Biomedical subjects

E Battaglia

Publications and source records attributed to E Battaglia.

At least 19 recordsLinked to original sources

PubMed2006

Treatment with botulinum toxin of octo-nonagerians with oesophageal achalasia: a two-year follow-up study.

BACKGROUND: Treatment of oesophageal achalasia with intrasphincteric injections of botulinum toxin has proved to be a successful alternative treatment modality. However, little is known about its long-term effects in very old patients. AIM: To evaluate the effects of such treatment in octo-nonagerians during a 2-year follow-up period. PATIENTS AND METHODS: Thirty-three patients with idiopathic oesophageal achalasia (range 81-94 years) entered the study. After basal evaluation and screening procedures, 100 U of botulinum toxin was injected at the lower oesophageal sphincter, and the procedure was repeated 1 month later. Data were collected at baseline and were compared after 1 and 2 years following the procedure. RESULTS: Seventy-eight per cent of patients were considered responders at 1 year and 54% were considered responders at 2 years. The weight gain at the end of the follow-up period was 2 (0-3) kg. No significant relationship was found between baseline lower oesophageal sphincter pressure and symptoms score after 1 and 2 years of follow-up; moreover, no major complications of botulinum toxin therapy were reported. CONCLUSION: Treatment of very old achalasic patients with botulinum toxin is safe, effective and yields good quality of life in a substantial proportion of these subjects.

Age Factors↗

PubMed2006

Brainstem involvement in Legionnaires' disease.

OBJECTIVE: To report a case of Legionella pneumonia with unusual neurologic involvement. INTERVENTION: Chest X-ray, lumbar puncture, magnetic imaging of the brain, electroencephalography, audiometry, brainstem acoustic evoked potentials and institution of oral antibiotics and steroids. MAIN RESULT: Gradual clinical improvement of neurologic and pulmonary illness within 4 weeks. CONCLUSION: Legionellosis should be considered in the differential diagnosis of neurologic involvement in the setting of pneumonia.

Adult↗

PubMed2005

Delivery of radiofrequency energy to the gastroesophageal junction (Stretta procedure) for the treatment of gastroesophageal reflux disease.

BACKGROUND: Radiofrequency (RF) energy treatment is increasingly offered before invasive surgical procedures for selected patients with gastroesophageal reflux disease (GERD). METHODS: Thirty-two patients undergoing the Stretta procedure were prospectively evaluated with upper endoscopy, manometry, 24-hour pH testing, SF-36 surveys, and GERD-specific questionnaires (GERD HRQL). RESULTS: Significant clinical improvement was observed in 91% of patients (29/32). Mean heartburn and GERD HRQL scores decreased (p = 0.001 and p = 0.003, respectively), and physical SF-36 increased (p = 0.05). At a minimum follow-up of 12 months, median esophageal acid exposure decreased (p = 0.79) and was normalized in eight patients. Median lower esophageal sphincter (LES) pressure was unchanged. Esophagitis healed in six of eight patients, but two patients with nonerosive disease developed asymptomatic grade A esophagitis during follow-up. At 12 months, 56% of patients were off proton pump inhibits. Morbidity was minimal. CONCLUSIONS: RF delivery to LES is safe and significantly improves symptoms and quality of life in selected GERD patients.

Electric Stimulation Therapy↗

PubMed2005

Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease.

BACKGROUND: Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis. AIMS: To investigate the interstitial cells of Cajal (the gut pacemaker cells), together with myenteric and submucosal ganglion and glial cells, in patients with diverticulosis. PATIENTS: Full thickness colonic samples were obtained from 39 patients undergoing surgery for diverticulosis. Specimens from tumour free areas of the colon in 10 age matched subjects undergoing surgery for colorectal cancer served as controls. METHODS: Interstitial cells of Cajal were assessed using anti-Kit antibodies; submucosal and myenteric plexus neurones and glial cells were assessed by means of anti-PGP 9.5 and anti-S-100 monoclonal antibodies, respectively. RESULTS: Patients with diverticulosis had normal numbers of myenteric and submucosal plexus neurones compared with controls (p = 0.103 and p = 0.516, respectively). All subtypes of interstitial cells of Cajal were significantly (p = 0.0003) reduced compared with controls, as were glial cells (p = 0.0041). CONCLUSIONS: Interstitial cells of Cajal and glial cells are decreased in colonic diverticular disease, whereas enteric neurones appear to be normally represented. This finding might explain some of the large bowel motor abnormalities reported to occur in this condition.

