bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of anatomical wrap position on the outcome of Nissen fundoplication
Authors: Donkervoort S C , Bais J E , Rijnhart-de Jong H , Gooszen H G
Published: July 2003

Background

The importance of anatomical reposition and fixation of the type I hiatal hernia during antireflux surgery has often been emphasized. It is not known whether the initial anatomical repair withstands the test of time and whether this repair is necessary for a successful outcome.

Methods

The relationship between the objective anatomical and subjective symptomatic outcome of Nissen fundoplication was investigated prospectively in 57 patients. Findings of herniation, telescoping and obstruction at the level of the lower oesophageal sphincter on barium swallow were scored 2 years after operation by investigators who were unaware of the symptoms, and were related to symptoms and patient satisfaction evaluated by a standard questionnaire.

Results

According to strict criteria, some 55 per cent of patients had some degree of anatomical failure; if only complete herniation, significant telescoping and signs of obstruction were scored as abnormal, 27 per cent had anatomical failure. There was no relation to subjective outcome; relief was reported by 48 of 49 patients, 25 of whom were cured and 23 significantly improved.

Conclusion

Anatomical repair during antireflux surgery does not stand the test of time. Although this has no demonstrable influence on the subjective outcome, the authors do not recommend deviating from well designed surgical guidelines. Current theories on the mechanism of antireflux surgery require further evaluation.
Magnetic resonance imaging for primary fistula in ano
Authors: Buchanan G N , Halligan S , Williams A B , Cohen C R G , Tarroni D , Phillips R K S , Bartram C I
Published: July 2003

Background

This was a prospective study designed to determine the therapeutic impact of magnetic resonance imaging (MRI) in primary fistula in ano, and to assess its effect on outcome.

Methods

Thirty patients with suspected primary fistula in ano underwent preoperative MRI, and the findings were revealed during surgery following examination under anaesthesia (EUA). Any effect on operative approach was noted. Outcome was assessed at a median of 12 months.

Results

Two patients had sinuses, one had no sepsis and 27 had fistulas: five superficial, seven intersphincteric, 14 trans-sphincteric and one suprasphincteric. MRI and EUA agreed in 15 patients and MRI findings altered the surgical approach in a further three (10 per cent); two of the latter patients were believed to have a sinus at EUA, which MRI correctly identified as a fistula, allowing definitive treatment. The therapeutic impact of MRI was therefore 10 per cent. Persisting disagreement between MRI and EUA in 12 patients mostly related to minor discrepancies in classification. Only one patient required further unplanned surgery, which was for skin-bridging rather than any new sepsis.

Conclusion

In experienced hands, MRI has a therapeutic impact of 10 per cent for primary fistula in ano, precipitating surgery that is likely to reduce recurrence in a small, but important, proportion of patients.
Randomized clinical trial of ultrasonicversuselectrocautery dissection of the gallbladder in laparoscopic cholecystectomy
Authors: Janssen I M C , Swank D J , Boonstra O , Knipscheer B C , Klinkenbijl J H G , van Goor H
Published: July 2003

Background

Laparoscopic cholecystectomy is frequently complicated by gallbladder perforation and loss of bile or stones into the peritoneal cavity. The aim of this study was to compare the use of ultrasonic dissection and electrocautery with respect to the incidence of gallbladder perforation and intraoperative consequences.

Methods

Between January 1998 and January 2000, 200 patients undergoing elective laparoscopic cholecystectomy were randomized to electrocautery or ultrasonic dissection of the gallbladder. The main outcome measures were gallbladder perforation, operating time and the number of times the lens was cleaned. Univariate and multivariate analyses were performed.

Results

The perforation rate differed significantly: 16 per cent for ultrasonic dissection (n = 96) and 50 per cent for electrocautery (n = 103) (P < 0·001). The operating time of the least experienced surgeons, who had performed fewer than ten laparoscopic cholecystectomies, was significantly shorter when ultrasonic dissection was used, compared with electrocautery. The number of times the lens needed to be cleaned was significantly lower when ultrasonic dissection was used in complicated gallbladders (P < 0·035). At logistic regression analysis, the risk of perforation in the electrocautery group was about four times higher (odds ratio 0·26, P < 0·001) than that in the ultrasonic group. When the groups were matched for prognostic factors, including body mass index and surgical experience, the results were similar to those obtained with univariate and multivariate analysis.

Conclusion

The use of ultrasonic dissection in laparoscopic cholecystectomy reduces the incidence of gallbladder perforation and helps the operation to progress. Less experienced surgeons benefit most from ultrasonic dissection, particularly in complicated intraoperative circumstances.
Perioperative detection of disseminated tumour cells is an independent prognostic factor in patients with colorectal cancer
Authors: Bosch B , Guller U , Schnider A , Maurer R , Harder F , Metzger U , Marti W R
Published: July 2003

Background

The objective of the present investigation was to assess the prognostic significance of disseminated tumour cells in peritoneal lavage, and peripheral and mesenteric venous blood in patients undergoing curative resection of colorectal cancer.

Methods

The prognostic impact of perioperative cytological and immunocytochemical detection of disseminated colorectal cancer cells was evaluated prospectively. Peritoneal lavage fluid, and peripheral and mesenteric venous blood from 53 consecutive patients undergoing curative surgery for colorectal cancer were analysed. The dichotomous results (positive versus negative) from the cytological and immunocytochemical analysis were used as a predictor along with other co-variates in proportional hazard regression models of disease-free and overall survival.

