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Biomedical subjects

J R Roberts

Publications and source records attributed to J R Roberts.

At least 127 records · Page 7Linked to original sources
PubMed1989

The effect of "superactive" charcoal and magnesium citrate solution on blood ethanol concentrations and area under the curve in humans.

Eleven healthy males between 21 and 37 years of age were enrolled into a non-randomized crossover study comparing superactive charcoal (SAC) given after ethanol administration. After receiving 0.6 gm/kg ethanol orally (95% V/V diluted in orange juice), blood was sampled at 0, 0.5, 1.0, 1.5, 2.0, 3.0, and 4.0 hours. Area under the curve (AUC) was calculated and the highest ethanol level was recorded. After a minimum of 1 week washout, the volunteers ingested an identical ethanol dose but in addition received 60 grams of SAC and 300 ml of 5.8% magnesium citrate solution 1 and 3 hours post ingestion. The data was compared using the paired t-test with p less than 0.05 considered significant. Nine volunteers completed the study. Volunteers had difficulty ingesting the full second 60 gram SAC dose. The AUC (mean 1184 mcg x hr/ml) and highest ethanol concentrations (mean 46.3 mg/dl) for the control group were not significantly greater than in the SAC group (mean AUC 1167 mcg x hr/ml and highest ethanol concentration of 49.0 mg/dl). The ethanol concentration in the SAC group was significantly less than control only at 2.0 hours (31.6 mg/dl vs 36.6 mg/dl, p less than 0.01). The peak ethanol concentration in the SAC group occurred at 1.0 hours in 7 of 9 volunteers, while in the control group, peak concentration occurred randomly between 0.5 and 2.0 hours. We conclude SAC in the dose used is not effective in decreasing AUC, highest ethanol concentration, and blood ethanol levels when given 1 and 3 hours after ethanol ingestion.

Administration, Oral↗
PubMed1989

Renal function in freshwater and chronically saline-stressed male and female Pekin ducks.

Hematocrit (Hct) and plasma ionic and osmotic concentrations were measured in Pekin Ducks, Anas platyrhynchos, drinking freshwater (FW), during rapid acclimation to sea water (RA), and after 6 mo exposure to 180-mM NaCl (SW). Glomerular filtration rate (GFR) and extracellular fluid volume (ECFV) were measured in FW and SW ducks. Estimated renal plasma flow (ERPF) was measured in SW ducks. During RA, Hct and plasma concentration increased significantly (P less than .05) when drinking water sodium concentration ([Na]dw) was 300 mM; body mass decreased (P less than .01) when [Na]dw was 375 mM. The Hct and plasma ionic or osmotic concentrations of FW and SW ducks were the same, except that female SW ducks had lower (P less than .05) plasma chloride concentrations than FW female ducks. Relative to body mass, the FW female duck ECFV (26.88%) was larger (P less than .01) than that of the male (17.50%). The ECFV was not affected by SW in either sex. Mean (+/- SE) GFR determined using inulin and polyethylene glycol (PEG) in the same five FW ducks, were the same, 4.4 +/- .7 and 4.7 +/- .6 mL(min.kg)-1, respectively. In female FW ducks, the GFR (PEG) was 5.00 +/- .30 mL(min.kg)-1, significantly (P less than .001) greater than that of the male, which was 3.07 +/- .21 mL(min.kg)-1. Female and male SW duck GFR were 3.96 +/- .57 and 2.60 +/- .37 mL(min.kg)-1, respectively, but the decrease in GFR was significant (P less than .05) only for females. The GFR were the same, relative to kidney mass, in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1988

Generation and characterization of peptide-specific antibodies that inhibit von Willebrand factor binding to glycoprotein IIb-IIIa without interacting with other adhesive molecules. Selectivity is conferred by Pro1743 and other amino acid residues adjacent to the sequence Arg1744-Gly1745-Asp1746.

