Biomedical subjects

M B Brennan

Publications and source records attributed to M B Brennan.

At least 19 recordsLinked to original sources

PubMed2006

Proopiomelanocortin heterozygous and homozygous null mutant mice develop pituitary adenomas.

Mice lacking all pro-opiomelanocortin (POMC)-derived peptides have been created by gene targeting of the POMC locus in embryonic stem cells. Phenotypes of the POMC null homozygous mutants include obesity, pigmentation defects, and adrenal insufficiency. Here, we report that both POMC null homozygous and heterozygous mutants also develop pituitary gland tumors, which result in their premature death. The tumors occur with 100% penetrance in both POMC heterozygous and homozygous genotypes. Histological examinations reveal that tumors start from hyperplastic focal points of melanotrophic cells within the intermediate lobe. Based on the morphological and immunohistological features, we have classified the tumors as non-invasive, non-secreting, intermediate lobe adenomas. These findings uncover potential novel roles of melanocortins in the regulation of cell proliferation.

Adenoma↗

PubMed2001

CD8(+) T cells are an in vivo reservoir for human T-cell lymphotropic virus type I.

It is thought that human T-cell lymphotropic virus type I (HTLV-I) preferentially infects CD4(+) T cells in vivo. However, observations of high HTLV-I proviral load in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis suggest that HTLV-I may infect other cell types in addition to CD4(+) T cells. To identify in vivo T-cell tropisms of HTLV-I, real-time quantitative polymerase chain reaction (PCR) and intracellular protein staining were used. A high amount of HTLV-I proviral DNA was detected from purified CD8(+) T cells by quantitative PCR (between 1.64 and 62.83 copies of HTLV-I provirus per 100 isolated CD8(+) T cells). CD8(+) T cells expressed HTLV-I-related antigens (HTLV-I Tax and p19 protein) after a short time in cultivation. These results demonstrate that CD8(+) T cells are also infected with HTLV-I and express HTLV-I antigens at levels that are comparable to HTLV-I-infected CD4(+) cells. Therefore, CD8(+) cells are an additional viral reservoir in vivo for HTLV-I and may contribute to the pathogenesis of HTLV-I-mediated disorders.

CD4-Positive T-Lymphocytes↗

PubMed2001

In vitro spontaneous lymphoproliferation in patients with human T-cell lymphotropic virus type I-associated neurologic disease: predominant expansion of CD8+ T cells.

Peripheral blood mononuclear cells (PBMCs) from patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) proliferate spontaneously in vitro. This spontaneous lymphoproliferation (SP) is one of the immunologic hallmarks of HAM/TSP and is considered to be an important factor related to the pathogenesis of HAM/TSP. However, the cell populations involved in this phenomenon have not yet been definitively identified. To address this issue, the study directly evaluated proliferating cell subsets in SP with a flow cytometric method using bromodeoxyuridine and Ki-67. Although both CD4+ and CD8+ T cells proliferated spontaneously, the percentage of proliferating CD8+ T cells was 2 to 5 times higher than that of CD4+ T cells. In addition, more than 40% of HTLV-I Tax11-19-specific CD8+ T cells as detected by an HLA-A*0201/Tax11-19 tetramer proliferated in culture. In spite of this expansion of HTLV-I-specific CD8+ T cells, HTLV-I proviral load did not decrease. This finding will help elucidate the dynamics of in vivo virus-host immunologic interactions that permit the coexistence of high HTLV-I-specific CD8+ cytotoxic T-lymphocyte responses and high HTLV-I proviral load in HAM/TSP.

Adult↗

PubMed2001

Impairment in motor learning of somatostatin null mutant mice.

