bluuebunny/crossref_metadata_2025 huggingface dataset:
Acid-Base State in Patients after Cardiac Transplantation
Authors: Frangiosa Annamaria , De Santo Luca Salvatore , De Santo Natale Gaspare , Anastasio Pietro , Favazzi Pietro , Cirillo Eleonora , Cotrufo Maurizio , Adroguè Horacio J.
Published: April 2003

Patients with advanced heart failure commonly develop simple or mixed acid-base disturbances. The altered acid-base homeostasis can occur as a consequence of the heart failure itself, the therapeutic interventions, or associated conditions. The present study examined acid-base disorders in patients with heart failure who received successful heart transplantation. The information collected should provide light on the determinants of acid-base disorders in this patient population. Seventy status 2 UNOS (United Network Organ Sharing) patients listed for heart transplantation were enrolled in this study. All patients received loop diuretics, spironolactone, ACE inhibitors, carvedilol and digitalis as needed. Patients were studied again at discharge after transplantation, under cyclosporine, azathioprine, steroids, loop diuretics and ACE inhibitors. After heart transplantation, a significant increase of ejection fraction from 19.7 ± 0.63 to 53.6 ± 0.9% (p < 0.0001) occurred along with a concomitant reduction of central venous pressure (p < 0.0001) from 12.6 ± 0.20 to 6.9 ± 0.21 mm Hg. Before heart transplantation there was high-normal pH (7.43 ± 0.009), slight loss of hydrogen ions (35.4 ± 0.4 nmol/l), slightly reduced pCO2 (37.6 ± 1.1 mm Hg). After heart transplantation a stability of blood pH and hydrogen ion concentrations was found but bicarbonate increased significantly (p < 0.02) from 24.2 ± 0.61 to 26.2 ± 0.51 mmol/l and pCO2 from 37.6 ± 1.1 to 39.3 ± 0.7 mm Hg (p < 0.05). Plasma renin activity averaged 3.80 ± 0.6 pg/ml before heart transplantation and 2.82 ± 0.4 pg/ml after (p < 0.01). Aldosterone concentration averaged 380 ±15 pg/ml before heart transplantation and 280 ± 10 pg/ml after (p < 0.01). These data suggest that in patients before heart transplantation there is a mixed acid-base imbalance that includes respiratory alkalosis and metabolic alkalosis. After transplantation the recovery of the abnormal circulatory status erased the initial respiratory alkalosis but metabolic alkalosis persisted and accounted for a further rise in plasma bicarbonate.
Effects of L-Threo-3,4-Dihydroxyphenylserine on Orthostatic Hypotension in Hemodialysis Patients
Authors: Iida Nobutoshi , Koshikawa Syozo , Akizawa Tadao , Tsubakihara Yoshiharu , Marumo Fumiaki , Akiba Takashi , Kawaguchi Yoshindo , Imada Akio , Yamazaki Chikao , Suzuki Masashi
Published: April 2003

Background: Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD as well as during the interdialytic period. L-Threo-3,4-dihydroxyphenylserine (L-DOPS) is a nonphysiological neutral amino acid that is directly converted to the neurotransmitter norepinephrine by aromatic L-amino acid decarboxylase. Methods: A placebo-controlled double-blind study for 4 consecutive weeks and a long-term study (24–52 weeks) were conducted to evaluate the efficacy of L-DOPS for OH after HD. The drug was administered orally 30 min before the start of each HD period in both studies. Doses of 400 mg of L-DOPS or placebo were given to HD patients with OH (45 and 41 patients, respectively) in the double-blind study, and doses of 200 or 400 mg of L-DOPS were given to 74 HD patients in the long-term study. Results: In the double-blind study, L-DOPS significantly ameliorated subjective symptoms related to OH, including dizziness/light-headed feeling, and malaise, throughout the interdialytic period. For 19 patients with delayed-type OH, hypotension with the lowest blood pressure recorded 10 min after standing, the decrease in blood pressure was suppressed significantly after L-DOPS treatment (10 patients) as compared with the placebo-treated group (9 patients). In the long-term study, the efficacy of L-DOPS was not attenuated, and the marked fluctuations in the plasma L-DOPS and norepinephrine levels were not noted after long-term use, without increases in incidence or severity of adverse reactions. Conclusions: These results indicate that L-DOPS is effective for improving OH-related interdialytic subjective symptoms in HD patients after short-term as well as after long-term administration.
Urate Nephropathy following Chronic Ileostomy Acidosis
Authors: Randall Jr. Russell E.
Published: April 2003

Normal renal function and normal urinalysis results in an 81-year-old man deteriorated over a 6-month period following an ileostomy, associated with metabolic acidosis, persistent aciduria, proteinuria, and a urinary sediment that showed numerous red blood cells, granular casts, and ‘reactive’ epithelial cells with intracellular uric acid (UA) crystals. These also formed extensive UA casts. Oral sodium bicarbonate therapy completely reversed all of the abnormalities. Renal biopsy, while it failed to demonstrate significant tubular obstruction, showed evidence of extensive epithelial cell injury. It is suggested that intestinal losses of bicarbonate resulted in persistent excretion of an acidic urine which promoted UA crystal formation within renal tubules and in epithelial cells which then caused cellular injury and the release of cytokines, leading to an altered regulation of the renal blood flow. The importance of microscopic techniques in the diagnosis is stressed along with the significance for managing both acute and chronic renal failure.
Laudable Pus – Lardaceous Kidneys
Authors: Brown H. , Luce P. , Dussek J. , Scoble J.E. , Goldsmith D.J.A.
Published: April 2003

