Noninvasive assessment of cardiac risk in type I diabetic patients being evaluated for combined pancreas-kidney transplantation using dipyridamole-MIBI perfusion tomographic scintigraphy

This study was performed to determine the value of dipyridamole-^{99 m}Tc-methoxy-isobutyl isonitrile perfusion (^{99 m}TC-MIBI) tomographic scintigraphy in the assessment of cardiac risk in patients being evaluated prior to combined pancreas-kidney transplantation (PKT). We performed perfusion tomographic scintigraphy using single photon emission computed tomography (SPECT) on 77 patients. The tomographic images did not show clinically relevant findings in 65 patients. In the remaining 12 patients, coronary arteriography was performed: 2 showed normal results, 4 showed no stenosis, and 6 showed significant stenosis ( ≥ 70 %). Seventy-two patients underwent PKT. During the follow-up (6–48 months), there were seven cardiac events, 4 patients with significant stenosis, and 3 with nonsignificant stenosis upon coronary arteriography, and all had pathological tomographic images. ^{99 m}Tc-MIBI tomographic scintigraphy may be useful in identifying patients at low risk of incurring cardiac events after PKT and may, in a large group of patients, obviate the need for routine coronary angiography. Received: 6 July 1999/Revised: 11 January 2000/Accepted: 30 May 2000     

Haematopoietic damage persists 1 year after autologous peripheral blood stem cell transplantation.

In the present study we have used cell culture assays in order to assess the damage in the haematopoietic system 1 year after peripheral blood stem cell transplantation (PBSCT), and to establish at what level, haematopoietic progenitor cells (HPC) or stroma, this damage occurs. Thirty-one patients, nine breast cancer (BC), 17 non-Hodgkin lymphoma (NHL) and five Hodgkin disease (HD), who had received autologous PBSCT were included. Forty-eight normal subjects who had given informed consent were used as controls. Results were also compared with a matched group of patients (25 cases) prior to PBSCT. Progenitor cells were analysed using CFU-GM and plastic adherent delta (Pdelta) assays. Long-term bone marrow cultures (LTBMC) in one and two stages were established. One year after transplant both the number of committed progenitor cells and the CFU-GM production in LTBMC were significantly reduced in the three groups of patients when compared with controls (P < 0.05 or P < 0.01). Two-stage LTBMC experiments showed that the impairment in CFU-GM production was due to damage in both patients' stroma and haematopoietic progenitor cells (HPC). All patients, except those with HD, showed a decreased stromal layer confluence (P < 0.05), with significant differences in cell composition as compared to normal bone marrow (P = 0.001). When all these variables were compared with pretransplant results, we observed that stroma formation was significantly lower after PBSCT (P < 0.05), while the number of progenitor cells analysed by the Pdelta assay was significantly increased (P < 0.05). We can conclude that even 1 year after PBSCT, both the committed HPC and BM stroma remain damaged.     

Hydrochlorothiazide versus spironolactone: long-term metabolic modifications in patients with essential hypertension

The metabolic side effects of thiazide diuretics are believed to be responsible for the failure of thiazide diuretics to reduce cardiovascular morbidity in patients with hypertension. However, the decrease in the incidence of osteoporotic fractures that are associated with thiazide administration may be relevant in elderly patients with arterial hypertension. Spironolactone (SP) appears not to influence the metabolic risk profile of the patient with hypertension, and no studies have examined its effect on calcium metabolism. Therefore, in 22 patients with mild to moderate essential hypertension, the authors performed a parallel, randomized, double-blind, placebo-controlled study that compared the effects on serum urate and lipid, potassium, magnesium, and calcium metabolism of hydrochlorothiazide (HC) (mean [+/- SD] dose, 72 +/- 26 mg/d) and SP (144 +/- 53 mg/d) during a 52-week period. As compared with placebo, HC significantly increased serum urate and total cholesterol concentrations, and decreased serum potassium levels. SP did not affect serum urate or cholesterol levels but increased serum potassium concentrations. Neither diuretic significantly modified magnesium metabolism. Little changes were seen in serum calcium levels during HC or SP treatment, whereas urinary calcium excretion was significantly decreased by HC (mean decrease, 45%; P less than .01) or SP (40%; P less than .01). The authors conclude that SP, in addition to its potassium-sparing properties, has a calcium-sparing effect that may be beneficial for patients in whom reduction of urinary calcium excretion has a therapeutic value.     

