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Biomedical subjects

C T Kennedy

Publications and source records attributed to C T Kennedy.

At least 19 recordsLinked to original sources

Six new HLA class I alleles detected by PCR-SSO genotyping.

This paper describes six new alleles; A*0240, A*2614, B*3924, B*4425, Cw*0807 and Cw*12023, which were discovered during routine genotyping with sequence specific oligonucleotides (SSO's). Five of the new alleles have changes in residues which belong to the antigen binding site of the HLA protein. These new variants may have altered antigen binding properties and may cause differential immunological responses that could affect transplantation outcome1.

Base Sequence↗

Assessment of ropivacaine as a local anesthetic for skin infiltration in skin surgery.

BACKGROUND: There has been limited examination of the use of ropivacaine, a relatively new amide local anesthetic, for skin surgery following local infiltration. Initial studies of ropivacaine show it to have a rapid onset and long duration of action. OBJECTIVE: To establish the injection characteristics of different concentrations of ropivacaine and to compare the pain of infiltration of ropivacaine with lidocaine 2% + epinephrine 1:80,000. METHOD: A double-blind placebo-controlled study was carried out on 18 healthy volunteers. Four concentrations of ropivacaine (1, 2, 5, and 7.5 mg/ml) were injected intradermally. Normal saline was used as the control. Sensation for pinprick was used to assess the onset and duration of anaesthesia. Pain of infiltration of ropivacaine and saline was additionally compared with lidocaine 2% + epinephrine 1:80,000. RESULTS: Pain of ropivacaine infiltation increased with increasing strength, but only 5 mg/ml was significantly more painful than the control P =.002). Lidocaine and epinephrine infiltration was significantly more painful than the control P =.0002) and 7.5 mg/ml ropivacaine (P =.0005). Mean times to reach full anesthesia were 74 seconds for 5 mg/ml and 51 seconds for 7.5 mg/ml. Mean times to regain full sensation were estimated as 692 minutes for 5 mg/ml and 773 minutes for 7.5 mg/ml. A vasoconstrictor effect was noted in the ropivacaine sites. CONCLUSION: Ropivacaine has a rapid onset and long duration of action. Ropivacaine produces vasoconstriction which may be clinically relevant. Even at maximum strength ropivacaine is less painful to inject than lidocaine with epinephrine.

Adult↗

Wiskott-Aldrich syndrome, vasculitis and critical aortic dilatation.

UNLABELLED: Wiskott-Aldrich syndrome is a rare X-linked disorder, comprising the triad eczema, thrombocytopenia and progressive immunodeficiency. The prognosis has been poor in the past but is now improving with therapeutic options including splenectomy and bone marrow transplantation. We report the case of a 21-year-old male with an established diagnosis of Wiskott-Aldrich syndrome, who developed aortic root dilatation with severe aortic regurgitation requiring aortic valve and root replacement. Histology confirmed a destructive, full-thickness, chronic aortitis. CONCLUSION: As treatment and prognosis improve, large vessel vasculitis may become an increasingly recognized late complication of this syndrome, which now extends into adult practice.

Adult↗

Routine HLA-B genotyping with PCR-sequence-specific oligonucleotides (PCR-SSO) detects eight new alleles: B*0807, B*0809, B*1551, B*3529, B*3532, B*4025, B*5304 and B*5508.

This paper describes eight new alleles (B*0807, B*0809, B*1551, B*3529, B*3532, B*4025, B*5304 and B*5508) that have been found by routine HLA-B genotyping with sequence-specific oligonucleotides (SSOs). All of the new alleles have variations which cause changes in residues that occur within antigen binding pockets and T-cell recognition sites of the antigen. The new polymorphisms within these new alleles may affect the nature and specificity of peptide binding and cause differential T-cell activation, which may have an affect in transplantation.

Alleles↗

Cutaneous presentation of steroid responsive blastoid natural killer cell lymphoma.

CD56+ lymphomas derived from natural killer (NK) cell lineage are rarely encountered in Western populations and their clinical and pathological features have not been fully defined. The majority of reported cases are lymphomas of the nasal cavity, which are most commonly seen in Asia. A subtype of CD56+ lymphoma has recently been described (blastoid NK-cell lymphoma) which characteristically presents in older patients with cutaneous infiltrates and disease at other nodal and extranodal sites. We describe a case that correlates well with the clinicopathological features of blastoid NK-cell lymphoma. An unusual feature in our patient was that the cutaneous features of the lymphoma showed complete resolution shortly following commencement of oral steroid therapy.

Aged↗

The epidemiology of head lice and scabies in the UK.

Anecdotal evidence suggests that the prevalence of both scabies and head lice is increasing and also that both conditions are becoming refractory to pesticide treatment. Using information obtained from the Office of National Statistics, Royal College of General Practitioners Weekly Returns Service, Department of Health, local surveys of school children from Bristol and drug sales of insecticides, we have confirmed that there has been a rise in the prevalence of both conditions. We have shown that scabies is significantly more prevalent in urbanized areas (P < 0.00001), north of the country (P < 0.000001), in children and women (P < 0.000001) and commoner in the winter compared to the summer. Scabies was also shown to have a cyclical rise in incidence roughly every 20 years. Head lice were shown to be significantly more prevalent in children and mothers (P < 0.000001) though both conditions were seen in all age groups. Head lice were also less common during the summer. Host behaviour patterns, asymptomatic carriage, drug resistance and tourism from countries or districts with a higher incidence may be important factors in the currently high prevalence of both scabies and head lice.

