Genetic polymorphism in the 3' ntranslated region of human phosphoglucomutase-1

A 317-bp segment of DNA from the 3' region of the human phosphoglucomutase-1 (PGMl) gene has been examined by a non-radioactive technique for the occurrence of single-strand conformation polymorphism (SSCP), Eight phenotypes were detected and attributed to the presence of four alleles. Genetic analysis of 75 unrelated individuals and six CEPH families whose PGMl protein phenotypes were known revealed strong association between the PGMl '+' and '−' isozyme phenotypes and the variation detected in this region, but no association with the PGMl 1 and PGMl 2 isozyme phenotypes. DNA sequence analysis demonstrated the presence of three nucleotide substitutions underlying the alleles, which were located in the untranslated region of the PGMl gene. There was complete correlation between the nucleotide sequence and the phenotype detected by SSCP analysis. This study provides support for the model that the PGMl isozyme polymorphism is determined at two distinct sites in the coding sequence, one coding for the '1' and '2' alleles and the other coding for the '+' and '−' alleles, separated by a region where intragenic recombination occurs.     

Economic impact of reducing hospitalization for mastectomy patients.

In 1985, two policies designed to reduce hospitalization charges for mastectomy patients were instituted at the M.D. Anderson Cancer Center at Houston. The first was a policy of "same-day" admissions for elective surgery patients, and the second was early postoperative discharge for mastectomy patients with suction catheter drains in place. The economic savings resulting from these policies was analyzed by comparing demographics, operation, stage of disease, hospital stay, hospital charges, and complications for two groups of patients. Fifty-nine consecutive mastectomy patients treated between 1983 and 1984, before these policy changes, had "standard management" consisting of hospital admission 24 hours before surgery and discharge only after the surgical drains were removed. Sixty-one consecutive mastectomy patients treated between 1986 and 1987, after these policy changes went into effect, were admitted from the recovery room after surgery and were discharged with drainage catheters in place, usually within 72 hours. All operations were performed by the same faculty surgeon as a representative experience of the General Surgery faculty. The average hospital stay was reduced from 10.5 to 4.3 days. A mean 39% reduction in hospital charges (from $4867.00 to $2981.00) was achieved by instituting the policies of "same-day" admission and early postoperative discharge with drainage catheters in place. Complication rates were not changed. Implementation of this policy resulted in an estimated savings of $750,000.00 in the hospital care of approximately 400 patients treated at the M.D. Anderson Cancer Center at Houston each year. Adjustments in patient care delivery systems from a predominantly inpatient to an outpatient setting required changes in outpatient nursing responsibilities (although not in new personnel). Patient education and written instructions for home care of surgical wounds and drainage catheters were essential for implementing an early discharge policy. With these facts in mind, hospital admission on the day of operation and early postoperative discharge with drainage catheters in place should be the goal for most mastectomy patients.     

The pharmacokinetics of doxifluridine and 5-fluorouracil after single intravenous infusions of doxifluridine to patients with colorectal cancer

Summary The disposition kinetics of a new 5-fluorouracil prodrug, 5-deoxy-5-fluorouridine (5dFUR, doxifluridine), were investigated in six patients with colorectal carcinoma. Each patient randomly received two single intravenous doses of 5dFUR (2 and 4 g · m^–2) on separate days.Plasma concentrations of 5dFUR fell rapidly with terminal half-lives ranging from 16.1 to 27.7 min. A disproportionate increase in the area under the curve with increasing dose was seen in most patients. Doubling the dose resulted in a 40% decrease in nonrenal clearance (0.60 to 0.37 l · min^–1) but no apparent change in renal clearance (0.32 to 0.29 l · min^–1) or steady-state apparent volume of distribution (19.8 to 20.4 l).The mechanism for dose-dependence of 5dFUR appears to be primarily due to nonlinear elimination associated with nonrenal processes rather than nonlinear plasma protein or tissue binding.     

