Clinical Significance of Pretransplant Donor-Specific Antibodies in the Setting of Negative Cell-Based Flow Cytometry Crossmatching in Kidney Transplant Recipients.

Antibodies to donor-specific HLA antigens (donor-specific antibodies [DSA]) detected by single-antigen bead (SAB) analysis prior to kidney transplant have been associated with inferior graft outcomes. However, studies of pretransplant DSA, specifically in the setting of a negative flow cytometry crossmatch (FCXM) without desensitization therapy, are limited. Six hundred and sixty kidney and kidney-pancreas recipients with a negative pretransplant FCXM from September 2007 to August 2012 without desensitization therapy were analyzed with a median follow-up of 4.2 years. All patients underwent cell-based FCXM and SAB analysis on current and historic sera prior to transplantation. One hundred and sixty-two patients (24.5%) had DSA detected prior to transplant. One-year acute rejection rates were similar in DSA-positive versus DSA-negative patients (15.4% vs. 11.4%, respectively; p = 0.18) and were higher in those with DSA mean fluorescence intensity (MFI) greater than or equal to 3000 in multivariable analysis (p = 0.046). The estimated glomerular filtration rate (eGFR) at 3 and 4 years was lower in the DSA(+) versus the DSA(-) group (p = 0.050 at 3 years) without an impact on 5-year death-censored graft survival (89.0% vs. 90.6%, respectively; p = 0.53). Timing (current or historic) of DSA detection did not alter these findings. In conclusion, pretransplant DSA in the setting of a negative FCXM confers minimal immunologic risk in the intermediate term, does not necessitate desensitization therapy and should not represent a barrier to renal transplant.

APOL1 Polymorphisms in a Deceased Donor and Early Presentation of Collapsing Glomerulopathy and Focal Segmental Glomerulosclerosis in Two Recipients.

Two common polymorphisms in APOL1 (G1 and G2) are conserved in persons of African ancestry, and the presence of two polymorphisms (commonly referred to as risk variants) has been identified as a risk factor for chronic kidney disease and focal seg-mental glomerulosclerosis. In kidney transplantation, deceased donors with two APOL1 risk variants carry an increased risk of renal allograft failure in the recipient. An emerging question is whether these data should influence deceased donor assessment or be used to refine prediction of allograft survival. We present the first detailed report of two cases of recipient glomerular disease in the first year following transplant from a deceased donor later defined as carrying two APOL1 risk variants. A possible "second hit" predisposing to renal disease in these recipients is discussed, one with active cytomegalovirus infection concurrent with collapsing glomerulopathy and renal failure and the other with chronic, slowly healing wound infection and focal segmental glomeru-losclerosis but stable renal function. In retrospect, awareness of the donor APOL1 risk alleles would not have influenced donor selection and ultimately did not influence posttransplant management. These case reports inform further discussion of the value of APOL1 testing for deceased donors.

Novel immunosuppressive agents in kidney transplantation.

The last several decades have seen a substantial decrease in the prevalence of acute allograft rejection in kidney transplant recipients, while equivalent improvements in long-term graft function have not been realized. As a result, the primary focus of new immunosuppressive drug development has expanded to include ease of use, improved side effect profiles, and reduced nephrotoxicity in addition to the more traditional goal of improved short-term outcomes. A number of novel drugs are currently under investigation in Phase I, II, or III clinical trials primarily to replace the nephrotoxic but highly effective calcineurin inhibitors. ISA247 (voclosporine) is a cyclosporine (CsA) analog with reduced nephrotoxicity in Phase III study. AEB071 (sotrastaurin), a protein kinase C inhibitor, and CP-690550, a JAK3 inhibitor, are small molecules in Phase II studies. Everolimus is derived from the mTOR inhibitor sirolimus and is in Phase III study. Belatacept is a humanized antibody that inhibits T-cell costimulation and has shown encouraging results in multiple Phase II and III trials. Alefacept and Efaluzimab are humanized antibodies that inhibit T-cell adhesion and are in Phase I and II clinical trials. This article reviews the mechanisms of action as well as published and preliminary results of the Phase I-III clinical trials involving these novel immunosuppressive agents.

Ammonium-nitrogen in green river formation oil shale.