Aged↗

PubMed2004

Acute recurrent diverticulitis is prevented by oral administration of a polybacterial lysate suspension.

AIM: The main cause of acute diverticulitis is the abnormal accumulation of fecal bacteria within the diverticular lumen, leading to a balancing between normal probiotic microflora and pathogenic species; Gram negative Entero-bacteriaceae, mainly Escherichia coli and Proteus spp, are the genders that usually cause the disease-related symptoms, due to their ability to adhere to intestinal mucosa. The intestine is well known as the largest human lymphoepithelial organ and daily produces more antibodies, mainly secretory IgAs, than do all other lymphoid tissues. IgAs have different immune and anti-inflammatory properties. The aim of this study was to verify the efficacy of an oral immunostimulant highly-purified, polymicrobial lysate in the prevention of recurrent attacks of diverticulitis and in the improvement of symptoms. METHODS: The study was carried out on 83 consecutive patients suffering from recurrent symptomatic acute diverticulitis and with at least 2 attacks in the previous year; patients were randomly assigned to receive (group A) an oral polybacterial lysate suspension or to a no-treatment clinical follow-up as controls (group B). RESULTS: A total of 76 patients (41 in group A and 35 in group B) terminated the study period. the sums of the scores for symptoms, reported on day schedules, were calculated and examined by means of ANOVA statistical analysis. Statistical differences between group A vs group B were recorded after 1 month (p<0.05) and 3 months (p<0.01) of treatment with the oral polybacterial lysate suspension. CONCLUSIONS: Our data suggest that the administration of an oral enterovaccine for the prophylaxis of recurrent diverticulitis is effective and well tolerated, probably due to a direct stimulation of IgA-mediated mucosal defences.

Acute Disease↗

PubMed2003

Relationship between lipids and bone mass in 2 cohorts of healthy women and men.

A number of recent findings seem to indicate that fat and bone metabolism are strictly connected. We investigated the relationship between lipid profile and bone mineral density (BMD) in 236 either pre- or postmenopausal women, aged 35-81 years, attending our osteoporosis center ("clinic group"). In order to verify the consistency of the results, 265 men and 481 women aged 68-75, participating in a population-based epidemiological investigation ("community cohort"), were also studied. Lumbar spine, femoral neck, total hip and total body BMD, total body fat, % fat mass and lean mass were measured using dual energy X-ray absorptiometry (DXA). In the clinic group, lumbar spine and hip BMD Z score values were both strongly related to all measured serum lipids: the relationship was negative for HDL cholesterol ( P < 0.05) and Apo A lipoprotein ( P < 0.000) and positive for LDL cholesterol ( P < 0.05), Apo B lipoprotein ( P < 0.001) and triglycerides ( P < 0.05). When BMD values were adjusted for body weight and BMI, most relationships remained statistically significant. In the community cohort, total body and hip BMD values were strongly related in both men and women to age, body weight, height, BMI, fat mass, lean mass, % fat mass. Total body and hip BMD were significantly related to serum lipids in both women and men. The relationship was negative for HDL cholesterol and positive for total cholesterol, triglycerides and LDL cholesterol. Most of these relationships (triglycerides, HDL cholesterol, LDL/HDL cholesterol ratio in women, and all measured lipids in men) remained statistically significant ( P values ranging from 0.000 to 0.03) when the BMD values were adjusted also for anthropometric measures (body weight, height, fat mass). This study demonstrates for the first time that the lipid profile is strictly related to bone mass in both men and women. The interpretation of this association remains hypothetical but it might open new perspectives for understanding the mechanisms controlling bone metabolism.

Absorptiometry, Photon↗

PubMed2003

Are colonic regular contractile frequency patterns in slow transit constipation a relevant pathophysiological phenomenon?

