Race-ethnicity and poverty after spinal cord injury.

STUDY DESIGN: Secondary analysis of existing data. OBJECTIVE: Our objective was to examine the relationship between race-ethnicity and poverty status after spinal cord injury (SCI). SETTING: A large specialty hospital in the southeastern United States. METHODS: Participants were 2043 adults with traumatic SCI in the US. Poverty status was measured using criteria from the US Census Bureau. RESULTS: Whereas only 14% of non-Hispanic White participants were below the poverty level, 41.3% of non-Hispanic Blacks were in poverty. Logistic regression with three different models identified several significant predictors of poverty, including marital status, years of education, level of education, age and employment status. Non-Hispanic Blacks had 2.75 greater odds of living in poverty after controlling for other factors, including education and employment. CONCLUSION: We may need to consider quality of education and employment to better understand the elevated risk of poverty among non-Hispanic Blacks in the US.

Measuring communicative participation using the FOCUS©: Focus on the Outcomes of Communication Under Six.

BACKGROUND: The FOCUS© is a new outcome tool for use by both parents and clinicians that measures changes in the communicative participation skills of preschool children. Changes in communicative participation skills as measured by the FOCUS were compared across three groups of children: those with speech impairments only (SI), those with language impairments only (LI) and those with both speech and language impairments (S/LI). METHODS: Participating families (n = 112, 75 male children) were recruited through 13 Canadian organizations. Children ranged from 10 months to 6 years 0 months (mean = 2.11 years; SD = 1.18 years) and attended speech-language intervention. Parents completed the FOCUS at the start and end of treatment. There were 23 children in the SI group, 62 children in the LI group and 27 children in the S/LI group. The average amount of the children's therapy varied from 7 to 10 h. RESULTS: The FOCUS captures changes in communicative participation for children with a range of communication disorder types and severities. All three groups of children made clinically important improvements according to their FOCUS scores (MCID ≥ 16 points). The FOCUS captured improvements in intelligibility, independent communication, play and socialization. CONCLUSIONS: The FOCUS measured positive changes in communicative participation skills for all three groups of children after 7-10 h of speech-language therapy. An outcome measure that targets only specific speech and language skills would miss many of the important social function changes associated with speech-language treatment.

Construct validity of the FOCUS© (Focus on the Outcomes of Communication Under Six): a communicative participation outcome measure for preschool children.

OBJECTIVE: The aim of this study was to establish the construct validity of the Focus on the Outcomes of Communication Under Six (FOCUS©). This measure is reflective of concepts in the International Classification of Functioning Disability and Health--Children and Youth framework. It was developed to capture 'real-world' changes (e.g. communicative participation) in preschoolers' communication following speech-language intervention. METHOD: A pre-post design was used. Fifty-two parents of 3- to 6-year-old preschoolers attending speech-language therapy were included as participants. Speech-language therapists provided individual and/or group intervention to preschoolers. Intervention targeted: articulation/phonology, voice/resonance, expressive/receptive language, play, and use of augmentative devices. Construct validity for communicative participation was assessed using pre-intervention and post-intervention parent interviews using the FOCUS© and the communication and socialization domains of the Vineland Adaptive Behavior Scales-II (VABS-II). RESULTS: Significant associations were found between the FOCUS©, measuring communicative participation, and the VABS-II domains for: (i) pre-intervention scores in communication (r = 0.53, P < 0.001; 95% CI 0.30-0.70) and socialization (r = 0.67, P < 0.001; 95% CI 0.48-0.80); (ii) change scores over-time in communication (r = 0.45, P < 0.001; 95% CI 0.201-0.65) and socialization (r = 0.39, P = 0.002; 95% CI 0.13-0.60); and (iii) scores at post-intervention for communication (r = 0.53, P < 0.001; 95% CI 0.30-0.70) and for socialization (r = 0.37, P = 0.003; 95% CI 0.11-0.50). CONCLUSIONS: The study provided evidence on construct validity of the FOCUS© for evaluating real-world changes in communication. We believe that the FOCUS© is a useful measure of communicative participation.