It has been assumed that all of the nitrogen in oil shale from the Green River Formation is present as organic nitrogen and that the nitrogen in spent shale from retorting is present in the char or coke. In fact, from 41 to 84 percent of the nitrogen is present as ammonium fixed within silicate minerals in five samples of raw oil shale and between 46 and 69 percent of the nitrogen is similarly fixed in two samples of spent shale. Both organic nitrogen and fixed ammonium-nitrogen are lost during retorting by the Fischer assay procedure; the loss of organic nitrogen is greater.

A Branchial Cyst in a Diamond Python (Morelia spilota).

A 9-year-old female diamond python (Morelia spilota) was presented with a submandibular swelling. The cytological, macroscopic and histological features of this lesion indicated a diagnosis of branchial (pharyngeal) cyst. Branchial cysts are benign lesions caused by anomalous development of the branchial apparatus and are described rarely in veterinary medicine. We suggest that possible persistence of branchial remnants should be included in the consideration of differential diagnoses for neck masses in adult snakes.

On the geometrically exact low-order modelling of a flexible beam: formulation and numerical tests.

This paper proposes a low-order geometrically exact flexible beam formulation based on the utilization of generic beam shape functions to approximate distributed kinematic properties of the deformed structure. The proposed nonlinear beam shapes approach is in contrast to the majority of geometrically nonlinear treatments in the literature in which element-based-and hence high-order-discretizations are adopted. The kinematic quantities approximated specifically pertain to shear and extensional gradients as well as local orientation parameters based on an arbitrary set of globally referenced attitude parameters. In developing the dynamic equations of motion, an Euler angle parametrization is selected as it is found to yield fast computational performance. The resulting dynamic formulation is closed using an example shape function set satisfying the single generic kinematic constraint. The formulation is demonstrated via its application to the modelling of a series of static and dynamic test cases of both simple and non-prismatic structures; the simulated results are verified using MSC Nastran and an element-based intrinsic beam formulation. Through these examples, it is shown that the nonlinear beam shapes approach is able to accurately capture the beam behaviour with a very minimal number of system states.

In vivo transplantation of fetal human gut-derived enteric neural crest cells.

The prospect of using neural cell replacement for the treatment of severe enteric neuropathies has seen significant progress in the last decade. The ability to harvest and transplant enteric neural crest cells (ENCCs) that functionally integrate within recipient intestine has recently been confirmed by in vivo murine studies. Although similar cells can be harvested from human fetal and postnatal gut, no studies have as yet verified their functional viability upon in vivo transplantation. We sought to determine whether ENCCs harvested from human fetal bowel are capable of engraftment and functional integration within recipient intestine following in vivo transplantation into postnatal murine colon. Enteric neural crest cells selected and harvested from fetal human gut using the neurotrophin receptor p75NTR were lentivirally labeled with either GFP or calcium-sensitive GCaMP and transplanted into the hindgut of Rag2- /γc- /C5- -immunodeficient mice at postnatal day 21. Transplanted intestines were assessed immunohistochemically for engraftment and differentiation of donor cells. Functional viability and integration with host neuromusculature was assessed using calcium imaging. Transplanted human fetal gut-derived ENCC showed engraftment within the recipient postnatal colon in 8/15 mice (53.3%). At 4 weeks posttransplantation, donor cells had spread from the site of transplantation and extended projections over distances of 1.2 ± 0.6 mm (n = 5), and differentiated into enteric nervous system (ENS) appropriate neurons and glia. These cells formed branching networks located with the myenteric plexus. Calcium transients (change in intensity F/F0 = 1.25 ± 0.03; 15 cells) were recorded in transplanted cells upon stimulation of the recipient endogenous ENS demonstrating their viability and establishment of functional connections.

Surgical resection of a primary tracheal fibrosarcoma in a dog.

A four-year-old, entire male Rottweiler was presented with a history of respiratory distress. A tracheal mass was diagnosed on thoracic radiographs and tracheoscopy. Surgical excision of three tracheal rings incorporating the tumour was performed. The mass was found to be a low-grade fibrosarcoma. Twenty-four months later, the owner reported that there was no recurrence of respiratory distress and the dog appeared to be doing well clinically. This case of primary tracheal fibrosarcoma suggests that this type of tumour should be listed in the differential diagnoses for tracheal neoplasia in dogs and that surgical treatment alone may be curative.

