Uncommon findings in idiopathic hypertrophic cranial pachymeningitis

Abstract.Background: Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare, poorly understood, inflammatory disease, usually involving the dura mater of skull base, tentorium, and falx, and presenting with headache, progressive cranial nerve palsies, and cerebellar dysfunction.Patients and Methods: In four patients, the diagnosis of IHCP has been made on the basis of extensive clinical, and radiological investigation, and confirmed by dural biopsy in three patients. The clinical follow-up ranges from 24 to 120 months.Results : At diagnosis, all the patients complained of severe, progressively increasing headache, two had simple or complex partial seizures, but none had cranial nerve palsies. Two patients had electrophysiological evidence of axonal peripheral neuropathy, biopsy-proved in one of them. In all the patients, MRI showed linear or focal thickening of the dura mater of the tentorium and/or of the convexity, sparing the skull base. In one patient, MRI findings resembled chronic subdural hematoma. Dural biopsy demonstrated fibrosis and prominent CD4+ T-cells inflammatory infiltrate. Pachymeningitis was highly responsive to steroid therapy, as was the peripheral neuropathy. In three patients, temporary steroids withdrawal led to dramatic clinical worsening including status epilepticus in one.Conclusions : In the patients here reported, absence of cranial nerve impairment, seizures, MRI findings resembling chronic subdural hematoma, and association with polineuropathy were unusual findings of IHCP. Moreover, the type of inflammatory infiltrate, lacking in previous reported cases, suggests a probable pathogenetic role for cell-mediated immunity of unknown origin.     

Language of dyspnea in panic disorder

Dyspnea is a key symptom in panic attacks. This study investigated different types of dyspnea induced by the 35% CO2 challenge test given to patients with panic disorder (PD). The types of dyspnea provide room for possible conjectures on neurophysiological pathways involved in the experience of breathing discomfort in PD and in the panic-respiration connection. Factor analysis applied to the Dyspnea Questionnaire identified three main factors: breathing effort, sense of suffocation, and rapid breath. Factor scores for breathing effort and sense of suffocation significantly discriminated between patients who did and those who did not report CO2-induced panic attacks. Factor scores for breathing effort significantly discriminated between patients whose reaction resembled their unexpected panic attacks and those whose reaction did not. A dissociation between an increased central respiratory command and a decreased mechanical efficiency of the respiratory response in patients with PD may underlie the breathing effort factor during the CO2 challenge. The sense of suffocation factor was found to be linked to chemosensitivity. Although involved in CO2 reactivity, it may not be a central factor in unexpected panic attacks.     

Pharmaceutical strategies against amyloidosis: old and new drugs in targeting a "protein misfolding disease"

The group of diseases caused by abnormalities of the process of protein folding and unfolding is rapidly growing and includes diseases caused by loss of function as well as diseases caused by gain of function of misfolded proteins. Amyloidoses are caused by gain of function of certain proteins that lose their native structure and self-assemble into toxic insoluble, extracellular fibrils. This process requires the contribution of multiple factors of which only a few are established, namely the conformational modification of the amyloidogenic protein, protein's post-translational modifications and the co-deposition of glycosaminoglicans and of serum amyloid P component. In parallel with the exponential growth of biochemical data regarding the key events of the fibrillogenic process, several reports have shown that small molecules, through the interaction with either the amyloidogenic proteins or with the common constituents, can modify the kinetics of formation of amyloid fibrils or can facilitate amyloid reabsorption. These small molecules can be classified on the basis of their protein target and mechanism of action, according to the following properties. 1) molecules that stabilize the amyloidogenic protein precursor 2) molecules that prevent fibrillogenesis by acting on partially folded intermediates of the folding process as well as on low molecular weight oligomers populating the initial phase of fibril formation 3) molecules that interact with mature amyloid fibrils and weaken their structural stability 4) molecules that displace fundamental co-factors of the amyloid deposits like glycosaminoglycans and serum amyloid P component and favor the dissolution of the fibrillar aggregate.     

