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Biomedical subjects

G Lucas

Publications and source records attributed to G Lucas.

At least 37 records · Page 2Linked to original sources

Transfusion-related acute lung injury associated with interdonor incompatibility for the neutrophil-specific antigen HNA-1a.

BACKGROUND AND OBJECTIVES: A patient transfused with two pooled platelet concentrates became breathless. Bilateral infiltrates were seen on chest X-ray. A diagnosis of transfusion-related acute lung injury (TRALI) was made. The patient received 100% oxygen and recovered after 5 days. MATERIALS AND METHODS: Antibody screening, cross-matching for granulocyte and lymphocyte antibodies and typing for granulocyte antigens was undertaken. RESULTS: The patient typed as HNA-1b/HNA-1b. Granulocyte and lymphocyte antibodies were not detected in the patient's serum or in any of the donor sera by cross-match. In antibody screening against typed panel granulocytes, complement-fixing anti-HNA-1a IgM antibodies were detected in the serum of one female donor. Two of the other donors who contributed to the pooled platelet concentrate containing the HNA-1a IgM antibodies typed as HNA-1a/HNA-1b. CONCLUSION: Anti-HNA-1a IgM antibodies may have formed immune complexes with white cell fragments or soluble FcgammaRIII from HNA-1a+ donors in the pooled platelet concentrate and initiated TRALI.

Adult↗

Macrophage-inflammatory protein-1alpha receptor expression on normal and chronic myeloid leukemia CD34+ cells.

We have assessed expression of MIP-1alpha binding sites on the surface of CD34+ cells from normal bone marrow (NBM) and chronic myeloid leukemia (CML) peripheral blood. This study has highlighted a small subpopulation of CD34+ (15.7 +/- 6.2% in NBM and 9 +/- 4% in CML), which has specific macrophage-inflammatory protein-1alpha (MIP-1alpha) cell surface binding sites. Further phenotypic characterization of the receptor-bearing cells has shown that they do not express the Thy-1 Ag, suggesting that they are committed progenitor cells rather than CD34+ Thy+ stem cells. However, more than 80% of methanol-fixed CD34+ cells do bind MIP-1alpha, suggesting that these cells may possess a pool of internal receptors, although we were unable to induce cell surface expression by cytokine stimulation. The percentage of these CD34+, MIP-1alpha-R+ cells present in the CD34 compartment of NBM is significantly higher than in CML, implicating lack of binding sites as part of the mechanism for the loss of response to this chemokine seen in CML. Specific Ab to the MIP-1alpha receptor implicated in HIV infection, CCR5, revealed that very few CD34+ cells expressed these receptors and that expression was confined to the CD34+ Thy- progenitor population. Data presented in this work suggest that active binding sites for the stem cell growth inhibitor MIP-1alpha are not constitutively expressed on the surface of most resting primitive multipotent cells, and that these cells are not potential targets for HIV-1 infection through CCR5.

Antigens, CD34↗

Laparoscopy for diagnosis and staging of malignancy.

The use of minimally invasive surgery for abdominal pathology, including malignancy, has increased significantly within the past decade. Despite the advances in radiographic imaging, the use of laparoscopy for diagnosing and staging abdominal malignancy has become an important tool in the overall care of these patients. A review of published series for a variety of abdominal malignancies is presented. With the growing experience in this technique, some preliminary conclusions and ongoing issues are discussed.

Abdominal Neoplasms↗

Laparoscopic repair of bilateral and recurrent hernias.