Adolescent↗

Identification of a novel mutation R42P in the gap junction protein beta-3 associated with autosomal dominant erythrokeratoderma variabilis.

We report a missense mutation in the gap junction protein beta-3 (encoding Connexin 31), which was detected in only the affected members of a family in which the autosomal dominant skin disease erythrokeratoderma variabilis was segregating. The nucleotide change results in an arginine to proline substitution in codon 42. This residue is positioned on the first transmembrane/first extracellular domain of the gap junction protein with the mutation replacing a negatively charged residue with a nonpolar residue. This change may disrupt the conformation of the protein and voltage gating polarity leading to impaired channel function.

Connexins↗

Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27.

Cerebral cavernous malformation (CCM) is a Mendelian model of stroke, characterized by focal abnormalities in small intracranial blood vessels leading to hemorrhage and consequent strokes and/or seizures. A significant fraction of cases is inherited as an autosomal dominant trait with incomplete penetrance. Among Hispanic Americans, virtually all CCM is attributable to a founder mutation localized to 7q ( CCM1 ). Recent analysis of non-Hispanic Caucasian kindreds, however, has excluded linkage to 7q in some, indicating at least one additional CCM locus. We now report analysis of linkage in 20 non-Hispanic Caucasian kindreds with familial CCM. In addition to linkage to CCM1, analysis of linkage demonstrates linkage to two new loci, CCM2 at 7p13-15 and CCM3 at 3q25.2-27. Multilocus analysis yields a maximum lod score of 14.11, with 40% of kindreds linked to CCM1, 20% linked to CCM2 and 40% linked to CCM3, with highly significant evidence for linkage to three loci (linkage to three loci supported with an odds ratio of 2.6 x 10(5):1 over linkage to two loci and 1.6 x 10(9):1 over linkage to one locus). Multipoint analysis among families with high posterior probabilities of linkage to each locus refines the locations of CCM2 and CCM3 to approximately 22 cM intervals. Linkage to these three loci can account for inheritance of CCM in all kindreds studied. Significant locus-specific differences in penetrance are identified. These findings have implications for genetic testing of this disorder and represent an important step toward identification of the molecular basis of this disease.

Cerebrovascular Disorders↗

The effects of topical doxepin on responses to histamine, substance P and prostaglandin E2 in human skin.

The tricyclic antidepressant, doxepin, is known to have H1 and H2 antihistaminic effects. Recently, 5% doxepin cream has been marketed in the U.S.A. for treatment of eczematous dermatoses. We investigated the effects of topical doxepin treatment on histamine-, substance P- and prostaglandin E2- (PGE2) induced responses in the skin of normal and atopic subjects. We compared the effects of topical doxepin with those of the oral antihistamine terfenadine. The weal volume and flare area responses to histamine were significantly reduced by treatment with topical doxepin or oral terfenadine in both normal and atopic subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 10 micrograms/site of histamine in non-atopics and atopics was 48 +/- 8% and 60 +/- 17% with terfenadine, and 54 +/- 12% and 81 +/- 4% with topical doxepin, respectively. The mean percentage reduction in weal volume for the same dose of histamine in non-atopics and atopics was 70 +/- 9% and 63 +/- 16% with terfenadine, and 96 +/- 2% and 89 +/- 6% with topical doxepin, respectively. The flare but not the weal response to substance P was inhibited by both treatments in all subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 200 pmol/site of substance P in non-atopics and atopics was 53 +/- 10% and 73 +/- 4% with terfenadine, and 74 +/- 7% and 75 +/- 4% with topical doxepin, respectively. The cutaneous responses to PGE2 were not affected by either drug. The inhibitory effects of doxepin were as great as those of terfenadine, and doxepin had a significantly greater effect than terfenadine in inhibiting the weal response to histamine and flare response to substance P in normal volunteers (P < 0.05). There was no significant difference between atopics and non-atopics in the percentage reduction of cutaneous responses by oral terfenadine or topical doxepin. Marked sedation occurred in three of the first 10 subjects treated with topical doxepin, necessitating a reduction in dosage for the remaining six subjects. In summary, topical doxepin was as effective as, and sometimes more effective than, a standard dose of oral terfenadine in the inhibition of histamine-induced and axon-reflex-mediated cutaneous responses. The marked sedative effect may limit its clinical use in some patients.

Administration, Topical↗

Facial granulomatous lymphoedema and syringomyelia.

The term orofacial granulomatosis was introduced for orofacial lesions which resemble Crohn's disease clinically and histologically in patients without gastrointestinal disease. The Melkersson-Rosenthal syndrome and its oligosymptomatic form Meischers granulomatous cheilitis are usually felt to be part of the same spectrum of disease. Oedema usually involves tissues of the lower half of the face. We describe a patient with histological changes consistent with those found in orofacial granulomatosis, but with isolated localized oedema of the right periorbital tissues. The patient also had syringomyelia which has not previously been described in association with orofacial granulomatosis.

Aged↗