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Biomedical subjects

J Reynolds

Publications and source records attributed to J Reynolds.

At least 19 recordsLinked to original sources
PubMed2006

Pamidronate reduces bone loss after allogeneic stem cell transplantation.

BACKGROUND: Rapid bone loss occurs from the proximal femur after allogeneic stem cell transplantation (alloSCT). OBJECTIVE: The objective of the study was to evaluate effects of high-dose pamidronate therapy on bone loss (BMD) after alloSCT. DESIGN: This was a randomized, multicenter, open-label, 12-month prospective study of iv pamidronate (90 mg/month) beginning before conditioning vs. no pamidronate. All 116 patients also received calcitriol (0.25 microg/d) and calcium (1000 mg/d), which were continued for another year. MAIN OUTCOME MEASURES: Primary objectives were to compare changes in BMD 12 months after alloSCT at the femoral neck, lumbar spine, and total hip between the treatment arms and assess influences of glucocorticoid and cyclosporin therapy on these changes. RESULTS: Pamidronate reduced bone loss at the spine, femoral neck, and total hip by 5.6, 7.7, and 4.9% (all P < or = 0.003), respectively, at 12 months. However, BMD of the femoral neck and total hip was still 2.8 and 3.5% lower than baseline, respectively (P < 0.05) with pamidronate. Only differences at the total hip remained significant between the two groups at 24 months. Benefits were restricted to patients receiving an average daily prednisolone dose greater than 10 mg and cyclosporin therapy for more than 5 months within the first 6 months of alloSCT. CONCLUSIONS: Pamidronate markedly reduced but did not completely prevent postallogeneic bone marrow transplantation bone loss. BMD benefits were greatest in patients on higher doses of immunosuppressive therapy, but most were lost 12 months after stopping pamidronate. Studies of more potent bisphosphonates or anabolic therapy with PTH after alloSCT are warranted with the aim of durable maintenance of bone mass.

Adolescent↗
PubMed2005

Dose-response for glycaemic and metabolic changes 28 days after single injection of long-acting release exenatide in diabetic fatty Zucker rats.

AIMS/HYPOTHESIS: Exenatide (exendin-4) injected subcutaneously twice daily reduces glycaemic deterioration in diabetic fatty Zucker (ZDF) rats and reduces HbA1c in humans with type 2 diabetes. Because tachyphylaxis may develop with continuous peptide exposure, we examined the activity of a long-acting-release (LAR) formulation of exenatide on HbA1c, insulin sensitivity and beta cell secretion in ZDF rats. METHODS: Single subcutaneous injections of a poly-lactide-glycolide microsphere suspension (3% peptide) containing 0, 1, 10, 100, 1,000, 3,000 or 9,000 mug exenatide were administered to 9-week-old ZDF rats with matched initial HbA1c values (n=7 rats/group). RESULTS: In contrast to the progressive 3.22+/-0.42% increase in HbA1c in control ZDF rats observed over 28 days, single exenatide-LAR injections dose-proportionally prevented such glycaemic deterioration (median effective dose 74 microg+/-0.1 log per rat; median effective concentration 52 pmol/l+/-0.06 log). Hyperinsulinaemic-euglycaemic clamp procedures incorporating an intraclamp glucose challenge performed 28 days after treatment revealed increases in beta cell response to the glucose challenge at lower exenatide-LAR doses, and up to a 2.1-fold increase in insulin sensitivity at higher exenatide-LAR doses. CONCLUSIONS/INTERPRETATION: The finding that a single dose of exenatide-LAR enhanced glucose control for 28 days in the ZDF rat model of type 2 diabetes suggests that tachyphylaxis is unlikely to be a feature of exenatide-LAR preparations, and supports further clinical exploration.

Animals↗
PubMed2005

Prognostic features for response and survival in elderly patients with de novo acute myeloid leukemia treated with mitoxantrone and intermediate dose cytarabine.

