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Biomedical subjects

D Griffiths

Publications and source records attributed to D Griffiths.

At least 55 records · Page 3Linked to original sources

Malignant degeneration of a mature cystic teratoma five decades after discovery.

Malignant degeneration of mature cystic teratomas has been reported in 1-3% of cases. A patient with the unusual occurrence of a stage IIIC squamous cell carcinoma arising in a mature teratoma over 50 years after initial diagnosis is presented. The patient was treated with pelvic radiotherapy. The role of serum squamous cell carcinoma antigen in detecting degeneration of mature cystic teratomas at an early stage is considered.

Aged↗

Basics of pressure-flow studies.

Pressure-flow studies of voiding contain information about urethral resistance or obstruction and about the detrusor contraction or contractility. A fundamental problem, discussed in this paper, is how to disentangle these two. A second, more difficult, problem is how to evaluate them in a simple, clinically useful way. Plots of detrusor pressure against flow rate during the course of voiding offer a helpful adjunct to conventional urodynamic curves showing changes with time. Many ways of assessing urethral obstruction from these plots have been proposed that have somewhat differing aims but, in practice, produce rather similar results. Agreement on a standard method is needed to allow the comparison of results obtained in different centers. Detrusor contractility has been less extensively studied but methods for assessing it are available.

Humans↗

Costs and management of urinary incontinence in long-term care.

The three aims of the study were (1) to assess the impact and cost of urinary incontinence in long-term care, (2) to determine whether 24-hour incontinence monitoring provides information that improves management, and (3) to ascertain whether costs (nursing time and laundry) could be reduced. The setting was two 24-bed long-term care units in an urban hospital. The research was conducted in three stages. During the initial stage, the impact of incontinence was measured on each unit. Impact was defined as total number of incontinent episodes, nursing time spent changing these patients, and laundry costs, measured during a 7-day period on each unit. After this phase of the investigation, individualized 24-hour incontinence monitoring, followed by recommendations and implementation of care plan, was carried out on one unit. No monitoring or recommendations for care were completed on the other unit, which served as a control. During the third phase of the study, the number of incontinent episodes, nursing time, and laundry costs were again measured on both units. Initially (58%) of residents (24/48) were incontinent, representing 859 episodes of urinary leakage each week that required 45 hours of nursing time to change clothing, containment devices, and bed linens. The direct costs of the nursing time and laundry, expressed in Canadian dollars were $8.60/day per incontinent resident. After 24-hour monitoring of 10 residents one on unit, suggestions were made for various incontinence management programs. An unexpected but simple recommendation was a change to a better containment system for urinary leakage. When impact was measured, a 13% reduction in the number of incontinent episodes was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Ultrastructural changes resulting from keratin-9 gene mutations in two families with epidermolytic palmoplantar keratoderma.

Palmoplantar keratoderma of Voerner type (or epidermolytic palmoplantar keratoderma) is an autosomal dominant inherited disorder of keratinization with histologic features of epidermolytic hyperkeratosis. We studied members of two large unrelated kindreds with epidermolytic palmoplantar keratoderma, and biopsy specimens of lesional palmar skin from both families confirmed the histologic changes of epidermolytic hyperkeratosis. Whorls of abnormally aggregated keratin filaments were seen ultrastructurally to be associated with signs of cellular disintegration in spinous and granular cells. Direct sequencing of genomic DNA samples obtained from several members of each family established the substitution of a highly conserved arginine by tryptophan (R162W) in the 1A region of the alpha-helical rod domain of keratin 9. This arginine residue in a highly conserved region of keratins 1 and 10 is affected by disruptive missense point mutations in many patients with bullous ichthyosiform erythroderma. An equivalent position in the sole and palm restricted keratin 9 appears to be the mutation hot spot in epidermolytic palmoplantar keratoderma. To date, R162W is the most prevalent genetic defect reported in this genodermatosis.

Base Composition↗

Long-term changes in urodynamic studies of voiding in the elderly.

