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Biomedical subjects

J E Thomas

Publications and source records attributed to J E Thomas.

At least 55 records · Page 3Linked to original sources

Fluoride in whole saliva, parotid ductal saliva and plasma in children.

The purpose was to investigate the relation between fluoride concentrations in whole saliva, parotid ductal saliva, and plasma in 5- to 10-year-old children (n = 17). Two stimulated whole-saliva samples were obtained from each child. Before the second sample was obtained, each child rinsed several times with a total of 100 ml of deionized water. Parotid saliva samples were obtained by use of a Lashley cup. Fluoride concentrations were determined by fluoride ion-specific electrode after diffusion with hexamethyldisiloxane. Rinsing with deionized water did not significantly reduce the fluoride concentration in whole saliva. The whole-saliva fluoride concentrations were not significantly related to those in plasma or parotid ductal saliva. Parotid fluoride concentrations, however, were significantly related to plasma fluoride concentrations (p < 0.0001) by a proportionality constant of 0.80. It was concluded that parotid salivary fluoride concentrations can be used to estimate plasma fluoride concentrations in 5- to 10-year-old children.

Child↗

Reversal of severe cerebral vasospasm in three patients after aneurysmal subarachnoid hemorrhage: initial observations regarding the use of intraventricular sodium nitroprusside in humans.

OBJECTIVE AND IMPORTANCE: The chronic delayed type of cerebral vasoconstriction that occurs after aneurysmal subarachnoid hemorrhage (SAH) is now the most important cause of mortality and neurological morbidity for patients who initially survive the rupture of cerebral aneurysms. Although intravascular volume expansion and cardiac performance enhancement have had a profound impact on the treatment of the chronic delayed type of cerebral vasoconstriction, this form of treatment is not tolerated by all patients and is unhelpful in some. A more specific and more reliable treatment for this condition has not been previously reported. Previous work in an animal model has demonstrated the efficacy of nitric oxide-donating compounds in reversing severe cerebral vasoconstriction when delivered to the adventitial side of the blood vessel. A clinical study was initiated after receiving approval from the United States Food and Drug Administration and the institutional review board. CLINICAL PRESENTATION: Three cases of prompt and substantial reversal of medically refractory vasospasm occurring after aneurysmal SAH in humans using an intrathecally administered nitric oxide donor and clinical, angiographic, and ultrasonographic documentation are presented. All patients developed severe vasospasm refractory to medical treatment 5 to 12 days after sustaining aneurysmal SAH. All patients manifested stupor of new onset (Glasgow Coma Scale score of 7) and new focal neurological deficit (hemiplegia). The condition was angiographically demonstrated in all cases. INTERVENTION: The patients were treated with intrathecally administered sodium nitroprusside, which caused the reversal of vasospasm, which was documented by angiography and transcranial Doppler ultrasonography up to 54 hours later and also by dramatic clinical improvement. Complications related to intracranial pressure elevation, changes in vital signs, and hemodynamic parameters were not observed during or after the procedures. Radiographic evidence of the reversal of vasospasm and brain ischemia was obtained. The clinical outcomes of the treated patients were excellent. All patients presented with hemiplegia and stupor that resolved or markedly improved (within several days, two patients; within 12 hours, one patient). All three patients were discharged and were living at home at the time of manuscript submission. CONCLUSION: These preliminary observations suggest that sodium nitroprusside delivered by an intrathecal route of administration may be a useful treatment for severe vasospasm complicating SAH in humans.

Adult↗

Therapeutic modalities for the management of cerebral vasospasm: timing of endovascular options.

