Kidney Transplantation After Hematopoietic Cell Transplantation in Plasma Cell Dyscrasias: Case Reports.

The plasma cell dyscrasias (PCDs) include a number of entities such as multiple myeloma, primary amyloidosis, and monoclonal immunoglobulin deposition disease. Hematopoietic cell transplant (HCT) is the only cure for a variety of hematologic and oncologic diseases. Clinically significant renal impairment is a common feature in plasma cell myeloma, affecting 20% to 55% of patients at initial diagnosis; 2% to 3% of patients present with failure sufficiently severe to require hemodialysis. This circumstance is associated with a high early mortality. The necessity for immunosuppression after HCT could complicate its management and may precipitate the development of complications. In some patients an effective alternative could be kidney transplant (KT); however, the presence of 2 transplants will require optimal adjustment of immunosuppression and management of complications. At present, there are few published cases of KT after HCT, and the experience of managing 2 transplants is limited. We would like to describe our experience with 4 patients who had a PCD and initially received HCT and received subsequent KT. In our experience the progress and outcome of KT after HCT were optimal. We would like to address that a higher incidence of cytopenia associated with the combination of immunosuppression (lenalidomide, tacrolimus, mycophenolate, etc.) and other drugs (ie, valganciclovir) should be considered together with an increased risk of opportunistic infections and PCD relapse.

Work function measurements using a field emission retarding potential technique.

Herein we describe the measurement of the work function of a metal with advanced equipment based on the field emission retarding potential (FERP) method using a carbon nanotube (CNT) as cathode. The accuracy of the FERP method using a CNT emitter is described and a comparison between measurements of the work functions of aluminum, barium, calcium, gold, and platinum with published data will be presented. Our FERP equipment could be optimized with the aid of particle tracing simulations. These simulations led us to insert a magnetic collimator to improve the collection efficiency at the anode.

Selective vitamin D receptor activation as anti-inflammatory target in chronic kidney disease.

Paricalcitol, a selective vitamin D receptor (VDR) activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD), has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m(2) and an intact parathyroid hormone (PTH) level higher than 110 pg/mL received oral paricalcitol (1 µg/48 hours) as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P < 0.01), TNF-α (11.9%, P = 0.01), and IL-6 (7%, P < 0.05), with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P = 0.01) and 35.4% (P = 0.01), respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD.

Analysis of influence of voltage on potential barrier on BiCuVOX and BiTiVOX ceramics.

The BiMeVOx family of compounds appears to be more attractive for applications at low temperatures when ionic conductivity is the determining parameter. The objective of this study was to analysis the influence of voltage of the behavior of the Schottky barrier in both BiCuVOX and BiTiVOX. The samples were analyzed by atomic force microscopy and electric force microscopy (EFM). EFM experiments were conducted to map the electric field distribution on the surface. The formation of Schottky barriers was observed, and their height and width measured. BiCuVOX samples show a barrier width of 140 nm, and BiTiVOX shows a barrier width of 350 nm. The applied voltage has no effect on the barrier width but increases the peak height as observed in the cantilever frequency as measured with the EFM technique.

Resequencing of the auxiliary GABA(B) receptor subunit gene KCTD12 in chronic tinnitus.

Tinnitus is a common and often incapacitating hearing disorder marked by the perception of phantom sounds. Susceptibility factors remain largely unknown but GABA(B) receptor signaling has long been implicated in the response to treatment and, putatively, in the etiology of the disorder. We hypothesized that variation in KCTD12, the gene encoding an auxiliary subunit of GABA(B) receptors, could help to predict the risk of developing tinnitus. Ninety-five Caucasian outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCTD12 open reading frame and the adjacent 3' untranslated region by Sanger sequencing. Allele frequencies were determined for 14 known variants of which three (rs73237446, rs34544607, and rs41287030) were polymorphic. When allele frequencies were compared to data from a large reference population of European ancestry, rs34544607 was associated with tinnitus (p = 0.04). However, KCTD12 genotype did not predict tinnitus severity (p = 0.52) and the association with rs34544607 was weakened after screening 50 additional cases (p = 0.07). Pending replication in a larger cohort, KCTD12 may act as a risk modifier in chronic tinnitus. Issues that are yet to be addressed include the effects of neighboring variants, e.g., in the KCTD12 gene regulatory region, plus interactions with variants of GABA(B1) and GABA(B2).

