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Biomedical subjects

M Machado

Publications and source records attributed to M Machado.

At least 19 recordsLinked to original sources
PubMed2006

Categorization of major and minor complications in the treatment of patients with resectable rectal cancer using short-term pre-operative radiotherapy and total mesorectal excision: a Delphi round.

BACKGROUND: To properly balance the benefit (reduction of local recurrence) of short-term pre-operative radiotherapy for resectable rectal cancer against its harm (complications), a consensus concerning the severity of complications is required. The aim of this study was to reach consensus regarding major and minor complications after short-term radiotherapy followed by total mesorectal excision in the treatment of rectal carcinoma, using the Delphi technique. METHODS: A Delphi round was performed in cooperation with 21 colo-rectal surgeons from the Netherlands, United Kingdom and Sweden. The key-question was: 'Which of the predefined complications, caused or substantially aggravated by radiotherapy, are so important (major) that they might lead to the decision to abandon short-term pre-operative radiotherapy (5 x 5Gy) when treating patients with resectable rectal cancer (T1-3N0-2M0)?' RESULTS: After three rounds, consensus was reached for 37 (68%) of 54 complications of which 13 were considered major and 24 considered minor. The following complications were considered to be major: mortality, anastomotic leakage managed by relaparotomy, anastomotic leakage resulting in persisting fistula, postoperative haemorrhage managed by relaparotomy, intra-abdominal abscess without healing tendency, sepsis, pulmonary embolism, myocardial infarction, compartment syndrome of the lower legs, long-term incontinence for solid stool, long-term problems with voiding, pelvic fracture with persisting pain, and neuropathy with persisting pain (legs). Three of 17 complications without consensus showed a tendency to be considered as major: perineal wound dehiscence managed by surgical treatment, small bowel obstruction leading to relaparotomy and long-term incontinence for liquid stool. CONCLUSION: The 13 major and three 'accepted as major' complications can be used to properly balance the benefit and harm of short-term pre-operative radiotherapy in resectable rectal cancer. This may eventually lead to improved treatment strategies for these patients.

Belgium↗
PubMed2003

Anatomic variations of the frontal sinus.

INTRODUCTION: Minimally invasive approaches are increasing in popularity. We have undertaken an anatomic and radiological study of the frontal sinus that is frequently involved in the supercilliary minicraniotomy used to access the parasellar region. OBJECTIVE: We wanted to evaluate the prevalence and morphological characteristics of the frontal sinus in a certain population sample. METHODS: 98 randomly assigned individuals were subjected to CT examinations. The antero-posterior diameter, sagittal diameter, transverse diameter and total volume of the frontal sinus were calculated. RESULTS: The frontal sinus tended to be larger in males than in females with the exception of the transverse diameter (p < 0.10). CONCLUSION: Knowledge of the anatomic variations of the frontal sinus is important in surgical approaches through the superciliary arc in order to avoid complications such as infections and CSF fistula.

Adult↗
PubMed2001

Thyroglobulin increases cell proliferation and suppresses Pax-8 in mesangial cells.

Thyroglobulin (Tg), has recently been identified as a transcriptional regulator of thyroid-restricted genes. The extrathyroidal expression of several of these genes (including the transcription factor Pax-8) together with the occurrence of specific Tg binding sites suggests a secondary role for Tg as a circulating hormone. In this study, we demonstrate using Northern analysis that Pax-8 is expressed in the mouse mesangial cell, and that its transcript levels are suppressed by Tg. These cells also express an asialoglycoprotein receptor, a receptor involved in Tg endocytosis in the thyroid, and a Tg transcript smaller than the 8.3-kb thyroidal form. Reverse transcriptase PCR showed that suppression of Pax-8 by Tg is correlated with reduced expression of bcl-2 apoptosis suppressor. Tg, but not triiodothyronine (T(3)) significantly increased MC proliferation above control as determined by DNA content of MC cultures. The effect of Tg on proliferation was not duplicated by either bovine serum albumin, gamma-globulins, lactoferrin, or the ASGPR-specific ligand,orosomucoid. These results suggest a possible endocrine role for Tg in regulating both Pax-8 related gene transcription and cell division in the mesangial cell.

Animals↗
PubMed2000

Systems for therapeutic angiogenesis in tissue engineering.

