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Biomedical subjects

M Schwartz

Publications and source records attributed to M Schwartz.

At least 163 records · Page 9Linked to original sources

The use of botulinum toxin for the treatment of temporomandibular disorders: preliminary findings.

PURPOSE: The aim of this study was to evaluate the response of patients with temporomandibular disorders to Botulinum toxin A (BTX-A) therapy. METHODS: The 15 subjects enrolled in this uncontrolled study were diagnostically categorized and treated with 150 units of BTX-A. Both masseter muscles received 50 units each under eletromyographic (EMG) guidance. Similarly, both temporalis muscles were injected with 25 units each. Subjects were assessed at 2-week intervals for 8 weeks. Outcome measures included subjective pain by visual analog scale (VAS), measurement of bite force, interincisal opening, tenderness to palpation, and a functional index based on multiple VAS. RESULTS: All mean outcome measures, with the exception of bite force, showed a significant (P = .05) difference between the preinjection assessment and the four follow-up assessments. No side effects were reported. CONCLUSIONS: BTX-A injections produced a statistically significant improvement in four of five measured outcomes, specifically pain, function, mouth opening, and tenderness. No statistically significant changes were found in mean maximum voluntary contraction or in paired correlation of factors such as age, sex, diagnosis, depression index, or time of onset.

Administration, Cutaneous↗

Angiographic criteria reliably predict when carotid endarterectomy can be safely performed without a shunt.

BACKGROUND: Selective shunting during carotid endarterectomy is widely performed, but the optimal approach for predicting when a shunt is unnecessary remains uncertain. We evaluated the ability of preoperative cerebral angiography to predict when carotid endarterectomy could be safely performed without a shunt. STUDY DESIGN: Eighty-seven patients undergoing carotid endarterectomy between August 1991 and December 1997 had preoperative cerebral angiograms. The angiograms were evaluated for the presence of collateral flow from the contralateral carotid through the anterior communicating artery and from the posterior circulation through the posterior communicating artery. Patients then underwent endarterectomy and were selectively shunted based on somatosensory evoked potential changes. Internal carotid artery stump pressure was routinely measured in all patients. RESULTS: Nine patients (10%) had a shunt placed based on somatosensory evoked potential changes and none of the 87 patients had a perioperative (30 days) stroke. Angiography revealed that 36 patients (41%) had no cross-filling from the contralateral carotid through the anterior communicating artery. Nine of these patients (25%) required a shunt; none of the 51 patients with adequate cross-filling (p < 0.001) did. Furthermore, 94% of the patients without cross-filling but with a patent ipsilateral posterior communicating artery did not require a shunt using somatosensory evoked potential changes as the standard for shunt insertion. Stump pressure measurements (> or = 25 mmHg) or (> or = 50 mmHg) did not reliably exclude the need for a shunt. Only 2 of 15 patients with contralateral carotid occlusion and 1 of 16 patients with a prior ipsilateral stroke required shunts. CONCLUSIONS: In the presence of cross-filling from the contralateral carotid artery, shunt insertion was uniformly unnecessary. In addition, routine shunting of patients with previous ipsilateral strokes or contralateral carotid occlusion was not always necessary. Stump pressures were less sensitive than angiographic criteria in determining when a shunt was unnecessary. Evaluation of cross-filling from the contralateral carotid artery on preoperative angiography can predict with certainty which patients will not require a shunt.

Aged↗

'Axogenic' and 'somagenic' neurodegenerative diseases: definitions and therapeutic implications.

Neurodegenerative diseases are characterized by a relentless loss of specific groups of neuronal subtypes. Many of these diseases share similar molecular mechanisms and extracellular mediators of neuronal loss. We now suggest that neurodegeneration originating in the neuronal cell bodies (e.g. in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis) should be distinguished from that originating in the axons (e.g. in glaucoma, certain peripheral neuropathies and spinal stenosis). We propose that the former group of diseases be defined as 'somagenic' and the latter as 'axogenic'. Although axogenic disorders may share common symptoms and mediators of toxicity with somagenic disorders, they have distinct temporal, subcellular and signal-transduction features. We further suggest that, by adopting this classification of disorders based on pathophysiological processes, we will come to recognize additional diseases (in particular, those defined as axogenic) as being neurodegenerative and therefore possibly amenable to neuroprotective therapy.

