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An experimental model is used to analyze the effects of ventricular stretching and verapamil on the activation patterns during VF. Ten Langendorff-perfused rabbit hearts were used to record VF activity with an epicardial multiple electrode before, during, and after stretching with an intraventricular balloon, under both control conditions and during verapamil (Vp) infusion (0.4-0.8 mumol). The analyzed parameters were dominant frequency (FrD) spectral analysis, the median (MN) of the VF intervals, and the type of activation maps during VF (I = one wavelet without block lines, II = two simultaneous wavelets with block lines, III = three or more wavelets with block lines). Stretch accelerates VF (FrD: 22.8 +/- 6.4 vs 15.2 +/- 1.0 Hz, P < 0.01; MN: 48 +/- 13 vs 68 +/- 6 ms, P < 0.01). On fitting the FrD time changes to an exponential model after applying and suppressing stretch, the time constants (stretch: 101.2 +/- 19.6 s; stretch suppression: 97.8 +/- 33.2 s) do not differ significantly. Stretching induces a significant variation in the complexity of the VF activation maps with type III increments and type I and II decrements (control: I = 17.5%, II = 50.5%, III = 32%; stretch: I = 7%, II = 36.5%, III = 56.5%, P < 0.001). Vp accelerates VF (FrD: 20.9 +/- 1.9 Hz, P < 0.001 vs control; MN: 50 +/- 5 ms, P < 0.001 vs control) and diminishes activation maps complexity (I = 25.5%, II = 60.5%, III = 14%, P < 0.001 vs control). On applying stretch during Vp perfusion, the fibrillatory process is not accelerated to any greater degree. However, type I and II map decrements and type III increments are recorded, though reaching percentages similar to control (I = 16.5%, II = 53%, III = 30.5%, NS vs control). The following conclusions were found: (1) myocardial stretching accelerates VF and increases the complexity of the VF activation pattern; (2) time changes in the FrD of VF during and upon suppressing stretch fit an exponential model with similar time constants; and (3) although stretching and verapamil accelerate the VF process, they exert opposite effects upon the complexity of the fibrillatory pattern.

Endothelial dysfunction is characterized by an impaired vasodilatory response to endothelial agonists as well as by alterations in adhesion and coagulation processes. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) have been shown to be useful in the reversal of endothelial dysfunction, an effect that may be independent of the reduction in cholesterol levels. Both the L-arginine-nitric oxide-cGMP and endothelin pathways are involved in the regulation of vascular tone. Here, we show that the basal transcription rate of the preproendothelin-1 gene was decreased by simvastatin (10 micromol/L) in bovine aortic endothelial cells. Transfection studies with the preproendothelin-1 gene promoter showed that mevalonate (100 micromol/L) was able to prevent the inhibitory effect mediated by simvastatin. Protein geranylgeranylation, but not farnesylation, proved to be crucial for a correct expression of the preproendothelin-1 gene. The C3 exotoxin from Clostridium botulinum that selectively inactivates Rho GTPases, the processing of which involves geranylgeranylation, reproduced the inhibitory effect of simvastatin on the expression of preproendothelin-1. Overexpression of dominant-negative mutants of RhoA and RhoB led to a significant reduction in the preproendothelin-1 promoter activity, whereas the expression of wild-type and constitutively active forms of these proteins resulted in an increase, in support that Rho proteins are required for the basal expression of the preproendothelin-1 gene. Finally, we show that the Rho-dependent activation of the preproendothelin-1 gene transcription was inhibited by simvastatin. Thus, the control of vascular tone and proliferative response mediated by endothelin-1 is regulated at multiple levels, among which the Rho proteins play an essential role.

