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K Russell

Publications and source records attributed to K Russell.

At least 19 recordsLinked to original sources
PubMed2006

Oral versus intravenous rehydration for treating dehydration due to gastroenteritis in children.

BACKGROUND: Dehydration associated with gastroenteritis is a serious complication. Oral rehydration is an effective and inexpensive treatment, but some physicians prefer intravenous methods. OBJECTIVES: To compare oral with intravenous therapy for treating dehydration due to acute gastroenteritis in children. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (March 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to March 2006), EMBASE (1974 to March 2006), LILACS (1982 to March 2006), and reference lists. We also contacted researchers, pharmaceutical companies, and relevant organizations. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing intravenous rehydration therapy (IVT) with oral rehydration therapy (ORT) in children up to 18 years of age with acute gastroenteritis. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed quality using the Jadad score. We expressed dichotomous data as a risk difference (RD) and number needed to treat (NNT), and continuous data as a weighted mean difference (WMD). We used meta-regression for subgroup analyses. MAIN RESULTS: Seventeen trials (1811 participants), of poor to moderate quality, were included. There were more treatment failures with ORT (RD 4%, 95% confidence interval (CI) 1 to 7, random-effects model; 1811 participants, 18 trials; NNT = 25). Six deaths occurred in the IVT group and two in the ORT groups (4 trials). There were no significant differences in weight gain (369 participants, 6 trials), hyponatremia (248 participants, 2 trials) or hypernatremia (1062 participants, 10 trials), duration of diarrhea (960 participants, 8 trials), or total fluid intake at six hours (985 participants, 8 trials) and 24 hours (835 participants, 7 trials). Shorter hospital stays were reported for the ORT group (WMD -1.20 days, 95% CI -2.38 to -0.02 days; 526 participants, 6 trials). Phlebitis occurred more often in the IVT group (NNT 50, 95% CI 25 to 100) and paralytic ileus more often in the ORT group (NNT 33, 95% CI 20 to 100, fixed-effect model), but there was no significant difference between ORT using the low osmolarity solutions recommended by the World Health Organization and IVT (729 participants, 6 trials). AUTHORS' CONCLUSIONS: Although no clinically important differences between ORT and IVT, the ORT group did have a higher risk of paralytic ileus, and the IVT group was exposed to risks of intravenous therapy. For every 25 children (95% CI 14 to 100) treated with ORT one would fail and require IVT.

Administration, Oral↗
PubMed2006

Long-lasting potentiation of a single-dose of rocuronium by amikacin: case report.

We report for the first time to our knowledge long-lasting (4 hours) potentiation of single intubating dose of rocuronium by a single bolus of amikacin given 55 minutes later in a woman having no precipitating factor (renal failure, hepatic failure, ionic disorder, other drugs influencing neuromuscular function). This patient had received the same rocuronium dose one month sooner in similar circumstances (without aminoglycoside antibiotic drug) and had not presented any prolonged neuromuscular blockade at this time. Neuromuscular blockade should be monitored in every patient receiving aminoglycoside antibiotic with even a single intubating dose of neuromuscular blocking drug.

Amikacin↗
PubMed2005

Isolation of S-locus F-box alleles in Prunus avium and their application in a novel method to determine self-incompatibility genotype.

This study characterises a series of 12 S-locus haplotype-specific F-box protein genes (SFB) in cherry (Prunus avium) that are likely candidates for the pollen component of gametophytic self-incompatibility in this species. Primers were designed to amplify 12 SFB alleles,including the introns present in the 50 untranslated region;sequences representing the S-alleles S1, S2, S3, S4, S40, S5,S6, S7, S10, S12, S13 and S16 were cloned and characterized. [The nucleotide sequences reported in this paper have been submitted to the EMBL/GenBank database under the following accession numbers: PaSFB1(AY805048), PaSFB2 (AY805049), PaSFB3 (AY805057),PaSFB4 (AY649872), PaSFB40 (AY649873), PaSFB5(AY805050), PaSFB6 (AY805051), PaSFB7 (AY805052),PaSFB10 (AY805053), PaSFB12 (AY805054), PaSFB13(AY805055), PaSFB16 (AY805056).] Though the coding regions of six of these alleles have been reported previously,the intron sequence has previously been reported only for S6. Analysis of the introns revealed sequence and length polymorphisms. A novel, PCR-based method to genotype cultivars and wild accessions was developed which combines fluorescently labelled primers amplifying the intron of SFB with similar primers for the first intron of S-RNase alleles. Intron length polymorphisms were then ascertained using a semi-automated sequencer. The convenience and reliability of this method for the determination of the self-incompatibility (SI) genotype was demonstrated both in sweet cherry cultivars representing alleles S1 to S16 and in individuals from a wild population encompassing S-alleles S17 to S22. This method will greatly expedite SI characterisation in sweet cherry and also facilitate large-scale studies of self-incompatibility in wild cherry and other Prunus populations.

