bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized study of coagulation and fibrinolysis during and after gasless and conventional laparoscopic cholecystectomy
Authors: Larsen J F , Ejstrud P , Svendsen F , Redke F , Pedersen V , Rahr H B
Published: March 2003

Background

Carbon dioxide pneumoperitoneum may be an important pathophysiological factor stimulating the coagulation system during conventional laparoscopic cholecystectomy. The aim of this study was to test the hypothesis that gasless laparoscopy produces smaller changes in the coagulation and fibrinolytic system than carbon dioxide pneumoperitoneum in patients undergoing laparoscopic cholecystectomy.

Methods

Fifty patients were allocated randomly to conventional (n = 26) or gasless (n = 24) laparoscopic cholecystectomy. Blood samples were obtained on admission, after induction of anaesthesia, after insufflation or traction, 30 min after introduction of the laparoscope, 10 min after exsufflation of carbon dioxide or traction, 4 h after extubation and 24 h after operation.

Results

The two groups were comparable with respect to age, sex, body mass index and duration of operation. Plasma levels of prothrombin fragment 1 and 2 (F1 + 2), soluble fibrin and d-dimer did not differ between the two groups. F1 + 2 levels varied significantly in both groups during and after operation (P < 0·001). Soluble fibrin and d-dimer levels did not change during operation in either group, but after operation the levels increased significantly in both groups (P < 0·001).

Conclusion

Carbon dioxide pneumoperitoneum does not enhance the activation of coagulation and fibrinolysis associated with laparoscopic cholecystectomy. The coagulation and fibrinolytic systems are activated during and after gasless as well as conventional laparoscopic cholecystectomy.
Microcirculatory effects of experimental acute limb ischaemia—reperfusion
Authors: Dammers R , Wehrens X H T , oude Egbrink M G A , Slaaf D W , Kurvers H A J M , Ramsay G
Published: March 2003

Background

The object of this study was to develop an animal model in which changes in microvascular haemodynamics and leucocyte–vessel wall interactions due to acute limb ischaemia–reperfusion (I/R) can be measured in the skin. Furthermore, it was investigated whether these changes are related to local muscle injury.

Methods

Male Lewis rats were subjected to unilateral limb ischaemia for 1 h (n = 8) or 2 h (n = 8) by cuff inflation, or to a sham protocol (n = 6). Intravital video microscopic measurements of leucocyte–vessel wall interactions, venular diameter, red blood cell velocity and reduced velocity (which is proportional to wall shear rate) were performed in skin venules before ischaemia and at 0·5, 1, 2, 3 and 4 h after the start of reperfusion. Oedema and leucocyte infiltration of ischaemic/reperfused skeletal muscle were quantified histologically.

Results

In skin venules, both 1 and 2 h of ischaemia induced a significant increase in leucocyte rolling (six and five times baseline, respectively; P < 0·05) and adherence during reperfusion (eight and four times baseline; P < 0·05). No significant increase in muscular leucocyte infiltration was detected. After an initial hyperaemic response of 180 per cent of baseline values (P < 0·05), blood flow decreased to about 60 per cent after 4 h of reperfusion in skin venules of both experimental groups. I/R induced tibial muscle oedema, the severity of which depended on the ischaemic interval (wet to dry ratio: control, 4·0; 1 h, 4·5 (P not significant); 2 h, 5·8 (P < 0·05)).

Conclusion

A non-invasive animal model was developed that enables investigation of the consequences of acute limb I/R.
Anorectal injury following pelvic radiotherapy
Authors: Hayne D , Vaizey C J , Boulos P B
Published: March 2003

Background

Current knowledge of the effects of radiation on the anorectum is based on a limited number of studies. Variability in delivery techniques, both currently and historically, combined with a paucity of prospective and randomized studies makes interpretation of the literature difficult. This review presents the existing evidence and identifies areas that require further work.

Methods

This review is based on a literature search (Medline and PubMed) and manual cross-referencing.

Results and conclusion

More than three-quarters of patients receiving pelvic radiotherapy experience acute anorectal symptoms and up to one-fifth suffer from late-phase radiation proctitis. About 5 per cent develop other chronic complications, such as fistula, stricture and disabling faecal incontinence. The risk of rectal cancer may be increased. Conservative treatment options are of limited value. Surgery may be considered if symptoms are severe, provided sphincter function is adequate and recurrent disease is excluded. Large prospective studies with accurate dosimetric data and long-term follow-up are needed to provide meaningful information on which to base new strategies to minimize the side-effects from radiotherapy.
Patterns of pelvic invasion are prognostic in the treatment of locally recurrent rectal cancer
Authors: Yamada K , Ishizawa T , Niwa K , Chuman Y , Akiba S , Aikou T
Published: March 2003

Background

Local recurrence of rectal cancer after curative resection remains a difficult clinical problem. The aim of this study was to elucidate prognostic risk factors after resection of recurrent cancer.

Methods

Between January 1983 and December 1999, 83 patients with locally recurrent rectal cancer were studied retrospectively for survival benefit by re-resection. Sixty patients underwent resection for recurrent cancer, including total pelvic exenteration in 30 patients and sacrectomy in 23 patients. The extent of locally recurrent tumour was classified by the pattern of pelvic invasion as follows: localized, sacral invasion and lateral invasion.

Results

Multivariate analysis showed that the pattern of pelvic invasion was a significant prognostic factor which independently influenced survival after resection of recurrent cancer (P < 0·001). The 5-year survival rates were 38 per cent in the localized type (n = 27), 10 per cent in the sacral invasive type (n = 16) and zero in the lateral invasive type (n = 17).

