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Biomedical subjects

A Gee

Publications and source records attributed to A Gee.

At least 19 recordsLinked to original sources
PubMed1999

Enhancement of 3H-N-methylspiperone binding but not 3H-raclopride binding in mouse striatum by MK-801: evidence that factors other than competition by endogenous dopamine are responsible for changes in D2 receptor binding in vivo. Short communication.

The effect of acute pretreatment with MK-801 on the binding in vivo of both 3H-N-methylspiperone (NMSP) and 3H-raclopride (RAC) were compared in mice. In the striatum, MK-801 significantly increase 3H-NMSP binding, whereas no significant alterations in 3H-RAC binding were seen. In contrast, binding in the cerebral cortex of both radiolabeled ligands was not changed by MK-801. Kinetic analysis revealed that the increase in 3H-NMSP binding induced by MK-801 was due to an increase in the rate constant k3(k3 = kon.Bmax). In vivo saturation experiments showed that Bmax for 3H-NMSP binding was relatively unchanged and an increase in the apparent association rate constant (kon) was the main reason for an increase in the k3 for 3H-NMSP binding. As 3H-RAC binding is known to be much more sensitive to competitive inhibition than is 3H-NMSP binding, these results strongly suggest that factors other than competition by endogenous dopamine may contribute to changes in receptor binding in vivo caused by NMDA-antagonism.

Animals↗
PubMed1999

Discrepancies in apparent dopamine D2 receptor occupancy between 3H-raclopride and 3H-N-methylspiperone.

Competitive inhibition of 3H-raclopride (RAC) and 3H-N-methylspiperone (NMSP) binding against haloperidol, raclopride and NMSP was measured in the mouse striatum. 3H-RAC binding was more sensitive to competitive inhibition by all three compounds compared with 3H-NMSP. For example, 0.3 mg/kg of haloperidol resulted in 95% inhibition of 3H-RAC binding, however only 60% of inhibition of 3H-NMSP binding was found at the same dose of haloperidol. The cross-inhibition experiments using non-radioactive RAC or NMSP as competitors indicated different binding sites for 3H-RAC and 3H-NMSP in mouse striatum. Specifically, about 40% of 3H-NMSP binding was not displaced by treatment with a very high dose of raclopride (3 mg/kg). The time course of inhibition of the specific binding of 3H-RAC and 3H-NMSP were measured following i.p. injection of 0.5 mg/kg of haloperidol. No significant differences in the kinetics of haloperidol inhibition were observed between two radioligands.

Animals↗
PubMed1999

Changes in apparent rates of receptor binding in the intact brain in relation to the heterogeneity of reaction environments.

Neuroreceptor imaging by PET or SPECT has been widely applied in the field of neurobiology, from basic to clinical investigations, and has the potential to reveal the neurochemical basis of various neurological and psychiatric diseases as well as to provide new knowledge in the field of neuropharmacology. In contrast to the static nature of in vitro systems, neurotransmission systems in the intact brain constitute part of a dynamic and communicating environment. Thus, it is important to develop new functional imaging methods that reflect neural communications and the dynamism of signal transmission in the living brain. In vivo receptor binding can be altered not only by competitive inhibition by endogenous neurotransmitters but by trans-synaptic effects, and investigation of neural interactions by detection of changes in receptor binding therefore presents a potential method for studying this phenomenon. Recently, several PET studies on in vivo neural interactions using the D2 receptor ligand [11C]-raclopride concluded that the phenomenon was mediated by changes in synaptic endogenous dopamine concentrations that compete with [11C]-raclopride binding for neuroreceptor occupancy. However, a growing body of evidence indicates that these changes in in vivo receptor binding cannot be fully explained by competitive inhibition by endogenous ligand, and alternative mechanisms for the interneuronal modulation of receptor binding are addressed. This review highlights some of the discrepancies observed between in vitro and in vivo receptor binding studies with respect to a number of phenomena, including the heterogeneity of the reaction field surrounding receptors. Quantitative receptor binding studies are usually analyzed by using 'static' binding parameters, such as the Bmax, and KD, which are normally determined by in vitro assays. In addition to these parameters, the apparent association and dissociation rate constants (kon, koff) play equally significant roles in receptor binding in the intact brain is expected. The concepts of "diffusion boundary" and "reaction volume" are introduced, and discussions on some of the discrepancies between in vivo and in vitro receptor binding phenomena are presented.

