Biomedical subjects

D A Ross

Publications and source records attributed to D A Ross.

At least 163 records · Page 9Linked to original sources

PubMed1993

Efficacy of transferrin receptor-targeted immunotoxins in brain tumor cell lines and pediatric brain tumors.

The efficacy and cytotoxic properties of immunotoxin conjugates directed against the transferrin receptor were examined in cell lines and operative specimens from pediatric brain tumors. Dose-response relationships were assessed for immunotoxin-mediated inhibition of protein synthesis for two immunotoxins, 454A12-rRA and anti-tfnR-CRM 107. Three target medulloblastoma cell lines (DAOY, D283MED, and D341MED), a glioblastoma (U373), and a neuroblastoma (SH-SY5Y) cell line exhibited similar sensitivity to both immunotoxins with IC50s in the 10(-9)-10(-10) M range. The time course of protein synthesis inhibition by the immunotoxins in DAOY cells showed that inhibition by anti-tfnR-CRM 107 was rapid and apparent by 6 h of incubation. In contrast, a response to 454A12-rRA was not observed until 16 h. Cell viability was decreased 30-40% by 24 h after removing 454A12-rRA (1 x 10(-9) M) and was maximally decreased 70-80% after 3 days. The efficacy of the immunotoxins on a variety of fresh specimens of pediatric brain tumors was also examined. The more aggressive and malignant tumor types such as glioblastoma multiforme and medulloblastoma had low IC50 values (10(-12) M), indicating that these tumors were extremely sensitive to transferrin receptor-targeted immunotoxins. In general, protein synthesis in slow-growing and benign tumors was not as greatly affected by immunotoxins. Immunoblots showed expression of transferrin receptors on the cell lines and tumors which correlated with in vitro sensitivity to immunotoxin. The results demonstrate that two immunotoxins targeted to the transferrin receptor are efficacious in killing brain tumor cell lines and primary tumor cultures at very low concentrations and that highly malignant tumors are especially sensitive to this cytotoxic response.

Brain Neoplasms↗

PubMed1993

Cytodiagnosis of breast disease using a liquid suspension medium.

Fine-needle aspiration cytology specimens from 187 breast lesions were processed using conventional slide cytology. Results were compared with those from 201 lesions prepared using a liquid suspension medium (Cytospin) for specimen collection, to assess the clinical utility of each technique. The frequency of diagnostic groups was similar for each method. No significant difference was found in sensitivity (conventional slide cytology 86 per cent versus Cytospin 82 per cent), specificity (72 versus 82 per cent) or diagnostic accuracy (88 versus 91 per cent). The Cytospin technique compares favourably with conventional slide cytology and can be recommended for ease of use in breast cytodiagnosis.

Biopsy, Needle↗

PubMed1993

Stereotactic localization using fast spin-echo imaging in functional disorders.

Fast Spin-Echo Magnetic Resonance Imaging facilitates multiplanar target and trajectory selection in functional disorders by rapidly delineating gray matter, white matter, vascular, and ventricular structures. Errors due to anatomic variation or co-existing lesions can be avoided as are movement artifacts. Although not a substitute for physiologic target corroboration, the method facilitates safety and efficacy of "functional" stereotactic procedures.

Brain↗

PubMed1993

The use of cerium nitrate-silver sulphadiazine as a topical burns dressing.

Infection remains the major cause of morbidity and mortality following the shock phase in the burn patient. Measures to reduce the risk of wound infection and subsequent sepsis include early excision where possible, and the use of topical antimicrobial creams such as silver sulphadiazine. Studies from the USA and Europe suggest the addition of cerium nitrate to this commonly used agent may improve its efficacy. We present the findings of a pilot study which investigated the action of a commercial preparation of cerium nitrate/silver sulphadiazine mixture (Flammacerium, Duphar B. V. Holland) on 20 patients considered unsuitable for surgery. There were no episodes of cellulitis or septicaemia. Flammacerium was noted to produce an adherent eschar that was easy to shave and which received split skin grafts well.

Administration, Topical↗

PubMed1993

Tubed radial fascial flap and reconstruction of the flexor apparatus in the forearm.

A reversed radial forearm fascial flap has been used as a vascularized tube through which tendon grafts may glide and in which nerve grafts may rest. It may have applications in the treatment of the severely damaged flexor system at wrist level. A further advantage of this technique is that it does not [corrected] sacrifice the radial artery in an already injured hand.

Adult↗

PubMed1993

Effect of porcine somatotropin on the response of growing pigs to acute challenges of glucose, insulin and epinephrine and during a hyperinsulinemic-euglycemic clamp.

