Integrative action of axonal membrane explored by trains of subthreshold stimuli applied to the peripheral nerve.

OBJECTIVE: The objective of this study was to provide evidence on the integrative action of axonal membrane in humans and its ability to integrate multipulse subthreshold stimuli and generate action potential. METHODS: The median nerve was stimulated at the wrist in six healthy subjects and 17 patients who underwent low spine surgery by means of percutaneous electrodes, with trains of one to nine near-threshold constant-current stimuli of 500-µs duration. The interstimulus interval between stimuli was 2 or 4 ms. The compound muscle action potential (CMAP) was recorded from the abductor pollicis brevis muscle using subcutaneous needle electrodes in patients and surface electrodes in healthy subjects. Total intravenous anesthesia (TIVA) without a muscle relaxant was used in all patients, and measurements were performed at the end of surgery. RESULT: A single near-threshold stimulus did not generate CMAP either in the healthy subjects or in the patients. However, when the number of near-threshold stimuli was increased to two to nine stimuli, and packed into a short train with interstimulus intervals of 2 or 4 ms, a CMAP of varying amplitude from 100 to 200 µV was successfully elicited. CONCLUSION: We concluded that the described phenomenon might be explained by the integrative action of the axonal membrane, which is able to summate the trains of subthreshold stimuli, increasing the resting potential to the firing level, and consequently generating CMAP. This is because the subthreshold stimuli make the axonal membrane hyperexcitable. SIGNIFICANCE: This phenomenon is not very well explored in clinical neurophysiology, and it needs to be studied further. This can explain some neurophysiologic phenomena during intraoperative monitoring.

Host and disease factors are associated with cognitive function in European HIV-infected adults prior to initiation of antiretroviral therapy.

OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study. METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models. RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/µL and 4.74 (4.28, 5.14) log10 HIV-1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA. CONCLUSIONS: In this large, European-wide, ART-naïve population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV-disease factors.

Smoking cessation in HIV patients: rate of success and associated factors.

BACKGROUND: Smoking is the modifiable cardiovascular (CV) risk factor that contributes most to causing premature CV disease. Prevalence of smoking in patients with HIV infection is double that of the general population. OBJECTIVES: To determine the rate of patients succeeding in quitting smoking after 12 months, factors associated with this success, and the characteristics of tobacco consumption and nicotine dependence. METHODS: Longitudinal descriptive study. Three hundred and sixty-eight HIV-infected patients were interviewed. Smokers in Prochaska's stage of action began a programme to quit smoking. We registered the variables related to tobacco consumption and the level of success of cessation. RESULTS: 63.9% of the patients were active smokers and 14% of them began the cessation programme. Average motivation for cessation was 7.8 +/- 1.4 (Richmond) and nicotine dependence rate 5.5 +/- 3.0 (Fagerström). After 1 year, 25% had quit smoking. Those patients who stopped smoking presented a higher motivation level (8.8 +/- 1.3 vs. 7.5 +/- 1.5, P=0.048). Cessation significantly reduced their CV risk at 12 months [2.5 [interquartile range (IQR) 2.0-5.2] vs. 1.7 [IQR 1.0-3.5], P=0.026]. CONCLUSIONS: The prevalence of smokers in our population of HIV-infected patients was 63.9%. Only 14% began a smoking cessation programme. Twelve months after a programme to quit smoking, cessation rate was 25%; this was influenced mostly by the level of motivation of the patient.

Patients' perception and effectiveness of a treatment containing enfuvirtide when used in HIV-infected patients without very advanced disease.

PURPOSE: To evaluate the satisfaction with self-injected enfuvirtide (ENF) and the clinical outcome of HIV-infected patients without very advanced disease. METHOD: ESPPE is a multicenter observational study that included 103 evaluated patients showing baseline characteristics predictive of positive outcome: CD4 >100 cells/mm3, viral load (VL) <100,000 copies/mL, previous treatment with a maximum of 10 antiretroviral drugs, and concomitant use of 2 active drugs. By using validated surveys, patients were questioned 6 months after the prescription of ENF about their quality of life (QoL) and acceptance of self-injections and adherence to the treatment. RESULTS: At 6 months, the mean CD4 increase was 121 cells/mm3 (p < .05) and 65% (intent-to-treat, ENF stopped=failure) had VL <50 copies/mL (p < .001). Fourteen patients discontinued the treatment, mostly due to intolerance (6). The majority (>89%) assessed all items relating QoL as "excellent," "very good," or "good." The treatment satisfaction index on a visual analog scale scored a median of 8.1 out of 10; when participants were asked about the interference of injections on their daily activities, 87% answered "never" or "only sometimes." CONCLUSION: Effectiveness and patients' perception about ENF remain good when ENF was used in patients without very advanced disease. QoL was not impaired after ENF use.