We have generated antibodies against a synthetic peptide corresponding to the sequence of human von Willebrand factor (vWF) between residues Glu1737-Ser1750 which includes the Arg-Gly-Asp sequence common to several adhesive molecules. Two anti-peptide antibodies, one polyclonal, and one monoclonal reacted with native vWF and inhibited its binding to platelet glycoprotein (GP) IIb-IIIa, but showed negligible cross-reactivity with fibrinogen, fibronectin, and vitronectin, three other molecules that contain the sequence Arg-Gly-Asp and bind to platelets. The structural bases for the specificity of the two antibodies were evaluated by testing the ability of peptides homologous to the parent sequence, but with single amino acid substitutions, to neutralize the binding of the two antibodies to vWF. The substitution of Pro1743, the residue immediately adjacent to the Arg-Gly-Asp sequence on the amino-terminal side, with Phe resulted in a peptide that failed to interact with either antibody. Thus, Pro1743 is important for maintaining a peptide conformation recognized by two antibodies specific for the GP IIb-IIIa-binding domain of vWF. Other residues important for optimal peptide reactivity with the polyclonal antibody were Ser1742, Arg1744, and Gly1745, whereas Gly1741, Gly1745, and Asp1746, but not Arg1744, were important for reactivity with the monoclonal antibody. The epitopes of both antibodies, therefore, included at least 2 of the residues in the sequence Arg-Gly-Asp considered the common cell-binding site of adhesive molecules that interact with GP IIb-IIIa. Nevertheless, both antibodies reacted only with vWF. These studies demonstrate that peptide-specific antibodies, unlike the promiscuous GP IIb-IIIa receptor, can recognize distinctive structural characteristics of the cell-binding domain of adhesive molecules imposed by residues adjacent to the sequence Arg-Gly-Asp.

Amino Acid Sequence↗
PubMed1988

Hyperthermia, hypertension, hypertonia, and coma in a massive thioridazine overdose.

This report characterizes an atypical presentation of a thioridazine overdose. Clinical manifestations included wide Q.R.S. complex, hyperthermia, hypertension, hypertonia, and coma. Plasma catecholamine levels were markedly elevated. The patient was treated with dantrolene sodium and supportive care. The patient's condition improved over time, with questionable response to dantrolene sodium. Supportive care was the mainstay of treatment.

Acute Disease↗
PubMed1988

Use of abbreviated mental status examination in the initial assessment of overdose patients.

Application of formal mental status testing in the emergency department (ED) to assess cognitive function has been hampered by the lack of a rapidly applied instrument. An Abbreviated Mental Status Examination (AMSE) with 10 test items that can be administered within five minutes by nursing personnel is described. Evaluation of the instrument on 296 ambulatory ED patients with grossly normal neurologic function showed that 93% of patients had a total score of seven or more correct answers and 83% of patients had eight or more correct answers. Application of the AMSE to 375 acute drug overdose patients at the same hospital showed a significant correlation with Glasgow Coma Scale (GCS) score. An AMSE score of seven or less was found to be more sensitive than a GCS score of 13 or less for admission to the intensive care unit (ICU) and complications in the ICU (P less than 0.001). The AMSE score may serve as a useful tool for stratifying cognitive function in acute drug overdose patients and for identifying patients at increased risk for an adverse outcome from their overdose.

Adult↗
PubMed1987

A heparin-binding domain of human von Willebrand factor. Characterization and localization to a tryptic fragment extending from amino acid residue Val-449 to Lys-728.

We have recently shown that the domain of von Willebrand factor (vWF) which interacts with the platelet glycoprotein Ib (GPIb) is located in a 52/48-kDa tryptic fragment of the molecule which begins with amino acid residue Val-449. We have now established that the fragment extends to residue Lys-728 and demonstrate here that a high affinity heparin-binding domain of vWF also lies within this region and in close proximity to that for GPIb. We have used an assay employing heparin coupled to Sepharose CL-6B to show that 125I-vWF binds to heparin in a time-dependent, saturable, and reversible manner. Binding could be completely inhibited by the 52/48-kDa fragment, but was not affected by other tryptic fragments of 55, 41, 13, and 22 kDa. NH2-terminal sequencing of these fragments showed that they were derived from different parts of the molecule, as follows: 13 kDa, Gln290-Thr-Met-Val-Asp-Ser-Ser; 55 kDa, Asn730-Ser-Met-Val-Leu-Asp-Val-Ala-Phe-Val-Leu-Glu; 41 kDa, Thr1352-Val-Gln-Arg-Pro-Gly-Gln-Thr-Cys-Gln-Pro-Ile-Leu-Glu-Glu-Gl n-Cys-Leu-Val ; 22 kDa, Val1927-Thr-Gly-Cys-Pro-Pro. Direct binding of the purified 52/48-kDa fragment to heparin-Sepharose was also shown. Furthermore, crossed immunoelectrophoresis revealed complex formation between the purified 52/48-kDa fragment and free heparin. Twelve monoclonal antibodies to the 52/48-kDa fragment were evaluated for their ability to block binding of 125I-vWF to heparin. With the exception of one weak inhibitor of heparin binding, their relative efficacy in blocking heparin binding was similar to that for blocking ristocetin-induced binding to GPIb. However heparin failed to block ristocetin-independent binding of the 52/48-kDa fragment to GPIb. It is therefore likely that the two binding domains are adjacent to one another, but are not precisely congruent.

