Dioxin and dioxin-like PCB exposure of non-breastfed Dutch infants.

The exposure of humans to PCDD/Fs (polychlorinated dibenzo-p-dioxins and dibenzofurans) and dioxin-like PCBs (dl-PCBs, i.e. polychlorinated non-ortho and mono-ortho biphenyls) occurs predominantly via the intake of food. Young children have a relatively high intake of these substances, due to their high food consumption per kilogram body weight. As the exposure of non-breastfed infants to these compounds has not been assessed before in The Netherlands, we studied the dietary intake of 17 PCDD/Fs and 11 dioxin-like PCBs in 188 Dutch non-breastfed infants between 4 and 13 months. The food intake of the infants was assessed by a 2-d food record. From these data PCDD/F and dioxin-like PCB intake was calculated using PCDD/F and dioxin-like PCB concentrations of food products sampled in 1998/1999 in The Netherlands. The long-term PCDD/F and dioxin-like PCB exposure of the infants was calculated using the statistical exposure model (STEM). For infants of 5 months the chronic exposure to PCDD/F and dioxin-like PCB was 1.1pg WHO-TEQ (toxic equivalents) per kilogram body weight (bw) per day (95th percentile: 1.7pg WHO-TEQ/kg bwxd), which mainly originated from infant formula and vegetables and increased to 2.3pg WHO-TEQ/kg bwxd (95th percentile 3.7pg WHO-TEQ/kg bwxd) for infants just over 1 year old eating the same food as their parents. The percentage of formula-fed infants with an exposure exceeding the TDI of 2pg WHO-TEQ/kg bwxd was 5% at 5 months, 49% at 9 months and 64% at 12 months.

Mitral valve surgery via a right anterior mini-thoracotomy with central aortic cannulation and no endoscopic assistance.

BACKGROUND: A variety of techniques have been described to reduce surgical access in mitral valve surgery: Mini-sternotomy (Gundry) involves partial division of the sternum while the right anterior mini-thoracotomy approaches described involve either Port Accesstradmark; (Heartport, Redwood City, CA), indirect endoscopic techniques (Chitwood) and more recently, robotic techniques (Intuitive Surgicaltradmark;). This report describes a simplified approach that "borrows" aspects from several techniques. METHODS: Using currently available technology, a simplified technique to perform mitral valve surgery (MVST) has been developed. MVST eliminates the need for endoscopic assistance and femoral arterial cannulation. The results of 50 of these patients were analyzed and compared with those of 66 patients who had isolated mitral valve surgery via a conventional approach (MVCS) over the same five-year interval. RESULTS: Between January 1, 1995 and December 31, 2000, 50 patients had mitral valve surgery performed with a simplified technique (MVST). Twenty-six (52%) of the MVST patients underwent mitral valve replacement and 24 (48%) underwent mitral valve repair. There were no in-hospital deaths in the MVST group, compared to a death rate of 7.1% in the MVCS group. There were no strokes and no perioperative myocardial infarctions in the MVST group. Average ICU stay was 3.4 days (1 day shorter than the MVCS group) and average hospital stay was 8.1 days, which was significantly less than the 12.5 day length of stay for the patients having MVCS (p<0.01). Blood was utilized in 36% of the MVST patients, compared to a 55% rate in the MVCS group. There were no wound infections in the MVST group. Two patients did develop bloody effusions requiring thoracentesis. Antegrade blood cardioplegia was used in 35 (70%) of the MVST patients. Antegrade and retrograde blood cardioplegia was used in 15 (30%) patients. Average cross-clamp time in the MVST group was 70 minutes compared to 85 in the MVCS group (p<0.05) and the average pump run was 98 minutes in the MVST group compared to 112 for the MVCS group (p=0.08). CONCLUSION: Mitral valve surgery using a simplified, less invasive technique can be successfully and safely performed in selected patients, resulting in less blood utilization and shorter hospital length of stay, with a cosmetic result that rivals that of robotically assisted techniques.

Multiple coronary artery bypass via mini left thoracotomy with conventional aortic occlusion.

BACKGROUND: Complete myocardial revascularization can be achieved through a mini left anterior thoracotomy. Our approach (West Coast Technique) takes advantage of the Port-Access (Heartport, Redwood City, CA) concept while utilizing conventional instrumentation. METHODS: Thirty-eight patients underwent multiple coronary artery bypass grafting (CABG). Aortic occlusion was performed using a transthoracic clamp, and all anastomoses were performed under a single cross-clamp. RESULTS: There were no deaths and no neurologic deficits. There was one perioperative myocardial infarction (MI), and one re-exploration for bleeding. Ten patients (26%) required blood transfusions, and five patients (13%) developed atrial fibrillation. The average number of grafts per patient was 2.9, and average hospital stay was 5.2 days. CONCLUSION: Multiple CABG can be accomplished safely through a minithoracotomy, which eliminates the need for endoaortic occlusion.