The goals in tissue engineering include the replacement of damaged, injured, or missing body tissues with biologically compatible substitutes. To overcome initial tissue-mass loss, improved vascularization of the regenerated tissue is essential. Two pathways of tissue neovascularization are known: vasculogenesis, the in situ assembly of capillaries from undifferentiated endothelial cells (EC), and angiogenesis, the sprouting of capillaries from preexisting blood vessels. Recent advances in our understanding of the process of bloodvessel growth have provided significant tools for the neovascularization of bioengineered tissues. Several growth factors serve as stimuli for EC proliferation and migration as well as the formation of new blood vessels. They convey their effects via specific receptors expressed on the surface of EC. Vascular epithelial growth factor (VEGF) is a major regulator of neovascularization. VEGF plays a major role in the early development of blood-cell progenitors. Basic fibroblast growth factor (bFGF) was identified as the first angiogenic factor. It is a potent inducer of EC proliferation and blood-vessel growth in vitro and in vivo. VEGF and bFGF have been injected into undervascularized ischemic tissues, resulting in new blood-vessel formation and tissue perfusion. Gene-therapy approaches using VEGF cDNA injection into ischemic tissues have augmented the formation of collateral vessels. Angiogenic factors such as VEGF and bFGF have also been incorporated into bioengineered tissues and have facilitated blood-vessel growth. Other approaches such as prevascularization of the matrix prior to cell seeding and incorporation of EC into the bioengineered tissues have produced encouraging results. This article reviews the process of blood-vessel growth and tissue vascularization, placing emphasis on strategies that can be employed for efficient vascularization of engineered tissues in vitro and in vivo.

Angiogenesis Inducing Agents↗
PubMed2000

Rectal tumour staging: MR imaging using pelvic phased-array and endorectal coils vs endoscopic ultrasonography.

The aim of this study was to compare MR imaging and endoscopic ultrasonography (EUS) for the local staging of rectal tumours. Forty-nine patients were examined on a 1.5-T MR unit using either a pelvic phased-array coil (n = 37) alone or combined with an endorectal coil (n = 12). Sagittal and axial sequences with T2-weighted fast spin-echo and axial T1-weighted spin-echo techniques were employed. The EUS technique was performed using a flexible endosonoscope. The results were compared with findings at histopathological sectioning of the specimen. The T-stage on MR correlated with histopathology in 32 of 49 patients and on EUS in 29 of 49 patients. The N-stage on MR correlated with histopathology in 22 of 49 patients and on EUS in 26 of 49 patients. Tumour penetration of the rectal wall was predicted by MR with 86 % sensitivity and 65 % specificity, and by EUS with 89% sensitivity and 33% specificity. Preoperative radiotherapy was administered to 40 of the patients after the examinations which may explain some of the overstaging by MR and EUS. Three patients with surgically and histopathologically confirmed invasion of neighbouring organs in the pelvis were detected preoperatively on MR but none on EUS. Tumour penetration of the rectal wall and local lymph node metastases cannot accurately be predicted with MR or EUS. Magnetic resonance, however, seems to be more useful for preoperative identification of clinically occult advanced disease.

Aged↗
PubMed2000

Reproduction/developmental toxicity screening test in rats with orally-administered 1-hexene.

This study was conducted to provide screening information concerning the potential systemic, reproductive and developmental toxicity of 1-hexene when administered orally, by gavage, to male and female rats using a modified OECD 421 protocol. 1-Hexene was administered at doses of 100, 500, and 1000 mg/kg/day in corn oil; the control group received the vehicle at an equivalent volume. The males were treated for 28 days prior to mating and until euthanasia (44 days of dosing). The females were treated for 14 days prior to mating and during mating, gestation, and lactation until euthanasia (41-55 total days of dosing). Females were allowed to deliver and rear their offspring until lactation day 4. The parental rats were subject to a gross and microscopic examination. Viability and development of the pups were followed through lactation day 4. There was no mortality, and there were no clinical signs of toxicity or differences in body weights, weight gain, feed consumption or organ weights. Copulation and fertility indices, precoital intervals, gestation lengths and pregnancy rates were comparable among the groups, and no signs of prolonged delivery or unusual nesting behaviors were noted. Pup viability, body weights, external observations and necropsy data were comparable among the groups. Pitted kidneys were observed at necropsy for two parental males in the 500 mg/kg/day group and three males in the 1000 mg/kg/day group. Microscopic changes in the kidneys of some male rats from the 100, 500, and 1000 mg/kg/day groups consisted of dose-related accumulations of hyaline droplets in the epithelial cells of the proximal convoluted tubules of the kidneys. In summary, the only treatment-related effect noted in this study was hydrocarbon nephropathy in male rats, which is not considered relevant for human health. The NOAEL for systemic and reproductive toxicity was 1000 mg/kg/day, excluding the finding of male rat hydrocarbon nephropathy.

