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Biomedical subjects

K Lafferty

Publications and source records attributed to K Lafferty.

At least 19 recordsLinked to original sources
PubMed2002

Making your mark again in surgery.

Accurate, durable pre-operative skin marking that withstands the necessary vigorous surgical skin preparation on the theatre table minimises confusion and the risk of mistakes occurring perioperatively, as well as assisting the surgeon with the technicalities of required skin incisions. Felt-tipped marker pens vary widely in achieving these objectives. A selection of markers, including a number used by junior surgical staff on the wards, was investigated.

Humans↗
PubMed2000

The role of autoantigens in autoimmune disease.

Many autoantigens have been identified in human patients and in rodent models. In numerous experimental settings, these autoantigens or related autoreactive lymphocytes can transfer autoimmunity. Although autoreactivity spreads to new epitopes during the course of disease, single-epitope-specific therapies show considerable efficacy in multi-epitope-induced models of autoimmunity. These observations may indicate that epitope-specific therapies operate at the level of regulating mechanisms of immune tolerance rather than exerting a direct effect on autoreactive T lymphocytes.

Animals↗
PubMed1999

A conformationally-constrained MHC class II I-Ag7-derived peptide protects NOD mice from the development of diabetes.

Allele-specific peptide vaccination against disease-associated MHC class II molecules is a promising new strategy for modulating self-antigen presentation to autoreactive T cells in autoimmune diseases. To evaluate the potential of this approach for treatment of insulin-dependent diabetes mellitus (IDDM), we have designed a cyclic peptide vaccine, DiavaX, from the third hypervariable region of the beta-chain of the NOD mouse MHC class II I-Ag7. NOD mice were treated at 5 and 9 weeks of age with 100 microg DiavaX emulsified in alum, a control peptide in alum, or alum alone. At the end of the study, 87% of alum treated mice had developed diabetes, compared with only 28% of DiavaX-treated mice. None of the control peptides, including a linear I-Ag7, a scrambled cyclic I-Ag7, or an analogous cyclic I-Aspeptide, reduced the incidence of diabetes, demonstrating that the protective effect of DiavaX is conformationally dependent and both allele- and sequence-specific. DiavaX treatment did not cause any general immune suppression, but did induce peptide-specific antibodies and memory T cells. DiavaX-induced protection from diabetes was associated with the maintenance of a non-destructive islet-associated autoimmune response. These data indicate that a conformationally constrained peptide from the disease-associated MHC represents a potential vaccine candidate for the prevention of clinical IDDM.

Amino Acid Sequence↗
PubMed1995

The use of Doppler ultrasound in the clinical management of acute testicular pain.

OBJECTIVE: To evaluate the reliability and the clinical application of the use of a hand-held Doppler ultrasound flowmeter probe as an aid to differential diagnosis in the assessment of cases with acute testicular pain presenting to a district general hospital. PATIENTS AND METHODS: Over a period of 1 year, testicular Doppler ultrasonic assessment was performed on 56 patients admitted with acute scrotal pain. A hand-held Doppler ultrasound probe was used, with a transducer operating at 8 MHz. All the patients were assessed pre-operatively by a single operator in the Accident and Emergency department before transfer to theatre. The decision to explore the testis was made purely on clinical grounds by which ever emergency surgical team was on duty. The operating surgeons were not informed of the result of Doppler examinations before surgical exploration. RESULTS: Twenty-two patients were subsequently shown to have torsion of the testis at surgical exploration, all of whom had no Doppler signal over the affected side. Of the remaining 34 patients, who were subsequently shown not to have torsion at operation, normal testicular blood flow and cord-compression tests were demonstrated confidently in 33 patients when examined pre-operatively. Thus the sensitivity was 100% (22/22) and the specificity 97% (33/34). CONCLUSION: Testicular Doppler examination using an 8 MHz probe in conjunction with the cord-compression test is a useful, simple and highly accurate clinical tool which can differentiate between testicular torsion and other conditions presenting with acute testicular pain. It is also inexpensive and readily available in the district general hospital situation.

Acute Disease↗
PubMed1995

Amplitude modulation of the soleus H reflex in the human during active and passive stepping movements.

