Bart Holland

Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly.

The objective of this study was to determine the effects of a year of Zn supplementation on Zn concentrations in circulating cells and on cellular immune functions in the elderly. Subjects, aged 60-89, were given a placebo, 15 mg Zn, or 100 mg Zn daily for 12 months. All subjects also received a multivitamin/mineral supplement that contained no additional Zn. Blood samples were drawn and immune functions assessed prior to and at 3, 6, 12, and 16 months after beginning Zn supplementation. Subject diets were also assessed at each visit. Dietary folate, pyridoxine, alpha-tocopherol, copper, zinc, and magnesium were consistently below recommended intakes. Although plasma Zn increased significantly in the 100 mg Zn treatment group, concentrations of Zn in erythrocytes, mononuclear cells, polymorphonuclear leukocytes, and platelets were not significantly increased by zinc supplementation. Natural killer cell activity was transiently enhanced by the 100 mg/day dose of Zn. There was a progressive improvement in delayed dermal hypersensitivity (DDH) and in lymphocyte proliferative responses to two mitogens; this may have been due to one or more components of the multivitamin/mineral supplement administered to all study subjects. The enhancement of DDH was significantly greater in the placebo group than in either zinc treatment group. Thus, zinc had a beneficial effect on one measure of cellular immune function while simultaneously having an adverse effect on another measure of cellular immunity.

Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome

Background Neurologic Post Treatment Lyme disease (nPTLS) and Chronic Fatigue (CFS) are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS. Methods and Principal Findings Pooled cerebrospinal fluid (CSF) samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry (MS), coupled with immunoaffinity depletion methods to reduce protein-masking by abundant proteins. Individual patient and healthy control CSF samples were analyzed directly employing a MS-based label-free quantitative proteomics approach. We found that both groups, and individuals within the groups, could be distinguished from each other and normals based on their specific CSF proteins (p<0.01). CFS (n = 43) had 2,783 non-redundant proteins, nPTLS (n = 25) contained 2,768 proteins, and healthy normals had 2,630 proteins. Preliminary pathway analysis demonstrated that the data could be useful for hypothesis generation on the pathogenetic mechanisms underlying these two related syndromes. Conclusions nPTLS and CFS have distinguishing CSF protein complements. Each condition has a number of CSF proteins that can be useful in providing candidates for future validation studies and insights on the respective mechanisms of pathogenesis. Distinguishing nPTLS and CFS permits more focused study of each condition, and can lead to novel diagnostics and therapeutic interventions.

Antiretroviral Resistance Mutations among Pregnant Human Immunodeficiency Virus Type 1–Infected Women and Their Newborns in the United States: Vertical Transmission and Clades

To assess the impact of antiretroviral resistance on perinatal transmission prevention efforts, human immunodeficiency virus type 1 (HIV-1) genotypic resistance testing was done for 220 HIV-1-infected, zidovudine (AZT)-exposed pregnant women and 24 of their infected infants. The women were prospectively enrolled in 4 US cities in 1991-1997. Phylogenetic and sequencing analyses revealed 5 women with non-clade B infections traced to western African origins. AZT-associated mutations were detected in 17.3% of pregnant women, whereas genotypic resistance to nonnucleoside reverse-transcriptase inhibitors and protease inhibitors was infrequent. No significant association was detected between perinatal transmission and the presence of either AZT or nucleoside reverse-transcriptase inhibitor resistance-associated mutations. AZT resistance mutations were detected in 2 (8.3%) neonatal samples, but the mutation pattern was not identical to the mothers. Although no effect of viral resistance on mother-infant transmission was demonstrated, the advent of more-potent drug classes and the potential for the rapid emergence of resistance warrant prospective surveillance.

Hemorrhagic complications of external ventricular drainage.

