Severe hemolysis resulting from D incompatibility in a case of ABO-identical liver transplant

BACKGROUND: Hemolysis due to D incompatibility in the setting of liver transplantation is less frequent than that associated with ABO incompatibility, but can represent an equally adverse event. Approximately 10 percent of ABO-compatible liver transplants involve a D- donor and a D+ recipient. CASE REPORT: A case of severe D incompatibility resulting from liver transplantation in a 50-year-old O Rh+ man with end-stage liver disease who received an O Rh- liver allograft is reported. A declining hemoglobin level complicated the patient's postoperative course with laboratory evidence of anti-D-mediated hemolysis. Investigations revealed that the transplanted liver was from a female O Rh- donor with detectable antibodies against D, C, and K. The severity of the hemolytic anemia was such that the patient required two separate red blood cell (RBC) exchanges and intermittent RBC transfusions over the course of almost a year. In addition to the use of RBCs negative for D, C, and K, the patient underwent a variety of B-cell suppressive therapies including glucocorticosteroids, mycophenolate mofetil, and rituximab. A normalization of hemoglobin levels and a decrease in serum bilirubin did not occur until after a splenectomy on postoperative Day 321. CONCLUSION: This represents the sixth and most severe case reported of hemolysis resulting from D incompatibility in liver transplantation. When unexpected serologic findings are identified in a transplant recipient, obtaining more information on the donor may help guide transfusion support.     

KLF5 is frequently deleted and down-regulated but rarely mutated in prostate cancer

BACKGROUNDS: Previous studies mapped a region at the q21 band of chromosome 13 (13q21), which is frequently deleted in various human cancers including prostate cancer, suggesting the existence of a tumor suppressor gene at 13q21. The target gene of deletion in prostate cancer, however, has not been identified at present. METHODS: We examined four non-neoplastic and 18 neoplastic prostatic cell lines or xenografts. Homozygous/hemizygous deletion was detected by assays of duplex PCR and real-time PCR. Expression levels of genes were determined by the methods of RT-PCR, real time PCR, and northern blot analysis. Mutations of KLF5 were detected by the approaches of single strand conformational polymorphism (SSCP) and direct sequencing. For the detection of promoter methylation, Southern blotting of genomic DNA and restriction digestion or SSCP analysis of methylation specific PCR products were used. Finally, an expression plasmid of KLF5 was introduced into prostate cancer cell lines with reduced KLF5 expression to investigate colony formation for cell growth. RESULTS: A 2-Mb region of homozygous deletion at 13q21 was detected in the LUCaP70 xenograft of prostate cancer. This region of deletion was further narrowed to 142 Kb by a hemizygous deletion in the NCI-H660 cell line. KLF5 was identified as the only complete gene in the smallest region of deletion. Quantitative deletion of KLF5 genome occurred in six of the 18 (33%) prostate cancer xenografts/cell lines. Each of the six samples with deletion also showed loss of expression for KLF5, suggesting that hemizygous deletion is one mechanism for loss of KLF5 expression. In total, 16 of the 18 cases (89%) showed loss of KLF5 expression at different degrees. In contrast, mutations and promoter methylations were not detected in any of the samples. Functionally, restoration of KLF5 in DU 145 and 22Rv1 cell lines significantly inhibited their growth in vitro. CONCLUSIONS: Frequent genomic deletion and loss of expression as well as cell growth suppression indicate that KLF5 is a reasonable candidate for the tumor suppressor gene at 13q21 in prostate cancer. Mutation and promoter methylation are not common mechanisms for the inactivation of KLF5 in prostate cancer.     

