Salvage with supracricoid partial laryngectomy after radiation failure

BACKGROUND: Supracricoid partial laryngectomy (SCPL) is an alternative to total laryngectomy (TL) for selected glottic and supraglottic carcinomas but its role in the setting of radiation failure is unclear. The aim of the present study was to present a series of patients with laryngeal cancer undergoing salvage surgery for local recurrence and examine the morbidity associated with this intervention. METHODS: A retrospective review of 111 patients presenting with laryngeal cancer between 1997 and 2002 was performed. A total of 21 patients with recurrent disease following radiation therapy were identified, of which salvage surgery was performed in 18 patients. Minimum follow up of survivors was 22 months. RESULTS: The 5-year cumulative local control and disease-specific survival was 76% and 85%, respectively. Surgical salvage consisted of TL in 12 patients and SCPL in six. The mortality and major morbidity rates for TL were 0% and 33%, and for SCPL they were 33% and 50%, respectively. Median length of hospital stay was similar in both groups (21 and 19 days). No patient undergoing SCPL developed recurrent disease at a median follow up of 19 months. CONCLUSIONS: Supracricoid partial laryngectomy is an oncologically sound alternative to TL as salvage for radiation failure. The operative morbidity and potential for mortality is high in this setting.     

Failure of conventional strategies to improve nutritional status in malnourished adolescents and adults with cystic fibrosis

The use of oral dietary supplements was compared with dietary counseling in 13 malnourished patients (3 males, mean age 18.1 years) with cystic fibrosis. Energy intake and nutritional status were evaluated over 3 months. There was no significant change in energy intake or percent ideal body weight in either group.     

C‐reactive protein levels and common polymorphisms of the interleukin‐1 gene cluster and interleukin‐6 gene in patients with coronary heart disease

C‐reactive protein (CRP) is an inflammatory marker associated with increased cardiovascular risk. Production of CRP is regulated by interleukin (IL)‐1β, IL‐1 receptor antagonist and IL‐6. In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL‐1B(?511), IL‐1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL‐1RN [IL‐1RN(VNTR)], IL‐6(?174) and IL‐6(?572). CRP values were logarithmically normalized (log‐CRP) for statistical calculations. In univariate analysis, carrier status for the IL‐1B(+3954)T allele and IL‐1RN(VNTR) allele 2 [IL‐1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log‐CRP values, respectively. Among the potential confounding factors analysed, smoking, body mass index, total cholesterol (P < 0.05 for all) and diabetes (P = 0.056) were positively correlated with CRP level. After adjustment for non‐genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL‐1B(+3954)T than in non‐carriers: mean log‐CRP (with 95% confidence interval) was 0.443 (0.311–0.574) for CT or TT genotypes compared with 0.240 (0.107–0.373) for the CC genotype, which corresponded to back‐transformed CRP levels of 2.77 and 1.74 mg l^?1, respectively. Adjusted association was also significant for IL‐1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log‐CRP value was 0.252 (0.115–0.388) for carriers and 0.421 (0.290–0.552) for non‐carriers (CRP 1.79 and 2.64 mg l^?1, respectively). When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL‐1B(+3954)T (P < 0.05), but not for IL‐1RN(VNTR)*2. We conclude that IL‐1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors. Our data also suggest a possible relationship of IL‐1RN(VNTR)*2 with lower CRP levels in the same patients.     

Comparison of the cytoskeleton in aortic endothelial cells in situ and in vitro

Using fluorescence microscopy and a previously developed technique for making en face preparations of aortic endothelial cells (EC), we have compared the distribution of microtubules, centriolar regions, and microfilaments in porcine EC in situ with that in EC from the same source grown in monolayers in vitro. The results show that the cytoskeleton of EC undergoes considerable reorganization when EC are removed from the blood vessel and cultured. In vivo the microtubules run helically along the longitudinal axis of EC. It is not clear that all of these microtubules originate from the centriolar region which is located at one end of the nucleus, usually toward the heart. Prominent bundles of microfilaments extend almost the full length of the cell in a direction parallel to blood flow. In contrast, in EC in culture almost all of the microtubules radiate from a single prominent perinuclear microtubule-organizing center toward the cell periphery. In adjacent cells this microtubule-organizing center, which contains the centrioles, is randomly oriented with respect to the nucleus. The microfilaments in EC in vitro form a much more complex pattern in which circumferentially, radially, and longitudinally oriented bundles are evident. These results indicate that a dramatic rearrangement in these components of the cytoskeleton takes place when EC from the aorta are cultured in vitro and that care should be exercised in applying results of in vitro observations on EC to the cells of the endothelium lining blood vessels.     

