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Biomedical subjects

W Carson

Publications and source records attributed to W Carson.

At least 19 recordsLinked to original sources
PubMed1998

Sentinel node biopsy in breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SNB) in breast cancer may be used in place of axillary lymph node dissection (ALND) if SNB accurately stages the axilla. This study assessed the success and accuracy of axillary SNB with isosulfan blue (ISB) and technetium-99 sulfur colloid (TSC) compared to ALND. METHODS: Forty-two women with T1 or T2 breast cancer underwent SNB and ALND. Sixty to 90 minutes before anesthetic induction, a mixture of 3 mL ISB and 1 mCi TSC was injected around the primary cancer or prior biopsy site. Intraoperatively, the SLN was identified using a gamma detector (Neoprobe 1000) or by visualization of the blue-stained lymph node and afferent lymphatics. The SLN was excised separately, and a level I/II ALND was completed. The histologic findings of the axillary contents and SLN were compared. RESULTS: An axillary SLN was found in 38 of 42 (90%) cases. SLN localization rate and predictive value were the same for women who had and those who had not undergone excisional biopsy before the date of SNB. Fifteen of 42 (36%) patients had lymph node metastases. The SLN was positive in all women with axillary metastases (negative predictive value, 100%). CONCLUSIONS: If confirmed by larger series, a negative SNB may eliminate the need for ALND for select women with breast cancer.

Adult↗
PubMed1998

Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients.

Linoleic acid is the most abundant fatty acid in human low density lipoproteins (LDL). Oxidation of LDL transforms linoleic acid to hydroperoxyderivatives. These are converted to 9-hydroxy-10,12-octadecadienoic acid (9-HODE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODE). 9-HODE is much more abundant in oxidized LDL than other lipid peroxidation products and therefore an indicator of lipid peroxidation (LPO). In this study the 9-HODE content in the LDL of 19 obviously healthy volunteers and 17 atherosclerotic patients was investigated. The level of 9-HODE obtained from LDL of young atherosclerotic patients (aged 36-47 years) was increased by a factor of 20 when compared with samples from healthy volunteers of the same age group. The content of 9-HODE in the LDL of atherosclerotic patients aged between 69 and 94 years increased 30-100 fold when compared with young healthy individuals, but when compared with 'healthy' individuals of the same age group it was only 2-3 fold increased. Obviously, as individuals grow older LDL becomes more and more oxidized. Consequently, assuming that LDL oxidation is a precondition for atherosclerosis--older individuals will suffer from atherosclerosis, even if no easy detectable visible signs of this disease are recognizable. According to 9-HODE determination, the onset of the disease starts slowly in most individuals at around 50 years of age.

Adult↗
PubMed1998

Interleukin-15 as a potential regulator of the innate immune response.

Interleukin-15 (IL-15) is a newly-discovered cytokine that is produced by activated monocytes early in the course of the innate immune response. IL-15 is able to bind to components of the interleukin-2 receptor (IL-2R) despite the fact that it has no sequence homology with IL-2. IL-15 stimulates human natural killer cell proliferation, cytotoxicity, and cytokine production and can substitute for IL-2 under most conditions. In vitro studies indicate that monocyte-derived IL-15 may be an important determinant of IFN-gamma production by NK cells. In addition, IL-15 is able to promote the survival of natural killer cells under serum-free conditions. The IL-15 receptor is a heterotrimeric complex which is composed of the IL-2R beta and gamma chains in combination with a unique alpha chain (IL-15 alpha). The IL-15R alpha chain has strong sequence homology to the IL-2R alpha chain and confers high affinity binding to the IL-15R. In contrast to IL-2, transcript for IL-15 and IL-15 alpha is expressed in a number of tissues and indicates that IL-15 may be an important ligand for cells that express components of the IL-2R.

