FDA approves system for digital mammography.
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Breast Diseases↗
Biomedical subjects
J White
Publications and source records attributed to J White.
Breast density and cancer risk: what is the relationship?
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Breast↗
IV glycine and oral D-cycloserine effects on plasma and CSF amino acids in healthy humans.
BACKGROUND: The amino acid glycine, modulates neurotransmission via actions at GLY-A receptor and GLY-B receptor. The latter are coagonist sites associated with N-Methyl-D-Aspartate (NMDA) glutamate receptors. The central bioavailability of peripherally administered glycine has not been adequately characterized in humans. METHODS: Healthy human subjects were administered either oral D-cycloserine (50 mg or placebo) and intravenous glycine (saline, 100 mg/kg or 200 mg/kg) in random order over 4 test days under double-blind conditions. Cerebrospinal fluid was collected by lumbar puncture performed on the first test day was analyzed to determine amino acid levels. The acoustic startle response was measured on the second test day. RESULTS: Intravenous glycine dose-dependently increased both serum and CSF glycine and serine levels. Neither glycine nor DCS produced any significant effects on behavior, cognition or the acoustic startle response. Neither IV glycine nor DCS were associated with any toxicity. CONCLUSIONS: Thus, peripheral glycine administration raised CSF glycine levels without producing any clear central nervous system effects. Glycine and D-cycloserine did not worsen cognitive test performance and did not induce behavioral symptoms on their own. The possibility that glycine and D-cycloserine enhanced cognitive test performance cannot be excluded given the psychometric limitations of the test battery.
Acoustic Stimulation↗
Structures of m-iodo Hoechst-DNA complexes in crystals with reduced solvent content: implications for minor groove binder drug design.
The DNA photosensitisers m-iodo Hoechst and m-iodo, p-methoxy Hoechst have been co-crystallised with the oligonucleotide d(CGCGAATTCGCG)(2)and their crystal structures determined. The crystals were then subjected to slow dehydration, which reduced their solvent contents from 40 (normal) to 30 (partially dehydrated) and then 20% (fully dehydrated) and caused a reduction in cell volume from 68,000 to 60,000 then 51,000 A(3). The dehydration resulted in a dramatic enhancement of diffraction resolution from approximately 2.6 to beyond 1.5 A. Crystal structures have also been determined for the partially and fully dehydrated states. The fully dehydrated crystals consist of an infinite polymeric network, in which neighbouring dodecamer duplexes are crosslinked through phosphate oxygens via direct bonding to bridging magnesium cations. This unique three-dimensional structure for DNA is described in detail in the following companion paper. The present paper details evidence from the sequence of crystal structures that the DNA is able to breathe locally, allowing the ligand to leave the minor groove, re-orient in the surrounding solvent medium and then re-enter the groove in a different orientation and location. The rearrangement of the minor groove binding ligands during the dehydration process mimics the binding behaviour of these ligands in solution and in vivo. We also present details of the DNA-ligand interactions that are consistent with a hydrogen atom ion mechanism for photocleavage of DNA.
Animals↗
Intermolecular interactions and water structure in a condensed phase B-DNA crystal.
By controlled dehydration, the unit cells of dodecamer DNA-drug crystals have been shrunk from 68,000 (normal state) to 60,000 (partially dehydrated intermediate state) to 51,000 A(3) (fully dehydrated state), beyond which no further solvent loss occurs. The total solvent content in the normal crystals is approximately 40% by volume, reducing to approximately 20% in the fully dehydrated phase. The 25% reduction in cell volume induced a dramatic enhancement in the resolution of the X-ray diffraction data (from 2. 6 to beyond 1.5 A). We have determined the structures of the normal, partially dehydrated and fully dehydrated crystals. Details of the ligand binding have been presented in the preceding article. The present paper describes the unique features of the structure of the fully dehydrated phase. This structure was refined with 9,015 unique observed reflections to R = 14.9%, making it one of the most reliable models of B -form DNA available. The crystals exist as infinite polymeric networks, in which neighbouring dodecamer duplexes are crosslinked through phosphate oxygens via direct bonding to magnesium cations. The DNA is packed so tightly that there is essentially only a single layer of solvent between adjacent molecules. The details of the crystal packing, magnesium bridging, DNA hydration and DNA conformation are described and compared with other experimental evidence related to DNA condensation.