Forty-three fit elderly patients with de novo acute myeloid leukemia (AML) received chemotherapy with mitoxantrone and intermediate dose cytarabine (MIDAC) in a phase II clinical trial conducted by the Australasian Leukaemia and Lymphoma Group. The main aim of the study was to evaluate the tolerability and efficacy of MIDAC in inducing durable remissions. While the chemotherapy was generally well tolerated, less than half the patients achieved complete remission (CR) after induction and many of those in CR could not receive planned consolidation cycles. The median overall survival for all patients was 6.5 months and the median disease-free survival for those achieving CR was 8.3 months. Only 2 patients survived beyond 4 years. Factors significantly associated with shorter survival were adverse cytogenetics, marrow dysplasia and increasing age. These results suggest that only selected elderly patients with AML are likely to benefit from aggressive chemotherapy and that novel therapies are required to improve the poor prognosis of this group.

Aged↗
PubMed2004

A double-pulsar system: a rare laboratory for relativistic gravity and plasma physics.

The clocklike properties of pulsars moving in the gravitational fields of their unseen neutron-star companions have allowed unique tests of general relativity and provided evidence for gravitational radiation. We report here the detection of the 2.8-second pulsar J0737-3039B as the companion to the 23-millisecond pulsar J0737-3039A in a highly relativistic double neutron star system, allowing unprecedented tests of fundamental gravitational physics. We observed a short eclipse of J0737-3039A by J0737-3039B and orbital modulation of the flux density and the pulse shape of J0737-3039B, probably because of the influence of J0737-3039A's energy flux on its magnetosphere. These effects will allow us to probe magneto-ionic properties of a pulsar magnetosphere.

Journal Article↗
PubMed2004

Hepatic resection for colorectal metastases - a national perspective.

BACKGROUND: Many consultant surgeons are uncertain about peri-operative assessment and postoperative follow-up of patients for colorectal liver metastases, and indications for referral for hepatic resection. The aim of this study was to assess the views the consultant surgeons who manage these patients. METHODS: A postal questionnaire was sent to all consultant members of the Association of Coloproctology of Great Britain and Ireland and of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland. The questionnaire assessed current practice for preoperative assessment and follow-up of patients with colorectal malignancy and timing of and criteria for hepatic resection of metastases. Number of referrals/resections were also assessed. RESULTS: The response rate was 47%. Half of the consultants held joint clinics with an oncologist and 89% assessed the liver for secondaries prior to colorectal resection. Ultrasound was used by 75%. Whilst 99% would consider referring a patient with a solitary liver metastasis for resection, only 62% would consider resection for more than 3 unilobar metastases. The majority (83%) thought resections should be performed within the 6 months following colorectal resection. During follow-up, 52% requested blood CEA levels and 72% liver ultrasound. Half would consider chemotherapy prior to liver resection and 76% performed at least one hepatic resection per year with a median number of 2 resections each year. CONCLUSIONS: A substantial proportion of patients are assessed for colorectal liver metastases preoperatively and during follow-up though there is spectrum of frequency of assessment and modality for imaging. Virtually all patients with solitary hepatic metastases are considered for liver resection. Patients with more than one metastasis are likely to be not considered for resection. Many surgeons are carrying out less than 3 resections each year.

Attitude of Health Personnel↗
PubMed2004

Effects of an injectable trace mineral supplement on first-service conception rate of dairy cows.

