Search PubMed⌕ Search

Biomedical subjects

J R Roberts

Publications and source records attributed to J R Roberts.

At least 19 recordsLinked to original sources
PubMed1992

Renal function and plasma arginine vasotocin during an acute salt load in feral chickens.

Renal clearance experiments were conducted on feral chickens descended from birds collected from a coral island off the coast of Queensland, Australia. Following a control period when 0.13 M NaCl was used as a vehicle for the renal function markers, a salt load was imposed by infusion of 1 M NaCl. The hypertonic NaCl infusion resulted in increases in glomerular filtration rate (GFR), effective renal blood flow (ERBF), and urine flow rate (V), whereas filtration fraction decreased. Haematocrit was reduced and plasma osmoality, sodium, chloride and potassium concentrations increased. Plasma arginine vasotocin (PAVT) levels increased from 31.4 +/- 2.3 pg.ml-1 during the control infusion to 56.0 +/- 1.7 pg.ml-1 following a salt load of 12 mmol NaCl.kg-1. The sensitivity of release of AVT was 0.69 +/- 0.11 pg.ml-1 per mosmol.kg-1. The concentrations of Na and Cl in urine increased, whereas urine osmolality and potassium concentration decreased. The expansion of the extracellular fluid volume induced by the salt loading would tend to suppress the release of AVT, whereas the osmotic stimulus would provide a stimulus for the release of AVT. In this study, GFR, ERBF and ERPF increased at the same time as PAVT increased.

Animals↗
PubMed1992

Acetyl-coenzyme A synthesis from methyltetrahydrofolate, CO, and coenzyme A by enzymes purified from Clostridium thermoaceticum: attainment of in vivo rates and identification of rate-limiting steps.

Many anaerobic bacteria fix CO2 via the acetyl-coenzyme A (CoA) (Wood) pathway. Carbon monoxide dehydrogenase (CODH), a corrinoid/iron-sulfur protein (C/Fe-SP), methyltransferase (MeTr), and an electron transfer protein such as ferredoxin II play pivotal roles in the conversion of methyltetrahydrofolate (CH3-H4folate), CO, and CoA to acetyl-CoA. In the study reported here, our goals were (i) to optimize the method for determining the activity of the synthesis of acetyl-CoA, (ii) to evaluate how closely the rate of synthesis of acetyl-CoA by purified enzymes approaches the rate at which whole cells synthesize acetate, and (iii) to determine which steps limit the rate of acetyl-CoA synthesis. In this study, CODH, MeTr, C/Fe-SP, and ferredoxin were purified from Clostridium thermoaceticum to apparent homogeneity. We optimized conditions for studying the synthesis of acetyl-CoA and found that when the reaction is dependent upon MeTr, the rate is 5.3 mumol min-1 mg-1 of MeTr. This rate is approximately 10-fold higher than that reported previously and is as fast as that predicted on the basis of the rate of in vivo acetate synthesis. When the reaction is dependent upon CODH, the rate of acetyl-CoA synthesis is approximately 0.82 mumol min-1 mg-1, approximately 10-fold higher than that observed previously; however, it is still lower than the rate of in vivo acetate synthesis. It appears that at least two steps in the overall synthesis of acetyl-CoA from CH3-H4folate, CO, and CoA can be partially rate limiting. At optimal conditions of low pH (approximately 5.8) and low ionic strength, the rate-limiting step involves methylation of CODH by the methylated C/Fe-SP. At higher pH values and/or higher ionic strength, transfer of the methyl group of CH3-H4folate to the C/Fe-SP becomes rate limiting.

Acetyl Coenzyme A↗
PubMed1992

Micropuncture study of avian kidney: effect of prolactin.

