Pharmacological profile of the vascular responses to dopamine in the canine external carotid circulation

The present study investigated the effects of dopamine on the canine external carotid circulation. One min. intracarotid artery (i.c.) infusions of dopamine (10-310 microg min.-1) produced dose-dependent decreases in the canine external carotid conductance without affecting blood pressure or heart rate. This effect was mimicked by the D1/2-like receptor agonist apomorphine (1-310 microg min-1), but not by the D2-like receptor agonist, bromocriptine (31-310 microg min.-1). In contrast, fenoldopam (1-310 microg min.-1, intracarotid), a D1-like receptor agonist, produced dose-dependent increases in external carotid conductance. The vasoconstrictor response to dopamine was abolished after intravenous administration of the antagonists, phentolamine (alpha1/2; 2000 microg kg-1) or rauwolscine (alpha2; 100 microg kg-1), but remained unaffected after prazosin (alpha1; 100 microg kg-1) or haloperidol (D2-like; 1000 microg kg-1). Interestingly, after phentolamine not only were the vasoconstrictor responses to dopamine abolished, but even a dose-dependent vasodilator component was unmasked. These vasodilator responses to dopamine remained unchanged after intravenous haloperidol or propranolol (1000 microg kg-1 each). On the other hand, the vasodilator responses to fenoldopam, which remained unchanged after intravenous saline (0.1 ml kg-1), propranolol (1000 microg kg-1) or vagosympathectomy, were abolished by the D1-like receptor antagonist, SCH-23390 (10 microg kg-1). Lastly, the responses to dopamine and fenoldopam were not significantly altered after intraperitoneal pretreatment with reserpine (5 mg kg-1; -24 hr). The above results suggest that the canine external carotid vasoconstrictor responses to dopamine: (i) are mainly mediated by alpha2-adrenoceptors; and (ii) overshadow a vasodilator component, which involves vascular D1-like receptors.     

Neoadjuvant chemotherapy and preoperative chemoradiotherapy in resectable carcinoma of the rectum

Introduction

The effectiveness of neoadjuvant chemotherapy (Mayo clinic schedule) and continuous oral chemotherapy (tegafur 400 mg and folinic acid 15 mg every 12 hours) administered during preoperative radiotherapy (4,500 cGy over 5 weeks) were studied

Materials and methods

A total of 53 patients with surgically-resectable rectal adenocarcinoma were treated.

Results

Toxicities of ≤ grade II were lower with neoadjuvant chemotherapy while the chemoradiotherapy had higher toxicity rates including grade III diarrhoea (4%), grade III mucositis (4%), and grade III–IV neutropenia (9%). Symptom improvement ocurred in 38% of patients after neoadjuvant chemotherapy coparative with 55% following the first week of chemoradiotherapy. Surgery was curative in 97% of the patients: abdominoperineal amputation in 24 patients (47%) and conservative surgery in 28 (53%). Down-staging ocurred in 24 patients (46%), and 7 patients (14%) showed pathological complete response. Overvall survival at 5 years, with a median follow-up of 50 months, was 70% (cancer-specific survival was 75%) with significant differences recorded between N+ and N0 patients (56% and 76%, respectively; p<0.001), and between T-0-1-2 and T3 patients (73% and 56%, respectively; p<0.001). Only 2 patients (3%) had local relapse.

Conclusion

This treatment scheme was well tolerated and had high rate of local control and longterm times.     

Interrelationship between bone turnover markers and dietary calcium intake in pregnant women: a longitudinal study

