Surgical management of aberrant sentinel lymph node drainage in cutaneous melanoma

BACKGROUND: Sentinel lymph node (SLN) mapping by lymphoscintigraphy has changed the surgical management of regional lymph node metastases for melanoma. SLNs lying outside of traditional nodal basins are now being identified. Our hypothesis is that when preoperative lymphoscintigraphy identifies aberrant SLNs, these nodes should be excised and, if histologically positive, lymphadenectomy of the aberrant nodal basin should be performed. METHODS: Patients with melanomas 1 mm or larger Breslow thickness and clinical stage N0M0 underwent lymphoscintigraphy and excision with SLN biopsy. Preoperative lymphoscintigraphy, intraoperative gamma probe, and intraoperative injection of isosulfan blue were performed to identify the SLN. Aberrant SLNs were defined as epitrochlear, supraclavicular, or popliteal nodes for extremity lesions and intramuscular nodes for truncal and head and neck lesions. RESULTS: Thirty-two patients were entered into the protocol. Seven (22%) were found to have aberrant nodes. Five of 19 patients with extremity melanoma had an aberrant SLN; 2 of 13 patients with truncal and head and neck melanoma had an aberrant SLN. CONCLUSIONS: This study demonstrates that (1) aberrant SLNs are encountered with similar frequency for extremity and truncal lesions, (2) biopsy should be performed on aberrant SLNs with intraoperative lymph node mapping with the gamma probe and blue dye, and (3) lymphadenectomy of the aberrant region should be considered if the aberrant SLN is positive.     

Dependence of both spontaneous and antibody-dependent, granule exocytosis-mediated NK cell cytotoxicity on extracellular signal-regulated kinases

Extracellular signal-regulated kinases (ERK, also known as mitogen-activated protein kinases) are serine-threonine kinases transducing signals elicited upon ligand binding to several tyrosine kinase-associated receptors. We have reported that ERK2 phosphorylation and activation follows engagement of the low affinity receptor for the Fc portion of IgG (CD16) on NK cells, and is necessary for CD16-induced TNF-alpha mRNA expression. Here, we analyzed the involvement of ERK in NK cell-mediated cytotoxicity and IFN-gamma expression induced upon stimulation with targets cells, coated or not with Abs. Our data indicate that, as with immune complexes, ERK2 phosphorylation occurs in human primary NK cells upon interaction with target cells sensitive to granule exocytosis-mediated spontaneous cytotoxicity, and that this regulates both target cell- and immune complex-induced cytotoxicity and IFN-gamma mRNA expression. A specific inhibitor of mitogen-activated protein kinase kinase reduced both spontaneous and Ab-dependent cytotoxicity in a dose-dependent manner involving, at least in part, inhibition of granule exocytosis without affecting effector/target cell interaction and rearrangement of the cytoskeleton proteins actin and tubulin. Involvement of ERK in the regulation of Ca2+-dependent cell-mediated cytotoxicity was confirmed, using a genetic approach, in primary NK cells infected with a recombinant vaccinia virus encoding an ERK inactive mutant. These data indicate that the biochemical pathways elicited in NK cells upon engagement of receptors responsible for either spontaneous or Ab-dependent recognition of target cells, although distinct, utilize ERK as one of their downstream molecules to regulate effector functions.     

Effects of endothelin-3 on water and sodium excretion during extracellular volume expansion

The aim of the present study was to elucidate the role of an IV dose of endothelin-3 (ET-3) (5 ng Kg-1 min-1) on mean arterial pressure (MAP), on diuresis and natriuresis in control and in volume expanded anesthetized rats. A systemic infusion of ET-3 in normal rats (Group I) increased MAP and produced a trend of increasing diuresis, without changes in natriuresis. A 10% body weight expansion (Group II) increased diuresis and natriuresis without changes in MAP. The simultaneous infusion of ET-3 and expansion with saline (Group III) resulted in an increase in MAP, an enhanced diuretic response, and a natriuresis of similar magnitude to that observed in Group II. These results suggest that the diuresis produced by a low dose of exogenous ET-3 in control rats, is independent of sodium excretion. Furthermore, the enhanced diuresis caused by ET-3 during expansion is greater than the addition of ET-3 and expansion effects, suggesting that new mechanisms are triggered in order to maintain volume and salt homeostasis in this state.     

Maternal feeding practices and childhood obesity: a focus group study of low-income mothers

OBJECTIVE: To identify maternal beliefs and practices about child feeding that are associated with the development of childhood obesity. DESIGN: Four focus groups. One group of dietitians from the Supplemental Nutrition Program for Women, Infants, and Children (WIC) in the Northern Kentucky Health District and 3 groups of mothers with children enrolled in WIC. SETTING: The WIC program in the Northern Kentucky Health District. PARTICIPANTS: Fifteen WIC dietitians and 14 mothers (14 to 34 years of age) with young children (12 to 36 months of age) enrolled in WIC. RESULTS: The mothers in this study (1) believed that it was better to have a heavy infant because infant weight was the best marker of child health and successful parenting, (2) feared that their infants were not getting enough to eat, which led them to introduce rice cereal and other solid food to the diets before the recommended ages, and (3) used food to shape their children's behaviors (eg, to reward good behavior or to calm fussiness). The mothers acknowledged that some of their child-feeding practices went against the advice of their WIC nutritionists and physicians. Instead, the participants relied on their mothers as their main source of information about child feeding. CONCLUSIONS: Physicians and allied health professionals discussing childhood growth with mothers should avoid implying that infant weight is necessarily a measure of child health or parental competence. Parents who use food to satisfy their children's emotional needs or to promote good behavior in their children may promote obesity by interfering with their children's ability to regulate their own food intake. Interventions to alter child-feeding practices should include education of grandmothers.     