Administration, Oral↗
PubMed1999

Rectal adenocarcinoma: assessment of tumour involvement of the lateral resection margin by MRI of resected specimen.

The aim of the present study was to investigate whether MRI could predict tumour involvement of the lateral resection margin on resected rectal cancer specimens. 26 specimens obtained after total mesorectal excision were examined in the sagittal and axial plane on a clinical 1.5 T MR system using phased-array surface coils. The shortest distance between the deepest point of tumour penetration and the lateral resection margin was measured. This distance is referred to as LRM. The results were correlated to measurements on digital images of giant histopathological sections. The total number of lymph nodes and lymph node metastases was also counted. LRM was less than or equal to 1 mm (a distance considered for non-radically excised tumours) in eight of the histopathological specimens. On MR images of the resected specimen, LRM was less than or equal to 1 mm in seven of these specimens. LRM was shorter in MR examinations than in histopathological giant sections in 11 specimens. The sensitivity, specificity, positive and negative predictive values for prediction of tumour involvement of the lateral resection margin (LRM < or = 1 mm) by MR of the resected specimen were 88%, 78%, 64% and 93%, respectively. Presence of lymph node metastases could not accurately be predicted by MR. However, it is concluded that the presence of a tumour free lateral resection margin can be predicted by MRI of resected rectal specimens when this exceeds 1 mm.

Adenocarcinoma↗
PubMed1998

[Minilaparotomy is a careful method in right colon tumor surgery].

In a series of 47 patients, right colon tumours were treated surgically with a minilaparotomy approach, entailing a skin incision of less than 10 centimetres. The procedure allows appropriate oncological management of the tumour, and is associated with a mild postoperative course and a rapid recovery and resumption of normal life. The short-term outcome in this series has been promising, and the minilaparotomy approach would thus appear to be an attractive alternative to traditional open surgery of the right colon.

Aged↗
PubMed1998

Minilaparotomy approach to tumors of the right colon.

OBJECTIVE: The study contained herein was undertaken to describe the minilaparotomy approach to tumors of the right colon. METHOD: Clinical data were prospectively registered from 47 patients who were undergoing resection of the right colon via minilaparotomy. RESULTS: Bowel function returned after two days and passage of stools after four days. Pain medication was necessary only during the first three postoperative days. Major complications were few, and no postoperative deaths occurred. Tumors 10 cm or smaller could be handled by minilaparotomy, and the technique allowed a relevant number of lymph nodes to be removed. No local recurrences were detected during the early postoperative period. CONCLUSION: The minilaparotomy approach to tumors of the right colon seems to be an attractive alternative to conventional colon surgery.

Aged↗
PubMed1998

Parathyroid function in long-term renal transplant patients: importance of pre-transplant PTH concentrations.

Lack of resolution of hyperparathyroidism after long-term renal transplantation is common. The relative roles of the graft function attained and the degree of pre-transplant hyperparathyroidism have not been established. Intact parathyroid hormone (iPTH) and several clinical parameters were studied before and 68.6+/-26.8 months (range: 30-124) after renal transplantation in 62 patients (20 females/42 males) with good renal function (creatinine <2 mg/dl). iPTH decreased from 214+/-229 pre-transplantation to 116+/-70 pg/ml post-transplantation (P<0.01). However, only 22.6% of patients had PTH concentrations in the normal range, and values greater than twice the upper normal limit were not uncommon (27.4%). Of the many variables analysed, creatinine (r=0.43; P=0.001) and pre-transplant PTH (r=0.31; P=0.02) significantly correlated with post-transplant PTH. After selecting patients with serum creatinine <1.5 mg/dl (n=46), pre-transplant PTH emerged as the more important predictor of post-transplant PTH (r=0.58; P<0.0001). After controlling for creatinine, the partial correlation was r=0.53, P<0.0001. We concluded that spontaneous resolution of hyperparathyroidism after renal transplantation is uncommon. In addition, the magnitude of pre-transplant hyperparathyroidism and the renal function determine the long-term post-transplant parathyroid function.

Adult↗
PubMed1997

Laparoscopic Antegrade Sphincterotomy.

