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Biomedical subjects

W Knowles

Publications and source records attributed to W Knowles.

13 recordsLinked to original sources
PubMed1995

Renal failure due to BK virus infection in an immunodeficient child.

We report a child with cartilage-hair hypoplasia and Hodgkin's disease who developed progressive renal failure and died following infection with a polyomavirus, BK virus. Renal biopsy showed interstitial inflammation, tubular atrophy, and intranuclear inclusions in tubular epithelium, with large numbers of papovavirus particles within the cells. BK virus infection was confirmed by polymerase chain reaction on renal biopsy material and in urine and the demonstration of a high titre of haemagglutination inhibition (HI) and IgM antibody to the virus in the patient's serum. This case emphasises the need to study in depth any unusual clinical manifestation in immunocompromised patients to delineate better the full clinical impact of less well-established pathogens such as BK virus.

Antibodies, Viral↗
PubMed1994

Latent autoimmune diabetes mellitus in adults (LADA): the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency.

Type 1 diabetes mellitus in adults may present in a manner similar to that of Type 2 diabetes but with a late development of insulin dependency. We studied 65 patients who presented with 'adult-onset' diabetes after the age of 30 years. Of these patients, 19 required insulin therapy. The insulin-treated patients were significantly younger, their onset of diabetes was at an earlier age, and their postprandial serum C-peptide levels were lower than those of the non-insulin-treated group. Moreover, the insulin-treated subjects had a higher mean concentration of antibodies to glutamic acid decarboxylase (GAD) (66.8 +/- 10.2 units) than the patients who did not require insulin (9.9 +/- 1.9 units) (p < 0.001) and their frequency of anti-GAD positivity was 73.7% versus 4.3% (p < 0.001). Thus, among patients attending a diabetes clinic, the majority (73.7%) of subjects who presented with diabetes after 30 years of age and who subsequently required therapy with insulin, actually have the islet cell lesion of Type 1 diabetes which progresses at a slower tempo than in children. We conclude that testing for anti-GAD in adult-onset non-obese diabetic patients should be a routine procedure in order to detect latent insulin-dependency at the earliest possible stage, since this assay can assist in the correct classification of diabetes, and more appropriate therapy.

Adult↗
PubMed1992

Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with type 1 (insulin-dependent) diabetes mellitus.

Antibodies to glutamic acid decarboxylase, previously known as the 64 kD antigen, appear to be more predictive of Type 1 (insulin-dependent) diabetes mellitus in Caucasoids than other autoantibodies to islet cell antigens. However, seropositivity to glutamic acid decarboxylase is not universal at the onset of Type 1 diabetes and the prevalence in Asians is low compared to Caucasoid patients. This suggests the involvement of multiple pancreatic autoantigens in the Type 1 diabetes autoimmune process or, genetic differences within and between ethnic groups that contribute to the heterogeneous autoimmune response to glutamic acid decarboxylase or both. Alternatively some cases of Type 1 diabetes could have an aetiology unrelated to autoimmunity. This study examined the differential response to glutamic acid decarboxylase according to HLA-DR and -DQ genotypes, as determined by RFLP, in 49 white Australian and 44 Asian patients with Type 1 diabetes. Among Australians heterozygous for HLA-DR3, DR4, 85% were positive for antibodies to glutamic acid decarboxylase, significantly different (p = 0.039) from the prevalence of 48% in patients with at least one HLA-DR antigen other than DR3 or DR4. Also, among Australians, the presence of "low risk" HLA-DQ antigens, namely DQw5, DQw6 or DQw7, reduced the prevalence of antibodies to glutamic acid decarboxylase by 40% (p = 0.064). Among Asians with Type 1 diabetes and with antibodies to glutamic acid decarboxylase, HLA-DR9 was significantly (p = 0.037) increased in frequency, at 63% compared with 22% in those without glutamic acid decarboxylase antibodies, and the presence of a "low risk" HLA-DQ allele reduced the antibody rates by 87% (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

JC virus associated meningoencephalitis in an immunocompetent girl.

JC virus is most commonly acquired during childhood, and no clinical illness has been associated with primary infection, which is assumed to be asymptomatic. The only disease associated with JC virus to date is progressive multifocal leucoencephalopathy (PML), which is usually caused by viral reactivation in immunocompromised adults. A chronic meningoencephalitis associated with an active JC virus infection in an immunocompetent 13 year old girl is described.

Adolescent↗
PubMed1991

Islet cell antibodies and other markers of autoimmunity and diabetes mellitus in Nauruans.

Among the population of Nauru there is a high prevalence of diabetes with onset in early adult life. To ascertain whether autoimmunity to islet cell antigens contributes to this diabetes, a population survey of serum autoantibodies was performed. Subjects were grouped into euglycaemic control subjects, those with impaired glucose tolerance, and those with diabetes subdivided according to duration of disease. No subject was positive by immunofluorescence for islet cell autoantibodies. Various other autoantibodies to nuclear, thyroid and gastric autoantigens were detectable, at comparable frequencies in the three groups. This population study on Nauruan subjects selected to include those in the early phases of disease negates a contribution from islet cell autoimmunity, and thus supports the concept that the disease is the Type 2 (non-insulin-dependent) type.

