Biomedical subjects

Cody A Koch

Publications and source records attributed to Cody A Koch.

12 recordsLinked to original sources

PubMed2006

Complement-dependent control of teratoma formation by embryonic stem cells.

The fetus has pluripotent stem cells that when transferred to mature individuals can generate tumors. However, for reasons yet unknown, tumors form rarely in the fetus and/or the mother during normal gestation. We questioned whether the complement system might protect against tumor formation by pluripotent stem cells. Murine embryonic stem cells were notably more susceptible than cardiomyocytes differentiated from those cells to lysis by complement in heterologous and homologous sera. Treatment of embryonic stem cells with heterologous serum averted tumor formation after residual cells were transplanted into mice. Confirming the importance of homologous complement in preventing formation of tumors, untreated embryonic stem cells formed tumors more quickly in C3-deficient than in wild-type mice. Susceptibility of embryonic stem cells to complement required an intact alternative pathway and was owed at least in part to a relative deficiency of sialic acid on cell surfaces compared with differentiated cells. Susceptibility to complement and resistance to tumors was inversely related to the number of cells transferred. These findings show that formation of tumors from embryonic stem cells is controlled in part by the alternative pathway of complement and suggest that susceptibility to complement might represent a general property of pluripotent stem cells that can be exploited to prevent tumor formation.

Animals↗

PubMed2006

A single-center experience with inflammatory breast cancer, 1985-2003.

HYPOTHESIS: "Up-front" surgery improves survival in inflammatory breast cancer (IBC). DESIGN: Retrospective cohort, 1985-2003. SETTING: Tertiary referral center. PATIENTS: Consecutive patients with a primary occurrence of IBC. MAIN OUTCOME MEASURES: All-cause and disease-free survival. RESULTS: One-hundred fifty-six patients were identified with IBC; 28 patients with metastatic disease were excluded from further analysis. The mean age of the remaining 128 patients was 53 years; 57% of women were postmenopausal. One hundred twenty-two patients had clinically apparent IBC. Tumors were palpable in 83 patients (mean diameter, 9.1 cm). Neoadjuvant chemotherapy was the initial therapy in 106 patients, while surgery was the initial therapy in 22 patients. The overall median survival was 37 months, with a median disease-free interval of 23 months. The 5-year survival was 42%, with a disease-free survival of 21%. Univariate analysis of recurrence identified previous hormone therapy (relative risk [RR], 0.50; P = .03), menopause (RR, 0.55; P = .01), and palpable adenopathy (RR, 1.57; P = .04) as significant factors. Univariate survival analysis highlighted previous hormone therapy (RR, 0.48; P = .04), radiotherapy (RR, 0.39; P = .02), sequence of therapy (P = .001), family history (RR, 0.47; P = .01), and palpable adenopathy (RR, 2.22; P<.001) as being important. Multivariate analysis of recurrence identified menopausal status as the key factor. Adenopathy at the initial examination was associated with decreased length of survival, while radiotherapy was associated with better survival. CONCLUSIONS: Survival from IBC remains poor. Although adenopathy and radiotherapy affected survival by multivariate analysis, the sequence of therapy was not associated with improved outcome.

Adenocarcinoma↗

PubMed2006

Incidence and risk factors for urinary retention after endoscopic hernia repair.

BACKGROUND: Postoperative urinary retention (PO-UR) frequently complicates the repair of inguinal hernias. The purpose of this study was to determine the incidence of and risk factors for developing PO-UR in patients undergoing endoscopic inguinal hernia repair. METHODS: The incidence of PO-UR was determined by a retrospective review of a prospective patient database for all patients undergoing inguinal hernia repair by 1 surgeon from 2001 to 2003 at a tertiary referral center. A case-control study was used to identify risk factors for the development of PO-UR. RESULTS: Thirty-four (22.2%) out of 153 patients undergoing endoscopic inguinal hernia repair developed PO-UR. The use of narcotic analgesia and the volume of intravenous postoperative fluid administered were significant risk factors (P < .05) for the development of PO-UR. CONCLUSIONS: Postoperative urinary retention is common after totally extraperitoneal and transabdominal preperitoneal inguinal hernia repairs and is associated directly with increased narcotic and postoperative intravenous fluid administration.