The authors describe the technique and results of laparoscopic antegrade sphincterotomy. The procedure was performed in 42 selected cases of choledocholithiasis. The indications for attempting laparoscopic antegrade sphincterotomy included impacted stones in the papilla, multiple common bile duct stones, one or more common hepatic or intrahepatic stones, dilated common bile duct requiring a drainage procedure, suspicion of papillary stenosis, whenever numerous fragments are found after lithotripsy, and as an adjunct procedure when the surgeon cannot completely remove all the stones in the bile ducts. No major complications or mortality was observed. One patient had a self-limited drop in the hematocrit and four patients presented with transitory mild hyperamylasemia that returned to normal levels in 72 hours. Laparoscopic antegrade sphincterotomy added an average of 17 minutes to the laparoscopic operation. The mean postoperative stay was 1.4 days. The results of this study conclude that laparoscopic antegrade sphincterotomy is an option of great therapeutic value for selected cases when drainage of the biliary tract concomitant to the treatment of choledocholithiasis is necessary.

Journal Article↗
PubMed1996

Influence of vitamin D receptor genotype on bone mass changes after renal transplantation.

Renal transplant patients immunosuppressed with cyclosporine A (CsA) exhibit both a significant bone loss and an increased rate of bone fractures. An association between common allelic variants of the the vitamin D receptor (VDR) gene and bone mineral density and turnover has been reported in adults. However, the genetic influence on the rate of bone loss after renal transplantation has not been explored. We prospectively determined the changes in spinal mineral density in 34 consecutive nondiabetic adults who received a cadaveric renal allograft. Serum biochemical markers of bone metabolism and the vertebral mineral density (VMD) assessed by quantitative computed tomography were determined at the time of transplantation and three and twelve months later. In fifteen patients the histomorphometric features of iliac bone were analyzed at baseline and twelve months after transplantation. VDR alleles were typed by a PCR assay based on a polymorphic BsmI restriction site. Patients with the so-called "favorable" bb genotype (N = 12) were compared with those with the Bb or BB genotype (N = 22). Baseline VMD was similar in patients with or without the favorable bb genotype. Three months after transplantation the mean (+/- SD) VMD decreased 14 +/- 13.3 percent in all patients (16.5 +/- 13.1% in patients homozygous for the b allele and 13.77 +/- 13.9% in those with Bb or BB genotypes). The rate of VMD loss at this time inversely correlated with pretransplant PTH levels (r = -0.40; P < 0.05). Between 3 and 12 months after transplantation, patients with the favorable bb genotype recovered more VMD than those with Bb or BB types and showed a significantly higher Z score at the end of the follow-up (-0.37 +/- 1.16 vs. -1.10 +/- 1.20, respectively; P < 0.05). The beneficial effect of bb genotype was independent of the prevailing PTH levels and was also observed in those patients with a baseline PTH level < 250 pg/ml (final Z score: bb, -0.42 +/- 1.3, N = 11; Bb/BB, -1.35 +/- 0.8, N = 11, P < 0.05). At the end of follow-up, the histomorphometric studies showed a higher bone formation rate adjusted for PTH levels in patients with the Bb or BB genotype than in those with the favorable bb genotype (0.29 +/- 0.06 vs. 0.21 +/- 0.08 micron3/micron2/day respectively; P < 0.05). In conclusion, high pretransplant PTH levels enhance the early trabecular bone loss after renal transplantation, and functionally different alleles of the vitamin D receptor gene may condition the bone turnover and the degree of recovery of the bone mass.

Adult↗
PubMed1996

Transient false-positive hepatobiliary scan associated with ceftriaxone therapy.

Drug related false-positive hepatobiliary imaging is uncommon. The authors present a case of a 54-year-old woman who was treated with intravenous ceftriaxone for bacterial meningitis. Symptoms of acute cholecystitis subsequently developed and a sonogram revealed a gallstone. A Tc-99m DISIDA hepatobiliary study was positive for cystic duct obstruction. After discontinuation of ceftriaxone, the patient's clinical condition improved and, 2 weeks later, a repeat hepatobiliary scan was normal. High doses of ceftriaxone and prolonged administration may lead to formation of pseudocholelithiasis and signs of acute cholecystitis. Although this condition is usually benign and reversible, discontinuation of the drug is warranted when symptoms of acute cholecystitis are accompanied by a positive hepatobiliary scan.

Ceftriaxone↗
PubMed1996

Mseleni joint disease--a molecular genetic approach to defining the aetiology.

