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T Ruuska

Publications and source records attributed to T Ruuska.

At least 19 recordsLinked to original sources
PubMed2007

Severe adverse reactions to Infliximab therapy are common in young children with inflammatory bowel disease.

UNLABELLED: Since 2000 we have introduced 141 Infliximab infusions to 23 children with severe inflammatory bowel disease. A total of seven severe adverse reactions occurred in 26% (6 of 23) of the children. Four reactions were acute (anaphylaxis n = 2; allergic reaction n = 2) and 3/4 of these children were younger than 10 years of age. Two children developed an abscess and one child had septicaemia and brain lesions related to progressive multifocal leucoencephalopathy. CONCLUSION: adverse reactions to Infliximab infusions are common. Young children seem to be prone to severe allergic reactions although they are on azathioprine and conventional glucocorticoid therapy.

Adolescent↗
PubMed2006

Oats in the treatment of childhood coeliac disease: a 2-year controlled trial and a long-term clinical follow-up study.

BACKGROUND: The exclusion of oats from the diet in coeliac disease is controversial. AIM: To study the long-term safety of oats in the treatment of children with coeliac disease. METHODS: Altogether 32 children with coeliac disease were enrolled in a 2-year controlled trial. Twenty-three children in remission were randomized either to oats or gluten challenge; when small bowel histological relapse was evident after gluten challenge, a gluten-free diet including oats was started. Furthermore, nine newly detected coeliac patients adopted an oat-containing gluten-free diet. Small bowel mucosal morphology, CD3+, alphabeta+ and gammadelta+ intraepithelial lymphocytes, human leucocyte antigen (HLA) DR expression and coeliac serology were determined. After the trial, the children were allowed to eat oats freely; follow-up was extended up to 7 years. RESULTS: In coeliac children in remission, oats had no detrimental effect on intestinal histology or serology during the 2-year trial. In contrast, the gluten-challenge group relapsed after 3-12 months. Complete recovery from the disease was accomplished in all relapsed and newly detected patients on an oat-containing gluten-free diet. After the trial, 86% of the children preferred to consume oats and they all remained in remission. CONCLUSION: In most children with coeliac disease, long-term consumption of oats is well tolerated, and it does not result in small bowel mucosal deterioration or immune activation.

Adolescent↗
PubMed2003

Upper endoscopic findings in children with active juvenile chronic arthritis.

AIM: To investigate the association between gastroduodenal mucosal damage and symptoms of the digestive tract in children with juvenile chronic arthritis (JCA). METHODS: This was a prospective, open, non-randomized study. Gastroscopy was performed on 45 children with active JCA in 1996-2000. Gastrointestinal symptoms before and during the treatment were noted, as was the length of antirheumatic medication, for which the data were retrospectively assessed. Plasma haemoglobin (Hb) and mean corpuscular volume (MCV) levels and erythrocyte sedimentation rate (ESR) were analysed. Mucosal biopsies were obtained for histology and Helicobacter pylori culture. All patients were taking non-steroidal anti-inflammatory drugs (NSAIDs) and 11 (24.4%) were on peroral steroids; 16 (35.6%) were receiving hydorxychloroquine, 9 salazopyrine, 5 myocrisine and 14 methotrexate. RESULTS: Seven children (15.6%) were found to have active inflammation in their gastric and/or duodenal mucosa, two having ulcers and two being infected with H. pylori. Abnormal endoscopic findings were more common in symptomatic children (n = 24) than in children without symptoms (n = 21) (75% vs 38%, p = 0.017). There was no clear association between the Hb or MCV level and the degree of gastroduodenal inflammation (p = 0.98 and 0.7, respectively). Significantly more children (66.6% vs 33.3%) experienced abdominal pain after beginning medical therapy than before therapy (p = 0.02). CONCLUSION: Endoscopic evaluation of patients with JCA and receiving NSAIDs should be considered at least in symptomatic cases.

Adolescent↗
PubMed2002

The natural course of gastroesophageal reflux disease in children.

