The risk of pneumonectomy over the age of 70. A case-control study.

OBJECTIVE: A higher mortality has been reported after pneumonectomy over the age of 70. The aim of the study was to quantify the additional risk due to age after standard pneumonectomy for lung cancer by a case-control study. METHODS: Our clinical database was reviewed to search for patients aged 70 years or more who underwent standard pneumonectomy for lung cancer between 1998 and 2005. A control group of patients younger than 70 (one case/two controls) was matched for sex, cardiovascular disease, American Association of Anaesthetists score, respiratory function, side of pneumonectomy, induction chemotherapy and stage. Overall mortality and morbidity were compared. Long-term survival data were also analysed. RESULTS: During the considered period, 35 patients aged 70 years or more underwent pneumonectomy (30 males, median age 73 years, 15 right-sided procedures). The control group was composed of 70 patients. The two groups were homogeneous in the variables used for matching. Overall mortality and morbidity were 11.4 and 54.2% in the elderly group as compared to 4.3 and 41.6% in controls (p-value not significant). Elderly patients experienced a higher rate of respiratory complications (25.7%) as compared to controls (8.3%, p=0.01). At univariate analysis, the only risk factor for death was the occurrence of respiratory complications (OR 6.5, CI 1.8-18.2). At multivariate analysis, age >or=70 years (OR 5.36, CI 1.48-19.3) and preoperative chemotherapy (OR 7.65, CI 2.04-28.6) were confirmed as predictors of respiratory complications. Five-year survival was 17.5% in the elderly group and 53.6% in the control group (p=0.003). Elderly patients with a better respiratory function (FEV1>70%) had a 5-year survival of 45.4%. CONCLUSIONS: In the elderly patients, the risk of respiratory complications after pneumonectomy is increased as compared to younger patients with equivalent respiratory function. Age and preoperative chemotherapy are independent risk factors for respiratory complications. A lower mortality and a better long-term survival are obtained in elderly patients with a better respiratory function (FEV1>or=70%).     

Acute oral captopril inhibits angiotensin converting enzyme activity in human cerebrospinal fluid

Angiotensin converting enzyme (ACE) activity in human plasma and cerebrospinal fluid (CSF), was measured by a fluorimetric method, following an acute oral dose (75 mg) of captopril. A decrease of approximately 60% in enzyme activity was observed in CSF, suggesting that the drug penetrates the blood/brain barrier (BBB) in sufficient amounts to inhibit the ACE in CSF. The activity of CSF enkephalinase, an enzyme present in human brain and inhibited in vitro by an elevated concentration of captopril, was, however, unaffected by the acute drug administration. It is proposed that the antihypertensive effect of captopril in humans may be due, at least in part, to the inhibition of ACE contained within brain structures.     

Novel therapeutic targets

Neurological Sciences - The need for novel therapeutic strategies for the treatment of migraine and other primary headaches is well recognised. Although the underlying mechanism(s) and the...     

3D facial morphometry in Italian patients affected by Aicardi syndrome

Aicardi syndrome (AIC) is a rare congenital neurodevelopmental disorder of unknown etiology, that affects almost exclusively females, originally characterized by corpus callosum agenesis, chorioretinal lacunae, and infantile spasms. The current diagnostic criteria also include qualitative facial features (prominent premaxilla, upturned nasal tip, decreased nasal bridge angle, sparse lateral eyebrows, and microphthalmia) that still need quantification. A three‐dimensional (3D) photogrammetric assessment of 11 Italian females, age 7–32 years, who satisfied AIC criteria, was performed. Linear distances and angles were computed from soft‐tissue facial landmarks coordinates. The z‐score values were calculated using data of 850 healthy reference females matched for age and compared by Mann–Whitney test (p < .01). Patients showed a shorter philtrum and right side orbital height (mean z‐scores: ?1.7, ?0.9), shorter superior, middle, and inferior facial depths (mean z‐scores: ?1.3, ?2.2, ?2.3), and a smaller length of mandibular ramus (mean z‐score: ?2.1); conversely, they showed larger nasal and lower facial widths, and lower facial convexity (mean z‐scores: 1.7, 1.4, 2.4). The inclinations of the orbit versus the true horizontal were increased bilaterally (mean z‐scores: 1.8, 1.1). Some common facial abnormalities were quantified in AIC patients using a noninvasive instrument. They may help clinicians in performing a definite AIC diagnosis in atypical or doubt cases.     