Animals↗
PubMed1998

Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography.

Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC), which usually is widespread in the liver at the time of the diagnosis and which has a median survival of approximately 6 months. Positron emission tomography (PET) is a noninvasive scanning method that allows the assessment of metabolism in vivo by means of positron-emitting radiolabeled tracers. [18F]Fluoro-2-deoxy-D-glucose (FDG) is a glucose analogue that accumulates in various malignant tumors because of their high glucose metabolic rates. The purpose of the study was to develop a PET method to detect small CC tumors in patients with PSC. PET scanning of the liver was performed after intravenous injection of 200 MBq FDG in 9 patients with PSC, 6 patients with PSC + CC, and 5 controls. The scanning was performed at successive time intervals for a total of 90 minutes with simultaneous successive arterial blood sampling for radioactivity concentration determination. In each of the PSC + CC patients, 2 to 7 "hot spots" were seen, with volumes of 1.0 to 45 mL (median, 4.4 mL). There were no hot spots in the two other patient groups. The localization of hot spots was confirmed by single-blind evaluation. Data were analyzed by the Gjedde-Patlak plot, yielding values of the net metabolic clearance of FDG, K [mL min(-1) 100 mL(-1) tissue]. In the CC hot spots, maximum K values were 1.59 to 4.17 (median, 2.34; n = 6); in the reference liver tissues of these patients, K values were 0.40 to 0.69 (median, 0.49); in PSC patients, they were 0.23 to 0.53 (median, 0.36); and in controls, they were 0.20 to 0.34 (median, 0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < .001). We conclude that FDG-PET seems to be able to detect small CC tumors and may be useful in the therapeutic management of PSC.

Adult↗
PubMed1998

Changes in apparent in vivo binding of [3H]raclopride and [3H]N-methylspiperone induced by oxotremorine.

The effects of muscarinic agonist, oxotremorine (0.3 mg/kg), and antagonist, scopolamine (0.5 mg/kg), on in vivo [3H]raclopride (RAC) and [3H]N-methylspiperone (NMSP) binding were investigated. Following tracer administration to control or pretreated mice, binding potentials, and the rate constants k3 and k4 were determined by kinetic analysis. Oxotremorine resulted in a 70% increase in striatal RAC binding potential compared with controls. RAC and NMSP showed almost identical decreases in k3 (40%), whereas k4 for RAC was unexpectedly decreased by 64%. Scopolamine resulted in no significant changes in RAC or NMSP binding. These results, in combination with previous data obtained in reserpinized mice, show that 1) competition by endogenous ligand may not be the only factor influencing the magnitude of apparent in vivo receptor binding, and 2) interneuronal communication may be partly mediated by changes in the rates of ligand-receptor binding.

Animals↗
PubMed1998

Nocardia crassostreae sp. nov., the causal agent of nocardiosis in Pacific oysters.