Results

Disseminated colorectal cancer cells were found in 13 of 53 patients (25 per cent) using cytology (CYT) and/or immunocytochemistry (ICC). The median follow-up at the time of the analysis was 37 months. In multivariate proportional hazard regression models CYT/ICC status was a significant predictor for disease-free (P = 0·002) and overall (P = 0·006) survival.

Conclusion

Disseminated tumour cells detected by CYT and ICC represent an independent prognostic factor in patients undergoing surgery for colorectal cancer and may identify patients at high risk of recurrence.
Value of the Glasgow Aneurysm Score in predicting the immediate and long-term outcome after elective open repair of infrarenal abdominal aortic aneurysm
Authors: Biancari F , Leo E , Ylönen K , Vaarala M H , Rainio P , Juvonen T
Published: July 2003

Background

This study aimed to explore the value of the Glasgow Aneurysm Score in predicting the immediate and long-term outcome after elective open repair of abdominal aortic aneurysm (AAA).

Methods

Some 403 patients underwent elective open repair of an infrarenal AAA and were classified retrospectively according to the criteria of the Glasgow Aneurysm Score (risk score = (age in years) + (7 for myocardial disease) + (10 for cerebrovascular disease) + (14 for renal disease)).

Results

Fourteen patients (3·5 per cent) died after operation, 23 (5·7 per cent) had a myocardial infarction and six (1·5 per cent) had a stroke. One hundred and nine patients (27·0 per cent) experienced severe postoperative complications. The Glasgow Aneurysm Score was predictive of postoperative death (area under the receiver–operator characteristic curve (AUC) 0·80, 95 per cent confidence interval (c.i.) 0·71 to 0·90), severe postoperative complications (AUC 0·67, 95 per cent c.i. 0·61 to 0·73), myocardial infarction (AUC 0·72, 95 per cent c.i. 0·62 to 0·82), myocardial infarction-related postoperative death (AUC 0·78, 95 per cent c.i. 0·63 to 0·94) and stroke (AUC 0·84, 95 per cent c.i. 0·74 to 0·95). Univariate analysis showed that this risk index was also predictive of long-term survival.

Conclusion

The Glasgow Aneurysm Score is a good predictor of outcome after elective open repair of AAA. Its simplicity and accuracy make it useful for preoperative risk stratification.
Randomized clinical trial and economic analysis of four-layer compression bandaging for venous ulcers
Authors: O'Brien J F , Grace P A , Perry I J , Hannigan A , Clarke Moloney M , Burke P E
Published: July 2003

Background

The aim of this study was to compare the cost-effectiveness of four-layer compression bandaging for venous leg ulcers with that of other available treatments.

Methods

In this pragmatic trial, 200 patients with a venous leg ulcer were randomized either to four-layer bandaging (intervention group; n = 100) or to continue their usual system of care (control group; n = 100). The follow-up for each patient was 12 weeks. Analysis was by intention to treat; the main outcome measures were time to healing and cost to the health board per leg healed.

Results

Baseline characteristics were well matched in the two groups. The Kaplan–Meier estimate of the healing rate at 3 months was 54 per cent with four-layer bandaging and 34 per cent in the control group. Throughout the 3 months, four-layer bandaging healed leg ulcers significantly earlier (P = 0·006). There was a significant reduction in the median cost per leg healed with four-layer bandaging (€210 versus €234; P = 0·040).

Conclusion

Four-layer bandaging is currently the most effective method of treating venous leg ulcers in a community setting.
Mid-term results for second-generation thoracic stent grafts
Authors: Bell R E , Taylor P R , Aukett M , Sabharwal T , Reidy J F
Published: July 2003

Background

Thoracic stent grafts offer an alternative to open surgery for thoracic aortic disease, but their long-term durability is unknown. This report includes mid-term follow-up for commercially available thoracic devices.

Methods

Data were collected prospectively for a series of endoluminal grafts used to treat thoracic aortic pathology.

Results

Between July 1997 and October 2002, 67 patients received thoracic stent grafts. Elective procedures incurred a 30-day mortality rate of 2 per cent (one of 42 patients) and urgent repair 16 per cent (four of 25). Paraplegia affected three (4 per cent) of 67 patients and three patients had a stroke. The median follow-up was 17 (range 2–64) months; four patients were lost. There were six late deaths, two from aneurysm rupture (rupture of a mycotic aneurysm at 5 months and stent migration at 28 months). Other device-related complications comprised three proximal endoleaks, one of which required open surgical correction with removal of the stent graft, and two distal endoleaks, which were successfully treated with distal extension cuffs.

Conclusion

In the mid term, endoluminal repair of thoracic aortic pathology appears to be a safe alternative to open surgery, but continued surveillance is essential.
Thromboprophylaxis can be omitted in selected patients undergoing varicose vein surgery and hernia repair
Authors: Enoch S , Woon E , Blair S D
Published: July 2003

Background

There is no current agreement on the routine use of thromboprophylaxis in patients undergoing varicose vein surgery and hernia repair. In the authors' hospital, prophylaxis is given only to those considered to be at an increased risk. A retrospective review was conducted to determine whether it was safe to omit prophylaxis in low-risk patients.

