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Biomedical subjects

K Syndulko

Publications and source records attributed to K Syndulko.

At least 37 records · Page 2Linked to original sources
PubMed1993

Human neuro-specimen banking 1961-1992. The National Neurological Research Specimen Bank (a donor program of pre- and post-mortem tissues and cerebrospinal fluid/blood; and a collection of cryopreserved human neurological specimens for neuroscientists).

The National Neurological Research Specimen Bank (The Bank) was established in 1961 to provide a vital service to neuroscientists. Our purpose is to support medical research which seeks the etiopathogenesis for devastating neurological disorders with no known cause, treatment or precise animal model. It serves as a bridge between the neurology clinician who diagnoses and cares for patients with incurable disease and the basic scientist who has need for specimens to find their etiopathogenesis. In the long run this service should advance neurologic diagnoses and serve as the basis for designing treatment. The Bank has grown to be the largest, most diverse neurological specimen bank of its kind in the world. It is a type of "tissue bank" where donor members "will" their central nervous system tissues to science. Then we collect, photograph, seal in air tight bags, quick freeze, cryogenically store and distribute on request the donated tissue to research scientists around the world. All tissue diagnoses are confirmed by clinical records and neuropathologic examination; further histology is conducted on request. In addition to brain and spinal cord tissues, the Bank has samples of other tissues. There are also samples of pre- and post-mortem CSF and sera from normal individuals and patients with various neurological disorders, especially serial specimens on multiple sclerosis patients and HIV-1 seropositive and at risk individuals. This paper outlines the global operations of our human brain bank, based on protocols developed and used by the authors. These operations include donor solicitation, tissue acquisition and documentation, tissue processing and storage, specimen dissemination to users, outcome assessment of banking, quality control, cost of our operation, table of organization and the future.

Blood Donors↗
PubMed1992

Cerebrospinal fluid (CSF) analyses in HIV-1 primary neurological disease.

This paper will focus on CSF findings in HIV-1 Neurological Disease (ND). Why use CSF as exploration window of the HIV-CNS involvement? Traditionally, CSF analysis has been an effective diagnostic method as well as a means of monitoring treatment in several infectious and immune pathologies of the CNS. Consequently there is an abundance of mature background information [113, 145, 147] particularly in terms of detecting infectious agents, using IgG findings as immunological indexes, and utilizing CSF findings to map the evolution of ND. We will explore the papers that utilize CSF variables as dependent measures to explore the effects of HIV disease, particularly HIV ND, cited in Index Medicus and MEDLINE data base, and published in Spanish, Italian and English, between 1985 to 1991. We will restrict our review to those studies that exclude HIV cases with CNS opportunistic infections or neoplasms, and thus focus on what the CSF can tell us about the primary effects of HIV on the brain as defined above. The primary long-term goal is to find some elements of the CSF that would lead to an understanding of the etiopathogenesis of HIV ND. However, an almost equally important aim is to determine which CSF variables may be clinically predictive of HIV ND occurrence and progression. The latter variables can also be expected to provide the best measures of HIV ND treatment efficacy. This is particularly important since it is our contention that treatment of HIV ND will eventually be initiated and monitored on the basis of laboratory markers of HIV ND, most likely from the CSF. Finally, this summarized information would be useful in drafting a CSF profile in order to have a reference pattern for cases with complications. The data of this review will be broken down, when the information permits, according to clinical stage and presence or absence of clinical manifestations of ND.

HIV Infections↗
PubMed1992

Cognitive function in non-demented older adults with hypothyroidism.