Amyloidosis frequently affects the kidney leading to proteinuria and loss of function. In cases of AA (reactive/inflammatory) amyloidosis, it is sometimes possible to quench the stimulus to chronic inflammation and by so doing stop further elaboration and deposition of amyloid fibrils. We describe the case of a man with a long-standing empyema who developed nephrotic syndrome and renal impairment. The empyema was resected and shortly afterwards proteinuria disappeared and renal function improved. Strenuous efforts are mandatory to locate and definitively treat underlying inflammatory foci in AA amyloidosis.
Chronic Hypercalcemia as the Presenting Feature of Tuberculous Peritonitis in a Hemodialysis Patient
Authors: Lee Chien-Te , Hung Kuei-Hung , Lee Chih-Hsiung , Eng Hock-Liew , Chen Jin-Bor
Published: April 2003

Hypercalcemia is a common electrolyte disturbance in chronic dialysis patients. Although most causes are easily identified, some are obscure. Tuberculosis, a granulomatous disease associated with hypercalcemia, can appear at anytime while the infection is active. Dialysis-associated tuberculosis is characterized by a higher risk than that in the general population, with a greater chance of extrapulmonary involvement and a high mortality rate. If the presentation of tuberculosis is atypical and its manifestation nonspecific, diagnosis can be delayed, leading to poor patient outcome. Herein, we report a case of tuberculous peritonitis in a hemodialysis patient. Asymptomatic hypercalcemia was noted 8 months before ascites became detectable. Nevertheless, the patient responded well to antituberculous therapy. We conclude that hypercalcemia can be an early sign of tuberculous peritonitis in the absence of other signs and symptoms. Remaining aware of the possibility of tuberculosis and testing for it, physicians can identify tuberculous infection earlier and initiate appropriate therapy in a timely manner.
Clinical Characteristics and Survival in End-Stage Renal Disease Patients with Arteriosclerosis obliterans
Authors: Nakamura Satoko , Sasaki Osamu , Nakahama Hajime , Inenaga Takashi , Kawano Yuhei
Published: April 2003

Background: Atherosclerotic disease (ASO) is considered a serious problem in dialysis patients. We tried to clarify the characteristics of ASO and to evaluate its impact on survival. Methods: Between January 1990 and December 1999, 525 patients with end-stage renal disease were admitted to our hospital. Among these patients, 71 (59 male and 12 female) had ASO. Blood pressure and blood samples were measured before and after hemodialysis, and were compared with the hemodialysis patients without any cardiovascular diseases. Mortality findings were collected until April 30, 2000. Results: Patients with ASO contained a larger percentage of males, hypertension, hyperlipidemia, diabetes mellitus, nephrosclerosis and smoking status. Their serum calcium, serum phosphate, triglyceride and C-reactive protein levels were also higher. During the follow-up period (2.8 ± 0.2 years), the mortality rate of the patients with ASO was higher than the hemodialysis patients without any cardiovascular diseases. Among the patients with ASO, the significant covariates concerning the cardiovascular mortality rate were age, hyperlipidemia and smoking status according to the Cox Proportional Hazards regression analysis. Conclusions: Hemodialysis patients with ASO had many traditional risk factors and uremic risk factors. Their survival rate was poorer and dependent on these risk factors.
Guillain-Barré Syndrome Associated with Minimal Change Glomerulopathy and Tubular Dysfunction – Related to Acetone-Based Organic Solvent?
Authors: Chen Jiann-Keh , Wu Mai-Szu , Yang Chih-Wei , Huang Jeng-Yi , Hsu Po-Yaur , Lin Chun-Liang , Huang Chiu-Ching
Published: April 2003

A 55-year-old woman presented with Guillain-Barré syndrome, nephrotic syndrome and multiple tubular dysfunction under occupational exposure to an organic solvent, which contained acetone as the principal solvent. In this case, the onset of the nephrotic syndrome and tubular dysfunction coincided with the development of the neurological manifestation. Renal biopsy demonstrated minimal change glomerulopathy with moderate tubulointerstitial nephritis. Several clearance tests that evaluated tubular transport functions revealed multiple tubular defects (including the Na+-K+-Cl– cotransporter of thick ascending limb and distal proton pump). The simultaneous occurrence of Guillain-Barré and nephrotic syndrome has previously been reported. However, both minimal glomerulopathy with multiple tubular dysfunction and progressive peripheral neuropathy under occupational exposure to an organic solvent remain unreported. Herein, we presented a rare association of minimal change nephrotic syndrome, tubular dysfunction with Guillain-Barré syndrome under the risk of exposure to an acetone-based cleansing solution; the case raises our concerns about possible chronic nephrotoxic or neurotoxic effects of common chemical organic solvents.
Successful Treatment of Steroid-Resistant Minimal Change Disease with Mycophenolate Mofetil
Authors: Mogyorósi András , Lippman H. Robert , Feldman George M.
Published: April 2003

Mycophenolate mofetil has been reported to be effective in the treatment of steroid-responsive minimal change disease. We report a case of steroid- and cyclosporin-resistant minimal change disease with severe nephrotic syndrome that responded to mycophenolate mofetil with complete remission. The patient remains in complete remission 1 year after the discontinuation of mycophenolate mofetil. The presented case argues for the need of a prospective controlled study with the goal of evaluating the efficacy of mycophenolate mofetil in the therapy of steroid-resistant minimal change disease.
Gentamicin Reduces Serum ACE Activity in Patients with Normal Kidney Function
Authors: Ziai Seyed Ali , Mooraki Ahmed , Mahmoudian Massoud
Published: April 2003