The optimal inguinal hernia repair has been controversial for decades. Since the advent of minimally invasive surgery, laparoscopic techniques have added to the controversy. Laparoscopic hernia repair has been advocated by many experts for the repair of bilateral and recurrent inguinal hernias. This study reviews the experience of a single community-based teaching hospital using the total extraperitoneal (TEP)-approach laparoscopic hernia repair for treating patients with bilateral and/or recurrent inguinal hernias. Since the TEP approach was adopted in June 1993, a total of 457 patients were treated for bilateral (322 patients) and/or recurrent (175) inguinal hernias (40 patients had recurrent and bilateral hernias). A total of 779 hernias were repaired with this technique. The average age of this patient group was 47 years, and there were 413 males and 44 females. Operative time averaged 68.3 minutes per patient, and there were 26 (5.7%) minor complications. There were 2 (0.4%) major complications, an enterotomy and a cystotomy, both early in the series and both in patients with previous lower abdominal surgery. There have been no deaths. With an average follow-up of 30 months (range, 1-60 months), there have been three (0.2%) recurrences. These recurrences were due to technical problems (inadequate mesh coverage), and each was repaired with a laparoscopic transabdominal approach or an anterior open approach. The use of the TEP-approach laparoscopic hernia repair is safe and effective in patients with recurrent and/or bilateral inguinal hernias.

Abdominal Muscles↗

[Transesophageal echocardiography before electric cardioversion for supraventricular arrhythmia].

OBJECTIVES: The aim of this prospective study was to assess the risks of electrical shock cardio-version in the treatment of supraventricular rhythm disorders when administered under effective-dose but short duration anticoagulation in patients with no intracavitary thrombus detectable by transesophageal echocardiography. PATIENTS AND METHODS: One hundred nineteen patients, mean age 66 years, with permanent arrhythmia due to atrial fibrillation (n = 102), atrial flutter (n = 16) or atrial tachycardia (n = 1) and taking no long-term anticoagulant therapy were treated by electrical shock cardioversion. The patients were given heparin at an effective dose 72 hours prior to cardioversion. A transthoracic and a transesophageal echocardiography were performed less than 24 hours prior to cardioversion. RESULTS: Twenty-one thrombi were evidenced in 16 patients (14.6%) including 18 in the left auricle, 1 in the left atrium and 2 in the right atrium. A spontaneous contrast was visualized in 38 patients (32%). Cardioversion was performed in 103 patients without thrombus and later in 9 of the 16 patients with thrombus after absorption under anticoagulant therapy as evidenced on the control transesophageal echocardiography. A sinus rhythm was obtained in 82% of the cases. All patients were given anti-vitamin K anticoagulants for one month. There were no clinical manifestation of ischemic vascular events during cardioversion nor during the one-month follow-up. CONCLUSION: Early use of electrical shock cardioversion in patients with supraventricular rhythm disorders can be proposed without long-term anticoagulation therapy if the absence of thrombi is demonstrated by transesophageal echocardiography and short-term heparin is given followed by oral anticoagulants for at least 4 weeks. A large-scale randomized prospective study comparing the conventional strategy with the protocol used in this study would be required to definitively validate this approach and determine its possible advantages.

Adult↗

Transfusion-related acute lung injury (TRALI) following autologous stem cell transplant for relapsed acute myeloid leukaemia: a case report and review of the literature.

A fatal case of transfusion-related acute lung injury (TRALI) in a child post-autologous stem cell transplant for relapsed acute myeloid leukaemia is described. The implicated product was a single unit platelet concentrate containing anti-HLA A2 and granulocyte-specific anti-NA1 antibodies. The recipient typed as HLA A2/A2, NA1/NA1. This is the first reported case of TRALI following a transplant procedure for a haematological condition. It is also unusual in that the patient failed to make a full recovery and that two relevant leucocyte antibodies of clear specificity were identified in the donor plasma. The literature relating to the pathophysiology, clinical sequelae and management of TRALI is reviewed.

Acute Disease↗

The ability of the chemiluminescence test to predict clinical outcome and the necessity for amniocenteses in pregnancies at risk of haemolytic disease of the newborn.