Response of tissues to homeostatic signals may play a role in the mediation of nutrient partitioning effects of somatotropin. To investigate this, the effects of exogenous porcine somatotropin (pST) on the metabolic responses to a series of intravenous challenges with dextrose, insulin and epinephrine were examined in twelve crossbred barrows (65 kg). In addition, the hyperinsulinemic-euglycemic clamp technique was used to further explore effects of pST on insulin resistance in eight of these animals. Pigs received daily sc injections of either pituitary-derived pST (120 micrograms/kg bw) or an equivalent volume of excipient for 28 d. Treatment with pST resulted in a chronic elevation of plasma glucose, insulin and non-esterified fatty acid concentrations and lowered glucagon concentrations. Acute iv challenges of dextrose (100 mg/kg bw), insulin (1.0 micrograms/kg bw), and epinephrine (2.2 micrograms/kg bw) were administered on days 21, 22, and 23 of the treatment period, respectively. Hyperinsulinemic-euglycemic clamps were carried out on day 28. Effects of pST were most dramatic for responses associated with insulin. In pST-treated pigs, insulin response to dextrose infusion was enhanced, while glucose response to insulin was attenuated and glucose clearance rate was reduced. During the hyperinsulinemic-euglycemic clamp, dextrose infusion rate required to maintain euglycemia during physiologic elevations of insulin was reduced in pST-treated pigs to 28% of control. In pST-treated pigs, glucose response to epinephrine challenge was halved, while insulin response was increased three-fold. Therefore, one mechanism by which pST shifts the nutrient partition is by altering metabolic responses to homeostatic signals. In growing pigs, this is especially evident for glucose response to insulin.

Animals↗

PubMed1993

Relationship between hepatic fatty acid oxidation and gluconeogenesis in the fasting neonatal pig.

Hepatocytes were isolated from sixteen fasting neonatal pigs and used in two experiments: (1) to determine the effect of various factors on the ability for hepatic oxidation of fatty acids and (2) to clarify the relationship between fatty acid oxidation and glucose synthesis. In Expt 1, newborn pigs were either fasted from birth for 24 h or allowed to suck ad lib. for 3 d followed by a 24 h fast. In the presence of pyruvate, oxidation of octanoate (2 mM) was about 30-fold greater than oleate (1 mM) regardless of age, but glucose synthesis was not enhanced beyond that observed for pyruvate alone. Inclusion of carnitine (1 mM), glucagon (100 nM) or dibutyryl cAMP (50 microM) in the incubation media did not stimulate either fatty acid oxidation (octanoate or oleate) or glucose synthesis. Extending the period of fasting to 48 h (Expt 2) failed to enhance the fatty acid oxidative capacity or glucose synthesis rate. Likewise, the redox potential of the gluconeogenic substrate (lactate v. pyruvate) did not influence glucose synthesis regardless of the oxidative capacity exhibited for fatty acids. These data indicate that fatty acid oxidative capacity is not the first limiting factor to full expression of gluconeogenesis in hepatocytes isolated from fasted newborn pigs.

Aging↗

PubMed1993

Influence of morbidity on serum retinol of children in a community-based study in northern Ghana.

Serum retinol concentrations decrease during illness and thus may not accurately reflect the vitamin A status of populations with a high prevalence of illness. To quantify the contribution of illness to low serum retinol in a field study of children aged 6-59 mo in northern Ghana, serum retinol values were compared with two indicators of recent illness; symptoms reported by parents and acute-phase protein concentrations in serum. Serum retinol was not associated with symptoms of illness but showed a significant negative correlation with both alpha 1-acid glycoprotein (AGP) and serum amyloid A (SAA). Elevated AGP was associated with a 24% decrease in mean serum retinol. A large proportion of asymptomatic children had elevated AGP or SAA concentrations, suggesting that subclinical infections may have had important effects on serum retinol. A significant negative correlation between malaria parasite density and serum retinol indicated that malaria may have been one of the subclinical infections responsible. Measurement of AGP may improve interpretation of serum retinol data from populations with a high prevalence of morbidity.

Child, Preschool↗

PubMed1993

Porcine somatotropin affects the dietary lysine requirement and net lysine utilization for growing pigs.

