An evaluation of the dental assistant utilization program at the University of Alabama School of Dentistry

Dr. Ramirez and the students assisting him, have performed, and now report an interesting study of the impact of the DA U Program on the practices of dental students of the University of Alabama after they graduate.     

Reduced ubiquinone plasma levels in patients with liver cirrhosis and in chronic alcoholics

Ubiquinone (CoQ₁₀ coenzyme) is part of the respiratory chain in mitochondria, and acts as a scavenger in oxidative stress in cell membranes. Ubiquinone is mainly synthesized in the liver and partly derived from the diet; its plasma levels significantly correlate with tissue levels in experimental animals and in pathological states in man. By means of an original high-performance liquid chromatography technique, we measured ubiquinone plasma levels in 10 healthy subjects, in 27 patients with cirrhosis and in 22 chronic alcoholics with normal liver function. Ubiquinone levels were markedly reduced in cirrhosis (0.25 [SD 0.21] μg/ml vs. 0.92 [0.38] in controls; P<0.001), without any difference between alcohol- and non-alcohol-related disease. Also, in chronic alcoholics ubiquinone levels were nearly halved (0.49 [0.24]). In cirrhosis, ubiquinone plasma levels significantly correlated with cholesterol (P<0.05), and with total bilirubin levels (P<0.01). Our study highlights a remarkable deficiency in ubiquinone levels in patients with cirrhosis and in chronic alcoholics, to which both reduced hepatic synthesis and nutritional defects may contribute.     

The Nutcracker Esophagus: A Late Diagnostic Yield Notwithstanding Chest Pain and Dysphagia

The nutcracker esophagus, a primary motor disorder, is frequently associated with noncardiac chest pain. However, there are no data on whether its diagnosis, as in other esophageal motility disorders, is delayed. Since the disorder is frequently heralded by alarming symptoms such as chest pain and dysphagia, diagnosis should be made as soon as possible. In this study we assessed the diagnostic delay, if any, in patients with the nutcracker esophagus. Moreover, we were interested in whether the abnormalities described in the distal esophagus could also involve the entire viscus. Fifty-four subjects (age range 23–78 yr) with the nutcracker esophagus were assessed for clinical and manometric variables as an overall group and after dividing them into subgroups according to their symptoms. The manometric variables were compared with those obtained in 61 controls (age range 21–67 yr). Overall, a diagnosis of nutcracker esophagus was made after an average period of 36 ± 6 months, and surprisingly, this was not different in the various subgroups complaining of either chest pain, dysphagia, or both. Analysis of manometric variables showed that the mean amplitude of contractions was significantly higher in the patients' group at all esophageal body levels, even in the proximal portions. Again, there were no significant differences among the subgroups of nutcracker esophagus with respect to the symptoms. Notwithstanding the presence of alarming symptoms, such as chest pain and dysphagia, the nutcracker esophagus is diagnosed on average after 3 years from the onset of symptoms. Manometric assessment seems to confirm that this entity may indeed represent a primary esophageal motor disorder. The major dysfunction is due to an abnormal increase of contraction amplitude of the entire esophageal body.     

Sequential treatment with exemestane and non-steroidal aromatase inhibitors in advanced breast cancer

BACKGROUND: The steroidal aromatase inactivator exemestane has demonstrated activity after prior failure of non-steroidal aromatase inhibitors (including third-generation inhibitors letrozole and anastrozole) in postmenopausal women with advanced breast cancer. If exemestane is used as first anti-aromatase agent, however, it is unclear whether patients can still benefit from letrozole or anastrozole after progression. PATIENTS AND METHODS: Postmenopausal patients with advanced, hormone receptor-positive or -unknown breast cancer were eligible for this study. Patients with no prior exposure to anti-aromatase drugs received exemestane, 25 mg daily, as first anti-aromatase agent. At the time of progression, patients were crossed-over to anastrozole or letrozole if further endocrine therapy was considered appropriate. Patients with prior exposure to anti-aromatase agents were also included in the study, and were given anastrozole or letrozole if they had previously received exemestane, or exemestane if they had previously received anastrozole or letrozole. The primary endpoint of the study was the clinical benefit rate (complete response + partial response + stabilization of disease for >or=24 weeks). RESULTS: Forty patients received exemestane 25 mg daily as first anti-aromatase agent, with a CB rate of 67.5% (95% CI 52.9-82.0%) and a median time to progression (TTP) of 9.6 months. In 18 patients, letrozole (n = 17) or anastrozole (n = 1) were used after failure of exemestane: the CB rate was 55.6% (95% CI 32.6-78.5%) with a median TTP of 9.3 months. In 23 patients, exemestane was used after failure of letrozole or anastrozole: the CB rate was 43.5% (95% CI 23.2-63.7%) with a median TTP of 5.1 months. CONCLUSIONS: Our study confirms that exemestane is active after prior failure of letrozole or anastrozole. We have also shown that patients can receive exemestane as their first anti-aromatase agent and still benefit from letrozole or anastrozole after progression. This suggests that the partial non-cross resistance between steroidal and non-steroidal anti-aromatase agents is independent of the sequence employed.     

Docking of 6-chloropyridazin-3-yl derivatives active on nicotinic acetylcholine receptors into molluscan acetylcholine binding protein (AChBP)

The crystal structure of Acetylcholine Binding Protein (AChBP), homolog of the ligand binding domain of nAChR, has been used as model for computational investigations on the ligand-receptor interactions of derivatives of 6-chloropyridazine substituted at C3 with 3,8-diazabicyclo[3.2.1]octane, 2,5-diazabicyclo[2.2.1]heptane and with piperazine and homopiperazine, substituted or not at N4. The ligand-receptor complexes have been analyzed by docking techniques using the binding site of HEPES complexed with AChBP as template. The good relationship between the observed binding affinity and the calculated docking energy confirms that this model provides a good starting point for understanding the binding domain of neuronal nicotinic receptors. An analysis of the possible factors significant for the ligand recognition has evidenced, besides the cation-pi interaction, the distance between the chlorine atom of the pyridazinyl group and the carbonylic oxygen of Leu B112 as an important parameter in the modulation of the binding energy.