Lymphoid Neogenesis in Murine Cardiac Allografts Undergoing Chronic Rejection

Lymphoid neogenesis is the process by which ectopic lymphoid accumulations that resemble lymph nodes arise in nonlymphoid tissues. Such lymphoid accumulations, known as tertiary lymphoid organs (TLO), are observed in chronic autoimmunity and they propagate immune pathology by setting up local antigen presenting sites. Whether lymphoid neogenesis occurs in transplanted organs and contributes to rejection is not well understood. To begin to address this question, we retrospectively analyzed 319 murine cardiac allografts for microscopic evidence of lymph-node-like structures. We found 78 allografts that had either classical TLO, characterized by discrete T- and B-cell zones and high endothelial venules (HEV) expressing peripheral node addressin (PNAd) (n = 34), or PNAd(+) HEV without organized lymphoid accumulations (n = 44). These changes were present in both short- and long-lived allografts and were invariably associated with rejection. Importantly, they occurred in 78% of allografts undergoing chronic rejection (n = 85) but in only 7% of allografts undergoing primarily acute rejection (n = 184). These findings indicate that, like autoimmunity, alloimmunity is associated with lymphoid neogenesis in the target organ and suggest a role for local T-cell activation in chronic allograft rejection.     

Juvenile progressive systemic sclerosis: report of five cases

Five cases of juvenile progressive systemic sclerosis (SSc) are reported (4 girls and 1 boy). The age of onset of the disease ranged from 4 to 13 years. The clinical features included Raynaud's phenomenon present in 4 of 5 cases; hyperpigmentation, skin tightening and contractures of the large joints were noted in all 5 cases. One patient initially diagnosed as having eosinophilic fasciitis developed SSc 3 months later. Another patient was diagnosed initially as having juvenile rheumatoid arthritis. There was one case of pulmonary fibrosis and another of mild restrictive lung disease. Two cases of esophageal and intestinal hypomotility were reported. Scleroderma nephropathy was absent in all 5 cases.     

Neuroprotective effect of memantine demonstrated in vivo and in vitro

The purpose of the present study was to test whether the anticonvulsant, memantine (1-amino-3,5-dimethyladamantane), can protect neurons against hypoxic or ischemic damage. To this end, we used a rat model of transient forebrain ischemia and cultured neurons from chick embryo cerebral hemispheres. Ischemia was induced for 10 min by clamping both carotid arteries and lowering the mean arterial blood pressure to 40 mm Hg; the rats were allowed to recover for 7 days. Cultured neurons were made hypoxic with 1 mmol/l NaCN added to the incubation medium for 30 min followed by a recovery period of 3 days. The possible effects of memantine were compared with those produced by a typical non-competitive NMDA antagonist, dizocilpine. Similar effects were obtained with both drugs. The drugs reduced the damage caused by transient ischemia to neurons of the hippocampal CA1 subfield. Memantine (10 and 20 mg/kg) had a dose-dependent effect when administered intraperitoneally to the rats 1 h before ischemia. Dizocilpine was active in this model at a dosage of 1 mg/kg. When administered after ischemia, 10 mg/kg memantine significantly protected CA1 neurons against ischemic damage. Furthermore, the drugs protected cultured neurons against hypoxic damage. The lowest effective concentration was 0.1 mumol/l for dizocilpine and 1 mumol/l for memantine. Thus, memantine possesses neuroprotective activity but is less potent than dizocilpine.     

Outcome of surgery in patients with hematological malignancies: A 12-year retrospective analysis

