Design, development, and testing of an environmental P-T cell for infrared spectroscopy measurements.

Water absorption bands due to superficially adsorbed molecules often dominate the near-infrared spectra of particulate minerals and rocks, when measured in the laboratory in the reflectance mode. In order to remove this, the spectral effect is thus necessary to acquire spectra of samples in vacuum and at higher temperatures. With the aim to accomplish this task, we developed an environmental cell to perform infrared spectroscopic measurements at controlled pressure-temperature conditions. Currently the cell allows one to measure reflectance spectra in the temperature range from room values up to 300 °C (573 K), in the pressure range of 103-10-6 mbar. The acquisition of spectra continuously in two distinct phases, namely, during a preliminary pumping stage (at room T) and subsequently during a heating stage (in vacuum), permits to highlight and characterize separately the effect of pressure and temperature on infrared spectra.

Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse.

Chronic migraine has been linked to the excessive use of acute headache medications. Medication overuse (MO) is commonly considered the most significant risk factor for the progression of migraine from an episodic to a chronic condition. Managing MO is a challenge. Discontinuation of the acute medication can result in withdrawal headache, nausea, vomiting and sleep disturbances. This review summarizes the results from two similarly designed, randomized, placebo-controlled, multicentre studies of chronic migraine conducted in the USA and European Union. Both studies demonstrate the efficacy and safety of the migraine preventive medication, topiramate, for the treatment of chronic migraine in patient populations both with and without MO. These studies may have important implications for the future of chronic migraine management, suggesting that detoxification prior to initiating prophylactic therapy may not be required in all patients if MO is present.

Weight change and clinical markers of cardiovascular disease risk during preventive treatment of migraine.

Migraine, particularly migraine with aura, and increased body weight are independent risk factors for cardiovascular disease (CVD). The association of weight change and clinical markers of CVD risk was evaluated in subjects participating in a randomized double-blind, parallel-group study of migraine-preventive treatment comparing 100 mg/day of topiramate and amitriptyline. Individuals from both treatment groups were pooled and stratified into three groups. The 'major weight gain' group gained > or = 5% of their baseline body weight at the conclusion of the study; the 'major weight loss' group lost > or = 5% of their baseline body weight. The third group had < 5% of weight change. The influence of weight change in headache outcomes, as well as in markers of CVD (blood pressure, cholesterol, C-reactive protein), was assessed using analysis of covariance. Of 331 subjects, 52 (16%) experienced major weight gain and 56 (17%) experienced major weight loss. Weight change was not associated with differential efficacy for the treatment of headache. However, contrasted with those with major weight loss, those who gained weight experienced elevations in mean diastolic blood pressure (+2.5 vs. -1.2 mmHg), heart rate (+7.6 vs. -1.3 beats per minute), glycosylated haemoglobin (+0.09% vs. -0.04%), total cholesterol (+6.4 vs. -6.3 mg/dl), low-density lipoprotein cholesterol (+7.0 vs. -4.4 mg/dl) and triglycerides (+15.3 vs. -10.4 mg/dl) and an increase in high-sensitivity C-reactive protein (+1.8 vs. -1.9 mg/l). Both groups experienced decreases in systolic blood pressure (-4.0 vs. -1.3 mmHg) and high-density lipoprotein cholesterol (-3.7 vs. -0.8 mg/dl). Increased weight during migraine treatment is not associated with poor headache treatment outcomes, but is associated with deterioration of CVD risk markers.

Placebo effects in oral triptan trials: the scientific and ethical rationale for continued use of placebo controls.

The aim of this study was to determine the characteristics of placebo effects in acute migraine treatment trials of triptans performed over 12 years and assess whether the use of placebo controls in trials of acute migraine treatment remains ethically and scientifically appropriate. We conducted a search for all controlled trials published in English between January 1991 and April 2002 in which adult subjects with migraine were randomly assigned to receive an oral triptan or placebo for the acute treatment of a migraine attack. Thirty-one trials met our criteria for inclusion. Placebo results for each study and pooled placebo results were calculated for the endpoints of headache response, pain-free response and adverse events. Heterogeneity was assessed using the Q statistic, and meta-regression using prespecified covariates was performed to investigate heterogeneity. The study results show a significant degree of heterogeneity. Efforts to explain heterogeneity with available data were not successful, with the exception of adverse event rates to placebo, for which study location (Europe vs. North America) partially explained differences in study results. AE rates were lower in European studies than in North American studies. Across all studies, the mean proportion of subjects who experienced a treatment response at two hours to placebo was 28.48 +/- 8.73% (range 17-50%). The mean proportion of subjects who experienced an adverse event to placebo was 23.40 +/- 14.05% (range 4.86-74%). The mean proportion of subjects who experienced a pain-free response to placebo at two hours was 6.08 +/- 4.43% (range 5-17%). Results of studies allowing use of prophylaxis did not differ significantly from those that did not allow prophylaxis. Placebo effects appear to be enhanced in studies involving children and adolescents. In contrast to an earlier, smaller review, our results do not suggest that randomization ratios influence placebo rates. We conclude that placebo effects in published trials of acute migraine medications are highly variable and often substantial. This variability in placebo response means that active control equivalence trials or the use of historical controls will not provide adequate proof of the safety or efficacy of new drugs, and will not differentiate between drugs that are active vs. placebo but of unknown efficacy relative to each other. The potential for approval of ineffective drugs, inability to compare results of studies performed in different locations, and poor characterization of the tolerability and safety profiles of new drugs represent a greater danger to migraineurs than does the limited-duration use of placebo in carefully monitored clinical trials of consenting subjects. These observations support the view that the inclusion of a placebo group remains of major scientific and ethical importance in trials of migraine medications.