Binding Sites↗
PubMed1987

The radiopacity of ingested medications.

We investigated prospectively the radiopacity of 312 pills found on a university hospital formulary by first radiographing them through 15 and 25 cm of water to duplicate the radiodensity of the human body. The pills that were radiodense through water were studied in a human cadaver model, and their densities were quantified by computed tomography (CT). Thirty-five of 312 pills were radiopaque in 15 cm or more of water, and 23 of these pills were radiopaque on a plain radiograph when placed in the stomach of a cadaver. Common mnemonics used to identify radiopaque pills were found to be incomplete and inadequate. Chloral hydrate, iron-containing preparations, calcium carbonate, iodinated compounds, acetazolamide, busulfan, and potassium preparations were consistently radiopaque. Antihistamines, phenothiazines, and tricyclic antidepressants demonstrated varying radiopacity. There was varying radiopacity among the same medications made by different manufacturers. The presence of an enteric coating did not assure that the pill would be radiopaque. Merely radiographing a pill that has been placed on a standard radiograph cassette will make pills that are actually radiolucent in the body appear radiopaque. This test cannot be used to predict radiopacity in vivo. Visibility when radiographed through 15 cm or more of water and a CT radiodensity of more than 1,300 Hounsfield units are predictors of the radiopacity of a pill in the stomach of a cadaver model on a standard KUB radiograph. Variables, such as the size of the patient, the arrangement of pills in the stomach, air contrasting a pill, and the specific composition of the enteric coating or the pillmatrix, affect the radiodensity of pills.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1987

Solid and papillary epithelial neoplasm of the pancreas. An ultrastructural and immunocytochemical study of six cases.

Solid and papillary epithelial neoplasms of the pancreas from six female patients were studied using immunohistochemistry and electron microscopy to define better their histogenesis. The tumors ranged in diameter from 5 to 15 cm (average: 9 cm), and, on cross section, most had areas of hemorrhage and necrosis, sometimes extensive. Microscopically, there was a solid and pseudopapillary pattern, with tumor cells typically having ovoid nuclei with delicate folding and indistinct nucleoli. Of note were the following: a relatively low mitotic rate (range: 0-6/20 hpf), the presence of hyaline globules (four of six cases), and collections of foam cells (three of six cases). Staining for cytoplasmic argyrophil granules was negative in each case. Ultrastructurally, the solid and papillary epithelial neoplasms of the pancreas showed evidence of acinar or ductular differentiation. Two contained zymogen granules, one had intermediate filaments (probably keratin), and three had abundant rough endoplasmic reticulum and mitochondria. Immunostaining was positive for chymotrypsin (six of six cases), trypsin (four of six), and amylase (three of six). None was positive for alpha-1-antitrypsin, neuron-specific enolase, pancreatic polypeptide, gastrin, glucagon, somatostatin, or insulin. The findings support an origin from exocrine pancreas, and follow-up indicates a low rate of malignancy, with local recurrence in two of the six patients.

Adolescent↗
PubMed1987

Cocaine intoxication: hyperpyrexia, rhabdomyolysis and acute renal failure.

Cocaine has become the recreational drug of abuse of the eighties. The prevalence of cocaine has been manifesting increases in intoxications and poisonings. Acute overdoses have been associated with hyperthermia, agitation, paranoid ideation, status epilepticus, ventricular fibrillation, ventricular tachycardia, myocardial infarction, coma, and death. This is the first reported case of cocaine intoxication resulting in severe hyperthermia, bizarre behavior, rhabdomyolysis, and acute renal failure. Treatment consisted of cooling via iced intravenous fluids, nasogastric lavage with ice water, and benzodiazepine sedation. To our knowledge, there is no case report which supports the allusions that cocaine intoxication may cause rhabdomyolysis and acute renal failure.