Activity of cholinesterases and adenosine deaminase in blood and serum of rats experimentally infected with Trypanosoma cruzi.

This study aimed to evaluate the activity of cholinesterases and adenosine deaminase (ADA) in blood and serum of rats infected with Trypanosoma cruzi. Twelve adult rats were used in the experiment divided into two uniform groups. Rodents from group A (control group) were non-infected and animals from group B served as infected, receiving intraperitoneally 3·3×10(7) trypomastigotes/each. Blood collection was performed at days 60 and 120 post-infection (PI) in order to evaluate the hemogram, blood activity of acetylcholinesterase, and serum butyrylcholinesterase and ADA activities. Hematological parameters did not differ between groups. A significant increase (P<0·05) of acetylcholinesterase activity was observed in blood while butyrylcholinesterase had a significant reduction (P<0·01) in serum of infected rats at days 60 and 120 PI. ADA activity in serum showed an inhibition in infected animals when compared to non-infected at day 120 PI. Based on these results, it is possible to conclude that the activity of cholinesterases and ADA were changed in animals infected with T. cruzi. The possible causes of these alterations will be discussed in this paper.

Hypoxic-ischemic brain injury stimulates inflammatory response and enzymatic activities in the hippocampus of neonatal rats.

Brain damage from neonatal hypoxia-ischemia (HI) plays a major role in neonatal mortality and morbidity. Using the Rice-Vannucci model of HI in rats, we verified that 8 days after HI injury, adenosine deaminase (ADA), N-acetyl-glucosaminidase (NAG) and myeloperoxidase (MPO) activities increased in the left hemisphere hippocampus (HI group); however, the activity of 5'-nucleotidase (5'NT) remained unchanged. In the hematoxylin-eosin analysis (HE), we detected selective and delayed degeneration of hippocampal pyramidal neurons and astroglial reaction accompanied by glial fibrillary acidic protein (GFAP)-positive and vimentin-positive in the immunohistochemistry analysis in the HI group compared with the control group. We observed the selective necrosis of neurons, vascular endothelial proliferation and inflammatory response accompanied by the increase of the key enzyme of adenosine metabolism in the HI group. The increase of ADA activity, despite the 5'NT activity was not altered, indicates the predominance of ADA activity in the postischemic homeostasis of extra cellular adenosine. The presence of leukocytes into the ischemic areas displays the possible importance of the neutrophil-macrophages associated with the increase of MPO and NAG activities 8 days after HI. These findings may contribute to the evaluation of some consequences of the damage caused by neonatal HI.

Assessment of uric acid and lipid peroxidation in serum and urine after hypoxia-ischemia neonatal in rats.

The aim of this study was to evaluate urinary uric acid (UA) and lipid peroxidation levels, plasma myeloperoxidase (MPO) and adenosine deaminase (ADA) activities, and serum UA in neonatal rats subjected to hypoxia-ischemia neonatal HI model. The relevance of the findings is the fact that urinary lipid peroxidation and UA levels were significantly higher in 8 days in HI group when compared with the control, returning to baseline levels 60 days after HI. Hence, being an indication of purinic degradation during these first days post-HI. Furthermore, the higher levels of malondialdehyde (MDA) in urine in this period may be related to inadequate scavenging abilities of the immature nervous system and being noninvasive it may suggest the use of urinary MDA measurement as a marker for lipid peroxidation after HI insult. In application terms, these findings can help develop therapeutic interventions as soon as 8 days after HI.

Evaluation of cerebrospinal fluid adenosine deaminase activity in HIV-seropositive subjects and its association with lactate dehydrogenase and protein levels.