Renal function was studied in anesthetized European starlings (Sturnis vulgaris) by micropuncture and clearance techniques. A previous study had shown some changes in the renal function of birds in molt. Endogenous prolactin levels have been shown to be elevated at this time. In the present study, renal function was studied during the infusion of an isotonic sodium chloride solution and then when ovine prolactin was added to the infusion. Ovine prolactin resulted in an elevation of plasma urate concentration but had no significant effects on other plasma parameters or on the concentration of the various ions in tubular fluid samples. Urine flow rate was significantly higher during prolactin infusion, although whole animal glomerular filtration rate, single nephron glomerular filtration rate, and the percentage fluid reabsorption in the proximal tubule (up to the point of micropuncture) were unaltered. The whole animal fractional excretions of sodium and chloride were significantly higher, those of magnesium and potassium were significantly lower, and the fractional excretion of phosphate tended to be lower during prolactin infusion. At the level of the proximal tubules of the reptilian-type nephrons, prolactin infusion caused a slight reduction in the net reabsorption of sodium and chloride. Therefore the main effects of prolactin on renal function are occurring in the distal nephron of the reptilian-type nephrons or in the mammalian-type nephrons. It appears that prolactin may affect renal function in avian species and that these actions may be modulated by a range of factors as has been demonstrated in mammals.

Absorption↗
PubMed1991

Multiple cranial nerve deficits after ethylene glycol poisoning.

We report the cases of two patients who developed cranial nerve palsies after drinking ethylene glycol. A 33-year-old man developed multiple cranial nerve deficits nine days after the ingestion of ethylene glycol in a suicide attempt. Clinical findings included profound bilateral cranial nerve VII palsies and severe dysfunction of cranial nerves IX and X. The neuropathy occurred despite treatment with hemodialysis. The dysphagia completely cleared within two weeks, but at six months a severe bilateral cranial nerve VII dysfunction persisted. A 22-year-old man undergoing hemodialysis for ethylene glycol-induced renal failure developed bilateral cranial nerve VII dysfunction 14 days after ingestion. At a three-month follow-up, the patient demonstrated only moderate functional recovery. The etiology of the cranial nerve deficits is unknown but may be related to oxalate crystal deposition of ethylene glycol-induced pyridoxine dysfunction.

Adult↗
PubMed1991

Clinical characteristics of angiotensin-converting enzyme inhibitor-induced angioedema.

We present the cases of two patients with angiotensin-converting enzyme (ACE) inhibitor-induced angioedema that required intubation for life-threatening airway compromise. This side effect has been previously reported with all ACE inhibitors, but its incidence and potential for a fatal outcome may not be fully appreciated. A review of the literature reveals 227 reports of this reaction with an overall incidence of approximately 0.1% to 0.2%. The etiology is nonimmunogenic and thought to be related to accentuated bradykinin activity. There is no clinical profile that identifies patients at increased risk for this side effect. There are unique clinical characteristics to this idiosyncratic reaction: angioedema may suddenly occur even though the drug has been well tolerated for months or years; symptoms may regress spontaneously while the patient continues the medication, erroneously prompting an alternative diagnosis; the pathology has a special predilection for the tongue, a circumstance that renders orotracheal and nasotracheal intubation difficult; symptoms may progress rapidly despite aggressive medical therapy, necessitating emergency airway procedures; and a rebound phenomenon following successful medical therapy has been described. We recommend intensive medical treatment before angioedema is severe enough to thwart standard methods to ensure a protected airway. Once even minor angioedema is attributed to an ACE inhibitor, an alternative class of antihypertensive medication should be chosen. Individuals with a history of idiopathic angioedema probably should not be given ACE inhibitors.

Angioedema↗
PubMed1991

Plasma catecholamine levels in cyclic antidepressant overdose.