Conclusion

Resection for locally recurrent rectal cancer is potentially curative in patients with localized or sacral invasive patterns of recurrence. Alternatives should be explored in patients with recurrence involving the lateral pelvic wall.
Outcome and resource utilization in gastroenterological surgery
Authors: Lång M , Niskanen M , Miettinen P , Alhava E , Takala J
Published: March 2003

Background

A small minority of patients undergoing gastroenterological surgery are at high risk for postoperative complications, which may lead to prolonged hospital stay, disproportionate use of resources and increased mortality. The nature and frequency of, and predictive factors for, postoperative complications were studied and the impact of complications on resource utilization was assessed.

Methods

A prospective observational study was undertaken of 503 patients undergoing gastroenterological surgery in a tertiary care centre. The incidence of cardiorespiratory, infective and surgical complications was assessed. The need for reoperation, intensive care and length of hospital stay, readmission, death at 6 months and costs were evaluated.

Results

Some 235 patients (47 per cent) had at least one complication, most commonly delayed oral intake (n = 70). Complications were associated with cardiovascular disease, prolonged operation, high Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity, and increased number of Shoemaker's criteria. The length of hospital stay of patients with complications was longer than that of those without complications (11 versus 6 days). Morbidity resulted in a twofold increase in median costs.

Conclusion

High-risk patients could be identified by simple clinical criteria, although the commonly used risk criteria were not very sensitive. A reduction in postoperative complication rates would result in marked cost savings.
Systematic review of the definition and measurement of anastomotic leak after gastrointestinal surgery
Authors: Bruce J , Krukowski Z H , Al-Khairy G , Russell E M , Park K G M
Published: March 2003

Background

Anastomotic leak after gastrointestinal surgery is an important postoperative event that leads to significant morbidity and mortality. Postoperative leak rates are frequently used as an indicator of the quality of surgical care provided. Comparison of rates between and within institutions depends on the use of standard definitions and methods of measurement of anastomotic leak. The aim of this study was to review the definition and measurement of anastomotic leak after oesophagogastric, hepatopancreaticobiliary and lower gastrointestinal surgery.

Methods

A systematic review was undertaken of the published literature. Searches were carried out on five bibliographical databases (Medline, Embase, The Cochrane Library, Cumulative Index for Nursing and Allied Health Literature and HealthSTAR) for English language articles published between 1993 and 1999. Articles were critically appraised by two independent reviewers and data on definition and measurement of anastomotic leak were extracted.

Results

Ninety-seven studies were reviewed and a total of 56 separate definitions of anastomotic leak were identified at three sites: upper gastrointestinal (13 definitions), hepatopancreaticobiliary (14) and lower gastrointestinal (29). The majority of studies used a combination of clinical features and radiological investigations to define and detect anastomotic leak.

Conclusion

There is no universally accepted definition of anastomotic leak at any site. The definitions and values used to measure anastomotic failure vary extensively and preclude accurate comparison of rates between studies and institutions.
Effect of oesophagectomy on monocyte-induced apoptosis of peripheral blood T lymphocytes
Authors: Kono K , Takahashi A , Iizuka H , Fujii H , Sekikawa T , Matsumoto Y
Published: March 2003

Background

Surgical stress has been reported to induce immunosuppression. The mechanisms giving rise to T-cell dysfunction following surgery are still unclear. The cellular mechanisms behind T-cell dysfunction following surgery were investigated, based on the induction of T-cell apoptosis and downregulation of T-cell signalling molecules.

Methods

Peripheral blood T cells were collected and separated before and after surgery in patients who had oesophagectomy, gastrectomy or cholecystectomy, and studied for their ability to produce cytokines, the induction of T-cell apoptosis with terminal deoxynucleotidyl transferase-mediated dUPT-biotin nick end labelling methods, and the expression of T-cell signalling zeta (TCR ζ) molecules with intracellular staining.

Results

The increased degree of T-cell apoptosis, downregulation of TCR ζ molecules and impaired cytokine production of T cells were significant on days 1 and 3 after operation in patients who had oesophagectomy, but not after gastrectomy or cholecystectomy. A higher level of T-cell apoptosis was observed in the co-culture with postoperative monocytes than with preoperative monocytes.

Conclusion

Peripheral blood T cells obtained after oesophagectomy underwent apoptosis that correlated with the downregulation of TCR ζ molecules. Postoperative monocytes induced by surgical stress were able to mediate the T-cell apoptosis.
Pattern of cervical lymph node metastases from papillary carcinoma of the thyroid
Authors: Sivanandan R , Soo K C
Published: March 2003

Introduction

The management of cervical metastases from papillary thyroid carcinoma ranges from selective removal (berry picking) to a formal comprehensive neck dissection. Without a clear understanding of the distribution of nodes at risk, the formulation of strategies on how best to manage the clinically positive neck is difficult. This study reports on observations made in patients who underwent a therapeutic comprehensive neck dissection for metastatic papillary thyroid carcinoma by defining lymph node involvement with respect to neck level.

Methods

The clinical records and pathological reports of 75 consecutive patients who underwent a neck dissection for cervical metastases from papillary thyroid carcinoma over a 10-year period were reviewed. All dissections were therapeutic in nature, being performed in patients with clinically positive neck nodes. Eighty neck dissection specimens were obtained and analyses were divided into three groups by virtue of the type of dissection performed: a bilateral comprehensive neck dissection, unilateral radical neck dissection and unilateral comprehensive neck dissection. The relative involvement of cervical nodes was analysed with reference to node levels I–V.

