Right iliac fossa pain from a grossly enlarged and torted appendix in a patient with known colitis.

A 27-year-old man with a background of well controlled colitis presented with a 12-hour history of central abdominal pain, nausea, vomiting and fever. A diagnostic laparoscopy revealed an extremely large, gangrenous appendix, which had descended into the pelvis posterior to adhesions in the right iliac fossa and was torted 720°. The decision was taken to convert to a lower midline laparotomy and as the base appeared healthy, a standard appendicectomy was performed. The patient recovered well and was discharged after two days. The appendix measured 104mm x 53mm x 51mm. Histology revealed acute haemorrhagic and necrotising appendicitis with foci of impending perforation. There was no malignancy or mucocoele. Acute torsion (or volvulus) of the appendix is an unusual cause of this common general surgical emergency.

Vascularized bone marrow-based immunosuppression inhibits rejection of vascularized composite allografts in nonhuman primates.

Vascularized composite allograft (VCA) transplantation (also referred to as composite tissue allotransplantation) has demonstrated clinical success in cases of hand, arm and face transplantation despite prior belief that skin provides an insurmountable barrier to allograft rejection. These overall good outcomes are facilitated by substantial immunosuppressive requirements in otherwise healthy patients, yet still demonstrate frequent rejection episodes. We developed a nonhuman primate model of facial segment allotransplantation to elucidate the unique pathophysiology and immunosuppressive requirements of VCA with addition of concomitant vascularized bone marrow (VBM). Heterotopically transplanted facial segment VCA with VBM treated only with tacrolimus and mycophenolate mofetil (MMF) demonstrated prolonged rejection-free survival, compared to VCA without VBM that demonstrated early rejection episodes and graft loss. While VCA with VBM demonstrated sporadic macrochimerism, acute and chronic rejection and graft loss occurred after discontinuation of immunosuppression. These data support an immunomodulatory role of VBM in VCA that reduces immunosuppressive requirements while providing improved outcomes.

Primary malignant melanoma of the colon in an oculocutaneous albino.

We describe the case of an elderly albino man who presented with the typical features of a caecal malignancy and underwent a right hemi-colectomy. Histological assessment subsequently revealed the tumour to be a primary malignant melanoma of the colon. This unexpected diagnosis raises interesting questions regarding the embryology and aetiology of this rare tumour and the anticipated prognosis. To the best of our knowledge, this is the first reported case of a primary colonic melanoma associated with oculocutaneous albinism.

Stoma formation for functional bowel disease.

OBJECTIVE: To assess the results of stoma formation for functional bowel disease. METHODS: A retrospective study of the indications for and complications of stoma formation in this group. A quality of life questionnaire was sent to the group. RESULTS: A very small proportion of patients with functional bowel disease have a stoma formed (< 1%). Stoma formation is often associated with problems requiring further operations. Their QOL is reported as poor and is improved upon by stoma formation. Most patients with a temporary stoma elected to keep it rather than suffer their previous problems. CONCLUSION: Some patients with functional bowel disease can be successfully managed by stoma formation. Their treatment is difficult, emotionally demanding and labour-intensive.

Sex differences in hippocampal slice excitability: role of testosterone.