Aims: We evaluated serum angiotensin-converting enzyme (ACE) as an indicator of gentamicin toxicity and compared it with N-acetyl-β-D-glucosaminidase (NAG) and creatinine. Methods: 20 bone fracture in-patients receiving gentamicin 80 mg TDS for 3 days. Subjects had normal kidney function and had no history or sign of hypertension. Serum and urine samples were collected before and 3 days after drug administration. Samples analyzed for ACE, NAG, BUN, creatinine, sodium, and potassium. Results: Our results showed that urine NAG activity increased significantly at the 3rd day. Serum creatinine level and glomerular filtration rate (GFR) while still at a normal range showed slight but significant changes at this time. This may indicate some renal damage. Serum ACE activity decreased significantly at the 3rd day. Conclusion: These results indicate serum ACE can be used as a good indicator of renal damage in patients receiving gentamicin.
Peripheral Arterial Disease Is Not Associated with an Increased Prevalence of Intradialytic Cramps in Patients on Maintenance Hemodialysis
Authors: Brass Eric P. , Adler Sharon , Sietsema Kathy E. , Amato Antonino , Esler Anne , Hiatt William R.
Published: April 2003

Background/Aims: Peripheral arterial disease (PAD) has been suggested as a contributing factor to the development of intradialytic muscle cramps in patients on maintenance hemodialysis. Methods: To test this hypothesis, 122 patients from two dialysis centers were studied. The presence of PAD was determined by measurement of the ankle-brachial index (ABI) in the lower extremities of patients pre- and postdialysis. The experience of intradialytic cramps was assessed using patient history and review of medical records. Results: PAD defined as a predialysis ABI ≤0.90 had an overall prevalence of 16.4% among patients studied. The prevalence of PAD was age-dependent, reaching 37.5% in patients 80–89 years old. Intradialytic muscle cramps were common, with 52.1% of patients reporting cramps within the previous two months, but there was no relationship between cramps during dialysis and PAD (p > 0.05). Conclusions: PAD was common in hemodialysis patients, but there was no association between the presence of PAD and the prevalence of intradialytic muscle cramps.
Vitamin K Status in Relation to Bone Metabolism in Patients with Renal Failure
Authors: Małyszko Jolanta , Wołczyński Sławomir , Skrzydlewska Elżbieta , Małyszko Jacek S. , Myśliwiec Michał
Published: April 2003

Vitamin K abnormalities may be involved in the pathogenesis of bone disease in patients with advanced renal failure since vitamin K plays a role in the synthesis of osteocalcin, a marker of bone formation. Vitamin K may also indirectly suppress parathyroid function. The aim of this study was to evaluate vitamin K status in patients with renal failure and in healthy volunteers in relation to some biochemical markers of bone turnover. The studies were performed on: patients with chronic renal failure (CRF) on conservative treatment; hemodialyzed patients treated with continuous ambulatory peritoneal dialysis (CAPD); kidney transplant patients, and a control group. Intact PTH, osteocalcin, vitamin 1,25-(OH)2D3, 25-OH-D3, bone-specific alkaline phosphatase, procollagen type-I cross-linked carboxyterminal telopeptide, deoxypyridinoline, and osteonectin were assayed using commercially available kits, and the vitamin K concentration by HPLC. We found that vitamin K concentrations did not differ significantly between all the groups studied. Only in CRF patients was the vitamin K concentation low, almost reaching statistical significance when compared to the healthy volunteers (p = 0.05) and correlated positively with age, serum calcium and osteonectin. No statistically significant correlations were found between vitamin K and osteocalcin, PTH or other biochemical parameters of bone metabolism studied in patients with CRF and renal replacement therapy. In patients after renal replacement therapy, the only significant positive correlation was found between phylloquinone and osteonectin (r = 0.027, p = 0.004). The same applied when we also included healthy volunteers. The correlations of osteonectin and vitamin K are of unknown clinical relevance. Our study does not support the hypotheses of a possible role of vitamin K deficiency in patients with CRF and the influence of vitamin K on bone metabolism.
A Retrospective Evaluation of 1,25-Dihydroxyvitamin D3 and Its Potential Effects on Renal Allograft Function
Authors: O’Herrin Jacquelyn K. , Hullett Debra A. , Heisey Dennis M. , Sollinger Hans W. , Becker Bryan N.
Published: April 2003

Background/Aims: 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) plays an important role in regulating immunologic responsiveness in addition to its effects on bone metabolism. This is potentially beneficial in the transplant setting. Animal studies have demonstrated the utility of 1,25-(OH)2D3 in prolonging allograft survival. Therefore, we evaluated the effects of 1,25-(OH)2D3 (oral calcitriol) in human renal transplant recipients. Methods: A case-control study was undertaken assessing the effects of calcitriol on transplant function. The effect of calcitriol on renal function was analyzed using general linear mixed modeling of the change in slope of serum creatinine (Scr) prior to and following the start of calcitriol therapy. Results: There was a significant increase in baseline Scr (p < 0.001) prior to starting calcitriol. Following initiation of calcitriol, there was a deceleration in the rate of loss of graft function (p = 0.031 at day 300 of therapy). Graft survival was also prolonged in calcitriol-treated patients compared to a control population with evidence of chronic allograft nephropathy but no calcitriol therapy (p < 0.03). Overall, there were no adverse or harmful effects related to calcitriol therapy. 1,25-(OH)2D3 therapy was associated with (1) a deceleration in the rate of loss of renal function in transplant recipients with more than one year of allograft function, and (2) no significant change in allograft function early after transplantation. Conclusion: These data suggest that short- and long-term prospective trials evaluating 1,25-(OH)2D3 or 1,25-(OH)2D3 analogs in human kidney transplantation are warranted. Such trials may help us elucidate mechanism and duration of action, as well as safety issues related to these novel immunomodulatory agents.
Effect of Soy Protein Added to Casein Diet on the Development of Glomerular Injury in Spontaneous Hypercholesterolemic Male Imai Rats
Authors: Sakemi Takanobu , Ikeda Yuji , Shimazu Kanako
Published: April 2003

