Search

Polymers usually utilized for gastroresistant film coating of tablets or pellets such as cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), hydroxypropylmethylcellulose phthalate (HPMCP), and Eudragit L and S were used in the preparation of drug/polymer matrix tablets. These tablets were prepared either by direct compression of both powders or by the formulation of microspheres that were then compressed. The microspheres were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffractometry analyses. Dissolution studies were finally carried out to verify if the tablets possessed gastroresistant or controlled-release characteristics. Except for Eudragit L, the polymers can be used under certain conditions in the formulation of modified-release tablets.

Objective: Psychiatric classification is still a topic of considerable discussion and debate in spite of major advances in the past two decades. The debate involves categorical versus dimensional approaches, cutoff numbers of symptoms to define a case, degree of impairment, objective diagnostic criteria versus more theoretically based criteria, episodic versus trait-like symptoms, and the role of atypical and subclinical symptoms. All of these issues have been raised for the anxiety disorders and depression. This article presents the conceptualization of a relatively novel and testable approach to the diagnosis and classification of panic and agoraphobia, the panic-agoraphobic spectrum, and pilot data on a new questionnaire to assess it., Method: Pilot testing of the Panic-Agoraphobic Spectrum Questionnaire was undertaken with 100 inpatients who had lifetime diagnoses of panic disorder, unipolar depression, comorbid panic and unipolar depressive disorders, or an eating disorder. The instrument emphasizes impairment related to 144 behaviors and experiences in seven panic-agoraphobic symptom domains., Results: Patients with panic disorder scored highest on the questionnaire, and those with comorbid depression showed even greater severity of illness. The scores of the patients with eating disorders and of the depressed patients differed from those of the other groups but also differed from 0., Conclusions: The spectrum model of panic and agoraphobia is a flexible and comprehensive means of describing this clinical complex. The proposed model, complementary to the categorical approach, presumably expresses a unitary pathophysiology. Its usefulness is discussed in terms of its value for patient-therapist communication, outcome measures, identification of subtle personality traits, and subtyping of patients for research and treatment.

The 3alpha-hydroxy metabolites of progesterone (P), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone, A-PREG) and 3alpha-hydroxy-5beta-pregnan-20-one (pregnanolone, PREG), have been found to be among the most potent ligands of gamma-aminobutyric (GABA)-A receptors; in experimental animals, they have been found to have anxiolytic, hypnotic and anticonvulsant effects. Similar to those of the benzodiazepines and barbiturates that interact with GABA-A receptors. The present study was undertaken to determine plasma A-PREG and PREG concentrations in the luteal phase in women with partial epilepsy, in order to determine if an impaired metabolism of P occurs in this convulsive disorder. We measured plasma P, A-PREG and PREG levels in 15 women with partial epilepsy in the intercritical phase, and in 15 age-matched healthy women, during the luteal phase of the ovarian cycle (22nd-24th day). The mean plasma +/- S.E. A-PREG levels (three blood samples) were 0.7 +/- 0.6 ng/ml in the epileptic women and 0.5 +/- 0.2 ng/ml in controls, with no significant difference between the two groups (p = NS); the PREG levels were also similar (1.4 +/- 1 ng/ml and 1 +/- 1.1 ng/ml, respectively: p = NS). A significant correlation was found between P levels and both A-PREG and PREG levels (r = 0.72, p < 0.001 and r = 0.79, p < 0.001, respectively). There were no significant differences between the two groups in terms of serum adrenocorticotropic hormone, cortisol, dihydroepiandrosterone-sulfate, follicle stimulating hormone, prolactin, luteinizing hormone or estradiol levels.

A nonconservative amino acid substitution (Ser857Asn) in the human delayed-rectifier potassium channel DRK1 (KCNB1 locus), a candidate gene for the low voltage alpha electroencephalogram (EEG) trait locus (LVEEG1) at 20q13.2, and its frequency in ethnic population samples are described. The frequency of Asn857 in seven different ethnic population samples, totalling more than 1600 individuals, ranged from zero to greater than 3%. However, no association was found between Asn857 and the low voltage alpha EEG trait (LVA) in a population of 105 subjects assessed for the EEG, 24 of whom actually had LVA.

