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Biomedical subjects

S A Kelly

Publications and source records attributed to S A Kelly.

At least 19 recordsLinked to original sources
PubMed1999

Fluoride intake from foods, beverages and dentifrice by young children in communities with negligibly and optimally fluoridated water: a pilot study.

UNLABELLED: While the level of fluoride intake that affords optimal cariostatic efficacy without causing dental fluorosis is not precisely known, it has been suggested that the threshold of fluoride exposure above which fluorosis may occur is between 0.05 and 0.07 mg/kg/day. OBJECTIVE: To monitor and compare fluoride intake from diet and dentifrice use (theoretical F: 0.10-0.11%) by three groups of 16- to 40-month-old children: two groups living in the negligibly water-fluoridated communities of San Juan, Puerto Rico, and Connersville, Indiana, and the third group residing in the optimally water-fluoridated region of Indianapolis, Indiana. METHODS: Fluoride intake from diet was monitored by the "duplicate plate" method, and fluoride ingested from dentifrice was determined by subtracting the amount of fluoride recovered after brushing from the amount originally placed on the child's toothbrush. RESULTS: The mean combined amount of fluoride ingested daily by children living in the negligibly fluoridated communities was not significantly different from that ingested by children in the fluoridated community. The major component of fluoride ingested by children in the negligibly fluoridated communities came from fluoridated dentifrice, and in the fluoridated area children ingested as much fluoride from toothpaste as they did from beverages. In San Juan mean daily fluoride intake was within the estimated range for safe fluoride exposure; however, in the "halo" community of Connersville and in Indianapolis, daily fluoride ingested by many of the children may have exceeded this level. CONCLUSION: Attention needs to be given, in negligibly water-fluoridated as well as in optimally water-fluoridated communities, to reducing the daily intake of fluoride by young children in order to avoid putting them at risk of developing dental fluorosis.

Analysis of Variance↗
PubMed1998

Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor alpha in endothelium.

Proinflammatory cytokines upregulate endothelial adhesion molecule expression, thereby initiating the microvascular inflammatory response. We re-evaluated the reported role of reactive oxygen metabolites (ROMs) in signalling upregulation of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by tumour necrosis factor alpha (TNF-alpha) in vitro. TNF-alpha upregulation of endothelial-cell ICAM-1 expression was inhibited by the cell-permeable antioxidants, or by the adenovirus-mediated intracellular overexpression of Cu,Zn-superoxide dismutase, but not by the exogenous (extracellular) administration of the cell-impermeable antioxidants, superoxide dismutase and/or catalase. This ICAM-1 upregulation was also inhibited by inhibitors of NADH dehydrogenase, cytochrome bc1 complex and NADPH oxidase. However, a measurable increase in net cellular ROM generation in response to TNF-alpha was not seen using four disparate sensitive ROM assays. Moreover, the stimulation of exogenous or endogenous ROM generation did not upregulate ICAM-1, nor enhance ICAM-1 upregulation by TNF-alpha. These findings suggest that an ambient background flux of ROMs, generated intracellularly, but not their net incremental generation, is necessary for TNF-alpha to induce ICAM-1 expression in endothelium in vitro.

Adenoviridae↗
PubMed1998

Protein tyrosine phosphorylation mediates TNF-induced endothelial-neutrophil adhesion in vitro.

Proinflammatory cytokines initiate the vascular inflammatory response via the upregulation of adhesion molecules on the luminal endothelial surface. We investigated directly the role of protein tyrosine phosphorylation in the upregulation of the endothelial adhesion molecules, intercellular adhesion molecule 1 (ICAM-1) and E-selectin, and the consequent adhesion of neutrophils, after tumor necrosis factor (TNF)-alpha-stimulation of human aortic endothelial cells in vitro. Time- and dose-dependent TNF-alpha-stimulated ICAM-1 and E-selectin upregulation and neutrophil adhesion each were suppressed by tyrosine kinase inhibitors, including genistein (200 microM), but not genistein, its isoflavone analog without tyrosine kinase inhibitory activity. Tyrphostin AG 126, a synthetic selective tyrosine kinase inhibitor, also suppressed ICAM-1 and E-selectin upregulation and neutrophil adhesion, each in a dose-dependent manner, whereas tyrphostin AG 1288 had no effect. Tyrosine phosphorylation of two proteins (85 and 145 kDa in the cytoskeleton fraction) found minutes after TNF-alpha-stimulation was also inhibited by genistein. These findings suggest that, in endothelial cells, TNF-alpha upregulates ICAM-1 and E-selectin expression and consequent neutrophil adhesion via protein tyrosine phosphorylation.