Biodegradation of 2-chlorophenol in forest soil: effect of inoculation with aerobic sewage sludge

Decontamination of 2-monochlorophenol-containing forest soil was studied in laboratory experiments. We found that in sterile soil, sorption of chlorophenol can occur. Chlorophenol disappearance of approximately 55% was observed in native soil; both soil sorption and degradation by indigenous soil populations caused this disappearance. In native soil, however, the rate of chlorophenol disappearance was enhanced up to slightly more than 90% by inoculation with a sludge taken from the aeration tank of a municipal wastewater treatment plant. In this sludge, the presence of Alcaligenes and Pseudomonas spp. was observed. In other experiments, addition to the soil of a laboratory culture preacclimated to 2-monochlorophenol did not lead to a greater increase in chlorophenol disappearance. In contrast to native soil, inoculation of sterile soil had no effect on disappearance of the chlorophenol. A possible explanation for the lack of cometabolic degradation is that autoclaving of the soil destroys the organic substances within it.     

Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly

BACKGROUND: Cardiac abnormalities develop in patients with acromegaly as a consequence of effects of GH/IGF-I on the heart and related cardiovascular risk factors. OBJECTIVE: To evaluate the possible contribution of postoperative variations in blood pressure (BP), glucose tolerance and insulin sensitivity to the cardiac improvement reported in patients who have been cured of acromegaly. DESIGN: Thirty-one patients with acromegaly were studied before and 6 Months after successful transsphenoidal surgery, defined by normal age-related IGF-I concentrations and glucose-suppressed GH concentrations <1 microg/l. METHODS: Cardiovascular parameters were assessed by Doppler echocardiography and 24-h ambulatory blood pressure monitoring. Insulin sensitivity indexes were calculated on the basis of fasting and post-load glycaemia and insulinaemia and referred to as HOMA(ISI) and OGTT(ISI), respectively. RESULTS: Successful surgery was confirmed to improve left ventricular mass index (LVMI) and diastolic filling significantly. Mean 24-h systolic BP values decreased (P=0.009) and BP rhythm was restored in 12 of 15 patients with a blunted preoperative profile. Glucose tolerance normalized in patients with preoperative glucose intolerance (n=7) or diabetes mellitus (n=3). HOMA(ISI) and OGTT(ISI) increased (P=0.0001 for each parameter), indicating a marked improvement in insulin sensitivity. The postoperative reduction in LVMI correlated with increased insulin sensitivity (P<0.001 for both indexes), but not with other parameters. Improved diastolic filling correlated with the reduction in LVMI. CONCLUSIONS: Successful surgery in patients with acromegaly induces a significant improvement in haemodynamic and metabolic risk factors. This study suggests a direct link between insulin resistance and acromegalic cardiomyopathy.     

Photodynamic therapy of circumscribed choroidal hemangioma

PURPOSE: To evaluate the safety and effectiveness of photodynamic therapy (PDT) in the treatment of symptomatic circumscribed choroidal hemangiomas (CCH) of the posterior pole. DESIGN: Prospective, consecutive, noncomparative case series. PARTICIPANTS: Ten eyes of 10 patients (six males and four females; age range, 38-64 years) reporting visual impairment caused by intraocular CCH. Follow-up was 7 to 16 months. METHODS: Photodynamic therapy was applied by Zeiss laser (Visulas 6905, Carl Zeiss-Meditech AG, Jeud Germany) emitting a light at 689 nm for photosensitization and by using verteporfin (Visudyne; Novartis Ophthalmics AG, Basel, Switzerland) at a dose of 6 mg/m(2) body surface administered intravenously before treatment. The diameter of the treatment spot was calculated on early frames of pretreatment indocyanine green angiography; the maximum treatment spot diameter was 6000 micro m using a Mainster wide-field lens (Ocular Instruments Inc., Bellevue, WA USA). In the case of peripapillary CCH, the laser spot was applied at a distance of 200 micro m from the optic disc edge. A laser beam was applied to the retina 15 minutes after the start of the infusion. Two different treatment procedures were used according to the height of the lesion. A radiant exposure of 100 J/cm(2) with an exposure time of 186 seconds was applied to lesions larger than 2 mm. For lesions smaller than 2 mm, a radiant exposure of 75 J/cm(2) with an exposure time of 125 seconds was used. MAIN OUTCOME MEASURES: Visual outcomes, pretreatment findings, and final findings were evaluated using biomicroscopy, fluorescein angiography (FA), indocyanine green angiography (ICGA), and ultrasound. RESULTS: After a follow-up of 7 to 16 months, FA and ICGA verified the nonperfusion of the vascular channels of the tumor in the treated areas. No retinal pigment epithelium (RPE) changes were observed in the patients who had undergone two PDT treatments, whereas minimal alterations were detected in two of the four patients who had undergone three treatment sessions. Angiographic cystoid macular edema and exudative macular detachment had completely regressed in all cases. Minimal intraretinal edema was observed on the FA frames in two cases. Ultrasound examination found no measurable tumor height in six (60%) cases and a marked reduction in the remaining four cases, even after one treatment (post treatment tumor height range, 0.86-1.82 mm). An improvement in visual acuity (one to six lines on the Early Treatment for Diabetic Retinopathy Study chart) was observed in all the cases. In four cases, the visual acuity returned to 20/20, of which three were extrafoveal and one was subfoveal with visual impairment caused by secondary exudative macular detachment without significant RPE alterations. Also in longstanding subfoveal cases, a marked visual acuity improvement was detected resulting from the disappearance of subretinal or intraretinal fluid, even if functional results were limited by pre-existing RPE alterations. In all cases no damage to retinal vessels was observed. CONCLUSIONS: Photodynamic therapy is a minimally invasive but effective method of treatment for CCH and may be considered as a treatment of choice, especially in patients with foveal location of the tumor. Because of its safety and repeatability, this technique can be used to treat frequent recurrences of the tumor.     