Collagen fibrils appear more closely packed in the prepupillary cornea: optical and biomechanical implications

PURPOSE: The size and organization of stromal collagen fibrils influence the biomechanical and optical properties of the cornea and hence its function. How fibrillar structure varies with position across the cornea has not been fully characterized. The present study was designed to quantify the collagen fibril spacing and diameter across the normal human cornea and to relate this to the properties of the tissue. METHODS: Small-angle x-ray diffraction was used to map in detail the variation in fibril spacing and fibril diameter along orthogonal medial-lateral and inferior-superior meridians of five normal human corneoscleral discs. RESULTS: Mean fibril diameters remained constant across all corneas up to the limbus, whereupon a sharp increase was observed. However, mean fibril spacing across the central 4 x 3 mm (prepupillary) cornea measured 5% to 7% lower than in the peripheral cornea. CONCLUSIONS: Collagen fibrils in the prepupillary cornea appear to be more closely packed than in the peripheral cornea. Anisotropy in fibril packing across the cornea has potential implications for the transparency and refractive index of the tissue. Biomechanically, it is possible that the higher packing density of stress-bearing collagen fibrils in the prepupillary cornea is necessary for maintaining corneal strength, and hence curvature, in a region of reduced tissue thickness. By inference, these results could have important implications for the development of corneal models for refractive surgery.     

Clinicopathologic analysis of solid papillary carcinoma of the breast and associated invasive carcinomas

Solid papillary carcinomas (SPCs) are uncommon tumors composed of circumscribed large cellular nodules separated by bands of dense fibrosis. The aim of this study was to further elucidate the characteristics of SPC, the types and significance of invasive carcinomas associated with these tumors, and the long-term clinical outcome. Fifty-eight SPCs were analyzed (mean follow-up, 9.4 years). Cases were divided into three groups: 1) SPC only (32.7%), 2) SPC with extravasated mucin (8.6%), and 3) SPC with invasive components (58.7%) consisting of neuroendocrine-like (29.5%), colloid (23.5%), ductal not otherwise specified (14.5%), lobular (3%), tubular (3%), or mixed (26.5%). The mean age was 72 years. All were estrogen receptor positive and 86% were histologic grade 1. The total size of the tumor measured 0.3 to 15 cm. In the group with invasive carcinoma, the size of invasion was 0.1 to 4 cm. Axillary nodes were involved in 13% of the cases (6 of 46); all of these had an invasive component in the primary tumor. Local recurrence was seen in 5 patients, all from the group with invasive carcinoma. Overall, 11.7% died of their tumor, 1 to 4 years after diagnosis (mean, 2.3 years); none of them belongs to the group of noninvasive SPC. Five of the 6 patients who died of tumor had invasive components. The sixth patient who died with "metastatic signet-ring cell carcinoma" at 10 years was in the group of patients with SPC with extravasated mucin where the SPC lesion had prominent signet-ring cell features. In conclusion, SPCs are heterogeneous lesions that arise in older women and have an indolent behavior. Lymph node and distant metastases are uncommon and generally limited to cases with (conventional) invasive components.     

Lead-associated deficits in stature,mental ability and behaviour in children in Karachi

This study was conducted to evaluate the cumulative and steady-state lead burden in children from Karachi, an area of high lead exposure, and to assess the degree of damage to physical growth and mental ability related to lead exposure. A cross-sectional survey was conducted in seven primary schools from around Karachi. Shed primary teeth and blood samples were collected from students of grades I to III (age range 6-10 years) and were analysed for lead by atomic absorption spectrophotometry. Haemoglobin concentration, height, weight and head circumference were measured. IQ was estimated using Raven's Standard Progressive Matrices. Classroom behaviour was rated by teachers and school performance was estimated from the percentage mark in a school examination taken just before the date of the IQ test. Complete data were available for 138 children. Over 80% of children had lead levels above the safety limit set by the United States Centers for Disease Control and Prevention. The blood lead levels in boys did not differ significantly from that in girls. Significant differences were observed between the schools. Univariate analysis showed negative association of blood lead with haemoglobin, IQ and height. Tooth lead was negatively associated with height, classroom behaviour and performance. When adjusted for other confounding variables, blood lead was negatively associated with haemoglobin and IQ, whereas tooth lead was negatively associated only with classroom behaviour. Height was negatively associated with blood or tooth lead. These results were further supported when the upper and lower quintiles for blood or tooth lead were compared. Tooth lead level was not a better marker of lead poisoning than blood lead level in our study population. These data demonstrate the association of increased lead with impaired learning and adverse behaviour in Karachi children and call for strict government regulations to limit environmental lead burden.     