A total of 825 dairy cows from a commercial dairy farm in central California were used to evaluate effects of one or 2 doses of an injectable trace mineral supplement containing 20 mg/mL of zinc, 20 mg/mL of manganese, 5 mg/mL of selenium, and 10 mg/mL of copper on first-service conception rate. Cows were randomly allocated into treatment or control group to either a single dose (experiment 1) or a double dose (experiment 2) of injected supplement. Allocation was based on days in lactation for experiment 1 and the length of gestation periods for experiment 2. In experiment 1, cows 38 to 45 d in lactation (n = 190) received a single dose of 5 mL of injected supplement. Similar cows were used as controls (n = 227). In experiment 2, cows and pregnant heifers received an initial injection of 5 mL of the mineral supplement from 2 to 3 wk precalving (n = 186). An equal dose was repeated 38 to 45 d in lactation. A similar group of cows and pregnant heifers served as controls for experiment 2 (n = 222). Health and reproductive events postcalving were recorded. In experiment 1, the odds of first-service conception were not significantly different for cows receiving a one-dose regimen of minerals compared with untreated control cows; conception rates were 26.8 and 27.5% for experiment 1 treatment and control groups, respectively. In experiment 1, the odds of first-service conception were significantly lower (odds ratio = 0.66) for cows and heifers given the 2-dose regimen of minerals compared with untreated controls; overall conception rates were 21.5 and 31.5% for experiment 2 treatment and control groups, respectively. In this intensively managed dairy herd, a single dose of injected trace minerals before breeding had no beneficial effects on first-service conception rate. However, dairy cows receiving a dose of trace minerals before calving and another dose before breeding had lower conception at first service.

Animals↗
PubMed2003

Dynamic force responses of skeletal muscle during stretch-shortening cycles.

Muscle damage due to stretch-shortening cycles (i.e., cyclic eccentric/concentric muscle actions) is one of the major concerns in sports and occupational related activities. Mechanical responses of whole muscle have been associated with damage in neural motor units, in connective tissues, and the force generation mechanism. The objective of this study was to introduce a new method to quantify the real-time changes in skeletal muscle forces of rats during injurious stretch-shortening cycles. Male Sprague Dawley rats ( n=24) were selected for use in this study. The dorsi flexor muscle group was exposed to either 150 stretch-shortening cycles ( n=12) or 15 isometric contractions ( n=12) in vivo using a dynamometer and electrical stimulation. Muscle damage after exposure to stretch-shortening cycles was verified by the non-recoverable force deficit at 48 h and the presence of myofiber necrosis. Variations of the dynamic forces during stretch-shortening cycles were analyzed by decomposing the dynamic force signature into peak force ( F(peak)), minimum force ( F(min)), average force ( F(mean)), and cyclic force ( F(a)). After the 15th set of stretch-shortening cycles, the decrease in the stretch-shortening parameters, F(peak), F(min), F(mean), and F(a), was 50% ( P<0.0001), 26% ( P=0.0055), 68% ( P<0.0001), and 50% ( P<0.0001), respectively. Our results showed that both isometric contractions and stretch-shortening cycles induce a reduction in the isometric force. However, the force reduction induced by isometric contractions fully recovered after a break of 48 h while that induced by stretch-shortening cycles did not. Histopathologic assessment of the tibialis anterior exposed to stretch-shortening cycles showed significant myofiber degeneration and necrosis with associated inflammation, while muscles exposed to isometric contractions showed no myofiber degeneration and necrosis, and limited inflammation. Our results suggest that muscle damage can be identified by the non-recoverable isometric force decrement and also by the variations in the dynamic force signature during stretch-shortening cycles.

Animals↗
PubMed2003

Origin and colonization history of the white-clawed crayfish, Austropotamobius pallipes, in Ireland.

The presence of the white-clawed crayfish Austropotamobius pallipes complex in Ireland is suspected to be a result of human translocations. Two hypotheses have been formulated about the origin of the crayfish: from British populations or from western French populations. In order to resolve this question, nine Irish crayfish populations (a total of 124 individuals) were sampled along a south-north cline and investigated by combining two molecular markers: mtDNA and RAPDs. The mtDNA marker, analysed by RFLP on the entire molecule, showed an absence of polymorphism within and among Irish populations. The RFLP haplotype found in Irish populations was only recorded in western French populations and was different from those found in English populations. This result may be explained by a human introduction of crayfish to Ireland from western French populations. RAPD analysis showed a clinal reduction of genetic variability within Irish populations from south to north, associated with an increase in their genetic differentiation. A stepwise model of translocation from the south to the north of Ireland is proposed and discussed.

