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Biomedical subjects

M Kellett

Publications and source records attributed to M Kellett.

At least 19 recordsLinked to original sources

Problems of correlations between explanatory variables in multiple regression analyses in the dental literature.

Multivariable analysis is a widely used statistical methodology for investigating associations amongst clinical variables. However, the problems of collinearity and multicollinearity, which can give rise to spurious results, have in the past frequently been disregarded in dental research. This article illustrates and explains the problems which may be encountered, in the hope of increasing awareness and understanding of these issues, thereby improving the quality of the statistical analyses undertaken in dental research. Three examples from different clinical dental specialties are used to demonstrate how to diagnose the problem of collinearity/multicollinearity in multiple regression analyses and to illustrate how collinearity/multicollinearity can seriously distort the model development process. Lack of awareness of these problems can give rise to misleading results and erroneous interpretations. Multivariable analysis is a useful tool for dental research, though only if its users thoroughly understand the assumptions and limitations of these methods. It would benefit evidence-based dentistry enormously if researchers were more aware of both the complexities involved in multiple regression when using these methods and of the need for expert statistical consultation in developing study design and selecting appropriate statistical methodologies.

Data Interpretation, Statistical↗

Reversible parkinsonism with normal beta-CIT-SPECT in patients exposed to sodium valproate.

After reports of reversible parkinsonism and cognitive impairment with sodium valproate (VPA), the authors examined 50 consecutive patients taking VPA and 20 patients taking carbamazepine. Three patients taking VPA exhibited unequivocal parkinsonism with Unified Parkinson Disease Rating Scale scores >30. VPA was withdrawn from two patients with improvement of symptoms. Reduction in VPA dosage in the third patient produced no improvement. beta-CIT-SPECT scans were normal, suggesting dopaminergic neuronal loss is not the underlying mechanism.

Adult↗

Thermal tolerance trade-offs associated with the right arm of chromosome 3 and marked by the hsr-omega gene in Drosophila melanogaster.

Drosophila melanogaster occurs in diverse climatic regions and shows opposing clinal changes in resistance to heat and resistance to cold along a 3000 km latitudinal transect on the eastern coast of Australia. We report here on variation at a polymorphic 8 bp-indel site in the heat shock hsr-omega gene that maps to the right arm of chromosome 3. The frequency of the genetic element marked by the L form of the gene was strongly and positively associated with latitude along this transect, and latitudinal differences in L frequency were robustly associated with latitudinal differences in maximum temperature for the hottest month. On a genetic background mixed for genes from each end of the cline a set of 10 lines was derived, five of which were fixed for the L marker, the absence of In(3R)P and 12 kb of repeats at a second polymorphic site at the 3' end of hsr-omega, and five that were fixed for the S marker, In(3R)P and 15 kb of hsr-omega repeats. For two different measures of heat tolerance S lines outperformed L lines, and for two different measures of cold tolerance L lines outperformed S lines. These data suggest that an element on the right arm of chromosome 3, possibly In(3R)P, confers heat resistance but carries the trade-off of also conferring susceptibility to cold. This element occurs at high frequency near the equator. The alternate element on the other hand, at high frequency at temperate latitudes, confers cold resistance at the cost of heat susceptibility.

Acclimatization↗

The management of paediatric urolithiasis.

