Effects of preoperative chemoradiotherapy on postsurgical morbidity and mortality in cT3-4 +/- cM1lymph cancer of the oesophagus and gastro-oesophageal junction.

OBJECTIVE: Very few studies have examined post-operative morbidity after resection of oesophageal carcinoma, especially in patients treated with induction chemo- and radiotherapy for locally advanced stages. This study assessed the effects of induction chemoradiotherapy on post-operative course after resection of locally advanced oesophageal carcinoma (cT3-4 + cM1lymph). METHODS: Induction therapy consisted of 5-fluorouracil days 1-5 and days 21-25, cisplatin day 1 + day 21 and concomitant radiotherapy 18-20 fractions of 2Gy (total dose 36-40Gy). Induction chemoradiotherapy was completed in 109 patients. Surgery was performed in 90 patients (operability: 90/109 = 83%): 85 patients underwent resection with curative intent (resectability: 85/109 = 78%), bypass operation was performed in five patients. Nineteen patients could not be operated on. Results were compared to a matched group of pT3M1LYM/pT4 patients (n = 86) who underwent primary surgery in the same period. RESULTS: Resection was complete (R0) in 68 patients (68/90 = 76%). Mean duration of surgery was 428 min (range: 240-690). Peroperative complications were haemorrhage in three patients (3/90 = 3.3%), tracheobronchial perforation in three patients (3/90 = 3.3%). Median total hospital stay was 20.5 days (range: 8-355). Mean duration of intubation was 7 days (range: 1-190); 67 patients (67/90 = 74.4%) were intubated for less than 24 h. Non-tumour related hospital mortality after resection was 8.3% (7/84 patients). Mortality after two-field lymphadenectomy was 5.2 versus 11.7% after three-field lymphadenectomy. After primary surgery (n = 86) overall mortality was 2.3% (P = 0.015) and nil after two- and three-field lymphadenectomy (P = 0.011). Medical morbidity consisted of pneumonia in 43 patients (43/90 = 48%), atelectasis in ten patients (10/90 = 11%), dysrhythmia in 21 patients (21/90 = 23%), sepsis in 11 patients (11/90 = 12%) and adult respiratory distress syndrome in ten patients (10/90 = 11%). Surgical morbidity included pleural effusion in 16 patients (16/90 = 18%), tracheal fistula in two patients (2/90 = 2%), chylothorax in two patients (2/90 = 2%) and acute pancreatitis in one patient (1/90 = 1%). Ten patients (10/90 = 11%) had a radiologically confirmed anastomotic leak; however only in four out of them with clinical manifestation; treatment was conservative in all four patients. Major morbidity occurred in 27 patients (27/90 = 30%). Overall rate of morbidity was significantly higher after three-field lymphadenectomy (85%) as compared to two-field lymphadenectomy (68.7%; P = 0.023). CONCLUSIONS: Chemoradiotherapy followed by resection of cT3-4 +/- cM1lymph oesophageal carcinoma is feasible with acceptable mortality. Mortality, however, seems to be significantly higher when compared to a group of pT3M1LYM/pT4 patients who underwent primary surgery (8.3 versus 2.3%; P = 0.015) in the same period in our department.     

A non-azole inhibitor of lanosterol 14 alpha-methyl demethylase in Candida albicans.

6-Hydroxy-N-methyl-N-(2-[4-phenylphenyl] ethyl)-1,2,3,4-tetrahydro-1- napthalene methanamine (A60586), a new non-azole inhibitor of ergosterol biosynthesis in Candida albicans ATCC62376 has been identified. In whole cells A60586 produced a dose related reduction of [14C]acetate incorporation into ergosterol and a concurrent increase in the radiolabelling of 4,4-dimethylated sterols. Similar observations were made with [14C]mevalonic acid lactone labelled cell free extracts. The IC50s for inhibition of ergosterol in the whole cell and cell free systems were 22 microM (10 mg/L) and 7.8 microM (3.5 mg/L), respectively. Analysis by gas chromatography of sterols from cells previously incubated at 37 degrees C for 24 h with A60586 (200 mg/L) confirmed the presence of lanosterol and 14 alpha-methyl fecosterol. These data indicate that A60586, inhibits the demethylation of the C-14 methyl group of lanosterol. The MIC of A60586 for several candida strains ranged from 12.5 to 50 mg/L, and against Cryptococcus albidus and Aspergillus niger ranged from 50 to 100 mg/L. The best in-vitro activity of A60586 was against Torulopsis glabrata (MIC range = 3.12 to 50 mg/L). The membrane permeabilizing effect of this compound (50% leakage of [14C]aminoisobutyric acid at 70 mg/L A60586) may have contributed to its in-vitro antifungal activity.     

Glutathione ester protects against hydroxynonenal-induced loss of auditory hair cells.

OBJECTIVE: Test the ability of glutathione monoethyl ester (GSH(e)) to protect auditory hair cells against the ototoxic effects of 4-hydroxy-2,3-nonenal (HNE). STUDY DESIGN AND SETTING: Organ of Corti explants were either untreated or treated with one of a series of four concentrations of GSH(e) for one day, then exposed to HNE. Counts of FITC-phalloidin-labeled hair cells determined both HNE ototoxicity and GSH(e) otoprotection. RESULTS: HNE was toxic to hair cells at physiologically relevant levels, eg, 400 muM, and GSH(e) provided a significant level of protection against HNE ototoxicity (P < 0.05) at all levels tested, ie, 1.16 to 9.3 mM. CONCLUSION: GSH(e) protects auditory hair cells from damage and loss initiated by a naturally occurring ototoxic molecule, ie, HNE (a by-product of oxidative stress). SIGNIFICANCE: Treatment with GSH(e) may be an effective therapy to protect the cochlea against the adverse effects of traumas (eg, electrode insertion) that generate oxidative stress.     