B-Lymphocytes↗
PubMed1996

Natural Killer Cell Subsets and Development

NK cells are large granular lymphocytes that are an important component of the innate immune system. Surface density expression of CD16 and CD56 can be used to classify functionally and developmentally distinct NK cell subsets. This notion has more recently been confirmed by the identification of unique cytokine receptor expression patterns within each NK cell subset. There are substantial data to suggest that NK cells are derived from proliferating bone marrow precursors. Murine studies have also shown that an intact marrow environment is necessary for the development of NK cells from their progenitor populations. Culture of bone marrow cells in IL-2-containing medium gives rise to effectors that are essentially indistinguishable from mature NK cells, and it has also been shown that NK cells can be generated in vitro by culture of CD34(+) bone marrow cells with IL-2. Several lines of evidence suggest that NK cells and T cells may share a common precursor. T cells and NK cells can both be generated from immature thymocytes in vitro, and both CD3(+) lymphocytes with functional TCR and CD3(-)CD16(+) NK cells can be generated from fetal liver cells under the appropriate culture conditions. One might therefore postulate the existence of a common NK/T-cell progenitor within the fetal liver that possesses the ability to differentiate into T lymphocytes under thymic influences. Alternatively, in the absence of these signals, or perhaps in response to other stimuli (i.e., IL-2), the NK/T-cell progenitor differentiates into cytolytic NK effectors. Although IL-2 has been found to be critical to the development of NK cells in vitro, it is important to note that NK cells are present in IL-2 knockout mice. Therefore, other cytokines that bind to components of the IL-2R may be important to the development of NK cells in vivo.

Journal Article↗
PubMed1995

Incidence of acute care complications in vertebral column fracture patients with and without spinal cord injury.

STUDY DESIGN: This study retrospectively analyzed vertebral column fractures in trauma patients during a 2-year period. Data from a multicenter trauma registry were used. OBJECTIVES: The purpose of this study was to ascertain and describe the initial in-hospital morbidity and mortality rates for patients with vertebral column fractures with and without spinal cord injury. SUMMARY OF BACKGROUND DATA: Patients with vertebral fractures and associated spinal cord injuries experience more medical complications than those without spinal cord injuries. However, the precise incidence and relative risk of complications during acute care hospitalization for these two groups are not well documented. METHODS: Vertebral column fractures in 419 adolescent and adult trauma patients hospitalized during a 2-year period were retrospectively analyzed using data from a multicenter trauma registry. RESULTS: Of the 419 patients, 104 (24.8%) had an associated spinal cord injury. More than half of the spinal cord injury patients (52.9%) and 20.6% of those without spinal cord injury had one or more complications during their hospitalization. Complications resulted in an average of 33.1 extra hospital days, which extrapolates nationally into 1.5 million additional days annually. The four complications differing most significantly in incidence between the spinal cord injury group and the non-spinal cord injury group were: urinary tract infections (24.0% vs. 8.6%), respiratory (23.1% vs. 8.6%), cardiac (11.5% vs. 3.2%), and decubitus ulcer (7.7% vs. 1.0%). Pneumonia, although not statistically different, was high in both groups (13.5% vs. 7.3%). CONCLUSIONS: The incidence of the 25 types of medical complications reported here provides specific and relevant information to assist health professionals in treating patients during their acute care. We estimate that complications during initial hospitalization add $1.5 billion annually to the cost of caring for patients with vertebral fractures in the United States.

Adolescent↗
PubMed1995

Vectorcardiography in experimental myocardial infarction. Serial changes and correlation between QRS loop change and the infarction size.