Benzylidene Compounds↗
PubMed1997

Lack of effect of long-term fluoride ingestion on blood chemistry and frequency of sister chromatid exchange in human lymphocytes.

Two studies were conducted to assess the potential for adverse physiologic and genotoxic effects of long-term fluoride ingestion in adults residing in three communities with varying water fluoride levels (0.2 ppm, 1.0 ppm, and 4.0 ppm). All were long-time (> or = 30 years) residents of their respective communities. Plasma and urine samples were collected for fluoride analyses. Additional plasma was collected to determine blood chemistry, and plasma lymphocytes were examined to determine the frequency of sister chromatid exchange. Significant differences in urine (P = 0.001) and plasma (P = 0.0001) fluoride levels were found in the three communities. Seven of the blood parameters were statistically different among the communities, although all were within the defined normal range of the pathology laboratory. Sister chromatid exchange frequency was statistically higher in the 4.0 ppm fluoride community as compared to the other communities. Because of the higher SCE frequency in the 4.0 ppm fluoride community, a second study was performed to determine if the increased frequency was potentially related to the fluoride level of the communal water supply. Of the 58 adults recruited; 30 had used city water and 28 had used well water (< or = 0.3 ppm fluoride) as their principal water source for 30 years. Data analyses showed that the sister chromatid exchange frequency did not differ between the groups, indicating that the increased sister chromatid exchange frequency was not related to the fluoride level of the communal water. The investigation provided evidence that the long-term ingestion of water containing 4.0 ppm fluoride did not have any clinically important physiologic or genotoxic effects in healthy adults.

Adult↗
PubMed1997

Orientation anisotropy and strabismus.

Monocular contrast sensitivity (CS) measurements were obtained in the two principal meridians of eight constant unilateral strabismic subjects and four subjects diagnosed with alternating strabismus. The results indicated that: (1) the CS of both the fellow and deviating eyes of patients with a constant unilateral deviation is significantly less than that of visually normal eyes at high spatial frequencies; (2) both the fellow and deviating eyes reveal a significant reduction in CS to vertically oriented gratings. This effect is frequency-specific, occurring only at the highest spatial frequencies; (3) the magnitude of the orientation anisotropy did not vary systematically with the degree of amblyopia; and (4) a mild orientation anisotropy was observed in only three of the eight alternating strabismic eyes tested. The etiology of the vertical effect is examined with respect to the role of anomalous binocular competition, suppression and abnormal eye movements.

Amblyopia↗
PubMed1997

An in situ interproximal model for studying the effect of fluoride on enamel.

This crossover study determined the ability of an interproximal, intra-oral model to demonstrate a fluoride dose response to 0-, 250- and 1,100-ppm fluoride (sodium fluoride) dentifrices with respect to fluoride uptake into, and remineralization of, incipient subsurface enamel lesions. Following a 1 week 'lead in' period during which 30 panelists were randomly assigned to use one of the products, two enamel specimens with artificial carious lesions were mounted into a specially designed functional partial denture worn by each panelist. Panelists continued to brush three times daily with their test dentifrice for 4 weeks, after which the specimens were removed and analyzed for fluoride uptake and remineralization. The procedure was repeated until each panelist had followed all three treatment regimens. Fluoride analyses were performed using a microdrill biopsy technique, and mineral content changes were determined by transverse microradiography. Fluoride uptake data were significantly different (p < 0.01) for all three products with the effect of 1,100 ppm F > 250 ppm F > placebo. The 1,100 ppm F dentifrice also effected significantly greater remineralization (p < 0.01) than did the 250-ppm-F or placebo dentifrices. Relative efficacy of the three fluoride dentifrices tested in this study was similar to that established in a clinical trial, and, therefore, supports the use of this model for in situ studies of the effects of fluoride-containing products on enamel lesions.

Adult↗
PubMed1996

Activated clotting time differential is a superior method of monitoring anticoagulation following coronary angioplasty.

