Kambo: Natural drug or potential toxic agent? A literature review of acute poisoning cases.

Kambo is the name of a natural substance derived from the glandular secretions of the amphibian Phyllomedusa bicolor, a species native to regions in South America. The communities living in these areas administer the substance generally transdermally during rituals for religious-purifying purposes, producing small skin burns. The scientific literature has reported some cases of intoxication following the use of Kambo but this aspect is still poorly understood. In fact, no shared therapy protocols exist for these events nor any real legislation on Kambo. The purpose of this work was to examine all cases of acute intoxication resulting from the administration of Kambo and published over the last 10 years, illustrating clinical signs, laboratory findings, instrumental tests, and therapy. The several cases identified in our review confirm that acute Kambo intoxication can occur, with serious and life-threatening effects. We developed a protocol aimed at the early diagnosis of cases of suspected acute intoxication by creating a treatment algorithm. The study aims to investigate the pathophysiology of these events in humans, proposing a protocol for the diagnosis and treatment of these cases that can be used by healthcare professionals.

Multiple sclerosis and celiac disease: is there an increased risk?

Multiple sclerosis and celiac disease are both considered immune-mediated diseases. Recently, improved serological screening methods provided a higher prevalence of celiac disease (CD) in the general population worldwide and also demonstrated gastrointestinal symptoms may be lacking. The aim of this study was to determine the prevalence of (CD) in an unselected group of 95 adults with multiple sclerosis using transglutaminase antibodies. No patients showed pathological values. Different immune and genetic basis between the two diseases may represent crucial insights to explain our results.

Long-term follow-up of isolated optic neuritis: the risk of developing multiple sclerosis, its outcome, and the prognostic role of paraclinical tests.

We evaluated the risk of developing clinically definite multiple sclerosis (CDMS) after an acute attack of isolated optic neuritis (ON) in 112 patients, in relation to demographic and paraclinical findings. Patients were examined by brain MRI, CSF analysis, and multiple evoked potentials (EPs); 10 were lost to follow-up, and the other 102 were enrolled in a prospective study (follow-up duration 6. 3 +/- 2.2 years). Of these, 37 (36.3%) developed CDMS after a mean interval of 2.3 +/- 1.6 years. The risk of developing CDMS was 13% after 2 years, 30% after 4, 37% after 6, and 42% after 8 and 10 years. Gender, age, and season of ON onset did not affect the risk. MS occurred in 37 of 71 patients (52.1%) with one MRI lesion or more; no patient with a normal MRI developed the disease. MS developed more frequently in patients with intrathecal IgG synthesis than in those without (43% vs. 28%), but the difference was not statistically significant. Multiple EPs showed a slight predictive value only including somatosensory EPs of the lower limb. Multiple sclerosis was mild in most cases (EDSS 2.2 +/- 1.9). The EDSS was less than 4 in 32 cases (86%), between 4 and 6 in 2 (5%), higher than 6.5 in 3 (8%).

Adhesion of mononuclear cells from multiple sclerosis patients to cerebral vessels in cryostat sections of normal human brain.

Leukocyte extravasation across the blood-brain barrier is a critical event in the pathogenesis of multiple sclerosis (MS). This complex multistep process includes the adhesion of leukocytes to the endothelial cells of the central nervous system microvasculature. To investigate this phenomenon in MS, we developed a modified version of the frozen-section assay. Peripheral blood mononuclear cells (PBM) from 26 MS patients, 26 healthy controls and 10 patients with other inflammatory non- neurological diseases (OIND) were co-incubated with cryostat sections of normal brain white matter, immunohistochemically labelled with anti-CD45 antibody and counterstained with Giemsa stain. CD45-positive PBM adherent to transected microvasculature were counted with an automated image analyzer. MS patients showed an increased number of vessel-bound PBM (48.8 +/- 36.4) with respect to healthy controls (27.4 +/- 20.7, P = 0.01) and OIND patients (22.6 +/- 7.8, P = 0.01). Significant differences were also obtained counting the number of vessel-bound PBM as a percent of total vascular cells between MS patients (12.7 +/- 7.2%) and healthy controls (6.9 +/- 5.4%, P = 0.002) or OIND patients (7.4 +/- 4.4%, P = 0.03). We confirm that PBM from MS patients show an increased potential of binding to cerebral vessels. The frozen-section assay provides a unique tool to study in situ the molecular interactions of leukocytes with brain vascular structures.