Seven strains of bacteria were isolated from Pacific oysters, Crassostrea gigas, with a focal or systemic disease. The strains were aerobic, Gram-positive, acid-fast, produced a mycelium which fragmented into irregular rod-like elements, had a peptidoglycan containing meso-diaminopimelic acid, arabinose and galactose as major sugars, mycolic acids with 46-58 carbon atoms and G + C-rich DNA. All of these properties are consistent with the classification of the organisms in the genus Nocardia. A partial sequence of the 16S rRNA gene of isolate NB4H was determined following isolation and cloning of the PCR-amplified gene. The sequence was aligned with those of representative mycolic-acid-containing taxa and a phylogenetic tree was generated using the neighbour-joining method. It was evident from the phylogenetic tree that the three strains tested, RB1, OB3P and NB4H, were identical and belonged to the Nocardia otitidiscaviarum rRNA sub-group. The biochemical, chemical, morphological and physiological properties of the isolates were also essentially identical and served to distinguish them from representative nocardiae. It is, therefore, proposed that the strains isolated from the diseased Pacific oysters be assigned to a new species, Nocardia crassostreae. The type strain is NB4H (= ATCC 700418).

Animals↗
PubMed1998

Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies.

PURPOSE: To investigate the use of a nonmyeloablative fludarabine-based preparative regimen to produce sufficient immunosuppression to allow engraftment of allogeneic stem cells and induction of graft-versus-leukemia/lymphoma (GVL) as the primary treatment modality for patients with chronic lymphocytic leukemia (CLL) and lymphoma. PATIENTS AND METHODS: Fifteen patients were studied. Six patients were in advanced refractory relapse, and induction therapy had failed in two patients. Patients with CLL or low-grade lymphoma received fludarabine 90 to 150 mg/m2 and cyclophosphamide 900 to 2,000 mg/m2. Patients with intermediate-grade lymphoma or in Richter's transformation received cisplatin 25 mg/m2 daily for 4 days; fludarabine 30 mg/m2; and cytarabine 500 mg/m2 daily for 2 days. Chemotherapy was followed by allogeneic stem-cell infusion from HLA-identical siblings. Patients with residual malignant cells or mixed chimerism could receive a donor lymphocyte infusion of 0.5 to 2 x 10(8) mononuclear cells/kg 2 to 3 months posttransplantation if graft-versus-host disease (GVHD) was not present. RESULTS: Eleven patients had engraftment of donor cells, and the remaining four patients promptly recovered autologous hematopoiesis. Eight of 11 patients achieved a complete response (CR). Five of six patients (83.3%) with chemosensitive disease continue to be alive compared with two of nine patients (22.2%) who had refractory or untested disease at the time of study entry (P = .04). CONCLUSION: These findings indicate the feasibility of allogeneic hematopoietic transplantation with a nonablative preparative regimen to produce engraftment and GVL against lymphoid malignancies. The ability to induce remissions with donor lymphocyte infusion in patients with CLL, Richter's, and low-grade and intermediate-grade lymphoma is direct evidence of GVL activity against these diseases. This approach appears to be most promising in patients with chemotherapy-responsive disease and low tumor burden.

Aged↗
PubMed1997

Altered ligand binding properties and enhanced stability of a constitutively active estrogen receptor: evidence that an open pocket conformation is required for ligand interaction.

