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Biomedical subjects

P Kirby

Publications and source records attributed to P Kirby.

At least 19 recordsLinked to original sources
PubMed2006

A cyclosporine-based immunosuppressive regimen may be better than tacrolimus for long-term liver allograft survival in recipients transplanted for hepatitis C.

UNLABELLED: Rapid recurrence of severe hepatitis C (HCV) after liver transplantation is a major barrier to survival of the transplanted liver. While cyclosporine (CsA) in vitro has been shown to suppress HCV replication, an effect is not seen with tacrolimus (Tac). Evidence is inconsistent whether or how this translates to clinical practice. To expand the evidence on this issue, we analyzed graft survival and histological outcomes after liver transplantation for HCV hepatitis. METHODS: Using our longitudinal database (1991 onward) graft outcomes for all liver transplant recipients with HCV were evaluated (105 grafts in 97 patients). Severe activity, severe fibrosis, and graft survival were analyzed. All liver biopsies were scored (blinded) according to the Ludwig scale. Immunosuppression was based on prednisone and a calcineurin inhibitor (Tac n = 89, 85%; CsA n = 15, 14%). Comparisons of outcomes using CsA versus Tac therapy were done using survival analysis via the log-rank test. RESULTS: Graft survival was significantly better in the CsA group. Although there was no apparent difference in severe activity (grade 2), there was a statistically significant difference in graft survival without fibrosing cholestatic hepatitis (P = .01) and a trend toward a difference in fibrosis-free survival (P = 0.1). The rate of sustained response to antiviral therapy was twice as high in the CsA group, 50% versus 22% (P = 0.16; NS). CONCLUSIONS: Graft survival in liver transplant recipients with HCV may be greater with CsA-based immunosuppression. There may also be a lower rate of fibrosing cholestatic hepatitis in this group.

Biopsy↗
PubMed2004

Evaluation of Urgotol plus K-Four compression for venous leg ulcers.

In this non-comparative clinical evaluation, 36 subjects with venous leg ulcers, 85% of which were indolent or deteriorating, were treated with Urgotul lipidocolloid wound dressing and the K-Four multilayer compression bandaging system for 12 weeks or to healing--whichever occurred first. Results show that Urgotul was an ideal dressing in combination with K-Four, being easy to apply (98.7%) and remove (98.1%), and largely pain-free (95.6%) and non-adherent (99.7%). In a patient group of "hard-to-heal" ulcers, 50% of the ulcers healed within the treatment period. Ulcers not healed after 12 weeks achieved almost 50% area reduction on average. The treatment combination proved safe, with only one of seven adverse events reported being probably related to the products used. This study supports the use of a combination of Urgotul dressing and K-Four compression to provide a "matched" treatment for venous leg ulcers.

Aged↗
PubMed2002

DMRT1 in a ratite bird: evidence for a role in sex determination and discovery of a putative regulatory element.

Unlike mammals, birds have a ZZ male/ZW female sex-determining system. In most birds, the Z is large and gene rich, whereas the W is small and heterochromatic, but the ancient group of ratite birds are characterized by sex chromosomes that are virtually homomorphic. Any gene differentially present on the ratite Z and W is therefore a strong candidate for a sex-determining role. We have cloned part of the candidate bird sex-determining gene DMRT1 from the emu, a ratite bird, and have shown that it is expressed during the stages of development corresponding to gonadal differentiation in the chicken. The gene maps to the distal region of the Z short arm and is absent from the large W chromosome. Because most sequences on the emu W chromosome are shared with the Z, the Z-specific location constitutes strong evidence that differential dosage of DMRT1 is involved in sex determination in all birds. The sequence of emu DMRT1 has 88% homology with chicken DMRT1 and 65% with human DMRT1. Unexpectedly, an unexpressed 270-bp region in intron 3 of emu DMRT1 showed 90% homology with a sequence in the corresponding intron of human DMRT1. This extraordinarily high conservation across 300 million years of evolution suggests an important function, perhaps involved in control of DMRT1 expression and vertebrate sex determination.

Amino Acid Sequence↗
PubMed2001

Ovarian cancer BRCA1 mutation detection: Protein truncation test (PTT) outperforms single strand conformation polymorphism analysis (SSCP).

