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Biomedical subjects

A Clark

Publications and source records attributed to A Clark.

At least 145 records · Page 8Linked to original sources
PubMed1996

An assessment of potential problems of home phototherapy treatment of psoriasis.

Very little has been reported about how patients use home ultraviolet B (UVB) phototherapy. A survey of thirty-one patients who were prescribed a home UVB phototherapy unit to treat psoriasis was performed as a pilot study of home UVB phototherapy usage; twenty-two patients responded. Generally, respondents reported home UVB phototherapy to be very helpful for their psoriasis. We conclude that home UVB is an effective and appropriate treatment for many patients with psoriasis, but screening and education of candidates for home UVB phototherapy is important to ensure compliance with the treatment program.

Adolescent↗
PubMed1995

Effect of pH and insulin on fibrillogenesis of islet amyloid polypeptide in vitro.

UNLABELLED: Islet amyloid polypeptide (IAPP) is the constituent of amyloid deposits in pancreatic islets of type 2 diabetes in man, monkeys, and cats. This 37 amino acid peptide aggregates in vitro to form beta-pleated sheet fibrils. Rodent IAPP has a different amino acid sequence and does not form amyloid either in vitro or in vivo. Fibrillogenic properties of human IAPP (hIAPP) were determined in vitro. The effect of pH and time course of fibril formation was studied by light scattering spectroscopy. Aggregation of hIAPP1-37NH2 and hIAPPTyr20-29 (0.25 mg/mL) was maximal at neutral/basic and acidic pH, respectively. The ultrastructure of hIAPP1-37NH2 fibrils (0.2 mg/mL) was examined using negative staining for electron microscopy. Short fibrils composed of 2 or more filaments were observed at pH 3-9 after 30 min incubation. At pH 7-9, IAPP fibrils formed a gel. After 6 months at pH 3, large sheets of parallel fibrils were seen. Specific binding of 125I-hIAPP1-37NH2 to preformed IAPP fibrils detected by quantitative autoradiography and radioassay was maximal at pH 3. Binding was enhanced by insulin (3.7 nmol/L) and unaffected by glucose, calcium, glucagon, and apolipoprotein E. 125I-hIAPP1-37NH2 bound specifically to islet amyloid in pancreatic tissue sections from type 2 diabetic patients. CONCLUSIONS: Binding to preformed IAPP fibrils is maximal at acid pH when hIAPP is largely in soluble form. IAPP is secreted together with insulin from the acidic secretory granules (pH 5.5) to the neutral pH of the extracellular space under normal conditions. These changes in pH together with increased accumulation of extracellular hIAPP in diabetes may promote amyloid formation.

Amino Acid Sequence↗
PubMed1995

High prevalence of pancreatic islet amyloid in patients with end-stage renal failure on dialysis treatment.

Islet amyloid polypeptide (IAPP) is the main proteinaceous component of pancreatic islet amyloid, which is a characteristic feature of type 2 diabetes. The factors responsible for amyloid deposition are unclear. Patients with end-stage renal failure (ESRF) on dialysis treatment have increased insulin resistance which is associated with hypersecretion of beta-cell products. Furthermore, elevated concentrations of circulating IAPP are found in these patients due to reduced renal clearance of IAPP. To determine the prevalence of islet amyloid in this group of patients, pancreas was examined from 23 non-diabetic [aged 62 (29-79) years, median and range] and four type 2 diabetic [aged 67 (56-72) years] patients with ESRF on dialysis treatment. Pancreatic specimens from 30 non-diabetic control subjects [aged 67.5 (56-86) years] and 14 type 2 diabetic subjects without renal disease [aged 69 (48-86) years] were used as control groups. Islet amyloid was present in all type 2 diabetic patients with ESRF and in 12 out of 14 type 2 diabetic control subjects (86 per cent). Amyloid deposits were found in 8 out of 23 non-diabetic patients with ESRF (35 per cent), which was a higher prevalence than that found in non-diabetic control subjects (3 per cent) (P < 0.01). This may be related to undiagnosed (pre)diabetes. Elevated secretion rates of IAPP due to insulin resistance and high circulating IAPP concentrations as a result of severely reduced renal clearance of IAPP will cause high pericellular concentrations of IAPP. This condition is likely to enhance amyloid fibril formation in pancreatic islets similar to that observed in type 2 diabetes.

Adult↗
PubMed1995

Mitochondrial DNA, diabetes and pancreatic pathology in Kearns-Sayre syndrome.

