Complex anal fistula with a recess above the levator ani muscles: report of a case complicated by haemorrhagic colitis

Anal fistula surgery offers very little in the way of new developments. As early as the 14th century John of Arden defined the rules for surgical therapy. The numerous classifications adopted are often contradictory and unclear, and no clearly defined pathogenesis of the condition has been established. Complex anal fistula with a recess above the elevator ani muscles requires very careful and meticulous therapeutic treatment because of the risk of damaging the sphincter. In the case reported here the patient presented a very complex fistula which was followed by onset of severe haemorrhagic colitis without any clinical, endoscopic, radiological, or histological evidence of inflammatory bowel disease prior to surgical treatment.     

Is carotid endarterectomy in octogenarians more dangerous than in younger patients?

AIM: The risk for developing stroke increases with the advancing age, peaking over age 80. In elderly patients, carotid endarterectomy may provide prophylaxis against stroke. Aim of our study was to compare patients 80 years or older with patients younger than 80 undergoing carotid endarterectomy. Endpoints were perioperative mortality and morbidity. METHODS: From January 1996 to December 2002, 1 659 patients underwent a 1 733 carotid endarterectomy for a symptomatic or asymptomatic significant carotid lesion. Among them, 125 patients were 80 years or older. We analyzed death and stroke rate from cerebrovascular accidents, TIA as well as non cerebrovascular complications and death rate postoperatively and in the long term follow-up. The Pearson's chi-squared(2) test was used for the statistical analysis on risk factors, morbidity and mortality. The Log rank test was used for cumulative stroke-free and survival rates between the 2 groups (level of confidence p<0.05). RESULTS: Risk factors were similar in both groups. No statistical difference was observed in the stroke, TIA, mortality and stroke free rates between the 2 groups. CONCLUSIONS: The results of our study show that perioperative and postoperative mortality and morbidity as well as the long-term stroke-free rate does not differ significantly in patients 80 years or older compared to patients younger than 80 undergoing carotid endarterectomy.     

L-Arginine erythrocyte transport in normal pregnant and preeclamptic women

OBJECTIVE: Uptake of L-arginine by the cell via amino acid transporter systems is the first step for nitric oxide (NO) production. The current study aimed to assess the total L-arginine uptake in erythrocytes of normal pregnant and preeclamptic women. STUDY DESIGN: Twenty-one normal pregnant and 21 preeclamptic women were studied. To measure total L-arginine uptake in erythrocytes, carbon 14 was used as a marker and Michaelis-Menten kinetic parameters (V(max) and K(m)) were evaluated. RESULTS: In preeclamptic women, there was a significant increase (P<.004) in the mean maximal capacity of transport in erythrocytes (V(max)=982.69 micromol/L cells/h+/-433.51) in comparison with normal pregnant women (V(max)=584.73 micromol/L cells/h+/-422.33). No significant difference was detected in the half-saturation constant (P=0.978). CONCLUSION: The transport kinetics of the NO precursor, L-arginine, is altered in erythrocytes of preeclamptic women. It is possible that abnormal L-arginine uptake may contribute to the pathophysiologic mechanisms of preeclampsia syndrome.     

Suprarenal fixation of endograft in abdominal aortic aneurysm treatment: focus on renal function

OBJECTIVE: The objective of this work was to evaluate any variation of renal function detected by renal scintigraphy after the suprarenal fixation of endografts for abdominal aortic aneurysm (AAA) repair. SUMMARY BACKGROUND DATA: In the few articles that have considered this problem, renal function was evaluated only by biochemical tests, which are inadequate in demonstrating small changes in renal function and in appreciating the worsening of a single kidney's function. METHODS: Between April 1999 and May 2002, 47 patients with an inappropriate infrarenal proximal neck had a suprarenal fixation for AAA. To assess renal function, a technetium-99m diethylene triamine penta-acetic acid (TC-DTPA) perfusion scintigraphy was performed preoperatively on the third postoperative day and at 6, 12 months, and then yearly thereafter. Worsening of renal function was defined as a decrease of glomerular filtration rate (GFR) > or =20% (detected with Gates method). Serum creatinine level was tested preoperatively and at the first and third postoperative day. RESULTS: Endograft deployment was technically successful in 44 patients (93.6%); clinical perioperative success was obtained in 46 patients (97.8%). In 12 patients (25.5%), a permanent reduction of the GFR was observed using postoperative TC-DTPA perfusion scintigraphy. By 99m TC-DTPA perfusion scintigraphy, a permanent reduction of GFR was observed postoperatively in 12 patients. A slight GFR reduction (<20%) was present in 7 (14.9%) patients, due to the planned occlusion of accessory renal arteries. A more significant GFR reduction (>20%) was present unexpectedly in 5 (10.6%) patients, in 3 of these a single kidney was involved, in 5 both with an increase of the serum creatinine level >20%. CONCLUSIONS: Suprarenal fixation of endografts in AAA treatment is a safe procedure with good early and midterm procedural results and a risk of GFR impairment (>20%) of 10.6%.     

PATE 2000 Sorrento: a modern, effective instrument for defining haemorrhoids. A multicentre observational study conducted in 930 symptomatic patients

In 2000, the Italian Society of Coloproctology and the UCP (Coloproctology Units) devised a new haemorrhoid classification system, named PATE 2000 Sorrento, which is capable of defining all the main characteristics of the disease. Any new system should be able to predict the real extent of hemorrhoids by means of a specific index in order to help physicians in choosing the best therapeutic option. The authors present the results of a national multicentre study of 930 patients with symptomatic haemorrhoids. Nineteen patients (2%) could not be classified with the old haemorrhoid classification, while PATE 2000 Sorrento proved successful in classifying all patients. The difference was statistically significant. The new classification enables us to establish a specific score for the disease. In order to better evaluate the clinical impact of the scores obtained with PATE 2000 Sorrento, the authors analyzed the correlation between the score itself and the therapy chosen by each individual centre. The highest scores always corresponded to the choice of surgical hemorrhoidectomy, while in the case of lower values each centre seemed to be in doubt between medical therapy and other less invasive procedure such as sclerotherapy or rubber band ligation. These data were statistically significant (P < 0.0001). On the basis of our findings, PATE 2000 Sorrento seems to confirm its scientific and clinical relevance and could be a useful tool for the choice of the best treatment for each individual patient.     

