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Biomedical subjects

C Dodd

Publications and source records attributed to C Dodd.

18 recordsLinked to original sources

Assessment of patellar maltracking using combined static and dynamic MRI.

Between January 1995 and Jul 1997, 474 patients with anterior knee pain resistant to conservative treatment were referred for MR of the knee. The MR examination consisted of routine sequences with an additional patellofemoral dynamic examination using a technique that has been developed at this institution. The dynamic study examines both knees simultaneously, with the patient supine and the quadriceps loaded. No gating or restraint apparatus is needed. Patellar subluxation or tilt was present in 188(40%) of cases, bilateral in 104 and unilateral in 84 cases (right 39, left 45). It was classified as mild in 51%, moderate in 39% and severe in 10%. Subluxation was more prevalent in females than males (42% vs. 37%) and this was most obvious in the severe group where 68% were female. In 90 knees selected at random, four measurements of patellofemoral morphology were obtained using reconstructed images from a volume gradient echo sequence. These measurements were correlated with the degree of subluxation or tilt. A tibial tubercle distance greater than 20 mm, a femoral sulcus angle greater than 150 degrees, sulcus depth less than 4 mm were specific for subluxation but no measurement proved to be sufficiently sensitive to preclude a tracking study. MRI can be used to define more precisely the anatomy of the extensor mechanism and its relationship to the femur and tibia, in both a static and dynamic setting. In this way, patients with anterior knee pain can be classified more accurately and the outcomes of treatment more reliably assessed.

Adult↗

The effect of interferon-alpha2b on an in vitro model Dupuytren's contracture.

The effects of interferon-alpha2b (IFN-alpha2b) on Dupuytren's and control palmar fibroblasts were evaluated using the fibroblast-populated collagen lattice model. Three paired strains of Dupuytren's and control fibroblasts were exposed to IFN-alpha2b for 96 hours before incorporation into triplicate collagen lattices. Contraction of the lattices was recorded and Northern blot analysis of cytoskeletal mRNA was performed. Comparisons of Dupuytren's and control fibroblasts revealed significantly increased contractility of the Dupuytren's fibroblasts in 2 of the 3 strains. Treatment with IFN-alpha2b significantly inhibited contraction in both Dupuytren's and control fibroblasts. In Dupuytren's fibroblasts, treatment with IFN-alpha2b significantly down-regulated mRNA expression for cytoplasmic beta-actin and gamma-actin.

Blotting, Northern↗

A genetic register for von Hippel-Lindau disease.

A genetic register for von Hippel-Lindau disease was set up in the north west of England in 1990. Population statistics, clinical features, age at onset, and survival of 83 people affected with von Hippel-Lindau (VHL) disease were studied. In addition, the effectiveness of the screening programme used and the occurrence of central nervous system haemangioblastomas in the general population were examined. The diagnostic point prevalence of heterozygotes in the North Western Region was 1 center dot 18/100 000 (1/85 000) people, with an estimated birth incidence of 2 center dot 20/100 000 (1/45 500) live births. The mutation rate was estimated directly to be 1 center dot 4 x 10(-6)/gene/generation (1/714 200). The mean age at onset of first symptoms was 26 center dot 25 years, with cerebellar haemangioblastoma being the most common presenting manifestation (34 center dot 9% of cases). The mean age at diagnosis of VHL disease was 30 center dot 87 years. Overall, 50 patients (60 center dot 2%) developed a cerebellar haemangioblastoma, 34 (41 center dot 0%) a retinal angioma, 21 (25 center dot 3%) a renal cell carcinoma, 12 (14 center dot 5%) a spinal haemangioblastoma, and 12 (14 center dot 5%) a phaeochromocytoma. Mean age at diagnosis of renal cell carcinoma (38 center dot 9 years) was significantly higher than that for cerebellar haemangioblastoma (30 center dot 0 years) and retinal angioma (21.1 years). Mean age at death was 40 center dot 9 years with cerebellar haemangioblastoma being the most common cause (47 center dot 7% of deaths). A total of 65 VHL manifestations were diagnosed asymptomatically following appropriate clinical and radiological screening tests, and failure to detect manifestations of VHL disease in spite of appropriate screening occurred on only two occasions. The use of DNA linkage analysis and direct mutation testing reduced the personal risk of carrying the VHL gene to below 1% in 14 people. In addition to the 83 clinically affected subjects, three obligate carriers who were considered to be lesion free in spite of extensive screening tests were identified. Fourteen percent of all CNS haemangioblastomas on the regionally based Cancer Registry were found to occur as part of VHL disease, but investigations for VHL in apparently sporadic disease appeared to be limited.