Animals↗
gamma delta T-cell lymphoma of the skin: a clinical, microscopic, and molecular study.
BACKGROUND: Only a few cases of primary gamma delta cutaneous T-cell lymphoma (CTCL) have been reported. We encountered 3 cases of this rare condition. OBJECTIVES: To characterize gamma delta CTCL by clinical, microscopic, and molecular methods and to investigate the role of Epstein-Barr virus (EBV) infection in its pathogenesis. DESIGN: Patients were evaluated by clinical examination, and biopsy specimens of lesional skin were examined by light microscopy and immunohistochemistry. Polymerase chain reaction amplification for T-cell receptor gamma gene rearrangements and in situ hybridization for EBV were performed on 3 biopsy specimens. SETTING: National Institutes of Health, a tertiary referral center. PATIENTS: Individuals with a clinical and histologic diagnosis of primary gamma delta CTCL. OUTCOME MEASURES: Clinical, light microscopic, and immunohistochemical features, and the presence of T-cell rearrangement and EBV RNA in biopsy specimens. RESULTS: Patients exhibited multiple plaques, tumors, and/or subcutaneous nodules primarily distributed over the extremities. Individuals exhibited an aggressive clinical course with resistance to multiagent chemotherapy and radiation. Microscopic examination revealed epidermotropism in 2 cases, a dermal infiltrate in all 3 cases, and subcutaneous involvement in 1 case. Immunohistochemical studies showed the presence of CD3(+)TCR delta(+) in 3 patients, CD8(+)in 1, and CD4(+), CD20(+), CD56(+), and beta F1(+) in none. All 3 cases exhibited an activated cytotoxic T-cell phenotype positive for T-cell intracellular antigen 1, perforin, and granzyme B. A clonal T-cell receptor gamma chain gene rearrangement was detected in all 3 cases by polymerase chain reaction. In situ hybridization was negative for EBV sequences in all 3 cases. CONCLUSION: gamma delta Cutaneous T-cell lymphomas are EBV-negative lymphomas that express a mature cytotoxic phenotype and have an aggressive clinical behavior. Arch Dermatol. 2000;136:1024-1032
Aged↗
Nutritional supplementation in stable chronic obstructive pulmonary disease.
BACKGROUND: Low body weight in patients with chronic obstructive pulmonary disease (COPD) is associated with an impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity and higher mortality rate when compared to adequately nourished individuals with this disease. Nutritional support may therefore be a useful part of their comprehensive care. OBJECTIVES: To conduct a systematic review of randomized controlled trials (RCTs) to clarify whether nutritional supplementation (caloric supplementation for at least 2 weeks) improved anthropometric measures, pulmonary function, respiratory muscle strength and functional exercise capacity in patients with stable COPD. SEARCH STRATEGY: Randomized controlled trials (RCTs) were identified from the Cochrane Airways Group register of RCTs, a hand-search of abstracts presented at international meetings and consultation with experts. SELECTION CRITERIA: Two reviewers independently selected trials for inclusion, assessed quality and extracted the data. DATA COLLECTION AND ANALYSIS: Within each trial and for each outcome, we calculated an effect size. The effect sizes were then pooled by a random-effects model. Homogeneity among the effect sizes was also tested. MAIN RESULTS: From 272 references, nine RCTs were ultimately included. Six papers were considered as high quality and only two studies were double-blinded. For each of the outcomes studied, the effect of nutritional support was small: the 95% confidence intervals around the pooled effect sizes all included zero. The effect of nutritional support was homogeneous across studies. REVIEWER'S CONCLUSIONS: Nutritional support had no significant effect on anthropometric measures, lung function or exercise capacity in patients with stable COPD.
Enteral Nutrition↗
Continuous positive airways pressure for obstructive sleep apnoea.