Animals↗
PubMed2001

A prospective randomized comparison of 270 degrees fusions to 360 degrees fusions (circumferential fusions).

STUDY DESIGN: Prospective randomized comparison of anterior lumbar interbody fusion (ALIF) plus transpedicular instrumentation plus posterolateral fusion (PLF) (360 degrees fusion) to ALIF plus transpedicular instrumentation without PLF (270 degrees fusion). OBJECTIVES: To compare the clinical outcomes, costs, and utilization of health resources of 360 degrees versus 270 degrees fusions. BACKGROUND: The 360 degrees fusion is effective, but its costs and utilization of health resources are high. The PLF often resorbs and may not be necessary. METHODS: Before and after surgery pain was measured by the Numerical Rating Scale (NRS), and function was measured by the Oswestry Low Back Disability Index (OSI). Costs were calculated by billing records. Operating times, blood loss, and hospital stays were measured at the time of hospital discharge. RESULTS: There were 48 patients: 21 women and 27 men. Mean age was 42 years. Follow-up averaged 35 months (range 24-45 months). In both 360 degrees and 270 degrees fusions, there were significant improvements in NRS and OSI, and the percentage of solid ALIF was high. Only 14% of PLF appeared solid bilaterally and 18% appeared solid on one side only. There were no significant differences in changes in NRS, changes in OSI, or percentage solid ALIF between the 360 degrees and 270 degrees fusions. However, the 270 degrees fusion group had significantly less blood loss, shorter operative times, shorter hospital stays, and lower professional fees, and although hospital charges were lower, this difference was not significant. CONCLUSION: Both the 360 degrees and 270 degrees fusions significantly reduce pain and improve function, and there are no significant clinical differences between them. However, there were shorter operating times, less blood loss, lower costs, and less utilization of health care resources associated with the 270 degrees fusions.

Adult↗
PubMed2001

Congenital left ventricular aneurysm: clinical, imaging, pathologic, and surgical findings in seven new cases.

BACKGROUND: Congenital left ventricular aneurysm is a poorly understood and potentially lethal entity. Methods and Results In a clinicopathologic study of 7 new cases, the major presenting features in 6 patients were congestive heart failure in 4, ventricular arrhythmias in a 32-week fetus, and multiple congenital anomalies in a fetus with trisomy 13. Accurate diagnosis was achieved in all 3 living patients by echocardiography, angiocardiography, and magnetic resonance imaging. The aneurysm was predominantly apical in 3 and involved most of the left ventricular free wall in 4. Of the 3 living patients, medical management alone sufficed in 2. The third, a newborn boy, underwent a new and successful aneurysm-exclusion left ventriculoplasty. The mitral valve was abnormal in all 4 autopsied cases, the papillary muscles being short, thin, or absent. The aneurysm was thinner and its area was larger than that of the nonaneurysmal left ventricle in all necropsied patients. CONCLUSIONS: Congenital left ventricular aneurysm appears to be a developmental anomaly, an idiopathic dysplasia of left ventricular endocardium and myocardium. No evidence of a viral etiology was found. Some neonates can be managed medically, but others require urgent surgical intervention. A new surgical operation is presented, a functional left ventricular aneurysmectomy that minimizes intraoperative and postoperative blood loss and that preserves the coronary arteries.

Female↗
PubMed2001

Expression and characterization of recombinant rat alpha 3(IV)NC1 and its use in induction of experimental autoimmune glomerulonephritis.