New digital method for quantitative assessment of nasal morphology.

Our aim was to develop and validate a new method to assess objectively and quantitatively the morphology of the nostrils after nasal or nasolabial surgery. We used digital analysis using specific mathematical algorithms to assess several geometric measurements, particularly of facial asymmetry, expressed in adimensional units. Forty-five patients with no facial anomalies (control group) were used initially to evaluate the method and to obtain variables for statistical reference. Thirty-five patients operated on for unilateral cleft lip and palate (cleft group) were then analysed and compared with the control group. Individual scores were obtained for each patient, computed, and correlated with those established by a lay panel. Statistical analysis showed good sensitivity and reliability (R>0.8).     

Modulation of beta-adrenergic receptors in the pituitary gland following adrenalectomy in rats

The effects of adrenalectomy on beta-adrenergic receptors in the rat pituitary were examined using quantitative in vitro autoradiography with 125I-iodocyanopindolol (125ICYP). 125ICYP binding in the anterior, intermediate and posterior lobes of the pituitary gland was significantly increased in chronically adrenalectomized rats. The increase in 125ICYP binding sites in the rat pituitary following adrenalectomy was not reversed by glucocorticoid replacement with dexamethasone. These data indicate that catecholamines of adrenomedullary origin are capable of modulating beta-adrenergic receptors in the pituitary gland and suggest that peripheral epinephrine may be important in regulating pituitary hormone secretion.     

An unexpected Q fever endocarditis. Report of a case

A man with blood culture negative endocarditis since 1983 received in October 1984 a mitral valve bioprosthesis. Reintervention in April 1985 was performed because of a paravalvular leak. In September 1985, mitral insufficiency reappeared and high-titer phase II Q fever antibody was detected, which has since then persisted with concomitant high-titers of phase I antibody. In serum from 1983, phase II antibody was detected on reexamination in September 1985. For unexplained reasons this antibody had not been detected in 1983. The patient has since September 1985 been successfully treated with doxycycline. The current literature is reviewed. Q fever endocarditis should be considered also in Belgium in culture negative endocarditis even in persons with no previous history of valvular disease and no known exposure to animals or unpasteurized dairy products. Quality of viral reagents and diagnosis present sometimes a challenge.     

Curietherapy using a ruthenium and iridium disk in the treatment of choroid melanoma

Following the experience of the German authors, the treatment of choroidal melanoma with ruthenium 106 disk was introduced in Lyon. Between 1983 and 1988, 127 patients were treated. Results are analysed on a group of 84 patients followed 18 months and more. In 72 cases a reduction of thickness was noted. It was complete in 33 cases. Enucleation was performed in 10 patients due to no response or regrowth. In 3 cases the tumor was sterilized. Five patients died of metastases, and 73 are alive, 3 of them with liver metastases. An afterloading iridium template disk was used in 8 patients. 4 of them with a tumor thickness between 6.5 and 8 mm had a good response. Edema of the fovea was observed in 21% of cases, while cataracts were very unusual with Ru 106. An enucleation was performed in 6 patients because of a complication. A useful vision may be preserved in 60% of cases. The scleral tolerance dose is close to 1,500 Gy. These results are in agreement with those of the literature and are considered to be satisfactory for tumors not exceeding 5 to 6 mm in thickness. If the tumor is located close to the fovea or the papilla, and/or if the thickness is 8 mm or more, proton beam could be a good alternative.     

Synthesis and pharmacological investigation of beta-substituted pyrrolo derivatives

A series of pyrroles bearing an ethanol- or an iso-propanolamine side-chain in the beta-position was prepared and their adrenergic activity evaluated. The absence of any appreciable activity suggests that the pyrrole ring is not suitable for replacing the phenol nucleus in derivatives possessing an adrenergic activity. Noteworthy is the amphetamine-like activity observed in amino-ketone (XXIII).     

Non-opiate effects of neuropeptides derived from beta-endorphin

Brain enzymes convert the opioid peptide beta-endorphin (beta E-(1-31)) to alpha- and gamma-endorphin and to several non-opioid fragments by further cleavage of the tyrosine residue or acetylation. Several of these peptides selectively affect brain functions. alpha-Endorphin (beta E-(1-16)) and relate non-opioid fragments (beta E-(2-16), beta E-(2-9) a.o.) like amphetamine, delay extinction of pole-jumping avoidance behavior and facilitate passive avoidance behavior. In addition these peptides enhance the stereotyped sniffing response induced by the injection of apomorphine into the nucleus caudatus. The fragment beta E-(10-16) inhibits, like serotonin and antidepressants, the behavioral effects of melatonin injected into the nucleus accumbens. gamma-Endorphin (beta E-(1-17)) has inherent opioid and neuroleptic-like properties, e.g. demonstrated by a naloxone reversible inhibition of hypermotility induced by apomorphine following injection into the nucleus accumbens. Also the non-opioid gamma-type endorphins (e.g. DT gamma E (beta E-(2-17) and DE gamma E (beta E-(6-17)) mimic certain effects of neuroleptics. These peptides facilitate extinction of pole-jumping avoidance behavior, attenuate passive avoidance behavior and antagonize the hypomotility and stereotyped sniffing induced by apomorphine injected into the nucleus accumbens and pyriform cortex respectively. These and other behavioral studies, including grasping responses, brain stimulation reward, food and other positively rewarded behavior, indicate that the action of alpha-type endorphins is in some aspects comparable to that of psychostimulants, while the effects of gamma-type endorphins are comparable to those of classical as well as atypical neuroleptics. Indeed, gamma-type endorphins have antipsychotic effects in a category of schizophrenic patients.