New approach for T-shaped uterus: Metroplasty with resection of lateral fibromuscular tissue using a 15 Fr miniresectoscope. A step-by-step technique.

T-shaped uterus is a congenital uterine malformation (CUM), only recently defined by the ESGE ESHRE classification as Class U1a. The uterus is characterised by a narrow uterine cavity due to thickened lateral walls with a correlation 2/3 uterine corpus and 1/3 cervix. Although the significance of this dysmorphic malformation on reproductive performance has been questioned, recent studies reported significant improvement of life birth rates after surgical correction in patients with failed in-vitro fertilisation (IVF) or recurrent miscarriage. The classical surgical technique to treat a T-shaped uterus is by performing a sidewall incision with the micro scissor or bipolar needle, resulting in a triangular cavity. In this video article, we describe a new surgical technique with a step-by-step method combining three- dimensional ultrasound (3D-US) and hysteroscopic metroplasty in an office setting, using a 15 Fr office resectoscope (Karl Storz, Tuttlingen, Germany), to treat a T-shaped uterus by resecting the lateral fibromuscular tissue of the uterine walls. No complications occurred and the postoperative hysteroscopy showed a triangular and symmetrical uterine cavity without any adhesions.

[Otoacoustic distortion products in sensorineural hearing loss in the cochlea]. / I prodotti di distorsione otoacustici nelle ipoacusie neurosensoriali di natura cocleare.

The purpose of the present work was to assess distortion-product otoacoustic emissions (DPOAE) in cochlear hearing loss and in its various morphologies. A total of 19 patients (30 ears) were selected for the study. They showed various pictures of neurosensorial hearing loss which were localized within the frequency range normally examined during audiometric tonal threshold testing. The DPOAEs were recorded using a Bray and Kemp ILO 92 instrument. The DPOAEs of several frequencies (750,1000,1500,2000,3000,4000 and 6000 Hz) were examined using an f2 tone of 696, 1001, 1587, 2002, 3147, 4004 and 6348 Hz, respectively. The results were as follows: a) At certain frequencies the overlap between hearing loss and the absence of, or reduction in, DPOAE amplitude was virtually total. b) There was a modest correlation between the degree of hearing loss and decrease in, or absence of, DPOAEs although there was a spectrum of intermediate hearing losses where the DPOAEs varied widely from one individual to another (this spectrum ranged from 10 to 45 dB HL on the audiometric tonal test). c) The absence of DPOAEs at 750 Hz is unable to predict hearing loss for this frequency as, at this frequency, there can be a lack of DPOAEs even when the 750 Hz audiometric threshold level is normal. Finally, what emerged from this study was that DPOAEs prove quite useful to complement the study of auditory brainstem responses (ABR), now universally accepted as the means for early diagnosis of hearing loss in children. In fact, ABRs provide precise data regarding a frequency field which is socially less important in terms of verbal communication and the development of spoken language. It is, however, unable to explore individual frequencies.

CAMPATH-1H in rheumatoid arthritis--an intravenous dose-ranging study.

Forty-one patients with active and refractory rheumatoid arthritis(RA) received a total of 100, 250 or 400 mg of CAMPATH-1H (CAMPATH is a trademark of Glaxo-Wellcome group companies, registered in the US Patent and Trademark Office) over 5 or 10 days in an open, uncontrolled study. Following therapy, patients were monitored for adverse effects and disease activity for 6 months. Therapy was associated with prolonged peripheral blood lymphopenia in all dosing cohorts. During the month immediately following therapy, lymphopenia was most profound in the 400 mg cohorts. The first dose of monoclonal antibody (Mab) was associated with a 'flu'-like syndrome, more pronounced at higher initial doses. One patient developed haemolytic-uraemic syndrome. There were a number of dose-related infections during the early post-treatment period and one fatal opportunistic infection which followed additional immunosuppressive therapy. Antiglobulin responses developed in 9 of 31 patients tested. The majority of patients showed symptomatic improvement following therapy and 20% of patients maintained a 50% Paulus response at 6 months, all of whom were in the 250 or 400 mg cohorts. CAMPATH-1H appears to be an effective treatment for RA. Allowing for the small number of patients treated, infections were more common with higher doses, although this was not true for adverse events overall, and therapeutic responses were more sustained at higher dosing levels. The broad specificity of CAMPATH-1H may be appropriate for the immunotherapy of RA and future studies should aim to define a dose with an optimal therapeutic ratio.

CAMPATH-1H, a humanized monoclonal antibody, in refractory rheumatoid arthritis. An intravenous dose-escalation study.

