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Biomedical subjects

G Kerr

Publications and source records attributed to G Kerr.

At least 19 recordsLinked to original sources
PubMed2001

Influence of HLA-DR phenotype on the risk of hepatitis C virus-associated mixed cryoglobulinemia.

OBJECTIVE: Circumstances predisposing hepatitis C virus (HCV)-infected patients to develop mixed cryoglobulinemia (MC), which may manifest as a small-vessel systemic vasculitis (MC vasculitis), remain unclear. Previous studies have failed to demonstrate a clear role of either viral factors (genotype, viral load) or host factors (lymphocytes or immunoglobulin subsets). This study was undertaken to examine a possible role of HLA class II alleles in HCV-associated MC. METHODS: One hundred fifty-eight HCV-infected patients, of whom 76 had MC (56 with type II MC and 20 with type III MC) and 82 did not have MC, were studied prospectively. MC vasculitis was noted in 35 HCV-infected patients with type II IgMkappa-containing cryoglobulins. HLA-DRB1 and HLA-DQB1 polymorphism was analyzed by hybridization using allele-specific oligonucleotides, after gene amplification. The odds ratio (OR) was calculated with Woolf's method. Then, using multivariate analysis, demographic, biologic, immunologic, virologic, and liver histologic factors associated with the presence of MC and MC vasculitis were investigated. RESULTS: HLA-DR11 was significantly more frequent in patients with type II MC than in those without MC (41.1% versus 17.1%; OR 3.4, corrected P [Pcorr] = 0.017), regardless of the presence of vasculitis accompanying the MC (37.1% of those with MC vasculitis, 34.1% of those with MC but no vasculitis). HLA-DR7 was less frequent in HCV-infected patients with MC than in those without MC (13.2% versus 30.5%; OR 0.34, P = 0.012, Pcorr not significant), with a particularly lower frequency in those with type II MC and those with MC vasculitis (12.5% and 8.6%, respectively). There was no significant difference in HLA-DQB1 distribution between the different patient groups. By univariate and multivariate analysis, HLA-DR11 was the only positive predictive factor, besides female sex and advanced age, for the presence of MC and HCV-associated MC vasculitis (OR 2.58). CONCLUSION: Our results indicate that the presence of the DR11 phenotype is associated with a significantly increased risk for the development of type II MC in patients with chronic HCV infection. In contrast, HLA-DR7 appears to protect against the production of type II MC. These results suggest that the host's immune response genes may play a role in the pathogenesis of HCV-associated MC.

Adult↗
PubMed2000

Spectrum of giant cell vasculitis.

Giant cell arteritis (GCA) is the commonest primary systemic vasculitis in the United States. Severe outcomes include blindness and stroke, and death may result from aortic dissection. Temporal artery biopsy remains the gold standard for diagnosis. Magnetic resonance imaging (MRI) of involved vessels shows promise as a useful noninvasive method for diagnosis and assessment of disease activity. Corticosteroid therapy is effective but is associated with considerable morbidity. Longitudinal studies with large numbers of patients are required to identify appropriate steroid-sparing agents. New insights into the immunopathogenesis of GCA have allowed us to identify heterogeneous subsets of patients with varying clinical presentations corresponding to specific cytokine profiles. The concept of the involved artery as an active participant in the events leading to luminal obstruction has been realized and provides the opportunity to evaluate novel therapies to modify the course of the disease.

Adult↗
PubMed1999

Takayasu's Arteritis.

Takayasu's arteritis is a worldwide entity that requires astuteness for early diagnosis. The challenge for the practicing physician is to document active disease, not only to justify immunosuppressive therapy but also to determine the appropriate timing for surgical intervention. No single laboratory assay or imaging modality establishes disease activity, though T2-weighted magnetic resonance imaging, magnetic resonance angiography, and spiral computed tomographic angiography have shown potential in identifying acute inflammatory changes within the vessel wall. Treatment consists primarily of glucocorticoids, but cytotoxic agents such as methotrexate and cyclophosphamide may be added to treat recalcitrant disease. New immunomodulating agents such as leflunomide and tumor necrosis factor inhibitors require further study before they can be added to the treatment armamentarium.

Journal Article↗
PubMed1999

Contribution of the MHC region to the familial risk of coeliac disease.

Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.

Celiac Disease↗
PubMed1996

Management of lung cancer in South East Scotland.

BACKGROUND: There are few reports which describe the management of unselected groups of patients with lung cancer. This study was undertaken to audit prospectively the presentation, diagnosis, management, and outcome of patients presenting with lung cancer in South East Scotland. METHODS: Data were recorded on all patients with newly diagnosed lung cancer who presented to a multidisciplinary group of clinicians over a 12 month period. Subsequent follow up data on treatment and survival were collected. RESULTS: Six hundred and twenty two patients were registered, 80% of whom were referred from primary care. There was a considerable variation in the length of history, but the diagnosis was rapidly made after referral (87% within two weeks). In 82% of patients the pathological examination was positive; 70% were treated with palliative intent. Only 36% of patients who underwent surgery had computed tomographic scanning and 55% had sampling of mediastinal nodes. A wide variety of regimens was used for treatment with radiotherapy and chemotherapy, and follow up data were difficult to obtain in these patients. Survival was poor in all patients treated with palliative intent. CONCLUSIONS: This audit confirms the importance of previously noted prognostic factors. Significant variation in referral practice, diagnostic and management evaluation has been shown. The data serve as a useful background for the formation of local management guidelines.

