Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain "C-region"

Structural variants of the hydrophobic side chain ("C region") of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (45Ca2+ influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, < 55) in order to obtain high potency. Combination of the information gained here about the "C-region" of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency.     

Spontaneous coronary artery dissection associated with oral contraceptive use

A 39-year-old woman presented with acute myocardial infarction due to spontaneous dissection of the left anterior descending artery. This was treated conservatively. She had been on combined oral contraceptive pills from the age of 22. Repeat coronary angiography 7 months later revealed spontaneous complete healing.     

The nervous system function of patients with periodontitis

Analysis of the function of the nervous system, based on clinical, neurological, and psychological studies in 78 patients with generalized periodontitis, revealed central regulation disorders without signs of organic lesions of the brain in 76% patients. The authors claim that stress and a high level of personal anxiety may be responsible for the development of these disorders, which was confirmed by the results of psychological testing.     

Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin

PURPOSE: Diagnostic strategies designed to identify the underlying primary malignancies in patients with unknown primary tumors (UPTs) have relied on retrospective analyses. We analyzed 879 consecutive patients referred with suspected UPTs to determine the yield and cost of a limited diagnostic evaluation, assess the contribution of specific studies to diagnosis, and analyze the survival patterns of patients in whom the primary tumor was diagnosed. PATIENTS AND METHODS: Data from patients with a suspected UPT were entered into a computerized data base, and the patients underwent a predefined limited diagnostic evaluation. Primary malignancies were diagnosed by pathologic review alone or by pathologic criteria plus a physical or radiographic finding. Survival was measured from diagnosis, estimated using the Kaplan-Meier method, and compared using the Cox-Mantel log-rank test. RESULTS: A primary tumor was found in 179 of 879 patients (20%). The survival duration of patients in whom the primary tumor was diagnosed was superior to that of patients in whom the primary tumor remained unknown. Specific patient subsets contributed most to the improved survival duration of the group in which the primary tumor was found, including lymphoma patients diagnosed solely by pathologic criteria and female patients with primary breast or ovarian cancer. The cost of diagnosis was mostly due to the extensive use of computed tomography. Except for ovarian cancer, computed tomography rarely identified treatable primary tumors. CONCLUSION: The limited diagnostic evaluation used in this study identified patients with treatable malignancies and increased the survival duration of a population of suspected UPT patients. Primary malignancies with the best survival can be diagnosed through careful pathologic review and focused evaluations for breast and ovarian cancer in women.     

Diagnosis of transfusion-associated graft-versus-host disease by polymerase chain reaction in fludarabine-treated B-chronic lymphocytic leukaemia

Transfusion-associated graft-versus-host disease (TA-GVHD), has rarely been reported associated with B-chronic lymphocytic leukaemia (B-CLL). We report a patient diagnosed with B-CLL, previously treated with fludarabine, who developed TA-GVHD after being transfused during surgery for splenectomy. Diagnosis was confirmed by polymerase chain reaction (PCR) detection of donor DNA in the patient, by amplification of Y-chromosome sequence and analysis of minisatellite polymorphisms. B-CLL patients treated with fludarabine appear to be at risk for TA-GVHD and should be regarded as candidates for transfusions with irradiated blood products. This case illustrates that PCR is a rapid technique for the early diagnosis of TA-GVHD.     

Swiss population data and forensic efficiency values on 3 tetrameric short tandem repeat loci-HUMTH01, TPOX, and CSF1PO-derived using a STR multiplex system

Allele and genotype frequencies for 3 tetrameric short tandem repeat loci were determined in a Swiss population sample (n = 100) using the GenePrint STR Multiplex System, electrophoresis of the PCR products in DNA sequencing gels and subsequent detection of allelic fragments by silver staining. The loci are HUMTH01, TPOX, and CSF1PO. The observed heterozygosities are 83.0%, 60.0%, and 72.0%, respectively. The discrimination power determined for the individual loci is 0.914, 0.780, and 0.860, respectively, and the combined discrimination power for the triplex is 0.997. All loci meet Hardy-Weinberg expectations and after Bonferroni correction there was no evidence that the population sample deviates from expectations of independence. Moreover, independence of alleles at these STR loci with other PCR-based loci derived from the same Swiss population sample, previously reported, were considered. These loci were DQA1, LDLR, GYPA, HBGG, D7S8, GC and D1S80. Again, after Bonferroni correction there was no evidence that the population sample deviates from expectations of independence among alleles at the 10 different PCR-based loci. Thus, the allelic frequency data can be used in human identity testing to estimate the frequency of a multiple PCR-based DNA profile in the Swiss population.     

The polyploidization characteristics of the hepatocytes of the mouse-like hamster Calomyscus mystax

A cytophotometric measurement of DNA content in hepatocytes of maturing mouse-like hamsters was made. Cells belonging to ordinary mammalian ploidy classes 2c, 2c x 2, 4c, and 4c x 2 made about 90% of the hepatocyte population. The share of binucleated cells wa high (about 80%), the majority of these cells being 2c X 2 hepatocytes. Binucleated cells with tetraploid and diploid nuclei occur in almost every animal. An average hepatocyte ploidy level in mouse-like hamster is 4.6c. The main peculiarity of parenchymal liver cell populations is that up 5% of hepatocytes contain 3--11 nuclei of different ploidy classes. Multinucleated cells increase in number from 1.5% to 4% within the period from one year (the age of maturation) to two years. Later on their percentage does not change. It is found that in binucleated and multinucleated hepatocytes DNA synthesis can proceed asynchronously. Asynchrony in DNA synthesis elevates as the number of nuclei increases. Among the 2c x 2 and 2c x 3 cells an uneven distribution of 3H-thymidine label can occur, respectively, in 5 and in 50% cases, whereas all the cells with more than 3 nuclei display an uneven an uneven 3H-thymidin label distribution. The formation of multinucleated cells is supposed to be associated with asynchrony in DNA-synthesis in binucleated cells and with the restitution of mitosis.