OBJECTIVES: To determine if a window of time could be defined during which angioplasty would be most effective in reversing neurological decline and ultimately improving outcome. METHODS: Of a group of 466 patients, 93 underwent endovascular management of clinical vasospasm that was medically refractory. Eighty-four of the 93 patients were available for follow-up for at least 6 months. All patients underwent mechanical angioplasty using compliant microballoon systems and, if distal spasm was present, the administration of papaverine. RESULTS: Fifty-one patients underwent endovascular management within a 2-hour window, and 33 patients underwent treatment more than 2 hours after the development of their symptoms. Compared with the group treated more than 2 hours after neurological decline (P < 0.01; chi2 = 8.02), the group that underwent endovascular management within a 2-hour window after the development of symptoms demonstrated sustained clinical improvement. CONCLUSION: When a patient develops symptomatic vasospasm and is unresponsive to traditional measures of critical care management, angioplasty may be effective in improving the patient's neurological status if this procedure is performed as early as possible. The results indicate that a 2-hour window may exist for restoration of blood flow to ultimately improve the patient's outcome.

Angioplasty, Balloon↗

Safety of intrathecal sodium nitroprusside for the treatment and prevention of refractory cerebral vasospasm and ischemia in humans.

BACKGROUND AND PURPOSE: The delayed type of cerebral vasoconstriction known as cerebral vasospasm (DCV) remains an important cause of permanent neurological injury and death following aneurysmal subarachnoid hemorrhage despite best current medical therapy. The mechanism of DCV remains unknown. A new treatment for refractory DCV using intrathecally delivered sodium nitroprusside and results in 21 patients is reported. METHODS: Candidates for treatment were patients with secured cerebral aneurysms presenting with clinical or radiographic SAH of grade 3 or higher. Patients with and without established DCV were treated. In 57% (12/21 patients) the diagnosis of severe DCV refractory to conventional treatment (HHH therapy and nimodipine) was established before treatment. Ten patients received ITSNP prophylactically. All patients with established DCV were in grave neurological condition before treatment. Procedures for vasospasm reversal were performed under simultaneous angiographic control with extensive hemodynamic and neurophysiologic monitoring. ITSNP was delivered by intraventricular or subdural catheter or by direct intraoperative suffusion. End points of intervention for established DCV were (1) durable angiographic reversal of vasoconstriction, (2) failure to effect reversal within 30 minutes, and (3) adverse effect. End points for DCV prevention were (1) post-SAH day 10 without evidence of vasoconstriction and (2) adverse effect. Cerebral angioplasty was used concomitantly in 9 treatments. The total number of treatments recorded was 171. RESULTS: The overall neurological outcome was good or excellent in 76% of patients (16/21) overall and in 88.9% of patients (16/18) having at least a 1-month follow-up. Of the 5 patients with less-than-good outcome, 4 had presented initially with severe neurological injury (clinical SAH grade 4). Angiography demonstrated reversal or amelioration of vasoconstriction in 83% (5/6 cases) of established DCV treated by ITSNP alone. Among patients treated prophylactically, none developed clinical DCV. CONCLUSIONS: These results suggest that ITSNP is a safe and potentially effective treatment for established DCV and cerebral ischemia refractory to conventional treatment. The preliminary results of prophylactic treatment are also favorable with regard to safety.

Adult↗

Helicobacter pylori colonization in early life.

Helicobacter pylori infection is a major cause of upper gastrointestinal disease throughout the world. Colonization begins in childhood, although little is known about its age of onset, rate, or mode of colonization. Our aim was to identify the age of acquisition of H. pylori colonization in Gambian children. A cohort of 248 Gambian children aged 3 to 45 months was studied at intervals of 3 months for 2 years, using the 13C-urea breath test, specific IgM and specific IgG serology. The prevalence of positive breath tests rose from 19% at 3 months of age to 84% by age 30 months. Elevated specific IgG and IgM antibody levels were associated with positive breath tests, although there was discrepancy between breath test results and serology, particularly IgG serology, during the 1st year of life. Neither IgG nor IgM serology could be validated as reliable diagnostic tools for infant H. pylori colonization compared with the 13C-urea breath test. Reversion to negative breath test, in association with declining specific antibody levels, occurred in 48/248 (20%) of children. On the assumption that the 13C-urea breath test is a reliable index of H. pylori colonization, we conclude that the infection is extremely common from an early age in Gambian children. Transient colonization may occur. Previous studies relying on serodiagnosis may have significantly underestimated the true early prevalence of colonization in the developing world, where the target age for intervention studies is probably early infancy.