Tachykinin-like immunoreactivity in the mammalian urinary bladder: correlation with the functions of the capsaicin-sensitive sensory nerves

The tachykinin-like immunoreactivity of the urinary bladder has been measured in various species by means of an antiserum (K12) having negligible cross-reactivity with substance P. The rank order for bladder content of tachykinin-like immunoreactivity was guinea-pig greater than mice greater than rat, similar to that found for substance P-like immunoreactivity. In all three species, both substance P- and tachykinin-like immunoreactivities were depleted by systemic capsaicin desensitization. The time course for depletion of substance P- and tachykinin-like immunoreactivities of the rat bladder following extrinsic denervation was almost superimposable. At reverse phase high pressure liquid chromatography, the major constituent of tachykinin-like immunoreactivity of the rat bladder co-eluted with neurokinin A. In vitro, the contractile response of the rat bladder to capsaicin (1 microM) was directly proportional to bladder tachykinin-like immunoreactivity while the response to field stimulation was not. In vivo, the volume threshold for reflex micturition was inversely proportional to bladder tachykinin-like immunoreactivity while amplitude of micturition contraction was not. Similar correlations were found in a previous study for substance P-like immunoreactivity. The contractile response to capsaicin or neurokinin A of the rat isolated bladder were significantly reduced by incubation with phenoxybenzamine at a concentration reported to produce a selective alkylation of neurokinin-2 receptors, while the response to substance P or KCl was unaffected. These findings indicate that multiple neurokinins co-exist in those bladder sensory nerves which are capsaicin-sensitive in adult rats. Both substance P- and tachykinin-like immunoreactivities in the rat bladder appear to be good functional markers of the sensory and "efferent" functions mediated by capsaicin-sensitive nerves, consistent with the hypothesis of a transmitter role for the corresponding peptides.     

Effects of capsaicin,tachykinins, calcitonin gene-related peptide and bradykinin in the pig iris sphincter muscle

Summary Capsaicin-sensitive sensory neurons of the rabbit iris, by releasing tachykinins, exert a major role in the control of pupil motility in response to various noxious stimuli. However, the contribution of sensory innervation to the regulation of iris smooth muscle tone in other mammals species is not known. We have studied the effects produced by electrical field stimulation, capsaicin, substance P, neurokinin A, calcitonin gene-related peptide (CGRP), and bradykinin in the isolated iris sphincter muscle of the pig.Capsaicin (10 M): a) contracted the isolated sphincter muscle and; b) released immunoreactivity for substance P (SP-LI) and CGRP (CGRP-LI) from this preparation. These two effects were no longer observed at the second exposure to the drug. Electrical field stimulation (10 Hz, 60 V, 0.5 ms for 5 s) produced a biphasic contractile response. The rapid component was inhibited by atropine (1 M), while the delayed response was blocked by previous exposure to capsaicin (10 M).Substance P and neurokinin A consistently produced contraction of the pig iris sphincter muscle, substance P being more potent than neurokinin A. CGRP induced a contractile response in more than 50% of the preparations. The tachykinin antagonist [D-Argl, D-Trp^7,9, Leu¹¹-substance P (3 M) blocked: a) the effect of substance P (1 nM); b) the delayed response to electrical field stimulation and; c) reduced by more than 50% response to capsaicin. Bradykinin (10 M) failed to release either SP-LI or CGRP-LI. The contractile response evoked by bradykinin was unaffected by in vitro pretreatment with capsaicin (10 M).The existence in the pig iris of capsaicin-sensitive sensory fibres releasing neuropeptides and thus regulating sphincter muscle tone is proposed. Send offprint requests to Dr. P. Geppetti at the above address     

