[Peripheral vascular disease of iliac and femoro-popliteal arteries: state-of-the-art endoluminal revascularization]. / Arterielle Verschlusskrankheit der Becken- und Oberschenkelarterien: State-of-the-art-Rekanalisation.

Endoluminal therapy is indicated in lower extremity ischaemia with Fontaine grades IIb, III and IV. In the presence of significant limitations, interventions are carried out even in grade IIa claudicants. In addition to the TASC A and B lesions, TASC C and D lesions are increasingly being treated endoluminally as well. Presently, technical success rates of revascularization procedures are above 90% in the iliac vessels and between 79% and 95% in the femoro-popliteal segments. Concentric, non-calcified iliac stenoses are primarily treated with balloon angioplasty (PTA) followed by optional stenting when necessary. For occlusions and heavily calcified lesions, primary stenting is recommended. Primary PTA is the mainstay of treatment in femoro-popliteal vessels with stents being used as a "bail-out" option in case of suboptimal PTA. However, initial reports proving the superiority of primary stenting over PTA with optional stenting have already appeared. Results of PTA with drug-coated balloons for prevention of early restenosis are promising. In the near future, primary PTA with optional stenting in the femoro-popliteal segments may give way to drug-coated balloon angioplasty or primary stenting.

Studies of a neurochemical link between depression, anxiety, and stress from [3H]imipramine and [3H]paroxetine binding on human platelets.

We measured platelet [3H]imipramine and [3H]paroxetine binding in patients with major depression (n = 11), dysthymia (n = 9), generalized anxiety (n = 18) and panic disorder (n = 10), and in healthy controls (n = 13). The [3H]imipramine binding capacity (Bmax) was lower in all patient groups; [3H]paroxetine binding was reduced in anxiety disorders, however, decreases in depression and dysthymia were not significant. There were no differences in the affinity constant (Kd) for either radioligand. We also examined the effects of examination stress on platelet binding in medical students. Compared to after vacation, when binding was similar to controls, [3H]imipramine (n = 19) and [3H]paroxetine (n = 14) Bmax values were significantly decreased during examinations and similar to patient values. Examinations were also associated with an increase in plasma cortisol levels. These findings suggest that there is a neurochemical link between depression, anxiety, and stress, and that disturbances in neurochemical functioning may be associated with specific symptomatology, independent of psychiatric diagnosis.

Trimipramine, anxiety, depression and sleep.

The presence of mixed symptoms of anxiety and depression are well known to every clinician. Panic, generalised anxiety and obsessive-compulsive disorder all have considerable overlap with major depressive illness. Factor analysis of anxiety and depression symptoms has sought to predict response to treatment as well as to establish a diagnosis. Sleep disturbances are important concomitants of both syndromes. The analysis of the architecture and phasing of sleep stages has been proposed as a biological marker to separate anxiety and depression. The modification of REM and delta sleep has been correlated with antidepressant action. The earliest studies of trimipramine noted antidepressant, anxiolytic and hypnotic effects. Further observations have shown this drug to have atypical effects on REM sleep. In addition, despite its structural similarity to other tricyclic antidepressants, its pharmacological profile in animals is very different: there is no synaptosomal reuptake of serotonin or noradrenaline, and no desensitisation of beta-adrenoceptors after long term administration. A series of studies was carried out on 99 patients. Admission criteria for the studies specified a minimum score of 20 on the Anxiety Status Inventory as well as the presence of moderate depression. An uncontrolled trial demonstrated the anxiolytic efficacy of trimipramine. Further controlled trials showed superior anxiolytic efficacy of trimipramine to amitriptyline and doxepin with comparable anxiolytic efficacy of trimipramine with maprotiline. All agents had equal antidepressant effects.

Neuronal activity in the medulla oblongata during vocalization. A single-unit recording study in the squirrel monkey.

In six squirrel monkeys (Saimiri sciureus), the medulla oblongata was explored with microelectrodes, looking for vocalization-correlated activity. The vocalizations were elicited by microinjections of glutamate agonists into the periaqueductal grey of the midbrain. Vocalization-related cells were found in greater numbers in the nucl. ambiguus (Ab) and retroambiguus (RAb), in the parvocellular, magnocellular and central reticular formation as well as in the solitary tract nucleus and spinal trigeminal nucleus. Small numbers were also found in the vestibular complex, cuneate nuclei, inferior olive and lateral reticular nucleus. A differentiation of the neuronal responses into 12 reaction types reveals that the frequency of each reaction type varies from brain structure to brain structure, thus allowing a specification of the different vocalization-related areas. According to this specification, it is proposed that initiation of vocalization takes place via the parvocellular reticular formation; vocal pattern control is mainly brought about by the parvocellular reticular formation, Ab, solitary tract nucleus and spinal trigeminal nucleus; expiratory control and respiratory-laryngeal coordination is carried out by the RAb, Ab and central nucleus of the reticular formation; vocalization-specific postural adjustments are carried out via the vestibular and cuneate nuclei.

Sleep studies and neurochemical correlates in panic disorder and agoraphobia.