Background: It is necessary to have an easy and quickly test to distinguish "false positive" rubella IgM results and residual antibodies from the antibodies produced in the primary infection, in pregnant women. The avidity of IgG antibodies test seems to differentiate between primary rubella infection and past infections, reinfections or postvaccination, showing its utility in the diagnosis of primary infection in other infectious diseases., Method: For 30 months, 178 sera from 157 patients with clinical and/or epidemiological rubella suspicion or with a positive rubella IgM result as result of an accidental serological finding, were remitted to our laboratory for a serological follow up. We distinguished 3 patient groups: outbreak group, 112; pregnant women, 36, and newborn 11. Rubella IgM antibodies by indirect EIA previous the rheumatoid factor absorption; IgG antibodies of low avidity by indirect EIA previous treatment of serum with 6 M urea, were detected in the sera. It considered a positive result, a rubella avidity index (AI) < 50%., Results: In the epidemic outbreak group, 90.2% of the patients were not vaccinated. 80% of cases occurred in young men between 14 an 20 years old. From 109 patients (97.3%) with rubella IgG antibodies, 92 (84.4%) showed AI-IgG lower than 50%. In this group, the mean rate of AI-IgG rubella was 29.0%. In the pregnant women group, except for two of them, rubella IgM antibodies were an accidental finding in a serological pregnancy screening. Thirty patients (83.8%) showed AI-IgG rubella > 50%. The two pregnant women who had evidence of clinical and epidemiological rubella showed AI-IgG rubella of 37.4% and 20.9%. Another four pregnant women showed AI-IgG rubella close to cut-off (44.7-49.0%). The mean AI-IgG rubella in this group was 71.8%. The mean AI-IgG Rubella between the epidemic outbreak group and the pregnant women group, 29.0 and 71.8% respectively, was statistical significance (p < 0.001)., Conclusions: The avidity IgG test is simple and quickly, and it allow to exclude most of positive results because of residual IgM antibodies and false reactive.

Background: The eastern region of Canary Islands presents certain climatic and atmospheric conditions which differentiate it from the accepted parameters in cases of Lyme disease. We present a serologic study of patients with clinical syndrome which is potentially compatible with Lyme disease, in an effort to clarify the presence of this disorder region., Material and Methods: We assayed type IgG and IgM antibodies against the flagellin antigen of the native Borrelia burgdorferii using indirect enzymeimmunoassay (EIA) as a screening technique. In the serum presenting positive screening we confirmed this result with immunoblot (IB) type IgG and/or IgM with synthetic peptides for the antigenic epitopes p14, p41, p100, OspA and OspC. We review the clinical history of the patients with reactive sera., Results: We studied a sample group of 1,452 patients considered clinically compatible with Lyme disease over a 42-months period, presenting the screening results for serologic positive 47 (3.2%). From this sample, 24 (1.65%) were IB reactive, independent of the type of immunoglobulin. Only two fulfilled the criteria of both IB-IgM positive, one with antibodies against OspC and p41 proteins finally diagnosed as arteriosclerotic encephalopathy suboccipital Binswanger and another with antibodies against p100 and p41 proteins, diagnosed as presenting a primary cytomegalovirus disease. The bands that, most often lead to reactive IB were p41 and p14. Of the 24 patients who presented reactive IB, 14 (58.3%) also presented other previous data wich produced the false positives, 8 with autoimmune disease, 5 viral infectious and one infection due to Treponema pallidum., Conclusion: Due to the lack of studies carried out in this field which would verify or rule out an epidemiologic chain in our region, our serologic and clinical data put the eastern Canary Islands in doubt as an endemic area of Lyme disease.

ROSWELL PARK, M.D., (1852-1914) is remembered for founding the world's first cancer institute that now bears his name a century ago, The Roswell Park Cancer Institute, and for an unfortunate association with the mortal wounding of President William McKinley in Buffalo, NY, in 1901. Park's accomplishments as a pioneer American neurosurgeon have been overlooked. After Park was appointed as Chair of Surgery at the University of Buffalo in 1884, he became the first American surgeon to precisely localize and remove a posttraumatic epileptic focus in the absence of external scars in 1886. Park introduced American physicians and surgeons to David Ferrier's research on localization of cerebral cortical function and Victor Horsley's techniques for extirpating epileptic foci. In 1895, Park became the first American surgeon to successfully treat spina bifida. In the same year, he wrote the first American monograph on surgery of the head. Park's case reports of successful operations on patients deemed almost incurable reveal boldness and ingenuity. Park's untimely death truncated a promising career.

The purpose of the present study was to assess an retrospective analysis on 167 children with chronic or severe headache, ranged in age from 2 to 14 years (7.19 +/- 2.36 years old) who were referred to the pediatric neurology service of Virgen del Rocio Hospital of Sevilla from december 1992 to december 1994. The most common type of headache was migraine which constituted 43.91% of all these cases. Tension headache accounted for 27.71%. A family history of headache, primarily maternal, was found in 114 patients in whom it could be evaluated. Children with migraine had a greater proportion of mothers with a history of migraine than those with tension headache. No significant variations were observed between chronic evolution and acute. We conclude that headache is not uncommon in children and it treatment must be individualized and requires more than just the use of pharmacotherapy.