Urodynamic studies were conducted in 80 incontinent elderly patients (27 men and 53 women; mean age, 77 years) and repeated 2-4 weeks later after patients had been subject to interventions. Interpretable voiding studies were performed in 84% of sessions. Interpretable initial and repeat studies were performed in 74% of patients. For detrusor pressure at maximum flow the intra-individual, between-sessions variability was +/- 11.7 cm H2O (SD) and the initial-repeat correlation coefficient was 0.61. For maximum flow rate the corresponding figures were +/- 4.7 ml/s and 0.44. Mean residual urine volume was 195 ml, with a between-sessions variability of +/- 113 ml (SD). These results suggest that there is substantial long-term variability in voiding function, including urethral resistance. Of the mean, 5% showed a change in obstruction classification (unobstructed/obstructed) between sessions. This variability and the modest proportion of interpretable studies should be taken into account when assessing urethral obstruction and designing clinical trials.

Aged↗

Cerebellopontine angle epithelial cyst. A case report.

A case of epithelial cyst in the cerebellopontine angle is reported. The cyst wall showed glandular epithelium with areas of non-keratinized stratified epithelium and flattened cuboidal cells. The glandular areas stained positively with antibodies to cytokeratin. In addition, the cyst wall contained areas of arachnoid tissue. This, and the unusual position of the cyst, suggest that the epithelial elements in the cyst wall may be metaplastic in origin. Similar previously described cysts were considered to be endodermal in origin.

Adult↗

Biosensors--what real progress is being made?

Biosensors have been hailed as the solution to many analytical problems in a wide range of industries. The heterogeneity of the proposed markets is equalled by that of the technologies called 'biosensors'. The many research groups worldwide are prolific in their publication of research papers and patents. Clearly, the field is not limited by a lack of information regarding the fundamental technology. However, there are, as yet, few successful commercial biosensor products available. The principle constraints on the commercial realization of such products concern the technical and manufacturing feasibility, market development and investment strategies. Whilst commercially viable biosensors will certainly emerge eventually, the timescale is longer than many would wish.

Biosensing Techniques↗

Inappropriate circumcision referrals by GPs.

One hundred and twenty boys were referred by GPs over a 12-month period to a paediatric urologist for circumcision. The reasons for referral were: ballooning in 36, non-retraction in 28, balanoposthitis in 36 or a combination in 15. On examination 53% had a retractile, 21% a partially retractile and 21% a non-retractile foreskin. Six patients had obvious balanitis xerotica obliterans. Only one quarter of the patients required a circumcision. The penis was not examined by the referring doctor in 15 patients. The implications of this survey are that a large proportion of general practitioners have difficulty in discriminating between a true phimosis and a developmentally non-retractile foreskin. This diagnostic inaccuracy was greatest when the referring doctor did not examine the patient.

Adolescent↗

Nitrous oxide sedation causes post-hyperventilation apnoea.

We have studied, in six normal subjects, the effect of nitrous oxide sedation on the ventilatory pattern and oxygen saturation using pulse oximetry (SpO2) after hyperventilation to an end-tidal carbon dioxide partial pressure (PE'CO2) of 3 kPa. This value of PE'CO2 was shown to be less than the apnoeic threshold of all these subjects when their ventilation vs PE'CO2 response curves were plotted. All subjects became apnoeic when told to relax following hyperventilation while breathing 75% nitrous oxide for 90 s. Apnoea was defined as cessation of breathing for 20 s or more. The mean duration of apnoea was 78 s (range 29-130 s). All subjects demonstrated arterial desaturation (mean SpO2 75%, range 44-87%). In contrast, following hyperventilation with air, no apnoea was seen in any subject, although there was some evidence of desaturation (mean SpO2 92.5%, range 88-98%). It was concluded that subjects who are sedated with nitrous oxide behave similarly to those who are anaesthetized rather than to those who were fully conscious, in that they become apnoeic below the apnoeic threshold point. The reduction in SpO2 after hyperventilation was explained almost entirely by apnoea and may explain abnormalities of respiratory control and hypoxaemia in patients recovering from general anaesthesia or sedation accompanied by hypocapnia. This mechanism may be of importance in obstetric patients after breathing Entonox, when apnoea and hypoxaemia may reduce oxygen delivery to the fetus.