BACKGROUND: Obstructive sleep apnoea (OSA) is the periodic reduction (hypopnoea) or cessation (apnoea) of breathing due to narrowing or occlusion of the upper airway during sleep. The mainstay of nocturnal treatment is continuous positive airway pressure (CPAP) therapy at home at night to prevent the resulting apnoea, hypoxia and sleep fragmentation which are believed to cause the symptoms of OSA. A number of clinical trials have evaluated the effectiveness of nasal CPAP) as a treatment. OBJECTIVES: The objective was to review the effects of CPAP in the treatment of obstructive sleep apnoea in adults. SEARCH STRATEGY: We searched Medline 1966 to 1996, Embase 1974 to 1996, Cinahl 1982 to 1995 and the reference lists of articles. We consulted experts in the field. SELECTION CRITERIA: Randomised trials comparing nocturnal CPAP with placebo or other treatments in adults with obstructive sleep apnoea and an apnoea/hypopnoea index greater than five per hour. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for missing information. MAIN RESULTS: Seven trials involving 177 people were included. All the studies had some methodological shortcomings. Six trials were of crossover design. Compared with placebo, CPAP showed significant improvements in several quality of life and depression measures. Patients preferred CPAP to placebo (odds ratio 0.4, 95% confidence interval 0.2 to 0.8). There was no significant effect on blood pressure or measures of sleepiness and sleep quality. Compared with oral appliances, CPAP significantly improved the apnoea/hypopnoea index (weighted mean difference -7.3, 95% confidence interval -10.0 to -4.7) and minimum oxygen saturation during sleep. Patients strongly preferred the oral appliance to CPAP (odds ratio 9.5, 95% confidence interval 4.3 to 21.1). REVIEWER'S CONCLUSIONS: CPAP appears to be more effective than placebo in improving some quality of life measures for people with obstructive sleep apnoea. It appears to be more effective than oral appliances in improving respiratory disturbances. People appear to prefer oral appliances over CPAP, but prefer CPAP over placebo.
Adult↗
Opioid antagonists and adrenergic agonists for the management of opioid withdrawal.
BACKGROUND: Managed withdrawal, or detoxification, is not in itself a treatment for opioid dependence, but it is a required first step for many forms of longer-term treatment. It may also represent the end point of an extensive period of treatment such as methadone maintenance. As such, managed withdrawal is an essential component of an effective treatment system. This review is one of a series that aims to assess the evidence as to the effectiveness of approaches to managing opioid withdrawal. OBJECTIVES: To assess the effectiveness of interventions involving the combined use of opioid antagonists an adrenergic agonists to manage the acute phase of opioid withdrawal. SEARCH STRATEGY: Multiple electronic databases, including Medline, Embase, Psychlit, Australian Medical Index and Current Contents, were searched using a strategy designed to retrieve references broadly addressing the management of opioid withdrawal. Reference lists of retrieved studies, reviews and conferences were handsearched. SELECTION CRITERIA: Studies that were included: involved administration of an opioid antagonist in combination with an alpha2 adrenergic agonist; had modification of the signs and symptoms of withdrawal as the aim of the intervention; involved participants who had been diagnosed as primarily opioid dependent and were undergoing clinically managed withdrawal; had as their primary focus the acute phase of withdrawal; reported detail of the type and dose of drugs used and the characteristics of study participants; reported information on the nature of withdrawal symptoms experienced, the occurrence of side effects OR rates of completion of withdrawal; and were randomized or quasi-randomized controlled clinical trials or prospective controlled cohort studies comparing the combination of opioid antagonists and adrenergic antagonists with another form of treatment. (The findings of prospective single group studies or case series, and controlled studies without a comparison treatment modality were considered in the narrative component of the review without being identified as included studies). DATA COLLECTION AND ANALYSIS: Potentially relevant studies were assessed for inclusion by one reviewer (LRG). Inclusion decisions were confirmed by consultation between all three reviewers. Included studies were assessed by all reviewers. One reviewer (LRG) undertook data extraction with the process confirmed by consultation between all three reviewers. Three studies compared treatment using an opioid antagonist-clonidine combination with treatment using clonidine only. This review incorporates data tables comparing maximum withdrawal scores and numbers of participants completing withdrawal for these three studies.. The capacity for data analysis is limited by differences in the assessment outcomes in the three studies and the likelihood of allocation bias in one study. Consequently, meta-analysis has not been undertaken to combine the findings of the three studies. MAIN RESULTS: Three studies (four reports) met the criteria for inclusi on in analytical components of this review. Six further studies were identified that managed withdrawal using opioid antagonists in combination with adrenergic agonists, but which did not meet the inclusion criteria (four were single group studies, 2 were controlled studies but did not include a comparison treatment modality). Findings of these studies are considered in narrative components of the review. Naltrexone was the primary opioid antagonist used to induce withdrawal. The most common approach was to administer naltrexone once a day, using an initial dose of 12.5mg, usually on day one or day two of treatment. Doses of clonidine were generally in the range of 01.-0.3mg three times a day. Five studies provided treatment on an outpatient basis, but all studies provided extended care on the day naltrexone was first administered. (ABSTRACT TRUNCATED)
Adrenergic alpha-Agonists↗
Buprenorphine for the management of opioid withdrawal.