Somatostatin was first identified as a hypothalamic factor which inhibits the release of growth hormone from the anterior pituitary (somatotropin release inhibitory factor, SRIF). Both SRIF and its receptors were subsequently found widely distributed within and outside the nervous system, in the adult as well as in the developing organism. Reflecting this wide distribution, somatostatin has been implicated regulating a diverse array of biological processes. These include body growth, homeostasis, sensory perception, autonomous functions, rate of intestinal absorption, behavior, including cognition and memory, and developmental processes. We produced null mutant mice lacking somatostatin through targeted mutagenesis. The mutant mice are healthy, fertile, and superficially indistinguishable from their heterozygous and wildtype littermates. A 'first round' phenotype screen revealed that mice lacking somatostatin have elevated plasma growth hormone levels, despite normal body size, and have elevated basal plasma corticosterone levels. In order to uncover subtle and unexpected differences, we carried out a systematic behavioral phenotype screen which identified a significant impairment in motor learning revealed when increased demands were made on motor coordination. Motor coordination and motor learning require an intact cerebellum. While somatostatin is virtually absent from the adult cerebellum, the ligand and its receptor(s) are transiently expressed at high levels in the developing cerebellum. This result suggests the functional significance of transient expression of SRIF and its receptors in the development of the cerebellum.

Animals↗

PubMed2001

Integrated control of appetite and fat metabolism by the leptin-proopiomelanocortin pathway.

Leptin deficiency results in a complex obesity phenotype comprising both hyperphagia and lowered metabolism. The hyperphagia results, at least in part, from the absence of induction by leptin of melanocyte stimulating hormone (MSH) secretion in the hypothalamus; the MSH normally then binds to melanocortin-4 receptor expressing neurons and inhibits food intake. The basis for the reduced metabolic rate has been unknown. Here we show that leptin administered to leptin-deficient (ob/ob) mice results in a large increase in peripheral MSH levels; further, peripheral administration of an MSH analogue results in a reversal of their abnormally low metabolic rate, in an acceleration of weight loss during a fast, in partial restoration of thermoregulation in a cold challenge, and in inducing serum free fatty acid levels. These results support an important peripheral role for MSH in the integration of metabolism with appetite in response to perceived fat stores indicated by leptin levels.

Animals↗

PubMed2001

Pronociceptive actions of dynorphin maintain chronic neuropathic pain.

Whereas tissue injury increases spinal dynorphin expression, the functional relevance of this upregulation to persistent pain is unknown. Here, mice lacking the prodynorphin gene were studied for sensitivity to non-noxious and noxious stimuli, before and after induction of experimental neuropathic pain. Prodynorphin knock-out (KO) mice had normal responses to acute non-noxious stimuli and a mild increased sensitivity to some noxious stimuli. After spinal nerve ligation (SNL), both wild-type (WT) and KO mice demonstrated decreased thresholds to innocuous mechanical and to noxious thermal stimuli, indicating that dynorphin is not required for initiation of neuropathic pain. However, whereas neuropathic pain was sustained in WT mice, KO mice showed a return to baselines by post-SNL day 10. In WT mice, SNL upregulated lumbar dynorphin content on day 10, but not day 2, after injury. Intrathecal dynorphin antiserum reversed neuropathic pain in WT mice at post-SNL day 10 (when dynorphin was upregulated) but not on post-SNL day 2; intrathecal MK-801 reversed SNL-pain at both times. Opioid (mu, delta, and kappa) receptor density and G-protein activation were not different between WT and KO mice and were unchanged by SNL injury. The observations suggest (1) an early, dynorphin-independent phase of neuropathic pain and a later dynorphin-dependent stage, (2) that upregulated spinal dynorphin is pronociceptive and required for the maintenance of persistent neuropathic pain, and (3) that processes required for the initiation and the maintenance of the neuropathic pain state are distinct. Identification of mechanisms that maintain neuropathic pain appears important for strategies to treat neuropathic pain.

Animals↗

PubMed2001

Generation of dynorphin knockout mice.

The opioid system has important roles in controlling pain, reward and addiction, and is implicated in numerous other processes within and outside the nervous system, such as mood states, immune responses, and prenatal developmental processes. The effects of the opioid system are mediated by at least three ligands, enkephalin, endorphin, and dynorphin, which act through the opioid receptors mu, delta, and kappa. In order to dissect the roles of individual components of the opioid system, mutant mice lacking single ligands or receptors are instrumental. We report here on the generation and initial characterization of a mutant mouse strain lacking pre-prodynorphin. Dynorphin 'knockout' mice are viable, healthy, and fertile and show no overt behavioral differences to wildtype littermates. Dynorphin knockout mice constitute a valuable tool for many research areas, among them research into pain, substance abuse, and epilepsy.