Structural and functional characteristics of the corpus callosum in schizophrenics, psychiatric controls, and normal controls. A magnetic resonance imaging and neuropsychological evaluation.

In 1986 Nasrallah and colleagues found that increased thickness of the corpus callosum may be specific to right-handed female schizophrenics. Male and female right-handed schizophrenics were compared with normal and psychiatric controls of comparable age, sex, education, and social class on measures of callosal thickness from a midsagittal magnetic resonance imaging cut and neuropsychological tests of interhemispheric transfer. The sex difference in anterior and posterior callosal thickness in normal controls was reversed in schizophrenics, with the corpus callosum being thicker in female schizophrenics and thinner in male schizophrenics. Similar findings were also observed in the psychiatric control group. These structural differences were not paralleled by evidence of impaired interhemispheric transfer on neuropsychological tasks. These results support the finding of sex-dependent callosal abnormalities in schizophrenia but indicate that these abnormalities may not be specific to this illness.

SCAN. Schedules for Clinical Assessment in Neuropsychiatry.

After more than 12 years of development, the ninth edition of the Present State Examination (PSE-9) was published, together with associated instruments and computer algorithm, in 1974. The system has now been expanded, in the framework of the World Health Organization/Alcohol, Drug Abuse, and Mental Health Administration Joint Project on Standardization of Diagnosis and Classification, and is being tested with the aim of developing a comprehensive procedure for clinical examination that is also capable of generating many of the categories of the International Classification of Diseases, 10th edition, and the Diagnostic and Statistical Manual of Mental Disorders, revised third edition. The new system is known as SCAN (Schedules for Clinical Assessment in Neuropsychiatry). It includes the 10th edition of the PSE as one of its core schedules, preliminary tests of which have suggested that reliability is similar to that of PSE-9. SCAN is being field tested in 20 centers in 11 countries. A final version is expected to be available in January 1990.

Progress toward achieving a common language in psychiatry. Results from the field trial of the clinical guidelines accompanying the WHO classification of mental and behavioral disorders in ICD-10.

In preparing for the 10th revision of the International Classification of Diseases (ICD-10), the Division of Mental Health of the World Health Organization organized an international field trial to help evaluate draft clinical descriptions and diagnostic guidelines that were produced to facilitate use of the chapter dealing with mental and behavioral disorders. These clinical guidelines were prepared in equivalent versions in most of the world's widely spoken languages. The field trial aimed to obtain data that would help in assessing whether the classification fits the diagnoses made in different countries, whether it is easy to use, and whether psychiatrists after a short period of familiarization with the classification can reach agreement about their diagnoses and classification. The field trial was carried out at 112 clinical centers in 39 countries by 711 clinicians who conducted 15,302 individual assessments. The trial included joint clinical assessments of patients and case history exercises. The results of the joint assessment part of the trial are reported here. Most clinicians reported that the draft document was easy to use and that the classification provided a good fit for the vast majority of the clinical conditions encountered. While interrater reliability was satisfactory for most categories, some (for example, those dealing with personality disorders) were somewhat difficult to use, and reliability of assignment for those was lower. The trial demonstrated that the ICD-10 chapter dealing with mental and behavioral disorders is on the whole suitable for general use. It provided valuable indications about changes needed for subsequent versions and demonstrated the feasibility of large-scale international research on classification and diagnosis in psychiatry.

A new peroxidase cDNA from white clover: its characterization and expression in root tissue challenged with homologous rhizobia, heterologous rhizobia, or Pseudomonas syringae.

Temporal reverse transcription-polymerase chain reaction (RT-PCR) expression analyses were performed on Trprx2, a new white clover peroxidase, with roots challenged with homologous rhizobia, heterologous rhizobia, and a pathogen, Pseudomonas syringae. Low levels of Trprx2 expression were evident in all rhizobial treatments but in P.syringae-treated clover background expression was dramatically reduced within 1 h and was undetectable in treatments inoculated for more than 3 h. Spraying 4 mM salicylic acid onto seedlings increased Trprx2 expression. These data suggest a defensive role for Trprx2 in white clover and indicate active defense suppression by the pathogen.