The purpose of this study was to investigate the role of ADA as additional marker of HIV infection as well as its association with other biochemical markers. This study included 55 patients, 26 being diagnosed as HIV positive and 29 patients diagnosed as HIV negative. Glucose, total protein, lactate dehydrogenase, and adenosine deaminase (ADA) activity were measured on cerebrospinal fluid (CSF). ADA activity on CSF was statistically different in HIV-seropositive subjects compared with HIV-negative subjects. The sensitivity and specificity of ADA activity on CSF was 50 and 82.76%, respectively. ADA activity was positively correlated with lactate dehydrogenase and protein in patients with HIV positive and it was negatively correlated with glucose levels. ADA determination in CSF could add information about inflammatory processes in patients with HIV infection.

Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in young rats: protective effects of grape seed extract.

The methotrexate (MTX) is an anti-folate used to treat cancer and some inflammatory diseases. The efficacy of MTX is often limited by its severe toxicity. The present study was undertaken to determine whether Grape seed (Cabernet Sauvignon) extract (GSE) could ameliorate the MTX-induced oxidative injury and the effect on adenosine deaminase activity (ADA) in rats. The rats were pretreated with 50 mg/kg of GSE, i.p., prior to MTX administration (10 mg/kg, i.p.) with a second dose given 4 h and a third dose 16 h after MTX administration. Biochemical parameters were investigated 48 h after the last MTX administration. The administration of MTX increased thiobarbituric acid reactive species (TBARS) levels in hippocampus, kidney and liver, whereas induced a significant decreased in the ADA activity in the cerebral cortex, kidney and liver tissues. MTX administration significantly increased the activity of ALT(alanine aminotransferase) and urea levels and decreased uric acid levels in the serum. Urinary uric acid levels decreased in the MTX group when compared to those of the control group. The GSE along with MTX-administration significantly reversed these parameters toward to near normal. These results indicated that GSE could reduce hepatic and nephritic damage induced by MTX-treatment in young rats therefore having free radical scavenging.

Adenosine deaminase activity, lipid peroxidation and astrocyte responses in the cerebral cortex of rats after neonatal hypoxia ischemia.

Hypoxia ischemia (HI) is a common cause of damage in the fetal and neonatal brain. Lifelong disabilities such as cerebral palsy, epilepsy, behavioral and learning disorders are some of the consequences of brain injury acquired in the perinatal periods. Inflammation and formation of free radicals appear to play key roles in neonatal HI. The aim of this study was to describe the chronological sequence of adenosine deaminase (ADA) activity, the oxidative damage changes and astrocyte response using the classic model of neonatal HI. We observed an increase in the activity of ADA and lipid peroxidation in the cerebral cortex 8 days after neonatal HI. This was accompanied by a GFAP-positive, and the degree of brain damage was determined histochemically by hematoxylin-eosin (HE). Taking into account the important anti-inflammatory role of adenosine, ADA may provide an efficient means for scavenging cell-surrounding adenosine and play an important part in subsequent events of neonatal HI in association with GFAP reactive gliosis. The present investigation showed that neonatal HI causes the increase of free radicals and significant damage in the cerebral cortex. The increase in ADA activity may reflect the activation of the immune system caused by HI because the morphological analysis exhibited a lymphocytic infiltration.

The hearing aid 'effect' revisited in young adults.

Hearing impairment is a common ailment in older adults. However, the acceptance of hearing aids by hearing-impaired individuals remains poor. The main reasons given by hearing-impaired individuals for not acquiring a hearing aid are primarily psychosocial in nature. Research suggests that individuals with hearing loss believe that wearing hearing aids will cause them to be perceived as old and/or less competent. The purpose of the present study was to determine the perceptions of young adults towards hearing loss and hearing aids and to compare them to the perceptions of older adults with hearing impairment. A version of the 'Attitudes Toward Loss of Hearing Questionnaire' was administered to young adults and older adults with hearing loss. Results suggest that young adults do not associate hearing aids with ageing or diminished cognitive function, although findings suggest reticence towards wearing amplification. The implications of this study are discussed in terms of increasing public awareness of hearing loss.

