Clinical implications of positive tests for antibodies to human immunodeficiency virus type 1 in asymptomatic blood donors

Of 693,000 volunteer blood donors in Washington, D.C., who were screened for infection with human immunodeficiency virus type 1 (HIV-1) from July 1985 through December 1988, 284 tested positive on both enzyme immunoassay and Western blot assay. To determine the clinical importance of confirmed positive test results in asymptomatic blood donors, we followed 156 donors with positive Western blot assays and 80 donors with positive enzyme immunoassays but negative or indeterminate Western blots at 6-month intervals for a mean of 28 months. As compared with Western blot-negative persons, those with positive Western blots were significantly more likely to be black, male, and first-time donors and to have a history of venereal disease, generalized lymphadenopathy on examination, CD4-cell counts lower than 0.4 x 10(9) per liter, IgG levels higher than 18 g per liter, and antibody to hepatitis B core antigen on initial evaluation. In 17 (11 percent) of the Western blot-positive donors, the disease progressed to Class IV (symptomatic disease), according to the Centers for Disease Control system. CD4 counts below 0.2 x 10(9) per liter, IgA levels above 4 g per liter, abnormal proliferative responses to tetanus toxoid, and positive viral cultures were the strongest predictors of disease progression. Among the 80 donors with repeatedly reactive assay results but either negative or indeterminate Western blot assays, there was no evidence of HIV exposure in their histories, physical examinations, or laboratory evaluations, and manifestations of HIV infection developed in none of them. We conclude that a small number of persons with HIV infection continue to donate blood, despite attempts to exclude them, but that donors who test positive on enzyme immunoassay but persistently negative or indeterminate on Western blot assay probably do not represent a risk for the transmission of HIV.     

Role of BCR affinity in T cell dependent antibody responses in vivo

Antibody affinity for antigen is believed to govern B lymphocyte selection during T-dependent immune responses. To examine antibody affinity in T cell dependent immune responses, we compared mice that carry targeted V(H)B1-8 antibody genes with high or low antigen-binding affinity. We found that high- and low-affinity B cells had the same intrinsic capacity to respond to antigen, but in experiments where limiting numbers of high- and low-affinity B cells were mixed in wild-type recipient mice, only the high-affinity B cells accumulated in germinal centers (GCs). In GCs, high-affinity B cells accumulated fewer V(H) somatic mutations than low affinity B cells. This effect was due to selections as the frequency of mutation in noncoding immunoglobulin gene DNA is the same in high- and low- affinity B cells. Thus, B cells recruited to the GC appeared to undergo a fixed mutation program, regardless of initial B cell receptor affinity. We conclude that in addition to the selection that occurs in GCs, stringent selection for high-affinity clones is also imposed in the early stages of the T cell dependent immune response in vivo.     

Prostate adenocarcinoma using Gleason scores correlates with prostate-specific antigen and prostate acid phosphatase measurements.

To evaluate a relationship between Gleason scores of histopathology of prostate carcinoma and concurrent serum prostate-specific antigen (PSA) and prostate acid phosphatase (PAP) values, 65 men with prostate carcinoma were studied. These patients' cumulative Gleason scores were obtained by totaling the primary and secondary patterns, resulting in two groups: 42 patients received high (6-10) and 23 received low (2-5) Gleason scores. Serum PSA and PAP values were measured by radioimmunometric assay 1 to 7 days before surgical procedures or biopsy for prostate carcinoma. Mean serum PSA for patients in the high Gleason score group was 134.39 ng/mL (normal range: 0 to 4), and the mean serum PSA for patients in the low Gleason score group was 23.62 ng/mL. Mean serum PAP for patients with high scores was 28.08 ng/mL (normal range: 0 to 5), and the mean serum PAP for patients with low scores was 18.19 ng/mL. Patients with high Gleason scores showed significantly greater elevation of serum PSA than those with low Gleason scores (P = .047), using two samples to test for groups having unequal variants. Prostate acid phosphatase levels of patients with high scores were not significantly higher than the levels in patients with low scores (P = .60). These results indicate that PSA levels but not PAP levels correlate with Gleason scores.     

Serum PSA and PAP measurements discriminating patients with prostate carcinoma from patients with nodular hyperplasia.

Prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) are the tumor markers for monitoring disease progression or improvement in patients with prostate adenocarcinoma. The clinical utility of PSA and PAP for early detection of prostate adenocarcinoma, however, requires distinction between prostate adenocarcinoma and prostate nodular hyperplasia. The serum PSA and PAP levels were measured in 20 men with histologically proven prostate adenocarcinoma and 28 men with histologically proven prostate nodular hyperplasia. Patients'' blood samples were collected 1 to 7 days prior to the prostate examination, which included a rectal digital examination, transurethral resection, cytoscopy, and prostate biopsy. Sensitivity, specificity, and predictive values of positive and negative results for the discrimination of prostate adenocarcinoma from prostate nodular hyperplasia were 85%, 89%, 85%, and 29%, respectively, for serum PSA (cutoff level: 10 ng/mL) and 40%, 96%, 89%, and 69%, respectively, for serum PAP (cutoff level: 10 ng/mL). Results indicate that marked elevation of serum PSA suggests prostate adenocarcinoma and that serum PSA can discriminate prostate adenocarcinoma from prostate nodular hyperplasia better than serum PAP.     

