The Prognostic Value of High-sensitivity C-reactive Protein and Prealbumin for Short-term Mortality in Acutely Hospitalized Multimorbid Elderly Patients: A Prospective Cohort Study.

OBJECTIVES: To establish the predictive value on mortality after 2 months from hospital admission of two laboratory markers of nutritional and inflammatory status, high-sensitivity C-reactive protein (hs-CRP) and prealbumin, in a cohort of frail multimorbid elderly without terminal illness. DESIGN: Prospective cohort study. SETTING: Internal medicine ward of a large teaching hospital in Italy. PARTICIPANTS: 544 Caucasian patients with acute disease consecutively admitted from January to June 2013. 102 were excluded for being younger than 65 years old, having life expectancy <30 days or not having frailty syndrome. Further 42 patients were excluded for missing data or withdrawn at follow-up. Final analysis was performed on 400 subjects (179 M, 221 F, mean age 79±10). MEASUREMENTS: Serum prealbumin and hs-CRP were measured at admission. Death within 2 months from hospital admission was assessed through a telephonic interview with the caregiver for each patient discharged alive. Inhospital mortality was also recorded. Survival was calculated from date of admission to our unit. RESULTS: Mean prealbumin at admission was 17.3±7.7 mg/dl, while hs-CRP median was 24.2 mg/L (IQR 8.7 to 51.8). 108 patients (27%) died within two months from admission. In an age- and sex-adjusted analysis, log(hs-CRP) levels at admission, but not prealbumin, were independently associated with an increased risk for mortality (HR 1.40, 95% CI 1.18 to 1.66, p<0.001). After multiple adjustments for covariates, including comorbidity burden measured through Charlson score, log(hs-CRP) remained significantly associated with mortality (HR 1.38, 95% CI 1.08 to 1.76, p=0.01). A Receiver Operating Characteristic (ROC) curve was performed to test the predictive value of hs-CRP at admission on two-month mortality (AUC 0.68, 95% CI 0.63 to 0.72, p<0.001). Cut-off value was set at 38.4 mg/L. After dichotomization of hs-CRP values according to this cut-off, hs-CRP≥38.4 mg/L at admission proved to be a significant risk factor for mortality (HR 2.10, 95% CI 1.23 to 3.58, p=0.006). CONCLUSION: Serum hs-CRP, but not prealbumin, values at admission are predictors of short-term mortality at hospital admission in elderly multimorbid patients. Inflammation seems to affect prognosis more than malnutrition in this setting and may therefore guide clinicians' attitude towards therapeutic choices.

Integrating Information from FDG - and Amyloid PET for Detecting Different Types of Dementia in Older Persons. A Case-series Study.

A significant progress has been made in the understanding of the neurobiology of Alzheimer's disease. The post-mortem studies are the gold standard for a correct histopathological diagnosis, contributing to clarify the correlation with cognitive, behavioral and extra-cognitive domains. However, the relationship between pathological staging and clinical involvement remains challenging. Neuroimaging, including positron emission tomography (PET) and magnetic resonance, could help to bridge the gap by providing in vivo information about disease staging. In the last decade, advances in the sensitivity of neuroimaging techniques have been described, in order to accurately distinguish AD from other causes of dementia. Fluorodeoxyglucose-traced PET (FDG-PET) is able to measure cerebral metabolic rates of glucose, a proxy for neuronal activity, theoretically allowing detection of AD. Many studies have shown that this technique could be used in early AD, where reduced metabolic activity correlates with disease progression and predicts histopathological diagnosis. More recently, molecular imaging has made possible to detect brain deposition of histopathology-confirmed neuritic ß-amyloid plaques (Aß) using PET. Although Aß plaques are one of the defining pathological features of AD, elevated levels of Aß can be detected with this technique also in older individuals without dementia. This raises doubts on the utility of Aß PET to identify persons at high risk of developing AD. In the present case-series, we sought to combine metabolic information (from FDG-PET) and amyloid plaque load (from Aß PET) in order to correctly distinguish AD from other forms of dementia. By selecting patients with Aß PET + / FDG-PET + and Aß PET - / FDG-PET +, we propose an integrated algorithm of clinical and molecular imaging information to better define type of dementia in older persons.