Results

Patients in the anterolateral group (levels II, III and IV) were at greatest risk of metastatic disease, with level III nodes consistently the most frequently involved, across all treatment groups. Only three patients exhibited level I involvement, all of whom had extensive neck disease involving all or almost all neck levels.

Conclusion

The majority of patients present with multiple level node disease, with the anterolateral group at greatest risk. A comprehensive neck dissection is recommended for all patients with palpable cervical lymphadenopathy.
Epidemiological study of oesophageal and gastric cancer in south-east England
Authors: Kocher H M , Linklater K , Patel S , Ellul J P M
Published: March 2003

Background

This epidemiological study was carried out to establish the magnitude of the changing incidence of gastric and oesophageal cancer.

Methods

Time-trend analyses of subsite-specific cancers of the oesophagus and stomach were performed using data from the Thames Cancer Registry database (1960–1996) for the South Thames Region. The changes in sex ratio and peak age of incidence are reported.

Results

In the upper two-thirds of the oesophagus there was no significant change in the incidence rate, but the lower third of the oesophagus showed a marked rise for both sexes (average annual change +0·05 for men, +0·009 for women). For the gastric cardia, the incidence in males increased (average annual change +0·025), while in females it remained unchanged. Cancers of the oesophagogastric junction showed a clear increase for both sexes (average annual change +0·07 for men, +0·009 for women). There were changes in the sex ratio and peak age of incidence for all subsite cancers for both sexes.

Conclusion

Over a 37-year period the incidence of cancer of the oesophagogastric junction increased threefold, while the incidence of cancers of the other subsites of the stomach decreased. Further studies are needed to investigate the aetiology of these changes.
Systematic review of randomized clinical trials of surgical treatment for carpal tunnel syndrome
Authors: Gerritsen A A M , Uitdehaag B M J , van Geldere D , Scholten R J P M , de Vet H C W , Bouter L M
Published: March 2003

Background

Carpal tunnel syndrome (CTS) is a common disorder for which several surgical treatment options are available. However, there is no consensus on the most effective method of treatment. The object of this systematic review is to compare the efficacy of the various surgical techniques in relieving the symptoms of CTS and promoting return to work and/or activities of daily living.

Methods

Computer-aided searches of Medline, EMBASE and the Cochrane Controlled Trials Register were conducted, together with reference checking. A rating system, based on the number of studies and their methodological quality and findings, was used to determine the strength of the available evidence for the efficacy of the treatment.

Results

Fourteen studies were included in the review. None of the alternatives to standard open carpal tunnel release (OCTR) seems to offer better relief of symptoms. There is conflicting evidence about whether endoscopic carpal tunnel release results in earlier return to work and/or activities of daily living.

Conclusion

Standard OCTR is still the preferred method of treatment for CTS. It is just as effective as the alternatives, but is technically less demanding, so incurs a lower risk of complications and of added costs.
Methodology and reporting in studies of local recurrence after curative excision of the rectum for cancer
Authors: Dent O F , Chapuis P H , Bokey E L , Newland R C
Published: March 2003

Background

Widely varying rates have been reported in the extensive literature published in the English language on local recurrence after curative excision of rectal carcinoma. These variations may be attributable to differences in the case mix of pathological factors influencing recurrence, differences in surgical technique or expertise, differences in the administration of adjuvant therapy and various combinations of these. They may also arise from methodological differences among studies.

Methods

This paper reviews the adequacy of methodology and reporting in 21 recent studies of local recurrence after curative resection of rectal cancer.

Results

Many flaws in reporting and apparent inadequacies in methodology were identified. On an index of 26 criteria examined, eight studies scored no more than 8 and only three studies scored more than 11.

Conclusion

To date, the value of reports of local recurrence rates following curative excision of rectal cancer has been limited by inadequacies in documentation and methodology. Suggestions are made for preferred procedures to be followed in the reporting of future studies.
Pro- and anti-inflammatory cytokine release in open versus endovascular repair of abdominal aortic aneurysm
Authors: Rowlands T E , Homer-Vanniasinkam S
Published: March 2003

Background

Pro- and anti-inflammatory cytokine release occurs with abdominal aortic aneurysm (AAA) repair although the relative contribution of each is currently poorly understood. Ischaemia–reperfusion injury is thought to play a greater role following open (OR) than endovascular (ER) repair, with resultant greater perioperative morbidity.

Methods

Thirty-two patients undergoing OR (n = 16) and ER (n = 16) of AAA were studied. Systemic venous (SV) blood was taken at induction (baseline), 0 h (last clamp off), 4, 24, 72 and 144 h, and femoral venous (FV) blood (indwelling catheter; lower torso venous effluent) at 0, 4 and 24 h. The cytokines interleukin (IL) 6, IL-8 and IL-10 were measured in these samples.

Results

In OR, SV and FV IL-6 increased from baseline to a peak at 24 h (SV 589 pg/ml (P = 0·001 versus baseline) and FV 848 pg/ml (P = 0·05)) before declining at 144 h. In ER, there was a similar pattern but the increase was smaller (24 h: SV 260 pg/ml (P = 0·003 versus baseline) and FV 319 pg/ml (P = 0·06)) at all equivalent timepoints compared with OR. IL-8 peaked earlier (4 h) from baseline in both groups before declining by 144 h, and significant differences between SV and FV were seen only in the OR group. IL-10 levels peaked in both groups at 24 h before declining at 144 h, and there were no significant locosystemic differences between the groups.