Alleles↗
PubMed2005

Association of a novel high molecular weight, serine-rich protein (SrpA) with fibril-mediated adhesion of the oral biofilm bacterium Streptococcus cristatus.

The surface of the oral plaque bacterium Streptococcus cristatus is decorated with a lateral tuft of fibrils. The fibrillar tuft functions in the adhesion of S. cristatus to heterologous bacterial species in the plaque biofilm. The tuft typically consists of a densely packed fringe of shorter fibrils 238 +/- 19 nm long with longer, less abundant fibrils 403 +/- 66 nm long projecting through the fringe of short fibrils. The two types of fibrils in the tufts of S. cristatus have been refractory to biochemical separation, complicating their characterization. A hexadecane partition assay was used to enrich for subpopulations of S. cristatus CR311 (type strain NCTC 12479) having distinct fibrillar morphotypes. Negative staining in the TEM revealed that cells of a hydrophobic subpopulation of S. cristatus (CR311var1) carried only the long fibrils (395 +/- 32 nm). A hydrophilic subpopulation of S. cristatus (CR311var3) consisted of mixed morphotypes having no fibrils or remnant short fibrils (223 +/- 49 nm). No long fibrils were observed on any cells in the CR311var3 subpopulation. The CR311var3 morphotype, unlike the wild-type strain and CR311var1, was not able to form corncobs with either Corynebacterium matruchotii or Fusobacterium nucleatum. Variant CR311var3 did not express the novel gene srpA, which encodes a high molecular weight (321,882 Da) serine-rich protein, SrpA. The SrpA protein contains two extensive repeat motifs of 17 and 71 amino acids and a gram-positive cell wall anchor consensus sequence (LPNTG). The unusual properties of SrpA most closely resemble those of Fap1, the fimbrial-associated adhesin protein of Streptococcus parasanguis. The association of long fibrils, high surface hydrophobicity, ability to form corncob formations, and expression of the srpA gene suggest that SrpA is a long fibril protein in S. cristatus.

Amino Acid Sequence↗
PubMed2005

Installation of the hand influences acceleromyography measurement. A comparison with mechanomyography during neuromuscular recovery.

Acceleromyography is commonly used to monitor perioperative neuromuscular blockade and to prevent residual neuromuscular blockade at the time of tracheal extubation. However, there are problems associated with this method, such as obtaining stable values, particularly beneath the surgical fields. We compared TOF ratios obtained on both hands simultaneously using on one side mechanomyography and on the other acceleromyography, installed in four different ways: the hand simply lying on a board, fingers fixed with tape, use of the hand adaptor or the TOF-tube. Further to maintaining free thumb movement, the TOF-tube improves feasibility of acceleromyography by reducing the measurement variability while retaining accuracy.

Adult↗
PubMed2004

Glucocorticoids for croup.