Cyclic antidepressant overdose is a major cause of morbidity and mortality in self-poisoned patients. The major cause of mortality with cyclic antidepressant overdose is cardiotoxicity. We determined plasma catecholamine levels in 41 symptomatic acute overdose patients to identify interactions between QRS duration (a marker for cardiotoxicity) and a presumed hyper-adrenergic state. Using a linear multivariable regression analysis, QRS duration correlated with the presence of cyclic antidepressant, plasma norepinephrine levels, the ratio of norepinephrine to epinephrine level, and pulse rate (p less than 0.001, r2 = 0.42). Commensurate physiologic changes were not found in the presence of elevated catecholamine levels in the cyclic antidepressant overdose group. One possible explanation for the blunted systemic response to the elevated catecholamine levels is adrenergic desensitization. Investigation of serial catecholamine levels during cyclic antidepressant overdose may lead to modification of our current theories of cardiotoxicity and therapy.

Adolescent↗
PubMed1990

Development of polyploidization in taxol-resistant human leukemia cells in vitro.

The effects of taxol on antitubulin immunofluorescent staining patterns, cellular DNA content, and labeling with [3H]thymidine were measured for the taxol-sensitive HL60 and taxol-resistant K562 cell lines after exposures for 0, 4, 12, and 24 h. Taxol caused a relative increase in the fraction of 4C interphase and metaphase cells in both lines although the 4C interphase accumulation was greater for the resistant K562 line. Of the cells with S-phase DNA content, taxol-treated HL60 cells were less likely to incorporate [3H]thymidine than taxol-treated K562 cells. However, a decrease in percentage of S-phase labeling for both lines relative to control cells was seen. Finally, taxol induced the development of polyploid cells (cells with DNA contents greater than that of the 4C G2-M peak) in the relatively taxol-resistant K562 cells, an effect not seen in the relatively taxol-sensitive HL60 line. After 24 h of taxol exposure 70% of all K562 cells were polyploid while only 8% of the HL60 cells were polyploid. The capacity of K562 cells to generate polyploidy in response to taxol correlated with taxol resistance by previous assay and may be a useful indicator of drug resistance.

Alkaloids↗
PubMed1990

Multiple epitope specificity of monoclonal antibodies to a single synthetic peptide: use in the characterization of the GP IIb-IIIa binding domain of von Willebrand factor.

Monoclonal antibodies have been induced against the synthetic peptide with sequence Tyr-Glu-Val-Val-Thr-Gly-Ser-Pro-Arg-Gly-Asp-Ser-Gln-Ser-Ser. This peptide represents residues Glu1737-Ser1750 of the mature von Willebrand factor (vWF) subunit and contains the sequence Arg-Gly-Asp, thought to be important in mediating binding to the platelet receptor glycoprotein (GP) IIb-IIIa complex. Twelve antibodies were obtained, eight of which bound to native vWF as well as to the peptide immunogen insolubilized onto agarose beads. These antibodies defined at least three distinct epitopes, as demonstrated by antibody interaction with peptides having a single phenylalanine substitution at each position in the sequence. In particular, two antibodies bound to epitopes on vWF that included one or more of the three residues (arginine, glycine, aspartic acid) thought to be involved in binding to GP IIb-IIIa, whereas one antibody bound to an epitope that did not include any of those residues. Nevertheless, the three antibodies cross-reacted with each other, a finding explained by the fact that the corresponding epitopes had at least two residues in common, namely Gly1741 and Ser1742. In spite of the cross-reactivity for binding to vWF, only the two antibodies whose epitopes included residues in the Arg-Gly-Asp sequence inhibited vWF interaction with GP IIb-IIIa. The third antibody had no inhibitory effect even though it was bound to an epitope located at a distance of only few residues on the amino terminal side of Arg-Gly-Asp. These results demonstrate that monoclonal antibodies raised against a single synthetic peptide with sequence limited to fifteen residues may exhibit distinct epitope specificity and may be used to define functional domains in macromolecules with a high degree of resolution.

Amino Acid Sequence↗
PubMed1990

Collecting duct carcinoma of the kidney.