1. It was hypothesized that passive movement of either the whole leg or its separate segments, in a manner mimicking human gait, leads to attenuation of the soleus H reflex. It was further hypothesized that this attenuation arises from presynaptic effects. Reflex amplitudes were observed in humans during natural bipedal and unipedal stepping on the spot, during passive stepping, during passive movement of the lower limb segments about the hip, knee, and ankle individually in a stepping fashion, and during passive movement with tonic contraction of the soleus muscle. 2. In natural stepping at a cadence of 54 steps/min, the reflex means were substantially depressed in the swing phase (P < 0.01). (Means, standing control 90.1%, unipedal 8.3%, bipedal 6.9%, of maximum M wave.) During the stance phase, reflex magnitudes were mildly and significantly elevated in four of six subjects, compared with standing controls (P < 0.05). 3. For passive stepping, subjects were dorsally tilted 20 and 90 degrees (lying supine) from the vertical position, to obtain quiet electromyograms (EMGs) in the postural muscles. Recorded during natural stepping, the right leg was manipulated to match the electrogoniometer traces of the three major joints. 4. At 20 degrees of tilt of the body, mean H reflexes were significantly lower, by 26.4%, compared with the supine position (P < 0.05). During passive stepping movement of the leg at 54 steps/min, the reflex was profoundly attenuated over the entire cycle (P < 0.01). The significantly attenuated reflexes during active stepping and during passive stepping movement of the whole leg were not significantly different at the point where the limb approached full flexion in the swing phase (P > 0.48). This was the case for measurements made at either body position, 20 degrees dorsal tilt or supine. 5. Passive flexion-extension, around either the hip or the knee, significantly inhibited the mean reflex magnitude close to full flexion, at either body position (P < 0.01). Such movement around the ankle resulted in significant inhibition of the reflex in two of the four subjects (P < 0.05). The numeric sum of the reflex depression arising from the flexion-extension of the individual joints was greater than that arising from movement of the whole limb. 6. With the ankle braced, the significant reflex attenuation remained when a tonic isometric contraction of the soleus muscle was introduced. This suggests premotoneuronal mechanisms for the inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

The 12th International Immunology and Diabetes Workshop. Orlando, Florida.

The 12th International Immunology of Diabetes Workshop was held during April 1993 in Orlando, Florida, to review research progress since the 11th Immunology of Diabetes Workshop meeting in Nagasaki, Japan, one and a half years before. The NOD mouse may have as many as 10 susceptibility genes, including its novel IA major histocompatibility complex antigen and a defective interferon-gamma receptor, whereas human IDDM is so far known to be encoded by cis and trans complementation products of certain DQ genes on chromosome 6q, and a gene in the insulin-like growth factor II region on chromosome 11p. A unique protein regulator of the X box promotor of the highly susceptible DQB1*0302 allele has also been found. Islet cell antibody negative siblings of IDDM patients appear to have lower than expected abilities to secrete insulin in response to intravenous glucose. Sera from patients before and/or after developing IDDM immunoprecipitate two native proteins of 64,000- and 38,000-M(r) glutamic acid decarboxylase (GAD65) reacting to conformational epitopes. However, a multitude of other autoantibodies often reacting to denatured proteins through linear epitopes have also been identified. The first workshop for GAD antibody assays was successfully completed; however, the 38,000-M(r) antigen has not yet been identified. Other autoantibodies reactive to gangliosides and to sulfatides continue to be reported. Insulitis has come to be recognized as a sometimes protective event. Protective insulitis predominates in older lesions. It can be induced by as disparate means as tuberculin antigen administration, by interleukin-4 treatments, by transfer of T-cell lines generated in autologous mixed lymphocyte responses, and by immunization to insulin B-chain, whereas oral islet cell antigens, such as insulin, can delay diabetes onset in the NOD mouse.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Pancreatic islet-specific T-cell clones from nonobese diabetic mice.

We have produced a panel of islet-specific T-cell clones from nonobese diabetic (NOD) mice. These clones proliferate and make interleukin 2 in an antigen-specific manner in response to NOD antigen-presenting cells and islet cells. Most of the clones respond to islet-cell antigen from different mouse strains but only in the presence of antigen-presenting cells bearing the class II major histocompatibility complex of the NOD mouse. In vivo, the clones mediate the destruction of islet, but not pituitary, grafts. Furthermore, pancreatic sections from a disease transfer experiment with one of the clones showed a pronounced cellular infiltration and degranulation of islets in nondiabetic (CBA x NOD)F1 recipients.

Animals↗
PubMed1989

Prevention of detrimental effect of cyclosporin A on vascular ingrowth of transplanted pancreatic islets with verapamil.

The revascularization of pancreatic islet clusters transplanted beneath the renal capsule was studied in a syngeneic mouse model. The degree of vascular ingrowth was visualized by in vivo fluorescence microscopy (fluorescein isothiocyanate-dextran) and judged by a semiquantitative method from coded video recordings. The recipients of isografts were divided into four groups, depending on their daily immunosuppressive treatment: 1) none (controls), 2) 15 mg/kg cyclosporin A (CsA), 3) 0.4 mg/kg verapamil + 15 mg/kg CsA, and 4) 20-30 mg/kg methylprednisolone. In control animals, capillary ingrowth was first demonstrated on day 6, followed by progressive vascularization up to day 34. After 6 mo, the vascular architecture was similar to that seen in normal islets in situ. CsA alone significantly decreased vascular ingrowth on day 14 compared with controls (P less than .02). Verapamil prevented the detrimental effect of CsA (P less than .01), probably by improving renal subcapsular blood flow. Methylprednisolone did not affect revascularization compared with control animals at day 14. We conclude that CsA inhibits vascular ingrowth into transplanted pancreatic islets, which is likely to have clinical implications. The prevention of CsA vascular ingrowth inhibition by a calcium antagonist indicates a possible approach to the correction of this problem, particularly when the renal capsule is used as the recipient's transplant site.