Methods

Data were extracted from the hospital database about all patients who underwent the above procedures between January 1997 and December 2001. The case notes of patients who developed venous thromboembolism (VTE) within 3 months of surgery were reviewed. The pharmacy database was then analysed to determine the effect of prophylaxis.

Results

A total of 4670 patients were identified. Some 2186 patients had varicose vein surgery; 1283 patients received prophylaxis, of whom four developed VTE. None of the 903 patients who did not receive prophylaxis developed VTE. A total of 2484 patients had hernia repair, of whom 1854 patients received prophylaxis and 630 did not; one patient from each group developed VTE.

Conclusion

Low-risk patients having hernia and vein surgery do not need thromboprophylaxis.
Surgical simulation—a ‘good idea whose time has come’
Authors: Champion H R , Gallagher A G
Published: July 2003

Technology assisted training will have a major impact worldwide
Randomized clinical trials to determine the role of topical glyceryl trinitrate in peripheral intravenous nutrition
Authors: Dobbins B M , Catton J A , Tighe M J , Miller G V , Martin I G , McMahon M J
Published: July 2003

Background

The contribution of glyceryl trinitrate (GTN) to prevention of peripheral vein thrombophlebitis (PVT) during peripheral intravenous nutrition delivered by fine-bore midline intravenous catheter is unclear. The aim of this study was to establish its role.

Methods

Two consecutive randomized clinical trials were conducted. In trial 1 patients were randomized to receive standard peripheral intravenous nutrition containing heparin and hydrocortisone with or without the placement of a topical GTN patch (triple therapy or dual therapy). In trial 2 patients were randomized to receive standard peripheral intravenous nutrition with either dual therapy or topical GTN alone (monotherapy).

Results

Dual therapy was as effective as triple therapy in preventing PVT (incidence 10 of 37 versus 11 of 39 patients respectively). Dual therapy reduced the incidence and increased the time to onset of PVT compared with monotherapy (14 of 41 versus 22 of 35 patients respectively, P = 0·012; median 17·3 (95 per cent confidence interval (c.i.) 13·4 to 21·1) versus 8·9 (95 per cent c.i. 6·7 to 11·0) days, P = 0·007).

Conclusion

Use of a topical GTN patch confers no benefit when peripheral intravenous nutrition is delivered via a fine-bore midline intravenous catheter.
Future perspectives in the acute management of head injury
Authors: Hutchinson P J
Published: July 2003

Observations on one of the commonest reasons for admission to hospital
Parastomal hernia
Authors: Carne P W G , Robertson G M , Frizelle F A
Published: July 2003

Background

Parastomal hernia following formation of an ileostomy or colostomy is common. This article reviews the incidence of hernia, the technical factors related to the construction of the stoma that may influence the incidence, and the success of the different methods of repair.

Methods

A literature search using the Medline database was performed to locate English language articles on parastomal hernia. Further articles were obtained from the references cited in the literature initially reviewed.

Results

Parastomal hernia affects 1·8–28·3 per cent of end ileostomies, and 0–6·2 per cent of loop ileostomies. Following colostomy formation, the rates are 4·0–48·1 and 0–30·8 per cent respectively. Site of stoma formation (through or lateral to rectus abdominis), trephine size, fascial fixation and closure of lateral space are not proven to affect the incidence of hernia. The role of extraperitoneal stoma construction is uncertain. Mesh repair gives a lower rate of recurrence (0–33·3 per cent) than direct tissue repair (46–100 per cent) or stoma relocation (0–76·2 per cent).

Conclusion

The incidence of parastomal hernia is between 0 and 48·1 per cent, depending on the type of stoma and length of follow-up. No technical factors related to the construction of the stoma have been shown to prevent herniation. If repair is required, a prosthetic mesh technique should be considered. Further randomized clinical trials (particularly of extraperitoneal stoma construction) are needed.
Extracorporeal shockwave lithotripsy in the management of salivary calculi (Br J Surg 2003; 90: 482–485)
Authors: Mahawar K K
Published: July 2003

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses can be sent electronically via the BJS website (www.bjs.co.uk) or by post. All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length. Letters submitted by post should be typed on A4-sized paper in double spacing and should be accompanied by a disk.
A fully hydrodynamic model for three‐dimensional, free‐surface flows
Authors: Chen XinJian
Published: July 2003

The hydrostatic pressure assumption has been widely used in studying water movements in rivers, lakes, estuaries, and oceans. While this assumption is valid in many cases and has been successfully used in numerous studies, there are many cases where this assumption is questionable. This paper presents a three‐dimensional, hydrodynamic model for free‐surface flows without using the hydrostatic pressure assumption. The model includes two predictor–corrector steps. In the first predictor–corrector step, the model uses hydrostatic pressure at the previous time step as an initial estimate of the total pressure field at the new time step. Based on the estimated pressure field, an intermediate velocity field is calculated, which is then corrected by adding the non‐hydrostatic component of the pressure to the estimated pressure field. A Poisson equation for non‐hydrostatic pressure is solved before the second intermediate velocity field is calculated. The final velocity field is found after the free surface at the new time step is computed by solving a free‐surface correction equation.