Immunostaining for MART-1 in the interpretation of problematic intra-epidermal pigmented lesions

The histopathologic distinction between pigmented actinic keratosis (PAK) and atypical junctional melanocytic proliferations (AJMP) is a common problem, and it is one with meaningful clinical significance. Previous publications have suggested that Melanocyte Antigen Related to T-cells-1 (MART-1)--a melanocytic marker related to host immune response--was not useful in making this interpretative separation. To revisit that assertion, the authors selected 68 specimens that concerned the diagnosis of PAK vs. AJMP. The degree of morphologic difficulty attached to each case was rated semiquantitatively using a three-tiered scale, and interpretative problems were caused by cytologic similarity between atypical keratinocytes and aberrant melanocytes, obscuring lichenoid inflammation, subepidermal fibrosis, and an absence of clearly defined cell nests at the dermoepidermal junction. Each biopsy sample was immunostained for MART-1 (using antibody clone A103) with azure-B counterstaining; the principal criterion for a diagnosis of AJMP was that of confluent cellular positivity over at least 1 high-power (x400) microscopic field, in conjunction with nested cell growth. The specimens were then re-examined diagnostically. Immunostaining definitely improved interpretative certitude in 65 examples (96% effectiveness); the final diagnosis was that of PAK for 21 lesions and AJMP for 47. Three specimens--all of which represented AJMP--did not benefit by MART-1 staining. It is concluded that MART-1 immunostaining with azure-B counterstaining is a useful adjunct in the interpretation of problematic intra-epidermal pigmented lesions.     

Cardiac autonomic innervation

The autonomic nervous system plays a key role in regulating changes in the cardiovascular system and its adaptation to various human body functions. The sympathetic arm of the autonomic nervous system is associated with the fight and flight response, while the parasympathetic division is responsible for the restorative effects on heart rate, blood pressure, and contractility. Disorders involving these two divisions can lead to, and are seen as, a manifestation of most common cardiovascular disorders. Over the last few decades, extensive research has been performed establishing imaging techniques to quantify the autonomic dysfunction associated with various cardiovascular disorders. Additionally, several techniques have been tested with variable success in modulating the cardiac autonomic nervous system as treatment for these disorders. In this review, we summarize basic anatomy, physiology, and pathophysiology of the cardiac autonomic nervous system including adrenergic receptors. We have also discussed several imaging modalities available to aid in diagnosis of cardiac autonomic dysfunction and autonomic modulation techniques, including pharmacologic and device-based therapies, that have been or are being tested currently.     

Characterisation of a Bioactive SiO2-CaO-CaF2-Na2O Glass Used in Composites

ObjectivesTo characterise the ion release, pH changes and apatite formation of a phosphate free bioactive glass.MethodsA SiO₂-CaO-CaF₂-Na₂O glass was synthesized by a melt route with a composition close to the reactive glass in the commercial Cention N® composite. The glass was characterized after immersion in three media: Artificial Saliva pH4 (AS4) Artificial Saliva pH7 (AS7) and in a high phosphate artificial saliva at pH6.5 (AS6.5). The pH and fluoride release were measured using a pH meter and an ion selective electrode. The concentration of Ca, P, Na and Si were measured by ICP-OES. The glass powders after immersion were characterized by FTIR, X-ray powder diffraction and ¹⁹F MAS-NMR.ResultsThe glass increased the pH in all three media. Fluoride was detected in all three media but was much higher in AS 6.5. Calcium fluoride formed in AS4 with a small amount of fluorapatite at long immersion times. Fluorapatite and calcium fluoride formed in AS7, whilst in AS6.5 fluorapatite formed.The ion concentrations in solution after immersion reflected the glass composition and the immersion media with fluorapatite being favoured by higher pHs and phosphate contents in the media.SignificanceThe results demonstrated the ability of the glass to increase the pH and to form fluorapatite in phosphate containing media. This may explain the low incidence of secondary caries found in the commercial composite. Unlike the commercial composite evidence was found for the precipitation of fluorite, which will act to reduce the release of fluoride for preventing secondary caries.