Animals↗

PubMed2001

Increased HTLV-I proviral load and preferential expansion of HTLV-I Tax-specific CD8+ T cells in cerebrospinal fluid from patients with HAM/TSP.

To date, high human T-cell lymphotropic virus type I proviral load in patients with human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis has been reported and is thought to be related to the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. However, the proviral load in cerebrospinal fluid has not been well investigated. We measured human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells from human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis patients using real-time quantitative polymerase chain reaction (TaqMan). Human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells were significantly higher than that of the matched peripheral blood mononuclear cells, and a high ratio of human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells to peripheral blood mononuclear cells were observed in patients with short duration of illness. Human T-cell lymphotropic virus type I Tax-specific CD8+ T cells, as detected by peptide-loaded HLA tetramers, accumulated in cerebrospinal fluid compared with that in peripheral blood mononuclear cells, while the frequency of cytomegalovirus-specific CD8+ T cells in cerebrospinal fluid was reduced. These observations suggest that accumulation of both human T-cell lymphotropic virus type I-infected cells and preferential expansion of human T-cell lymphotropic virus type I-specific CD8+ cells in cerebrospinal fluid may play a role in the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.

Adolescent↗

PubMed2001

Elevated serum and cerebrospinal fluid levels of soluble human herpesvirus type 6 cellular receptor, membrane cofactor protein, in patients with multiple sclerosis.

Membrane cofactor protein (CD46) is a member of a family of glycoproteins that are regulators of complement and prevent activation of complement on autologous cells. Recently, CD46 has been identified as the cellular receptor for human herpesvirus Type 6 (HHV-6). Elevated levels of soluble CD46 have been described in several autoimmune disorders, and may be implicated in the pathogenesis of these diseases. As several reports have supported an association of HHV-6 and multiple sclerosis, it was of interest to compare levels of soluble CD46 in the sera of multiple sclerosis patients to that of healthy controls, other neurological disease controls, and other inflammatory disease controls. Using an immunoaffinity column comprised of immobilized monoclonal antibodies to CD46, serum levels of soluble CD46 were found to be significantly elevated in multiple sclerosis patients compared with healthy and other neurological disease controls. Moreover, multiple sclerosis patients who tested positive for HHV-6 DNA in serum had significantly elevated levels of soluble CD46 in their serum compared with those who were negative for HHV-6 DNA. A significant increase in soluble CD46 was also found in the serum of other inflammatory disease controls tested compared to healthy controls. Additionally, a significant correlation was demonstrated between levels of soluble CD46 in the serum and cerebrospinal fluid of multiple sclerosis patients. Collectively, these data suggest that elevated levels of soluble CD46 may contribute to the pathogenesis of inflammatory diseases, including multiple sclerosis.

Antigens, CD↗

PubMed2001

Recurrence rates in patients with central or retroareolar breast cancers treated with mastectomy or lumpectomy.

BACKGROUND: Although breast conservation with lumpectomy and radiation treatment has become a commonly used treatment for breast cancer, there are little data to support the use of lumpectomy for central and retroareolar breast cancers. In this study, we investigate the local and distant recurrence rates of patients with central or retroareolar breast cancers treated with lumpectomy compared with mastectomy. METHODS: This study provides a retrospective analysis of 99 patients, from 1981 to 2000, with central or retroareolar breast cancers treated with mastectomy or lumpectomy to determine the frequency of local and distant recurrence. The mastectomy and lumpectomy patients were compared with respect to recurrence and other prognostic factors including: tumor location, tumor size, axillary nodal status, and final surgical margins. RESULTS: The overall frequency of local recurrence was 5 of 99 (5.0%) in the entire group, 3 of 67 (4.5%) and 2 of 32 (6.3%) of patients who underwent mastectomy and lumpectomy, respectively (P >0.99). Overall, 3 patients experienced a distant recurrence as a first event, with 2 patients (3.0%) in the mastectomy group and 1 patient (3.1%) in the lumpectomy group (P >0.99). The type of surgical management was not statistically significant related to either local or distant disease recurrence, with median time to local recurrence of 3.0 years for the mastectomy patients and 5.0 years for lumpectomy patients. Of the patients with central tumors who underwent mastectomy 2 of 42 (4.8%) developed local recurrences compared with those who had a lumpectomy, 1 of 21 (4.8%). Similarly for retroareolar tumors, the local recurrence rate was 1 of 25 (4.0%) for patients undergoing mastectomy and 1 of 11 (9.1%) for those undergoing lumpectomy (P >0.99). CONCLUSIONS: In this study there was no significant difference in local or distant failure rates of those patients with central or retroareolar tumors treated with mastectomy versus lumpectomy. We conclude lumpectomy to be a reasonable treatment option for selected patients with central or retroareolar breast cancers.