Background: We have already reported an attenuating effect of a semipurified alcohol extract of soy protein (mainly consisting of isoflavones) on glomerular injury. Therefore, in the present study, we investigated whether soy protein itself has an ability to attenuate glomerular injury when added to casein diet in male Imai rats of a spontaneous focal segmental glomerulosclerosis model. Method: Male Imai rats were used and allocated into five groups. Group A of control casein diet (Ca) was fed standard diets containing 24.5% casein as a protein source. Group B of control soy protein diet (SP) was fed soy protein diet containing 24.5% protein that substituted a soy protein isolate for casein. Groups C (Ca-SP10) and D (Ca-SP20) were fed a mixture diet of casein (24.5%) and SP (10%) or SP (20%). Group E (Ca-Ca) was fed high casein diet containing the same quantity in protein content (44.5% casein) as the Ca-SP20 diet. Body weight, urinary protein, serum constituents and systolic blood pressure were investigated every 4 weeks from 12 weeks through 24 weeks of age. At 24 weeks of age, rats were studied morphologically. Results: Animals fed control SP diet showed a significantly greater body growth than animals fed the other 4 test diets. No significant differences were found in body growth among the other 4 groups except for group E, which showed a stunt at the end of the experiment. Control SP diet significantly decreased proteinuria and serum cholesterol and attenuated glomerular injury and glomerular hypertrophy as compared with control casein diet. Added SP failed to attenuate glomerular injury, but when compared with high casein diet (group E), added SP resulted in less proteinuria, less hyperlipidemia, less hypoalbuminemia, less glomerular hypertrophy and less renal histological damage despite the quantity being the same in protein content. Conclusion: The present study indicates that soy protein added to conventional casein diet did not have the ability to attenuate glomerular injury, but soy protein is not as harmful as casein as a protein source when added to casein diet in the development of glomerular injury in the rat model of spontaneous focal glomerular sclerosis.
Therapeutic Approach to Hyperkalemia
Authors: Kim Ho-Jung , Han Sang-Woong
Published: April 2003

The foremost step in the initial clinical management of hyperkalemia is to decide whether a hyperkalemic patient requires immediate treatment to avoid a life-threatening situation (serum potassium concentration >6.0 mEq/l and EKG changes). When the decision for urgent treatment of hyperkalemia is based on EKG changes, an important caveat for clinicians is that absent or atypical EKG changes do not exclude the necessity for immediate intervention. Once an urgent situation has being handled with intravenous push of a 10% calcium salt, the initiation of short-term measures can be launched by either a single or combined regimen of the three agents that cause a transcellular shift of potassium – insulin with glucose, β2-agonist (albuterol), and NaHCO3. As the first choice among these available options, we favor an intravenous bolus of 10 units of insulin with 50 ml of 50% glucose alone or in combination with 10–20 mg of albuterol by nebulizer. These can be repeated as required until the institution of hemodialysis. The combination of insulin with glucose and NaHCO3 as an another option needs further clarification for its additive effects. However, NaHCO3 has lost its favor because of its poor efficacy as a potassium-lowering agent when used alone. The next step is to remove potassium from the body – diuretics (furosemide), cation exchange resin (kayexelate) with sorbitol, and dialysis (preferably hemodialysis). The final important step for the managements of hyperkalemia is a long-term plan to prevent its recurrence or worsening. In addition to every effort to elucidate underlying causes and pathophysiologic mechanisms for hyperkalemia, an extensive search must be made to uncover overt or sometimes covert medications that may have led to the development of hyperkalemia. Furthermore, one must obtain detailed dietary and medical history of hyperkalemic patients.
Association Analysis for Serotonin Transporter Promoter Polymorphism and Auditory Evoked Potentials for Major Depression
Authors: Chen Tai-Jui , Yu Younger W.-Y. , Chen Ming-Chao , Tsai Shih-Jen , Hong Chen-Jee
Published: April 2003

The serotonergic system has been implicated in the production of the N1 and P2 components of auditory evoked potentials (AEPs). Moreover, studies have indicated the influence of heritability in the genesis of these AEP components. The serotonin transporter is the major site of serotonin reuptake into the presynaptic neuron, and it has been determined that variants in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) may affect gene transcription activity. The present study tested the hypothesis that the 5-HTTLPR genetic polymorphism is associated with the N1 and P2 components of AEPs in a sample of 127 Chinese patients (mean age: 41.6 years; male/female ratio: 58/69) diagnosed with major depression. Analysis of the results revealed a significantly shorter P2 latency for patients bearing the s/s genotype in comparison with l allele carriers, especially for the female patients (p = 0.004). The 5-HTTLPR polymorphism accounted for 3.4% of the variance in P2 latency. Our findings suggest a relationship between the 5-HTTLPR polymorphism and AEP P2 latency, and further studies of other genetic polymorphisms in the serotonergic system may help to predict this latency.
Hippocampal Volume in Schizophrenia and Its Relationship with Risperidone Treatment: A Stereological Study
Authors: Savas Haluk A. , Unal Bunyami , Erbagci Hulya , Inaloz Serap , Herken Hasan , Canan Sinan , Gumusburun Erdem , Zoroglu S. Salih
Published: April 2003