OBJECTIVE: To evaluate the efficacy and safety of the management of paediatric urolithiasis by extracorporeal shock wave lithotripsy (ESWL), endoscopic ureterolithotomy, percutaneous nephrolithotomy (PCNL) and open nephrolithotomy. PATIENTS AND METHODS: In a 3-year period (1997-1999), 59 children were treated for urolithiasis and underwent a total of 79 procedures. Thirty-two ESWL sessions were performed in 23 children (mean age 7.4 years, median 6.0). PCNL was undertaken in 30 renal units in 25 children (mean age 6.4 years, median 4.0). Eight patients (mean age 7.8 years, median 5) underwent 17 ureteroscopic procedures, six of which involved the use of a holmium laser. Three children with staghorn calculi underwent open nephrolithotomy under conditions of renal ischaemia and hypothermia. RESULTS: Of the 23 children treated using ESWL, 21 (91%) became stone-free; 17 underwent one ESWL session (74%), three had two sessions and three (13%) had three sessions. All eight patients who underwent ureteroscopy became stone-free. Four patients in whom the stone could not be reached by ureteroscopy initially had a JJ stent inserted, and the stone and stent subsequently removed. Stones were cleared using PCNL in 27 of 30 renal units (90%); three patients who had residual stone fragments were rendered stone-free by ESWL. Two of three children undergoing open nephrolithotomy were stone-free after surgery and the remaining one rendered stone-free with ESWL. Metabolic evaluation showed that 25 of 45 children (55%) had a urinary infection, eight (18%) had hyperoxaluria, three (7%) had hypercalciuria, two (4%) had cystinuria, and no identifiable cause was found in seven (16%). Treatment by a single modality rendered 52 of the 59 children (88%) stone-free; when the different modalities were combined, 57 of 59 patients (97%) were cleared of their stones. CONCLUSIONS: Technological advances in ESWL, ureteroscopy and PCNL have had a significant effect on the management of urolithiasis in children, allowing a safe and successful outcome. The comprehensive care of children with urolithiasis should include a full metabolic evaluation. Anatomical anomalies contribute to the complexity of many cases, necessitating a close liaison between adult and paediatric urologists, nephrologists and radiologists to optimize stone management in children.

Adolescent↗

Glove powder: implications for infection control.

Gloves are increasingly promoted for use by healthcare workers, but this use is not without risk. Data associating powdered gloves with an increased risk of latex allergy is available and there is circumstantial evidence that the powder used may increase bacterial environmental contamination. In animal models, corn starch, the material used as glove powder, promotes wound infection. Infection control teams need to be aware of this evidence and should support switching from use of powdered to powder free gloves.

Gloves, Protective↗

The relationship between the supply of cardiac catheterization laboratories, cardiologists and the use of invasive cardiac procedures in northern New England.

OBJECTIVES: Utilization rates of coronary angiography and cardiac revascularization have been found to vary between areas. This study addresses the relationship between resource supply and procedure rates. METHODS: We compared the association of per capita catheterization laboratories, per capita cardiologists and multi-provider markets (where more than one hospital offers coronary angiography services) with the utilization rates for angiography and cardiac revascularization in northern New England, USA. Administrative data were used to capture invasive cardiac procedures. Small area analyses were used to create coronary angiography service areas. Linear regression methods were used to measure associations between the resource supply and utilization rates. RESULTS: Variation in the use of invasive cardiac procedures was strongly associated with the population-based availability of catheterization facilities and multi-provider markets and unrelated to cardiologist supply or need (as reflected in the hospitalization rates for myocardial infarction). In the multivariate model, an increase of 1 catheterization laboratory per 100,000 population was associated with an increase in the angiography rate of 1.62 per 1000 population; those service areas with multi-provider markets were associated with an additional increase in the angiography rate of 1.27 per 1000 population (R2 = 0.84, P = 0.0006). There was a moderately strong relationship between the catheterization laboratories per capita and the revascularization rates (R2 = 0.43, P = 0.029). Angiography rates were highly associated with cardiac revascularization rates: an increase in the angiography rate of 1 per 1000 population was associated with a 0.46 per 1000 increase in the cardiac revascularization rate (R2 = 0.85, P = 0.0001). CONCLUSIONS: Our work suggests that current efforts to address variation in cardiac procedures through activities such as appropriateness criteria, guidelines and utilization review are misdirected and should be redirected towards capacity, in this case the supply of catheterization facilities.

Cardiac Catheterization↗

Plaque abrasion and intra-aortic balloon leak.

STUDY OBJECTIVE: To determine and correct cause of high incidence of intra-aortic balloon leaks (ruptures). DESIGN: Epidemiologic investigation of factors associated with intra-aortic balloon leak, and sequential application of corrective measures evaluated by continued concurrent data collection. SETTING: Thirty-four-bed ICU in 598-bed tertiary care medical center. INTERVENTIONS: Procedure changed to place smaller balloons (34 mL instead of 40 mL) in patients less than 163 cm in height. MEASUREMENTS AND RESULTS: Demographic and clinical data on all patients showed no change after initial interventions, followed by significant drop (8 to 2%) in incidence of balloon leak when smaller, shorter balloons were placed in shorter patients. CONCLUSIONS: Placement of larger, longer balloons in patients increases risk of perforation of balloon by calcific plaque in the distal thoracic and abdominal aorta.