Recent studies have shown that the BRCA1 tumor suppressor gene plays a role in the development of both hereditary and sporadic ovarian cancer. Since several different mechanisms may give rise to tumor gene defects, a better understanding of these mechanisms may identify BRCA1 as an attractive therapeutic target in ovarian cancer. Sequencing this large gene is not practical on a population-wide basis. The optimal screening strategy is yet to be determined. The purpose of our study is to compare two common screening techniques: the protein truncation test (PTT) and single strand conformational polymorphism analysis (SSCP). Ninety-four patients with epithelial ovarian cancer and available snap-frozen tissue were screened for BRCA1 mutations by both PTT (five individual PCR reactions with complete translation of the product in the TNT System (Promega, Madison, WI)) and SSCP (41 individual PCR reactions covering the entire coding sequence). All abnormal results were confirmed by sequencing. A paired peripheral blood DNA sample was utilized to determine if the sequence abnormality was a germline mutation. Twenty-three mutations in BRCA1 were found in 22 patients (14 germline, eight somatic, one unknown) including four novel mutations: E489X, 3558delT, 3871delGTCT, del exon 7-10. Although the predictive value of a negative test was close for the two methods (PTT 99.1%, SSCP 99.8%), the comparison of positive predictive value overwhelmingly favored PTT (100.0%, vs. 26.4%, respectively). The specificity for PTT was 100.0% while the sensitivity was 82.6%. While for SSCP, the specificity was 99.0% and the sensitivity was only 60.9%. The concordance rate for the two screening tests was 88.9%. Only SSCP can detect missense mutations. PTT is a superior screening test for truncating BRCA1 mutations that are expected to be of clinical significance.

BRCA1 Protein↗
PubMed2001

Abundant human beta-defensin-1 expression in milk and mammary gland epithelium.

Human beta-defensin-1 (HBD-1) was detected in breast milk in concentrations of approximately 1 to 10 microg/mL. Breast tissue during lactation showed HBD-1 expression in mammary gland epithelia and within luminal secretions. The peptide demonstrated antimicrobial activity against Escherichia coli. HBD-1 may augment neonatal host defenses through antimicrobial effects or prime the adaptive immune system at mucosal surfaces.

Breast↗
PubMed2001

Is Mycoplasma hominis a vaginal pathogen?

OBJECTIVE: To evaluate the role of Mycoplasma hominis as a vaginal pathogen. DESIGN: Prospective study comprising detailed history, clinical examination, sexually transmitted infection (STI) and bacterial vaginosis screen, vaginal swabs for mycoplasmas and other organisms, follow up of bacterial vaginosis patients, and analysis of results using SPSS package. SETTING: Genitourinary medicine clinic, Royal Liverpool University Hospital. PARTICIPANTS: 1200 consecutive unselected new patients who had not received an antimicrobial in the preceding 3 weeks, and seen by the principal author, between June 1987 and May 1995. MAIN OUTCOME MEASURES: Relation of M. hominis isolation rate and colony count to: (a) vaginal symptoms and with the number of polymorphonuclear leucocytes (PMN) per high power field in the Gram stained vaginal smear in patients with a single condition--that is, candidiasis, bacterial vaginosis, genital warts, chlamydial infection, or trichomoniasis, as well as in patients with no genital infection; (b) epidemiological characteristics of bacterial vaginosis. RESULTS: 1568 diagnoses were made (the numbers with single condition are in parenthesis). These included 291 (154) cases of candidiasis, 208 (123) cases of bacterial vaginosis, 240 (93) with genital warts, 140 (42) chlamydial infections, 54 (29) cases of trichomoniasis, and 249 women with no condition requiring treatment. M. hominis was found in the vagina in 341 women, but its isolation rates and colony counts among those with symptoms were not significantly different from those without symptoms in the single condition categories. There was no association between M. hominis and the number of PMN in Gram stained vaginal smears whether M. hominis was present alone or in combination with another single condition. M. hominis had no impact on epidemiological characteristics of bacterial vaginosis. CONCLUSION: This study shows no evidence that M. hominis is a vaginal pathogen in adults.

Adult↗
PubMed2001

Invasive M-type 3 Streptococcus pyogenes affecting a family and a residential home.

This paper describes the first recognised United Kingdom outbreak of M-type 3 streptococci for 12 years. Four epidemiologically-linked invasive infections occurred in a residential home in northern England over two weeks. The index patient was admitted from home with necrotising fasciitis of the leg. Infection was subsequently detected in her husband (fatal pneumonia) another resident (fatal pneumonia) and a member of the care staff (parapharyngeal abscess). Screening of staff and residents in the home did not reveal any further infection or carriage. There is a substantial risk of serious secondary infection amongst the contacts of a patient with invasive Streptococcus pyogenes infection. Guidance is lacking, but needed, on the advisability of chemoprophylaxis in these circumstances.