Adolescent↗

PubMed2005

Intrinsic resistance of hepatocytes to complement-mediated injury.

When activated on or in the vicinity of cells, complement usually causes loss of function and sometimes cell death. Yet the liver, which produces large amounts of complement proteins, clears activators of complement and activated complexes from portal blood without obvious injury or impaired function. We asked whether and to what extent hepatocytes resist injury and loss of function mediated by exposure to complement. Using cells isolated from porcine livers as a model system, we found that, in contrast to endothelial cells, hepatocytes profoundly resist complement-mediated lysis and exhibit normal synthetic and conjugative functions when complement is activated on their surface. The resistance of hepatocytes to complement-mediated injury was not a function of cell surface control of the complement cascade but rather an intrinsic resistance of the cells dependent on the PI3K/Akt pathway. The resistance of hepatocytes to complement might be exploited in developing approaches to the treatment of hepatic failure or more broadly to the treatment of complement-mediated disease.

Animals↗

PubMed2005

Toward the survival and function of xenogeneic hepatocyte grafts.

Xenogeneic hepatocyte transplantation might offer an unobtrusive alternative to whole liver allotransplantation. Having previously found that the immune response to such grafts can be controlled by immunosuppression, we sought approaches to collection and delivery that would optimize survival and function after transplantation. Porcine hepatocytes were isolated by a 2-step collagenase technique and then: 1) used immediately; 2) stored in University of Wisconsin (UW) solution at 4 degrees C; 3) cultured in supplemented Williams E medium; or 4) cryopreserved in UW solution with 10% dimethyl sulfoxide (DMSO). The fate and function of the hepatocytes was determined after they were injected into the spleens of immunodeficient mice. Freshly isolated hepatocytes had better viability (92.2 +/- 1.9%) than hepatocytes cultured for 24 hours (78.4 +/- 6.3%), hypothermically preserved in UW solution for 24 hours (85.8 +/- 3.1%), or cryopreserved (65.0 +/- 2.6%). Freshly isolated hepatocytes secreted more albumin after transplantation than hepatocytes that were cultured, hypothermically stored, or cryopreserved. In conclusion, culture and storage profoundly compromises the function of isolated hepatocytes after transplantation. Freshly isolated hepatocytes are the preferred source for transplantation.

Albumins↗

PubMed2004

Accommodation: preventing injury in transplantation and disease.

Humoral immunity, as a cause of damage to blood vessels, poses a major barrier to successful transplantation of organs. Under some conditions, humoral immunity causes little or no damage to an organ graft. We have referred to this condition, in which a vascularized graft functions in the face of humoral immunity directed against it, as "accommodation." In this paper, we review changes in the graft and in the host that may account for accommodation, and we consider that what we call accommodation of organ grafts may occur widely in the context of immune responses, enabling immune responses to target infectious organisms without harming self-tissues.

Animals↗

PubMed2004

Xenograft transplantation.

Interest in xenotransplantation has increased because conventional organ transplantation has been limited by a shortage of human organs. Although xenotransplantation could alleviate the existing and anticipated need for tissues and organs, the application is hindered by various biologic obstacles. This article reviews the basis for the demand for xenotransplantation, the obstacles to clinical application, and potential approaches to overcoming those obstacles.

Anesthesia↗

PubMed2004

Platelet-rich plasma serotonin levels in chronic myeloproliferative disorders: evaluation of diagnostic use and comparison with the neutrophil PRV-1 assay.

