Recent advances in cancer therapy

The treatment of cancer has developed substantially from its conception in the first years of the 20th century. Since the introduction of alkylating agents during second World War, the oncology specialty has markedly grown. In the recent years, new drugs have been approved for the treatment of cancer. Such examples include the taxanes (Docetaxel and Paclitaxel), Vinorelbine, Irinotecan, Topotecan, Gemcitabine and Gliadel. We will discuss these new chemotherapuetic agents, their pharmacology, indications, toxicity and appropriate dosing. There is no doubt that further clinical research is needed to determine the optimal use of these agents.     

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Systemic methotrexate toxicity. A pharmacological study of its occurrence after intrathecal administration in a patient with renal failure

Methotrexate pharmacokinetic studies, performed on a patient with renal impairment who had toxic effects following 20 mg/sq m of intrathecally administered methotrexate, demonstrated prolonged serum concentrations of the drug, which accounted for the condition. After the return of normal renal function, pharmacokinetic studies were repeated following the same dose and route of administration of methotrexate. On this occasion there was a rapid clearance of serum methotrexate below toxic levels.     

Bone marrow transplantation for severe aplastic anemia: has outcome improved?

Bone marrow transplants for severe aplastic anemia were first performed in the 1970s. Transplant regimens, supportive care, and patient selection have changed substantially since then. Our objective was to determine the impact of these changes on transplant outcome. We studied 1,305 recipients of HLA-identical sibling transplants for aplastic anemia between 1976 and 1992, reported to the IBMTR by 179 centers. We compared survival of transplants performed in three intervals (1976 through 1980 [n = 186], 1981 through 1987 [n = 648], and 1988 through 1992 [n = 471]) using Cox proportional hazards regression. Five-year survival (+/-95% confidence interval) increased from 48% +/- 7% in the 1976-1980 cohort to 66% +/- 6% in the 1988-1992 cohort (P < .0001). Risks of graft-versus-host disease (GVHD) and interstitial pneumonia decreased over time, but the risk of graft failure did not. Higher long-term survival resulted primarily from decreased mortality in the first 3 months posttransplantation. Late mortality risks were low and changed little over the intervals studied. In multivariate analysis, changes in transplantation strategies accounted for most but not all of the improved outcome. Use of cyclosporine to prevent GVHD was the most important factor. Changes in patient selection did not seem to explain improved survival. Survival after HLA-identical sibling bone marrow transplantations for aplastic anemia has improved since 1976. Changes in GVHD prophylaxis account for much of this improvement. Other changes may also operate.     

Mesh inguinal herniorrhaphy: a ten-year review

Inguinal herniorrhaphy remains one of the most common surgical operations, with approximately 10 to 20 per cent performed for recurrence. Reviews by specialized hernia centers show mesh repair has a recurrence rate of 0.2 per cent. Detractors of this repair include increased cost, technical difficulty, and risk for infection. The purpose of this study was to compare mesh versus nonmesh inguinal herniorrhaphy at a large teaching institution. From 1985 to 1994, 892 patients underwent primary repair for inguinal hernia at the Veterans Administration Hospital at Memphis, TN. Patients were stratified by repair [Lichtenstein (Mesh), open anterior (Bassini, Marcy, McVay, and Shouldice), laparoscopic (Lap), and preperitoneal (Post)]. Operative time for Mesh repair (111 +/- 2 minutes) was longer than for Bassini or McVay (91 +/- 2 and 98 +/- 2 minutes; P < 0.05), and Lap repairs were longer than all others (192 +/- 16 minutes; P < 0.05). Hospital stay averaged 2.2 +/- 0.1 days for Mesh versus 2.6 +/- 0.1 days for all repairs combined (P = not significant). Mesh patients developed four wound infections (1.0%), none requiring mesh removal, versus nine infections (1.8%) in other groups (P = not significant). One Mesh patient (0.3%) developed recurrence, compared with 16 (3.5%) with open anterior repair (P < 0.01). Inguinal herniorrhaphy using an open mesh repair technique provides superior recurrence rates without increasing risk for infection, length of stay, or technical difficulty.     

Systemic arterial blood pressure and urine protein/creatinine ratio in dogs with hyperadrenocorticism

OBJECTIVE: To determine prevalence and severity of systemic arterial hypertension and proteinuria in dogs with naturally developing hyperadrenocorticism and to determine whether these abnormalities resolve with adequate management of the disease. DESIGN: Case series and cohort study. ANIMALS: 77 dogs with naturally developing hyper-adrenocorticism examined once; 15 dogs examined before and after treatment. RESULTS: Among dogs examined only once, hypertension was diagnosed in 21 of 26 dogs with untreated pituitary-dependent hyperadrenocorticism (PDH), 17 of 21 with inadequately controlled PDH, 8 of 16 with well-controlled PDH, 10 of 10 with an untreated adrenocortical tumor, and 0 of 4 that had undergone adrenalectomy because of an adrenocortical tumor. Untreated dogs and dogs with inadequately controlled PDH had significantly higher blood pressures than did other dogs. Proteinuria was documented in 12 of 26 dogs with untreated PDH, 5 of 16 with inadequately controlled PDH, 3 of 14 with well-controlled PDH, 5 of 8 with an untreated adrenocortical tumor, and 1 of 3 that had undergone adrenalectomy. Dogs with untreated PDH and dogs with an untreated adrenocortical tumor had higher urine protein/creatinine ratios than did dogs with well-controlled PDH. Among dogs evaluated before and after treatment, blood pressure and urine protein/creatinine ratio did not change in 8 dogs with inadequately controlled hyperadrenocorticism, but decreased in 7 dogs with well-controlled disease. CLINICAL IMPLICATIONS: Results suggest that systemic hypertension and proteinuria are common in dogs with untreated hyperadrenocorticism and that successful treatment of hyperadrenocorticism will result in resolution of these abnormalities in many, but not all, dogs.