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Biomedical subjects

S Webb

Publications and source records attributed to S Webb.

At least 55 records · Page 3Linked to original sources
PubMed1997

Analysis of the cost of population screening for haemochromatosis using biochemical and genetic markers.

AIMS: To estimate the cost of population screening for haemochromatosis in Australia and to compare the cost of alternative screening strategies. METHODS: The costs of screening for haemochromatosis were analysed in a hypothetical study using transferrin saturation as the primary screening test, with confirmation of the diagnosis by either liver biopsy or DNA testing for the recently-described haemochromatosis gene. RESULTS: Screening, with confirmation of the diagnosis by liver biopsy, would cost between US$5079 and US$8813 per case detected (excluding administrative costs), depending on the screening strategy (Aust$ = US$0.80). If a DNA test were used instead of liver biopsy, the cost would be reduced to an estimated US$3954-US$4410 per case. This would be further reduced to US$2457 by detection of additional cases by screening family members. The least costly strategy utilised a transferrin saturation threshold of 55% and DNA testing for confirmation of the diagnosis; however, a transferrin saturation threshold of 45% increased the cost only marginally. The initial screening step (transferrin saturation) accounted for 74%-94% of the estimated cost of the screening programme. CONCLUSIONS: Screening for haemochromatosis using transferrin saturation involves relatively modest costs which may be recovered if complications of haemochromatosis can be prevented by early detection and treatment. The most cost-effective strategies utilised transferrin saturation for initial screening, followed by DNA testing. Reduction in the cost of transferrin saturation would lead to a significant reduction in total screening costs. Additional benefits of a screening programme include detection of other iron overload disorders and iron deficiency.

Biopsy↗
PubMed1997

The safety profile of GH replacement therapy in adults.

OBJECTIVE: The benefits of GH replacement in GH-deficient adult patients are becoming accepted but the safety profile continues to be defined. The GH deficiency in adults may have arisen i either childhood or during adult life and these two groups differ with regard to history of disease. The aid of the present report was to study differences in safety profile between these two groups during long-term replacement therapy with recombinant human GH (hGH). Possible factors which placed a patient at risk of experiencing an adverse event were also examined. PATIENTS AND DESIGN: GH-deficient adult patients were randomized into two study protocols, differing only in age of onset of the GH deficiency syndrome. There were 98 patients with adult-onset and 67 patients with childhood-onset GH deficiency. Each study consisted of a 6-month double-blind placebo-controlled phase followed by an open-label hGH treatment phase. Glucose tolerance, incidence of treatment-emergent adverse events and relationship to IGF status were studied throughout the 36 months of treatment. RESULTS: Human growth hormone-related adverse events were reported less commonly in childhood-onset patients compared with adult-onset patients. Adult-onset patients who continued into the open-label therapy phase reported an increased incidence of arthralgia, myalgia and paraesthesia. There were significant increases in fasting glucose with hGH therapy but values remained within the normal range. Hypertension was reported in 7.7% of adult-onset patients at 18 months of hGH, which was within the expected prevalence for the number of patients, but was not reported for any childhood-onset patients. Only in adult-onset patients were sufficient adverse events reported to enable analysis of risk factors. Patients reporting hGH-related adverse events were significantly heavier and, therefore, received more hGH. There was a significantly greater increase in IGF-I and IGFBP-3 in the first month in patients who experienced hGH-related adverse events compared with those who did not. CONCLUSION: The risks of replacement therapy with hGH in GH-deficient adults varied with pathogenesis of disease; hGH-related adverse events occurred more frequently in patients with adult-onset compared with those childhood-onset GH deficiency. In the adult-onset patients there was an increased risk of adverse events in heavier patients and those who had the greatest increases in IGF-I and IGFBP-3 at 1 month of therapy.

Adult↗
PubMed1997

The effect of stair-step leaf transmission on the 'tongue-and-groove problem' in dynamic radiotherapy with a multileaf collimator.

