A study of the changes during heating of paracetamol

Fanconi anaemia (FA) is an accepted indication for treatment with allogeneic HLA-identical BMT. Most patients, however, lack a suitable HLA-identical donor. In our centre, six FA patients were transplanted with a matched unrelated donor. Due to hypersensitivity to DNA cross-linking agents, a low-dose cyclophosphamide (CY) and thoraco-abdominal irradiation (TAI) regimen is recommended for conditioning in FA. We added Ara-C upfront and anti-T cell antibodies to enhance engraftment and to prevent GVHD, in combination with T cell depletion in four out of six of the first transplants. One patient did not engraft. In three patients rejection was observed. In three of these four patients a second BMT, using full bone marrow grafts, resulted in successful engraftment. The other patient died before a second BMT could be performed. The incidence and severity of acute GVHD was low: only one patient with grade III acute GVHD was seen. Two out of four surviving patients suffered from chronic GVHD. Four patients survived (median survival time 43 months after BMT), three with good and one with acceptable quality of life. Two patients died, one patient due to adenoviral reactivation with multi-organ failure, and one due to sepsis complicated by ARDS. In conclusion, MUD BMT is feasible in FA patients with bone marrow failure in whom no HLA-identical sibling donor is available. In our study group, the major problem was graft rejection, despite the administration of a combination of graft enhancing anti-T cell antibodies. Multicentre studies are needed to determine a more intensive, but still tolerable, conditioning regimen.     

Antimicrobial resistance in Neisseria gonorrhoeae in the United States, 1988-1994: the emergence of decreased susceptibility to the fluoroquinolones

Antimicrobial susceptibilities of Neisseria gonorrhoeae have been prospectively determined in the Gonococcal Isolate Surveillance Project of the Centers for Disease Control and Prevention. From 1988 through 1994, susceptibilities were determined for 35,263 isolates from 27 clinics. Patients were demographically similar to those in nationally reported gonorrhea cases. In 1994, 30.5% of isolates had chromosomally or plasmid-mediated resistance to penicillin or tetracycline. Penicillin resistance increased from 1988 (8.4%) to 1991 (19.5%) and then decreased in 1994 (15.6%). Tetracycline resistance decreased from 1988 (23.4%) to 1989 (17.3%) and then increased in 1994 (21.7%). Most isolates (99.9%) were highly susceptible to broad-spectrum cephalosporins. Isolates with decreased susceptibility to ciprofloxacin increased from 1991 (0.4%) to 1994 (1.3%); 4 isolates were ciprofloxacin-resistant. Ciprofloxacin-resistant strains may not respond to therapy with recommended doses of fluoroquinolones, and the clinical importance of strains with decreased susceptibility is unknown. The emergence of fluoroquinolone resistance in N. gonorrhoeae in the United States threatens the future utility of this class of antimicrobials for gonorrhea therapy.     

US case of the day. Diffuse large B-cell lymphoma (posttransplant lymphoproliferative disorder [PTLD])

OBJECTIVE: We describe two new CT findings of congestive heart failure (CHF): enlarged mediastinal lymph nodes and hazy heterogeneous mediastinal fat. MATERIALS AND METHODS: Forty-six patients were retrospectively identified who had major and minor clinical signs of congestive heart failure and had undergone chest CT during their symptomatic period. Two radiologists reviewed the CT studies and by consensus documented the presence or absence of imaging findings of CHF, including interstitial abnormalities, vascular redistribution, axial thickening, pleural effusions, cardiac enlargement, and mediastinal abnormalities. RESULTS: Smooth septal thickening, bilateral pleural effusions, vascular redistribution, and cardiac enlargement were the most common CT findings in patients with CHF. Enlarged mediastinal lymph nodes and hazy mediastinal fat were seen in 55% and 33% of cases, respectively. In a cohort of 17 patients with elevated pressures in the pulmonary capillary wedge documented within 24 hr of CT, CT scans revealed lymphadenopathy in 14 patients (82%) and inhomogeneous fat in 10 patients (59%). CONCLUSION: Enlarged mediastinal lymph nodes and hazy mediastinal fat occur in patients with CHF and are revealed by CT. Lymphadenopathy in patients with CHF does not necessarily indicate malignancy or an infectious process.     

Vaccination against ergot alkaloids and the effect of endophyte-infected fescue seed-based diets on rabbits

Three sequential experiments were conducted with rabbits to 1) determine the effect of endophyte-infected (E+) tall fescue seed on rabbit performance and examine the effect of anti-ergot alkaloid immunization on rabbit performance and protectiveness against fescue toxicosis, 2) compare immunogens designed to elicit systemic anti-ergot alkaloid antibodies, and 3) select a superior adjuvant. In Exp. 1, rabbits (n = 6/treatment) fed E+ fescue seed diets (20%, 340 ppb total ergot alkaloids) had reduced (P < .05) intake and weight gain compared with endophyte-free (E-) controls, whereas apparent diet digestibility was not different between E+ and E-. Rabbits immunized against ergot alkaloids (E+ vac) with lysergol conjugated to human serum albumin (Ly-HSA) had greater (P < .05) intake than E+ rabbits during the wk 1 of a 3-wk dietary challenge. In Exp. 2, rabbits (n = 4/treatment) were immunized with Ly-HSA, with H100-B (ergot alkaloid hapten, H100-different protein carrier, B conjugate), or combinations of both with alum as adjuvant. Greatest (P < .001) anti-ergot alkaloid antibody (Ab) titer developed in the group immunized with H100-B. In Exp. 3, rabbits (n = 4/treatment) were immunized with the immunogen H100-B in conjunction with six adjuvants. Freund's incomplete adjuvant (FIA) in combination with DEAE-dextran and FIA alone gave highest anti-ergot titers. In summary, rabbit weight gain and intake were reduced by feeding E+ fescue seed diets, immunization against ergot alkaloids provided temporary improvement in intake, and H100-B conjugate with FIA or FIA + DEAE-dextran as adjuvants elicited a superior anti-ergot immune response. We believe that rabbits may serve as a model animal for fescue toxicosis research.     

Subclinical multisystemic autoimmunity presenting as a progressive myelopathy

Autoimmunity can manifest clinically in many ways; however, despite the various efforts to classify autoimmune disorders into specific disease entities, the borders between these disorders remain, in many cases, unclear. In this report we describe a young woman with subclinical Sj?gren's syndrome and biliary cirrhosis, who presents clinically with symptoms exclusively from the central nervous system. This neurological syndrome is consistent with a progressive myelopathy. Although the patient has a serologically and histologically confirmed multisystemic autoimmune disorder, she fulfills none of the classification criteria for the diagnosis of a specific connective tissue disease.