BACKGROUND: Managed withdrawal, or detoxification, is not in itself a treatment for opioid dependence, but it is a required first step for many forms of longer-term treatment. It may also represent the end point of an extensive period of treatment such as methadone maintenance. As such, managed withdrawal is an essential component of an effective treatment system. This review is one of a series that aims to assess the evidence as to the effectiveness of the variety of approaches to managing opioid withdrawal. OBJECTIVES: To assess the effectiveness of interventions involving the short-term use of buprenorphine to manage the acute phase of opioid withdrawal. SEARCH STRATEGY: Multiple electronic databases, including Medline, Embase, Psychlit, Australian Medical Index and Current Contents, were searched using a strategy designed to retrieve references broadly addressing the management of opioid withdrawal. Reference lists of retrieved studies, reviews and conference abstracts were handsearched. SELECTION CRITERIA: We included randomised or quasi-randomised controlled clinical trials or prospective controlled cohort studies comparing buprenorphine (treatment 10 days or less) with another form of treatment. Studies were required to provide detailed information on the type and dose of drugs used and the characteristics of patients treated. Studies were also required to provide information on the nature of withdrawal signs and symptoms experienced, the occurrence of adverse effects OR rates of completion of the withdrawal episode. DATA COLLECTION AND ANALYSIS: Potentially relevant studies were assessed for inclusion by one reviewer (LG). Inclusion decisions were confirmed by consultation between reviewers. Included studies were assessed by all reviewers. One reviewer (LG) undertook data extraction with the process confirmed by consultation between all three reviewers. MAIN RESULTS: Five studies met the criteria for inclusion in the review. No data tables are included in this review and no meta-analysis has been undertaken because of differences in treatment regimes and the assessment of outcomes in these studies. Four studies compared buprenorphine with clonidine. All found withdrawal to be less severe in the buprenorphine treatment group. In three of these studies all participants were withdrawing from heroin. Participants in one study were withdrawing from methadone, with doses reduced to 10mg/day prior to treatment with buprenorphine. Three of the studies commented on residual symptoms experienced by participants treated with buprenorphine to manage heroin withdrawal. Aches, restlessness, yawning, mydriasis, tremor, insomnia, nausea and mild anxiety were reported as being experienced by some participants. Rates of completion of withdrawal were able to be calculated for all studies included in the review but the definition of completion varied between studies. Rates ranged from 65% to 100%. None of the studies included in the review reported adverse effects. However, approximately approximately Lintzeris 1999a approximately approximately (a single-group study which therefore did not meet the inclusion criteria) reported 50% of participants withdrawing from heroin experienced headaches, 28% sedation, 21% nausea, 21% constipation, 21% anxiety, 17% dizziness and 17% itchiness during withdrawal. These adverse effects were most common in the first 2-3 days of treatment and then subsided. In four of the five studies treatment was undertaken on an inpatient basis. Only approximately approximately O'Connor 1997 approximately approximately provided outpatient treatment. However, two studies that did not meet the inclusion criteria ( approximately approximately Diamant 1998 approximately approximately and approximately approximately Lintzeris 1999a approximately approximately ) also provided outpatient treatment. The findings of these studies support the feasibility of heroin withdrawal being managed with buprenorphine on an outpatient basis
Acute Disease↗
The olfactory receptor gene superfamily: data mining, classification, and nomenclature.
