Implementation of Fourier transform infrared spectroscopy for the rapid typing of uropathogenic Escherichia coli.

In this paper, we demonstrate that Fourier transform infrared (FT-IR) spectroscopy is able to discriminate rapidly between uropathogenic Escherichia coli (UPEC) of key lineages with only relatively simple sample preparation. A total of 95 bacteria from six different epidemiologically important multilocus sequence types (ST10, ST69, ST95, ST73, ST127 and ST131) were used in this project and principal component-discriminant function analysis (PC-DFA) of these samples produced clear separate clustering of isolates, based on the ST. Analysis of data using partial least squares-discriminant analysis (PLS-DA), incorporating cross-validation, indicated a high prediction accuracy of 91.19% for ST131. These results suggest that FT-IR spectroscopy could be a useful method for the rapid identification of members of important UPEC STs.

Global field synchrony during general anaesthesia.

BACKGROUND: Anaesthetic agents may disrupt consciousness by inhibiting long-range synchronization of brain activity. In the current study, the patterns of widespread and spatially localized synchrony during anaesthesia are investigated using a measure called global field synchrony (GFS). METHODS: The EEG obtained during routine surgery in 29 patients was analysed with GFS over the following frequency bands: δ (1.5-3.5 Hz), θ (3.5-7.5 Hz), α1 (8-10 Hz), α2 (10.5-12 Hz), ß1 (12.5-18 Hz), ß2 (18.5-21 Hz), ß3 (21.5-30 Hz), γ1 (30.5-40 Hz), and γ2 (60-80 Hz). In addition, localized GFS estimations over aggregate brain areas were performed. GFS was estimated over 2 s non-overlapping windows. The differences in GFS values between 'wakefulness' and 'anaesthesia' were assessed with the two-sided Wilcoxon rank-sum tests (α=0.05). RESULTS: Anaesthetic administration caused significant GFS changes in all frequency ranges and electrode combinations studied: (i) widespread synchrony increased in the α2 and ß1 ranges and decreased in all other ranges, with the exception of α1 and ß2, where no specific pattern was identified; and (ii) localized synchrony decreased in all areas in the δ and γ2 ranges, while location-specific changes were observed in the remaining frequency ranges. The most consistent findings were statistically significant decreases over all areas in the γ2 range, with GFS decrease over the central-right temporal being the most consistent change. CONCLUSIONS: Significant frequency- and location-dependent changes in GFS were induced by anaesthetic administration, with more robust changes identified in the γ range. GFS can act as an aid for further and more detailed analysis regarding the particular combinations of frequency ranges and spatial locations that are most informative for the study of anaesthetic-induced unconsciousness.

The carbon footprint of arthroscopic procedures.

INTRODUCTION: The healthcare sector contributes the equivalent of 4.4% of global net emissions to the climate carbon footprint; between 20% and 70% of healthcare waste originates from a hospital's operating theatre and up to 90% of waste is sent for costly and unneeded hazardous waste processing. This study aimed to quantify the amount and type of waste produced during an arthroscopic anterior cruciate ligament reconstruction (ACLR) and an arthroscopic rotator cuff repair (RCR), calculate the carbon footprint and assess the cost of the waste disposal. METHODS: The amount of waste generated from ACLR and RCR procedures was calculated across a range of hospital sites. The waste was separated primarily into clean and contaminated, paper or plastic. Both carbon footprint and cost of disposal across the hospital sites was subsequently calculated. RESULTS: RCR generated 3.3-15.5kg of plastic waste and 0.9-2.3kg of paper waste. ACLR generated 2.4-9.6kg of plastic waste and 1.1-1.6kg of paper waste. The cost to process waste varies widely between hospital sites, waste disposal contractors and method of waste disposal. The annual burden of the included hospital sites for the arthroscopic procedures undertaken was 6.2 tonnes of carbon dioxide. CONCLUSIONS: The data collected demonstrated a significant variability in waste production and cost for waste disposal between hospital sites. At a national level, consideration should be given to the procurement of appropriate products such that waste can be efficiently recycled or disposed of by environmentally sustainable methods.

High bone mass phenotype in a cohort of patients with Osteogenesis Imperfecta caused due to BMP1 and C-propeptide cleavage variants in COL1A1.

