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Biomedical subjects

M Clarke

Publications and source records attributed to M Clarke.

At least 145 records · Page 8Linked to original sources

Sonography of normal cranial sutures.

OBJECTIVE: The purpose of this study was to describe the normal sonographic appearance and measurement of normal major cranial sutures in neonates and infants. SUBJECTS AND METHODS: High-resolution sonograms of sagittal, coronal, and lambdoid sutures were obtained for two autopsy specimens and correlated with histologic sections obtained at identical locations. Also, 50 neonates and infants (0-5 months old [corrected age]) who had normally shaped craniums underwent sonography of the brain that produced normal findings. These neonates and infants also underwent sutural sonograms. The width and thickness of each of the major cranial sutures (sagittal, coronal, and lambdoid) were measured, with mean values established. Measurements were analyzed with paired t tests for interobserver variability. Linear regression was used for correlation of measurements with age. RESULTS: With a scan plane perpendicular to the suture line, sonograms revealed sutures as hypoechoic gaps between two hyperechoic bony plates. On sonograms, sagittal sutures had an end-to-end appearance instead of the beveled junction seen throughout most of the coronal and lambdoid sutures. In the 50 patients, sonograms revealed the mean width to be 0.89 +/- 0.35 mm (mean +/- SD) for coronal sutures. 0.93 +/- 0.28 mm for sagittal sutures, and 0.96 +/- 0.39 mm for lambdoid sutures. On sonograms, mean thickness was 1.97 +/- 0.54 mm for coronal sutures, 1.88 +/- 0.56 mm for sagittal sutures, and 2.49 +/- 0.86 mm for lambdoid sutures. We found no interobserver variability (p < or = .05). With linear regression analysis, we found no correlation between suture width or thickness and patient age (r = .01). CONCLUSION: In our study, high-resolution sonography proved to be a reliable and inexpensive technique capable of defining cranial sutures. Preliminary normative data obtained for cranial suture width and thickness showed no correlation with age in our population group. The normative data obtained will allow recognition of abnormal sutures, particularly synostotic or diastatic sutures.

Cranial Sutures↗

Combating tuberculosis--lessons learnt from a rural community project in the Klein Drakenstein area of the Western Cape.

OBJECTIVE: To describe and evaluate a lay worker project designed to enhance the effective control of tuberculosis in a rural/farm setting. DESIGN: A descriptive cohort study using both qualitative and quantitative research methodology. SETTING AND PARTICIPANTS: Farming community in the Klein Drakenstein area of Paarl, Western Cape, with health services provided by the Cape Metropolitan Council. The adherence of patients receiving tuberculosis treatment from 1 January 1993 to 31 December 1995 was analysed. The acceptability of the project was assessed using indepth interviews with key stakeholders. RESULTS: A cohort of 402 tuberculosis patients was included in the study. This cohort was divided into the patients from farms that had participated in the project (intervention group) and those that had not (non-intervention group). The adherence data for children and adults were analysed separately. The adherence rates for children in both groups were the same (RR = 1.00, 95% Cl 0.88-1.14), whereas the adherence rate for the adult intervention group was significantly better than that of the non-intervention group (RR = 1.19, 95% Cl 1.08-1.31). The qualitative component of the investigation indicated a high level of commitment to the intervention from the members of the implementation team, the farm health workers and their employers. The farm health workers described how their role had assisted their communities and had improved their own perceptions of self-efficacy. The close bond that they had developed with the formal health sector had improved the access of the labourers on the farm to primary health care. Although the project had commenced as a tuberculosis initiative, the farm health workers were dealing with a variety of health issues. Their ongoing training was designed to facilitate this development. The formal health sector found their activities facilitated by the easy access that they had with a representative from each farm. The employers were satisfied that the project had increased the cost-effectiveness of their economic endeavours. CONCLUSION: This farm worker project appears to be a model of a well-designed and expertly managed community-based project for tuberculosis control in rural/farm areas.

Adolescent↗

A pilot survey of sexual function and quality of life following 3D conformal radiotherapy for clinically localized prostate cancer.

