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Biomedical subjects

B Jones

Publications and source records attributed to B Jones.

At least 253 records · Page 14Linked to original sources

The achievement of isoeffective bronchial mucosal dose during endobronchial brachytherapy.

PURPOSE: The use of endobronchial brachytherapy in the treatment of lung cancer is increasing due to the more widespread availability of high dose rate afterloading equipment. The complications include small airway (segmental and small lobar bronchi) fibrosis, stenosis, and obstructive complications in addition to hemorrhage. A progressive reduction in the diameter of the bronchial lumen occurs at each division of the bronchial tree. If uniform dwell times along a bronchial catheter treatment length are used, this will result in higher doses being given to the bronchial mucosa in the distal part of the treatment volume where the brachytherapy source mucosa distances are smaller, and underdosage proximally, where the source mucosa distances are larger. METHODS AND MATERIALS: The known mathematical relationships of the sequential reductions in the diameter of the bronchial lumen have been incorporated into two methods of optimization, which have been compared to uniform dwell times along a treatment length from trachea to segmental bronchus. RESULTS: The resulting isodose plots are presented, and demonstrate the extent of the overdosage distally, and the underdosage proximally when using uniform dwell times, and the achievement of isoeffective mucosal doses when using differential dwell times. CONCLUSION: This refinement in brachytherapy technique offers the potential for reduced normal tissue complications and possibly improved tumor control by reducing overdosage and underdosage, respectively.

Brachytherapy↗

Intrasphincteric botulinum toxin for the treatment of achalasia.

BACKGROUND: Achalasia is a disorder of swallowing in which the lower esophageal sphincter fails to relax. We report the use of botulinum toxin, a paralytic agent, for the treatment of this condition. METHODS: In a double-blind trial, 21 patients with achalasia received either 80 units of botulinum toxin or placebo, injected endoscopically into the lower esophageal sphincter. One week later, the response to treatment was assessed on the basis of changes in the symptom scores (measured on a scale from 0 to 9), pharyngoesophagograms, and results of esophageal manometric and scintigraphic studies. Patients who received placebo initially were subsequently treated with botulinum toxin. After six months, esophageal scintigraphy was repeated. RESULTS: One week after treatment, the mean decrease in the symptom score was 5.4 points for the patients treated with botulinum toxin and 0.5 point for the placebo group (P = 0.001). The mean decrease in the pressure of the lower esophageal sphincter was 33 percent in the treatment group, as compared with a mean increase of 12 percent in the placebo group (P = 0.02), and the mean increase in the width of the opening of the lower esophageal sphincter was 204 percent in the treatment group, as compared with a mean decrease of 14 percent in the placebo group (P = 0.02). Nineteen of the 21 patients treated with botulinum toxin had symptomatic improvement initially; after six months 14 patients were still in remission. This improvement was accompanied by a decrease in esophageal retention that was sustained at six months (46 percent, as compared with a pretreatment value of 77 percent; P = 0.04). There were no serious adverse effects. CONCLUSIONS: Injection of botulinum toxin into the lower esophageal sphincter is an effective, safe, and simple method of treatment for achalasia, with results that are sustained for several months.

Adult↗

A rapid and sensitive method of identification of HTLV-II subtypes.

There are 2 subtypes of human T-cell lymphoma/leukemia virus type II (HTLV-II), A and B. HTLV-II is increasingly associated with rare forms of lymphocytic neoplasia and a neurodegenerative disorder, characterized by hyperspasticity and ataxia. We have used PCR to amplify, clone and sequence 140 bp of the pol gene from many isolates of HTLV-IIA and HTLV-IIB from around the world. Analysis of these and other published sequence established that all HTLV-IIA sequences contained a unique Hinf I site and all HTLV-IIB sequences a unique Mse I site. A rapid and specific oligomer restriction (OR) assay was developed utilizing the primer pair SK110/SK111 and subsequent digestion with these enzymes. Concordance between sequenced and OR-based subtyping of DNA amplified by PCR was absolute among 22 HTLV-II isolates tested. Further OR or sequence analyses on an additional 30 other isolates indicated that the majority of North American non-indian HTLV-II isolates were subtype A, while all Paleo-Amerindian samples, including those from the Seminole of Florida; the Guaymi from Panama; and the Toba, Chorote, Wichi, and Chulupe of Argentina, belonged to subtype B. The SK110/SK111 PCR-OR format should facilitate molecular epidemiology studies of HTLV-II infection and allow for subtype stratification in assessing the sensitivity and specificity of HTLV detection formats and HTLV-II disease association.

