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Biomedical subjects

R Hill

Publications and source records attributed to R Hill.

At least 73 records · Page 4Linked to original sources
PubMed1999

Engraftment of primates with G-CSF mobilized peripheral blood CD34+ progenitor cells expanded in G-CSF, SCF and MGDF decreases the duration and severity of neutropenia.

We used a primate model of autologous peripheral blood progenitor cell (PBPC) transplantation to study the effect of in vitro expansion on committed progenitor cell engraftment and marrow recovery after transplantation. Four groups of baboons were transplanted with enriched autologous CD34+ PBPC collected by apheresis after five days of G-CSF administration (100 microg/kg/day). Groups I and III were transplanted with cryopreserved CD34+ PBPC and Groups II and IV were transplanted with CD34+ PBPC that had been cultured for 10 days in Amgen-defined (serum free) medium and stimulated with G-CSF, megakaryocyte growth and development factor (MGDF), and stem cell factor each at 100 etag/ml. Group III and IV animals were administered G-CSF (100 microg/kg/day) and MGDF (25 microg/kg/day) after transplant, while animals in Groups I and II were not. For the cultured CD34+ PBPC from groups II and IV, the total cell numbers expanded 14.4 +/- 8.3 and 4.0 +/- 0.7-fold, respectively, and CFU-GM expanded 7.2 +/- 0.3 and 8.0 +/- 0.4-fold, respectively. All animals engrafted. If no growth factor support was given after transplant (Groups II and I), the recovery of WBC and platelet production after transplant was prolonged if cells had been cultured prior to transplant (Group II). Administration of post-transplant G-CSF and MGDF shortened the period of neutropenia (ANC < 500/microL) from 13 +/- 4 (Group I) to 10 +/- 4 (Group III) days for animals transplanted with non-expanded CD34+ PBPC. For animals transplanted with ex vivo-expanded CD34+ PBPC, post-transplant administration of G-CSF and MGDF shortened the duration of neutropenia from 14 +/- 2 (Group II) to 3 +/- 4 (Group IV) days. Recovery of platelet production was slower in all animals transplanted with expanded CD34+ PBPC regardless of post-transplant growth factor administration. Progenitor cells generated in vitro can contribute to early engraftment and mitigate neutropenia when growth factor support is administered post-transplant. Thrombocytopenia was not decreased despite evidence of expansion of megakaryocytes in cultured CD34+ populations.

Animals↗
PubMed1999

Follow-up of the original cohort with the Ahmed glaucoma valve implant.

PURPOSE: To study the long-term results of the Ahmed glaucoma valve implant in patients with complicated glaucoma in whom short-term results have been reported. METHODS: In this multicenter study, we analyzed the long-term outcome of a cohort of 60 eyes from 60 patients in whom the Ahmed glaucoma valve was implanted. Failure was characterized by at least one of the following: intraocular pressure greater than 21 mm Hg at both of the last two visits less than 6 mm Hg at both of the last two visits, loss of light perception, additional glaucoma surgery, devastating complications, and removal or replacement of the Ahmed glaucoma valve implant. Devastating complications included chronic hypotony, retinal detachment, malignant glaucoma, endophthalmitis, and phthisis bulbi; we also report results that add corneal complications (corneal decompensation or edema, corneal graft failure) as defining a devastating complication. RESULTS: The mean follow-up time for the 60 eyes was 30.5 months (range, 2.1 to 63.5). When corneal complications were included in the definition of failure, 26 eyes (43%) were considered failures. Cumulative probabilities of success at 1, 2, 3, and 4 years were 76%, 68%, 54%, and 45%, respectively. When corneal complications were excluded from the definition of failure, 13 eyes (21.5%) were considered failures. Cumulative probabilities of success at 1, 2, 3, and 4 years were 87%, 82%, 76%, and 76%, respectively. Most of the failures after 12 months of postoperative follow-up were because of corneal complications. CONCLUSIONS: The long-term performance of the Ahmed glaucoma valve implant is comparable to other drainage devices. More than 12 months after the implantation of the Ahmed glaucoma valve implant, the most frequent adverse outcome was corneal decompensation or corneal graft failure. These corneal problems may be secondary to the type of eyes that have drainage devices or to the drainage device itself. Further investigation is needed to identify the reasons that corneal problems follow drainage device implantation.