Liver function studies in the assessment of head and neck cancer patients.

BACKGROUND: Serum liver function tests (LFTs) are used in the initial evaluation of patients with head and neck squamous cell carcinoma (SCC) to evaluate hepatic function and to screen for liver metastases. METHODS: One hundred forty patients initially seen with SCC between 1988 and 1991 were followed for a minimum of 2 years to determine the significance of abnormal LFTs at presentation. RESULTS: Abnormal values were found in 69 patients (49%), including elevated alkaline phosphatase in 37 (26%) and lactic dehydrogenase in 25 (18%). Abnormal values were most commonly attributed to alcohol-related liver disease. No liver metastases were identified at initial screening. LFTs were normal at presentation in all three patients subsequently identified with liver metastases during follow-up. CONCLUSIONS: Abnormal LFTs are commonly encountered but are of little value in identifying patients with liver metastases during initial assessment. Modest elevation of LFTs should not necessitate costly and time-consuming investigation to exclude hepatic metastasis.

Transient increase of serum IgD levels after allogeneic bone-marrow transplantation.

Serum IgD levels were followed longitudinally twice a week for up to 100 days in 60 children undergoing allogeneic bone-marrow transplantation (n = 52) or immunosuppression (n = 8) for the treatment of leukaemia, severe aplastic anaemia or severe combined immunodeficiency. In 40 out of the 49 post-transplantation periods analysed (82%), a transient sharp increase of serum IgD was detected, irrespective of initial disease. A similar peak was found in one out of five children after immunosuppressive treatment. A second IgD peak was only recorded in grafted patients (14/49 post-transfusion periods). Peak levels of IgD ranged from 1.3 to 185.7 IU/ml (median 12.2 IU/ml), which represents a 2.6 to 22.4-fold increase over 'baseline' levels. In the transplanted leukaemia and aplastic anaemia patients, the rise of serum IgD occurred at the same time (geometric mean 16 days after transplantation) and was shown to represent heterogeneous polyclonal IgD in six of them. The onset of the serum IgD peak was significantly delayed in children suffering from severe combined immunodeficiency (P less than 0.05) and was demonstrated in one patient to consist of homogeneous IgD. No relation was found between either the occurrence of clinical acute graft-versus-host disease or infections after treatment, and the time of onset of IgD elevations. To detect transient serum IgD peaks as described here, frequent sampling of sera is necessary. The origin of the early IgD peaks seems to reside within the recipient's cells by an unknown mechanism. The late IgD peaks are most probably an expression of gradual reconstitution of the immune system following bone-marrow transplantation.

Dose-response effects in immunizations with keyhole limpet haemocyanin and rabies vaccine: shift in some immunodeficiency states.

We investigated the primary antibody response to the antigens keyhole limpet haemocyanin (KLH) and rabies vaccine (RV). Eighty-one healthy volunteers were injected with nine doses of KLH (ranging from 10 to 2500 micrograms) and 66 volunteers with six doses of RV (ranging from 17 to 680 micrograms protein). Anti-KLH and anti-RV antibodies were determined by ELISA and immunofluorescence (IF) immediately before and 14 days after primary immunization. On the basis of the dose-response curves, optimal and supra-optimal antigen doses were chosen for the assessment of humoral immunocompetence in two groups of patients with uraemic disease, who were treated either by chronic intermittent (hospital) haemodialysis (HD) (n = 16), or continuous ambulatory peritoneal dialysis (CAPD) (n = 23). The patients were randomly immunized with 250 micrograms or 2.5 mg KLH and 170 micrograms or 680 micrograms RV and their antibody responses were compared with those obtained in healthy individuals. We found a definite deficiency in the primary response in haemodialysis patients after challenging with a suitable antigen dose. However, the differences in response rate between patients and controls tended to disappear upon stimulation with a supra-optimal antigen dose. This might indicate that the dose-response curve of a particular antigen is shifted towards higher doses of antigen in immunodeficiency states, which could have important consequences for the testing of immunocompromised patients.

