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The present survey study examines whether satisfaction with health care predicts breast cancer patients' psychological adjustment and esteem for their communities. Forty-nine women undergoing radiation therapy for breast cancer completed measures of satisfaction with health care, psychological well-being, community esteem, depression, perceived health status, and demographics. As predicted, the results showed that breast cancer survivors' satisfaction with their health care was predictive of their psychological well-being even when controlling for relevant variables such as depression and health status. Also, breast cancer survivors' satisfaction with their health care predicted their level of community esteem. These findings are discussed in terms of their implications for the psychological adjustment of breast cancer survivors. doi:10.1300/J077v25n02_04. [ABSTRACT FROM AUTHOR]

Objective: There is currently a wide range of cleansing and irrigation solutions available for wounds, many of which contain antimicrobial agents. The aim of this study was to assess the safety of HydroClean Solution (HARTMANN, Germany), a polyhexamethylene biguanide (PHMB)-containing irrigation solution, in a standard cytotoxicity assay, and to assess its effect in a three-dimensional (3D) full-thickness model of human skin., Method: A number of commercially available wound cleansing and irrigation solutions, including the PHMB-containing irrigation solution, were tested in a cytotoxicity assay using L929 mouse fibroblasts (ISO 10993-5:2009). The PHMB-containing irrigation solution was then assessed in an in vitro human keratinocyte-fibroblast 3D full-thickness wounded skin model to determine its effect on wound healing over six days. The effect of the PHMB-containing irrigation solution on tissue viability was measured using a lactate dehydrogenase (LDH) assay, and proinflammatory effects were measured using an interleukin-6 (IL-6) production assay., Results: The PHMB-containing irrigation solution was shown to be equivalent to other commercially available cleansing and irrigation solutions when tested in the L929 fibroblast cytotoxicity assay. When assessed in the in vitro 3D human full-thickness wound healing model, the PHMB-containing irrigation solution treatment resulted in no difference in levels of LDH or IL-6 when compared with levels produced in control Dulbecco's phosphate-buffered saline cultures. There was, however, a pronounced tissue thickening of the skin model in the periwound region., Conclusion: The experimental data presented in this study support the conclusion that the PHMB-containing irrigation solution has a safety profile similar to other commercially available cleansing and irrigation solutions. Evidence also suggests that the PHMB-containing irrigation solution does not affect tissue viability or proinflammatory cytokine production, as evidenced by LDH levels or the production of IL-6 in a 3D human full-thickness wound healing model. The PHMB-containing irrigation solution stimulated new tissue growth in the periwound region of the skin model.

Objective: Antiseptics are widely used in wound management to prevent or treat wound infections, and have been shown to have antibiofilm efficacy. The objective of this study was to assess the effectiveness of a polyhexamethylene biguanide (PHMB)-containing wound cleansing and irrigation solution on model biofilm of pathogens known to cause wound infections compared with a number of other antimicrobial wound cleansing and irrigation solutions., Method: Staphylococcus aureus and Pseudomonas aeruginosa single-species biofilms were cultured using microtitre plate and Centers for Disease Control and Prevention (CDC) biofilm reactor methods. Following a 24-hour incubation period, the biofilms were rinsed to remove planktonic microorganisms and then challenged with wound cleansing and irrigation solutions. Following incubation of the biofilms with a variety of concentrations of the test solutions (50%, 75% or 100%) for 20, 30, 40, 50 or 60 minutes, remaining viable organisms from the treated biofilms were quantified., Results: The six antimicrobial wound cleansing and irrigation solutions used were all effective in eradicating Staphylococcus aureus biofilm bacteria in both test models. However, the results were more variable for the more tolerant Pseudomonas aeruginosa biofilm. Only one of the six solutions (sea salt and oxychlorite/NaOCl-containing solution) was able to eradicate Pseudomonas aeruginosa biofilm using the microtitre plate assay. Of the six solutions, three (a solution containing PHMB and poloxamer 188 surfactant, a solution containing hypochlorous acid (HOCl) and a solution containing NaOCl/HOCl) showed increasing levels of eradication of Pseudomonas aeruginosa biofilm microorganisms with increasing concentration and exposure time. Using the CDC biofilm reactor model, all six cleansing and irrigation solutions, except for the solution containing HOCl, were able to eradicate Pseudomonas aeruginosa biofilms such that no viable microorganisms were recovered., Conclusion: This study demonstrated that a PHMB-containing wound cleansing and irrigation solution was as effective as other antimicrobial wound irrigation solutions for antibiofilm efficacy. Together with the low toxicity, good safety profile and absence of any reported acquisition of bacterial resistance to PHMB, the antibiofilm effectiveness data support the alignment of this cleansing and irrigation solution with antimicrobial stewardship (AMS) strategies.