This study was conducted to determine the effects of exogenous porcine somatotropin (pST) on the dietary lysine requirement and efficiency of absorbed lysine utilization for pigs during the 20- to 60-kg phase of growth. Seventy-two crossbred pigs (20 +/- 0.7 kg body wt) received daily intramuscular injections of either excipient (0 dose) or pST (150 micrograms/kg body wt) and were fed diets in which protein and lysine concentrations ranged from 6.4 to 23.5 g/100 g diet and from 0.40 to 1.48 g/100 g diet, respectively. Nutrient density was altered to compensate for reduced feed intake with pST, but diets were approximately isocaloric. Rate and efficiency of gain and whole-body protein accretion rate exhibited a dose-response improvement (P < 0.01) to increases in dietary protein for both excipient and pST-treated pigs. Pigs receiving pST grew more rapidly and more efficiently than control counterparts (P < 0.01). Treatment with pST improved the rate of protein accretion (P < 0.01) at all but the lowest level of dietary protein. The net lysine utilization for lysine accretion and maintenance was 0.46 for control pigs and 0.57 for pigs receiving pST, a 24% improvement in the efficiency. Thus, treatment with pST increased the maximum rate of protein accretion as well as the partial efficiency with which dietary lysine is used for protein accretion. Consequently, only a 9% increase in dietary lysine was required to maximize protein deposition in pST-treated pigs, because the metabolic efficiency of lysine utilization was improved.

Animals↗

PubMed1993

Purified human oral mucosal Langerhans cells function as accessory cells in vitro.

Oral mucosal Langerhans cells (OMLC) may have an important role in the induction of immune responses to oral pathogens. In this study, anti-HLA-DR antibody-coated immunomagnetic beads were used to purify OMLC from suspensions of normal human buccal epithelium and the capacity of the purified cells to function as accessory cells (AC) was investigated. Electron microscopy was used to show that the purified cells possessed all recognized ultrastructural features previously described in epidermal Langerhans cells. Using T lymphocyte proliferation assays in hanging drop microcultures, it was found that purified OMLC could function as AC for responses to concanavalin A by autologous T cells. Purification of OMLC from small biopsies of oral mucosa has enabled us to show that OMLC, like epidermal Langerhans cells, can function as AC in vitro.

Adult↗

PubMed1993

In vivo cerebral metabolism and central benzodiazepine-receptor binding in temporal lobe epilepsy.

Positron emission tomography measured interictal cerebral glucose metabolism with [18F]fluorodeoxyglucose and central benzodiazepine-receptor binding with [11C]flumazenil in 10 mesial temporal lobe epilepsy (TLE) patients and in normal subjects. Eight TLE patients had mesial temporal, lateral temporal, and thalamic hypometabolism ipsilateral to EEG ictal onsets, with additional extratemporal hypometabolism in four. One had unilateral anterior mesial temporal hypometabolism only, and one had normal metabolism. Each patient had decreased benzodiazepine-receptor binding in the ipsilateral anterior mesial temporal region, without neocortical changes. Thus, interictal metabolic dysfunction is variable and usually extensive in TLE, whereas decreased central benzodiazepine-receptor density is more restricted to mesial temporal areas. Metabolic patterns in TLE may reflect diaschisis, while benzodiazepine-receptor changes may reflect localized neuronal and synaptic loss that is specific to the epileptogenic zone. [11C]Flumazenil imaging may be useful in presurgical evaluation of refractory complex partial seizures.

Adult↗

PubMed1993

Stereotactic management of benign pineal region cysts: report of two cases.

Recent case reports describing the open resection of symptomatic benign cysts of the pineal region have noted that the results of stereotactic management of such cysts have not been reported. We report the results of the stereotactic aspiration of benign pineal region cysts in two patients with symptomatic ventriculomegaly secondary to obstruction of the aqueduct. Stereotactic aspiration produced several cubic centimeters of brown-to-yellow fluid that was negative for tumor on cytological examination. Ventriculomegaly and symptoms were relieved without complications by the procedure in one patient who remains asymptomatic after 30 months of follow-up. In the second patient, persistent ventriculomegaly demonstrated on computed tomography resulted in the placement of a ventriculoperitoneal shunt; however, this was removed several months later during an episode of appendicitis and the patient remained asymptomatic without the shunt. The symptoms and ventriculomegaly recurred 71 months postaspiration, and the cyst was reaspirated. Ten months later, she remains asymptomatic. Options for managing such patients include open resection, shunting, and stereotactic aspiration. The relative merits of each approach are discussed.

Adult↗

PubMed1993

A simple stereotactic retractor for use with the Leksell stereotactic system.

The author has designed a simple and inexpensive cylindrical stereotactic retractor that is compatible with the Leksell stereotactic system. The device allows the stereotactic localization and open resection of appropriate intracranial lesions through a 3-cm craniotomy, using standard microsurgical techniques and a completely sterile field. The device and its use are described.

Biopsy, Needle↗

PubMed1993

A percutaneous epidural screw electrode for intracranial electroencephalogram recordings.

A new epidural electrode for monitoring brain electrical activity is described. The electrode is a tapered screw that is easily inserted percutaneously and removed without general anesthesia. The epidural screw has been used without complications for ictal and interictal electroencephalogram recordings in four patients with medically refractory complex-partial seizure disorders. The epidural screw electrode offers the advantages of easy insertion and removal, patient comfort, artifact-free electroencephalogram recordings, and minimal risk of intracranial infection or hemorrhage.

