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L Nathanson

Publications and source records attributed to L Nathanson.

At least 19 recordsLinked to original sources
PubMed1995

Laparoscopic exploration of the common bile duct: lessons learned from 129 consecutive cases.

Since the introduction of laparoscopic cholecystectomy there has been widespread debate about the best way to manage common bile duct (CBD) calculi. Between August 1991 and July 1994, 129 patients underwent laparoscopic exploration of the CBD. Fifteen patients of median age 52 years were managed by glucagon-induced relaxation of the sphincter of Oddi and saline flushing of the bile duct through a cholangiogram catheter. This had a success rate of 73 per cent and took a median of 90 min including cholecystectomy. The technique has now been replaced by Dormia basket exploration of the CBD. Transcystic common duct exploration using a Dormia basket was used in 79 patients of median age 47 years. Duct clearance was achieved in 96 per cent of cases with a median operating time of 55 min. Thirty-five patients of median age 52 years were managed by choledochotomy and T tube placement, with a 91 per cent duct clearance rate and a median operating time of 120 min. Overall duct clearance was achieved in 92 per cent of patients with an operative morbidity rate of 5.4 per cent. Duct clearance using either a Dormia basket or choledochotomy and T tube placement was obtained in 95 per cent of patients. Laparoscopic exploration of the CBD is an important alternative in the management of common duct calculi.

Adult↗
PubMed1995

Inhibition of the melanoma cell cycle and regulation at the G1/S transition by 12-O-tetradecanoylphorbol-13-acetate (TPA) by modulation of CDK2 activity.

The growth of malignant melanoma cells is inhibited by 12-O-tetradecanoylphorbol-13-acetate (TPA) while the growth of normal melanocytes is stimulated. We previously demonstrated that TPA inhibits the growth of Demel melanoma cells and leads to arrest at both at the G1/S and G2/M cell cycle transitions. To investigate the mechanism by which TPA arrests melanoma cell growth at the G1/S transition we have examined its effects on the levels of cyclins and cyclin dependent kinases (CDKs) and activation of CDK2 kinase activity. Addition of TPA in G1 blocked the increase in the level of p34cdc2 mRNA, but not of CDK2 mRNA. When TPA was added in G1, it inhibited the mobility shift of CDK2 reflecting a change in phosphorylation state. This corresponded to inhibition of the increase in CDK2 histone H1 kinase activity. There was little effect on the level of CDK4. Treatment with TPA during G1 caused a three to four fold increase in cyclin D1 mRNA expression, but blocked the increase in the expression of cyclin A and cyclin B mRNAs later in the cell cycle. TPA caused a small increase in levels of cyclin D1 and had little effect on cyclin E, suggesting these G1 cyclins were not limiting. Addition of TPA in G1 prevented an increase in cyclin A levels, suggesting cyclin A might play an important role in mediating the growth inhibition. Examination of the levels of the CDK inhibitors p21Cip1 and p27Kip1 showed that the level of these inhibitors was higher in G1 and dropped as cells entered S phase. In the presence of TPA this decrease did not occur. These results demonstrate that TPA blocks the G1/S transition in Demel melanoma cells in late G1 by mechanisms which regulate phosphorylation and activation of the CDK2 kinase. These mechanisms include preventing the decrease in p21Cip1 and p27Kip1 kinase inhibitors and limiting the amount of cyclin A.

CDC2 Protein Kinase↗
PubMed1995

Laparoscopic splenectomy and lymph node biopsy for hematologic disorders.

OBJECTIVE: The authors audit the introduction of laparoscopic splenectomy and laparoscopic intra-abdominal lymph node biopsy and compare outcomes with a parallel cohort of patients undergoing open splenectomy. SUMMARY BACKGROUND DATA: Laparoscopic splenectomy was first reported in 1992. It was introduced into clinical practice at the Royal Brisbane Hospital in 1991. Between June 1991 and March 1994, 24 patients have undergone laparoscopic splenectomies and 23 patients have had laparoscopic intra-abdominal lymph node biopsies. METHODS: Laparoscopic splenectomy was performed using a four- or five-port technique. The splenic hilum was secured using a linear stapler cutter, and the spleen was removed after placing it in a laparoscopic bag. Lymph node biopsy was performed using a three- or four-port technique, depending on the site and size of the lymphadenopathy. RESULTS: Laparoscopic splenectomy was completed in 22 patients (92%). Median hospital stay was 3 days (range 2-7 days) and morbidity occurred in two patients (8%). Lymph node biopsy was completed laparoscopically in 21 of 23 patients (91%), with morbidity in two cases (9%). Median hospital stay was 2 days (range 1-6 days), with a diagnostic accuracy of 90%. Comparison with open splenectomy revealed that the laparoscopic approach took significantly longer to perform (p = 0.0002), but resulted in a significantly shorter hospital stay (p = 0.0005). CONCLUSIONS: Both laparoscopic splenectomy and laparoscopic lymph node biopsy currently are used as the treatments of choice for hematologic disease in our institution.