Adult↗

PubMed2000

Tissue distribution and variant characterization of human herpesvirus (HHV)-6: increased prevalence of HHV-6A in patients with multiple sclerosis.

Human herpesvirus (HHV)-6 has been associated with the pathogenesis of multiple sclerosis (MS) on the basis of serologic, molecular, and histopathologic studies. This study sought to determine the distribution of HHV-6 in different MS body fluids, including serum, saliva, urine, and peripheral blood lymphocytes. The study results extend the observation of an increased frequency of HHV-6 DNA in serum of patients with MS to the unique detection of viral sequences in urine of a subset of patients with MS. Moreover, the HHV-6 identified in these cell-free compartments was predominantly the HHV-6A variant, which has been reported to be neurotropic. These results support the hypothesis that HHV-6 may contribute to the MS disease process.

Adult↗

PubMed2000

Does sentinel lymphadenectomy improve staging and alter therapy in elderly women with breast cancer?

BACKGROUND: Routine axillary lymph node dissection (ALND) for elderly women with invasive breast cancer has been questioned because it rarely alters therapy yet carries a significant morbidity rate. Sentinel lymphadenectomy (SLND) improves axillary staging and alters therapy in women with T1 breast cancer, but it is not clear whether SLND alters therapy in elderly women with breast cancer. METHODS: A prospective breast cancer data base was used to identify women 70 years old and older who underwent SLND for axillary staging of invasive breast cancer between 1991 and 1998. RESULTS: There were 75 invasive breast cancers in 73 women. The mean patient age was 74.5 years (range, 70-90 years). Median tumor size was 1.4 cm (range, 0.1-6.2 cm). Of the 75 tumors, 42 (56%) had favorable primary characteristics; the remaining tumors had unfavorable characteristics. SLND was performed alone in 17 cases (23%) and was followed by completion ALND in 58 cases (77%). Positive lymph nodes were identified in 32 cases (43%); 26 (81.3%) were detected by hematoxylin and eosin stains, and 6 (18.7%) were detected by immunohistochemistry alone. Five patients (6.9%) received adjuvant chemotherapy. Seven patients (9.6%) received axillary/supraclavicular radiation for positive nodes. Ten (13.7%) of 73 patients had obvious alterations in therapy because of axillary nodal status. As a result of SLND, 3 (13.6%) of 22 patients with tumors 1.0 cm or smaller received tamoxifen, and 7 (15%) of 46 patients with tumors between 1.0 and 3.0 cm in size had changes in therapy. When patient and tumor characteristics were analyzed to determine relationships to therapeutic decision-making, nodal status was the variable most significantly associated with changes in therapy (P = .0001). CONCLUSIONS: SLND improves axillary staging in elderly women with invasive breast cancer. Results of immunohistochemistry do not alter therapy in this group of individuals (P = .6367). In patients with small primary tumors, SLND alters therapy by increasing the number of patients receiving tamoxifen. In addition, SLND affects adjuvant systemic chemotherapy and regional radiotherapy in a significant number of patients with larger tumors, particularly tumors between 1.0 and 3.0 cm.

Aged↗

PubMed2000

New diagnostic techniques and treatments for early breast cancer.