Dietary style and acid load in an Italian population of calcium kidney stone formers.

BACKGROUND AND AIMS: Animal protein intake may cause an acid load that predisposes individuals to stones by influencing calcium and citrate excretion. These associations were not confirmed in recent studies. Therefore the present study was aimed to compare acid load of diet in stone formers and controls. METHODS AND RESULTS: Participants to the study were 157 consecutive calcium stone formers and 144 controls. Diet was analyzed in these subjects using a software that evaluated nutrient intake from a three-day food intake diary. This software also estimated the potential renal acid load (PRAL, mEq/day). Twenty-four-hour urine excretion of ions and citrate was measured in stone formers. Stone former diet had lower intake of glucose, fructose, potassium and fiber and higher PRAL in comparison with controls. The multinomial logistic regression analysis showed that stone risk decreased in association with the middle and the highest tertiles of fiber intake and increased in association with the highest tertile of PRAL. The linear multiple regression analysis showed that calcium excretion was associated with the sodium excretion and that citrate excretion was associated with the PRAL and animal protein intake in stone formers. CONCLUSION: Our findings suggest that stone formers may undergo a greater dietary acid load sustained by a low vegetable intake and base provision. Dietary acid load does not appear as the main determinant of calcium excretion, but may promote stone risk by decreasing citrate excretion. Sodium intake may predispose to stones by stimulating calcium excretion.

The role of malnutrition in older persons with mobility limitations.

Movement disability has a high prevalence in elderly population, either healthy or with chronic disease. Impaired nutritional status is a very common condition in geriatric patients too, especially if we consider elderly subjects admitted to hospital. There are growing evidences that nutrition and disability are strictly interconnected. On the one side, nutritional status is one of the multiple elements that influence the onset and the course of a functional disability; on the other side, disability itself may contribute to malnutrition onset and worsening. Nutrition may not be the sole factor involved in movement impairment in the elderly, but consciousness of its importance in frail elderly population is growing among clinicians and scientific community. In this paper we review the existing knowledge of these complex relationships, discussing the main observational and interventional studies that explored the role of nutrition in movement disability onset and recovery. We also point out how specific kinds of diet, such as Mediterranean diet or high-protein diet, are involved in disability prevention. Finally, we take a look at the existing evidence of the role of single nutrient dietary intake, such as carotenoids, selenium or vitamin D, in mobility impairment in the elderly population.

The role of PKCε-dependent signaling for cardiac differentiation.

Protein kinase Cepsilon (PKCε) exerts a well-known cardio-protective activity in ischemia-reperfusion injury and plays a pivotal role in stem cell proliferation and differentiation. Although many studies have been performed on physiological and morphological effects of PKCε mis-expression in cardiomyocytes, molecular information on the role of PKCε on early cardiac gene expression are still lacking. We addressed the molecular role of PKCε in cardiac cells using mouse cardiomyocytes and rat bone marrow mesenchymal stem cells. We show that PKCε is modulated in cardiac differentiation producing an opposite regulation of the cardiac genes NK2 transcription factor related, locus 5 (nkx2.5) and GATA binding protein 4 (gata4) both in vivo and in vitro. Phospho-extracellular regulated mitogen-activated protein kinase 1/2 (p-ERK1/2) levels increase in PKCε over-expressing cells, while pkcε siRNAs produce a decrease in p-ERK1/2. Indeed, pharmacological inhibition of ERK1/2 rescues the expression levels of both nkx2.5 and gata4, suggesting that a reinforced (mitogen-activated protein kinase) MAPK signaling is at the basis of the observed inhibition of cardiac gene expression in the PKCε over-expressing hearts. We demonstrate that PKCε is critical for cardiac cell early gene expression evidencing that this protein is a regulator that has to be fine tuned in precursor cardiac cells.

