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Biomedical subjects

L Clements

Publications and source records attributed to L Clements.

14 recordsLinked to original sources

The value of performing head CT in screening for cerebral metastases in patients with potentially resectable non-small cell lung cancer: experience from a UK cardiothoracic centre.

AIM: To evaluate the whether screening for cerebral metastases in neurologically intact patients with potentially resectable non-small cell lung cancer patients is both worthwhile and cost-effective. METHODS: We prospectively performed computed tomography (CT) of the head in 105 consecutive patients with potentially resectable lung cancer over an 18-month period. None of these patients had neurological symptoms or signs. RESULTS: Five patients (4.8%) with cerebral metastases were identified using CT. At our institution the financial saving of avoiding five thoracotomies was pound sterling 45,000, whilst the cost of performing 105 head CTs was pound sterling 16,000. This represented a substantial saving for the healthcare provider and preserved the quality of life in five patients. CONCLUSIONS: We conclude that screening for cerebral metastases in neurologically intact patients with potentially resectable non small cell lung cancer patients is both worthwhile and cost effective.

Adenocarcinoma↗

How does a g993t mutation in the emerin gene cause Emery-Dreifuss muscular dystrophy?

X-linked Emery-Dreifuss muscular dystrophy is usually caused by absence of the nuclear membrane protein, emerin, due to nonsense mutations or deletions, but a few missense mutations also exist. A pathogenic g993t mutation causes a Q133H change in the nuclear targeting region of emerin, but it may also reduce emerin levels by affecting mRNA splicing. We have introduced the g993t mutation by in vitro mutagenesis and studied the effect of Q133H on nuclear targeting by transfection of COS-7 cells. No qualitative or quantitative differences in nuclear targeting were observed between normal and mutant emerin. Quantitative BIAcore analysis showed no significant change in lamin A binding to emerin when the mutation was present. We conclude that Q133 is not essential for nuclear targeting of emerin or its interaction with lamin A. Reduced emerin levels due to altered splicing or defective interaction with an unidentified binding partner remain possible pathogenic mechanisms.

Biosensing Techniques↗

The R482Q lamin A/C mutation that causes lipodystrophy does not prevent nuclear targeting of lamin A in adipocytes or its interaction with emerin.

Most pathogenic missense mutations in the lamin A/C gene identified so far cause autosomal-dominant dilated cardiomyopathy and/or Emery-Dreifuss muscular dystrophy. A few specific mutations, however, cause a disease with remarkably different clinical features: FPLD, or familial partial lipodystrophy (Dunnigan-type), which mainly affects adipose tissue. We have prepared lamin A with a known FPLD mutation (R482Q) by in vitro mutagenesis. Nuclear targeting of lamin A in transfected COS cells, human skeletal muscle cells or mouse adipocyte cell cultures (pre- and post-differentiation) was not detectably affected by the mutation. Quantitative in vitro measurements of lamin A interaction with emerin using a biosensor also showed no effect of the mutation. The results show that the loss of function of R482 in lamin A/C in FPLD does not involve loss of ability to form a nuclear lamina or to interact with the nuclear membrane protein, emerin.

Adipocytes↗

Direct interaction between emerin and lamin A.

Emerin is the protein of the inner nuclear membrane that is affected by mutation in X-linked Emery-Dreifuss muscular dystrophy. The autosomal dominant form of the disease is caused by mutations in the lamin A/C gene. Several lines of circumstantial evidence have suggested an interaction of emerin with lamins in the nuclear lamina but direct interaction between the two proteins has not yet been demonstrated. We now demonstrate direct interaction between recombinant emerin and lamin A molecules using biomolecular interaction analysis (BIA) and monoclonal antibodies. An emerin-lamin A interaction system may be related in function to the LAP2-lamin B system at the inner nuclear rim.

Antibodies, Monoclonal↗

The relationship between voluntary electromyogram, endurance time and intensity of effort in isometric handgrip exercise.