Bone Screws↗

PubMed1993

Applying critical pathways to neurosurgery patients at the University of Michigan Medical Center.

UNLABELLED: Project Overview: In April 1990, The University of Michigan Hospitals began a major, multidisciplinary project to standardize care processes in order to increase efficiency and reduce costs while maintaining the quality of clinical care. A team of nurses began the project by developing critical pathways for two neurosurgery procedures--lumbar laminectomy and transphenoidal pituitary tumor resection. The pathways were reviewed by physicians and other staff from other disciplines and were implemented in January of 1991. KEY FINDINGS: Data from the first 14 months show a decrease in patients' average lengths of stay in both the intensive care unit (ICU) and routine care unit. Costs and variance data are being analyzed and further improvements to the pathways are being made. Eleven critical paths are now being used for neurosurgery patients. In retrospect, participants learned that physicians should be involved at the earliest stages of critical pathway development and in the process of implementation.

Academic Medical Centers↗

PubMed1993

Human cartilage aggrecan CS1 region contains cryptic T-cell recognition sites.

Cartilage proteoglycan aggregates (PG) are candidate T-cell autoantigens in the pathogenesis of rheumatoid arthritis (RA). We have investigated the possibility that responses to class II-restricted T-cell recognition sites in human cartilage aggrecan (core protein) may depend upon whether these sites are available as free peptide antigens or as part of intact monomers. Analysis of mouse T-cell responses to intact or deglycosylated monomers, purified from human articular cartilage, and to synthetic peptides of the chondroitin sulphate (CS) attachment region homologous repeat sequence showed that recognition of T-cell epitopes in the CS1 region was strongly dependent upon the form of antigen used. The results show that the CS1 region contains cryptic T-cell recognition sites and raise the possibility that fragments of PG, released through the action of extracellular proteases in inflamed joints, may be capable of activating T cells with specificities for epitopes which are not made available following processing of intact PG. T cells with specificities for cryptic epitopes in PG may play a role in the pathogenesis of RA.

Aggrecans↗

PubMed1992

Charcot-Marie-Tooth neuropathy type 1A mutation: apparent crossovers with D17S122 are due to a duplication.

A locus for the slow conducting form of Charcot-Marie-Tooth neuropathy (CMT1A) was localised to the proximal short arm of chromosome 17, in band p11.2, distal to D17S58. Linkage studies of CMT1A in 3 large Australian families with the marker loci D17S58, D17S71, and D17S57 suggested the order, pter-CMT1A-D17S71-D17S58-centromere-D17S57. However, the estimate of the recombination fraction between CMT1A and D17S122, also assigned to p11.2, was incompatible with known map distances. The impasse was resolved when the D17S122 genotypes were revised to take into account a dosage effect due to a duplication. After correction of the genotypes, the maximum lod score between CMT1A and D17S122 increased from 0.53 at a recombination fraction of 0.3 to 34.28 at zero recombination. This result emphasizes that genotypes for markers in the p12-p11.2 region should be examined very carefully as ignoring the duplication changes the linkage results dramatically. The fact that no crossovers were found between CMT1A and D17S122 suggests that the duplication may cause the disease phenotype.

Charcot-Marie-Tooth Disease↗

PubMed1992

A study of the heterogeneity of the mucoepidermoid tumor and the implication for future therapies.

Mucoepidermoid carcinomas are common head and neck neoplasms whose wide distribution includes the major salivary glands, especially parotid, the minor salivary glands within the oropharynx, sites within the larynx, and the submucosal bronchial glands. These tumors are heterogeneous neoplasms composed of intermediate, squamous, and mucous cell subpopulations and have been traditionally classified as low or high grade based on their histological nature and tendency for invasion and metastasis. To gain a better understanding of the heterogeneity of these tumors, we conducted in-depth studies of the different cellular subpopulations obtained from primary human mucoepidermoid carcinomas from various sites, and a derived cell line grown in monolayer culture and as a nude mouse xenograft. Flow cytometric and clonal dilution studies indicate that the intermediate cell behaves as a reserve cell capable of differentiating into either the squamous cell or mucous cell. Immunocytochemical studies of bromodeoxyuridine uptake and Ki-67 antigen expression indicate that whereas the squamous and mucous cells are terminally differentiated and permanently arrested in G0, the intermediate cell actively enters G1 and S. Studies of invasion utilizing a human amnionic membrane indicate that only the intermediate cell is capable of active invasion. Because the mucous and squamous cells are incapable of further division or invasion, therapeutic strategies aimed at differentiating the intermediate cell in vivo into either mucous or squamous directions would serve as useful adjuncts to surgery by reducing the rate of recurrence and the incidence of metastasis.

Animals↗