Lymphoid chimerism after allogeneic bone marrow transplantation. Y-chromatin staining of peripheral T and B lymphocytes and allotyping of serum immunoglobulins.

Lymphoid cell engraftment was monitored for several years after bone marrow transplantation by Y-chromatin staining of T and B lymphocytes in the peripheral blood and/or by immunoglobulin allotyping in the serum of 20 of 52 pediatric patients grafted successively between October 1973 and October 1983. Data on 2 patients with severe combined immunodeficiency, grafted earlier in December 1968 and April 1971, are also included. These children received an allogeneic bone marrow graft for leukemia (n = 7), severe aplastic anemia (n = 11), or severe combined immunodeficiency (n = 4) and were informative for this study, because they differed from their donor by sex (n = 16) and/or by immunoglobulin phenotype (n = 13). Of 16 pairs in which the donor was of the opposite sex, 11 patients ultimately showed circulating T and B lymphocytes of donor origin after bone marrow transplantation; in the remaining 5, there was an incomplete chimerism of the circulating lymphoid cells. Of 13 pairs with a difference in immunoglobulin phenotype between donor and recipient, 8 patients exhibited donor allotypes 3 months or later after transplantation, in 3 of them together with recipient allotypes. In the remaining 5 patients, recipient allotypes were detected after transplantation, but the simultaneous presence of donor-type immunoglobulin production could not be excluded in 4. The persistence of either a split (T lineage of donor origin and B lineage of recipient origin) or mixed (T and/or B lineage of donor and recipient origin) chimerism was related to the type of disease. In 3 children circulating B cells of donor-origin did not fit with the recipient origin of the sessile immunoglobulin-secreting plasma cells. This implies that different immune compartments--e.g., bone marrow and peripheral lymphoid tissues--should be investigated following allogeneic bone marrow transplantation. A prolonged presence of recipient-type lymphoid cells increased the risk of leukemic relapse in the patients investigated.

Transient elevation of serum IgE after allogeneic bone-marrow transplantation.

Serum IgE levels were followed longitudinally twice a week for up to 100 days in 60 children treated for leukemia, severe aplastic anemia or severe combined immunodeficiency: 52 underwent allogeneic bone-marrow transplantation and 8 immunosuppressive treatment. In 55 of 58 treatment periods which could be analyzed (95%), a transient sharp increase of serum IgE was detected, irrespective of the initial diagnosis and mode of treatment. A second IgE peak was recorded in 16% of evaluable treatment periods. In the transplanted leukemia and aplastic anemia patients, the rise of serum IgE levels occurred at the same time, i.e. at a mean of 14 days after transplantation; it occurred significantly later in children grafted for severe combined immunodeficiency. In children who received immunosuppression for the treatment of severe aplastic anemia, IgE elevations were always seen within 2 weeks after institution of therapy. No relation was found between either the occurrence of clinically acute graft-versus-host disease or infections after treatment, and the time of onset of IgE elevations. It is suggested that the phenomenon of IgE peaks in the population of patients investigated was due to disturbance of T-cell regulation, i.e. a temporary impairment of T-suppressor cell activity.

Measurement of primary in vivo IgM- and IgG-antibody response to KLH in humans: implications of pre-immune IgM binding in antigen-specific ELISA.

The antigen Keyhole Limpet Hemocyanin (KLH) is often used to test the primary in vivo antibody response capacity in humans. However, measurement of IgM anti-KLH antibodies in ELISA is complicated by the presence of natural antibodies in human serum. This problem occurs particularly at low antibody levels, i.e. after immunization with low doses of antigen and, under these conditions, it was found to be impossible to assess a dose-response curve by immunizing a series of individuals with different suboptimal doses of KLH. This problem was circumvented by choosing conditions for minimal binding of pre-immune IgM and to correct for such binding. Although signal-to-background ratios were markedly improved by modifying the ELISA conditions, pre-immune IgM still showed binding to KLH due to interaction with polysaccharide determinants. This non-specific binding was correlated with the total IgM content of the samples. When anti-KLH activities before and after immunization were expressed relative to total serum IgM, a significant correction was achieved, resulting in a diminished inter-individual variability with respect to both pre-immune and post-immunization values. As with IgG-class antibodies to KLH, virtually no binding was observed in pre-immune sera. After expression of the anti-KLH response as a ratio between the post-immunization and pre-immunization titres, a dose of 50 micrograms was found to be sufficient to evoke a detectable IgG-antibody response in the 10 subjects tested. To elicit a positive IgM response, a minimal dose of 250 micrograms was required.