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Biomedical subjects

N Gordon

Publications and source records attributed to N Gordon.

At least 37 records · Page 2Linked to original sources

Muscular strength and physical function.

PURPOSE: The purpose of this study was to evaluate the potential association of muscular strength and endurance at baseline with the prevalence of functional limitations at follow-up. METHODS: Study participants were 3,069 men and 589 women (30-82 yr) who received a clinical examination including a strength evaluation at the Cooper Clinic between 1980 and 1989 and responded to a 1990 mail-back survey. Participants also had to achieve at least 85% of their age-predicted maximal heart rate on a maximal exercise treadmill test and have no history of heart attack, stroke, diabetes, high blood pressure, cancer, or arthritis at their first visit. A strength index composite score (0-6) was calculated using age- and sex-specific tertiles from bench press, leg press, and sit-up tests. Those scoring 5 or 6 were categorized in the high strength group. Functional health status was assessed by responses to questions about the participant's ability to perform light, moderate, and strenuous recreational, household, daily living, and personal care tasks. RESULTS: After an average follow-up of 5 yr, 7% of men and 12% of women reported at least one functional limitation. A logistic regression model including age, aerobic fitness, body mass index, and new health problems at follow-up found that, relative to those with lower levels of strength, the odds of reporting functional limitations at follow-up in men and women categorized as having higher levels of strength were 0.56 (95%CI = 0.34, 0.93) and 0.54 (95%CI = 0.21, 1.39), respectively. CONCLUSIONS: These findings, if replicated in other populations, suggest that maintenance of strength throughout the lifespan may reduce the prevalence of functional limitations.

Activities of Daily Living↗

Carbohydrate-deficient glycoprotein syndromes.

Four types of carbohydrate-deficient glycoprotein syndrome have been described, and the cause of two of them has been found. The symptoms and signs of these syndromes are described, with variations that occur at different ages. The commonest is type Ia with an autosomal recessive form of inheritance, and the gene responsible has been mapped to 16p. The typical pathology is atrophy of the cerebellum and brainstem, sometimes also involving the cortex, although both the pathology and the biochemical deficiencies vary between different types of syndrome. The diagnosis depends firstly on recognising the clinical features, including the presence of complications such as thyroid disorders. Then biochemical tests can be carried out, especially chromatographic carbohydrate-deficient transferrin assay and isoelectric focusing of serum transferrin. The prognosis depends on the complications, renal, hepatic, and cardiac, but affected children will be severely handicapped. Therefore treatment consists mainly of coping with the complications, and supporting the child and the family. Oral infusion of mannose can be effective in type Ib disease.

Adult↗

Retinoid signaling in immortalized and carcinoma-derived human uroepithelial cells.

This paper investigates the presence and functionality of retinoid signaling pathways in human urinary bladder carcinoma and SV40-immortalized uroepithelial cell lines. Only two of eight cell lines were proliferation-inhibited by 10 microM of either all-trans or 13-cis-retinoic acid. Transactivation of the CAT gene under control of a retinoid-responsive element demonstrated functionality of the signaling pathway in both sensitive cell lines and four of six resistant cell lines. Relative RT-PCR analysis of a panel of retinoid-responsive and inducible genes demonstrated changes in expression levels of all the genes in response to-retinoic acid treatment together with numerous aberrations dysregulations. We conclude that retinoid signaling may be a target for inactivation during tumorigenesis by uncoupling gene expression, proliferation and differentiation. Therefore retinoids are more likely to be effective for chemoprevention than for treatment of bladder carcinomas.

Apoptosis↗

The role of botulinus toxin type A in treatment--with special reference to children.

Although botulinum toxin A was first introduced to treat strabismus and blepherospasm it is now used in an increasing number of conditions, many in the field of pediatrics. Its action results from a prevention of the release of acetylcholine from nerve terminals. A number of studies recording the effects of the toxin in the treatment of spastic cerebral palsy are reviewed, and although these can be criticized, there seems to be no doubt that it can be of benefit. It is few side effects, but it may reveal an underlying weakness. Other disadvantages are its cost and the need for repeated injections. It can be used for the relief of rigidity, although the effects in the extrapyramidal form of cerebral palsy are not so dramatic. Also it can be beneficial in some forms of dystonia, rarely if this is generalized, but certainly if it is focal, and especially if there is accompanying pain. There are several conditions seen in children, such as strabismus, blepherospasm and tremors, in which this form of treatment will rarely be indicated; but they will be mentioned. An exception may be spasmodic torticollis during adolescence if it does not respond to other therapy, as it is so disabling. Botulinum toxin can be used to block the discharges from cholinergic sympathetic and parasympathetic terminals. Focal hyperhidrosis can be very distressing among older children, and the use of the toxin should sometimes be considered in this and other autonomic disorders.

Autonomic Nervous System Diseases↗

The acute porphyrias.