Antibodies, Bacterial↗

Interpreting the 13C-urea breath test among a large population of young children from a developing country.

The 13C-urea breath test is a noninvasive tool for the diagnosis of gastric Helicobacter pylori infection. However, it has not been validated in young children from the developing world, where infection is very common. 13C urea breath tests were performed on 1532 occasions on 247 Gambian infants and children aged from 3 to 48 mo. The means and variances of the separate sub-populations of 13C enrichment results contained within the overall dataset were estimated by a Genstat procedure using the EM algorithm, thereby identifying a cut-off value to discriminate positive from negative results. To illustrate the appropriateness of this calculated cut-off value, 13C urea breath tests were performed upon a small group of 14 patients aged 6 to 28 mo undergoing diagnostic upper endoscopy. Fixed gastric antral biopsies were examined to identify H. pylori. Two subpopulations were identified within the large dataset. A cut-off value of 5.47 delta per thousand relative to Pee Dee Belemnite limestone above baseline at 30 min identified 95% of the normally distributed negative sub-population and 99.4% of the log normal distributed positive sub-population. Comparison with endoscopic data confirmed that this cut-off value was appropriate for this population, as 7/7 children without H. pylori on their gastric biopsies had negative urea breath tests, and 6/7 children with gastric H. pylori colonization had positive urea breath tests. These findings confirm the value of the urea breath test as a diagnostic tool in young children from developing countries. They also offer a way to calculate the most appropriate cut-off value for use in different populations and the likelihood that it will correctly assign any value into the appropriate sub-population, without the need for endoscopy.

Breath Tests↗

Carotid angioplasty and stenting for recurrent and radiation-induced stenosis: preliminary experience.

Carotid endarterectomy for atherosclerotic occlusive disease has become the standard of care for the treatment of symptomatic and asymptomatic occlusive disease of the carotid bifurcation, based on the results of the North American Symptomatic Carotid Endarterectomy Trial, as well as the Asymptomatic Carotid Atherosclerosis Study. For surgical treatment to be of benefit, the perioperative complication rate for neurological events should be 6% or less in the symptomatic population and 3% or less in the asymptomatic group. The performance of carotid endarterectomy for recurrent stenosis and radiation-induced stenosis has reported neurological events ranging from 4 to 10%. It is in this particular population that carotid angioplasty and stent placement may play a role. The authors performed a retrospective analysis of 11 patients who underwent carotid angioplasty and stent placement for recurrent or radiation-induced stenosis. One patient in whom endarterectomy was performed by the vascular surgery service had a critical stenosis distal to the endarterectomy site and awoke with a neurological deficit. This patient underwent reexploration and placement of a stent in the artery distal to the arteriotomy site. The follow-up period ranged from 7 to 12 months. Patient age ranged from 65 to 77 years (mean 75 years). Five of eight patients underwent angioplasty and stent placement for recurrent atherosclerotic disease. Two patients had radiation-induced stenosis, and one patient had a stent placed intraoperatively. All patients, with the exception of the one who underwent intraoperative stent placement, had posttreatment stenoses of less than 15%. The surgical patient had a 30% residual stenosis distally. There were no intra- or postoperative transient ischemic attacks, major or minor strokes, or deaths. Patients who have recurrent or radiation-induced stenosis are potential candidates for angioplasty and stent placement. Before this can be recommended as an alternative to surgical correction, a longer follow-up period is required.

Journal Article↗

Therapeutic options for endovascular therapy for intracranial aneurysms.

Endovascular surgical technology is in the early stages of evolution. A critical phase of this development has been microcatheter technology, which has permitted sufficiently precise intravascular navigation to safely engage the lumen of the aneurysm itself. Digital subtraction angiography, rapid filming techniques and image acquisition, and simultaneous multiplanar imaging capability are indispensable tools that are constantly being refined in the setting of ever-improving computer technology. The marriage of these different technologies has allowed effective endovascular treatment of difficult-to-access aneurysms in medically compromised patients for whom open microsurgery has inherently higher risks.