OBJECTIVES: Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; extra-skeletal features in OI include blue sclerae, dentinogenesis imperfecta, skin laxity and joint hyper-extensibility. Most patients with OI are thought to have a low bone mass but contrary to expectations there are certain forms of OI with high bone mass which this study explores in further detail. METHOD: A cohort of n = 6 individuals with pathogenic variants in BMP1 and the C-propeptide cleavage variants in COL1A1 were included in this study. Detailed clinical and radiological phenotyping was done and correlated with genotype to identify patterns of clinical presentation and fracture history in this cohort of patients. This data was compared to previously reported literature in this group. RESULTS: 2 patients with BMP1 and 4 patients with pathogenic variants in C-propeptide region in COL1A1 were deep-phenotyped as part of this study and 1 patient with C-propeptide variant in COL1A1, showed low bone mineral density. In those with an elevated bone mineral density, this became even more apparent on bisphosphonate therapy. Patients in this cohort had variable clinical presentation ranging from antenatal presentation to more of an insidious course resulting in later confirmation of genetic diagnosis up to 19 years of age. CONCLUSIONS: Patients with pathogenic variants in the C-propeptide region of COL1A1/A2 and BMP1 appear to have a high bone mass phenotype with increased sensitivity to bisphosphonate therapy. It is important to closely monitor patients with these genotypes to assess their response to therapy and tailor their treatment regime accordingly.

Fourier transform infrared spectroscopy and multivariate analysis for the detection and quantification of different milk species.

The authenticity of milk and milk products is important and has extended health, cultural, and financial implications. Current analytical methods for the detection of milk adulteration are slow, laborious, and therefore impractical for use in routine milk screening by the dairy industry. Fourier transform infrared (FT-IR) spectroscopy is a rapid biochemical fingerprinting technique that could be used to reduce this sample analysis period significantly. To test this hypothesis we investigated 3 types of milk: cow, goat, and sheep milk. From these, 4 mixtures were prepared. The first 3 were binary mixtures of sheep and cow milk, goat and cow milk, or sheep and goat milk; in all mixtures the mixtures contained between 0 and 100% of each milk in increments of 5%. The fourth combination was a tertiary mixture containing sheep, cow, and goat milk also in increments of 5%. Analysis by FT-IR spectroscopy in combination with multivariate statistical methods, including partial least squares (PLS) regression and nonlinear kernel partial least squares (KPLS) regression, were used for multivariate calibration to quantify the different levels of adulterated milk. The FT-IR spectra showed a reasonably good predictive value for the binary mixtures, with an error level of 6.5 to 8% when analyzed using PLS. The results improved and excellent predictions were achieved (only 4-6% error) when KPLS was employed. Excellent predictions were achieved by both PLS and KPLS with errors of 3.4 to 4.9% and 3.9 to 6.4%, respectively, when the tertiary mixtures were analyzed. We believe that these results show that FT-IR spectroscopy has excellent potential for use in the dairy industry as a rapid method of detection and quantification in milk adulteration.

A consensus exercise identifying priorities for research into clinical effectiveness among children's orthopaedic surgeons in the United Kingdom.

Aims: High-quality clinical research in children's orthopaedic surgery has lagged behind other surgical subspecialties. This study used a consensus-based approach to identify research priorities for clinical trials in children's orthopaedics. Methods: A modified Delphi technique was used, which involved an initial scoping survey, a two-round Delphi process and an expert panel formed of members of the British Society of Children's Orthopaedic Surgery. The survey was conducted amongst orthopaedic surgeons treating children in the United Kingdom and Ireland. Results: A total of 86 clinicians contributed to both rounds of the Delphi process, scoring priorities from one (low priority) to five (high priority). Elective topics were ranked higher than those relating to trauma, with the top ten elective research questions scoring higher than the top question for trauma. Ten elective, and five trauma research priorities were identified, with the three highest ranked questions relating to the treatment of slipped capital femoral epiphysis (mean score 4.6/ 5), Perthes' disease (4.5) and bone infection (4.5). Conclusion: This consensus-based research agenda will guide surgeons, academics and funders to improve the evidence in children's orthopaedic surgery and encourage the development of multicentre clinical trials. Cite this article: Bone Joint J 2018;100-B:680-4.

Recursive partitioning identifies patients at high and low risk for ipsilateral tumor recurrence after breast-conserving surgery and radiation.