The objectives of this study were to examine the serial vectorcardiographic changes following acute myocardial infarct and to assess the relationship between QRS loop changes and infarct size. Fifty adult male Long-Evans rats of 250-350 gm body weight were used to study experimental acute myocardial infarction induced by coronary artery ligation. Vectorcardiograms (VCG) of the Frank lead system were recorded before, and 1 day and 7 days after operation. Animals were sacrificed on the 7th day for histological quantitation of infarct area ratios. We found that (1) before operation, rats have ST elevation, probably due to early repolarization. (2) After coronary artery ligation, ECG showed characteristic dome-shaped ST elevation at 1 hr after ligation which returned to normal during the first day. Abnormal Q waves appeared thereafter. (3) After ligation, maximum QRS vector, ST vector and maximum T vector were reduced in magnitude the first day and recovered by the 7th day. The vectors tended to shift their direction to the right and to the posterior. QRS-T angle, however, widened as time went on. About half of the rats revealed changes in the inscription direction of the QRS loop and abnormal QRS morphology also appeared in about half of the ligated rats. (4) Those in whom abnormal QRS loop morphology and/or biting appeared had significantly larger infarct area ratios (p < 0.01). (5) Change in QRS loop inscription direction seemed not to be related to the infarct size. (6) In the LS plane, the difference in max QRS vector magnitude between the 1st and 7th days significantly correlated with the infarct area ratio (r = 0.533, p < 0.05). In the H plane, the change in the max QRS vector magnitude at the 7th day correlated with the infarct area ratio (r = -0.531, p < 0.05). In the F plane, changes in the direction of the max QRS vector were significantly correlated to the infarct area ratio both on the first (r = 0.431, p < 0.05) and 7th days (r = 0.531, p < 0.05). It is concluded that the VCG, like the ECG, had evolutional changes in AMI and that the QRS loop seen on vectorcardiography has only a slight correlation with the histological myocardial infarct size.

Animals↗
PubMed1994

Results of aggressive treatment of gastric sarcoma.

BACKGROUND: Leiomyosarcoma and leiomyoblastoma and subtypes of gastric smooth muscle tumors. These rare tumors are usually treated with surgical resection. However, there is controversy regarding the optimal surgical management for these malignancies and little information is available on the efficacy of radiation and chemotherapy in the adjuvant or palliative setting. METHODS: The records of 32 patients with gastric leiomyosarcoma or leiomyoblastoma were reviewed. Survival data were obtained and patient outcome was analyzed with respect to the type of treatment given. Four different staging systems were compared for their ability to predict survival. RESULTS: Thirty patients with leiomyosarcoma and two patients with leiomyoblastoma were followed after surgery. All 32 patients were explored, and 21 curative and 11 palliative procedures were performed. Adjacent organs were included in 38% of resections. Only three patients did not undergo gastric resection. Local recurrence developed in eight patients after curative resection for a local control rate of 62%. Eight other patients developed metastatic disease for an overall recurrence rate of 76% after curative resection. Median survival of patients undergoing curative resection was 40 months compared with 8 months for those having a palliative procedure. The estimated 5-year survival was 34% and 10%, respectively (p = 0.05). Twenty-five patients with advanced disease received systemic, hepatic arterial, or intraperitoneal chemotherapy. Eighty percent of patients received a regimen including doxorubicin. Four partial and one complete response were noted. Seven patients received postoperative radiation therapy. Fourteen patients underwent debulking surgery of recurrent or persistent disease in conjunction with chemotherapy. Chemotherapy, radiation therapy, and debulking surgery did not result in statistically significant prolongation of survival. Seven patients remain alive, two with liver metastases. Four different staging systems for gastric sarcomas were compared, but none of them were found to be clearly superior in predicting survival. CONCLUSIONS: Curative gastric resection was achieved in 66% of patients and resulted in a significant prolongation of survival as compared with patients who had a palliative procedure. Wedge resection of tumor or partial gastric resection appears to be an acceptable surgical approach to these tumors as long as negative margins can be obtained. Chemotherapy, radiation therapy and debulking surgery did not result in significant prolongation of survival in the face of advanced disease. None of the staging systems for gastric sarcoma currently in use is completely satisfactory. Tumor grade and extent of disease seem to be the most important factors when determining prognosis or considering adjuvant therapy.

Adolescent↗
PubMed1994

Lobular carcinoma in situ: observation without surgery as an appropriate therapy.