The purpose of this study was to assess the significance of the hippocampal volume differences and its relation with risperidone treatment in schizophrenia. In schizophrenic patients who were on risperidone treatment (n = 11) and in healthy volunteers (n = 11), volumes of the hippocampi were estimated using magnetic resonance images (MRIs). A detailed systematic series of coronal MRIs of the entire brain (3 mm thickness, T1-weighted, TR/TE 400/10 ms) was obtained for each subject. All estimations were done according to Cavalieri’s method by a modified point-counting grid placed on surface areas of hippocampal slices. The mean right and left hippocampal volumes in schizophrenics and control subjects were 1,059.4 and 1,003.2 mm3, and 1,780.1 and 1,589.1 mm3, respectively. The corresponding coefficients of errors were 0.05 and 0.068, and 0.059 and 0.081, respectively. The volumes of left and right hemispheres were not significantly different in both schizophrenic patients and controls (p > 0.05). However, a statistically significant difference (p < 0.05) was found between hippocampal volumes of the schizophrenic patients and controls. In conclusion, the hippocampal volume of the schizophrenic patients is significantly smaller than of the healthy controls. The patients who responded well to risperidone treatment had significantly greater hippocampal volumes than the patients who did not respond properly. Thus, hippocampal volume may be a predictor of the treatment response of schizophrenics to risperidone.
Comparison of Plasma Levels of Mature Adrenomedullin and Natriuretic Peptide as Markers of Cardiac Function in Hemodialysis Patients with Coronary Artery Disease
Authors: Osajima Akihiko , Okazaki Masahiro , Tamura Masahito , Anai Hirofumi , Kabashima Narutoshi , Suda Takeshi , Iwamoto Masako , Ota Takayuki , Watanabe Yuujiro , Kanegae Kaori , Nakashima Yasuhide
Published: April 2003

Background: It has been suggested that, like ANP and BNP, high plasma levels of mature adrenomedullin (mAM) indirectly reflect the severity of heart failure or renal failure. However, the relationship between mAM levels and hemodynamics and cardiac function has not been examined in hemodialysis (HD) patients with coronary artery disease (CAD). The best marker, among mAM, ANP and BNP, for left-ventricular function in those patients is also unclear. Patients and Methods: Plasma levels of mAM, total AM (tAM), ANP and BNP were determined before HD in chronic HD patients with CAD (group 1; n = 17) and were compared with those of HD patients without cardiac disease (group 2; n = 22). We examined their relationship to hemodynamics and cardiac function in group 1 using data obtained by cardiac catheterization. Results: Plasma levels of ANP and BNP were significantly higher in group 1 than in group 2, but there was no significant difference in plasma levels of mAM and tAM between the two patient groups. Plasma levels of both mAM and tAM significantly correlated with right atrial pressure (RAP), and only plasma tAM levels correlated with pulmonary artery pressure (PAP) and pulmonary artery wedge pressure (PAWP). However, no correlations were found between levels of the two forms of AM and ejection fraction (EF). In contrast, plasma ANP and BNP levels significantly correlated with both PAP and PAWP, and also with EF, although they did not correlate with RAP. The correlation of PAP and PAWP with ANP and BNP levels was closer than that with tAM levels. The most significant correlation was between BNP levels and EF (r = –0.756, p < 0.0001). Conclusions: Our results suggest that the mAM level may be less useful than natriuretic peptide levels as a marker of cardiac function in HD patients with CAD, and that the BNP level might be the best indicator of left-ventricular function. In addition, cardiac disease such as CAD may have a minor impact on mAM levels compared to renal failure.
Descriptive Epidemiology of Head Injury in Romagna and Trentino
Authors: Servadei Franco , Verlicchi Angela , Soldano Franca , Zanotti Bruno , Piffer Silvano
Published: April 2003

We studied the occurrence of head injury in two different Italian regions: Romagna and Trentino. Both geographical areas attract large numbers of seasonal tourists. The study was carried out over 1 year (January 1, 1998 to December 31, 1998), prospectively in Romagna and retrospectively in Trentino because of their different head injury management protocols. The study was based on all admissions to hospital extracted by medical staff from the case records, and all cases were identified by the ICD-9 codes (ranges: 800.0–800.3, 801.0–801.3, 803.0–803.3, 850, 851.0–851.1, 852.0–852.1, 853.0–853.1, 854.0–854.1). The annual incidence of hospitalization for head injury was 314/100,000, 297 for Romagna and 332 for Trentino. The causes of head trauma and the type of injuries were similar to those reported in the international literature, and so were the characteristics of the population at risk. Romagna recorded a higher incidence of head injury among the elderly, probably due to the widespread use of bicycles without safety helmets. In Romagna, where neurosurgery departments exist, hospital mortality was low (8/100,000/year). Based on similar international literature findings, different prevention measures are suggested to reduce the occurrence and severity of head injury.
Reliability of the El Escorial Diagnostic Criteria for Amyotrophic Lateral Sclerosis
Authors: Beghi Ettore , Balzarini Carla , Bogliun Graziella , Logroscino Giancarlo , Manfredi Luigi , Mazzini Letizia , Micheli Anna , Millul Andrea , Poloni Marco , Riva Riccardo , Salmoiraghi Fabrizio , Tonini Clara , Vitelli Eugenio
Published: April 2003