Axonal Transport↗

EMG related anxiety and pain: a prospective study.

BACKGROUND: Electromyography (EMG) is a useful test, but unfortunately also painful. We frequently encounter patients who worry about its painful nature, but tolerate it very well. OBJECTIVES: We evaluated anxiety levels of patients referred for EMG to explore the possible correlating and contributing factors to high anxiety. METHODS: A structured questionnaire, including the State-Trait Anxiety Inventory was completed by patients immediately before EMG testing. Emergency, hospitalized, and seriously ill patients were excluded. RESULTS: Seventy-nine cases with ages ranging from 19-72 years (mean 43) were included. Thirty-five (44%) patients had a high pre-test anxiety level. The likelihood of high anxiety was increased if the patient was worried about the test (p < 0.001) or about other issues unrelated to the test or underlying diagnosis (p < 0.001), or was taking an anti-psychotic or anxiolytic drug (p = 0.008). The degree or source of knowledge regarding the test procedure, did not affect the pre-test anxiety level. CONCLUSIONS: The information about EMG testing received by patients in this group did not affect pre-test anxiety levels. The patient's expectations regarding the test did influence anxiety levels and this may reflect generalized anxiety regarding testing procedures or misinformation regarding the nature of the test, as patients in general reported a better than anticipated experience following the test.

Adult↗

Epidemiologic correlates of serum folate and homocysteine levels among users and non-users of vitamin supplement.

Lower serum folate and higher serum homocysteine levels are known risk factors for various conditions. Thus, epidemiologic correlates with these measurements were studied for 256 multivitamin users and 230 non-users who were middle-aged women. Both serum folate and homocysteine levels increased with advancing age in both multivitamin users (P < 0.01 and P < 0.01) and non-users (P = 0.08 and P < 0.01). Among non-users, higher intake of vegetables, fruits, cold cereals and total protein were associated positively with serum folate and inversely with homocysteine levels. There were 25-74% increases in serum folate and 10-15% decreases in serum homocysteine between 1st and 4th quartiles of intake of these food/nutrients. In addition, 26% lower serum folate and 18% higher serum homocysteine were observed for those smoking 20 or more cigarettes per day compared with non-smokers. Among multivitamin users, body weight was correlated inversely with serum folate (P < 0.01) and positively with serum homocysteine levels (P = 0.04), while no correlates were found among lifestyle factors. Regular use of multivitamins increased serum folate about fourfold and decreased homocysteine twofold. These results suggest that multivitamin use can offset the effects of an unhealthy lifestyle on these serum markers, and that levels of serum folate and homocysteine can also be favorably influenced by healthier diet and abstinence from smoking.

Adult↗

Haptic perception of the distance walked when blindfolded.

The ability to detect the distance walked when blindfolded using only haptic information generated by the walking activity was investigated. Participants walked a straight path until told to stop, turned, and attempted to return to their starting point. The path was completely featureless. Counting was prevented. Blindfolded, sighted participants traveled with a long cane or a trained sighted guide. Gait was varied or distorted. In all experiments the return distance was a linear function of the set distance, with some participants giving and some conditions resulting in remarkably sensitive performances. The magnitude of errors was a linear function of step length.

Adult↗

Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy.

Autoimmunity to antigens of the central nervous system is usually considered detrimental. T cells specific to a central nervous system self antigen, such as myelin basic protein, can indeed induce experimental autoimmune encephalomyelitis, but such T cells may nevertheless appear in the blood of healthy individuals. We show here that autoimmune T cells specific to myelin basic protein can protect injured central nervous system neurons from secondary degeneration. After a partial crush injury of the optic nerve, rats injected with activated anti-myelin basic protein T cells retained approximately 300% more retinal ganglion cells with functionally intact axons than did rats injected with activated T cells specific for other antigens. Electrophysiological analysis confirmed this finding and suggested that the neuroprotection could result from a transient reduction in energy requirements owing to a transient reduction in nerve activity. These findings indicate that T-cell autoimmunity in the central nervous system, under certain circumstances, can exert a beneficial effect by protecting injured neurons from the spread of damage.

