Funding cuts compromise sexual health care.
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Budgets↗
Biomedical subjects
B Anderson
Publications and source records attributed to B Anderson.
Nursing service adapts to changing needs and funding.
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Capital Financing↗
Kohonen neural networks and language.
Kohonen neural networks are a type of self-organizing network that recognizes the statistical characteristics of input datasets. The application of this type of neural network to language theory is demonstrated in the present note by showing three brief applications: recognizing word borders, learning the limited phonemes of one's native tongue, and category-specific naming impairments.
Anomia↗
Prevalent CD8(+) T cell response against one peptide/MHC complex in autoimmune diabetes.
Spontaneous autoimmune diabetes in nonobese diabetic (NOD) mice is the result of a CD4(+) and CD8(+) T cell-dependent autoimmune process directed against the pancreatic beta cells. CD8(+) T cells play a critical role in the initiation and progression of diabetes, but the specificity and diversity of their antigenic repertoire remain unknown. Here, we define the structure of a peptide mimotope that elicits the proliferation, cytokine secretion, differentiation, and cytotoxicity of a diabetogenic H-2K(d)-restricted CD8(+) T cell specificity (NY8.3) that uses a T cell receptor alpha (TCRalpha) rearrangement frequently expressed by CD8(+) T cells propagated from the earliest insulitic lesions of NOD mice (Valpha17-Jalpha42 elements, often joined by the N-region sequence M-R-D/E). Stimulation of splenic CD8(+) T cells from single-chain 8. 3-TCRbeta-transgenic NOD mice with this mimotope leads to preferential expansion of T cells bearing an endogenously derived TCRalpha chain identical to the one used by their islet-associated CD8(+) T cells, which is also identical to the 8.3-TCRalpha sequence. Cytotoxicity assays using islet-derived CD8(+) T cell clones from nontransgenic NOD mice as effectors and peptide-pulsed H-2K(d)-transfected RMA-S cells as targets indicate that nearly half of the CD8(+) T cells recruited to islets in NOD mice specifically recognize the same peptide/H-2K(d) complex. This work demonstrates that beta cell-reactive CD8(+) T cells mount a prevalent response against a single peptide/MHC complex and provides one peptide ligand for CD8(+) T cells in autoimmune diabetes.
Amino Acid Sequence↗
Brain size, head size, and intelligence quotient in monozygotic twins.
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Adult↗
Two mechanisms for the non-MHC-linked resistance to spontaneous autoimmunity.
Genetic susceptibility and resistance to most autoimmune disorders are associated with highly polymorphic genes of the MHC and with non-MHC-linked polygenic modifiers. It is known that non-MHC-linked polymorphisms can override or enhance the susceptibility to an autoimmune disease provided by pathogenic MHC genes, but the mechanisms remain elusive. In this study, we have followed the fate of two highly diabetogenic beta cell-specific T cell receptors (Kd and I-Ag7 restricted, respectively) in NOR/Lt mice, which are resistant to autoimmune diabetes despite expressing two copies of the diabetogenic MHC haplotype H-2g7. We show that at least two mechanisms of non-MHC-linked control of pathogenic T cells operate in these mice. One segregates as a recessive trait and is associated with a reduction in the peripheral frequency of diabetogenic CD8+ (but not CD4+) T cells. The other segregates as a dominant trait and is mediated by IL-4- and TGF-beta1-independent immune suppressive functions provided by lymphocytes that target diabetogenic CD4+ and CD8+ T cells, without causing their deletion, anergy, immune deviation, or ignorance. These results provide explanations as to how non-MHC-linked polymorphisms can override the susceptibility to an autoimmune disease provided by pathogenic MHC haplotypes, and demonstrate that protective non-MHC-linked genes may selectively target specific lymphoid cell types in cellularly complex autoimmune responses.
Amino Acid Sequence↗
Successful prevention of post-transfusion Rh alloimmunization by intravenous Rho (D) immune globulin (WinRho SD).
Alloimmunization to the D blood group antigen following the transfusion of D-positive red blood cells to a D-negative recipient may be prevented in most persons by a prompt and adequate dose of Rho (D) immune globulin (RhIG). Until recently, the only RhIG approved by the US Food and Drug Administration (FDA) for this indication required intramuscular injection, an inconvenient and painful route for the relatively large volume that may be required. We describe the successful prevention of Rh alloimmunization following the unintentional transfusion of D-positive red blood cells to a D-negative infant by the intravenous infusion of WinRho SD, a new RhIG that is FDA-approved for prevention of post-transfusion Rh alloimmunization by intravenous administration. We believe that this more convenient and less painful approach should be the treatment of choice for preventing Rh alloimmunization following the transfusion of D-positive red cells to a D-negative recipient.