PURPOSE: Recursive partitioning analysis (RPA), a method of building decision trees of significant prognostic factors for outcome, was used to determine subgroups at significantly different risk for ipsilateral breast tumor recurrence (IBTR) in early-stage breast cancer. PATIENTS AND METHODS: Nine hundred twelve women underwent breast-conserving surgery, axillary dissection, and radiation. Systemic therapy was chemotherapy with or without tamoxifen in 32%, tamoxifen in 27%, or none in 41%. RPA was used to create a decision tree according to predictive variables that classify patients by IBTR risk, and the Kaplan-Meier method was used to calculate 10-year risks. Median follow-up was 5.9 years. RESULTS: Age was the first split in the partition tree. Patients more than 55 years old had a 4% 10-year IBTR, the only further division being use of tamoxifen or not (2% v 5%, P =.03). For patients

Postmenopausal hormone replacement therapy: effect on diagnosis and outcome in early-stage invasive breast cancer treated with conservative surgery and radiation.

PURPOSE: To compare the pretreatment characteristics and outcome of postmenopausal women with stage I-II breast cancer treated with conservative surgery and radiation who had a history of hormone replacement therapy (HRT) with those who had never received HRT. MATERIALS AND METHODS: From 1979 to 1993, 485 postmenopausal women underwent excisional biopsy, axillary dissection, and radiation for stage I-II breast cancer. The median follow-up was 5.9 years. One hundred forty-one patients reported a history of HRT. The median length of use was 5 years. Three hundred forty-four patients reported no history of HRT. RESULTS: Statistically significant differences between the two groups were observed for median age (HRT 60 years v no HRT 64 years; P =.0009), median weight (HRT 142 lbs v no HRT 152 lbs; P =.004), clinical tumor size < or = 2 cm (HRT 77% v no HRT 66%; P =.02), and the use of re-excision (HRT 62% v no HRT 49%; P =.01). The method of detection by mammogram only (HRT 52% v no HRT 42%; P =.06) was of borderline statistical significance. The HRT patients had a statistically significant increased cumulative incidence of ipsilateral breast tumor recurrence (8% v 2%; P =.02), a statistically significant decreased cumulative incidence of distant metastases (HRT 6% v no HRT 17%; P =.01), and a borderline statistically significant improvement in cause-specific survival at 10 years (HRT 92% v no HRT 86%; P =.07). Postmenopausal women with a history of HRT did not have an increased risk of contralateral breast cancer or second non-breast cancer malignancy. CONCLUSION: This study failed to identify an adverse effect of HRT on breast cancer mortality in patients with stage I-II disease treated with conservative surgery and radiation.

Comment on "Performance of different synchronization measures in real data: a case study on electroencephalographic signals".

We agree with Duckrow and Albano [Phys. Rev. E 67, 063901 (2003)] and Quian Quiroga [Phys. Rev. E 67, 063902 (2003)] that mutual information (MI) is a useful measure of dependence for electroencephalogram (EEG) data, but we show that the improvement seen in the performance of MI on extracting dependence trends from EEG is more dependent on the type of MI estimator rather than any embedding technique used. In an independent study we conducted in search for an optimal MI estimator, and in particular for EEG applications, we examined the performance of a number of MI estimators on the data set used by Quian Quiroga in their original study, where the performance of different dependence measures on real data was investigated [Phys. Rev. E 65, 041903 (2002)]. We show that for EEG applications the best performance among the investigated estimators is achieved by -nearest neighbors, which supports the conjecture by Quian Quiroga in Phys. Rev. E 67, 063902 (2003) that the nearest neighbor estimator is the most precise method for estimating MI.

Squamous carcinoma arising from a true tracheal bronchus: Management and case report.

A case of a squamous carcinoma arising in a "True" tracheal bronchus is described. The presentation and management of this case is discussed.

Second cancers after conservative surgery and radiation for stages I-II breast cancer: identifying a subset of women at increased risk.