Background: The El Escorial diagnostic criteria are the most commonly used in clinical studies and therapeutic trials in patients with amyotrophic lateral sclerosis (ALS). The accuracy of the El Escorial criteria was tested in clinical practice, but the reliability is unknown when the diagnosis of ALS must be assessed on the basis of medical records. Objective: To assess the reliability of the El Escorial criteria for the diagnosis of ALS in different settings. Design and Methods: Semistructured forms were used to include the main diagnostic information on 20 patients with definite (n = 6), probable (n = 6), possible (n = 6), and suspected ALS (n = 2) and 19 patients with clinical conditions considered in the differential diagnosis. Agreement was tested by comparing the diagnosis made by the attending physician (the ‘gold standard’) with that of 4 raters with different backgrounds: a teaching neurologist with research and practical experience in the field of motor neuron disorders, a neurologist with specific interest in motor neuron disorders and neurophysiological background, a neurophysiologist, and a general neurologist with only occasional ALS patients. Sources of disagreement were discussed and the agreement was tested further on the medical records of 98 additional cases taken from an ongoing ALS registry. Eight additional cases (ALS: 4; other conditions: 4) were examined directly by the 4 raters. Results: The interrater agreement on the medical records was poor (overall kappa 0.05–0.29). When the differential diagnosis was made between ALS (all diagnostic levels) and other conditions, interrater agreement was at best modest, with moderate variations when raters were compared in pairs (kappa 0.03–0.58) and when each rater was compared with the physician (kappa 0.27–0.51). Agreement was higher after direct examination of the patients (kappa 0.33–1) and increased significantly on the medical records after training (overall kappa 0.52–0.79). However, concordance was low (overall kappa 0.08–0.36), even after training, at the lowest diagnostic level (definite to suspected ALS vs. other conditions). Conclusions: The El Escorial criteria are a poor diagnostic indicator when patients’ records are examined. Although medical education significantly improves the reliability of the criteria, concordance is still modest when the diagnosis includes suspected ALS.
Testicular Amyloidosis
Authors: Corvino C. , Balloni F. , Meliani E. , Giannini A. , Serni S. , Carini M.
Published: April 2003

Rapid testicular enlargement is usually strongly suggestive of tumor. Primary testicular infiltration due to amyloidosis is rare. We report a new case of primary testicular amyloidosis in a 72-year-old white man who presented with a short history of painless right testis enlargement.
Detection of Connective Tissue Growth Factor in Human Aqueous Humor
Authors: van Setten G.-B. , Blalock Timothy D. , Grotendorst Gary , Schultz Gregory S.
Published: April 2003

Purpose: Connective tissue growth factor (CTGF) has been shown to be substantially involved in various processes of fibrosis. We investigated if CTGF is present in aqueous humor (AH). Methods: Samples from AH were collected from 10 volunteers during cataract surgery. Specific ELISA analysis was performed with goat IGG against human CTGF. Results: CTGF was above the detection limit of the assay in 80% of the samples. The concentration of CTGF in the anterior chamber fluid was 1.24 ± (SD) 0.26 ng/ml. Conclusion: CTGF is present in a majority of AH samples, possibly representing a constant component in this fluid. The origin and physiological importance of CTGF is yet unclear. The involvement of CTGF in processes of intraocular fibrosis and wound healing is possible.
Use of Epidermal Equivalents Generated from Follicular Outer Root Sheath Cells in vitro and for Autologous Grafting of Chronic Wounds
Authors: Limat Alain , Hunziker Thomas
Published: April 2003

During wound healing, outer root sheath (ORS) cells of hair follicles can substitute for interfollicular epidermal keratinocytes and thus act as precursor cells for interfollicular epidermal keratinocytes. Owing to improved culture techniques, ORS cells can be induced to develop highly differentiated epidermal equivalents, which are close to the normal human epidermis in terms of histological, ultrastructural, biochemical and immunohistological criteria. Such epidermal equivalents provide a versatile system for various applications in vitro, e.g. the study of epidermal homeostasis, cell interactions, pigmentation as well as toxicity testing and metabolism of xenobiotics. The easy and repeated availability of ORS cells, their successful multiplication in culture irrespective of the age of the hair follicle donor as well as the extended tissue normalization of epidermal equivalents prepared with ORS cells prompted us to test the usefulness of autologous epidermal equivalents for the treatment of recalcitrant chronic wounds. Autologous grafting of such epidermal equivalents in more than 50 recalcitrant leg ulcers of a mainly vascular origin resulted in an initial take rate of around 90%, with subsequent complete closure of the ulcers in about 45% and a significant size reduction in another 40% within 8 weeks. These positive results are probably due to the large compartment of proliferative cells as well as to the well-developed horny layer, which prevents rapid disintegration of the grafts. Practical advantages of this technology are its noninvasiveness and thus repeated availability, the fact that surgical facilities are not necessary and the short immobilization period after grafting, allowing a strategy of sequential application in an outpatient setting as an alternative to surgical autografting.
Molecular Basis of Red Cell Membrane Disorders
Authors: Delaunay Jean
Published: April 2003