Aged↗

A multicentered clinical study on posterior resin-bonded bridges: the 'Manchester trial'.

This study was designed to investigate and identify factors relevant to the success and failure of posterior resin-bonded bridges (PRBBs) related to the patient, technique, operator and bridge design. It was a long-term controlled clinical trial and formed part of a multicentered study on PRBBs. Data are presented 2.5 years from the start of the study. Following a strict protocol for case selection, 54 posterior, resin-bonded, fixed-fixed, three unit bridges were placed in 45 patients. Twenty-four patients with 27 PRBBs attended for 2.5-year recall. Treatment variables were limited to one of two operators and either a conventional tooth preparation or a more extensive modified preparation was performed. The allocation of treatment modalities was performed using a computer program to balance patient variables such as age, gender, location of bridge, restoration of abutment teeth. All bridges were produced in one laboratory, treated to produce a silicate-coating bond and placed using Microfill Pontic C (Kulzer, Wehrheim, Germany). Data relating to the patients, the open spaces, bridge preparation, bridge placement and subsequent annual evaluation were recorded. The survival of PRBBs in the maxilla was 77% and in the mandible 47%.

Adolescent↗

Measurement of in vivo proliferation in human colorectal mucosa using bromodeoxyuridine.

In vivo bromodeoxyuridine (BrdUrd) labelling of the human large bowel was performed and a detailed histochemical localisation of label in sections of crypts was undertaken using a monoclonal antibody to BrdUrd containing DNA. Flow cytometric studies on extracted nuclei were also performed (data presented elsewhere). The average crypt in the human large bowel (excluding the rectum) was 82 cells in height and 41 cells in circumference, with a total of about 2000 cells (assuming a topographical correction factor of 0.6). Ten per cent of the cells were replicating their DNA--that is, were in the S phase of the cell cycle--and 0.4% were in mitosis. The median position for the labelling index versus cell position frequency plot is at the 20th cell position--at a quarter of the crypt height. The lower and upper limits of the cell proliferation are given by the 5th and 95th percentiles at cell positions 4 and 43 respectively. The peak labelling index is about 30% and it occurs at cell position 15. The labelling index at the crypt base, the probable stem cell zone, is about 14%, suggesting that these cells have a longer cell cycle. Taking a value of 8.6 hours for the duration of the S phase (deduced from the flow cytometric data) and assuming a growth fraction of 1.0 for the mid-crypt, these data provide an estimate of about 30 hours for the cell cycle time. The rectal crypts are about the same size but contain about 30% fewer S phase cells. The data also yielded a per cent BrdUrd labelled mitosis curve.

Aged↗

Proliferation in human gastrointestinal epithelium using bromodeoxyuridine in vivo: data for different sites, proximity to a tumour, and polyposis coli.

The distribution of DNA synthesising cells in the crypts of the epithelium in human small and large bowel after injection of bromodeoxyuridine into patients has been studied in relation to the position of the cells in the crypt using immunohistochemistry. Different sites of normal epithelium have been studied. The ileum has a shorter crypt and a very significantly smaller total cell population size. However, it has similar peak labelling index (LI) values to the colon, while the rectum has a lower peak LI value. The mean position of the label occurs at the 17th cell position in the ileum and at about the 22nd position in both the colon and rectum. The overall mean LI is significantly higher in the ileum at 17.8%, intermediate in the colon at 10.3%, and lowest in the rectum at 8.5%. There is thus an inverse relation between the likelihood of developing a tumour and the rate of cell proliferation as measured by the LI. Assuming a value of 8.6 hours for the duration of S, the data suggest that the cell cycle time in the mid crypt region is about 30 hours for the ileum and colon and about 37 hours for the rectum. Samples taken adjacent (within 1 cm) to a tumour show a general dampening of proliferative activity at all cell positions compared with samples taken more than 5 cm from a tumour. This is illustrated by the average LI, which is about 5.4% in the colon adjacent to a tumour compared with 10% distant; comparable values for the rectum are 4.6% and 8.5%. Samples taken from two patients with polyposis coli show distributions with a significant difference in skewness compared with normal colon and a general shifting of the distribution to the right, that is to higher cell positions. There is a significant increase in the mean cell position and the position of the peak LI in the polyposis coli samples.