The vertebrate olfactory receptor (OR) subgenome harbors the largest known gene family, which has been expanded by the need to provide recognition capacity for millions of potential odorants. We implemented an automated procedure to identify all OR coding regions from published sequences. This led us to the identification of 831 OR coding regions (including pseudogenes) from 24 vertebrate species. The resulting dataset was subjected to neighbor-joining phylogenetic analysis and classified into 32 distinct families, 14 of which include only genes from tetrapodan species (Class II ORs). We also report here the first identification of OR sequences from a marsupial (koala) and a monotreme (platypus). Analysis of these OR sequences suggests that the ancestral mammal had a small OR repertoire, which expanded independently in all three mammalian subclasses. Classification of "fish-like" (Class I) ORs indicates that some of these ancient ORs were maintained and even expanded in mammals. A nomenclature system for the OR gene superfamily is proposed, based on a divergence evolutionary model. The nomenclature consists of the root symbol 'OR', followed by a family numeral, subfamily letter(s), and a numeral representing the individual gene within the subfamily. For example, OR3A1 is an OR gene of family 3, subfamily A, and OR7E12P is an OR pseudogene of family 7, subfamily E. The symbol is to be preceded by a species indicator. We have assigned the proposed nomenclature symbols for all 330 human OR genes in the database. A WWW tool for automated name assignment is provided.
Animals↗
Aortic valve replacement: is valve size important?
OBJECTIVE: We sought to determine whether aortic prosthesis size adversely influences survival after aortic valve replacement. METHODS: A total of 892 adults receiving a mechanical (n = 346), pericardial (n = 463), or allograft (n = 83) valve for aortic stenosis were observed for up to 20 years (mean, 5.0 +/- 3.9 years) after primary isolated aortic valve replacement. We used multivariable propensity scores to adjust for valve selection factors, multivariable hazard function analyses to identify risk factors for all-cause mortality, and bootstrap resampling to quantify the reliability of the results. RESULTS: Twenty-five percent of patients had indexed internal orifice areas of less than 1.5 cm(2)/m(2) and more than 2 SDs (Z-value) below predicted normal aortic valve size. Mechanical valve orifices were smaller (1.3 +/- 0. 29 cm(2)/m(2), Z = -2.2 +/- 1.16) than pericardial (1.9 +/- 0.36 cm(2)/m(2), Z = -0.40 +/- 1.01) or allograft valves (2.1 +/- 0.50, Z = 0.24 +/- 1.17). The overall survival was 98%, 96%, 86%, 69%, and 49% at 30 days and 1, 5, 10, and 15 years postoperatively. Univariably, survival was weakly and inversely related to manufacturer valve size (P =.16) and internal orifice diameter (P =. 2) but completely unrelated to indexed valve area (P =.6) or Z-value (P =.8). These, and univariable differences among valve types (P =. 004), were accounted for by different prevalences in patient risk factors and not by valve size or type per se. Bootstrap resampling indicated that these findings had a less than 15% chance of being incorrect. CONCLUSIONS: Survival after aortic valve replacement is strongly related to patient risk factors but appears not to be adversely affected by moderate patient-prosthesis mismatch (down to about 4 SDs below normal). Aortic root enlargement to accommodate a large prosthesis may be required in few situations.
Adolescent↗
Clinical features and management of Hadronyche envenomation in man.
Using case reports and a review of the literature, the clinical features of envenomation by the genus of Australian funnel web spiders known as Hadronyche, are characterised. Five cases are reported here, including the first life-threatening envenomation by Hadronyche species 14 (the Port Macquarie funnel web). Two severe envenomations by Hadronyche cerberea (the Southern Tree funnel web) and one each by Hadronyche formidabilis (the Northern Tree funnel web) and Hadronyche infensa (the Darling Downs funnel web) are also described. The clinical experience of the authors' provided the five cases described in detail one of which has previously been reported in brief. Eight cases of Hadronyche envenomation from the literature (Medline 1966-1998 and Embase 1980-1998) were analysed in order to draw comparisons between this syndrome and the well described envenomation syndrome of Atrax robustus (the Sydney funnel web). Reports of funnel web spider antivenom use to Commonwealth Serum Laboratories (CSL) between 1995 and June 1998 were also examined. The biology of these dangerous spiders, their geographic distribution, venom characteristics and management issues are addressed. It is concluded that bites from at least six Hadronyche species have produced a life-threatening envenomation syndrome clinically indistinguishable from that of Atrax robustus. Atrax robustus derived antivenom is effective although antivenom requirements may be greater than for Atrax envenomation. Antivenom supplies are limited and sufficient stocks to treat a severe envenomation are unlikely to be found in any one institution. Pressure-immobilisation first aid is effective in delaying onset of envenomation, may enhance local inactivation of venom and early removal can result in rapid clinical deterioration.