Optimal conditions for lentiviral transduction of engrafting human CD34+ cells.

Cytokines are required for γ-retroviral transduction of human CD34+ cells. However, cytokines may reduce engraftment of CD34+ cells and may not be necessary for their lentiviral transduction. We sought to optimize transduction and engraftment of human CD34+ cells using lentiviral vectors. Single 24 h transduction of human CD34+ cells with human immunodeficiency virus type 1 (HIV1)-based lentiviral vectors in media containing stem cell factor (SCF), FMS-like tyrosine kinase 3 (FLT3) ligand, thrombopoietin (each 100 ng ml⁻¹) and 10% fetal bovine serum was compared with various cytokine conditions during ex vivo culture and assayed using humanized xenograft mice for 6 months after transplantation. Serum-free media improved transduction efficiency of human CD34+ cells. Interleukin-3 (20 ng ml⁻¹) had little effect on transduction efficiency or engraftment. Threefold higher cytokine mixture (each 300 ng ml⁻¹) reduced engraftment of CD34+ cells. SCF alone (100 ng ml⁻¹) proved insufficient for maintaining engraftment ability and reduced transduction efficiency. Short-term prestimulation had little effect on transduction efficiency or engraftment, yet 24 h prestimulation showed higher transduction efficiency, higher gene expression levels and lower engraftment. In summary, 24 h prestimulation followed by single 24-h lentiviral transduction in serum-free media with SCF, FLT3 ligand and thrombopoietin yields high transduction efficiency to engrafting human CD34+ cells, and is applicable in human clinical gene therapy trials.

Composite tissue vasculopathy and degeneration following multiple episodes of acute rejection in reconstructive transplantation.

Transplant vasculopathy has not been systematically investigated in composite tissue allotransplantation (CTA). The impact of multiple acute rejections (ARs) on long-term graft outcomes in reconstructive transplantation remains unknown. This study in a rat hind-limb allotransplantation model systematically analyzes vasculopathy and tissue-specific pathological changes secondary to multiple AR episodes. LEW rats were transplanted with BN rat hind limbs and treated as follows: Group 1 (Iso): isografts. Group 2 (CsA): Cyclosporine (CsA) qd; Group 3 (mult AR): CsA and dexamethasone only when AR was observed. No AR was observed in Groups 1 and 2. Multiple AR were observed in Group 3, and each episode was completely reversed (clinically) with pulsed CsA + dexamethasone treatment. Group 3 animals demonstrated significant vascular lesions along with skin and muscle atrophy, upregulation of profibrotic gene expression and fibrosis when compared to Groups 1 and 2. In addition, allograft bone was sclerotic, weak and prone to malunion and nonunion. Interestingly, vasculopathy was a late finding, whereas muscle atrophy with macrophage infiltration was seen early, after only a few AR episodes. Taken together, multiple AR episodes lead to vasculopathy and tissue-specific pathology in CTA. This is the first evidence of 'composite tissue vasculopathy and degeneration (CTVD)' in CTA.

DNA hypermethylation regulates the expression of members of the Mu-class glutathione S-transferases and glutathione peroxidases in Barrett's adenocarcinoma.