Follow-up in pulmonary sarcoidosis: comparison between HRCT and pulmonary function tests.

PURPOSE: The authors assessed the clinical usefulness of high-resolution computed tomography (HRCT) for monitoring sarcoidosis by comparing changes on HRCT with those on pulmonary function test (PFT) results over time. MATERIALS AND METHODS: The baseline and follow-up (after 13 months, range 15-63 months) HRCT scans of 14 consecutive patients with sarcoidosis were reviewed by a single observer. Each follow-up HRCT examination was assessed as stable, improved (when the extent of HRCT findings was reduced compared with baseline) and worsened (when the extent of HRCT findings was increased and/or when HRCT pattern had become fibrotic compared with baseline). Any increase or decrease in forced vital capacity (FVC)≥10% from baseline was considered significant. Changes on HRCT were then compared with those on FVC. RESULTS: During a median follow-up of 33 (range 15-63) months, HRCT findings worsened in 8/14 (58%) cases, improved in 3/14 (21%) and remained stable in 3/14 (21%). Agreement between changes on HRCT and FVC was moderate (κ=0.49). In 9/14 (64%) cases, HRCT changes were in line with those on FVC. In 4/5 discordant cases, the worsened HRCT findings were not mirrored by FVC changes. CONCLUSIONS: Despite the small size of our study population, our results suggest that HRCT may provide clinicians with additional information about the evolution of sarcoidosis.

Mean temperature and humidity variations, along with patient age, predict the number of visits for renal colic in a large urban Emergency Department: results of a 9-year survey.

BACKGROUND: A marked geographic variability has been reported in stone disease, partially attributed to the Mean Annual Temperature (MAT), as well as to the seasonal fluctuations of climatic conditions. Accordingly, peaks in Emergency Department (ED) visits for renal colic are commonplace during the summer. MATERIALS AND METHODS: The aim of this study was to assess the influence of day-by-day climate changes on the number of visits as a result of renal colic in the ED (City of Parma, northern Italy, temperate continental climate). A total of 10,802 colic episodes were retrieved from the database during a period of 3286days (January 2002 to December 2010). RESULTS: The analysis of the data confirms a peak of renal colic cases during the summer, especially in July (maximum number of 4.1 cases of renal colic per day), and a winter nadir (minimum number of 2.7 cases of renal colic per day, in February). The linear regression analysis shows a high and significant correlation between the mean number of cases of renal colic per day and both the mean daily temperature (positive association, R=0.93; p<0.0001) and the mean daily humidity (negative association, R=-0.82; p<0.0001). The influence of temperature and humidity on the incidence of renal colic cases varied widely among age groups, the highest incidence seen in patients aged between 30 and 40years, and the lowest seen for those aged <20 and >70years of age. CONCLUSION: The combined data suggest that the hot and dry climate would favor an acceleration of the process of stone formation, which seems more pronounced in the older population.

[Artificial nutrition in acute renal failure]. / Nutrizione artificiale nell'insufficienza renale acuta.

Artificial nutrition in course of acute renal failure (ARF) is reviewed, on the basis of recent concepts on epidemiology and prognosis of the syndrome in critically ill patients. The relationships between nutritional status and ARF are evaluated, analyzing the possible role of nutritional status alterations as comorbidities and complications; pathogenetic mechanisms and consequences of hypercatabolism are described, with special regard to the peculiar metabolic derangements which are the hallmark of ARF. The effects of artificial nutrition on mortality and morbility in ARF are illustrated, along with quantitative and qualitative aspects of nutritional support (energy and protein needs, trace elements, vitamins etc). A rational approach to nutritional management of ARF patients is proposed, stressing the potential role of enteral nutrition, as well as the need for a full integration between nutritional support and renal replacement therapies.