Female↗
PubMed1999

Rapid oral hydration results in hydronephrosis as demonstrated by bedside ultrasound.

STUDY OBJECTIVE: To determine whether vigorous oral hydration (20 mL/kg) causes hydronephrosis as determined by bedside ultrasound. METHODS: We conducted a prospective laboratory trial in 35 healthy volunteers weighing less than 90 kg and between the ages of 18 and 50 years. The right kidney of the volunteers was scanned by emergency physicians at time 0 both before and after voiding, and the volunteers then drank 20 mL/kg of bottled water. The kidney was scanned in the transverse and sagittal planes both before and after voiding at 60 and 90 minutes after completion of the water load. The scans were interpreted by a physician trained and credentialed in emergency ultrasound, blinded to the volunteers' identity, the time of the scan, and the volume of urine voided by the subject. Images were rated as to the degree of hydronephrosis according to literature-established criteria, as follows: grade 0=no hydronephrosis, grade 1=mild, grade 2=moderate, and grade 3=severe hydronephrosis. RESULTS: Hydronephrosis was present in 3 (8.6%) of the 35 subjects at time 0 (prehydration), 24 (68.6%) at 60 minutes, and 20 (57.1%) at 90 minutes. Overall, hydronephrosis occurred at least once in 28 (80%) of the 35 subjects after oral hydration compared with 3 (8.6%) of the 35 subjects before hydration. Hydronephrosis was found to be significantly related to forced hydration for all posthydration times (60 minutes, 90 minutes, and 60+90 minutes combined) versus prehydration time 0 (P <.001). CONCLUSION: Without prior fluid intake, even mild degrees of hydronephrosis were relatively uncommon, and seen in only 8.6% of study patients. In the presence of vigorous oral hydration, however, mild or moderate hydronephrosis is a frequent occurrence seen at least once in 80% of our study of healthy volunteers after hydration. Caution is warranted in this setting when interpreting mild or moderate hydronephrosis found on bedside ultrasound by emergency physicians.

Adolescent↗
PubMed1999

Behavioral and pharmacologic interventions: the Raynaud's Treatment Study.

The Raynaud's Treatment Study (RTS) exemplified clinical trials with treatments that differ qualitatively both in their modes and in their methods of delivery. The RTS compared finger-temperature biofeedback to slow-release nifedipine, a calcium channel blocker, in patients with primary Raynaud's disease. Factors influencing the study design were the nature of the interventions and control measures of the protocol, the possibility of perceived differences by the patients between the treatments once the final protocol was developed, and concern on the part of the investigators over the fact that the primary endpoint was self-reported. This paper presents the final statistical model: a double parallel design with both a placebo group and a nonspecific behavioral control group.

Biofeedback, Psychology↗
PubMed1999

The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.

Many damage-sensing neurons express tetrodotoxin (TTX)-resistant voltage-gated sodium channels. Here we examined the role of the sensory-neuron-specific (SNS) TTX-resistant sodium channel alpha subunit in nociception and pain by constructing sns-null mutant mice. These mice expressed only TTX-sensitive sodium currents on step depolarizations from normal resting potentials, showing that all slow TTX-resistant currents are encoded by the sns gene. Null mutants were viable, fertile and apparently normal, although lowered thresholds of electrical activation of C-fibers and increased current densities of TTX-sensitive channels demonstrated compensatory upregulation of TTX-sensitive currents in sensory neurons. Behavioral studies demonstrated a pronounced analgesia to noxious mechanical stimuli, small deficits in noxious thermoreception and delayed development of inflammatory hyperalgesia. These data show that SNS is involved in pain pathways and suggest that blockade of SNS expression or function may produce analgesia without side effects.