The chemiluminescence test measures the ability of anti-D to sensitise red cells for recognition by monocytes. It predicts clinical outcome in haemolytic disease of the newborn with greater precision than quantification of anti-D levels by AutoAnalyzer. However, whether or not the chemiluminescence test can, or should, affect clinical management is not clear. Of 56 alloimmunised women referred to a single fetal medicine unit, 30 underwent a total 63 amniocenteses to establish the extent of fetal haemolysis. Overall, chemiluminescence test results were a better predictor of amniocenteses with elevated bilirubin levels than the AutoAnalyzer (P < 0.01). Chemiluminescence results > 30% were always associated with elevated bilirubin levels. The chemiluminescence test might be used to prompt the direct evaluation of fetal haemolysis in patients with borderline levels of anti-D (5-15 IU/mL). However, the ability of the test to predict amniocenteses with normal bilirubin levels was less clear.

Amniocentesis↗

The hazard of spatial disorientation during helicopter flight using night vision devices.

INTRODUCTION: Night Vision Devices (NVDs) provide an enormous advantage to the operational effectiveness of military helicopter flying by permitting flight throughout the night. However, compared with daytime flight, many of the depth perception and orientational cues are severely degraded. These degraded cues predispose aviators to spatial disorientation (SD), which is a serious drawback of these devices. METHODS: As part of an overall analysis of Army helicopter accidents to assess the impact of SD on military flying, we scrutinized the class A-C mishap reports involving night-aided flight from 1987 to 1995. The accidents were classified according to the role of SD by three independent assessors, with the SD group further analyzed to determine associated factors and possible countermeasures. RESULTS: Almost 43% of all SD-related accidents in this series occurred during flight using NVDs, whereas only 13% of non-SD accidents involved NVDs. An examination of the SD accident rates per 100,000 flying hours revealed a significant difference between the rate for day flying and the rate for flight using NVDs (mean rate for daytime flight = 1.66, mean rate for NVD flight = 9.00, p < 0.001). The most important factors associated with these accidents were related to equipment limitations, distraction from the task, and training or procedural inadequacies. CONCLUSIONS: SD remains an important source of attrition of Army aircraft. The more than fivefold increase in risk associated with NVD flight is of serious concern. The associated factors and suggested countermeasures should be urgently addressed.

Accidents, Aviation↗

8-OH-DPAT, a 5-HT1A agonist and ritanserin, a 5-HT2A/C antagonist, reverse haloperidol-induced catalepsy in rats independently of striatal dopamine release.

In this study, both catalepsy and changes in extracellular levels of striatal dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC) induced by the typical neuroleptic haloperidol (HAL) were simultaneously assessed, using intracerebral microdialysis in freely moving rats, in the presence of either the 5-HT1A agonist 8-OH-DPAT or the 5-HT2A/C antagonist ritanserin. HAL (1 mg/kg, SC) elicited a strong cataleptic state, reaching its maximal intensity (about 240 s) 2 h after the drug administration. This effect was paralleled by a long-lasting enhancement of striatal DA and DOPAC extracellular levels, reaching 230 and 350% of basal values, respectively. 8-OH-DPAT (0.1 mg/kg, SC) given 2.5 h after, and ritanserin (0.63 and 1.25 mg/kg, IP), given 15 min prior to HAL, significantly reduced the neuroleptic-induced catalepsy. However, both 5-HT agents failed to modify basal DA and DOPAC striatal outflow as well as the stimulatory effect of HAL on these parameters. It can thus be concluded that the anticataleptic effect of these compounds is not related to an alteration of DA release within the striatum.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Serotonin stimulation of 5-HT4 receptors indirectly enhances in vivo dopamine release in the rat striatum.