Although panic disorder is classified by the DSM III among the anxiety disorders, there is evidence from epidemiological and neurochemical studies that links panic to the affective disorders. In addition several of the effective pharmacological treatments suggest, as in the depressive disorders, serotonergic involvement. As part of the evaluation of patients who would take part in the Cross National Collaborative Panic study, polysomnography, the dexamethasone suppression test and platelet imipramine binding and 5HT-uptake were scheduled. 44 patients who met DSM III criteria on the SCID interview schedule for Panic Disorder consented to enter the study. After being medication free for two weeks, these patients had three consecutive all night polysomnograms, followed by a dexamethasone suppression test and platelet study of imipramine binding and 5HT-uptake. In our studies we were unable to find for the panic group as a whole a correlation with reported parameters of sleep architecture in endogenous depression. Similarly the imipramine binding differentiated the panickers from the depressed group. Only the 5HT-uptake was similar in both groups. We also found a subgroup of panickers who resembled depressives in terms of the imipramine binding, 5HT-uptake platelet studies and REM latency. In the analysis of the imipramine and 5HT-uptake over the treatment period, we noted changes which suggest a role for serotonin, certainly in a subgroup of panickers and possibly for the group of panic disorder as a whole.

A double-blind, placebo-controlled, multicenter study with alprazolam and extended-release alprazolam in the treatment of panic disorder.

This is a double-blind, placebo-controlled, flexible-dose, multicenter, 6-week study comparing regular alprazolam (compressed tablet, CT), given four times per day, and extended release alprazolam (XR), given once in the morning. The aim of the XR preparation is to offer less frequent dosing and to reduce interdose anxiety. Of the intent-to-treat group of 209 patients, 184 completed 3 weeks of medication and were evaluated according to protocol. There was a completer rate for the 6 weeks of 94% (CT), 97% (XR), and 87% (placebo). On global measures, Hamilton Rating Scale for Anxiety, phobia rating, and work disability measures, both active treatment groups were equally effective and significantly more efficacious than the placebo cell on endpoint MANOVA analysis. On analysis of the panic factor with endpoint data, both active treatment groups were equally effective throughout the 6-week trial and significantly more efficacious than the placebo group. Drowsiness occurred more frequently with CT alprazolam (86% of patients) than with the XR preparation (79%) or placebo (49%).

Fluoxetine in panic disorder: pharmacologic and tritiated platelet imipramine and paroxetine binding study.

Serotonergic implication in panic disorder has been demonstrated by the efficacy of serotonin reuptake blockers in treatment. Fluoxetine, a potent 5-HT reuptake blocker, has been suggested to have anti-panic efficacy. This open study examines 30 patients (eight males and 22 females) with an average age of 36.9 years, ranging from 18 to 62, who were treated for eight weeks with fluoxetine (mean dose 20 mg per day). All patients fulfilled DSM-III-R criteria of panic disorder with agoraphobia as determined in a SCID interview schedule. Out of 28 patients who started medication, 64% of the patients completed the clinical trial and 36% of the patients dropped out of treatment because of increased anxiety or a lack of efficacy. Thirty-two percent of the patients had zero panic attacks by week 3. By the end of eight weeks of treatment, 48% of the patients had zero panic attacks. There was a significant reduction in anxiety and phobic avoidance and panic attacks. Tritiated platelet imipramine and paroxetine bindings revealed significantly lower maximal binding for patients with panic disorder in comparison with controls. Paroxetine Bmax showed a trend to increase in the direction of control values by the end of the trial.

Gepirone and the treatment of panic disorder: an open study.

Gepirone, an azapirone, is a potent 5-hydroxytryptamine 1A (5-HT1A) agonist. We report an uncontrolled 6-week study in 21 patients (4 men, 17 women: mean age, 36.71 years) with a concurrent DSM-III-R diagnosis of generalized anxiety disorder and panic disorder with agoraphobia. After a 2-week medication-free period, patients were started on 2 mg of gepirone per day increasing over 3 weeks to 12 mg/day. Three patients dropped out in the first week, and one patient violated the protocol. They were therefore excluded from analysis. Two patients who dropped out at weeks 4 and 5 because they found the treatment ineffective were included. Twelve of the 17 patients (70.6%) had at least a 50% reduction in their panic attacks by week 6, and 9 of them had at least a 50% reduction by week 3. Ten patients had "0" panic attacks by week 6 (59%). On the Hamilton Anxiety Scale, 65% had a 50% or greater reduction in total score, mostly beginning in week 1. On Global Assessment, by week 6, 11 were much improved or better (65%). Adverse effects were rare and consisted of stomach upset, dizziness, or headaches. This preliminary study suggests the possible efficacy of gepirone in panic disorder.

Relationship of social support to [3H]imipramine binding during and after examination stress.

The relationship between social support, depressive symptoms and the maximal binding capacity of [3H]imipramine (Bmax) in platelets was examined in medical students during and after a period of examination stress. There was a positive correlation between the students' perception of their social support and [3H]imipramine Bmax values during examinations, and their perception of social support contributed significantly to the prediction of Bmax by depressive symptomatology. The results suggest that psychosocial factors may be associated with alterations in serotonergic neurotransmission, rendering an individual more physiologically vulnerable to psychological disturbances.