We will consider an array of genetic disorders of the red cell membrane. Some affect well-known genes. The mutations of most cases of hereditary spherocytosis (HS) are located in the following genes: ANK1, SPTB, SLC4A1, EPB42 and SPTA1, which encode ankyrin, spectrin β-chain, the anion exchanger 1 (band 3), protein 4.2 and spectrin α-chain, respectively. A dominant form of distal renal tubular acidosis also stems from distinct mutations in the SLC4A1 gene. The mutations responsible for hereditary elliptocytosis (HE) and its aggravated form, poikilocytosis (HP), lie in the SPTA1 and SPTB gene, already mentioned, and in the EPB41 gene encoding protein 4.1. Whereas in HS, the SPTA1 and SPTB gene mutations tend to abolish the synthesis of the corresponding chains, in HE/HP, they hinder spectrin tetramerization. Allele αLELY is a common polymorphic allele which plays the role of an aggravating factor when it occurs in trans of an elliptocytogenic allele of the SPTA1 gene. Southeast Asian ovalocytosis results from a 27- nucleotide deletion in the SLC4A1 gene. Besides these conditions in which the mutations were reached from known alterations in the proteins, other conditions required a positional cloning approach. Such are the genetic disorders of membrane permeability to monovalent cations. Knowledge is the most advanced as regards dehydrated hereditary stomatocytois (DHS). DHS was shown to belong to a pleiotropic syndrome: DHS + fetal edema + pseudohyperkalemia, which maps to 16q23–24. Concerning DHS and another disease of the same class, overhydrated hereditary stomatocytosis, splenectomy almost certainly appears to elicit thromboembolic accidents.
Evolutionary Clues to the Molecular Function of Fanconi Anemia Genes
Authors: Blom Eric , van de Vrugt Henri J. , de Winter Johan P. , Arwert Fré , Joenje Hans
Published: April 2003

Fanconi anemia (FA) is an autosomal recessively inherited disease with diverse clinical symptoms including developmental anomalies, predisposition to neoplasia, and a deficiency of hematopoietic stem cells resulting in progressive aplastic anemia. FA is genetically heterogeneous with at least 8 genes being implicated on the basis of functional complementation studies. To date, six FA genes are known: FANCA, FANCC, FANCD2, FANCE, FANCF and FANCG, all of which encode orphan proteins sharing no homology to each other nor to any other known protein. In addition, they do not appear to possess any domains with homology to currently known protein domains, which makes a prediction about their molecular action difficult. Studying the molecular evolution of FA genes and their products using sensitive database search methods such as PSI-BLAST may provide novel insight into the nature of the FA pathway and its relationship to hematopoiesis, embryonic development and the origin of malignancies. Preliminary results of such an approach show that at least one FA protein, FANCG, may contain a known domain, suggesting that this protein is a member of the family of tetratricopeptide repeat-containing proteins.
Antithrombotic Therapy in Patients with Any Form of Intracranial Haemorrhage: A Systematic Review of the Available Controlled Studies
Authors: Keir Sarah L. , Wardlaw Joanna M. , Sandercock Peter A.G. , Chen Zhengming
Published: April 2003

Patients with intracranial haemorrhage may sometimes require antithrombotic drugs or be inadvertently given antithrombotic therapy. We systematically reviewed all published trials comparing any antithrombotic agent with control among patients with any form of intracranial haemorrhage. We extracted data on deaths, recurrent intracranial haemorrhage and functional outcome. There were 9 randomised trials of 5 different antithrombotic agents versus control in patients with subarachnoid haemorrhage (6 trials, n = 1,224) or with acute intracerebral haemorrhage (3 trials, n = 819). The overall odds ratio (OR) for death among patients with any intracranial haemorrhage given an antiplatelet agent (8 trials, 1,997 patients) was 0.85 (95% confidence interval, CI, 0.63–1.15), and for recurrent intracranial haemorrhage it was 1.00 (95% CI 0.73–1.37). The corresponding ORs for patients with intraparenchymal cerebral haemorrhage were 0.96 (0.62–1.5) and 1.02 (0.5–1.8), respectively, but 65% of these patients received only a few doses of antithrombotic treatment. The overall OR for death in patients with any intraparenchymal cerebral haemorrhage given heparin compared with control (3 trials, 819 patients, subcutaneous heparin) was 0.96 (95% CI 0.38–2.40), and for recurrent intracranial haemorrhage it was 2.00 (95% CI 0.86–4.70). There were no reliable data on the effects of antithrombotic agents on functional outcome. These scant data do not support reliable conclusions about the safety or otherwise of antithrombotic agents in patients with acute intracranial haemorrhage. Antithrombotic agents should be avoided where possible in patients with acute intracerebral haemorrhage.
High Incidence Rates of Stroke in Örebro, Sweden: Further Support for Regional Incidence Differences within Scandinavia
Authors: Appelros Peter , Nydevik Ingegerd , Seiger Åke , Terént Andreas
Published: April 2003

Background and Purpose: As a basis for comparison of differences in stroke incidence in Scandinavian countries, a community-based stroke register was established in Örebro in the centre of Sweden. Methods: All first-ever cases of stroke were registered during a 12-month period 1999–2000. The study population was 123,503. The WHO definition of stroke was used. Cases were searched inside as well as outside hospital. Multiple overlapping sources and ‘hot pursuit’ technique were used in the process of case ascertainment. Results: 388 cases of first-ever stroke were found, corresponding to a crude incidence rate of 314 (95% CI, 283–348) per 100,000 per year, 337 (95% CI, 294–386) for females, and 289 (95% CI, 248–336) for males. Adjusted to the European population, the corresponding rates were 254 (95% CI, 227–284) per 100,000 per year, 273 (95% CI, 238–311) for females and 232 (95% CI, 206–261) for males. The overall 28-day case-fatality rate was 19% (95% CI, 15–23). The case-fatality rates for the different subtypes of stroke were as follows: brain infarction, 10%; intracerebral haemorrhage, 20%; subarachnoidal haemorrhage 45%, and undetermined pathological type 56%. Conclusions: The present study as well as other studies in northern and middle Scandinavia show significantly higher incidence rates than studies from other regions. The crude incidence rate, reflecting the age distribution of the population, is even higher, indicating a burden to the community that is rather increasing than decreasing.
Fiblast (Trafermin) in Acute Stroke: Results of the European-Australian Phase II/III Safety and Efficacy Trial
Authors: Bogousslavsky Julien , Victor Stephen J. , Salinas Eliseo O. , Pallay Allan , Donnan Geoffrey A. , Fieschi Cesare , Kaste Markku , Orgogozo Jean-Marc , Chamorro Angel , Desmet Anne
Published: April 2003