Acute polyradiculoneuropathy occurring after hymenoptera stings: a clinical case study.

Hymenoptera stings may be responsible for both local and systemic reactions; these can be immediate or delayed, depending on the time between the sting and the development of signs or symptoms. Delayed clinical reactions have been reported, although unusual, due to serum sickness and/or affecting organs or systems generally not involved in the immediate reaction, such as heart, kidneys, central and peripheral nervous systems. This paper describes the clinical and immunological findings in a 51-year-old subject, who, after two stings of paper wasps, the second one after the third venom immunotherapy (VIT) injection, presented immediate large local and systemic allergic reactions which quickly improved after e.v. methylprednisolone administration. About 40 hours later, he developed acute polyradiculoneuropathy with muscle weakness, paresthesia, difficulties in standing up and walking. Skin tests and specific IgE determination showed allergy to paper wasp. The activation, by wasp venom, of peripheral blood mononuclear cells in primary culture, evaluated by tritiated thymidine incorporation proliferation assay, showed an important hypersensitivity to wasp venom. Therefore our results suggest the hypothesis that the polyradiculoneuritis causative etiopathogenetic mechanism might be a delayed immunological response to wasp antigens followed by an allergy-triggered autoimmune reaction, as previously suggested by other authors; they found lymphocytic infiltrates in demyelinization areas and at perivascular levels, by histologic examination of autoptical and bioptical material of patients with nervous system lesions after hymenoptera stings.

[Post-acute long stay and extensive rehabilitation: study of the first year of work at a long stay university hospital unit]. / Lungodegenza post-acuzie e riabilitazione estensiva: studio sul primo anno di attività di un'Unità di Lungodegenza Ospedaliera-Universitaria.

Long stay is a new type of hospital admission geared to internal medicine patients requiring long-term stays in hospital and prolonged treatment for the purposes of stabilization or clinical rehabilitation. Given the lack of specific experience, we monitored the progress of a Long-Stay Unit with the aim to estimate the clinical and organizational impact. We studied 263 patients (59.3% females, 40.7% males; mean age 76.3 +/- 11.5 years, 42.2% all in their late eighties) coming from medical wards (75%) and from surgical wards (25%). The clinical complexity was prospectively estimated by a form divided into 3 sections: the first part was filled out at the time of transfer, the second part at set intervals throughout the period and the third at the end of the stay. Mean length of stay for medical patients was 33.2 days, for surgical patients 28.6 days (NS). Main transfer diagnosis: 50% of the patients fell into two diagnostic groups: malignant neoplasm (33.1%) and cerebral ictus (17.5%). Some data evidenced remarkable clinical complexity: 93.9% of the patients had one or more secondary diagnoses; when initially admitted 89.4% already presented with complications or serious outcomes; while in the Long-Stay Unit 83.3% required medical treatment and extensive nursing care; 87.1% had further major complications; 56.3% was totally dependent; 42.6% was totally bedridden and 35.4% died. In conclusion, the majority of long-stay patients in a medium-to-large polyclinic hospital present with several concomitant diseases, with extremely invalidating complaints, characterized over the short-to-mid term by serious clinical complications. They require a great deal of competent medical/nursing care as well as highly qualified internal medicine specialists.

Essential arterial hypertension and stone disease.