BACKGROUND: The consequences of chronic gastroesophageal reflux disease (GERD) starting in childhood have not been widely studied. Our aim was to evaluate the usefulness of endoscopy in the primary diagnosis of GERD and to investigate the long-term course of this disease in children. METHODS: Between 1989 and 1999, 136 children had been endoscoped because of persisting symptoms of GER. After exclusions (neurological impairment, infant GER), 96 subjects were included, and files from 76 were available for the final evaluation. Twenty-four hour pH-monitoring had been performed primarily on 67 children and at follow-up on 28, and endoscopy to 69 subjects and at follow-up to 33, respectively. Medical therapy as well as symptoms prior to the therapy were registered. Clinical outcome was assessed at the end of the follow-up period. RESULTS: Presenting symptoms were recurrent abdominal pain, heartburn, regurgitation and vomiting. Twenty-two patients had respiratory symptoms in addition to the gastrointestinal complaints. PH-recording was normal in 17/67 subjects, slightly pathological in 33 and severe reflux was diagnosed in 13 patients. Histologically, minimal changes associated with GER were diagnosed in 22 and mild esophagitis in 7. Thirty-six patients had been treated with prokinetic drugs. H2-blockers had been used in 24 children and proton-pump inhibitors in 4. After a mean follow-up period of 28 months, only 24% of patients had become symptom-free. Control endoscopy showed no progression of the esophageal inflammation in any of the subjects. CONCLUSIONS: Pathological reflux in children is associated with no or mild esophageal inflammation, which is unlikely to deteriorate. Therefore endoscopic control could be limited to cases with severe esophagitis.

Adolescent↗
PubMed2002

Blisters in the small intestinal mucosa of coeliac patients contain T cells positive for cyclooxygenase 2.

BACKGROUND AND AIMS: Coeliac disease is characterised by atrophy of the villi and hyperplasia of the crypts in the mucosa of the small intestine. It is caused by an environmental trigger, cereal gluten, which induces infiltration of the mucosa by inflammatory cells. We hypothesised that these inflammatory cells express cyclooxygenase 2 (COX-2), an enzyme that contributes to the synthesis of pro and anti-inflammatory prostaglandins and is known to be expressed at sites of inflammation in the stomach and colon. We have investigated expression of COX-2 in the coeliac disease affected small intestinal mucosa where it may be an indicator of either disease induction or mucosal restoration processes. PATIENTS AND METHODS: Small intestinal biopsy samples from 15 coeliac patients and 15 non-coeliac individuals were stained immunohistochemically for COX-2. Samples from 10 of the patients were also stained after these patients had been on a gluten free diet for 6-24 months. Various cell type marker antigens were used for immunohistochemical identification of the type of cell that expressed COX-2. To further verify colocalisation of the cell type marker and COX-2, double immunoperoxidase and immunofluorescence methods were employed. Immunoelectron microscopy was used to investigate the subcellular location of COX-2. RESULTS: In all samples taken from coeliac patients, clusters of cells with strong immunoreactivity for COX-2 were found in those areas of the lamina propria where the epithelium seemed to blister or was totally detached from the basement membrane. These clusters were reduced in number or totally absent in samples taken after a gluten free diet. No such clusters were seen in any control samples. The density of COX-2 positive cells lining the differentiated epithelium decreased significantly from 13.5 (5.1) cells/10(5) microm(2) (mean (SD)) in the untreated patient samples to 6.5 (2.0) cells/10(5) microm(2) after a gluten free diet (p<0.001), and was 3.3 (1.9) cells/10(5) microm(2) in control samples (p<0.001 compared with untreated or diet treated coeliac samples). Staining for COX-2 was localised to CD3+ T cells and CD68+ macrophages in the mucosal lesions but not all of these cells were positive for COX-2. Immunoelectron microscopy revealed that the ultrastructure of the COX-2 positive cells resembled that of lymphocytes, and the immunoreaction was localised to the rough endoplasmic reticulum and the nuclear envelope. CONCLUSIONS: Our results show that in coeliac disease, blistering of small intestinal epithelial cells is associated with accumulation of COX-2 positive T cells, and the number of these cells decreases after a gluten free diet. These observations suggest that COX-2 mediated prostanoid synthesis contributes to healing of the coeliac mucosa and may be involved in maintenance of intestinal integrity.

Adolescent↗
PubMed2001

Helicobacter pylori and iron deficiency anaemia in children.