The standard high-range activated clotting time (sHR ACT) is used to monitor anticoagulation postangioplasty (PTCA), but may be unreliable. We assessed the accuracy of a new method we termed the ACT differential (ACT Diff), obtained by measuring the difference between an sHR ACT and a heparinase ACT from the same sample. Heparinase removes heparin from its sample and provides a current heparin-free baseline. For phase 1 of the study, the sHR ACT, ACT Diff, and laboratory APTT were measured in 250 samples from 75 PTCA patients. In 125 samples with an APTT prolonged but within measurement range, linear regression against the APTT was performed. The correlation coefficient was 0.74 for the ACT Diff and 0.24 for the sHR ACT. An ACT Diff of 15-25 sec was found to equal an APTT of 2.5-3.5 x control. In 50 samples with a normal activated partial thromboplastin time (APT), there was good differentiation by the ACT Diff of results from those adequately heparinized, with a value of 0.9 +/- 4.4 sec. The sHR ACT was 114 +/- 15.5 sec, and could not reliably distinguish between anticoagulated and nonanticoagulated samples. In 75 samples obtained with a high APTT (above measurement range), the ACT Diff was > 30 sec in 95% of samples, and again this allowed differentiation from therapeutic samples. The equivalent sHR ACT was 148 sec, and could not reliably distinguish between anticoagulated and overanticoagulated samples as the ACT Diff could. In phase 2, to examine the clinical usefulness of the ACT Diff, 286 patients were managed post-PTCA by starting heparin when ACT Diff fell to < 50 sec, maintaining ACT Diff at 15-25 sec during heparin infusions, and following cessation of heparin, by removing sheaths when the ACT Diff was < 7 sec. These patients were compared to a control group of 250 patients. Major bleeding (5% vs. 0.5%, P < 0.005) and minor bleeding (30% vs. 13%, P < 0.001) were significantly reduced in the group managed using the ACT Diff. The reduction in bleeding was thought to be due to the rapid availability of reliable results. Abrupt closure was low in both groups (0% with ACT Diff vs. 0.8%). No other thrombotic events occurred. Following phases 1 and 2, the ACT Diff replaced the APTT in all PTCA patients at this institution. In the 18 mo from July 1993, 1,104 patients were managed this way. Incidence of major bleeding (0.2%), transfusion requirement (0.1%), false anneurysm (0.6%), and abrupt closure during heparin infusion (0.1%) remained low. In conclusion, the ACT Diff is more accurate than an sHR ACT, and its clinical use in PTCA patients is associated with a very low incidence of complications from anticoagulation. Its routine use should be considered by units unable to obtain rapid APTT results.

Adult↗
PubMed1996

Active minimisation of radiation scatter during breast radiotherapy: management implications for young patients with good-prognosis primary neoplasms.

BACKGROUND AND PURPOSE: Radiotherapy is used to reverse or prevent local tumour growth but is also a carcinogen in its own right. A recent audit of post-radiotherapy second malignancies in this institution revealed a striking preponderance of tumours originating near the outside edge of the treatment field. Since this finding suggests the existence of a critical subtherapeutic dose range predisposing to tumourigenesis, we attempted to define and reduce this radiation scatter dose. MATERIALS AND METHODS: We undertook a dosimetric review of 6 MV scatter from a linear accelerator in sites matching the putative tumourigenic region, and then extended this analysis to patients and tissue phantoms. RESULTS: A wide range of radiation scatter doses was confirmed-for example, doses 3 cm from the field edge varied from 1.7 to 22% of the therapeutic dose depending upon the field parameters. Scatter doses were then assessed in a sample of eight patients undergoing standard breast radiotherapy. Contralateral breast sites 4-12 cm from the midline received 4-10% of the therapeutic dose, or 200-500 cGy for a 50 Gy treatment, approximating historical estimates of the tumourigenic range. The deep component of this scatter dose from medial field breast irradiation was reduced 19% simply by replacing the 15 degrees medial tangential field wedge with a 30 degrees lateral wedge. Other manoeuvres which reduced contralateral breast dose by up to 46% included making the posterior field edges co-planar and shielding the breast during medial field irradiation. CONCLUSIONS: These results suggest that the risk of radiogenic second malignancies could be significantly decreased by careful attention to the treatment details. Greater awareness of these measures may prove particularly relevant to the conservative management of young patients with good-prognosis breast neoplasms such as ductal carcinoma in situ.

Breast↗
PubMed1996

Elemental analysis of femoral bone from patients with fractured neck of femur or osteoarthrosis.