Bacterial toxins are thought to play a role in delayed wound healing in critically colonised and infected wounds. Endotoxins are released from Gram-negative bacteria when they are lysed by host phagocytic cells during an immune response, or by antimicrobial agents, potentially leading to a detrimental effect on the host tissues. Endotoxins can affect all aspects of the wound healing process, leading to delayed healing and contributing to wound chronicity. Release of endotoxins by bacteria can also have serious systemic effects (for example, septic shock) that can lead to high levels of patient mortality. This review summarises the role and implications on wound healing of bacterial endotoxins, describing the impact of endotoxins on the various phases of the wound healing response. There is a paucity of in vivo/clinical evidence linking endotoxins attributed to a wound (via antibiotic treatment) or their release from infecting bacteria with parameters of delayed wound healing. Future work should investigate if this link is apparent and determine the mechanism(s) by which such detrimental effects occur, offering an opportunity to identify possible treatment pathways. This paper describes the phenomenon of antimicrobial-induced endotoxin release and summarises the use of wound dressings to reduce wound bioburden without inducing microbial death and subsequent release of endotoxins, thus limiting their detrimental effects.

Ventilation is of primary concern for maintaining healthy indoor air quality and reducing the spread of airborne infectious disease, including COVID-19. In addition to building-level guidelines, increased attention is being placed on room-level ventilation. However, for many universities and schools, ventilation data on a room-by-room basis are not available for classrooms and other key spaces. We present an overview of approaches for measuring ventilation along with their advantages and disadvantages. We also present data from recent case studies for a variety of institutions across the United States, with various building ages, types, locations, and climates, highlighting their commonalities and differences, and examples of the use of this data to support decision making., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The COVID-19 pandemic increased the demand for indoor air cleaners. While some commercial electronic air cleaners can be effective in reducing primary pollutants and inactivating bioaerosol, studies on the formation of secondary products from oxidation chemistry during their use are limited. Here, we measured oxygenated volatile organic compounds (OVOCs) and the chemical composition of particles generated from a hydroxyl radical generator in an office. During operation, enhancements in OVOCs, especially low-molecular-weight organic acids, were detected. Rapid increases in particle number and mass concentrations were observed, corresponding to the formation of highly oxidized secondary organic aerosol (SOA) (O:C ∼ 1.3), with an enhanced signal at m / z 44 (CO 2 + ) in the organic mass spectra. These results suggest that organic acids generated during VOC oxidation contributed to particle nucleation and SOA formation. Nitrate, sulfate, and chloride also increased during the oxidation without a corresponding increase in ammonium, suggesting organic nitrate, organic sulfate, and organic chloride formation. As secondary species are reported to have detrimental health effects, further studies should not be limited to the inactivation of bioaerosol or reduction of particular VOCs, but should also evaluate potential OVOCs and SOA formation from electronic air cleaners in different indoor environments., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Objective: To assess the efficacy of five silver-containing gelling fibre wound dressings against single-species and multispecies biofilms using internally validated, UKAS-accredited in vitro test models., Method: Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans single- and multispecies biofilms were cultured using Centres for Disease Control (CDC) biofilm reactors and colony drip flow reactors (CDFR). Following a 72 hour incubation period, the substrates on which biofilms were grown were rinsed to remove planktonic microorganisms and then challenged with fully hydrated silver-containing gelling fibre wound dressings. Following dressing application for 24 or 72 hours, remaining viable organisms from the treated biofilms were quantified., Results: In single-species in vitro models, all five antimicrobial dressings were effective in eradicating Staphylococcus aureus and Pseudomonas aeruginosa biofilm bacteria. However, only one of the five dressings (Hydrofiber technology with combination antibiofilm/antimicrobial technology) was able to eradicate the more tolerant single-species Candida albicans biofilm. In a more complex and stringent CDFR biofilm model, the hydrofiber dressing with combined antibiofilm/antimicrobial technology was the only dressing that was able to eradicate multispecies biofilms such that no viable organisms were recovered., Conclusion: Given the detrimental effects of biofilm on wound healing, stringent in vitro biofilm models are increasingly required to investigate the efficacy of antimicrobial dressings. Using accredited in vitro biofilm models of increasing complexity, differentiation in the performance of dressings with combined antibiofilm/antimicrobial technology against those with antimicrobial properties alone, was demonstrated.