Effects of bolus somatostatin in preventing pancreatitis after endoscopic pancreatography: results of a randomized study.

BACKGROUND: Pancreatitis is a potential problem in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Natural somatostatin reduces pancreatic secretion and has been administered in acute pancreatitis. To establish whether an injection of a single "bolus" of natural somatostatin is useful in preventing pancreatic reactions after endoscopic pancreatography, a randomized study was carried out in 160 patients undergoing pancreatography, associated or not, with endoscopic sphincterotomy. METHODS: Pancreatitis was considered to be present when there was the simultaneous appearance of serum amylase above 600 IU/mL and serum lipase above 200 IU, upper abdominal pain with tenderness, nausea and/or vomiting, and associated ileus, not completely resolved within 18 hours after the procedure and prolonging hospital stay. RESULTS: The incidence of pancreatitis (10% vs. 2.5%, p < 0.05) was higher in the placebo group than in the somatostatin-treated group. The difference in frequency of pancreatitis was statistically significant (18% vs 0%, p < 0.05) in the ERCP plus sphincterotomy subgroup but not significant (6% versus 4%) in the ERCP subgroup. CONCLUSIONS: These results suggest that the administration of a single bolus injection of natural somatostatin just before cannulation of the papilla may be useful in preventing pancreatitis. This procedure is useful in patients undergoing sphincterotomy. Further studies should be performed to determine whether this drug is useful in cases in which cannulation of the papilla is difficult or when therapeutic procedures require prolonged and/or aggressive manipulation of the papilla.

Chest pain at rest in patients with coronary artery disease. Myocardial ischemia, esophageal dysfunction, or panic disorder?

Severe nonexertional (resting) chest pain may be due to myocardial ischemia, esophageal dysfunction, psychiatric disorder, or any combination thereof and frequently poses a difficult diagnostic challenge. Our aim was to investigate causes of chest pain in patients with coronary artery disease. Forty-five patients with angiographically proven obstructive coronary lesions and recurrent chest pain at rest were studied; 18 had refractory pain despite cardiac therapy (problem group), and 27 had documented myocardial ischemia (control group). Esophageal manometry, edrophonium provocation, 24-hr pH studies, and psychiatric interview were performed in all patients. The clinical evolution and the outcome of specific treatment during follow-up was used to establish the etiology of chest pain. Esophageal dysfunction was identified in all problem patients and in 52% of controls, and the esophagus was incriminated as the source of pain in 8 (44%) and 5 (18.5%), respectively. After a mean follow-up of 49 months (range 24-76 months), the cause of chest pain in the problem group was identified as panic disorder in 9 patients (50%), gastroesophageal reflux in 6 (33%), esophageal dysmotility in 2 (11%), and gallstone disease in 1 (6%). Of the control patients, 18 (67%) had ischemic pain alone, while 9 had concurrent causes: panic disorder in 5 (19%) and esophageal dysfunction in 4 (15%). Esophageal dysfunction and psychiatric disturbances are common in patients with coronary artery disease presenting with resting chest pain, and may contribute to patients' symptoms.

High amplitude contractions in the middle third of the oesophagus: a manometric marker of chronic alcoholism?