The numerical method was validated with several analytical solutions and laboratory experiments. Model results agree reasonably well with analytical solutions and laboratory results. Model simulations suggest that the numerical method presented is suitable for fully hydrodynamic simulations of three‐dimensional, free‐surface flows. Copyright © 2003 John Wiley & Sons, Ltd.
Microbial controls on methane fluxes from a polygonal tundra of the Lena Delta, Siberia
Authors: Wagner D. , Kobabe S. , Pfeiffer E.‐M. , Hubberten H.‐W.
Published: July 2003

Permafrost soils of high‐latitude wetlands are an important source of atmospheric methane. In order to improve our understanding of the large seasonal fluctuations of trace gases, we measured the CH4 fluxes as well as the fundamental processes of CH4 production and CH4 oxidation under in situ conditions in a typical polygon tundra in the Lena Delta, Siberia. Net CH4 fluxes were measured from the polygon depression and from the polygon rim from the end of May to the beginning of September 1999. The mean flux rate of the depression was 53.2 ± 8.7 mg CH4 m−2 d−1 with maximum in mid‐July (100–120 mg CH4 m−2 d−1), whereas the mean flux rate of the dryer rim part of the polygon was 4.7 ± 2.5 CH4 m−2 d−1. The microbial CH4 production and oxidation showed significant differences during the vegetation period. The CH4 production in the upper soil horizon of the polygon depression was about 10 times higher (38.9 ± 2.9 nmol CH4 h−1 g−1) in July than in August (4.7 ± 1.3 nmol CH4 h−1 g−1). The CH4 oxidation behaved exactly in reverse: the oxidation rate of the upper soil horizon was low (1.9 ± 0.3 nmol CH4 h−1 g−1) in July compared to the activity in August (max. 7.0 ± 1.3 nmol CH4 h−1 g−1). The results indicated clearly an interaction between the microbiological processes with the observed seasonal CH4 fluctuations. However, the CH4 production is primarily substrate dependent, while the oxidation is dependent on the availability of oxygen. The temperature plays only a minor role in both processes, probably because the organisms are adapted to extreme temperature conditions of the permafrost. For the understanding of the carbon dynamics in permafrost soils, a differentiated small‐scale view of the microbiological processes and the associated modes of CH4 fluxes is necessary, especially at key locations such as the Siberian Arctic. Copyright © 2003 John Wiley & Sons, Ltd.
Dissolved organic carbon fluxes in a discontinuous permafrost subarctic alpine catchment
Authors: Carey Sean K.
Published: July 2003

The sources and fluxes of dissolved organic carbon (DOC) were investigated within a subarctic catchment with discontinuous permafrost (Granger Basin, Yukon) from 23 June 2001 to 22 June 2002. During spring freshet, stream DOC increased rapidly on the rising limb of the hydrograph, peaked prior to maximum discharge, then declined exponentially to pre‐baseflow levels while flows remained high. During summer storms, a similar pattern was observed whereby DOC increased on the ascending hydrograph limbs and peaked prior to maximum flows. Suction lysimeter and well data indicate that most of the DOC was mobilized from within near‐surface organic soils. Comparisons between permafrost and seasonal frost slopes indicate that permafrost slopes are a greater source of DOC due to their thicker organic soils and wetter antecedent conditions that promote lateral flow in the shallower soil layers of the active layer. In contrast, slopes with seasonal frost encourage percolation and sorption of DOC in deeper mineral layers. Mass balance estimates of DOC export using actual and extrapolated data from regressions of DOC versus discharge indicate that 1.64 g C m−2 was exported from Granger Basin during the study year, 69% of this occurred during the 13 May to 22 June snowmelt period. Copyright © 2003 John Wiley & Sons, Ltd.
Impact of the timing and duration of seasonal snow cover on the active layer and permafrost in the Alaskan Arctic
Authors: Ling Feng , Zhang Tingjun
Published: July 2003

Variations in the timing and duration of seasonal snow cover are critical to the ground thermal regime at high latitudes, due to changes in surface conditions and the associated ground surface energy balance. This study uses a one‐dimensional heat transfer model with phase change, combined with a surface energy balance equation to analyse the impact of changes in the timing and duration of seasonal snow cover on the thermal regime of the active layer and permafrost. Based on meteorological data collected at Barrow, Alaska, a series of simulation cases was conducted by varying the snowpack onset date in autumn and the disappearance date in spring during 1997–98. Results show that the ground thermal regime is sensitive to variations in the timing and duration of seasonal snow cover. Delaying the snow cover onset date by 10 days in autumn and the disappearance date by 10 days in spring results in a decrease in ground temperature. The maximum ground temperature decreases at depths of 0.0, 0.5, 1.0, and 2.0 m were 9.0, 2.9, 2.0, and 1.1°C, respectively, and the mean annual ground temperature decreases were 0.7, 0.5, 0.4, and 0.4°C. Advancing the snow cover disappearance date by 10 days in spring leads to an increase in ground temperature. The maximum ground temperature increases at depths of 0.0, 0.5, 1.0, and 2.0 m were 6.6, 2.2, 1.5, and 0.7°C, and the mean annual ground temperature increases were 0.2, 0.2, 0.1, and 0.1°C, respectively. Variations in the timing and duration of seasonal snow cover also have an influence on active layer thickness, but the effect is limited. Copyright © 2003 John Wiley & Sons, Ltd.
Effects of permafrost degradation on woody vegetation at arctic treeline on the Seward Peninsula, Alaska
Authors: Lloyd Andrea H. , Yoshikawa Kenji , Fastie Christopher L. , Hinzman Larry , Fraver Matthew
Published: July 2003