Objective: To assess the in vitro antimicrobial performance of a non-medicated hydro-responsive wound dressing (HRWD) on the sequestration and killing of wound relevant microorganisms found on the World Health Organization (WHO) priority pathogens list., Methods: Suspensions of Pseudomonas aeruginosa, Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) were placed on petri dishes. Dressings were each placed on top, incubated for 30 minutes and then removed from the inoculated petri dish. The surface of the dressings previously in contact with the bacterial suspensions were placed directly onto a tryptone soy agar (TSA) plate and incubated for 24 hours. Dressings were then removed from the TSA plate and the level of bacterial growth on the plates was assessed. Sequestered microorganism viability was assessed using LIVE/DEAD viability kits and visualisation by epifluorescence., Results: Our results indicated that HRWDs sequester and retain Pseudomonas aeruginosa, Acinetobacter baumannii and MRSA within the dressing. Non-medicated HRWDs containing bound PHMB (polyhexamethylene biguanide, HRWD+PHMB) killed the microorganisms sequestered within the dressing matrix., Conclusion: These data suggest that non-medicated HRWD+PHMB is an effective against WHO priority pathogens and promoting goal of antimicrobial stewardship in wound care.

Antibacterial copper-hydroxyapatite (Cu-HA) composite coatings on titanium were synthesized using a novel process consisting of two consecutive electrochemical reactions. In the first stage, HA nanocrystals were grown on titanium using the cathodic electrolytic synthesis. The HA-coated titanium was then used as the cathode in a second reaction stage to electrochemically reduce Cu 2+ ions in solution to metallic Cu nanoparticles. Reaction conditions were found that result in nanoscale Cu particles growing on the surface of the HA crystals. The two-stage synthesis allows facile control of copper content in the HA coatings. Antibacterial activity was measured by culturing Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) in the presence of coatings having varying copper contents. The coatings displayed copper concentration-dependent antibacterial activity against both types of bacteria, likely due to the slow release of copper ions from the coatings. The observation of antibacterial activity from a relatively low loading of copper on the bioactive HA support suggests that multifunctional implant coatings can be developed to supplement or supplant prophylactic antibiotics used in implant surgery that are responsible for creating resistant bacteria strains.

