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Biomedical subjects

D Jenkins

Publications and source records attributed to D Jenkins.

At least 145 records · Page 8Linked to original sources
PubMed1994

Lack of effect of preoperative norfloxacin on bacterial contamination of anterior chamber aspirates after cataract surgery.

Eighty patients undergoing routine standardised extracapsular cataract surgery with lens implantation were divided randomly into two groups in a prospective double blind study comparing effects of preoperative norfloxacin eyedrops with placebo on bacterial contamination of anterior chamber aspirates after surgery. Pathogenic organisms were identified from 19 (24%) of the aspirates. The most commonly isolated organisms were coagulase negative Staphylococcus species. There was no statistical difference between the norfloxacin treated and placebo groups. This study demonstrates that routine use of topical preoperative antibiotics to eliminate the entry of bacteria into the eye during surgery is debatable.

Anterior Chamber↗
PubMed1994

Interobserver variation in the reporting of the histopathological grading of anal intraepithelial neoplasia.

AIM: To assess the consistency in the histological reporting of anal intraepithelial neoplasia (AIN) among experienced histopathologists. METHOD: One hundred anal biopsy specimens were retrieved from archival material at St Mark's Hospital, London and graded by five histopathologists according to criteria outlined by Fenger (six point scale, ranging from normal to invasive carcinoma). RESULTS: There was only moderate agreement among the pathologists, with unweighted k scores ranging from 0.09 to 0.48, and weighted k scores of 0.17 to 0.60. CONCLUSIONS: There is considerable interobserver variation in the reporting of AIN. A simplified system of grading may help to abolish this.

Anus Neoplasms↗
PubMed1994

Cytological screening and management of abnormalities in prevention of cervical cancer: an overview with stochastic modelling.

AIMS: To develop a mathematical model of the histological changes of precancer and the development of invasive cancer and how these are related to cytological findings. To use this to investigate the effects on incidence of cervical cancer, number of smear tests and colposcopies, of different schedules for cervical screening, and the clinical management policies for dyskaryosis. METHODS: A stochastic model was developed relating the available data on tissue progression to the cytological findings. Two strategies, A and B, were compared: under A, women with any abnormal smear receive immediate colposcopy and treatment; under B, women with mild or borderline dyskaryosis have repeated smears at six monthly intervals with colposcopy only for persistent abnormalities. RESULTS: The model predicted an incidence of invasive cervical cancer in an unscreened population of women aged over 18 years of 5.9 per 10,000 per year. With 70% coverage and three yearly screening under strategy A, the incidence fell to 2.00 and under B to 2.10. The number of smears required was similar but A required two to three times as many colposcopies as B. Raising the coverage to 90% reduced the incidence to around 1 per 10,000 per year but changing the screening interval, the specificity or sensitivity of cytology had much less effect. CONCLUSION: The model has been tested under a wide range of possible variations in natural history, specificity and sensitivity of cytology. For low grade smear abnormalities, open colposcopic referral is predicted to reduce invasive cancer only slightly more than repeat cytology, at the expense of much additional colposcopy. Improving cytological coverage is suggested as more effective in reducing invasive cancer than increased use of colposcopy or more frequent screening.

Colposcopy↗
PubMed1994

The Bgl II RFLP associated with type 1 diabetes in DR3-positive subjects is not due to a DQA1 promoter region polymorphism.

Type 1 (insulin-dependent) diabetes is strongly associated with the HLA genes encoding DR3 and DR4 and their associated DQ alleles. While 70% of all Caucasian diabetic patients carry the DR3-associated allele DQA1*0501, this allele also occurs in up to 40% of the healthy population. A DQA1 Bgl II 7.2 kb RFLP has been shown to identify a disease-associated subset of DR3-positive subjects. We examined the frequency of this RFLP pattern in 43 diabetic and 25 control DR3-positive subjects and found it to be present in 27 (65%) and 5 (20%) respectively (p = 0.0012). The promoter of the DR3-associated DQA1*0501 allele was amplified in four diabetic subjects who were positive, and four control subjects who were negative, for the 7.2 kb band. The promoter was digested with Bgl II to determine whether polymorphism within the promoter created a disease-associated Bgl II restriction site, which might influence disease susceptibility by an effect on gene transcription. No amplified promoter fragment contained a Bgl II restriction site, suggesting that the disease-associated 7.2 kb band does not result from DQA1 promoter region polymorphism but may be due to polymorphism elsewhere on the DR3 haplotype.