OBJECTIVE: To evaluate the biologic response, tolerability, and potential clinical effect of a humanized antilymphocyte monoclonal antibody, CAMPATH-1H, in patients with rheumatoid arthritis (RA). METHODS: Forty adult patients with active, refractory RA were treated with CAMPATH-1H, given intravenously, in a multicenter, open, single-dose-escalation study. Patients were assigned to dose groups of 1, 3, 10, 30, 60, and 100 mg CAMPATH-1H. RESULTS: There was a profound, immediate, and sustained reduction of the peripheral lymphocyte count; the most susceptible were the levels of CD4+ and CD8+ cells, which remained depressed during the study period. Sixty-three percent of patients developed antibodies to CAMPATH-1H. Side effects occurred frequently throughout the first 24 hours following infusion, and included fever, headache, nausea, vomiting, and hypotension. All of the immediate drug toxicities resolved within the initial 24-hour postdosing period. One patient developed a reactivation of Mycobacterium xenopi infection 10 weeks following infusion. Sixty-five percent of patients developed a clinical response; the mean duration of response was 2 weeks. CONCLUSION: CAMPATH-1H is a lymphocyte-depleting antibody that is biologically potent even after single-dose therapy. There was no correlation between biologic effect and clinical response. Sustained lymphocyte suppression was observed. Acute infusion toxicities were observed in most patients. The role of depleting monoclonal antibodies in the treatment of RA should be reevaluated.

Sensorimotor gating and habituation evoked by electro-cutaneous stimulation in schizophrenia.

The present study has been performed in order to evaluate two relevant phenomena related to startle reflex (SR) evoked by electro-cutaneous stimulation in schizophrenic patients: 1) the effect of different interstimulus intervals on R1, R2 magnitude and on R2 latency in schizophrenia in order to verify if the gating effect influences all blink reflex (BR) parameters and 2) to replicate and extend our previous data on SR habituation. Our data have confirmed the existence of an impairment of habituation and an abnormal facilitatory effect of R1 component of BR in schizophrenics compared to healthy controls. The present study provides further evidence of specific defective mechanisms of information processing in schizophrenia. The methodology used for SR paradigm appears to be founded on a sound research basis and represents an advantageous paradigm for assessing attentional variables of information processing in mental disorders.

Chronic tension-type headache, mood depression and serotonin: therapeutic effects of fluvoxamine and mianserine.

Forty out-patients affected by chronic tension-type headache were selected according to the diagnostic criteria of International Headache Society (IHS) Headache Classification Committee. In a controlled trial patients received placebo for a four-week baseline period, then they were randomized in double-blind fashion to therapy with mianserine (30-60 mg/day) of fluvoxamine (50-100 mg/day) for another eight-week period. Frequency of headache, pain severity and analgesic consumption were evaluated using a self-monitoring system. Mood depression was evaluated at 0, 4 and 8 weeks by using Zung's Self-Rating Depression Scale and Hamilton Rating Scale for Depression. Both drugs were beneficial in the treatment of chronic tension-type headache. Non-depressed subjects with more severe headache responded best to fluvoxamine, whereas mianserine was more effective in the treatment of depressed patients with moderate headache. These results suggest that central serotoninergic neurotransmission can play a role in the pathophysiology of chronic tension-type headache also in non-depressed patients.

A multicentre 12-week open study of a lipid-soluble folate antagonist, piritrexim in severe psoriasis.

An open, 12-week, multicentre study was conducted to assess the efficacy of piritrexim isethionate in the treatment of severe psoriasis. Piritrexim isethionate is a lipid-soluble dihydrofolate reductase inhibitor which cannot form polyglutamates, and may be as effective as methotrexate in the treatment of psoriasis. If, as is suspected, but as yet unproven, methotrexate polyglutamates are responsible for the hepatotoxicity of methotrexate, piritrexim should be less hepatotoxic, and may offer an alternative to methotrexate therapy. Fifty-five patients were enrolled, of whom 41 completed the study. Patients were allocated to receive either 150, 225, 300, or 450 mg of piritrexim weekly, in divided doses over 72 h (low-dose groups, 150 and 225 mg), or over 36 h (300 and 450 mg groups). Twenty-four of the 41 patients who completed the study had a greater than 50% improvement in the severity of their psoriasis, as demonstrated by a reduction in the Psoriasis Severity Score, a measure analogous to the PASI scoring system. Adverse events were common, but mild, and were controlled by dose reduction. Piritrexim appears to be an effective therapy for severe psoriasis at doses of 300 and 450 mg weekly, in three divided doses over 36 h.

Acoustic and electrically elicited startle reaction: similar patterns of habituation and reflex modifications in humans.