BACKGROUND: Pathogenesis of slow transit constipation still remains elusive. Some studies have shown several colonic motor abnormalities; however, it is not easy to understand the relative importance of the single ones. AIMS: Since it has been hypothesized that an excess of periodic distal motor activity may be of pathophysiological importance in patients with slow transit constipation, we evaluated regular colonic contractile frequencies in a homogeneous cohort of these patients. PATIENTS: A total of 26 female patients (age range 34 to 67 years) fulfilling the Rome II criteria for constipation entered the study. No patient had evidence of secondary forms of constipation and distal obstruction. METHODS: Twenty-four hour colonic manometric studies were obtained for each patient. Regular contractile patterns (with frequencies ranging from 2 to 8 cycles/min) were calculated for the entire recording period and in single colonic segments. RESULTS: Overall, regular patterns accounted for about 3% of the total colonic motor activity (average 30 min/day per subject), with the 3 cycles/min being the predominant contractile rhythm. Most of this activity was present in the sigmoid colon, accounting for >50% of the total amount of motility, and it was more prevalent than in the descending and transverse colon; no differences were revealed in the descending with respect to the transverse colon. No daily fluctuations of regular contractile activity, nor a cyclic pattern, nor migration between recording points were observed. CONCLUSIONS: Regular colonic frequency patterns are probably of minor pathophysiological importance in slow transit constipation, even in the light of the scant amount of such phenomena previously documented in healthy subjects.

Adult↗

PubMed2003

Intravenous intermittent neridronate in the treatment of postmenopausal osteoporosis.

Bisphosphonates have been used with success in the treatment of osteoporosis, but oral therapy often lacks compliance. Here we report the results of clinical trial with aminobisphosphonate neridronate administered intravenously (i.v.). The study included 78 postmenopausal women with spine bone mineral density (BMD) at least -2.5 SD below peak. Patients were randomized to receive for 2 years either 50 mg i.v. neridronate bimonthly and 500 mg calcium plus 400 U vitamin D supplements daily (n=39) or calcium-vitamin D supplements alone (control group, n=39). Treatment was continued over 2 years with an additional 1 year follow-up of calcium-vitamin D supplements alone. Neridronate was well tolerated with the appearance of typical clinical signs of an acute phase reaction in only 3 of the patients after the first infusion. In the control group no significant changes in BMD or bone markers were observed. In the neridronate group BMD rose progressively at the spine rose up to 7.4% +/- 6.1% (SD) and at the femoral neck up to 5.8% +/- 8.2% (SD) at the end of the second year. In the succeeding follow-up these gains were maintained at both skeletal sites. Serum bone alkaline phosphatase (bone ALP) and serum type I collagen C-telopeptide (s-CTX) significantly decreased within 2 months. The bone ALP values reached a -35% plateau after 6 months, while s-CTX attained the lowest mean value (-47%) only by the end of the treatment with neridronate. Both bone markers returned almost to baseline values 1 year after treatment discontinuation. Treatment of postmenopausal osteoporosis with 50 mg i.v. neridronate bimonthly results in clinically relevant increases in BMD, among the largest so far observed with any other bisphosphonate.

Aged↗

PubMed2001

Regioselective and stereospecific glucuronidation of trans- and cis-resveratrol in human.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol present in wine, which has been reported to have anti-inflammatory, anti-platelet, and anti-carcinogenic effects. The glucuronidation of this compound and that of the cis-isomer also naturally present, has been investigated in human liver microsomes. Both isomers were actively glucuronidated. The reaction led to the formation of two glucuronides (3-O- and 4'-O-glucuronides), whose structure was characterized by LC-MS and proton NMR. Glucuronidation was regio- and stereoselective. It occurred at a faster rate with the cis-isomer and preferred the 3-position on both isomers. In addition, the glucuronidation of resveratrol was tested using several recombinant UDP-glucuronosyltransferase (UGT) isoforms. The reaction was catalyzed by UGT of the family 1A (UGT1A1, 1A6, 1A7, 1A9, 1A10). The bilirubin conjugating UGT1A1 was mainly involved in the 3-O-glucuronidation of trans-resveratrol, whereas the phenol conjugating UGT1A6 activity was restricted to cis-resveratrol. The UGT1A9 and 1A10 were active toward both isomers. The activity supported by UGT2B7 and UGT2B15 was very low and restricted to cis-resveratrol. UGT1A3, 1A4, 2B4, and 2B11 were unable to form resveratrol glucuronides.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

A unique multifunctional transporter translocates estradiol-17beta -glucuronide in rat liver microsomal vesicles.

