Search PubMed⌕ Search

Biomedical subjects

D Chang

Publications and source records attributed to D Chang.

311 records · Page 18Linked to original sources
PubMedDate not supplied

Peritoneal carcinomatosis from an unknown primary site. Management of 15 patients.

AIMS AND BACKGROUND: Peritoneal carcinomatosis from an unknown primary site is a rare and ill-defined entity. This work attempts to identify clinical and pathological features of patients with this disease and report the results of an aggressive combined treatment modality. METHODS: Retrospective analysis was performed of medical records of 15 patients with peritoneal carcinomatosis with no primary site identified at a single institution between 1989 and 2000. A primary gastrointestinal cancer was ruled out after a thorough endoscopic and radiologic work-up and complete exploratory surgery. RESULTS: Four women and 11 men were identified; the average age was 49 years. All patients had cytoreductive surgery with peritonectomies; 4 patients underwent a second-look operation. Perioperative intraperitoneal chemotherapy was given to 10 of the 15 patients, and 9 patients received post-cytoreduction chemotherapy given intraperitoneally (1), systemically (7) or both intraperitoneally and systemically (1). Overall median survival from diagnosis was 19.0 months; 1 patient is alive with disease at 21 months; and 3 patients are disease-free at 17, 38, and 60 months from diagnosis. Significant positive predictive factors for survival were a small volume of ascites (P = 0.02), a large number of peritonectomies performed (P = 0.001), second-look cytoreduction (P = 0.003), perioperative intraperitoneal chemotherapy (P = 0.008) and postoperative chemotherapy (P= 0.01), either intraperitoneal or systemic. CONCLUSIONS: Peritoneal carcinomatosis from an unknown primary site is a rare subset of primary peritoneal malignancy. Aggressive treatment may provide prolonged palliation with occasional long-term survival.

Adult↗
PubMedDate not supplied

Pharmacokinetics of intraperitoneal gemcitabine in a rat model.

BACKGROUND: Gemcitabine (2'-2' difluorodeoxycytidine) has been shown to possess a broad spectrum of antitumor activity against various malignancies, particularly pancreatic carcinoma. For cancers occurring within the abdominal cavity, the advantage of intraperitoneal (i.p.) chemotherapy over intravenous (i.v.) chemotherapy is the high drug concentration that can be achieved locally. In addition, the cytotoxic effect of several anticancer agents can be enhanced by hyperthermia. Using a rat model, this study was designed to compare i.p. vs i.v. gemcitabine and to evaluate the effect of hyperthermia on i.p. gemcitabine. METHODS: In the first phase of this study, 18 Sprague Dawley rats were given a single dose of gemcitabine then randomized into three groups according to dose and route of delivery of chemotherapy (12.5 mg/kg--i.v., 12.5 mg/kg--i.p. or 125 mg/kg--i.p.). In a separate experiment (phase 2), 12 Sprague Dawley rats were given a continuous i.p. perfusion of gemcitabine (12.5 mg/kg in 150 mL total perfusate) and randomized into two groups according to the temperature of the peritoneal perfusate (normothermic or hyperthermic). During the course of both experiments, peritoneal fluid and blood were sampled using a standardized protocol. At the end of the procedure the rats were sacrificed and all urine was extracted. Selected tissue samples were taken from rats in the second phase of the study. The concentration of gemcitabine in all samples was determined by high performance liquid chromatography (HPLC). RESULTS: When gemcitabine was delivered at 12.5 mg/kg (phase 1) the area under the curve (AUC) was significantly higher with i.p. administration as compared to i.v. administration (P = 0.001). The AUC ratio (AUC peritoneal fluid/AUC plasma) was 12.5+/-3.2 for i.p. delivery as opposed to 0.2+/-0.2 for i.v. delivery (P = 0.0002). The AUC ratio for i.p. gemcitabine at 125 mg/kg was 26.8+/-5.8. Although there was no significant difference in drug concentrations between samples from the normothermic and hyperthermic groups, all tissue samples (except stomach) in the hyperthermic group exhibited increased gemcitabine concentrations. CONCLUSION: These experiments demonstrated that the exposure of peritoneal surfaces to gemcitabine is significantly increased with i.p. gemcitabine. Intraabdominal hyperthermia had no significant effect on the pharmacokinetics of i.p. gemcitabine but there was evidence of increased absorption of gemcitabine in most intraabdominal tissues. Due to the likelihood of a high incidence of microscopic residual disease after resection of a pancreatic carcinoma, clinical studies to evaluate i.p. hyperthermic gemcitabine may be indicated.

Animals↗
PubMedDate not supplied

Benign intracranial hypertension and chronic renal failure.

Benign intracranial hypertension (also called pseudotumor cerebri, otitic hydrocephalus, or meningeal hydrops) is a syndrome of markedly elevated intracranial pressure in the absence of intracranial mass, inflammation, or obstruction. Numerous disease processes and medications have been associated with it. However, renal failure has not been documented as an associated condition. In this report, the case of a 27-year-old Native American man with chronic renal failure of unknown etiology is described, with new-onset headache, papilledema, and elevated intracranial pressure. After normal cerebrospinal fluid, computed tomography, and magnetic resonance imaging studies, a diagnosis of benign intracranial hypertension was made. Despite repeated lumbar punctures with cerebrospinal fluid removal, the patient's headaches persisted, and intracranial pressures remained in the 200 to 400 mm H2O range. After initiation of hemodialysis due to progressive deterioration of renal function, the patient's headaches became less severe and eventually disappeared. This case represents a unique association of chronic renal failure with benign intracranial hypertension.

Adult↗
PubMedDate not supplied

An improved low racemization solid-phase method for the synthesis of reduced dipeptide (psi CH2NH) bond isosteres.

Preparation of peptides containing a reduced bond isostere reveals that the solid-phase procedure introduced by D.H. Coy is prone to generate significant levels of peptide diastereomers. A systematic study was conducted analyzing reaction conditions and reagents for causes of this epimerization. These studies show that trapping of the intermediate imine is the major contributor to generation of peptide diastereomers in the final product. These studies also suggest that careful adjustments of solvent and pH are necessary to suppress epimerization. Thus, an improved solid-phase procedure has been devised that efficiently traps the intermediate imine, resulting in extremely low levels of peptide diastereomers. These improved procedures have been successfully used in synthesis from 0.25 mmol to > 50 mmol batch sizes.

Chromatography, High Pressure Liquid↗