In vivo fluctuations in gonadal hormones alter hippocampal excitability and modulate both physiological and pathological hippocampal processes. To assess hormonal effects on excitability within a functional hippocampal circuit, extracellular CA1 field responses were compared in slices from intact male, intact female, orchidectomized male, and ovariectomized female rats. Secondly, the effects of in vitro applications of 17-beta estradiol, progesterone, or testosterone on baseline excitability of slices from gonadectomized rats were assessed versus pre-hormone baseline measures. Finally, using the in vitro kindling model of slice epileptogenesis, steroid hormone effects on interictal-like activity were also examined. Significant sex differences in excitatory postsynaptic potential amplitude were observed, with slices from males having larger excitatory postsynaptic potential amplitudes than those from females. Gonadectomy significantly decreased excitatory postsynaptic potential amplitude in slices from male rats. Slices from gonadectomized male and female rats also showed a decreased dendritic excitatory postsynaptic potential slope relative to slices from intact male and females rats. In vitro application of testosterone significantly increased excitatory postsynaptic potential amplitudes in slices from both orchidectomized males and ovariectomized females and the population spike amplitude of slices from ovariectomized females. Following in vitro kindling, slices from intact males showed greater spontaneous burst rates than slices from intact females, further suggesting an excitatory effect of testosterone. These results suggest: (1) a sex difference in the level of baseline excitability between slices from intact males and females as measured by excitatory postsynaptic potential amplitudes, (2) testosterone has excitatory effects on baseline physiology and kindled hippocampal responses, and (3) slices from males show a greater level of excitability than those from females in the in vitro kindling model.

The effects of Tween 20 and sucrose on the stability of anti-L-selectin during lyophilization and reconstitution.

We have chosen an anti-L-selectin antibody as a model protein to investigate the effects of sucrose and/or Tween 20 on protein stability during lyophilization and reconstitution. Native anti-L-selectin secondary structure is substantially retained during lyophilization in the presence of sucrose (1 or 0.125%). However, aggregation of the protein during reconstitution of lyophilized protein powders prepared without sucrose is not reduced by the presence of sucrose in the reconstitution medium. Aggregate formation upon reconstitution is completely inhibited by freeze drying the protein with sucrose and reconstituting with a 0.1% Tween 20 solution. Tween 20 (0.1%) also partially inhibits loss of native anti-L-selectin secondary structure during lyophilization. However, upon reconstitution the formulations lyophilized with Tween 20 contain the highest levels of aggregates. The presence of Tween in only the reconstitution solution appears to inhibit the transition from dimers to higher order oligomers. Potential mechanism(s) for the Tween 20 effects were investigated. However, no evidence of thermodynamic stabilization of anti-L-selectin conformation (e.g., by Tween 20 binding) could be detected.

Experience with a one-stop colorectal clinic.

BACKGROUND AND OBJECTIVE: Colorectal services have traditionally been arranged for the convenience of hospitals rather than patients. This model is not ideal, particularly for minor interventions and diagnostic procedures. In order to address this a one-stop colorectal clinic was set up. PATIENTS AND METHODS: Weekly clinics ran from 6.00 to 9.30 p.m. on Wednesdays for a period of 6 months. Patients with rectal bleeding, altered bowel habit, anorectal symptoms and those requesting screening advice were seen by a consultant or specialist registrar. Patients were asked to fill in a questionnaire at the end of their clinic attendance. RESULTS: 197 patients were seen in 17 clinics; 134 underwent proctoscopy, 72 had a rigid sigmoidoscopy and 85 had a flexible sigmoidoscopy carried out. Twenty-four patients subsequently had a barium enema and 3 were listed for colonoscopy. The main diagnosis was haemorrhoids (n = 104); 14 colorectal neoplasms were discovered (5 cancers and 9 polyps). During the study period the number of patients waiting for lower gastrointestinal endoscopy fell from 119 to 63; 2 months after ending the pilot scheme, the number had risen to 108. CONCLUSION: The clinic was found to have significantly improved patient care. The majority of patients were satisfied with an evening clinic. Flexible sigmoidoscopy without sedation was well tolerated and the ability to perform this at initial assessment had a marked effect on the number of patients awaiting lower gastrointestinal endoscopy.

Anti-epileptiform effects of audiogenic seizure priming on in vitro kindling in rat hippocampus.