BACKGROUND: Oesophageal motor abnormalities have been reported in alcoholism. AIM: To investigate the effects of chronic alcoholism and its withdrawal on oesophageal disease. PATIENTS: 23 chronic alcoholic patients (20 men and three women; mean age 43, range 23 to 54). METHODS: Endoscopy, manometry, and 24 hour pH monitoring 7-10 days and six months after ethanol withdrawal. Tests for autonomic and peripheral neuropathy were also performed. Motility and pH tracings were compared with those of age and sex matched control groups: healthy volunteers, nutcracker oesophagus, and gastro-oesophageal reflux disease. RESULTS: 14 (61%) alcoholic patients had reflux symptoms, and endoscopy with biopsy showed oesophageal inflammation in 10 patients. One patient had an asymptomatic squamous cell carcinoma. Oesophageal motility studies in the alcoholic patients showed that peristaltic amplitude in the middle third was > 150 mm Hg (95th percentile (P95) of healthy controls) in 13 (57%), the ratio lower/ middle amplitude was < 0.9 in 15 (65%) (> 0.9 in all control groups), and the lower oesophageal sphincter was hypertensive (> 23.4 mm Hg, P95 of healthy controls) in 13 (57%). All three abnormalities were present in five (22%). Abnormal reflux (per cent reflux time > 2.9, P95 of healthy controls) was shown in 12 (52%) alcoholic patients, and was unrelated to peristaltic dysfunction. Subclinical neuropathy in 10 patients did not effect oesophageal abnormalities. Oesophageal motility abnormalities persisted at six months in six patients with ongoing alcoholism, whereas they reverted towards normal in 13 who remained abstinent; reflux, however, was unaffected. CONCLUSIONS: Oesophageal peristaltic dysfunction and reflux are frequent in alcoholism. High amplitude contractions in the middle third of the oesophagus seem to be a marker of excessive alcohol consumption, and tend to improve with abstinence.

[Thoracic pain of esophageal origin. Assessment of 125 consecutive patients with resting angina and angiographically normal coronary arteries]. / Dolor torácico de origen esofágico. Evaluación de 125 pacientes consecutivos con angina de reposo y arterias coronarias angiográficamente normales.

BACKGROUND: The esophagus may be the origin of chest pain clinically indistinguishable from that of myocardial ischemia. Gastroesophageal reflux (GER) and esophageal motility disorders (EMDs) are the main causes of esophageal chest pain, and esophageal motility tests are important for an appropriate diagnosis. We studied 125 unselected patients with angiographically normal coronary arteries presenting with atypical (resting) angina which was shown not to be of cardiac origin. METHODS: Stationary esophageal manometry and 24-hour pH studies were performed in all patients, and 116 of them were submitted to edrophonium provocation test (Tensilon, 10 mg as IV bolus). RESULTS: Spastic EMDs were identified as an isolated abnormality in 23 patients (18%), whereas GER was documented in 70 patients (56%). Esophageal dysmotility at baseline manometry (n = 40), a positive edrophonium test (n = 19), abnormal acid reflux indices by 24-hour pH recording (n = 62), and association of chest pain with acid reflux during pH testing (n = 24) variably overlapped in many patients. The esophagus was directly blamed as the source of atypical angina in 33 patients (26%) who had induction of their usual chest pain by cholinergic stimulation and/or association of spontaneous pain events with acid reflux. CONCLUSIONS: Esophageal dysfunction in common in patients with atypical angina considered not to be of cardiac origin and contributes to patients' symptoms. Because they may detect treatable causes of chest pain such as GER or contribute to management by assessing the diagnosis of EMD, esophageal motility tests are indicated in many patients with noncardiac chest pain.

Value of Nissen fundoplication in patients with gastro-oesophageal reflux judged by long-term symptom control.

A total of 160 patients treated by Nissen fundoplication for uncomplicated gastro-oesophageal reflux disease were studied over a 20-year period. Recurrent reflux and side-effects were assessed yearly after surgery. No objective tests for reflux were performed during follow-up if patients were asymptomatic. Perioperative mortality and technique-related morbidity rates were both 2 per cent. At the latest evaluation, 79 per cent of patients were completely relieved of reflux symptoms, 85 per cent had symptoms of Visick grade 1 or 2 and 89 per cent would be willing to undergo surgery again under the same conditions. Actuarial analysis showed that the success rate of fundoplication was 92 per cent at 20 years. Fourteen patients (9 per cent) developed side-effects after fundoplication and had continuing disability. Nissen fundoplication achieves permanent control of reflux symptoms in most patients with few complications and has a high degree of patient satisfaction.

Predictive factors of the long term outcome in gastro-oesophageal reflux disease: six year follow up of 107 patients.