Permafrost degradation leads to substantial changes in soil thermal and hydrologic characteristics. We investigated the effects of changes in active layer thickness and soil drainage on vegetation distribution near the arctic treeline on the Seward Peninsula, Alaska. We measured active layer thickness, soil moisture, density of tall shrub species, cover of low shrub species, and reconstructed white spruce establishment history along transects across the banks of a network of thaw ponds. We found that active layer thickness did not vary along our transects, but soils on thaw pond banks were significantly drier than those on level tundra or in thaw‐pond channels. Thaw‐pond banks were the only sites in which trees successfully established, and shrub communities on thaw‐pond banks were taller and more dominated by tall shrub species like willow and shrub birch. The data suggest that the establishment of tree and tall shrub species at the arctic treeline can be limited by the availability of well‐drained microsites, and the response of these species to regional climatic changes will be constrained by the availability of such microsites and thus contingent upon further degradation of the permafrost. Copyright © 2003 John Wiley & Sons, Ltd.
A model for regional‐scale estimation of temporal and spatial variability of active layer thickness and mean annual ground temperatures
Authors: Sazonova T. S. , Romanovsky V. E.
Published: July 2003

High‐latitude ecosystems where the mean annual ground surface temperature is around or below 0°C are highly sensitive to global warming. This is largely because these regions contain vast areas of permafrost, which begins to thaw when the mean annual temperature rises above freezing. The Geophysical Institute Permafrost Lab has developed a new interactive geographical information systems (GIS) model to estimate the long‐term response of permafrost to changes in climate. An analytical approach is used for calculating both active layer thickness (ALT) and mean annual ground temperatures (MAGTs). When applied to long‐term (decadal or longer time scale) averages, this approach shows an accuracy of ±0.2–0.4°C for MAGTs and ±0.1–0.3 m for ALT calculations. The relative errors do not exceed 32% for ALT calculations, but typically they are between 10 and 25%. A spatial statistical analysis of the data from 32 sites in Siberia indicated a confidence level of 75% to have a deviation between measured and calculated MAGTs of 0.2–0.4°C. A detailed analysis has been performed for two regional transects in Alaska and eastern Siberia that has validated the use of the model. The results obtained from this analysis show that a more economical (in terms of computational time) analytical approach could be successfully used instead of a full‐scale numerical model in the regional and global scale analysis of permafrost spatial and temporal dynamics. This project has been a successful contribution to the Arctic Climate Impact Assessment project. Copyright © 2003 John Wiley & Sons, Ltd.
Shrinking thermokarst ponds and groundwater dynamics in discontinuous permafrost near council, Alaska
Authors: Yoshikawa Kenji , Hinzman Larry D.
Published: July 2003

The purpose of this study was to characterize the geomorphological processes controlling the dynamics of ponds and to identify and characterize groundwater infiltration and surface water dynamics for a tundra terrain located in discontinuous permafrost near Council, Alaska. Thermokarst processes and permafrost degradation were studied, focusing upon the interaction between surface and groundwater systems via an open talik. Synthetic aperture radar (SAR) data were used for classification of terrain units and surface water properties, while historical aerial photographs and satellite images (IKONOS) were used for assessment of pond shrinking and recent thermokarst progression. Geophysical surveys (ground penetrating radar and DC resistivity) were conducted to detect permafrost thickness and talik formations. Temperature boreholes and hydrological observation wells were monitored throughout the year and provided ground truth for validation of remotely‐sensed data and geophysical surveys. Field and laboratory analyses enabled quantitative determination of subsurface hydrologic and thermal properties. We found many areas where alluvium deposits and ice‐wedge polygonal terrain had developed thermokarst features within the last 20 years. Thermokarst ponds located over ice‐wedge terrain have decreased in surface area since at least the early 20th Century. Small thermokarst features initially developed into tundra ponds perched over permafrost in response to some local disturbance to the surface. These thermokarst ponds grew larger and initiated large taliks that completely penetrated the permafrost. These taliks allowed internal drainage throughout the year causing the ponds to shrink under recent climatic conditions. Shrinking pond surface areas may become a common feature in the discontinuous permafrost regions as a consequence of warming climate and thawing permafrost. Copyright © 2003 John Wiley & Sons, Ltd.
Vegetation‐soil‐thaw‐depth relationships along a low‐arctic bioclimate gradient, Alaska: synthesis of information from the ATLAS studies
Authors: Walker D. A. , Jia G. J. , Epstein H. E. , Raynolds M. K. , Chapin III F. S. , Copass C. , Hinzman L. D. , Knudson J. A. , Maier H. A. , Michaelson G. J. , Nelson F. , Ping C. L. , Romanovsky V. E. , Shiklomanov N.
Published: July 2003

