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P Jones

Publications and source records attributed to P Jones.

At least 343 records · Page 19Linked to original sources
PubMed1990

Cyclosporine-induced changes in glomerular filtration rate and urea excretion.

PURPOSE: Cyclosporine is the mainstay of many immunosuppressant protocols, but confers a significant risk of nephrotoxicity. We sought to clarify the effects of cyclosporine on renal function in renal transplant recipients after induction of mild intravascular volume depletion. PATIENTS AND METHODS: Two groups of renal transplant patients with normal allograft function at least 6 months after transplantation whose immunosuppressive regimens differed only by the presence or absence of cyclosporine usage were enrolled in a 10-day in-hospital protocol. After a 3-day control period, intravascular volume depletion was produced by dietary restriction of sodium chloride for 4 days and the administration of furosemide. Creatinine and urea clearances, true glomerular filtration rate (GFR) (by radioisotope technique), and the fractional excretion of sodium were measured. The patients were subsequently given a high amount of sodium chloride by intravenous infusion (3.8 mEq/kg body weight/day) for 3 days and the studies were repeated. RESULTS: Ten patients treated with azathioprine and prednisone (azathioprine-treated) and nine patients treated with cyclosporine, azathioprine, and prednisone (cyclosporine-treated) were enrolled. The two groups developed a similar degree of intravascular volume depletion; blood pressure did not change and urine flow rates did not differ between the groups throughout the protocol. The cyclosporine-treated patients showed significant decreases in GFR, creatinine clearance, and urea clearance, and increases in blood urea nitrogen (BUN) and percent urea reabsorption after intravascular volume depletion; these findings resolved after challenge with the sodium chloride load. In contrast, the azathioprine-treated patients' BUN, urea clearance, GFR, and creatinine clearance did not significantly change throughout the protocol. The decrease in the fractional excretion of sodium after intravascular volume depletion was significantly greater in the cyclosporine-treated patients. CONCLUSION: Cyclosporine predisposes to acute reversible nephrotoxicity by compromising the renal compensatory mechanisms. Proximal tubular function, as manifested by urea and sodium reabsorption, remains intact.

Adult↗
PubMed1990

Comparison and evaluation of a disease activity index for use in patients with rheumatoid arthritis.

An algorithm (Stoke index) has been designed to give a global measure of disease activity in rheumatoid arthritis. This algorithm has been created as an easy to use flow diagram based on two objective laboratory measures (C-reactive protein and erythrocyte sedimentation rate), one subjective and two semi-objective clinical measures (morning stiffness, synovitis score and Ritchie articular index). Results of six clinical markers and seven laboratory markers of disease activity on a cohort of 371 rheumatoid patients have been used to evaluate the algorithm and compare it with a previously described index of disease activity (Mallya-Mace index). Principal component analysis validates its ability to measure disease activity. Sensitivity is described by the distribution of patients between the two index scores. Change in index score by patients over a 6-month period indicates reversibility. The Stoke index demonstrates greater sensitivity and reversibility than the Mallya-Mace index. These findings indicate that the algorithm described provides a useful index of global disease activity for use in the assessment of rheumatoid arthritis.

Adult↗
PubMed1990

Absence of effect of dipyridamole on renal and platelet function in diabetes mellitus.

We evaluated the effect of dipyridamole (5 mg/kg/day) for 12 months on renal and platelet function in 53 children with insulin dependent diabetes mellitus (IDDM) in a prospective double blind placebo controlled trial. Urine albumin excretion (expressed as the geometric mean albumin to creatinine concentration ratio (UA/UC) was measured every three months throughout the study. At 12 months, the geometric mean UA/UC was no different in diabetic children receiving dipyridamole, 0.60 mg/mmol, when compared with those receiving placebo, 0.87 mg/mmol. Glomerular filtration rate, urinary excretion of retinol binding protein, and N-acetyl-beta-D-glucosaminidase (NAG), blood pressure, and spontaneous platelet aggregation in response to stirring whole blood did not differ between the two groups at 12 months. Subgroup analysis to include only those children with high UA/UC before entry into the study also failed to show an effect of the drug on UA/UC. Eleven children had either persistently high UA/UC (n = 8: four on dipyridamole, four on placebo) or progression to high UA/UC (n = 3: two on dipyridamole, one on placebo). These children had significantly higher urinary excretion of retinol binding protein and NAG, bigger kidneys, and higher diastolic blood pressure both before and after treatment than the remaining 42 children, whereas there was no difference in spontaneous platelet aggregation between the two groups. These observations on the associations between UA/UC and other parameters of renal function suggest that measurement of 'tubular' proteins and diastolic blood pressure as well as UA/UC may contribute to the identification of those at risk of developing nephropathy.

Adolescent↗
PubMed1990

[Pulpectomy. Why? When?].