Conclusion

Venous pro-inflammatory cytokine changes (IL-6) are consistent with significantly greater lower-torso reperfusion injury in patients undergoing OR. Smaller responses were seen after ER (IL-6 and IL-8), although both groups showed a similar anti-inflammatory response (IL-10); this pro- and anti-inflammatory imbalance may account for the increased morbidity assoicated with OR.
Systemic levels of glyceryl trinitrate following topical application to the anoderm do not correlate with the measured reduction in anal pressure
Authors: Jonas M , Barrett D A , Shaw P N , Scholefield J H
Published: March 2003

Background

Topical 0·2 per cent glyceryl trinitrate (GTN) lowers resting anal pressure (RAP) and heals two-thirds of chronic anal fissures. Over 50 per cent of patients experience headache, presumably through systemic absorption, but the pharmacokinetics of GTN ointment are unknown. This study evaluated the systemic absorption profile of GTN, and correlation between plasma GTN levels, RAP, haemodynamic variables and side-effects.

Methods

Thirty healthy volunteers were recruited with local medical school ethics committee approval. Continuous static anal manometry was performed for 10 min before and 2 h after application of 0·2 per cent GTN (0·5 g) to the anoderm. Blood samples were taken from an intravenous cannula, and pulse and blood pressure were measured before application of GTN, and 10, 20, 30, 40, 50, 60, 90, 120 and 180 min thereafter. Details of side-effects were recorded.

Results

GTN was detected in the plasma 10 min to 3 h after topical application. RAP was significantly reduced after 10 min, but had returned to pretreatment values by 120 min. Pulse was statistically unchanged during the study; systolic blood pressure was significantly lower 20–90 min after GTN application, and diastolic pressure was decreased throughout the study. Headaches were experienced by 14 of 30 volunteers after a median (range) of 41 (4–120) min, persisting for 74 (30–176) min, with an intensity score of 19 (5–30) mm represented on a 100-mm linear visual analogue scale. There was no correlation between plasma GTN concentration, RAP, and the onset, duration or intensity of headaches.

Conclusion

Topical GTN acts locally on the internal anal sphincter; systemic levels do not contribute significantly to the reduction in RAP. There is marked interindividual variation in plasma GTN levels, and no correlation with haemodynamic variables and side-effects.
Prospective study of open preperitoneal mesh repair for recurrent inguinal hernia
Authors: Kurzer M , Belsham P A , Kark A E
Published: March 2003

Background

Recurrent inguinal hernia presents a significant clinical problem with high re-recurrence and complication rates, particularly when an anterior approach is used. This study evaluated the open preperitoneal approach for repair of recurrent inguinal hernia.

Methods

This was a prospective cohort study of 101 consecutive patients with 114 recurrent inguinal hernias. All were operated on using an open preperitoneal technique and prosthetic mesh by the method of Stoppa or Wantz. Follow-up was at 2–6 weeks, 15 and between 42 and 54 months.

Results

There were no major complications. There was one infection and one case of retention of urine. There were no testicular complications. There were five recurrences, all within 6 months of operation, four of which were among the first 20 cases. Modifications to the original technique were made, and one recurrence occurred in the remaining 81 patients (1 per cent) or 106 hernias (1 per cent).

Conclusion

Preperitoneal mesh repair gives results far superior to those of the commonly used anterior approach. It is safer and easier to learn than laparoscopic repair and is the procedure of choice for complex multirecurrent inguinal hernia.
Early detection of colorectal cancer using high-magnification chromoscopic colonoscopy
Authors: Hurlstone D P , Fujii T , Lobo A J
Published: March 2003

Background

Endoscopic techniques aimed at early detection of colorectal cancer (CRC) and its precursors, permitting targeted in vivo luminal treatments, have been developed by the Japanese since the early 1990s. The introduction of this new technology to the UK (i.e. magnification endoscopes) may permit earlier and more accurate diagnosis. According to Japanese data, magnification chromoscopy can be used to predict histology and invasive depth of cancer, and help in the detection of flat and depressed colonic lesions. Flat and depressed lesions are not purely Japanese phenomena: they exist with a similar incidence in the UK.

Methods

A Medline search was performed for the years 1955–2001 using the following medical subject headings and search methodology: colorectal cancer and colonoscopy or aberrant crypt foci or molecular kinetics or flat/depressed lesions or chromoscopy.

Results and conclusion

Early CRC, in the form of flat or depressed lesions, can be difficult to detect using conventional colonoscopic techniques and penetrate the colonic mucosa deeply. The implications of detecting these lesions in relation to current approaches to the prevention of CRC are profound.
Structural studies of a cell wall polysaccharide of Trichosporon asahii containing antigen II
Authors: Ichikawa Tomoe , Nishikawa Akemi , Ikeda Reiko , Shinoda Takako
Published: March 2003