A wide array of drugs, xenobiotics, and endogenous compounds undergo detoxification by conjugation with glucuronic acid in the liver via the action of UDP-glucuronosyltransferases. The mechanism whereby glucuronides, generated by this enzyme system in the lumen of the endoplasmic reticulum (ER), are exported to the cytosol prior to excretion is unknown. We examined this process in purified rat liver microsomes using a rapid filtration technique and [(3)H]estradiol-17beta-d-glucuronide ([(3)H]E(2)17betaG) as model substrate. Time-dependent uptake of intact [(3)H]E(2)17betaG was observed and shrinkage of ER vesicles by raffinose lowered the steady-state level of [(3)H]E(2)17betaG accumulation. In addition, rapid efflux of [(3)H]E(2)17betaG from rat liver microsomal vesicles suggested that the transport process is bidirectional. Microsomal uptake was saturable with an apparent K(m) and V(max) of 3.29 +/- 0.58 microm and 0.19 +/- 0.02 nmol.min(-1).mg protein(-1), respectively. Transport of [(3)H]E(2)17betaG was inhibited by the anion transport inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and probenecid. Specificity of the transport process was investigated by studying the cis-inhibitory effect of anionic metabolites, as well as substrates of the plasma membrane multidrug resistance-associated proteins on the uptake of [(3)H]E(2)17betaG. Collectively, these data are indicative of a novel multifunctional and bidirectional protein carrier for E(2)17betaG and other anionic compounds in the hepatic ER. This intracellular membrane transporter may contribute to the phenomenon of multidrug resistance.

Animals↗

PubMed2001

Twenty-four hour recordings of colonic motility in patients with diverticular disease: evidence for abnormal motility and propulsive activity.

INTRODUCTION: Diverticular disease of the colon is one of the most common pathologic entities in western countries. Although altered motility of the large bowel is commonly believed to be one of the major pathophysiologic mechanisms, no convincing evidence has been reported yet. In fact, only a few conflicting studies concerning distal colonic motility (with no information on forceful propulsive activity) are available in the literature. PURPOSE: The purpose of the present study was to investigate basal and stimulated (postprandial) colonic motility from the transverse (not affected), descending, and sigmoid colon in patients with diverticular disease, together with detection of high-amplitude propagated contractions (mass movements). Motility data from patients were compared with those obtained in healthy control subjects. METHODS: Ten patients and 16 control subjects of both sexes were recruited for the study. In all subjects, colonic motility was recorded for a 24-hour period by a colonoscopically positioned manometric catheter. Two 1000-kcal mixed meals were served during the study. RESULTS: Compared with control subjects, patients with diverticular disease displayed significantly increased amounts of motility in the affected segments; the response to a physiologic stimulus (meal) was also abnormal in the patients' group. Diverticular disease patients also had a significant increase of forceful propulsive activity compared with control subjects (average = 10.3 +/- 2.7/subject/day high-amplitude propagated contractions for patients and 5.5 +/- 0.8/subject/day for control subjects; P = 0.051); interestingly, about 20 percent of such activity was abnormal, being propagated in a retrograde fashion. CONCLUSIONS: We concluded that patients with diverticular disease of the colon have abnormal motor and propulsive activities of the large bowel, which are confined to the affected segments.

Adult↗

PubMed2001

[Esophageal motility disorders].

Esophageal motility abnormalities are usually diagnosed when esophageal manometry is performed in patients with unexplained non-cardiac chest pain, non obstructive dysphagia or as a part of the preoperative evaluation for surgery of gastroesophageal reflux. Classification of these abnormalities has been a subject of controversy. These esophageal contraction abnormalities can be separated manometrically from the motor pattern seen in normal subjects, however, their clinical relevance is still unclear and debated. Many patients demonstrate motility abnormalities in the manometry laboratories, but may lack correlation with their presenting symptoms. Medical treatment can decrease symptoms particularly chest pain or acid reflux but there is no significant changes in the manometric patterns. Such motor abnormalities may not reflect a true disease state, but they could be markers of other abnormalities and they can modify the initial manometric findings in time.

English Abstract↗

PubMed2000

Manometric investigation of anorectal function in early and late stage Parkinson's disease.