The usefulness of adenosine 99mTc tetrofosmin SPECT for the diagnosis of left anterior descending coronary artery disease in patients with chest pain and left bundle branch block

OBJECTIVES: The aim of this study was to assess the usefulness of 99mTc tetrofosmin single photon emission computed tomography (SPECT) for the diagnosis of left anterior descending (LAD) coronary artery disease in 60 subjects with left bundle branch block (LBBB) admitted for chest pain. METHODS AND RESULTS: Adenosine 99mTc tetrofosmin SPECT, transthoracic echocardiogram and coronary angiography were performed, by protocol, in 60 non-infarcted consecutive patients. The mean left ventricular ejection fraction (LVEF) was 41.6 +/- 10.8%. A significant angiographic disease of the LAD was found in 15 (25%) patients. The sensitivity and the specificity of SPECT was found to be 75% and 89%, respectively; the positive predictive value (PPV) was 70% with a negative predictive value (NPV) of 91%. During the adenosine infusion the QRS complex width reduced from 131.3 +/- 29.6 ms to 125.5 +/- 28.6 ms in the patients without LAD involvement (P = 0.008) but remained unchanged in LAD disease patients (P = 0.1). Combining SPECT information and QRS analysis the sensitivity increased to 87% with unchanged specificity, the PPV was 74% and the NPV resulted 95%. At 2-year follow-up 13 (22%) patients experienced a cardiac event. Using Kaplan-Meier analysis, an LVEF of < or = 35% was the only predictor of cardiac events (P = 0.01, log-rank 6.2). CONCLUSIONS: A quarter of patients with LBBB complaining of chest pain had LAD coronary disease. The highly negative predictive value of adenosine SPECT could help in the exclusion of LAD disease, especially when the SPECT image is combined with the QRS analysis.     

3-(4-Aroyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamides as a new class of synthetic histone deacetylase inhibitors. 2. Effect of pyrrole-C2 and/or -C4 substitutions on biological activity

Previous SAR studies (Part 1: Mai, A.; et al. J. Med. Chem. 2003, 46, 512-524) performed on some portions (pyrrole-C4, pyrrole-N1, and hydroxamate group) of 3-(4-benzoyl-1-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide (1a) highlighted its 4-phenylacetyl (1b) and 4-cynnamoyl (1c) analogues as more potent compounds in inhibiting maize HD2 activity in vitro. In the present paper, we investigated the effect on anti-HD2 activity of chemical substitutions performed on the pyrrole-C2 ethene chains of 1a-c, which were replaced with methylene, ethylene, substituted ethene, and 1,3-butadiene chains (compounds 2). Biological results clearly indicated the unsubstituted ethene chain as the best structural motif to get the highest HDAC inhibitory activity, the sole exception to this rule being the introduction of the 1,3-butadienyl moiety into the 1a chemical structure (IC50(2f) = 0.77 microM; IC50(1a) = 3.8 microM). IC50 values of compounds 3, prepared as 1b homologues, revealed that between benzene and carbonyl groups at the pyrrole-C(4) position a hydrocarbon spacer length ranging from two to five methylenes is well accepted by the APHA template, being that 3a (two methylenes) and 3d (five methylenes) are more potent (2.3- and 1.4-fold, respectively) than 1b, while the introduction of a higher number of methylene units (see 3e,f) decreased the inhibitory activities of the derivatives. Particularly, 3a (IC50 = 0.043 microM) showed the same potency as SAHA in inhibiting HD2 in vitro, and it was 3000- and 2.6-fold more potent than sodium valproate and HC-toxin and was 4.3- and 6-fold less potent than trapoxin and TSA, respectively. Finally, conformationally constrained forms of 1b,c (compounds 4), prepared with the aim to obtain some information potentially useful for a future 3D-QSAR study, showed the same (4a,b) or higher (4c,d) HD2 inhibiting activities in comparison with those of the reference drugs. Molecular modeling and docking calculations on the designed compounds performed in parallel with the chemistry work fully supported the synthetic effort and gave insights into the binding mode of the more flexible APHA derivatives (i.e., 3a). Despite the difference of potency between 1b and 3a in the enzyme assay, the two APHA derivatives showed similar antiproliferative and cytodifferentiating activities in vivo on Friends MEL cells, being that 3a is more potent than 1b in the differentiation assay only at the highest tested dose (48 microM).     

Rivastigmine in vascular dementia

Patients with vascular dementia (VaD) show cholinergic deficits that may result in characteristic clinical syndromes for different subtypes of the condition. Subcortical VaD is characterised by executive dysfunction and behavioural problems, reflecting deterioration of the frontal lobe. Based on limited open-labelled controlled studies of rivastigmine in VaD, this article aims to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), has any effects on the typical symptoms of subcortical VaD. Long-term rivastigmine treatment is safe and effective. Improvements in domains that characterise subcortical VaD were observed, indicating that rivastigmine may have provided targeted treatment in areas of the brain that are particularly affected in this patient population. A large, double-blind study of rivastigmine in patients with VaD is clearly warranted.