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Graded exercise results not only in the modulation of adrenergic mediated smooth muscle tone and a preferential increase in blood flow to the active skeletal muscle termed 'functional sympatholysis', but is also paralleled by metabolically induced reductions in pH. We therefore sought to determine whether pH attenuates α(1)-adrenergic receptor sensitivity in human feed arteries. Feed arteries (560 ± 31 μm i.d.) were harvested from 24 humans (55 ± 4 years old) and studied using the isometric tension technique. Vessel function was assessed using KCl, phenylephrine (PE), ACh and sodium nitroprusside (SNP) concentration-response curves to characterize non-receptor-mediated and receptor-mediated vasocontraction, as well as endothelium-dependent and -independent vasorelaxation, respectively. All concentration-response curves were obtained from (originally contiguous) vessel rings in separate baths with a pH of 7.4, 7.1, 6.8 or 6.5. Reduction of the pH, via HCl, reduced maximal PE-induced vasocontraction (pH 7.4 = 85 ± 19, pH 7.1 = 57 ± 16, pH 6.8 = 34 ± 15 and pH 6.5 = 16 ± 5% KCl(max)), which was partly due to reduced smooth muscle function, as assessed by KCl (pH 7.4 = 88 ± 13, pH 7.1 = 67 ± 8, pH 6.8 = 67 ± 9 and pH 6.5 = 58 ± 8% KCl(max)). Graded acidosis had no effect on maximal vasorelaxation. In summary, these data reveal that reductions in extracellular pH attenuate α(1)-mediated vasocontraction, which is partly explained by reduced smooth muscle function, although vasorelaxation in response to ACh and SNP remained intact. These findings support the concept that local acidosis is likely to contribute to functional sympatholysis and exercise hyperaemia by opposing sympathetically mediated vasoconstriction while not impacting vasodilatation.

Heat and cold exposure can decrease and increase total peripheral resistance, respectively, in humans. With unique access to human skeletal muscle feed arteries, we sought both to characterize these vessels and to determine the interaction between temperature and α(1)-adrenergic receptor responsiveness. We hypothesized that α(1)-mediated vasocontraction of human feed arteries would be attenuated in response to 39 or 35°C. Skeletal muscle feed arteries were harvested from thirty-two human volunteers and studied using isometric techniques. Vessel function was assessed using KCl, sodium nitroprusside (SNP), phenylephrine (PE) and ACh dose-response curves to characterize non-receptor- and receptor-mediated vasocontraction and vasorelaxation. Single doses of PE (1 mm) and KCl (100 mm) were administered at 37°C and then, in a balanced design, repeated at both 35 and 39°C. The KCl and PE dose-response curves elicited significant vasocontraction (2009 ± 407 and 1974 ± 508 mg developed tension, respectively), whereas SNP and ACh induced the expected vasorelaxation (102 ± 6 and 73 ± 10% relaxation, respectively). Altering the temperature had no effect on inherent smooth muscle function (KCl response), but both a reduction (35°C) and an increase in temperature (39°C) decreased the vasocontractile response to 1 mm PE (37°C, 1478 ± 338 mg; 35°C, 546 ± 104 mg; and 39°C, 896 ± 202 mg; P < 0.05) or across PE dose (P < 0.05, 35 and 39 versus 37°C). Despite clear heterogeneity between both the human volunteers and the feed arteries themselves, this novel approach to the procurement of human vessels revealed a robust 'inverted U' response to altered temperature, such that α(1)-mediated vasocontraction was attenuated with either warming or cooling.

Background: Verruciform xanthoma (VX) is a rare, benign neoplasm arising predominantly in the oral cavity, but it has been reported to occur on the genital skin and mucosa as well. VX has also been described in association with epidermal nevi and squamous cell carcinoma. Because of the clinical and histologic similarities between VX and condyloma acuminata, and a recent report of HPV 6 in association with VX, we investigated the role of human papilloma virus (HPV) in the development of this entity. Methods: In situ hybridization and a nested PCR approach utilizing degenerate primers were utilized to establish whether HPV infection could be playing a role in the development of the VX. Results: In situ hybridization failed to identify HPV DNA. The highly sensitive nested PCR approach also failed to detect HPV DNA. Conclusions: The failure to detect HPV DNA, even by very sensitive methods, provides strong evidence that our case of VX is not an HPV-induced lesion. A review of other possible etiologies, including alternative infectious agents and genetic associations, are discussed.

Arterial aging is an important risk factor for cardiovascular disease. Telomeres are non-coding DNA repeats that protect coding DNA and shorten with each cell cycle in all mitotic tissues. Telomere...

The Radiation Therapy Oncology Group (RTOG) initiated a phase I/II study of intraoperative radiotherapy (IORT) in advanced or recurrent rectal cancer to assess therapeutic efficacy, toxicity, and establish quality control guidelines prior to beginning a phase III trial. From October 1985 through December 1989, 87 patients with histologically proven adenocarcinoma of the rectum or rectosigmoid with recurrent/persistent disease after surgery or those primarily inoperable were entered by 14 institutions. Of 86 evaluable patients, 42 patients received IORT either alone (n = 15) or in combination with external beam (n = 27). Local control was dependent on the amount of residual disease prior to IORT, with 2-year actuarial local control of 77% if no gross residual disease remained vs. 10% with gross residual disease (P = 0.0001). For the recurrent/residual group (n = 33), this observation was also significant with a 2-year actuarial local control rate of 64% if no gross residual remained vs. 10% with gross residual disease (P = 0.004). Local control translated into an improved survival for all patients and the recurrent/residual group with 2-year actuarial survival of 88% and 89% if no gross residual disease remained vs. 48% and 45% with gross residual disease, respectively (P = .0005, 0.006). Six patients (14.6%) experienced four grade 3 and three grade 4 complications as a possible result of IORT during follow-up with a 2-year actuarial risk of major complications of 16%. We conclude that IORT is feasible within a cooperative group and can be performed with acceptable complication rates. A phase III trial to demonstrate a therapeutic advantage for IORT over external beam alone is currently in progress. © 1993 Wiley-Liss, Inc.

Breast cancer in women 30 years of age or less accounts for 2% of all breast cancers seen today. At M. D. Anderson Hospital, 310 young women in this age group were seen, 141 of whom received their primary treatment there. After excluding all those with inflammatory and noninvasive carcinomas, 125 patients were analyzed for survival according to nodal status, lesion size, and pregnancy status. This group was compared to a similarly matched group of 3,380 women over age 30 years also treated at this institution. Young women with negative nodes and those with lesions less than 5 cm in size were found to have significantly poorer survivals than older women in the same groups, in contrast to several recent reports on this subject.