Animals↗
PubMed1988

Cataract and health status: a case-control study.

Data from 97 cataract patients and 105 normal controls with ages less than 67 years were collected with respect to sex, age, disease status, drug intake, and blood chemistries. The statistical method of fitting log-linear models was used to determine the association between the case-control indicator variable and the other variables. The following variables were shown to be important and to associate independently with the risk of developing cataracts: age, allergy, diabetes, hypotension, hypertension, use of analgesics and coronary disease.

Adult↗
PubMed1987

Cataract epidemiological study: correlation of cataract morphology with health status.

Data on 288 cataract patients were collected with respect to sex, age, disease status, drug intake, and blood chemistry. Eight different types of lens opacities could be discriminated using slit-lamp examination, Scheimpflug photography of the anterior eye segment, and microdensitometric image analysis of the film negatives. The statistical method of fitting log linear models was used to investigate the association between cataract morphology and other variables. The following variables were shown to be important and to contribute independently to the differentiation of cataract types: cholelithiasis, pneumonia, heart insufficiency, allergy, and age.

Adult↗
PubMed1987

Long-term follow-up of lens changes with Scheimpflug photography in diabetics.

This study was designed to document and quantify changes in lens clarity over 24 months in a group of diabetic patients. One hundred thirty-four type I and type II diabetics of 3 months' to 45 years' duration with an average age of 53.5 +/- 7 years volunteered to participate in this prospective study. Patients were evaluated upon entry and at 6-month intervals. Scheimpflug lens photographs (Topcon SL45) were taken at each visit. All photographs were evaluated by densitometry which allowed quantification of the light scattering in the various lens layers. A significant and progressive (4-7% every 6 months) increase in light scattering was observed in the lens anterior superficial lens cortex over 24 months. The rate of change in lens clarity was similar in all patients regardless of the clinically observable lens change type (nuclear, cortical, posterior subcapsular, or mixed). Patients who were younger at enrollment, having diabetes of shorter duration and higher glycosylated hemoglobin values (a measure of long-term glucose control), were identified to be at greater risk of having increased densitometry values in the anterior superficial lens cortex. Only a few patients had significant changes in visual acuity during 24 months, and the correlation of superficial cortical lens clarity changes to clinical cataract formation and visual impairment remains to be established.

Adolescent↗
PubMed1987

Evaluation of cataract-related risk factors using detailed classification systems and multivariate statistical methods.

The well-known different morphological features observed in so-called senile cataract are probably symptoms of various pathogenetic mechanisms in the lens. In order to identify a relationship between type of cataract and special risk factors, a cataract classification system using Scheimpflug photography has been developed. Data of 288 cataract patients (case histories and blood chemistries) have been grouped according to differences in cataract morphology. The multivariate analyses showed the following five variables to be important and to contribute independently to the differentiation of cataract types: cholelithiasis, allergy, heart insufficiency, pneumonia, and age. A case-control study without consideration of cataract morphology showed the following variables to be important and to associate independently with the risk of developing cataracts: age, allergy, diabetes, hypotension, hypertension, use of analgesics, and coronary disease.

Age Factors↗
PubMed1983

Spectrin: structure, function, and abnormalities.

A number of proteins that make up the membrane skeleton have been identified, and we have a rough but tantalizing picture of the ways in which they interact to maintain its integrity. An approximate molecular model of spectrin has been proposed, and many new analytic procedures have been developed to search for biochemical variants that may be related to membrane defects. Even at this rudimentary stage of molecular description we have been able to identify structural changes in spectrin that are correlated with pathophysiologic states. The prospects for some genuine insights into the pathogenesis of some congenital hemolytic anemias seem good.

Anemia, Hemolytic, Congenital↗
PubMedDate not supplied

Ophthalmic bioequivalence of steroid/antibiotic combination formulations.

This study compared the relative ocular bioavailability in rabbits of the antibiotic/steroid combination of 0.3 per cent tobramycin and 0.1 per cent fluorometholone acetate to each of the two single-entity products. Two separate studies were conducted, one measuring fluorometholone acetate in cornea and aqueous humour through 240 min and the other measuring tobramycin in the cornea through 120 min. The results for fluorometholone acetate show that the combination product is 15 per cent higher in AUC for the cornea than the single-entity product (0.05 less than p less than 0.1). However, the combination product is only 4.4 per cent higher in AUC when aqueous humour levels are compared (N.S.). The single-entity fluorometholone acetate ointment yielded cornea and aqueous humour levels which were 20 per cent (p less than 0.01) and 6 per cent (N.S.) higher in AUC than the same tissues measured after topical instillation of the suspension. Statistical treatment of the data indicated that the suspension and ointment products, were bioequivalent with respect to fluorometholone acetate in aqueous humour, but not with respect to corneal concentrations. Tobramycin was measured in the cornea following instillation of either the single-entity solution or the combination suspension. Per cent bound (tobramycin to rabbit antibodies determined in vitro from the radioimmunoassay results) was used for statistical analyses of all group means and standard errors. The results indicated that the products were bioinequivalent.

Animals↗