Afferent Pathways↗
PubMed1999

Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370.

This study investigated whether the selective 5HT1F receptor agonist LY334370 has other possible antimigraine mechanisms in addition to the proposed inhibition of dural plasma extravasation. LY334370 (up to 10(-5) M) had no vasoconstrictor effects on human cerebral arteries in vitro. It had no effect (up to 10 mg kg-1, i.v.) on neurogenic vasodilation of dural blood vessels produced by electrical stimulation of the dura mater in anesthetized rats. Nor had it any effect (at 3 mg kg-1, i.v.) on the hyperalgesia produced by injection of carrageenan into the paw of conscious rats or on nociceptive reflex responses in the spinalized, decerebrate rabbit (up to 3 mg kg-1, i.v.), indicating that it has no general analgesic properties. However, it significantly inhibited activation of second-order neurons in the trigeminal nucleus caudalis produced by electrical stimulation of the dura mater in anesthetised rats at 3 mg kg-1, i.v. These results provide evidence to suggest that LY334370 has a central mechanism of action in blocking the transmission of nociceptive impulses within the trigeminal nucleus caudalis and that this may represent a mechanism through which it has its antimigraine effect.

Animals↗
PubMed1999

Dosimetric verification of a commercial inverse treatment planning system.

A commercial three-dimensional (3D) inverse treatment planning system, Corvus (Nomos Corporation, Sewickley, PA), was recently made available. This paper reports our preliminary results and experience with commissioning this system for clinical implementation. This system uses a simulated annealing inverse planning algorithm to calculate intensity-modulated fields. The intensity-modulated fields are divided into beam profiles that can be delivered by means of a sequence of leaf settings by a multileaf collimator (MLC). The treatments are delivered using a computer-controlled MLC. To test the dose calculation algorithm used by the Corvus software, the dose distributions for single rectangularly shaped fields were compared with water phantom scan data. The dose distributions predicted to be delivered by multiple fields were measured using an ion chamber that could be positioned in a rotatable cylindrical water phantom. Integrated charge collected by the ion chamber was used to check the absolute dose of single- and multifield intensity modulated treatments at various spatial points. The measured and predicted doses were found to agree to within 4% at all measurement points. Another set of measurements used a cubic polystyrene phantom with radiographic film to record the radiation dose distribution. The films were calibrated and scanned to yield two-dimensional isodose distributions. Finally, a beam imaging system (BIS) was used to measure the intensity-modulated x-ray beam patterns in the beam's-eye view. The BIS-measured images were then compared with a theoretical calculation based on the MLC leaf sequence files to verify that the treatment would be executed accurately and without machine faults. Excellent correlation (correlation coefficients > or = 0.96) was found for all cases. Treatment plans generated using intensity-modulated beams appear to be suitable for treatment of irregularly shaped tumours adjacent to critical structures. The results indicated that the system has potential for clinical radiation treatment planning and delivery and may in the future reduce treatment complexity.

Algorithms↗
PubMed1999

Theoretical considerations of monitor unit calculations for intensity modulated beam treatment planning.

A treatment planning system to compute intensity modulated radiotherapy (IMRT) treatments using inverse planning was investigated. The system was designed to optimize the intensity patterns required to treat a specified target volume with specified normal structure constraints. A beam model that uses the convolution of pencil beams was used to compute the dose distributions. A multileaf collimator leaf-setting sequence intended to produce the intensity pattern was computed along with the monitor units required to deliver each of a number of fixed-gantry modulated fields. Computer calculations are commonly verified using an independent manual procedure. It is difficult to calculate treatment delivery monitor units for this variant of IMRT using manual methods. Since manual calculations are not feasible, it is important both to understand and to verify the calculation of treatment monitor units by the planning system algorithm. A formal analysis was made of the dose calculation model and the monitor unit calculation embedded in the algorithm. Experimental verification of the dose delivered by plans computed with the methodology demonstrated an agreement of better than 4% between the dose model and measurements.