Evidence for in vitro expression of B1 receptor in the mouse trachea and urinary bladder

1. Motor responses to des-Arg9-bradykinin and bradykinin were studied in the isolated mouse trachea (precontracted with carbachol, 10 microM) and the urinary bladder of either Swiss, C57B1/6J or bradykinin B2 receptor knockout (Bk2r(-/-)) mice after 1-6 h in vitro. The expression of mRNA for the mouse B1 receptor in tracheal and urinary bladder tissues was also studied by using Northern blot analysis. 2. In isolated tracheae, des-Arg9-bradykinin produced a relaxant response that increased over time: no response was observed after 1 h of incubation, whereas after 6 h the maximum response (1 microM) was 68-84% of the relaxation produced by isoproterenol (1 microM) in the three mouse strains. The relaxant response to bradykinin (1 microM) observed at 1 h (38-51% of isoproterenol) was increased (62-65% of isoproterenol) after 6 h in Swiss and C57B1/6J mice, but was absent in Bk2r(-/-) mice. In the presence of cycloheximide, des-Arg9-bradykinin did not cause any response at 6 h. 3. Similar findings were obtained in the urinary bladder: at 1 h des-Arg9-bradykinin (1 microM) did not cause any motor effect, whereas at 6 h it caused a contraction that was 28-59% of that produced by carbachol (1 microM) in the three mouse strains. Cycloheximide blocked the response to des-Arg9-bradykinin. Bradykinin (1 microM) contracted urinary bladders at 1 h (34-35% of carbachol), as well as at 6 h (66-77% of carbachol) in Swiss and C57B1/6J strains, but was without effect in Bk2r(-/-) mice. 4. Northern blot hybridization with a specific cDNA probe against mouse B1 receptor mRNA using total RNA extracted from tracheae and urinary bladders freshly removed from Swiss and Bk2r(-/-) mice revealed minimal expression. However, marked hybridization was detected 150 min after in vitro exposure in both tissues. 5. Evidence is provided that in vitro exposure of mouse trachea and urinary bladder causes a time-dependent induction of B1 receptors that cause relaxation and contraction, respectively.     

Five-year Prospective Audit of Routine Intravenous Cholangiography and Selective Endoscopic Retrograde Cholangiography with or without Intraoperative Cholangiography in Patients Undergoing Laparoscopic Cholecystectomy

Consensus has never been reached regarding the need or the imaging technique for evaluating the common bile duct (CBD) in patients considered for cholecystectomy. With the advent of laparoscopic cholecystectomy there has been a resurgence of interest in the role of preoperative intravenous cholangiography (IVC) as an alternative for evaluating the CBD. The purpose of this audit was to assess whether a diagnostic workup based on IVC, which permits selective use of intraoperative cholangiography (IOC) and endoscopic treatment of CBD stones before surgery, could be useful in patients undergoing laparoscopic cholecystectomy (LC). In patients without jaundice, gallstone pancreatitis, a prior diagnosis of CBD stones, a prior history of contrast allergy, or a risk of contrast-associated acute renal failure, IVC was performed routinely. Patients suspected to have CBD stones based on IVC results or with inconclusive IVC and patients with a strong clinical suspicion of CBD stones were referred for endoscopic retrograde cholangiography (ERC). IOC was carried out in patients who had a history of contrast allergy or risk of contrast-associated acute renal failure and whenever the surgeon was in doubt as to the biliary anatomy or CBD clearance. IVC was carried out in 1155 patients, ERC in 225, and IOC in 54. IVC was conclusive in 1132 patients, with a diagnostic accuracy of 99%. Our workup permitted the sequential endoscopic-laparoscopic treatment of cholecystocholedocholithiasis in 162 cases. During the follow-up period residual CBD stones were detected in four patients. Our diagnostic workup showed that routine IVC exposes the population to a large radiation burden, and the cost is high for the small number of patients who benefit. Moreover, it does not seem helpful in reducing the incidence of CBD injuries during LC.