Temporomandibular joint: morphology and signal intensity characteristics of the disk at MR imaging

Magnetic resonance (MR) imaging has been used in the temporomandibular joint (TMJ) primarily to define the disk position. This report examines altered morphology and signal intensity characteristics of the TMJ disk as they relate to the severity of internal derangement. Two hundred sixteen joints in 133 patients with a history of such derangement. were imaged with MR. Disk position, signal intensity, morphology, and the presence of osteoarthritis were determined for each joint. The normal disk was not anteriorly displaced and had a normal "bow-tie" shape. A grade 1 disk was anteriorly displaced and had a normal shape; a grade 2 disk was anteriorly displaced and had an abnormal shape. Forty (19%) joints were considered normal; none of these exhibited osteoarthritis. One hundred thirty-nine (64%) joints were grade 1; osteoarthritis was found in 17%. Thirty-seven (17%) were grade 2; osteoarthritis was found in 95%. All forty normal joints had high or intermediate signal intensity in the disk. Osteoarthritic joints had a higher percentage of disks with diminished intensity (P less than .0001). Severe or untreated osteoarthritis is known to be a complication of TMJ internal derangements; hence this grading system seems to correlate with the severity of internal derangement.     

Area postrema-lesions increase operant responding to sucrose in rats

Rats with lesions of the area postrema (APX) are known to exhibit an enhanced intake of highly palatable foods such as sweetened condensed milk and cookies. These observations suggest the possibility that APX rats find these foods more rewarding and will work harder to obtain these foods. Sham and APX rats were tested on fixed ratio (FR) and progressive ratio (PR) schedules. APX rats consistently pressed more times to receive sucrose solution and attained both FR 3 and FR 5 criteria significantly faster than sham-lesioned control rats. Furthermore, rats with APX had significantly higher break points than sham-lesioned control rats on a progressive ratio schedule. These results support the hypothesis that rats with lesions of the area postrema will consistently work harder to obtain a highly palatable food reward.     

Malignant neoplastic emboli to the coronary arteries: report of two cases and review of the literature

Two patients were seen with malignant neoplastic emboli to the coronary arteries. One, a 61-year-old woman with a malignant fibrous histiocytoma of the thigh and a solitary pulmonary metastatic lesion, died of an acute myocardial infarction due to a neoplastic coronary embolus after lobectomy. The other, a 51-year-old woman with bronchogenic adenocarcinoma, died of extensive cerebral metastases. At autopsy, she also was found to have had an acute myocardial infarction associated with a neoplastic coronary embolus.     

Cannabinoid agonist, CP 55,940, facilitates intake of palatable foods when injected into the hindbrain

Cannabinoids have been shown to influence food intake, and until recently, the neural pathways mediating these effects have remained obscure. It has been previously shown that intracerebroventricular injection of delta-9-tetrahydrocannabinol (Δ⁹-THC) causes increased consumption of palatable foods in rats, and we postulated the involvement of the hindbrain in this cannabinoid-induced food intake. Cannulated rats (both female and male groups) trained to consume sweetened condensed milk received either lateral or fourth ventricle injections of CP 55,940 and were presented with sweetened condensed milk 15 min after injection. Rats were injected over a range of doses between 100 pg and 10 μg per rat. Milk intake was recorded for a total of 3 h. Lateral ventricle injection of CP 55,940 increased milk intake at doses in the microgram range. However, CP 55,940 was effective in increasing food intake at nanogram doses when injected into the fourth ventricle. Finally, male rats appeared to be more sensitive to CP 55,940 than female rats inasmuch as milk consumption was increased at the 1 ng dose in male rats, whereas only the 10 ng dose was effective in females. These results indicate that CP 55,940 may act in the hindbrain to influence feeding behavior in rats.     

Teratogenicity of anticonvulsant drugs. IV: The association of clefting and epilepsy

Cleft lip with or without cleft palate (CL/P) is the most common congenital malformation reported among infants of epileptic mothers. This study sought to examine the relative roles of anticonvulsant teratogenicity and other factors responsible for this association. Among 175 families with a proband with isolated CL/P, there were 13 parents with epilepsy and a high frequency of other family members with CL/P and epilepsy. Evaluation of the 13 cases suggested that teratogenicity of anticonvulsant drugs was not the primary factor responsible for the observed association of maternal epilepsy and clefting. Among 140 families with a proband with clefting other than CL/P, there were no instances of parental epilepsy observed.