Adenomatous Polyposis Coli↗

A comparison of in vivo cell proliferation measurements in the intestine of mouse and man.

Using tritiated thymidine (3HTdR) labelling in vivo in the mouse we have determined the labelling index (LI%) at each cell position along the sides of sections of crypts in the small and large bowel. We have compared LI versus cell position frequency plots obtained in this way with those obtained using bromodeoxyuridine (BrdUrd) in vivo in the small intestine. Both thymidine analogues give identical patterns and similar levels of labelling: for example, the overall LI is 29.1% after 3HTdR and 34.7% after BrdUrd in the mouse ileum. Similar data have been obtained following in vivo labelling in humans with BrdUrd prior to gastrointestinal surgery for cancer and in mouse colon following 3HTdR labelling. Comparisons between the mouse and human data show that the spatial distribution of label within the crypts occurs at the same relative positions in the two species. However, the intestinal crypts are between 2-fold and 4-fold larger, particularly in their length, in the human: for example, 250 and 450 cells per crypt for ileum and 590 and 2000 cells per crypt for the colon in mouse and human respectively. The absolute value of the maximum LI in the mouse small intestine (56.5%) is higher than it is in the human (26.3%). However, the patterns of proliferation are similar in the two species under steady-state conditions.

Animals↗

A topographical study of the circadian rhythm in labelling index of mouse gingival and floor-of-mouth epithelium, including changes in labelling activity with individual cell position on the epithelial ridges.

A continuous strip of epithelium from the mandibular teeth to the ventral surface of the tongue of B6D2F-1 mice was examined autoradiographically after tritiated thymidine flash-labelling. Five areas were defined: area 1, the gingival sulcus epithelium adjacent to tooth enamel; area 2, the free gingival margin epithelium; area 3, the attached gingiva; area 4, the floor of mouth with undulating basement membrane; area 5, the floor of mouth with flat basement membrane. Data for the circadian variation in the proportion of DNA synthetic cells were recorded into a microcomputer, which enabled a large number of cells to be scored. The topographical position of each basal cell along the rete ridges and the incidence of labelling were noted. In each of the five areas a statistically significant circadian variation in labelling index (LI) was demonstrated, with a peak at 04.00-06.00 h and a trough at 20.00 h, although area 1 was slightly out of phase with the rest. The 24-h average LI values were almost double those obtained from a single flash-labelling at 10.00 h. The peak to trough ratio in LI was greatest in area 5 and fell towards area 1. Within the attached gingiva, cells deepest in the epithelial ridges had a larger peak to trough ratio than more superficial basal cells. For a group of mice labelled at 10.00 h the mean LI of the basal epithelial cells in areas 1-5 was 7.5 +/- (3.0)% (SD). Various aspects of the distribution of DNA synthesis in relation to topography were examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ro 22-5417, a new clavam antibiotic from Streptomyces clavuligerus. I. Discovery and biological activity.

Streptomyces clavuligerus NRRL 3585, a culture which produces a variety of beta-lactam antibiotics in the penicillin, cephalosporin and clavam families, was found to produce a new beta-lactam antibiotic, Ro 22-5417. The compound, which was neither a substrate for nor inhibitor of several beta-lactamases, showed antimicrobial activity in defined minimal medium but little or no inhibitory activity in nutrient-rich medium. The activity was bacteriostatic against Bacillus species ATCC 27860 and was antagonized by D- and L-methionine, L-cystathionine, L-homocystine and O-acetyl-L-homoserine but not by L-homoserine, L-aspartate, L-cysteine or other common amino acids, vitamins and nucleosides. Our results are consistent with Ro 22-5417 acting as an inhibitor in methionine biosynthesis.

Anti-Bacterial Agents↗