Persistent or recurrent carpal tunnel syndrome following prior endoscopic carpal tunnel release

Immunohistochemistry was applied in the investigation of the possible existence of serotonin in human skin. It was found that epidermal melanocytes express a serotonin-like immunoreactivity. The immunoreactivity was associated with both the cytoplasm and the cellular membrane, though the latter was only found in certain cells. The serotonin anti-serum labeled the same cells as NKI-beteb, which is known as a reliable marker of melanocytes. Blocking experiments showed that both serotonin and NKI-beteb have different epitopes in the melanocytes. In in vitro studies, serotonin-like immunoreactivity appeared in approximately 90% of cultured human melanocytes, and was found both in the cytoplasm and also in the nuclei. Thus, we believe the melanocytes to be the origin of serotonin (or a serotonin-like molecule) in the skin.     

DNA and a CpG oligonucleotide derived from Babesia bovis are mitogenic for bovine B cells

DNAs from bacteria and variety of nonvertebrate organisms, including nematodes, mollusks, yeasts, and insects, cause polyclonal activation of murine B lymphocytes. Similar studies have not been reported for bovine B cells, and to date no studies have reported mitogenic properties of protozoal DNA for any species. However, we and others have observed that protozoal parasite antigens can induce the proliferation of lymphocytes from nonexposed donors. Extending these studies, we now show that the mitogenic property of protozoal antigen preparations is in part attributable to parasite DNA and that Babesia bovis DNA is directly mitogenic for bovine B cells. DNase treatment of B. bovis extracts abrogated B. bovis-induced proliferation of peripheral blood mononuclear cells from nonexposed cattle. Like DNAs from other organisms that were mitogenic for murine B cells, B. bovis DNA is largely nonmethylated and induced a dose-dependent proliferation of bovine B cells, which was reduced upon methylation. Furthermore, B. bovis and E. coli DNAs enhanced immunoglobulin secretion by cultured B cells, inducing moderate increases in immunoglobulin G1 and stronger increases in immunoglobulin G2. Because certain nonmethylated CpG motifs present in bacterial DNA are known to stimulate proliferation of murine and human B cells, an 11-kb fragment of B. bovis DNA was analyzed for CG dinucleotide content and for the presence of known immunostimulatory sequences (ISS) centered on a CG motif. The frequency of CG dinucleotides was approximately one-half of the expected frequency, and several CpG hexameric sequences with known activity for murine B cells were identified. An oligodeoxynucleotide containing one of these ISS (AACGTT), which is present within the rhoptry-associated protein-1 (rap-1) open reading frame, was shown to stimulate B-cell proliferation. These ISS may be involved in host immune modulation during protozoal infection and may be useful as vaccine adjuvants.     

Role of 55- and 75-kDa TNF receptors in the potentiation of Fc-mediated phagocytosis in human neutrophils

OBJECTIVE: To compare the effect of epidural vs general anesthesia on the incidence of long-term cognitive dysfunction after total knee replacement surgery in older adults. DESIGN: Randomized controlled clinical trial. SETTING: Orthopedic specialty academic hospital. PATIENTS: A total of 262 patients undergoing elective primary total knee replacement with a median age of 69 years; 70% women. INTERVENTION: Random assignment to either epidural or general anesthesia. MAIN OUTCOME MEASURES: A thorough neuropsychological assessment was performed preoperatively and repeated at 1 week and 6 months postoperatively. Cognitive outcome was assessed by within-patient change on 10 tests of memory, psychomotor, and language skills. Prospective standardized surveillance for cardiovascular complications was performed to allow simultaneous assessment of anesthetic effects on cognitive and cardiovascular outcomes. RESULTS: The two groups were similar at baseline in terms of age, sex, comorbidity, and cognitive function. There were no significant differences between the epidural and general anesthesia groups in within-subject change from baseline on any of the 10 cognitive test results at either 1 week or 6 months. Overall, 5% of patients showed a long-term clinically significant deterioration in cognitive function. There was no difference between the anesthesia groups in the incidence of major cardiovascular complications (3% overall). CONCLUSIONS: The type of anesthesia, general or epidural, does not affect the magnitude or pattern of postoperative cognitive dysfunction or the incidence of major cardiovascular complications in older adults undergoing elective total knee replacement. This is the largest trial of the effects of general vs regional anesthesia on cerebral function reported to date, with more than 99% power to detect a clinically significant difference on any of the neuropsychological tests.