BACKGROUND: The accumulation of reactive oxygen species and subsequent oxidative DNA damage underlie the development of Barrett's oesophagus (BO) and its progression to Barrett's dysplasia (BD) and adenocarcinoma (BAC). METHODS: The promoter regions of 23 genes of the glutathione S-transferase (GST) and glutathione peroxidase (GPX) families were systematically analysed. Quantitative bisulfite pyrosequencing, real-time RT-PCR, western blot and immunohistochemical (IHC) analysis methods were utilised in this study. RESULTS: 14 genes were identified that have CpG islands around their transcription start sites: GSTs (GSTM2-M5, GSTA4, GSTP1, GSTZ1, GSTT2, GSTO1 and GSTO2) and GPXs (GPX1, GPX3, GPX4 and GPX7). Analysis of an initial set of 20 primary samples demonstrated promoter DNA hypermethylation and mRNA downregulation of GPX3, GPX7, GSTM2, GSTM3 and GSTM5 in more than half of the BAC samples. Further analysis of 159 primary human samples (37 normal, 11 BO, 11 BD and 100 BACs) indicated frequent hypermethylation (>or=10% methylation) of GPX3 (62%), GPX7 (67%), GSTM2 (69.1%) and GSTM3 (15%) in BACs. A significant inverse correlation between DNA methylation and mRNA expression level was shown for GPX3 (p<0.001), GPX7 (p = 0.002), GSTM2 (p<0.001) and GSTM5 (p = 0.01). Treatment of oesophageal cancer cell lines with 5-aza-2'-deoxycytidine and trichostatin-A led to reversal of the methylation pattern and re-expression of these genes at the mRNA and protein levels. The IHC analysis of GPX3, GPX7 and GSTM2 on a tissue microarray that contained 75 BACs with normal squamous oesophageal samples demonstrated an absent to weak staining in tumours (52% for GPX3, 57% for GPX7 and 45% for GSTM2) and a moderate to strong immunostaining in normal samples. CONCLUSION: Epigenetic inactivation of members of the glutathione pathway can be an important mechanism in Barrett's tumourigenesis.

'They're part of the team': participant evaluation of the ACTIVE intervention.

This study used participant feedback to qualitatively evaluate an intervention (Assessing Caregivers for Team Intervention through Videophone Encounters [ACTIVE]) that used videophone technology to include patients and/or their family caregivers in hospice interdisciplinary team meetings. Data were generated during individual interviews with hospice staff members and family caregivers who participated in ACTIVE intervention. Modified grounded theory procedures served as the primary analysis strategy. Results indicated that ACTIVE intervention enhanced team functioning in terms of context, structure, processes and outcomes. Participants discussed challenges and offered corresponding recommendations to make the intervention more efficient and effective. Data supported the ACTIVE intervention as a way for hospice providers to more fully realise their goal of maximum patient and family participation in care planning.

Composite tissue allotransplantation for the reconstruction of congenital craniofacial defects.

Facial disfigurement in children with congenital craniofacial defects can lead to decreased self-esteem and poor self-perception. Traditional methods of reconstruction can fail to achieve a normal appearance in patients with severe disfigurements. Composite tissue allotransplantation (CTA) in children could offer a unique reconstructive opportunity. A discussion of the usage of CTA for congenital craniofacial defects is thus warranted. Treatment of severe craniofacial clefts, Treacher-Collins syndrome, hemifacial microsomia, and some vascular anomalies can yield unsatisfactory results, even after multiple surgeries. CTA provides the advantage of intact vascularized bone that would not need to be reshaped to fit the defect, with the correct donor match. CTA also provides reconstruction with similar tissue type in regions of the central midface such as the nose, lips, and eyelids. With advances in transplant immunology to devise mechanisms to decrease immunosuppression and induce donor antigen-specific tolerance, CTA may be a future reality in the pediatric population.

Investigation of antibody-mediated rejection in composite tissue allotransplantation in a rat limb transplant model.

BACKGROUND: Despite the widely accepted implication of antidonor antibodies and complement in solid organ transplantation, their role in reconstructive allotransplantation is not clear. The aim of this study was to analyze the humoral immune response using a rat orthotopic limb transplantation model. METHODS: We used the Brown Norway to Lewis rat orthotopic hind-limb transplant model: Group 1, isografts; group 2, allografts with daily continuous cyclosporine treatment to prevent acute rejection; and group 3, allografts undergoing multiple episodes of acute rejection. Samples were taken at 30, 60, and 90 days. Serum was analyzed by FACS for antidonor antibodies. Tissue deposition of antibodies and complement was investigated by immunofluorescence. RESULTS: By day 90, animals in group 3 had undergone 19 (+/-3.2) acute rejection episodes. There was no difference in the occurrence of serum antidonor antibodies between the three groups at any time point. However, at 90 days, anti-third-party antibodies were significantly greater among group 3. There was no difference in antibody or complement deposition in muscles between the 3 groups. CONCLUSION: Despite the increased antibody against a third party after multiple rejection episodes in this animal model, there was no clear evidence of an antibody-mediated alloresponse in limb transplantation.