Algorithms↗
PubMed1998

High-altitude cerebral edema evaluated with magnetic resonance imaging: clinical correlation and pathophysiology.

CONTEXT: Because of its onset in generally remote environments, high-altitude cerebral edema (HACE) has received little scientific attention. Understanding the pathophysiology might have implications for prevention and treatment of both this disorder and the much more common acute mountain sickness. OBJECTIVES: To identify a clinical imaging correlate for HACE and determine whether the edema is primarily vasogenic or cytotoxic. DESIGN: Case-comparison study. SETTING: Community hospitals accessed by helicopter from mountains in Colorado and Alaska. PATIENTS: A consecutive sample of 9 men with HACE, between 18 and 35 years old, 8 of whom also had pulmonary edema, were studied after evacuation from high-altitude locations; 5 were mountain climbers and 4 were skiers. The control group, matched for age, sex, and altitude exposure, consisted of 3 subjects with high-altitude pulmonary edema only and 3 who had been entirely well at altitude. Four patients with HACE were available for follow-up imaging after complete recovery. MAIN OUTCOME MEASURES: Magnetic resonance imaging (MRI) of the brain during acute, convalescent, and recovered phases of HACE, and once in controls, immediately after altitude exposure. RESULTS: Seven of the 9 patients with HACE showed intense T2 signal in white matter areas, especially the splenium of the corpus callosum, and no gray matter abnormalities. Control subjects demonstrated no such abnormalities. All patients completely recovered; in the 4 available for follow-up MRI, the changes had resolved entirely. CONCLUSIONS: We conclude that HACE is characterized on MRI by reversible white matter edema, with a predilection for the splenium of the corpus callosum. This finding provides a clinical imaging correlate useful for diagnosis. It also suggests that the predominant mechanism is vasogenic (movement of fluid and protein out of the vascular compartment) and, thus, that the blood-brain barrier may be important in HACE.

Adult↗
PubMed1998

Development and characterisation of human 5-HT1B- or 5-HT1D-receptor specific antibodies as unique research tools.

The serotonin 5-HT1B/1D-receptor family comprises of two closely related receptors encoded by two distinct genes. There are no pharmacological ligands which can adequately distinguish between these two receptor subtypes in human tissues. Therefore, we have developed human 5-HT1B- and 5-HT1D-receptor subtype specific polyclonal antibodies. Rabbits were immunised with synthetic peptides identical to unique amino acid sequences located in the third intracellular loops of these receptors. Polyclonal antibodies were subjected to immunoaffinity purification and were characterised using ELISA, dot blot analysis and immunostaining of stably-transfected CHO cell lines expressing either human 5-HT1B-receptors or 5-HT1D-receptors and in human trigeminal ganglia. The antibodies were specific for either the 5-HT1B- or 5-HT1D-receptors and did not cross-react. Both 5-HT1B- and 5-HT1D-immunoreactivities were detected on cell bodies in human trigeminal ganglia. In the absence of selective pharmacological agents, these antibodies represent unique and essential research tools to study the anatomical distribution of 5-HT1B/1D-receptor subtypes in human tissue.

Amino Acid Sequence↗
PubMed1998

Radioresistant MTp53-expressing rat embryo cell transformants exhibit increased DNA-dsb rejoining during exposure to ionizing radiation.