When intensity-modulated fields are created using a multileaf collimator with dynamic leaf movement the potential problem for underdosage beneath the tongue-and-groove interleaf regions has been identified and a solution based on leaf-movement synchronization has been provided by Van Santvoort and Heijmen. Their first-order analysis ignored the transmission through an exposed stair-step. In this brief Note we provide the extended analysis including this contribution and show the effect on irradiation with synchronization. The result is that the synchronization approach of Van Santvoort and Heijmen solves the tongue-and-groove problem even when the transmission through the stair-step is considered, but partial synchronization is generally sufficient.

Health Physics↗
PubMed1997

A family with hereditary spastic paraparesis and epilepsy.

PURPOSE: We describe a family with hereditary spastic paraparesis (HSP) in which 4 of 6 affected members also have epilepsy. METHODS: All family members were examined by 2 neurologists. Four affected and 3 unaffected family members had EEG recordings. Four affected members were investigated for other causes of spastic paraparesis and epilepsy. RESULTS: Epileptic symptoms varied among family members: 1 had complex partial seizures, another had focal myoclonic epilepsy, and 2 had simple partial seizures secondarily generalized. All 4 had clinical or EEG evidence to support a focal origin for the epilepsy, and 2 had photoparoxysal responses on EEG. Symptoms were more severe and occurred earlier in the younger generation, suggesting genetic anticipation in this family. The onset of epilepsy developed simultaneously with, or < or = 18 years before, onset of gait disturbance. Three unaffected family members had normal EEGs. CONCLUSIONS: The association of HSP and epilepsy should no longer be assumed to be fortuitous.

Adolescent↗
PubMed1997

Intensity-modulated radiotherapy by means of static tomotherapy: a planning and verification study.

There is currently much research interest in developing, evaluating, and verifying intensity-modulation techniques. Of particular interest is how well the delivery of intensity-modulated profiles can be simulated by planning algorithms, and how accurately these profiles can be delivered given the specification constraints of linear accelerators. In this paper we present a planning and verification study based on delivering radiation in "static-tomotherapy" mode via the NOMOS MIMiC (Multileaf intensity-modulation collimator), which sheds some light on these issues. An inverse-planning algorithm was used to compute intensity-modulated profiles for a 9-coplanar-field plan for a body phantom. The algorithm makes several approximations about the form of the elementary fluence profile through bixels during delivery. Specifically, it is independent of the state of adjacent bixels (i.e., open or closed) and obeys the superposition principle. From the standpoint of comparing the predicted versus the delivered dose, these assumptions were made irrelevant by a final one-step forward dose calculation performed using the optimized intensity profiles. This forward dose calculation took into account the penumbral characteristics of the delivery system by decomposing the intensity profiles into the set of delivery components. Each component was assigned the appropriate penumbral functions thereby ensuring that the calculated dose distribution closely predicted the delivered dose distribution. The nine intensity modulated fields were delivered to a perspex phantom with the same geometry, containing a verification film. In general good agreement was found between the predicted and the measured delivered dose distributions. All the main features of the predicted dose distribution are seen in the delivered. The 90% isodoses were consistently in spatial agreement to within 3 mm. At the 50% isodose level consistent spatial agreement was again found to within 3 mm, the largest deviation being about 5 mm. The close correspondence between the predicted and measured dose distribution demonstrates the potential of the MIMiC delivery system. Our results indicate the level of dose conformation that is achievable in practice and the accuracy of the dose computation algorithm. However, this study only concerned delivery of radiation to a 2 cm thick slice, and the dose distribution was only verified in the central plane of the phantom where the film was placed. We therefore cannot comment as yet on what happens to the dose distribution away from the central film-plane.

Algorithms↗
PubMed1997

Two families with autosomal recessive spastic paraplegia, pigmented maculopathy, and dementia.

OBJECTIVE: Two families with autosomal recessive hereditary spastic paraplegia and pigmented maculopathy are described. METHODS: All family members were examined by two neurologists. An assessment of cognitive function in affected members was made using the mini mental state examination (MMSE) or Cambridge cognitive examination (CAMCOG). RESULTS: Six patients from two families presented with a slowly progressive, autosomal recessive, spastic tetraplegia. Although they were always considered to be intellectually slower than their peers, further intellectual deterioration was noted during the second decade. Five had a pigmented maculopathy with mild decrease in visual acuity and all had distal amyotrophy, mild cerebellar signs, and developed faecal and urinary incontinence late in the course of the disease. CONCLUSION: The association of hereditary spastic paraplegia and pigmented maculopathy has rarely been described; only 11 families with 32 affected members have been reported, showing considerable heterogeneity in presentation. These described conditions may be allelic or more probably reflect mutations at different genetic loci.