Mseleni joint disease (MJD) is an unusual form of progressive and widespread degenerative osteoarthropathy that has been identified in several hundred people in the remote Mseleni region of northern Zululand. Affected individuals experience articular discomfort in childhood and may be seriously handicapped as adults, often requiring prosthetic hip joint replacement. Although the condition clusters in families, there is no evidence of Mendelian inheritance and assessment of affected kindreds has not shown any evidence of genomic imprinting. To date our molecular work-up has entailed the study of 47 affected individuals from MJD kindreds to investigate familial predisposition based on the inheritance of a subset of markers and/or genes on the human genome, particularly those associated with the cartilage matrix. In addition, we have collected blood specimens form 111 unaffected but unrelated individuals from the same population group in order to determine whether any relationship exists between genetic components of the human leucocyte antigen (HLA) system and the MJD phenotype. Our investigations show the following: (i) there is no association between MJD and the HLA system which has previously been associated with non-Mendelian genetic conditions; (ii) COL2A1, which has been implicated in some forms of spondylo-epiphyseal dysplasia, may be involved in at least a subset of MJD patients; and (iii) type VI collagen is overabundant in degenerated hip joint cartilage.

Black People↗
PubMed1995

Achondroplasia is defined by recurrent G380R mutations of FGFR3.

Genomic DNA from 154 unrelated individuals with achondroplasia was evaluated for mutations in the fibroblast growth factor receptor 3 (FGFR3) transmembrane domain. All but one, an atypical case, were found to have a glycine-to-arginine substitution at codon 380. Of these, 150 had a G-to-A transition at nt 1138, and 3 had a G-to-C transversion at this same position. On the basis of estimates of the prevalence of achondroplasia, the mutation rate at the FGFR3 1138 guanosine nucleotide is two to three orders of magnitude higher than that previously reported for tranversions and transitions in CpG dinucleotides. To date, this represents the most mutable single nucleotide reported in the human genome. The homogeneity of mutations in achondroplasia is unprecedented for an autosomal dominant disorder and may explain the relative lack of heterogeneity in the achondroplasia phenotype.

Achondroplasia↗
PubMed1995

[Surgical treatment of hepatocarcinoma in cirrhosis].

In 1986, our institution published the first results of surgical resection of hepatocarcinoma in cirrhotic patients. The aim of this paper is to present long term results of this surgical management. From April 1978 to February 1992, 74 patients were operated on at the surgical clinic of University Medical Center of Rennes (35000) France. There were 60 hepatectomies and 14 transplantations. The mean age was 60.2 years +/- 9 years and the sex ratio: 70 males and 4 females. The etiology was alcoholic in 43 patients (58%), post hepatitis (B and C) in 22 patients (30%) and due to hemochromatosis in 9 patients (12%). According to the Child Pugh classification, 48 patients were Child A, 11 Child B and one Child C in the hepatectomy group and 9 patients Child A and 5 Child B in transplantation group. The operative mortality was 10% in hepatectomy group and 35.7% in liver transplantation group. Overall survival was 61.8% at 1 year, 47.1% at 2 years, 38.2% at 3 years and 20% at 5 years. 5 year survival is 21.4% after transplantation and 18.5% after resection. This difference is not significant. In conclusion, according to 5 years survival and to operative mortality the treatment of choice is hepatectomy in HCC in cirrhotic patients. However the best treatment is the prevention of cirrhosis.

Aged↗
PubMed1993

Ablation of irreversibly rejected renal allograft by embolization with absolute ethanol: a new clinical application.

Surgical allograft nephrectomy has been the conventional therapy for removing failed kidney allografts when clinical manifestations of graft intolerance appear. However, removal of a transplanted kidney is an extensive surgical procedure. On the other hand, transcatheter vascular embolization (TVE) has proven useful in ablating organs and could be applied to renal transplant ablation. The aim of this study was to present the results of TVE for the treatment of graft intolerance syndrome (GIS) in failed allograft kidneys. Transcatheter vascular embolization was performed in 14 allograft recipients (33 +/- 13 years of age; 10 men and four women) affected by GIS after irreversible kidney allograft failure. Graft intolerance syndrome was diagnosed by fever (93%), hematuria (50%), graft pain (36%), flu-like symptoms (29%), and increased graft size (29%). Absolute ethanol (0.1 mL/kg body weight) was injected in the allograft artery, and in seven patients a stainless steel coil was left in the renal artery following ethanol injection. All patients showed clinical disappearance of the GIS. No major complication occurred, although a postembolization syndrome of pain, fever, hematuria, numbness, and paresthesia of the affected area appeared in 11 of the 14 patients. After 2 to 56 months of follow-up no late complications occurred, with the exception of a graft abscess formation in one patient after 6 months of embolization. Subsequent transplantectomy was uneventful. In conclusion, TVE is a safe and effective method for kidney graft ablation, and it may become an alternative treatment for GIS following irreversible rejection.

Adult↗