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Purpose: The prospective Neoadjuvant Breast Registry Symphony Trial compared the 80-gene molecular subtyping signature with clinical assessment by immunohistochemistry and/or fluorescence in situ hybridization in predicting pathologic complete response (pCR) and 5-year outcomes in patients with early-stage breast cancer., Methods: Standard-of-care neoadjuvant chemotherapy combined with trastuzumab or trastuzumab plus pertuzumab was given to patients with human epidermal growth factor receptor 2 (HER2)-positive tumors (n = 295). pCR was the primary end point, with secondary end points of distant metastasis-free survival and overall survival at 5 years., Results: Among clinically defined HER2-positive (cHER2) tumors, the 80-gene assay identified 29.5% (87 of 295) as Luminal-Type (cHER2/gLuminal), 14.9% (44 of 295) as Basal-Type (cHER2/gBasal), and 55.6% (164 of 295) as HER2-Type (cHER2/genomically classified as HER2 [gHER2]). Patients with cHER2/gHER2 tumors had a higher pCR rate (61.6%) compared with non-gHER2 tumors (26.7%; P < .001). Dual targeting for cHER2/gHER2 tumors yielded a higher pCR rate (75%) compared with those treated with single HER2-targeted therapy (54%; P = .006). For cHER2/gBasal tumors, the 42.9% pCR rate observed with dual targeting was not different from that with trastuzumab alone (46.4%; P = .830). Among those with cHER2/gBasal tumors, 5-year distant metastasis-free survival (68.6%; 95% CI, 49.1 to 81.9) was significantly worse than in patients with cHER2/gLuminal tumors (88.9%; 95% CI, 78.0 to 94.6) and cHER2/gHER2 tumors (87.4%; 95% CI, 80.2 to 92.2; P = .010), with similar corresponding overall survival differences., Conclusion: The 80-gene assay identified meaningful genomic diversity in patients with cHER2 disease. Patients with cHER2/gHER2 tumors, who benefitted most from dual HER2-targeted therapy, accounted for approximately half of the cHER2 cohort. Genomically Luminal tumors had low pCR rates but good 5-year outcomes. cHER2/gBasal tumors derived no benefit from dual therapy and had significantly worse 5-year prognosis; these patients merit special consideration in future trials., Competing Interests: Pat W. WhitworthEmployment: Integra LifeSciences (I)Leadership: Integra LifeSciences (I)Stock and Other Ownership Interests: Targeted Medical Education Inc, Integra LifeSciences (I)Honoraria: Puma BiotechnologyConsulting or Advisory Role: ImpediMed, Prelude Therapeutics, Becton DickinsonResearch Funding: Prelude Therapeutics, Agendia, MedneonTravel, Accommodations, Expenses: Targeted Medical Education Inc Peter D. BeitschEmployment: InvitaeLeadership: Targeted Medical Education IncStock and Other Ownership Interests: Targeted Medical Education Inc, InvitaeResearch Funding: InvitaeExpert Testimony: Dune Medical Devices, ImpediMedUncompensated Relationships: Medneon Paul D. RichardsStock and Other Ownership Interests: NanoViricidesResearch Funding: Carrick Therapeutics (Inst) James V. PellicaneStock and Other Ownership Interests: PreludeDxHonoraria: Agendia, PreludeDxSpeakers' Bureau: Agendia, PreludeDx Beth B. DupreeLeadership: Caliber MedicalStock and Other Ownership Interests: Videra SurgicalHonoraria: Medtronic, Perimeter Medical William DooleyLeadership: Shaga Medical LLCStock and Other Ownership Interests: Shaga MedicalResearch Funding: Agendia, XoftPatents, Royalties, Other Intellectual Property: patent pending—microendoscopy system Shiyu WangEmployment: Agendia Patricia DauerEmployment: AgendiaStock and Other Ownership Interests: AgendiaTravel, Accommodations, Expenses: Agendia Andrea R. MenicucciEmployment: Agendia Erin B. YoderEmployment: AgendiaStock and Other Ownership Interests: AgendiaTravel, Accommodations, Expenses: Agendia Lisa E. BlumencranzEmployment: Agendia William AudehEmployment: AgendiaLeadership: AgendiaStock and Other Ownership Interests: AgendiaConsulting or Advisory Role: Celanese, Private HealthResearch Funding: AgendiaTravel, Accommodations, Expenses: AgendiaNo other potential conflicts of interest were reported.