BACKGROUND: Both iron deficiency anaemia and Helicobacter pylori infection are rare in developed countries. A possible connection has been suggested between these two diseases and our aim was to define the clinical picture and to study the effect of bacterial eradication in H. pylori colonized children with severe anaemia. METHODS: Eight children with iron deficiency anaemia refractory to iron supplementation were examined with gastroscopy because of suspicion of H. pylori infection. Anaemia was treated with oral ferrous sulphate. Two patients needed blood transfusions. Eradication therapy was given either with combination of colloidal bismuth subcitrate and metronidazole or with omeprazole, clarithromycin and amoxycillin. Eradication was confirmed by urea breath test 4 weeks post-treatment. RESULTS: H. pylori infection was confirmed histologically and microbiologically in all children, who also presented with chronic, active gastritis. Bacteria were successfully eradicated in 7/8 patients. Correction of haemoglobin values was observed post-treatment, iron stores still being deficient at control in 4/8 children. CONCLUSIONS: Our results suggest that H. pylori might have a role in causing iron deficiency anaemia in school-age children. Screening for H. pylori should be extended to cover those patients with other clinical manifestations than symptoms from gastrointestinal tract.

Adolescent↗
PubMed2001

Mucosal pathology of the foregut associated with food allergy and recurrent abdominal pains in children.

UNLABELLED: To determine whether children with recurrent abdominal pain (RAP) include an excess of children with food allergy (FA), this study examined a consecutive series of 84 children (43M, 41F, mean age 7.9 y, range 1.6-15 y) referred during 1 y to 2 university hospitals. In addition to a clinical examination, the patients underwent gastroduodenoscopy with three biopsy specimens, skin-prick and patch tests, and comprehensive laboratory tests for atopic allergy. Based on an open elimination-challenge test, a total of 28 (33%) subjects were diagnosed for FA. In the whole material, specific endoscopic abnormalities were found in 38 (45%) subjects: oesophagitis in 17, gastric erosions in 8, lymphonodular duodenitis in 12 and erosive duodenitis in 5. FA showed a close relationship with duodenal lesions, but no significant association with oesophagitis and gastritis. The histological findings were mild, although some alterations could be observed in up to 66 (79%) subjects, equally often in patients with and without FA. None showed villous atrophy or severe infiltration of eosinophilic or mononuclear cells. Slightly increased densities of eosinophilic cells were significantly associated with endoscopic findings, especially oesophagitis. At least one positive skin-prick test with food allergens was found in 11 subjects and a positive patch test in 21 subjects, but neither showed an association with the endoscopic or histological findings, or even with clinical FA. CONCLUSION: Since the children with FA showed significantly more often concomitant mucosal pathology of the foregut than those without FA, FA may be considered one of the major factors underlying RAP. The report suggests the trial of an elimination diet in cases with RAP if lymphonodular hyperplasia or duodenitis is seen on gastroduodenoscopy.

Abdominal Pain↗
PubMed2001

Gastroesophageal endoscopic findings and gastrointestinal symptoms in preterm neonates with and without perinatal indomethacin exposure.

BACKGROUND: The aim of this study was to investigate whether perinatal indomethacin treatment has effects on the development of esophageal and gastric lesions in preterm infants and to evaluate other potential etiologic factors behind these lesions. METHODS: Sixty-nine infants were born at less than 33 weeks' gestation. Forty-five of these infants underwent treatment with perinatal indomethacin (study group) and 24 did not (control group). All underwent upper gastrointestinal tract endoscopy and biopsy during the neonatal period. The correlation between gastrointestinal symptoms, abnormal endoscopic findings, and the factors correlating with the development of esophageal and gastric mucosal lesions was evaluated. RESULTS: Abnormal endoscopic findings were equally common in the study group (77.8%) and in controls (83.3%). There was no dependence between gastrointestinal symptoms and endoscopic findings because only 15 infants (21.7%) were symptomatic before endoscopy. The interval between endoscopy and the last perinatal indomethacin dose correlated significantly with abnormal esophageal findings and gastric mucosal lesions. Shorter duration of enteral feeding before endoscopy correlated with greater risk of abnormal esophageal findings. Older gestational age and need of ventilator treatment at the time of endoscopy remained the risk factors associated with abnormal gastric findings. CONCLUSIONS: Esophageal and gastric lesions diagnosed by endoscopy correlate poorly with the gastrointestinal symptoms of patients. Short duration of enteral feeding seems to be correlated with an increased risk of esophageal mucosal lesions, increasing gestational age and ventilator treatment with gastric mucosal lesions, and perinatal indomethacin with esophageal and gastric mucosal lesions in preterm infants. Ventilator-treated preterm infants not receiving enteral nutrition and patients with indomethacin exposure might benefit from ulcer prophylaxis.