Argentina↗

Subdural intracranial pressure monitoring in craniosynostosis: its role in surgical management.

In the management of craniosynostosis subdural intracranial pressure (ICP) monitoring has proved a useful and safe means of identifying those children with raised ICP who are at risk from its long-term sequelae and who would benefit from early surgical intervention. Overnight subdural ICP recordings have been obtained in 136 unoperated cases of craniosynostosis. Fifteen patients were studied both before and after cranial vault remodelling procedures. ICP was raised (> 15 mmHg) in 35%, borderline (10-15 mmHg) in 37% and normal (< 10 mmHg) in 27% of cases. Raised ICP was present in 28/53 of the syndromic craniofacial dysostosis cases and in 20/83 non-syndromic craniosynostosis cases investigated (P < 0.001). Raised mean ICP and periodic plateaux of sustained ICP during sleep were particularly associated with the syndromic cases. Of the 15 patients studied following cranial vault surgery, 9 showed a reduction in ICP, 3 were unchanged and 3 had higher ICP postoperatively. The results of ICP monitoring can contribute significantly to formulating a rational and staged surgical management plan incorporating the need to normalise ICP and correct the frequently severe functional and cosmetic consequences of these disorders.

Adolescent↗

Cloning and restriction endonuclease mapping of herpes simplex virus type-1 strains H129 and +GC.

EcoRI fragments of herpes simplex virus I (HSV-1) strains H129 and +GC were cloned and the EcoRI and BglII restriction enzyme sites were mapped. Comparison of these enzyme sites with the sequence of HSV-1 strain 17syn+ demonstrated that all EcoRI sites were identical. For H129, the BglII sites were also found to match strain 17syn+ BglII sites. With one exception, the BglII sites in strain +GC also aligned with the strain 17syn+ sequence. The one exception was a missing BglII site from strain +GC located between bases 25,149 and 25,154 in the EcoRI D fragment within the viral deoxyribonuclease gene (UL12). The BglII site represents the first difference to be mapped within HSV-1 strains H129 and +GC which have unique pathobiological properties in animal models of acute and reactivated infections.

Cloning, Molecular↗

Supernumerary isochromosome 4p in ANLL-M4 myelomonocytic type is associated with favorable prognosis.

A case of an acute non-lymphocytic leukemia of M4 type with a supernumerary isochromosome (4p) in 100% of the initial bone marrow metaphase cells is reported. The origin of the extra chromosome is verified by the fluorescence in situ hybridization technique using a whole chromosome 4 painting probe. A possible favorable prognosis of the ANLL-M4 case showing a supernumerary isochromosome (4p) is cautiously emphasized.

Chromosomes, Human, Pair 4↗

Cell loss factors and the linear-quadratic model.

A method is described for incorporating a variable cell loss factor (phi) within the linear-quadratic (LQ) model. By allowing for a progressive reduction in phi as treatment progresses, the revised model behaves in a way which is consistent with the apparent presence of accelerated tumour repopulation during fractionated radiotherapy. Predictions based on a slowing of the cell loss process, rather than a true increase in clonogen proliferation rate, are consistent with the phenomenon of 'unmasking' of potential doubling time described by Fowler (Fowler, J.F. Rapid repopulation in radiotherapy: a debate on mechanism. Radiother Oncol 24: 125, 1992). An optional time delay factor may be included, to allow for the fact that progressive reduction in cell loss may not begin until part of the treatment has been delivered. The model provides a description of the manner in which tumour control doses are likely to increase as overall treatment time is increased.

Cell Death↗

Effects of an antiperspirant with emollients on foot-sweat accumulation and blister formation while walking in the heat.