Adult↗
PubMed1995

Proprioceptive coordination of discrete movement sequences: mechanism and generality.

A "discrete" movement sequence is defined as a movement with a single goal that involves a series of overlapping joint rotations. Reaching-and-grasping and throwing are examples of discrete movement sequences. The central nervous system (CNS) can use reafferent proprioceptive information from one joint rotation in a sequence to coordinate subsequent rotations at other joints. The experiments reported in this paper demonstrate how the human CNS uses proprioceptive information to coordinate discrete movement sequences. We examined the mechanism (at an information processing level) underlying proprioceptive coordination and the generality (i.e., the boundary conditions) of these mechanisms as they apply to everyday movement sequences. Adult human subjects performed a discrete movement sequence that resembles backhand throwing: elbow extension followed by hand opening. The task was to open the hand as the elbow passed through a prescribed "target" angle. We eliminated visual information and made the arrival time at the target angle unpredictable so that the available kinematic information was provided exclusively by proprioception. The subjects were capable of performing this motor task with a high degree of precision, thereby demonstrating that the nervous system can use proprioceptive input to coordinate discrete movement sequences. Our data indicate that precise coordination is achieved by extracting kinematic information related to both the velocity of elbow rotation as well as the elbow position during movement (i.e., "dynamic position"). Dynamic position information appears to be encoded as both absolute joint angle and angular distance, although more precisely as angular distance. Although our experiments were conducted under rather restrictive laboratory conditions, this mechanism of motor coordination might also apply to everyday movement. Our results suggest that this mechanism could be employed for passive as well as active movement sequences, with and without opposing loads; it could exert its influence in discrete movement sequences as brief as 210 ms or as long as 1.5 s; and it does not involve any significant degree of learning (this proprioceptive mechanism appears to be readily available for use on the first attempt of a novel motor task).

Adult↗
PubMed1994

Takayasu's arteritis.

Takayasu's arteritis has become increasingly recognized as a worldwide entity with a variable spectrum of disease expression. Although evidence for immune mechanisms of disease exist, the precise etiopathogenesis remains elusive. Improvements in the evaluation of disease activity beyond the current parameters of clinical symptoms, erythrocyte sedimentation rate, and angiographic findings are needed. Assessment of disease is handicapped by radiologic techniques that may detect diseased vessels but do not distinguish active from chronic lesions. A large proportion of patients with active disease respond to treatment with glucocorticoids, but a significant proportion will either require additional immunosuppression to prevent steroid toxicity or will remain unresponsive to treatment. At present, methotrexate appears to be an effective steroid-sparing agent in the treatment of active Takayasu's arteritis. Surgery continues to play a critical role in the long-term management of Takayasu's arteritis and is recommended when appropriate during inactive disease. Renal autograft transplantation has been offered as a new technique in the management of hypertension in Takayasu's arteritis.

Adult↗
PubMed1992

Effect of potassium on ventilation in the rhesus monkey.

Increasing the concentration of arterial plasma K+ to 6-8 mM increased ventilation in two sedated analgesic-treated rhesus monkeys who had their end-tidal CO2 held constant during euoxia (arterial oxygen pressure, Pa,O2, ca 100 Torr) and hypoxia (Pa,O2, ca 40 Torr). During euoxia and hypoxia, hyperkalaemia increased ventilation up to 40 and 250%, respectively. This effect was reduced in euoxia and virtually abolished in hypoxia following an abrupt switch to 100% oxygen. Thus the ventilatory response of this primate to hyperkalaemia is at least as sensitive as that of the cat and if hypoxia is added the two stimuli generate a powerful drive to breathing.

Animals↗
PubMed1989

Development of a universal wheelchair narrower.

A wheelchair user's mobility may be hampered by narrow doorways and restricted turning spaces. Mobility may be improved by undertaking expensive building alterations in the wheelchair user's own home and work environment. However, other environments, including modes of public transport, may still present considerable difficulties. One way of improving mobility is to reduce the overall width of a wheelchair with the occupant still seated within it. This is achieved by using a clamp, known as a "wheelchair narrower" which can be fitted and operated either by the wheelchair user or an attendant. The narrower takes advantage of the inherent design of a wheelchair which permits folding for storage. A universal wheelchair narrower was manufactured and tested at Tayside Rehabilitation Engineering Services. It was designed to be used on 69% of wheelchairs issued through the National Health Service in Scotland. Tests revealed that wheelchairs could be narrowed by between 38 and 127 mm depending upon the type of wheelchair. Active wheelchair users reported that the device was particularly useful when travelling.

Equipment Design↗