Precise regulation of major histocompatibility complex class II (MHC-II) gene expression plays a crucial role in the control of the immune response. A major breakthrough in the elucidation of the molecular mechanisms involved in MHC-II regulation has recently come from the study of patients that suffer from a primary immunodeficiency resulting from regulatory defects in MHC-II expression. A genetic complementation cloning approach has led to the isolation of CIITA and RFX5, two essential MHC-II gene transactivators. CIITA and RFX5 are mutated in these patients, and the wild-type genes are capable of correcting their defect in MHC-II expression. The identification of these regulatory factors has furthered our understanding of the molecular mechanisms that regulate MHC-II genes. CIITA was found to be a non-DNA binding transactivator that functions as a molecular switch controlling both constitutive and inducible MHC-II expression. The finding that RFX5 is a subunit of the nuclear RFX-complex has confirmed that a deficiency in the binding of this complex is indeed the molecular basis for MHC-II deficiency in the majority of patients. Furthermore, the study of RFX has demonstrated that MHC-II promoter activity is dependent on the binding of higher-order complexes that are formed by highly specific cooperative binding interactions between certain MHC-II promoter-binding proteins. Two of these proteins belong to families of which the other members, although capable of binding to the same DNA motifs, are probably not directly involved in the control of MHC-II expression. Finally, the facts that CIITA and RFX5 are both essential and highly specific for MHC-II genes make possible novel strategies designed to achieve immunomodulation via transcriptional intervention.

Presentation of exogenous protein antigens to T lymphocytes is based on the intersection of two complex pathways: (a) synthesis, assembly, and transport of major histocompatibility complex (MHC) class II-invariant chain complexes from the endoplasmic reticulum to a specialized endosomal compartment, and (b) endocytosis, denaturation, and proteolysis of antigens followed by loading of antigenic peptides onto newly synthesized MHC class II molecules. It is believed that expression of MHC class II heterodimers, invariant chain and human leukocyte antigen-DM is both necessary and sufficient to reconstitute a functional MHC class II loading compartment in antigen-presenting cells. Expression of each of these essential molecules is under the control of the MHC class II transactivator CIITA. Unexpectedly, however, whereas interferon gamma stimulation does confer effective antigen-processing function to nonprofessional antigen presenting cells, such as melanoma cells, expression of the CIITA transactivator alone is not sufficient. Activation of antigen-specific T cells thus requires additional CIITA-independent factor(s), and such factor(s) can be induced by interferon gamma.

We bring to reader's attention the book Medical-Moral Account of the Most Troublesome and Rigorous Illness of Epilepsy, written in 1754 by the Mexican physician Pedro de Horta. This book is the earliest text on epilepsy written in the New World. We examine Pedro de Horta's medical and religious concepts of epilepsy and analyze concepts of epilepsy in Hispanic communities during the eighteenth century.

Craig Colony in Sonyea, New York, was America's first comprehensive public epilepsy center. The background to its establishment (the first patients were admitted in 1896) and its role as a model for other institutions is described. The history of the first 25 years of the Colony is recounted and the contributions to epileptology, and the legacy to health care, of the founders--William Pryor Letchworth, Frederick Peterson, Roswell Park, William P. Spratling and Frederick Munson--are assessed.

The DRB1 sequence of the homozygous cell line HAG (DR13-DwHAG-DQ7) represents a new DRB allele assigned DRB1*1103, whereas its DRB3 sequence corresponds to the previously described DRB3*0101 (DR52a) allele. The DRB1*1303 gene product is undetectable by current sera used in routine serology typing. We report here direct evidence that the MHC molecule encoded by the DRB1*1303 gene is functional in antigen presentation and in T-cell restriction. We describe a T-cell clone specific for tetanus toxin whose restriction pattern strictly follows the DRB1*1303 allele, as defined by oligonucleotide typing. It also follows the serologic reactivity with the serum LYGUE and also the DwHAG MLC-defined specificity pattern, with one exception. The potential functional sites for the DRB1*1303 gene product involved in T-cell restriction were deduced from sequence comparisons between DRB1*1303 and closely related DRB1 alleles. The relevant as substitutions were located within close proximity to each other on the HLA class II structural model. Our results demonstrate that 1) DRB1*1303 is functional in antigen presentation and T-cell restriction 2) the functional region involved in antigen presentation and T-cell restriction by DRB1*1303 can be defined structurally.

Although neither a physician nor a scientist, William Pryor Letchworth significantly improved the care and treatment of epileptics at the beginning of this century. As commissioner of the New York State Board of Charities and later president, he established Craig Colony, America's first comprehensive epilepsy facility. In Care and Treatment of Epileptics, he summarized contemporary medical and social knowledge of epilepsy. As cofounder and president of the National Association for the Study of Epilepsy, he introduced from Europe his improvements of the colony plan of construction and financed Transactions, the society's scholarly journal. He combined a sensitivity to the needs of the unfortunate with the resolve of a successful businessman. Although William Pryor Letchworth is remembered for his philanthropy and the park in western New York that bears his name, his signal contributions to modern concepts of epilepsy are unknown to most physicians. This article will acquaint readers with the life and accomplishments of this philanthropist and pioneer epileptologist.