Journal Article↗

Early and aggressive treatment of medically intractable cerebral vasospasm with pentobarbital coma, cerebral angioplasty and ICP reduction.

The authors present the unique experience of one neurovascular service under the direct supervision of the senior author, for which surgical, endovascular, and intensive care treatments were conducted in a select group of 32 patients with aneurysmal subarachnoid hemorrhage who had medically intractable symptomatic vasospasm. A protocol of early and aggressive treatment was instituted using pentobarbital coma, cerebral angioplasty, and intracranial pressure (ICP) reduction. The patient population consisted of 25 women and seven men, whose ages ranged from 34 to 60 years (average 47 years). The patients' Hunt and Hess grades on presentation were as follows: Grade 0 (one); Grade I (three); Grade II (two); Grade III (nine); Grade IV (10); Grade V (seven). Microsurgical clipping alone was performed in 15 of 32 patients, endosaccular occlusion was performed in 17 of 20 patients, and two patients underwent combined treatment. Subsequent angioplasty was performed in 26 of 32 patients. Additionally, all 32 patients underwent treatment of increased ICP with ventriculostomy placement, removal of the bone flap (11), evacuation of associated intracranial hematoma (five), and decompressive obectomy (four). Twenty-one patients survived and 11 died. Of the 21 survivors, seven have returned to work, live independently, and have no neurological deficits; eight require minimal assistance at home; four are in rehabilitation with moderate deficits at 3 months; and two remain in a persistent vegetative state. In this group of aggressively treated patients who received pentobarbital cerebral protection, successful treatment of medically intractable cerebral vasospasm was related to time of treatment (< 2 hours), expeditious reduction of elevated ICP, and angioplasty.

Journal Article↗

Calcitonin responsiveness and receptor expression in porcine and murine osteoclasts: a comparative study.

The presence of the calcitonin (CT) receptor is a distinguishing characteristic of osteoclasts; however, species variability exists with respect to functional responsiveness to CT. In the present study, CT responsiveness and temporal expression of the CT receptor in differentiating cultures of porcine osteoclasts was examined and compared to murine osteoclasts. In vitro porcine osteoclast differentiation was evaluated using bone marrow cultures from neonatal pigs. Murine osteoclast differentiation was studied using cocultures of murine bone marrow and BALC cells, a calvarial-derived cell line. In the presence of 1,25 (OH)2D3, a time-dependent increase in osteoclast differentiation was observed in porcine and murine cultures. Salmon CT (sCT) and porcine CT (pCT) inhibited 1,25 (OH)2D3-stimulated porcine osteoclast differentiation at 10(-8) and 10(-7) mol/L (60% with 10(-7) mol/L sCT and 85% inhibition with 10(-7) mol/L pCT). Treatment of murine cocultures with sCT (10(-17)-10(-7) mol/L) resulted in a concentration-dependent decrease in osteoclast differentiation with a maximal inhibition of 70%. Osteoclast differentiation was inhibited in a concentration-dependent manner by recombinant human transforming growth factor-beta1 (rhTGF-beta1) in both species. The effects of CT on resorption lacunae formation were determined by culturing in vitro generated porcine or murine osteoclasts on bovine cortical bone slices for 18 h in the presence or absence of CT. With both porcine and murine osteoclasts, a concentration-dependent decrease in resorption lacunae formation was observed between 10(-13) and 10(-7) mol/L sCT with the highest concentrations completely abolishing resorption. However, pCT only inhibited porcine osteoclastic resorption at 10(-7) mol/L. CT receptor messenger ribonucleic acid (mRNA) expression was determined at different time points during in vitro osteoclast differentiation. In porcine cultures, expression of CT receptor mRNA correlated with the presence of osteoclasts. In murine cocultures, mRNA for the CT receptor was observed at each time point examined and was independent of the presence of multinucleated osteoclasts. Thus, porcine and murine differentiating osteoclast cultures express CT receptor mRNA; however, receptor expression correlates with osteoclast formation only in the porcine cultures. In summary, porcine and murine osteoclasts express CT receptor mRNA and functional responsiveness to CT. These findings suggest that the effects of sCT on osteoclast resorption are similar in murine and porcine cells, but that sCT is a less potent inhibitor of porcine than murine osteoclast differentiation.