PURPOSE: To assess the risk and patterns of second malignancy in a group of women treated with conservative surgery and radiation in a relatively contemporary manner for early-stage invasive breast cancer, and to identify a subgroup of these women at increased risk for a second cancer. METHODS AND MATERIALS: From 1978 to 1994, 1,253 women with unilateral Stage I-II breast cancer underwent wide excision, axillary dissection, and radiation. The median follow-up was 8.9 years, with 446 patients followed for >or= 10 years. The median age was 55 years. Sixty-eight percent had T1 tumors and 74% were axillary-node negative. Radiation was directed to the breast only in 78%. Adjuvant therapy consisted of chemotherapy in 19%, tamoxifen in 19%, and both in 8%. Factors analyzed for their association with the cumulative incidence of all second malignancies, contralateral breast cancer, and non-breast cancer malignancy were: age, menopausal status, race, family history, obesity, smoking, tumor size, location, histology, pathologic nodal status, region(s) treated with radiation, and the use and type of adjuvant therapy. RESULTS: One hundred seventy-six women developed a second malignancy (87 contralateral breast cancers at a median interval of 5.8 years, and 98 non-breast cancer malignancies at a median interval of 7.2 years). Nine women had both a contralateral breast cancer and non-breast cancer second malignancy. The 5- and 10-year cumulative incidences of a second malignancy were 5% and 16% for all cancers, 3% and 7% for contralateral breast cancer, 3% and 8%, for all second non-breast cancer malignancies, and 1% and 5%, respectively, for second non-breast cancer malignancies, excluding skin cancers. Patient age was a significant factor for contralateral breast cancer and non-breast cancer second malignancy. Young age was associated with an increased risk of contralateral breast cancer, while older age was associated with an increased the risk of a second non-breast cancer second malignancy. A positive family history increased the risk of contralateral breast cancer, but not non-breast cancer malignancies. The risk of a contralateral breast cancer increased as the number of affected relatives increased. Tamoxifen resulted in a nonsignificant decrease in contralateral breast cancer and an increase in non-breast cancer second malignancies. The 5-and 10-year cumulative incidences for leukemia and lung cancer were 0.08% and 0.2%, and 0.8% and 1%, respectively. There was no significant effect of chemotherapy or the regions treated with radiation on contralateral breast cancer or non-breast cancer second malignancy. The most common types of second non-breast cancer malignancies were skin cancers, followed by gynecologic malignancies (endometrial), and gastrointestinal malignancies (colorectal and pancreas). CONCLUSION: The 10-years cumulative incidence of a second cancer in this study was 16%. Young age and family history predicted for an increased risk of contralateral breast cancer, and older age predicted for an increased risk of non-breast cancer malignancy. The majority of patients treated with conservative surgery and radiation with or without adjuvant systemic therapy will not develop a second cancer. Long-term follow-up is important to document the risk and patterns of second cancer, and knowledge of this risk and the patterns will influence surveillance and prevention strategies.

Patients with early stage invasive cancer with close or positive margins treated with conservative surgery and radiation have an increased risk of breast recurrence that is delayed by adjuvant systemic therapy.

PURPOSE: The association between a positive resection margin and the risk of ipsilateral breast tumor recurrence (IBTR) after conservative surgery and radiation is controversial. The width of the resection margin that minimizes the risk of IBTR is unknown. While adjuvant systemic therapy may decrease the risk of an IBTR in all patients, its impact on patients with positive or close margins is largely unknown. This study examines the interaction between margin status, margin width, and adjuvant systemic therapy on the 5- and 10-year risk of IBTR after conservative surgery and radiation. METHODS AND MATERIALS: A series of 1,262 patients with clinical Stage I or II breast cancer were treated by breast-conserving surgery, axillary node dissection, and radiation between March 1979 and December 1992. The median follow-up was 6.3 years (range 0.1-15.6). The median age was 55 years (range 24-89). Clinical size was T1 in 66% and T2 in 34%. Seventy-three percent of patients were node-negative. Only 5 % of patients had tumors that were EIC-positive. Forty-one percent had a single excision, and 59% had a reexcision. The final margins were negative in 77%, positive in 12%, and close (< or = 2 mm) in 11%. The median total dose to the tumor bed was 60 Gy with negative margins, 64 Gy with close margins, and 66 Gy with positive margins. Chemotherapy +/- tamoxifen was used in 28%, tamoxifen alone in 20%, and no adjuvant systemic therapy in 52%. RESULTS: The 5-year cumulative incidence (CI) of IBTR was not significantly different between patients with negative (4%), positive (5%), or close (7%) margins. However, by 10 years, a significant difference in IBTR became apparent (negative 7%, positive 12%, close 14%, p = 0.04). There was no significant difference in IBTR when a close or positive margin was involved by invasive tumor or DCIS. Reexcision diminished the IBTR rate to 7% at 10 years if the final margin was negative; however, the highest risk was observed in patients with persistently positive (13%) or close (21%) (p = 0.02) margins. The median interval to failure was 3.7 years after no adjuvant systemic therapy, 5.0 years after chemotherapy +/- tamoxifen, and 6.7 years after tamoxifen alone. This delay to IBTR was observed in patients with close or positive margins, with little impact on the time to failure in patients with negative margins. The 5-year CI of IBTR in patients with close or positive margins was 1% with adjuvant systemic therapy and 13% with no adjuvant therapy. However, by 10 years, the CI of IBTR was similar (18% vs. 14%) due to more late failures in the patients who received adjuvant systemic therapy. CONCLUSION: A negative margin (> 2 mm) identifies patients with a very low risk of IBTR (7% at 10 years) after conservative surgery and radiation. Patients with a close margin (< or = 2 mm) are at an equal or greater risk of IBTR as with a positive margin, especially following a reexcision. A margin involved by DCIS or invasive tumor has the same increased risk of IBTR. A reexcision of an initially close or positive margin that results in a negative final margin reduces the risk of IBTR to that of an initially negative margin. A close or positive margin is associated with an increased risk of IBTR even in patients who are EIC-negative or receiving higher boost doses of radiation. The median time to IBTR is delayed; however, the CI is not significantly decreased by adjuvant systemic therapy in patients with close or positive margins-the 5 year results in these patients underestimate their ultimate risk of recurrence.

