Peroxisome proliferator-activated receptor (PPAR)-alpha activation lowers muscle lipids and improves insulin sensitivity in high fat-fed rats: comparison with PPAR-gamma activation.

Peroxisome proliferator-activated receptor (PPAR)-alpha agonists lower circulating lipids, but the consequences for muscle lipid metabolism and insulin sensitivity are not clear. We investigated whether PPAR-alpha activation improves insulin sensitivity in insulin-resistant rats and compared the effects with PPAR-gamma activation. Three-week high fat-fed male Wistar rats were untreated or treated with the specific PPAR-alpha agonist WY14643 or the PPAR-gamma agonist pioglitazone (both 3 mg x kg(-1) x day(-1)) for the last 2 weeks of high-fat feeding. Like pioglitazone, WY14643 lowered basal plasma levels of glucose, triglycerides (-16% vs. untreated), and leptin (-52%), and also muscle triglyceride (-34%) and total long-chain acyl-CoAs (LCACoAs) (-41%) (P < 0.05). In contrast to pioglitazone, WY14643 substantially reduced visceral fat weight and total liver triglyceride content (P < 0.01) without increasing body weight gain. WY14643 and pioglitazone similarly enhanced whole-body insulin sensitivity (clamp glucose infusion rate increased 35 and 37% and glucose disposal 22 and 15%, respectively, vs. untreated). Both agents enhanced insulin-mediated muscle glucose metabolic index (Rg') and reduced muscle triglyceride and LCACoA accumulation (P < 0.05). Although pioglitazone had more potent effects than WY14643 on muscle insulin sensitization, this was associated with its greater effect to reduce muscle LCACoA accumulation. Overall insulin-mediated muscle Rg' was inversely correlated with the content of LCACoAs (r = -0.74, P = 0.001) and with plasma triglyceride levels (r = -0.77, P < 0.001). We conclude that even though WY14643 and pioglitazone, representing PPAR-alpha and PPAR-gamma activation, respectively, may alter muscle lipid supply by different mechanisms, both significantly improve muscle insulin action in the high fat-fed rat model of insulin resistance, and this effect is proportional to the degree to which they reduce muscle lipid accumulation.

Troglitazone corrects metabolic changes but not vascular dysfunction in dietary-obese rats.

Insulin resistance has been attributed to the defect in vascular function associated with obesity, type 2 diabetes and dyslipidaemia. We have investigated vascular effects of chronic (3-week) administration of troglitazone on female Wistar rats with moderate dietary obesity. Compared with lean controls, untreated obese rats had significantly higher body weights, fat pad masses, plasma triglycerides, free fatty acids and leptin levels (for all P < 0.01). These metabolic changes were corrected by troglitazone treatment. In mesenteric arteries, responses to noradrenaline or KCl were similar in all groups. However, in noradrenaline-preconstricted arteries, vasorelaxations to acetylcholine and insulin were significantly (50-60% less than in lean, P < 0.001) attenuated in both untreated and troglitazone-treated obese rats. Relaxations to sodium nitroprusside showed similar but lesser impairment in both untreated and troglitazone-treated obese animals. Our data show that although troglitazone markedly improved obesity-induced metabolic changes, it failed to correct vascular dysfunction associated with obesity in female Wistar rats.

Carcinoma in situ of the larynx.

A retrospective study of carcinoma in situ of the larynx at the British Columbia Cancer Institute indicates that radiotherapy, using a tumoricidal dose of Co 60, is the treatment of choice for this condition. Between 1940 and 1972, 43 patients with carcinoma in situ of the vocal cords were seen. A follow-up of five years or more was possible in 28 of these cases. Twenty-two were treated primarily with a tumoricidal dose of radiotherapy. Twenty-one of the 22 were free of disease for at least five years. This study, therefore, shows a five-year cure rate of almost 100 percent for patients treated with radiotherapy. It also brings out two further points regarding carcinoma in situ of the larynx; namely, an apparent increase in its incidence, and the presence of co-existing invasive carcinoma in some cases. We feel that since the incidence of laryngeal carcinoma has not increased, this apparent increase probably represents a greater awareness by both the pathologist and the clinician. We have also achieved more accurate diagnosis since the introduction of routine microlaryngoscopy. The single radiotherapy failure in our series was due to failure to diagnose co-existing invasive carcinoma. This would seem to be the most likely cause of similar failures reported in the literature.

Solubilization kinetics of a triglyceride/n-alkane mixture in a non-ionic surfactant solution.