Differences in the summer insulative value of the zonal vegetation mat affect the depth of thaw along the Arctic bioclimate gradient. Toward the south, taller, denser plant canopies and thicker organic horizons counter the effects of warmer temperatures, so that there is little correspondence between active layer depths and summer air temperature. We examined the interactions between summer warmth, vegetation (biomass, Leaf Area Index, Normalized Difference Vegetation Index), soil (texture and pH), and thaw depths at 17 sites in three bioclimate subzones of the Arctic Slope and Seward Peninsula, Alaska. Total plant biomass in subzones C, D, and E averaged 421 g m−2, 503 g m−2, and 1178 g m−2 respectively. Soil organic horizons averaged 4 cm in subzone C, 8 cm in subzone D, and 14 cm in subzone E. The average late‐August thaw depths in subzones C, D, and E were 44 cm, 55 cm, and 47 cm respectively. Non‐acidic soils in equivalent climates generally have shorter‐stature sedge‐dominated canopies and many frost boils, and consequently have thicker active layers than acidic soils. The trends reported here are useful for palaeo‐ecological reconstructions and predictions of future ecosystem changes in the Low Arctic. Climate change will not lead to uniform thickening of the active layer, and could lead to shallower active layers in some presently dry areas due to paludification. Copyright © 2003 John Wiley & Sons, Ltd.
On the analysis of viral load endpoints in HIV vaccine trials
Authors: Hudgens Michael G. , Hoering Antje , Self Steven G.
Published: July 2003

First generation HIV vaccines are not likely to provide complete protection from HIV‐1 infection. Therefore, it is important to assess a vaccine's effect on disease progression and infectiousness of infected vaccinees in an efficacy trial; however, direct assessment of such vaccine effects is not feasible within current trial designs. Viral load in HIV‐infected individuals correlates with infectiousness and disease progression in a natural history setting, and thus is a reasonable candidate for a surrogate outcome in vaccine efficacy trials. We consider comparisons of viral load of infected vaccinees to that of infected trial participants in the control group. Dramatic differences in viral loads between these groups would suggest a vaccine effect on disease progression. However, modest differences, even if statistically significant, could be consistent with an imperfect vaccine effect on susceptibility to infection and not an effect on disease progression, that is, a selection effect of the vaccine. Thus, the usual statistical tests for no difference between groups do not test the biologically and clinically relevant hypothesis. We propose a model for the possible selective effects of a vaccine and develop several test statistics for assessing a direct effect of the vaccine on viral load given this selection model. Finite sample properties of these tests are evaluated using computer simulations. Copyright © 2003 John Wiley & Sons, Ltd.
Multivariate meta‐analysis
Authors: Nam In‐Sun , Mengersen Kerrie , Garthwaite Paul
Published: July 2003

Meta‐analysis is now a standard statistical tool for assessing the overall strength and interesting features of a relationship, on the basis of multiple independent studies. There is, however, recent acknowledgement of the fact that in many applications responses are rarely uniquely determined. Hence there has been some change of focus from a single response to the analysis of multiple outcomes. In this paper we propose and evaluate three Bayesian multivariate meta‐analysis models: two multivariate analogues of the traditional univariate random effects models which make different assumptions about the relationships between studies and estimates, and a multivariate random effects model which is a Bayesian adaptation of the mixed model approach. Our preferred method is then illustrated through an analysis of a new data set on parental smoking and two health outcomes (asthma and lower respiratory disease) in children. Copyright © 2003 John Wiley & Sons, Ltd.
Novel designs for multi‐arm clinical trials with survival outcomes with an application in ovarian cancer
Authors: Royston Patrick , Parmar Mahesh K. B. , Qian Wendi
Published: July 2003

With the increasing pace of drug development, it is not unusual for several promising treatment regimens to be ready simultaneously for testing in a randomized phase III setting. Various limiting factors, including the time needed to transfer research results to clinical practice and a narrow ‘window of opportunity’, may make it unfeasible to perform trials to test such regimens sequentially against a control treatment in a traditional two‐arm parallel group design. We present an approach to trial design based on eliminating inferior contenders at an early stage, allowing through to a second stage only treatments that show a predefined degree of advantage against a control treatment. The first stage of testing utilizes a marker known to be a valid intermediate outcome measure or surrogate for the definitive outcome. The experimental arms are compared pairwise with control according to this intermediate outcome measure. Arms that survive the comparison enter a second stage of patient accrual culminating in comparisons against control on the outcome measure of primary interest. We show how the design may be realized in practice by considering hypothetically distinct trials at stages 1 and 2, each with their own operating characteristics. The overall operating characteristics are computed from the stage 1 and 2 size and power and the correlation between the treatment effects on the intermediate and primary outcome measures according to a bivariate Normal approximation. The correlation is estimated by bootstrapping individual patient data from previous trials. We illustrate the general approach in a design of a real trial of four new chemotherapy regimens for advanced ovarian cancer. The intermediate outcome measure is progression‐free survival. An international randomized controlled trial using the new design is already under way. Copyright © 2003 John Wiley & Sons, Ltd.
Estimating the distribution of lag in the effect of short‐term exposures and interventions: adaptation of a non‐parametric regression spline model
Authors: Rachet B. , Abrahamowicz M. , Sasco A. J. , Siemiatycki J.
Published: July 2003

Information on the distribution of lag duration between exposure or intervention and the subsequent changes in risk can help in assessing the impact of exposure, predicting cost‐effectiveness of intervention, and understanding the underlying biological mechanisms. Previous approaches focused more on optimizing the strength of the exposure–disease association than on directly estimating lag duration. We propose an alternative approach applicable to the analysis of the lagged effects of binary exposure variables. The density function of the distribution of lags is estimated based on flexible modelling of changes in hazard ratio of exposed versus unexposed subjects. The methodology is evaluated in a simulation study and is applied to the Framingham data to investigate the lagged effect of smoking cessation on coronary heart disease risk. Copyright © 2003 John Wiley & Sons, Ltd.
Titrating and evaluating multi‐drug regimens within subjects
Authors: Shih Margaret , Gennings Chris , Chinchilli Vernon M. , Carter Walter H.
Published: July 2003