Background: The Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status., Methods: The observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18-90 years who received neoadjuvant chemotherapy and had clinical and genomic data available. Chemosensitivity and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed. In a post hoc subanalysis, results were stratified by age (≤ 50 vs. > 50 years) and menopausal status in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) tumors., Results: MammaPrint and BluePrint further classified 23% of tumors to a different subtype compared with immunohistochemistry, with more precise correspondence to pCR rates. Five-year DMFS and OS were highest in MammaPrint Low Risk, Luminal A-type and HER2-type tumors, and lowest in MammaPrint High Risk, Luminal B-type and Basal-type tumors. There was no significant difference in chemosensitivity between younger and older patients with Low-Risk (2.2% vs. 3.8%; p = 0.64) or High-Risk tumors (14.5% vs. 11.5%; p = 0.42), or within each BluePrint subtype; this was similar when stratifying by menopausal status. The 5-year outcomes were comparable by age or menopausal status for each molecular subtype., Conclusion: Intrinsic preoperative chemosensitivity and long-term outcomes were precisely determined by BluePrint and MammaPrint regardless of patient age, supporting the utility of these assays to inform treatment and surgical decisions in early-stage breast cancer., (© 2022. The Author(s).)

Background: A prognostic model was developed and validated using cancer registry data. This underpins an online decision support tool, informing primary treatment choice for women aged 70 years or older with hormone receptor-positive early breast cancer., Methods: Data from women diagnosed between 2002 and 2010 in the English Northern and Yorkshire and West Midlands regions were used to develop the model. Primary treatment options of surgery with adjuvant endocrine therapy or primary endocrine therapy were compared. Models predicting the hazard of breast cancer-specific mortality and hazard of other-cause mortality were combined to derive survival probabilities. The model was validated externally using data from the Eastern Cancer Registration and Information Centre., Results: The model was developed using data from 23 842 women, and validated externally on a data set from 14 526 patients. The overall model calibration was good. At 2 and 5 years, predicted mortality from breast cancer and other causes differed from the observed rate by less than 1 per cent. At 5 years, there were slight overpredictions in breast cancer mortality (2629 predicted versus 2556 observed deaths; P = 0·142) and mortality from all causes (6399 versus 6320 respectively; P = 0·583). The discrepancy varied between subgroups. Model discrimination was 0·75 or above for all mortality measures., Conclusion: A prognostic model for older women with oestrogen receptor-positive early breast cancer was developed and validated in the present study. This forms a basis for an online decision support tool (https://agegap.shef.ac.uk/)., (© 2020 The Authors. British Journal of Surgery published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Aims: Adjuvant chemotherapy is recommended as a treatment for women with high recurrence risk early breast cancer. Older women are less likely to receive chemotherapy than younger women. This study investigated the impact of chemotherapy on breast cancer-specific survival in women aged 70 + years using English registry data., Materials and Methods: Cancer registration data were obtained from two English regions from 2002 to 2012 (n = 29 728). The impact of patient-level characteristics on the probability of receiving adjuvant chemotherapy was explored using logistic regression. Survival modelling was undertaken to show the effect of chemotherapy and age/health status on breast cancer-specific survival. Missing data were handled using multiple imputation., Results: In total, 11 735 surgically treated early breast cancer patients were identified. Use of adjuvant chemotherapy has increased over time. Younger age at diagnosis, increased nodal involvement, tumour size and grade, oestrogen receptor-negative