Clozapine-associated postoperative ileus: case report and review of the literature.
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Adenocarcinoma↗
Biomedical subjects
D M Morris
Publications and source records attributed to D M Morris.
Pharmacokinetics, absolute bioavailability, and absorption characteristics of lamivudine.
Lamivudine is a novel cytosine nucleoside analog, reverse transcriptase inhibitor that has shown activity against human immunodeficiency virus (HIV) types 1 and 2 and hepatitis B virus in vitro. This study was conducted to compare the absolute bioavailability, pharmacokinetics, and absorption characteristics of oral solution, 100-mg capsule, and 100-mg tablet formulations of lamivudine with those of intravenous lamivudine. Twelve patients with HIV were enrolled in a single-center, randomized, open-label, four-way cross-over study. Treatment arms consisted of 100 mg intravenous lamivudine (administered over 1 hour), 100 mg oral lamivudine (1 mg/mL), a 100-mg capsule, and a 100-mg tablet, each followed by a 3- to 14-day washout period. Serial blood samples over 24 hours were obtained after each dose administration. Serum concentration data were analyzed to determine pharmacokinetic parameter estimates including area under the curve (AUC), terminal half-life (t1/2), mean residence time (MRT) for each formulation, systemic clearance, oral clearance, and apparent volume of distribution (Vd). Absolute bioavailability and in vivo mean absorption time (MAT) and mean dissolution time (MDT) were calculated for the oral formulations. Deconvolution techniques were used to calculate the input rate for the oral solution, capsule, and tablet. The two one-sided t test was used to determine bioequivalency among oral formulations with respect to logarithmic transformed estimates of AUC and maximum peak concentration (Cmax). Mean (CV) systemic clearance and Vdss after intravenous administration of lamivudine were 22.6 L/h (15%) and 99 L (28%), respectively; mean t1/2 ranged from 8.41 to 9.11 hours for all formulations; and MRT ranged from 4.42 to 5.77 hours for all formulations. Mean absolute bioavailability ranged from 86% to 88% for the oral solution, capsule, and tablet. All oral formulations were considered bioequivalent for AUC and Cmax. The MAT was 1.32 hour for the oral solution, and MDT was 0.03 and -0.11 hours for the capsule and the oral solution, respectively. The oral formulations of lamivudine examined in this study demonstrated acceptable bioavailability for oral administration. The solid oral formulations (capsule and tablet) show rapid dissolution properties with an absorption rate similar to or exceeding those observed with the oral solution. This suggests that dissolution is not an important factor for the rate of absorption of lamivudine. The use of deconvolution techniques using PCDCON provides valuable insight into the absorption characteristics of lamivudine.
Absorption↗
Determination of the novel sialic acid analog GG167 (GR121167X) in human urine by liquid chromatography: direct injection with column switching.
GG167 is a novel compound which selectively inhibits viral neuraminidase and has demonstrated activity against influenza A and B. A liquid chromatography (LC) method for the determination of GG167 in human urine has been developed and validated. The method allows direct injection of urine (7 microliters) using LC column switching followed by UV detection. Initial chromatography is performed using a Nucleosil-Diol column (7 microns, 250 mm x 4.6 mm), eluted with 20 mM phosphate buffer (pH 2.5):acetonitrile (18:82, v/v) at 2.0 ml min-1. GG167 is "heart-cut" to a Spherisorb-SCX column (5 microns, 100 mm x 4.6 mm) and eluted with 35 mM phosphate buffer (pH 2.5):acetonitrile (50:50, v/v) at 1.5 ml min-1 for final separation. GG167 is detected by UV absorbance at lambda = 238 nm. UV detection and peak shape are enhanced at pH < 2.5. The quantitation range of the assay is 0.3-100 micrograms ml-1. The method has demonstrated sufficient ruggedness to be used in support of GG167 clinical trials.
Administration, Intranasal↗
Early gallbladder cancer discovered at the time of laparoscopic cholecystectomy.
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Cholecystectomy, Laparoscopic↗
High-performance liquid chromatographic assay for 2'-deoxy-3'-thiacytidine in human serum.