PURPOSE: To assess the impact of high dose three-dimensional conformal radiotherapy (3D CRT) for prostate cancer on the sexual function-related quality of life of patients and their partners. METHODS AND MATERIALS: Sixty of 124 consecutive patients (median age 72.3 years) treated with 3D CRT for localized prostate cancer were surveyed and reported being potent prior to treatment. The answers to survey questions assessing the impact of quality of life related to sexual function from these 60 patients and their partners forms the basis for this retrospective analysis. RESULTS: Following 3D CRT, 37 of 60 patients (62%) retained sexual function sufficient for intercourse. Intercourse at least once per month was reduced from 71 to 40%, whereas intercourse less than once per year increased from 12 to 35%. Following treatment, 25% of patients reported that the change in sexual dysfunction negatively affected their relationship or resulted in poor self-esteem. This outcome was associated with impotence following treatment (p < 0.01). Patients who had partners and satisfactory sexual function appeared to be at a higher risk of having a negatively affected relationship or losing self-esteem if they become impotent (p < 0.05). Partners of patients who reported a negatively affected relationship or loss of self-esteem appear to be less likely to return the survey instrument used (p = 0.02). CONCLUSIONS: More work is needed to evaluate the impact of radiotherapy and other treatments on the quality of life of patients and their partners to allow adequate informed consent to be given.

Adenocarcinoma↗

Chronic lung disease following neonatal ventilation. II. Changing incidence in a geographically defined population.

The objective of this study was to examine the change in incidence of chronic lung disease following neonatal ventilation in a geographically defined population. Prospective data were collected over two 1-year periods (1987-1988 and 1990-1991) in the Trent Health Region, England. All infants were < or = 32 weeks gestation and/or < or = 1500g birthweight, born to mothers normally resident in the Trent Health Region. The principal outcome measures were mortality rate, presence of chronic lung disease, days of ventilation, and oxygen used by each infant. The proportion of low gestation, low birthweight babies was 1.5% in each period, made up of 897 and 925 babies from 61,050 and 63,350 births, respectively. There was a significant fall in mortality in infants of 750-1500g birthweight. However, the incidence of chronic lung disease (using either of two definitions) rose significantly between the two periods, with a corresponding large rise in the amount of respiratory care required. The contribution of various antenatal factors previously thought to be related to the development of chronic lung disease was examined. Birthweight and gestation were shown to be of overwhelming significance. We concluded that improvements in neonatal care, including the introduction of surfactant therapy, improved survival for some infants at the expense of an increased incidence of chronic lung disease. Clearly the hoped-for cost saving following the introduction of surfactant therapy has not occurred.

Bronchopulmonary Dysplasia↗

The effects of malignant glioma on the EEG and seizure thresholds: an experimental study.

Generalised or partial seizures are a common problem with many supratentorial gliomas. Their underlying pathophysiological mechanisms are poorly understood. To investigate this problem clinical and EEG seizure thresholds were investigated in experimental rodent gliomas using the epileptogenic drug pentylenetetrazole (PTZ). Mixed C6/A15A5 malignant gliomas were grown in adult Wistar rats after unilateral stereotactic implantation of a 50:50 cell mix into the caudoputaminal region. Eleven to 14 days later EEG (raw and spectrally analysed) was recorded bilaterally from the frontal and parietal regions under mixed alpha-chloralose and urethane anaesthesia. Baseline EEG (15 minutes), EEG during and after (30 minutes) PTZ infusion (100 microliters/min) and the time to appearance of seizure manifestations after starting PTZ were recorded. Fourteen animals were studied (5 normal, 5 with tumours, 4 sham implants) and mean BP, PaCO2, PaO2 and temperature were similar in the three groups. Baseline raw EEG showed predominate slow wave activity with lower amplitude and less spontaneous activity overlying tumours. Following PTZ infusion a sequence of vibrissal twitching (following a mean of 14.5 mg/kg PTZ in control and sham animals); jaw/nasal twitches (17.5 mg/kg); fore and hind limb jerking (46 mg/kg); myoclonic jerking (47 mg/kg); and status (77.5 mg/kg) was observed. The seizure thresholds for all PTZ induced seizure phenomena were, except for status epilepticus, highest in the tumour bearing animals. The time to 70% seizure activity on the EEG was also significantly longer in the tumour bearing animals. Spectral analysis of the EEG, although showing increased alpha and theta activity after PTZ infusion, did not discriminate between the three experimental groups either before or after PTZ activation. These studies have confirmed that experimental gliomas alter baseline EEG and both the EEG and behavioural response to PTZ. The reasons for the raised seizure threshold in the glioma bearing animals and the relevance of this experimental paradigm to human tumour associated epilepsy are discussed.