The relationship between relative force, electromyogram (EMG) and time to fatigue was examined in seven male and seven female subjects [mean (SD) age, 21.7 (3.2) years] during isometric handgrip exercise. Subjects performed sustained submaximal contractions of the right handgrip at three different intensities: 30%, 50%, and 75% of the pretrial maximum voluntary contraction (MVC). EMG was sampled in 1-s epochs every 15 s during the contractions, and the integrated EMG (IEMG) values were then normalized to that of the pretrial MVC. As expected, time to fatigue was longest at 30% MVC and shortest at 75% MVC, but women performed consistently longer than men at each of the three intensities [woman vs men; 400.7 (35.8) vs 364.3 (34.4) s, 205.1 (15.6) vs 139.4 (13) s, and 89.9 (11.4) vs 66.4 (6.4) s, for 30%, 50%, and 75% MVC, respectively; P < 0.05)]. IEMG increased in a non-linear fashion over time during each trial, with the magnitude of IEMG being proportional to the intensity of the contraction. At the endurance limit, IEMG was greatest in the 75% MVC trial, however, no IEMG values reached those obtained in the related MVC [30%, 57.2 (6.9)%, 50%, 84.6 (5.7)%; 75%, 92.8 (7.4)%]. In conclusion, endurance time during sustained submaximal isometric handgrip exercise is dependent up on the intensity of the effort, with women having significantly larger endurance times than men. The related increase in IEMG is also proportional to the intensity of effort, however, the factors causing force to fail prior to the final IEMG reaching its predicted maximum remain to be elucidated.

Adult↗

Migration and Helicobacter pylori seroprevalence: Bangladeshi migrants in the U.K.

Helicobacter pylori, an infectious agent of worldwide public health importance, has higher seroprevalence in developing countries than in developed countries. We investigated whether Bangladeshi women, born in Bangladesh, have a greater H. pylori seroprevalence than Bangladeshi women born in the U.K. and, in addition, whether there is an association between H. pylori seropositivity and age of migration to the U.K. amongst Bangladeshi women. Women attending antenatal clinics at the Royal London Hospital were screened using ELISA for anti-H. pylori IgG. In Bangladeshi individuals born in the U.K., 13/16 (81%, 95% confidence interval (CI) 54%-96%) and, in Bangladeshi individuals born in Bangladesh 91/137 (66%, 95% CI 59%-74%) had antibodies to H. pylori. No significant association was found between H. pylori seropositivity and country of birth, or age at migration to the U.K. Public health strategies concerning H. pylori should consider migrant populations with high seroprevalence of H. pylori.

Adolescent↗

Helicobacter pylori infection in dentists--a case-control study.

To test the null hypothesis that frequent and multiple salivary exposure is not a risk factor for developing H. pylori infection, serum anti-H. pylori IgG from 179 dentists and dental students and 179 age-, sex- and socioeconomic-matched controls were assayed using an ELISA. Seroprevalence in dentists was 16% (11/70); clinical dental students 6% (3/47); and pre-clinical dental students 10% (6/62). There were no differences in H. pylori seropositivity between cases and controls. There was an increase in H. pylori seropositivity with age (chi (trend)2 9.04, p = 0.003). These data provide evidence that adults are not at high risk of developing H. pylori infection as a result of exposures to saliva from multiple sources.

Adolescent↗

High prevalence of Helicobacter pylori metronidazole resistance in migrants to east London: relation with previous nitroimidazole exposure and gastroduodenal disease.

A high prevalence of metronidazole resistance in Helicobacter pylori is reported in developing countries. This study examined whether migrants referred for diagnostic gastroscopy at a United Kingdom centre (n = 54), had a higher prevalence of metronidazole resistance than subjects born in the United Kingdom attending endoscopy (n = 46). Records of nitroimidazole treatment prescribed in the United Kingdom was obtained in 83 patients to find out if there was an association between H pylori metronidazole resistance and previous ingestion of either metronidazole or tinidazole. The prevalence of metronidazole resistant isolates varied according to country of birth: Bangladesh (90%, 27 of 30), other countries (67%, 16 of 24), and United Kingdom (37%, 17 of 46) (p < 0.001). Among those born in the United Kingdom, women were more likely to harbour resistant H pylori than men (54% v 18% respectively, p = 0.01) and more likely to have a history of previous nitroimidazole ingestion (41% v 11% respectively, p = 0.02). Patients previously exposed to either metronidazole or tinidazole were more likely to harbour resistant strains (84% (27 of 32) v 41% (21 or 51), p < 0.0001). The distribution of gastroduodenal disease, assessed endoscopically, was not affected by metronidazole resistance status.

Adult↗

Relationship between infective load of Helicobacter pylori and reactive oxygen metabolite production in antral mucosa.