Peripheral benzodiazepine receptor expression on leukocytes and neutrophil function during anticonvulsant monotherapy.

Epileptic patients on long-term therapy with a single anticonvulsant showed enhanced expression of peripheral benzodiazepine receptors (pBZrs) on neutrophils, monocytes and lymphocytes. N-Formyl-methionyl-leucyl-phenylalanine-induced chemotaxis was significantly impaired in neutrophils from patients on carbamazepine (p < 0.01 vs. controls). Neutrophils from patients on phenytoin had enhanced phorbol myristate acetate-stimulated O-2 production (p < 0. 01 vs. controls) and neutrophils from patients on valproic acid had impaired phagocytosis frequency and Staphylococcus aureus lethality index (p < 0.01 vs. controls). Overexpression of pBZrs on leukocytes may reflect the clinical response to anticonvulsants and may play a role in the immunological effects of some of these drugs.

Carbamazepine affects neutrophil function through an action on peripheral benzodiazepine receptors.

The aims of this study were to assess the possible role of peripheral benzodiazepine receptors (pBZrs)1 in mediating the in vitro effects of carbamazepine (CBZ) on some neutrophil functions in healthy volunteers and to investigate neutrophil function and pBZr expression in patients with epilepsia on CBZ monotherapy for at least 1 year. In vitro CBZ (42-168 microM) concentration-dependently inhibited chemotaxis induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP) or lipopolysaccharide (LPS)-activated human serum. CBZ did not affect random migration, phagocytosis index, phagocytosis frequency, NBT reduction frequency, C. albicans lethality index and resting superoxide production. The pBZr antagonist PK 11195 (1 microM, per se ineffective) reversed the inhibitory effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP. The pBZr agonist Ro 5-4864 (10-100 microM) mimicked the effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP and had no effect on the other parameters. Neutrophils from epileptic patients on chronic CBZ monotherapy had impaired FMLP- and serum-induced chemotaxis and enhanced expression of pBZrs on neutrophils. These data strongly suggest an involvement of pBZrs in mediating the in vitro effects of CBZ on chemotaxis; furthermore, impairment of the same neutrophil function parameters and overexpression of pBZrs in patients are consistent with the hypothesis of an in vivo interaction of CBZ with pBZrs.

In vitro cytokine, sCD23 and IgG secretion in multiple sclerosis.

Synthesis of IgG by peripheral blood mononuclear cells from patients with multiple sclerosis (MS) and with other neurological diseases and from healthy controls was induced by Pokeweed mitogen (PWM) in short-term cultures. As expected, MS patients produced more immunoglobulin (Ig) G and had a higher percentage of 'high responders' to PWM stimulation as compared to controls. Interleukin (IL)-4 was undetectable in all samples. IL-6 and tumor necrosis factor (TNF)-alpha synthesis was induced by PWM stimulation in all groups, but MS patients showed the most significant increase of both cytokines. Interestingly, only MS patients showed a significant increase of the soluble form of CD23 receptor (sCD23). Moreover, only sCD23 levels correlated with in vitro IgG production in MS patients. The levels of IL-6, TNF-alpha, sCD23 were greater in high responders compared to low responders in all groups. The mean value of each molecule, however, did not differ significantly among overall groups. A highly significant difference was reported for sCD23 in MS patients. We suggest that sCD23, also known as B cell growth factor, may play a role in the well-documented phenomenon of in vitro IgG hypersynthesis in MS patients, adding support to the concept of B cell up-regulation in the peripheral blood of these patients.

Erectile impotence in multiple sclerosis: a neurophysiological study.

