Lymphadenectomy prior to rat hind limb allotransplantation prevents graft-versus-host disease in chimeric hosts

In previous rat studies, the use of mixed allogeneic chimerism (MAC) to induce host tolerance to hind limb allografts has resulted in severe graft-versus-host disease (GVHD). The purpose of this study was to determine if immunocompetent cells in bone marrow (BM) and/or lymph nodes (LNs) of transplanted limbs were responsible for inducing GVHD in mixed chimeric hosts. [ACIWistar Furth] chimeric rats received ACI hind limbs that were non-irradiated, irradiated (1050 cGy) or lymphadenectomized. Rejection, GVHD and donor chimerism was assessed. Chimeric hosts rejected none of their limbs. However, hosts of non-irradiated hind limbs succumbed to GVHD 22.4±0.8 days after transplantation. In contrast, chimeras that received irradiated or lymphadenectomized ACI hind limbs showed no clinical or histological signs of GVHD at 5 months. We conclude that mixed chimeric hosts are susceptible to GVHD due to the immunocompetent cell load provided by the LNs, not the BM, of hind limb allografts.Abbreviations BM Bone marrow - CPM Counts per minute - CTA Composite tissue allograft - FACS Fluorescence activated cell sorter - FITC Fluorescent iso-thiocyanate - GVH Graft-versus-host - GVHD Graft-versus-host disease - HVG Host-versus-graft - LN Lymph node - MAC Mixed allogeneic chimerism - MHC Major histocompatibility complex - MLR Mixed lymphocyte reaction - MoAb Monoclonal antibody - PBL Peripheral blood lymphocytes - SEM Standard error of mean - TBI Total body irradiation - TCD T-cell depletion/T-cell depleted - TCR T-cell receptor     

Comparison of conventional bacteriology with nucleic acid amplification (amplified mycobacterium direct test) for diagnosis of tuberculous meningitis before and after inception of antituberculosis chemotherapy

The role of nucleic acid amplification techniques in the rapid diagnosis of tuberculous meningitis remains uncertain. We compared the performance of Ziehl-Neelsen (ZN) staining, the Gen-Probe amplified Mycobacterium tuberculosis direct test (MTD), and culture with 341 cerebrospinal fluid specimens from 152 adults (73 with and 79 without tuberculous meningitis) before and after inception of antituberculosis chemotherapy. The sensitivity, specificity, and positive and negative predictive values of ZN staining before treatment were 34/66 (52%), 79/79 (100%), 34/34 (100%), and 79/111 (71%), compared with 25/66 (38%), 78/79 (99%), 25/26 (96%), and 79/120 (66%) for MTD. The sensitivity of combined ZN staining and MTD (either positive) was 45/66 (68%). The sensitivity of staining and culture fell more rapidly than that of MTD after the start of treatment: after 5 to 15 days of treatment, MTD was more sensitive than ZN staining (12/43 [28%] versus 2/43 [2%]; P = 0.013). Slower bacterial clearance was observed if M. tuberculosis was resistant to isoniazid and/or streptomycin: resistant organisms were more likely to be cultured from cerebrospinal fluid after 2 to 5 days of treatment than fully sensitive organisms (P < 0.001). The sensitivities of ZN staining, MTD, and the two tests combined were improved by repeated sampling to 38/59 (64%), 35/59 (59%), and 49/59 (83%), respectively. In conclusion, ZN staining of the cerebrospinal fluid is at least as good as MTD for the rapid diagnosis of tuberculosis and is much faster and less expensive. However, the combination of these methods on serial samples detects more cases. Alternative tests are still urgently required.     

Diagnostic accuracy of patients in performing skin self-examination and the impact of photography

OBJECTIVE: To determine the sensitivity and specificity of skin self-examination (SSE) to detect new and changing moles with and without the aid of baseline digital photographs in patients with dysplastic nevi. DESIGN AND INTERVENTION: Patients had baseline digital photography and mole counts of their back, chest, and abdomen and were instructed to perform a baseline SSE. Print copies of the images were provided to the patient. Following the baseline examination, the appearance of existing moles was altered and new moles were created using cosmetic eyeliner. The number of moles altered and/or created totaled approximately 10% of each patients' absolute mole count. SETTING AND PATIENTS: Fifty patients with 5 or more dysplastic nevi from the outpatient clinic at Memorial Sloan-Kettering Cancer Center, New York, NY. MAIN OUTCOME MEASURE: Skin self-examinations with and without access to the baseline photographs to identify the number of new and altered moles. RESULTS: The sensitivity and specificity of SSE for detection of both altered and new moles without photography were 60.2% and 96.2%, respectively. Skin self-examination with photography yielded a sensitivity and specificity of 72.4% and 98.4%, respectively. The findings were similar when stratified by site (back vs chest or abdomen). The sensitivity and specificity for new moles were higher compared with altered moles. CONCLUSIONS: Access to baseline photography improved the diagnostic accuracy of SSE on the back and chest or abdomen and improved detection of changing and new moles. Our results suggest that baseline digital photography in tandem with SSE may be effective in improving the diagnostic accuracy of patients performing SSE.     

