Magnetic resonance spectroscopy: use in monitoring MELAS treatment.

BACKGROUND: Sodium dichloroacetate has been used to treat patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Magnetic resonance spectroscopy (MRS) has been used to assess cerebral metabolism in MELAS, but to our knowledge, the findings of serial MRS studies performed after therapeutic intervention of strokelike episodes have not been reported. METHODS: Proton MRS was serially used to measure brain metabolites in strokelike regions and in clinically uninvolved brain regions in a patient with MELAS. PATIENT: A patient with MELAS and a strokelike episode clinically improved after treatment with sodium dichloroacetate. An elevated lactate-creatine ratio in the "stroke" region decreased on MRS studies after treatment. After a second episode, the lactate-creatine ratio increased from baseline in a region of the brain that was normal on magnetic resonance imaging scans. CONCLUSIONS: To our knowledge, this is the first study to assess the response to treatment of a MELAS strokelike episode and the first to show an increase in the lactate-creatine ratio in a brain region that was associated with a clinical abnormality, even though it appeared normal on magnetic resonance imaging. We conclude that MRS may help to monitor therapeutic efficacy in mitochondrial encephalomyopathies.

Immunologic reactivity against Borrelia burgdorferi in patients with motor neuron disease.

Of 19 unselected patients with the diagnosis of amyotrophic lateral sclerosis (ALS) living in Suffolk County, New York (an area of high Lyme disease prevalence), 9 had serologic evidence of exposure to Borrelia burgdorferi; 4 of 38 matched controls were seropositive. Eight of 9 seropositive patients were male (8 of 12 male patients vs 2 of 24 controls). Rates of seropositivity were lower among patients with ALS from nonendemic areas. All patients had typical ALS; none had typical Lyme disease. Cerebrospinal fluid was examined in 24 ALS patients--3 (all with severe bulbar involvement) appeared to have intrathecal synthesis of anti-B burgdorferi antibody. Following therapy with antibiotics, 3 patients with predominantly lower motor neuron abnormalities appeared to improve, 3 with severe bulbar dysfunction deteriorated rapidly, and all others appeared unaffected. There appears to be a statistically significant association between ALS and immunoreactivity to B burgdorferi, at least among men living in hyperendemic areas.

A double blind randomized controlled trial of Maharishi Vedic vibration technology in subjects with arthritis.

To explore ancient Vedic medical techniques, one hundred and seventy-six subjects with arthritis participated in a controlled study through the non-pharmacologic approach known as the Maharishi Vedic Vibration Technology (MVVT). Using a double-blinded and randomized experimental design, the findings showed significant reductions of pain and stiffness, and improvement in range of motion in the study sample. One hundred percent relief of symptoms was the most commonly reported category of improvement due to treatment. For the group as a whole, differences in mean response of treatment and control conditions with respect to relief of pain, limitation of motion, and reduction in stiffness were highly significant: t values ranged from a low of 5.609 in stiffness to a high of 20.950 in pain, p = 0.000009 to <10-49 respectively. Analysis by sub-categories of peripheral arthritis, painful conditions of the spine, and rheumatoid arthritis likewise produced significant results. Mechanisms of action were proposed, drawing on Maharishi Vedic Science, developments in quantum field theory, and specifically the theories of chaos and self-organizing systems as they relate to physiological functioning. The instantaneous relief of pain and improvement in function in such a high proportion of subjects with chronic arthritis is unparalleled in modern medical science

The application of color Doppler technology to the study of fetal swallowing.

OBJECTIVE: To investigate the mechanics of fetal swallowing using color Doppler technology. METHODS: The fetal face and a profile were imaged sagitally in ten fetuses at 36-41 weeks' gestation. Color-flow Doppler signals were superimposed on each gray-scale image to assess the direction and location of amniotic fluid (AF) flow with respect to anatomic structures of the fetal upper gastrointestinal and respiratory tracts during the act of swallowing. Further analysis of fetal swallowing movements was performed by a review of the ultrasonography videotapes at a slow speed. RESULTS: An initial stage of fetal swallowing was characterized by two to six sucking movements and the introduction of an AF bolus into the oral cavity. The soft palate superiorly and the tongue posteriorly and inferiorly obstructed the further flow of AF. The final stage of swallowing was characterized by low-frequency tongue movements, upward laryngeal and epiglottic movements, and narrowing of the lumen of the pharynx, directing the fluid bolus caudally. However, some AF was directed into the nasopharynx as well as the trachea. CONCLUSION: The swallowing pattern in the term fetus differs from that in the infant and adult, in that the oral and pharyngeal phases appear to be less completely developed.

Immunohistochemical demonstration of catechol-o-methyltransferase in mammalian brain.

Catechol-O-methyltransferase (COMT)(EC 2.1.1.6) was localized using fluorescence immunohistochemistry in rat liver and kidney and in rat, chinchilla, and bovine brains. In the brain, specific fluorescence was visable only in non-neuronal cellular elements in all three species. Ventricular ependymal cells and cells of the choroid plexuses exhibited the greatest intensity of immunofluorescence. Glial immunofluorescence appeared prominently in large myelinated fiber tracts. Interfascicular and perineuronal satellite oligodendrocytes as well as fibrous astrocytes were immunoreactive, though myelin itself did not exhibit a positive reaction. Bergmann glial cells in the cerebellum also stained brightly for COMT. Although this study indicates that the predominant localization of COMT is non-neuronal, it is important to note that the presence of small quantities of this enzyme in neurons cannot be excluded. The patterns of localization observed in the non-neuronal elements suggest that this enzyme may function as a barrier to free diffusion of catechol compounds within the central nervous system.