Randomized Controlled Trial Comparing the Effects of Far-Infrared Emitting Ceramic Fabric Shirts and Control Polyester Shirts on Transcutaneous PO2.

Our aim was to confirm earlier studies showing tcPO2 to be higher under clothing made with polyethylene terephalate (PET) fabric containing ceramic particles (CEL) compared to standard PET fabric. In previous studies PET garments were donned first to avoid possible persistent effects from ceramic particles. This study randomized donning sequence to avoid bias. METHODS: Subjects were randomized to don either PET shirts first (PETF n=73) or CEL first (CELF n=80), switching garments after 90 minutes. Skin temperature (ST), arterial oxygen saturation (O2sat), and tcPO2 were measured every 30 minutes. RESULTS: Baseline ST and O2 sat were nearly identical in the two groups. Baseline tcPO2 was modestly higher in the CELF group than with PETF: 66.4 ± 18.9 vs. 63.9 ± 18.8 mmHg (n.s). Independent of donning sequence, tcPO2 measurements 90 minutes after wearing CEL were 6.7% higher than after 90 minutes wearing PET (p<0.0003). Sequence analysis found tcPO2 in PETF subjects to gradually rise before and after switching garments, but tcPO2 fell immediately after switching garments in CELF subjects. PETF baseline O2sat of 98.1 ± 1.3 increased insignificantly after 90 minutes, and then increased further to 98.6 ± 0.8 after wearing CEL ninety minutes (p=0.0001). CELF baseline O2sat of 97.9 ± 1.7 increased to 98.5 ± 1.1 90 minutes after donning CEL (p=0.0002) and fell to 98.3 ± 1.0 ninety minutes after switching to PET (p=0.0033). CONCLUSIONS: The ability of ceramic-embedded fabric to induce higher tcPO2 measurements is not due to sequence bias.

Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice.

The KvLQT1 gene encodes a voltage-gated potassium channel. Mutations in KvLQT1 underlie the dominantly transmitted Ward-Romano long QT syndrome, which causes cardiac arrhythmia, and the recessively transmitted Jervell and Lange-Nielsen syndrome, which causes both cardiac arrhythmia and congenital deafness. KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer. Because of the diverse human disorders and organ systems affected by this gene, we developed an animal model by inactivating the murine Kvlqt1. No electrocardiographic abnormalities were observed. However, homozygous mice exhibited complete deafness, as well as circular movement and repetitive falling, suggesting imbalance. Histochemical study revealed severe anatomic disruption of the cochlear and vestibular end organs, suggesting that Kvlqt1 is essential for normal development of the inner ear. Surprisingly, homozygous mice also displayed threefold enlargement by weight of the stomach resulting from mucous neck cell hyperplasia. Finally, there were no features of BWS, suggesting that Kvlqt1 is not responsible for BWS.

Whole-eye transplantation: a look into the past and vision for the future.

Blindness afflicts ~39 million people worldwide. Retinal ganglion cells are unable to regenerate, making this condition irreversible in many cases. Whole-eye transplantation (WET) provides the opportunity to replace diseased retinal ganglion cells, as well as the entire optical system and surrounding facial tissue, if necessary. Recent success in face transplantation demonstrates that this may be a promising treatment for what has been to this time an incurable condition. An animal model for WET must be established to further enhance our knowledge of nerve regeneration, immunosuppression, and technical aspects of surgery. A systematic review of the literature was performed to evaluate studies describing animal models for WET. Only articles in which the eye was completely enucleated and reimplanted were included. Study methods and results were compared. In the majority of published literature, WET can result in recovery of vision in cold-blooded vertebrates. There are a few instances in which mammalian WET models demonstrate survival of the transplanted tissue following neurovascular anastomosis and the ability to maintain brief electroretinogram activity in the new host. In this study we review in cold-blooded vertebrates and mammalian animal models for WET and discuss prospects for future research for translation to human eye transplantation.