Pudendal evoked potentials, motor evoked potentials of the bulbocavernosus muscle to magnetic stimulation and bulbocavernosus reflex were recorded in 34 patients with multiple sclerosis (MS). Responses were delayed in 26, 20 and 3 cases respectively. No relationship was found between neurophysiological abnormalities and the presence or severity of erectile dysfunction, showing that these tests have little diagnostic usefulness in MS patients with impotence. Nocturnal penile tumescence was assessed in 14 cases: the test result was normal in 10 patients, including 3 severely paraplegic subjects.

Natural interferon-beta in chronic progressive multiple sclerosis: results after 2 years of treatment and 2 years of follow up.

Seventeen chronic progressive multiple sclerosis patients were treated with natural interferon-beta (IFN-ß) for 2 years, thereafter they were followed up for 2 years. IFN-ß was given 1 million IU/day i.m. for 1 week, then 3 million IU daily for 3 weeks followed by a maintenance regimen of 2 million IU twice a week for 23 months. Kurtzke Expanded Disability Status Scale score was 5.5 at entry and did not change at the end of the first year. It increased to 5.8 at the end of the second year and to 6.5 at the end of the follow-up. Three patients worsened after 1 year, six after 2 years and nine at the end of the follow-up. Brain MRI was performed at entry and after 1 year: mean lesion score increased by 13.4%. MRI changes were not correlated with clinical course. Natural IFN-ß seemed to have some beneficial effect when high doses were given: this effect tended to disappear after IFN-ß was reduced, followed by a more severe disease progression after its withdrawal.

Interleukin-2 receptor expression on blood monocytes of patients with multiple sclerosis.

We studied the expression of class II MHC product (HLA DR) and IL-2 receptor on circulating monocytes (M phi) in MS patients, neurological and healthy controls, by double color flow cytometry. In all groups most M phi were DR+ without significant differences. More interesting, low percentages of IL-2+ M phi were detectable in healthy and neurological controls, whilst a few MS patients with active disease showed higher levels. This finding is in agreement with similar studies in other T-cell mediated diseases and with the report of rare IL-2+ macrophages in MS plaques. Although the actual role of IL-2+ M phi in the immune response still needs elucidation, our findings suggest their relevance to the pathological process of demyelinating disease.

Perineal motor potentials to magnetic stimulation, pudendal evoked potentials and perineal reflex in women.

Motor potentials to transcranial and lumbar magnetic stimulation were recorded from the perineum in 14 healthy women. The response to transcranial stimulation presented an onset at 20.2 +/- 1.3 ms and a negative peak at 25.1 +/- 1.9 ms. Lumbar responses presented an onset at 5.1 +/- 0.8 ms, and the motor central conduction time measured 14.4 +/- 1.5 ms. Perineal reflex, cortical and lumbar pudendal evoked potentials were recorded after electrical stimulation of the labia minora. These tests are of possible clinical use in the evaluation of sphincter disturbances as they investigate the afferent and efferent pathways concerning pudendal nerve function.

Motor potentials of inferior orbicularis oculi muscle to transcranial magnetic stimulation. Comparison with responses to electrical peripheral stimulation of facial nerve.

Magnetic stimulation at the vertex evoked a motor potential (MP) in the inferior orbicularis oculi muscle of 10 healthy subjects with an onset latency of 8-13 msec. Its amplitude increased and its latency decreased when the muscle was contracted: the latency measured 9.5 +/- 1.3 msec with an intensity of stimulation 10-15% above threshold in the contracted muscle. This MP is secondary to excitation of the motor cortex. With the coil placed over the occipital scalp and the same stimulation intensity, an MP was recorded with an onset latency at 4.5 +/- 0.6 msec. This response reflects the activation of the facial nerve root. The peripheral electrical stimulation of the facial nerve at the mandible angle elicited an MP with an onset latency at 3.5 +/- 0.4 msec. Most records showed the presence of late components at about 30 msec for all types of stimulation.

Study of central and peripheral motor conduction in normal subjects.