The various types of acute porphyria are discussed, as well as their mode of inheritance and the enzyme deficiencies responsible for the symptoms. The symptoms and signs of an acute attack are then described, especially those due to neuropathies and to disturbances of behaviour. Agents which can precipitate attacks are listed. These are most frequently drugs, and as they include those used for anti-epileptic treatment problems soon arise as seizures often occur in this condition. The main complications are hypertension and renal failure, and examples of hyponatraemia and folate deficiency are illustrated. The urgency to diagnose this disorder lies in the need to avoid precipitating factors. Screening tests are discussed, and those needed to confirm the diagnosis. The prognosis has improved over the years, due to increased awareness of the disorder, and better management. During an acute attack the treatment of pain and vomiting will be of particular importance, and then haematin or chelating agents can be tried. With better management most of those who have inherited acute porphyria should be able to lead a normal life.

Acute Disease↗

Treating depression in staff-model versus network-model managed care organizations.

OBJECTIVE: To compare primary care providers' depression-related knowledge, attitudes, and practices and to understand how these reports vary for providers in staff or group-model managed care organizations (MCOs) compared with network-model MCOs including independent practice associations and preferred provider organizations. DESIGN: Survey of primary care providers' depression-related practices in 1996. SETTING AND PARTICIPANTS: We surveyed 410 providers, from 80 outpatient clinics, in 11 MCOs participating in four studies designed to improve the quality of depression care in primary care. MEASUREMENTS AND MAIN RESULTS: We measured knowledge based on depression guidelines, attitudes (beliefs about burden, skill, and barriers) related to depression, and reported behavior. Providers in both types of MCO are equally knowledgeable about treating depression (better knowledge of pharmacologic than psychotherapeutic treatments) and perceive equivalent skills in treating depression. However, compared with network-model providers, staff/group-model providers have stronger beliefs that treating depression is burdensome to their practice. While more staff/group-model providers reported time limitations as a barrier to optimal depression treatment, more network-model providers reported limited access to mental health specialty referral as a barrier. Accordingly, these staff/group-model providers are more likely to treat patients with major depression through referral (51% vs 38%) or to assess but not treat (17% vs 7%), and network-model providers are more likely to prescribe antidepressants (57% vs 6%) as first-line treatment. CONCLUSIONS: Whereas the providers from staff/group-model MCOs had greater access to and relied more on referral, the providers from network-model organizations were more likely to treat depression themselves. Given varying attitudes and behaviors, improving primary care for the treatment of depression will require unique strategies beyond enhancing technical knowledge for the two types of MCOs.

Chi-Square Distribution↗

New variant Creutzfeldt-Jakob disease.

It is now recognised that new variant Creutzfeldt-Jakob disease (CJD) can present during adolescence, so it may be within the experience of any paediatrician. Some observations on prion proteins are made, and some of the features of classical CJD are reviewed. Reports of patients with new variant CJD are given. The possible links between this condition and bovine spongiform encephalopathy (BSE) are considered, especially the finding that certain people who are homozygous for methionine at codon 129 of the prion protein may be particularly susceptible to this infection. The diagnosis of new variant CJD can be difficult. Early sensory and psychiatric symptoms can be suggestive, so can the initial signs of ataxia and involuntary movements. The EEG does not help in this variety. Although not specific some serum and CSF tests may give diagnostic support. It has been claimed that tonsillar biopsy may confirm the diagnosis, but this often necessitates brain biopsy; or the diagnosis may only be made at autopsy. Beliefs about the way infections spread will have to be modified, and more must be learnt about the nature of prions, how they enter the body, and how they spread in the brain.

Adolescent↗

Characterization of large-pore polymeric supports for use in perfusion biochromatography.

Perfusion chromatography is uniquely characterized by the flow of a portion of the column eluent directly through the resin in the packed bed. The benefits of this phenomenon and some of the properties of perfusive resins have been described before, and can be summarized as enhanced mass transport to interior binding sites. Here we extend the understanding of this phenomenon by comparing resins with different pore size distributions. Resins are chosen to give approximately the same specific pore volumes (as shown in the characterization section) but the varying contribution of large pores is used to control the amount of liquid flowing through the beads. POROS R1 has the largest contribution of throughpores, and therefore the greatest intraparticle flow. POROS R2 has a lower contribution of throughpores, and a higher surface area coming from a greater population of diffusive pores, but still shows significant mass transport enhancements relative to a purely diffusive control. Oligo R3 is dominated by a high population of diffusive pores, and is used comparatively as a non-perfusive resin. Although the pore size distribution can be engineered to control mass transport rates, the resulting surface area is not the only means by which binding capacity can be controlled. Surface coatings are employed to increase binding capacity without fundamentally altering the mass transport properties. Models are used to describe the amount of flow transecting the beads, and comparisons of coated resins to uncoated (polystyrene) resins leads to the conclusion that these coatings do not obstruct the throughpore structures. This is an important conclusion since the binding capacity of the coated product, in some cases, is shown to be over 10-fold higher than the precursor polystyrene scaffold (i.e., POROS R1 or POROS R2).