PURPOSE: (1) to evaluate objectively changes in cognitive function and electrophysiologic characteristics associated with hypothyroidism of varying severity and duration in primarily older persons; (2) to determine whether these changes are reversible when a euthyroid state has been attained after treatment with thyroid hormone. SUBJECTS AND METHODS: We enrolled 54 non-demented hypothyroid patients (31-99, mean 68.6 +/- 16.4 years) with biochemical evidence of hypothyroidism (38 had overt and 14 had minimal hypothyroidism) and 30 euthyroid controls (31-96, mean 63.7 +/- 18.4 years) screened for good general health. We evaluated attention, orientation, memory, learning, visual-spatial abilities, calculation, language, visual scanning, and motor speed using standardized neuropsychological tests. Electrophysiological measures of neurocognitive function included the P300 latency component of the auditory Event-Related Potentials (ERP) and conduction speed from eye to cortex, the P100 latency component of the Patterned Visual-Evoked Potential (PVEP). All patients were studied when hypothyroid. A subset of patients with minimal initial test abnormalities were available to be retested when euthyroid, 5 and 9 months after onset of thyroid replacement therapy. RESULTS: Hypothyroid patients showed significantly lower scores on the Mini-Mental Status Test (MMS) and on five of 14 neuropsychological tests as compared to controls. The neuropsychological tests affected were copying a cube (visual-spatial function), the Inglis Paired Associates Learning Test-Low and Medium association items (memory and learning), Animal Naming (word fluency/production), and the Trail Making A test (attention, visual scanning and psychomotor function. Hypothyroidism also was associated with longer P100 latencies of PVEPs to 20' checks, but showed no significant differences in PVEP P100 latency to 50' checks, nor in the latency of the auditory ERP component P300. There was a statistically significant correlation between a laboratory index of the severity of hypothyroidism (serum T4) and the Inglis Medium Association items and Animal Naming. There was a statistically significant improvement after 5 months of treatment on three of the timed performance tests that previous studies have shown to be most sensitive to brain dysfunction. CONCLUSION: Hypothyroidism in non-demented older adults is associated with impairments in learning, word fluency, visual-spatial abilities, and some aspect of attention, visual scanning, and motor speed. The MMS by itself was sensitive in differentiating hypothyroid patients with cognitive deficits from controls, while electrophysiological measures did not generally differentiate the hypothyroid patients from normal controls. The MMS was not sensitive to treatment effects, but treatment was associated with significant improvements in three of the most sensitive measures of cognitive dysfunction.

Adult↗
PubMed1991

Neopterin and beta 2-microglobulin and the assessment of intra-blood-brain-barrier synthesis of HIV-specific and total IgG.

In HIV-seropositive patients, we evaluated the clinical utility of measuring combinations of serum and CSF levels of neopterin and beta 2-microglobulin (beta 2-M) (by RIA), as well as the intra-blood-brain-barrier (IBBB) IgG synthesis rate, IgG index, and HIV antibody index (by rate nephelometry, EIA, and formulae) for the assessment of HIV infection of the CNS. We studied paired sera and CSF from 31 HIV-seropositive patients: asymptomatic (16), ARC (12), and AIDS (3). A normal serum neopterin level predicts normal levels of serum beta 2-M, CSF neopterin, or CSF beta 2-M in 90%, 100%, and 100%, respectively, of our patients. An elevated serum neopterin level predicts an elevated level of serum beta 2-M or CSF neopterin in 81% and 62%, respectively, of cases. The HIV antibody index and IBBB IgG synthesis rate or IgG index must be determined separately because they do not predict each other and are not predicted by levels of neopterin or beta 2-M.

Antibodies, Viral↗
PubMed1990

Quantitative multiple sclerosis plaque assessment with magnetic resonance imaging. Its correlation with clinical parameters, evoked potentials, and intra-blood-brain barrier IgG synthesis.

Magnetic resonance imaging (MRI) of the cerebrum, cerebellum, brain stem, and upper cervical cord was performed in 62 individuals with clinically definite chronic, progressive multiple sclerosis (MS). The total area of MRI-demonstrated lesions was measured from film enlargements for each region using an interactive image analysis system. While the MRI was abnormal in 60 (97%) of 62 patients, the visual-evoked potentials in 51 (85%) of 60 patients, the brain stem auditory-evoked potentials (BAEPs) in 24 (46%) of 52 patients, and the somatosensory-evoked potentials (SSEPs) in 45 (89%) of 54 patients, an abnormal intra-blood-brain barrier (BBB) IgG synthesis rate, IgG oligoclonal bands, or both were found in all 62 patients. The total area of MRI abnormality in the cerebrum was significantly correlated only with the intra-BBB IgG synthesis rate, abnormal visual-evoked potentials, impaired performance on the Symbol Digit Modalities Test (SDMT), and one test of standing duration in the quantitative examination of neurologic function (QENF). The brain stem lesion area correlated with the Kurtzke expanded disability status scale and brain stem functional systems score, the ambulation index, abnormal BAEPs, and impaired performance on the SDMT as well as multiple tests of upper and lower extremity function in the QENF. The cerebellar lesion area correlated with impaired performance on the SDMT and primarily upper extremity testing in the QENF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Multiple sclerosis intra-blood-brain-barrier IgG synthesis: effect of pulse intravenous and intrathecal corticosteroids.

