Comparison of GENEHUNTER and MFLINK for analysis of COGA linkage data

We compared the NPLALL statistic from GENEHUNTER with two-point and three-point MALODs and MFLODs from MFLINK for all autosomal markers in the Collaborative Study on the Genetics of Alcoholism (COGA) data set. In general MFLINK produced more significant results than GENEHUNTER and implicated two regions containing candidate genes (ADH3 and DRD2). Many regions of interest identified in other studies reported at this workshop produced MALODs significant at p < or = 0.05, but these would not have been picked up by GENEHUNTER unless a less significant threshold were used.     

Back to the future for wound care?

The European Renaissance was a time of enormous change and rapid progress in the arts, sciences, and medicine. A glimpse of wound care in the last phase of the European Renaissance is provided by the analysis of work by Wilhelm Fabry, the "father of German surgery," as provided in his book De Combustionibus ("Burns") which details his range of treatments for the burn wound, as well as his approach to the later problems of scarring and contracture. We describe some of the historic events which may have stimulated Fabry's writings, in particular, the influences passed down from the medical school of Padua which thereby advanced the cause of wound care and surgery. Finally, we briefly explore the potential of such an approach to the works of our medical forefathers.     

Lysis of venous clots by local intraarterial Thrombolysin injection in the rat

Intravascular coagulation is the final common pathway of failure in replanted digits and "free" tissue transfers. To address this clinical problem, a model based upon intimal damage and stasis in the rat femoral vein was developed. The ability of local, intraarterially administered Thrombolysin to achieve "local" clot lysis was investigated. "Systemic anticoagulation" was measured by standard hematologic monitoring and "systemic thrombolysis" by lysis of a contralateral standard femoral vein clot. The mean drug volume required for local clot lysis was proportional to the clots' duration time; 7.8 ml required for the 30-minute, and 17.0 ml required for the 60-minute clot (p less than 0.05). Lysis was achieved by local intraarterial Thrombolysin in 87% of the clots of 30 minutes' duration and in 94% of the clots of 60 minutes' duration. Overall, just 3.6% of contralateral clots lysed (p less than 0.001). Systemic anticoagulation did not occur.     

Aspirin usage and its influence on femoro-popliteal vein graft patency. The Femoro-popliteal Bypass Trial Participants.

As part of the Femoro-popliteal Bypass Trial patients undergoing femoro-popliteal vein bypass were randomised to aspirin 300 mg and dipyridamole 150 mg twice daily or identical placebo tablets. Blood was taken from a subgroup of 145 patients (mean age 66.3 years) with patent grafts at 6 months. Serum salicylate analysis revealed that of the 65 randomised to receive placebo 18 (28%) had evidence of salicylate in their sample (greater than 50 ng ml-1). Similarly, in those randomised to active treatment and considered to be good compliers 16/61 (26%) had no evidence of salicylate in their serum sample (less than 50 ng ml-1). Analysis of primary graft patency by "intention to treat" failed to detect a difference by life table, the risk being slightly higher in the group assigned to placebo (RR = 1.33, 95% confidence internal C.I. 0.64-2.78, p = 0.438). When comparing patients with no detectable serum concentration (less than 50 ng ml-1) with patients with serum salicylate over 50 ng ml-1 there was a significant difference in graft patency at 66 versus 83% respectively at 3 years (RR = 2.38, 95%C.I. 1.08-5.26, p = 0.024). When corrected for a number of possible risk factors this significant difference was maintained (RR = 2.78, 95%C.I. 1.15-6.67, p = 0.017). Although these findings are based on observational data they provide indirect evidence of an improvement in graft patency with aspirin. This result combined with the finding of a significant reduction in cardiovascular events in the main trial results support the use of aspirin and dipyridamole in patients undergoing femoro-popliteal vein bypass.     

DNA repair in human bronchial epithelial cells

The purpose of this investigation was to compare the responseof human cell types (bronchial epithelial cells and fibroblastsand skin fibroblasts) to various DNA damaging agents. Repairof DNA single strand breaks (SSB) induced by 5 krads of X-raywas similar for all cell types; 90% of the DNA SSB were rejoinedwithin one hour. During excision repair of DNA damage from u.v.-radiation,the frequencies of DNA SSB as estimated by the alkaline elutiontechnique, were similar in all cell types. Repair replicationas measured by BND cellulose chromatography was also similarin epithelial and fibroblastic cells after u.v.-irradiation.Similar levels of SSB were also observed in epithelial and fibroblasticcells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene;benzo[a]pyrene diol epoxidle (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine.Significant repair replication of BPDE-induced DNA damage wasdetected in both bronchial epithelial and fibroblastic cells,although the level in fibroblasts was 40% of that in epithelialcells. The pulmonary carcinogen asbestos did not damage DNA.DNA-protein crosslinks induced by formaldehyde were rapidlyremoved in bronchial cells. Further, epithelial and fibroblasticcells, which were incubated with formaldehyde and the polymeraseinhibitor combination of cytosine arabinoside and hydroxyurea,accumulated DNA SSB at approximately equal frequencies. Theseresults should provide a useful background for further investigationsof the response of human bronchial cells to various DNA damagingagents.     

Auditory toxicity effects of long-term cis-dichlorodiammineplatinum II therapy in genitourinary cancer patients

To determine the auditory toxicity effects of long-term cis-dichlorodiammineplatinum II therapy, pure tone hearing thresholds were measured prior to therapy and repeated before each subsequent treatment. CDDP was given by a slow intravenous drip method at a low dose of 1 mg/kg body weight, with 37.5 gm mannitol, once a week for six treatments and every 3 weeks thereafter. From a group of 173 genitourinary cancer patients treated, 50 male patients were selected who received at least 12 months of CDDP with no active conductive ear pathology, and whose audiograms obtained at baseline, 6th weeks, 26th weeks, and 52nd weeks of treatment were all available for comparison. Pure tone threshold levels deteriorated across time particularly by the 52nd week and at the higher frequencies. Threshold differences across time were statistically significant and within a linear trend. Of the 50 cases, 30% showed suspect or no ototoxicity, 26% mild, 32% moderate, 2% marked, and 4% showed severe ototoxic changes. Of the two cases who developed severe ototoxicity, one showed complete recovery. There was partial recovery in 26% and no recovery in 54%. Individual variability in susceptibility to and recovery from ototoxicity necessitates systematic audiometric monitoring throughout the therapy.     

Gastrinoma of duodenal G-cell origin.

A 65-year-old man with hypergastrinemia associated with the Zollinger-Ellison syndrome was found to have a duodenal "carcinoid-islet cell tumor." Gastrin levels have remained normal for more than 1 year following total gastrectomy and removal of the duodenal tumor. Immunohistochemical studies for gastrin localization revealed positive staining of the tumor and of a population of nonneoplastic G-cells in the adjacent duodenal mucosa and Brunner's glands. These results support the hypothesis that gastrinomas may arise as primary tumors from duodenal G-cells rather than from ectopic pancreatic tissue. "Carcinoidislet cell tumors," like other tumors of APUD-cell origin, may express dual biochemical functions in the form of polypeptide hormone and/or amine secretion. Their content of specific hormonal products may be predicted on the basis of sensitive histochemical and immunohistochemical techniques.     

From state hospital to integrated human service system: managing the transition

If a human service facility can treat a mental patient at one-fifth the cost incurred at a parallel state mental hospital, and do it better, there is compelling reason for mental health care managers to consider the benefits of matrix organization.