Mitochondrial DNA (mtDNA) mutations are associated with diabetes mellitus but their role in the onset of hyperglycaemia is unclear. A patient presented with diabetes requiring insulin therapy at the age of 7 years, followed by diagnosis of Kearns-Sayre syndrome (KSS). Beta-cell function was absent at age 19 years as shown by lack of glucose-stimulated C-peptide secretion. Following development of a cardiac conduction defect the patient died aged 21 years. Analysis of mtDNA in blood and several tissues revealed related re-arranged deletions, duplications and deletion dimers in addition to normal mtDNA with the highest levels of duplications in kidney and blood. Pancreatic tissue from the KSS patient was compared with tissue from an insulin-dependent diabetic patient with a similar clinical history of diabetes. Islets in KSS were small, regular in shape and contained predominantly glucagon-containing cells with no evidence of beta cells. In comparison, a small number of beta cells were present in some of the larger more irregularly-shaped islets from the insulin-dependent diabetic patient. These data together suggest that in KSS the loss of beta cells at the onset of diabetes is less disruptive to islet architecture: a small proportion of beta cells or their gradual destruction over a long period would allow retention of islet shape. Abnormal function of the re-arranged mtDNA could affect both development and function of pancreatic islet cells since glucose-stimulated insulin secretion is energy dependent.

Adult↗
PubMed1995

Pancreatic pathology in non-insulin dependent diabetes (NIDDM).

NIDDM is a heterogeneous disease and subgroups of NIDDM include MODY (Maturity Onset Diabetes of the Young), Malnutrition-related diabetes (MRDM) and Fibrocalculus pancreatic diabetes (FCPD). Endocrine cell population is relatively unchanged in NIDDM: B-cells are reduced by up to 30% and A-cells increased by 10%. Islet amyloid is found in 96% of subjects occupying up to 80% of the islet associated with a reduction in B-cells. Amyloid formation is unlikely to cause diabetes but progressive accumulation increases the severity of the disease. Islet amyloid is formed from the islet amyloid polypeptide (IAPP), a normal constituent of B-cells, co-secreted with insulin. The causal factors for IAPP fibrillogenesis are unknown but abnormal synthesis or overproduction could be involved: stimulation of B-cell secretion in NIDDM by obesity, hyperglycaemia or suphonylurea therapy may promote amyloidosis and further aggravate islet pathology. A mutation of the glucokinase gene in MODY leads to diminished B-cell secretion but not amyloid formation. Diabetes and mutations of mitochondrial DNA is associated with poorly developed islet structure. Exocrine pancreatic size is reduced and there is evidence of sub-clinical chronic pancreatitis in NIDDM. In MRDM and FCPD, chronic pancreatitis and exocrine necrosis is associated with reduced insulin secretion. Unlike cystic fibrosis where islet amyloid is present in diabetic individuals, amyloid is absent from subjects with FCPD. Pathological changes in the exocrine and endocrine pancreas in NIDDM results from and contributes to the pathophysiology of insulin secretion in NIDDM.

Amyloid↗
PubMed1995

Reflecting on reflection: a personal encounter.

This paper reports a retrospective study of a Senior Lecturer in Nursing Studies experience of supervising a student teacher who, as part of her teaching placement experience, utilised 'Critically Reflective Analysis of an Educational Event' as a means to assess her teaching in the practice setting. The Senior Lecturer and student nurse teacher used an external 'advisor' to facilitate their meta-reflection on the theoretical perspectives that informed the process in which they were engaged. The paper raises the following questions for consideration--What is the link between ability to reflect and quality of practice? Is it possible to utilise reflective tutorials as a means of assessing professional competence whilst at the same time encouraging personal and professional development? Is the ability to reflect on practice dependent on the context? Should we assume that all practitioners have the necessary skills to supervise students in practice and what preparation and support is needed? The paper demonstrates that by introducing 'Critically Reflective Analysis of an Education Event' into the student teachers' curriculum the role of both supervisor and student teacher was challenged and changed. The paper also demonstrates that reflective tutorials are not wholly a retrospective business. They are creative, or recreative of a teaching experience, as well as to some extent representing it. Finally, even if one cannot speak in Kuhnian parlance, of a conceptual revolution, it would seem legitimate to say, in Schon's terms, that the contextual frame in which professional problems are addressed has undergone significant change.

Education, Nursing, Baccalaureate↗
PubMed1995

Apert's syndrome and androgen receptor staining of the basal cells of sebaceous glands.

We report two cases of Apert's syndrome, each of whom developed the severe acne in adolescence which is a feature of this disorder. Both responded to isotretinoin therapy. Immunohistochemical techniques, using a mouse monoclonal antibody, were employed to stain sebocyte androgen receptors in the two patients, and in five controls. This showed no difference in the number of cells with androgen receptor expression between the patients with Apert's syndrome and controls. These results support the concept that the underlying problem in Apert's syndrome is an abnormal sensitivity to normal circulating levels of androgens, and not an excess number of androgen receptors.

Acne Vulgaris↗
PubMed1994

Perineal bladder neck ultrasound: appearances before and after continence surgery.