Localization of catechol-O-methyltransferase in the leptomeninges, choroid plexus and ciliary epithelium: implications for the separation of central and peripheral catechols.

Catechol-O-methyltransferase (COMT) was localized in cells of the pia-arachnoid, and in epithelial cells of the choroid plexus, using an indirect immunofluorescence technique. The specific activity of COMT derived from these tissues was determined by radioenzymatic assay, and in the case of the choroid plexus was found to be 9-fold greater than that measured in whole rat brain. The level of COMT specific activity in pia-arachnoid was twice as high as that in whole brain. Indirect immunofluorescence studies also revealed an intensity of COMT immunofluorescence in the ciliary epithelium at the blood-aqueous barrier in the rat eye, similar to that visualized in the epithelium of the choroid plexus at the blood-cerebrospinal fluid barrier. The localization of COMT in the leptomeninges, choroid plexus, and ciliary epithelium is consistent with a role for this enzyme in the separation of catechol compounds synthesized in the central nervous system, from those of peripheral origin. Thus, catecholamines derived from the peripheral sympathetic system may be prevented from entering the brain parenchyma, which is innervated by the functionally distinct central catecholaminergic systems.

Immunohistochemical localization of catechol-O-methyltransferase in circumventricular organs of the rat: potential variations in the blood-brain barrier to native catechols.

Catechol-O-methyltransferase (COMT) was localized in the organum vasculosum of the lamina terminals, subfornical organ, subcommissural organ and area postrema of rat brain using an indirect immunofluorescence technique. COMT immunofluorescence was apparent in neuroglia within the organum vasculosum and was most intense in the ependyma between this structure and the optic recess of the third ventricle. In both the subfornical organ and the area postrema, COMT was localized in a neuroglial network, but was noticeably absent in the ependymal layer. COMT immunofluorescence in the ependyma of the subcommissural organ was continuous with the more intense immunofluorescence of the cuboidal ependyma of the third ventricle. Each of the circumventricular organs studied, with the exception of the subcommissural organ, lies outside the blood-brain barrier. However, the unique pattern of COMT immunofluorescence in the area postrema and the subfornical organ suggests that these two structures, of all circumventricular organs, are most likely to permit the entry of peripherally circulating catechols to the cerebrospinal fluid.

Diurnal non-stress test variations in healthy term fetuses. A call for evening appointments for fetal testing.

OBJECTIVE: The null hypothesis is that the time of day during which non-stress testing is performed does not influence the reactivity of the test. STUDY DESIGN: Fetal heart rate (FHR) monitoring was performed in 65 healthy term fetuses at 09:00, 14:00 and 21:00 h, in a quiet room exposed to daylight 2 h after maternal meals. Each session lasted 20 min. Smoking mothers were excluded. Statistical analysis was performed using a double-tailed t-test. RESULTS: Diurnal non-stress test (NST) variations exist and are manifested by a higher incidence of a reactive NST at 21:00 h compared to a 09:00 h assessment, and an increased number and longer duration of accelerations during a 20-min observation period at 21:00 h compared to a 09:00 h assessment. CONCLUSIONS: Evening appointments for fetal assessments may eliminate the need for additional tests due to the decreased incidence of nonreactive NSTs. These in turn will decrease both maternal anxiety and the expense of further testing.

Size disparity of the choroid plexuses of the lateral ventricles: prenatal diagnosis and neonatal outcome.

Fetal choroid plexuses have attracted the attention of perinatologists and geneticists because of the reported association between intrachoroid cysts and chromosomal abnormalities. This report deals with another variation in choroid plexus sonographic appearance-size variation. Sonographic follow-up results as well as neonatal outcome were analysed in five fetuses with these findings. All fetuses had a normal karyotype. Disparate choroid plexuses were not associated with other structural anomalies. None of the fetuses developed ventriculomegaly.

Fetal responses to inadvertent contact with the needle during amniocentesis.

Fetal responses in 7 cases of mid-trimester amniocentesis, complicated by inadvertent contact between the amniocentesis needle and fetal parts, were analyzed by retrospective videotape review. The incidence of inadvertent needle contact with the fetus was 0.4% (7 of 1,458). Responses included brisk withdrawal of the 'involved' small part in all cases, with the exception of a fetus with lumbosacral meningomyelocele, which failed to withdraw the foot upon direct contact with the needle. Neurologic examination was normal in all neonates except for one with meningomyelocele whose defect was at the L3-L5 level. This patient exhibited paralysis of intrinsic foot muscles and hip extensors. Surgical closure of the defect was performed 12 h after birth. At 2 years of age, no significant improvement in this patient's neurologic condition was noted. Further research is needed to assess the validity of the response to needle contact as a predictor of neonatal neurologic compromise.

Anti-catechol-O-methyltransferase: demonstration of specificity and immunological cross-reactivity with the enzyme from rat liver, kidney, brain, and choroid plexuses.

An antiserum to rat liver catechol-O-methyltransferase (COMT) was utilized in the immunological characterization of COMT from rat kidney, brain, and choroid plexuses, in addition to rat liver. The presence of anti-COMT activity was confirmed by the direct inhibition of the activity of the enzyme from rat liver by small quantities of the antiserum and by the inhibition of the activity of the enzyme from rat brain. The specificity of the antiserum was demonstrated both by immunoelectrophoresis of rat liver COMT, and by a partial purification of rat liver COMT in which changes in COMT specific activity were correlated with the appearance of a precipitin line in double-immunodiffusion experiments. The antigenic similarity of the enzyme derived from rat liver, kidney, brain, and choroid plexuses was demonstrated by the formation of a precipitin line of identity when preparations from these four tissues were diffused against the antiserum.