Abnormal gastrointestinal function is relatively frequent in Parkinson's disease, and constipation is a disturbing symptom in many patients. However, it remains to be established whether anorectal abnormalities are characteristic of the late stages of the disease. Clinical and anorectal manometric function were investigated in groups of early and late stage parkinsonian patients. Thirty one patients (19 men, 12 women, age range 22 to 89 years) entered the study. The disease severity was assessed by Hoehn and Yahr staging: there were four (12.9%) stage I, seven (22.6%) stage II, 10 (32.2%) stage III, and 10 (32.2%) stage IV patients. Anorectal variables were measured by standard manometric equipment and techniques. Values obtained in early stage patients (Hoehn and Yahr stage I and II) were compared with those obtained in late stage patients (Hoehn and Yahr stage III and IV). Overall, more than 70% of patients complained of chronic constipation, with chronic laxative use reported in more than 30%. Late stage patients were slightly older than their early stage counterparts. Pelvic floor dyssynergia was documented in more than 60% of patients. Manometric variables were not different in the two groups. In conclusion, defecatory dysfunction is frequent in Parkinson's disease, it is not confined to late stage patients, and it is found early in the course of the disease. This has potential implications for a targeted therapeutic approach.

Adult↗

PubMed2000

Platelet-activating factor enhances vascular endothelial growth factor-induced endothelial cell motility and neoangiogenesis in a murine matrigel model.

We previously reported that platelet-activating factor (PAF) enhances the angiogenic activity of certain polypeptide mediators such as tumor necrosis factor and hepatocyte growth factor by promoting endothelial cell motility. The purpose of the present study was to evaluate whether the synthesis of PAF induced by vascular endothelial growth factor (VEGF) might affect endothelial cell motility, microvascular permeability, and angiogenesis. The neoangiogenesis and synthesis of PAF induced by VEGF were studied in vivo in a murine Matrigel model. Dermal permeability was studied in mice by injection of (125)I-albumin. The synthesis of PAF, cell motility, and the increased (125)I-albumin transfer across endothelial monolayers were studied in vitro by using cultures of human umbilical cord vein-derived endothelial cells (HUVECs). The results obtained demonstrate that the neoangiogenesis induced by VEGF in vivo was associated with a local synthesis of PAF and was inhibited by WEB2170 and CV3988, 2 chemically unrelated, specific PAF-receptor antagonists. In contrast, WEB2170 did not inhibit VEGF-enhanced dermal permeability, suggesting that the latter was independent of the synthesis of PAF. In vitro, it was found that VEGF induced the synthesis of PAF by HUVECs in a dose- and time-dependent manner. The cell motility induced by VEGF was inhibited by PAF-receptor antagonists. In contrast, VEGF-induced proliferation of HUVECs and albumin transfer through HUVEC monolayer were unaffected by PAF-receptor antagonists. These results suggest that the synthesis of PAF induced by VEGF enhances endothelial cell migration and contributes to the angiogenic effect of VEGF in the in vivo Matrigel model.

Animals↗

PubMed1999

Photoaffinity labeling of the aglycon binding site of the recombinant human liver UDP-glucuronosyltransferase UGT1A6 with 7-azido-4-methylcoumarin.

7-Azido-4-methylcoumarin (AzMC) is a fluorescent photoactive compound structurally related to 4-methylumbelliferone (4-MU), a marker substrate of the human liver recombinant UDP-glucuronosyltransferase (UGT) 1A6. AzMC was synthesized and utilized to label the substrate binding site of UGT1A6. AzMC exhibits a fluorescence spectrum with maximum excitation and emission wavelengths of 380 and 442 nm, respectively. Upon irradiation, the probe irreversibly inhibited glucuronidation activity measured with para-nitrophenol (pNP) as substrate and interacted with UGT1A6 according to a saturable process indicative of reversible binding before covalent incorporation of the photoaffinity label. This inhibition was both time and concentration dependent and led to the calculation of an inhibition constant, k(2) = 0.113 mM min(-1), and dissociation constant, K(d) = 2.89 mM, for the reaction. Partial photoinactivation of UGT1A6 with AzMC revealed that the probe decreased the apparent V(max) of the pNP glucuronidation reaction, but not the K(m). Moreover, inhibition was partially prevented by 1-naphthol, a surrogate substrate for the enzyme, or by preincubation with an active-site directed inhibitor, 5'-O-[[(2-decanoylamino-3-phenyl-propyloxycarbonyl)amino]-su lfonyl]-2 ',3'-O-isopropylideneuridine. In contrast, UDP-glucuronic acid (UDP-GlcUA) did not have any protective effect against photoinactivation and AzMC did not affect the photoaffinity labeling of UGT1A6 by 5-[beta-(32)P]N(3)UDP-GlcUA, a photoaffinity analog of UDP-GlcUA. Additionally, in the absence of irradiation, AzMC was found to be a competitive inhibitor of 4MU glucuronidation. Collectively, these results strongly indicate that AzMC specifically binds to the UGT1A6 aglycon binding site. Amino acid alignment of phenol-binding proteins revealed a conserved motif, YXXXKXXPXP. It is possible that this motif is involved in phenol binding to UGT1A6 and other phenol-accepting proteins.