Monocyte count is an underlying marker of lacunar subtype of hypertensive small vessel disease.

BACKGROUND: In the hypertensive small vessel disease (HSVD), it remains unclear why some patients develop lacunar infarcts (LIs) whilst others develop deep intracerebral hemorrhages (dICHs). Inflammation might be related to LI, and leukocyte and monocyte counts are regarded as an inflammatory marker of ischemic stroke. OBJECTIVE: We investigated the relationship between leukocyte and monocyte counts determined in the first 24 h after stroke onset in HSVD patients. METHODS: We prospectively studied 236 patients with first acute stroke because of HSVD (129 LI and 107 dICH). We analyzed demographic data, vascular risk factors, and white blood cell count subtypes obtained in the first 24 h after stroke. RESULTS: The multivariate analysis showed that LI subtype of HSVD was correlated with hyperlipidemia (P < 0.0001), a higher monocyte count (P = 0.002), and showed a trend with current smoking (P = 0.051), whereas dICH subtype was correlated with low serum total cholesterol (P = 0.003), low serum triglycerides (P < 0.0001), and high neutrophil count (P = 0.050). CONCLUSIONS: In patients who developed HSVD-related stroke, high monocyte count, current smoking, and hyperlipidemia are prothrombotic factors related to LI, whereas low cholesterol and triglyceride values are related to dICH. Monocyte count might be an inflammatory risk marker for the occlusion of small vessels in hypertensive patients.

Anorectal dysfunction in multiple sclerosis.

OBJECTIVE: To ascertain the prevalence of anorectal dysfunction (ARD) in patients with multiple sclerosis (MS) and its relationship with MS clinical characteristics. METHODS: Prospective transversal study in 193 patients with MS. All patients fulfilled a protocol that included: demographic variables, clinical characteristics of MS and the presence of ARD and urinary dysfunction (UD). RESULTS: One hundred and ninety-three patients: 66.8% women, an average age of 42.8 (12.1) years; 67.8% of patients had relapsing remitting MS, 21.2% a secondary progressive and 10.9% a primary progressive form. The average duration of MS was 10.7 (9.4) years and the EDSS 2.8 (2.3). ARD was present in 93 patients (48.2%), and UD in 50.2%. ARD associated to UD was present in 35.7% of cases. The univariate study revealed that patients with ARD were older (P <0.001), had greater disability (P <0.0001), longer disease duration (P <0.001) and a greater association with UD (P<0.0001). ARD was more frequent in progressive forms (P<0.0001). The logistic regression analysis showed that female sex (P = 0.015), EDSS (P = 0.002) and UD (P = 0.003) were independent factors related to ARD. CONCLUSION: ARD is a highly prevalent disorder in MS. Female sex, EDSS and UD are independent predictors of ARD development.

Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.

Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.