Objective: The aim of this in vitro study was to investigate the transfer of viable Pseudomonas aeruginosa biofilm microorganisms following treatment with debridement tools., Method: The level of viable biofilm microorganisms transferred by debridement tools was compared following treatment that reflected the clinical practice of each product., Results: A significant level of microorganism transfer was seen in response to the mechanical debridement tool. Minimal transfer of microorganisms was seen when in vitro-established biofilms were treated with hydroresponsive wound dressing + polyhexamethylene biguanide (HRWD+PHMB, HydroClean plus). Less Pseudomonas aeruginosa was recovered from explants exposed to dressings compared with those exposed to debridement tools suggesting that there was less transfer of bacteria by dressings., Conclusion: The reduced transfer of viable microorganisms by HRWD+PHMB may be the result of significant binding and retention of microbes by the superabsorbent polymer within the dressing, together with enhanced sequestered bacterial killing within the dressing by polymer-bound PHMB. The high levels of microbial transfer/transmission seen for debridement tools suggests that, in the clinical setting, a significant level of bacterial spread over the wound surface and/or surrounding skin by these cleansing tools is likely.

Objective: The objective of this study was to evaluate the ability of a non medicated, hydro-responsive wound dressing (HRWD) to effectively aid in the removal of bacteria known to reside (and cause infections) within the wound environment., Method: A series of in vitro studies were undertaken using Staphylococcus aureus and Pseudomonas aeruginosa biofilms to evaluate the capabilities of the HRWD to disrupt and disperse biofilms., Results: Biofilms can be broken up and dispersed by HRWD and both Staphylococcus aureus and Pseudomonas aeruginosa numbers can be reduced by a greater than log 2 reduction in the presence of HRWD. However, no 'active' agents are released into the wound environment that have an antimicrobial effect., Conclusion: Overall, these studies have shown that this dressing acts as an effective debridement tool, and there are other 'physical' antimicrobial mechanisms impacting bacterial residence. These mechanisms include 1) breaking up and dispersal of biofilms so that the resultant planktonic bacteria are absorbed by the dressing and then 2) sequestered and retained (trapped) within its matrix. Additionally, when PHMB (polyhexamethylene biguanide) is bound within the dressing core but is not released into the wound environment there is the added antimicrobial effect resulting from 3) physical contact with this antiseptic component. Reducing the pathogenicity of the bacteria still further is the dressings ability to 4) absorb and sequester the damaging proteases released by pathogenic bacteria.

Background: The purpose of this study is to determine prognostic factors and survival in patients who present with combined small-cell lung cancer (SCLC)., Methods: A retrospective review of combined SCLC histology in patients treated between1995-2010 was undertaken. Demographics, diagnostic information, disease characteristics, treatment modality, and survival were captured. Survival estimates were performed using Kaplan Meier analysis. Statistical significance was defined as P < 0.05., Results: Forty-one patients were identified, and 35 records were available for analysis. Median age at diagnosis was 68 (range 50-85). The study included 20 (57%) women and 15 (43%) men; and 94% had a current or former history of smoking. Histology was SCLC/large cell carcinoma not otherwise specified in 28 (80%), and SCLC/adenocarcinoma or SCLC/squamous cell carcinoma in seven (20%). Cardiac or pulmonary comorbidities were present in 80% of patients, and 24 patients had metastatic disease at presentation. Twenty-eight patients received treatment of chemotherapy (n = 24), cranial radiotherapy (n = 5), or thoracic radiotherapy (n = 7). Staging was as follows: stage I-III (n = 11), stage IV (n = 24). Median survival was 15.4 months (range <1-53 months) and 3.4 months (range <1-21.9 months) for American Joint Committee on Cancer (AJCC) stage I-III and stage IV, respectively. Estimated overall six and 12 month survival was 82%, 55%, 37%, and 17% for stage I-III and stage IV, respectively. An improved overall survival rate was found for patients with an Eastern Cooperative Oncology Group performance status of <2, and no weight loss (P < 0.05)., Conclusion: Akin to SCLC, advanced stage combined SCLC portends a poor prognosis. Perhaps novel chemotherapeutic drugs or targeted agents may improve outcomes for future patient populations.