BACKGROUND: Since the initial version of this systematic review in 1997, a number of randomised trials examining the benefit of glucocorticoids have been published, reflecting a continued interest in the use of glucocorticoids to treat patients with croup. The objective of this review was to provide evidence to guide clinicians in their treatment of patients with croup by determining the effectiveness of glucocorticoids and to identify areas of uncertainty for future research. OBJECTIVES: To determine the effect of glucocorticoids for children with croup. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1, 2003), MEDLINE (January 1966 to April 2003) and Excerpta Medica/EMBASE (January 1974 to August 2003). We also contacted authors of identified croup trials published in the last ten years to inquire about additional published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials that examine children with croup and objectively measure the effectiveness of glucocorticoid treatment. DATA COLLECTION AND ANALYSIS: Based on review of the title and abstract (when available), two researchers identified studies for potential relevance. The complete text was retrieved and using a priori inclusion criteria, the studies were independently reviewed for relevance by two reviewers. Two observers independently assessed quality. Differences with respect to inclusion status and quality assessment were resolved by consensus. Data were extracted using a structured form by one reviewer and checked for accuracy by a second reviewer. Standard statistical analyses were performed. MAIN RESULTS: Thirty-one studies were deemed relevant for inclusion (N = 3736). Glucocorticoid treatment was associated with an improvement in the Westley score at six hours with a weighted mean difference of -1.2 (95% confidence interval -1.6 to -0.8) and at 12 hours -1.9 (-2.4 to -1.3); at 24 hours this improvement was no longer significant (-1.3, -2.7 to 0.2). Fewer return visits and/or (re)admissions occurred in patients treated with glucocorticoids (relative risk 0.50; 0.36 to 0.70). Length of time spent in accident and emergency or hospital (weighted mean difference 12 hours, five to 19 hours) was significantly decreased for patients treated with glucocorticoids. Use of epinephrine decreased for children treated with a glucocorticoid (risk difference 10%; 1 to 20). No other decreases in additional treatments were found in the primary analysis. Publication bias does not impact results importantly. No between-trial significant differences were found between populations with mild and moderate croup. Oral dexamethasone may be superior to intramuscular dexamethasone. REVIEWER'S CONCLUSIONS: Dexamethasone and budesonide are effective in relieving the symptoms of croup as early as six hours after treatment. Fewer return visits and/or (re)admissions are required and the length of time spent in hospital is decreased in inpatients. Dexamethasone is also effective in mild croup populations. Research is required to examine the most beneficial method for disseminating croup practice guidelines and to increase the uptake of evidence to improve outcomes.

Croup↗
PubMed2004

Epinephrine for bronchiolitis.

BACKGROUND: Bronchodilators are commonly used in the management of bronchiolitis. A recent systematic review showed that bronchodilators produce modest short-term benefit among patients with mild or moderate bronchiolitis. OBJECTIVES: To compare epinephrine versus placebo and other bronchodilators in infants less than 2 years of age with bronchiolitis. SEARCH STRATEGY: Electronic searches were conducted on the following bibliographic databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1, 2003), MEDLINE (January 1966 to May 2003), and EMBASE (January 1988 to May 2003). The reference lists of all selected articles were examined for relevant studies. Primary authors were contacted for information on additional trials. SELECTION CRITERIA: Studies were included if they: 1) were RCTs comparing epinephrine with placebo or other bronchodilator; 2) involved children less than two years with bronchiolitis; 3) presented at least one quantitative outcome. DATA COLLECTION AND ANALYSIS: Searches were screened and inclusion criteria applied independently by two reviewers. Quality was assessed by two reviewers using the Jadad scale and allocation concealment. Data were extracted by one reviewer using a structured form and checked by a second. Separate analyses were conducted for the two types of control groups (placebo, non-epinephrine bronchodilators) and for patient status (inpatient, outpatient). MAIN RESULTS: Fourteen studies were included. Quality ranged from one to five (Jadad scale) with a median of three (inter-quartile range: two to three). Allocation concealment was adequate in six trials and unclear in eight. Among inpatient studies comparing epinephrine and placebo (n = five), there was one significant outcome favouring epinephrine: change in clinical score at 60 minutes post-treatment (SMD -0.52; 95% CI -1.00,-0.03). For outpatient studies (n = three), change in clinical score at 60 minutes (SMD -0.81; -1.56,-0.07), change in oxygen saturation at 30 minutes (WMD 2.79;1.50,4.08), respiratory rate at 30 minutes (WMD -4.54;-8.89-0.19), and "improvement" (OR 25.06; 4.95,126.91) favoured epinephrine. Heart rate at 60 minutes post-treatment favoured placebo (WMD 11.80; 5.20,18.40). Admission rates and change in oxygen saturation at 60 minutes post-treatment were not significantly different. For inpatient studies comparing epinephrine and salbutamol (n = four), only one of the seven outcomes was statistically significant: respiratory rate at 30 minutes favoured epinephrine (WMD -5.12; -6.83;-3.41). Among outpatient studies (n = four), change in oxygen saturation at 60 minutes (WMD 1.91; 0.38,3.44), heart rate at 90 minutes (WMD -14.00; -22.95;-5.05), respiratory rate at 60 minutes (WMD -7.76; -11.35,-4.17) post-treatment and "improvement" (OR 4.51; 1.93,10.53) favoured epinephrine. Admission rates were not significantly different (OR 0.40; 0.12,1.33). Pallor at 30 minutes post-treatment was significantly higher in the epinephrine group (OR 6.00; 1.33,27.00). REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of epinephrine for the treatment of bronchiolitis among inpatients. There is some evidence to suggest that epinephrine may be favourable to salbutamol and placebo among outpatients. A number of large, multi-centered trials are required to examine the effectiveness of epinephrine compared to placebo and salbutamol for infants presenting to outpatient settings. There is a need to develop a validated, reliable scoring system that is sensitive to important clinical changes in patients with bronchiolitis.