OBJECTIVES: To review diagnostic techniques and treatments for early breast cancer, including radiologic techniques, biomarkers, surgical techniques, radiation therapy, adjuvant chemotherapy regimens, and hormonal therapy. DATA SOURCES: Scientific and review articles, book chapters, and clinical practice. CONCLUSIONS: Breast cancer is a major health problem. The advances in diagnosis and treatment of early breast cancer and the amount of information available make it difficult for patients to make diagnostic and treatment decisions. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses need to be knowledgeable in the many advances in diagnostic and treatment techniques for early breast cancer to assist patients with difficult decisions.

Antineoplastic Agents↗

PubMed2000

Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer.

PURPOSE: Immediate complete axillary lymphadenectomy (ALND) after sentinel lymphadenectomy (SLND) has confirmed that tumor-negative sentinel nodes accurately predict tumor-free axillary nodes in breast cancer. Therefore, we hypothesized that SLND alone in patients with tumor-negative sentinel nodes would achieve axillary control, with minimal complications. PATIENTS AND METHODS: Between October 1995 and July 1997, 133 consecutive women who had primary invasive breast tumors clinically </= 4 cm in diameter and no axillary lymphadenopathy were prospectively entered onto a trial of SLND using vital blue dye. Sentinel nodes were examined by standard microscopy or immunohistochemistry. SLND was the only axillary surgery if sentinel nodes were tumor-free. Completion ALND was performed only if sentinel nodes contained metastases or if they were not identified. Excluded from subsequent analysis were patients with unsuspected multifocal carcinoma and those who refused completion ALND. The complication and axillary recurrence rates after SLND without ALND were determined. RESULTS: Sentinel nodes were identified in 132 (99%) of 133 patients. Eight patients were excluded from further analysis. Of the 125 assessable patients, 57 had tumor-positive sentinel nodes and one had an unsuccessful mapping procedure; these patients underwent completion ALND. In the remaining 67 patients (54%), SLND was the only axillary procedure. Complications occurred in 20 patients (35%) undergoing ALND after SLND but in only two patients (3%) undergoing SLND alone (P =.001). There were no local or axillary recurrences at a median follow-up of 39 months. CONCLUSION: Complication rates are negligible after SLND alone. An absence of axillary recurrences supports SLND as an accurate staging alternative for breast cancer and suggests that routine ALND can be eliminated for patients with histopathologically negative sentinel nodes.

Adult↗

PubMed1999

Lymph node metastasis from ductal carcinoma in situ with microinvasion.

BACKGROUND: Widespread use of mammography has increased the detection of ductal carcinoma in situ with microinvasion (DCISM) in pathology specimens. Currently there is disagreement regarding the incidence of axillary metastasis from DCISM. The controversy centers on whether complete lymphadenectomy is indicated for axillary staging, given its morbidity and the reportedly minimal rate of axillary involvement in these patients. Intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) may obviate complete axillary lymph node dissection in selected breast carcinoma patients. In intraoperative lymphatic mapping, isosulfan blue dye is used to demonstrate the course of lymphatic flow from the breast tumor to the first draining or sentinel lymph node. This blue-stained lymph node is selectively excised for pathologic examination; its tumor status is used to predict the tumor status of the other axillary lymph nodes. The authors examined whether SLND would be suitable for staging DCISM. METHODS: From February 1992 to January 1997, 14 patients with DCISM underwent intraoperative lymphatic mapping and SLND at the John Wayne Cancer Institute in Santa Monica, California. Clinical and pathologic data were prospectively collected. RESULTS: Primary DCISM tumors ranged in size from 0.9 to 6.5 cm. Nine patients presented with mammographic abnormalities, two patients presented with Paget's disease and a palpable lesion, and three patients presented with palpable lesions. Two patients (14.3%) had tumor-involved sentinel lymph nodes. One of these patients had two sentinel lymph nodes, both of which contained single cancer cells identified by immunohistochemistry. The other patient had 1 sentinel lymph node, in which a 0.3-cm metastasis was revealed by light microscopy. Completion axillary dissection was performed on both patients and revealed no further tumor positive lymph node metastases. CONCLUSIONS: SLND can detect lymph node micrometastases (tumor deposits <2 mm) in patients with DCISM. The clinical relevance of these micrometastases is unknown, but their existence shows that DCISM can involve the lymph nodes.