OBJECTIVE: Despite the widespread use of external ventricular drainage (EVD), the frequency of associated hemorrhagic complications remains unclear. This retrospective study examined the frequency of hemorrhagic complications of EVD and attempted to discern associated risk factors. METHODS: Treatment records from 160 patients admitted during a 2.5-year period who required EVD placement were reviewed. Indications for placement of EVD included acute complications of cerebrovascular disease (n = 94), traumatic brain injury (n = 36), primary hydrocephalus (n = 16), and tumor (n = 14). Patients received either a 3.0 or 2.5-mm outer diameter ventricular catheter (n = 82 and 78, respectively). Postinsertion computed tomographic scans were obtained within 24 hours on all patients and were analyzed for any new hemorrhage related to the ventricular catheter. Patient age, sex, catheter type, and dimensions of hemorrhage were also analyzed. RESULTS: The incidence of EVD-related hemorrhage was 33 ± 0.04%. However, the incidence of detectable change in the clinical neurological examination was 2.5%. A significant proportion of EVD-related hemorrhages were small (<4 cm3), punctate, intraparenchymal hematomas. Patients with cerebrovascular disease exhibited an increased incidence (39%) of hemorrhage. The mean volume of intraparenchymal hemorrhage was larger in patients who received the 2.5-mm ventricular catheter, as well as those admitted for cerebrovascular disease. CONCLUSION: Hemorrhagic complications of EVD placement are more common than previously suspected. Admitting diagnosis seems to have an effect on the development of an associated hemorrhage and its size. Catheter gauge has an effect on hematoma volume. Most of the hemorrhages seen on postinsertion computed tomographic scans do not cause detectable changes in the clinical examination.

Nontuberculous mycobacteria in children with acquired immunodeficiency syndrome

Among 139 children with acquired immunodeficiency syndrome at Childrens Hospital of New Jersey, 20 had positive cultures for non-tuberculous mycobacteria. Eighty-five percent had Mycobacterium avium complex isolated and 70% had definite evidence of disseminated disease. Ninety-three percent had CD4 lymphocyte counts < 100 cells/mm3 and 95% had met acquired immunodeficiency syndrome criteria before the time of first positive culture. Clinical findings included failure to gain weight, anorexia, fever, abdominal pain/tenderness and anemia. The median age at onset of symptoms was 46 months and the median time between onset of symptoms and positive culture

Quantitative determination of surface antibody binding capacities of immune subsets present in peripheral blood of healthy adult donors

The objective of this study was to quantitate the antibody binding capacity (ABC) of CD3, CD4, CD8, CD16, and CD19 on lymphocytes and CD4 on monocytes from healthy adult donors. Peripheral blood was collected over three consecutive days and repeated in the same format two weeks later for comparison to initial measurements. Immune subsets were labeled by direct single or two-color staining in whole blood followed by lysis of erythrocytes. Fluorescence intensity measurements were made by carefully calibrating the flow cytometer and then measuring the intensity of monoclonal antibody staining on labeled cells and on Quantum Simply Cellular Microbeads. The effect of paraformaldehyde fixation on intensity measurements and coefficient of variation of thirty replicates for each phenotype were also studied. We found a small change in calculated ABC following overnight fixation with a greater change following 48 h of fixation prior to flow cytometric analysis. We found excellent precision could be achieved for measuring the ABC of most markers with some improvement desirable for expression of CD4 on monocytes and CD16+ lymphocytes. Between donors we found a high-low range of CD3+ = 134,349-45,905; CD4+ (lymphocytes) = 54,174-36,106; CD4+ (monocytes) = 9,246-3094; CD8+ = 268,868-190,622; CD3+CD8+ = 269,858-212,024; CD16+ = 38,307-336; and CD19+ = 25,252-11,689. For the total donor group, the observations at week 1 and week 2 were not significantly different (alpha = .05) for any of the immunophenotypes we studied. The data presented here continue to show that it is possible to perform quantitative intensity measurements of immune subsets when performing immunophenotyping studies.