Prognostic factors in symptomatic Waldenstrom's macroglobulinemia

We analyze the prognostic value of the presenting features of a series of patients with symptomatic Waldenstrom's macroglobulinemia who were homogeneously treated. A total of 215 patients (119 males) with a median age of 62.6 years (range, 24.9 to 91.6) were retrospectively analyzed. The median overall follow-up was 57.6 months (range, 0.6 to 281): 58 (0.9 to 281) for living patients and 52.2 (0.6 to 261.3) for those who died. All patients were treated with alkylating agent-based chemotherapy. The overall median survival was 77.2 months, without significant differences based on the duration of the previous monoclonal gammopathy of undetermined significance (MGUS) phase. The multivariate Cox analysis performed on the whole population showed that age, hemoglobin level, and serum albumin level predicted survival. The addition of beta(2)-microglobulin, available in the subgroup of 60 patients diagnosed after 1990, in a Cox stepwise selection showed that this parameter was by far the main prognostic determinant. Application of the Dhodapkar, Morel, and Gobbi scoring systems to this population of patients showed that all three stratified the population into groups with significantly distinct prognoses. A prognostic index based on age, hemoglobin, and albumin is capable of identifying various groups of patients with different therapeutic needs.     

Thalidomide and deep vein thrombosis in multiple myeloma: risk factors and effect on survival

Thalidomide has antiangiogenic properties and was found to be effective in patients with multiple myeloma (MM) when used in the setting of posttransplantation relapse. We have now analyzed risk factors associated with development of deep vein thrombosis (DVT) in a cohort of 535 patients treated with thalidomide with cytotoxic chemotherapy (VAD [vincristine/doxorubicin/dexamethasone], CAD [cyclophosphamide/doxorubicin/dexamethasone], DCEP [dexamethasone/cyclophosphamide/etoposide/cisplatin], or DT-PACE [dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide] or without cytotoxic chemotherapy (thalidomide and dexamethasone only). A total of 82 patients developed DVT, and the frequency was affected by a number of baseline characteristics. On multivariate analysis, the combination of thalidomide with chemotherapy including doxorubicin was associated with the highest odds ratio (OR) for DVT (4.3; P < or = 0.001); in addition, newly diagnosed disease (OR, 2.5; P = 0.001) and chromosome 11 abnormality (OR, 1.8; P = 0.048) were also independent predictors for DVT. With a median follow-up of 2.9 years, survival was inferior in patients with chromosome 13 abnormalities (P = 0.001), age > 60 years (P = 0.001), lactate dehydrogenase level > or = 190 IU/L (P = 0.002), and creatinine level > or = 2 mg/dL (P < 0.001). However, the development of DVT did not adversely affect survival when examined as a time-dependent variable and adjusted for standard risk features (hazard ratio, 0.8; P = 0.162).