Bacterial Proteins↗
PubMed1993

Both DQA1 and DQB1 genes are implicated in HLA-associated protection from type 1 (insulin-dependent) diabetes mellitus in a British Caucasian population.

Inherited susceptibility to Type 1 (insulin-dependent) diabetes mellitus is partly determined by HLA genes. It has been suggested that protection from disease may be conferred by HLA-DQB1 genes which encode molecules with aspartate at position 57. We investigated the contributions of HLA-DRB1, DQA1 and DQB1 genes to protection from disease. Restriction fragment length polymorphism and sequence specific oligonucleotide analysis in 156 British Caucasian Type 1 diabetic and 116 control subjects showed protection from disease was associated with DR2, DRw6 and DR7 haplotypes. The most protective DQA1 allele was DQA1*0102 which occurred on both DR2 and DRw6 haplotypes. The DQB1 alleles DQB1*0303, DQB1*0602 and DQB1*0603 were associated with protection, as was DQB1*0604, which encodes an Asp-57 negative DQ beta molecule. Heterozygosity for both protective and predisposing HLA markers was reduced in diabetic compared with control subjects. We conclude that both DQA1 and DQB1 genes are implicated in HLA-associated protection from Type 1 diabetes in this British Caucasian population. The overall structure of the DQ heterodimer is critical and DQ beta-Asp 57 is of secondary importance in determining protection from disease. The effect of protective HLA types may predominate over that of predisposing markers.

Adult↗
PubMed1993

Euglycaemic diabetic ketoacidosis: does it exist?

The original criteria described for euglycaemic ketoacidosis (initial blood glucose less than 16.7 mmol/l and plasma bicarbonate equal to or less than 10 mmol/l) were identified in 23 of 722 consecutive episodes (3.2%) of diabetic ketoacidosis. True euglycaemic ketoacidosis (initial blood glucose 10 mmol/l or less) was rare, occurring in 0.8-1.1% of all episodes depending on the defining plasma bicarbonate concentration. Management of euglycaemic ketoacidosis with low-dose continuous intravenous infusion of insulin together with adequate fluid replacement was effective. The clinical and biochemical data did not support the concept of euglycaemic ketoacidosis as a separate entity. The importance of ketone testing rather than glucose testing in the diagnosis of ketoacidosis is, however, emphasized. The importance of adequate insulin and fluid therapy in those few episodes where blood glucose is normal or near normal at presentation is also highlighted.

Bicarbonates↗
PubMed1993

Definition of human papillomavirus type 16 DNA levels in low and high grade cervical lesions by a simple polymerase chain reaction technique.

Human papillomavirus type 16 (HPV 16) is associated with a high proportion of cervical cancers and pre-cancers but has also been reported by some workers to be widely distributed in the normal population. Using a semi-quantitative polymerase chain reaction technique (PCR) operated with carefully regulated sensitivity we have established two distinct levels of HPV 16 DNA which distinguish between high and low grade cervical lesions. The potential use of such an approach in the understanding and management of HPV related cervical disease is discussed.

Biopsy↗
PubMed1993

Immunoaffinity concentration of human lung DNA adducts using an anti-benzo[a]pyrene-diol-epoxide-DNA antibody. Analysis by 32P-postlabelling or ELISA.