Albuterol↗
PubMed2004

Graduated driver licensing for reducing motor vehicle crashes among young drivers.

BACKGROUND: Graduated driver licensing (GDL) has been proposed as a means of reducing crash rates among novice drivers by gradually introducing them to higher risk driving situations. OBJECTIVES: To examine the effectiveness of GDL systems in reducing crash rates of young drivers. SEARCH STRATEGY: Studies were identified through searches of MEDLINE, EMBASE, CINAHL, Healthstar, Web of Science, NTIS Bibliographic Database, TRIS Online, SIGLE, the World Wide Web, relevant conference proceedings, consultation with experts and authors, and reference lists. The search was not restricted by language or publication status. SELECTION CRITERIA: Studies were included if: 1) they compared outcomes pre- and post-implementation of a GDL program within the same jurisdiction, 2) comparisons were made between jurisdictions with and without GDL, or 3) both. Studies had to report at least one objective, quantified outcome. Two reviewers independently screened searches and assessed the full text of potentially relevant studies for inclusion using a standard form. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked by a second. Additional data were requested from authors. Results were not pooled due to substantial heterogeneity between studies. Percentage change was calculated for each year after the intervention, using one year prior to the intervention as the baseline rate. Results were adjusted by internal controls. Analyses were stratified by different denominators (population, licensed drivers). Results were calculated for the different crash types (overall, injury, fatal, night-time, alcohol, and those resulting in hospitalization). Results were presented for 16 year-olds alone and all teenage drivers combined. MAIN RESULTS: We included 13 studies evaluating 12 GDL programs that were implemented between 1979 and 1998 in the US (n=7), Canada (3), New Zealand (1), and Australia (1). Programs varied in their restrictions during the intermediate stage: e.g. night curfews (8); limitations of extra passengers (2); roadway restrictions (1). Based on the Insurance Institute for Highway Safety classification scheme, no programs were good, six were acceptable, five were marginal, and one was poor. Reductions in crash rates were seen in all jurisdictions and for all crash types. Among 16 year-old drivers, the median decrease in per population overall crash rates during the first year was 31% (range 26-41%). Per population injury crash rates were similar (median 28%, range 4-43%). Results for all teenage drivers, rates per licensed driver, and rates adjusting for internal controls were generally reduced when comparing within jurisdictions. REVIEWERS' CONCLUSIONS: The existing evidence shows that GDL is effective in reducing the crash rates of young drivers, although the magnitude of the effect is unclear. The conclusions are supported by consistent direction of the findings, and the temporal relationship and plausibility of the association. The reviewers have made recommendations for primary research on GDL (e.g. study methods, standardized reporting of outcomes and results, long-term follow-up). The project has also shown what is needed to carry out systematic reviews of observational studies (e.g. quality assessment instruments).

Accidents, Traffic↗
PubMed2003

Comparative mapping between quercus and castanea using simple-sequence repeats (SSRs).

Simple sequence repeat (SSR) markers from Quercus and Castanea were used for comparative mapping between Quercus robur (L.) and Castanea sativa (Mill.). We tested the transferability of SSRs developed in Quercus to Castanea and vice-versa. In total, 47% (25) of the Quercus SSRs and 63% (19) of the Castanea SSRs showed a strong amplification product in the non-source species. From these 44 putative comparative anchor tags, 19 (15 from Quercus and 4 from Castanea) were integrated in two previously established genetic linkage maps for the two genera. SSR loci were sequenced to confirm the orthology of the markers. The combined information from both genetic mapping and sequence analysis were used to determine the homeology between seven linkage groups, aligned on the basis of pairs or triplets of common markers, while two additional groups were matched using a single microsatellite marker. Orthologous loci identified between Q. robur and C. sativa will be useful as anchor loci for comparative mapping studies within the Fagaceae family.

