochlear impairment. The resulting D5 values could reflect the delay in wave V solely due to the neural dysfunction. A significant relationship between these D5 values and tumour size seems to support this hypothesis.

Effects of different noises on speech discrimination by the elderly.

Elderly people often complain of difficulty in speech discrimination, especially in noise environments. The effects of 4 competing noises on sentence intelligibility were evaluated: speech noise, cocktail party noise, traffic noise and continuous discourse. A comparison was made between young and old normally hearing subjects and young and old hearing-impaired subjects with similar audiograms. The old people with normal hearing had slightly reduced discrimination compared to the young during competing speech noise and cocktail noise. Discrimination in the hearing-impaired elderly was also significantly worse than in the young people with normals hearing, during competing cocktail party noise, traffic noise and continuous discourse. The young hearing-impaired had results between young normal-hearing subjects and old hearing-impaired, except for continuous discourse. Thus the effects of age on speech discrimination in noise are subtle, becoming more pronounced in the presence of hearing loss. Age-related changes in primary speech discrimination were particularly evident during competing continuous discourse.

[New therapeutic prospects in acute acoustic trauma]. / Nuove prospettive terapeutiche del trauma acustico acuto.

A total of 50 young soldiers hospitalized for high frequency hearing loss and tinnitus following exposure to gun impulse noise was studied in order to ascertain the effects of two kinds of medical treatment. A first group (18 subjects) was treated for 10 consecutive days with cerebral gangliosides. In a second group (17 subjects) gangliosides were associated with subcutaneous infiltration of bupivacaine chlorhydrate (0.5%). A third group (15 subjects) was taken as control. An improvement in hearing threshold (= greater than 20 dB at 4-8 kHz) and a consistent relief of tinnitus was respectively found in 52% and 66% of the treated subjects, while hearing status and tinnitus persisted unchanged among the control group subjects. The amount of hearing improvement over the control group proved to be statistically significant, although no significant difference was demonstrated between the two kinds of medical treatment. Since therapy was initiated 5 to 21 days after acoustic trauma, these results indicate that a pharmacological treatment may be effective even in cases where diagnosis is forwarded relatively late in respect to the trauma.

[Quantitative abnormalities in nystagmus induced by caloric stimulation in multiple sclerosis]. / Anormalità quantitative del nistagmo indotto da stimolazioni termiche nella sclerosi multipla.

Vestibular nystagmus induced by caloric stimulation (20 degrees and 44 degrees C) was evaluated in terms of duration, frequency and slow phase velocity in 80 patients suffering from clinically defined multiple sclerosis. Criteria of abnormality were established with reference to 3 confidence levels from normative data of a 15-subject control group. Abnormal data representative of vestibular hypo- and hyperreflexia were found ranging between 27 and 53% depending on different parameters and diagnostic criteria. Significant differences in occurrence of nystagmus abnormalities became evident by analyzing 6 different windows of the vestibular response. Different distributions of hypo- and hyperreflexia were observed in relation to the time-course of the normal cumulative response curve, as well as to different stimulus temperatures. For each subject the abnormal data of the 2 stimulated ears X 2 caloric stimulations X 6 analysis windows were cumulated, yielding an overall outcome of pathological results in 66% to 90% of the patients, depending on the different diagnostic criteria.