The effect of priming for audiogenic seizures (AGS) on the development of epileptiform activity in the hippocampus was studied using in vitro kindling (IVK) in Long-Evans rats. AGS priming consists of intense auditory stimulation during a critical period of auditory development, resulting in sound-induced clonic convulsions upon subsequent testing. Between postnatal day (PND) 28 and 50, slices from subjects primed and sham-primed for AGS on PND 18 were used for recording responses in area CA1 of hippocampus following Schaffer collateral stimulation from stratum radiatum of area CA2/CA3. The developmental priming procedure, which enhances auditory brainstem excitability, resulted in fewer afterdischarges in slices from primed subjects across initial IVK stimulation sequences. These results suggest that changes in excitability that occur with acoustic priming can initially diminish selective epileptiform response characteristics in forebrain areas such as the hippocampus.

Anaesthesia for caesarean section in a patient with Ehlers-Danlos syndrome and mitral valve prolapse.

We report the successful use of single-shot spinal anaesthesia for elective caesarean section in a multigravid woman with Ehlers-Danlos syndrome, complicated by mitral valve prolapse. This is a rare inherited collagen disorder that has been reported to have a high pregnancy-related morbidity and mortality, particularly from uterine rupture and uncontrolled bleeding from friable vessels, coagulopathy and major vessel rupture. The literature concerning obstetric anaesthetic management for different types of Ehlers-Danlos syndrome and the management of mitral valve prolapse in pregnancy are reviewed.

Effect of zinc binding and precipitation on structures of recombinant human growth hormone and nerve growth factor.

Metal-induced precipitation of protein therapeutics is being used and further developed as a processing step in protein formulation and may have utility in protein purification and bulk storage. In such processes, it is imperative that native protein structure is maintained and the metal complexation is reversible. In the current study, we investigated the effects of zinc-induced precipitation on recombinant human growth hormone (rhGH) and recombinant human nerve growth factor (rhNGF). On the addition of ethylenediaminetetraacetic acid (EDTA), the precipitates were dissolved, yielding complete recovery of native protein in both cases. Both proteins have specific metal binding sites and require specific molar ratios of zinc to protein to initiate precipitation (zinc:rhGH > 2:1; zinc:rhNGF > 18:1). Furthermore, the secondary structures of both proteins were unperturbed in soluble zinc complexes and zinc-induced precipitates, as measured by infrared and circular dichroism spectroscopies. The soluble zinc complex of rhGH had minor tertiary structural alterations, whereas zinc binding did not alter the tertiary structure of rhNGF. These studies indicated that metal-induced precipitation provides a method to maintain proteins in their native state in precipitates, which may be useful for purification, storage, and formulation.

Psychometric testing of fatigue instruments for use with cancer patients.

BACKGROUND: Cancer treatment-related fatigue (CRF) is a common side effect of cancer treatment. A problem identified in most reviews of CRF is lack of sound approaches to measurement that are congruent with the conceptualization of CRF as a self-perceived state. The diversity of instruments available to measure fatigue and the lack of comprehensive testing of several promising instruments with cancer patients undergoing treatment provided the rationale for this study. The purpose of this article is to report the results of psychometric testing of several fatigue instruments in patients undergoing cancer treatment. OBJECTIVES: The aims of this study were to determine the reliability, validity, and responsiveness of each instrument and to determine the ability of each instrument to capture CRF. METHODS: Existing fatigue instruments with published psychometric information that indicated suitability for further testing were selected and included the Profile of Mood States Short Form fatigue subscale (F_POMS-sf), Multidimensional Assessment of Fatigue (MAF), Lee Fatigue Scale (LFS), and the Multidimensional Fatigue Inventory (MFI). Data were collected at a university-based clinical cancer center and a freestanding comprehensive cancer center. Subjects completed all study instruments, which were presented in random order, at a time when CRF was expected to be high and again when it was expected to be low. A subset of subjects completed the instruments within 48 hours of one of the data collection points when CRF was expected to be relatively unchanged to provide stability data. RESULTS: Reliability estimates using Cronbach's alpha indicated that all instruments examined had good internal consistency. Test-retest correlations showed good stability for total scores on all the instruments, but some subscales of the LFS and MFI had marginal stability. Factor analysis of all instruments indicated that only the LFS and the F_POMS-sf fully supported their construct validity. All of the instruments showed responsiveness to changes in CRF related to treatment. CONCLUSIONS: The results of the study provide researchers and clinicians with detailed comparisons of the performance of established fatigue measures in cancer patients undergoing treatment to use when selecting measures of CRF.