In a prospective study of 109 subjects, an enzyme-linked immunosorbent assay (ELISA) was used to measure platelet-rich plasma (PRP) serotonin levels in patients with polycythaemia vera (PV; n = 27), essential thrombocythaemia (ET; n = 14), myelofibrosis with myeloid metaplasia (MMM; n = 30), secondary or spurious polycythaemia (SP; n = 22) and controls (n = 16). Nine study subjects who were taking a selective serotonin reuptake inhibitor (SSRI) all displayed a markedly decreased PRP serotonin level (median, 24.2 ng/10(9) platelets; range, 0-49.3) and were therefore excluded from further analysis. Among the remaining 100 subjects, the median and range of PRP serotonin levels, in ng/10(9) platelets, was significantly lower in MMM (89.5; 0-278.3), PV (204.8; 0-496.0) and ET (385.3; 136.8-1025.7) compared with both SP (608.8; 369.0-1780.1) and controls (567.2; 359.9-1071.1). Neutrophil polycythaemia rubra vera-1 (PRV-1) expression was concurrently assayed by real-time polymerase chain reaction in 69 patients (23 PV, 17 SP, 12 ET, seven MMM, 10 controls). PRP serotonin measurement performed as well as the PRV-1 assay in distinguishing PV from SP (93% vs. 86% test accuracy). The current study suggests that PRP serotonin concentration might be considered as one of the several biological markers that complement each other for the diagnosis of PV.

Adolescent↗

PubMed2003

Natural mechanisms for evading graft rejection: the fetus as an allograft.

Most primitive multicellular animals mount allogeneic immune responses to protect themselves from invasion by foreign organisms. The reproductive success of eutherian mammals, in which the maternal immune system is in direct contact with the semi-allogeneic fetus, depends on the ability to control allogeneic immune responses. Multiple, overlapping mechanisms exist to prevent maternal allogeneic immune responses towards the fetus while maintaining the capacity to mount a defense against infectious organisms. The formation of an anatomical barrier between mother and fetus, lack of maternal immune responsiveness, and a lack of expression of allogeneic molecules by the fetus have been proposed as mechanisms to account for the lack of fetal rejection during pregnancy. These mechanisms have helped us begin to understand how rejection of the fetus is avoided; however, these mechanisms do not completely explain how the fetus evades the maternal immune system. Site-specific suppression, in which maternal immune responses are controlled locally at the maternal- fetal interface, plays a fundamental role in controlling maternal allogeneic immune responses. Stem cells, both adult and embryonic, might use mechanisms similar to those of the fetus to avoid rejection. Future discoveries in the field of reproductive immunology will help us understand not only immune regulation during pregnancy, but also how immune responses towards organ and cellular transplants might be controlled.

Animals↗

PubMed2003

Confirmation of research publications reported by neurological surgery residency applicants.

OBJECTIVE: Previous studies have reported that as many as 30% of resident and fellow applicants misrepresent their publication record on their residency and fellowship applications. To determine if neurologic surgery residency applicants were guilty of similar rates of misrepresentation, we reviewed the applications submitted to our institution in the year 2001-2002. METHODS: There were 102 applications submitted to our neurologic surgery residency program for the 2001-2002 academic year. All publications listed by applicants on the Central Application Service for Neurologic Surgery were verified using various online bibliographic databases including MEDLINE and an interlibrary search. Manuscripts listed as being "in press" were authenticated by contacting the journals' editorial office while those listed as either "in preparation" or "submitted for publication" were excluded. RESULTS: Seventy-three (71.6%) candidates reported 212 published citations, including 129 (61%) journal articles, 13 (6%) book chapters, and 70 (33%) printed abstracts. Twelve of these applicants also listed 13 papers as being "in press." Overall, among the entire applicant pool, there were nine examples of possible misrepresentation in six applicants (6%). One applicant provided inadequate information to verify a book chapter. Another candidate cited four journal articles with the authors' names, even though his name was not listed among them. Two applicants included one citation each without listing any of the authors' names. Verification of these citations revealed that neither of them was a coauthor, although one was acknowledged. Among the articles listed as "in press," one was still under consideration for publication, and one could not be verified because of the journal's discontinuation. CONCLUSIONS: We confirmed that applicants who reported their names along with their published citations did so honestly and accurately. In our study, misrepresentation of published manuscripts among neurologic surgery residency applicants was rare when compared to candidates in other specialties.