Acute Kidney Injury↗
PubMed1987

The immunopathology of sequential tumor biopsies in patients treated with interleukin-2. Correlation of response with T-cell infiltration and HLA-DR expression.

Sequential tumor biopsies from 9 patients with disseminated cancers were obtained before, during, and after treatment with interleukin-2 (IL-2) with or without the adoptive transfer of lymphokine-activated killer (LAK) cells. Infiltrating lymphoid and tumor cells were characterized in frozen sections by the use of monoclonal antibodies and the avidin-biotin complex (ABC) immunoperoxidase technique. Five patients had objective tumor regression (1 complete response of a follicular lymphoma, 4 partial responses of melanomas). Four patients (2 melanomas, 1 renal cell carcinoma, 1 breast carcinoma) were nonresponsive after treatment. After treatment, responsive tumors showed a pronounced infiltration of T cells, mainly Leu-2+ (CD8, primarily cytotoxic/suppressor) cells. Macrophages, although increased, were fewer than the T cells, and Leu-7+ or Leu-11+ (NK and K) cells were virtually absent. In nonresponders, there was no significant increase in lymphoid cells after therapy, and no differences were noted between groups before therapy. In 4 of 5 responders, tumor cells were positive for HLA-DR before therapy; and in the remaining responder, the tumor became positive during treatment. Tumor cells in all biopsy specimens from nonresponders were DR- before and after the start of therapy. It is concluded that the expression of HLA-DR by tumor cells may play a role in the response to IL-2 with or without LAK and that marked infiltration by T cells accompanies, and possibly mediates, such a response.

Adult↗
PubMed1986

The von Willebrand factor-binding domain of platelet membrane glycoprotein Ib. Characterization by monoclonal antibodies and partial amino acid sequence analysis of proteolytic fragments.

The glycoprotein Ib (GPIb), a two-chain integral platelet membrane protein, acts as a receptor for von Willebrand factor. In order to obtain information on the domain involved in this function, as well as on the structural organization of GPIb, the protein has been purified and submitted to limited proteolysis using three different enzymes. The resulting fragments were topographically oriented by means of partial NH2-terminal sequence analysis and immunological identification using monoclonal antibodies. One of these antibodies (LJ-Ib1) inhibited the von Willebrand factor-GPIb interaction completely, one (LJ-P3) partially, and one (LJ-Ib10) had no inhibitory effect. Three distinct fragments, the 38-kDa fragment produced by Serratia marcescens protease as well as the 45- and 35-kDa fragments produced by trypsin, had the same NH2 terminus as the intact GPIb alpha-chain (apparent molecular mass = 140 kDa). These fragments and the alpha-chain reacted with the inhibitory antibodies. On the other hand, three fragments produced by Staphylococcus aureus V8 protease, one of 92 kDa similar to the previously described "macroglycopeptide" and two others of 52 and 45 kDa, had NH2-terminal sequences different from that of the GPIb alpha-chain and reacted only with the noninhibitor monoclonal antibody LJIb10. Thus, the binding domain for von Willebrand factor resides near the NH2 terminus of the GPIb alpha-chain, whereas the carbohydrate-rich region is part of the innermost portion of GPIb and does not appear to be involved in the von Willebrand factor binding function.

Amino Acid Sequence↗
PubMed1986

von Willebrand factor. A reduced and alkylated 52/48-kDa fragment beginning at amino acid residue 449 contains the domain interacting with platelet glycoprotein Ib.

We have purified a reduced and alkylated tryptic fragment of von Willebrand factor (vWF) which migrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a 52/48-kDa doublet, but behaved as a single 46-kDa species after partial deglycosylation. After extensive treatment with denaturants, the 52/48-kDa polypeptide retained its ability to inhibit ristocetin-induced platelet aggregation in the presence of native vWF, as well as aggregation induced by desialylated vWF alone. Therefore, the 52/48-kDa polypeptide interacts with the platelet glycoprotein Ib receptor even in the absence of ristocetin. Both the 52/48- and the 46-kDa species inhibited ristocetin-induced binding of the intact molecule to platelets, but did not affect thrombin-induced binding. Determination of the NH2-terminal sequence of both members of the doublet gave identical results: VTLNPSDPEHCQ. This provided additional evidence that differences between the doublet constituents were only of carbohydrate composition and established the position of this peptide within the vWF polypeptide chain of approximately 2050 amino acid residues as beginning with the residue tentatively designated 449. These studies suggest that native conformation is not necessary for binding of vWF to platelets at the glycoprotein Ib receptor and that a linear amino acid sequence following residue 449 defines a domain responsible for this interaction.