Attitudes of psychologists and psychologists-in-training to homosexual women and men: an Australian study.

Homophobic reactions of Australian psychologists (n = 43), postgraduate psychology students (n = 17) and undergraduate psychology students (n = 44) were compared using Van de Ven's (1994) measures of cognitive, affective and behavioral dimensions of homophobia. Results suggested that undergraduates were significantly more homophobic than psychologists in their thinking, intentional behavior and feelings of fear or discomfort in relation to lesbians and gay men. No other significant group differences were found. Gender differences were found only in relation to one affective dimension of homophobia. Low levels of positive affective response to homosexuals were observed across groups and gender. The study underscores the importance of assessing homophobic response multidimensionally. Implications for the training of Australian psychologists are discussed.

Fatigue patterns observed in patients receiving chemotherapy and radiotherapy.

The purpose of this study was to describe the patterns of cancer-related fatigue (CRF) and vigor in patients receiving chemotherapy or radiation therapy. Five studies that measured fatigue and vigor with the Profile of Mood States were used to describe the pattern of CRF and vigor during and after both types of treatment. Repeated-measures ANOVA was used to determine differences over time in each study. Results demonstrate different patterns of CRF for patients receiving chemotherapy and radiation therapy. Chemotherapy-related CRF peaks in the days after chemotherapy, whereas radiation therapy-related CRF gradually accumulates over the course of treatment. The CRF associated with both forms of treatment gradually declines over time. The prevalence, intensity, and persistence of CRF during treatment and for months after treatment is complete make this symptom one that cannot be ignored.

Plastic bag asphyxia in southeast Scotland.

Death resulting from plastic bag asphyxia has been recognized for >40 years, but relatively little is known about either its epidemiology or its pathophysiology. Over 15 years (1984-1998), 30 deaths were attributed to plastic bag asphyxia among the 14,560 autopsies performed in the Forensic Medicine Unit in Edinburgh. These 30 deaths involved 20 male and 10 female subjects, with an age range of 13 to 81 years. Eleven had some alcohol measurable in the blood, with four having levels >80 mg/dl. Only one individual appeared to have ingested a drug overdose, but inhaled substances within the plastic bag may have contributed to death in five cases. The absence of childhood accidental deaths may reflect successful preventive measures. The 3 accidental deaths involved adults (including 2 who died of autoerotic asphyxia), and the remaining deaths were 27 suicides. Of those who committed suicide, most (59%) had chronic psychiatric illness rather than chronic debilitating or terminal physical illness. In contrast with reports from the United States, publicity associated with "self-deliverance" did not result in an increased number of deaths from plastic bag asphyxia (4 deaths in this series). Analysis of the circumstances of all the deaths revealed them to be difficult to predict and hence prevent.

Consequences to chicks hatched from Escherichia coli-inoculated embryos.

An Escherichia coli causing negligible mortality in embryonated chicken eggs was adapted to grow in media containing nalidixic acid. This isolate (EcNAL) was inoculated into 12-day-old embryonated eggs. Additional embryos inoculated with tryptose phosphate broth (TPB) served as controls. Six days later, all surviving eggs were moved to hatching units. One hatcher contained half of the TPB-inoculated eggs; the chicks hatching from these eggs served as negative controls. The EcNAL-inoculated eggs and the remaining TPB-inoculated eggs were moved to a second hatcher and allowed to hatch together; chicks hatching from these TPB-inoculated eggs served as contact controls. On day of hatch and at intervals thereafter, chicks from each of the treatment groups were sampled. Their body and yolk weights were recorded, and various tissues were cultured for the presence of the EcNAL bacterium. Hatchability of the EcNAL-inoculated embryos was markedly lower than that of either control group. Chicks from EcNAL-inoculated embryos also had low but detectable levels of mortality, lowered body weights, and increased yolk-to-body weight ratios. These same chicks had persistently high levels of EcNAL in the yolk and lower but detectable levels of the organism in the lungs and tracheas, which lasted a few days. The contact controls, on the other hand, were similar to the negative controls as far as having negligible mortality, steadily increasing body weights, and declining yolk-to-body weight ratios. However, in contrast to the negative controls, EcNAL was recovered primarily from the respiratory tract of the contact controls for a brief period of 3-4 days after hatch.