Animals↗

Retrotransposon-like sequences integrated into the genome of pineapple, Ananas comosus.

Retrotransposon-like sequences have been serendipitously detected in the genome of commercial pineapple, Ananas comosus. The sequence from a 2.6 kb cloned fragment of this element had greatest similarity to the del1 Lilium henryi retrotransposon and the gypsy/Ty3 group of retroelements. The order of the genes from 5' to 3' was reverse transcriptase, ribonuclease H and integrase. The integrase domain contained the amino acid sequence motifs which have been associated with recognition of the long terminal repeats and with the cutting/joining reactions required for integration of similar retroelements into the host genome. The retrotransposon existed as a population of variable sequences which were dispersed throughout the genome of pineapple. Southern hybridisation showed that the retrotransposon had integrated repeatedly into the pineapple genome. The reading frame of the element was not interrupted by stop codons, suggesting that it is still potentially capable of transposing. This is the first report of a retrotransposon in pineapple, which we have called deal (for dispersed element of Ananas).

Amino Acid Sequence↗

Helicobacter pylori infection, gastric acid secretion, and infant growth.

BACKGROUND: Helicobacter pylori infection is very common in Gambian infants and children, who are also at risk of chronic diarrhoea and undernutrition. Acute H. pylori infection is associated with depressed gastric acid secretion, and loss of the gastric acid barrier may predispose to enteric infections. METHODS: In a prospective study a noninvasive test of gastric acid output (measurement of change in urine acid output before and after a feed) was performed on a population of Gambian infants at high risk of H. pylori infection. The 13C urea breath tests was used to measure the prevalence of H. pylori infection and growth was measured by serial anthropometry. RESULTS: In 101 infants aged 3 to 12 months, there was a significant relation between H. pylori infection and depressed urine acid output in those aged 6 months, during weaning when growth failure and malnutrition begin. Those infants with sustained H. pylori infection grew less well than those without. CONCLUSIONS: We speculate that H. pylori, acquired in infancy, could be a "key that opens the door" to enteric infection in childhood, leading to recurrent diarrhoea, malnutrition, and growth failure.

Breath Tests↗

Human milk IgA concentrations during the first year of lactation.

AIMS: To measure the concentrations of total IgA in the milk secreted by both breasts, throughout the first year of lactation, in a cohort of Gambian mothers of infants at high risk of infection. SUBJECTS AND METHODS: Sixty five women and their infants were studied monthly from the 4th to 52nd postpartum week. Samples of milk were obtained from each breast by manual expression immediately before the infant was suckled. Milk intakes were measured by test weighing the infants before and after feeds over 12 hour periods; IgA concentrations were determined by enzyme linked immunosorbent assay. RESULTS: A total of 1590 milk samples was measured. The median (interquartile range) concentration of IgA for all samples was 0.708 (0.422-1.105) g/l; that in milk obtained from the left breast was 0.785 (0.458-1.247) g/l, and that in milk obtained from the right breast was 0.645 (0.388-1.011) g/l (p < 0.0001). There was no significant change in milk or IgA intakes with advancing infant age, but there was a close concordance of IgA concentrations between the two breasts, with "tracking" of the output of the left and right breasts. There was a significant (p < 0.01) negative correlation between maternal age and parity, and weight of milk ingested by infants. During the dry season (December to May) the median (interquartile range) IgA concentration was significantly higher at 0.853 (0.571-1.254) g/l than during the rainy season (June to November), when it was 0.518 (0.311-0.909) g/l (p < 0.0001). CONCLUSIONS: Sustained IgA secretion is likely to protect suckling infants from microbial infection.

Aging↗

Measurement of smoothed Wigner phase-space distributions for small-angle scattering in a turbid medium.