Background: Surgical intervention in patients with malignant hematological disorders is a major undertaking due to the expected risks of bleeding, infection and poor wound healing. Methods and materials: A retrospective study of patients treated at the Riyadh Armed Forces Hospital, Saudi Arabia between January 1991 and December 2002 was conducted. The results of patients with acute leukemia and lymphoma who underwent surgical procedures (study group) were compared with those of a control group composed of patients with the same spectrum of disorders treated over the same period of time and given the same treatment protocols but never required any surgery. Results: No single death occurred intraoperatively or in the immediate postoperative period due to surgical therapy per se. However, follow up of both groups of patients revealed a shorter long‐term survival and higher rates of relapse and severe invasive infections in the surgical group compared to the control group of patients. The mean survival for the study group was 1871 ± 307 days versus 3094 ± 279 days for the control group of patients (P = 0.0027). Thirty (75%) study patients suffered relapses of their malignant hematological disorders versus 23 (37.1%) control patients. Forty‐five relapses were encountered in the study group of patients (1.5 relapses per relapsed patient) versus 26 relapses in the control group (1.13 relapses per relapsed patient). Various infections occurred in 37 (92.5%) study patients and 32 (51.6%) control patients. Recurrent infections developed in 30 (75%) study patients and 22 (35.5%) control patients (P = 0.00008). Infections causing tissue invasion were encountered in 29 (72.5%) study patients and 22 (35.5%) control patients. Conclusion: Even major surgical procedures can be performed in patients with leukemia or lymphoma provided enough preparatory measures are made to minimize bleeding and infectious complications. Surgery may, however, be associated with long‐term complications such as a high incidence of relapse of the primary malignant hematological disorder and an increased rate of severe and invasive infections.     

Cystic fibrosis detection in high-risk Egyptian children and CFTR mutation analysis.

BACKGROUND: Knowledge about Cystic Fibrosis (CF) in Egypt is very limited. The objective of this study was to screen for CF in Egyptian children with suggestive clinical features and to identify causative genetic mutations. METHODS: Sixty-one patients from the Chest Unit, Cairo University Children's Hospital, Egypt, were included. Subjects presented with persistent or recurrent respiratory symptoms, failure to thrive, diarrhea and/or steatorrhea and unexplained persistent jaundice. Patients were screened using the CF Indicatortrade mark sweat test system (PolyChrome Medical, Inc., Brooklyn Center, MN). A quantitative sweat testing was conducted on 10 of the 12 positive patients. Seven probands and one sibling underwent molecular analysis by direct DNA sequencing of the coding region and of the intronic sequences adjacent to the 27 exons of the CFTR gene. RESULTS: Of 61 patients, 12 (20%) had positive sweat chloride screening. Ten of the 12 patients underwent quantitative sweat testing and were positive. Eight CFTR sequence changes were identified in seven affected probands and two were confirmed in one sibling by direct DNA sequencing. CONCLUSION: The study results suggest that CF is more common in Egypt than previously anticipated. Larger studies are warranted to identify the incidence, molecular basis and clinical pattern of CF in the Egyptian population.     

Determination of hepatitis C virus genotype by Pyrosequencing

A simple sequencing-based assay is described for genotyping of hepatitis C virus (HCV). RT-PCR was employed to amplify a 237-nucleotide-long fragment from the 5' untranslated region (UTR) of the genome using one biotinylated and one normal primer. Subsequent to capture of the PCR products on streptavidin-coated beads, single-stranded DNA separation, and hybridization of sequencing primer, Pyrosequencing was performed. The genotype of 98 samples out of which 77 samples were from American veterans and 21 samples were from Iran was determined. The samples from the American veterans contained six different subtypes, while five subtypes were found in Iranian samples. For rapid population-specific HCV subtyping, a multiplex assay was developed. This study demonstrates the suitability of this technology for low-cost, high throughput and accurate microbial genotyping.     

Management of Isolated Blunt Duodenal Injury

Five cases of duodenal injuries were treated in our hospital between January 1, 1975 and June 18, 1979. They belonged to the Class II and early Class III of duodenal injuries. They were treated with simple closure of the perforation in a single or double layer with external drainage. Only in one case were gastrojejunostomy and bilateral vagotomy added because the patient had a history of ulcer disease. The delay in operative treatment ranged between five and 48 hours. All responded well to the surgical treatment. In the instance of the longest operative delay, a purulent drainage occurred and it responded promptly to a selective antibiotic therapy. The average hospitalization stay was nine days for the patients operated upon early, whereas it was 15 days for the two delayed cases. No mortality was recorded.