DNA, isolated from 15 human lung autopsy samples, was examined for the presence of polycyclic aromatic hydrocarbon (PAH) DNA adducts. Using the nuclease P1 modification of the 32P-postlabelling technique, between 1 and 12 adducts/10(8) nucleotides were detected prior to immunoconcentration. Autoradiograms from most of the samples revealed a diagonal smear of radioactivity consistent with complex mixture (cigarette smoking) DNA damage. The DNA samples were digested to oligonucleotides, made single-stranded and subsequently applied to immunoaffinity columns containing immobilised anti-benzo[a]pyrene (B(a)P)-7,8-diol-9,10-epoxide (BPDE) DNA polyclonal rabbit antibody. The material remaining bound to the column, in addition to that passing through, was analysed using both ELISA and 32P-postlabelling techniques. Column-bound adducts comprised between 0% and 78% of any particular sample. Immunoconcentration, followed by 32P-postlabelling of the material which had been bound to the column, revealed the presence of a number of discrete adduct spots in autoradiograms of the more heavily adducted samples. Sample DNA not retained by the columns was also analysed; the chromatographic pattern obtained was a dense zone of radioactive material migrating from the origin. This evidence suggests that the composition of PAH-DNA adducts found in human lung samples exhibits wide inter-individual variation.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1993

The influence of HLA-DR and -DQ alleles on progression to multiple sclerosis following a clinically isolated syndrome.

A 5-year follow-up study was performed on 70 Caucasian patients presenting with isolated neurological syndromes of the optic nerve, brain stem, or spinal cord to assess the risk of progression to MS. The influence on patient prognosis of HLA-DR and -DQ alleles and presentation with disseminated brain lesions, demonstrated by MRI scanning, was determined. Clinical progression to MS was observed in 61% of optic neuritis patients, 50% of patients with a brain-stem syndrome, and 35% of patients with a spinal cord disturbance. MS and the isolated clinical syndromes were positively associated with DRB1*1501, DQA1*0102, and DQB1*0602; the frequency of these alleles in the latter group was intermediate between that seen in MS patients and healthy controls. Conversion to MS was positively associated with the DRB1*1501.DQA1*0102.DQB1*0602 haplotype, but the influence of HLA was only significant in patients with disseminated brain lesions at presentation (MRI positive); MS developed in 86% of MRI-positive, DRB1*1501-positive patients compared with 55% of MRI-positive, DRB1*1501-negative patients (p < 0.025). The data suggest that these HLA alleles are involved in susceptibility to initial demyelinating lesion formation and are important in the subsequent development of MS in MRI-positive patients.

Adult↗
PubMed1993

An investigation of the association between HLA-DQ heterodimers and type 1 (insulin-dependent) diabetes mellitus in five racial groups.

The association between HLA-DQ alpha Arg52-HLA-DQ beta non-Asp57 heterodimers and type 1 (insulin-dependent) diabetes was compared in Japanese, Chinese, Caucasian, North Indian Asian, and Afro-Caribbean patients to determine their importance in disease susceptibility. The potential to encode four Arg52-non-Asp57 DQ heterodimers, two in cis and two in trans, was significantly associated with increased risk of type 1 diabetes in all races except the Japanese. The possibility of encoding two Arg52-non-Asp57 heterodimers was also significantly associated with increased risk of the disease in all races except the Japanese. The possibility of encoding one heterodimer was not significantly associated with type 1 diabetes in any of the races studied. Heterogeneity testing revealed significant differences in RR values for four, two, and one heterodimers in all races except the Japanese and significant differences in RR for four and two heterodimers when compared across the races. This, together with the lack of an association between Arg52-non-Asp57 heterodimers and type 1 diabetes in the Japanese, suggests that, assuming the same genetic basis for disease in all races, the heterodimer is unlikely to be of primary importance in susceptibility to the disease.

Diabetes Mellitus, Type 1↗
PubMed1993

Advances in medical therapy for pituitary disease: treating patients with growth hormone excess and deficiency.