Anemia, Sickle Cell↗
Intraperitoneal alpha-interferon alternating with cisplatin in residual ovarian carcinoma: a phase II Gynecologic Oncology Group study.
OBJECTIVE: The aim of this study was to study the combination of intraperitoneal alpha-interferon and cisplatin administered second-line in an alternating sequence in small volume residual epithelial ovarian cancer after second-look surgery and the activity of this combination based on prior response to first-line platinum compounds. METHODS: Sixty-two patients with minimal residual (<0.5 cm) epithelial ovarian cancer at reassessment laparotomy were entered into a multicenter trial of intraperitoneal alpha-interferon alternating with cisplatin given for eight cycles unless disease progression or unacceptable toxicity occurred. The patients were considered favorable if they were platinum-sensitive and/or relapsed 6 months or longer after completing treatment. Another reassessment laparotomy was performed within 12 weeks of completion of treatment in patients who were in clinical remission. RESULTS: Fifty-four patients were clinically evaluable and 18 were surgically reassessed, 5 of whom had a negative reassessment operation (20% complete response and 8% partial response). Of the 54 patients evaluable for toxicity, the most common adverse effects of more than grade 2 were gastrointestinal in 13 (47%), neutropenia in 9 (17%), and leukopenia in 6 (12%). Grade 4 toxicity was seen in 10 instances: 4 gastrointestinal, 2 neutropenia, 2 thrombocytopenia, 1 wound infection, and 1 allergic reaction. CONCLUSIONS: alpha-Interferon and cisplatin are active agents in favorable patients with minimal residual epithelial ovarian cancer at second-look. The combination of the two drugs administered in an alternating sequence appears to be associated with more side effects than when either drug is administered alone. The combination produced response rates similar to those seen when either drug is given alone.
Adult↗
Surgical experiences and training of residents: perspective of experienced gynecologic oncologists.
OBJECTIVE: The aim of this study was to report the opinions of experienced gynecologic oncologists concerning the surgical education and experiences of residents. METHODS: The 1997 membership directory of the Society of Gynecologic Oncologists was used to identify individuals who were members for at least 5 years and on the faculty of residency training programs. One hundred seventy members were identified and a nine-question survey was mailed to them. RESULTS: One hundred nineteen (70%) surveys were returned. One hundred seventeen individuals were on the faculty of residency training programs and involved in the surgical training of residents. Ninety-six percent reported that gynecologic oncologists were a major resource for surgical education at their institution. Eight-nine (76%) reported a change in the volume of major abdominal and vaginal surgical procedures performed for noninvasive disease over the past 5 years. Of these 89, 16 (18%) reported that surgical volume at their institution decreased by 10%, 38 (43%) reported that surgical volume decreased by 10-25%, and 17 (19%) reported that surgical volume decreased by more than 25%. Sixty-three percent of all respondents reported that residents were not as well versed in pre- and postoperative care when compared to those of 5 years ago. Sixty-five percent of all respondents reported that graduating residents were less prepared in surgical techniques when compared to those of 5 years ago. Seventy-five percent of respondents reported that the primary care requirements of the RRC have decreased the amount of surgical experience, ICU rotations, and anesthesia rotations. Sixty percent of all respondents operated with other attending surgeons on more difficult cases, and 29% had changed to this practice within the past 5 years. Eighty-two percent believed that more time during residency training needs to be devoted gynecologic surgical experience. CONCLUSIONS: Experienced gynecologic oncologists on the faculty of residency training programs report a decrease in surgical skills and surgical experiences when compared to residents trained 5 years ago.
General Surgery↗
A computational model of neglect dyslexia.
This paper presents a straightforward theory of neglect (a pre-attentive salience system selects objects' centers for the focus of an attentional "spotlight") as a computational model. This construction permits simulations of model "lesions" and allows checking unequivocally the model's implications. The current model can account for some of the common patterns of observations of neglect dyslexia: that errors increase with word length and that short words may be read as "too long". Most importantly, it also accounts for a dissociation between neglect dyslexia and neglect on line bisection tasks. A two stage model can account for the patterns of performance seen in many neglect subjects, but more important is the demonstration that a theory's implementation as a computational model permits unambiguous evaluation of the theory's implications.
Computer Simulation↗
The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere.
BACKGROUND: We retrospectively analyzed preoperative and postoperative radiographic tumor volumes in 92 patients who underwent hemispheric glioblastoma multiforme operations (107) to determine the factors that affect time to tumor progression (TTP) and overall survival. METHODS: Quantification of tumor volumes was based on a previously described method involving computerized image analysis of contrast enhancing tumor on computerized tomography or magnetic resonance imaging scans. RESULTS: Among the variables analyzed, preoperative Karnofsky Performance Status (KPS) (p < 0.05), chemotherapy (p < 0.05), percent of resection (POR) (p < 0.001), and volume of residual disease (VRD) (p < 0.001) had a significant effect on TTP. Factors that affected survival were age (p < 0.05), preoperative KPS (p = 0.05), postoperative KPS (p < 0.005), POR (p < 0.0005), and VRD (p < 0.0001). Greater resections did not compromise the quality of life, and patients without any residual disease had a better postoperative KPS than those patients who received less than total resections. CONCLUSIONS: The extent of tumor removal and the amount of residual tumor volume, documented on postoperative imaging studies, are highly significant factors affecting the median time to tumor progression and median survival for patients with glioblastoma multiforme of the cerebral hemisphere.