Purpose. Arteriovenous malformations (AVMs) in the basal ganglia and thalamus have a more aggressive natural history with a higher morbidity and mortality than AVMs in other locations. Optimal treatment-complete obliteration without new neurological deficits-is often challenging. We present a patient with a large bilateral basal ganglia and thalamic AVM successfully treated with hypofractionated stereotactic radiosurgery (HFSRS) with intensity modulated radiotherapy (IMRT). Methods. The patient was treated with hypofractionated stereotactic radiosurgery to 30 Gy at margin in 5 fractions of 9 static fields with a minimultileaf collimator and intensity modulated radiotherapy. Results. At 10 months following treatment, digital subtraction angiography showed complete obliteration of the AVM. Conclusions. Large bilateral thalamic and basal ganglia AVMs can be successfully treated with complete obliteration by HFSRS with IMRT with relatively limited toxicity. Appropriate caution is recommended.

Horse wounds have a high risk of becoming infected due to their environment. Infected wounds harbour diverse populations of microorganisms, however in some cases these microorganisms can be difficult to identify and fail to respond to antibiotic treatment, resulting in chronic non-healing wounds. In human wounds this has been attributed to the ability of bacteria to survive in a biofilm phenotypic state. Biofilms are known to delay wound healing, principally due to their recalcitrance towards antimicrobial therapies and components of the innate immune response. This study describes the presence of bacterial biofilms within equine wounds. Thirteen 8-mm diameter tissue samples were collected from (n=18) chronic wounds. Following histological staining, samples were observed for evidence of biofilms. Fifty one wounds and control skin sites were sampled using sterile swabs. Control skin sites were on the uninjured side of the horse at the same anatomical location as the wound. The isolated bacteria were cultured aerobically and anaerobically. The biofilm forming potential of all the isolated bacteria was determined using a standard crystal violet microtitre plate assay. Stained tissue samples provided evidence of biofilms within 61.5% (8 out of 13) equine wounds. In total 340 bacterial isolates were identified from all the equine wound and skin samples. Pseudomonas aeruginosa and Enterococcus faecium were the most predominantly isolated bacterial species from equine wound and skin samples respectively. Staphylococcus was the most commonly isolated genus in both environments. Bacteria cultured from chronic and acute wounds showed significantly (P<0.05) higher biofilm forming potential than bacteria isolated from skin. This paper highlights preliminary evidence supporting the presence of biofilms and a high microbial diversity in equine chronic wounds. The presence of biofilms in equine wounds partly explains the reluctance of many lower limb wounds to heal. Non-healing limb wounds in horses are a well documented welfare and economic concern. This knowledge can be used to shape future treatments in order to increase the healing rate and decrease the costs and suffering associate with equine wounds., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Fifty patients with histologically confirmed stage III breast cancer were enrolled in this study of doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 intravenously infused over 1 hour every 21 days with granulocyte colony-stimulating factor for 4 cycles. This was followed by surgery (mastectomy or lumpectomy) and 4 more cycles of doxorubicin/docetaxel postoperatively, then radiation and tamoxifen as indicated. Forty-six of the 50 patients (92%) completed neoadjuvant chemotherapy, and 38 patients (76%) completed adjuvant chemotherapy. Clinical response (defined as > 50% decrease in size of tumor) was achieved after 2 cycles in 37 patients (74%) and after 4 cycles in 42 of the 46 patients (91%) who finished neoadjuvant chemotherapy. Pathologic complete response (pCR; no pathologic invasive cancer) at the primary site was obtained in 7 of 46 patients (15%); 11 had no residual gross disease but did have microscopic persistence or microscopic complete response (mCR), for a combined pCR and mCR of 18 of 46 patients (39%). No treatment-related deaths occurred, but 3 patients died during treatment: 1 from progressive disease, 1 from a gastrointestinal bleeding, and 1 from unexplained sudden cardiac death. Dose-limiting toxicities were hematologic (grade 3 neutropenia in 5 patients and grade 4 in 23 patients). Congestive heart failure developed in 4 of 50 patients (8%), with a mean decrease in left ventricular ejection fraction (LVEF) of 20% in affected patients and 1 asymptomatic decrease in LVEF of 25%. At last follow-up, 10 patients had died of progressive disease, and 1 each from sudden cardiac death and lower gastrointestinal bleeding. In locally advanced breast cancer, neoadjuvant doxorubicin/docetaxel is a very active regimen that achieved pCR of 15% and a combined pCR and mCR of 39%, for an overall clinical response rate of 91%. Adjuvant chemotherapy was complicated by dropouts and congestive heart failure. This regimen should be used with close monitoring of cardiac function.

