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Biomedical subjects

N Gordon

Publications and source records attributed to N Gordon.

At least 55 records · Page 3Linked to original sources

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↗

Arthrogryposis multiplex congenita.

The common factor causing congenital arthrogryposis is lack of fetal movements. This can result from a large number of disorders. They may be neuropathic, affecting the brain, the spinal cord, or the peripheral nerves; they may be abnormalities of the muscles, such as myasthenia gravis, congenital muscular dystrophies or mitochondrial cytopathies; they may be diseases of the connective tissues; or they may be conditions which limit the space within the uterus; or they may result from defects of the uterine environment. These are discussed in turn. Typical clinical findings are given and it is emphasised that the arthrogryposis is often a manifestation of certain syndromes, some the result of abnormal chromosomes. Although it is not within the scope of this review article to describe these in detail, examples are given. In particular the subgroup of distal arthrogryposes and amyoplasia are considered. The importance of trying to define a cause is especially the need to give reliable genetic advice to the parents and also to establish a prognosis. The diagnosis will often be made by the associated symptoms and signs, and sometimes by tests such as electromyography and muscle biopsy. Although some of the diseases will be fatal early in life, there are many instances when the child will survive into adult life; if due attention is given to the treatment, particularly orthopedic procedures, and to social and educational management. This can only be done realistically if there is a good idea of the natural history of the condition underlying the arthrogryposis.

Arthrogryposis↗

Thermographic imaging in the beating heart: a method for coronary flow estimation based on a heat transfer model.

Intraoperative thermographic imaging in open-chest conditions can provide the surgeon with important qualitative information regarding coronary flow by utilizing heat transfer analysis following injection of cold saline into the aortic root. The heat transfer model is based on the assumption that the epicardial temperature changes are mainly due to convection of heat by the blood flow, which may, therefore, be estimated by measuring the temperature variations. Hearts of eight dogs were exposed and imaged by a thermographic camera. Flow in the left arterial descending (LAD) coronary branch was measured by a transit-time flowmeter. 20 ml of cold saline were injected into the aortic root (just after the aortic valve) and the epicardial temperature images were recorded at end-diastole, for 20-30 s. Different flow rates were achieved by 1 min occlusion of the LAD, which affected a reactive hyperemic response. The dynamics of the temperature in the arterial coronary tree was obtained by averaging the temperature over an edge-detected arterial segment for each frame. The heat transfer equation was curve-fitted, and the flow-dependent heat transfer index was correlated with the experimentally determined coronary flow (r = 0.69, p < 0.001). In summary: a method for quantitative estimation of coronary blood flow by thermography and heat transfer analysis was developed and tested in animal experiments. This method can provide important information regarding coronary blood flow during open-chest surgical procedures.

Animals↗

Colour blindness.

The physiology of colour vision is discussed; as is the way in which the human eye can detect various combinations of red, green and blue. Red-green colour blindness, with X-linked inheritance, is the most common, but other types are also considered. Methods of testing relating to the age of the child are reviewed. The use of colours in teaching is widespread, but there is controversy over the difficulties this may cause a colour blind child. A review of the literature does not reveal much information on this, and any problems that do arise are likely to be individual to the child, and to depend on such factors as overall intelligence, the attitude of the teacher, and the personality of the child. There is not doubt that it is essential to recognise colour vision defects when it comes to choosing a career, and that tests must be done during secondary schooling, but in order to avoid some affected children being disadvantaged there is enough evidence to support testing at school entry.

Child↗

Estimation of coronary blood flow by ECG gated cardiac thermography in open-chest conditions.

Thermography is suggested as a tool to estimate myocardial and coronary epicardial flow in open-chest heart surgery. To test the feasibility and compare various methods for coronary flow estimation in open-chest surgery, thermographic imaging was applied to eight open-chest dogs which were injected with cold saline into the aortic root. Blood flow in the left arterial descending (LAD) coronary vessel was measured by a transit-time flowmeter. ECG gated images were acquired for 20-30 s, while the cold saline (20 ml) was injected into the aortic root. Several flow levels were achieved during repeated hyperaemic response to transient occlusions of the LAD. A temperature response curve for each flow level was obtained by averaging over an edge-detected arterial segment for each image frame. Several indices were calculated from the temperature curve and correlated with the measured coronary flow. These include: an index based on a corrective heat transfer model (r = 0.69, p < 0.001), the slope of the descending part of the response curve (r = 0.76, p < 0.001), the peak temperature difference (r = 0.66, p < 0.001), and the area above the temperature response curve (r = 0.61, p < 0.01). As shown, coronary flow can be estimated quantitatively by intraoperative epicardial thermography, and may therefore provide important on-line information regarding blood flow during open-chest surgical procedures. Further studies are required for optimal application of this technique so as to increase its potential as a valid clinical tool.

Animals↗

Multidimensional chromatography coupled with mass spectrometry for target-based screening.

The synthesis of structural analogs and the process of drug discovery have evolved dramatically through recent advances in solid-phase synthesis reagents and automated screening systems. As molecular diversity strategies emerge, the need for automated target-based selection of lead candidates becomes equally important. Multidimensional automated chromatographic techniques coupled to electrospray ionization mass spectrometry facilitate the selection process and provide maximum characterization information in a single screening run. The capture of tightly bound affinity leads by target biomolecules, followed by subsequent release and high-resolution separation with sensitive detection, significantly reduces the time required to identify and characterize lead compounds. This automated multidimensional chromatographic approach coupled with mass spectrometry, Selectronics, was used with several organic and natural libraries to demonstrate an automated target-based screening technique to select for high-affinity binders as potential lead compounds.