A B‐Vitamin mixture reduces the requirements of diclofenac after tonsillectomy: a double‐blind study

Pain observed after tonsillectomy is often severe and frequently requires the use of opioid analgesics. Non‐steroidal anti‐inflammatory drugs (NSAIDs) may reduce the need or avoid the use of opioids, but gastrointestinal side effects may limit their use. Sparing analgesic agents may reduce the requirement for NSAIDs and consequently their toxicity. It has been proposed that a B‐vitamin mixture produces analgesia in experimental pain models. The present study was carried out to establish if a B‐vitamin mixture was additive with the NSAID, diclofenac, in the treatment of postquirurgic pain. Two groups of 20 subjects, participated in the study. Group 1 received a B‐vitamin mixture infusion for 12 h before the tonsillectomy, whereas Group 2 received vehicle. Both groups received a 50‐mg diclofenac i.v. 8 h before surgery. Two hours after tonsillectomy, Group 1 received another B‐vitamin mixture infusion for 12 h and Group 2 again received vehicle. Pain intensity was evaluated by a visual analog scale (VAS). Then diclofenac (50 mg i.v.) was administered as required by the patient without exceeding 150 mg daily. Diclofenac consumption was recorded and VAS was evaluated for 54 h. Group 1 exhibited a lower pain intensity 2 h after tonsillectomy. Both groups showed similar analgesia. However, diclofenac consumption was approximately 30% lower in the group treated with the B‐vitamin mixture. These results indicate that B vitamins can spare the use of analgesic agents. Drug Dev. Res. 66:36–39, 2006. © 2006 Wiley‐Liss, Inc.     

Quantified 99mTc-MIBI scintigraphy for predicting chemotherapy response in breast cancer patients: factors that influence the level of 99m Tc-MIBI uptake.

The aim of this study was to establish whether tumour uptake of 99mTc-MIBI can predict response to chemotherapy in patients with breast carcinoma. Forty women suffering from breast carcinoma confirmed by tumour biopsy were studied prospectively. Fifteen patients subsequently underwent surgery and 25 were candidates for neoadjuvant chemotherapy. Breast scintigraphy was performed and planar and tomographic views (single photon emission computed tomography (SPECT)) were obtained after injection of 740 MBq of 99mTc-MIBI. The tumoural uptake was quantified by computer analysis. P-glycoprotein was evaluated by immunohistochemistry only in operable patients. The response to chemotherapy was evaluated at 3 months upon completion of treatment. The results of this study showed no relationship between 99mTc-MIBI uptake and the histological type or tumour size. There was an inverse correlation with the degree of tumour differentiation (P<0.05). 99mTc-MIBI uptake in negative P-glycoprotein lesions (2.36+/-1.72) was higher than in positive P-glycoprotein lesions (1.53+/-1.29), although the difference was not statistically significant. Lesions which responded to chemotherapy (16) showed higher 99mTc-MIBI uptake (7.70+/-5.20) than non-responding lesions (nine) (2.21+/-1.0) (P<0.001). In conclusion, there is a correlation between 99mTc-MIBI uptake in breast cancer and response to chemotherapy. Furthermore, 99mTc-MIBI uptake may be influenced by other factors such as the degree of tumour differentiation or tumour P-glycoprotein levels.     

Connective tissue growth factor induces renal fibrosis via epidermal growth factor receptor activation

