Tissue distribution and macromolecular interactions of 14[C-ring] melphalan in the rat

Summary The kinetics of uptake and elimination, covalent binding, and macromolecular interactions of ¹⁴[C-ring] melphalan was studied after a single oral dose (20 mg/kg, 0.1 mCi/kg) in normal rats. Peak radioactivity level in tissues was observed at 2–4 h after administration. Uptake of label in most tissues was rapid, with a t_1/2 of less than 1 h. Elimination was biphasic. Tissues of the gastrointestinal tract showed the most rapid rates of elimination, with t_1/2 of 13, 24, 18, and 19 h for stomach, duodenum, and small and large intestines, respectively. Bone marrow also showed a fast rate of elimination of radioactivity, with a t_1/2 of 30 h. Tissues with the slowest rates of elimination were skin, eye, spleen, pancreas, and lung, with t_1/2 of 333, 241, 149, 122, and 109 h, respectively. Covalent binding studies showed that melphalan, or its metabolites, bound irreversibly to all tissue macromolecular fractions. The percentage of covalently bound radioactivity increased with time in all tissues except kidney and eye, reaching up to 70%–80% of the total radioactivity remaining at 72 h. Elimination of covalently bound radioactivity was slower in the DNA fractions of the tissues of the gastrointestinal tract and heart compared with the elimination rate from lipid, protein, or RNA fractions. Slow elimination rates of ¹⁴[C-ring] melphalan equivalents from the protein fraction were observed in the skin, eye, and brain. Accumulation, rather than elimination, of radioactivity in this fraction was most prominent in the pancreas. In the bone marrow accumulation of radioactivity was observed in the lipid fraction.Abbreviations used in this paper are L-Pam Melphalan, l-phenylalanine mustard 4-bis (2-chloroethyl) amino-1-phenylalanine - l-DOH 4-bis (2-hydroxyethyl) amino-1-phenylalanine - l-MOH 4-2 hydroxyethyl 2 chloroethyl amino-1-phenylalanine - HPLC high-pressure liquid chromatography - TCA trichloroacetic acid - AUC area under the curve - GIT gastrointestinal tract     

Diffuse leiomyomatosis of the esophagus

BACKGROUND: Leiomyomas are rare esophagus neoplasms. They are usually solitary, and the diffuse lesion is extremely rare. CASE REPORT: A 19-year-old male presented with a 3-year history of occasional dysphagia and postprandial regurgitation. The chest radiographs showed a huge mass in the posterior mediastinum. Barium esophagograms showed narrowing of the middle third esophagus with proximal dilatation. The fibroesophagoscopy demonstrated multiple submucosal nodules below a level 22 cm from the incisor and covered with intact mucosa. CT scans of the chest showed a long segment of circumferential soft tissue in the posterior mediastinum which encircled and involved the upper two thirds of the esophagus. An intrathoracic esophagectomy with cervical esophagogastrostomy via the substernal route was performed. Grossly, multiple confluent myomatous nodules circumferentially involved the upper and middle third of the esophagus. Histologic findings showed diffuse leiomyomatosis of the esophagus. CONCLUSION: Esophageal leiomyomatosis should be considered in a young patient with long-standing dysphagia in whom smooth, tapered esophageal narrowing on barium study and circumferential esophageal wall thickening on CT scan are seen. An esophagectomy combined with a reconstruction procedure is indicated.     