To elucidate the ligand binding properties of the estrogen receptor (ER) and how ligand access to and release from the ligand binding pocket is affected by the conformational state of the receptor, we have measured the rates of estradiol association and dissociation, the equilibrium binding, and the stability of estradiol binding to denaturants, comparing wild-type human ER and a point mutant (Y537S ER) that shows full constitutive activity, i.e., the same full transcriptional activity in the absence or presence of estrogen. Ligand binding kinetics and affinity were measured with the full-length (1-595) ERs and with truncated forms of both receptors containing domains C through F (including the DNA binding, hinge, and ligand binding domains, amino acids 175-595) or domains E and F (the ligand binding domain; amino acids 304-595). With all ERs, the rates of ligand association and dissociation were considerably slower with the Y537S mutant ER than with wild-type ER (6-fold and 3-4-fold, respectively). These marked differences in ligand on and off rates for the wild-type and Y537S receptors result in a predicted (k-1/k+1) and measured Kd that is 2-fold lower for Y537S ER compared to wild-type ER. The binding of estradiol by wild-type ER was disrupted by high concentrations of urea (above 2 M), whereas the Y537S ER was distinctly more resistant to this disruption. These results are consistent with a model in which wild-type ER in the absence of ligand adopts a transcriptionally inactive collapsed pocket conformation, stabilized by specific interactions of Y537 with nearby regions of ER. When estradiol is bound, the wild-type ER adopts a transcriptionally active, closed pocket (ligand occupied) conformation. By contrast, the Y537S mutant ER favors the transcriptionally active closed pocket conformation, whether occupied by ligand or not, the latter state (closed pocket but unoccupied) accounting for its constitutive activity. Our findings suggest that the entry or exit of ligand from the binding pocket requires that ER adopt an open pocket conformation. The reduced rates of ligand association and dissociation in the constitutively active form of the ER, as well as its greater resistance to disruption of ligand binding by urea, support the supposition that the rate at which this open pocket conformation can be accessed from the unoccupied or ligand-occupied Y537S ER is slower than from the unoccupied or occupied forms of wild-type ER. Thus, the binding and release of ligand by ER require that the receptor access an open pocket state, and the ease with which this state can be accessed is affected by mutations that alter receptor conformation.

Binding Sites↗
PubMed1997

In vivo estimation of cerebral blood flow, oxygen consumption and glucose metabolism in the pig by [15O]water injection, [15O]oxygen inhalation and dual injections of [18F]fluorodeoxyglucose.

There is a need for suitable non-primate laboratory animals for studies of brain function by positron emission tomography (PET). To provide a comparative index of the circulatory physiology of the pig, we have applied novel PET tracer methodology to seven anaesthetized pigs, and measured cerebral regional oxygen consumption (CMR[O2]), cerebral blood flow (CBF), and cerebral glucose metabolism (CMR[glc]). Blood flow and flow-metabolism couple were estimated for selected cerebral regions of interest. We found an average hemispheric CMR(O2) of 171 +/- 18 micromol/100 cm3/min. Individual hemispheric CBF measurements varied between 33 and 41 ml/100 cm3/min, with an average of 37 +/- 3 ml/100 cm3/min at an average PaCO2 of 4.3 +/- 0.9 kPa. The blood flow dependency on arterial PCO2 was calculated from the results of the carbon dioxide response in two pigs in which the CBF measurements obeyed the equation CBF (ml/100 cm3/min) = 8.9 PaCO2 (kPa). In each pig, CMR(glc) was studied twice with a double-injection FDG method. In the first session, the values of CMR(glc) averaged 27 +/- 3 and 23 +/- 4 micromol/100 cm3/min, estimated by multilinear and linear regression analysis, respectively. In the second session, the corresponding averages were 27 +/- 3 and 24 +/- 3 micromol/100 cm3/min, respectively. The average oxygen extraction fraction was 0.46 +/- 0.09 and the oxygen-glucose ratio was 6.1 +/- 0.8. The findings indicate that the pig is suitable for PET studies of cerebral blood flow, cerebral oxygen consumption and glucose metabolism.

Administration, Inhalation↗
PubMed1997

Regional distribution of 11C-labeled lidocaine, bupivacaine, and ropivacaine in the heart, lungs, and skeletal muscle of pigs studied with positron emission tomography.

The regional myocardial uptake and kinetics of 11C-lidocaine, 11C-bupivacaine, and 11C-ropivacaine were examined in the pig, utilizing positron emission tomography to determine whether disproportionate distribution exists among these agents. The three drugs were rapidly distributed to the myocardium and lung with mean peak radioactivities occurring between 0.35 and 0.48 min post-injection in myocardium and 0.35 and 0.65 min in lung. Radioactivities peaked later in skeletal muscle than in the myocardium and lung, occurring between 1.1 and 2.7 min post-end injection. Blood radioactivities for bupivacaine and ropivacaine were significantly higher than those of lidocaine, whereas myocardial, lung, and muscle uptakes for the three agents were not significantly different. Myocardium-blood partition coefficients were similar for bupivacaine and ropivacaine (0.55 and 0.49 respectively), while it was three times higher for lidocaine (1.4). A similar relationship existed for skeletal muscle- and lung-blood partition coefficients. Bupivacaine and ropivacaine t1/2z in skeletal muscle were significantly longer than those of lidocaine. The results of this study indicate that the increased cardiotoxicity associated with bupivacaine does not appear to be related to disproportionate distribution in the myocardium when compared to lidocaine and ropivacaine.