This paper reviews the literature on the epidemiological, biological and clinical features of benzodiazepine dependence and withdrawal syndrome, focusing on clinical problems associated with the long-term use of benzodiazepine (BZs) in mood and anxiety disorders. These conditions represent the most frequent mental disorders for which BZs are overprescribed. In addition to dependence and withdrawal phenomena, the presence of chronic subtle toxicity and the interference with the underlying psychopathology observed with BZ use suggests a need for a more careful evaluation of the risk-benefit ratio in the long-term administration of BZs.

In a controlled study of 100 patients, mean age 65 years old, suffering from chronic peripheral obliterative arterial disease, Leriche's stage II, were randomised in two groups treated respectively with defibrotide (400 mg bid) or heparan-sulfate (40 mg bid) by the oral route for a period of 6 months. At basal and after 30, 90 and 180 treatment days, patients were assessed for pain, paresthesias, rigidity and or tiredness in the leg, Winsor index (WI) relative and absolute walking distance (RWD, AWD), and time of recovery from pain. In order to evaluate microcirculation the following parameters were tested: resting flow (RF), standing flow (SF), veno-arteriolar reflex (VAR) and a capillaroscopy study was conducted. All patients showed an improvement in the clinical and instrumental parameters but more pronounced in the defibrotide group; the difference between the beginning and the end of the therapy was significantly better for defibrotide (p < 0.01). The tolerability observed was good, no side-effects were reported during the study.

Centrally administered oxytocin has been reported to facilitate affiliative and social behaviours, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3' untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma.

Anxiety and mood disorders are among the psychic afflictions which tend to lead to prolonged benzodiazepine intake. This is also one of the reasons why doctors are faced with a difficult task when having to differentiate between these phenomena and the anxiolytic withdrawal syndrome. Since preexisting psychiatric pathology may modify withdrawal symptoms, thus making differential diagnosis between withdrawal syndrome and recrudescence of the previous disorder even more difficult, it is necessary carefully to assess clinical phenomenology both in relation to its course and to its variability with possible emergence of new symptoms. In addition to drawing attention to the diagnostic elements that can be most useful for identifying the withdrawal syndrome in mood disturbances and panic attack disorder, the authors also report the data of an experimental study of benzodiazepine withdrawal in patients suffering from generalized anxiety.

Benzodiazepines (BDZ) are widely prescribed in clinical practice for many pathological conditions, because of their anxiolytic, sedative, myorelaxant and anticonvulsant properties. The effectiveness, specificity and rapidity of action, the few side effects and the virtual absence of toxicity, have contributed to the widespread use of these compounds. In the last decade, however, the attitude towards BDZ has greatly changed, due to growing awareness and concern about dependence liability, withdrawal phenomena, and long-term side effects. Withdrawal symptoms have been singled out and specified in the contest of a well-defined syndrome with foreseeable onset, duration and remission. Psychic and physical symptoms and disorders of sensory perception can be observed. These manifestations can be suppressed by resuming treatment. The symptomatic and developmental aspects of BDZ withdrawal syndrome are discussed, according to the available literature, with particular reference to clinical features of patients suffering from anxiety and mood disorders.

Pharmacological and biochemical studies indicate that for many receptors, distinct subtypes exist; the multiplicity and diversity of signal reception proteins increase the information-handling capacity of neurons, thus contributing to neural plasticity. This is also the case for the allosteric modulatory-centre omega of the GABA-A receptor. Binding studies suggest the presence of at least two pharmacologically distinct omega receptors in the human brain; furthermore, molecular biological studies have confirmed the existence of genes encoding different omega subtypes. As omega receptors are the site of action of benzodiazepines and other anxiolytic compounds, this knowledge may be useful for developing new subtype-specific drugs, with more selective therapeutic effects.

The presence of benzodiazepine binding inhibitory activity (B.B.I.A.) in sera from 44 psychiatric patients and from 14 healthy volunteers, prompted us to investigate whether or not this activity underwent changes in stressful situations. We measured the inhibitory units (IU) of deproteinized sera of 12 subjects, immediately before and 2 weeks after sitting for a difficult university exam. Our results showed significantly higher IU values (i.e., higher B.B.I.A. concentrations) in the samples taken just before the exam. This preliminary finding clearly suggests the involvement of B.B.I.A. in anxiety mechanisms.