There are many circumstances under which the condition of the pulp calls for root canal work, due to the real or potential risk of pain, infection, inflammation or functional difficulties (acute, irreversible pulpitis, chronic pulpitic conditions, necrosis and its consequences, etc.). Other circumstances exist in which injury to the pulp is not necessarily irreversible: initial pulpitis, iatrogenic fracture of the pulp, traumatisms, dystrophic deteriorations. The high success rate for endodontic therapy could argue for elimination of impaired or necrose-prone pulp. In fact, however, unsuccessful pulpectomies often lead to loss of the dental organ and successful endodontic treatment severely weakens the whole tooth structure and often implies prosthetic restoration, with the consequent increase in tissular loss. In order to preserve pulp and crown tissues, pulpal vitality should be protected in all cases where such conservative efforts do not worsen the prognosis for maintaining the tooth on its arch or jeopardize a planned restoration. Solutions are presented for various types of situations, according to the risks encountered.

Contraindications↗
PubMed1990

Lipid peroxidation and expression of copper-zinc and manganese superoxide dismutase in lungs of premature infants with hyaline membrane disease and bronchopulmonary dysplasia.

The putative involvement of reactive oxygen species in the etiology of lung damage in infants receiving mechanical ventilation has been examined by comparing the levels of peroxidation and expression of the antioxidant enzymes, CuZn and Mn superoxide dismutase, in lungs from control and affected infants as well as from fetuses and infants who died postnatally after term delivery. Mean levels (+/- SD) of lung peroxidation, determined with a thiobarbituric acid method, were similar in affected and control premature neonates and in fetal subjects (1.87 +/- 1.26, 1.92 +/- 2.07, and 1.19 +/- 1.36 nmol/mg protein, respectively). Expression of CuZn and Mn superoxide dismutases was also similar in these subjects and in the patients who died postnatally. Thus activity measurements and immunoblotting studies showed continuous expression of these enzymes throughout development with no apparent change in protein levels or size. Immunohistochemical examination of lung tissue showed expression of CuZn and Mn superoxide dismutases in epithelial, smooth muscle, endothelial, and some mesenchyme components. In patients with bronchopulmonary dysplasia, alveolar walls were thickened by an excess of fibrous tissue and terminal air spaces were lined mainly by type II pneumatocytes. All structures, including abnormal fibrous components, were positive for both CuZn and Mn superoxide dismutase. Our data show that, unlike some experimental animals, expression of at least these antioxidant enzymes in human infants born prematurely is similar to that in adults, and indicate that such infants are better adapted for life in an oxygen-containing environment than previously suspected.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchopulmonary Dysplasia↗
PubMed1989

The development expression of alpha-, mu- and pi-class glutathione S-transferases in human liver.

The developmental expression of the alpha, mu and pi class glutathione S-transferases has been defined in human liver using radioimmunoassay and immunohistochemistry. Expression of alpha and mu class isoenzymes increased significantly at birth, while that of the pi isoenzyme declined during the first trimester. Mu-class isoenzymes (GST1 1, GST1 2, GST1 2-1) were expressed in hepatocytes but not in other liver cell types.

Aging↗
PubMed1989

Primary sequence and domain structure of chicken vinculin.

We have determined the complete sequence of chick vinculin from two overlapping cDNA clones. The vinculin mRNA consists of 262 bp of 5' untranslated sequence, an open reading frame of 3195 bp (excluding the initiation codon) and a long 3' untranslated sequence (greater than 2 kb). Chick vinculin contains 1066 amino acid residues, and has a deduced molecular mass of 116,933 Da. Analysis of the domain structure of vinculin shows that the molecule can be cleaved by V8 proteinase into a 90 kDa globular head and a 32 kDa tail region, the latter of which could further be cleaved into a 27 kDa polypeptide. The 90 kDa globular head contains the N-terminus of vinculin, three 112-residue repeats (residues 259-589), and extends to approximately residue 850. Gel overlay experiments show that it also contains a binding site for the cytoskeletal protein talin. The talin-binding domain was further localized to the N-terminal 398 amino acid residues of the protein by expression in vitro of this region from a vinculin cDNA cloned into the Bluescript SK+ vector. The head and tail domains are apparently separated by a proline-rich region that contains V8-proteinase-cleavage sites and a candidate tyrosine (822)-phosphorylation site. Secondary-structure prediction suggests that the head and tail domains contain alpha-helical regions separated by short stretches of turn/coil. Comparison of the chick with a partial human sequence reveals that vinculin is a highly conserved protein. In chickens Southern-blot analysis is consistent with a single vinculin gene, and it is therefore likely that vinculin, and its higher-molecular-mass isoform termed metavinculin, arise through alternative splicing.

Amino Acid Sequence↗
PubMed1989

A simple method for elution of IgA deposits from the skin of patients with dermatitis herpetiformis.

To better understand the role of autoimmunity in the pathogenesis of dermatitis herpetiformis, linear IgA bullous dermatosis or other skin disorders, the antigenic specificity of the immune reactants bound in vivo in the skin must be identified. In order to do so, one must first be able to elute these immune reactants from the skin. We describe here a simple method of eluting not only specifically bound IgG, but also IgA and other immunoglobulins and complement components from skin biopsy material. The method involves cutaneous washing of the entrapped serum proteins in PBS pH 7 and pH 5 buffers followed by specific immunoglobulin elutions at pH 3 and 2. The IgA deposits which could not be removed by this treatment were eluted by a combination of low pH (0.5 M citrate pH 2) and a chaotropic agent (2 M NaCl). The relative concentration of IgA in eluates when quantitated by fluoroimmunoassay were three- to five-fold higher in dermatitis herpetiformis skin biopsy specimens, than in eluates of bullous pemphigoid or normal skin biopsy specimens.