BACKGROUND: Cross-sectional studies have shown that nephrolithiasis is more frequently found in hypertensive patients than in normotensive subjects, but the pathogenic link between hypertension and stone disease is still not clear. METHODS: Between 1984 and 1991, we studied the baseline stone risk profile, including supersaturation of lithogenic salts, in 132 patients with stable essential hypertension (diastolic blood pressure of more than 95 mm Hg) without stone disease and 135 normotensive subjects (diastolic blood pressure less than 85 mm Hg) without stone disease who were matched for age and sex (controls). Subsequently, both controls and hypertensives were followed up for at least five years to check on the eventual formation of kidney stones. RESULTS: Baseline urine levels in hypertensive males were different from that of normotensive males with regards to calcium (263 vs. 199 mg/day), magnesium (100 vs. 85 mg/day), uric acid (707 vs. 586 mg/day), and oxalate (34.8 vs. 26.5 mg/day). Moreover, the urine of hypertensive males was more supersaturated for calcium oxalate (8.9 vs. 6.1) and calcium phosphate (1.39 vs. 0.74). Baseline urine levels in hypertensive females were different from that of normotensive females with regards to calcium (212 vs. 154 mg/day), phosphorus (696 vs. 614 mg/day), and oxalate (26.2 vs. 21.7 mg/day), and the urine of hypertensive females was more supersaturated for calcium oxalate (7.1 vs. 4.8). These urinary alterations were only partially dependent on the greater body mass index in hypertensive patients. During the follow-up, 19 out of 132 hypertensive patients and 4 out of 135 normotensive patients had stone episodes (14.3 vs. 2.9%, chi-square 11.07, P = 0.001; odds ratio 5.5, 95% CI, 1.82 to 16.66). Of the 19 stone-former hypertensive patients, 12 formed calcium calculi, 5 formed uric acid calculi, and 2 formed nondetermined calculi. Of the urinary factors for lithogenous risk, those with the greatest predictive value were supersaturation of calcium oxalate for calcium calculi and uric acid supersaturation for uric acid calculi. CONCLUSIONS: A significant percentage of hypertensive subjects has a greater risk of renal stone formation, especially when hypertension is associated with excessive body weight. Higher oxaluria and calciuria as well as supersaturation of calcium oxalate and uric acid appear to be the most important factors. Excessive weight and consumption of salt and animal proteins may also play an important role.

Relationship between supersaturation and calcium oxalate crystallization in normals and idiopathic calcium oxalate stone formers.

BACKGROUND: In an earlier study on recurrent CaOx stone formers with no detectable abnormalities, we found that the urine of these subjects had a lower tolerance to oxalate load than controls and that the removal of urinary macromolecules with a molecular weight greater than 10,000 D improved their tolerance to oxalate. METHODS: The effects on CaOx crystallization of reduced urinary supersaturation of calcium oxalate (CaOx), induced by night water load, were studied in 12 normal males and in 15 male OxCa stone formers who were free from urinary metabolic abnormalities. The effect of the macromolecules, purified and retrieved from the natural and diluted urine, were analyzed in a metastable solution of CaOx. RESULTS: The water load caused an increase in urine volume (from 307 +/- 111 to 572 +/- 322 ml/8 hr, P = 0.014 in normal subjects, and from 266 +/- 92 to 518 +/- 208 ml/8 hr, P = 0.001 in the stone formers) and a concomitant reduction of the relative CaOx supersaturation (from 8.7 +/- 2.5 to 5.1 +/- 2.5 ml/8 hr, P = 0.001 in normal subjects, and from 10.4 +/- 3.5 to 5.0 +/- 2.7 ml/8 hr, P = 0.001 in the stone formers). The decrease in CaOx supersaturation was accompanied by an increase of the permissible increment in oxalate, both in normal subjects (from 43.8 +/- 10.1 to 67.2 +/- 30. 3 mg/liter, P = 0.018) and in the stone formers (from 25.7 +/- 9.4 to 43.7 +/- 17.1 mg/liter, P = 0.0001), without any significant variations of the upper limit of metastability for CaOx (from 21.6 +/- 5.3 to 20.5 +/- 4.2 mg/liter in normal subjects, and from 18.7 +/- 4.5 to 17.1 +/- 3.7 mg/liter in the stone formers). The inhibitory effect of urinary macromolecules with molecular weight greater than 10,000 Daltons did not undergo any change when the latter were recovered from concentrated or diluted urine, either in normal subjects or in the stone formers. CONCLUSIONS: Reduced CaOx supersaturation by means of water load has a protective effect with regards to CaOx crystallization in subjects who do not present any of the common urinary stone risk factors.