Two recent developments in the medical treatment of patients with pituitary disease are discussed. Conventional treatment for patients with acromegaly has been surgery and/or radiotherapy. Dopamine agonist therapy may be useful. Somatostatin is a naturally occurring neuropeptide that inhibits growth hormone (GH) secretion. The development of long-acting preparations has resulted in a considerable advance in the medical treatment of acromegaly, though some caution remains about the long-term side-effects of such therapy (e.g. cholelithiasis) and its cost/benefit analysis. Although further epidemiological studies are required, hypopituitarism appears to be associated with an increased mortality rate, and this has largely been attributed to GH deficiency. With the widespread availability of recombinant GH (thereby circumventing any risks from cadaveric GH) many adult GH-deficient patients are now being treated. Beneficial effects on body composition, nitrogen and calcium balance and bone mass have already emerged, although studies on 'well being' have been conflicting. The debate continues concerning the minimum effective dose and who exactly should be treated, in view of the costs incurred. The endocrinologists' use of long-acting somatostatin analogues and recombinant GH will undoubtedly increase over the next few years. Whilst it is clear that many patients with both acromegaly and hypopituitarism will benefit, long-term controlled trials are still required to establish firmly the benefit in terms of major morbidity.

Acromegaly↗
PubMed1993

Persisting mortality in diabetic ketoacidosis.

An overall hospital mortality rate of 3.9% was found in 929 episodes of diabetic ketoacidosis treated in single centre over a 21-year period. The mortality rate in the first half of the survey (4.4%) was not significantly different from that in the second half of the survey (3.4%). Six deaths in patients under 50 years of age occurred in the first half, but only one death under 50 years occurred in the second half of the survey. The number of deaths from a metabolic cause where no other illness was identified also fell from nine (43% of deaths) in the first half to five (33% of deaths) in the second half of the study (not significant). The remaining deaths were due to concurrent illness, mainly myocardial infarction and serious infections. Many of the residual deaths occurred in elderly patients with such medical illness in addition to the ketoacidosis. It may, therefore, prove difficult to reduce mortality further in diabetic ketoacidosis.

Age Factors↗
PubMed1992

Mild cervical dyskaryosis: safety of cytological surveillance.

How best to manage women who are found on cervical screening to have mild dyskaryosis remains controversial. Cytological surveillance misses some lesions picked up by colposcopy, but colposcopy is emotionally traumatic for women, the majority of whom will have a normal result. To determine what proportion of lesions are missed by cytological surveillance, and whether any abnormalities persist after colposcopy, we studied, by means of colposcopy and biopsy, the prevalence of cervical intraepithelial neoplasia (CIN) and subclinical human papillomavirus infection (HPVI) in two groups of patients who had had a first smear showing mild dyskaryosis at least 24 months earlier. One group was recruited from a centre practising cytological surveillance, with colposcopy for patients showing persistent or progressive cytological abnormality. The other group all had early colposcopy and treatment. Of 214 patients recruited into the cytological surveillance group, 70 (33%) had been referred for colposcopy within 24 months. Colposcopy of the remaining 144 (after a mean interval of 27 months from presentation) revealed that 54 (38%) were disease free, 64 (44%) had HPVI/CIN1, 8 (6%) had CIN2, and 18 (12%) had CIN3. A smear at that time identified 12 of the 18 (67%) with CIN3 as needing close cytological follow-up (1 patient) or prompt referral for colposcopy (11 patients). 137 women in the early colposcopy group attended for the study colposcopy (after a mean interval of 32 months from presentation). 37% were found to have some abnormality persisting after an earlier colposcopy, but none had CIN3. Cytological surveillance of mild dyskaryosis resulted in a 12% risk of patients having a small CIN3 lesion after 2 years, but this risk was reduced to 4% by the addition of a third repeat smear 12 months after the second. With such a policy only about a third of women would require colposcopy, and the risk of missing serious underlying precancerous changes would be low.

Adult↗