Humans↗

PubMed2003

Spinal meningiomas in patients younger than 50 years of age: a 21-year experience.

OBJECT: Spinal meningiomas occur most frequently in older patients. They are well-circumscribed and slow-growing tumors that are associated with good patient outcomes following surgery. Spinal meningiomas occurring in younger patients may be more aggressive, with a worse prognosis. The authors present their 21-year experience with spinal meningiomas in patients younger than 50 years of age. METHODS: The authors reviewed data obtained in 40 patients (age < 50 years) treated at the Mayo Clinic, Rochester, during the past 21 years; in all cases the lesions were histologically confirmed spinal meningiomas. Five men (12.5%) and 35 women (87.5%) (mean age 34.5 +/- 10.9 years) underwent 52 operations for 41 tumors. The mean follow-up duration was 82 +/- 93 months (range 0-445 months). The data obtained in these patients were compared with those derived from a random control cohort of 40 patients older than age 50 years in whom spinal meningiomas were resected at the Mayo Clinic during a similar period. In this cohort, there were 33 women and seven men whose mean age was 67.1 +/- 9.5 years. The mean follow-up duration for the older group was 88 +/- 72.3 months (range 18-309 months). Compared with the random cohort of older patients, younger patients there tended to have more tumors located in the cervical spine (39%) as well as a greater number of predisposing factors such as neurofibromatosis Type 2, radiation exposure, or trauma. Nine (22%) of the patients younger than 50 years of age required reoperation for residual or recurrent tumor compared with two (5%) in the older patient control group. The overall mortality rate at the completion of the study for the younger patients was 10%. CONCLUSIONS: Spinal meningiomas in younger patients have a worse prognosis than similar tumors in older patients.

Adolescent↗

PubMed2003

Nonhepatosplenic extramedullary hematopoiesis: associated diseases, pathology, clinical course, and treatment.

OBJECTIVE: To define associated clinical conditions, pathology, natural history, and treatment outcome of nonhepatosplenic extramedullary hematopoiesis (NHS-EMH). PATIENTS AND METHODS: We retrospectively reviewed the medical charts of all patients identified as having NHS-EMH from 1975 to 2002. Diagnosis was made by tissue biopsy, fine-needle aspiration biopsy, or radionuclide bone marrow scanning. RESULTS: We identified 27 patients with antemortem diagnosis of NHS-EMH. The most common associated condition and disease site were myelofibrosis with myeloid metaplasia (MMM) (in 18 patients [67%]) and the vertebral column (in 7 patients [26%]; all involving the thoracic region), respectively. At the time of diagnosis of NHS-EMH, concurrent splenic EMH (in 22 patients [82%]; 15 [56%] had undergone splenectomy) and red blood cell transfusion dependency (in 12 patients [44%]) were prevalent. Of the 27 patients, 9 (33%) required no specific therapy. Specific therapy was radiation (in 7 patients with a 71% response rate) and surgical excision (in 6 patients with a 67% response). Treatment-associated complications were limited to surgery. Radiation therapy was not used in the non-MMM group, but low-dose radiation therapy was used in the MMM group for paraspinal or intraspinal EMH (median dose, 1 Gy; range, 1-10 Gy), pleural or pulmonary disease (median dose, 1.25 Gy; range, 1.00-1.50 Gy), and abdominal or pelvic disease (median dose, 2.02 Gy; range, 150-4.50 Gy). Median survival after the diagnosis of NHS-EMH was 13 months in the MMM group and 21 months in the non-MMM group. CONCLUSIONS: This retrospective study suggests that NHS-EMH is rare, is often associated with MMM, and preferentially affects the thoracic spinal region. Asymptomatic disease may require no specific treatment, whereas symptomatic disease is best managed with low-dose radiation therapy.

Adult↗