BACKGROUND: The finding of lobular carcinoma in situ (LCIS) in the breast has generally prompted treatment with unilateral or bilateral mastectomy. Most experts now feel that LCIS simply identifies a woman who is at high risk to develop future breast cancer and requires only close clinical and mammographic follow-up. This approach has been recommended at our institution for > 15 years. This study defines the natural history of a population of women with LCIS who were treated by observation alone. METHODS: Women with a pathologic diagnosis of LCIS were identified by tumor registry search. Records and pathology were reviewed. Radiographic-pathologic correlation was performed on women who had undergone mammographic-localized breast biopsies. One hundred forty-nine women with LCIS were identified. Eighty four were excluded from analysis because of synchronous invasive cancer or ductal carcinoma in situ (DCIS). The remaining 65 women formed the basis of this report. RESULTS: Sixty-five women with LCIS were treated from 1963 through 1990. Median follow-up was 83 months. No women were lost to follow-up. Median age at diagnosis was 48 years (range 37-81), and 32% had a family history of breast cancer. Clinical findings leading to biopsy were breast mass in 43, nipple discharge in three, and mammographic abnormality in 19. Mammographic-pathologic correlation showed that the focus of LCIS in these 19 women was not associated with the mammographic abnormality. Fourteen of 65 women underwent mastectomy after diagnosis of LCIS (nine ipsilateral, five bilateral). Fifty-one of 65 women elected observation alone. In the observation group, 13 of 51 women (25%) underwent a second breast biopsy for a clinical or mammographic abnormality during the follow-up period. The median interval to biopsy was 50 months. Pathology was benign in two, LCIS in seven, DCIS in one, and invasive cancer in three. All seven women with LCIS on subsequent biopsy continued with observation and none developed breast cancer. All four cancers were detected by mammography without an associated palpable mass. Three of four cancer masses were < 1 cm in diameter. The woman with DCIS was 47 years of age and developed DCIS 106 months after LCIS diagnosis. She was treated by total mastectomy and is disease free 108 months later. The three women with invasive cancer developed this at 41, 53, and 69 months after diagnosis of LCIS. All were < 50 years of age. All three cancers were in the same breast as the previous LCIS. Two women were treated by modified radical mastectomy, and the third had wide excision/axillary dissection followed by radiation therapy. They are alive and disease-free at 16, 82, and 116 months. CONCLUSIONS: Four of 51 women treated with observation alone after diagnosis of LCIS developed breast cancer. All were detected by screening at an early stage. LCIS appeared to be an incidental finding on biopsy of mammographic abnormalities. The policy of observation alone for the finding of LCIS spares women mastectomy. Furthermore, cancers that develop in follow-up are likely to be detected at an early stage and be amenable to curative therapy. Observation alone is appropriate treatment for women with LCIS.

Adult↗
PubMed1994

Maximal spatial ST-vector patterns in patients with acute anteroseptal myocardial infarction.

Seventy patients with acute myocardial infarction were studied by serial vectorcardiography. Eleven out of 70 patients had acute myocardial infarction, which consistently met the vectorcardiographic QRS-loop criteria of anteroseptal myocardial infarction within the 21 days follow-up period. From the first vectorcardiographic tracings three types of the maximal spatial ST-vector were seen. Their directions belonged to one of the following octants: (1) right-anterior-superior, (2) left-anterior-superior, or (3) left-anterior-inferior. The directions were the same as the types of initial activity of the normal depolarization process of the interventricular septum revealed by the intracardiac mapping in dogs. The subsequent vectorcardiograms showed no change in direction of the maximal spatial ST-vector in all patients except one. This study suggested that there are three types of the maximal spatial ST-vector concealed in patients with first acute anteroseptal myocardial infarction. Each type of the maximal spatial ST-vectors is capable of causing S-T segment elevation from leads V1 to V3 in the acute electrocardiogram. Why the subgroup of the right-anterior-superior maximal spatial ST-vector in patients with acute anteroseptal myocardial infarction had poor outcomes during the acute stage needs further investigation.

Aged↗
PubMed1994

Biochemical features in patients with their first acute inferior myocardial infarction.