Adult↗

The complement-inhibiting protein, protectin (CD59 antigen), is present and functionally active on glomerular epithelial cells.

Protectin (CD59 antigen) is a 20-kD phosphatidyl-inositol-linked membrane protein that inhibits formation of the membrane attack complex (MAC) of complement on homologous cells. Although the antigen has been identified in a number of human tissues, until recently a functional role had been demonstrated only in circulating cells. Using immunofluorescence techniques we have shown the presence of protectin on human glomerular epithelial cells (GEC) in culture and on GEC, tubular epithelial cells and endothelial cells in frozen sections of normal human renal cortex. In addition, we present evidence that this protein functions in protection of GEC from homologous complement: cultured cells incubated with the Fab2 fragment of a monoclonal anti-protein antibody were markedly more susceptible to killing by homologous serum than were cells in the absence of Fab2 anti-protectin. These findings suggest that this protein may be important in the maintenance of glomerular integrity in vivo, and may be of relevance in certain renal diseases.

Animals↗

Asymptomatic hypothyroidism and hypercholesterolaemia.

Hypothyroidism is a cause of secondary hyperlipidaemia. This study investigates the frequency of biochemically diagnosed hypothyroidism and its relationship with plasma cholesterol concentration in apparently healthy people. Thyroid function tests (total T4, TSH, and free T4) were performed on 272 apparently healthy men and women (179 vegetarians, 93 meat eaters) with a plasma cholesterol concentration above 7 mmol/l and on 90 individuals with a plasma cholesterol below 4.1 mmol/l who were matched for age, sex and dietary habits. Six per cent of those with a plasma cholesterol above 7 mmol/l had biochemical evidence of hypothyroidism as defined by a TSH greater than 10 mIU/l (reference range 1-6) and a low free T4 below 10 pmol/l (reference range 10.1-25). Eighty per cent of these people had a high titre of thyroid anti-microsomal antibodies. Of the 90 individuals with a plasma cholesterol level below 4.1 and the 25 randomly selected participants none had biochemical evidence of hypothyroidism. Hypothyroidism is relatively common in apparently healthy people with a raised plasma cholesterol. It appears no commoner in vegetarians than in meat eaters.

Adult↗

Nitrendipine once or twice daily in hypertensive non-insulin-dependent diabetes mellitus.

Twenty (12 male, 8 female) hypertensive patients were recruited into the study; their mean (+/- SD) sitting blood pressure (BP) was 166 +/- 13/101 +/- 4 mm Hg, age 59.6 +/- 5.8 years, weight 83.4 +/- 14.2 kg, and glycosylated hemoglobin (HbA1) 9.9 +/- 2.6%. After a run-in period of 4 weeks, patients were randomized to receive nitrendipine once or twice daily, with 15 patients completing the 12-week study period. Prior to treatment with nitrendipine, the patients subsequently treated on a twice-daily regimen had a higher sitting systolic BP (SBP) of 173 +/- 15 mm Hg compared to the once-daily patient group at 159 +/- 7 mm Hg (p less than 0.05). There were no differences between the two treatment groups in weight or diabetes control. Once-daily nitrendipine effectively reduced the sitting SBP and diastolic BP (DBP), i.e., SBP fell from 159 +/- 7 to 147 +/- 12 mm Hg (p less than 0.05) and DBP fell from 100 +/- 4 to 86.3 +/- 8 mm Hg (p less than 0.001). Nonsignificant reductions in weight from 81.5 +/- 11.3 to 80.9 +/- 11.2 kg and HbA1 from 9.8 +/- 3.3 to 8.4 +/- 1.3% were also seen. Similarly, with twice-daily nitrendipine, a significant (p less than 0.01) fall in sitting systolic BP from 173 +/- 15 to 148 +/- 9 mm Hg and DBP 103 +/- 4 to 85 +/- 8 mm Hg was also achieved. Little or no change was observed in weight or glycemic control in this patient group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives.

A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.

Administration, Oral↗