Enteric-coated pancreatic enzyme with bicarbonate is equal to standard enteric-coated enzyme in treating malabsorption in cystic fibrosis

OBJECTIVES: To compare the efficacy of an enteric-coated buffered pancreatic enzyme (EC buffered PE) containing 1.5 mEq of bicarbonate per capsule with a conventional enteric-coated enzyme (EC-PE) capsule in cystic fibrosis patients with signs or symptoms of moderate to severe malabsorption. METHODS: In a double-blind crossover study, subjects were randomly assigned to two consecutive, 2-week phases using an EC buffered PE product and conventional EC-PE product. Seventy-two hour stool collections from each phase were analyzed for energy, fat, and nitrogen content and expressed as percent of estimated intake. RESULTS: Twenty-one patients with cystic fibrosis and pancreatic insufficiency (14 female, mean age 20.6 +/- 11.5 years, range 8.8-41.9) completed the study. There was no significant difference in percent malabsorption of energy (19.4% vs. 19.0%), fat (20.7% vs. 20.2%), or nitrogen (10.4% vs. 10.7%) between the EC buffered PE product and the conventional EC-PE product. However, patients taking the EC buffered PE product received less enzyme based on actual enzyme activity measured in vitro (3,468 +/- 1,434 U lipase/g fat vs. 3,978 +/- 1,474 U lipase/g fat, P < 0.02). CONCLUSIONS: In the doses used, nutrient absorption of patients taking EC buffered PE preparation offers no advantage over a conventional EC-PE preparation.     

Alternative mutations of a positively selected residue elicit gain or loss of functionalities in enzyme evolution

All molecular species in an organism are connected physically and functionally to other molecules. In evolving systems, it is not obvious to what extent functional properties of a protein can change to selective advantage and leave intact favorable traits previously acquired. This uncertainty has particular significance in the evolution of novel pathways for detoxication, because an organism challenged with new xenobiotics in the environment may still require biotransformation of previously encountered toxins. Positive selection has been proposed as an evolutionary mechanism for facile adaptive responses of proteins to changing conditions. Here, we show, by saturation mutagenesis, that mutations of a hypervariable residue in human glutathione transferase M2-2 can differentially change the enzyme's substrate-activity profile with alternative substrates and, furthermore, enable or disable dissimilar chemical reactions. Crystal structures demonstrate that activity with epoxides is enabled through removal of steric hindrance from a methyl group, whereas activities with an orthoquinone and a nitroso donor are maintained in the variant enzymes. Given the diversity of cellular activities in which a single protein can be engaged, the selective transmutation of functional properties has general significance in molecular evolution.     

Prolonged interval between sentinel pseudotumoral demyelination and development of primary CNS lymphoma.

Primary central nervous system lymphoma (PCNSL) can be associated with preceding demyelinating pseudotumoral brain lesions. The 'sentinel' demyelinating lesions recede spontaneously or with corticosteroid, and are followed by development of PCNSL typically within 12 months. This report describes a 29 year-old post-partum woman who developed PCNSL 4 years after a biopsy-proven pseudotumoral demyelinating episode. She presented with focal seizures in February 2005. She subsequently developed hemiparesis and raised intracranial pressure. MRI showed two contrast enhancing lesions in the right frontal lobe, which were hypermetabolic on (18)F-FDG PET. A provisional diagnosis of tumefactive multiple sclerosis was made. Symptoms recurred despite multiple courses of high dose corticosteroid. Brain biopsy confirmed large B-cell non-Hodgkin's lymphoma. This patient illustrates the importance of considering PCNSL in patients presenting with a space-occupying lesion, even with previously confirmed demyelination, and that the interval between the two events may be several years.