or human epidermal growth factor receptor 2-positive disease were all associated with increased probability of receiving chemotherapy. Chemotherapy was associated with a significant reduction in the hazard of breast cancer-specific mortality in women with high risk cancer, after adjusting for patient-level characteristics (hazard ratio 0.74, 95% confidence interval 0.67-0.81)., Discussion: Chemotherapy is associated with an improved breast cancer-specific survival in older women with early breast cancer at high risk of recurrence . Lower rates of chemotherapy use in older women may, therefore, contribute to inferior cancer outcomes. Decisions on potential benefits for individual patients should be made on the basis of life expectancy, treatment tolerance and patient preference., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Primary endocrine therapy is used as an alternative to surgery in up to 40 per cent of women with early breast cancer aged over 70 years in the UK. This study investigated the impact of surgery versus primary endocrine therapy on breast cancer-specific survival (BCSS) in older women., Methods: Cancer registration data for 2002-2010 were obtained from two English regions. A retrospective analysis was performed for women with oestrogen receptor (ER)-positive disease, using statistical modelling to show the effect of treatment (surgery or primary endocrine therapy) and age and health status on BCSS. Missing data were handled using multiple imputation., Results: Cancer registration data on 23 961 women were retrieved. After data preprocessing, 18 730 of 23 849 women (78·5 per cent) were identified as having ER-positive disease; of these, 10 087 (53·9 per cent) had surgery and 8643 (46·1 per cent) had primary endocrine therapy. BCSS was worse in the primary endocrine therapy group than in the surgical group (5-year BCSS rate 69·4 and 89·9 per cent respectively). This was true for all strata considered, although the difference was less in the cohort with the greatest degree of co-morbidity. For older, frailer patients the hazard of breast cancer death had less relative impact on overall survival., Conclusion: BCSS in older women with ER-positive disease is worse if surgery is omitted. This treatment choice may contribute to inferior cancer outcomes. Selection for surgery on the basis of predicted life expectancy may permit choice of women for whom surgery confers little benefit., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Pertuzumab became a standard part of neoadjuvant therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancers approximately halfway through Neoadjuvant Breast Registry Symphony Trial (NBRST) enrollment, providing a unique opportunity to determine biologically which clinical HER2+ patients benefit most from dual targeting. As a neoadjuvant phase 4 study, NBRST classifies patients by both conventional and molecular subtyping., Methods: Of 308 clinical HER2+ patients enrolled in NBRST between 2011 and 2014 from 62 U.S. institutions, 297 received neoadjuvant chemotherapy (NCT) with HER2-targeted therapy and underwent surgery. This study compared the pathologic complete response (pCR) rate of BluePrint versus clinical subtypes with treatment, specifically differences between trastuzumab (T) treatment and trastuzumab and pertuzumab (T/P) treatment., Results: In this study, 60% of the patients received NCT-T, and 40% received NCT-T/P. The overall pCR rate (ypT0/isN0) was 47%. BluePrint classified 161 tumors (54%) as HER2 type, with a pCR rate of 65%. This was significantly higher than the pCR rate for the 91 HER2+ tumors (31%) classified as luminal (18%) (p = 0.00001) and the 45 tumors (15%) classified as basal (44%) (p = 0.0166). The patients treated with T/P had higher pCR rates than those treated with trastuzumab alone. The difference was most pronounced in the BluePrint luminal patients (8 vs. 31%). The highest pCR was reached by the BluePrint HER2-type patients treated with T/P (76%)., Conclusions: The addition of pertuzumab leads to increased pCR rates for all HER2+ patient groups except for the BluePrint basal-type patients. This better response was most pronounced for the BluePrint luminal-type patients.