Adult↗

Annual visits to patients over the age of 75--who is missed?

BACKGROUND: In the UK, the GP contract requires annual consultations and offers of home visits to the elderly. However, as many as 50% of elderly people refuse the offer of a health screen. OBJECTIVE: To describe the characteristics of elderly people who declined the offer of an annual home visit. METHOD: All elderly people aged 75 years and over, registered with a general practice of 13 full time and 3 part time doctors with a list size of 33,000 people, were offered a home visit. Data from this prospective cohort were linked with data from a community survey two years previously, which had achieved a 95% response rate. The main outcome measures were perceived health status, perceived loneliness, morale score, physical and mental disability, use of primary care and social services. RESULTS: Thirty-six percent of all elderly people registered with the practice declined to take up the offer of a home visit. Those refusing a visit had not recently joined the practice and had very similar distributions of all demographic and most health and wellbeing characteristics to those who took up the offer. However, those declining appeared to have higher levels of morale (P = 0.010) and less contact with the general practitioner (P = 0.021) including an average of three weeks longer since last consultation with their general practitioner than those accepting the visit. CONCLUSIONS: There appears little evidence in this population that elderly people who decline a home visit are necessarily part of an 'iceberg' of unmet need.

Activities of Daily Living↗

Physical function and perceived health: cohort differences and interrelationships in older people.

Differences between seven-year birth cohorts in physical functioning (as measured by independence in activities of daily living) are compared with corresponding inter-cohort differences in perceived health, in people aged 75 years and over. Age-period-cohort models were fitted to two linked cross-sectional surveys undertaken in 1981 (N = 1,203) and 1988 (N = 1,579). The proportion of older people who were dependent in ADLs was lower in succeeding cohorts but, by contrast, the proportion with less than good self-perceived health was higher. These inter-cohort differences in perceived health were particularly marked for the comparison between 1981 and 1988 of men aged 75-81 years in the dependent subpopulation. Furthermore, self-perceived health remained as strong a predictor of mortality in 1988 as in 1981. Self-perceived health may be indexing a higher prevalence of mild chronic conditions in newer cohorts of older people, with implications for primary health care providers.

Activities of Daily Living↗

Nasal rather than rectal benzodiazepines in the management of acute childhood seizures?

Benzodiazepines are routinely used by the rectal route for the treatment of acute epileptic seizures: if a benzodiazepine was absorbed from nasal administration this could provide a more acceptable alternative to rectal administration. Nineteen children (age range 7 months to 14 years) with intractable epilepsy were chosen. The EEG's showed unequivocal epileptic activity persisting during the recording. The midazolam was dripped slowly into the anterior nares. Fifteen had a positive response, a dramatic improvement in their EEG or cessation of fits. Drug induced beta activity occurred in 14 children. The mean time to appearance of beta activity was 111.5 secs (SD = 95.3 secs). The reduction in spike count pre and post midazolam was statistically significant (p < 0.01). The improvement in EEG background was also statistically significant. Midazolam is absorbed via the i.n. route. With the dosages used it suppressed epileptic activity and produced an improvement in EEG background. The children and parents found the method acceptable. This is the first study to use the i.n. route for anti-convulsant drugs.

Acute Disease↗

Transdominant mutants of I kappa B alpha block Tat-tumor necrosis factor synergistic activation of human immunodeficiency virus type 1 gene expression and virus multiplication.