Biopsy↗
PubMed2000

Stress-induced gastric findings in critically ill newborn infants: frequency and risk factors.

OBJECTIVE: To evaluate whether infants treated in neonatal intensive care units have stress-induced bleeding from gastrointestinal tract or gastric lesions and to define risk factors for these findings. DESIGN: Part one: retrospective; part two: prospective. SETTING: Tampere University Hospital, neonatal intensive care unit. PATIENTS AND INTERVENTIONS: In part one, 100 consecutive newborn infants treated in intensive care were retrospectively evaluated for gastrointestinal tract bleeding and risk factors, and in part two 89 gastroscopied and mechanically ventilated infants were prospectively evaluated for further risk factors for gastric mucosal lesions. The statistical evaluation of risk factors was made by multivariate analysis using logistic regression modeling. MAIN RESULTS: Of infants treated in the neonatal intensive care unit 20 % had signs of gastrointestinal bleeding. Mechanical ventilation was the only risk factor (OR = 4.06, 95 % confidence interval 1.21-12.3). In part two, when mechanically ventilated infants were prospectively evaluated, 53 % had remarkable gastric mucosal lesions. The analysis showed three other risk factors: abnormal and delayed delivery and hypotension after birth. CONCLUSIONS: Newborn infants treated in the intensive care unit had a high frequency of stress-induced gastric hemorrhage with gastric lesions similar to adults and children treated in intensive care. Mechanical ventilation is the main risk factor. Also mode of delivery and hypotension after birth increase the risk of stress-induced gastric lesions. These infants should be the target for prophylactic gastroprotective treatment.

Critical Illness↗
PubMed2000

Early development of human gastric H,K-adenosine triphosphatase.

BACKGROUND: Little is known about the early development of the gastric acid secretion in human neonates. The purpose of this study was to examine the early development of gastric H,K-adenosine triphosphatase (ATPase) by analyzing human gastric biopsy specimens. METHODS: Eighty-eight neonates from week 25 to week 42 of gestation who were treated in a neonatal intensive care unit underwent gastroscopy with biopsy specimens obtained from the corpus. The expression of gastric H,K-ATPase protein in the gastric biopsy specimens was assessed by Western blot analysis, using an antibody directed against the gastric H,K-ATPase. The amount of H,K-ATPase expressed was compared with age, gender, clinical factors, diseases, and the macroscopic and histologic findings at endoscopy. RESULTS: The expression of human gastric H,K-ATPase increased significantly with gestational age. There was a significant increase in the expression of gastric H,K-ATPase during the first 82 days after birth. Boys had a significantly higher expression of gastric H,K-ATPase than girls did, when it was adjusted for gestational and postnatal age. Neither the clinical features nor treatments showed significant correlations with the expression of human gastric H,K-ATPase when controlling for gestational and postnatal age. CONCLUSIONS: This study shows that human gastric H,K-ATPase is expressed from week 25 of gestation, which agrees with earlier findings of gastric pH in preterm infants. The amount of enzyme expressed increases with gestational and postnatal age. The authors speculate that the susceptibility to gastric lesions seen in neonates is not related to the amount of H,K-ATPase. However, studies elucidating the ontogeny of gastric mucosal defense mechanisms are warranted.

Biopsy↗
PubMed1999

Changing jejunal gamma delta T cell receptor (TCR)-bearing intraepithelial lymphocyte density in coeliac disease.