Adult↗
Mitral valve surgery in patients with severe left ventricular dysfunction.
OBJECTIVES: The objectives of this study were to determine (1) survival, (2) functional status and freedom from readmission for heart failure and (3) change in postoperative left ventricular (LV) dimensions and function following mitral valve repair or replacement in patients with severe LV dysfunction and mitral regurgitation. PATIENTS AND METHODS: Between 1990 and 1998, 44 patients with mitral regurgitation and a LV ejection fraction <35% (mean+/-SD, 28+/-6%) underwent isolated mitral repair (n=35) or replacement (n=9). The etiology of regurgitation was valvular in 18 (40%) patients, ischemic in 13 (30%) patients and dilated idiopathic cardiomyopathy in 13 (30%) patients. Every patient had been hospitalized one to six times for symptoms of heart failure (mean+/-SD, 2.3+/-1.5). All patients were receiving maximal drug therapy with 15 (34%) in New York Heart Association (NYHA) class III and 12 (27%) in class IV. Seven (16%) patients were initially referred for consideration of transplantation. The mean+/-SD duration of follow-up was 40+/-21 months. RESULTS: One (2.3%) patient died 9 days postoperatively of acute bronchopneumonia. The mean+/-SD duration of ICU and hospital stay was 41+/-34 h and 9+/-3 days, respectively. The 1-, 2- and 5-year survival rates were 89, 86 and 67%, respectively. Heart failure and sudden death accounted for 62% of the late deaths. The NYHA class improved for survivors from 2.8+/-0.8 preoperatively to 1. 2+/-0.5 at follow-up (P<0.0001). Freedom from readmission for heart failure was 88, 82 and 72% at 1, 2 and 5 years, respectively. No patient has been listed for transplantation. CONCLUSIONS: Mitral valve surgery offers symptomatic improvement and survival benefit in patients with severe LV dysfunction and mitral regurgitation. More liberal use of this surgery for cardiomyopathy patients is warranted.
Adult↗
The clinical significance of flow cytometry crossmatching in heart transplantation.
OBJECTIVE: Flow cytometry crossmatching (FCXM) is more sensitive than the cytotoxic crossmatch in identifying preformed antibodies to donor alloantigens, but its clinical importance is controversial. The objective of this study was to determine the association of a FCXM with survival and incidence of vascular rejection in cardiac transplant recipients with a negative cytotoxic crossmatch. METHODS: Between 1993 and 1998, 357 heart transplant recipients with a negative T cell cytotoxic crossmatch were studied by three-color FCXM to quantitate anti-donor IgG reactions against B and T lymphocytes. Reactions positive against both were consistent with human leukocyte antigen (HLA) Class I reactivity, and those against B cells only were considered to be against HLA Class II antigens. Endpoints were episodes of vascular rejection, death from acute and chronic rejection and overall survival. RESULTS: Fifty patients were FCXM for Class I-positive, 144 for Class II-positive, and 163 were negative. At 1 month, freedom from vascular rejection was 64% in Class I patients, but 90% and 96% in Class II or negative crossmatch patients (P<0.0001). Survival of the negative crossmatch group was higher than either Class I or II groups (94%, 74% and 76%, respectively, at 3 years; P<0.0001). Death from acute rejection was 3% and 2% at 3 years in negative or Class II-positive patients, but 19% in Class I patients (P<0.0001). Death from chronic rejection occurred only in Class II patients (P=0.002). CONCLUSIONS: Despite a negative T-cell cytotoxic crossmatch, a positive flow cytometry crossmatch correlates with important clinical events after heart transplantation.
Adolescent↗
A multicentre phase II pilot study of epirubicin and Taxol (paclitaxel) in patients with advanced breast cancer.
