Pharmacologic effect of imipramine, paroxetine, and sertraline on 35% carbon dioxide hypersensitivity in panic patients: a double-blind, random, placebo-controlled study

The effects of short treatment (7 days) with the tricyclic antidepressant imipramine and the two selective serotonin reuptake inhibitors paroxetine and sertraline on the reactivity to inhalation of 35% CO2/65% O2 were compared in 70 panic patients who had positive responses to 35% CO2 inhalations. A double-blind, random, placebo-controlled design was applied. Each patient was given the 35% CO2 challenge on days 0 (before starting the treatment), 3, and 7. In the placebo group, there were no significant changes in the reactivity to 35% CO2 in the three sessions whereas there were significant similar reductions of reactivity to 35% CO2 in all three drug-treated groups. These results confirm the good reproducibility of 35% CO2 reactivity and the negligible effects of placebo on reactivity to CO2 and suggest that short treatments with imipramine, paroxetine, and sertraline decrease reactivity to 35% CO2, possibly as an expression of their antipanic properties.     

Homeopathy in the perspective of scientific research

A significant portion of the traditional concepts of homeopathy (similia principle, experimentation on healthy humans, the cure of whole person, the use of minimum doses or high dilution/potency of medicines) are amenable to investigations conducted according to criteria accepted by biomedical science. Even though many randomized and controlled clinical studies seem to demonstrate the efficacy of some homeopathic medicines and their superiority to placebo, other trials have given negative results. A definite clear answer is not yet possible due to the scarce quality of some published reports, to lack of reproduction by independent investigators and to the uncertainty regarding the methodologies to be used for testing the claims of homeopathy. As regards the possible physiopathological, biophysical and pharmacological explanations for the action of homeopathic remedies, there are models which tend to set the similia principle as a general expression of the action-reaction principle, within the context of dynamic systems theory. The clarification of the more controversial aspects regarding dilution/potency of medicines remains tied to several promising developments in physics of condensed matter, in chaos theory and in biophysics.     

Plantar fibromatosis: an immunohistochemical and ultrastructural study

The analogies between plantar fibromatosis and Dupuytren's disease (palmar fibromatosis) are well known. The latter is clinically more frequent and has been the object of extensive immunohistochemical and ultrastructural studies, with a view to investigating its pathogenesis. By contrast, such data on plantar fibromatosis are quite scarce. A histochemical, immunohistochemical, and ultrastructural study was performed on nodule tissue from six patients who were subjected to total fasciectomy for plantar fibromatosis. The study of myofibroblasts revealed features suggestive of their fibroblastic origin and evidenced a cytoskeleton and an extracellular filamentous system that could enable myofibroblasts to generate and exert the intracellular forces that contribute to the contraction of the aponeurosis. These aspects are similar to those observed in Dupuytren's disease and seem to lend support to the theory that the two diseases are expressions of the same disorder.     

Modulation of acute and chronic inflammatory processes by cacospongionolide B, a novel inhibitor of human synovial phospholipase A2

1. Cacospongionolide B is a novel marine metabolite isolated from the sponge Fasciospongia cavernosa. In in vitro studies, this compound inhibited phospholipase A2 (PLA2), showing selectivity for secretory PLA2 (sPLA2) versus cytosolic PLA2 (cPLA2), and its potency on the human synovial enzyme (group II) was similar to that of manoalide. 2. This activity was confirmed in vivo in the 8 h zymosan-injected rat air pouch, on the secretory enzyme accumulating in the pouch exudate. Cacospongionolide B, that is bioavailable when is given orally, reduced the elevated levels of sPLA2 present in paw homogenates of rats with adjuvant arthritis. 3. This marine metabolite showed topical anti-inflammatory activity on the mouse ear oedema induced by 12-O-tetradecanoylphorbol acetate (TPA) and decreased carrageenin paw oedema in mice after oral administration of 5, 10 or 20 mg kg(-1). 4. In the mouse air pouch injected with zymosan, cacospongionolide B administered into the pouch, induced a dose-dependent reduction in the levels of eicosanoids and tumour necrosis factor alpha (TNFalpha) in the exudates 4 h after the stimulus. It also had a weak effect on cell migration. 5. The inflammatory response of adjuvant arthritis was reduced by cacospongionolide B, which did not significantly affect eicosanoid levels in serum, paw or stomach homogenates and did not induce toxic effects. 6 Cacospongionolide B is a new inhibitor of sPLA2 in vitro and in vivo, with anti-inflammatory properties in acute and chronic inflammation. This marine metabolite was active after oral administration and able to modify TNFalpha levels, and may offer an interesting approach in the search for new anti-inflammatory agents.     

Evaluation of vesico-urethral and sweating function in disorders presenting with parkinsonism

Investigation of vesico-urethral and sweating function was performed in twelve patients with classical idiopathic Parkinson's disease and ten patients with parkinsonism associated with features suggestive of more extensive involvement of the nervous system, as in the Shy—Drager syndrome. The urodynamic studies revealed detrusor hyperreflexia with reduction of maximal cystometric capacity in only one patient with Parkinson's disease (8%), but in nine patients with parkinsonism associated with other features (90%). Urethral sphincter electromyography did not indicate denervation in any patient of either group. Delayed or incomplete relaxation of the urethral sphincter during micturition was observed in seven patients with Parkinson's disease (58%) and in two patients of the other group (20%). Decreased sweating responses were found in both groups of patients when compared with control subjects. Hypohidrosis was more pronounced in parkinsonism associated with other features than in Parkinson's disease. Differences in sweating between the two sides of the body were observed in both groups of patients. Although there are differences in vesico-urethral and sweating function, they do not precisely differentiate between patients with classical Parkinson's disease and those with parkinsonism associated with features suggestive of more extensive involvement of the nervous system.     

Focal segmental membranous glomerulonephropathy associated with other glomerular diseases

In four patients with the nephrotic syndrome, renal biopsy revealed focal segmental membranous glomerulonephropathy (FSMGN) associated with the histologic patterns of "nil" disease (two cases), hereditary nephritis and diffuse diabetic glomerulosclerosis. The occurrence of FSMGN in association with other glomerular diseases, presumably unrelated to immune complex deposition, is infrequent in our experience. Rather than necessarily representing an early stage or milder form of membranous glomerulonephropathy, it may be an epiphenomenon. This interpretation has prognostic and therapeutic implications and raises important pathogenetic questions. In particular, this study suggests that in some instances, preexisting functional and structural abnormalities may play a role either in the deposition of preformed circulating immune complexes or in the local formation of immune complexes.     

Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL)

The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the "Gruppo Italiano per lo Studio della Nefrite Lupica" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL.(ABSTRACT TRUNCATED AT 250 WORDS)