Investigation of protein-surfactant interactions by analytical ultracentrifugation and electron paramagnetic resonance: the use of recombinant human tissue factor as an example.

PURPOSE: The purpose of this work is to utilize electron paramagnetic resonance (EPR) spectroscopy in conjunction with analytical ultracentrifugation (AUC) to investigate the binding of surfactants to proteins with a transmembrance domain. As an example these methods have been used to study the interaction of a nonionic surfactant, C12E8, to recombinant human tissue factor (rhTF) in liquid formulations. The complementary nature of the two techniques aids in data interpretation when there is ambiguity using a single technique. In addition to binding stoichiometries, the possibility of identifying the interacting domains by using two forms of rhTF is explored. METHODS: Two recombinant, truncated forms of human tissue factor were formulated in the absence of phospholipids. Neither of the recombinant proteins, produced in E. coli, contains the cytoplasmic domain. Recombinant human tissue factor 243 (rhTF 243) consists of 243 amino acids and includes the transmembrane sequences. Recombinant human tissue factor 220 (rhTF 220), however, contains only the first 221 amino acids of the human tissue factor, lacking those of the transmembrane region. EPR and AUC were used to investigate the interactions between these two forms of rhTF and polyoxyethylene 8 lauryl ether, C12E8. RESULTS: Binding of C12E8 to rhTF 243 is detected by both EPR spectroscopy and AUC. Although a unique binding stoichiometry was not determined, EPR spectroscopy greatly narrowed the range of possible solutions suggested by the AUC data. Neither technique revealed an interaction between rhTF 220 and C12E8. CONCLUSIONS: The complementary nature of EPR spectroscopy and AUC make the combination of the two techniques useful in data interpretation when studying the interactions between rhTF and C12E8. By utilizing these techniques in this study, the binding stoichiometry of rhTF 243 to C12E8 ranges from 1.2:1 to 1.3:0.6 based on an aggregation number of 120. This binding is consistent with previously reported activity data that showed an increase in clotting rate when rhTF 243 is in the presence of C12E8 micelles. From the rhTF 220 data, it can further be concluded that the transmembrane domain of rhTF is necessary for interactions with C12E8.

Planning and conducting a multi-institutional project on fatigue.

PURPOSE/OBJECTIVES: To describe the process used in proposal development and study implementation for a complex multisite project on cancer treatment-related fatigue (CRF), identify strategies used to manage the project, and provide recommendations for teams planning multisite research. DATA SOURCES: Information derived from project team meeting records, correspondence, proposals, and personal recollection. DATA SYNTHESIS: The project was built on preexisting relationships among the three site investigators who then built a team including faculty, research coordinators, staff nurses, and students. Study sites had a range of organizational models, and the proposal was designed to capitalize on the organizational and resource strengths of each setting. Three team members drawn from outside oncology nursing provided expertise in measurement and experience with fatigue in other populations. Planning meetings were critical to the success of the project. Conference calls, fax technology, and electronic mail were used for communication. Flexibility was important in managing crises and shifting responsibility for specific components of the work. The team documented and evaluated the process used for multisite research, completed a major instrumentation study, and developed a cognitive-behavioral intervention for CRF. CONCLUSIONS: Accomplishments during the one-year planning grant exceeded initial expectations. The process of conducting multisite research is complex, especially when the starting point is a planning grant with specific research protocols to be developed and implemented over one year. Explicit planning for decision-making processes to be used throughout the project, acknowledging the differences among the study settings and planning the protocols to capitalize upon those differences, and recruiting a strong research team that included a member with planning grant and team-building expertise were essential elements for success. IMPLICATIONS FOR NURSING PRACTICE: Specific recommendations for others planning multisite research are related to team-building, team membership, communication, behavioral norms, role flexibility, resources, feedback, problem management, and shared recognition.