A high-performance liquid chromatographic method for the determination of 2'-deoxy-3'-thiacytidine (3TC), a novel dideoxy-nucleoside analogue, in human serum is described. 3TC was extracted from serum samples using Bond Elut Certify solid-phase extraction cartridges prior to reversed-phase chromatography with UV detection. The method has been shown to be valid over the concentration range 10-5000 ng/ml using a 1-ml sample volume, both before and after heat treatment of the samples at 60 degrees C for 3 h. The method has been automated using a Zymark robot and used in the analysis of serum samples from HIV positive patients.
Antiviral Agents↗
Coexistent thyroid cancer and pregnancy.
OBJECTIVE: A study was performed to determine the appropriate time for the initiation of therapy for thyroid carcinoma first diagnosed during pregnancy. DATA SOURCES: Material on thyroid cancer cases was obtained from the New Mexico Tumor Registry, Albuquerque, a computerized population-based registry for the state of New Mexico, and the Indian reservation facilities in New Mexico and Arizona (a Surveillance, Epidemiology, and End Results Registry funded by the National Cancer Institute, Bethesda, Md) for the period 1970 to 1991. STUDY SELECTION: All cases of thyroid cancer, except medullary and anaplastic, in patients aged 18 to 46 years were evaluated. Subgroups were established for (1) all women who were noted to be pregnant at the time of their initial diagnosis and (2) all women with thyroid cancer in the 18- to 46-year-old age group. DATA EXTRACTION: The information was extracted by a certified tumor registrar for age, sex, thyroid cancer, specific type of thyroid cancer, period, race, year of diagnosis, accession date, last date seen, tumor status, treatment, and patient status. DATA SYNTHESIS: There have been no deaths in the pregnant group with a follow-up ranging from 0.5 to 20 years. There was no statistically significant difference in observed survival rates between the pregnant group and 465 women, aged 18 to 46 years, with comparable thyroid cancers or in the death rates of women aged 18 to 67 years in the general population. CONCLUSIONS: Surgical treatment for patients with well-differentiated thyroid cancer diagnosed during pregnancy can be delayed until after parturition.
Adolescent↗
Peritoneal cultures and antibiotic therapy in pediatric perforated appendicitis.
We retrospectively reviewed 70 cases of perforated appendicitis in children to examine the relationship between postoperative antibiotic selection and culture results from the peritoneal cavity. Initial antibiotic therapy chosen for the children consisted of a three-drug combination in 54 (77%) patients. Peritoneal cultures were performed in 58 (83%) patients. Escherichia coli and Bacteriodes fragilis were the most common bacterial isolates from the peritoneal culture. Only 7 (10%) patients had their antibiotic regimen changed after the culture results were available, of which 2 changes brought drug therapy into compliance with the cultures and 5 changes were inappropriate with respect to the peritoneal cultures. Of the remaining 51 patients with culture data available, 39 should have had changes to bring the antibiotic therapy into compliance with the observed culture results. These data indicate that surgeons select antibiotic therapy for perforated appendicitis in children based on assumptions of which organisms should be present in the infection and not on culture data. There appears to be no clinical usefulness to the routine culturing of the peritoneal cavity in children with perforated appendicitis.
Anti-Bacterial Agents↗
Determination of 2'-deoxy-3'-thiacytidine (3TC) in human urine by liquid chromatography: direct injection with column switching.
3TC (GR109714X) is a cytidine dideoxynucleoside analogue which has been shown to have in vitro activity against a variety of strains of HIV-1 and is currently being investigated in clinical trials as a treatment for HIV infection. An HPLC method for the determination of 3TC in human urine has been developed and validated. The method allows direct injection of urine (10 microliters) using HPLC column switching followed by UV detection. On-line extraction is performed using a Spherisorb-SCX (5 microns, 20 x 4.0 mm) eluted with deionized water at 1 ml min-1. 3TC is retained while the bulk of urine constituents are eluted to waste. The SCX column is then backflushed to a BDS-Hypersil-C18 (5 microns, 250 x 4.6 mm) and eluted with 100 mM acetate pH 4.5-methanol (95:5, v/v) for final separation. 3TC is detected by UV absorbance at lambda = 285. The quantitation range of the assay was 0.5-500 micrograms ml-1. The method has demonstrated sufficient ruggedness to be used in support of 3TC clinical trials. Application to other cytidine analogues including DDC has been demonstrated.