The kinetics of solubilization in a non-ionic surfactant solution of pure n-hexadecane, pure triolein and a mixture of the two oils have been investigated. The rates were determined from observations of the dissolution of a single, microscopic droplet, using a drop-on-fibre technique. Conditions were such that negligible saturation of the micellar surfactant with solubilizate occurred. The rate of solubilization of each of the pure oils was found to be independent of time, hexadecane solubilization on a volume basis being about 8 times as rapid as that for triolein. The rate of solubilization of a mixture of the two oils, having a volume fraction 0.69 for triolein, was found to vary in the medium term, the rates apparently being steady both initially and (at a lower value) in the long term. These observations can be related quantitatively to the rates found for the pure oils.

Repair of supraglottic laryngeal stenosis with postcricoid involvement. A case report.

A supraglottic stenosis with postcricoid stenosis was successfully corrected in a single stage procedure by excising the scar tissue and the arytenoid cartilage and the use of mucosal flaps to recover the right side of the larynx and postcricoid area. By obtaining good mucosal approximation without tension the need for a free skin graft or mucosal graft was avoided.

Glottic squamous cell carcinoma (T(2)): a retrospective study.

Seventy-three patients with T(2) glottic squamous cell carcinoma were treated primarily with a full course of cobalt radiotherapy. This series covered the time period between 1960 and 1972 and, therefore, all patients were eligible for five-year follow-up. Only seven patients, or 9.6%, have died of or with recurrent laryngeal carcinoma. Fourteen patients suffered recurrence of disease after radiotherapy and 12 of this group underwent salvage surgery. Surgery was successful in controlling recurrent disease in 7 of 12 patients, 3 of whom are still alive and free of disease. Forty-two patients, or 57.5%, are alive and free of disease five or more years after diagnosis. Twenty-four patients died without evidence of disease; 11 lived more than five years and 13 died in less than five years. On the basis of these findings, we feel that the best treatment for T(2) glottic squamous cell carcinoma is a full course of cobalt radiotherapy followed, when necessary, by salvage surgery.

Phrenic nerve reinnervation of the cat's larynx: a new technique with proven success.

Reinnervation of the posterior cricoarytenoid muscle (PCA) should provide vocal cord abduction on inspiration, and passive adduction to enable phonation. Previous investigators have shown that reinnervation is possible, but results have not been clinically encouraging. When reinnervation was successful, the question remained whether it was provided by the transplanted nerve or by the ingrowth of adjacent nerves. In this study the phrenic nerve was transplanted directly into the PCA in a series of 12 cats. Fibrin glue was used to overcome nerve trauma and to prevent retraction of the nerve from the PCA. Laryngoscopy, electromyography, and retrograde labeling of the phrenic motoneurons provided evidence of functional reinnervation in 9 cats. Partial or complete failure in the remaining 3 was due to retraction of the nerve from the muscle. These results appear to justify trials of the procedure in humans.

Effects of treatment for sound errors in apraxia of speech and aphasia.

This investigation was designed to examine the acquisition, generalization, and maintenance effects of a treatment for sound errors in speakers with co-occurring apraxia of speech and aphasia. Three speakers with chronic apraxia of speech and aphasia were studied in the context of a multiple baseline design across speakers and behaviors. Treatment combined the use of minimal contrast pairs with traditional sound production training techniques such as integral stimulation and articulatory placement cueing and was applied sequentially to sounds that were determined to be consistently in error before training. Results revealed increased correct sound productions for all speakers in trained and untrained words. Response generalization effects across sounds and stimulus generalization effects varied, but appeared to be limited for most speakers. Although positive maintenance effects were evidenced, some loss of treatment gains was noted following cessation of treatment.

Facilitating generalized requesting behavior in Broca's aphasia: an experimental analysis of a generalization training procedure.

The effects of a generalization training procedure on requesting by 4 subjects with chronic Broca's aphasia were examined using a multiple baseline design across behaviors and subjects. Subjects were trained to request information on three topics sequentially. Generalization across topics and persons was assessed in weekly probe sessions consisting of 5-min conversational interactions with trainers and unfamiliar volunteers in a nontreatment setting. Results revealed generalization effects were greatest when trainers, as opposed to unfamiliar volunteers, served as conversational participants. Nevertheless, subjects' requests increased with all conversational participants to a level comparable to a normal comparison group assessed under conditions identical to the experimental probes. Social validation of treatment effects using a subjective evaluation procedure revealed significant improvement on the parameters of talkativeness, inquisitiveness, and conversational success.