The present study was performed in order to verify two relevant phenomena related to Startle Reaction in normal subjects: 1) the response habituation, that consists of an exponential decrement of the R2 component of Blink Reflex after repeated identical stimuli, and 2) the modification of R1 magnitude, R2 magnitude and latency when the startle eliciting stimulus is preceded by a warning stimulus. Our data confirm: 1) that habituation is independent of paradigm and type of stimulation (acoustic vs electrocutaneous), and 2) an electrical prestimulus has a facilitatory effect on the R2 latency of the electrically elicited Blink Reflex onset with an inhibition of R2 magnitude. The present study support the view of a systemic supramodal central mechanism of information processing and sensorial gating with super-imposable effects on the different sensorial pathways.

Startle reflex habituation in functional psychoses: a controlled study.

The habituation of the startle reflex in a paradigm using electrical stimulation was studied in 17 psychotic patients and 18 healthy controls. The magnitude of the R2 component of the blink reflex differed between the groups (ANOVA, F = 5.81; P = 0.022) and during the course of trials (F = 25.72; P < 0.0001). Furthermore a statistically significant interaction of diagnosis x trials (F = 3.34; P = 0.022) emerged suggesting that an impairment in habituation of startle is present in patients but not in healthy controls despite a comparable reactivity.

An evaluation of the antihistamine activity of acrivastine and its onset in human skin.

In a double-blind, two-period crossover study, 24 healthy volunteers were evaluated to establish the time of onset of action of activity of acrivastine in suppressing the weal and flare response to intradermally injected histamine. Volunteers received single doses of 8 mg acrivastine and placebo according to a fully randomized, balanced treatment plan. Acrivastine significantly (P less than 0.002) reduced the flare response induced by 0.4 micrograms histamine challenge 15 min after oral acrivastine dosing when compared with placebo. A significant (P less than 0.001) reduction of the weal response was noted at 25 min, although trends in this direction were already present at earlier time points.

[Bipolar affective disorders and role of intraneuronal calcium. Therapeutic effects of the treatment with lithium salts and/or calcium antagonist in patients with rapid polar inversion]. / Disturbi affettivi bipolari e ruolo del calcio intraneuronale. Effetti terapeutici del trattamento con sali di litio e/o calcio antagonista in pazienti con rapida inversione di polarità.

Treatment with lithium salts produces improvements in bipolar affective disorders. Up to date, the relationship between neurochemical and behavioural effects of lithium and its actions on intraneuronal free calcium ions is not well known. Some calcium antagonist drugs resulted active in the treatment of bipolar affective syndromes, with therapeutic effects similar to lithium salts. Some studies suggest that also lithium salts act as calcium antagonist at intraneuronal level. In this preliminary open study the activity of nimodipine, a selective neuronal calcium antagonist drug, was evaluated alone and in association with lithium salts in the treatment of rapid cycling bipolar manic-depressive illness. During three periods of 6 months 12 rapid cycling patients were treated with lithium salts, lithium salts plus nimodipine 30 mg x 3/day, nimodipine 30 mg x 3/day. The association of lithium with nimodipine resulted more effective than lithium alone or nimodipine alone in the reduction of episodes of affective disorder. These results suggest a probable sinergic activity of both treatments. Further studies will be necessary to confirm the mechanism of action, perhaps calcium antagonism, at the basis of therapeutic effects of both treatments. The results seem to confirm the hypothesis that a calcium-ionic disorders play a role in the pathogenesis of bipolar affective disorders.

The use of interferon-alpha in virus infections.

The interferons (IFN) act too slowly to arrest acute viral infections, but interferon-alpha (IFN alpha) preparations have proved useful in some chronic infections and will clearly be used increasingly in these in the future. In the preparations derived from human leucocytes or cultured B lymphoblastoid cells, which are in routine clinical use, mixtures of a number of distinct subtypes of human IFN alpha have been identified. There are also 3 slightly different versions of the same single subtype, IFN alpha-2, made by recombinant DNA procedures in bacteria. IFN alpha preparations are injected intramuscularly or subcutaneously. Dose-related side effects are common but usually tolerable, but prolonged treatment may cause increasing fatigue and depression. Some patients form neutralising antibodies which block the effects of the IFN; these appear to be relatively more common after recombinant IFN alpha-2 than after IFN derived from human cells. Given intranasally, IFN alpha can prevent a subsequent experimental rhinovirus infection, or the spread of natural colds within a family. Repeated administration progressively damages the nasal mucosa, so that long term prophylaxis is not possible. IFN alpha has proved useful in patients with papillomavirus warts of the larynx, ano-genital region (condyloma acuminata) and skin (common warts). Treatment regimens remain to be optimised and are likely to include surgery or other treatments. IFN alpha and zidovudine (azidothymidine) synergistically inhibit the growth of HIV in vitro, and combination are on trial in patients with early AIDS. Very large doses of IFN alpha are effective against Kaposi's sarcoma in some AIDS patients. In chronic hepatitis B, continuing virus replication may lead to cirrhosis or primary liver cancer. Earlier clinical trials with IFN alpha gave inconclusive results, but recent large studies have confirmed that 25 to 40% of patients obtain benefit; this probably results from both the antiviral and the immunomodulatory effects of IFN alpha. In patients with chronic hepatitis C, the biochemical markers usually improve rapidly during IFN alpha administration, but relapse if treatment is stopped after only a few months; to increase the chances of sustained cure, the treatment period is now being prolonged.