The function of jejunal intraepithelial gamma delta+ T cells is obscure, but they are commonly implicated as playing a role in inflammatory and autoimmune conditions. In coeliac disease (CoD), there are controversial reports as to gluten dependency of these cells. We have now studied the small bowel mucosal intraepithelial T cell densities, and the ratios of gamma delta+ to CD3+ T cells and gamma delta+ to alpha beta+ T cells during early disease development and on a gluten-free diet. Nine children initially excluded for CoD were followed up and rebiopsy after 0.8-4.5 years showed mucosal deterioration. Further, 21 biopsy specimens from newly diagnosed CoD patients were studied, together with 20 specimens taken from children on a gluten-free diet. During CoD development the density of gamma delta+ and alpha beta+ T cells as well as the ratios of gamma delta+ to CD3+ T cells and gamma delta+ to alpha beta+ T cells increased. In the latent stage of CoD when the small bowel mucosal architecture was still normal, two children had clearly normal densities of gamma delta+ (< 2.5 cells/100 epithelial cells) and alpha beta+ (< 25.0 cells/100 epithelial cells) T cells, and low ratios as well. In patients with newly diagnosed CoD the densities decreased significantly on a long-term gluten-free diet. We conclude that the density of intraepithelial gamma delta+ T cells as well as alphabeta+ T cells in CoD is gluten-dependent. CoD can develop in a child ingesting normal amounts of gluten and having normal jejunal mucosal morphology on biopsy and a normal density of gamma delta+ T cells.

Adolescent↗
PubMed1999

Reverse transcription-polymerase chain reaction in the diagnosis of Helicobacter pylori infection in Finnish children.

BACKGROUND: The purpose of this study was to design a simplified polymerase chain reaction (PCR) technique for the detection of Helicobacter pylori and to compare it with conventional diagnostic methods-culture and histology of gastric biopsy specimens. In addition, the capability of this technique to detect H. pylori in the gastric mucosal biopsies of originally H. pylori-negative children with gastritis or recurrent abdominal pain was investigated. METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR) using polymerase from Thermus thermophilus was applied to detect H. pylori 16S rRNA. Twenty-five children H. pylori-positive by culture and/or histology were used as positive control subjects. Sixteen healthy H. pylori-negative children served as negative control subjects. Biopsy specimens from gastric antrum and corpus from 81 children were examined by RT-PCR. Altogether, 30 had histologic gastritis and 51 had nonspecific abdominal pain only, with no disease in histologic specimens. Histology and culture of H. pylori were negative in both patient groups. RESULTS: Reverse transcription-polymerase chain reaction detected 24 of 25 tissue-positive and 0 of 16 tissue-negative cases, indicating 96% sensitivity and 100% specificity for the test. None of the culturally and histologically H. pylori-negative samples showed H. pylori colonization when analyzed by RT-PCR. CONCLUSIONS: RT-PCR using Thermus thermophilus polymerase is a fast and simple means of detecting H. pylori in gastric biopsy specimens. It is at least as specific and sensitive as conventional methods. In pediatric patients it may be necessary to take more than two biopsy specimens to increase sensitivity in cases of local or patchy colonization.

Abdominal Pain↗
PubMed1998

Outcome of patients operated on for esophageal atresia: 30 years' experience.

PURPOSE: The aim of this study was to evaluate the outcome and late sequelae of patients with esophageal atresia or tracheoesophageal fistula. METHODS: Sixty patients with esophageal atresia or tracheoesophageal fistula (EA-TEF) were treated in Tampere University Hospital in the years 1963 through 1993. Long-term outcome was evaluated with a questionnaire, pulmonary and esophageal function test results, 24-hour pH level monitoring, tracheobronchoscopy findings, and esophagogastroscopy with biopsy sections and samples for bacterial cultures. RESULTS: One third of the respondents reported having impaired quality of life because of respiratory infections, dyspnea, and difficulties in swallowing and coughing at night. Eighteen percent had gastroesophageal reflux (GER) symptoms. The rate of symptoms decreased with age. Impaired pulmonary function, GER, abnormal esophageal peristalsis, and transit time were registered. Tracheobronchoscopy showed tracheal narrowing and inflammation in one third; in histopathologic analysis, however, the rate of inflammation was more than doubled. Histologically, esophageal inflammation was found in 51%, Barrett's esophagus in 6%, and a Helicobacter pylori infection in 21% of cases. The severity of GER, esophageal peristaltic abnormality, tracheal inflammation, and impairment of pulmonary function seems to be alleviated with age. CONCLUSIONS: Although the long-term outcome of EA-TEF patients seems to be favorable, respiratory and gastrointestinal symptoms as well as functional abnormalities remain frequent. Gastric metaplasia in the esophagus and the high rate of tracheal, esophageal, and gastric inflammation indicate a need for long-term follow-up.

Adolescent↗
PubMed1998

Growth of prepubertal children with inflammatory bowel disease.