Helicobacter pylori infection has been associated with stimulation of gastric mucosal reactive oxygen metabolite production. To provide further evidence of a causal relationship we looked for a dose-response relationship. We studied antral biopsy material from 110 patients. Quantitative H. pylori assessments were made using histologic and microbiologic methods. Reactive oxygen metabolite production was measured by luminol-dependent chemiluminescence. The usefulness of timed urease test colour changes as a guide to infective load was assessed. There was a positive association between mucosal reactive oxygen metabolite production and histologic (p = 0.002, n = 69) and microbiologic (Spearman's R = +0.6, p = 0.05, n = 18) quantitative H. pylori assessments. H. pylori infective load varied markedly over small areas (coefficient of repeatability of paired cultures (in colony-forming units/mg) = 1.9 x 10(6). Urease test timing correlated with histologic (p = 0.01) and microbiologic (p = 0.03) H. pylori quantitation. Histologically assessed mucosal damage was related to quantitative H. pylori assessment and to mucosal reactive oxygen metabolite production (p = 0.0001). These results support the hypothesis that H. pylori stimulates gastric mucosal reactive oxygen metabolite production and that this phenomenon is of pathogenic importance.

Adolescent↗

Computed tomography in abdominal trauma: an audit of usage and image quality.

The use and quality of computed tomography (CT) in the evaluation of blunt abdominal trauma has been assessed by a retrospective review of 122 patients referred in the first 8 years following the installation of CT of the body. The referral patterns were analysed, and the quality of the images was assessed, with particular reference to unsatisfactory (unacceptable or poor) images. Referrals increased over the 8 years following installation. A large proportion of these examinations were performed outside normal working hours (58/122, 48%). In 64 out of 122 (52%) of examinations the images were considered of unsatisfactory quality with inadequate use of intravenous contrast medium cited as the most common cause for unsatisfactory examinations. Image quality did not improve with time. Image quality was unsatisfactory in a larger proportion of those examinations performed outside normal working hours (35/58, 60%) than those during the routine working day (29/64, 45%), although this difference did not reach statistical significance (0.1 greater than p greater than 0.05). Fewer unsatisfactory examinations were produced by a system dedicated to body CT (31/74, 42%) than by a neuroradiological system (33/48, 69%) (p less than 0.01). The proportion of unsatisfactory abdominal examinations was lower when the CT study concentrated on the abdomen (26/65, 40%) than when multiple regions (head, chest, abdomen, etc.) were examined (38/57, 67%) (p less than 0.01). This audit revealed many unsatisfactory examinations. In order to complete the audit loop we have addressed many of the contributory factors. A new CT system now provides images of high quality and is used for all abdominal work. Guidelines, which describe an optimized technique, have been issued to radiographers and radiologists. In particular, we have emphasized that there is no place for a poorly supervised "quick look" at the abdomen following a cranial or thoracic study.

Abdominal Injuries↗

A model role of occupational therapy in back education.

This paper presents a description of the Canadian Back Education Units (CBEU) which was formed in 1974. It presently has three programmes; hospital, community and industry. The authors describe the basic philosophy and objectives of the CBEU with specific emphasis on the role of occupational therapy. The paper illustrates how occupational therapy is particularly essential in the community and industrial settings. The authors mention recommendations for expansion of the role of occupational therapy in community and industrial settings.

Back Pain↗

Gastrointestinal cancer studies in the human to nude mouse heterotransplant system.

Human gastrointestinal cancer xenografts were established in the nude mouse. Grafts were accomplished with gastric adenocarcinomas, gastric leiomyosarcoma, histiocytic lymphoma of the stomach and gallbladder, pancreatic tumors, colonic cancers and cell lines of duodenal (HUTU-80) and pancreatic (HS-766-T) cancers, melanoma (SK-Mel-5), and murine metastasizing Lewis lung carcinoma. The rate of successful xenografting of these tumors varied from virtually 100% with colon and duodenal cancer, 50% for a pancreatic cancer (P-1), to only 17% for gastric adenocarcinoma. Pancreas and colon adenocarcinomas have been maintained by successive xenotransplantation over 16 and 19 months, respectively. Human xenografts retained morphological identity with tissues of origin through several transplant generations and shared some of their ultrastructural characteristics but did not metastasize. Rodent xenografts, of heterogenous origin were characterized by differences in the duration of the latent period and in the rate of their initial development as described by the average doubling times and average slopes (B) of their growth curves. Differences between B of the Lewis lung carcinoma and all of the human xenografts and between B of a pancreatic adenocarcinoma and three other neoplasms were significant (P less than 0.05 to 0.04). Labeling indices determined for 14 cancer transplants were in the range of previously reported data for similar neoplasms in patients or other xenograft systems. These findings suggest that the nude mouse model can be used to evaluate endogenous properties of gastrointestinal cancers and their responses to exogenous agents.

Adenocarcinoma↗