An objective method of quantifying suture tension during bladder neck elevation for genuine stress incontinence has long been sought. Perineal ultrasonography has been used to measure bladder neck position and excursion in continent and incontinent women. This study used perineal ultrasound findings to determine surgical positioning of the bladder neck and predict outcome. Eighteen asymptomatic controls and 72 women with genuine stress incontinence were studied before and after continence surgery. Perineal ultrasonography was used to plot bladder neck position at rest and on maximum Valsalva maneuver on an x, y co-ordinate system to allow comparison between groups. Logistic regression analysis was then performed to derive an equation for the likelihood of continence. In both pre-and postoperative analysis, the best correlation with continence was achieved with the use of the patient's age and the distance of the bladder neck resting position measured along the x-axis. An equation was derived to give the probability of continence. The equation is easily calculated using a pocket calculator. The distance of the bladder neck along the x-axis is under the direct control of the surgeon, so the patient's age can be put into the equation and the distance along the x-axis most likely to make the patient continent can be calculated. This can be done during surgery to provide an objective method for evaluating suture tension.

Journal Article↗
PubMed1994

Intra- and extracellular amyloid fibrils are formed in cultured pancreatic islets of transgenic mice expressing human islet amyloid polypeptide.

Islet amyloid polypeptide (IAPP) is the constituent peptide of amyloid deposits found in the islets of non-insulin-dependent diabetic patients. Formation of islet amyloid is associated with a progressive destruction of insulin-producing beta cells. Factors responsible for the conversion of IAPP into insoluble amyloid fibrils are unknown. Both the amino acid sequence of human IAPP (hIAPP) and hypersecretion of hIAPP have been implicated as factors for amyloid fibril formation in man. We have generated transgenic mice using rat insulin promoter-hIAPP or rat IAPP (rIAPP) gene constructs. No fibrillar islet amyloid was detectable in vivo in these normoglycemic mice, although small amorphous perivascular accumulations of IAPP were observed in hIAPP mice only. To determine the effects of glucose on IAPP secretion and fibrillogenesis, pancreatic islets from transgenic and control mice were examined in vitro. Islet IAPP secretion and content were increased in transgenic islets compared with control islets. IAPP-immunoreactive fibrils were formed at both intra- and extracellular sites in isolated hIAPP islets cultured with glucose at 11.1 and 28 mM for only 7 days. At 28 mM glucose, fibrils were present in deep invaginations of beta cells as observed in non-insulin-dependent diabetic patients. No fibrils were present at low glucose concentrations in hIAPP islets or at any glucose concentration in rIAPP or control islets. Thus, glucose-induced expression and secretion of hIAPP in transgenic mouse islets can lead to formation of amyloid fibrils similar to that found in non-insulin-dependent diabetes mellitus.

Amyloid↗
PubMed1994

Molecular physiology of the islet amyloid polypeptide (IAPP)/amylin gene in man, rat, and transgenic mice.

Islet amyloid polypeptide ("amylin") is the major protein component of amyloid deposits in pancreatic islets of type 2 (non-insulin-dependent) diabetic patients. Islet amyloid polypeptide consists of 37 amino acids, is co-produced and co-secreted with insulin from islet beta-cells, can act as a hormone in regulation of carbohydrate metabolism, and is implicated in the pathogenesis of islet amyloid formation and of type 2 diabetes mellitus. Rat islet amyloid polypeptide differs from human islet amyloid polypeptide particularly in the region of amino acids 25-28, which is important for amyloid fibril formation. In rat and mouse, diabetes-associated islet amyloid does not develop. To study the genetic organization and biosynthesis of islet amyloid polypeptide, we have isolated and analyzed the human and rat islet amyloid polypeptide gene and corresponding cDNAs. Both genes contain 3 exons, encoding precursor proteins of 89 amino acids and 93 amino acids, respectively. Apart from a putative signal sequence, these precursors contain amino- and carboxy-terminal flanking peptides in addition to the mature islet amyloid polypeptide. To understand regulation of islet amyloid polypeptide gene expression, we have identified several potential cis-acting transcriptional control elements that influence beta-cell-specific islet amyloid polypeptide gene expression. Using antisera raised against synthetic human islet amyloid polypeptide we developed a specific and sensitive radioimmunoassay to measure levels of islet amyloid polypeptide in plasma and tissue extracts. Also antisera raised against the flanking peptides will be used in studying human islet amyloid polypeptide biosynthesis. Elevated plasma islet amyloid polypeptide levels have been demonstrated in some diabetic, glucose-intolerant, and obese individuals, as well as in rodent models of diabetes and obesity. To examine the potential role of islet amyloid polypeptide overproduction in the pathogenesis of islet amyloid formation and type 2 diabetes, we generated transgenic mice that overproduce either the amyloidogenic human islet amyloid polypeptide or the nonamyloidogenic rat islet amyloid polypeptide in their islet beta-cells. Despite moderately to highly (up to 15-fold) elevated plasma islet amyloid polypeptide levels, no marked hyperglycemia, hyperinsulinemia or obesity was observed. This suggests that chronic overproduction of islet amyloid polypeptide "per se" does not cause insulin resistance. No islet amyloid deposits were detected in mice up to 63 weeks of age, but in every mouse producing human islet amyloid polypeptide (as in man), accumulation of islet amyloid polypeptide was observed in beta-cell lysosomal bodies. This may represent an initial phase in intracellular amyloid fibril formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1994