BACKGROUND: Friction blisters are a common injury in sports activities and military operations. Blisters can compromise performance, so it is important to devise preventive strategies to reduce these injuries. OBJECTIVE: This study investigated the influence of an antiperspirant with emollient additives on frequency and severity of friction blisters, hot spots, and irritant dermatitis. METHODS: Twenty-three healthy men walked on a treadmill (1.39 m/sec, 1% grade) in a warm environment (28 degrees C, 25% relative humidity) carrying a total mass of 21 +/- 1 kg. For 4 consecutive days before the walk, the subjects' feet were treated with either (1) an antiperspirant (20% aluminum zirconium tetrachlorohydrex glycine concentration plus water) with emollient additives, (2) emollient additives alone (placebo control), or (3) nothing (nontreated). In two separate trials (1 month apart) each participant received the antiperspirant treatment and both control treatments (emollient [placebo] and no treatment). RESULTS: No differences were seen among treatment conditions for sweat accumulation (p = 0.86), blister incidence (p = 0.36), hot spot incidence (p = 0.83), or blister severity (p = 0.31). Irritant dermatitis was not reported in any of the treatment conditions. CONCLUSION: The use of an antiperspirant with emollients reduces irritant dermatitis but does not reduce total foot-sweat accumulation, blister or hot spot incidence, or blister severity.

Adult↗

Ruthenium Red potently inhibits immune responses both in vitro and in vivo.

Targeted drug screening revealed a compound, Ruthenium Red, which potently blocked proliferation of human T-cells. This compound is not generally cytotoxic or cytostatic, as judged by its lack of effect on the proliferation of a panel of transformed cell lines, but it exhibits true immunosuppressive properties. Ruthenium Red inhibits the T-cell proliferative response (with an IC50 approximately 100 nM) to a wide variety of agents, including viral antigens from herpes simplex virus, tetanus toxoid, alloantigens and IL-2. This compound did not alter the growth of an M-CSF-dependent cell line (M-NFS-60) in response to added growth factor. Time course studies revealed that Ruthenium Red could be added as late as 24 h after the initiation of T-cell stimulation by antigen and still produce maximal inhibition, indicating that later stages of signaling events are being effected. Ruthenium REd was then tested for its ability to abrogate immune response in vivo. It was discovered that this compound dramatically reduced the expansion of lymphocytes in draining lymph nodes of mice immunized with cytochrome c in adjuvants. Furthermore, Ruthenium Red also suppressed specific antibody production in mice following challenge with this antigen. The functional properties of Ruthenium Red have been compared with other immunosuppressive agents and reveal that this compound is most similar to rapamycin in its overall profile. The chemical structure of Ruthenium Red is quite different from these other agents; therefore, it may be extremely useful in helping dissect the activation pathway of T-cells. It will be important to explore further the therapeutic potential of this unique compound.

Animals↗

Entry of microbes into the host: using M cells to break the mucosal barrier.

Enteric microbial pathogens interact with the gut epithelium to establish infection. Recently, it has become clear that many microorganisms that colonize or traverse the intestinal mucosa do so via the specialized M cells. Recent work has shown that Shigella flexneri and Salmonella typhimurium specifically target M cells to initiate infection of the host.

Animals↗

The geographical epidemiology of ocular diseases: some principles and methods.

With the increasing availability of geographically referenced data in health research the time is ripe to review the use of particular geographical and spatial analysis techniques in ophthalmic research. Analysis of the geographical distribution of ocular diseases, particularly in Britain, has not had a high profile, but there are certain diseases, such as congenital eye malformations in children, where such analysis methods are particularly appropriate. We review the data requirements and then a variety of analytical techniques, some of which partition geographical space into areal units (such as counties or electoral wards), others of which treat space as continuous. We conclude with some comments on software that is available for such analyses.

Data Collection↗

Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes.

Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have been identified in Crouzon syndrome, an autosomal dominant condition causing premature fusion of the cranial sutures (craniosynostosis). A mutation in FGFR1 has been established in several families with Pfeiffer syndrome, where craniosynostosis is associated with specific digital abnormalities. We now report point mutations in FGFR2 in seven sporadic Pfeiffer syndrome patients. Six of the seven Pfeiffer syndrome patients share two missense mutations, which have also been reported in Crouzon syndrome. The Crouzon and Pfeiffer phenotypes usually breed true within families and the finding of identical mutations in unrelated individuals giving different phenotypes is a highly unexpected observation.