Amino Acid Sequence↗

Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study.

Accumulating evidence suggests that folate, which is plentiful in vegetables and fruits, may be protective against colorectal cancer. The authors have studied the relationship of baseline levels of serum folate and homocysteine to the subsequent risk of colorectal cancer in a nested case-control study including 105 cases and 523 matched controls from the New York University Women's Health Study cohort. In univariate analyses, the cases had lower serum folate and higher serum homocysteine levels than controls. The difference was more significant for folate (P < 0.001) than for homocysteine (P = 0.04). After adjusting for potential confounders, the risk of colorectal cancer in the subjects in the highest quartile of serum folate was half that of those in the lowest quartile (odds ratio, OR = 0.52, 95% confidence interval, CI = 0.27-0.97, P-value for trend = 0.04). The OR for the highest quartile of homocysteine, relative to the lowest quartile, was 1.72 (95% CI = 0.83-3.65, P-value for trend = 0.09). In addition, the risk of colorectal cancer was almost twice as high in subjects with below-median serum folate and above-median total alcohol intake compared with those with above-median serum folate and below-median alcohol consumption (OR = 1.99, 95% CI = 0.92-4.29). The potentially protective effects of folate need to be confirmed in clinical trials.

Aged↗

Carbohydrate-deficient glycoprotein syndrome type 1A: expression and characterisation of wild type and mutant PMM2 in E. coli.

We have identified the PMM2 genotypes of 22 unrelated Danish patients with carbohydrate-deficient glycoprotein syndrome type 1A: R141H/F119L (18), R141H/C192G (1), F119L/F119L (1), F119L/G117R (1) and D223E/T237R (1). The lack of patients homozygous for R141H is statistically highly significant, but unexplained. In order to investigate the effect of PMM2 mutations on phosphomannomutase (PMM2) activity, PMM2-cDNA was cloned into a pET3a vector. Following introduction of mutations into PMM2-cDNA by site-specific mutagenesis, wild type and mutant PMM2-cDNA were expressed in E. coli Bl21(DE3) cells, and the activity of PMM2 was determined by an enzymatic assay using mannose 1-phosphate as substrate. Recombinant R141H, G117R, and T237R PMM2 had no detectable catalytic activity, and the F119L PMM2 had 25% of the activity of the wild type. The activity of the C192G and D223E PMM2 was in the normal range, but the affinity for their substrate was lower, and the proteins were more sensitive to increased temperatures. Each patient has at least one mutation which retains residual PMM2 activity. Our results support the hypotheses that a genotype conveying residual PMM2 catalytic activity is required for survival, and that homozygosity for R141H impairs PMM2 to a degree incompatible with life.

Acyl Carrier Protein↗

Rapid and simple determination of hereditary haemochromatosis mutations by multiplex PCR-SSCP: detection of a new polymorphic mutation.

Hereditary haemochromatosis is a common inherited disorder leading to excessive accumulation of iron in various organs. Two missense substitutions at the HFE-gene have recently been associated with the disease, 187C G and 845G-->A (mutations H63D and C282Y, respectively). We present a simple, rapid PCR-SSCP multiplex screening method allowing the simultaneous detection of both substitutions. Furthermore, testing the method on 420 Danish blood donors revealed the presence of a hitherto undetected third substitution in 13 individuals. The new substitution, a 193A-->T transversion, affects codon 65 changing the code for serine to that of cysteine (S65C). It may thus have functional consequences for the HLA class protein encoded by the HFE-gene. The allele frequencies observed were: H63D 14.8%, C282Y 6.2% and S65C 1.5%, which for the two former alleles are in agreement with frequencies reported for other North European population samples.

Adolescent↗

Effect of pentachlorophenol (PCP) on frog cornea epithelium.