Adolescent↗
Critical pathways: application to selected patient outcomes following coronary artery bypass graft.
As health care reform evolves in the United States, many hospitals are implementing strategies to contain the cost of coronary artery bypass graft (CABG) surgery. The purpose of this study was to examine the length of stay in the intensive care unit (ICU) after CABG surgery relative to the number of hours, postoperation, when ambulation occurred, and to examine the overall postoperative length of hospital stay. The study found a significant difference between ICU length of stay and the time when ambulation was initiated (t(150) = -2.68; p = .004). These results suggest that CABG patients with shorter ICU stays begin ambulation sooner, thus potentially reducing the risk of postoperative complications as well as cost. No other significant differences were demonstrated.
Adult↗
Thiotepa-associated cardiomyopathy during blood or marrow transplantation: association with the female sex and cardiac risk factors.
Thiotepa (TT) has not been reported to cause cardiomyopathy, whereas cyclophosphamide (Cy)-related cardiomyopathy is well characterized. To search for cases of acute onset cardiomyopathy associated with TT, we retrospectively reviewed 171 patients who received TT-containing conditioning regimens for blood or marrow transplantation (BMT). Nine of 171 patients (5.3%) developed clinical congestive heart failure in the post-BMT period. The median time to onset of heart failure was 15 days after BMT (range 5-30). The median pre-BMT left ventricular ejection fraction (LVEF) was 50% (range 42-65%) as determined by two-dimensional echocardiogram, or gated blood pool scan. At the time of cardiomyopathy onset, LVEF was 30%. Six patients died of causes unrelated to heart failure. All affected patients who developed congestive heart failure following administration of TT had some evidence of cardiac dysfunction prior to transplantation. Significant risk factors for the development of cardiomyopathy included low pre-BMT-LVEF and female sex--particularly in females receiving allogeneic transplantation. The incidence of congestive heart failure with TT-containing regimens was similar to the incidence using other regimens with and without Cy. The mean time to clinical evidence of TT-associated cardiomyopathy was longer than the mean time reported with Cy. We recommend caution in using high-dose TT-containing regimens for patients with histories of cardiac dysfunction.
Adult↗
IgY antiporcine endothelial cell antibodies effectively block human antiporcine xenoantibody binding.
Avian IgY antibodies are structurally different from mammalian IgGs and do not fix mammalian complement components or bind human Fc receptors. As these antibody-mediated interactions are believed to play significant roles in both hyperacute rejection (HAR) and acute vascular xenograft rejection (AVXR), IgY antibodies to xenoantigen target epitopes may inhibit these rejection processes. In this report, we show that chicken IgY antibodies to alpha-Gal antigen epitopes and to other porcine aortic endothelial cell (PAEC) antigens block human xenoreactive natural antibody binding to both porcine and rat cardiac tissues and porcine kidney tissues. Chicken IgY antibodies blocked complement-mediated lysis of PAECs by human serum, and inhibited antibody-dependent cell-mediated lysis of PAECs by heat-inactivated human serum plus peripheral blood leukocytes. Binding of IgY to porcine endothelial cells did not affect cell morphology nor expression of E-selectin. These results suggest that avian IgYs could be of potential use in inhibiting pig-to-human xenograft rejection.
Animals↗
Cyclosporin A reverses chemoresistance in patients with gynecologic malignancies.
Multidrug resistance is a major obstacle in successful systemic therapy of gynecologic malignancies. The objectives of this study are to evaluate the activity of cyclosporin A used to overcome drug resistance in a variety of gynecologic malignancies. Forty women (29 with ovarian cancer, 7 with uterine cancer, 3 with cervical cancer, and 1 with choriocarcinoma) were treated with cyclosporin A, 4 mg/kg intravenously, 6 hours before and 18 hours after the specific chemotherapeutic agent, to which the tumor had developed drug resistance. All patients had shown resistance to the chemotherapy agent used in combination with cyclosporin A. All patients had been heavily pretreated (mean, 2.8 previous chemotherapy regimens). Overall, among 38 available patients with gynecologic malignancies, a 29% objective response rate was observed. Twenty-six (65%) of all patients received three or more cycles of cyclosporin A. There was a 25% response rate for patients with ovarian cancer patients and 50% for those with uterine cancer. There were no responses among the three patients with cervical cancer, and the patient with choriocarcinoma had a complete response. All patients were evaluable for toxicity. Leukopenia and nausea were the most common toxic reactions, but in most cases they were transient, and only three patients required a treatment delay. The most common grade 3 or 4 toxicity was thrombocytopenia, which was observed in 22% of the patients. Cyclosporin A is well tolerated and has significant potential for reversal of chemoresistance in heavily pretreated patients with ovarian and uterine malignancies.