Amides↗
PubMed1997

Cortical sites of sustained and divided attention in normal elderly humans.

Human brain mechanisms subserving attention have been assigned to prefrontal, midfrontal, and posterior parietal cortices, as well as to the anterior cingulate and the thalamus. To map these mechanisms in the brain, most studies have used selective attention tasks; few studies have mapped the brain under sustained or divided attention. The present study was designed to create maps of regional activity associated with sustained and divided attention using two different sensory modalities: visual checkerboard stimulation and vibrotactile stimulation of the right hand. Five cerebral PE-tomograms of 15O-labeled water uptake were acquired from 16 elderly healthy subjects during sustained or divided attention to the frequency of stimulation. To locate active brain regions, the t-statistic map of relative changes in cerebral blood flow was coregistered to the subjects' averaged brain MR images and to the standard Talairach brain coordinate system. Attention was associated with activity in two sites, the right middle frontal gyrus (Brodmann area 46) and the right inferior parietal lobule (Brodmann area 40). The frontal site was more active when the subjects attended to the visual stimulus and when the attention was divided, while the parietal site was more active during attention to the vibrotactile stimulus and during simple sustained attention. Our observations are consistent with the hypotheses (1) that the right posterior parietal attention center subserves attention to several sensory modalities and (2) that a cortical network of specific neuronal sites subserves both sustained and divided attention. These hypotheses must be tested in further studies.

Aged↗
PubMed1997

Three-dimensional spatial compounding of ultrasound images.

One of the most promising applications of 3-D ultrasound lies in the visualization and volume estimation of internal 3-D structures. Unfortunately, the quality of the ultrasound data can be severely degraded by artefacts and speckle, making automatic analysis of the 3-D data sets very difficult. In this paper we investigate the use of 3-D spatial compounding to reduce speckle. We develop a new statistical theory to predict the improvement in signal-to-noise ratio with increased levels of compounding, and verify the predictions empirically. We also investigate how registration errors can affect automatic volume estimation of structures within the compounded 3-D data set. Having established the need to correct these errors, we present a novel reconstruction algorithm which uses landmarks to register each B-scan accurately as it is inserted into the voxel array. In a series of in vitro and in vivo trials, we demonstrate that 3-D spatial compounding is very effective for improving the signal-to-noise ratio, but correction of registration errors is essential.

Algorithms↗
PubMed1997

An audit of the treatment of carcinoma of the uterine cervix using external beam radiotherapy and a single line source brachytherapy technique.