BACKGROUND: The autoantigen in Goodpasture's disease is known to be the non-collagenous domain of the alpha3 chain of type IV collagen, alpha 3(IV)NC1. There is mounting evidence that alpha 3(IV)NC1 is also a target of autoimmunity in experimental autoimmune glomerulonephritis (EAG). Sado et al. [Kidney Int 1998; 53, 664-671] have reported that recombinant human alpha 3(IV)NC1 and alpha4(IV)NC1 are nephritogenic in WKY rats. We have proposed that immunization with homologous antigen is more appropriate for detailed investigation of autoimmunity in EAG. METHODS: To this end, we have cloned and sequenced rat alpha 3(IV)NC1 and expressed it in COS-7 cells. Recombinant rat alpha 3(IV)NC1, secreted into the COS-7 cell supernatant, was purified on an anti-M2 FLAG affinity column and characterized by western blotting. Recombinant antigen was then used to immunize WKY rats, in order to induce EAG. RESULTS: The recombinant material was antigenic as judged by binding to sera from patients with Goodpasture's disease and a mAb to alpha 3(IV)NC1. Immunization of WKY rats (n=5), with recombinant rat alpha 3(IV)NC1 in FCA at a dose of 1 mg/kg resulted in circulating anti-GBM antibodies directed towards alpha 3(IV)NC1, linear deposits of IgG on the GBM, albuminuria, deposits of fibrin in the glomeruli, severe focal necrotizing glomerulonephritis with crescent formation, and glomerular influx of CD8+ T cells and macrophages. Western blot analysis demonstrated that sera from these rats bound strongly to recombinant rat alpha 3(IV)NC1, as well as to collagenase-solubilized human and rat GBM. The pattern of binding was indistinguishable from that of sera from patients with Goodpasture's disease. CONCLUSIONS: This purified recombinant rat alpha 3(IV)NC1, which is both antigenic and nephritogenic, will be of value in analysing autoimmune responses in experimental anti-GBM disease.

Albuminuria↗
PubMed2001

A systematic approach to pacemaker assessment.

Despite the increasing use of pacemaker therapy, assessment of pacemaker function and electrocardiogram (ECG) interpretation continue to challenge even experienced critical care nurses. Accurate assessment of pacemaker function is essential in the evaluation of patients, especially patients with symptoms that may be related to pacemaker malfunction such as syncope or palpitations. This article will review pacing concepts and pacing system components. A systematic approach to ECG interpretation will be presented that can be used in a variety of clinical settings.

Arrhythmias, Cardiac↗
PubMed2001

Molecular characterisation of four cases of intrachromosomal triplication of chromosome 15q11-q14.

CONTEXT: Chromosomal abnormalities that involve the proximal region of chromosome 15q occur relatively frequently in the human population. However, interstitial triplications involving one 15 homologue are very rare with three cases reported to date. OBJECTIVE: To provide a detailed molecular characterisation of four additional patients with interstitial triplications of chromosome 15q11-q14. DESIGN: Molecular analyses were performed using DNA markers and probes specific for the 15q11-q14 region. SETTING: Molecular cytogenetics laboratory at the University of Chicago. SUBJECTS: Four patients with mild to severe mental retardation and features of Prader-Willi syndrome (PWS) or Angelman syndrome (AS) were referred for molecular cytogenetic analysis following identification of a suspected duplication/triplication of chromosome 15q11-q14 by routine cytogenetic analysis. MAIN OUTCOME MEASURES: Fluorescence in situ hybridisation (FISH) was performed to determine the type of chromosomal abnormality present, the extent of the abnormal region, and the orientation of the extra chromosomal segments. Molecular polymorphism analysis was performed to determine the parental origin of the abnormality. Methylation and northern blot analyses of the SNRPN gene were performed to determine the effect of extra copies of the SNRPN gene on its methylation pattern and expression. RESULTS: Fluorescence in situ hybridisation (FISH) using probes within and flanking the Prader-Willi/Angelman syndrome critical region indicated that all patients carried an intrachromosomal triplication of proximal 15q11-q14 in one of the two chromosome 15 homologues (trip(15)). In all patients the orientation of the triplicated segments was normal-inverted-normal, suggesting that a common mechanism of rearrangement may have been involved. Microsatellite analysis showed the parental origin of the trip(15) to be maternal in three cases and paternal in one case. The paternal triplication patient had features similar to PWS, one maternal triplication patient had features similar to AS, and the other two maternal triplication patients had non-specific findings including hypotonia and mental retardation. Methylation analysis at exon 1 of the SNRPN locus showed increased dosage of either the paternal or maternal bands in the paternal or maternal triplication patients, respectively, suggesting that the methylation pattern shows a dose dependent increase that correlates with the parental origin of the triplication. In addition, the expression of SNRPN was analysed by northern blotting and expression levels were consistent with dosage and parental origin of the triplication. CONCLUSIONS: These four additional cases of trip(15) will provide additional information towards understanding the phenotypic effects of this abnormality and aid in understanding the mechanism of formation of other chromosome 15 rearrangements.