Anthracyclines are the gold standard monotherapy for metastatic breast cancer. Higher response rates are seen with drug combinations, especially with newer agents such as taxanes. The purpose of this study was to evaluate the toxicity and activity of the combination of paclitaxel and epirubicin in patients with advanced breast cancer. Thirty-five women with locally advanced or metastatic breast cancer (first and second relapse) were treated with epirubicin 75 mg/m2 and paclitaxel 200 mg/m2 3-weekly. Six centres recruited 35 patients; 34 (97%) were assessable for response. Eighteen had undergone prior chemotherapy, including six (17%) with anthracycline-containing regimens. Grade 4 neutropenia was found in 33 patients (94%), which was of 4 days' average duration; however, infective complications were rare, with only nine cycles (6%) complicated by neutropenic sepsis. There were two sepsis-related deaths. Symptomatic cardiotoxicity was infrequent, although a >15% decline in cardiac function was recorded in five patients (14%). Grade 3 peripheral neuropathy occurred in three patients (9%). The overall response rate was 50% (95% confidence interval 33-67) (complete response 12%; partial response 38%), with a median duration of response of 31 weeks. The median time to progression was 27 weeks, with a median survival of 48 weeks. This regimen appears to be a relatively safe, tolerable and effective treatment for advanced breast cancer. A United Kingdom Co-ordinating Committee for Cancer Research Phase III trial (AB-01) comparing this combination of epirubicin and paclitaxel with cyclophosphamide and paclitaxel completed accrual in November 1999.
Adult↗
Hereditary non-polyposis colorectal cancer: an updated review.
INTRODUCTION: Colorectal cancer is the commonest cause of death due to malignancy in non-smokers in the western countries. The two main hereditary types of colorectal cancer are familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), constituting approximately 10% of all cases of colorectal cancer. The main aim of this review is to reappraise the current advances in the genetics and diagnosis of HNPCC. METHODS: A Medline search was carried out to identify papers published from 1970 to 1999 on HNPCC. Embase and Cochrane databases were also searched. Reference lists of retrieved articles were carefully searched for additional articles. RESULTS AND CONCLUSIONS: Recent technological advances in the genetics of HNPCC have refined the criteria for diagnosis and management of HNPCC, however current policies regarding the testing of pedigrees are not clearly established. We believe that with the rapid development in this area definitive clinical guidelines will need to be available in future for the management of HNPCC.
Colorectal Neoplasms, Hereditary Nonpolyposis↗
Improving longevity of prosthetic dialysis grafts in patients with disadvantaged venous outflow.
OBJECTIVE: Angioaccess for hemodialysis in an extremity with disadvantaged venous outflow has reduced long-term patency. We hypothesized that arteriovenous bridge graft patency could be improved in patients with disadvantaged venous outflow by preoperative venous duplex mapping. METHODS: The charts of 114 patients who underwent 115 prosthetic arteriovenous bridge grafts were reviewed. Disadvantaged venous outflow was defined on the basis of any combination of prior arteriovenous bridge graft, multiple venipunctures, and clinical examination. Patients were grouped according to the presence or absence of disadvantaged venous outflow. Three groups were analyzed: those with normal venous outflow who had an initial arteriovenous bridge graft (NML), those with disadvantaged venous outflow who had only a clinical examination before redo arteriovenous bridge graft (REDO/DVO), and those with disadvantaged venous outflow who underwent preoperative duplex scanning venous evaluation (MAP/DVO). Life table primary and secondary 12-month patency rates were compared by means of log-rank analysis. RESULTS: Life table analysis yielded 6-month primary patency rates of 65.9% +/- 5.7%, 66.4% +/- 7.3%, and 43.8% +/- 10.9% for NML, MAP/DVO, and REDO/DVO, respectively. The secondary patency rates at 6 months for NML (91.9% +/- 3.4%) and MAP/DVO (91.1% +/- 4. 9%) were statistically equivalent, and both were significantly better than the patency for REDO/DVO (75.0% +/- 10.0%; P =.004 and P =.04, respectively). This trend persisted beyond 12 months. CONCLUSION: Preoperative evaluation of venous anatomy in patients with disadvantaged venous outflow results in an arteriovenous bridge graft patency comparable to that seen in patients undergoing initial arteriovenous bridge grafts. Vein mapping improves arteriovenous bridge graft durability in the patient with disadvantaged venous outflow by allowing the surgeon to select venous return that is in direct continuity with the central venous system.
Adult↗