The structure of a cell‐wall polysaccharide containing antigen II from Trichosporon asahii was investigated. A purified glucuronoxylomannan (GXM) antigen was found to contain O‐acetyl groups that contribute to the serological reactivity. The structure of GXM was analyzed by partial acid hydrolysis, methylation analysis, controlled Smith degradation, NMR studies, and fluorophore‐assisted carbohydrate electrophoresis. GXM has an α‐(1→3)‐d‐mannan backbone with a β‐d‐glucopyranosyluronic acid residue bound to O‐2 of a mannopyranosyl residue and the same number of β‐d‐xylopyranosyl residues as mannose. Side chains of β‐d‐xylopyranosyl‐d‐xylopyranose, forming a nonreducing terminus, and β‐d‐xylopyranosyl residues were attached to O‐2, O‐4, and O‐6 of the mannose residues.
Thermal unfolding of monomeric and dimeric β‐lactoglobulins
Authors: Fessas Dimitrios , Iametti Stefania , Schiraldi Alberto , Bonomi Francesco
Published: March 2003

The thermal stabilities of dimeric bovine β‐lactoglobulin and monomeric equine β‐lactoglobulin were investigated at neutral pH by means of differential scanning calorimetry, circular dichroism, tryptophan fluorescence, and by binding of an hydrophobic probe. Differential scanning calorimetry showed the presence of two structural domains with different thermal stabilities in both proteins. Thermodynamic analysis of the calorimetric signal revealed that the two domains unfold independently according to a mechanism where an equilibrium step is followed by an irreversible transition. The spectroscopic data supported this model and allowed recognition of the structural regions corresponding to the more thermally stable domain. The differences in thermal stability between the two proteins can be primarily ascribed to the properties of the less stable domain.
Directed mutagenesis studies of the C‐terminal fingerprint region of Bacillus subtilis pyrophosphatase
Authors: Shizawa Nobuko , Uchiumi Toshio , Taguchi Junko , Kisseleva Natalya A. , Baykov Alexander A. , Lahti Reijo , Hachimori Akira
Published: March 2003

The sequence SRKKQxxP near the C‐terminus is conserved in pyrophosphatases of the recently discovered family II and includes a triplet of positively charged residues, two of which (Arg295 and Lys296 in Bacillus subtilis pyrophosphatase) are part of the active site and one (Lys297) is not. The importance of this triplet for catalysis by B. subtilis pyrophosphatase has been estimated by mutational analysis. R295K and K296R substitutions were found to decrease the catalytic constant 650‐ and 280‐fold, respectively, and decrease the pKa of the essential acidic group by 1.1 and 0.5, respectively. K297R substitution was found to increase the catalytic constant 4.7‐fold and to markedly change the protein circular dichroism spectrum in the range 250–300 nm. These results, together with the results of theoretical modelling of the enzyme–substrate complex, provide support for the direct involvement of Arg295 and Lys296 in substrate binding in family II pyrophosphatases.
Structural and functional studies of cinnamomin, a new type II ribosome‐inactivating protein isolated from the seeds of the camphor tree
Authors: Xie Liang , Wang Bao‐Zhong , Hu Rong‐gui , Ji Hong‐bin , Zhang Li , Liu Wang‐Yi
Published: March 2003

Cinnamomin is a new type II ribosome‐inactivating protein (RIP). Its A‐chain exhibits RNA N‐glycosidase activity to inactivate the ribosome and thus inhibit protein synthesis, whereas the glycosylated B‐chain is a lectin. The primary structure of cinnamomin, which exhibits approximately 55% identity with those of ricin and abrin, was deduced from the nucleotide sequences of cDNAs of cinnamomin A‐ and B‐chains. It is composed of a total of 549 amino‐acid residues: 271 residues in the A‐chain, a 14‐residue linker and 264 residues in the B‐chain. To explore its biological function, the cinnamomin A‐chain was expressed in Escherichia coli with a yield of 100 mg per L of culture, and purified through two‐step column chromatography. After renaturation, the recovery of the enzyme activity of the expressed A‐chain was 80% of that of native A‐chain. Based on the modeling of the three‐dimensional structure of the A‐chain, the functional roles of five amino acids and the only cysteine residues were investigated by site‐directed mutagenesis or chemical modification. The conserved single mutation of the five amino‐acid residues led to 8–50‐fold losses of enzymatic activity, suggesting that these residues were crucial for maintaining the RNA N‐glycosidase activity of the A‐chain. Most interestingly, the strong electric charge introduced at the position of the single cysteine in A‐chain seemed to play a role in enzyme/substrate binding.
Expression and characterization of active site mutants of hevamine, a chitinase from the rubber tree Hevea brasiliensis
Authors: Bokma Evert , Rozeboom Henriëtte J. , Sibbald Mark , Dijkstra Bauke W. , Beintema Jaap J.
Published: March 2003

Hevamine is a chitinase from the rubber tree Hevea brasiliensis. Its active site contains Asp125, Glu127, and Tyr183, which interact with the −1 sugar residue of the substrate. To investigate their role in catalysis, we have successfully expressed wild‐type enzyme and mutants of these residues as inclusion bodies in Escherichia coli. After refolding and purification they were characterized by both structural and enzyme kinetic studies. Mutation of Tyr183 to phenylalanine produced an enzyme with a lower kcat and a slightly higher Km than the wild‐type enzyme. Mutating Asp125 and Glu127 to alanine gave mutants with ≈ 2% residual activity. In contrast, the Asp125Asn mutant retained substantial activity, with an approximately twofold lower kcat and an approximately twofold higher Km than the wild‐type enzyme. More interestingly, it showed activity to higher pH values than the other variants. The X‐ray structure of the Asp125Ala/Glu127Ala double mutant soaked with chitotetraose shows that, compared with wild‐type hevamine, the carbonyl oxygen atom of the N‐acetyl group of the −1 sugar residue has rotated away from the C1 atom of that residue. The combined structural and kinetic data show that Asp125␣and Tyr183 contribute to catalysis by positioning the␣carbonyl oxygen of the N‐acetyl group near to the C1 atom. This allows the stabilization of a positively charged transient intermediate, in agreement with a previous proposal that the enzyme makes use of substrate‐assisted catalysis.
Serum angiogenin concentrations in young patients with diabetes mellitus
Authors: Chiarelli F. , Pomilio M. , Mohn A. , Tumini S. , Verrotti A. , Mezzetti A. , Cipollone F. , Wasniewska M. , Morgese G. , Spagnoli A.
Published: March 2003