Nine severely disabled clinically definite chronic progressive multiple sclerosis (MS) patients who had at least one determination of intra-blood-brain-barrier (BBB) IgG synthesis rate of greater than 7 mg/day (upper limit of normal = 3.3) participated in this study. Seven patients were given 1 gram of methylprednisolone sodium succinate (MP) by intravenous infusion over 30 minutes once a day for 3 days. Statistically significant (p less than .05) reduction in intra-BBB IgG synthesis (mg/day) was seen in 4/7 patients, but in only 2 were normal levels of synthesis rate (less than 3.3 mg/day) attained. Rebound of IgG synthesis to premedication rates occurred within 30 days in 2/4 patients. There was no change in intensity or pattern of cerebrospinal fluid (CSF) oligoclonal IgG bands by isoelectric focusing, immunofixation, and silver staining. A subsequent course of intrathecal methylprednisolone acetate (MPA) (80 mg twice a week for 5 weeks) was given to 5 of the 7 patients and to 2 additional patients not previously treated. In spite of signs of subarachnoid inflammation, a statistically significant depression of intra-BB synthesis, which far exceeded that from the pulse treatment occurred in all 7, including the 2 patients whose intra-BBB IgG synthesis rates were previously resistant to pulse steroid administration. Normal levels of synthesis were rapidly reached in 4/7 patients; however, an IgG synthesis rebound occurred in 3/7 patients which was just as rapid. One out of 7 patients showed a temporary reduction in the number of cathodic IgG oligoclonal bands in the CSF. Two patients required discontinuation of treatment due to aseptic meningitis in one and progressive weakness in the other. Clinically, these severely afflicted patients with fixed deficits remained unchanged with either treatment protocol. While MPA and ACTH have similar initial effect on the central nervous systems (CNS) inflammatory response in MS, the well documented risk of serious adversities with MPA prohibit its clinical use in MS in its present form.

Adult↗
PubMed1989

A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis.

Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose "pulse" and alternate-day regimen. The "intent-to-treat" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.

Adolescent↗
PubMed1988

The long march of the cerebrospinal fluid profile indicative of clinical definite multiple sclerosis; and still marching.

Much progress has been made, especially in the last two decades, in laboratory aids to diagnosis and to follow the course of patients with multiple sclerosis (MS). The cerebrospinal fluid (CSF) profile indicative of MS, though not pathognomonic of MS, is present in almost every case of clinical definite MS in a chronic progressive phase (probably also true for early MS). The cardinal aspect of the profile is intra-blood-brain barrier (BBB) IgG synthesis which can be qualitatively detected by determining unique CSF oligoclonal IgG bands and quantitated by rate formula, mg/day. We believe that intra-BBB IgG synthesis is caused by a persistent antigen, most likely a virus, possibly measles. A number of issues about the profile are proposed and opportunities are presented to resolve them.

Antibodies↗
PubMed1988

Copolymer 1 as therapy for multiple sclerosis: the cons.

One of the hallmarks of multiple sclerosis (MS) is intra-blood-brain-barrier (BBB) IgG synthesis, a byproduct of plasma cells located in and around active inflammatory demyelinating plaques. The rate of IgG synthesis can be measured by plugging CSF and blood IgG and albumin concentrations into our equation. When done in conjunction with CSF and serum analyses for IgG oligoclonal bands, 99% of definite MS patients demonstrate intra-BBB IgG synthesis. At autopsy the pathologic criterion of an inactive plaque of demyelination is absence of inflammatory cells. Hence, we propose that modulation downward or eradication of intra-BBB IgG synthesis (ie, a manifestation of reduced white matter inflammation) in a living patient is a reasonable therapeutic criterion and goal of MS therapy. In a preliminary trial of five severely disabled MS patients, we evaluated the effects of copolymer 1 (COP-1) in daily intramuscular doses of 20 mg (2 patients) and twice daily subcutaneous doses of 15 mg (3 patients) on clinical parameters and on intra-BBB IgG synthesis over a 2-month study period. The results of this trial showed no beneficial effect on neurologic function or on inflammatory demyelination, as assessed by monitoring of intra-BBB IgG synthesis.

Adult↗
PubMed1986

Search for virus nucleic acid sequences in postmortem human brain tissue using in situ hybridization technology with cloned probes: some solutions and results on progressive multifocal leukoencephalopathy and subacute sclerosing panencephalitis tissue.

