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Biomedical subjects

S Mitchell

Publications and source records attributed to S Mitchell.

At least 91 records · Page 5Linked to original sources

New variant Creutzfeldt-Jakob disease: psychiatric features.

BACKGROUND: An apparently new variant of Creutzfeldt-Jakob disease (CJD), new variant CJD (nvCJD), was identified in the UK in 1996. There have now been 21 cases of nvCJD in the UK and one in France. Psychiatric symptoms are prominent in the initial presentation in these cases. METHODS: Cases of nvCJD are identified mainly by direct referral from neurologists and neuropathologists. Detailed clinical information was obtained by review of case notes and interviewing patients' relatives. We report the psychiatric features of the first 14 cases on nvCJD in the UK. Psychiatric notes were examined in all 13 of these cases who were seen by a psychiatrist. RESULTS: Eight cases were women. All 14 cases had early psychiatric features and in nine, the first symptom was psychiatric. 13 cases were seen by a psychiatrist and the majority were diagnosed as suffering from depression or depression secondary to organic disease. Two cases suffered from first-rank symptoms suggestive of psychotic illness and transient delusions and auditory or visual hallucinations occurred in the majority. All cases were referred to a neurologist as the illness evolved and neurological signs developed. INTERPRETATION: Psychiatric symptoms are a consistent early clinical feature in nvCJD. Analysis of the psychiatric symptoms does not suggest specific features that readily allow distinction from more common psychiatric disorders, although the occurrence of associated persistent sensory symptoms may raise the possibility of this diagnosis. Neurological signs, including ataxia, involuntary movements and cognitive impairment developed in all cases and the evolution of increasing neurological deficits is likely to remain critical to the clinical diagnosis of nvCJD.

Adult↗

BAC and PAC contigs covering 3.5 Mb of the Down syndrome congenital heart disease region between D21S55 and MX1 on chromosome 21.

Chromosome 21 is a model for the study of human chromosomal aneuploidy, and the construction of its physical and transcriptional maps is a necessary step in understanding the molecular basis of aneuploidy-dependent phenotypes. To identify the gene(s) responsible for Down syndrome congenital heart disease (DS-CHD), we constructed a physical map of the D21S55 to MX1 region. A bacterial artificial chromosome (BAC) library was screened using several YACs spanning the interval, and a P1-derived artificial chromosome (PAC) library was screened using radiolabeled STS PCR products and whole BACs in gap-filling initiatives. FISH confirmed the location of all BAC and PAC clones to 21q22.2-q22.3. Overlaps were established using clone-to-clone Southerns and 24 new STSs, generated from the direct sequencing of BAC and PAC ends, along with 35 preexisting STSs. Approximately 3.5 Mb of the 4- to 5-Mb D21S55 to MX1 interval is covered in 85 BACs and 24 PACs, representing fourfold coverage within the contigs. These BAC and PAC contigs are valuable reagents for isolating the genes for DS-CHD.

Base Sequence↗

The effect of human endothelial cell-derived proteoglycans on human smooth muscle cell growth.

Extracellular proteoglycans (PGs) purified from cultured human arterial endothelial cells were tested for their effects on the proliferation of human vascular smooth muscle cells (VSMC). Fractions containing perlecan, the basement membrane heparan sulphate (HS) PG, the large chondrotin sulphate (CS) proteoglycan from connective tissue and other immunoreactive CS did not inhibit the proliferation of human VSMC. Native endothelial extracellular matrix, which was shown to contain the same PGs, demonstrated a pronounced stimulatory effect on the proliferation of human VSMCs. This stimulatory effect was not removed by pre-incubation of the matrix with 1 M NaCl, heparin, platelet extract or plasmin. These experiments demonstrate that PGs produced by human arterial endothelial cells do not inhibit the proliferation of VSMC. These data do not support the hypothesis that human endothelial cells, in vivo, control the activation or proliferation of VSMCs directly by the secretion of a non-proliferative molecule. Instead they support the hypothesis that the endothelial cells counteract intimal hyperplasia of VSMC indirectly by providing a barrier from activating factors in the plasma.

Arteries↗

Severe opioid toxicity and somatization of psychosocial distress in a cancer patient with a background of chemical dependence.