Blotting, Northern↗
PubMed2001

Confirmation that offspring from families with alcohol-dependent individuals have greater hypothalamic-pituitary-adrenal axis activation induced by naloxone compared with offspring without a family history of alcohol dependence.

BACKGROUND: This study was designed to confirm our previous findings that nonalcoholic offspring from families with alcohol-dependent individuals have greater hypothalamic-pituitary-adrenal axis activation induced by opioid blockade compared with nonalcoholic subjects without a family history of alcohol dependence. METHODS: Sixty-four nonalcoholic subjects aged 18 to 25 years were enrolled in the protocol. Twenty-seven subjects were offspring from families with alcohol dependence and were designated as family history-positive subjects (FHP). Thirty-seven subjects were biological offspring of non-alcohol-dependent parents and were designated as family history-negative subjects (FHN). Subjects received naloxone hydrochloride (0, 50, 125, 375, and 500 microg/kg) in double-blind, randomized order; adrenocorticotropin (ACTH) and cortisol were monitored over 120 min. RESULTS: No hormone differences at baseline or during placebo administration were identified between FHP and FHN subjects. FHP subjects had greater ACTH and cortisol response to opioid receptor blockade induced by naloxone hydrochloride compared with FHN subjects. CONCLUSIONS: These observations confirm previous findings that differences in ACTH and cortisol dynamics between FHP and FHN subjects can be unmasked by opioid receptor blockade.

Adolescent↗
PubMed2001

Randomised controlled trial of training health visitors to identify and help couples with relationship problems following a birth.

BACKGROUND: Stresses imposed by parenthood can provoke or intensify relationship problems between parents. These problems, which are often associated with postnatal depression, can have serious consequences for family well-being but are often not revealed to primary health care personnel. AIM: To evaluate a means of extending the primary health care team's ability to identify and respond to relationship problems of mothers and their partners in the postnatal period. DESIGN OF STUDY: Cluster randomised controlled trial. SETTING: Specially trained health visitors in nine 'intervention' clinics--each matched with a 'control' clinic' in an outer London borough. METHOD: Health visitors in intervention clinics invited mothers attending for the six-to-eight-week developmental check to complete a screening scale for relationship problems, and offered help (supportive listening, advice, or referral) if needed. When visiting the clinic for the 12-week immunizations, mothers from all clinics were asked to complete a follow-up self-report questionnaire. After the completion of the trial, 25 women who had attended the intervention clinics and had been offered support with a relationship problem were interviewed to elicit their views on the acceptability and value of the intervention. All 25 of the health visitors engaged in the intervention were asked to complete a questionnaire on their experience. RESULTS: Screening led to striking differences between intervention and control clinics in the percentage of women identified at the six-to-eight-week check as potentially in need of help with a relationship problem (21% versus 5%, P = 0.007) and in the percentage actually offered help (18% versus 3%, P = 0.014). About one-half of the mothers so identified were also identified as having postnatal depression. At the 12-week visit for immunizations, the intervention group was twice as likely (P = 0.006) as the control group to report having discussed relationship problems with the health visitor and 75% more likely (P = 0.046) to report having received help with a problem. CONCLUSION: The intervention offers a useful way of extending the primary health care team's ability to respond to problems that often have serious consequences for family well-being.