Adult↗
PubMed1997

Outcome of anxiety and depressive disorders in primary care.

BACKGROUND: Factors related to the outcome of depression and anxiety in primary care are not fully understood. METHOD: Adult patients in general practice with depressive, anxiety or panic disorder (n = 148; DSM-III-R criteria) were studied prospectively for six months to determine the factors most closely associated with outcome. The Psychiatric Assessment Schedule, Hamilton Depression Rating Scale, Clinical Anxiety Scale and Life Events and Difficulties Schedule interviews were performed at index consultations and repeated six months later. Variables associated with outcome were assessed by multiple regression analysis. RESULTS: Good outcome was predicted by mild depression at initial assessment, high educational level, and being in employment. At follow-up the most important predictor of improvement was reduction in marked difficulties over the six months. Recognition and management by the GP was most frequent in patients with severe disorder; such patients were least likely to improve because of the severity of their depression and marked social difficulties. CONCLUSIONS: This naturalistic study helps to provide a framework for further studies with more precisely defined groups of people with depression. An effective treatment strategy for people with marked depression and ongoing social difficulties is especially needed.

Adolescent↗
PubMed1997

Methods for transferring patient and plan data between radiotherapy treatment planning systems.

The effectiveness of conformal radiotherapy can ultimately only be assessed by the use of clinical trials. As large multicentre clinical trials become more widespread, methods of transferring patient and plan data between radiotherapy treatment planning systems become increasingly important. In this paper, the general strategy for the transfer of data is discussed, and also illustrated with reference to two specific systems: TARGET 2 (GE Medical Systems) and VOXELPLAN (DKFZ-Heidelberg). The transfer method involves using a computer program to translate the data formats used by each of the two systems for CT scans, patient outlines, plan information and block descriptions. This paper does not address the question of transferring beam data between systems: beam data must first be entered separately into both machines. The physical concepts encountered when transferring plans are described, with specific reference to the two planning systems used. Differences in the strategies used by the two planning systems for definition of irregular field shapes are compared. The dose calculations used by the two systems are also briefly evaluated. Isodoses produced by VOXELPLAN around a circular target volume are found to be up to 3 mm different in location to those produced by TARGET 2, owing to the use of a smooth field shape contour as opposed to a stepped field shape which closely models the leaves of a multileaf collimator. In general, dose distributions generated by both systems are comparable, but some differences are found in the presence of large tissue inhomogeneities. It is concluded that the transfer of patient and plan data between two different treatment planning systems is feasible, provided that any differences in field shape definition methods or dose calculation methods between the two systems are understood.

Humans↗
PubMed1997

Smoking cessation interventions in rural family practices: an UPRNet study.

BACKGROUND: Primary care physicians are urged to offer smoking cessation counseling to their patients. Many studies have sought to determine which smoking interventions are most effective in medical office settings. As a result, routine identification of smokers, brief counseling, referral to smoking cessation programs, and nicotine replacement therapy are advocated. The context of patient visits during which smoking cessation advice is given, however, has received little attention. The objective of this study was to determine if patients' reasons for visits and self-reported readiness to quit smoking are associated with likelihood and type of smoking cessation intervention offered by family physicians. METHODS: The study was conducted in the Upper Peninsula Research Network (UPRNet), a voluntary association of family physicians in 15 medical clinics located in rural areas of northern Michigan. Practice coordinators administered a 1-page exit questionnaire to every other adult patient seen by a participating physician immediately after the office visit. Clinicians were blinded to the specific purpose of the questionnaire. During the study, 2317 questionnaires were administered, yielding information on 455 smokers. RESULTS: The overall rate of physicians' providing any smoking cessation intervention at any type of visit was 47%. There was a significant association between frequency of smoking cessation intervention and reasons for visits (chi 2 = 10.46, P = .01). There was a statistically significant difference between stages of readiness to quit and frequency of smoking cessation intervention offered (chi 2 = 26.5, P < .001). Clinicians offered smoking cessation interventions to smokers in the precontemplative stage significantly less often than to smokers in the contemplation, preparation, or action stages. CONCLUSIONS: UPRNet practitioners vary the frequency of smoking cessation interventions according to patients' reasons for the medical visit and their readiness to quit smoking.

