Studies on pyridonecarboxylic acids. 1. Synthesis and antibacterial evaluation of 7-substituted-6-halo-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3- carboxylic acids.

A series of [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids and their esters were prepared and evaluated for antibacterial activity. The derivatives with a hydrogen or methyl group at C-1, fluorine at C-6, and piperazinyl or 4-methyl-1-piperazinyl group at C-7 showed superior in vitro antibacterial activity, and the derivatives with 4-methyl-1-piperazinyl group at C-7 had potent in vivo activity. Compound 29a (NM394) showed excellent in vitro antibacterial activity and low toxicity but poor absorption from the gastrointestinal tract. Compound 29ee (NM441), an N-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl] derivative of 29a, was found to possess a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in experimental animals.     

Lymphoscintigraphy as a predictor of lymphatic drainage from cutaneous melanoma

Background: If cutaneous lymphoscintigraphy (CL) is accurate in predicting the draining lymph node basins at risk from primary axial melanomas, then regional metastases should only occur in those lymph node basins identified by CL. Methods: This study is a retrospective review of patients undergoing CL for primary axial melanomas from June 1, 1985, until June 31, 1992. Data retrieved included age, gender, number of basins identified, location of basins identified, management of basins, recurrence in lymphatics, development of distant disease, and long-term follow-up. Results: A total of 181 patients underwent elective LND, and 48 patients (27%) had melanoma in the nodes within the dissected basin. Of these 181 patients, seven developed nodal metastases as their site of first recurrence. All seven recurrences were seen at sites dissected or at sites indicated by CL, which the primary surgeon elected not to treat initially. Of the 116 patients observed, 16 (14%) developed lymph node metastases as their first site of recurrence. Fifteen of these 16 patients had their site of lymph node metastases predicted by CL. In this study, CL predicted 98.6% of all lymph node metastases. Conclusions: The high overall reliability of CL as demonstrated by long-term follow-up indicates that the information obtained by CL can be reliably used to guide intervention. Initial evaluation of patients with high-risk cutaneous melanomas at sites with ambiguous lymphatic drainage must include CL in order to determine the draining lymph node basins and to plan therapy. Presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

Specific [125I]brain natriuretic peptide-26 binding sites in rat and pig kidneys

Specific binding sites for porcine brain natriuretic peptide-26 (BNP-26), a member of the atrial natriuretic peptide family (ANPs), were investigated in the kidney by using receptor autoradiographic and membrane binding techniques with [125I]BNP-26. The binding sites were discretely localized in rat and porcine kidney areas corresponding anatomically to the glomeruli and inner medulla. There were no differences between the localization of [125I]BNP-26 and [125I]alpha-rat ANP binding sites in the kidney. [125I]BNP-26 binding to solubilized membranes from isolated glomeruli of the rat kidney was saturable, and a single class of high-affinity sites was labeled with a KD of 372 pM. The radioligand bound to two sites in solubilized inner medullary membranes of the rat, a low-affinity site with a KD of 30 nM, and a high-affinity site with a KD of 33 pM. The rank order of potency to inhibit binding was BNP-26 = alpha-rat ANP-(1-28) greater than atriopeptin III (ANP-(103-126)) much greater than atriopeptin I (ANP-(103-123)) greater than des-Cys105,Cys121- ANP-(104-126). Thus, [125I]BNP-26 presumably recognizes ANP receptors in the kidney. The possibility that BNP-26 regulates, as a circulating hormone, kidney functions by binding to ANP receptors would have to be considered.     

The impact of left ventricular dysfunction on cardiac donor transplant rates.

BACKGROUND: Because of the shortage of heart donors in the United States, efforts are necessary to maximize the yield of donor screening. The purpose of this study was to quantify the effects of left ventricular (LV) systolic dysfunction on heart donor use. METHODS: Using the California Transplant Donor Network database, the records of all potential organ donors screened between January 1997 and June 1998 were reviewed. After excluding subjects for whom family consent could not be obtained and subjects <13 or >or=60 years old, a study group of 223 potential heart donors was analyzed. The number of hearts not used because of LV dysfunction, coronary artery disease (CAD), valvular disease, and LV hypertrophy were quantified. A logistic regression model was developed to quantify the independent effect of LV dysfunction on donor use rates after adjustment for age, weight, and cause of death. RESULTS: Ninety-nine (44%) of the 223 potential donor hearts were not transplanted. Thirty-six of these hearts were not transplanted because of cardiac causes, primarily LV dysfunction (26 cases) and CAD (8 cases). The multivariable analysis showed that after adjusting for other donor variables, ejection fraction was the most significant predictor of non-use, with an odds ratio of 1.48 per 5-point decrease in ejection fraction. CONCLUSIONS: Left ventricular dysfunction is an important cause of failure to transplant adult donor hearts. Efforts to improve the yield of heart donor screening should focus on prevention or reversal of LV dysfunction.     

A protocol for the urine dipstick/pad method.

The urinary tract accounts for nearly one third of all infections in the long-term care setting. This article reviews factors that influence nitrite and leukocyte esterase results obtained from traditional urine dipstick analysis for assessment of urinary tract infections in elderly long-term care residents. This article also proposes a protocol for a urine dipstick pressed into an incontinence pad as an alternative to dipstick analysis of a clean-catch or catheterized urine specimen.