Algorithms↗

Accelerated recombinant protein purification process development automated, robotics-based integration of chromatographic purification and analysis.

Recovery of recombinant proteins from endogenous, host molecules can be an experimentally intensive and time-consuming task. Often the time to analyze material during development of recovery procedures is the rate-limiting step. Nowadays, modern techniques and equipment are being specifically engineered to make this effort much more efficient. We present a case study to illustrate how a new, automation tool, designed for easy, systematic methods development, can be used for very rapid process and analytical optimization. This tool uses robotics to integrate process development with rapid LC-based analysis requiring no user intervention. The methods and procedures described can be generalized to any recombinant protein recovery campaign.

Chromatography, High Pressure Liquid↗

Some influences on cognition in early life: a short review of recent opinions.

Many factors can affect a child's ability to learn, and these may operate before, during, and after birth. Some of these are considered, and are hopefully important, but not necessarily the most obvious. The intrauterine environment may not be so influential as the infant's genetic endowment, but nevertheless is of considerable importance. For example, malnutrition resulting from placental insufficiency leading to small-for-date babies can impair brain development. Also a relationship between birth weight and cognitive function in early adult life has been demonstrated; and the babies' condition at birth can be a risk factor for various disabilities. Lack of stimulation in infancy, for example if postnatal depression interferes with the mother's interaction with her baby, can significantly affect the infant's learning capacity. A good paradigm is the development of language, which starts with the way mothers 'talk' to their babies; and this continues into childhood. The importance of nutrition also continues, and is one of the factors which favours breast feeding against formula foods. The whole subject has to be viewed against the background of normal development, and the great loss of neurons and synapses that occur in early life. If neural circuits are formed at this time, and these neurons and synapses are not lost, the easier it will be to exploit them. This emphasizes the importance of early education, which is not always sufficiently acknowledged.

Brain↗

A diagnostic in vitro urine assay for interstitial cystitis.

OBJECTIVES: A low molecular weight urine factor that inhibits the proliferation of normal bladder epithelial cells in vitro was previously shown to be present significantly more often in the urine of patients with interstitial cystitis (IC) than in the urine of asymptomatic age-, race-, and sex-matched control subjects. We sought to determine the specificity of this finding for IC by determining whether the urine of patients with other urogenital inflammatory disorders also contains a factor that inhibits bladder epithelial cell proliferation. METHODS: Urine was collected from women with IC, acute bacterial cystitis, or vulvovaginitis, as well as from asymptomatic control women. The proliferation of primary normal adult bladder epithelial cells was determined by measuring 3H-thymidine incorporation in vitro. RESULTS: Osmolality- and pH-corrected urine specimens from 50 (86%) of 58 women with IC significantly inhibited human bladder epithelial cell proliferation compared with 3 (8%) of 36 asymptomatic control women, 7 (12%) of 58 women with bacterial cystitis, and 0 (0%) of 12 women with vulvovaginitis (P < 0.001 for the comparison of mean percent change in 3H-thymidine incorporation with IC urine versus urine from each of the control groups). Optimal sensitivity and specificity values of 91.4% and 90.6%, respectively, were achievable at a cutoff of 25% inhibition of 3H-thymidine incorporation, using all three control groups. CONCLUSIONS: The measurement of urine antiproliferative activity may be a useful noninvasive means for diagnosing IC in women.

Adult↗

Episodic ataxia and channelopathies.

Clinical details are given of different types of episodic ataxia: type 1, with myokymia, and attacks which usually last a few minutes, and may occur several times a day, and treatment with acetazolamide can reduce the number of attacks; type 2, with interictal nystagmus, and attacks which last for several hours to a day or more, and treatment with acetazolamide is very effective; paroxysmal choreoathetosis with episodic ataxia, with attacks lasting for about 20 min and occurring at varying intervals; and familial hemiplegic migraine, with transient hemiplegia presenting during the aura of a migraine headache, the symptoms improving on treatment with acetazolamide. Their inheritance is of dominant type; and the gene for type 1 is mapped to chromosome 12p near to a cluster of potassium channel genes, and that for type 2 and for familial hemiplegic migraine to chromosome 19p near to calcium channel genes. The differential diagnosis from other conditions with a periodic symptomatology is discussed, especially from a number of metabolic disorders. Treatment is effective for many of these, and the treatment of the episodic ataxias with acetazolamide can sometimes have a dramatic effect. The possible role of the channelopathies in the causation of some periodic neurological disorders is considered; with the expectation that further research will improve the identification of specific diseases, and lead to more effective treatment.

Acetazolamide↗