Background  Angiogenin serum levels were measured in a large group of type 1 diabetic young patients, looking at whether increased Angiogenin concentrations are associated with long‐term glycemic control and microvascular complications.

Materials and methods  Four groups of patients were compared to 223 age‐ and sex‐ matched healthy controls: 196 type 1 diabetic patients (age range 3–24 years, onset of diabetes before the age of 12 years; duration of disease longer than 2 years), without microvascular complications were divided into three groups on the basis of age (group 1, n = 37, age < 6 years; group 2, n = 71, age 6–12 years; group 3, n = 88, age > 12 years); 53 adolescents and young adults (age 16·1–29·7 years) with diabetic microvascular complications (background, preproliferative or proliferative retinopathy, albumin excretion rate 20–200 µg min−1) (group 4).

Results  Angiogenin serum levels were significantly increased in diabetic pre‐school and pre‐pubertal children, and particularly elevated in pubertal subjects compared with age‐ and sex‐matched controls. Adolescents and young adults with microvascular complications had very high angiogenin concentrations. One‐year mean HbA1c values were correlated with angiogenin levels (r = 0·389; p < 0·01). In poorly controlled diabetics (HbA1c > 10%), long‐term (2 years) improvement of glycemic control determined a significant reduction of angiogenin concentrations in both pre‐school and pre‐pubertal children as well as in pubertal youngsters.

Conclusions  Angiogenin serum concentrations are increased in diabetic children even before puberty. Severity of microvascular complications is associated with markedly increased angiogenin serum levels. Long‐term tight glycemic control determines a consistent reduction of angiogenin concentrations.
Evidence of an affinity threshold for IgE‐allergen binding in the percutaneous skin test reaction
Authors: Pierson‐Mullany L. K. , Jackola D. R. , Blumenthal M. N. , Rosenberg A.
Published: March 2003

Background Atopy is an aberrant immune response involving allergen‐specific IgE production, though serum IgE concentration is not an entirely reliable diagnostic tool, particularly for epidemiological and genetic studies. There is no clear correlation between IgE and other indicators of atopy such as skin prick tests (SPT)s, and physiological associations are difficult to justify in cases with detectable IgE but negative SPT results.

Objective IgE reflects the number of molecules available to produce an atopic response, but the degree of the response is determined by the binding strength (affinity) between receptor‐bound IgE and the allergen. We sought to determine if there was an association between binding affinity and SPT results in people with histories of atopy.

Methods Standard SPTs (whole allergen extracts) were administered to people with histories of sensitivities to ragweed and house dust mite. The concentrations and affinities of serum allergen‐specific IgEs were determined using the purified allergens Amb a 1 and Der p 1.

Results There was a positive correlation between weal area and allergen‐specific IgE among SPT‐positive donors. However, for those individuals with detectable amounts of allergen‐specific IgE, there was considerable overlap of IgE values between SPT‐positive and ‐negative groups. Among sensitized donors, IgE–allergen interactions were characterized by two or three specific reactions of very high affinity (KA range 108−1011 M). Negative SPT reactions were associated with lowered IgE binding affinities to major allergens. This delimited two groups with atopic disorders: specific IgE(+)/SPT(+) and specific IgE(+)/SPT(–).

Conclusion The product of antibody affinity and concentration, which we define as antibody capacity (CAP = KA × IgE), is more informative with regard to describing allergen sensitivity than antibody concentration alone. Antibody binding capacity provides physiological evidence of atopy in some subjects who do not test positively by common methods and suggests an affinity threshold to produce a positive SPT reaction.
Determination of allergenicity to three cow's milk hydrolysates and an amino acid‐derived formula in children with cow's milk allergy
Authors: Caffarelli C. , Plebani A. , Poiesi C. , Petroccione T. , Spattini A. , Cavagni G.
Published: March 2003

Background Products based on hydrolysed cow milk proteins or amino acid mixtures are recommended in children with cow's milk hypersensitivity. However, some children who are allergic to cow's milk and who clinically react to substitute milk formulas have been observed.

Objective To determine the tolerance and allergenicity of protein hydrolysate or amino acid‐derived formulas in children with IgE‐mediated cow's milk allergy.

Methods Twenty children with positive cow's milk challenges, positive skin prick tests and/or serum‐specific IgE antibodies to cow's milk were selected. Oral challenges, skin prick tests and serum‐specific IgE antibodies to extensively hydrolysed whey formula, partially hydrolysed whey formula, extensively hydrolysed casein formula and amino acid‐derived formula were performed.