Dye binding probes of lipid-binding structures. An investigation of 2-p-toluidinylnaphthylene-6-sulfonate binding to human and bovine prothrombin and fragment 1 in the presence and absence of calcium and magnesium ions.

TNS (2-p-toluidinylnaphthylene-6-sulfonate) binds to human and bovine prothrombin and Fragment 1 in the absence and presence of added Ca2+. The stoichiometry of TNS binding is 1:1 for human and bovine prothrombin and Fragment 1. The Ca2+-dependence of the fluorescence of TNS bound to bovine prothrombin Fragment 1 yields a modified Hill plot slope of 2.7, which is consistent with the slope obtained by monitoring the Ca2+ dependence of protein fluorescence quenching, CD changes and phospholipid binding. Mg2+ has have no effect on the fluorescence of TNS-prothrombin fluorescence. TNS binding to the amino-terminal region of prothrombin is the first relatively simple probe of the subtle and complex relationship which exists between protein structure and phospholipid binding.

Functional studies on the anti-pathoangiogenic properties of CM101.

Group B streptococcus (GBS) isolated from human neonates diagnosed with sepsis and respiratory distress produces a polysaccharide exotoxin (CM101) which has been previously described as GBS toxin. CM101 infused i.v. into tumor-bearing mice causes rapid tumor neovascularitis, infiltration of inflammatory cells, inhibition of tumor growth and tumor apoptosis. CM101 has successfully completed phase I studies in refractory cancer patients with very encouraging results. We have now demonstrated a mechanism of action for CM101. Using a normal mouse tumor model, we have examined tumor and normal tissues which were harvested at 0, 5, 15, 30 and 60min post-infusion of either CM101 or dextran. We present evidence that CM101 is rapidly (within the first 5min) bound to the tumor neovasculature. Complement is activated by the alternative pathway (C3) and leukocytes start to infiltrate the tumor within the first 5min. Through RT-PCR and immunohistochemical techniques, we demonstrate that proinflammatory cytokines, interleukin-6 and tumor necrosis factor (TNF)-alpha, are up-regulated in infiltrating leukocytes and TNF receptor 2 is up- regulated in the targeted tumor neovasculature. Combined, these events constitute possible explanations for the observed pathophysiology of tumor ablation.

Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer.

Esophageal cancer is a major cause of morbidity and mortality worldwide. Although patients often present with apparently resectable disease, systemic spread frequently occurs before the development of symptoms and detection of tumor. The use of combined chemoradiation therapy, particularly before resection, appears to prolong survival and increase cure rates in certain histologic subtypes. Four randomized phase III trials compared preoperative chemoradiotherapy plus surgery with surgery alone. In trials including only patients with squamous histology, no improvement in survival was observed with preoperative chemoradiation therapy; however, in a trial including only patients with adenocarcinoma histology, improved median and overall survival were observed. Paclitaxel has been evaluated as a single agent in a phase II trial in previously untreated patients with locally advanced unresectable or metastatic esophageal cancer; the overall response rate was 32% and median survival was 13.2 months. Paclitaxel-based combinations also have been evaluated in esophageal cancer; particularly encouraging preliminary results have been achieved with paclitaxel/cisplatin/5-fluorouracil. Because paclitaxel is a potent radiosensitizer, it also has been evaluated in combination with radiation therapy for esophageal and other thoracic cancers, alone and in combination with other chemotherapeutic agents. Preliminary results suggest that neoadjuvant therapy with paclitaxel-based combinations (including 5-fluorouracil and cisplatin) and radiation is highly active, with variable toxicity. A goal of future trials is to assess paclitaxel-based combined modality therapy in combination with other new chemotherapeutic agents.