Headaches and their relationship to sleep.

Despite the complex influences of normal sleep physiology and sleep disorders on the development or presentation of headache, it is important to recognize and understand these relationships. Successful outcomes depend on the provision of treatment interventions specifically directed toward each condition. Nocturnal or early morning headaches that are associated with OSA are often eradicated after the sleep disorder is successfully managed with CPAP, oral appliances, or surgery. Substantial improvement in headache can also result from the successful management of other sleep disorders that may incite headaches such as heavy snoring, PLMS, or the various forms of insomnia. To improve headache patterns associated with bruxism and TMD, it is often necessary to formulate a multidisciplinary treatment approach that combines oral appliance therapy, stress management, biofeedback, oromandibular physical therapy, and, at times, pharmacologic treatment (i.e., tricyclic antidepressant, intramuscular botulinum toxin injections). There are still many gaps in the understanding of the interrelationships of sleep physiology and headache pathophysiology. More well-designed clinical trials are needed so that enough data can be amassed for the formulation of evidence-based guidelines or consensus statements that can better delineate the identification, diagnostic evaluation, and treatment of sleep-related headache disorders and headaches that develop as a consequence of disordered sleep.

Cervicogenic headache: diagnostic evaluation and treatment strategies.

Cervicogenic headache is a chronic, hemicranial pain syndrome in which the source of pain is located in the cervical spine or soft tissues of the neck but the sensation of pain is referred to the head. The trigeminocervical nucleus is a region of the upper cervical spinal cord where sensory nerve fibers in the descending tract of the trigeminal nerve converge with sensory fibers from the upper cervical roots. This convergence of upper cervical and trigeminal nociceptive pathways allows the referral of pain signals from the neck to the trigeminal sensory receptive fields of the face and head. The clinical presentation of cervicogenic headache suggests that there is an activation of the trigeminovascular neuroinflammatory cascade, which is thought to be one of the important pathophysiologic mechanisms of migraine. Another convergence of sensorimotor fibers has been described involving intercommunication between the spinal accessory nerve (CN XI), the upper cervical nerve roots, and ultimately the descending tract of the trigeminal nerve. This neural network may be the basis for the well- recognized patterns of referred pain from the trapezius and sternocleidomastoid muscles to the face and head. Diagnostic criteria have been established for cervicogenic headache but its presenting characteristics may be difficult to distinguish from migraine, tension-type headache, or hemicrania continua. A multidisciplinary treatment program integrating pharmacologic, nonpharmacologic, anesthetic, and rehabilitative interventions is recommended. This article reviews the clinical presentation of cervicogenic headache, its diagnostic evaluation, and treatment strategies.

Geriatric headache. How to make the diagnosis and manage the pain.

Approximately 10% of women and 5% of men at age 70 experience severe recurrent or constant headaches. Severe headache presenting for the first time in a patient over age 50 is unusual and requires a thorough medical and neurologic examination. Primary headache etiologies in older patients include migraine, tension-type, cluster, and the rare hypnic headache. For all of these, effective pain control includes pharmacologic and nonpharmacologic interventions. Secondary etiologies include temporal arteritis, medication-induced headache, cerebrovascular or cardiac ischemia, and intracranial hemorrhage or tumors. Head pain may also be cervicogenic or related to glaucoma or sleep apnea. In secondary cases, pain management is specific to treatment of the underlying structural or systemic disease.

Cervicogenic headache: mechanisms, evaluation, and treatment strategies.