Amino Acid Sequence↗
PubMed1986

Sustained-release terbutaline vs sustained-release theophylline in young patients with asthma.

Twenty patients with asthma (mean age, 10.9 +/- 2 years) entered a six-week, randomized, double-blind, crossover comparison of sustained-release (S-R) terbutaline sulfate (Bricanyl Durules) vs S-R theophylline (Theo-Dur). In each two-week study period each patient received S-R theophylline twice daily in doses previously adjusted to give serum theophylline concentrations in the range of 10 to 20 mg/L (56 to 111 mumol/L); or S-R terbutaline sulfate, 5 mg twice daily; or S-R terbutaline sulfate, 7.5 mg twice daily. All treatment regimens produced significant improvement in one or more pulmonary function test values compared with prestudy values. The incidence of acute asthma episodes were similar during each treatment regimen. No clinically significant difference occurred between the regimens for daily symptom scores, peak expiratory flow rates, or use of a terbutaline metered-dose inhaler. At the end of the theophylline treatment period, the mean (+/- SD) theophylline level 12 to 14 hours after the last dose was 10.1 +/- 3.3 mg/L (56 +/- 18 mumol/L); at the end of the terbutaline treatment periods, the mean trough terbutaline levels were 2.22 micrograms/L (9.9 +/- 4.4 nmol/L) (S-R terbutaline sulfate, 5 mg twice daily) and 3.07 micrograms/L (13.7 +/- 5.4 nmol/L) (S-R terbutaline sulfate, 7.5 mg twice daily). Adverse effects, including tremor, occurred with similar frequency during all three drug regimens. Sustained-release formulations of theophylline and terbutaline, in the dosages studied, provided comparable control of asthma symptoms.

Adolescent↗
PubMed1986

Forskolin (cyclic adenosine monophosphate)-dependent protein phosphorylation in isolated gastric glands.

Improved management of peptic ulcer disease requires elucidation of cellular processes underlying gastric secretion. The intracellular execution of regulatory commands to secretory cells involves protein phosphorylation. We studied cyclic adenosine monophosphate (cAMP)-dependent phosphorylation in isolated gastric glands (IGGs) using forskolin, which directly stimulates adenylate cyclase. Forskolin stimulated secretion by both parietal and chief cells. In a separate set of studies, IGGs were incubated for 45, 90, and 105 minutes in modified Ham's F-10 medium containing orthophosphate labeled with phosphorus 32. The forskolin (10(-4) M) was added to some IGG preparations at 90 minutes. The reaction was terminated with sodium dodecyl sulfate and boiling. The proteins were resolved on sodium dodecyl sulfate-polyacrylamide gels, stained with Coomassie blue, and autoradiographed. Incorporation of phosphorus 32 increased progressively at 45, 90, and 105 minutes. Forskolin enhanced phosphorylated bands around 92 kilodaltons. These results are consistent with the major role of cAMP in the regulation of gastric cellular function. The study of cAMP-stimulated phosphorylation may be an important tool in the elucidation of intracellular regulatory mechanisms of gastric secretion. Modulation of these mechanisms may be the ideal therapeutic modality for treatment of acid-secretory disorders.

Aminopyrine↗
PubMed1986

The bodystuffer syndrome: a clandestine form of drug overdose.

The case histories of five people who ingested drugs in an attempt to conceal illegal substances when they were confronted by police are reported. They presented to an emergency department in various clinical states ranging from asymptomatic to comatose. This syndrome has been called "bodystuffing" by the authors, who differentiate it from "bodypacking," which is the ingestion of drugs for the purpose of smuggling. Bodystuffers may ingest one or more drugs, usually deny the ingestion, and are often not discovered until symptoms develop. Bodystuffers tend to be known drug dealers and are often drug abusers themselves. The ingestion is often unsuspected by authorities, but the act may also be witnessed but regarded as trivial. A common scenario is that of a person who is in an asymptomatic state when arrested and is later found comatose in jail. A variant of the syndrome is the ingestion of drugs to produce a medical condition that could defer incarceration.

Adult↗