The elemental composition of bone has been determined by inductively coupled atomic emission and mass spectrometry to test the hypothesis that changes in major or minor elemental concentrations may contribute to the risk of fracture. Femoral bone was obtained from patients at operation for the treatment of fracture and compared with that of patients with osteoarthrosis and a necropsy control group. The data suggest that there are no major differences in bone elemental composition in patients with fractures compared with the control group. Bone adjacent to joints with osteoarthrosis tends to be less mineralized (per unit trabecular bone volume) than control bone and bone from fracture patients, and has significantly lower concentrations of boron, lead and, zinc. These observations may reflect the more rapid turnover of bone close to the arthritic joint.

Aged↗
PubMed1995

Risk factors for pneumothorax during percutaneous Hickman line insertion in patients with solid and haematological tumours.

The purpose of this study was to identify risk factors for pneumothorax during percutaneous subclavian Hickman line insertion in patients with haematological (HT) or solid tumours (ST). One hundred and twelve patients (55 HT, 57 ST) had 132 subclavian Hickman lines inserted under fluoroscopic control. Lines were inserted on the left on 116 occasions and the right in 16. Thirty-five single, 29 double and 68 triple lumen catheters were inserted. Variables included in the analysis were age, sex, side of insertion, catheter gauge and nutritional status as indicated by the body mass index (BMI kg/m2). Both univariate and logistic regression analyses were performed. There were ten pneumothoraces, all occurring in patients with STs. Univariate analysis revealed that patients with STs were older (median age 59 versus 36 years; P = 0.0001) and more cachectic (median BMI 21.9 versus 24.2 kg/m2; P = 0.03) than those with HTs, and the patients experiencing pneumothorax were older (median age 57 versus 44 years; P < 0.01) and more cachectic (median BMI 19.6 versus 24.0 kg/m2; P = 0.004) than those undergoing uncomplicated procedures. For patients with a BMI < 19 kg/m2 versus those with a BMI > 19 kg/m2, the pneumothorax rate was 5/8 versus 5/124 (P < 0.00001). Logistic regression analysis confirmed the significantly older age of the patients with STs (P < 0.001) and of those experiencing pneumothorax (P = 0.02). This analysis also confirmed the lower BMI of patients experiencing pneumothorax (P = 0.002). The patients' sex, the side of line insertion and the catheter gauge were not associated with pneumothorax on either the univariate or logistic regression analyses. From these data we conclude that pneumothorax complicating a subclavian Hickman line is significantly more likely in elderly patients with a low BMI. Such patients are more likely to have STs than HTs. In patients with a BMI < 19 kg/m2, the subclavian route should be used with caution.

Adult↗
PubMed1995

Palliation of obstructive nephropathy due to malignancy.

OBJECTIVE: To conduct a prospective study of patients with malignant obstructive uropathy treated actively by percutaneous nephrostomy and J-J ureteric stents. PATIENTS AND METHODS: Forty-two patients (27 men, 15 women, median age 62 years, range 29-83) with obstructive nephropathy secondary to malignancy underwent urinary diversion followed, where appropriate, by active treatment of the underlying cancer. RESULTS: The median survival of all patients was 133 (range 7-712) days. Seventeen patients (40%) survived for > 6 months and five (12%) for < 1 month. Patients who had received no prior therapy and for whom further therapeutic options were available were more likely to benefit from urinary diversion. In nine patients (21%) nephrostomy insertion failed to relieve renal failure. In 20 patients (48%) obstructive nephropathy recurred. The procedure was complicated by urinary tract or nephrostomy site infection in 16 patients, by septicaemia in six patients, by percutaneous urine leak in 13 patients and by pelvi-calyceal perforation in two patients, but not by haemorrhage or death. The median percentage of the patients' remaining life which was spent in hospital was 23.6% (range 2.2-100). CONCLUSIONS: Patients likely to benefit from nephrostomy were those for whom there were therapeutic options available for the treatment of their malignancy. Prolonged survival is possible in obstructive nephropathy secondary to malignancy, which should no longer be cited as an absolute contra-indication to urinary diversion. Patients unlikely to benefit from urinary diversion can also be identified and they should not routinely undergo this intervention.

Adult↗
PubMed1995

Dental fluorosis and caries prevalence in children residing in communities with different levels of fluoride in the water.