Acute Disease↗
PubMed1997

Genetic and ecological data on the Anisakis simplex complex, with evidence for a new species (Nematoda, Ascaridoidea, Anisakidae).

Isozyme analysis at 24 loci was carried out on anisakid nematodes of the Anisakis simplex complex, recovered from various intermediate/paratenic (squid, fish) and definitive (marine mammals) hosts from various parts of the world. A number of samples were found to belong to A. simplex sensu stricto and Anisakis pegreffii, widely extending the geographic ranges and the number of hosts of these 2 species. In addition, a new distinct gene pool was detected, showing different alleles with respect to A. simplex s. str and A. pegreffii at 5 diagnostic loci (99% level). Samples with this gene pool were assigned to a new species, provisionally labeled A. simplex C. Reproductive isolation between A. simplex C and the other 2 Anisakis species was directly assessed by the lack of hybrid and recombinant genotypes in mixed samples from sympatric areas, i.e., Pacific Canada for A. simplex C+A. simplex s. str., South Africa and New Zealand for A. simplex C+A. pegreffii, even when such samples were recovered from the same individual host. Similar levels of genetic divergence were observed among the three species (DNei from 0.36 to 0.45). At the intraspecific level, Canadian Pacific and Austral populations of A. simplex C were found to be genetically rather differentiated from one another (average DNei = 0.08), contrasting with the remarkable genetic homogeneity detected within both A. simplex s. str. and A. pegreffii (average DNei about 0.01). Accordingly, a lower amount of gene flow was estimated within A. simplex C (Nm = 1.6) than within the other 2 species (Nm = 5.4 and 17.7, respectively). Anisakis simplex C showed the highest average values of genetic variability with respect to both A. simplex s. str. and A. pegreffii, e.g., expected mean heterozygosity. Hr = 0.23, 0.16, and 0.11, respectively, in the 3 species. Data on geographic distribution and hosts of the 3 members so far detected in the A. simplex complex are given. Their ecological niche is markedly differentiated, with a low proportion of hosts shared. Intermediate and definitive hosts of A. simplex s. str. and A. pegreffii appear to belong to distinct food webs, benthodemersal, and pelagic, respectively; this would lead to different transmission pathways for the parasites.

Animals↗
PubMed1997

Three-dimensional dosimetry for intralesional radionuclide therapy using mathematical modeling and multimodality imaging.

UNLABELLED: A method of dosimetry is described that quantifies the three-dimensional absorbed-dose distribution resulting from an intralesional administration of a radiolabeled monoclonal antibody, allowing for both spatial and temporal heterogeneity of distribution of the radionuclide and without the need for a calibration scan. METHODS: A mathematical model was developed to describe the distribution of activity as a function of time resulting from infusion at a single point within the solid component of a tumor. The parameters required for this model are either known directly or may be obtained from SPECT image data registered to computed tomography. Convolution of this distribution with a point-source dose kernel enabled the three-dimensional absorbed-dose distribution to be obtained. RESULTS: This method was applied to a set of patient data acquired in the course of a clinical study performed at our center, and dose profiles and dose-volume histograms were produced. It was shown that the three-dimensional distribution of dose was significantly nonuniform. CONCLUSION: Initial results suggest that this method offers a means of determining the absorbed dose distribution within a tumor resulting from intralesional infusion. This method extends the Medical Internal Radiation Dose computation, which, in these circumstances, would make erroneous assumptions. Furthermore, it will enable individual patient treatment planning and optimization of the parameters that are within the clinician's control.

Humans↗
PubMed1997

Effect of basic fibroblast growth factor. An in vitro study of tendon healing.