Animals↗
PubMed1988

Thermal entrainment methods for studying Raynaud's phenomenon.

Entrainment occurs when an externally applied periodic temperature stimulus forces the peripheral bloodflow component of thermoregulation to oscillate at the same frequency. This phenomenon can be demonstrated using frequency transforms to analyse the spectral content of the bloodflow, and can be used as a diagnostic test for Raynaud's phenomenon. Correlations were performed between the clinical diagnosis and the objective tests. The average inter-clinical correlation coefficient was r = 0.66. When the average clinical diagnosis was compared with a combination of thermal entrainment and digital patency testing the correlation coefficient rose to r = 0.68. These results highlight the difficulties encountered when assessing patients with Raynaud's phenomenon and the necessity of applying both physiological and clinical techniques.

Blood Volume↗
PubMed1988

An epidemiological survey of Raynaud's phenomenon.

A questionnaire was sent to 1000 patients with Raynaud's phenomenon (RP) and an equal number of controls in order to accumulate one of the largest patient data banks currently available. Five-hundred and seventy-one correctly completed paired returns were processed so as to investigate the association between Raynaud's phenomenon and other factors suspected of influencing the condition. The involvement of female sex hormones in RP was indicated by the predominance of women (93%), a 6% (P less than 0.02) higher incidence of infertility and the influence of menstruation (15%), the menopause (73%) and pregnancy (53%) on symptoms. Patients with scleroderma had a 5% higher incidence of stillbirths. A familial predisposition for RP was noted dependent on age at onset of symptoms (age less than 30, 14% greater than 30, 4.9%). The Raynaud's group overall had a significantly higher percentage who had been treated for migraine (7% higher P less than 0.01), angina (3% higher P less than 0.05) and duodenal ulcer (3% higher P less than 0.001). Of the respondents who had undergone sympathectomy (n = 140, 24.5% of the total), 18.6% claimed lasting benefit and 66.4% claimed no benefit after one year. The mean age at sympathectomy was 38.6 years (S.D. +/- 13 range 14-78) with a mean age of start of symptoms of 29.2 years (S.D. +/- 14.7, range 0-70). There was no significant difference between the effects of sympathectomy on those patients with and those without associated conditions.

Adolescent↗
PubMed1988

T-lymphocyte clone specific for pancreatic islet antigen.

A cloned T-lymphocyte line, BDC-2.5, was derived from a nonobese diabetic (NOD) mouse and has been found to exhibit specificity for islet cell antigen in vitro and in vivo. This clone is a CD4+ T-lymphocyte that proliferates and makes lymphokine in response to islet cell antigen- and NOD antigen-presenting cells. In an in vivo transplantation system in which islet grafts were made in the presence or absence of the BDC-2.5 T-lymphocytes, it was found that incorporation of the islet-specific T-lymphocytes into the graft site resulted in complete destruction of the transplanted tissue. Similar grafts made with pituitary tissue were not affected by the T-lymphocyte clone. These results suggest that the islet-specific T-lymphocytes mediate islet destruction in a tissue-specific manner.

Animals↗
PubMed1987

Ruptured abdominal aortic aneurysm in Marfan's syndrome.

A rare case of ruptured abdominal aortic aneurysm in Marfan's syndrome is described. The patient was treated successfully with a straight aortic tube graft. Histology of the aneurysm wall showed changes typical of cystic medial necrosis.

Adult↗
PubMed1987

The effect of adjuvant oxygen therapy on transcutaneous pO2 and healing in the below-knee amputee.

The effects on tissue oxygenation of postoperative adjuvant oxygen have been studied in a group of 20 patients undergoing below-knee (BK) amputation for vascular disease. Ten patients received no therapy, the remainder receiving 28% oxygen for 48 hours following surgery. The results showed that the transcutaneous pO2 in the amputation flaps fell significantly by some 20 mmHg (p less than 0.01) following surgery and that this fall was prevented by the use of adjuvant oxygen. The fall was not observed in the non-amputated limbs. TcpO2 took almost two weeks to reach its pre-operative levels in the amputated limbs. The effect on stump healing of adjuvant oxygen therapy was investigated in a randomized controlled trial in a series of 39 patients undergoing BK amputation. There were 22 patients in the control (untreated) group and 17 in the treated group (adjuvant oxygen for 48 hours). In the treated group 14 patients healed primarily and three amputations failed. In the untreated group 14 limbs healed primarily, one secondarily and there were 7 failures. The pre-operative transcutaneous values in the stumps which failed (26 mmHg +/- 14) was significantly lower (p less than 0.005) than in those which healed (40 mmHg +/- 9). The mean pre-operative TcpO2 in the patients in whom healing occurred in the treated group (35 mmHg +/- 10) was significantly lower (p less than 0.001) than the mean pressure observed in the untreated group (44 mmHg +/- 9).

Aged↗