OBJECTIVES: This study investigated the prevalence of dental fluorosis and caries in 7-14-year-old children residing in communities with negligible (NF: 0.2 ppm), optimal (OPF: 1.0 ppm), and four-times optimal (4X OPF: 4.0 ppm) naturally occurring fluoride in their water systems. METHODS: Examinations were performed on 344 children who were lifetime residents of their communities. RESULTS: Whether using the tooth surface index of fluorosis or Dean's index, children examined in the 4X OPF community had the highest prevalence of dental fluorosis. While the severity of fluorosis seen in the OPF and NF communities was mild in appearance, the results indicate that fluorosis does occur in optimally and negligibly fluoridated communities. Compared to the NF community, DMFT and DMFS scores in the OPF community were 9.2 percent and 21.2 percent lower, respectively. CONCLUSIONS: The ingestion of water containing 1 ppm or less fluoride during the time of tooth development may result in dental fluorosis, albeit in its milder forms. However, in these times of numerous products containing fluoride being available, children ingesting water containing 1 ppm fluoride continue to derive caries protection compared to children ingesting water with negligible amounts of fluoride. Thus, the potential for developing a relatively minor unesthetic condition must be weighed against the potential for reducing dental disease.

Adolescent↗
PubMed1994

An audit of Hickman catheter use in patients with solid tumours.

The purpose of this study was to analyse the use and relative complication rates of Hickman lines inserted by angiographic and surgical routes in patients with solid tumours. Sixty-one patients (median age 55 years; range 21-81) with solid tumours had 71 Hickman catheters inserted. Fifty-three patients had 58 catheters inserted angiographically and eight patients had 13 catheters inserted surgically. Indications were as follows: for administration of infusional chemotherapy (48 patients), poor venous access (nine patients), needle phobia (four patients). The catheters remained in situ for 7981 days (median 105; range 10-750). Immediate complications occurred only in angiographically placed catheters (ten pneumothoraces, one tachydysrhythmia). Pneumothorax was associated with poor nutritional status but not with age, side of insertion or catheter gauge. The median body mass indices (BMIs) were 19.65 kg/m2 and 22.8 kg/m2 in those with and without pneumothorax respectively (P = 0.0045). Five of six patients with BMI < 19 kg/m2 developed a pneumothorax, compared with five of 52 with BMI > 19 kg/m2 (P = 0.0003). The overall sepsis rate was 2.38 per 1000 catheter days. Systemic sepsis was significantly increased for surgically inserted lines (3.94 versus 0.60 per 1000 catheter days; P = 0.001), although there was no significant difference in superficial sepsis (2.36 versus 1.04 per 1000 catheter days; P = 0.22). We conclude that Hickman catheters provide safe, long-term venous access in patients with solid tumours. Angiographic insertion carries a greater risk of acute complications in patients of poor nutritional status but a significantly lower risk of late systemic infective complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Myxoedematous infiltrate of the forehead in treated hypothyroidism.

A 42-year-old man presented with a 3 month history of erythema and thickening of the forehead skin. He had been diagnosed as hypothyroid 10 years previously and treated with thyroxine at adequate dosage, according to thyroid function tests. Histology confirmed a myxoedematous infiltrate. The forehead is an unusual site for deposition of mucin and the late appearance, 10 years after treatment, is also uncharacteristic. Myxoedema in the usual pretibial site is a feature of Graves' disease. This man, however, had been hypothyroid with no features of Graves' disease suggesting that there are additional factors other than thyroid status and thyroid autoimmune disease which may be important in the development of myxoedematous infiltrates.

Adult↗
PubMed1992

Pathological variables determining the prognosis of non-Hodgkin's lymphomas.

The aim of the study was to assess the role of pathological grade, cell proliferation, ploidy, immunophenotype and site in determining the prognosis of non-Hodgkin's lymphomas. Of particular interest was the relative value of grades derived from the Kiel classification as opposed to the National Cancer Institute (NCI) working formulation. The study consisted of 181 cases, treated in a relatively uniform way over an 18-month period spanning 1986. Using life table analysis, both NCI working formulation grade and Kiel grade correlated strongly with survival. However, the differences between grades were entirely due to an excess of early deaths in the high-grade and intermediate-grade categories. In patients surviving greater than 0.1 years (37 days), phenotype, site, ploidy and cell proliferation had no effect on survival. There was no evidence that intermediate-grade tumours, when subdivided into Kiel low- and high-grade types, differed in survival from tumours graded as low- or high-grade by both methods. However, NCI working, formulation high-grade tumours, especially those with a high proliferation rate, formed a group with a very high likelihood of death within 0.1 years.

Adult↗