In 1892, Frederick Peterson described the experiences of humans exposed to magnetic fields of strength comparable to those currently used in magnetic resonance imaging. These investigations were conducted in the Edison Laboratory. None of the subjects exposed to constant and to time-variable magnetic fields suffered any ill effects. Peterson concluded that the human organism was in no way appreciably affected by the most powerful magnets known to nineteenth-century science. Peterson can be credited with the first truly scientific assessment of the biological effects of high-intensity magnetic fields. His experiments on humans, done one century ago with great cogency and skill, provide a source of inspiration to modern studies on magnetic resonance imaging.

10 patients with chronic sequelae from vitamin B12 deficiency showed a characteristic profile of abnormalities of median and peroneal somatosensory evoked potentials: mild to moderately slow peripheral conduction to Erb's point, normal conduction or mild slowing across the cervical portion of the median somatosensory evoked potentials, and absence or severe slowing of impulse propagation along the spinal cord with the peroneal somatosensory evoked potentials. These findings are compared with those of other published series of somatosensory evoked potentials in vitamin B12 deficiency. These results shed light on the chronic physiological and anatomical residuals in the nervous system of patients treated for vitamin B12 deficiency.

Neurologic manifestations of vitamin B12 deficiency are protean, including neuropathy, depression, and dementia. We present evidence to dispel confounding myths about vitamin B12 deficiency. Hematologic indices are normal in up to 30% of patients with vitamin B12 deficiency, and results of the Schilling test may be normal in patients with symptoms of deficiency. Isolated neuropathy or myelopathy may occur independently, but often appear concurrently. The neuropathy is primarily axonal and predominantly sensory. Myelopathy is caused by demyelinated areas in posterior and lateral columns. After therapy, recovery from neuropathy is incomplete or may extend for several years. Vitamin B12 replacement should not be withheld from patients with borderline vitamin B12 levels, since the consequences of allowing myelopathy, neuropathy, dementia, and mental disorders to worsen clearly outweigh any disadvantage of therapy.

Simultaneous occurrence of a cerebral arteriovenous malformation and a primary brain tumor is rare. A case of a left occipital meningioma and a right parietotemporal arteriovenous malformation is reported. Clinical, radiological, and postmortem findings are described. Thirty previous reports of arteriovenous malformations associated with primary brain tumors are reviewed. In 18 cases the two lesions were intermixed or in close proximity. This spatial relationship between the lesions suggests more than a coincidental association. Several hypotheses are proposed to explain common causal connections.

From biblical times to 1886, tremors were partially characterized by patterns of activation and associated disease states. William Richard Gowers and Frederick Peterson devised methods to determine the frequencies of the tremors of Parkinson's disease, alcoholism, hysteria, and other diseases. Their values concur closely with the contemporary ranges of 4.0 to 7.0 Hz in Parkinson's disease and 8.1 to 11.0 Hz in chronic alcoholism. This review properly credits these authors' pioneer investigations made with simple instruments a century ago.

Reports of the incidence and severity of physiological abnormalities of vitamin B12 deficiency sharply differ. To resolve these controversies we performed evoked response and nerve conduction studies in 10 males with vitamin B12 deficiency. The minimum criteria for this diagnosis were diminished position and vibration sensation and vitamin B12 levels less than 220 pg/ml. We found normal BAERs in 9/10 patients. The central interpeak latencies of the median and peroneal SERs were abnormal in 4/10 and 8/8 patients, respectively. The VERs were abnormal in 7/10 patients. We found absent or diminished amplitudes of sural sensory and peroneal motor action potentials in 8/10 patients. Abnormal peroneal F response chronodispersion was present in 7/10 patients. Nerve conduction velocities (NCV) were normal in 9/10 patients. EMG demonstrated abnormalities consistent with denervation in lower extremity muscles in 8/10 patients. These studies present a profile of vitamin B12 deficiency: essentially normal BAERs, mildly abnormal VERs and median SERs, and markedly abnormal peroneal SERs. NCV studies are consistent with sensory-motor axonopathy.

