Specificity of panic response to CO(2) inhalation in panic disorder: a comparison with major depression and premenstrual dysphoric disorder

OBJECTIVE: The behavioral response to CO(2) inhalation has been used to differentiate panic disorder patients from normal subjects and other clinical populations. This study extended examination of the diagnostic specificity of CO(2)-induced anxiety by testing panic disorder patients and clinical populations with reported low and high sensitivity to CO(2) inhalation (patients with major depression and patients with premenstrual dysphoric disorder, respectively). METHOD: The behavioral responses to inhalation of 5% and 7% CO(2), administered by means of a respiratory canopy, were studied in 50 patients with panic disorder, 21 with major depression, and 10 with premenstrual dysphoric disorder and in 34 normal comparison subjects. Occurrence of panic attacks was judged with DSM-IV criteria by a blind rater. Subjects were rated on three behavioral scales at baseline and after each CO(2) inhalation. RESULTS: Panic disorder patients had a higher rate of CO(2)-induced panic attacks than depressed patients and normal subjects, whose panic rates were not distinguishable. The panic rate for patients with premenstrual dysphoric disorder was similar to that for panic disorder patients and higher than that for normal subjects. Subjects with CO(2)-induced panic attacks had similarly high ratings on the behavioral scales, regardless of diagnosis, including the small number of panicking normal subjects. Seven percent CO(2) was a more robust panicogen than 5%, and response to 7% CO(2 )better distinguished panic disorder patients from normal subjects than response to 5% CO(2). CONCLUSIONS: Patients with panic disorder and patients with premenstrual dysphoric disorder are highly susceptible to CO(2)-induced panic attacks, and depressed patients appear to be insensitive to CO(2) inhalation. The symptoms of CO(2)-induced panic attacks have a similar intensity regardless of the subject's diagnosis.     

Arterial thrombolysis in peripheral arterial occlusions--where are the limits of the realm and what are the responsibilities of a vascular surgeon?

Arterial thrombolysis is a well established treatment for acute myocardial ischaemia, with respectable results. It is gaining ground in peripheral vascular surgery as well, particularly in the treatment of acute ischaemia due to occlusion of a sclerotic artery or an arterial graft. However, in case of myocardial ischaemia diagnosis (coronary angiogram), treatment (thrombolysis, PTCA or revascularisation) and recognition for the need for acute surgical treatment are in the same hands in cardiology, in case of peripheral arterial occlusions diagnostics (and therapy in some extent) are provided by radiologists, while patients are usually referred to vascular surgeons. They can provide limited diagnostics (intraoperative angiogram) and can treat patients by non-surgical means (i.e. intraoperative thrombolysis). Although co-operation between radiology and vascular surgical services is crucial and can save limbs and lives, in everyday practice we frequently have to decide whether the ischaemic limb can be treated by thrombolysis only (carried out by radiologists) or the extent and stage of ischaemia are such that they require the faster surgical reconstruction, often completed with intraoperative angiogram and thrombolysis. Whose decision should it be? Should vascular surgeons force thrombolysis, should they do it themselves? What are the cost implications of the successful and unsuccessful thrombolysis?     

Species susceptibilities to chemical carcinogens: a critical appraisal of the roles of sex hormones (endocrine status) and nutritional influences

The objective of the present evaluation was to assess the possible roles of the sex hormones (endocrine status), nutritional influences and other factors in regard to species susceptibilities to chemical carcinogens. By reviewing the experimental and epidemiological data, it was concluded that there are compelling indications, particularly in the fields of physiology and metabolism, to conclude the limited usefulness of the various animal species in sex hormone research. The findings allow only restricted inferences for the human species. On the other hand, as far as nutritional influences on cancer development are concerned, similar mechanisms operate with regard to high or low calorie, fat, protein and carbohydrate intakes in animals and humans. Consequently, the findings obtained in laboratory animals can be transmitted with some modifications to the human species. This assessment is the continuation of an earlier work, which appraised the roles of genetic and viral agents, concerning species susceptibilities to chemical carcinogens.     

Intermittent short courses of cyclosporine microemulsion for the long-term management of psoriasis: a 2-year cohort study

BACKGROUND: Cyclosporine is effective in psoriasis, but long-term continuous therapy may be limited by renal impairment and hypertension. Intermittent short courses of treatment should minimize side effects and improve the risk-benefit ratio. OBJECTIVE: Our purpose was to assess the long-term efficacy and safety of intermittent short courses of the microemulsion formulation of cyclosporine (Neoral) in the management of chronic plaque psoriasis unresponsive to topical therapies. METHODS: In a multicenter open cohort study, 76 subjects were treated intermittently over a 2-year period. Patients with chronic plaque psoriasis were treated with cyclosporine until clearance of psoriasis or for a maximum of 12 weeks. Patients were then randomized into two groups. Group A stopped cyclosporine abruptly, whereas group B had the dose reduced by 1 mg/kg per day each week until cessation, which was within 4 weeks. On relapsing, patients received further courses of cyclosporine. Intermittent treatment was continued in this way for 2 years. RESULTS: There was no statistically significant difference in the percentage of time in remission during the 2-year period between patients randomized to stop cyclosporine abruptly (56.2%) and patients randomized to taper cyclosporine within 4 weeks (61.8%). The mean percentage of time that patients received treatment during the study was 40.5% for randomization group A, 46.2% for randomization group B, and 42.8% overall. The median time to relapse was 115.5 days after the first treatment course but became progressively shorter after multiple treatment courses. Mean blood pressure and serum creatinine levels did not show any clinically significant changes over time. CONCLUSIONS: This study indicates that intermittent short courses of cyclosporine are effective in patients with moderate to severe psoriasis for up to 2 years while improving the safety profile relative to continuous cyclosporine monotherapy.     