Prospective data are needed to ascertain the impact of iron chelation therapy in patients with myelodysplastic syndromes. The present 5-year prospective registry analysis was conducted to compare clinical outcomes between chelated and nonchelated patients with lower-risk myelodysplastic syndromes and transfusional iron overload. In an interim analysis at 24 months, we previously reported that chelation therapy was associated with longer median overall survival and a tendency toward longer leukemia-free survival and fewer cardiac events. In the present report, we detail findings from the final analysis at 5 years. We confirm, at the conclusion of this 5-year, prospective, non-interventional study, that overall survival was significantly longer in patients who received iron chelation therapy vs those who did not. Causes of death in the overall population were predominantly myelodysplastic syndromes/acute myeloid leukemia followed by cardiac disease. Time to progression to acute myeloid leukemia was also significantly longer in patients receiving chelation therapy, and significantly fewer patients progressed to leukemia vs those not receiving chelation therapy. Limitations of the study include a potential for clinical bias, as patients with longer predicted survival may have been chosen for chelation therapy, the differences present in concomitant conditions at baseline, and the possibility that some high-risk patients were not identified due to limited cytogenetic classification., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Use of antiangiogenic agents in treatment of metastatic breast cancer (MBC) remains controversial. We evaluated the efficacy and safety of ramucirumab and eribulin versus eribulin alone as third- to fifth-line therapy in women with advanced breast cancer., Patients and Methods: In this randomized (1:1), open-label, phase II study, US women aged 18 years or older with 2 to 4 previous chemotherapy regimens for locally recurrent or MBC, previous anthracycline and taxane treatment, and Eastern Cooperative Oncology Group performance status of 0 or 1 received ramucirumab with eribulin or eribulin alone in 21-day cycles (eribulin 1.4 mg/m 2 intravenously on days 1 and 8; ramucirumab 10 mg/kg intravenously on day 1). Randomization was stratified according to previous antiangiogenic therapy and triple-negative status. The primary end point was progression-free survival (PFS) in the intention to treat population., Results: One hundred forty-one women were randomized to ramucirumab with eribulin (n = 71) or eribulin alone (n = 70). Median PFS for ramucirumab with eribulin was 4.4 months (95% confidence interval [CI], 3.1-6.7) compared with 4.1 months (95% CI, 3.2-5.6) for eribulin (hazard ratio [HR], 0.83; 95% CI, 0.56-1.23; P = .35). Median overall survival in patients who received ramucirumab with eribulin was 13.5 months (95% CI, 10.4-17.9) compared with 11.5 months (95% CI, 9.0-17.3) in patients who received eribulin alone (HR, 0.91; 95% CI, 0.59-1.41; P = .68); objective response rate was 21% (13 of 62 patients) for the combination and 28% (17 of 60 patients) for eribulin alone. No unexpected toxicity was identified for the combination., Conclusion: Ramucirumab combined with eribulin did not significantly improve PFS in advanced MBC., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Trabectedin is an alkylating agent that binds to the minor groove of DNA. Early studies with trabectedin suggested efficacy in triple-negative and HER2-overexpressing metastatic breast cancer (MBC). The efficacy and safety of trabectedin in pretreated patients with these tumors were evaluated in this parallel-cohort phase II trial. Patients received a 3-h infusion of trabectedin 1.3 mg/m(2) intravenously every 3 weeks until progression or unmanageable/unacceptable toxicity. The primary objective was to evaluate the efficacy using the objective response rate (ORR) as per Response Evaluation Criteria In Solid Tumors (RECIST). Secondary objectives comprised time-to-event endpoints and safety assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.3.0. Patients with heavily pretreated triple-negative (n = 50) or HER2-overexpressing (n = 37) MBC were enrolled. No confirmed responses were found in triple-negative MBC patients, with median progression-free survival (PFS) of 2.2 months (95 % CI 1.3-2.7 months). Confirmed partial responses occurred in 4 of 34 evaluable HER2-overexpressing MBC patients (ORR = 12 %; 95 % CI 3-27 %) and lasted a median of 12.5 months (95 % CI, 6.2-14.7 months); median PFS was 3.8 months (95 % CI, 1.8-5.5 months). Most trabectedin-related adverse events were mild or moderate, and the most frequent were fatigue, nausea, vomiting, constipation, and anorexia. Severe neutropenia and transaminase increases were non-cumulative and transient and were mostly managed by infusion delays or dose reductions. Single-agent trabectedin is well tolerated in aggressive MBC and has moderate activity in HER2-overexpressing tumors. Further studies are warranted to evaluate trabectedin combined with HER2-targeted treatments in this subtype.

Soybean farming has brought economic development to parts of South America, as well as environmental hopes and concerns. A substantial hope resides in the decoupling of Brazil's agricultural sector from deforestation in the Amazon region, in which case expansive agriculture need not imply forest degradation. However, concerns have also been voiced about the potential indirect effects of agriculture. This article addresses these indirect effects forthe case of the Brazilian Amazon since 2002. Our work finds that as much as thirty-two percent of deforestation, or the loss of more than 30,000 km 2 of Amazon forest, is attributable, indirectly, to Brazil's soybean sector. However, we also observe that the magnitude of the indirect impact of the agriculture sector on forest loss in the Amazon has declined markedly since 2006. We also find a shift in the underlying causes of indirect land use change in the Amazon, and suggest that land appreciation in agricultural regions has supplanted farm expansions as a source of indirect land use change. Our results are broadly congruent with recent work recognizing the success of policy changes in mitigating the impact of soybean expansion on forest loss in the Amazon. However, they also caution that the soybean sector may continue to incentivize land clearings through its impact on regional land markets.