Base Sequence↗
PubMed2003

Whole-body protein turnover of a carnivore, Felis silvestris catus.

The cat (Felis silvestris catus) has a higher dietary protein requirement than omnivores and herbivores, thought to be due to metabolic inflexibility. An aspect of metabolic flexibility was examined with studies of whole-body protein turnover at two levels of dietary protein energy, moderate protein (MP; 20 %) and high protein (HP; 70 %), in five adult cats in a crossover design. Following a 14 d pre-feed period, a single intravenous dose of [15N]glycine was administered and cumulative excretion of the isotope in urine and faeces determined over 48 h. N flux increased (P<0.005) with dietary protein, being 56 (se 5) mmol N/kg body weight (BW) per d for cats fed the MP diet and 146 (se 8) mmol N/kg BW per d for cats fed the HP diet. Protein synthesis was higher (P<0.05) on the HP diet (75 (se 10) mmol N/kg BW per d; 6.6 (se 1) g protein/kg BW per d) than the MP diet (38 (se 5) mmol N/kg BW per d; 3.4 (se 0.4) g protein/kg BW per d). Protein breakdown was higher (P<0.05) on the HP diet (72 (se 8) mmol N/kg BW per d; 6.3 (se 0.7) g protein/kg BW per d) than the MP diet (44 (se 3) mmol N/kg BW per d; 3.9 (se 0.3) g protein/kg BW per d). Compared with other species the rate of whole-body protein synthesis in the well-nourished cat (9.7 (se 1.3) g protein/kg BW0.75 per d) is at the lower end of the range. These results show that feline protein turnover adapts to dietary protein as has been shown in other species and demonstrates metabolic flexibility. Further work is required to determine exactly why cats have such a high protein requirement.

Adaptation, Physiological↗
PubMed2003

Circulating recombinant form CRF02_AG in South America.

With the objective of monitoring the distribution of HIV-1 subtypes and circulating recombinant forms (CRFs)in South America, population-based surveillance studies were performed in seven countries. Peripheral blood mononuclear cell, filter paper, fresh blood, and cocultivation samples were collected from HIV-positive patients from Colombia, Ecuador, Peru, Bolivia, Chile, Argentina, and Uruguay, during a 7-year period(1995-2001). DNA was prepared and HIV envelope subtypes were determined by heteroduplex mobility as-say and DNA sequencing from 1289 HIV-positive samples. While subtypes B and F were the most commonly observed subtypes, two CRF02_AG strains were detected, in Ecuador. This is the first report of the existence of this CRF in South America.

Adult↗
PubMed2002

Tissue adhesives for traumatic lacerations in children and adults.