The dosing of combination therapies is commonly undertaken empirically by practising physicians, and a coherent algorithm to approach the problem of combination dosing is currently lacking. Current methods of evaluating multiple drug combinations in clinical trials fail to provide information regarding the location of more effective doses when the combination is not found to differ from the standard, even though the absence of a difference does not necessarily mean the new combination is ineffective. Moreover, in studies where the new combination is found more effective, often a large proportion of the study participants obtain no benefit from the trial. Even with early stopping rules, the time these subjects spend on inferior treatments can have lasting detrimental effects, leading to problems with patient enrolment and adherence to study protocol. This paper describes an evolutionary operation (EVOP) direct‐search procedure to titrate combination doses within individual patients. The Nelder–Mead simplex direct‐search algorithm is used to titrate combinations of drugs within individual subjects. Desirability functions are utilized to define the main response of interest and additional responses or constraints. Statistical methodology for determining whether the titrated treatment combination has resulted in an improvement in subject response and for evaluating for therapeutic synergism is developed. Inferences can then be made about the efficacy of the combination or about the individual drugs that comprise the combination. The advantages of this approach include affording every patient the potential to benefit from the combination under study and permitting the consideration of multiple endpoints simultaneously. Copyright © 2003 John Wiley & Sons, Ltd.
Predictive accuracy and explained variation
Authors: Schemper Michael
Published: July 2003

Measures of the predictive accuracy of regression models quantify the extent to which covariates determine an individual outcome. Explained variation measures the relative gains in predictive accuracy when prediction based on covariates replaces unconditional prediction. A unified concept of predictive accuracy and explained variation based on the absolute prediction error is presented for models with continuous, binary, polytomous and survival outcomes. The measures are given both in a model‐based formulation and in a formulation directly contrasting observed and expected outcomes. Various aspects of application are demonstrated by examples from three forms of regression models. It is emphasized that the likely degree of absolute or relative predictive accuracy often is low even if there are highly significant and relatively strong covariates. Copyright © 2003 John Wiley & Sons, Ltd.
Two distinct calcium‐calmodulin interactions with N‐terminal regions of the olfactory and rod cyclic nucleotide‐gated channels characterized by NMR spectroscopy
Authors: Orsale Maria , Melino Sonia , Contessa Gian Marco , Torre Vincent , Andreotti Giuseppina , Motta Andrea , Paci Maurizio , Desideri Alessandro , Cicero Daniel O
Published: July 2003

The interactions of calcium‐calmodulin with two fragments of the N‐terminal domains of the olfactory α‐subunit and rod β‐subunit cyclic nucleotide‐gated channels have been investigated using nuclear magnetic resonance spectroscopy. The results indicate that in the two cases both the N‐terminal and the C‐terminal calmodulin lobes are involved in the interaction. The olfactory cyclic nucleotide‐gated channel segment forms a 1:1 complex with calmodulin, whereas the rod fragment forms a 2:1 complex. The correlation times of the two complexes, as estimated by15N relaxation studies, are compatible with the observed stoichiometries. These results indicate differences in the mode of action by which calmodulin modulates the activity of both channels, and suggest either that the rod channel is modulated through a simultaneous interaction of two β‐subunits with calmodulin or that other regions of the N‐terminus are necessarily implicated in the binding.
Transferrins selectively cause ion efflux through bacterial and artificial membranes
Authors: Aguilera Oscar , Quiros Luis M , Fierro José F
Published: July 2003

Serum transferrin, ovotransferrin and lactoferrin constitute the most notable members of the transferrin family. Among their multiple biological functions, they possess an important antibacterial activity. These proteins can permeate the Escherichia coli outer membrane, reaching the inner membrane where they selectively cause permeation of ions, resulting in dissipation of the electrical potential without affecting the pH gradient. Similar results were obtained using artificial liposomes, suggesting a direct action of the proteins on the lipid bilayer, which was mediated by detectable conformational changes in their structures.
Identification of the nuclear receptor CAR:HSP90 complex in mouse liver and recruitment of protein phosphatase 2A in response to phenobarbital
Authors: Yoshinari Kouichi , Kobayashi Kaoru , Moore Rick , Kawamoto Takeshi , Negishi Masahiko
Published: July 2003

The nuclear receptor CAR, a phenobarbital (PB)‐responsive transcription factor, translocates into the nucleus of hepatocytes after PB induction. In non‐induced mice, CAR forms a physical complex with heat shock protein 90 (HSP90) in the cytoplasm. In response to PB induction, protein phosphatase 2A is recruited to the CAR:HSP90 complex. This recruitment may lead CAR to translocate into the nucleus, consistent with the inhibitions of nuclear CAR accumulation in PB‐induced mouse primary hepatocytes by okadaic acid as well as by geldanamycin.
Differential expression of sphingolipids in P‐glycoprotein or multidrug resistance‐related protein 1 expressing human neuroblastoma cell lines
Authors: Dijkhuis Anne-Jan , Douwes Jenny , Kamps Willem , Sietsma Hannie , Kok Jan Willem
Published: July 2003