Urine volume: stone risk factor and preventive measure.

BACKGROUND: A high fluid intake is the oldest existing treatment for kidney stones, and, up until a few decades ago, it was the only preventive measure at the physician's disposal for stone recurrences. METHODS: Using the data available in literature and partly unpublished personal research, we examine the role of urine volume as a stone risk factor, its impact on calcium crystallization mechanisms and its real importance as a means of prevention. RESULTS: To sum up, the most important findings are: (1) a low urine volume must be considered as a real risk factor, both as regards the onset of renal calculi and stone relapses; (2) an increase in urine volume induced by a high water intake produces favourable effects on the crystallization of calcium oxalate and does not reduce the activity of natural inhibitors; (3) a sufficiently high intake of water and probably other fluids such as coffee, tea, beer and wine has a preventive effect on nephrolithiasis and its recurrence, and (4) the role of fruit juice is still to be defined. CONCLUSIONS: A high intake of fluids, especially water, is still the most powerful and certainly the most economical means of prevention of nephrolithiasis, and it is often not used to advantage by stone formers.

Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study.

PURPOSE: We define the role of urine volume as a stone risk factor in idiopathic calcium stone disease and test the actual preventive effectiveness of a high water intake. MATERIALS AND METHODS: We studied 101 controls and 199 patients from the first idiopathic calcium stone episode. After a baseline study period the stone formers were divided by randomization into 2 groups (1 and 2) and they were followed prospectively for 5 years. Followup in group 1 only involved a high intake of water without any dietetic change, while followup in group 2 did not involve any treatment. Each year clinical, laboratory and radiological evaluation was obtained to determine urinary stone risk profile (including relative supersaturations of calcium oxalate, brushite and uric acid by Equil 2), recurrence rate and mean time to relapse. RESULTS: The original urine volume was lower in male and female stone formers compared to controls (men with calcium oxalate stones 1,057 +/- 238 ml./24 hours versus normal men 1,401 +/- 562 ml./24 hours, p < 0.0001 and women calcium oxalate stones 990 +/- 230 ml./24 hours versus normal women 1,239 +/- 440 ml./24 hours, p < 0.001). During followup recurrences were noted within 5 years in 12 of 99 group 1 patients and in 27 of 100 group 2 patients (p = 0.008). The average interval for recurrences was 38.7 +/- 13.2 months in group 1 and 25.1 +/- 16.4 months in group 2 (p = 0.016). The relative supersaturations for calcium oxalate, brushite and uric acid were much greater in baseline urine of the stone patients in both groups compared to controls. During followup, baseline values decreased sharply only in group 1. Finally the baseline urine in patients with recurrences was characterized by a higher calcium excretion compared to urine of the patients without recurrences in both groups. CONCLUSIONS: We conclude that urine volume is a real stone risk factor in nephrolithiasis and that a large intake of water is the initial therapy for prevention of stone recurrences. In cases of hypercalciuria it is suitable to prescribe adjuvant specific diets or drug therapy.

Effects of urinary macromolecules on the nucleation of calcium oxalate in idiopathic stone formers and healthy controls.