Objective assessment of auditory thresholds in noise‐induced hearing loss using steady‐state evoked potentials

Objective assessment of auditory thresholds in noise‐induced hearing loss using steady‐state evoked potentials The purpose of this study is to evaluate whether steady‐state evoked potential (SSEP) can be used for objective estimation of auditory thresholds in patients with noise‐induced hearing loss (NIHL). Eleven subjects (22 ears) with a characteristic audiometric notch between 3000 and 6000 Hz participated in this study. Both pure‐tone thresholds and SSEP thresholds were obtained for each ear of all subjects. The correlation of SSEP thresholds and pure‐tone thresholds was assessed. The results show that SSEP thresholds predicted pure‐tone thresholds with correlation coefficients (r) of 0.86, 0.92, 0.94 and 0.95 at 500, 1000, 2000 and 4000 Hz respectively. Typically, the SSEP thresholds overestimate the pure‐tone thresholds by 10–20 dB, but they closely reflect the configuration of the audiogram. The strength of the relationship between SSEP and pure‐tone thresholds increased with increasing frequency and increasing degree of hearing loss. In conclusion, SSEP can be used as a reliable and objective tool to assess auditory thresholds in patients with noise‐induced hearing loss with high‐frequency dips.     

Technetium-99m tetrofosmin SPECT predicts chemotherapy response in small cell lung cancer.

The multidrug resistance gene 1 encoding human P-glycoprotein (Pgp) is thought to play an important role in the multidrug resistance of lung cancer. The purpose of this study was to predict chemotherapy response by technetium-99m tetrofosmin (Tc-99m TF) lung single photon emission computed tomography (SPECT) and compare Pgp expression in patients with untreated small cell lung cancer (SCLC). Forty patients with untreated SCLC received Tc-99m TF lung SPECT prior to chemotherapy. The chemotherapy response was evaluated in the 3rd month after completion of treatment. Immunohistochemical staining of Pgp expression was performed on multiple nonconsecutive sections of biopsy specimens. By quantitative analyses, tumor to background ratios were 1.86 +/- 0.27 and 1.17 +/- 0.26 for patients with a good and poor response, respectively (p < 0.05). All of the 20 patients with a good chemotherapy response also had a positive Tc-99m TF lung SPECT and negative Pgp expression. In contrast, only 4 of the 20 patients with a poor chemotherapy response had a positive Tc-99m TF lung SPECT. Moreover, 10 of the 20 patients with a poor chemotherapy response also had negative Pgp expression (p < 0.05). Therefore, we concluded that Tc-99m TF lung SPECT can accurately predict the chemotherapy response, and Tc-99m TF lung SPECT findings can be partially compatible with Pgp expression in patients with untreated SCLC.     

Dietitian intervention improves lipid values and saves medication costs in men with combined hyperlipidemia and a history of niacin noncompliance

We asked if medical nutrition therapy (MNT) administered by registered dietitians could lead to beneficial clinical and financial outcomes in men with combined hyperlipidemia (hypercholesterolemia and hypertriglyceridemia). A retrospective chart review was conducted on 73 men with combined hyperlipidemia who were being considered for statin therapy because of a previous history of noncompliance with niacin therapy. Subjects participated in an 8-week dietitian intervention program as a qualifying requirement, before statin therapy. Patient records were reviewed to determine the beginning and ending serum lipid concentrations and the number and length of dietitian sessions. Complete information was available on 43 subjects, aged 60.7 +/- 10.1 years (mean +/- standard deviation). Total dietitian intervention time was 169 +/- 19 minutes in 2.7 +/- 0.6 sessions (range = 2 to 4 sessions) during 6.5 +/- 2.2 weeks of MNT (range = 4 to 8 weeks). MNT lowered levels of total cholesterol 11% (P < .001), low-density lipoprotein cholesterol 9% (P < .001), and triglycerides 22% (P < .0001) and body mass index 2% (P < .0001); MNT raised high-density lipoprotein cholesterol levels 4%. After dietitian intervention, only 15 of 30 eligible patients required antihyperlipidemic medications, which led to an annual cost savings of $27,449.10 or $638.35 per patient. A cost saving of $3.03 in statin therapy was realized for each dollar spent on MNT. We conclude that an average of 3 individualized dietitian visits of 1 hour each over an 8-week period has a beneficial effect in treating patients with combined hyperlipidemia and recommend consideration of MNT as a cost-effective intervention.