Acrocephalosyndactylia↗

Radiotherapy and chemotherapy for inoperable non-small cell lung cancer.

Non-small cell lung cancer is a major cause of mortality and significant morbidity in the UK. The majority of patients are inoperable and the optimum management of these patients requires a multidisciplinary approach involving the cooperation of respiratory physicians, thoracic surgeons and clinical oncologists (radiotherapists). Treatment techniques are constantly being refined and new approaches developed.

Aged↗

Pancreaticogastrostomy and the Whipple procedure: radiographic appearance and complications.

PURPOSE: To evaluate the radiographic appearance of a pancreaticogastrostomy (PG) and its complications. MATERIALS AND METHODS: Seventy-two patients underwent pancreaticoduodenectomy and PG or pancreaticojejunostomy. Those who underwent PG and were evaluated postoperatively with T-tube cholangiography and upper gastrointestinal (UGI) series constitute the study group (n = 22; 10 men, 12 women; age range, 33-88 years). RESULTS: Twenty-one of the patients had a gastric filling defect radiographically detected. Four patients had clinically apparent delayed gastric emptying and one patient had a clinically apparent pancreatic fistula not detected radiographically. Two patients outside the study group had complications: One had a pancreatic fistula seen only with sinography, and one had a PG leak seen only with repeat UGI series and computed tomography (CT). CONCLUSION: PG caused a gastric filling defect in most patients. Suspected pancreatic fistulas are best confirmed with sinography, and suspected PG leaks may require repeat evaluation and CT. Clinical findings of delayed gastric emptying do not correlate with findings of UGI.

Adult↗

Derivation of the optimum dose per fraction from the linear quadratic model.

The linear quadratic equation for fractionated radiotherapy has already been adapted to include a time factor for tumour repopulation: loge cell kill (E) is given as a function of dose per fraction (d), number of fractions (n), overall treatment time (T) and the clonogen doubling time (Tp). By incorporating a normal tissue isoeffect and replacing the relationship between T and n by a function f, the equation for E can be rewritten as a more complex function of d. In this form, E and d are continuous variables so that the dose per fraction (d') required to produce maximum values of E for isoeffective late normal tissue effects can be found by differential calculus. The derived equation takes the form (beta kTp-alpha Tp)d2 + 1.386fd + 0.693fk = 0 and when solved for d provides a direct estimation of the optimum dose per fraction. Where normal tissue sparing is possible and the tumour dose z is related to the normal tissue dose d, the optimum dose per fraction z' can be found by solving the equation (beta kTp-alpha gTp)z2 + 1.386fgz + 0.693fk = 0 The results show that a critical minimum dose per fraction is required to counteract rapid tumour clonogen repopulation in both conventional and accelerated radiotherapy. The calculus method is reasonably accurate for larger fraction numbers, when clonogen doubling times are 3.5 days or longer and for conventional radiotherapy given 5 days per week. The model is even more accurate for accelerated hyperfractionated radiotherapy providing that there is complete repair between successive fractions. Where greater normal tissue sparing is possible, as with focal teletherapy methods and brachytherapy, higher tumour doses per fraction can be used to increase further the tumour cell kill without exceeding normal tissue tolerance. These predicted doses per fraction are consistent with clinical experience when the given constraints in terms of frequency of treatment are considered. The model described can be used for tumours in which repopulation occurs at a constant rate throughout treatment. For tumours in which accelerated repopulation occurs, the optimum dose per fraction can be separately calculated for the initial phase of slow repopulation (for which very small doses per fraction are optimal) and also for the second phase of rapid repopulation (for which either accelerated hyperfractionated treatments or hypofractionated focal methods of treatment would be appropriate). The limitations of the model are fully discussed including the need for accurate radiobiological predictive assays. In the future such assays of pre-treatment doubling times and tumour cell radiosensitivities could be used to determine reasonable ranges for the optimum dose per fraction in experimental tumours and subsequently in clinical trails. This approach could produce major improvements in the therapeutic potential of radiotherapy.

Cell Division↗