Recent data suggest that aberrant function of the wild type p53 protein (WTp53) may alter cellular survival following DNA damage through cellular pathways involving apoptosis and cell-cycle checkpoints, but little is known concerning it's possible role in DNA repair. In the present study, the ionizing radiation sensitivity was determined for a series of rat embryo fibroblast (REF) cell lines transfected with an activated form of the H-ras oncogene alone, or in combination with a variety of missense-mutant p53 (MTp53) alleles. Transformed REF clones which expressed exogenous MTp53 and p21ras proteins (CLASS II clones) were generally radioresistant in culture as determined by higher values for the surviving fraction after 2 Gy (SF2 value) and the radiation dose required to reduce survival to a fraction of 0.1 (D10 value), compared either to transformed REF clones expressing p21ras protein alone (CLASS I clones), or to non-transfected REF control cell lines expressing baseline endogenous levels of p21ras and WTp53 protein. The increased radioresistance observed in the CLASS II clones (following both HDR- and LDR-irradiation), was significantly correlated with increased expression of MTp53 protein, and a decreased radiation-induced G1 arrest response. The variability observed in clonogenic radiosensitivity among REF clones was not explained by differential radiation-induced apoptosis. Using the Comet assay performed after continuous low dose-rate (LDR)-irradiation, MTp53-expressing REF clones were also found to be more proficient at the rejoining of DNA double-strand breaks (DNA-dsb), compared to WTp53-expressing REF clones. These results suggest that an enhanced DNA and cellular repair capacity may, in part, explain the increased radiation survival observed in some MTp53-expressing transformed fibroblasts and tumours.

Animals↗
PubMed1998

A comparison of digital retinal images and 35 mm colour transparencies in detecting and grading diabetic retinopathy.

We compared digital retinal images and 35 mm colour transparencies taken with the Canon CR5 retinal camera for the detection and grading of diabetic retinopathy in a clinical setting, in a randomized, blinded study of diabetic patients with a spectrum of severity of diabetic retinopathy. Forty patients were photographed, giving a total of 75 eyes including non-diabetic eyes as controls. Images were graded according to the validated European guidelines. There was exact agreement between grades obtained from both the 2 field 45 degrees 35 mm colour transparencies and digital images in 93.3% (70/75) of eyes, with Cohen's Kappa statistic for the comparison being 0.92. Overall, when grading from the digital images 5.3% (4/75) eyes were undergraded with three cases of sight threatening diabetic retinopathy (STDR) graded as non-sight threatening (NSTDR) (3/48, 6.3%). One eye was overgraded (1/75, 1.3%). Two of the three cases of STDR undergraded as NSTDR had small numbers of intra-retinal microvascular abnormalities (IRMA) discernible on the colour transparencies but which were not visible from the digital image. The third had multiple small cotton wool spots graded as laser photocoagulation scars from the digital images. In conclusion there is good to excellent agreement between retinopathy grades using the Canon CR5 digital retinal imaging system compared to 35 mm colour transparencies.

Diabetic Retinopathy↗
PubMed1998

Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats.

1. Kavapyrones have well-known psychotropic properties. The most common actions of the extract are relaxation and euphoria, depending on the circumstances of ingestion, whereas higher doses cause sleepiness and skeletal muscle relaxation. Several other actions have been reported such as anticonvulsant properties, neuroprotection and analgesia. No interactions with neuroreceptors have yet been found that would explain the multiple actions. 2. To reveal neuronal functions affected by the kavapyrones the authors studied their actions on the mesolimbic reward system using in vivo microdialysis. 3. A small dose of kava extract (20 mg/kg body weight i.p.) caused changes in rat behaviour and concentrations of dopamine in the nucleus accumbens. Higher doses (120 mg/kg i.p.) increased the levels of dopamine. With respect to the individual compounds, D,L-kawain induced in low doses a decrease in dopamine levels and in higher amounts either an increase or no change in dopamine concentrations. Yangonin resulted in a decrease of dopamine levels to below the detection limit and desmethoxyyangonin in an increase of dopamine levels. Dihydrokawain, methysticin and dihydromethysticin did not produce any significant changes of dopamine levels. D,L-kawain caused a decrease in 5-HT concentrations. Some of the other kavapyrones affected 5-HT levels as well. 4. The results suggest that the relaxing and slightly euphoric actions may be caused by the activation of the mesolimbic dopaminergic neurones. Changes of the activity of 5-HT neurones could explain the sleep-inducing action.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

In vivo skeletal response and biomechanical assessment of two novel polyalkenoate cements following femoral implantation in the female New Zealand White rabbit.