Urinary macromolecules have attracted great interest because of their possible role as both promoters and inhibitors of calcium oxalate (CaOx) crystallization and it remains unclear whether there is any difference, in their nucleating activity, between stone formers and controls. We selected 9 male idiopathic CaOx stone formers whose 24-h urines presented no evidence of common urinary stone risk factors such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia, hypomagnesiuria or low glycosaminoglycans excretion and 12 male controls (matched for age and body weight) whose 24-h urines did not differ from those of stone formers. The study of urinary CaOx nucleation was made in freshly voided overnight urines whose biochemical composition was almost identical in the two groups. In filtered (0.22 micron) and ultrafiltered (10 kDa) urine we performed an oxalate tolerance test to determine the permissible increment of oxalate, the oxalate level for nucleation and the permissible increment of CaOx relative supersaturation (CaOx RS). In filtered urine from stone formers the permissible increment of oxalate was lower than controls (30 +/- 10.2 vs. 46.7 +/- 9.7 mg/l, P = 0.001), the oxalate level for nucleation was lower (64.4 +/- 14.2 vs. 79.5 +/- 15.6 mg/l, P = 0.035) and the permissible increment of CaOx RS was also lower (9.71 +/- 2.59 vs. 13.39 +/- 3.62, P = 0.018). In ultrafiltered urine these differences disappeared because the removal of macromolecules in stone formers significantly enhanced the oxalate-tolerance values. The difference between the change of the oxalate permissible increment of filtered and ultrafiltered urine allowed a distinction to be made between stone formers and controls that was not feasible in other ways (7.6 +/- 5.3 vs. 3.3 +/- 5.9 mg/l, P < 0.0001). The study suggests that, in idiopathic CaOx stone formers free from common urinary risk factors of CaOx crystallization, there is an increased tendency for CaOx nucleation in urine, which is mediated by macromolecular components.

Nifedipine and methylprednisolone in facilitating ureteral stone passage: a randomized, double-blind, placebo-controlled study.

Expulsive medical therapy of ureteral stones is not well established. To test the efficacy of a calcium antagonist (nifedipine) associated with a corticosteroid (methylprednisolone) in facilitating ureteral stone passage, we studied 86 patients with a unilateral ureteral radiopaque stone not larger than 15 mm. in maximum diameter, confirmed in each case by drop excretory urography. Patients were randomly treated for a maximum of 45 days under double-blind conditions with 16 mg. methylprednisolone plus 40 mg. nifedipine daily (group 1-13 women and 30 men, mean age 45 +/- 14 years, standard deviation) and with 16 mg. methylprednisolone plus placebo daily (group 2-18 women and 25 men, mean age 43 +/- 14 years). All patients also received 2 l. of low mineral content water daily. The average maximum diameter of the stones was 6.7 +/- 3.0 mm. in group 1 and 6.8 +/- 2.9 mm. in group 2 (not significant). Partial ureteral obstruction was present in approximately half of the patients in both groups. Four patients in group 1 and 6 in group 2 dropped out of the study. In group 1, 34 patients had successful results (stone passage without surgical manipulation) and 5 failed (success rate 87%), compared to 24 and 13, respectively, in group 2 (success rate 65%). This difference was significant (p = 0.021, Fisher's exact test). No difference was present in the maximum stone diameter among the successful cases in groups 1 and 2 (6.4 +/- 2.8 and 5.3 +/- 2.2 mm., respectively, not significant). In both groups the maximum diameter of the stone was larger in the failed than in the successful cases (group 1-10.4 +/- 3.0 versus 6.4 +/- 2.8 mm., p = 0.005, and group 2-9.3 +/- 2.5 versus 5.3 +/- 2.2 mm., p = 0.0001). In group 1 the mean interval for stone passage in the successful cases was 11.2 +/- 7.5 days, compared to 16.4 +/- 11.0 days in group 2 (p = 0.036, Student's t test). We conclude that nifedipine associated with methylprednisolone is effective in facilitating ureteral stone passage.

Hot occupation and nephrolithiasis.