BACKGROUND: Growth retardation has been reported in children with chronic inflammatory bowel disease, especially in those with Crohn's disease. Most of these studies concern adolescent patients. METHODS: The growth of 47 prepubertal children (20 boys and 27 girls, mean age at diagnosis 7 years) with inflammatory bowel disease was studied at Tampere University Hospital, Department of Paediatrics. The mean height and height velocity standard deviation scores were calculated at diagnosis and, after that, yearly. The cumulative doses of oral and rectal prednisone per year were calculated. The severity of the disease was scored. The statistical analysis was carried out using the analysis of variance for repeated measurements. RESULTS: During the year preceding the diagnosis, children with inflammatory bowel disease had grown more slowly than their healthy peers. At diagnosis, they were slightly shorter as a group than are healthy children. During treatment and follow-up the mean height velocity of children with inflammatory bowel disease increased (change in the mean height velocity standard deviation scores from -0.84 to +1.08), normalizing the mean heights of these children compared with those of their healthy peers (change in the mean height standard deviation scores from -0.32 to +0.05). In the analysis of covariance, the poorest growth was seen in children with Crohn's disease, scored as severe, and the best growth in children with mild ulcerative colitis. No difference was seen in groups with or without prednisone treatment. CONCLUSIONS: Growth retardation is an important sign of chronic inflammatory bowel disease in prepubertal as well as adolescent children. During treatment, increasing growth velocity brings these children as a group to normal heights for age and sex.

Child↗
PubMed1997

A randomized, controlled study of prophylactic ranitidine in preventing stress-induced gastric mucosal lesions in neonatal intensive care unit patients.

OBJECTIVE: To assess endoscopically the effect of prophylactic short-term ranitidine treatment in the prevention of stress-induced gastric lesions in neonatal intensive care unit (ICU) patients. DESIGN: Prospective, randomized study. SETTING: Department of Neonatal Intensive Care, University Hospital of Tampere. PATIENTS: Fifty-three infants were enrolled in a randomized, controlled study. Forty-eight (90%) of these patients underwent endoscopic examination and were evaluated. INTERVENTIONS: A histamine-2-receptor blocker, ranitidine, was given prophylactically after birth for 4 days to infants mechanically ventilated and treated in the neonatal ICU. The gastric mucosa was both visually and histologically evaluated after 3 to 6 days, and the outcome of the infants was registered. MEASUREMENTS AND MAIN RESULTS: In the 23 infants prophylactically treated with ranitidine, the gastric mucosa was visually classified as normal in 14 (61%) infants as compared with five (20%) of 25 controls (p < .004). Histologic lesions showed parallel results (57% vs. 16%, p < .004). Eight gastric ulcers were diagnosed endoscopically in the control group vs. none in the treatment group. The ulcers were all clinically "silent" at the time of endoscopy. According to logistic regression modeling, the decreased risk for gastric mucosal lesions in infants receiving prophylactic ranitidine was 0.03 (95% confidence interval 0.003 to 0.178). Surfactant treatment for infant respiratory distress syndrome also decreased the risk for stress-induced gastric mucosal lesions (odds ratio 0.083; 95% confidence interval 0.009 to 0.788), whereas other variables (birth weight, gestational age, Apgar scores, cord blood pH, and duration of intubation) had no significant effect. No side effects could be attributed to the ranitidine treatment. CONCLUSION: We conclude that short-term prophylactic ranitidine treatment prevents gastric mucosal lesions in newborn infants under stress.

Birth Weight↗
PubMed1996

Neonatal and infantile upper gastrointestinal endoscopy using a new small diameter fibreoptic gastroscope.

Using a new prototype (Olympus XPGIF 5.2/ N30) gastroscope, upper gastrointestinal endoscopy was safely performed under sedation on 99 infants (weights 0.9 to 10.1 kg). No complications occurred. Macroscopic and microscopic abnormalities were found in 60%, including abnormal duodenal biopsies in 47% of cases with protracted diarrhoea. Duodenal biopsy material was, however, of suboptimal standard for histologic assessment in 25% of the cases. In 52% of those under 3.5 kg diagnoses were made that would not have otherwise been possible and, in 75% of those in the Intensive Care Unit, abnormalities were found. The use of this new endoscope represents a significant advance in clinical practice.

Biopsy↗