Serotonin (5-HT) applied at 1, 3, and 10 microM into the striatum of halothane-anesthetized rats by in vivo microdialysis enhanced dopamine (DA) outflow up to 173, 283, and 584% of baseline values, respectively. The 5-HT effect was partially reduced by 1 or 10 microM GR 125,487, a 5-HT4 antagonist, and by 100 microM DAU 6285, a 5-HT3/4 antagonist, whereas the 5-HT1/2/6 antagonist methiothepin (50 microM) was ineffective. In the presence of tetrodotoxin the effect of 1 microM 5-HT was not affected by 5-HT4 antagonists. In addition, tetrodotoxin abolished the increase in DA release induced by the 5-HT4 agonist (S)- zacopride (100 microM). In striatal synaptosomes, 1 and 10 microM 5-HT increased the outflow of newly synthesized [3H]DA up to 163 and 635% of control values, respectively. The 5-HT4 agonists BIMU 8 and (S)-zacopride (1 and 10 microM) failed to modify [3H]DA outflow, whereas 5- methoxytryptamine (5-MeOT) at 10 microM increased it (62%). In prelabeled [3H]DA synaptosomes, 1 microM 5-HT, but not (S)-zacopride (1 and 10 microM), increased [3H]DA outflow. DAU 6285 (10 microM) failed to modify the enhancement of newly synthesized [3H]DA outflow induced by 5-MeOT or 5-HT (1 microM), whereas the effect of 5-HT was reduced to the same extent by the DA reuptake inhibitor nomifensine (1 microM) alone or in the presence of DAU 6285. These results show that striatal 5-HT4 receptors are involved in the 5-HT-induced enhancement of striatal DA release in vivo and that they are not located on striatal DA terminals.

Animals↗

Penetration of trovafloxacin into cerebrospinal fluid in humans following intravenous infusion of alatrofloxacin.

A single-dose study was conducted to determine concentrations of trovafloxacin (CP-99,219) achieved in the cerebrospinal fluid (CSF) relative to those in the serum of healthy subjects after intravenous infusion of alatrofloxacin (CP-116,517), the alanyl-alanyl prodrug of trovafloxacin. Twelve healthy subjects were administered single doses of alatrofloxacin at a trovafloxacin equivalent of 300 mg as an intravenous infusion over 1.0 h. CSF samples were taken by lumbar puncture at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 24 h after the start of the infusion; each subject was sampled at only one time point. Serum samples were taken from each subject at the time of CSF collection. A mean concentration of 5.8 microg of trovafloxacin per ml was present in serum 1.0 h after the start of the infusion. CSF/serum ratios ranged from 0.14 to 0.33 in the postdistribution phase (5 to 24 h postinfusion), with a mean ratio of 0.25. The most common adverse events were dizziness, nausea, and rash and were mild or moderate in intensity. The potency of trovafloxacin against susceptible organisms, coupled with its rapid penetration of CSF following the intravenous administration of alatrofloxacin, suggests that it may be useful in the treatment of bacterial meningitis in humans.

Adolescent↗

Pheochromocytoma, chronic renal insufficiency, and hemodialysis: a combination leading to a diagnostic and therapeutic dilemma.

Pheochromocytomas are functioning paragangliomas often presenting with paroxysmal hypertension due to catecholamine secretion. The preferential diagnostic workup includes urine and serum catecholamine measurements. Therapeutic management consists of pharmacologic cardiovascular manipulation and volume expansion with subsequent surgical resection. We have encountered a symptomatic pheochromocytoma in a chronic renal insufficiency patient on hemodialysis. The diagnostic dilemma arose due to the patient's anuric status and the inherent increase in serum catecholamine levels noted in anuric patients. The therapeutic dilemma arose in the proper pharmacologic management and volume expansion in this patient on hemodialysis. The patient underwent successful resection of the pheochromocytoma and has done well. An analysis of our diagnostic and therapeutic processes as well as a review of the literature are presented to assist in the management of this difficult clinical situation.

Adrenal Gland Neoplasms↗

Eosinophilic colitis presenting as a left-sided colocolonic intussusception with secondary large bowel obstruction: an uncommon entity with a rare presentation.

Eosinophilic gastroenteritis is a quite uncommon clinical entity usually involving the stomach or small bowel. Occasionally, the colon is involved. We have encountered a case of eosinophilic colitis leading to a left-sided colocolonic intussusception and subsequent large bowel obstruction. This is a unique presentation that, to our knowledge, has not been previously reported. We present our case in detail as well as a review of the literature to better understand this rare clinical entity.