Fansidar® (sulfadoxine/pyrimethamine) and Coartem® (artemether/lumefantrine) are drugs that destroy malarial parasites and also produce free radicals which cause hemolysis of malaria-parasitized erythrocytes. This study investigated the effect of these drugs on the viscoelasticity of erythrocytes of ten healthy female subjects using the BioProfiler. The concentration for each of the two drugs were determined based on the therapeutic dose as normal, half the therapeutic dose as low and double the therapeutic dose as high. For Fansidar®, the concentrations were 0.15/0.01 mg/ml (low), 0.30/0.02 mg/ml (normal) and 0.60/0.04 mg/ml (high) based on the adult therapeutic dose of 1500/75 mg of sulfadoxine/pyrimethamine in the drug combination. For Coartem®, the concentrations were 0.03/0.19 mg/ml (low), 0.06/0.38 mg/ml (normal) and 0.12/0.76 mg/ml (high) based on the adult therapeutic dose of 320/1920 mg of artermether/lumefantrine in the drug combination. There was a statistically significant (p < 0.05) decrease in viscosity, elasticity and relaxation time with Coartem® at normal and high doses. Fansidar® also showed significant (p < 0.05) reductions in these parameters only in the high dose. This suggests that Coartem® generated significant free radicals at normal and high doses, with Fansidar® only in the high dose, resulting in increased hemolysis and ultimately reduced viscoelasticity.

Garrett et al 's recent letter (2013 Environ. Res. Lett. 8 044055) shows the trade value of Brazil's production of non-genetically modified (GM) crops, and argues that production for this niche market laid the foundation for the expansion of a variety of non-GM and eco-certification systems. We argue that the conditions underlying the development and perpetuation of the non-GM certification systems are transient. The expansion of soy production has dampened the conditions that promoted the dominance of non-GM soy in the region. The state at the heart of the production of conventional soy, Mato Grosso, already has transitioned to almost 90% GM soy in the most recent agricultural season. The continued viability of eco-certification systems depends on strengthening institutions on the demand side, and ensuring farm-level costs on the supply side match price premiums reaching the farm level.

Introduction: A multicenter, open-label phase III study was conducted to test whether sunitinib plus paclitaxel prolongs progression-free survival (PFS) compared with bevacizumab plus paclitaxel as first-line treatment for patients with HER2(-) advanced breast cancer., Patients and Methods: Patients with HER2(-) advanced breast cancer who were disease free for ≥ 12 months after adjuvant taxane treatment were randomized (1:1; planned enrollment 740 patients) to receive intravenous (I.V.) paclitaxel 90 mg/m(2) every week for 3 weeks in 4-week cycles plus either sunitinib 25 to 37.5 mg every day or bevacizumab 10 mg/kg I.V. every 2 weeks. [corrected], Results: The trial was terminated early because of futility in reaching the primary endpoint as determined by the independent data monitoring committee during an interim futility analysis. At data cutoff, 242 patients had been randomized to sunitinib-paclitaxel and 243 patients to bevacizumab-paclitaxel. Median PFS was shorter with sunitinib-paclitaxel (7.4 vs. 9.2 months; hazard ratio [HR] 1.63 [95% confidence interval (CI), 1.18-2.25]; 1-sided P = .999). At a median follow-up of 8.1 months, with 79% of sunitinib-paclitaxel and 87% of bevacizumab-paclitaxel patients alive, overall survival analysis favored bevacizumab-paclitaxel (HR 1.82 [95% CI, 1.16-2.86]; 1-sided P = .996). The objective response rate was 32% in both arms, but median duration of response was shorter with sunitinib-paclitaxel (6.3 vs. 14.8 months). Bevacizumab-paclitaxel was better tolerated than sunitinib-paclitaxel. This was primarily due to a high frequency of grade 3/4, treatment-related neutropenia with sunitinib-paclitaxel (52%) precluding delivery of the prescribed doses of both drugs., Conclusion: The sunitinib-paclitaxel regimen evaluated in this study was clinically inferior to the bevacizumab-paclitaxel regimen and is not a recommended treatment option for patients with advanced breast cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The organic component of the avian eggshell can be divided into 3 portions, the shell membranes, the matrix and the cuticle. These have been well characterised in the chicken but little has been published with regard to the ostrich (Struthio camelus). A number of recent studies have indicated that the cause of intra-shell embryonic deaths in the ostrich is similar to intra-shell embryonic deaths that occur in the chicken. These deaths in the chicken are associated with the loss of or damage to the waxy cuticle and other organic components of the eggshell, which is reported to be absent in the ostrich eggshell. In this study, preliminary morphological and histochemical analyses, at the level of the light and electron microscope, have characterised the various organic components of the ostrich eggshell. The results of the histochemical and electron microscopical analyses suggest that there may only be 1 shell membrane in this species, which could play a major role in the limitation of bacterial penetration to the embryonic chamber The shell membrane has a distinct elemental profile as determined by EDS analysis. The matrix is shown to decrease in mesh size from the mammillary layer to the vertical crystal layer. The closer packing of the mesh may indicate the presence of a morphologically discernible termination signal to calcification or the remnants of an evolutionary calcified cuticle. The matrix of the pores may also form a defensive barrier against bacterial invasion, which could be damaged as a result of dipping the eggs before incubation.