Internal mammary node irradiation neither decreases distant metastases nor improves survival in stage I and II breast cancer.

PURPOSE: To compare outcome for ipsilateral breast tumor recurrence (IBTR), or regional node recurrence, initial and subsequent distant metastases, and overall and cause-specific survival in women treated with conservative surgery and radiation based on whether or not radiation was targeted to the internal mammary nodes (IMN). METHODS AND MATERIALS: From 1979-1994, 1383 women with Stage I-II breast cancer underwent wide excision, axillary node dissection with >/=10 nodes removed, and radiation. Median follow-up was 6 years; median age was 55 years. A total of 114 women had radiation targeted to the IMN with deep tangents and 1269 did not. Women who received IMN treatment were more often axillary node-positive (40% vs. 25%, p = 0. 002), had central or inner quadrant tumors (61% vs. 40%, p = 0.001), and had T2 tumors (47% vs. 31%, p = 0.001). All axillary node-positive women received adjuvant chemotherapy and/or tamoxifen. For axillary node-negative women, 13% of the IMN treatment group received adjuvant systemic therapy compared to 37% of the no treatment group (p = 0.001). Radiation was directed to the breast only in 97% of the axillary node-negative women who had IMN treatment and 99% of the no IMN treatment group. For axillary node-positive women, 98% of the IMN-treated group had radiation to the breast and supraclavicular nodes +/- a posterior axillary field compared to 77% of the no IMN treatment group (p = 0.001). There were no significant differences between the two groups for median age, menopausal status, histology, final surgical margin, estrogen and progesterone receptor status, or the number of positive nodes. RESULTS: There were no significant differences in the 5- and 10-year cumulative incidence of an IBTR, regional node recurrence, initial or total distant metastases for the two groups. Similarly 5- and 10-year actuarial overall and cause-specific survival were not significantly different. However, subset analysis revealed a statistically significant increase in initial (29% vs. 15% at 10 yr, p = 0.002) and total (30% vs. 17% at 10 yr, p = 0.01) distant metastases and a significant decrease in cause-specific survival (76% vs. 89% at 10 yr, p = 0.02) for postmenopausal women who received IMN treatment. These findings could not be attributed to differences in the use of systemic therapy or the number of positive nodes. Axillary node-positive patients did not experience a significant decrease in initial (36% vs. 22% at 10 yr, p = 0.21) or total distant metastases (37% vs. 28% at 10 yr, p = 0.62) or a significant improvement in cause-specific survival (72% vs. 76% at 10 yr, p = 0.76) with IMN treatment regardless of whether the tumor was lateral or medial/central in location. IMN treatment was not associated with an increase in non-breast cancer deaths during this period of observation. CONCLUSIONS: This retrospective series was unable to identify a significant benefit for IMN irradiation in terms of distant metastases or cause-specific survival for the entire patient population, and in particular, for patients with positive axillary nodes and medially located lesions. The results of the proposed or ongoing prospective randomized trials will further address this controversial issue.