Cervicogenic headache is a chronic, hemicranial pain syndrome in which the sensation of pain originates in the cervical spine or soft tissues of the neck and is referred to the head. The trigeminocervical nucleus is a region of the upper cervical spinal cord where sensory nerve fibers in the descending tract of the trigeminal nerve converge with sensory fibers from the upper cervical roots. This convergence of nociceptive pathways allows for the referral of pain signals from the neck to the trigeminal sensory receptive fields of the face and head as well as activation of the trigeminovascular neuroinflammatory cascade, which is generally believed to be one of the important pathophysiologic mechanisms of migraine. Also relevant to this condition is the convergence of sensorimotor fibers of the spinal accessory nerve (CN XI) and upper cervical nerve roots, which ultimately converge with the descending tract of the trigeminal nerve. These connections may be the basis for the well-recognized patterns of referred pain from the trapezius and sternocleidomastoid muscles to the face and head. Diagnostic criteria have been established for cervicogenic headache, but presenting characteristics of this headache type may be difficult to distinguish from migraine, tension-type headache, or paroxysmal hemicrania. This article reviews the clinical presentation of cervicogenic headache, its proposed diagnostic criteria, pathophysiologic mechanisms, and methods of diagnostic evaluation. Guidelines for developing a successful multidisciplinary pain management program using medication, osteopathic manipulative treatment, other nonpharmacologic modes of treatment, and anesthetic interventions are presented.

Relationship between volatile components of citrus fruit essential oils and antimicrobial action on Penicillium digitatum and penicillium italicum.

This study examined the effect of volatile components of citrus fruit essential oils on P. digitatum and P. italicum growth. The hydrodistilled essential oils of orange (Citrus sinensis cvv. "Washington navel", "Sanguinello", "Tarocco", "Moro", "Valencia late", and "Ovale"), bitter (sour) orange (C. aurantium), mandarin (C. deliciosa cv. "Avana"), grapefruit (C. paradisi cvv. "Marsh seedless" and "Red Blush"), citrange (C. sinensis x Poncirus trifoliata cvv. "Carrizo" and "Troyer"), and lemon (C. limon cv. "Femminello", collected in three periods), were characterized by a combination of GC and GC/MS analyses. The antifungal efficacy of the oils was then examined at progressively reduced rates. Findings showed a positive correlation between monoterpenes other than limonene and sesquiterpene content of the oils and the pathogen fungi inhibition. The best results were shown by the citrange oils, whose chemical composition is reported for the first time, and lemon. Furthermore P. digitatum was found to be more sensitive to the inhibitory action of the oils.

Expression and functional analysis of murine B7 delineated by a novel monoclonal antibody.

The B cell surface molecule designated B7 has been shown to be expressed by activated human B cells and monocytes and to be a ligand for the CD28 and CTLA-4 molecules on T cells. B7/CD28 interactions can provide a second signal to T cells (in addition to occupancy of the T cell antigen receptor) that is needed for T cell activation. COS cells transfected with the mouse homologue of B7 have been demonstrated to provide a stimulatory signal to murine and human T cells. In this report we describe a rat anti-mouse B7 mAb designated 1G10. Scatchard and/or FACS analyses utilizing 1G10 demonstrated that B7 was not expressed on resting splenic T cells or B cells, but could be induced at high levels on B cells cocultured with a syngeneic I-Ak-restricted autoreactive T cell hybridoma. Furthermore, activation of B cells with dibutyryl-cAMP (db-cAMP), a second messenger for class II MHC signaling, or with LPS induced the expression of B7 and the two agents showed additive effects. In contrast to B cells, freshly isolated mouse peritoneal macrophages constitutively expressed B7. Antibody-blocking experiments indicated that anti-B7 antibody partially inhibited T cell proliferative responses to primary antigenic stimulation but had no effect on the responses of previously activated T cells to antigenic restimulation.

Identification of the discontinuous binding site in human interleukin 1 beta for the type I interleukin 1 receptor.

Human interleukin 1 beta (IL-1 beta) exerts its diverse biological effects by binding to specific receptors on target cells. Two types of IL-1 receptor (IL-1R) have been identified: the type I IL-1R (p80) and the type II IL-1R (p68). Using site-specific mutagenesis, we have identified the binding site on IL-1 beta for the murine type I IL-1R. Analogs of the IL-1 beta protein containing defined amino acid substitutions were produced and tested for competitive binding to the two IL-1Rs. Substitutions of the amino acids at seven positions resulted in analogs that had greater than or equal to 100-fold reductions in competitive binding to the type I IL-1R, while maintaining substantial binding to the type II IL-1R. These seven amino acids (Arg-4, Leu-6, Phe-46, Ile-56, Lys-93, Lys-103, and Glu-105) are clustered in the IL-1 beta molecule, forming a discontinuous binding site. The side chains of all seven residues are exposed on the surface of IL-1 beta. The cumulative binding energies contributed by each of the residues predict a binding affinity that is consistent with the observed Kd of the wild-type protein for the type I IL-1R.

Antiproliferative effect of interleukin-1 on human ovarian carcinoma cell line (NIH:OVCAR-3).