The effect of basic fibroblast growth factor on the proliferative and chemotactic response of cultured rat patellar tendon fibroblasts was studied in an in vitro wound closure model. In quiescent confluent fibroblast culture, a uniform cell free zone, or wound, was generated mechanically as an in vitro wound. The width of the cell free zone was measured at 0, 6, 12, and 24 hours after the injury, in the presence of 0, 2, 10, or 50 mg/mL of basic fibroblast growth factor. Basic fibroblast growth factor, at a concentration of 10 ng/mL, significantly accelerated wound closure, resulting in almost complete closure by 24 hours after the injury. Basic fibroblast growth factor, at a concentration of 2 ng/mL, significantly enhanced cell proliferation as estimated by 5-Bromo-2'-deoxyuridine incorporation, but increasing the concentration of the growth factor to 50 ng/mL did not show additional improvement. Thus, the enhancement of wound closure by basic fibroblast growth factor may be caused by the cell proliferative response, rather than by chemotaxis.

Animals↗
PubMed1996

Endocardial cushion development and heart loop architecture in the trisomy 16 mouse.

Murine trisomy 16 (Ts16) is a model for Down's syndrome and has close to a 100% incidence of atrioventricular septal defects (AVSDs). These have been proposed to result from abnormal development of the endocardial cushions, but the mechanisms are unknown. We aim to identify the initial defects in Ts16 hearts, both to characterise the pathogenesis of AVSDs and as a first step in the search for molecular mechanisms. In 38 litters from an Rb(11.16)2H/Rb(16.17)7Bnr x C57BL/6J cross, which was examined on days 10 and 11 of gestation, 28.4% of embryos were trisomic. Trisomic embryos were uniformly retarded compared to their normal litter mates, having on average 3.3 fewer somite pairs. All further comparisons were made between embryos of the same somitic stage. Twenty-one trisomic and 21 normal embryos of between 15 and 43 somites were serially sectioned, and stereomorphometric methods were used to reconstruct the volumes of the endocardial cushions and to count their number of mesenchymal cells. There were fewer cells in Ts16 superior and inferior cushions. In contrast, the volumes of trisomic cushions were significantly greater than normal. Thus, cell density was markedly lower in trisomic cushions. Importantly, the volumes of the cushions in trisomic embryos were already greater than normal at the 18 somite stage, prior to the invasion of cushions by mesenchymal cells. The architecture of Ts16 heart tubes in 15-25 somite embryos was subtly abnormal. This was reflected in the angle between the axis of the atrioventricular canal and the first pharyngeal cleft, which was significantly larger in trisomic hearts and showed a different relationship to somite stage when compared to normal embryos. These observations suggest that the primary cardiac defect in Ts16 mice may be localised to the myocardium, thus influencing the shape of the heart tube, with changes in the mesenchymal population of the endocardial cushions being later events. Whether AVSDs arise from one or both of these abnormalities remains to be established.

Animals↗
PubMed1996

The structure of the mouse heart in late fetal stages.

Because of the opportunities for genetic manipulation, the mouse has become the major species for models of human disease. Recently, targeted and insertional mutations have induced many novel models of developmental abnormality, including several of congenital heart defects. Interpretation and use of such models requires a precise understanding of the similarities and differences between mouse and human in terms of cardiac development and structure. To this end, we have characterised the late fetal mouse heart using scanning electron microscopy and serial histological sections. Right atrial anatomy is dominated by the venous valves, which separate the orifices of the caval veins from the musculature of the primary atrium. Their structure and location suggest that the pulmonary vein is unlikely to develop from the venous sinus. The pectinated wall of the appendage serves to distinguish the morphologically right atrium, in that it runs around the atrioventricular junction, from the left atrium in which this vestibular region is smooth-walled. The persistence of the left superior caval vein draining to the right atrium, along with a solitary opening for the pulmonary vein in the left atrium, distinguishes the atrial anatomy of the mouse from that of the human. The flap valve of the oval foramen is extensive and represents the embryonic primary atrial septum. The superior rim of the foramen is an infolding of the atrial roof, as has been described in the human, showing that, contrary to orthodox opinion, there is no extensive formation of a secondary atrial septum. The region of the membranous septum seen in the human heart is a relatively thick structure in the late fetal mouse, and is located exclusively in an atrioventricular position. Unlike the human, there is little distinction between the apical trabeculations of the left and right ventricles of the mouse heart.

Animals↗