Accuracy of the extent of axillary nodal positivity related to primary tumor size, number of involved nodes, and number of nodes examined.

PURPOSE: While a number of studies have evaluated the minimum number of axillary nodes that need to be examined to accurately determine nodal positivity or negativity, there is little information on the number of nodes which must be examined to determine the extent of nodal positivity. This study attempts to determine for patients with 1-3 positive nodes the probability that the number of positive nodes reported is the true number of positive nodes as well as the probability that 4 or more nodes could be positive based on primary tumor size and number of nodes examined. MATERIALS AND METHODS: From 1979 to 1998, 1652 women with Stages I-II invasive breast cancer underwent an axillary dissection as part of their breast conservation therapy and had more than 10 lymph nodes examined. The mean and median number of nodes identified in the dissection was 19 and 17 (range, 11-75). The median age was 55 years. A total of 1155 women had T1 tumors and 497 had T2 tumors. Of the 459 node-positive women, 72% had 1-3 positive nodes, 18% had 4-9 positive nodes, and 10% had 10 or more positive nodes. A mathematical model based on tumor size and number of nodes examined was created using the hypergeometric distribution and Bayes Theorem. The resulting model was used to estimate the accuracy of the reported number of positive nodes and the probability of 4 or more positive nodes based on various observed sampling combinations. RESULTS: For patients with T1 tumors and 1, 2, or 3 positive nodes, the minimum number of nodes examined needed for a 90% probability of accuracy is 19, 20, and 20. For T2 tumors and 1, 2, or 3 positive nodes, a minimum of 20 nodes is required. The probability of 4 or more positive nodes increases as tumor size and the number of reported positive nodes increase and as the number of examined nodes decreases. For a 10% or less probability of 4 or more positive nodes, a patient with a T1 tumor and 1, 2, or 3 observed positive nodes would require a minimum of 8, 15, and 20 nodes removed. For a T2 tumor and 1, 2, or 3 observed positive nodes, the corresponding numbers are 10, 16, and 20. CONCLUSION: The accuracy of the extent of axillary nodal positivity is influenced by the number of observed positive nodes, tumor size, and the number of nodes examined. Underestimation of the number of positive nodes will result in errors in the assessment of an individual's risk for locoregional recurrence, distant disease, and breast cancer death and will adversely impact on treatment recommendations. This model provides the clinician with a means for assessing the accuracy of the number of positive nodes reported in patients with 1-3 positive nodes.

Should internal mammary lymph nodes in breast cancer be a target for the radiation oncologist?

PURPOSE: The elective treatment of internal mammary lymph nodes (++IMNs) in breast cancer is controversial. Previous randomized trials have not shown a benefit to the extended radical mastectomy or elective IMN irradiation overall, but a survival benefit has been suggested by some for subgroups of patients with medial tumors and positive axillary lymph nodes. The advent of effective systemic chemotherapy and potential for serious cardiac morbidity have also been factors leading to the decreased use of IMN irradiation during the past decade. The recent publishing of positive trials testing postmastectomy radiation that had included regional IMN irradiation has renewed interest in their elective treatment. The purpose of this study is to critically review historical and new data regarding IMNs in breast cancer. METHODS AND MATERIALS: The historical incidence of occult IMN positivity in operable breast cancer is reviewed, and the new information provided by sentinel lymph node studies also discussed. The results of published randomized prospective trials testing the value of elective IMN dissection and/or radiation are analyzed. The data regarding patterns of failure following elective IMN treatment is studied to determine its impact on local-regional control, distant metastases, and survival. A conclusion is drawn regarding the merits of elective IMN treatment based on this review of the literature. RESULTS: Although controversial, the existing data from prospective, randomized trials of IMN treatment do not seem to support their elective dissection or irradiation. While it has not been shown to contribute to a survival benefit, the IMN irradiation increases the risk of cardiac toxicity that has effaced the value of radiation of the chest wall in reducing breast cancer deaths in previous randomized studies and meta-analyses. Sentinel lymph node mapping provides an opportunity to further evaluate the IMN chain in early stage breast cancer. Biopsy of "hot" nodes may be considered in the future to select patients who are most likely to benefit from additional regional therapy to these nodes. CONCLUSIONS: Irradiation of the IMN chain in conjunction with the chest wall and supraclavicular region should be considered only for those with pathologically proven IMNs with the goal of improving tumor regional control.