Adult↗
PubMed1997

The 'worn-out athlete': a clinical approach to chronic fatigue in athletes.

Chronic fatigue in the athletic population is a common but difficult diagnostic challenge for the sports physician. While a degree of fatigue may be normal for any athlete during periods of high-volume training, the clinician must be able to differentiate between this physiological fatigue and more prolonged, severe fatigue which may be due to a pathological condition. As chronic fatigue can be the presenting symptom of many curable and harmful diseases, medical conditions which cause chronic fatigue have to be excluded. The clinician must then be able to differentiate between chronic fatigue associated with training or chronic fatigue from other medical causes, and also between the chronic fatigue syndrome and the overtraining syndrome. Once the clinician has excluded all of the above medical conditions which cause chronic fatigue in athletes, a significant proportion of fatigued athletes remain without a diagnosis. Novel data indicate that skeletal muscle disorders may play a role in the development of symptoms experienced by the athlete with chronic fatigue. The histological findings from muscle biopsies of athletes suffering from the 'fatigued athlete myopathic syndrome' are presented. We have designed a clinical approach to the diagnosis and work-up of the athlete presenting with chronic fatigue. The strength of this approach is that it hinges on the participation of a multidisciplinary team in the diagnosis and management of the athlete with chronic fatigue. The athlete, coach, dietician, exercise physiologist and sport psychologist all play an important role in enabling the physician to make the correct diagnosis.

Chronic Disease↗
PubMed1996

Bone densitometry at a district general hospital: evaluation of service by doctors and patients.

OBJECTIVE: To assess doctors' and patients' views about a district general hospital bone densitometry service and to examine existing practice to influence future provision. DESIGN: Three postal surveys: (a) of doctors potentially using the service, (b) of patients undergoing a bone densitometry test during a six month period, and (c) of the referring doctors of the patients undergoing the test. SETTING: Bone densitometry service at South Cleveland Hospital, Middlesbrough and two district health authorities: South Tees and Northallerton. SUBJECTS: All general practitioners (n=201) and hospital consultants in general medicine, rheumatology, obstetrics and gynaecology, orthopaedics, radio therapy and oncology, haematology, and radiology (n=61); all patients undergoing an initial bone densitometry test (n=309) during a six month period; and their referring doctors. MAIN MEASURES: Service awareness and use, knowledge of clinical indications, test results, influence of test results on patient management, satisfaction with the service and its future provision. RESULTS: The overall response rates for the three surveys were 87%, 70%, and 61%. There was a high awareness of the service among doctors and patients; 219(84%) doctors were aware and 155 of them (71%) had used it, and patients often (40%) suggested the test to their doctor. The test was used for a range of reasons including screening although the general use was consistent with current guidelines. Two hundred (65%) bone densitometry measurements were normal, 71(23%) were low normal, and 38(12%) were low. Although doctors reported that management of patients had been influenced by the test results, the algorithm for decision making was unclear. Patients and doctors were satisfied with the service and most (n=146, 68%) doctors wanted referral guidelines for the service. CONCLUSIONS: There was a high awareness of, use of, and satisfaction with the service. Patients were being referred for a range of reasons and a few of these could not be justified, many tests were normal, and clinical decision making was not always influenced by the test result. It is concluded that bone densitometry services should be provided but only for patients whose management will be influenced by test results and subject to guidelines to ensure appropriate use of the technology.

Absorptiometry, Photon↗
PubMed1995

High grade anal dysplasia in visually normal mucosa in homosexual men: seven cases.

BACKGROUND: Anal cancer and anal human Papillomavirus (HPV) infection are increased in homosexual men. METHODS: We screened high risk homosexual men as part of a longitudinal study examining the effect of HIV infection on the risk of development of high grade anal intraepithelial neoplasia (AIN II, III). RESULTS: We found seven men who had histological evidence of AIN II-III with visually normal findings by anoscopy. Two men were HIV-seronegative, five were HIV-seropositive, and only one of the HIV-seropositive men had a low CD4 count < 200. Abnormal cytological results seen over follow-up periods of 3 months to 2.5 yr suggest the persistence of visually inapparent anal abnormalities. Two of the men had had small internal warts at earlier examinations, and three of the seven men subsequently developed visually abnormal anal findings. All men had HPV 16 DNA detected at some point. CONCLUSIONS: We hypothesize that high grade anal neoplasia may develop deep in the glands and can be detected by cytology before visible lesions are detected even with the aid of a colposcope. However, the implications of finding high grade anal cytology are not known at this time. Natural history studies are ongoing.

