Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

Absence of antibody production in patients treated with botulinum A toxin

To test the possibility of the formation of an antibody to botulinum A toxin after multiple injections of this potent neurotoxin, we collected serum samples from 28 patients who received 57 doses. These injections over a nine-month period with as much as 50 units per injection formed no detectable antibody.     

Extradural lymphoma presenting as an acute surgical emergency

Extradural lymphoma can present as an acute neurosurgical emergency. The clinical presentation and radiological appearance may suggest epidural hematoma or meningioma. Lymphoma should be considered as a rare but possible diagnosis before operation. High resolution computed tomography using direct coronal imaging with and without contrast enhancement may aid in suggesting the correct preoperative diagnosis.     

Unannounced simulated patients' observations of physician STD/HIV prevention practices.

Studies describing sexually transmitted disease (STD) and human immunodeficiency virus (HIV) prevention practices of primary care physicians have relied on physician or patient reports. This study describes physician STD/HIV prevention practices as observed by unannounced simulated patient evaluators (SPEs). SPEs visited sixty-five primary care physicians. Each SPE portrayed a sexually active female, new to the area, requesting a consultation on STD prevention. One-third of the physicians in the study asked no risk questions, and over 80% failed to ask the SPE specifically about her sexual practices. Most physicians discussed the risks of STDs and HIV and covered basic recommendations (use condoms and know partners better); however, few physicians provided any individualized information or advice about safer sexual practices and the specifics of condom use, such as how to use them or what kind to use. These observations support the low rates of STD/HIV prevention indicated in physicians' self-report and further identify specific deficiencies in the thoroughness of their risk assessment and preventive counseling practices.     

Mechanism of Pseudomonas aeruginosa persistence during treatment with broad-spectrum cephalosporins of lung infections in patients with cystic fibrosis.

Beta-lactam resistance in Pseudomonas aeruginosa detected only during ceftazidime therapy of cystic fibrosis patients was studied. Evaluation of resistant and susceptible isolates from one patient and resistant laboratory derivatives indicated that elevated beta-lactamase levels were the primary determinant of resistance. Susceptible isolates outgrew resistant isolates on antibiotic-free medium.     

A personal computer database system for head and neck cancer records

The computerized database system described was initially developed in 1986 to facilitate analysis of retrospective head and neck cancer data from the Royal Adelaide Hospital Department of Otolaryngology. This has now been expanded to become an on-going patient information management system. It is based on the dBase-III-Plus database package and is implemented on an IBM XT compatible computer. The system was designed to be used by staff without specialist computer skills and is therefore largely “menu-driven.” The main functions include patient record creation, update, and retrieval, and the production of reports including graphical presentations. There is also a powerful but easy to use query facility. The system has already provided much useful epidemiological material but is now beginning to fulfill an even more important role in patient follow-up and in assisting evaluation of alternative treatment protocols.     

Protection from pathogenic SIV challenge using multigenic DNA vaccines

To assess DNA immunization as a strategy for protecting against HIV infection in humans, we utilized SIVmne infection of Macaca fascicularis as a vaccine challenge model with moderate pathogenic potential. We compared the efficacy of DNA immunization alone and in combination with subunit protein boosts. All of the structural and regulatory genes of SIVmne clone 8 were cloned into mammalian expression vectors under the control of the CMV IE-1 promoter. Eight M. fascicularis were immunized twice with 3 mg of plasmid DNA divided between two sites; intramuscular and intradermal. Four primed macaques received a further two DNA immunizations at weeks 16-36, while the second group of four were boosted with 250 microg recombinant gp160 plus 250 microg recombinant Gag-Pol particles formulated in MF-59 adjuvant. Half of the controls received four immunizations of vector DNA; half received two vector DNA and two adjuvant immunizations. As expected, humoral immune responses were stronger in the macaques receiving subunit boosts, but responses were sustained in both groups. Significant neutralizing antibody titers to SIVmne were detected in one of the subunit-boosted animals and in none of the DNA-only animals prior to challenge. T-cell proliferative responses to gp160 and to Gag were detected in all immunized animals after three immunizations, and these responses increased after four immunizations. Cytokine profiles in PHA-stimulated PBMC taken on the day of challenge showed trends toward Thl responses in 2/4 macaques in the DNA vaccinated group and in 1/4 of the DNA plus subunit vaccinated macaques; Th2 responses in 3/4 DNA plus subunit-immunized macaques; and Th0 responses in 4/4 controls. In bulk CTL culture, SIV specific lysis was low or undetectable, even after four immunizations. However, stable SIV Gag-Pol- and env-specific T-cell clones (CD3+ CD8+) were isolated after only two DNA immunizations, and Gag-Pol- and Nef-specific CTL lines were isolated on the day of challenge. All animals were challenged at week 38 with SIVmne uncloned stock by the intrarectal route. Based on antibody anamnestic responses (western, ELISA, and neutralizing antibodies) and virus detection methods (co-culture of PBMC and LNMC, nested set PCR- of DNA from PBMC and LNMC, and plasma QC-PCR), there were major differences between the groups in the challenge outcome. Surprisingly, sustained low virus loads were observed only in the DNA group, suggesting that four immunizations with DNA only elicited more effective immune responses than two DNA primes combined with two protein boosts. Multigenic DNA vaccines such as these, bearing all structural and regulatory genes, show significant promise and may be a safe alternative to live-attenuated vaccines.