Background: Sphincter-sparing alternatives to abdominoperineal resection (APR) in the treatment of rectal cancer often are underused out of concern for inadequate distal margins and local failure. The present study addresses whether sphincter-sparing techniques with distal margins < or = 1 cm adversely influence oncological outcome in patients given preoperative chemoradiotherapy., Methods: Thirty-seven patients with rectal cancer < or = 8 cm from the anal verge were enrolled in the study. Preoperative external beam radiotherapy (5400 Gy) was administered together with continuous infusion of 5-fluorouracil (300 mg/m2/day). Surgical resection was performed in 36 patients with pathological assessment of tumor response and margins. Patients with sphincter-sparing resection and distal margins > 1 cm or < or = 1 cm and those who underwent APR were compared., Results: Thirty-six patients completed preoperative chemoradiotherapy, with successful sphincter-preservation in 28 patients. At a median follow-up of 33 months, there were 12 recurrences overall, which included 11 distant failures and four pelvic failures. Disease-free survival (DFS) was not different between those who had an APR compared with sphincter-sparing resection with distal margins < or = 1 cm. DFS was worse (P < .02) when radial margins were < or = 3 mm compared with > 3 mm., Conclusions: Sphincter preservation is feasible in more than 75% of patients with tumors < or = 8 cm from the anal verge after preoperative chemoradiotherapy. Sphincter-sparing surgery with distal margins < or = 1 cm can be used without adversely influencing local recurrence or DFS. Limited radial margins (< or = 3 mm), however, are associated with increased disease recurrence.

Both CA1 and dentate gyrus regions of the hippocampal slice exhibit an irreversible loss of synaptic transmission after exposure to in vitro ischemic conditions (buffer without oxygen and glucose). However, after shorter durations of ischemia (8-10 min) the CA1 region shows an irreversible loss of synaptic responses, whereas the dentate gyrus region completely recovers synaptic responses upon reoxygenation. To determine biochemical mechanisms underlying this differential susceptibility, we have examined changes in Ca2+/calmodulin-dependent protein kinase II (CaM-KII) and cyclic AMP-dependent protein kinase activities in homogenates from CA1 and dentate gyrus regions of the hippocampal slice after increasing durations of in vitro ischemia. Time-dependent changes in CaM-KII activities were correlated with changes in electrophysiological responses. CA1 homogenates from slices exposed to 1 min of ischemia showed significant increases in CaM-KII activity, whereas there was no significant change in kinase activity in dentate homogenates after 1 min of ischemia. However, after longer durations of ischemia (5, 10, and 20 min) we found a time-dependent reduction in CaM-KII activity in both CA1 and dentate gyrus regions, whereas no change was detected in cyclic AMP-dependent protein kinase activity. Irreversible depression of CaM-KII activity was seen at shorter durations of ischemia (10 min) in the CA1 region than in dentate region (20 min), which correlated with irreversible effects on synaptic responses. Immunoblot analysis showed that the decrease in CaM-KII activity was not due to degradation of CaM-KII protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiation therapy is an acceptable alternative for the treatment of many malignancies of the skin. Results are gratifying, and long-term sequelae are few. In basal cell and squamous cell carcinomas, radiation is often the best treatment when surgery is expected to cause excessive morbidity or mortality or require extensive reconstruction. Radiation should be considered as first-line treatment for tumors in the midfacial triangle. It is also very acceptable treatment for Kaposi's sarcoma and mycosis fungoides. Radiation can be used for melanoma, although it is not standard first-line therapy. Radiation is probably the treatment of choice for Merkel cell carcinoma.