Connective tissue growth factor (CCN2/CTGF) is a matricellular protein that is overexpressed in progressive human renal diseases, mainly in fibrotic areas. In vitro studies have demonstrated that CCN2 regulates the production of extracellular matrix (ECM) proteins and epithelial–mesenchymal transition (EMT), and could therefore contribute to renal fibrosis. CCN2 blockade ameliorates experimental renal damage, including diminution of ECM accumulation. We have reported that CCN2 and its C‐terminal degradation product CCN2(IV) bind to epidermal growth factor receptor (EGFR) to modulate renal inflammation. However, the receptor involved in CCN2 profibrotic actions has not been described so far. Using a murine model of systemic administration of CCN2(IV), we have unveiled a fibrotic response in the kidney that was diminished by EGFR blockade. Additionally, in conditional CCN2 knockout mice, renal fibrosis elicited by folic acid‐induced renal damage was prevented, and this was linked to inhibition of EGFR pathway activation. Our in vitro studies demonstrated a direct effect of CCN2 via the EGFR pathway on ECM production by fibroblasts and the induction of EMT in tubular epithelial cells. Our studies clearly show that the EGFR regulates CCN2 fibrotic signalling in the kidney, and suggest that EGFR pathway blockade could be a potential therapeutic option to block CCN2‐mediated profibrotic effects in renal diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Effects of high-frequency jet ventilation on intracranial pressure and cerebral elastance in dogs

In order to assess the effect of high-frequency jet ventilation (HFJV) on intracranial pressure (ICP) and cerebral elastance (CE), a model of progressive intracranial hypertension was developed. Six healthy dogs were ventilated using HFJV and another six with conventional mechanical ventilation. ICP and its pulse amplitude (Amp) were measured by means of an epidural transducer, and CE was assessed by analysis of the relationship between the Amp and the mean ICP. The mean ICP, under basal conditions, did not differ between the two forms of ventilation, the Amp and the slope of the relationship Amp/ICP being lower with HFJV (p less than .001). Since the lower airway pressure created with HFJV was the only difference, it is suggested that the differences found in this study are related to these pressures.     

Improvement of spoligotyping with additional spacer sequences for characterization of Mycobacterium bovis and M. caprae isolates from Spain

Spoligotyping is a typing tool used worldwide for epidemiological studies on Mycobacterium tuberculosis complex organisms; however it has received little attention regarding improvement of its discriminatory power (DP). In this study, we have evaluated a spoligotyping membrane prepared with 25 novel spacer sequences selected from a previous study [van der Zanden AG, Kremer K, Schouls LM. Improvement of differentiation and interpretability of spoligotyping for Mycobacterium tuberculosis complex isolates by introduction of new spacer oligonucleotides. J Clin Microbiol 2002;40:4628-39] on 308 M. bovis and 88 M. caprae Spanish isolates in comparison with the traditional spoligotyping membrane. The results obtained by combining the two membranes together revealed an improvement of 45 patterns instead of 31. The spacers used in the second membrane were able to distinguish 8 out of the 16 M. bovis types that had more than one isolate. Seven of these types were differentiated into two subtypes with the second-generation membrane, while spb-7, the most prevalent in Spain, was further differentiated into eight subtypes. This second-generation membrane also differentiates M. bovis from M. caprae. A set of 39 spacers (1, 2, 4-8, 10-15, 17-21, 23, 26-32, 37, 44-49, 51-54, 56 and 57) contain all the DP for both M. bovis and M. caprae isolates; and a set of 35 spacers (1, 2, 4-8, 10-15, 17-21, 26-32, 37, 44-48, 52-54 and 57) had all the DP for the M. bovis isolates. Our results show that the research on new spacers and the design of a new membrane may be useful for epidemiological studies of M. bovis and M. caprae isolates.     

Risk factors of developing asthma in children with recurrent wheezing in the first three years of life

Introductionrecurrent wheezing is a common problem during the first years of life, but it is still difficult to identify which of these children may develop asthma in the future.ObjectivesTo study risk factors of developing asthma in a group of patients with frequent wheezing during the first three years of life.Material and methodsA prospective study was performed of a group of 60 patients, aged below three, referred to our Hospital for recurrent wheezing. Age, sex, parental and personal history of atopy, clinical features, laboratory tests, evolution and response to treatment were analyzed.Results60 patients were enrolled in study. Most of children were boys and have had the first episode of wheezing after the 6 months of life. 63 % had personal history of atopy and 55 % parental history of allergy. The group of atopic children had more wheezing exacerbations and worse evolution than the group of non atopic. They also had more treatment necessities.ConclusionsThe identification of young children at high risk of developing asthma could permit an early intervention before irreversible changes in the airway appeared.