Reliability of lymphoscintigraphy in indicating the number of sentinel nodes in melanoma patients

Background: This study was undertaken to establish the reliability of lymphoscintigraphy in indicating the number of sentinel nodes in patients with melanoma. Methods: Lymphoscintigraphy was performed with dynamic imaging after injection of 60 MBq^99mTc-nanocolloid (1.6 mCi) and static imaging after 2 hours in 200 patients with clinically localized primary melanoma of the skin. The following day, sentinel nodes were retrieved with the blue dye technique and a gamma detection probe (Neoprobe 1000/1500). The discrepancies between the number of sentinel nodes indicated by lymphoscintigraphy and the actual number of sentinel nodes as established by the surgeon were evaluated. Results: Lymphoscintigraphy showed drainage to 393 sentinel nodes in 255 lymphatic fields in 199 patients. In 48 lymphatic fields (19%) in 46 patients (23%), the number of sentinel nodes was different from the number that was visualized with scintigraphy. Additional sentinel nodes were found by the surgeon because a lymphatic vessel was not seen on the lymphoscintigraphy (43%), because a sentinel node was not visualized separately from other hot nodes or vessels or the injection site (36%), or because a sentinel node was blue and not hot (4%). Fewer sentinel nodes were found than suggested by scintigraphy because a lymphangioma was mistaken for a sentinel node (4%) or because a single elongated node was depicted as two hot spots (6%). Conclusions: Although lymphoscintigraphy is indispensable for lymphatic mapping, the predicted number of sentinel nodes is accurate in only 81% of lymph node fields. The limited discriminating power of the gamma camera is an important cause of discrepancies. Presented at the 4th World Conference on Melanoma, Sydney, Australia, June 10–14, 1997, and the First World Congress of Surgical Oncology, WFSOS/SSO meeting, San Diego, California, March 26–29, 1998.     

Inulin Hydrogels as Carriers for Colonic Drug Targeting: I. Synthesis and Characterization of Methacrylated Inulin and Hydrogel Formation

Purpose. Vinyl groups were introduced in inulin chains in order to form hydrogels of this sugar polymer by free radical polymerization. Methods. Inulin was reacted with glycidyl methacrylate in N,N-dimethylformamide in the presence of 4-dimethylaminopyridine as catalyst. ¹H and ¹³C NMR spectroscopy were used for the characterization of the obtained reaction product. Solid state ¹³C NMR spectroscopy revealed the conversion of the incorporated vinyl groups into covalent cross-links upon free radical polymerization of aqueous solutions of the derivatized inulin. Results. During reaction of inulin with glycidyl methacrylate, transesterification occurred, leading to the direct attachment of the methacryloyl group to inulin. Consequently, the obtained reaction product is methacrylated inulin. The extent of chemical modification of inulin could be tuned by varying the molar ratio of glycidyl methacrylate to inulin in the reaction mixture. Aqueous solutions of methacrylated inulin were converted into cross-linked hydrogels by free radical polymerization using ammonium persulphate and N,N,N,N-tetramethylethylenediamine as initiating system. Conclusions. Inulin hydrogels can be formed by free radical polymerization of aqueous solutions of methacrylated inulin.     

Genetic Susceptibility in Solvent Induced Neurobehavioral Effects

The aim of this investigation was to study the influence of genetic polymorphisms of biotransformation enzymes and dopamine receptors on neurobehavioral effects in referents (n = 53), solvent-workers (n = 144), and chronic toxic encephalopathy (CTE) patients (n = 33). All participants were interviewed for exposure data and confounding factors and underwent a clinical examination. Neurobehavioral complaints (neurotoxicity symptom checklist-60) and effects [simple reaction time (SRT), symbol digit substitution (SDS), hand–eye coordination (HEC), and digit span backwards (DSB)] were evaluated with a computer assisted test battery. The following genotypes were determined: GSTM1, GSTT1, GSTP1, DRD2 Taq1A, DRD2 Taq1B, and DRD2-141Cdel. Neurotoxic effects and complaints were significantly higher in CTE patients and were related to both duration and level of exposure. An equal distribution of genotypes was found between all groups. Logistic regression analysis revealed that GSTT1 was negatively associated with sleep and sensorimotor complaints. GSTM1 had a protecting influence on the relationship between logDSB and the cumulative exposure index and between logSRT and cumulative exposure index and degree of exposure, respectively. This effect was also found when correcting for age, education level, alcohol consumption, and smoking. DRD2-141Cdel polymorphisms had a negative influence on the relationship between logSDS and the total exposure time. GSTT1 might be protective against sleep and sensorimotor complaints, whereas GSTM1 seems to decrease sustained attention and short-term memory problems in relation to solvent exposure. Individuals possessing DRD2-141Cdel variant experienced more visuomotor problems.     

Promiscuity of the AlloHLA-A2 restricted T cell repertoire hampers the generation of minor Histocompatibility antigen-specific cytotoxic T cells across HLA barriers.