Involvement of those cranial nerves subserving taste is common in the Guillain-Barré syndrome, yet seldom reported are disturbances of taste. This may reflect relative sparing of taste fibers, which are small thinly myelinated fibers. However, the true incidence of taste disturbances in GBS is probably underestimated since formal taste testing is often not performed, particularly in those cases where patients have been intubated. We observed two patients with GBS and abnormalities of taste. Disturbances of taste are often neglected clinically and the clinical evaluation of taste has been hampered by lack of standardization of stimuli and lack of quantification of responses.

Contact thermography using liquid crystals provides a simple, inexpensive method of evaluating carotid disease. It does not duplicate information provided by other noninvasive methods, because, whereas Dopplers give an indication of flow and degree of stenosis in the artery, thermography measures the actual hypoperfusion as demonstrated by diminished temperature in areas of the forehead supplied by branches of the ophthalmic artery. A 74-year-old man presented with bilateral carotid distribution TIAs. Carotid Dopplers and angiography revealed 99% occlusion of both internal carotid arteries. Contact thermography showed diminished temperature in the right supraorbital artery territory. The patient subsequently underwent carotid endarterectomy. Following induction of anesthesia but prior to carotid clamping, the patient became transiently hypotensive. Intraoperative EEG monitoring showed marked attenuation of the background rhythm on the right with preservation of background on the left. Normal rhythm was quickly restored with pharmacologic restoration of the blood pressure. This case illustrates the usefulness of thermography, which predicted the hemisphere in jeopardy when Dopplers and angiography showed equal bilateral disease.

Brainstem auditory evoked potentials were bilaterally normal, and somatosensory evoked potentials were unilaterally abnormal in a patient with a large pontine infarct causing a "locked-in" syndrome. In the post mortem examination, the lesion extended unilaterally into the pontine tegmentum, partially involving the left medial lemniscus. The P14 potential was absent and the N20 potential was diminished in amplitude with right median nerve stimulation. The origin of the P14 potential has been debated in the literature. This case provides evidence for the P14 generator being located at the pontine level, in relation to a lemniscal area above the decussation of the somatosensory pathway. Evoked potentials can help to determine the tegmental extension of the pontine infarcts in the "locked-in" syndrome, especially in patients unable to cooperate with clinical examination.

Paresis of the oculomotor nerve is a very rare complication of an unruptured arteriosclerotic fusiform aneurysm of the basilar artery. A handful of cases are described in the world literature. A fifty-four-year-old man with a history of hypertension and diabetes mellitus presented with painless partial oculomotor palsy of sudden onset. A cerebral angiogram demonstrated a tortuous fusiform deformity of the basilar artery and the origin of the posterior cerebral arteries, indicative of an arteriosclerotic aneurysmal dilation. A sudden onset of a pupil-sparing ophthalmoplegia is the typical history of a microvascular infarct of the third nerve, whereas pupillary sparing in aneurysmal oculomotor paresis is a very rare event. Special emphasis has been placed on the pupillary size as a guide for the indication of arteriography. The many exceptions to this rule suggest that cerebral arteriography may be indicated more often than generally believed.

Trophic alterations in the skin take place consequent to interruption of its motor, sensory, and autonomic innervation. The hair in denervated areas is often less abundant and grows more slowly. Syringomyelia is a common cause of cutaneous trophic alterations that are often unilateral. They occur predominantly in the upper extremities and seldom involve the skin over the face and scalp. A patient with syringomyelia exhibited a unilateral impairment of pain and temperature sensation in the entire right side of the scalp. A dissimilarity of hair length between the right and left side of the scalp was noticed, with a sharp demarcation along the midline. This peculiar trophic change has not been previously described in the medical literature.

Traumatic cerebral aneurysms (TCAs) are rare: few more than 100 cases are recorded in the world literature. TCAs are located predominantly in the supratentorial compartment and are classified as either "true" or "false." A true aneurysm is a dilation resulting from partial disruption of the arterial wall. A false aneurysm results from a full-thickness tear, with the scar from the brain tissue or an organized hematoma acting as the aneurysmal wall. The authors present a case of a false traumatic aneurysm of the pericallosal artery, which was discovered in a young patient fourteen months after a self-inflicted gunshot wound to his head. The aneurysm was an incidental finding on a CT scan performed for the investigation of his late posttraumatic seizures. Its presence was confirmed by angiography. The interval between the traumatic episode and the diagnosis of a TCA usually ranges from a few hours to a few weeks, for most are discovered by angiography performed in the acute or subacute stage of a head injury. The long interval between the injury and the diagnosis in our case is exceptional. A previous CT scan done four months after the injury did not reveal the aneurysm, which strongly suggests a protracted growth of the aneurysmal sac long after the trauma.