Amino Acid Isomerases↗

Nutrition and cognitive function.

The work of the Medical Research Council Dunn Nutrition Unit, Cambridge, on the influence of early diet on the development of preterm infants is reviewed. Then further consideration is given to the implication of the findings. Malnutrition during a sensitive period may result in disease in adult life, and studies strongly suggest the development of the brain and retina can be affected. This may be due to the lack of essential fatty acids, and will particularly involve premature babies born at a time when cell membrane development is especially vulnerable. These findings must sometimes be viewed with caution, as genetic and environmental influences can be paramount. There are many reasons to favour breast feeding, rather than giving formula feeds, including improved cognition and visual function. For example breast milk contains docosahexaenoic acid and arachidonic acid, essential for normal brain development, and often absent or in short supply in formula feeds. Although the advantages in developmental status may be due, in part anyhow, to factors such as the mother's ability and education, and to the child being given greater opportunities, the evident importance of the composition of human breast milk cannot be denied. Formula feeds do contain a higher nutrient value than breast milk, which can result in improved height and weight of infants fed in this way: if it is necessary to use them the challenge for future research is to improve their composition. Although this may be of more importance for premature babies, term babies can also be affected; this has both medical and social implications.

Adolescent↗

The Landau-Kleffner syndrome: increased understanding.

The Landau-Kleffner and the continuous spike and wave discharges during slow sleep (CSWS) syndromes are described and possible links between the two are discussed. They certainly overlap, with clinical and electroencephalographic features in common. Potential causes are discussed. There is seldom a definite reason for the seizures but it way well be that the spike and wave discharges seen in the EEG, whatever their origin, may disrupt the development of language and cognitive function at a critical stage. If neurons and axons are involved in this disorganized activity they surely cannot perform normally. The evidence that these discharges in the Landau-Kleffner syndrome can have a focal origin in areas important for language supports this hypothesis. Certain variations among studies quoted may be due to factors such as age of onset, the duration of the paroxysmal activity, its intensity and especially its localization. Also, if development has been distorted subsequent progress is likely to be disturbed after the primary condition has ceased to exist. The diagnosis can sometimes present difficulties, for example from deafness, psychiatric condition, post-ical dysphasia and from progressive degenerative neurological disorders. If the possible role of the epileptic activity is accepted, there are strong reasons for advocating anti-epileptic treatment, even if overt seizures are rare. The response to drugs is varied. Fits will usually stop, but not so often the spike and wave discharges, and it is justifiable to try various regimes. Subpial resection has been reported to be successful, possibly by preventing the cortex generating seizures, and their spread.

Child↗

Medication misadventures resulting in emergency department visits at and HMO medical center.

Medication misadventures resulting in visits to the emergency department of a health maintenance organization (HMO) were studied. The records of patients who visited the emergency department at a California HMO between August 1992 and August 1993 were evaluated for evidence of medication misadventures brought to the department. The definition of misadventure included noncompliance and inappropriate prescribing but excluded intentional overdoses and substance abuse. If it seemed probable that a misadventure occurred, a pharmacist interviewed the patient by telephone. During the 12-month study, 1,074 (1.7%) of 62,216 visits to the emergency department were due to medication misadventures. The patients who had had a misadventure were predominantly female (62%); 38% were 15-44 years of age and 33% were 65 or older. Interviews were possible with 962 patients. Only 30.6% of the patients had a good understanding of the potential adverse effects of their regimen, and only 29.0% had a good understanding of the potential interactions. Misadventures were most often due to allergies or medication underuse among patients < or = 14 years of age and to adverse effects and inappropriate dosage in elderly patients. Of the 1,074 misadventures, 152 (14.1%) resulted in hospital admission. Three areas of particular concern were identified (1) noncompliance with respiratory agents in the young, (2) nonsteroidal anti-inflammatory use leading to hospital admission, and (3) the frequency of problems in the elderly. Medication misadventures accounted for 1.7% of emergency department visits and 1.0% of hospital admissions at an HMO medical center.

Adolescent↗

Heterotopic pregnancy after ovulation induction and assisted reproductive technologies: a literature review from 1971 to 1993.

OBJECTIVE: To review and analyze records on heterotopic pregnancy occurring after ovulation induction and assisted reproductive technologies. DATA IDENTIFICATION: Case reports in the English literature related to the topic were identified through a computerized bibliography search up to December 1993. CONCLUSIONS: The incidence of heterotopic pregnancies increased in recent years because of the escalating use of new reproductive technologies in infertile patients and has stabilized at approximately 1:100 pregnancies with these procedures. The main reasons for development of such a condition in these patients are past tubal or pelvic disease and multiple ovulations or multiple ET. Progress has been made in diagnosis of heterotopic pregnancy during the last two decades, mainly because of development of ultrasonographic techniques, especially transvaginal ultrasonography. Treatment of heterotopic pregnancy should be prompt to avoid maternal morbidity and mortality from extensive intraperitoneal bleeding. No increased intrauterine fetal mortality due to hemoperitoneum has been proven in the present review, except in advanced cornual pregnancies. More experience is needed for application of new treatment modalities such as salpingocentesis, which are used successfully for ectopic pregnancy, in treatment of heterotopic pregnancy. With early diagnosis and skillful treatment, the outcome of the intrauterine pregnancy is favorable and its survival rate should increase in the future.

Female↗