BACKGROUND: Tissue adhesives have been used for many years to close simple lacerations as an alternative to standard wound closure (sutures, staples, adhesive strips). They offer many potential advantages over standard wound closure, including ease of use, decrease in pain and time to apply, as well as not requiring a follow-up visit for removal. Many studies have compared tissue adhesives and standard wound closure to determine the cosmetic outcome as well as these other secondary outcomes in their respective study populations. However, due to the wide variation in study parameters, there are no generalisable, definitive answers about the effectiveness of tissue adhesives. No study has been adequately powered to assess differences in complications, which are rare. OBJECTIVES: To summarize the best available evidence for the effect of tissue adhesives in the management of traumatic lacerations in children and adults. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (CD ROM 2001 Issue 4), the Cochrane Wounds Group Specialized Trials Register (Nov 2001), MEDLINE (1966 to Oct 1, 2001), and EMBASE (1988 to Sept 1, 2001) for relevant randomised controlled trials (RCTs). We also searched the citations of selected studies, and we contacted relevant authors and manufacturers of tissue adhesives to inquire about other published and unpublished trials. SELECTION CRITERIA: We included RCTs comparing tissue adhesives versus standard wound closure or tissue adhesive versus tissue adhesive for acute, linear, low tension, traumatic lacerations in an emergency or primary care setting. Trials evaluating tissue adhesives for surgical incisions or other types of wounds were not considered. DATA COLLECTION AND ANALYSIS: Data from eligible studies were extracted by one reviewer and checked for accuracy by a second reviewer. Two reviewers independently assessed masked copies for quality. Outcomes of cosmesis (subgroups of age, wound location and need for deep sutures), pain, procedure time, ease of use and complications were analysed separately for two comparisons: 1) tissue adhesive versus standard wound care; and 2) tissue adhesive versus tissue adhesive. MAIN RESULTS: Eight studies compared a tissue adhesive with standard wound care. No significant difference was found for cosmesis at any of the time points examined, using either Cosmetic Visual Analogue Scale (CVAS) or Wound Evaluation Score (WES). Data were only available for subgroup analysis for age; no significant differences were found. Pain scores (Parent VAS WMD -15.7 mm; 95% CI -21.9, -9.5) and procedure time (WMD -5.6 minutes; 95% CI -8.2, -3.1) significantly favoured tissue adhesives. No studies reported on ease of use. Small but statistically significant risk differences were found for dehiscence (favouring standard wound care NNH 25 95% CI 14, 100) and erythema (favouring tissue adhesive NNH 8 95% CI 4, 100). Other complications were not significantly different between treatment groups. Only one study was identified that compared two tissue adhesives (butylcyanoacrylate (Histoacryl TM) versus octylcyanoacrylate (Dermabond TM)) for pediatric facial lacerations. No significant difference was found for cosmesis using CVAS at 1-3 months, or using WES at 5-14 days and 1-3 months. Similarly, no significant difference was found in pain, procedure time or complications. Results for ease of use were incomplete as reported. REVIEWER'S CONCLUSIONS: Tissue adhesives are an acceptable alternative to standard wound closure for repairing simple traumatic lacerations. There is no significant difference in cosmetic outcome between tissue adhesives and standard wound closure, or between different tissue adhesives. They offer the benefit of decreased procedure time and less pain, compared to standard wound closure. A small but statistically significant increased rate of dehiscence with tissue adhesives must be considered when choosing the closure method (NNH 25).

Adult↗
PubMed2002

Factors influencing visual outcome in anisometropic amblyopes.

AIM: To identify which factors influence the final visual acuity in children with anisometropic amblyopia. METHODS: A retrospective analysis of 112 children with anisometropic amblyopia, identified from examining all case notes of children who had failed preschool or school screening. RESULTS: The age at presentation had no effect on the final visual outcome (p=0.804). Both the degree of refractive error and the degree of anisometropia at presentation correlated with final visual acuity (p<0.001 and p=0.001). Those with strabismus had a poorer final outcome. CONCLUSIONS: The age at presentation of a child with anisometropic amblyopia appears to have no significant effect on the final visual acuity. The amount of refractive error and degree of anisometropia at presentation do correlate strongly with final visual acuity. This would suggest, firstly, that children with poorer visual acuity at presentation and higher degrees of anisometropia should be treated more aggressively and that, secondly, children with anisometropic amblyopia should be treated regardless of age.

Age Factors↗
PubMed2002

"Molecular rulers" for calibrating phenotypic effects of telomere imbalance.

As a result of the increasing use of genome wide telomere screening, it has become evident that a significant proportion of people with idiopathic mental retardation have subtle abnormalities involving the telomeres of human chromosomes. However, during the course of these studies, there have also been telomeric imbalances identified in normal people that are not associated with any apparent phenotype. We have begun to scrutinize cases from both of these groups by determining the extent of the duplication or deletion associated with the imbalance. Five cases were examined where the telomere rearrangement resulted in trisomy for the 16p telomere. The size of the trisomic segment ranged from approximately 4-7 Mb and the phenotype included mental and growth retardation, brain malformations, heart defects, cleft palate, pancreatic insufficiency, genitourinary abnormalities, and dysmorphic features. Three cases with telomeric deletions without apparent phenotypic effects were also examined, one from 10q and two from 17p. All three deletions were inherited from a phenotypically normal parent carrying the same deletion, thus without apparent phenotypic effect. The largest deletion among these cases was approximately 600 kb on 17p. Similar studies are necessary for all telomeric regions to differentiate between those telomeric rearrangements that are pathogenic and those that are benign variants. Towards this goal, we are developing "molecular rulers" that incorporate multiple clones at each telomere that span the most distal 5 Mb region. While telomere screening has enabled the identification of telomere rearrangements, the use of molecular rulers will allow better phenotype prediction and prognosis related to these findings.

