Franco Taggi

Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin.

We investigated whether the glomerular synthesis of prostacyclin modulates the renal blood flow and glomerular filtration rate in chronic glomerular disease. The urinary excretion of 6-keto-prostaglandin F1 alpha, a stable breakdown product of prostacyclin, was significantly (P less than 0.01) reduced in 20 women with chronic glomerular disease, as compared with 19 controls, whereas excretion of urinary prostaglandin E2 was unchanged. In 10 patients randomly assigned to one week of treatment with ibuprofen, excretion of urinary 6-keto-prostaglandin F1 alpha and prostaglandin E2 was reduced by 80 per cent, the level of serum creatinine was increased by 40 per cent, and creatinine and para-aminohippurate clearances were reduced by 28 and 35 per cent, respectively. The reduction of both clearances was inversely related (P less than 0.01) to the basal urinary excretion of 6-keto-prostaglandin F1 alpha but not of prostaglandin E2. No functional changes were detected in five healthy women, despite a similar suppression of renal prostacyclin synthesis by ibuprofen. In contrast, one week of treatment with sulindac did not affect renal prostacyclin synthesis or renal function in the other 10 patients, despite a marked inhibition of extrarenal cyclooxygenase activity. We conclude that in patients with mild impairment of renal function, the renal blood flow and glomerular filtration rate are critically dependent on prostacyclin production. In such patients sulindac may be a safe substitute for other nonsteroidal antiinflammatory drugs.

Systematic review: endoscopic dilatation in Crohn’s disease

Background  Endoscopic dilatation for Crohn’s disease has been evaluated only in some small and heterogeneous studies.

Renal bone disease in 76 patients with varying degrees of predialysis chronic renal failure: a cross-sectional study

BACKGROUND Renal osteodystrophy has been studied less extensively in predialysis than in dialysis patients. Different types or histological patterns in their natural evolution from moderate to advanced severity of renal insufficiency are only partially known, with special regard to adynamic bone disease and its relationship with osteomalacia. METHODS We conducted a cross-sectional retrospective study on 76 unselected patients with chronic renal failure undergoing conservative treatment, with a wide range of severity of renal insufficiency. All the patients were subjected to bone biopsy for histological and histomorphometric evaluation. The patients, 44 males and 32 females ranging in age from 18 to 72 years and with serum creatinine 1.2-11.4 mg/dl, had not been exposed to aluminium-containing drugs and had never been treated with vitamin D or calcitriol. RESULTS Ten patients had normal bone, nine were diagnosed with adynamic bone disease, 26 with mild mixed osteodystrophy, seven with predominant osteomalacia, 22 with advance mixed osteodystrophy, and two with predominant hyperparathyroidism. Patients with adynamic bone disease had less severe chronic renal failure than the other pathological subgroups, intact PTH above the upper limit of normal, normocalcaemia, and reduced serum osteocalcin in line with a significantly lower ObS/BS. Osteomalacia was found in a more advanced stage of chronic renal failure with relative hypocalcaemia and more severe metabolic acidosis. A creatinine clearance of 20 ml/min served as a clear demarcation between this histological group and adynamic bone disease. CONCLUSIONS It is postulated that adynamic bone disease is a form of renal osteodystrophy, separate from osteomalacia, appearing when bone resistance to PTH develops, probably a transient stage to more hyperparathyroid histological classes with increasing severity of chronic renal failure.

Effect of Italy’s motorcycle helmet law on traumatic brain injuries

Objectives: To evaluate the impact of a revised Italian motorcycle-moped-scooter helmet law on crash brain injuries. Design: A pre-post law evaluation of helmet use and traumatic brain injury (TBI) occurrence from 1999 to 2001. Setting: Romagna region, northeastern Italy, with a 2000 resident population of 983 534 persons. Participants: Motorcycle-moped rider survey for helmet use compliance and all residents in the region admitted to the Division of Neurosurgery of the Maurizio Bufalini Hospital in Cesena, Italy for TBI. Outcome measures: Helmet use compliance and change in TBI admissions and type(s) of brain lesions. Results: Helmet use increased from an average of less than 20% to over 96%. A comparison of TBI incidence in the Romagna region shows that there was no significant variation before and after introduction of the revised helmet law, except for TBI admissions for motorcycle-moped crashes where a 66% decrease was observed. In the same area TBI admissions by age group showed that motorcycle mopeds riders aged 14–60 years sustained significantly fewer TBIs. The rate of TBI admissions to neurosurgery decreased by over 31% and epidural hematomas almost completely disappeared in crash injured moped riders. Conclusions: The revised Italian mandatory helmet law, with police enforcement, is an effective measure for TBI prevention at all ages.