The effects of the stimulus repetition rate over the habituated auditory cortical evoked responses were studied. The stimulation pattern consisted of trains of pure tone bursts with interstimulus interval (ISI) of 1 s, and intertrain interval (ITI) of 5 s, delivered with constant time and intensity parameters during 93 min. The analysis of the responses was based upon across averaging of the trains, each single response being evaluated in the latency and amplitude parameters. Two time-dependent factors affected the responses in a distinct way: the habituation throughout the whole stimulation and the rate effect within the train. The linear regressions of the time/amplitude functions of the responses were calculated in relation to the duration of ISI and ITI. By introducing a correction factor depending on the repetition rate it was possible to evaluate the relationships between habituation and repetition rate. Changes in the repetition rate do not have any effect on the habituation process. The two phenomena are completely distinct, and they probably have neurophysiologic substances corresponding to different levels in the central nervous system (CNS).

1. Experiments were performed in 18 chloralose-anaesthetized, curarized cats in order to study the callosal transfer of somatic information originated in exteroceptive and proprioceptive receptors. Several cutaneous and deep nerves of the forelimb were prepared and stimulated with graded intensities, so as to activate selectively afferent fibres pertaining to the different groups of Lloyd's classification. Simultaneous records were taken (and averaged on-line by means of a multichannel analyzer) from the distal end of a cut dorsal rootlet (C7-C8), from the cerebral cortex (SI, SII or area 3a, according to the experiment) and from the somesthetic callosal region (SCR). 2. The low-threshold afferent fibres (Group II) of cutaneous origin were found to have a wide projection to the SCR, with the maximal density in its middle portion. Some of the fastest corticocallosal impulses are relayed monosynaptically at cortical level. Plots of the amplitude of cortical and callosal responses as a function of stimulus strength showed that both central responses have the same threshold and exhibit a parallel, sharply-rising amplitude increase, thus suggesting that the cortico-callosal re-transmission system for afferent impulses of cutaneous origin is very powerful in nature. Impulses elicited in afferent fibres of higher threshold (Group III) do not enhance the cortical and callosal positive waves provoked by Group II afferent volleys. 3. Afferent fibres of deep origin were also found to send a wide projection to the SCR, although less substantial than that of cutaneous fibres. Stimulation of the deep radial nerve elicited mass responses in the whole SCR, provided the strength of stimuli was high enough to engage the Group II fibres. Only in the central portion of the SCR were small potentials recorded in response to pure Group I volleys of DRN. Experiments performed with selective stimulation of pure muscular branches of forelimb deep nerves as well as of articular and mixed (muscular and articular) branches gave evidence making it possible to ascertain the origin of deep afferent fibres projecting to the SCR. Stimulation of the forelimb muscular branches with strength provoking full activation of Group I afferent and additional engagement of those of Group II, did not provoke mass responses in the whole extent of the SCR. In order to obtain callosal potentials upon stimulation of pure muscular nerves, it was necessary to increase the stimulus strength at or above the threshold for Group III fibres. On the contrary, the same callosal foci unresponsive to Group I and II muscular afferent volleys exhibited clear-cut responses to stimulation of the lowest-threshold Group I and/or Group II afferents of articular and mixed nerves. From the results it might be inferred that only proprioceptive information originating from articular receptors and from extrafusal muscular afferents has access to the callosal interhemispheric transfer.

The whole pattern of the fast, middle and long latency auditory evoked potentials (AEP) was recorded simultaneously from the scalp surface of 13 normal-hearing adults. The individual responses were displayed on a nonlinear time axis in order to improve identification of the components. Stimulation consisted of 2048 unfiltered clicks, delivered monaurally at 80, 60, 40 dB HL with an ISI of 750 ms. Changes in mean latency and amplitude of each AEP component were statistically evaluated in relation to intensity and electrode montage (vertex-mastoid ipsi- and contralateral to the stimulated ear). The latencies of fast components I-VI and the slow P1 increase significantly with declining stimulus intensity. The amplitudes of the fast, I, II, III, V and the slow P1-N1, P2-N2 decrease significantly with intensity. As regards differences due to the electrode montage the contralateral recording causes significant changes in latency of the fast potentials up to wave IV, and changes in amplitude of the fast up to wave V, and of the slow P1-N1 and P2-N2. Therefore, as their latency and amplitude seem to be less closely related to the stimulus and electrode placement, the middle components behave differently, compared with the preceding and following components. Based on parametric comparisons of potentials ranging widely in latency, but each one evoked by an equal sensory input, this kind of AEP evaluation may be useful both for neurophysiological and clinical studies of the whole auditory pathway function.