Serum hepatitis B virus DNA in healthy HBsAg-negative Chinese adults evaluated by polymerase chain reaction

Serum hepatitis B virus (HBV) DNA was assayed using polymerase chain reaction, in 107 HBsAg-negative normal Chinese subjects. The results showed that eight subjects (7.5%) had HBV DNA. In the subgroup with antibody to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc), 7.3% (5/68) were positive for HBV DNA; HBV DNA was not detected in six individuals with anti-HBs only and in nine with anti-HBc only. In four persons with anti-HBc and anti-HBe, one had HBV DNA. In 20 subjects negative for all hepatitis B serological markers, two (10%) were found to have HBV DNA. This study indicates that serological markers are not adequate to rule out HBV infection, and it further implies that present blood donor screening methods may need improving.     

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

An allergic reaction following intrauterine insemination

Intrauterine insemination is a common procedure used for the treatment of different causes of infertility. Adverse reactions associated with this procedure are very rare and usually the procedure is well tolerated by the patient. We report a case of an allergic reaction after intrauterine insemination. The patient developed fever, difficulty breathing and wheezing in both lung fields. Although a low concentration of penicillin in the medium was used, it caused a significant allergic reaction. When intrauterine insemination was performed in subsequent cycles with an antibiotic-free medium, no allergic reaction occurred, and the procedure was well tolerated by the patient. A careful allergy history is essential in patients pursuing infertility treatment where antibiotics are utilized. Patients who are known to be allergic to penicillin should have semen prepared by an antibiotic-free medium.      

Impact of cadaveric organ donation on Taiwanese donor families during the first 6 months after donation

OBJECTIVE: Organ donation is a complex decision for family members of Asian donors. The impact of cadaveric organ donation on both Chinese and Western donor families has not been well investigated within a cultural framework. The purposes of this study were to follow Chinese family members' appraisal of their decision to donate organs, to explore the possible negative and positive impacts of organ donation on their family life, and to determine what help they expected from healthcare providers during the first 6 months after donation. METHODS: Twenty-two family members (10 men and 12 women) of cadaveric organ donors who signed consent forms at an organ transplant medical center in Taiwan participated in this project and completed in-depth interviews during the sixth month after donation. RESULTS: Participants were 25 to 56 years old (mean = 48.15 +/- 8.31 years). The type of kinship of the participants included the donor's parents, older sister, and spouse. Subjects reported several negative impacts: worry about the donor's afterlife (86%), stress due to controversy among family members over the decision to donate (77%), and stress due to others' devaluation of the donation (45%). Positive impacts reported by the subjects included having a sense of reward for helping others (36%), having an increased appreciation of life (32%), having closer family relationships (23%), and planning to shift life goals to the study of medicine (9%). Subjects expected the transplant team to provide information about organ recipients (73%), to submit the necessary documents so that family members could receive healthcare payments from the insurance company (68%), to help resolve legal proceedings and settlements associated with accidents (64%), and to not overly publicize their decision to donate (64%). CONCLUSIONS: Although all of the subjects reported that organ donation was the right decision, the decision to donate did not protect Taiwanese donor families from negative psychocognitive bereavement. The impacts of organ donation were affected by the subject's social cultural, spiritual, and legal context and the nature of their bereavement.     

Dynamic wedge versus physical wedge: a Monte Carlo study

The purpose of this study is to analyze the characteristics of dynamic wedges (DW) and to compare DW to physical wedges (PW) in terms of their differences in affecting beam spectra, energy fluence, angular distribution, contaminated electrons, and dose distributions. The EGS4/BEAM Monte Carlo codes were used to simulate the exact geometry of a 6 MV beam and to calculate 3-D dose distributions in phantom. The DW was simulated in accordance with the segmented treatment tables (STT). The percentage depth dose curves and beam profiles for PW, DW, and open fields were measured and used to verify the Monte Carlo simulations. The Monte Carlo results were found to agree within 2% with the measurements performed using film and ionizing chambers in a water phantom. The present EGS4 calculation reveals that the effects of a DW on beam spectral and angular distributions, as well as electron contamination, are much less significant than those for a PW. For the 6 MV photon beam, a 45 degrees PW can result in a 30% increase in mean photon energy due to the effect of beam hardening. It can also introduce a 5% dose reduction in the build-up region due to the reduction of contaminated electrons by the PW. Neither this mean-energy increase nor such dose reduction is found for a DW. Compared to a DW, a PW alters the photon-beam spectrum significantly. The dosimetric differences between a DW and a PW are significant and clearly affect the clinical use of these beams. The data presented may be useful for DW commissioning.