Peyronie’s Disease: Prevalence and Association with Cigarette Smoking

Objectives: We present a multicenter, population–based epidemiological survey aimed at assessing the prevalence of Peyronie’s disease (PD) and its potential risk factors in the general population. Methods: In each of the ten centers throughout Italy, a uroandrologist contacted all the men in the age range 50–69 years registered with a general practitioner (GP). The subjects recruited were evaluated on the basis of their medical history, including alcohol consumption and cigarette smoking. The following questionnaires were administered: IIEF, IIPSS symptom score, premature ejaculation and PD. Results: All the subjects registered with a GP were invited to participate in the study. Of the 1,180 subjects, 647 (53%) entered over survey. In this population, 46 cases of PD were identified, accounting for a prevalence of 7.1%. The prevalence rate increased with age even if the trend is not statistically significant. The multivariate analysis showed a significant correlation between cigarette smoking and PD, with an odds ratio (OR) of 4.6 (CL 95%) confidence limit 1.506– 14.287). Smoking as single variable had an OR of 7.2 (95% CL 2.34–24.93). No significant association was observed between PD and the other variables such as cardiovascular diseases, diabetes, hypertension and alcohol consumption. Conclusions: PD is a much more frequent condition in the general population than previously reported. According to our results, cigarette smoking may be considered a risk factor for developing PD. If further and more targeted studies confirm that giving up smoking may reduce the risk of developing PD, then there will be new prospects for primary and secondary prevention and for curbing the progression of the disease.

Renal Osteodystrophy in Predialysis and Hemodialysis Patients: Comparison of Histologic Patterns and Diagnostic Predictivity of Intact PTH

Background: Comparison of renal osteodystrophy in predialysis and hemodialysis has been rarely reported. Distinct patterns of renal osteodystrophy could be found in these conditions. In addition the use of parathyroid hormone (PTH) and other markers for noninvasive diagnosis may result in different predictive values in predialysis and hemodialysis patients. Methods: 79 consecutive patients with conservative chronic renal failure and 107 patients on hemodialysis were studied. All patients were subjected to bone biopsy for histological and histomorphometric evaluation. The patients had no exposure to aluminium before dialysis and relatively low exposure while on hemodialysis. Results: In the predialysis patients, bone biopsies showed 9 cases of adynamic bone disease (ABD) and 8 cases of osteomalacia (OM), 50 patients with mixed osteodystrophy and 2 cases of hyperparathyroidism. Among the hemodialysis patients 12 cases had ABD, 3 cases OM, 30 mixed osteodystrophy, and 61 patients hyperparathyroidism. In the predialysis patients with chronic renal failure, bone aluminium was on average 4.5 mg/kg dry weight, while in dialysis patients the average value was 35.4 mg/kg dry weight. Discriminant analysis of low turnover osteodystrophy (ABD and OM) by intact PTH showed higher accuracy in dialysis than in predialysis patients. Correlation studies of intact PTH versus bone formation rate, osteoblast surface/bone surface and osteoclast surface/bone surface showed significantly steeper slopes in dialysis than in predialysis patients, which indicates that bone resistance to PTH is more marked in predialysis patients. Conclusions: The prevalence of ABD and OM in the geographic area investigated is lower than in other reports. Aluminium exposure does not seem to be the cause of low turnover osteodystrophy in the present population. The predictive value of intact PTH in the noninvasive diagnosis of renal bone disease is higher in hemodialysis patients than in predialysis patients. Predialysis chronic renal failure, when compared to the dialysis stage, seems to be characterized by resistance of bone tissue to PTH.

Progression of Coronary Artery Calcification in Renal Transplantation and the Role of Secondary Hyperparathyroidism and Inflammation

BACKGROUND AND OBJECTIVES Transplantation should favorably affect coronary calcification (CAC) progression in dialysis; however, changes in CAC score in the individual patient are not reliably evaluated. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS The authors used special tables of reproducibility limits for each score level to study, by multislice computed tomography and biochemistries, the 2-year changes in CAC in 41 transplant patients (age 48 +/- 13 yr, 25 men, dialysis vintage 4.8 +/- 4.3 yr, underwent transplant 6.2 +/- 5.5 yr prior). Thirty balanced dialysis patients served as controls. RESULTS In the study group, Agatston score was stable, and C-reactive protein decreased, whereas fetuin and osteoprotegerin increased. In the control group, Agatston score increased, parathyroid hormone and phosphate decreased, and inflammation markers were persistently twice as high as in the study group. With regard to individual changes, 12.2% transplant patients worsened, compared with 56.6% of patients in dialysis (P < 0.0001). Patients without calcification at entry showed slower progression in transplantation (8.3%) than in dialysis (44.4%; P < 0.034), and the difference was similar to that observed in cases with CAC (17.6% versus 61.9%; P < 0.007). Discriminant analysis indicated parathyroid hormone, the modality of therapy (dialysis or transplantation), and erythrocyte sedimentation rate as the variables most associated with worsening. CONCLUSIONS Renal transplantation lowers but does not halt CAC progression. Inflammation and hyperparathyroidism are associated with progression in the populations studied.