Results Five out of 17 (5/17) children reacted to partially hydrolysed whey formula, (3/16) to extensively hydrolysed whey formula, (2/10) to amino acid‐derived formula, (1/16) to extensively hydrolysed casein formula. Only extensively hydrolysed casein formula was tolerated by at least 90% (with 95% confidence intervals) of children. Hydrolysates provoked early and delayed clinical reactions, amino acid mixtures only delayed reactions. Partially hydrolysed whey formula elicited a significantly higher number of positive skin prick test reactions than other formulas. Two children had specific IgE antibodies to extensively hydrolysed whey formula, one to partially hydrolysed whey formula, one to extensively hydrolysed casein formula and none to amino acid‐derived formula.

Conclusion In this study, none of the cow's milk substitutes has been found to be non‐allergenic. Our results suggest that in children with IgE‐mediated cow's milk allergy, the first ingestions of extensively hydrolysed cow's milk protein formulas require strict medical supervision because of immediate reactions. This is not the case for amino acid‐derived formula. Moreover, our data suggest that treatment of children allergic to cow's milk with cow's milk substitutes should be monitored for several days to document tolerance.
Towards family‐centred practice in paediatric occupational therapy: A review of the literature on parent–therapist collaboration
Authors: Hanna Karen , Rodger Sylvia
Published: March 2003

The importance of parent involvement in intervention with children has always been recognised by occupational therapists. Current trends in paediatric service delivery have been towards family‐centred care, with a central component of this approach being parent–therapist collaboration in planning and evaluating intervention. This paper reviews issues and provides suggestions for clinical practice from the literature on parent–therapist collaboration, including consideration of parents’ diversity and unique perspectives, development of effective parent–therapist relationships, establishment of shared goals and priorities when planning intervention, and development of services that support parent–therapist collaboration. Further research is needed in Australian settings to explore the nature of parent–therapist partnerships, the impact of parent participation throughout the intervention process and the extent to which collaboration with parents results in better therapy outcomes for the child and their family.
Inhibition of vasoconstriction by AJ‐2615, a novel calcium antagonist with α1‐adrenergic receptor blocking activity in human conduit arteries used as bypass grafts
Authors: Liu Ming‐Hui , Floten Storm H. , Yang Qin , He Guo‐Wei
Published: March 2003

Aims  Graft spasm may develop during coronary artery bypass grafting and reversal of spasm is still challenging. The purpose of this study was to investigate the in vitro vascular relaxant properties of AJ‐2615 in human internal mammary artery (IMA).

Methods  We studied 264 IMA rings taken from 65 patients undergoing coronary artery bypass grafting surgery with organ bath technique. The interaction between AJ‐2615 and various vasoconstrictors was investigated in two ways.

Results  AJ‐2615 caused complete relaxation in methoxamine‐contracted IMA rings (100.0±0.0%; n = 8) and nearly full relaxation in potassium chloride‐contracted IMA rings (91.4±5.7%; n = 8) or noradrenaline‐contracted IMA rings (89.3±2.8%; n = 8). AJ‐2615 also induced remarkable relaxation in IMA rings contracted by other vasoconstrictors. In comparison with the α1‐adrenoceptor antagonist prazosin, AJ 2615 showed similar maximal relaxation in IMA rings contracted by methoxamine or norepinephrine. On the other hand, incubation with AJ‐2615 (0.1–1 µm) significantly inhibited all the vasoconstrictor‐mediated vasoconstriction except endothelin‐1 in a concentration‐dependent manner.

Conclusions  The results suggested that in human IMA, AJ‐2615 has an inhibitory effect on vasoconstriction mediated by a variety of vasoconstrictors and the mechanism of relaxation may be related to its calcium antagonism and α1‐adrenergic receptor blocking activity. AJ‐2615 may have important clinical implications for patients undergoing coronary artery bypass surgery for reversing and preventing graft spasm.
Contrasting effects of verapamil and amlodipine on cardiovascular stress responses in hypertension
Authors: Lefrandt Johan D. , Heitmann Jörg , Sevre Knut , Castellano Maurizio , Hausberg Martin , Fallon Maura , Urbigkeit Anja , Rostrup Morten , Agabiti‐Rosei Enrico , Rahn Karl H. , Murphy Michael , Zannad Faiez , De Kam Pieter‐Jan , Smit Andries J.
Published: March 2003

Aims  To compare the effects of two long‐acting calcium antagonists of different types on cardiovascular stress responses in hypertension.

Methods  One‐hundred and forty‐five patients with mild to moderate hypertension and a mean (± s.e.mean) age of 51 ± 0.9 years received for 8 weeks the phenylalkylamine verapamil sustained release (240 mg) and the dihydropyridine amlodipine (5 mg) in a double‐blind cross‐over design, both after 4 weeks of placebo. Blood pressure, heart rate and plasma noradrenaline were monitored during 3 min of sustained isometric handgrip and 2 min of cold pressor.

Results  Blood pressure was equally reduced by both drugs. After 3 min handgrip, systolic blood pressure, heart rate and rate‐pressure product were lower with verapamil compared with amlodipine. Verapamil attenuated the increases in systolic blood pressure (25 ± 2 vs 30 ± 2 mmHg, difference 4.6, 95% CI (1.0, 8.1), P < 0.01) and rate‐pressure product (3.1 ± 0.2 vs 3.6 ± 0.3 × 103 mmHg × beats min−1, difference 0.5, 95% CI (0.1, 0.9), P < 0.01) during handgrip compared with amlodipine. Similar results were observed during cold pressor. Plasma noradrenaline levels were lower with verapamil compared with amlodipine at rest and after both tests, but the increases in plasma noradrenaline were not significantly different.