1. The histochemistry and ultrastructure of pheasant eggs were compared on the basis of blue or brown shell colour. 2. Differences in lectin histochemistry of the outer shell membrane calcification surface indicate a biochemical disruption of the calcification sites in blue eggs. 3. Significant differences were observed in all aspects of eggshell ultrastructure with blue eggs having thinner shells with structural defects. 4. Poor hatchability of blue eggs may reflect high rates of weight loss associated with a defective eggshell.

Change in medical curricula is a worldwide trend. Concomitant with this is a change in the role of the microscope and its contribution to a student's career. In this questionnaire-based study the perceptions of medical, dental and veterinary students to microscopy and alternative forms of histology tuition, as well as the role of microscopy in their future careers, was assessed. Veterinary students indicate a strong preference for the microscope and microscopy training due to the importance of the microscope in their chosen career, whilst medical and dental students are somewhat ambivalent. However, the students would not choose to eliminate the microscope entirely from their studies.

The ultrastructure of the eggshell of the domestic hen has been well researched and structural studies of other avian species, such as the ostrich, often base their interpretation of egg shell structure on that of the chicken. In the ostrich, lowered hatchability and hatching trauma may be due to shell ultrastructural abnormalities. In the present study the ultrastructure of the calcified portion, and the outer shell membrane (OSM), of domesticated ostrich eggshells was investigated using standard electron microscopic techniques. Transmission and scanning electron microscopy studies demonstrated intimate contact between cup-shaped structures present on the OSM and the mammillary layer of the calcified portion of the shell. The initial calcium carbonate growth of the calcified shell was of a dendritic nature with nucleation sites on the surface of the cup's contents. The dendritic growth gave way to a more randomly-orientated, smaller crystallite growth structure, which changed in form as it neared the vertical crystal layer (VCL). The VCL is described as being both amorphous and 'crumbly' depending on the plane of fracture. These observations suggest that firstly, initial calcification is contained within the cups and is then directed outwards to form the shell and that secondly, the VCL may contain an evolutionary, calcified cuticular layer. These observations serve as a baseline for studies investigating the effect of shell structure and strength on hatchling trauma and the influence of maternal diet.

Objective: To determine the incidence of Rotavirus infection in children under five years of age presenting with diarrhoea., Design: Cross sectional study., Setting: Mapulaneng Hospital, Bushbuckridge, Republic of South Africa., Subjects: 50 children under five years of age presenting with diarrhoea., Main Outcome Measures: Rotavirus seroprevalence., Results: Out of 50, 24 (48%) had detectable Rotavirus particles in their stools. The highest incidence of infection was observed among the seven to 12 months age group. Out of the 245 positive subjects 22 (91.7%) were breast fed., Conclusion: This study shows that diarrhoea in children under five years of age is probably caused by Rotavirus in Bushbuckridge. We therefore recommend that all children presenting with diarrhoea should be screened for Rotavirus.