Buffers↗
PubMed1989

Zidovudine: experience at the Newcastle Haemophilia Centre.

Zidovudine was first prescribed for patients from the anti-human immunodeficiency virus (HIV) positive cohort of haemophiliacs in Newcastle in May 1987. Prior to this therapy, seven patients had died of acquired immune deficiency syndrome, and episodes of serious opportunistic infection were common. To date, 22 patients have received zidovudine, seven with or without acyclovir in a prospective Wellcome trial. Of the 22 patients, three were children and one was an adult female. All haemophilic patients were infected around 1982 as a result of factor VIII concentrate contamination with HIV. There have been five deaths, two occurring within 6 weeks of the start of zidovudine therapy. A third death was due to myocardial infarction in week 45. The other two deaths occurred at 41 weeks and 47 weeks in transfusion dependent patients. Only three serious opportunistic infections (pneumocystis pneumonia) have been observed in the remaining patients, one within a week of starting therapy and one in a non-compliant patient at week 24. The latter patients had a further episode of Pneumocystis carinii pneumonia in week 51. The transfusion dependent patients who died presented with anaemia at weeks 5 and 13, and required 48 and 28 units of packed cells respectively. A further patient required a single transfusion at week 7 and at week 43 continues to maintain an acceptable haemoglobin level.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Identification of a talin binding site in the cytoskeletal protein vinculin.

Binding of the cytoskeletal protein vinculin to talin is one of a number of interactions involved in linking F-actin to cell-matrix junctions. To identify the talin binding domain in vinculin, we expressed the NH2-terminal region of the molecule encoded by two closely similar, but distinct vinculin cDNAs, using an in vitro transcription translation system. The 5' Eco RI-Bam HI fragment of a partial 2.89-kb vinculin cDNA encodes a 45-kD polypeptide containing the first 398 amino acids of the molecule. The equivalent restriction enzyme fragment of a second vinculin cDNA (cVin5) lacks nucleotides 746-867, and encodes a 41-kD polypeptide missing amino acids 167-207. The radiolabeled 45-kD vinculin polypeptide bound to microtiter wells coated with talin, but not BSA, and binding was inhibited by unlabeled vinculin. In contrast, the 41-kD vinculin polypeptide was devoid of talin binding activity. The role of residues 167-207 in talin binding was further analyzed by making a series of deletions spanning this region, each deletion of seven amino acids contiguous with the next. Loss of residues 167-173, 174-180, 181-187, 188-194, or 195-201 resulted in a marked reduction in talin binding activity, although loss of residues 202-208 had much less effect. When the 45-kD vinculin polypeptide was expressed in Cos cells, it localized to cell matrix junctions, whereas the 41-kD polypeptide, lacking residues 167-207, was unable to do so. Interestingly, some deletion mutants with reduced ability to bind talin in vitro, were still able to localize to cell matrix junctions.

Amino Acid Sequence↗
PubMed1989

Combination therapy with gold and hydroxychloroquine in rheumatoid arthritis: a prospective, randomized, placebo-controlled study.

We studied combination therapy with two slow-acting antirheumatic drugs given concurrently in active rheumatoid arthritis (RA). A 12-month prospective randomized controlled trial compared gold and hydroxychloroquine in 52 patients to gold and placebo in 49. The patients continued to receive non-steroidal anti-inflammatory drugs and analgesics. They were selected from three rheumatology centres in the West Midlands. Combination therapy led to a greater number of withdrawals due to adverse reactions (18 cases compared to 10 receiving gold/placebo). Patients completing 12 months' therapy (27 taking gold/hydroxychloroquine and 32 on gold/placebo) were compared using five clinical, seven laboratory, and one radiological measure. All 13 variables favoured gold/hydroxychloroquine with an overall advantage of 20-25% for the combination. This only reached statistical significance (at the 1% level) for C-reactive protein. An overall disease activity index was better at 12 months (at the 5% level) and showed a more rapid response with gold/hydroxychloroquine. This is the first randomized prospective placebo-controlled trial to show a significant advantage from a combination of two slow-acting drugs. There are many different ways of giving such combinations and we consider these should be explored to maximize the effectiveness of treatment for RA.

Adult↗
PubMed1989

North Staffordshire/Wigan assisted delivery trial.

In a trial conducted at the North Staffordshire and Billinge Maternity Hospitals (NSMH and BMH) a total of 264 women who required an assisted delivery in the second stage of labour were randomly assigned to be delivered either by Kobayashi silicone cup ventouse or by forceps. A larger proportion (90%) of those assigned to the forceps group were actually delivered by the allocated instrument compared to those in the silicone cup group (73%). However, there was a significantly higher rate of maternal morbidity in terms of perineal trauma and discomfort in the forceps group. No differences in neonatal morbidity were detected.

Adult↗