Hematopoietic system-specific miHAs are ideal targets for adoptive immunotherapy after allogeneic HLA (alloHLA)-matched SCT. Adoptive immunotherapy with cytotoxic T cells targeting hematopoietic system-specific miHAs restricted by alloHLA molecules is an attractive strategy to treat relapsed hematologic malignancies after HLA-mismatched SCT. As a proof of principle, we exploited 2 new strategies to generate alloHLA-A2-restricted miHA-specific T cells from HLA-A2(neg) donors using a HLA/miHA multimer-guided approach. In one strategy, autologous DCs coated with HLA-A2/miHA complexes were used for in vitro generation of miHA-specific T cells from HLA-A2(neg) male donors. In the other strategy, miHA-specific T cells were directly isolated from the peripheral blood of HLA-A2(neg) parous females with HLA-A2(pos) offspring. Both methods introduced recombinant HLA-A2/miHA complexes as the sole allogeneic target antigen. However, neither method yielded high avidity miHA-specific T cells or prevented the emergence of peptide-dependent promiscuous T cells. The latter T cells resembled miHA-specific T cells so closely with regard to tetramer binding and cytokine production that only extensive testing at a clonal level revealed their nonspecific nature. Therefore, promiscuity of the alloHLA-A2 T cell repertoire of HLA-A2(neg) individuals hampers in vitro generation of genuine miHA-specific T cells and limits its use for adoptive immunotherapy after HLA-A2 mismatched SCT.     

Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers

Dopamine transporter imaging is a valuable tool to investigate the integrity of the dopaminergic neurons. To date, several reports have shown an age-associated decline in dopamine transporters in healthy volunteers. Although animal studies suggest an effect of gender on dopamine transporter density, this gender effect has not yet been confirmed in human studies. To study the influence of age and gender on dopamine transporter imaging in healthy volunteers, we performed single-photon emission tomography imaging with [¹²³I]FP-CIT to quantify dopamine transporters. Forty-five healthy volunteers (23 males and 22 females) were included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h after injection of ±110 MBq [¹²³I]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [¹²³I]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [¹²³I]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [¹²³I]FP-CIT binding in young adults. Finally, females were found to have significantly higher [¹²³I]FP-CIT binding ratios than males. This effect of gender on [¹²³I]FP-CIT binding ratios was not related to age. The results of this study are consistent with findings from previous studies, which showed that dopamine transporter density declines with age. The intriguing finding of a higher dopamine transporter density in females than in males is in line with findings from animal studies. Received 29 January 2000 and in revised form 27 March 2000     

Fetoscopic surgery: encouraged by clinical experience and boosted by instrument innovation

Today, modern ultrasound equipment and the wide implementation of screening programmes allow the timely diagnosis of many congenital anomalies. For some of these, fetal surgery may be a life-saving option. In Europe, open fetal surgery became poorly accepted because of its invasiveness and the high incidence of postoperative premature labour and rupture of the fetal membranes. In the 1990s, the merger of fetoscopy and advanced video-endoscopic surgery formed the basis for endoscopic fetal surgery. We review the current applications of fetal surgery via both methods of access. The first clinical fetoscopic surgeries were interventions on the umbilical cord and the placenta, often referred to as obstetrical endoscopy. The outcome of a randomized clinical trial demonstrating that fetoscopic laser coagulation of chorionic plate vessels is the most effective treatment for twin–twin transfusion syndrome (TTTS) has revived interest in endoscopic fetal therapy. Operating on the fetus is another more challenging enterprise. Clinical fetal surgery programmes were virtually non-existent in Europe until minimally invasive fetoscopic surgery made such operations clinically possible as well as maternally acceptable. At present, most experience has been gathered with fetal tracheal occlusion as a therapy for severe congenital diaphragmatic hernia. As in other fields, minimally invasive surgery has pushed back boundaries and now allows safe operations to be performed on the fetal patient. Whereas minimal access seems to solve the problem of preterm labour, all procedures remain invasive, and carry a risk to the mother and a substantial risk of preterm prelabour rupture of the membranes (PPROM). The latter problem may prove to be a bottleneck for further developments, although treatment modalities are currently being evaluated.     

Human papillomavirus (HPV) detection among human immunodeficiency virus-infected pregnant Thai women: implications for future HPV immunization

BACKGROUND: Human immunodeficiency virus (HIV)-infected women are at increased risk for developing cervical cancer and for infection with human papillomavirus (HPV). Prophylactic vaccines targeting HPV types 16 and 18 are being evaluated for efficacy among young women. GOAL: The goal was to assess the prevalence of HPV among HIV-infected pregnant women in Bangkok and to evaluate the need for prophylactic HPV vaccines studies in this population. STUDY DESIGN: The study population consisted of 256 HIV-infected pregnant women who participated in a mother-to-child HIV transmission trial. Stored cervicovaginal lavage samples were tested for the presence of HPV DNA by polymerase chain reaction with PGMY09/11 primers and reverse line-blot hybridization for determination of anogenital HPV types. RESULTS: HPV prevalence was 35.5% (91/256); high-risk HPV prevalence was 23.4% (60/256). HPV type 16 or 18 was present in 8.2% (21/256). Almost half of all infections were multiple. Furthermore, overall HPV detection was associated with abnormal cervical cytology (P<0.001) and higher HIV-plasma viral load (P=0.007). CONCLUSIONS: Only one-quarter of HIV-infected pregnant women in Bangkok had high-risk HPV types; less than 10% had HPV types 16 or 18. As the HPV prevalence is expected to increase during HIV disease, prophylactic vaccines targeting HPV types 16 and 18 should be studied among HIV-infected women not yet infected with these HPV types and not previously exposed.