Carcinoma in Situ↗

PubMed1999

Risk of diphtheria among schoolchildren in the Russian Federation in relation to time since last vaccination.

BACKGROUND: Between 1990 and 1996, more than 110,000 cases and 2900 deaths from diphtheria were reported in the Russian Federation. In 1994, because disease rates were high among children aged 7-10 years, the age of administration of the second booster dose of diphtheria vaccine was lowered from 9 years to 6 years, the age of school entry. To assess the impact of this policy change, we did a matched case-control study in three Russian cities. METHODS: Children aged 6-8 years who had diphtheria between September, 1994, and December, 1996, were each matched with five to seven children acting as controls who were within 3 months of age of the case and were from the same class at school. We did a matched analysis using conditional logistic regression. FINDINGS: We analysed the immunisation records of 58 cases and 306 controls. All but one case and all controls had received at least three doses of diphtheria-toxoid vaccine. 19 (33%) cases and 144 (47%) controls had received a booster dose of diphtheria toxoid within the previous 2 years. Cases were more likely than were controls to have received only four doses rather than five (odds ratio 2.8 [95% CI 1.2-6.5]) and to have a time since the last dose of diphtheria toxoid of 3-4 years (3.1 [1.1-9.1]) or 5-7 years (15.0 [2.5-89.0]), compared with children for whom it was 2 years or less. On multivariate analysis only a time since the last dose of 5-7 years remained significantly associated with disease (matched odds ratio adjusted for total number of doses 10.9 [1.6-75.1]). CONCLUSION: A booster dose of diphtheria-toxoid vaccine given to children in the Russian Federation at 6-8 years of age reduced the interval since the last dose of diphtheria toxoid and improved protection against diphtheria.

Case-Control Studies↗

PubMed1999

The impact of genomics on mammalian neurobiology.

The benefit of genomics lies in the speeding up of research efforts in other fields of biology, including neurobiology. Through accelerated progress in positional cloning and genetic mapping, genomics has forced us to confront at a much faster pace the difficult problem of defining gene function. Elucidation of the function of identified disease genes and other genes expressed in the Central nervous system has to await conceptual developments in other fields.

Alcoholism↗

PubMed1999

Sentinel node metastasis in patients with breast carcinoma accurately predicts immunohistochemically detectable nonsentinel node metastasis.

BACKGROUND: Sentinel lymphadenectomy is highly accurate for identifying axillary metastasis from a primary breast carcinoma. Nonsentinel axillary lymph nodes (NSNs) are unlikely to contain tumor cells if the axillary sentinel node (SN) is tumor free. We previously showed that the size of the primary tumor and the size of its SN metastasis predict the risk of NSN tumor involvement detected by hematoxylin and eosin staining. This study used immunohistochemical staining (IHC) to determine the likelihood of NSN axillary metastasis in the presence of SN metastasis. METHODS: Between 1991 and 1997, axillary lymphadenectomy was performed in 156 women (157 axillary basins) who had primary breast carcinoma with SN metastasis. By hematoxylin and eosin staining, we identified NSN metastasis in 55 axillae (35%). IHC was then used to re-examine all NSNs (1827 lymph nodes) from the remaining 102 axillae. The incidence of IHC-detected NSN involvement was analyzed with respect to clinical and tumor characteristics. RESULTS: By using IHC, we identified NSN metastasis in 15 (14.7%) of the 102 axillae. By multivariate analysis, the size of the SN metastasis (P = .0001) and the size of the primary tumor (P = .038) were the only independent variables predicting NSN metastasis determined by using either hematoxylin and eosin staining or IHC. Only the number of SN metastases (1 vs. >1) was a significant (P = .04) predictor of IHC-detected NSN metastasis. CONCLUSIONS: Use of IHC increases the likelihood of detection of NSN metastasis, and the risk of IHC-detected metastasis increases with the size of the SN metastasis and the size of the primary tumor. If SN involvement is micrometastatic (< or =2 mm) or detected by using IHC, tumor cells are unlikely to be found in other axillary lymph nodes in patients with a small primary tumor. The clinical significance of micrometastatic disease in lymph nodes is controversial, and a prospective randomized study is necessary to resolve this important issue.

Adult↗