Progress toward achieving a common language in psychiatry, II: Results from the international field trials of the ICD-10 diagnostic criteria for research for mental and behavioral disorders.

OBJECTIVE: In preparing for the publication of ICD-10, the Division of Mental Health of the World Health Organization developed several versions of chapter V, which deals with mental and behavioral disorders. The version for research purposes is called the Diagnostic Criteria for Research (ICD-10 DCR) and gives operational criteria for the diagnosis of mental disorders. This article describes the results of international field trials undertaken to evaluate the draft criteria and refine them further. METHOD: Data were obtained to assess interrater agreement, the confidence with which diagnoses could be made, and the ease of use of the criteria. Additional substudies examined the concordance between ICD-10 DCR, ICD-10 Clinical Descriptions and Diagnostic Guidelines, and other national classification systems (e.g., DSM-IV). The field trials were carried out at 151 clinical centers in 32 countries by 942 clinician/researchers who conducted 11,491 individual assessments of patients. Results for cases assessed by at least two raters are reported here. RESULTS: Most clinician/researchers found the criteria to be explicit and easy to apply. Interrater agreement was high for most diagnostic categories. For some categories, such as those dealing with certain polymorphic psychotic disorders or milder forms of affective disorders, the criteria were rated as somewhat difficult to use, and reliability was lower. Comparison of the results of these field trials with those of the ICD-10 Clinical Descriptions and Diagnostic Guidelines demonstrated that there are increases in interrater agreement when the operational criteria are used. CONCLUSIONS: The use of internationally accepted research criteria enhances the reliability of diagnosis of mental disorders made in research settings worldwide.

Prevalence survey of infections and their predisposing factors at a hospital-based nursing home care unit.

A prevalence survey was performed at a Veterans Administration nursing home care unit to detect the frequency, demographics, features, and potential risk factors associated with infections, compare different methods for calculating infection rates, and compare prevalence data with routine physician reporting of infections during a one-month period. In 176 evaluable residents, 22 nursing home-acquired infections were detected, with rates of 12.5% by infections per residents at risk, and 4.6% by infections per 1000 resident-days. Fifty percent of these infections (11 of 22) involved the urinary tract, seven of which were associated with indwelling catheters. Factors potentially associated with increased overall infection rates included immobility (P less than .02), acute-care hospitalization in the 28 days preceding the study (P less than .01) and antibiotics given preceding the infection (P less than .001). An indwelling urinary catheter (P less than .01) potentially was associated with an increased urinary tract infection rate. During the concurrent period, routine physician reporting of infection detected four of the 22 infections (18%) that were identified by the survey. These findings suggest that physician reporting of infection underestimates infection risk as compared with conventional surveillance practices, and that hospital-based care units may have infection problems more similar to acute-care hospitals than to community nursing homes. Identification of potential risk factors is critical in planning preventive practices based on institution-specific needs.

Nosocomial exposure to parvovirus B19: low risk of transmission to healthcare workers.

OBJECTIVE: To evaluate the risk of nosocomial transmission of parvovirus B19 (B19) infection to healthcare workers (HCWs) exposed to patients with transient aplastic crisis (TAC) caused by acute B19 infection. DESIGN: Cohort study. SETTING: 1,000-bed, urban teaching hospital in Atlanta, Georgia. PARTICIPANTS: Eighty-seven exposed HCWs who cared for two patients with TAC prior to the time they were isolated and a comparison group of 88 unexposed HCWs from wards or clinics where the patients did not receive care. INTERVENTION: Self-administered questionnaire on hospital contact with index patients, B19 community risk factors, and signs and symptoms suggestive of B19 disease. Serology for B19-specific IgM and IgG antibodies measured by antibody-capture enzyme-linked immunosorbent assay. RESULTS: 1 (3.1%) of the 32 nonimmune exposed HCWs had serologic evidence of recent B19 infection compared to 3 (8.1%) of the 37 nonimmune HCWs in the comparison group (P = .6). In a subgroup analysis of exposed HCWs who cared for index patients during the time when the virus load was expected to be greatest, a recent infection rate of 5.8% (1/17) was found among nonimmune HCWs. CONCLUSIONS: The finding of similar rates of recent infection in nonimmune exposed and unexposed HCWs suggests that transmission to HCWs did not occur, despite failure to place the patients in isolation at the onset of hospitalization.