The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) contains two binding sites for the NF-kappa B/Rel family of transcription factors which are required for the transcriptional activation of viral genes by inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1. In the present study, we examined the effect of transdominant mutants of I kappa B alpha on the synergistic activation of the HIV-1 LTR by TNF-alpha and the HIV-1 transactivator, Tat, in Jurkat T cells. The synergistic induction of HIV-1 LTR-driven gene expression represented a 50- to 70-fold stimulation and required both an intact HIV-1 enhancer and Tat-TAR element interaction, since mutations in Tat protein (R52Q, R53Q) or in the bulge region of the TAR element that eliminated Tat binding to TAR were unable to stimulate LTR expression. Coexpression of I kappa B alpha inhibited Tat-TNF-alpha activation of HIV LTR in a dose-dependent manner. Transdominant forms of I kappa B alpha, mutated in critical serine or threonine residues required for inducer-mediated (S32A, S36A) and/or constitutive (S283A, T291A, T299A) phosphorylation of I kappa B alpha were tested for their capacity to block HIV-1 LTR transactivation. I kappa B alpha molecules mutated in the N-terminal sites were not degraded following inducer-mediated stimulation (t1/2, > 4 h) and were able to efficiently block HIV-1 LTR transactivation. Strikingly, the I kappa B alpha (S32A, S36A) transdominant mutant was at least five times as effective as wild-type I kappa B alpha in inhibiting synergistic induction of the HIV-1 LTR. This mutant also effectively inhibited HIV-1 multiplication in a single-cycle infection model in Cos-1 cells, as measured by Northern (RNA) blot analysis of viral mRNA species and viral protein production. These experiments suggest a strategy that may contribute to inhibition of HIV-1 gene expression by interfering with the NF-kappa B/Rel signaling pathway.

3T3 Cells↗

Lipid screening in an elderly population: difficulty in interpretation and in detection of occult metabolic disease.

AIMS: To determine lipid profiles and associations with other metabolic disease in a representative British elderly population. METHODS: Part of a prevalence survey of dementia in all 75+ year olds conducted from the large general practice serving the town and surrounding area of Melton Mowbray, Leicestershire (the M-old study). Patients (n = 224) aged from 75 to 98 years, and representative of the overall population, also provided pre-prandial blood samples on which various age and nutrition related analytes were determined. These included documented medical history, thyroid stimulating hormone (TSH), glucose, immunoglobulins, and lipid profile in plasma. RESULTS: Cholesterol and lipid variables showed wide scatter, with some negative trends but no significant associations with age for total cholesterol, high density lipoprotein (HDL) cholesterol, the ratio of total to HDL cholesterol or triglycerides. Women had significantly higher concentrations of total and HDL cholesterol at all ages. Serum TSH was above 6.0 mU/1 in 10/205 patients, random glucose was above 11.2 mmol/l in nine of 207 patients, borderline dysglobulinaemia was present in four of 210 patients, all without correlation with cholesterol concentrations. CONCLUSION: This British data is consistent with an inverse correlation between survival and cholesterol, but wide scatter restricts reliance on single result lipid data in individual patient management. Random lipid screening is also unhelpful, inefficient and without added value in revealing other age related and unrecognised occult metabolic disease.

Aged↗

The vacuolar proton pump of Dictyostelium discoideum: molecular cloning and analysis of the 100 kDa subunit.

The vacuolar proton pump is a highly-conserved multimeric enzyme that catalyzes the translocation of protons across the membranes of eukaryotic cells. Its largest subunit (95-116 kDa) occurs in tissue and organelle-specific isoforms and thus may be involved in targeting the enzyme or modulating its function. In amoebae of Dictyostelium discoideum, proton pumps with a 100 kDa subunit are found in membranes of the contractile vacuole complex, an osmoregulatory organelle. We cloned the cDNA that encodes this 100 kDa protein and found that its sequence predicts a protein 45% identical (68% similar) to the corresponding mammalian proton pump subunit. Like the mammalian protein, the predicted Dictyostelium sequence contains six possible transmembrane domains and a single consensus sequence for N-linked glycosylation. Southern blot analysis detected only a single gene, which was designated vatM. Using genomic DNA and degenerate oligonucleotides based on conserved regions of the protein as primers, we generated products by polymerase chain reaction that included highly variable regions of this protein family. The cloned products were identical in nucleotide sequence to vatM, arguing that Dictyostelium cells contain only a single isoform of this proton pump subunit. Consistent with this interpretation, the amino acid sequences of peptides derived from a protein associated with endosomal membranes (Adessu et al. (1995) J. Cell Sci. 108, 3331-3337) match the predicted sequence of the protein encoded by vatM. Thus, a single isoform of the 100 kDa proton pump subunit appears to serve in both the contractile vacuole system and the endosomal/lysosomal system of Dictyostelium, arguing that this subunit is not responsible for regulating the differing abundance and function of proton pumps in these two compartments. Gene targeting experiments suggest that this subunit plays important (possibly essential) roles in Dictyostelium cells.

Amino Acid Sequence↗

Tapping the television cable.