We study Wigner phase-space distributions W (x, p) in position (x) and momentum (p) for light undergoing multiple small-angle scattering in a turbid medium. Smoothed Wigner phase-space distributions are measured by using a heterodyne technique that achieves position and momentum resolution determined by the width and the diffraction angle of the local oscillator beam. The sample consists of 5.7-micron-radius polystyrene spheres suspended in a water-glycerol mixture. The momentum distribution of the transmitted light is found to contain a ballistic peak, a narrow diffractive pedestal, and a broad background. The narrow diffractive pedestal is found to decay more slowly than the ballistic peak as the concentration of scatterers is increased. The data are in excellent agreement with a simple theoretical model that explains the behavior of the narrow pedestal by including multiple diffractive scattering and treating large-angle scattering as a loss.

Light↗

Frequency of cerebral vasospasm in patients treated with endovascular occlusion of intracranial aneurysms.

UNLABELLED: The purpose of this study was to retrospectively compare a group of 19 patients treated with craniotomy and aneurysmal clipping with a group of 18 patients who were treated via endovascular occlusion with Guglielmi detachable coils in regard to frequency and severity of cerebral vasospasm. METHODS: All patients were treated within 48 hours of ictus. In the endovascular group, nine patients had Hunt and Hess grade I subarachnoid hemorrhage, five patients had grade II aneurysms, and four patients had grade III. According to the Fisher classification, one aneurysm was grade I, nine were grade II, and eight were grade III. Twelve of the aneurysms were on the anterior circulation and seven were on the posterior circulation. In the surgical group, 10 patients had Hunt and Hess grade I hemorrhage, seven had grade II aneurysms, and two had grade III. Nine of these were Fisher grade II and 10 were grade III. Eighteen aneurysms were on the anterior circulation and one was on the posterior circulation. Endovascularly treated patients were medically treated identically to those in the surgical group, with prophylactic volume expansion and hemodilution immediately after endovascular occlusion, except that they also received 48 hours of full heparinization followed by 24 hours of dextran infusion after endovascular occlusion. RESULTS: All four patients in the endovascular group in whom delayed neurologic deficits developed as a result of vasospasm responded to elevation of blood pressure and did not require either mechanical or chemical angioplasty to reverse their symptomatology. In the surgical group, 14 of 19 developed clinical vasospasm, with elevation of their transcranial Doppler velocities, and required maximum triple-H (hypertensive, hypervolemic, hemodilutional) therapy. Three of these patients required mechanical and pharmacologic angioplasty. No surgical complications were incurred as a direct result of the craniotomy. One patient in the endovascular group developed a femoral pseudoaneurysm as a complication of the procedure and postocclusion anticoagulation. No thromboembolic events were noted in this group. CONCLUSION: In patients with similar Hunt and Hess grades and Fisher grades, preliminary data suggest that the frequency and severity of cerebral vasospasm may be reduced in those treated by endovascular occlusion of their aneurysm as compared with those treated by direct surgical clipping.

Adult↗

Molecular biological considerations in cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

Chronic delayed cerebral vasospasm (CDCV) remains a serious and often fatal complication of aneurysmal subarachnoid hemorrhage (SAH). The current understanding of its fundamental mechanisms and molecular biological characterization is rudimentary. Two important vasoactive substances have been implicated in CDCV: endothelin-1 (ET-1) and nitric oxide (NO). A 21--amino acid vasoconstrictor peptide, ET-1 has generated interest as a possible important contributor to cerebral vasospasm on the basis of both clinical and experimental evidence suggesting abnormally enhanced production. Nitric oxide is a cell membrane--permeable free radical gas that accounts for the vasodilatory effect of endothelium-derived relaxation factor and is a physiological antagonist of ET-1. As with ET-1, abnormalities of NO production have been implicated in several pathological conditions including cerebral vasospasm. This brief report reviews some of the physiological and regulatory features of these two molecules and explores the possibility of their relationship to cerebral vasospasm.

Journal Article↗