A case of severe opioid toxicity is described in a 52-year-old cancer patient. The patient presented with classical clinical features of central hyperexcitability associated with opioid toxicity: delirium, myoclonus, hallucinations, hyperalgesia, and a possible seizure. This patient had a background of severe psychosocial distress and somatization in addition to a history of benzodiazepine dependence and alcohol abuse. The occurrence of opioid toxicity in this patient highlights the risks of a unidimensional approach to cancer pain, which ignores the non-organic components of pain, such as psychosocial distress, which will not respond to escalating doses of opioid medication.

Alcoholism↗

Comparison of the gold reduction and stripping processes at platinum, rhodium, iridium, gold and glassy carbon micro- and macrodisk electrodes.

The gold AuIII + 3e(-)-->Au0 reduction and Au0-->AuIII + 3e- oxidation stripping processes in dilute aqua regia electrolyte (0.1 M HCl + 0.32 M HNO3) were examined at platinum, rhodium, iridium, gold and glassy carbon disk electrodes. After ascertaining that the preferred material was platinum, the effect of electrode size was evaluated by using nine different platinum disk electrodes having diameters ranging from 2 to 2000 microns. The optimum analytical response was obtained with a 50 microns diameter platinum disk electrode. With this electrode diameter, a sharp symmetrical gold stripping peak was obtained and the deposition process occurred predominantly under conditions of radial diffusion so that stirring of the solution was not required. In contrast, larger sized platinum electrodes produced a broader, asymmetric stripping response for the gold oxidation peak, whereas electrodes of smaller diameter provided poorer signal-to-noise ratios. The limit of detection and limit of quantification were calculated to be 4.4 x 10(-7) M (86 ppb) and 13.1 x 10(-7) M (258 ppb), respectively, at the 50 microns diameter platinum disk electrode under conditions of linear sweep stripping voltammetry at a scan rate of 200 mV s-1 and a 140 s deposition time. The optimum electrode gave a very well defined gold oxidation signal with negligible background current when applied to the determination of gold in a gold ore sample.

Electrochemistry↗

Symmetry of neurological signs in Pakistani patients with probable inherited spastic cerebral palsy.

Seven Pakistani families are described with children manifesting a spastic cerebral palsy-like syndrome. One feature common to all affected patients was symmetry of neurological signs. Only one of these families had been offered genetic counselling and fewer than half had undergone clinical investigations. The importance of symmetry of neurological signs is reaffirmed as an indicator of a probable genetic aetiology in children with spasticity. Many families at risk of recurrence are not offered appropriate genetic advice, and some children with potentially diagnosable conditions are given a label of cerebral palsy without investigation of possible underlying inherited disorders.

Age of Onset↗

Discontinuation symptoms after treatment with serotonin reuptake inhibitors: a literature review.

BACKGROUND: The discontinuation of many pharmacologic agents is associated with characteristic withdrawal symptoms. Antidepressants, particularly the tricyclic antidepressants (TCAs), are known to be associated with a group of common symptoms upon discontinuation. Serotonin reuptake inhibitors (SRIs) are also taking their respective place in the literature with reports of discontinuation symptoms. This review summarizes case reports and reports that allow systematic assessment of discontinuation symptoms following SRI discontinuation. METHOD: A computerized literature search was conducted using a MEDLINE search to identify reports of withdrawal effects following discontinuation of SRIs. Additional reports were found in the bibliographies of various published reports. RESULTS: SRI discontinuation symptoms in adults are summarized in 24 case reports and 9 reports from controlled clinical trials. Additionally, 3 case reports addressing SRI discontinuation in the neonate are described. The reports describe clusters of symptoms commonly associated with the discontinuation of an SRI. CONCLUSION: We propose to define an antidepressant discontinuation syndrome as the onset of a cluster of somatic and psychic symptoms following the discontinuation of an SRI and not attributable to other causes (e.g., concomitant medication, illness). These symptoms include dizziness, light-headedness, insomnia, fatigue, anxiety/agitation, nausea, headache, and sensory disturbance. The syndrome may last up to 3 weeks and may be improved by restarting the antidepressant or starting an antidepressant with a similar pharmacologic profile.

1-Naphthylamine↗

Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer.