Medication effects on referent communication in schizophrenic patients: an evaluation with a structured task.

Objective measures of communication efficiency were collected twice on 10 schizophrenic patients while they participated in a structured interactive task which has seen considerable use in developmental studies of communication skills. Referential communication and thought disorder were assessed while patients were off and then on neuroleptic medication. While medicated, subjects produced more informative task-related responses. Drug-free subjects produced more unclear references and episodes of bizarre speech. These "interruptive" tendencies appeared to be a problem of dialogue maintenance and attentional focus, which improved with medication.

Adult↗
PubMed1994

A thermal clearance probe for continuous monitoring of cerebral blood flow.

Cortical thermal clearance provides a practical means of continuous assessment of cerebral blood flow. A probe which can be used to monitor cerebral cortical thermal clearance is described. It has proved a reliable method of predicting oligaemia, showing good correlation between measured thermal clearance and the onset of clinical signs of ischaemia. The limitations are its size, invasiveness, small sample volume and difficulty with quantification. It is a useful additional tool in the management of patients suffering from acute neurosurgical disorders.

Blood Flow Velocity↗
PubMed1994

Oral androgens in the treatment of hypogonadal impotent men.

A study was designed to assess the effect of supplemental oral methyltestosterone in the treatment of impotence associated with low total serum androgen levels. A total of 22 hypogonadal impotent men underwent a comprehensive investigation of erectile dysfunction, including an evaluation of the pituitary-gonadal axis. The patients then received a 1-month course of 2 different commercial preparations of oral methyltestosterone. Hormonal changes induced by the medication were assessed on days 15 and 30 of treatment. The patients kept daily records of sexual activity, and completed visual analogue scales to assess energy levels, mood and sensation of well being on a weekly basis. Supra-physiological levels of total serum testosterone were achieved in every patient but the free fraction of the hormone did not increase proportionally and in many cases a marked decrease was recorded. In all but 1 subject there was a decrease in circulating sex hormone binding globulin. Pituitary gonadotropin levels showed a marked decrease at the end of treatment. The clinical response was disappointing. Only 9% of the patients reported a complete recovery of sexual function. Visual analogue scales did not reveal noticeable changes for any individual in the levels of energy, mood or feeling of well being between pretreatment and posttreatment assessments. Oral methyltestosterone is of limited effectiveness in men with hypogonadal impotence. The positive responses in this study were recorded in men with the most profound deficiency. Exogenous administration of androgens to impotent men should be limited to those with profound hypogonadism as documented by at least 2 abnormal serum free testosterone determinations.

Administration, Oral↗
PubMed1994

Interactive communication between children: learning how to make language work in dialogue.

In this paper we investigate the development of interactive communication skills in 170 children aged seven to thirteen. Using a communication task that allows extended dialogues between pairs of young speakers, we are able to assess both the overall communicative success achieved by any pair; and from an analysis of the dialogues we can identify several interactive strategies that characterize older and more successful communicators. Successful communication involves the active involvement of both participants: asking and answering questions, volunteering information and responding sensitively to contributions from their partners. In contrast to the process of language acquisition, the development of these interactive skills takes place over an extended time period and subjects vary greatly in their ability to communicate effectively. For many analyses differences in the communicative success achieved by subjects differ more within than between age groups. For example, a substantial minority of our oldest subjects communicate no better than children six years younger.

Adolescent↗
PubMed1994

The syntactic role of pauses in the speech of schizophrenic patients with alogia.

This study examines the relation between alogia and pausing. The authors analyzed the flow of speech of 17 male schizophrenic patients during an interview, particularly the pauses that occurred within and between syntactic clauses and those that occurred as the turn switched from the interviewer's question to the patient's response. The strongest predictor of alogia ratings was the duration of switching pauses; the frequency of long within-clause pauses was also significantly related to alogia, but the frequency of between-clause pauses showed a trend toward a negative relation with alogia. Words following within-clause pauses were more likely to be content words than function words, and the content words were less frequent in the English language than the speaker's other words. This suggests that alogic patients have difficulty in word finding and in thought formulation, as well as a general increase in the duration of all pauses.

Adult↗