[Hereditary neuropathy with liability to pressure palsies: study of six Spanish families]. / Neuropathies héréditaires sensibles à la pression: étude de six familles espagnoles.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited demyelinating neuropathy typically characterized by recurrent episodes of acute painless peripheral nerve palsies often preceded by minor trauma or compression at entrapment sites. However, less classical phenotypes have been reported. A 1.5 Mb deletion in chromosome 17 p11.2 has been shown to be the genetic basis of the disease in the majority of HNPP patients. The few families without this deletion harbored a mutation in the PMP22 gene. We performed a clinical, neurophysiological and molecular genetic study of 6 Spanish HNPP families. Five families (22 individuals) showed the classical chromosome 17 p11.2 deletion and one family (3 individuals) had a novel 3'splice-site mutation in PMP22. Neurophysiological abnormalities were detected in all symptomatic (n=21) and asymptomatic (n=4) deletion or mutation carriers, even in childhood. In addition to the typical presentation we observed other phenotypes: recurrent focal short-term sensory symptoms, a progressive mononeuropathy, a Charcot-Marie-Tooth (CMT) disease-like chronic progressive polyneuropathy, a chronic sensory polyneuropathy and a chronic inflammatory demyelinating polyneuropathy. We report new or very rare phenotypesThese atypical clinical aspects and intrafamilial heterogeneity are present in families with the HNPP deletion as well as in the family with the PMP22 mutation. However, the CMT disease-like chronic polyneuropathy was more common in the PMP22 mutation family. Intrafamilial heterogeneity also seemed to be more pronounced in this kinship. Patients in this family had a mild chronic motor and sensory polyneuropathy neurophysiologically characterized by delayed distal latencies, reduced nerve conduction velocities (NCV) within the demyelinating range, mildly decreased amplitudes of motor and sensory evoked potentials and absence of conduction blocks. In contrast, patients with the common HNPP deletion, regardless of their phenotype, had a diffuse increase in distal motor latencies contrasting with moderately reduced motor NCVs, preserved sensory nerve action potentials, slowing of NCVs at the common entrapment sites and occasionally conduction blocks. In this study we confirm the clinical and molecular heterogeneity of HNPP, emphasizing the need for a mutation analysis of the PMP22 gene when the common 17p11.2 deletion is not found in clinically suspected HNPP patients. We conclude that the 3'splice-site mutation in PMP22 and the common HNPP deletion have largely the same functional consequences although some clinical and neurophysiological differences were observed.

Prevention of nevirapine-associated exanthema using slow dose escalation and/or corticosteroids.

OBJECTIVE: The appearance of rash is one of the most frequent and limiting side-effects during the first 4 weeks of treatment with nevirapine (NVP). We explored the efficacy and safety of four different strategies for reducing the incidence of this complication. PATIENTS AND METHODS: Four-hundred and sixty-nine patients were assigned randomly to accomplish the induction phase of NVP following either the standard recommendation of 200 mg daily during the first 2 weeks (n = 166), or any of three new strategies: adding prednisone 50 mg each other day during the first 2 weeks (n = 93); using a slowly escalating dose, beginning with 100 mg daily the first week, and increasing the dose by 100 mg/week up to the full daily dose of 400 mg (n = 107); and combining both the addition of prednisone with the slowly escalating dose (n = 103). A pharmacokinetic substudy was performed in seven patients receiving 100 mg of NVP during the first week. RESULTS: The incidence of rash diminished from 18.7% using the standard recommendation to 9.2% using the alternative approaches (P = 0.003). Rash appeared in 11.2%, 8.6%, and 7.7% of subjects assigned to receive the slowly escalating dose, prednisone, or both, respectively, without significant differences among them. The rate of drug discontinuation was also diminished by one-half using the new approaches (8.5% versus 4.3%; P = 0.06). NVP plasma concentrations within the first week of treatment using 100 mg daily were above the 90% inhibitory concentration for wild-type HIV-1 in all instances. CONCLUSION: The incidence of rash complicating the first few weeks of treatment with NVP can be diminished by adding corticosteroids for 2 weeks to the standard recommendation, or by using a slowly escalating dose. This second approach is proven to be pharmacokinetically safe.

[Chronic demyelinating auto-immune acquired neuropathy: Lewis-Sumner syndrome]. / Neuropatías adquiridas autoinmunes desmielinizantes crónicas: síndrome de Lewis-Sumner.

INTRODUCTION: Knowledge of the chronic auto-immune acquired neuropathies has progressed rapidly since the recent description of the Lewis-Sumner syndrome and multifocal motor neuropathy. Some of the most interesting aspects of these conditions are the presence of persistent conduction blocks and the challenge of understanding the mechanisms involved. These blocks are difficult to identify. CLINICAL CASE: We describe the case of a female patient with Lewis-Sumner syndrome, with persistent sensory and motor blocks. The electrophysiological characteristics and differential diagnosis of the two conditions are reviewed.