Serum Levels of Calcification Inhibition Proteins and Coronary Artery Calcium Score: Comparison between Transplantation and Dialysis

Vascular calcifications in CKD are now linked to serum alterations of both divalent ions and calcification inhibitory proteins. Due to possible biochemical differences between dialysis (D) and transplantation (Tx), we examined the entity and severity of these biochemical modifications and of coronary artery calcium score separately in these two populations. We assayed, besides standard markers of inflammation, divalent ions and serum levels of fetuin, matrix Gla protein (MGP) and osteoprotegerin (OPG), in 51 Tx patients (age 45 ± 12 years; 30 males, 21 females; previous D duration 4.8 ± 4.2 years; Tx since 6.6 ± 5.5 years; Cr 1.8 ± 0.6 mg/dl) and in 49 D patients (age 49 ± 14 years; 30 males,19 females; D duration 5.6 ± 4.8 years). Additionally, coronary calcium score (AS) was evaluated by cardiac multi-slice CT. Compared with D patients, Tx patients had better values of divalent ions and inflammation markers, and lower prevalence (65 vs. 86%; p < 0.02) and severity (AS = 570 ± 1,637 vs. 1,311 ± 3,128; p < 0.008) of coronary calcification. In addition, a tendency toward normalization for all of the three calcification inhibitory proteins was evident. In both Tx and D, AS correlated with age and OPG (Tx: rs = 0.439, p < 0.001, and rs = 0.510, p < 0.0001; D: rs = 0.471, p < 0.001, and rs = 0.403, p < 0.005, respectively); in D patients, a correlation was present also with D duration (rs = 0.435; p < 0.002), other markers of inflammation and, notably, fetuin (rs = –0.442; p < 0.002). Regression analysis selected previous time on D in Tx patients (rm = 0.400; p < 0.004), and C-reactive protein and OPG in D patients (rm = 0.518; p < 0.004) as the most predictive parameters of AS. Discriminant analysis confirmed the major role of age and D duration in the appearance of AS and evidenced male gender as a distinct risk condition. At variance, Tx duration was never associated with AS. In conclusion, as compared to D, renal Tx patients show serum levels of calcification inhibition proteins and of divalent ions closer to normal. As this is associated with a lower prevalence and severity of AS, it is suggested that Tx antagonize the accelerating role of D in the progression of vascular calcification. Assessment of both coronary calcifications and serum levels of calcification inhibitory proteins may be of value to identify those subjects at higher risk of development and progression of vascular lesions, among whom males have the highest rate.

A preliminary investigation of road traffic accident rate after severe brain injury

Primary objective: to investigate the road traffic accident rate in patients who have resumed driving after severe brain injury. Research design: a retrospective study conducted by means of telephone interviews. Methods and procedures: The caregivers of 90 patients suffering from severe brain injury were included. All of the patients had sustained severe brain injury and prolonged coma, i.e. lasting for at least 48 hours. The caregivers were interviewed by means of a Questionnaire that investigated several aspects of driving competence after coma and the incidence of road traffic accidents. Main outcomes and results: All patient outcomes were evaluated by means of the Glasgow Outcome Scale (GOS). The 90 caregivers reported that 29 patients (32%) had resumed driving and that 11 of the 29 (38%) were subsequently involved in road traffic accidents. During the total duration of our patient population risk exposure, we found 11 cases in our study group, against the 4.7 expected cases calculated in the normal population. The relative risk of road traffic accidents in severe brain injury patients versus uninjured individuals was 2.3. Conclusions: Our preliminary data show that a subject who has suffered from severe brain injury and coma lasting for at least 48 hours has a statistically significant higher risk of being involved in a road traffic accident.

Ischemic Nephropathy in an Elderly Nephrologic and Hypertensive Population

Background: Atherosclerotic renovascular disease is a frequent cause of end-stage renal failure leading to dialysis in the elderly population. Its prevalence is known from autopsy or retrospective arteriographic investigations. This prospective study was conducted in 133 subjects with the inclusion criteria of hypertension and/or chronic renal failure starting after 50 years of age. Renal failure was unrelated to other known causes of renal disease. Methods: The patients were subjected to echo-color doppler ultrasonography of renal arteries (104) and/or to renal scintigraphy (112). Thirteen of 27 patients with positivity using one or both noninvasive techniques were subjected to digital selective angiography. Results: All the patients with positivity of echo-color doppler technique were true positives, with a consequent predictive value reaching 100%. Renal scintigraphy was of markedly lower predictive value. Based on the echo-color doppler investigation, percentage positivity for hemodynamically significant stenosis (>50%) was 3.2 (16.3% had mild nonsignificant stenosis of renal arteries) in the 50- to 59-year-old group, 20% (plus 12.5% with nonsignificant stenosis) in the 60- to 69-year-old group and 25% (plus 17.8% nonsignificant stenosis) in the >70-year age group. Patients with significant stenosis also had a significantly higher degree of renal insufficiency and received a higher number of hypotensive drugs (p < 0.013). The percentage of hypertensive patients was not different in the stenotic and nonstenotic groups. Conclusions: A large percentage of the elderly population is affected by renal vascular obstructive disease and is at risk of developing end-stage renal failure. Considering the wide number of cases with foreseeable renal arterial stenosis in the vast population meeting the selection criteria, it is possible to conclude that not all cases evolve to renal failure due to different rates of progression or to untimely nonrenal death.