PURPOSES/OBJECTIVES: To test the hypothesis that women participating in a walking exercise program during radiation therapy treatment for breast cancer would demonstrate more adaptive responses as evidenced by higher levels of physical functioning and lower levels of symptom intensity than women who did not participate. DESIGN: Experimental, two-group pretest, post-test. SETTING: Two university teaching hospital outpatient radiation therapy departments. SAMPLE: 46 women beginning a six-week program of radiation therapy for early stage breast cancer. METHODS: Following random assignment, subjects in the exercise group maintained an individualized, self-paced, home-based walking exercise program throughout treatment. The control group received usual care. Dependent variables were measured prior to and at the end of radiation therapy. In addition, symptoms were assessed at the end of three weeks of treatment. MAIN RESEARCH VARIABLES: Participation in the walking exercise program, physical functioning fatigue, emotional distress, and difficulty sleeping. FINDINGS: Hypothesis testing by multivariate analysis of covariance, with pretest scores as covariates, indicated significant differences between groups on outcome measures (p < 0.001). The exercise group scored significantly higher than the usual care group on physical functioning (p = 0.003) and symptom intensity, particularly fatigue, anxiety, and difficulty sleeping. Fatigue was the most frequent and intense subjective symptom reported. CONCLUSIONS: A self-paced, home-based walking exercise program can help manage symptoms and improve physical functioning during radiation therapy. IMPLICATIONS FOR NURSING PRACTICE: Nurse-prescribed and -monitored exercise is an effective, convenient, and low-cost self-care activity that reduces symptoms and facilitates adaptation to breast cancer diagnosis and treatment.

Adult↗

Treatment-emergent changes in sexual function with selective serotonin reuptake inhibitors as measured with the Rush Sexual Inventory.

Rates of antidepressant-associated treatment emergent changes in sexual function and satisfaction vary with method of ascertainment. We used the Rush Sexual Inventory (RSI) to assess the effect of SSRIs on sexual function and satisfaction. The RSI is a comprehensive, succinct, patient-rated scale designed to provide an accurate depiction of premorbid, current, and followup changes in sexual function and satisfaction. We assessed 42 outpatients, diagnosed with major depressive disorder with or without comorbid obsessive-compulsive disorder, over their first 8 weeks of treatment with paroxetine 20 mg/day, sertraline 50-200 mg/day, or fluoxetine 20-60 mg/day. Males and females were found to experience similar rates of treatment emergent sexual dysfunction at 60 percent and 57 percent, respectively. Despite the same mechanism of action, medication treatment groups experienced varying levels of changes in sexual function and satisfaction over time. No variation existed between responders and nonresponders over time.

1-Naphthylamine↗

Ventral pallidostriatal pathway in the monkey: evidence for modulation of basal ganglia circuits.

This study describes the organization of the ventral and dorsal pallidostriatal pathway in the monkey. Both retrograde and anterograde tracers were injected into various regions of the ventral and dorsal pallidum as well as into the striatum. The data indicate that the pallidostriatal pathway is an extensive pathway in the monkey. The projections are organized in a topographic manner preserving a general, but not strict medial-to-lateral and ventral-to-dorsal organization. The terminal arrangement of pallidostriatal fibers is widespread. Non-adjacent pallidal regions send fibers to the striatum which overlap considerably, suggesting convergence of terminals from different pallidal regions. The pallidostriatal pathway is found to have a reciprocal but also a large non-reciprocal component to the striatopallidal pathway. On the basis of these data it is concluded that segregation of different corticobasal ganglia-cortical pathways is maintained in the striatopallidal direction as described earlier (Haber et al. [1990] (J. Comp. Neurol. 293:282-298). However, the pallidostriatal projection to a large region of the striatum allows the modulation of several cortico-basal ganglia circuits.

Animals↗

Molecular cloning of MADM: a catalytically active mammalian disintegrin-metalloprotease expressed in various cell types.