Oligonucleotide DNA probes were used to determine the distribution of mRNAs encoding the alpha- and beta-subunits of Ca2+/calmodulin-dependent protein kinase type II (CaM-KII) in developing rat brain. The regional and temporal distribution of these mRNAs closely paralleled the distribution and developmental appearance previously reported for their respective protein subunits. alpha-Subunit mRNA was barely detectable in sagittal sections at 4 d postnatal but increased as much as 10-fold in frontal cortex by day 16. beta-Subunit mRNA, on the other hand, was readily detected at 4 d postnatal and changed only slightly during development. Telencephalic structures exhibited the highest levels of CaM-KII mRNA and the brain stem displayed the least. alpha-Subunit mRNA was not observed in cerebellar granule cells and was barely detectable in Purkinje cells, while the beta-mRNA was easily detected in both neuronal types. mRNAs for both alpha- and beta-subunits were present in many neuronal cell bodies; however, only the alpha-subunit mRNA was localized to molecular layers of the hippocampus and lamina I of the frontal cortex. These layers of neuropil are relatively cell sparse and contain extensive dendritic arborizations and synaptic contacts. Since polyribosomes have been observed near hippocampal dendritic spines, the localization of alpha-subunit mRNA to dendrites of pyramidal and dentate granule cells suggests that this subunit is synthesized in situ at postsynaptic sites. The co-localization of translational machinery and high concentrations of CaM-KII in postsynaptic elements suggests an important relationship between alpha-subunit synthesis and the maintenance and plasticity of postsynaptic structures.

Estimates of the gain in survival, if all local failures were eliminated, indicate that many more patients could be cured provided the efficacy of treatment of the primary and regional disease were substantially improved. The expected gain in survival is assumed to be the gain in local control, less the loss due to distant metastases and intercurrent disease among the new local control subjects. The observed incidence of DM among local failure patients may be higher than among local control patients; this excess in incidence of DM is assumed to result from metastases established secondary to the persistent or recurring tumor. A powerful argument that higher local control rates would result in more cured patients is the high incidence of long-term survivors after salvage surgery for local failures. Examples of higher survival associated with more effective local therapy are presented from the literature for medulloblastoma, ependymoma, carcinoma of the oral cavity-oropharynx, carcinoma of the urinary bladder, carcinoma of the prostate and carcinoma of the rectum. For Stage I-II cancer of the breast, the reduction of an already low local failure rate by combining surgery and radiation has a very small impact. For tumors, such as, early stage breast cancer, where the possible decrease in local failure is small and the loss due to DM is high, a demonstrable gain in survival is not likely. The potential increase in number of survivors among the U.S. cancer population, if the primary-regional disease were regularly treated successfully, indicates large gains for patients with cancer of the uterine cervix, oral cavity-oropharynx, ovary, colo-rectum, non-oat cell cancer of lung, prostate cancer, and bladder cancer. These provide powerful bases for aggressive investigation of new approaches to improvement of local-regional therapies.

The influence of estrous cycle and intrastriatal implants of 17 beta-estradiol (17 beta-estradiol). 17 alpha-estradiol (17 alpha-estradiol) or cholesterol on the number of footfaults made by female rats traversing a narrow suspended beam was investigated. Female rats made fewer footfaults on estrus than on other days of the cycle. This was true when testing occurred during either the light or dark phase of the light:dark cycle. Intrastriatal implants of 30% 17 beta-estradiol for 6 hours resulted in a significant improvement in sensorimotor performance as soon as 4 hours after hormone implant and persisting for days. In contrast, intrastriatal implants of either 30% 17 alpha-estradiol or cholesterol had no influence on performance. The extent of hormone diffusion away from the implant cannula was minimal, and the resulting concentration of 17 beta-estradiol in the striatum was less than 10 pg/mg. It is concluded that estradiol has a direct, stereospecific effect in the striatum that influences performance of a skilled motor act in the female rat.