Chromatography, High Pressure Liquid↗
Electrical potential measurements in human breast cancer and benign lesions.
Electrical potentials were measured on the breast and at other sites in 110 women with palpable breast masses. The tumor site was significantly electropositive compared with control sites only when the tumor was a cancer, as determined by a subsequent biopsy; the electrical potentials were not influenced by age or menstrual cycle. The results indicate that, on average, altered electrical potentials detected by a noninvasive measurement on the skin reflect the presence of transformed cells in patients with breast cancer. Previous in vitro studies of breast tissue and breast epithelial cells suggest that the observed effect was due to a change in interstitial K+ concentration that arose from alterations in the activity of K+ channels. Electrical potentials may be suitable for diagnosis of individual patients if refinements are made in the measurement technique.
Adolescent↗
Pancreaticogastrostomy: preferred reconstruction for Whipple resection.
Anastomotic leak is the main complication after Whipple procedures. We reviewed retrospectively our experience with pancreatic cancer patients treated with Whipple resection and reconstruction with a pancreaticogastrostomy (PG) or a pancreaticojejunostomy (PJ). Ten patients operated between 1966 and 1990 composed the PJ group. Eight patients operated recently made up the PG group. Data on age, length of stay (LOS), survival, and complications (early and late) were noted from patient's charts. Patients in the PJ group had an average age of 58.3 years, a mean LOS of 60.3 days (median, 48 days), and a mean survival of 14.5 months. PG group patients had a mean age of 64.5 years, an average LOS of 14.3 days (median, 14 days), and an average survival of 10+ months. None of these differences were significant. Major complications in the PJ group included 2 leaks, 2 cases of pancreatic insufficiency, and 2 deaths related to the anastomotic leaks. Eleven other major complications occurred. The PG group patients did not have any leaks. One developed pancreatic insufficiency. Complications in the PG group were much less serious than those in PJ group. The longest hospital stay in the PG group was 20 days (range, 2-20) and 144 days (range, 11-144) in the PJ group. We conclude that PG is superior to PJ because of the decreased incidence of anastomotic leaks and the less serious nature of the complications associated with PG.
Aged↗
Sustained pulmonary hypertension in surgical patients.
Twenty-two consecutive critically ill surgical patients who had a Swan-Ganz thermodilution catheter inserted as part of their intensive care unit therapy were studied prospectively. Patients were divided into two groups. Group I consisted of 17 patients whose pulmonary artery diastolic pressure minus pulmonary artery wedge pressure (PADP-PAWP) gradient was less than 5 mm Hg or if greater than 5 mm Hg persisted for less than 12 hours. Group II was composed of 5 patients whose PADP-PAWP gradient was greater than 5 mm Hg for at least 12 hours or more. The two groups were equally matched in terms of risk factors that predispose to an elevated gradient or factors that falsely lower the gradient. Nine other physiologic parameters were measured in patients in Group II during the period of the elevated gradient and were compared with the same parameters measured in patients in Group I. An elevated pulmonary vascular resistance was the only parameter associated with an elevated gradient. An elevated PADP-PAWP gradient greater than 5 mm Hg that persisted for 12 hours or more was associated with a 60 per cent mortality rate.
Aged↗
Electrochemical modification of tumor growth in mice.
We evaluated the effect of direct electrical current on large tumors in mice. Lewis lung carcinoma greater than 1 cm in the shortest dimension was treated percutaneously with 20 mA for 15 min. Separate groups were given one or more than one (two or three) percutaneous electrical treatments (PET). A third group was given sham electrical treatment, and a fourth group had surgical excision of the tumor. Animals in both PET groups survived longer and had smaller primary tumors at death compared with the sham group. PET did not alter the systemic course of the disease, judged by lung and spleen weights and by histological observation of the extent of metastatic burden in the lung. Surgery resulted in long-term survival of 17% and an increase in average survival time compared with both PET and sham treatment. PET produced rapid and polarity-dependent alterations in physiological solutions in vitro, and it is likely that similar electrochemical processes mediated the observed reduction in tumor growth. PET is potentially useful as an adjuvant modality because it reduces local tumor mass but does not alter the extent of metastasis.