The deaf child must receive sound amplification before he reaches the age of two years. At this age the hearing threshold is best measured objectively by electrocochleography (ECochG) and auditory brainstem response (ABR) audiometry. When used correctly, both methods allow an exact threshold estimation which is informative enough for adequate hearing aid prescription. Both methods have advantages and disadvantages when used in children. The advantages of ECochG are: (a) a more exact threshold estimation and (b) strictly monaural evaluation. The advantages of ABR are: (a) ease of performance; it is not invasive and does not require general anaesthesia and (b) allows for exploration of higher levels in the auditory pathway up to the midbrain. We believe that ECochG and ABR are compatible and complementary in the diagnosis of childhood deafness. ABR could be used in first instance, while ECochG could be reserved for doubtful cases and for those who cannot be adequately sedated. Extra-audiological factors such as the availability of anaesthetists and varying hospital facilities, play a further role in determining the choice of electric response technique.

The fast Fourier transform (FFT) was employed to analyze the frequency spectra of the second heart sound in 19 healthy subjects. The data obtained show that the second heart sound is mainly composed of low-frequency vibrations, and that the frequency vs. amplitude spectra for the various filters do not exceed 150 Hz. The different spectra obtained can represent a useful reference to compare with pathological acoustical findings.

The auditory brainstem responses (ABRs) obtained in 47 subjects with asymmetric hearing loss (12 with surgically confirmed cerebello-pontine angle tumours, 35 without otoneurologic and/or neuroradiologic evidence of tumour) were evaluated by means of an index named delta V. The calculation of this index was based upon the patient's wave V absolute latency obtained at a fixed intensity of 90 dB HL and the value of latency predictable by means of the normative data. The index clearly separates retrocochlear from cochlear sites of lesion. Moreover delta V values obtained in defined cochlear lesions show a linear relation with the patient's pure tone hearing loss at 2 and 4 kHz; this behaviour is probably due to a reduction of the auditory dynamic range in the recruiting ears. delta V appears to have clinical usefulness because of two main points: first it is based upon an evaluation of the monaurally evoked ABR; second, it improves the diagnostic specificity of the responses. The rate of false positive results can be further reduced by combining delta V and IT5 values.

The brainstem responses (BER) evoked by binaural clicks (0.1 ms) with interaural time differences (delta t) from 0 to 3.5 ms were studied in 6 normal subjects. The responses analysis was carried out via computer in two different ways: (a) Comparison between binaural BER and templates obtained with the addition of two monaural BERs. (b) Extraction from the binaural BER of the second delayed pattern. The results suggest that an algebraic addition of the responses from the two stimulated sides is the main mechanism of the binaural BER generation. In comparison with the templates, the binaural response shows some differences which are evident at delta t = 0--1.5 ms and are limited in the region of VI and VII waves. Such differences are caused essentially to an amplitude decrease of the second pattern--that is response to the delayed stimulus--mainly at delta t 1.5 ms. However these results do not allow us to say if the phenomenon recorded at the surface is due to central adaptation or to specific mechanism of binaural interaction.

Auditory evoked potentials (AEP) can be simultaneously recorded on-line as a succession of 11 waves, through a single input channel of a mini-computer. Since the response waves differ widely in frequency, a computing routine has been developed to display the whole response pattern in a single picture. Based upon a non-linear samples reduction of the digitized response, this routine allows a logarithmic transformation of the time axis. The method improves the identification of the AEP components and provides an objective estimate of the central auditory pathway for both neurophysiological and neuroclinical studies.

Preliminary findings regarding the presence of plasmatic benzodiazepine binding inhibitory activity (BBIA) in 14 psychiatric patients prompted us to investigate it further in larger samples of psychiatric patients (n = 44) and in healthy controls (n = 14). The results have shown that BBIA is present in all the subjects included with statistically significant differences between the patients and controls. The highest concentrations were found in the patients with no difference between anxious or depressed patients, and the lowest in the healthy controls. These findings indicate that BBIA might play a role in the pathophysiology of some manifestations of anxiety.