Collecting duct carcinoma is an unusual variant of renal cell carcinoma, whose appearance and behavior are not well established. We identified six cases of collecting duct carcinoma in our files. The clinical, pathologic, and immunohistochemical characteristics of these tumors are reported. The most common symptom was gross hematuria (four cases). Two patients had cervical adenopathy due to metastatic tumor. Four rapidly developed systemic metastases and died within 4 to 24 months. The primary renal tumors were located predominantly in the renal medulla and pelvis and had a partially cystic white-gray appearance. Histologic examination showed prominent tubulopapillary structures, nests of clear cells, and infiltrating tubules in a dense desmoplastic stroma. Atypical hyperplastic changes were found in some of the adjacent collecting ducts. Mucicarminophilic material was present in glandular elements in all six cases. Immunohistochemical studies revealed positivity with antibodies to epithelial membrane antigen, keratins, peanut agglutinin, vimentin, Leu M1 and lysozyme. The location of this tumor in the medulla, its distinctive histologic appearance, mucin positivity, expression of high molecular weight cytokeratins, and peanut agglutinin suggest that this is a distinct clinicopathologic entity which has an aggressive clinical course.

Adult↗
PubMed1990

Prospective evaluation of gastric emptying in the self-poisoned patient.

The authors prospectively studied the effect of gastric emptying (GE) and activated charcoal (AC) upon clinical outcome in acutely self-poisoned patients. Presumed overdose patients (n = 808) were treated using an alternate day protocol based on a 10-question cognitive function examination and presenting vital sign parameters. Asymptomatic patients (n = 451) did not receive GE. AC was administered to asymptomatic patients only on even days. GE in the remaining symptomatic patients (n = 357) was performed only on even days. On emptying days, alert patients had ipecac-induced emesis while obtunded patients received gastric lavage. AC therapy followed gastric emptying. On nonemptying days, symptomatic patients were treated only with AC. No clinical deterioration occurred in the asymptomatic patients treated without GE. AC use did not alter outcome measures in asymptomatic patients. GE procedures in symptomatic patients did not significantly alter the length of stay in the emergency department, mean length of time intubated, or mean length of stay in the intensive care unit. Gastric lavage was associated with a higher prevalence of medical intensive care unit admissions (P = .0001) and aspiration pneumonia (P = .0001). The data support the management of selected acute overdose patients without GE and fail to show a benefit from AC in asymptomatic overdose patients.

Adolescent↗
PubMed1990

The Syme amputation: success in elderly diabetic patients with palpable ankle pulses.

The Syme amputation is an old operation that has been used during this century primarily as a means of treating traumatic injuries to the forefoot in military patients. In 1984 we made a deliberate attempt to perform the operation in a highly selective group of dysvascular patients with forefoot necrosis who happened to have a palpable posterior tibial pulse. We reviewed the charts of 26 patients who underwent a one-stage (3 patients) or two-stage (23 patients) Syme amputation. The mean age was 60 years, (range 32 to 74 years). There were 17 insulin-dependent diabetic patients, and 3 diet-controlled diabetic patients. Twenty-two patients (85%) had a palpable posterior tibial pulse before surgery. Fourteen patients (54%) underwent a preliminary Ray (4) or transmetatarsal (10) amputation to rid the forefoot of an active infection. Overall, 20 patients (77%) had successful Syme amputations. Nineteen of 22 patients (85%) with a palpable posterior tibial pulse had a successful amputation in contrast to one out of four patients (25%) who did not have a palpable pulse before surgery (p = 0.04). The mean follow-up of all patients was 23 months. The durability of the operation was demonstrated in finding that only one patient in 20 initially successful Syme amputations required revision to the below-knee level. The two-stage Syme amputation can be a very gratifying operation with success rates approaching 85%, even if offered to elderly diabetic patients. The single most important feature for success is to limit the operation to those patients with a palpable posterior tibial pulse before operation.

Amputation, Surgical↗
PubMed1990

Changes in blood pressure during isometric contractions to fatigue in the cat after brain stem lesions: effects of clonidine.