Affinity Labels↗

PubMed1999

Thrombopoietin stimulates endothelial cell motility and neoangiogenesis by a platelet-activating factor-dependent mechanism.

In this study, we demonstrate that human umbilical cord vein-derived endothelial cells (HUVECs) expressed c-Mpl, the thrombopoietin (TPO) receptor, and that TPO activates HUVECs in vitro, as indicated by directional migration, synthesis of 1-alkyl-/1-acyl-platelet-activating factor (PAF) and interleukin-8 (IL-8), and phosphorylation of the signal transducers and activators of transcription (STAT) STAT1 and STAT5B. The observation that WEB 2170 and CV3988, 2 structurally unrelated PAF receptor antagonists, prevented the motility of HUVECs induced by TPO suggests a role of PAF as secondary mediator. Moreover, kinetic analysis of TPO-induced tyrosine phosphorylation of STAT demonstrated that STAT5B activation temporally correlated with the synthesis of PAF. PAF, in turn, induced a rapid tyrosine phosphorylation of STAT5B and PAF receptor blockade, by WEB 2170, preventing both TPO- and PAF-mediated STAT5B activation. The in vivo angiogenic effect of TPO, studied in a mouse model of Matrigel implantation, demonstrated that TPO induced a dose-dependent angiogenic response that required the presence of heparin. Moreover, the in vivo angiogenic effect of TPO was inhibited by the PAF receptor antagonist WEB 2170 but not by the anti-basic fibroblast growth factor neutralizing antibody. These results indicate that the effects of TPO are not restricted to cells of hematopoietic lineages, because TPO is able to activate endothelial cells and to induce an angiogenic response in which the recruitment of endothelial cells is mediated by the synthesis of PAF. Moreover, biochemical analysis supports the hypothesis that STAT5B may be involved in the signaling pathway leading to PAF-dependent angiogenesis.

Animals↗

PubMed1999

Structural and functional studies of UDP-glucuronosyltransferases.

UDP-Glucuronosyltransferases (UGTs) are glycoproteins localized in the endoplasmic reticulum (ER) which catalyze the conjugation of a broad variety of lipophilic aglycon substrates with glucuronic acid using UDP-glucuronic acid (UDP-GIcUA) as the sugar donor. Glucuronidation is a major factor in the elimination of lipophilic compounds from the body. In this review, current information on the substrate specificities of UGT1A and 2B family isoforms is discussed. Recent findings with regard to UGT structure and topology are presented, including a dynamic topological model of UGTs in the ER. Evidence from experiments on UGT interactions with inhibitors directed at specific amino acids, photoaffinity labeling, and analysis of amino acid alignments suggest that UDP-GIcUA interacts with residues in both the N- and C-terminal domains, whereas aglycon binding sites are localized in the N-terminal domain. The amino acids identified so far as crucial for substrate binding and catalysis are arginine, lysine, histidine, proline, and residues containing carboxylic acid. Site-directed mutagenesis experiments are critical for unambiguous identification of the active-site architecture.

Amino Acids↗

PubMed1999

Identification of thiopurine methyltransferase (TPMT) polymorphisms cannot predict myelosuppression in systemic lupus erythematosus patients taking azathioprine.

OBJECTIVE: To determine whether the presence of polymorphisms associated with reduced or absent activity of thiopurine methyltransferase (TPMT), an enzyme involved in azathioprine metabolism, can predict side-effects, particularly myelosuppression, in patients taking this drug. METHODS: The TPMT genotype was determined in 120 patients with systemic lupus erythematosus (SLE) together with 15 patients with inflammatory bowel disease (IBD) and correlated with the effects of clinical exposure to azathioprine. RESULTS: TPMT polymorphisms were detected in eight patients. Severe marrow toxicity occurred in the single homozygote identified. Azathioprine was generally well tolerated, but 11 drug-associated neutropenias were detected. In only one of the 11 cases was a TPMT polymorphism identified. CONCLUSION: Homozygous TPMT deficiency was associated with severe marrow suppression. In the majority of cases, however, TPMT genotyping prior to azathioprine therapy would not have predicted myelosuppressive events and may augment, but not replace, regular blood monitoring.

Azathioprine↗