Background: Trafermin (basic fibroblast growth factor) has been shown to reduce infarct volume in acute ischemic stroke models, and to promote functional recovery and new synapse formation when given to animals with completed cerebral infarction. A previous study in acute stroke patients suggested that trafermin was safe and well tolerated when given over a 3-hour period over a wide dose range. Methods and Results: Double-blind, parallel group, placebo-controlled trial of a single 24-hour intravenous infusion of trafermin. Patients having onset of stroke symptoms within 6 h and a baseline score of ≧7 on the NIH Stroke Scale (≧2 motor) were randomized to receive 5 or 10 mg of trafermin or placebo intravenously infused over 24 h. The primary efficacy outcome was a categorized combination of the Barthel and Rankin scales assessed at 90 days. A total of 286 patients had been enrolled at 55 sites in 11 countries when the sponsor directed that enrollment be stopped because an interim analysis of efficacy data predicted too small a chance of demonstrating a statistically significant benefit after recruitment of the planned 900 patients. The 5-mg group showed a slight but nonsignificant advantage over placebo (OR 1.2, 95% CI 0.72–2.00, p = 0.48); the 10-mg group showed a nonsignificant disadvantage (OR 0.74, 95% CI 0.44–1.22, p = 0.24). Mortality rates at 90 days were 17% in the 5-mg group, 24% in the 10-mg group and 18% in the placebo group. Treatment with trafermin was associated with an increased leukocytosis and a decrease in blood pressure: mean decrease in systolic blood pressure from baseline was 19 mm Hg in the 5-mg group, 22 mm Hg in the 10-mg group and 8 mm Hg in the placebo group. In a post hoc subgroup analysis, patients in the 5-mg group treated more than 5 h after the onset of symptoms showed an apparent advantage over placebo (OR 2.1, 95% CI 1.00–4.41, p = 0.044; after age adjustment: OR 1.9, 95% CI 0.91–4.13, p = 0.08). Conclusions: With the proper treatment regimen, trafermin can likely be given safely to stroke patients. The 5-mg dose showed a trend toward a treatment advantage. The ideal time window for this agent may exceed 5 h. This may open new avenues for acute stroke therapy, aiming at enhancing recovery mechanisms rather than immediate neuroprotection.
Zinc Status of Human IMR-32 Neuroblastoma Cells Influences Their Susceptibility to Iron-Induced Oxidative Stress
Authors: Mackenzie Gerardo G. , Keen Carl L. , Oteiza Patricia I.
Published: April 2003

The current work tested the hypothesis that the zinc status of a cell influences its sensitivity to iron-induced oxidative stress. Human IMR-32 neuroblastoma cells were cultured for 24 h in nonchelated control media (5 µM zinc; 4.5 µM iron), or in media that was treated with DTPA to reduce its zinc content (chelated media). Chelated media was supplemented with zinc to achieve concentrations of 1.5–50 µM Zn. The media was then replaced with serum-free complex media (0.9 µM Zn) with either no added iron (0.6 µM Fe), or iron (FeCl3) added at concentrations ranging from 15 to 100 µM. Cells were cultured for an additional 3- to 24-hour period. Over the 24-hour period, cells cultured in the control iron media had good viability, and they displayed the gross morphology typical of these cells in culture. With 100 µM iron, cell viability was low in all groups. After 24 h and at iron concentrations between 15–50 µM, cells that had been cultured in the low zinc-chelated media (1.5 µM Zn) showed a concentration-dependent increase in 5 (or 6)-carboxy-2’7’-dichlorodihydrofluorescein diacetate (DCDCDHF) fluorescence (oxidative stress) and decrease in cell viability. A positive correlation between both parameters was observed (r = 0.92). These cells had altered morphology and high level of nucleosomes suggestive of cell death by apoptosis. These results support the concept that the zinc status of IMR-32 neuroblastoma cells modulates their sensitivity to iron overload.
Microcirculatory Changes Associated with Gastric Tube Formation in the Pig
Authors: Schröder W. , Beckurts K.T.E. , Stähler D. , Stützer H. , Fischer J.H. , Hölscher A.H.
Published: April 2003

The standard reconstruction after esophagectomy is the formation of a gastric tube with partial devascularization of the lesser curvature. The purpose of this experimental study was to establish an animal model in order to analyze microcirculation associated with the formation of a gastric tube. In 17 pigs tissue perfusion was measured with a laser Doppler imager (LDI) and partial tissue oxygen pressure (ptO2) with a Clark-type polarographic oxygen electrode before and after formation of a gastric tube in well-defined regions of the stomach. The operative procedure included the dissection of the left gastric and short gastric arteries; the left gastroepiploic artery along the greater curvature was preserved. LDI and ptO2 baseline measurement were significantly lower in the fundus compared to the antrum and corpus. After formation of a gastric tube LDI and ptO2 baseline values calculated from the mean measurements of the antrum, corpus and fundus decreased significantly (LDI: 1,099 PU ± 228 SD to 601 PU ± 125 SD, p < 0.0001; ptO2: 50.8 mm Hg ± 5.9 SD to 40.7 mm Hg ± 9.3 SD, p = 0.0003). Microcirculatory changes did not correlate with changes of cardiac output and systemic vascular resistance. This study suggests that the pig is an appropriate model to investigate microcirculation associated with gastric tube formation. Its use for esophageal reconstruction by pull-up of the gastric interponate is limited.