Animals↗
Work-site nutrition intervention and employees' dietary habits: the Treatwell program.
In a randomized, controlled study of the Treatwell work-site nutrition intervention program, which focused on promoting eating patterns low in fat and high in fiber, 16 work sites from Massachusetts and Rhode Island were recruited to participate and randomly assigned to either an intervention or a control condition. The intervention included direct education and environmental programming tailored to each work site; control work sites received no intervention. A cohort of workers randomly sampled from each site was surveyed both prior to and following the intervention. Dietary patterns were assessed using a semiquantitative food frequency questionnaire. Adjusting for work site, the decrease in mean dietary fat intake was 1.1% of total calories more in intervention sites than in control sites (P less than .005). Mean changes in dietary fiber intake between intervention and control sites did not differ. This study provides evidence that a work-site nutrition intervention program can effectively influence the dietary habits of workers.
Adolescent↗
Diagnosis and management of esophageal perforations.
Esophageal perforation remains a difficult diagnostic and management problem. Recommendations regarding treatment remain controversial. A 15-year experience with perforation of the esophagus from all causes was reviewed at Louisiana State University and Veterans Administration, Medical Centers (Shreveport, LA). The majority of the injuries involved the thoracic esophagus (28 or 54%), followed by the cervical (21 or 40%), and the intraabdominal esophagus (3 or 6%). Iatrogenic causes constituted most of the injuries (52%), followed by external trauma (23%), barogenic rupture (15%), and ingested foreign bodies (10%). Diatrizoate methylglucamine 66 per cent, sodium diatrizoate 10 per cent (Gastrografin; Squibb, Princeton, NJ) contrast studies and flexible esophagoscopy were performed in 44 and 22 patients, respectively. In the cervical esophagus, contrast studies were more sensitive and specific than endoscopy (P less than .01), but both studies were equally effective as diagnostic methods in thoracic perforations. Cervical perforations were treated with either drainage alone (7 patients) or primary repair with drainage (14 patients) with an operative mortality of 4.8 per cent. Several procedures were used in thoracic perforations, which carried a mortality of 36 per cent and were more lethal than cervical tears (P less than 0.2). Any thoracic esophageal perforation treated more than 24 hours after the onset of symptoms, irrespective of what procedure was used, was associated with a significantly higher mortality than if operated on earlier (P less than .001). Five patients with perforated carcinomas were treated by esophageal resection with no mortality. Significantly higher mortality was seen with a delay in diagnosis, thoracic perforations, and Boerhaave's Syndrome. A subset of patients with perforated carcinomas may benefit from esophageal resection with delayed reconstruction.
Adolescent↗
Hormonal receptors in locally advanced breast cancer: change with response to neoadjuvant chemotherapy?
Twenty-one cancers in 20 patients with locally advanced breast cancer were studied. Incisional biopsy was performed without using electrocautery. Tissue was obtained for histology and estrogen (ER) and progesterone (PR) receptors. Patients received chemotherapy after biopsy. All responded and had radical mastectomy performed. Tissue was removed from the mastectomy specimen to confirm residual tumor and for repeat receptor measurements. Initial receptor levels were negative in 13 cancers. Following chemotherapy, both ER and PR levels were unchanged in 11 cancers. Levels in one cancer changed from ER-PR- to ER+PR- and one changed from ER-PR- to ER+PR+. Six cancers were ER+PR+ at initial examination. Repeat receptor levels after chemotherapy were ER+PR+ in three. One ER+PR+ tumor became ER-PR+, one changed to ER+PR-, and one to ER-PR-. One ER+PR- cancer remained ER+PR- after treatment and an ER-PR+ cancer became ER-PR- after treatment. Chemotherapy dose not significantly alter hormonal levels in breast cancer tissue.