Adolescent↗
PubMed1995

Laparoscopic biliary and gastric bypass: a useful adjunct in the treatment of carcinoma of the pancreas.

Over 90% of patients with inoperable carcinoma of the pancreas are successfully palliated by endoscopic retrograde cholangiopancreatography and stent insertion. Treatment of the residual 10% of patients often entails a laparotomy, which is difficult to justify when median survival of these patients is only 150 days. Laparoscopic biliary and gastric bypass offers a less invasive alternative than open surgery with shorter hospital stay and more rapid return to normal activity. Between August 1991 and March 1994, 16 patients (median age 69 years, range 31-85) had laparoscopic bypass surgery. The indications for surgery were gastric outlet obstruction at initial presentation (n = 4), blocked biliary stent (n = 8), and metastatic tumour at laparoscopy (n = 4). Surgery took the form of cholecystjejunostomy (n = 7), gastroenterostomy (n = 5), both procedures (n = 3), and failed operation (n = 1). Operative duration was 75 minutes (range 45-190) and hospital stay four days (range 3-33) and all apart from two patients were discharged from hospital in seven days or less. Morbidity occurred in two patients (13%) in the form of a cerebrovascular accident and delayed gastric emptying. Median survival in 10 patients who have died is 201 days (range 20-525). Laparoscopic biliary and gastric bypass is possible in most patients in whom endoscopic stenting has failed and in those who subsequently develop gastric outlet obstruction. Hospital stay is shorter than after open surgery and recovery more rapid.

Adult↗
PubMed1992

12-O-tetradecanoylphorbol-13-acetate induces transient cell cycle arrest in G1 and G2 in metastatic melanoma cells: inhibition of phosphorylation of p34cdc2.

The growth of Demel human metastatic melanoma cells was inhibited by 12-O-tetradecanoylphorbol-13-acetate (TPA) and other nonphorbol tumor promoters including palytoxin and okadaic acid. Using flow cytometry, we have demonstrated that the cells arrested growth in G1 and G2 phases of the cell cycle. Detailed analysis of the kinetics of the growth arrest in unsynchronized cells showed that (a) the growth arrest was transient and peaked 16-20 h following addition of TPA; (b) effects of TPA on cell growth began within 1-2 h after the addition; and (c) cells completed S phase and arrested in G2. In addition, TPA induced a pronounced morphological change, which peaked by 1 h and gradually subsided over 24 h. In populations of cells synchronized in G1 using lovastatin, (a) addition of TPA blocked the onset of DNA synthesis up to the end of G1; (b) the lag between addition of the drug and onset of DNA synthesis was less than 30 min; and (c) addition of TPA at the end of G1 prevented the increased phosphorylation of p34cdc2, as determined by immunoprecipitation. The experiments reported here show that TPA transiently blocked the proliferation of Demel melanoma cells at the G1-S border and in G2, thus preventing cells from progressing through the cell cycle. These experiments suggest that pathways involving protein kinase C interact with and rapidly alter the molecular pathways involving p34cdc2 which regulate the onset of DNA synthesis and the G2-M transition.

Breast Neoplasms↗
PubMed1987

Carcinoma of the anal canal.

During the period 1973 to 1982, 35 patients with carcinoma of the anal canal were seen at this hospital. The main form of treatment was abdominoperineal excision, unless specific contraindications to this procedure were present. Between 1982 and 1984, a further 18 such patients were seen; the primary method of treatment then was combination chemotherapy and radiotherapy. Abdominoperineal excision was reserved for those patients who failed to respond to therapy or whose carcinoma recurred during the period of follow-up. The over-all five-year survival rate for the first 35 patients was 50%; the actuarial disease-free survival at two years for those who went into complete remission was 78% in the 18 patients who were seen in the second part of the study. We conclude that conservative treatment by chemoradiation is of value in the management of anal carcinomas.

Adult↗
PubMed1987

Bilateral adult Wilms' tumor.

Bilateral Wilms' tumors in children are not uncommon but in the adult are quite rare. A two-mutation theory of oncogenesis has been proposed in which a prezygotic gene mutation and a postzygotic mutation lead to the development of Wilms' tumor. However, the recent discovery of a postzygotic deletion within the 11p13 band of chromosome 11 in adult cases of Wilms' tumor may explain the rarity of the bilateral form in later years. Early diagnosis is difficult because of the nonspecificity of signs and symptoms. Computer tomography, ultrasonography, and arteriography are important modalities in the earlier diagnosis of adult Wilms' tumor. Because of the rarity of these tumors, no definitive guidelines for treatment have emerged. However, a multidisciplinary approach incorporating surgery, chemotherapy and/or radiation therapy has been used most often but with varying success. This report documents the second case of bilateral adult Wilms' tumor presenting as perinephric hematomas which partially resolved.

Female↗
PubMed1987

A first-year medical school pilot program for early clinical exposure.