Adult↗
PubMed1993

Anal dysplasia in homosexual men: role of anoscopy and biopsy.

BACKGROUND: Both anal squamous cell cancer and human papilloma virus (HPV) are increased in homosexual men. This study evaluates histology of internal anal abnormalities in a high-risk population of human immunodeficiency virus (HIV) seropositive and seronegative homosexual men. METHODS: Ninety men with abnormalities of the internal anal canal (referred from a cross-sectional study of 512 homosexual men) were evaluated by anoscopy, anal cytology, and directed biopsy. CD4 cell counts from blood and HPV types from anal tissue were also obtained. RESULTS: Seventy-eight (86%) men had HPV-associated abnormalities: discrete warts in 39 (43%), a wart ring in 23 (26%), and flat white epithelium in 18 (20%). Dysplasia was detected by cytology in 36% and by biopsy in 92% (27% high grade). High-grade dysplasia was equally common in HIV-seropositive and -seronegative men. The morphology of anal lesions did not predict the presence of dysplasia. Both high- and low-risk HPV types were common in many of the biopsy specimens. CONCLUSIONS: Anal dysplasia is common in biopsy specimens from homosexual men with visible HPV-associated internal anal abnormalities. Natural history studies are needed to determine the clinical significance of anal dysplasia, rates of progression to cancer, and the role of screening and therapy.

AIDS-Related Opportunistic Infections↗
PubMed1993

Association of anal dysplasia and human papillomavirus with immunosuppression and HIV infection among homosexual men.

OBJECTIVE: To examine and quantify the association between anal squamous intraepithelial lesions (ASIL), anal human papillomavirus (HPV) infection and immunosuppression among HIV-seropositive and HIV-seronegative homosexual men. DESIGN: Cross-sectional study among homosexual men presenting at a community-based clinic for HIV serologic screening. RESULTS: Anal HPV DNA was detected in 55 and 23% of 285 HIV-seropositive and 204 HIV-seronegative men, respectively, by Southern transfer hybridization (STH) [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.7-6.2], and in 92 and 78% by polymerase chain reaction (PCR) (OR, 3.1; 95% CI, 1.6-5.8). ASIL was noted in 26% of HIV-seropositive men and in 8% of HIV-seronegative men (compared with men with negative cytologic findings: OR, 5.6; 95% CI, 3.0-10.5), with high-grade lesions noted in 4% of HIV-seropositive and in 0.5% of HIV-seronegative men. Among HIV-infected men, ASIL, detection of specific anal HPV types, and detection of high levels of anal HPV DNA (i.e., levels of HPV DNA detectable by both STH and PCR) were all associated with immunosuppression. Nevertheless, HIV-seropositive men with CD4 counts > 500 x 10(6)/l had a higher prevalence of both anal HPV and ASIL than men without HIV infection. Overall, detection of HPV at high levels was associated with ASIL. However, after adjustment for level of detectable HPV DNA, the risk of ASIL among HIV-seropositive men with CD4 counts < 500 x 10(6)/l was increased 2.9-fold (95% CI, 1.4-6.2) over that of HIV-seropositive men with CD4 counts > 500 x 10(6)/l. CONCLUSION: Given the high rates of ASIL in HIV-seronegative and both immunosuppressed and non-immunosuppressed HIV-seropositive homosexual men, natural history studies are now needed to assist in the development of strategies for the detection and management of such lesions. The increased prevalence of ASIL seen among immunosuppressed HIV-seropositive men may be the result of both a non-specific increase in productive HPV infection and HIV-induced immune alterations of HIV-related neoplasia.

Adolescent↗
PubMed1993

Homozygous variegate porphyria: an evolving clinical syndrome.

Variegate porphyria is one of the most frequently encountered genetic conditions in South Africa. It is inherited as an autosomal dominant disease and in excess of 300 heterozygous cases have been studied by the Cape Town unit. Despite this, the homozygous condition has not previously been encountered in South Africa. We report two cases of homozygous variegate porphyria, one of whom represents the first South African case. We delineate a syndrome principally characterized by growth retardation, developmental delay, epileptic seizures, photosensitivity and an abnormal porphyrin excretion pattern. In addition we describe, in one case, two features not previously reported: skin disease in areas unexposed to light and a severe sensory neuropathy which may account at least in part for the hand deformities of this disorder.

Bone and Bones↗