Sixty eight patients with their first acute inferior myocardial infarction were studied within 24 h of the onset of chest pain by vectorcardiography and biochemical indicators. Patients were divided into three groups according to the vectorcardiographic findings: Group 1 (31 patients with inferior myocardial infarction); Group 2 (26 patients with inferior myocardial infarction and right ventricular involvement); and Group 3 (11 patients with inferior-posterior infarction). Biochemical studies showed that the tendency for the magnitude of enzyme release varied with the site inferior-posterior > inferior+right ventricular > inferior groups. However, the differences between inferior and inferior plus right-ventricular groups were not significant. This suggests that the left ventricle dominates enzyme release regardless, with or without right ventricular involvement in patients with acute inferior myocardial infarction. When the enzyme levels in inferior and inferior-posterior myocardial infarction are compared, the HBDH and CK-MB were significantly higher (2P < 0.02 and 2P < 0.05 respectively). This confirms that when the vectorcardiographic QRS loop changes are large, more enzyme is released during acute myocardial infarction.

Acute Disease↗
PubMed1994

Homocysteine: relationship to serum cobalamin, serum folate, erythrocyte folate, and lobation of neutrophils.

Serum levels of total homocysteine were studied in the following: 26 healthy adults; 79 hospitalised patients in whom serum cobalamin, serum folate, and erythrocyte folate were greater than 230 pmol/L, 12 nmol/L, and 600 nmol/L, respectively; 32 hospitalised patients whose serum cobalamin was less than 147 pmol/L, compared to 25 patients whose serum cobalamin was greater than 147 pmol/L but unmatched in any other parameter; and 194 patients in whom samples were sent for determination of cobalamin and folate from a neurological service. None of this last group had megaloblastic anaemia. There was a relationship between the elevated concentrations of total homocysteine in serum and low concentrations of serum cobalamin and of erythrocyte folate. This relationship was most evident in samples with serum cobalamin < 86 pmol/L and erythrocyte folate < 335 nmol/L, although elevated homocysteine levels were found in some samples where serum cobalamin and erythrocyte folate levels were greater than these. Serum folate correlated poorly with serum total homocysteine. There was only a poor-to-fair correlation of neutrophil lobe counts to total serum homocysteine.

Adult↗
PubMed1993

Synthesis and characterization of a bioactive 82-residue sphingolipid activator protein, saposin C.

The sphingolipid activator protein, saposin C (also termed SAP 2), was chemically synthesized, purified, and characterized. The fully protected 82-residue protein was synthesized by automated solid-phase methods, with multiple recoupling steps resulting in a high average coupling efficiency of 98.8%. The overall yield was estimated to be approx 40%. Deprotection and cleavage of the peptide from the resin was followed by folding in the absence of chaotropic agents at pH 8.5. The protein was purified by reversed-phase high pressure liquid chromatography (HPLC) and its purity determined by capillary electrophoresis and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The composition of the synthetic saposin C was determined by amino acid analysis. Its sequence was verified by Edman sequence analysis of overlapping peptide fragments generated by chymotryptic and Staphylococcus aureus V8 digestions. The sequence at the C-terminus was determined by digestion with carboxypeptidase P, followed by phenylthiohydantoin (PTH) derivitization and HPLC analysis of the released amino acid residues. Deglycosylated native saposin C appeared as a lower molecular-weight species than synthetic saposin C on SDS-PAGE. This has been explained by amino acid and C-terminal analysis showing native saposin C to be two amino acids shorter at the C terminus than a deduced sequence (from cDNA) previously published. Synthetic saposin C displayed 85% of full biological activity as determined by its ability to stimulate glucocerebrosidase activity in vitro: Synthetic and native saposin C increased glucocerebrosidase catalyzed hydrolysis of 4-methylumbelliferyl beta-D-glucoside by factors of 6.0 and 7.1, respectively. Furthermore, synthetic and native saposin C share similar K(act) values (0.5 and 1.5 microM respectively) indicating that they bind to glucocerebrosidase with similar affinities.

Amino Acid Sequence↗