Adolescent↗

Urinary excretion kinetics of 1-hydroxypyrene in volunteers exposed to pyrene by the oral and dermal route.

Two well-informed human volunteers were exposed to 500 micrograms pyrene by ingestion and by dermal application, in two separate experiments. Urinary measurements of 1-hydroxypyrene (1-OHP) were performed on all micturitions taken at intervals of 0.5-4 h for a total period of 48 h after dosing. Following the absorption phase, 1-OHP is excreted with a first order apparent half-life of approximately 12 h for both volunteers and both exposure routes. These results compare well with other previously published studies. A more refined analysis of the data was performed using a two-compartment toxicokinetic model for 'pyrene' (its fraction eventually excreted as 1-OHP). As it was found that a classical first-order system did not adequately fit the data, a non-linear term was introduced in the model for the elimination of urinary 1-OHP. Computer iteration performed on the oral absorption data allowed an estimation of various toxicokinetic parameter values. The mean intercompartmental exchange (k12 and k21) and elimination coefficients were 0.010, 0.006 and 0.012 min-1, respectively. The first two values compare well with those previously published for the rat, whereas the latter is smaller in humans. These values were used to satisfactorily simulate the experimental data for both routes of exposure, adjusting only for kabs which was estimated at 0.014 and 0.0029 min-1 for the oral and dermal exposure, respectively. The proposed model generates new hypotheses on the metabolism of pyrene. The information collected will contribute to the validation of the utilisation of 1-OHP as a biological indicator of exposure to pyrene.

Administration, Cutaneous↗

Severe Gardner syndrome in families with mutations restricted to a specific region of the APC gene.

Familial adenomatous polyposis (FAP) is associated with a number of extraintestinal manifestations, which include osteomas, epidermoid cysts, and desmoid tumors, often referred to as "Gardner syndrome." Recent studies have suggested that some of the phenotypic features of FAP are dependent on the position of the mutation within the APC gene. In particular, the correlation between congenital hypertrophy of the retinal pigment epithelium (CHRPE) and APC genotype indicates that affected families may be divided into distinct groups. We have investigated the association between the dentoosseous features of GS on dental panoramic radiographs (DPRs) and APC genotype in a regional cohort of FAP families. DPRs were performed on 84 affected individuals from 36 families, and the dento-osseous features of FAP were quantified by a weighted scoring system. Significant DPR abnormalities were present in 69% of affected individuals. The APC gene mutation was identified in 27 of these families, and for statistical analysis these were subdivided into three groups. Group 1 comprised 18 affected individuals from seven families with mutations 5' of exon 9; these families (except one) did not express CHRPE. Groups 2 comprised 38 individuals from 16 families with mutations between exon 9 and codon 1444, all of whom expressed CHRPE. Group 3 comprised 11 individuals from four families with mutations 3' of codon 1444, none of whom expressed CHRPE. Families with mutations 3' of codon 1444 had significantly more lesions on DPRs (P < .001) and appeared to have a higher incidence of desmoid tumors. These results suggest that the severity of some of the features of Gardner syndrome may correlate with genotype in FAP.

DNA↗

A comparison of pain experienced during hysterosalpingography and in-office falloposcopy.

OBJECTIVE: To determine patient perception of the intensity of pain during in-office falloposcopy compared with hysterosalpingography (HSG). DESIGN: A prospective quality assurance study using a formal pain scale to compare two procedures. SETTING AND PATIENTS: Patients attending a tertiary level infertility clinic. INTERVENTIONS: In-office falloposcopy or HSG using analgesics. MAIN OUTCOME MEASURES: The mean pain score and area under the pain curve experienced during each investigation. RESULTS: Using our technique, in-office falloposcopy was associated with a significantly lower mean intensity of pain and with a longer procedure. The duration of the falloposcopic examination declined significantly with physician experience. Flushing adjacent to the uterotubal ostium, ostial cannulation, and rapid eversion provoked episodes of acute pain during falloposcopy. CONCLUSION: These results support the patient acceptability of in-office falloposcopy.