The human ovarian carcinoma cell line, NIH:OVCAR-3, possesses high affinity receptors for interleukin-1 (IL-1). Binding experiments with 125I-IL-1 alpha indicate a dissociation constant of approximately 55 pM and the presence of approximately 7800 receptors/cell. These receptors bind both IL-1 alpha and IL-1 beta and internalize IL-1. Proliferation is NIH:OVCAR-3 cells is inhibited by IL-1. Half-maximal inhibition is observed with 2-3 units/ml of IL-1 alpha or IL-1 beta. A maximal effect (80% inhibition of cell proliferation) is achieved by treatment of cells with greater than or equal to 10 units/ml of IL-1 for 3 days. The antiproliferative effect of IL-1 is blocked by IL-1 receptor antagonist. Light and electron microscopy studies show that IL-1 treatment causes cytopathological changes and a reduction in the number of mitotic figures in NIH:OVCAR-3. IL-1 stimulates prostaglandin E2 release by NIH:OVCAR-3 cells, but this response is unrelated to the antiproliferative effect of IL-1. Interferon-alpha A (IFN-alpha A) also inhibits growth of NIH:OVCAR-3 cells in a concentration-dependent manner. Combination of IFN-alpha A and IL-1 gives synergistic inhibition of NIH:OVCAR-3 cell proliferation. IL-1 alone or in combination with IFN-alpha A or other agents may be useful for treatment of human ovarian cancer.

Conversion of the interleukin 1 receptor antagonist into an agonist by site-specific mutagenesis.

Interleukin 1 (IL-1) receptor antagonist (IL-1ra) is a naturally occurring protein that binds to the IL-1 receptor present on T cells, fibroblasts, and other cell types and acts to block IL-1-induced responses. IL-1ra is a pure antagonist and has no agonist activity in in vitro or in vivo systems. By site-specific mutagenesis, an analog of IL-1ra was created that contained a substitution of a single amino acid, Lys-145----Asp. This analog, IL-1ra K145D, exhibited partial agonist activity in the D10.G4.1 cell proliferation assay. The newly acquired agonist activity could not be neutralized by antisera to IL-1 alpha or IL-1 beta, but it could be blocked by a monoclonal antibody to the T-cell IL-1 receptor. The analog also showed agonist activity as assayed by increased prostaglandin E2 synthesis from CHO cells expressing recombinant mouse IL-1 receptor. These results with IL-1ra K145D demonstrate the importance of the region surrounding the corresponding Asp-145 residue in IL-1 beta for triggering the biological response to IL-1.

Cerebral air embolism treated by pressure and hyperbaric oxygen.

We used pressure and hyperbaric oxygen to treat 2 patients with cerebral air embolism, occurring as the result of invasive medical procedures, and neither suffered any permanent damage detectable by clinical examination and MRI. This outcome contrasts with reports of infarct and disability among untreated victims of air embolism.

High-dose intravenous immunoglobulin in the treatment of demyelinating neuropathy associated with monoclonal gammopathy.

We treated 2 patients with IgM monoclonal paraproteinemic demyelinating peripheral neuropathy (PPN) with monthly intravenous human immunoglobulin. Both patients had a steadily progressive course in spite of steroid and other immunosuppressive therapy for 3 years before starting the immunoglobulin therapy. Both had a rapid clinical improvement noticeable 5 to 10 days after the 1st immunoglobulin infusion lasting on the average of 3 to 6 weeks. Retreatment caused improvement after each consecutive infusion. There were no significant adverse side effects. High-dose IV human immunoglobulin can be a useful therapy in the treatment of PPN and warrants a large-scale controlled therapeutic trial.

Colangiografia transparietohepatica en el recien nacido. / Transparietohepatic cholangiography in the newborn

Se presenta el caso de un recien nacido con el diagnostico inicial de ictericia obstructiva. Los estudios clinicos y bioquimicos practicados para detectar enfermedades infecciosas o geneticometabolicas fueron negativos. La colangiografia transparietohepatica realizada con la aguja de Chiba demostro la indemnidad y permeabilidad de la via biliar intra y extrahepatica. Aunque la practica de este procedimiento es muy dificil en un recien nacido, se concluye que es un metodo alternativo de estudio en pacientes con sospecha de padecer una atresia de la via biliar extrahepatica previo a una mas agresiva laparotomia

Colangiografia transparietohepatica en el recien nacido. / Transparietohepatic cholangiography in the newborn

Se presenta el caso de un recien nacido con el diagnostico inicial de ictericia obstructiva. Los estudios clinicos y bioquimicos practicados para detectar enfermedades infecciosas o geneticometabolicas fueron negativos. La colangiografia transparietohepatica realizada con la aguja de Chiba demostro la indemnidad y permeabilidad de la via biliar intra y extrahepatica. Aunque la practica de este procedimiento es muy dificil en un recien nacido, se concluye que es un metodo alternativo de estudio en pacientes con sospecha de padecer una atresia de la via biliar extrahepatica previo a una mas agresiva laparotomia