Nodular regenerative hyperplasia in partial hepatectomy specimens.

To investigate possible associations of nodular regenerative hyperplasia (NRH) with antitumor chemotherapy, we reviewed 72 partial hepatic resections (55 with metastatic tumor, 12 hepatocellular carcinomas, and five benign neoplasms). Thirty autopsy livers from adults without malignancies served as controls. Studies included hematoxylin and eosin, reticulin, and trichrome stains and immunostaining for proliferating cell nuclear antigen (PCNA). Five of 72 livers (7%) had NRH. All five patients had received chemotherapy, one by intrahepatic artery infusion. Four had received chemotherapy 2 months or less before undergoing partial hepatectomy. These five cases represented 15% of the 33 patients who received chemotherapy. No NRH was seen in autopsy control livers. In contrast to NRH, multiple hyperplastic foci were seen in 28 of 72 livers (39%). This finding did not correlate with chemotherapy. Two of 30 control livers (7%) showed similar mild regenerative changes. In only one case of NRH was PCNA staining increased over controls. A band of PCNA-positive hepatocytes was seen adjacent to the tumor in 21 cases, suggesting that the presence of tumor may cause a local increase in PCNA expression. Mitoses in hepatocytes and assessment of the thickness of liver cell plates were more sensitive indicators of regeneration than PCNA. Vascular changes, such as sinusoidal fibrosis (11 of 72 cases), thickened hepatic arterioles (13 of 72 cases), and mild thickening of central veins (10 of 72 cases), did not correlate with NRH, hyperplastic foci, or chemotherapy. No cases of hepatoportal sclerosis were identified.

Gastrointestinal pathology in patients with common variable immunodeficiency and X-linked agammaglobulinemia.

Review of the medical records of 43 patients with common variable immunodeficiency (CVID) and 23 patients with X-linked agammaglobulinemia (XLAG) revealed a high incidence of chronic gastrointestinal complaints, most commonly diarrhea. Thirty-eight biopsies, four small-bowel resection specimens, and one autopsy from 10 patients with CVID and one patient with XLAG showed a wide range of abnormalities. A pattern resembling acute graft-versus-host disease, with apoptotic bodies and lymphocytes in crypts, was seen in the stomach (four patients), small bowel (three patients), and colon (three patients). Small-bowel specimens from three CVID patients with malabsorption showed mild to severe villous atrophy. Three CVID patients had Giardia in biopsies. Two cases of small bowel lymphoma associated with nodular lymphoid hyperplasia were identified in CVID patients. One patient's small bowel contained foamy histiocytes in the lamina propria, resembling Whipple's disease or chronic granulomatous disease, with numerous apoptotic bodies in crypts. Ultrastructurally, the histiocytes contained cellular debris. The patient with XLAG had recurrent fissuring necrosis of small bowel resembling Crohn's disease; a patient with CVID had colitis with features similar to ulcerative colitis. Poorly formed granulomas were seen in the stomach (one CVID patient) and the colon (two CVID patients). Lymphocyte populations were dominated by T cells; B cells were scarce except in lymphoid follicles in CVID patients with nodular lymphoid hyperplasia. Patients with CVID and XLAG manifest a spectrum of abnormalities in the gastrointestinal tract, with patterns superficially resembling graft-versus-host disease, inflammatory bowel disease, and Whipple's disease, but often lacking some of the diagnostic features of the diseases. Many of the CVID patients with chronic gastrointestinal complaints (62%) also had evidence of autoimmune phenomena, suggesting that in some patients the inflammatory process in the gastrointestinal tract has an autoimmune component.

Endoscopic tattoo agents in the colon. Tissue responses and clinical implications.