Relapsing polyneuropathy in the post-partum period

A patient had five relapses of polyneuropathy: four developed during post-partum. The rapid onset of symptoms with subsequent complete recovery are in favor of a recurrent Guillain-Barré syndrome rather than a chronic relapsing inflammatory polyneuropathy.     

A dural fistula as a rare cause for a pulse-synchronized tinnitus aurium

Pulse-synchronized tinnitus aurium is commonly caused by vascular processes within the area of the temporal bone. With a microphone or a stethoscope in the external ear or on the mastoid perceptible noises can be heard by the physician. The most important differential diagnoses of an objective tinnitus are paraganglioma of the glomus jugulare or the glomus tympanicum, vascular stenosis, arteriovenouse malformations, aneurysms and atypic findings of the bulbus venae jugularis interna of the temporal bone. In case of a pulse-synchronized tinnitus purposeful use of neuroradiological diagnostic can lead to a correct diagnosis. The indication for invasive intervention of dural fistulas depends on the number and the hemodynamic relevance of these fistulas and on individual suffering of the patient. Even if it does not succeed, all to embolize AV-short-circuits, it is possible to reduce the intensity of the tinnitus in order to continue with conservative therapy.     

Acute panic inventory symptoms during CO(2) inhalation and room-air hyperventilation among panic disorder patients and normal controls.

There is scant literature on anxiety symptoms induced during respiratory challenges developed to induce panic symptoms and attacks. Here we report on the prevalence of Acute Panic Inventory (API) symptoms during three consecutive respiratory challenges to patients with panic disorder (PD) and normal controls (NC). The challenges performed using a closed canopy system included voluntary room air hyperventilation (RAH), inhalation of 5% CO(2), and 7% CO(2)-enriched air. The PD patients were 41 men and 53 women whose mean age was 33.4 (SD = 8.55). The normal comparison group consisted of 35 men and 27 women with a mean age of 31.3 (SD = 9.21). The diagnosis of panic disorder was made using the Structured Clinical Interview for DSM-III-R. All potential normal controls underwent structured clinical interview using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version Modified for the Study of Anxiety Disorders (SADS-LA), and must have been free of a lifetime history of anxiety disorders, affective disorders, substance use disorders, and schizophrenia. All participants also had a complete medical evaluation and were in good health. The experiment consisted of seven experimental epochs: three baseline/recovery periods each followed by a respiratory challenge, and then a final recovery epoch. The API was administered at the end of each epoch. Clinical staff trained and experienced in rating panic attacks rated participants' response during each challenge as panic or no panic. Three groups were defined for analysis: PD patients who panicked, PD patients who did not panic, and NC who did not panic. Staff ratings indicated that the 7% CO(2) challenge was the most panicogenic, followed by the 5% CO(2), and the RAH challenges. Conventional statistics (analysis of variance and partial correlations) indicated that many baseline symptoms as well as symptom increments differed across groups, and were associated with the outcome of panic/no panic during each challenge. However, logistic regression analysis indicated that only a few symptoms independently predicted the panic/no panic outcome because many symptoms were redundant. The symptom cluster of fear in general, dizziness, difficulties with concentrating, and doing one's job predicted panic to RAH. The cluster of fear in general, confusion, dyspnea, and twitching/trembling predicted the response to 5% CO(2). Finally, fear in general, confusion, twitching/ trembling and dizziness predicted the response to 7% CO(2). While univariate analyses indicated that many symptoms distinguished between panic and no panic outcome, logistic regression revealed that group differences were subsumed under a few prominent symptoms, namely, fear in general, confusion, dizziness, twitching/trembling, and dyspnea. The results are discussed in the context of patient (having a diagnosis of PD) and panic effects (rated as panicking to a challenge).     

Effects of MgATP on ATP utilization and force under normal and simulated ischaemic conditions in rat cardiac trabeculae

The dependency of ATP utilization and isometric force on [MgATP] was studied in skinned rat trabeculae under normal (pH 7.0) and simulated ischaemic (pH 6.2, 30 mM added Pi) conditions at 20+/-1 degrees C. At saturating [Ca2+], mean (+/-SEM) ATP utilization at 5 mM MgATP (A0) was 0.48+/-0.03 mM/s and force (F0) was 37+/-2 kN/m2. At 10 microM MgATP under normal conditions ATP utilization decreased gradually to 66+/-3% of A0, and force increased to 169+/-7% of F0. Under ischaemic conditions at 10 microM MgATP, ATP utilization decreased from 30+/-5% to 11+/-2% of A0 whereas force increased eightfold from 12+/-4% to 97+/-7% of F0. The [MgATP] at half-maximal ATP utilization (Km) under ischaemic conditions was 21+/-3 microM. At pH 7.0, Km was estimated to be less than 10 microM. These results show that tension cost decreases markedly with decreasing MgATP. Under ischaemic conditions parallel changes in Ca2+ sensitivity of force and ATP utilization were observed, corresponding to 1.3 pCa units. Reducing [MgATP] from 0.5 to 0.05 mM caused a modest reversal of this change in Ca2+ sensitivity. These changes in Ca2+ sensitivity are consistent with a marked reduction in active force and force-related ATP utilization during ischaemia but are insufficient to explain the ischaemic contracture on the basis of active force development.