Glass-ionomer cements (GIC) offer several advantages over the conventional acrylic-based bone cements. The formation of an adhesive bond with bone and metals, a low setting exotherm and no systemic or local toxicity are some of the advantages cited. This study examines the in vivo biological and biomechanical behavior of two polyalkenoate cements (LG26 and LG30) implanted for 6 wk into the submetaphyseal spongiosa of the rabbit femur. Cements were implanted as both set cement rods and unset cement dough. Implantation of set rods resulted in the formation of variably mineralized osteoid/woven bone at the bone-cement interface. Mechanical (push-out) testing revealed the strength of this bone-cement interface was of similar magnitude to control (PMMA-rod implanted) animals. The bone of LG cement-dough implanted animals exhibited demineralization of pre-existing bone local to the site of implantation, accumulation of aluminum both locally and at a distance from the site of implantation, and defective mineralization of newly formed osteoid. The histological picture following LG implantation was strikingly similar to human renal osteodystrophy, in which skeletal accumulation of aluminum is a noted feature. The development of a GIC with low/no aluminum release from the unset cement dough is a priority in the further development of these cements for possible orthopaedic applications.

Journal Article↗
PubMed1998

Effects of spacing and repetition on amnesic patients' performance during perceptual identification, stem completion, and category exemplar production.

The effects of repetition and spacing of repetitions on amnesic patients' implicit task performance was studied. Amnesic patients and control participants performed a perceptual identification task, a word-stem completion task, and a category exemplar production task after the presentation of target words repeated within a list. Repetition proved to have no effect on perceptual identification or on word-stem completion, but it did play a role in category exemplar production. As expected, the amnesic patients demonstrated normal performance on the perceptual identification and word-stem completion tasks. However, on category exemplar production, the amnesic patients' performance was significantly below that of the control participants, and the 2 groups differentially responded to repetition. The normal control participants' spontaneous ability to analyze semantic features of words led to unconscious priming of the category and its links to the exemplars after only one presentation of a word. Amnesic patients, on the other hand, seemed to rely more on the fluency produced by multiple presentations.

Aged↗
PubMed1998

Remifentanil prevents an increase in intraocular pressure after succinylcholine and tracheal intubation.

We have studied changes in intraocular pressure (IOP) in 30 patients after succinylcholine (suxamethonium) and tracheal intubation following administration of propofol 2 mg kg-1 and either remifentanil 1 microgram kg-1 (group R) or saline (group S). IOP was measured before induction, before administration of succinylcholine and the study drug, before intubation and for every 1 min after intubation for 5 min. There was a significant decrease in IOP in group R compared with group S from the time of administration of the study drugs to the end of the study (P < 0.006).

Adult↗
PubMed1998

The value of electrophysiology study and prophylactic implantation of cardioverter defibrillator in patients with hypertrophic cardiomyopathy.

Fifty-three consecutive patients with hypertrophic cardiomyopathy (HCM) and no history of sudden death underwent electrophysiology (EP) study. Sustained polymorphic ventricular tachycardia (VT) or ventricular fibrillation (VF) was induced in 19 patients (35%). Patients with prior syncope or near syncope had a higher incidence of VT/VF inducibility. An implantable cardioverter defibrillator (i.c.d.) was placed in 14 of the 19 patients. Of the remaining 5 patients with inducible VT/VF, three refused ICD implantation, while two underwent septal myectomy and VT/VF was no longer inducible after the operation. None of the patients received antiarrhythmic drugs. During a mean follow-up period of 47 +/- 31 (2-117) months, no events occurred in the 34 patients with negative EP study. Three events occurred among the 19 patients with inducible VT/VF. One patient died suddenly, one developed wide complex tachycardia which required resuscitation, and one patient received an appropriate ICD shock. In conclusion, sustained polymorphic VT/VF was inducible in about one-third of patients with HCM. Noninducibility of VT/VF appeared to predict a favorable prognosis. Although the overall event rate was low in patients with inducible VT/VF, prophylactic ICD implantation in patients with multiple risk factors may be appropriate.

Adult↗