Donors with cardiac arrest: improved organ recovery but no preconditioning benefit in liver allografts.

Background. Historically, organ recovery rates in donors with cardiac arrest (CA) have been low, presumably from hemodynamic instability. We hypothesized that donor resuscitation has improved hemodynamic stability and organ recovery in CA donors, and that CA triggers ischemic preconditioning (IP) in liver grafts. Methods. A total of 131 donor pairs with and without CA were matched in age, gender, and year of recovery. Hemodynamic stability was determined by vasopressor use. Abdominal and thoracic organs recovered and livers transplanted were compared between the groups. Liver graft function, injury, and IP benefit were examined by comparing liver chemistries after transplantation and postperfusion biopsies between recipients of grafts from both groups (n=40 each). Results. Hemodynamic stability was similar in both groups, but recovery of thoracic organs was significantly lower in CA versus non-CA donors (35 vs. 53%, P <0.01). On the other hand, recovery rates of three or more abdominal organs from CA donors approached those of non-CA donors (77 vs. 87%, not significant). Although significantly fewer livers were transplanted from CA donors (69 vs. 85%, P <0.01), posttransplantation graft function and injury parameters were similar between the two groups, and CA did not appear to trigger IP. Conclusion. Compared with historical data, cardiovascular stability and abdominal organ recovery rates have improved considerably in CA donors. Liver grafts from CA donors function similarly to grafts from non-CA donors with no IP from CA. Our data support the increased use of livers and other organs from donors with CA.

Self‐reported non‐adherence to immune‐suppressant therapy in liver transplant recipients: demographic, interpersonal, and intrapersonal factors

Lamba S, Nagurka R, Desai KK, Chun SJ, Holland B, Koneru B. Self‐reported non‐adherence to immune‐suppressant therapy in liver transplant recipients: demographic, interpersonal, and intrapersonal factors. 
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01489.x. 
© 2011 John Wiley & Sons A/S.

Gray Matter Is Targeted in First-Attack Multiple Sclerosis

The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We found that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.

Vitamin Profile of 563 Gravidas during Trimesters of Pregnancy

Objective: Gestation imposes metabolic stress on the mother which heightens as pregnancy progresses. The need for quantifying circulating vitamins is important for identifying pitfalls in metabolic imbalance and nutritional status. For this reason we wanted to analyze blood vitamin concentrations of B12, thiamin, biotin, pantothenate, B6, niacin, riboflavin, folate, vitamins A, C, E and total carotenes to determine if imbalances occur during the trimesters of pregnancy. Methods: We randomly selected 563 gravidas who volunteered for this study from the obstetrical clinic of New Jersey Medical School; 132 were in 1st trimester, 198 were in 2nd trimester, and 233 were in 3rd trimester. All were healthy, taking a good diet and supplemented with vitamins. Blood, from an antecubital vein, was analyzed for thiamin, biotin, B12, B6, pantothenate, riboflavin, nicotinate, folates, vitamins A, E, C and total carotenes. Gravidas were classified as being normovitaminemic, hypervitaminemic or hypovitaminemic compared with blood vitamins seen in healthy non-pregnant, non-vitamin supplemented women. Result: Hypervitaminemic levels of folate, biotin, pantothenate and riboflavin were found during any trimester of pregnancy due to vitamin supplementation. Despite the vitamin supplementation, a high percent of vitamin A, B6, niacin, thiamin and B12 hypovitaminemia was noted during pregnancy trimesters. An especially high percentage of niacin deficiency was seen during the 1st trimester; it worsened in later trimesters; B12 deficits increased during the late trimesters. Combination deficits of niacin, thiamin, vitamins A, B6, B12 were noted in each of the trimesters. Conclusions: Despite vitamin supplementation, a vitamin profile of pregnancy indicates that vitamin deficits exist during the trimesters. Also, combination hypovitaminemias of deficient vitamins were noted; this indicates that a vitamin deficit during pregnancy does not occur in isolation.