A single line source brachytherapy (BT) technique has been developed at Clatterbridge to boost the dose to the primary tumour after whole pelvis external beam radiotherapy (EBRT) for the radical treatment of carcinoma of the cervix. 226 patients with invasive carcinoma of the uterine cervix were treated with radiotherapy alone using this technique (median age 57 years; range 25-87 years). 49 patients had Stage IB disease, 97 had Stage II, 73 had Stage III and seven patients had biopsy confirmed Stage IVA disease. Patients with low bulk disease were given 40-42.5 Gy in 20 fractions while those with bulky disease received 45 Gy in 20 fractions or 50 Gy in 25 fractions. On completion of EBRT, 186 patients (82.3%) proceeded to intracavitary BT using a linear arrangement of sources with the Selectron (Nucletron) remote afterloading unit. Most of the patients (137/226, 60.6%) received a single insertion of 20 Gy to point "A", at a preferred dose rate within the range 0.95-1.05 Gy h-1. In another 30 patients (13.3%), BT was possible at a later date after further tumour regression. Only 10 patients (4.4%) did not receive BT as part of their treatment. The 5 year actuarial cause-specific survival rate was 79% in Stage I disease, 61% in Stage II, 31% in Stage III and 71% in the small number of patients with Stage IVA disease. The 5 year pelvic control rates were 88% for Stage I, 69% for Stage II, 45% for Stage III and 71% for Stage IVA. Significant prognostic variables for survival and local pelvic control on univariate analysis included disease stage, patient age, tumour bulk, nodal status, anaemia, renal failure and overall treatment time. Tumour grade was a significant prognostic variable for survival but not for local tumour control. The extent of parametrial involvement was a significant prognostic variable for survival and local control for Stage IIB but not for Stage IIIB. There was a statistically significant decrease in survival and local tumour control for patients receiving > or = 70 Gy to point "A", or > or = 55 Gy to point "B". On multivariate analysis, the independent prognostic variables for survival and local control were disease stage, overall treatment time and renal failure. Patient age was also an independent prognostic variable for survival while nodal status was an independent prognostic variable for local control. A high proportion of the patients had adverse prognostic features resulting in a very high actuarial risk of distant metastases of 38.1% at 5 years (68.8% for Stage III patients). The overall treatment time was significantly longer in Stage III patients compared with Stage I and Stage II patients. The actuarial rate of Grade 2 late radiation morbidity was 2.7% and 4.3% for the urinary tract and bowel respectively while that of Grade 3 morbidity was only 0.6% and 1.4%, respectively. Good local control can be achieved for patients with nonbulky tumours using relatively low biological doses while minimizing the risk of late treatment related toxicity. Several changes in treatment policy have been made in an attempt to improve local tumour control and possibly survival, particularly for Stage III patients and patients with bulky disease.

Adult↗
PubMed1997

Attenuation of plasma low density lipoprotein cholesterol by select 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in mice devoid of low density lipoprotein receptors.

Low density lipoprotein (LDL) reduction independent of LDL receptor regulation was investigated using HMG-CoA reductase inhibitors in LDL receptor-deficient mice. In males, LDL cholesterol dose-dependently decreased with atorvastatin treatment after 1 week. As untreated mice grew older, their LDL cholesterol progressively rose above basal levels, but was quelled with atorvastatin treatment. In females, atorvastatin treatment time-dependently decreased LDL cholesterol levels and induced hepatic HMG-CoA reductase activity. Unlike males, cholesterol-lowering effects of the drug were sustained in females. Lovastatin, simvastatin, and pravastatin also reduced total and LDL cholesterol; however, additional studies in females demonstrated that atorvastatin caused the greatest dose-dependent and sustained effect after 2 weeks. In females, hepatic HMG-CoA reductase mRNA inversely correlated with LDL cholesterol lowering, with atorvastatin showing the greatest increase in mRNA levels (17.2-fold), followed by lovastatin (10.7-fold), simvastatin (4.1-fold), and pravastatin (2.5-fold). Atorvastatin effects on lipoprotein production were determined after acute (1 day) or chronic (2 week) treatment prior to intraperitoneal injection of Triton WR1339. Acute treatment reduced cholesterol (-29%) and apoB (-16%) secretion, with no change in triglyceride secretion. In contrast, chronic treatment elevated cholesterol (+20%), apoB (+31%), and triglyceride (+57%) secretion. Despite increased cholesterol and apoB secretion, plasma levels were reduced by 51% and 46%, respectively. Overall, under acute or chronic conditions, apoB paralleled cholesterol secretion rates, and triglyceride to cholesterol secretion ratios were elevated by 38% and 32%, respectively. We propose that atorvastatin limits cholesterol for lipoprotein assembly, which is compensated for by triglyceride enrichment. In addition, with either acute or chronic atorvastatin treatment, apoB-100 secretion was blocked, and compensated for by an increased secretion of apoB-48. The apoB-48 particles produced are cleared by LDL receptor-independent mechanisms, with an overall effect of reducing LDL production in these mice. These studies support the idea that HMG-CoA reductase inhibitors modulate lipoprotein levels independent of LDL receptors, and suggest they may have utility in hyperlipidemias caused by LDLreceptor disorders.