We investigated the prevalence of stone disease and urinary stone risk factors in machinists chronically exposed to a hot environment and massive sweating, without interference of nephrotoxic metals or other lithogenic compounds. The study was performed at a glass plant and exposure to heat stress was estimated by the Wet Bulb Globe Temperature climatic index. The prevalence of nephrolithiasis on the entire population of the machinists was 8.5% (20 of 236), while the prevalence on the controls working in normal temperature was 2.4% (4 of 165) (p = 0.03). A high incidence (38.8%) of uric acid stones was present in the workers exposed to heat stress. Among the urinary stone risk indexes determined for 3 days during the 8-hour work shift on a randomly selected sample of 21 workers exposed and 21 workers not exposed to heat stress without any evidence of stone disease significant differences were found in uric acid concentration (722 +/- 195 versus 482 +/- 184 mg./l., p < 0.001), specific gravity (1,026 +/- 4 versus 1,021 +/- 6, p < 0.005) and pH (5.31 +/- 0.28 versus 5.64 +/- 0.54, p < 0.02), respectively. Thus, high uric acid relative supersaturation was present during occupation in hot temperatures (8.67 +/- 3.49) compared to occupation in normal temperatures (4.15 +/- 2.7) (p < 0.001). This study confirms that chronic dehydration represents a real lithogenic risk factor, mainly for uric acid stones, and adequate fluid intake is recommended during hot occupations.

Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing calcium stone recurrences.

We examined the biochemical changes and the efficacy of indapamide in the prevention of calcium stone recurrences. Seventy-five patients with calcium nephrolithiasis and hypercalciuria were randomly assigned to three different therapies: diet and fluid (group A), diet and fluid plus indapamide 2.5 mg/day (group B), and diet and fluid plus indapamide 2.5 mg/day plus allopurinol 300 mg/day (group C). Before treatment and after 6, 12, 24, and 36 months of therapy, we evaluated blood pressure, serum and urine risk parameters (including relative supersaturations of calcium oxalate, calcium phosphate and uric acid), stone rate, and the proportion of calculi-free patients. During the 3 years of treatment, urinary calcium greatly decreased in groups B and C, dropping to 50% of the pretreatment values; urinary oxalate also significantly declined in group B (-24%) and group C (-27%). Relative supersaturations of calcium oxalate and calcium phosphate decreased to the same extent in groups B and C (about one-half of the pretreatment value), and relative supersaturation of uric acid was particularly reduced in group C (-65% of the pretreatment value). The stone rate improved in all three groups (p < 0.005), but using actuarial analysis in the evaluation of calculi-free patients, indapamide, and indapamide plus allopurinol groups were found to have a significantly more favorable effect than diet and fluid treatment (p < 0.02), without any difference between the two drug groups. Because indapamide has fewer side effects than thiazide diuretics, we conclude that indapamide could be an interesting alternative to thiazides in the prevention of calcium stones in hypercalciuric patients.

Vertebral mineral content in diet-dependent and diet-independent hypercalciuria.

The vertebral mineral content was measured using dual photon absorptiometry in 41 calcium stone patients with idiopathic hypercalciuria. These patients had been previously divided into 2 groups (diet-dependent and diet-independent hypercalciuria) during a low sodium and low calcium diet. In some of the patients (11 with diet-dependent and 11 with diet-independent hypercalciuria) the vertebral mineral content was evaluated in relation to serum ionized calcium, intact parathyroid hormone, alkaline phosphatase and osteocalcin determined after a low sodium and low calcium diet. The vertebral mineral content, expressed as Z-VMD, was normal in diet-dependent and lower in diet-independent hypercalciuric stone patients (-0.30 +/- 1.19 versus -0.26 +/- 1.18, p less than 0.02). In 7 of 21 patients (33.3%) the vertebral mineral content was less than 2 standard deviations of the normal value, indicating a true involvement in bone metabolism. Serum intact parathyroid hormone and osteocalcin levels were not different from the controls in both groups, while alkaline phosphatase activity and ionized calcium were higher in diet-independent hypercalciuric patients. Serum ionized calcium was negatively correlated with bone vertebral density. The results suggest that an increased bone turnover may be a primary event in causing hypercalciuria in calcium stone patients unable to decrease urinary calcium to less than the calcium intake.