Clinical characteristics of acute HSV-2 retinal necrosis

PURPOSE: To report the clinical features and evaluate the visual outcome of eleven cases of herpes simplex virus-2 (HSV-2) related acute retinal necrosis syndrome (ARN). DESIGN: Retrospective interventional case series. METHODS: Twelve eyes of eleven patients from two European centers, diagnosed with HSV-2 related acute retinal necrosis syndrome were retrospectively reviewed. Herpes simplex virus-2 DNA was detected by polymerase chain reaction in intraocular fluids (aqueous and/or vitreous). Findings at initial examination, clinical evolution with antiviral therapy, complications and final visual acuity were evaluated. RESULTS: Herpes simplex virus-2 DNA was detected in all cases. No sample was positive for more than one virus. The mean age of disease in the first eye was 36 years (ranged from 10 to 57 years). Five patients were women and six were men. All patients were immunocompetent. Previous medical history included neonatal herpes (n = 1), previous ARN (n = 3), trauma (n = 1) and systemic corticosteroid administration before occurrence of ARN (n = 3). Preexisting pigmented chorioretinal scars were found in three cases. Patients were treated with high dose intravenous acyclovir or foscarnet +/- intravitreal ganciclovir +/- interferon. The mean follow-up was 14.5 months (from 5 to 22 months). At the end of the follow-up period, five eyes (41.7%) showed improvement of visual acuity of two or more lines. Final visual acuity was 20/60 or better in four eyes (33.3%), 20/400 or better in four eyes (33.3%) and less than 20/400 in four eyes. CONCLUSION: History of neonatal herpes, triggering events such as neurosurgery, periocular trauma, high-dose corticosteroids, and chorioretinal scars suggest that HSV-2 retinitis reflects reactivation of HSV-2 infection.     

Coexisting epithelioid trophoblastic tumor and choriocarcinoma of the uterus following a chemoresistant hydatidiform mole

The epithelioid trophoblastic tumor is an unusual type of trophoblastic tumor. Herein, we describe a patient with coexisting epithelioid trophoblastic tumor and choriocarcinoma in the uterus. The patient had a history of hydatidiform mole with recurrent elevation of human chorionic gonadotrophin level that is resistant to chemotherapy. Histopathologic and immunohistochemical examination showed distinctive differences between the 2 trophoblastic tumors. The development of epithelioid trophoblastic tumor may be related to the persistence of locally invasive disease, which was unresponsive to chemotherapy. The patient responded well to surgery. The presence of an epithelioid trophoblastic tumor should be considered in chemoresistant gestational trophoblast tumor.     

Cycle-to-cycle variation in utero-ovarian hemodynamic indices in ovarian stimulation and natural cycles of the same women and its effect on the outcome of assisted reproduction treatment

OBJECTIVE: To investigate the blood flow parameters between cycles of the same women to assess whether parameters predicting a successful pregnancy in a stimulation cycle could be used to determine the outcome of subsequent natural cycles. DESIGN: A prospective study. SETTING: Assisted reproduction unit, the University of Hong Kong. PATIENT(S): Fifty-eight IVF cycles and 40 natural cycles were evaluated. INTERVENTION(S): Assessments of the utero-ovarian pulsatility indices (PIs), resistance indices (RIs), and endometrial color signals. RESULT(S): In IVF cycles, the pregnancy rate (27%) was similar to that in frozen-thawed embryo transfer (FET) (28%) cycles. The utero-ovarian PIs and RIs in IVF cycles were significantly lower than those in the natural cycles. There was a significant correlation between the uterine PI in stimulation cycles and that in natural cycles. In IVF cycles, the pregnancy rate declined significantly when the uterine PI was >2.70 and the RI was >0.9. In FET cycles, no decline in pregnancy rate was seen. Conceptional FET cycles showed significantly higher uterine PI, uterine RI, and endometrial color signals compared with conceptional IVF cycles. CONCLUSION(S): Hemodynamic parameters in stimulation cycles are different from those in natural cycles, and the values of various parameters in predicting pregnancy are also different.     

Preterm premature rupture of membrane and twin-to-twin transfusion syndrome before 20 weeks: a favourable outcome

We describe a monochorionic twin gestation with a severe twin-to-twin transfusion syndrome associated with a preterm premature rupture of membranes at 20 weeks of gestation in the polyhydramniotic sac. The pregnancy was managed expectantly and outcome was favourable for the 2 neonates. We discuss how these two severe pathologies seem to counteract each other by compensations of their symptoms.     

Diabetes mellitus is a recurrence-independent risk factor in patients with hepatitis B virus-related hepatocellular carcinoma undergoing resection

OBJECTIVES: The prognostic impact of diabetes mellitus and its association with virological factors on patients with hepatocellular carcinoma (HCC) are unclear. This study aimed to investigate the outcome in HCC patients undergoing resection with and without diabetes mellitus and the interaction with hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: A total of 239 HCC patients were included. Survival and tumour recurrence were analysed according to the status of diabetes mellitus and viral hepatitis. RESULTS: Diabetic patients tended to have an overall decreased survival compared with non-diabetic patients in 32 +/- 19 months of follow-up. A total of 113 (47%) patients developed tumour recurrence during the follow-up period. No significant difference of tumour recurrence between diabetic and non-diabetic patients, or between patients seropositive and seronegative for HBV surface antigen (HBsAg), was noted. Stratified analysis showed that diabetic patients with HBV but not with HCV infection had a poor long-term outcome. In the HBV group, the one-, three- and five-year survival rates were 83%, 51% and 41% versus 90%, 78% and 73% in diabetic and non-diabetic patients, respectively, compared with 90%, 83% and 42% versus 91%, 73% and 73% in the HCV group with and without diabetes mellitus, respectively. Cox multivariate analysis disclosed that diabetic patients seropositive for HBsAg had a significantly poor survival. CONCLUSIONS: Diabetes mellitus does not affect the long-term survival in HCV-related HCC but is a recurrence-independent poor prognostic factor for HBV-related HCC.