Neuropatías adquiridas autoinmunes desmielinizantes crónicas: síndrome de Lewis-Sumner / Chronic demyelinating auto-immune acquired neuropathy: Lewis-Sumner syndrome

Introducción. El conocimiento de las neuropatías adquiridas autoinmunes crónicas evoluciona rápidamente con la reciente descripción del síndrome de Lewis-Sumner y la neuropatía motora multifocal. Algunos de los puntos que mayor interés han despertado ambas entidades son la presencia de bloqueos de conducción persistentes y el reto de entender su mecanismo. Los bloqueos son difíciles de objetivar. Caso clínico. Presentamos el caso de una paciente con síndrome de Lewis-Sumner con bloqueos persistentes sensitivos y motores. Revisamos sus características clínico-electrofisiológicas y el diagnóstico diferencial de las dos entidades (AU)

Economic impact of HIV protease inhibitor therapy in the global use of health-care resources.

OBJECTIVE: To evaluate the clinical and economical impact of the introduction of HIV protease inhibitor (PI) therapy in the current clinical care of HIV-infected patients. METHODS: Cohort study with 155 HIV-infected patients with a full year of follow-up before and after the introduction of PI by June 1998. The setting was a large urban tertiary teaching hospital in Madrid, Spain. The main outcomes measures were clinical and immunological evolution, pharmacy, out-patient, emergency room and in-patient medical costs evaluated by diagnostic-related group classification, and the global economic costs of clinical care in HIV-infected patients (AIDS and non-AIDS). RESULTS: The cost of PI therapy was compensated fully by savings related to reduction of the number, length and severity of hospital admissions in AIDS cases. In contrast, more modest clinical effects with increased costs were observed in non-AIDS cases. Globally, there was an increase of about 20% in the total health-care costs of HIV-infected patients (P < 0.01). CONCLUSIONS: PI therapy is highly cost-effective in AIDS patients. Its value in less severely immunosuppressed patients requires further evaluation.

[Macro-electromyography findings in neuropathies and myopathies]. / Hallazgos de la macroelectromiografía en neuropatías y miopatías.

The possibility of overall recording of the electrical activity generated by muscle fibres making up the motor unit in its entire territory, is the characteristic and main objective of macro-EMG studies. This is possible because of the technical characteristics of the electrode and the recording conditions whose methodology is described. We describe how parameters of macro-EMG are obtained in normal healthy people, and define changes in parameters in pathological neurogenic and myogenic disorders and their value in the follow-up of reinnervation processes.

High plasma levels of endothelin-1 and atrial natriuretic peptide in patients with acute ischemic stroke.

The plasma levels of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) have been measured in 37 patients with acute ischemic stroke, on admission and 3 and 7 days thereafter. The plasma ET-1 levels at the onset of symptoms were about two-fold those observed in age-matched normal volunteers (3.5 +/- 2.26 v 1.54 +/- 0.9 pg/mL, respectively; P < .001). These levels remained significantly elevated during the 7-day study period. The neurologic deficit was assessed daily by Mathew's modified scale (MS). A significant correlation was found between neurologic status on admission and ET-1 plasma values; patients with worse neurologic status (MS < 45 points) had higher ET-1 plasma values than those with better neurologic status (MS > 45 points) (5.4 +/- 2.34 v 3.05 +/- 2.04 pg/mL, respectively, P < .05). The plasma ET-1 values did not correlate either with the site of the infarction or with its primary cause (cardioembolic, lacunar, or atherothrombotic). No significant differences were seen in plasma ET-1 concentrations between patients who eventually died and those who survived the acute event. The plasma ANP were about 18-fold higher in ischemic stroke patients on admission than in controls at admission (110.9 +/- 29.5 v 5.84 +/- 3.96 pg/mL, respectively, P < .01). These values remained significantly elevated on days 3 and 7. There was no correlation between the ANP plasma values and the neurologic status, the site or mechanism of the stroke, or the plasma ET-1 levels. In conclusion, ischemic stroke is associated with marked acute and long-duration increases of ET-1 and ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

[Epidermoid carcinoma of the pancreas associated with malignant humoral hypercalcemia]. / Carcinoma epidermoide de páncreas asociado a hipercalcemia humoral maligna.

Pure squamous carcinoma is a rare pancreas cancer histological variety. Moreover the association of malign humoral hypercalcemia and neoplasia of the pancreas exocrine portion is extremely rare. The case of a patient with pure squamous pancreas carcinoma and hypercalcemia is discussed. The absence of bone metastasis allowed to classify it within the malign humoral hypercalcemia syndrome. It is the first case described in the spanish scientific literature and the third in the international literature of an epidermoid pancreas carcinoma associated to malign humoral hypercalcemia.