This longitudinal study evaluated bone turnover and the interrelationship between changes in bone biomarkers and habitual dietary calcium intake during pregnancy in a group of women ranging widely with regard to dietary calcium intake. Thirty-nine healthy pregnant and 30 nonpregnant women were studied. Calcium, phosphorus, 1alpha,25-dihydroxyvitamin D (1,25diHOD), bone alkaline phosphatase (bALP), carboxyterminal propeptides of type I procollagen (PICP) and carboxyterminal telopeptides of type I collagen (betaCTX and ICTP) were measured in serum and calcium, and creatinine and aminoterminal telopeptide (NTX) were determined in urine. Serum calcium and phosphorus did not change but the urinary Ca/Creat ratio and 1,25diHOD increased throughout pregnancy (P < 0.001 and P < 0.0001, respectively). Serum b-ALP and PICP increased during the last two trimesters (P < 0.0001 and P < 0.001, respectively). All studied bone resorption markers increased compared to nonpregnant values throughout pregnancy. The highest increment was observed in the third trimester. The level of significance decreased as follows: betaCTX > NTX >ICTP. Serum 1,25 diHOD versus calcium intake showed a positive and significant correlation (r = 0.51, P < 0.02). A negative correlation between the absolute change in betaCTX, NTX, and b-ALP between the third and second trimester and calcium intake at the end of pregnancy was observed in pregnant women who did not cover adequately calcium intake requirements (r = -0.47, P < 0.03; r = -0.41, P < 0.05; and r = -0.43, P < 0.05, respectively). These results suggest that skeletal response to pregnancy may not be entirely independent of maternal calcium intake, especially in women with usually low calcium intake. In summary, not only hormonal changes in calcium metabolism that occur during pregnancy but also other considerations, such as low dietary calcium intake, may lead to an increment in the biological activity of the skeleton. Additional studies must be conducted to confirm our findings and to gain a better understanding of skeletal response to a low calcium intake during pregnancy.     

Management of N0 neck in laryngeal carcinoma. Impact on patient's survival

Management of patients with carcinoma of the larynx should systematically include an appropriate treatment of lymph nodes according to the TNM stage. One of the most controversial points of the treatment in these patients is the management of the clinically negative neck (N(0)). A retrospective study of 295 patients with laryngeal carcinoma and N(0) neck undergoing treatment in our centre between 1983 and 1993 is presented. We observed a significant decrease in the survival of clinically N(0) patients with histologically affected lymph nodes. Lymphadenopathy was more frequently detected in patients with supraglottic tumours (38 per cent) when compared to glottic tumours (16 per cent). In our experience, routine bilateral and unilateral dissection of N(0) necks in all supraglottic tumours and in T3-T4 glottic tumours, respectively, is the most beneficial approach for patients in terms of survival.     

Familial isolated unilateral large vestibular aqueduct syndrome

Large vestibular aqueduct syndrome (LVAS) is one of the most frequent inner ear malformations. It is associated with varying degrees of hearing loss, that may be progressive, sudden or fluctuant; nevertheless normal hearing in cases with LVAS has been described. Although unilateral LVAS has been described, all patients show clinical and radiological findings in both ears, in contrast to the family presented here, where 2 siblings are affected by unilateral sensorineural hearing loss associated with ipsilateral LVAS, with an autosomal recessive pattern. In order to search for the origin of this inner ear malformation, mutations in genes GJB2 (connexin-26 gene), PDS (Pendred's syndrome gene) and mitochondrial 12sRNA were studied, without positive results. In this paper we hypothesize the probable embryological origin for this malformation.     

CT colonography with teleradiology: effect of lossy wavelet compression on polyp detection--initial observations

PURPOSE: To assess the consequences of lossy compression on the diagnostic accuracy of CT colonography for detecting colonic polyps. MATERIALS AND METHODS: Helical CT images of cleansed colonic segments were evaluated. Source images were compressed to 1:1, 10:1, and 20:1 ratios with lossy wavelet compression. Two independent readers blinded to corresponding colonoscopic results analyzed 144 randomly ordered colonic segments in multiplanar and volume-rendered endoscopic views. Sensitivity, specificity, and receiver operating characteristic curves were generated for each compression ratio on the basis of expressed confidence in lesion presence. Similar analyses were performed to assess distention and bowel preparation adequacy and evaluation time required. RESULTS: Results based on video colonoscopy-confirmed lesions revealed 100% (four of four) sensitivity for lesions larger than 10 mm for compression ratios 1:1, 10:1, and 20:1 for both readers; sensitivities for all lesions smaller than 10 mm were 50%-78%, 38%-67%, and 38%-67% for respective ratios for both readers. Differences in diagnostic performance for each reader across ratios were not significant (P =.30-.99, McNemar test). The time required to evaluate and assess bowel preparation and distention adequacy did not change significantly across ratios. CONCLUSION: On the basis of the patient sample, lossy compression of transverse source images to at least a 20:1 ratio did not adversely affect diagnostic performance or evaluation time for CT colonography.