Motor potentials to transcranial and cervical magnetic stimulation and F-wave were recorded in 37 arms of 25 normal subjects. Clockwise and anticlockwise cervical stimulation were performed over C5, C7 and T2 spinous processes. A significant correlation was found between height and measurements of central and peripheral motor conduction. Peripheral motor conduction measured by F-wave derived techniques (Kimura formula) was 0.5 msec higher as compared with responses to cervical magnetic stimulation. The site and current flow direction of cervical magnetic stimulation influenced the amplitude of responses but not their latency: responses were larger in the right arm when the centre of the coil was placed over the C5 spinous process and clockwise stimuli were used. The same results were obtained in the left arm when the coil was reversed.

Multimodality evoked potentials in amyotrophic lateral sclerosis.

Visual, brainstem auditory and somatosensory evoked potentials to medial nerve stimulation were recorded in 27 patients affected by amyotrophic lateral sclerosis. VEP N75, P100, N140, N75-P100 latencies and P100 amplitude, BAEP I-III, III-V and I-V interpeak-latencies were within normal limits in all ALS patients. Somatosensory evoked potentials were abnormally delayed in 8 patients: in 3 arms because of a delayed N9-N13 latency, in 9 arms because of a delayed N13-N19 latency.

[Clinical, immunologic and electrophysiologic correlations in evaluating multiple sclerosis in relation to its development]. / Correlazioni cliniche, immunologiche ed elettrofisiologiche nella valutazione della sclerosi multipla in rapporto all'evoluzione.

49 patients with multiple sclerosis (MS) were evaluated on several lines of investigation: clinical examination with disability rating scale, disease activity staging, multimodal evoked potentials and cerebrospinal fluid analysis. 24 patients were monthly re-examined and T-cell subsets were analysed in the peripheral blood. Evoked potentials were re-evaluated every 3 months in 24 patients. All paramethers were correlated in transversally and longitudinally during a 3 to 18 months follow-up. The results are discussed in the view of a methodological approach to a laboratory evaluation of disease evolution in its natural course and during therapeutic trials.

[Action of trazodone on pyramidal hypertension. Clinical study]. / Azione del trazodone sull'ipertono piramidale. Studio clinico.

18 patients with severe stabilized pyramidal hypertonia were treated with Trazodone for a minimum period of 60 days with a daily oral dose of 200-300 mg. The reduction of hypertonia was assessed using the Ashworth Scale to evaluate symptoms and signs. On the whole 12 patients showed a clinical improvement; eight of them showed an improvement of at least 2 items on the Ashworth Scale. The reduction of hypertonia began on the 4-5th day of therapy, progressing until the 10-12th day of treatment and then remained constant. Tolerance was very good. Despite the low number of patients in the study the authors obtained good results suggesting that Trazodone should be studied further in this field.

A case of myasthenia gravis associated with optic neuritis.

A case of myasthenia gravis is described in association with optic neuritis in which brain-stem auditory and somatosensory evoked potentials were normal. CSF contained alkaline oligoclonal IgG bands. Blood lymphocyte subpopulations showed a decreased number of T-suppressor cells.

[A case of Creutzfeldt-Jakob disease. Electroencephalographic and immunobiological aspects]. / A propostio di un caso di malattia di Creutzfeld Jakob. Aspetti elettroencefalografici ed immunobiologici.

A case of Creutzfeld Jakob disease is described from an E.E.G. and immunological point of view. The E.E.G. data at various stages of the disease are described and the presence of intrathecally produced IgG antibodies is pointed out.

Multiple tests in the diagnosis of multiple sclerosis.

Visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs), E-UFA test and CSF isoelectrofocusing (IEF) were applied to 42 multiple sclerosis patients. VEPs were abnormal in 29 cases. SEPs in 31 cases, E-UFA in 30 cases, CSF IEF in 38 cases. At least two tests were abnormal in 41 out of 42 patients; 16 cases revealed pathological responses in three tests (38,1%), 15 in four of them (35,7%). The authors discuss the value of using several tests in the diagnosis of multiple sclerosis and emphasize their importance for the purpose of diagnostic classification.