There is little information concerning the long term outcome of patients with gastro-oesophageal reflux disease (GORD). Thus 109 patients with reflux symptoms (33 with erosive oesophagitis) with a diagnosis of GORD after clinical evaluation and oesophageal testing were studied. All patients were treated with a stepwise approach: (a) lifestyle changes were suggested aimed at reducing reflux and antacids and the prokinetic agent domperidone were prescribed; (b) H2 blockers were added after two months when symptoms persisted; (c) anti-reflux surgery was indicated when there was no response to (b). Treatment was adjusted to maintain clinical remission during follow up. Long term treatment need was defined as minor when conservative measures sufficed for proper control, and as major if daily H2 blockers or surgery were required. The results showed that one third of the patients each had initial therapeutic need (a), (b), and (c). Of 103 patients available for follow up at three years and 89 at six years, respective therapeutic needs were minor in 52% and 55% and major in 48% and 45%. Eighty per cent of patients in (a), 67% in (b), and 17% in (c) required only conservative measures at six years. A decreasing lower oesophageal sphincter pressure (p < 0.001), radiological reflux (p = 0.028), and erosive oesophagitis (p = 0.031), but not initial clinical scores, were independent predictors of major therapeutic need as shown by multivariate analysis. The long term outcome of GORD is better than previously perceived.

Healing of erosive esophagitis with sucralfate and cimetidine: influence of pretreatment lower esophageal sphincter pressure and serum pepsinogen I levels.

Forty-eight patients with erosive reflux esophagitis were allocated to either sucralfate tablets, 4 g/day, or cimetidine, 1.6 g/day, for 8 weeks in a randomized, prospective, single-blind, cross-over therapeutic trial. Pretreatment lower esophageal sphincter (LES) pressure and serum pepsinogen I (PG-I) levels were investigated as possible predictors of healing with either drug. The trial was completed by 41 patients (21 in the sucralfate group and 20 in the cimetidine group); one patient in each group was removed because of side effects. Symptom improvement occurred to a similar extent in both groups. Endoscopic results after 8 weeks of treatment with sucralfate revealed complete healing of esophageal erosions in 48% (cimetidine, 55%) and improvement in an additional 19% (cimetidine, 20%). Neither of these differences was statistically significant. Some patients refractory to one drug had endoscopic healing of esophagitis when treated with the other drug after crossover. LES pressure did not influence outcome in patients treated with sucralfate, whereas significantly (p = 0.024) more patients refractory to cimetidine had an LES pressure less than 7 mm Hg than did those with a good response to the histamine-2 (H2)-receptor blockade. Patients whose esophagitis healed or improved after sucralfate tended to have lower serum PG-I levels than those with treatment failure (104 +/- 35 ng/mL vs 125 +/- 45 ng/mL), whereas the opposite occurred in patients treated with cimetidine (132 +/- 58 ng/mL in responders vs 78 +/- 27 ng/mL in nonresponders, p = 0.048). The results confirm that sucralfate is a valuable alternative to H2-receptor inhibitors for the treatment of reflux esophagitis. They also provide preliminary evidence that LES pressures and serum PG-I levels may have predictive value of the response to one or the other of these two drugs.

[Growth in children fed exclusively with breast milk during the first 6 months of life]. / El crecimiento de los niños alimentados exclusivamente con leche materna durante los seis primeros meses de vida.

To study first year growth patterns in exclusively breast-fed children, the growth (weight and height) of 232 children who had received only breastmilk during the six first months of life was followed over a period extending from 1983 to 1987. The follow-ups were done in the pediatric dispensary at Taguatinga Health Center No. 7 in the Federal District of Brazil. The children were from low-income families and represented various racial mixes. All were single products of pregnancy, had no pathological history, and had been breast-fed on demand. The percentile distribution (90, 75, 50, 25, and 10) of weight and height at birth and at 1, 2, 3, 4, 6, 9, and 12 months of age showed that the average quarterly increases in these variables were greater in the first quarter and less in subsequent quarters. The weight of the boys doubled between the third and fourth months, while that of the girls doubled in the fourth month. The results indicate that the growth of these children was satisfactory.