The aim of this study was to determine whether the ultrastructure of the non-neoplastic myometrial portion (host myometrium) of fibromyomatous uteri is normal or abnormal when compared to that of fibromyomata and normal myometria. Myometrial samples from 23 normal and 54 fibromyomatous uteri were examined at the ultrastructural level using standard electron microscopy techniques. Ultrastructural abnormalities of certain cellular organelles were noted in myocytes of fibromyomata but not in those of normal or host myometria. The sarcolemmal dense bands of host myometrial myocytes were of significantly greater length than those of normal myometria, but not significantly different to those of fibromyomata. Consequently, the numbers of caveolae in host myometria and fibromyomata are conceivably decreased in comparison to normal myometria. Host myometria can be, therefore, considered to be structurally abnormal. The specific structural abnormality noted may affect calcium metabolism in these tissues by causing a decrease in the cellular calcium extrusion mechanism and thus raising intracellular calcium concentrations. Such an abnormality may provide an answer, in terms of contraction abnormalities, for the unexplained infertility that occurs in a small percentage of symptomatic myomatous patients.

The enzyme adenylyl cyclase (AC) plays a pivotal role in smooth muscle relaxation. Biochemical evidence suggests that AC is predominantly located in the outer layers of the myometrium; however, neither immunocytochemical nor histochemical studies have been undertaken to demonstrate the specific cellular distribution of the enzyme in this tissue. As part of an ongoing study of the human myometrium, a polyclonal antibody against types V and VI AC was used to detect the presence of these isoforms in sections of formalin-fixed, wax-embedded myometrial tissue. A positive reaction was seen in the cytoplasm of the smooth muscle cells with the midmyometrial area having the greatest number of positive cells, when compared to the subserosal and subendometrial areas. It is hypothesized that AC isoform type VI is the predominant isoform present in the myometrium and that the percentage distribution of positive cells reflects the area of highest myometrial activity during parturition.

The histochemistry technique for localizing adenylate cyclase has been developed over the past two decades. Early efforts were directed at overcoming the criticism of the lead capture technique, the inhibition of the enzyme by fixation, and problems associated with the substrate. The introduction of alternative metal ions, strontium and cerium, offered solutions to the criticism of the lead capture technique. The inhibition of the enzyme by the various fixation methods used has been rarely overcome satisfactorily and the use of non-fixed material during incubation is one of the alternatives that has been suggested. The introduction of adenylate (beta-gamma-methylene) diphosphate as an alternative substrate offers a solution to the problems associated with commercially available adenylyl imidodiphosphate. Although no standard medium or method has been accepted by all researchers, the histochemical technique still has a place in the arsenal of the modern cell biologist. The technique localizes the active enzyme, as opposed to the protein, active and nonactive, by immunocytochemistry and the precursors of the protein by in situ hybridization methods.

Cosmid probes specific for the major BCR/ABL rearrangement (commercially available probes) were employed by us to evaluate 134 patients with the clinical diagnosis of chronic myelocytic leukemia (CML). The following represent our main observations: 1) No significant statistical difference regarding a false positive fusion signal was seen in the distribution pattern between the Ph negative (-) cases (110) and the normal controls (3.23 +/- 1.97 vs 2.8 +/- 1.92, respectively). 2) The mean percentage of cells with a positive fusion signal in the Ph positive (+) CML cases at presentation was 70 +/- 12.3 in bone marrow samples (12 cases) and 45 +/- 12.4 in blood samples (3 cases). 3) A significant discrepancy was seen between the interphase FISH and cytogenetics data in the monitoring of four out of eight patients post-therapy. The clinical significance of this observation needs to be clarified. 4) Three Ph(-) patients with significant leukocytosis had closely adjacent but not fused signals (20%, 16%, and 20% of cells, respectively, vs. the control: 4%). This may indicate a temporal and spatial association between chromosomes 9 and 22 prior to the BCR/ABL rearrangement (Ph chromosome formation).