A weekly out-patient elective in a medical oncology clinic was established for first- and some second-year medical students. Interviews were carried out immediately after the elective experience and two years later to evaluate the degree of success in achieving specific goals in this elective. Such clinical experience appeared to introduce the medical students to some of the major medical and psychosocial issues involved in the clinical care of patients, to be highly motivating for the students with regard to their standard concurrent basic science curriculum, and to relieve the impatience that first-year medical students have for clinical exposure. The usefulness of the elective, as perceived by the participating students, appeared to increase from the first to the second interview, that is as the students entered the clinical teaching program. The clinical setting was perceived by the students as more useful than either their increased understanding of medicine or observation of physicians as role models. The students' perception and understanding of physician-patient communication, and of the problems facing an oncology patient, appeared to be more favorably influenced than increasing confidence in the ability of the student to deal with patient interaction. Thus, a clinical oncology out-patient experience for first-year medical students appears to be sufficiently rewarding to justify the time and effort to develop such an elective.

Clinical Medicine↗
PubMed1985

In vivo and in vitro inhibition of B16 melanoma growth by vitamin B6.

The effect of vitamin B6 on the growth of B16 melanoma cells in vivo and in vitro was studied. B16 melanoma cells grown for three days in medium supplemented with 5.0 mM pyridoxine or 0.5 mM pyridoxal showed an 80% reduction in cell proliferation compared with control culture. Cells cultured for six hours in medium supplemented with 0.5 mM pyridoxal took up and incorporated 13 and 32% less [3H]thymidine, respectively, than did control cultures. A 17% reduction in [3H]glucose uptake was observed at this time point. When the incubation time was decreased to three hours, an inhibition of cellular uptake of [3H]thymidine (22%), [3H]uridine (14%), and [3H]glucose (15%) was observed; however, little or no inhibition in incorporation was detected. In in vivo studies, mice pretreated with pyridoxal for two weeks and then injected with B16 melanoma cells had a 62% reduction in tumor weight compared with controls at the end of a three-week period. If tumors were first established in mice and then treated with pyridoxal for six days, a 39% reduction in tumor growth was observed. There were no differences observed in body weights or liver weights in any of the animal groups. These results indicate that supraphysiological doses of vitamin B6 can inhibit the growth of B16 melanoma cells both in vitro and in vivo. The exact mechanism by which pyridoxal exerts its inhibitory effect was not ascertained, but experiments suggest that the vitamer may be acting on the plasma membrane to reduce precursor transport into the cell.

Adenosine Triphosphate↗
PubMed1985

Thrombotic thrombocytopenic purpura.

This serious disorder of young adults is characterized by fever, hemolytic anemia, hemorrhagic signs, various neurologic abnormalities and renal dysfunction. Laboratory findings include a negative Coombs' test for hemolytic anemia, severe thrombocytopenia, and fragmented erythrocytes on the peripheral blood smear. Without treatment, mortality may exceed 80 percent. Early diagnosis and prompt therapy with high-dose corticosteroids and antiplatelet agents, as well as exchange plasmapheresis when indicated, bring about remission in 60 to 80 percent of patients.

Adrenal Cortex Hormones↗
PubMed1985

Suppression of DNA synthesis in NEL-M1 human melanoma cells by triamcinolone acetonide.

The present study characterizes the biological response of a cloned human melanotic melanoma cell line (NEL-M1) to glucocorticoid treatment. Scatchard analysis of the binding of [3H]-triamcinolone acetonide to the glucocorticoid receptor showed a binding capacity of 170 fmol/mg protein and a dissociation constant (KD) of 1.76 X 10(-9) M. When the 3H-labeled cytosol was warmed to 25 degrees C for 30 min and then incubated with DNA-cellulose at 4 degrees C for 45 min, 32% of the specific glucocorticoid-receptor complexes were bound to DNA-cellulose. Additional studies showed that when NEL-M1 cells were cultured for 72 h with 1 X 10(-7) M triamcinolone acetonide, a 36% reduction in cellular growth was observed compared to the control cultures. The calculated population doubling time for the control cells was 17.5 h compared to 20.3 h for the triamcinolone acetonide-treated cells. Analysis of the effect of triamcinolone acetonide on macromolecular synthesis revealed that, over a 24-h incubation period, triamcinolone acetonide (a) inhibited [3H]thymidine incorporation by 51%; (b) increased the incorporation of the melanin precursor, L-3,4-dihydroxy[3H]phenylalanine, by 59%; and (c) had essentially no effect on [3H]leucine or [3H]uridine incorporation. During this same incubation period, triamcinolone acetonide inhibited [3H]glucose uptake by 19%. Further studies using synchronized NEL-M1 cells clearly show that the earliest detectable action of triamcinolone acetonide was the inhibition [3H]thymidine incorporation during the S phase of the cell cycle. Thus, these findings show that the human melanoma cell line, NEL-M1, is biologically responsive to glucocorticoid treatment. Continued studies using NEL-M1 cells may eventually lead to ascertaining the exact mechanism by which glucocorticoids regulate DNA synthesis.

Cells, Cultured↗