Immediate access to patient data is essential to support good clinical decision making and support. However, away from the surgery, the doctor is currently unable to have any access to the clinical database. Solutions exist to support remote access, such as modems or radio data networks, but these are slow, with typical speeds in the 2-10 kbaud region. We propose a novel solution, to use the TV cable already installed in many homes. Using this technology, a suitably equipped computer (RF modern) is capable of connecting at speeds in excess of 500 kbaud and will run applications in exactly the same way as if connected to a surgery network: the cable TV becomes a LAN, but on a metropolitan scale. Brunel University, in collaboration with the Cable Corporation, has been piloting such a network. Issues include not only levels of service, but also security on the network and access, since the data are being effectively received in every home. However, close scrutiny of channel use can create closed networks reserved for specific users. The technology involves use of an RF modem to transmit data on a reverse channel (based at 16 MHz) on each subnet to a router at the head end of the cable network. This frequency translates the packet and retransmits it to all the subnets on a forward channel (based at 178 MHz). Each channel occupies the bandwidth normally allocated to one TV channel. Access is based on a modified CSMA/CD protocol, so treating the cable network as single multiple access network. The modem comes as a standard card installed in a PC and appears much as an ethernet card, but at reduced speed. With an NDIS driver it is quite able to support almost any network software, and has successfully demonstrated Novell and TCP/IP. We describe the HomeWorker network and the results from a pilot study being undertaken to determine the performance of the system and its impact on working practice.

Computer Communication Networks↗

Bcl-2, p53, CD44, and CD44v6 isoform expression in neuroendocrine tumors of the lung.

Immunohistochemical expression of p53, bcl-2, CD44 standard (CD44S), and the v6 isoform of CD44 (CD44v6) proteins were studied in 14 typical carcinoid tumors (TCs), 11 atypical carcinoids (ACs), and eight small cell carcinomas (SCLCs) in an attempt to use these markers of mutational events and cellular adhesion to discriminate neoplasms demonstrating neuroendocrine differentiation. p53 and bcl-2 overexpression were associated with more aggressive neuroendocrine cell types. p53 nuclear staining was weakly positive in 21% of the TCs, whereas strong nuclear staining was seen in 64% of the ACs and 88% of the SCLCs (P = 0.0047). bcl-2 was present in 21% of the TCs, 91% of the ACs, and 100% of the SCLCs (P = 0.0001). In contrast, CD44S and CD44v6 were inversely correlated with more aggressive types of neuroendocrine tumors. CD44S expression was moderate to strong in all of the TCs and 91% of the ACs but in only 37% of the SCLCs (P = 0.0018). There was no correlation between expression of these markers and tumor size or nodal status, although loss of CD44v6 was associated with lymph node metastases in the TC group only. In the spectrum of neuroendocrine tumors of the lung, p53 and bcl-2 overexpression correlates with more aggressive histologic cell types. The decreasing CD44S expression in AC and SCLC is similar to findings in cancer of the colon and in non-small cell carcinoma of the lung, where loss of CD44S is associated with poor prognosis. In AC and SCLC, but not in cancer of the colon, loss of CD44v6 correlates with more aggressive neoplasms and might correlate with lymph node metastases in TCs.

Adult↗

PSF and CMF, autocrine factors that regulate gene expression during growth and early development of Dictyostelium.

Throughout growth and development, Dictyostelium cells secrete autocrine factors that accumulate in proportion to cell density. At sufficient concentration, these factors cause changes in gene expression. Vegetative Dictyostelium cells continuously secrete prestarvation factor (PSF). The bacteria upon which the cells feed inhibit their response to PSF, allowing the cells to monitor their own density in relation to that of their food supply. At high PSF/bacteria ratios, which occur during late exponential growth, PSF induces the expression of several genes whose products are needed for cell aggregation. When the food supply has been depleted, PSF production declines, and a second density-sensing pathway is activated. Starving cells secrete conditioned medium factor (CMF), a glycoprotein of Mr 80 kDa that is essential for the development of differentiated cell types. Antisense mutagenesis has shown that cells lacking CMF cannot aggregate, and preliminary data suggest that CMF regulates cAMP signal transduction. Calculations indicate that a mechanism of simultaneously secreting and recognizing a signal molecule, as used by Dictyostelium to monitor cell density, could also be used to determine the total number of cells in a tissue.

Animals↗