Adolescent↗
PubMed2000

Effects of amoxicillin/clavulanate or azithromycin on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae in children with acute otitis media.

The effect of antibiotic therapy on nasopharyngeal colonization by Streptococcus pneumoniae and Haemophilus influenzae was evaluated in children diagnosed with acute otitis media. Children were randomly assigned to receive either amoxicillin/clavulanate or azithromycin therapy, and nasopharyngeal swabs were obtained for culture before and after starting therapy. Amoxicillin/clavulanate therapy eradicated or suppressed all strains of S. pneumoniae susceptible to penicillin, 75% of strains with intermediate resistance, and 40% of strains resistant to penicillin. Azithromycin therapy cleared two-thirds of azithromycin-susceptible strains of S. pneumoniae but none of azithromycin-nonsusceptible strains. Selection for antibiotic-resistant strains in individual children was not observed in children who received amoxicillin/clavulanate therapy but was observed in 2 children who received azithromycin therapy. Carriage of H. influenzae was also reduced by antimicrobial therapy but more so by amoxicillin/clavulanate. Antibiotic therapy does not directly increase the number of resistant strains in the population but, by eradicating susceptible strains, allows greater opportunity for carriage and spread of resistant strains.

Acute Disease↗
PubMed2000

Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes.

BACKGROUND: Troglitazone promotes adipocyte differentiation in vitro and increases insulin sensitivity in vivo. Therefore, troglitazone may have therapeutic benefit in lipoatrophic diabetes. OBJECTIVE: To determine whether troglitazone ameliorates hyperglycemia and hypertriglyceridemia or increases fat mass in lipoatrophic patients. DESIGN: Open-labeled prospective study. SETTING: United States and Canada. PATIENTS: 20 patients with various syndromes associated with lipoatrophy or lipodystrophy. INTERVENTION: 6 months of therapy with troglitazone, 200 to 600 mg/d. MEASUREMENTS: Levels of hemoglobin A1c triglycerides, free fatty acids, and insulin; respiratory quotient; percentage of body fat; liver volume; and regional fat mass. RESULTS: In the 13 patients with diabetes who completed 6 months of troglitazone therapy, hemoglobin A1c levels decreased by a mean of 2.8% (95% CI, 1.9% to 3.7%; P < 0.001). In all 19 study patients, fasting triglyceride levels decreased by 2.6 mmol/L (230 mg/dL) (CI, 0.7 to 4.5 mmol/L [62 to 398 mg/dL]; P = 0.019) and free fatty acid levels decreased by 325 micromol/L (CI, 135 to 515 micromol/L; P = 0.035). The respiratory quotient decreased by a mean of 0.12 (CI, 0.08 to 0.16; P < 0.001), suggesting that troglitazone promoted oxidation of fat. Body fat increased by a mean of 2.4 percentage points (CI, 1.3 to 4.5 percentage points; P = 0.044). Magnetic resonance imaging showed an increase in subcutaneous adipose tissue but not in visceral fat. In one patient, the serum alanine aminotransferase level increased eightfold during the 10th months of troglitazone treatment but normalized 3 months after discontinuation of treatment Liver biopsy revealed an eosinophilic infiltrate, suggesting hypersensitivity reaction as a cause of hepatotoxicity. CONCLUSION: Troglitazone therapy improved metabolic control and increased body fat in patients with lipoatrophic diabetes. The substantial benefits of troglitazone must be balanced against the risk for hepatotoxicity, which can occur relatively late in the treatment course.

Adipose Tissue↗