Aggressive fibromatosis of the spermatic cord. A typical lesion in a "new" location.

The authors describe a 31-year-old man with a 7 cm aggressive fibromatosis (desmoid tumor) of the spermatic cord presenting as a swelling in the left inguinal area that was excised along with the testis and cord. The desmoid tumor is histologically typical, but such tumors arising primarily from the paratesticular structures have apparently not been previously reported and the diagnosis would not be questioned if it not for the unusual site. This tumor is histologically and immunohistochemically indistinguishable from abdominal wall desmoid tumor, with or without Gardner's syndrome. Desmoid tumors at this location should be distinguished from reactive processes, such as pseudosarcomatous myofibroblastic proliferation (so-called "proliferative funiculitis") and inflammatory fibrous pseudotumor, all of which exhibit fibroblastic/myofibroblastic differentiation. Paratesticular fibrosarcoma and leiomyosarcoma should also be differentiated from desmoid tumor that does not have the metastatic potential of sarcomas. Thirty-four months post-operatively, an 8 cm local recurrence in the remaining portion of the left vas deferens causing left hydroureter and hydronephrosis was detected.

A septicaemic disease of East African snakes associated with enterobacteriaceae.

A bacterial epizootic disease of snakes at a snake farm in Kenya is described. The condition shows characteristic clinical signs and post mortem lesions and is characterized by a bacteraemia and septicaemia. The mortality rate is high and newly captured snakes die within a few weeks. Attempted control of the disease is discussed briefly and attention is drawn to the significance of such a condition in a commercial enterprise.

Diagnostic problems in liaison psychiatry and the ICD-10.

Liaison psychiatry is an area fraught with diagnostic problems due to the complex overlap between psychopathology and physical illness. The worst difficulties arise where patients also exhibit maladaptive behaviour such as deliberate self harm. In these situations a number of professionals may become involved including physicians, psychiatrists and social workers. As the level of complexity of a case increases an accurate formulation and diagnosis become essential. The International Classification of Diseases 10th revision (ICD-10) in its 1986 draft is currently being field tested. Chapter V (F) 'Mental, Behavioural and Developmental Disorders, is a descriptive clinical psychiatric classification, which will soon be incorporated into a multi-axial schema. This draft classification was used to make a diagnosis for 50 consecutive referrals to a liaison psychiatrist working in a large District General Hospital. This report assesses the applicability of ICD-10, V (F) in liaison psychiatry, and also comments on the characteristics of this group of patients. This leads to a discussion of the requirements for the other axes that would be needed to produce a multi-axial schema capable of allowing complex problems to be accurately formulated.

Some factors inhibiting amplification of the Staphylococcus aureus enterotoxin C1 gene (sec+) by PCR.

PCR amplification of the sec+ gene for staphylococcal enterotoxin C1 (SEC1) can be achieved from as little as 10 fg total genomic DNA (equivalent to less than 10 cells) using two nested primer pairs. The presence of bacterial cells, particularly thermonuclease-producing staphylococci, and the thermonuclease enzyme (TNase) itself, were found to be factors which individually and together reduced the sensitivity of PCR amplification.

Effects of female sterilization: one year follow-up in a prospective controlled study of psychological and psychiatric outcome.

A prospective controlled study of the psychological effects of elective interval and postpartum tubal sterilization was carried out on a selected sample of women. Subjects were interviewed pre-operatively (n = 138) and one year post-operatively (n = 116; 83%), using standardized instruments and procedures, including the Present State Examination. No differences within or between sterilization and control groups were found over the follow-up year in the prevalence of psychiatric morbidity, which was no higher than would be expected in a general population sample. Beneficial effects of sterilization were reported on a number of psychosexual variables. Adverse effects such as regret or deterioration in marital relationship were rare, but were more likely to occur in postpartum subjects, among whom abdominal pain was also reported more commonly at one year follow-up than pre-operatively. The relevance of "normal" postnatal events and of the role of pre-operative counselling are considered in relation to these findings. Less favourable outcome at one year follow-up was commonly associated with higher PSE scores pre-operatively.