Pentachlorophenol (PCP) is a toxic substance that affects many tissues adversely. Present experiments, using an in vitro preparation, were designed to study whether PCP affected the electrophysiological parameters of the bullfrog cornea epithelium, specifically, the Na+/K+ ATPase pump and the K+ conductance located in the basolateral membrane and the Cl- conductance located in the apical membrane. For this purpose, corneas were impaled with microelectrodes and experiments were done under short-circuit current (Isc) conditions. Addition of PCP to a concentration of 5 x 10-5 M to the tear solution gave a marked decrease in Isc; a marked depolarization of the intracellular potential, Vo; and minimal but significant decreases in the apical membrane fractional resistance, fRo, and in the transepithelial conductance, gt. Isc experiments in Cl--free solutions with amphotericin B in the tear solution confirm results indicating that PCP inhibits the active transepithelial transport mechanism and produces a small increase in the basolateral membrane resistance due to a decrease in the K+ conductance.

Amphotericin B↗

Efficacy of providing nicotine in a liquid diet to rats.

To determine if rats would consume nicotine at psychoactive levels, a nutritionally balanced diet with 0, 20, 60, or 200 mg of nicotine tartrate per kg of diet was provided. Diet consumption and body weight differences were recorded for 14 days after which, following 16 hr of withdrawal, animals were given access to a two-bottle choice of the previously presented diet and a nicotine-free diet. Spontaneous horizontal motor activity was recorded 8, 16, and 24 hr after withdrawal. By Day 14, all animals showed a significant increase in diet consumption and significant weight gain compared to Day 1. Animals consumed an average of 2.1, 6.8, or 19.5 mg/kg/day of nicotine on the low, medium, and high-nicotine diets, respectively. However, animals receiving the high-nicotine diet consumed less diet and gained less weight than the control, low, and medium nicotine groups. During only the first 4 hr of the two-bottle choice (16-20 hr postwithdrawal), the high-nicotine group consumed significantly higher amounts of nicotine base than the other groups, but also consumed more of the control diet during the first 2 hr. In a replicate experiment, animals receiving the medium-nicotine diet showed an increased consumption of the nicotine diet and increased preference for nicotine following a 14-day exposure compared to the control-fed animals and compared to a baseline preference test. Also, this group showed differences in locomotor activity consistent with other studies using an injection regimen or subcutaneuos pumps to induce dependence. Finally, animals in all three groups exhibited high plasma nicotine and cotinine (a major nicotine metabolite) levels. Because animals in all groups tolerated the diet well, gained weight, selected the nicotine diet in a choice test, and showed withdrawal symptoms, we conclude that the liquid diet proved to be a satisfactory method of inducing nicotine dependence in rats.

Administration, Oral↗

Differential T cell response in central and peripheral nerve injury: connection with immune privilege.

The central nervous system (CNS), unlike the peripheral nervous system (PNS), is an immune-privileged site in which local immune responses are restricted. Whereas immune privilege in the intact CNS has been studied intensively, little is known about its effects after trauma. In this study, we examined the influence of CNS immune privilege on T cell response to central nerve injury. Immunocytochemistry revealed a significantly greater accumulation of endogenous T cells in the injured rat sciatic nerve than in the injured rat optic nerve (representing PNS and CNS white matter trauma, respectively). Use of the in situ terminal deoxytransferase-catalyzed DNA nick end labeling (TUNEL) procedure revealed extensive death of accumulating T cells in injured CNS nerves as well as in CNS nerves of rats with acute experimental autoimmune encephalomyelitis, but not in injured PNS nerves. Although Fas ligand (FasL) protein was expressed in white matter tissue of both systems, it was more pronounced in the CNS. Expression of major histocompatibility complex (MHC) class II antigens was found to be constitutive in the PNS, but in the CNS was induced only after injury. Our findings suggest that the T cell response to central nerve injury is restricted by the reduced expression of MHC class II antigens, the pronounced FasL expression, and the elimination of infiltrating lymphocytes through cell death.

Animals↗

Injury-induced gelatinase and thrombin-like activities in regenerating and nonregenerating nervous systems.