The ventral epidermis of the frog Rana fuscigula is a typical tight epithelium which acts as a functional syncytium in the active transepithelial transport of sodium ions. Transport across this epithelium is regulated by cyclic adenosine monophosphate (cAMP). This study was undertaken to formulate an optimal protocol for the localization, within this epithelium, of adenylate cyclase; the enzyme involved in cAMP synthesis. The ventral epithelium of R. fuscigula was collagenase treated and processed using five different fixation/incubation protocols. The components of a basal incubating medium were modified by changing the localizing agent, adding adenylate cyclase stimulators and inhibitors of other enzymes. Control incubations undertaken included a) leaving the substrate out, b) prior heat inactivation of the enzyme, c) specific blockers and d) incubation for alkaline phosphatase as an alternative enzyme. The samples were then processed for electron microscopy. Localization of adenylate cyclase was best obtained, when fixing the tissue after incubation for 30 min at 37 degrees C. The medium that gave the best and most consistent localization contained magnesium chloride; as a required ion, theophylline, dithiothreitol, ouabain, levamisole; as enzyme inhibitors, forskolin; as a stimulator of adenylate cyclase, lead nitrate; as the capture agent and column purified adenylyl imidodiphosphate; as the substrate.

A modified cytochemical technique with 5'-adenylylimidodiphosphate as substrate, was used to examine the distribution of adenylate cyclase in cells comprising the transepithelial Na+ transport pathway in isolated frog skin epithelium. Particular attention was paid to the effects of fixation on the activity and localization of adenylate cyclase. Fixation in glutaraldehyde alone or in combination with paraformaldehyde reduced the amount of reaction product, while better results were obtained using unfixed tissues. Optimum results were obtained following stimulation of adenylate cyclase with forskolin and in the presence of specific metabolic inhibitors. Adenylate cyclase was localized in the basolateral membranes of the principal cells which constitute a functional syncytium for Na+ transport and was absent from the apical membranes of the outermost granulosum cells. This distribution is consistent with the transepithelial Na+ transport model and defines the functional morphology of the cells involved in Na+ transport across frog skin. The results are compatible with the process of Na+ re-absorption across other epithelial cells, verifying that frog skin is a convenient model-tissue to study Na+ transport mechanisms. Adenylate cyclase was also found in membranes of the mitochondria-rich cells, a minor and parallel Na+ transporting pathway.

We have examined hair bulb and skin melanocytes of rufous albinos from Southern Africa to further characterize this form of albinism. In the skin melanocytes we find both eumelanosomes and pheomelanosomes at various stages of melanization and, in addition, there appeared to be many aberrant incompletely melanized melanosomes. On average, rufous melanosomes are 30% smaller than normal black skin melanosomes. In the keratinocytes, the melanosomes are packaged into distinct aggregations, whereas in normal black skin, they occur singly. We suggest that the reddish skin color of these albinos is a consequence of an increase in the pheomelanin synthesis resulting in a raised pheomelanin/eumelanin ratio and that the aggregation of melanosomes results in a skin color slightly lighter than normal. In hair bulb melanocytes, only eumelanosomes were seen and these were mostly incompletely melanized. These findings correlate with our visual observations that the hair color of Southern African albinos is very pale (light brown or ginger). Based on our observations, we speculate on the possible cause of rufous albinism.

Six strains of an undescribed, leaf-borne species of the genus Sporobolomyces were recovered. A description of the new species, Sporobolomyces phylladus, is given.

Four strains of an undescribed, soil-borne species of the genus Myxozyma were recovered. A description of the new species, Myxozyma kluyveri, and a key to the species accepted in the genus are given.

A new, insect-associated species of the emended genus Sterigmatomyces, St. wingfieldii, is described. A key to the emended genus is given.

The efficacy of secobarbital sodium plus chlorpromazine (SC) in the prevention of cisplatin induced emesis was compared to the combination of metoclopramide, diphenhydramine, and dexamethasone (MDD). Twenty-three patients were entered onto protocol. Eighteen were evaluable. Good to excellent antiemetic prophylaxis was obtained in 72% with MDD versus 17% with SC (P less than 0.01). Sedation and anticholinergic side effects were more common with SC. Extrapyramidal reactions were more commonly seen with MDD. Significantly more patients preferred the combination of metoclopramide, diphenhydramine, and dexamethasone (P less than 0.05).

A strain of an undescribed, leaf-borne species of the genus Sporobolomyces was recovered. A description of the new species, Sporobolomyces kluyveri-nielii, is given.

Three strains of an undescribed, leaf-borne species of the genus Sporobolomyces were recovered. A description of the new species, Sporobolomyces phyllomatis, is given.