Adult↗

Improved procedure for the high-performance liquid chromatographic determination of monohydroxylated PAH metabolites in urine.

An improved high-performance liquid chromatographic (HPLC) method for the determination of 3-hydroxybenzo(a)pyrene (3-OHBaP) in urine was developed. The sensitivity and reproducibility of the technique was greatly improved by the addition of 1 mg/L ascorbic acid to the methanol eluent of the HPLC system. This procedure also eliminated the peak splitting and band broadening of the 3-OHBaP peak otherwise observed. Furthermore, it corrected the urine matrix effect on the slope of standard curves. In fact, in the absence of ascorbic acid in the HPLC system, slopes of standard curves were steeper when prepared in a methanolic extract of control rat urine (121 L.nmol-1) than in methanol only (86 L.nmol-1). Both these slopes were smaller than that obtained with the modified mobile phase (244 L.nmol-1). The effect of the latter on the shape and intensity of the 1-hydroxypyrene (1-OHP) chromatographic peak was also investigated. Again, slopes were greater when the standards, prepared in a methanolic extract of urine, were chromatographed with ascorbic acid (380 L.nmol-1) than without (157 L.nmol-1). Therefore, it seems that ascorbic acid, like certain substances in urine, may act by masking specific adsorption sites--probably uncapped silanol residues on the LC 18 column that can retain free 3-OHBaP and 1-OHP metabolites.

Animals↗

Non-penetrance and late appearance of polyps in families with familial adenomatous polyposis.

One case of non-penetrance of the familial adenomatous polyposis (FAP) gene at 59 years of age and late onset of polyps on endoscopy and biopsy in this and two other families is described. Screening protocols should include dental screening as well as indirect ophthalmoscopy and endoscopy to detect minimal manifestations of the gene. In the absence of a specific DNA predictive test, bowel screening should continue well beyond 30 years of age.

Adenomatous Polyposis Coli↗

Reversibility of left ventricular hypertrophy by differing types of antihypertensive therapy.

Left ventricular hypertrophy (LVH), as assessed by ECG or echocardiography, is a powerful independent coronary risk factor. The present overview of 104 studies sets out to compare the ability of various forms of antihypertensive therapy to reverse LVH as assessed by echocardiography. Most observations involved four classes of treatment--combination therapy, ACE inhibitors, beta-blockers and calcium antagonists (mainly dihydropyridines). The former two therapies were significantly more effective than the latter two in reversing LV mass, independently of length of time on treatment and degree of fall in blood pressure. Possible reasons for these differences are discussed. The clinical significance of these results is unclear although preliminary data indicate that regressing LVH is associated with fewer cardiovascular events.

Antihypertensive Agents↗

Arthroscopy in acute knee injuries: a prospective controlled trial.

Eighty-two patients took part in a prospective trial to assess the need and timing for arthroscopy in acute knee injuries. Patients with a suspected ligament injury, a suspected meniscal tear, or a haemarthrosis in the absence of fracture were included in the trial. Patients were entered randomly into two groups. In group I early arthroscopy was performed (within 48 h), in group II arthroscopy was performed within 21 days, but only when it was felt to be clinically indicated. Patients were assessed using the OAK knee score 1 year after the injury. There was no difference in the final result between the two groups. Early arthroscopy (within 48 h) showed no beneficial effect when compared with delayed arthroscopy (3 to 21 days after the injury). Indeed, an important diagnosis was missed at early arthroscopy in three cases, which led to delay in subsequent diagnosis and treatment. Arthroscopy raised the diagnostic accuracy from 61 per cent to 93 per cent. Considerable morbidity arises as a result of acute knee injuries. Clinical judgment will correctly define the need for arthroscopy in most cases at the time of injury, and arthroscopy is not necessary in all cases of acute haemarthrosis.

Acute Disease↗

Fluorescence detection in automated DNA sequence analysis.

We have developed a method for the partial automation of DNA sequence analysis. Fluorescence detection of the DNA fragments is accomplished by means of a fluorophore covalently attached to the oligonucleotide primer used in enzymatic DNA sequence analysis. A different coloured fluorophore is used for each of the reactions specific for the bases A, C, G and T. The reaction mixtures are combined and co-electrophoresed down a single polyacrylamide gel tube, the separated fluorescent bands of DNA are detected near the bottom of the tube, and the sequence information is acquired directly by computer.

Automation↗