A peptide sequence of a metalloprotease purified from bovine brain [Chantry, Gregson and Glynn (1989) J. Biol. Chem. 264, 21603-21607] was used to design an oligonucleotide probe for screening a bovine brain cDNA library. A contig of the two overlapping cDNA clones that were isolated encoded a 748-amino-acid polypeptide with similarity to the disintegrin-metalloprotease precursor proteins of haemorrhagic snake venom. The bovine protein has been named MADM, for mammalian disintegrin-metalloprotease. The predicted mature protein has 534 amino acids arrayed as extracellular metallo-protease and disintegrin (potential integrin-binding) domains, a transmembrane helix and a basic/proline-rich cytoplasmic C-terminus. Highly conserved homologues of bovine MADM were found in cDNA libraries of rat brain and a human U937 histiocytic lymphoma cell line. A wide variety of mammalian cell lines expressed low levels of MADM mRNA (4.5 and 3.2 kb transcripts) and mature polypeptide (M(r) 62000), as assessed by Northern analysis and Western blotting with an antiserum raised to a peptide within the disintegrin domain. MADM appears to be a rather distantly related member of the reprolysin protein family, which includes both the snake venom disintegrin-metalloproteases and a number of predicted cell-surface disintegrin-containing mammalian proteins.

Amino Acid Sequence↗

Rapid high-performance liquid chromatographic assay for atovaquone.

A rapid high-performance liquid chromatography assay has been developed for the drug atovaquone, which is currently being used to treat Pneumocystis carinii pneumonia and Toxoplasma gondii encephalitis associated with the acquired immunodeficiency syndrome (AIDS). Protein is precipitated from plasma with acetonitrile-aqueous 1% acetic acid (85:15). The supernatant is assayed on a C6 column using methanol-10 mM triethylamine in aqueous 0.2% trifluoroacetic acid (76:24) with detection at 254 nm. The working assay range was 0.5 to 50 micrograms/ml. Recovery was 97% and the between-day coefficients of variation were 2.1% at 50 micrograms/ml and 10.3% at 1 microgram/ml. A number of drugs commonly used to treat AIDS and its complications did not interfere with the assay.

Acquired Immunodeficiency Syndrome↗

6-OHDA lesions of the nucleus accumbens accentuate memory deficits in animals with lesions to the forebrain cholinergic projection system: effects of nicotine administration on learning and memory in the water maze.

The separate and combined effects of lesions to the forebrain cholinergic projections system (FCPS) and to dopamine (DA) terminals in the nucleus accumbens (n.acc) were assessed in two water maze tasks: (1) standard acquisition using two trials/day with a 10 min intertrial interval (ITI) for 15 days with the platform in the same position and (2) a working memory task requiring matching to a platform position located by chance on Trial 1, with four trials/day separated by a 30-s ITI and a different platform position on each of 4 days. Effects of nicotine (0.1 mg/kg) were also examined in animals with FCPS, n.acc, and combined lesions in order to determine whether facilatory effects of nicotine in FCPS lesioned animals are mediated by dopamine release in the n.acc. The FCPS and combined lesion groups were impaired in both tasks, but the combined lesion group was substantially worse than animals with FCPS lesions alone. The n.acc lesion group did not differ from controls. Nicotine did not affect acquisition in either the FCPS or combined lesion group, but impaired learning in animals with n.acc lesions. In the working memory task nicotine exerted a nonspecific facilatory effect in the FCPS and combined lesion groups, by reducing latency to find the platform both on the first trial and on the subsequent matching to position trials. Choline acetyltransferase (ChAT) activity was reduced in hippocampus and cortex in the FCPS lesion group, whereas DA levels in n.acc were increased. Conversely, in the n.acc lesion group accumbal DA levels were reduced, while cortical and hippocampal ChAT activity was increased, suggesting that reciprocal changes were induced by the separate lesions. However the combined lesion group showed mixed and more widespread effects; ChAT activity was unaltered in cortex and substantially reduced in hippocampus, and DA levels were reduced in both n.acc and caudate. The results indicate that combined FCPS and n.acc lesions impair spatial learning and working memory far more severely than FCPS lesions alone, although this does not reflect simple additive reductions in DA and ChAT activity. Nicotine improved spatial search strategy, and effect detected in the in the working memory task with daily changes in platform position, rather than in the standard acquistion task, but did not appear specifically to improve working memory. Since the facilitatory effect of nicotine was seen in both FCPS and combined lesion groups, the findings suggest that nicotine-induced improvements do not depend on accumbal DA release.

Animals↗