It is now widely accepted that injured nerves, like any other injured tissue, need assistance from their extracellular milieu in order to heal. We compared the postinjury activities of thrombin and gelatinases, two types of proteolytic activities known to be critically involved in tissue healing, in nonregenerative (rat optic nerve) and regenerative (fish optic nerve and rat sciatic nerve) neural tissue. Unlike gelatinases, whose induction pattern was comparable in all three nerves, thrombin-like activity differed clearly between regenerating and nonregenerating nervous systems. Postinjury levels of this latter activity seem to dictate whether it will display beneficial or detrimental effects on the capacity of the tissue for repair. The results of this study further highlight the fact that tissue repair and nerve regeneration are closely linked and that substances that are not unique to the nervous system, but participate in wound healing in general, are also crucial for regeneration or its failure in the nervous system.

Animals↗

A phase I study of chemoembolization with cisplatin, thiotepa, and lipiodol for primary and metastatic liver cancer.

Thirty patients with primary hepatocellular carcinoma or liver metastases were entered into a program of chemoembolization with cisplatin, lipiodol, and escalating doses of thiotepa. Doses of cisplatin were 100/m2, and thiotepa doses ranged from 9 mg/m2 to 24 mg/m2. Two of three patients with ocular melanoma had partial responses in the liver metastases for 3+ and 16 months. In patients with either hepatocellular carcinoma (15 patients) or primary cholangiocarcinoma of the liver (three patients), there were two partial responses, for 22 and 33 months. Five patients had minor responses: four with a 40% reduction in tumor and one with a mixed response. There were four early deaths, which involved sepsis in two patients, respiratory failure in one, and acute myocardial infarction in one. Otherwise, toxicity was tolerable and reversible and included abdominal pain and transient elevation of serum creatinine, bilirubin, and transaminases. Less common toxicities included ototoxicity and peripheral neuropathy. Chemoembolization of the liver with cisplatin, thiotepa, and lipiodol can produce responses, but toxicity can be significant. The recommended starting phase II dose for future studies is thiotepa 24 mg/m2 and cisplatin 100 mg/m2.

Adult↗

Potential repair of rat spinal cord injuries using stimulated homologous macrophages.

The failure of the adult mammalian central nervous system (CNS) to regenerate after injury has long been viewed as a unique phenomenon resulting from the specific nature of this system. The finding that some CNS axons could be induced to regrow if provided with a permissive environment suggested that this failure is a result, at least in part, of the nature of the postinjury neuronal environment. It was further shown that the involvement of inflammatory cells, particularly macrophages, in postinjury processes in the CNS is limited. We have suggested that, to achieve recovery after injury, the adult mammalian CNS may require the assistance of the same postinjury factors as those involved in the recovery of spontaneously regenerating systems but that its accessibility to such assistance is restricted. Accordingly, we proposed that it might be possible to circumvent the restriction, allowing regeneration to occur. We showed that the implantation of autologous macrophages, which had been prestimulated by exposure to a regenerative (sciatic) nerve, into completely transected spinal cords of adult rats led to partial motor recovery. This treatment intervenes in the postinjury process by simulating in the axotomized CNS the events that occur naturally in spontaneously regenerating systems.

Animals↗

Self-consistent expansion for the Kardar-Parisi-Zhang equation with correlated noise.

A minor modification of the self-consistent expansion (SCE) for the Kardar-Parisi-Zhang (KPZ) system with uncorrelated noise is used to obtain the exponents in systems where the noise has spatial long-range correlations. For d-dimensional systems with correlations of the form D((-->)r-(-->)r',t-t')=2D(0)/(-->)r-(-->)r'/2 rho-d)delta(t-t'), (rho>0), we find a lower critical dimension d(0)(rho)=2+2 rho, above which a perturbative Edwards-Wilkinson (EW) solution appears. Below the lower critical dimension two solutions exist, each in a different, distinct region of rho. For small rho's the solution of KPZ with uncorrelated noise is recovered. For large rho's a rho-dependent solution is found. The existence of only one solution in each region of rho is not a result of a competition between two solutions but a direct outcome of the SCE equation.

Journal Article↗