Animals↗
PubMed1996

Highly purified CD34-positive cells reconstitute hematopoiesis.

PURPOSE: The objective of this study was to characterize CD34+ cell grafts, obtained using a novel technique, from children undergoing autologous bone marrow transplantation (BMT) for cancer therapy. In particular, we wanted to determine if the CD34+ marrow cell grafts generated hematopoietic reconstitution, since a positive result would motivate further development and use of this methodology. PATIENTS AND METHODS: This pilot feasibility clinical trial involved 13 patients < or = 25 years of age with advanced solid tumors, including seven children with neuroblastoma. Harvested bone marrow underwent immunomagnetic CD34+ selection. RESULTS: In three of 13 enrolled patients, low purities of the CD34+ preparations disqualified the use of the CD34+ marrow grafts. Ten patients received myeloablative chemotherapy with etoposide, carboplatin, and cyclophosphamide, then were transplanted with CD34+ marrow grafts. In the 10 patients transplanted with CD34(+)-selected cells, the CD34+ cell purity (nucleated RBCs excluded) in the cell graft preparation was 91% total cell recovery from the starting light-density cells 2.2%, CD34+ cell recovery 38%, colony-forming unit-granulocyte-macrophage (CFU-GM) recovery 23%, and estimated tumor-cell depletion 2.6 logs (medians). The CD34+ marrow grafts administered to these patients contained a median of 2.3 x 10(6) nucleated cells, 1.4 x 10(6) CD34+ cells, and 1.3 x 10(4) CFU-GM per kilogram patient weight. Most patients experienced only the toxicities previously observed with this myeloblative chemotherapy regimen, although two unusual toxicities were observed. All 10 patients transplanted with CD34+ cell grafts engrafted. CONCLUSION: The CD34+ purified grafts were enriched in stem/progenitor cells, with five of these 10 preparations containing > or = 94% CD34+ cells. Engraftment with CD34(+)-purified cell grafts as pure as 99% confirms that autologous CD34+ cells, alone, are sufficient to provide hematopoietic rescue for myeloablated patients. The best purification results were obtained on small marrow harvests from patients with neuroblastoma. The engraftment of highly purified CD34+ cells obtained by this technology and the antitumor effect of the transplant, by which two of 10 poor prognosis patients remain clinically free of tumor, have stimulated further clinical trials.

Adolescent↗
PubMed1996

Survival of contaminating bacteria in over-the-counter artificial tears.

BACKGROUND: The use of OTC artificial tears is becoming increasingly widespread. Unintentional contamination of artificial tear products potentiates a risk of developing bacterial keratitis or exacerbating an existing eye infection. Presently, no published study has investigated recovery from bacterial contamination of artificial tear products. METHODS: Four different over-the-counter (OTC) artificial tear products were contaminated with two types of bacteria. Staphylococcus aureus and pseudomonas aeruginosa were analyzed for the survivability of the microorganisms at various times following contamination. RESULTS: In this cross-sectional study, it was found that all the preserved brands showed a significant recovery rate from contamination compared to the preservative-free brand. After 9 hours, the preservative-free brand did not completely regain sterility after contamination with either bacteria. CONCLUSIONS: This study indicates that preserved artificial tears recover from bacterial contamination at a significantly faster rate than preservative-free products. It is likely that the recovery from bacterial contamination is not solely attributed to the preservative, but that other variables may contribute.

Colony Count, Microbial↗