The sphingolipid composition and multidrug resistance status of three human neuroblastoma cell lines were established. SK‐N‐FI cells displayed high expression and functional (efflux) activity of P‐glycoprotein, while multidrug resistance‐related protein 1 was relatively abundant and most active in SK‐N‐AS cells. These two cell lines exhibited higher sphingolipid levels, compared to SK‐N‐DZ, which had the lowest activity of either ATP‐binding cassette transporter protein. SK‐N‐DZ cells also differed in ganglioside composition with predominant expression of b‐series gangliosides. In conclusion, these three neuroblastoma cell lines offer a good model system to study sphingolipid metabolism in relation to ATP‐binding cassette transporter protein function.
A gene‐specific effect of an internal deletion in the Bdp1 subunit of the RNA polymerase III transcription initiation factor TFIIIB
Authors: Ishiguro Akira , Kassavetis George A
Published: July 2003

The Saccharomyces cerevisiae RPR1 gene encodes the RNA subunit of its RNase P, which processes RNA polymerase (pol) III primary transcripts. RPR1, which is transcribed by pol III, has been isolated as a multicopy suppressor of a specific small internal deletion (amino acids 253–269) in the Bdp1 subunit of transcription factor TFIIIB, the core pol III transcription factor. The selective effect of this Bdp1 deletion on RPR1 transcription has been analyzed in vitro. It is shown that TFIIIC‐dependent assembly of TFIIIB on the RPR1 promoter is specifically sensitive to this Bdp1 deletion, leading to gene‐specifically defective single‐round and multiple‐round transcription.
Over‐expression of wild‐type and mutant HFE in a human melanocytic cell line reveals an intracellular bridge between MHC class I pathway and transferrin iron uptake
Authors: Fergelot Patricia , Orhant Magali , Thénié Agnès , Loyer Pascal , Ropert‐Bouchet Martine , Lohyer Stéphanie , Le Gall Jean‐Yves , Mosser Jean
Published: July 2003

Hereditary hemochromatosis (HH) is a frequent recessive disorder of iron metabolism characterised by systemic iron overload. In Northern Europe, more than 90% of HH patients are homozygous for a mis‐sense mutation (C282Y) in the HFE1 gene product. The HFE protein is the heavy chain of a MHC class I‐related molecule and associates with β2 microglobulin and the transferrin receptor. Its precise roles in iron metabolism and in the pathophysiology of HH are still unclear. In order to identify the cellular processing of HFE, an important step towards the understanding of the function of the protein, we stably over‐expressed the wild type and mutated forms fused to the Green Fluorescent Protein in a melanocytic MHC class I expressing cell line, the Mel Juso cell line. In wild type and mutant clones, the fusion proteins were not detected at the cell surface but only in the cytoplasm. Their sub‐cellular localisation was determined by co‐labelling of cells with organite‐specific antibodies and confocal microscopy. HFE‐GFP followed initially HLA class I intracellular processing but co‐localised with transferrin in early endosomes without recycling at the cell surface. The C282Y‐GFP fusion protein followed a different folding pathway to exit endoplasmic reticulum. Over‐expression of the wild‐type protein lead to a decrease in diferric transferrin uptake. Our model will be of use in the elucidation of the functional interaction between intracellular HFE and iron transporters transferrin/transferrin receptor complexes and Slc11A2 (also named N‐Ramp2 or DMT1) in different endosomal compartments.
Scapholunate Fusion in Chronic Symptomatic Scapholunate Instability
Authors: ZUBAIRY A. I. , JONES W. A.
Published: July 2003

Since 1989 scapholunate fusion has been performed on 13 patients with chronic scapholunate instability causing debilitating symptoms. These cases were reviewed at a mean 93 (range, 60–132) months after surgery. Establishing whether bony fusion had been achieved proved extremely difficult even after CT scanning, but fusion was unequivocally achieved in four cases. Ten patients were subjectively satisfied with their treatment. Two patients who had no symptomatic improvement subsequently underwent total wrist arthrodesis. A method of fusing the scaphoid and lunate is described, though we accept that a firm fibrous union may be all that is achieved in most patients. However, this appears sufficient to restore stability with a high patient satisfaction.
Local Anaesthetic Infusion for Postoperative Pain
Authors: KULKARNI M. , ELLIOT D.
Published: July 2003

The role of continuous bupivacaine infusion either into the wound or as a local nerve block, following hand surgery was investigated in 100 patients. After excluding six patients with complex pain problems in whom neither the bupivacaine infusion nor any other conventional analgesic techniques provided adequate analgesia post-operatively, 86 of 94 (91%) patients were adequately treated for post-operative pain by this system during the first night after surgery, when pain is presumed to be greatest. This system also provided adequate on-going analgesia for up to 1 week after surgery controlling nerve pain and allowing mobilization of tendons after tenolysis. Continuous bupivacaine infusion is of particular use in these two groups of patients and after major hand injuries, when considerable pain can be anticipated. Pain during the first night was not controlled adequately by the bupivacaine infusion system in eight of the 94 patients (8%). All eight had a technical failure of the system, which was rectified in six cases to restore adequate analgesia by the infusion system. Two patients developed infection at the infusion cannula insertion site, which occurred only after 1 week and was successfully treated by removal of the cannula and oral antibiotics.