Contribution of frontal cerebral blood flow measured by (99m)Tc-Bicisate spect and executive function deficits to predicting treatment outcome in alcohol-dependent patients

Aim: To determine whether inhibition and working memory deficits, and reduced regional cerebral blood flow (rCBF) (previously shown to be related), measured at the end of a detoxification programme, predict alcoholic relapse 2 months later. METHODS: Twenty uncomplicated alcoholic inpatients were investigated at the end of detoxification, at least 7 days since the last dose of diazepam, and a mean of 18.8 days since the last drink. Their performance was assessed on the inhibition (Hayling) test, working memory (Alpha-span task), episodic memory (California Verbal Learning Test) and abstract reasoning (Progressive Matrices). Frontal CBF was assessed at the same time with a semiquantitative (99m)Tc-Bicisate SPECT procedure. Patients were contacted 2 months later. Patients who abstained (n = 9) did not differ from those who relapsed (n = 11) on age, gender, smoking, duration of alcohol misuse, number of previous detoxifications, amount of ethanol consumed the month prior to admission to the detoxification programme, state anxiety, trait anxiety, or depression. RESULTS: Relapsed subjects had shown a lower uptake of (99m)Tc-Bicisate in the bilateral medial frontal gyrus (n = 9; mean ratio +/- SD = 0.69 +/- 0.006) than abstainers (n = 11; 0.85 +/- 0.19), and poorer performance on the Alpha-span task and the Hayling test. The other tests were not different. CONCLUSIONS: Inhibition and working memory deficits, associated with low levels of CBF in the medial frontal gyrus, are related to the difficulty of maintaining short-term abstinence from alcohol.     

Perforation in cancer of the colon and rectum

Summary The management of patients with perforation of the colon in association with cancer of the colon presents a unique and difficult surgical problem. Surgical care of the perforation and its resultant peritonitis or abscess must take precedence over that of the cancer. In this study of 45 patients with the combined lesions, perforation occurred at the site of the tumor in 32. Ten patients were managed by primary resection with a mortality rate of 30%; 16 were managed by colostomy and drainage or a bypass procedure with a mortality rate of 50%. Six patients were moribund on admission and died before any operation could be performed. While the mortality rate would indicate that primary resection is superior to less radical forms of management, it must be recognized that those patients selected for resection were generally in better condition than the others. Therefore, mortality figures alone do not resolve the problem. Perforation occurred proximal to the tumor in 12 patients, ten of whom underwent an operative procedure. Exteriorization or resection was used in four patients, and one died. Cecostomy or closure of the perforation was used in six patients, and of these, there were four deaths. Exteriorization or resection appear to offer better results. The gravity of the combination of perforation and cancer of the colon and the poor long-term survival rates, combined with the apparently better results of a more radical approach, suggest that immediate resection should be considered more often and should be the object of a carefully controlled clinical study. Read at the meeting of the American Proctologic Society, New Orleans, Louisiana, April 17 to 19, 1967. Supported in part by grant #AI 01600 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Public Health Service.     

The normal microbial flora

Summary In a qualitative and quantitative study of bacteria, the mid small intestine and colon of rabbits and dogs, and the upper jejunum and terminal ileum of surgical patients were sampled at laparotomy.The small intestine of rabbits, dogs, and humans was not sterile. The bacterial groups found most frequently were also those present in the greatest numbers. In rabbits and dogs the small intestine contained varied and quantitatively large flora. In man, the small intestine contained only slight median numbers of coliforms and streptococci. These findings support the view that the small intestine of man contains sparse, transient, bacterial flora.Presented at a postgraduate course, Advances in Gastroenterology—Enterocolonic Disease and Dysfunction (Oct. 22–24, 1964) , sponsored by Louisiana State University School of Medicine, New Orleans, La.Supported in part by Grants Al 00524 and Al 01600 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, U. S. Public Health Service.     

Ancient haplotypes resulting from extensive molecular rearrangements in the wheat A genome have been maintained in species of three different ploidy levels

Plant genomes, in particular grass genomes, evolve very rapidly. The closely related A genomes of diploid, tetraploid, and hexaploid wheat are derived from a common ancestor that lived <3 million years ago and represent a good model to study molecular mechanisms involved in such rapid evolution. We have sequenced and compared physical contigs at the Lr10 locus on chromosome 1AS from diploid (211 kb), tetraploid (187 kb), and hexaploid wheat (154 kb). A maximum of 33% of the sequences were conserved between two species. The sequences from diploid and tetraploid wheat shared all of the genes, including Lr10 and RGA2 and define a first haplotype (H1). The 130-kb intergenic region between Lr10 and RGA2 was conserved in size despite its activity as a hot spot for transposon insertion, which resulted in >70% of sequence divergence. The hexaploid wheat sequence lacks both Lr10 and RGA2 genes and defines a second haplotype, H2, which originated from ancient and extensive rearrangements. These rearrangements included insertions of retroelements and transposons deletions, as well as unequal recombination within elements. Gene disruption in haplotype H2 was caused by a deletion and subsequent large inversion. Gene conservation between H1 haplotypes, as well as conservation of rearrangements at the origin of the H2 haplotype at three different ploidy levels indicate that the two haplotypes are ancient and had a stable gene content during evolution, whereas the intergenic regions evolved rapidly. Polyploidization during wheat evolution had no detectable consequences on the structure and evolution of the two haplotypes.     

Immunization of ovarian cancer patients with a synthetic Lewis(y)-protein conjugate vaccine: a phase 1 trial

As the initial step in developing carbohydrate-based vaccines for the treatment of ovarian cancer patients in an adjuvant setting, 25 patients were immunized with a Lewis(y) pentasaccharide (Le(y))-keyhole limpet hemocyanin (KLH)-conjugate vaccine together with the immunological adjuvant QS-21. Four different doses of the vaccine, containing 3, 10, 30, and 60 microg of carbohydrate were administered s.c. at 0, 1, 2, 3, 7, and 19 weeks to groups of 6 patients. Sera taken from the patients at regular intervals were assayed by ELISA for reactivity with naturally occurring forms of Le(y) (Le(y)-ceramide and Le(y) mucin) and by flow cytometry and a complement-dependent cytoxicity assay for reactivity with Le(y)-expressing tumor cells. The majority of the patients (16/24) produced anti-Le(y) antibodies as assessed by ELISA, and a proportion of these had strong anti-tumor cell reactivity as assessed by flow cytometry and complement-dependent cytotoxicity. One serum, analyzed in detail, was shown to react with glycolipids but not with glycoproteins or mucins expressed by ovarian cancer cell line OVCAR-3. The vaccine was well tolerated and no gastrointestinal, hematologic, renal, or hepatic toxicity related to the vaccine was observed. On the basis of this study, Le(y)-KLH should be a suitable component for a polyvalent vaccine under consideration for the therapy of epithelial cancers.