Laparoscopic surgery frequently requires tattooing of endoscopically identified sites for localization during surgery. Some tattooing agents cause serious tissue injury, which must be recognized in pathologic examination. Seven surgically resected colons were reviewed after injection with methylene blue or India ink at intervals of 1 day to 7 weeks before surgery. Early reactions to India ink included necrosis, edema, and neutrophilic infiltration in the submucosa and muscularis propria. Vessels were inflamed but without fibrinoid necrosis. Early reactions to methylene blue included ischemic ulceration, necrosis, and eosinophilic infiltration in the submucosa as well as fibrinoid necrosis of vessel walls. In the repair of methylene-blue injury, obliterative intimal fibrosis was seen in vessels. Such changes were absent in the colons injected with India ink. The India ink remained remained visible with the naked eye and microscopically 7 weeks after injection. Methylene blue was not grossly visible 7 days after injection, and only microscopic particles of pigment remained in widely scattered macrophages. In light of these findings, the amount of ink injected should be minimized and the injection site should be completely resected at surgery. Methylene blue is a poor tattoo agent, but its occasional use continues, and pathologists should recognize the resulting reaction.

Gastric graft-versus-host disease: a blinded histologic study.

Acute graft-versus-host disease (GvHD) of the upper gastrointestinal (GI) tract is common after allogeneic bone marrow transplantation (BMT). However, diagnosis cannot be made on clinical presentation and endoscopic findings alone, because these are nonspecific, and histologic confirmation is often desirable. The diagnosis of gastric GvHD is often based on subtle findings with considerable potential for variability in interpretation. Evaluation of the reproducibility of diagnosis and recognition of histologic features of gastric GvHD was based on blinded review of 56 gastric biopsies (24 from patients with allogeneic BMT or unrelated umbilical cord blood transplantation and 32 control biopsies from patients who did not undergo BMT, of whom eight had active GI cytomegalovirus [CMV] infection). Histologic criteria for GvHD were apoptosis and gland destruction, sparse inflammatory infiltrate, and granular eosinophilic debris in dilated glands. Seventeen patients (22 biopsies) were judged to have clinical GvHD on the basis of skin or liver involvement and GI symptoms without other known cause. Eighteen of these 22 gastric biopsies were classified as GvHD by at least two of the three pathologists on initial review. Blinded histologic diagnosis of GvHD had a positive predictive value of 69%, a sensitivity of 82%, and specificity of 76%. False-positive results occurred in CMV gastritis, human immunodeficiency virus (HIV) infection, primary immunodeficiency, and after renal transplantation. Of individual features, granular debris in glands was a specific (94% specificity), but insensitive (41% sensitivity) marker for GvHD. Distinction between GvHD and CMV infection can be difficult, and GvHD can be confused with changes seen in HIV infection and other immunodeficiency states.

Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas.

CD44, an integral membrane glycoprotein expressed by many cell types, serves as the principal transmembrane hyaluronate receptor and may be a determinant of metastatic and invasive behavior in carcinomas. The expression of CD44 in 23 gastric adenocarcinoma and 12 peptic ulcer disease (PUD) resection specimens and gastric carcinoma cell lines HS746t and KATO III was examined by immunohistochemistry using the murine monoclonal antibody A3D8 on formalin-fixed, paraffin-embedded tissue or cells. Western blot analysis of whole cell lysates of KATO III and HS746t cells showed protein bands at 85 to 90 kd with KATO III cells expressing an additional band at 145 kd. In normal stomach gastric epithelium was negative. In PUD foveolar epithelium was focally positive, but staining did not correlate with the extent of gastritis. In carcinoma cases intensity of staining was progressively stronger comparing intestinal metaplasia with dysplasia with intramucosal carcinoma. Invasive carcinoma was invariably more strongly positive than dysplasia or intramucosal carcinoma. Twelve adenocarcinomas were weakly positive and 11 were strongly positive. The staining intensity of metastases (12 cases) was the same or weaker than the primary tumor. For the 12 patients whose carcinomas were weakly positive, mean length of survival for the six who died was 23.3 months. Five of the 11 patients whose carcinomas strongly expressed CD44 died within the study period with a mean length of survival of 11.0 months. A key consequence of CD44 overexpression in gastric carcinomas may be development of the invasive phenotype and strong expression may indicate a poorer prognosis.