Calibration↗
PubMed2001

Long-term urinary function after transperineal brachytherapy for patients with large prostate glands.

PURPOSE: To summarize longer-term postbrachytherapy morbidity in patients with prostate glands >50 cm3. METHODS AND MATERIALS: From 1997 to 1998, 33 patients with a transrectal ultrasound-based prostate volume >50 cm3 were treated at the University of Washington by 125I (144 Gy) or 103Pd (115 Gy) implantation for prostate carcinoma. These 33 patients comprised 7% of the total implant patient population. Twelve patients were treated with neoadjuvant androgen ablation before implantation. The (125)I source strength ranged from 0.34 to 0.5 mCi and the 103Pd source strength ranged from 1.1 to 1.4 mCi (pre-NIST-99). The total number of sources implanted was 94-223 (median 155). Despite the typical implant-related volume increase, the postimplant CT-defined prostate volumes were generally well-covered by the prescription isodose (median coverage 92%, range 80-100%). The preimplant urinary obstructive symptoms were quantified by the criteria of the American Urological Association. RESULTS: Of the 33 patients, 12 developed acute postimplant urinary retention, all presenting within 24 h of implantation. Patients who developed postimplant retention lasting >1 week were generally treated with intermittent self-catheterization. By 1 month, 85% of patients were catheter free. By 1 year, only 1 patient (4%) remained in urinary retention; the remainder of cases had resolved spontaneously. With follow-up of 1.7-2.6 years, the last American Urological Association scores were higher than the pretreatment scores in 15 patients and lower in 7 patients. No patient developed permanent urinary incontinence. Long-term changes in the American Urological Association scores were unrelated to whether the patient had been in urinary retention after implantation. Two patients developed rectal fistulas; they had preimplant transrectal ultrasound prostate volumes of 53 and 59 cm3, in the low range for this group of patients. No other patient had persistent rectal bleeding suggestive of clinically significant proctitis. The pretreatment serum prostate-specific antigen level was 3.3-15 ng/mL (median 7.2) and the last serum prostate-specific antigen level 0.1-1.6 ng/mL (median 0.2). CONCLUSION: Patients with larger prostate volumes appear to have moderate morbidity and a satisfactory technical outcome with brachytherapy. We do not believe the occurrence of two severe rectal complications was related to the prostate volume per se. Our experience and that of others calls into question the validity of using prostate volume as a criterion for patient suitability for prostate brachytherapy.

Brachytherapy↗
PubMed2001

Discovery of novel, orally active dual NK1/NK2 antagonists.

Exploration of the SAR around selective NK2 antagonists, SR48968 and ZD7944, led to the discovery that naphth-1-amide analogues provide potent dual NK1 and NK2 antagonists. ZD6021 inhibited binding of [3H]-NKA or [3H]-SP to human NK1 and NK2 receptors, with high-affinity (K(i)=0.12 and 0.62nM, respectively). In functional assays ZD6021 had, at 10(-7)M, in human pulmonary artery pK(B)=8.9 and in human bronchus pK(B)=7.3, for NK1 and NK2, respectively. Oral administration of ZD6021 to guinea pigs dose-dependently attenuated ASMSP induced extravasation of plasma proteins, ED(50)=0.5mg/kg, and NK2 mediated bronchoconstriction, ED(50)=13mg/kg.

Administration, Oral↗
PubMed2001

The use of P-aminobenzoic acid and chromic oxide to confirm complete excreta collection in a carnivore, Felis silvestris catus.

Complete excreta collection is a pre-requisite for several protocols in protein metabolism, and lack of confidence in achieving this may be increased when working with carnivores. Recovery of p-aminobenzoic acid (PABA) as a check for complete urine collection and chromic oxide for complete faeces collection were assessed in the cat. A single oral dose of PABA (4 mg/kg BW) was excreted more slowly than has been reported in the human (82% recovery at 6 h). A daily dose of PABA proved a useful method for confirming complete urine collection in the cat, and was 99% excreted in 72 h. Chromic oxide (500 mg/cat) was administered orally and recovery of chromium in the faeces was 90% after 96 h. A HPLC method for the analysis of PABA in cat urine was developed, and from the application of the techniques to a nitrogen balance study, it was concluded that PABA and chromic oxide are useful checks for complete excreta collection in the cat.

4-Aminobenzoic Acid↗