STUDY OBJECTIVE: The aim was to determine whether areas in the periaqueductal grey matter, medial dorsal raphe, or ventrolateral medulla might be involved with the integration of blood pressure and heart rate during isometric exercise. DESIGN: Cats were anaesthetised with alpha chloralose (75 mg.kg-1) and catheters inserted into the right jugular vein and carotid artery. Isometric contractions were generated using a microprocessor controlled stimulator and sleeve electrode around the tibial nerve. Bilateral lesions were made in the dorsal periaqueductal grey matter (P1.0, LR2.0, HD + 1.5 mm) or two sites in the ventrolateral medulla (P12.0, RL 2.0, HD -10 mm; or P12.0, RL 2.0, HD -8.5 mm). Lesions were also made in the medial dorsal raphé nuclei (P1.0, RL 0.0, HD +1.5 mm). Clonidine was injected into the cerebral aqueduct to determine whether it would exert an antipressor effect during muscle contraction after the lesions were made. Only one site of lesion was made in a group of animals. Bilateral injections of clonidine (250 ng in 0.5 microliter) were made into the intact ventrolateral medulla (P11.5, RL 4.0, HD -8.5 mm) to explore its role further. Fatiguing contractions were performed before and after the lesions were made, or clonidine was injected, and changes in arterial blood pressure and heart rate were measured. Verification of the lesion sites or the microinjection sites, and the extent of the lesion or spread of the clonidine, was made from histological examination of brain tissue after each experiment. EXPERIMENTAL MATERIAL: Adult cats of either sex, n = 20, weight 2.4 (SD 0.4) kg, were used. MEASUREMENTS AND MAIN RESULTS: Fatiguing isometric contractions in control conditions caused mean arterial pressure to increase by 45-50 mm Hg and heart rates by 20-25 beats.min-1. Bilateral lesions in the dorsal periaqueductal grey matter did not alter resting mean arterial pressure but attenuated the pressor response during contractions. Injections of clonidine into the cerebral aqueduct had no further antipressor effects after the lesions. Lesions of the medial dorsal raphé nuclei or injections of clonidine into the intact medial dorsal raphé nuclei did not affect the pressor response to fatiguing isometric contractions. Injections of clonidine into the intact ventrolateral medulla eliminated the pressor response to isometric contractions. Bilateral lesions of the ventrolateral medulla near the rostral lateral border of the inferior olivary tract nuclei (P12.0, LR 2.0, HD -10 mm) also attenuated the muscle pressor response, while subsequent injections of clonidine into the cerebral aqueduct depressed the changes in blood pressure further. CONCLUSIONS: Ergoreceptor information may be processed through the periaqueductal grey matter through the ventrolateral medulla to control arterial blood pressure during isometric exercise to fatigue.

Animals↗
PubMed1990

Micropuncture study of the avian kidney: infusion of mannitol or sodium chloride.

Renal function was studied in anesthetized starlings by micropuncture and clearance techniques. The effects of intravenous infusions of isosmotic sodium chloride and hyposmotic mannitol solutions were compared. In the proximal tubules of the superficial reptilian-type nephrons, there is net reabsorption of sodium, chloride, and potassium; net secretion of calcium and urate; and either net secretion or no net secretion or reabsorption of magnesium and phosphate. The fractional delivery of ions and urate to the site of micropuncture, the percent of fluid reabsorbed, and the single nephron glomerular filtration rate (SNGFR) were not significantly different between the two infusion treatments. However, in the sodium chloride-infused birds, whole kidney GFR and the fractional excretion of sodium and chloride by the whole animal were higher, and fractional excretion of magnesium and potassium were lower. The data for each infusion group were further subdivided on the basis of whether the birds were in molt. In starlings, molt is associated with elevated levels of plasma prolactin. For the sodium chloride infusion, sodium and water reabsorption to the site of micropuncture was greater in the birds in molt than in those not in molt.

Animals↗