Neurological soft signs in schizophrenia.

A standardised clinical examination which focused on neurological soft signs (NSS) was used by a neurologist blind to diagnosis to assess the presence of neurological soft signs. A comparison of NSS score was made among three groups of subjects consisting of 58 DSM-III schizophrenics, 31 of their healthy first-degree relatives and 38 normal controls. The schizophrenic group had significantly higher NSS total scores than normal controls but did not differ significantly from their first-degree relatives' group. The relatives' group showed higher NSS total scores than did normal controls although to a lesser extent than schizophrenics.

Double-blind controlled study on the clinical efficacy and safety of fluoxetine vs clomipramine in the treatment of major depressive disorders.

In the present double-blind controlled study the efficacy and safety of fluoxetine 20 mg/day versus clomipramine 75 mg/day was evaluated during 5 weeks of treatment in 30 hospitalized patients. The sample was selected according to DSM III criteria for major depressive disorders with a score of at least 18 on the first 17 items of the Hamilton Rating Scale for Depression (HRSD). Therapeutic efficacy was evaluated weekly by using HRSD, Zung Self Rating Scale for Depression, Montgomery-Asberg Scale for Depression, Clinical Global Impression for severity and improvement of depressive symptoms. Safety was monitored weekly by recording body weight, blood pressure, pulse rate, temperature, physical conditions, laboratory tests, adverse experiences and concomitant medication. The results confirm the effectiveness and good tolerability of fluoxetine in the treatment of depressive disorders.

Double-blind study on the hypnotic and antianxiety effects of zopiclone compared with nitrazepam in the treatment of insomnia.

The effects of zopiclone (7.5 mg/per os/day), a new non-benzodiazepine drug, on anxiety levels, time of sleep induction, hours of sleep, number of nocturnal arousals, quality of sleep and of daytime arousal were evaluated by using psychometric ratings. A random double-blind cross-over study versus nitrazepam (5.0 mg/per os/day) was performed on 20 patients affected by insomnia and generalized anxiety disorder (DSM III-R). The effects were evaluated by using the Hamilton Rating Scale for Anxiety, the Toulouse-Pieron Attention Test and a time-signed quantitative scale for anxiety. The results of the trial confirmed the effectiveness of zopiclone in the treatment of insomnia with effects similar to nitrazepam on the quality and duration of sleep and number of nocturnal arousals, but with an improvement in all the other parameters.

Acrivastine: a review of its dermatopharmacology and clinical activity.

The general human and skin pharmacology of acrivastine, its clinical utility and some important concepts of the use of H1-antihistamines in dermatology are discussed. The drug has potent H1-antihistamic activity yet a low sedative profile as compared with first generation agents. Acrivastine is rapidly absorbed with peak inhibition of flare areas occurring at 90 min and peak activity against weals at 120 min after drug administration. No accumulation of the drug following multiple dosing has been demonstrated. Due to these effects the drug has a high level of patient acceptability and a high level of useful activity in a range of histamine-mediated dermatoses.

A comparison of acrivastine versus clemastine and placebo in the treatment of patients with chronic idiopathic urticaria.

Twenty patients of mean age 41.3 years, with a diagnosis of chronic idiopathic urticaria were assessed in a fully randomized, double-blind, crossover study to investigate the efficacy of acrivastine at two doses (8 mg and 4 mg) versus 1 mg clemastine and placebo, given three times per day. All active preparations were found to be effective, and significantly better than placebo, in controlling the signs and symptoms of urticaria. There was a higher incidence of sedation with clemastine than with either acrivastine or placebo, although this difference did not achieve statistical significance in this small study.

Acrivastine--an evaluation of initial and peak activity in human skin.

Twenty-four healthy volunteers were entered into a double-blind, crossover study conducted to establish the time of onset of action and the time to peak activity of acrivastine in suppressing the weal and flare responses to intradermally injected histamine. Volunteers received single doses of 8 mg acrivastine and placebo according to a fully randomized, balanced treatment plan. Acrivastine significantly (P less than 0.001) reduced both the weal and flare responses induced by histamine challenge 30 min after oral dosing, as compared with placebo. Peak inhibition of the flare response was seen at 90 min, and maximal suppression of the weal response occurred at 120 min after administration of acrivastine.