Choriocarcinoma↗
Perforin-independent beta-cell destruction by diabetogenic CD8(+) T lymphocytes in transgenic nonobese diabetic mice.
Autoimmune diabetes in nonobese diabetic (NOD) mice results from destruction of pancreatic beta cells by T lymphocytes. It is believed that CD8(+) cytotoxic T lymphocytes (CTLs) effect the initial beta-cell insult in diabetes, but the mechanisms remain unclear. Studies of NOD.lpr mice have suggested that disease initiation is a Fas-dependent process, yet perforin-deficient NOD mice rarely develop diabetes despite expressing Fas. Here, we have investigated the role of perforin and Fas in the ability of beta cell-reactive CD8(+) T cells bearing a T-cell receptor (8.3-TCR) that is representative of TCRs used by CD8(+) CTLs propagated from the earliest insulitic lesions of NOD mice, and that targets an immunodominant peptide/H-2Kd complex on beta cells, to effect beta-cell damage in vitro and in vivo. In vitro, 8.3-CTLs killed antigenic peptide-pulsed non-beta-cell targets via both perforin and Fas, but they killed NOD beta cells via Fas exclusively. Perforin-deficient 8.3-TCR-transgenic NOD mice expressing an oligoclonal or monoclonal T-cell repertoire developed diabetes even more frequently than their perforin-competent littermates. These results demonstrate that diabetogenic CD8(+) CTLs representative of CTLs putatively involved in the initiation of autoimmune diabetes kill beta cells in a Fas-dependent and perforin-independent manner.
Animals↗
Airway management in Ludwig's angina.
A 37-year-old 91 kg man presented with features of Ludwig's angina. Anaesthesia for incision and drainage of his submandibular abscess was undertaken by two specialist anaesthetists with an otorhinolaryngological surgeon prepared for immediate tracheostomy. After preoxygenation, gas induction with sevoflurane in oxygen was followed by a gush of pus into the oral cavity and laryngospam causing acute upper airway obstruction. This resolved with 25 mg of suxamethonium and an endotracheal tube was passed into the trachea with difficulty. Options for management of the difficult airway in Ludwig's angina are discussed.
Adult↗
Distant metastases in ovarian cancer: association with p53 mutations.
Distant metastases are unusual occurrences at presentation and during the progression of epithelial ovarian cancer. There are no good clinical predictors of this phenomenon. Because p53 dysfunction is common in ovarian cancer, we chose to investigate whether specific types of mutations predicted a predisposition to distant metastasis. We hypothesized that the complete absence of intact p53 protein as seen with p53 null mutations may be associated with an enhanced tendency to develop distant metastatic disease. The complete coding sequence of 130 tumor DNA samples was screened for p53 mutations by single-strand conformational polymorphism analysis. Abnormal single-strand conformational polymorphism findings were correlated with the specific DNA sequence abnormalities and outcome. Ninety-four (72%) tumors carried p53 mutations. Sixty-two were missense mutations, and 32 were null mutations (6 nonsense mutations, 23 frameshift mutations, and 3 splice-site mutations). Twenty-eight patients were found to have distant metastases (pericardium, brain, parenchymal liver, spleen, or lung) either at presentation or during the course of their treatment. Distant metastases were nearly 8-fold more common in patients whose tumors carried a null mutation (66%) than in those with either missense mutations (8%) or wild-type p53 (8%; P<0.001). When a null mutation was present, 25% of the tumors were associated with distant metastases at initial diagnosis. No individual with wild-type p53 or a missense mutation in the tumor presented with distant metastasis. Tumors with null mutations were more likely to be associated with lymph node metastasis (P = 0.003), advanced stage (stage III/IV; P<0.001) and high grade (grade II/III; P<0.001), at presentation. These tumors progressed with distant metastases more swiftly than did tumors with either missense mutations (mean, 1.18 versus 2.71 years; P = 0.04) or wild-type p53 (3.57 years; P = 0.015). In contrast to the popular dogma, distant metastases in ovarian cancer do not necessarily result from prolonged treatment of disease. They may be predicted to occur early in the disease course due to a specific molecular genetic abnormality: null mutation of the p53 tumor suppressor gene. These findings need to be carefully considered when choosing between regional versus systemic treatment modalities.
Adult↗