Effect of Tween 20 on freeze-thawing- and agitation-induced aggregation of recombinant human factor XIII.

Agitation- and freeze-thawing-induced aggregation of recombinant human factor XIII (rFXIII) is due to interfacial adsorption and denaturation at the air-liquid and ice-liquid interfaces. The aggregation pathway proceeds through soluble aggregates to formation of insoluble aggregates regardless of the denaturing stimuli. A nonionic surfactant, polyoxyethylene sorbitan monolaurate (Tween 20), greatly reduces the rate of formation of insoluble aggregates as a function of surfactant concentration, thereby stabilizing native rFXIII. Maximum protection occurs at concentrations close to the critical micelle concentration (cmc), independent of initial protein concentration. To study the mechanistic aspects of the surfactant-induced stabilization, a series of spectroscopic studies were conducted. Electron paramagnetic resonance spectroscopy indicates that binding is not occurring between Tween 20 and either the native state or a folding intermediate state of rFXIII. Further, circular dichroism spectroscopy suggests that Tween 20 does not prevent the secondary structural changes induced upon guanidinium hydrochloride-induced unfolding. Taken together, these results imply that Tween 20 protects rFXIII against freeze-thawing- and agitation-induced aggregation primarily by competing with stress-induced soluble aggregates for interfaces, inhibiting subsequent transition to insoluble aggregates.

Normal and aberrant functions of integrins in the adult central nervous system.

Integrins are heterodimeric proteins mediating cell-cell and cell-extracellular matrix adhesive connections (Springer T.A., 1990, Nature 346, 425-434) and signal transduction across the plasma membrane. The important roles of integrins in neural development and cancer, where they subserve process outgrowth and cell migration, are well documented, but information on integrins in the adult central nervous system has been slower to arrive. Now that strong evidence, both molecular biological and immunocytochemical, has been collected, it is useful to speculate on what these interesting proteins may be doing in the adult central nervous system. Suggestive data now points to roles in functions characterized in part by morphological rearrangements, such as learning and memory, and injury responses.

Bovine luteal cells elicit major histocompatibility complex class II-dependent T-cell proliferation.

Major histocompatibility complex (MHC) class II molecules are expressed in the bovine corpus luteum (CL) in a manner correlating with luteolysis. Whether bovine luteal cells can stimulate T-cell proliferation in a class II-restricted manner was investigated. Staphylococcal enterotoxin B (SEB) enhances T-cell proliferation by a mechanism requiring MHC class II molecules and was used to examine stimulation of T-cell proliferation by luteal cells. Luteal cells from midcycle or regressing CL (induced by prostaglandin F2 alpha) were cocultured with autologous T cells in the presence of no treatment, SEB (1 microgram/ml), or SEB + anti-MHC class II antibody (3 micrograms/ml); and proliferation was assessed by incorporation of tritiated thymidine. T cells proliferated in the presence of cells from regressing CL more than when in the presence of midcycle cells (118,309 +/- 20,567 vs. 75,261 +/- 12,494 cpm; p < 0.05). Anti-MHC attenuated this response of cells from regressing CL (81,108 cpm +/- 13,249; p < 0.05). Without SEB, T cells proliferated when cultured with cells from regressing, but not midcycle, CL (4637 +/- 816 vs. 2117 +/- 589 cpm; p < 0.03). These results suggest that luteal cells can function as antigen-presenting cells in vitro and that prostaglandin F2 alpha may enhance their ability to present antigen.