The influence of L-tryptophan and monoamine oxidase inhibitors on catecholamine metabolism in rat brain.

1. L-Tryptophan (100 mg/kg) was administered to rats with or without pretreatment with a monoamine oxidase inhibitor and the concentration of 5-hydroxyindoleacetic acid, homovanillic acid, dihydroxyphenylacetic acid, 3-methoxy 4-hydroxyphenyl glycol, normetanephrine, noradrenaline and dopamine measured in whole brain one hour later. 2. L-Tryptophan increased the concentration of 5-hydroxyindoleacetic acid, homovanillic acid, dihydroxyphenylacetic acid, 3-methoxy 4-hydroxyphenyl glycol and normetanephrine. The concentration of noradrenaline did not change whilst that of dopamine increased significantly. 3. In animals pretreated chronically with a monoamine oxidase inhibitor, tryptophan increased the concentration of dihydroxyphenylacetic acid and homovanillic acid compared to monoamine oxidase alone. 4. The results suggest either a release of dopamine and noradrenaline by 5-hydroxytryptamine, with a compensatory increase in their synthesis, or an increase in the firing of dopaminergic and noradrenergic neurones after L-tryptophan.

Uptake of 5-hydroxytryptamine in the catecholamine containing areas of the hypothalamus of the rat after treatment with phenelzine and tryptophan.

1 Uptake of 5-hydroxytryptamine in the catecholamine containing nerve endings of the hypothalamus in the rat brain was found after intraperitoneal injection of phenelzine sulphate (25 mg/kg) and tryptophan (100 and 400 mg/kg). 2 The results were obtained by fluorescence microscopy and microspectrofluorimetry.

Massive hemoptysis. Review of 123 cases.

Case histories of 123 patients with massive hemoptysis were reviewed. The causes of hemorrhage were active pulmonary tuberculosis (47), bronchiectasis (37), chronic necrotizing pneumonia (11), lung abscess (six), lung cancer (six), bronchovascular fistula (five), primary pulmonary fungal infection (four), and miscellaneous (seven). Conservative management was used in 66 patients, with 21 deaths (31.8%). Surgical management was used in 34 patients, with six deaths (17.6%). Endobronchial iced saline lavage was used in 23 patients, with one death. All patients treated by lavage stopped bleeding, and further therapy, either surgical (five) or medical (18), was given as appropriate. The early control of tracheobronchial hemorrhage by endoscopic means is an effective though transitory holding procedure. The unpredictability of massive hemoptysis is underscored by eight deaths from sudden, engulfing hemorrhage in seemingly stable patients awaiting endoscopy or operation.

The effect of chronic lithium administration on dopamine metabolism in rat striatum.

Striatal dopamine and its metabolites were studied in rats given lithium chloride in the diet. Results showed an increase in homovanillic acid and 3,4-dihydroxyphenylacetic acid levels but no significant change in dopamine concentration after 3 weeks of lithium administration. There was no change in tyrosine hydroxylase activity after 1, 2, and 3 weeks treatment. The results indicate an increase in the release and turnover of dopamine in the lithium-treated animals.

Pessimism concerning palliative bypass procedures for established malignant esophagorespiratory fistulas: a report of 18 patients.

Eighteen patients with established malignant esophagorespiratory fistulas due to primary esophageal cancer were managed by substernal gastric bypass and isolation of the cancerous esophageal segment. Seven fistulas were esophagotracheal and 11 were esophagobronchial. Ten patients died in the hospital between two days and six weeks after operation. Eight patients left the hospital, surviving an average of 3 1/2 months, but 2 patients lived 5 and 7 months, respectively. Unrelenting respiratory infection and clinical inanition caused 7 hospital deaths in patients reestablished on oral alimentation with their fistulas disconnected. Anastomotic leaks occurred in 5 patients; three of these leaks closed. In the other 2 patients, cervicomediastinal sepsis and bilateral pneumonia with respiratory failure caused death. One patient died of anoxic cardiac arrest 48 hours postoperatively. Fifteen of the 18 patients resumed oral alimentation, but the overall results of palliative surgical therapy achieved in this series were not observably worthwhile for the majority.