Aged↗
Loop colostomies are totally diverting in adults.
Temporary colostomy is a mainstay in the treatment of patients with colon injuries. Common teaching is that loop colostomies are not totally diverting. We performed this study to determine whether loop colostomies are totally diverting. Twenty-three patients presenting for closure of loop colostomies were given barium by mouth. Serial abdominal films were obtained at intervals over 24 hours. Scout films were obtained after bowel preparation to see if flushing the colon could cause passage of barium into distal bowel. We could not demonstrate passage of barium into the distal limb of the colon in any patient studied. This was true even in long-established loop colostomies. Bowel preparation did not cause passage of barium into the distal colon. Loop colostomies constructed over a rod and matured immediately totally divert the fecal stream. Most surgeons would agree that this type of colostomy is more easily and quickly created and closed. Since it fulfills the criteria for fecal diversion, the use of divided colostomies should be abandoned when a loop colostomy can be utilized.
Adolescent↗
Antibiotic treatment for surgical peritonitis.
The charts of 480 patients with secondary bacterial peritonitis were reviewed. The antibiotics used were compared with the culture and sensitivity data obtained at surgery, and the outcomes of patients were evaluated. Patients treated with a single broad-spectrum antibiotic had a better outcome than patients treated with multiple drug treatment. Inadequate empiric antibiotic treatment was associated with poorer outcome than any other type of treatment. The outcome of this inadequate treatment group could not be improved by any antibiotic response to culture and sensitivity information after operation. Those patients treated with antibiotic coverage for anticipated organisms and having no cultures taken did as well as patients having cultures taken. Surgeons typically ignore culture data after operation, and only 8.8% of patients in this study had an appropriate change in antibiotic treatment after operation. A benefit from obtaining operative cultures could not be identified.
Acute Disease↗
Inhibition of peripheral aromatization in the male cynomolgus monkey by a novel nonsteroidal aromatase inhibitor (R 76713).
R 76713 (6-[(4-chlorophenyl)(1-H-1,2,4-trizol-1-yl)methyl]1-H benzotriazole) is a highly potent and selective inhibitor of the aromatase enzyme both in vitro and in vivo. The ability of R 76713 to inhibit peripheral aromatization of androstenedione (A) to estrone (E1) in vivo was studied in male cynomolgus monkeys (Macaca fascicularis). Peripheral aromatization was measured using a primed constant infusion of [3H] A and [14C]E1 for 3.5 h. Blood samples, collected during the final hour of infusion, were analyzed for plasma radioactivity as infused and product steroids. MCRs, conversion ratios (CR), and percent conversion of A to E1 were calculated. R 76713 (0.03-10 microgram/kg) or vehicle (10% hydroxypropyl-beta-cyclodextrin) were administered iv 90 min before beginning the infusion of radiolabeled steroids. In vehicle-treated monkeys, the aromatization of A (mean +/- SEM, 1.35 +/- 0.11%) was similar to that previously reported for cynomolgus and rhesus monkeys, baboons, and humans. Aromatization of A, measured 4-5 h after injection of R 76713, was dose-dependently decreased from the control value by 87 +/- 3%, 85 +/- 2%, 61 +/- 5%, and 33 +/- 8% (all P less than 0.05) at doses of 10.0, 3.0, 0.3, and 0.03 micrograms/kg, respectively, with an ID50 of 0.13 microgram/kg, iv (95% confidence interval, 0.06-0.21). When measured 15-16 h after iv administration of 3.0 micrograms/kg R 76713, aromatization (0.55 +/- 0.13%) was significantly inhibited by 53 +/- 11% compared to that in control monkeys (1.16 +/- 0.18%). The CRs between androgens, the CRs between estrogens, and the MCRs of A and E1 were not significantly altered by R 76713 compared to those after vehicle treatment. R 76713 potently decreased peripheral conversion of androgen to estrogen in vivo in male cynomolgus monkeys and may be a useful therapeutic agent in treating estrogen-dependent diseases, including post-menopausal breast cancer.
Androstenedione↗