Conclusions  Verapamil is more effective in reducing blood pressure and rate‐pressure product responses to stress compared with amlodipine. Although plasma noradrenaline is lower with verapamil at rest and after stress, the increase during stress is not different.
Comparison of the clinical efficacy of standard and mucoadhesive‐based nasal decongestants
Authors: Tzachev Christo T. , Mandajieva Mariana , Minkov Evgeniy H. , Popov Todor A.
Published: March 2003

Aims  To compare two xylometazoline 0.1% preparations: reference commercial solution (RS) and test mucoadhesive solution (TS).

Methods  Twenty subjects with perennial allergic rhinitis (age range 18–69 years, 5 atopic, 7 men) applied randomly in turn TS and RS for 5 days in a double‐blind crossover clinical trial. Nasal airflow resistance (NAR), nasal symptoms (6 grade scoring), frequency of application (times/day), and side‐effects were recorded.

Results  Mean ratio TS/RS of areas under the resistance/time curves for NAR ±90% CI: 3.56 ± 0.92; mean TS‐RS differences ±95% CI: for congestion: −1.12 ± 0.59, for frequency of application: −1.10 ± 0.20. Subjects experienced fewer side‐effects with TS.

Conclusions

 A mucoadhesive solution with a decongestant had a greater and longer lasting effect on nasal congestion in subjects with perennial allergic rhinitis than the commercially available decongestant solution. It also caused fewer side effects.
Spatial correlations of Diceroprocta apache and its host plants: evidence for a negative impact from Tamarix invasion
Authors: Ellingson Aaron R. , Andersen Douglas C.
Published: March 2003

Abstract 1. The hypothesis that the habitat‐scale spatial distribution of the Apache cicada Diceroprocta apache Davis is unaffected by the presence of the invasive exotic saltcedar Tamarix ramosissima was tested using data from 205 1‐m2 quadrats placed within the flood‐plain of the Bill Williams River, Arizona, U.S.A. Spatial dependencies within and between cicada density and habitat variables were estimated using Moran's I and its bivariate analogue to discern patterns and associations at spatial scales from 1 to 30 m.

2. Apache cicadas were spatially aggregated in high‐density clusters averaging 3 m in diameter. A positive association between cicada density, estimated by exuvial density, and the per cent canopy cover of a native tree, Goodding's willow Salix gooddingii, was detected in a non‐spatial correlation analysis. No non‐spatial association between cicada density and saltcedar canopy cover was detected.

3. Tests for spatial cross‐correlation using the bivariate IYZ indicated the presence of a broad‐scale negative association between cicada density and saltcedar canopy cover. This result suggests that large continuous stands of saltcedar are associated with reduced cicada density. In contrast, positive associations detected at spatial scales larger than individual quadrats suggested a spill‐over of high cicada density from areas featuring Goodding's willow canopy into surrounding saltcedar monoculture.

4. Taken together and considered in light of the Apache cicada's polyphagous habits, the observed spatial patterns suggest that broad‐scale factors such as canopy heterogeneity affect cicada habitat use more than host plant selection. This has implications for management of lower Colorado River riparian woodlands to promote cicada presence and density through maintenance or creation of stands of native trees as well as manipulation of the characteristically dense and homogeneous saltcedar canopies.
Corona Phenomenon as Visual Aura Symptom in Migraine
Authors: Podoll K , Robinson D
Published: March 2003

The visual illusion of a typical corona phenomenon was represented as a visual migraine aura symptom in six of 562 Migraine Art pictures, whereas another five pictures illustrated atypical variants of the said illusion. The extra edges of the corona phenomenon are commonly seen around the perceptual images of objects, but in atypical cases they can similarly surround illusory images and both elementary and complex hallucinatory images. The corona phenomenon is strongly associated with visual loss and the presence of elementary geometric hallucinations.
Mechanisms of Tension-Type Headache
Authors: Jensen R
Published: March 2003

Despite tension-type headache represents one of the most frequent and costly diseases in modern society only very little research on this disease has actually been carried out. In contrast to former belief tension-type headache is a separate entity that can and should be separated from migraine. No specific biochemical abnormalities have yet been identified but a reliable human model of tension-type headache has been developed by means of infusion of a NO-donor, glyceryl trinitrate. Myofascial factors and peripheral sensitization of nociceptors play an important role in the episodic form, and central sensitization has been demonstrated in the chronic form. As chronic tension-type headache usually evolves from the episodic form, prevention and reversal of this central sensitization may be an important target for future pathophysiological studies and drug development.
Important causes of hypoglycaemia in patients with diabetes on peritoneal dialysis
Authors: Mehmet S. , Quan G. , Thomas S. , Goldsmith D.
Published: March 2003

Aim  Diabetes is now the commonest cause of end‐stage renal failure, so there are many diabetic patients receiving dialysis therapy. There are several important ways in which dialysis practice can impinge unfavourably on glucose control. This study focuses on the interaction between maltose‐derived metabolites in a new peritoneal dialysis fluid and blood glucose measurements using reagent sticks that depend on the glucose dehydrogenase method.

Case report We report the cases of three patients, with insulin‐treated diabetes and end‐stage renal disease treated with peritoneal dialysis, who experienced symptomatic hypoglycaemia with inaccurate glucose readings on reagent strips when converted to icodextrin.

Conclusion Careful teamwork between diabetes and renal physicians and specialist nurses is highly desirable to achieve good glucose control in a group of patients at particular risk of microvascular and macrovascular complications.

Diabet. Med. 18, 679–682 (2001)