Adult↗

Expression of either the TCL1 oncogene, or transcripts from its homologue MTCP1/c6.1B, in leukaemic and non-leukaemic T cells from ataxia telangiectasia patients.

Patients with the recessively inherited disorder ataxia telangiectasia (A-T) have a high level of specific chromosome translocations which can be easily observed in peripheral T cells and show a greatly increased predisposition to leukaemia/lymphoma, mainly of T cell origin. Some translocation cells proliferate into a large clone and may develop into T cell prolymphocytic leukaemia (T-PLL). By the time of diagnosis of T-PLL, the clone contains many more genetic changes in the form of additional translocations. T-PLL is also seen in non-A-T individuals where expression of either TCL1 (at 14q32) or the c6.1B/MTCP1 A1 transcript (at-Xq28) has been demonstrated in just a few instances. We show here, that expression of TCL1 occurs in leukaemic T cells from A-T patients with chromosome 14 rearrangements. Expression of TCL1 also occurs in the preleukaemic clone cells of A-T patients containing the primary translocation alone. Some expression of TCL1 could also be detected in randomly selected A-T patients without large cytogenetic clones and without any evidence of leukaemic change. We also show that expression of the B1 transcript from a second gene, MTCP1, occurred at a relatively high level only in two T-PLL tumours from A-T patients with t(X;14) translocations whereas the MTCP1/A1 transcript is much more widely expressed in both tumour and non tumour cells of A-T and non-A-T individuals.

Ataxia Telangiectasia↗

A comparison of the effect of bcr/abl breakpoint specific phosphothiorate oligodeoxynucleotides on colony formation by bcr/abl positive and negative, CD34 enriched mononuclear cell populations.

In chronic myeloid leukaemia, the expression by clonal cells, of a leukaemia specific bcr/abl chimeric mRNA, makes the condition suitable for the application of "antisense" strategies. Furthermore, the origin of the condition in a pluripotential progenitor allows enrichment of leukaemic clonogenic cells by selection for CD34 expression, together with a useful reduction in contaminating accessory cells. In a methylcellulose clonogenic assay system we incubated bcr/abl expressing (n = 9) and bcr/abl negative (n = 8), CD34 enriched progenitors with phosphothiorate oligodeoxynucleotides (PS oligomers), antisense and sense to the b3a2 and b2a2 chimeric bcr/abl junctional sequences. All samples were cloned in the presence of both antisense, and sense PS oligomers to provide appropriate controls. For bcr/abl positive progenitors, the mean number of colonies formed was reduced by 21 (39%) (P < 0.05) in the presence of the specific antisense oligomer, 11 (20%) (P < 0.05) with the antisense oligomer directed to the alternative junctional breakpoint, and colony formation was not significantly altered by either sense PS oligomer. Colony formation by bcr/abl negative progenitors was not reproducibly reduced by any of the PS oligomers. These results confirm that PS oligomers can have a sequence dependent inhibitory effect on a CD34 enriched progenitor population from patients with chronic myeloid leukaemia.

Antigens, CD34↗

Serotonin enhances striatal dopamine outflow in vivo through dopamine uptake sites.

Serotonin (5-HT) administered at 1, 3, and 10 microM into the striatum of halothane-anesthetized rats by in vivo microdialysis increased extracellular dopamine (DA) in a concentration-dependent manner (approximately 65, 190, and 440%, respectively). These effects were reduced by 50% in the presence of 1 microM tetrodotoxin (TTX) or in the absence of Ca2+ ions. The DA uptake blocker nomifensine (0.1 microM) significantly lowered (by 50%) the enhancement of DA outflow induced by 3 microM 5-HT. Nomifensine (1 microM) coperfused with 1 microM TTX abolished the 1 and 3 microM 5-HT-induced DA outflow, whereas the effect of 10 microM 5-HT was significantly reduced by 1 (-55%) and 10 micro M (-70%) nomifensine. These data demonstrate that, in vivo, striatal DA uptake sites are partially involved in the DA-releasing action of 5-HT.

Animals↗