In order to obtain a useful and readily applicable in situ hybridization (ISH) protocol for progressive central nervous system (CNS) diseases of unknown etiology that are possibly due to persistent viral infection, known and well described diseases were studied, namely, progressive multifocal leukoencephalopathy (PML) and subacute sclerosing panencephalitis (SSPE). The procedures described were validated by confirming results obtained by other investigators using histology, immunocytochemistry, electron microscopy, and ISH. A number of frequently encountered problems of tissue preparation are addressed as well as techniques to reduce autoradiography exposure times. A multi-staged specific, sensitive, reliable, and valid procedure for detection of viral genomes, mRNA and proteins is approached. Formalin-fixed and paraffin-embedded (FFPE) brain material from six patients who died with PML and one patient who died from SSPE were studied using ISH with a tritium-labeled cloned JC virus DNA probe and a measles-cloned nucleocapsid (NC) gene cDNA probe, respectively. This report constitutes a methodological framework as well as a detailed neuropathological analysis of identified brain cell populations within which in situ hybridization was detected. In early PML lesions, swollen nuclei or oligodendrocytes were the predominant cells labeled, whereas older lesions revealed increased numbers of reactive and bizarre hypertrophic astrocytes hybridized at the outer periphery of the demyelinated lesions. The hybridization varied greatly in intensity in different cells. Intense hybridization was noted very rarely in microglial cells, including rod cells and rarely in venular pericytes, intravascular mononuclear cells, or in vascular endothelial cells. These results, considered together with previous findings, indicate that in PML the viral infection runs different courses in the various cells: in astrocytes the viral genome persists for a long time inducing pathological changes in some cells. In oligodendrocytes the infection rapidly lyses the cells. There was a good correlation between chromatic changes observable in routinely stained sections and virus presence. In addition, in situ hybridization using a measles-NP-cloned probe in white matter from FFPE SSPE brain is presented confirming earlier results in SSPE cryopreserved brain.

Adult↗
PubMed1985

The basis of intra-blood-brain-barrier IgG synthesis.

We hold that the intra-blood-brain-barrier (BBB) IgG synthesis (SYN) rate can be quantitated reliably and validly. Although several formulas distinguish patients with multiple sclerosis from normal controls equally well, only the SYN rate formula has been validated in humans using isotopic tracer techniques. Our formula for the IgG SYN rate is reducible to Reiber's formula; therefore, both can be used to quantify the IgG SYN rate in a manner not possible using the IgG index. Although our SYN rate formula has been validated for a modest range of BBB abnormalities (cerebrospinal fluid/serum albumin ratios), there is evidence to suggest that it may be used even in patients having severe BBB damage. We question the acceptance of unique cerebrospinal fluid IgG bands as indisputable evidence of intra-BBB IgG SYN in the presence of a modest to severely damaged BBB. Finally, the utility of quantitation and detection of intra-BBB IgG SYN by standardized methods in a group of asymptomatic, normal individuals compared with a group of patients with clinical definite multiple sclerosis is presented.

Blood-Brain Barrier↗
PubMed1984

Use of P300 and a dementia rating scale in the evaluation of cognitive dysfunction in MS.

The assessment of mental dysfunction in multiple sclerosis and discrimination from the secondary effects of sensory and motor deficits has comparability to similar work done on dementia in Alzheimer's disease and Parkinson disease. Two approaches to testing might include adaptation of the Alzheimer Disease Assessment Scale and inclusion of the P300 component of the event-related auditory evoked potential.

Alzheimer Disease↗
PubMed1983

Multimodality evoked potentials and neurophysiological tests in multiple sclerosis. Effects of hyperthermia on test results.

Data on critical frequency of photic driving (CFPD), frequency following response (FFR), and visual, somatosensory (peroneal nerve), and brain-stem auditory evoked potentials (EPs) were obtained from 20 patients who had clinically definite multiple sclerosis and ten healthy normal subjects in a controlled, balanced study under normothermic and hyperthermic (+1 degrees C) conditions with a test-retest interval of one week. Normal subjects' test results showed no changes during hyperthermia. Patients' EP and CFPD data correlated well with history, clinical signs, and symptoms during both normothermia and hyperthermia. The FFR test data were equivocal and not fully analyzed. Data from the four other tests showed additional patient abnormalities during hyperthermia. Multimodality testing increased the number of patient abnormalities compared with single tests, and the number increased further during hyperthermia. Test-retest reproducibility was higher during hyperthermia.

Adult↗