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Biomedical subjects

R Lawrence

Publications and source records attributed to R Lawrence.

At least 91 records · Page 5Linked to original sources

Brugia pahangi infections in immune-compromised rats demonstrate that separate mechanisms control adult worm and microfilarial numbers.

The immunological basis of resistance to Brugia pahangi infection in rats was studied. Infections were investigated in athymic rnu/rnu rats and in rats treated with the immuno-suppressive agents cyclosporin A (CsA) or cyclophosphamide (Cy). The recovery of adult worms in normal rats was 1-2% in comparison to 12.2% recovery in athymic rats. CsA and Cy treated rats did not have increased adult worm burdens. Microfilarial (Mf) levels (expressed as Mf per ml per adult worm) were highly elevated in both athymic and Cy treated rats but not in CsA treated rats. IgG and IgM levels to B. pahangi antigens were severely depressed in both athymic and Cy treated rats. IgG levels but not IgM levels were abrogated in CsA treated rats. These results implied that control of larval establishment or adult killing, and regulation of Mf levels are separate T-cell dependent mechanisms and act independently of IgG antibody. Control of Mf levels is associated with a specific IgM response which is Cy sensitive but CsA resistant.

Animals↗

Anti-lymphocyte, anti-monocyte, and anti-endothelial cell antibodies in chronic haemodialysis patients.

Patients receiving chronic haemodialysis treatment are known to have a high prevalence of anti-panel antibodies (anti-lymphocyte, anti-monocyte, and anti-endothelial cell) originating from a number of different possible sensitizing events such as blood transfusions, multiparity, or renal transplantation. In this study the prevalence of these antibodies in 123 chronic haemodialysis patients was evaluated. Anti-lymphocyte antibodies and anti-monocyte antibodies were found in 27.6% and 21.9% of the patient group respectively. Following exclusion of twelve patients within the study population with a history of previous graft rejection, anti-monocyte antibodies were encountered more frequently in transfused patients than those never having been transfused (22.4% versus 0%, P less than 0.05), whilst the prevalence of anti-lymphocyte antibodies was similar in both groups (28.2% versus 19.2%). Multiparity, patient age, or duration of dialysis treatment could not be demonstrated to significantly alter the prevalence of either of these antibodies. Of 12 patients with an episode of previous graft rejection, eight were positive for anti-monocyte antibodies and five for anti-lymphocyte antibodies. Anti-endothelial cell antibodies were common in patients in this group, being present in seven of eight individuals investigated.

Adolescent↗

Delayed recognition of human immunodeficiency virus infection in preadolescent children.

Thirty-two (18%) of 181 children cared for at our institution who were infected with the human immunodeficiency virus type 1 (HIV-1) were first seen, and HIV was diagnosed, when they were 4 years of age and older. Initial complaints or diagnoses for these children included the following: hematologic disorders (5) (3 idiopathic thrombocytopenic purpura, 1 neutropenia, 1 anemia); recurrent bacterial infections (10); Pneumocystis carinii pneumonia (3); developmental delay (1); skin disorders (2) (1 genital wart, 1 chronic zoster); weight loss (3); malignancy (1); and nephropathy (1). Eight children were referred for evaluation because of maternal HIV-1 infection. The risk factors for HIV-1 infection included maternal/perinatal exposure (22), perinatal blood transfusion (6), blood transfusion during infancy (2), and sexual abuse (2). Ten (31%) of the 32 children have subsequently died. The longest survival from perinatal infection was 12 years. HIV-1 infection in children can result in a prolonged clinical latency and can masquerade as other pathologic conditions. The absence of clinical symptoms in older children at risk for HIV-1 infection should not deter HIV testing.

Child↗

Thrombocytopenia in children infected with human immunodeficiency virus: long-term follow-up and therapeutic considerations.

Among 180 children infected with human immunodeficiency virus (HIV-1), 14 (8%) developed thrombocytopenia during the course of the disease and have been followed for an average period of 18.8 months. Eight of 14 patients had clinical signs of bleeding. Increased levels of anti-platelet IgG antibodies were detected in 86% of patients tested and did not correlate with severity of disease. Eight patients were treated initially with intravenous immunoglobulins (IVIG) and responded with a transient increase in the platelet count of at least 30 x 10(9)/L. Sustained remission could not be achieved in the patients treated with IVIG alone. Corticosteroids were used in 6 patients who became refractory to IVIG and resulted in sustained remission in only one patient. Spontaneous remission of thrombocytopenia occurred in one patient. Ten patients were treated with zidovudine (ZVD) for a period of 3-20 months. Sustained improvement in the platelet counts occurred in only three of the children treated with ZVD.

Acquired Immunodeficiency Syndrome↗

Concerted modulation of alpha 1(XI) and alpha 2(V) collagen mRNAs in bovine vascular smooth muscle cells.

We have isolated a partial cDNA for alpha 1(XI) collagen from a bovine smooth muscle cell (SMC) library. Previously, this collagen was not known to be expressed in SMCs. Comparison of the nucleotide and deduced amino acid sequence of the 2.7-kilobase bovine clone and the human alpha 1(XI) sequence indicates 92 and 98% homology, respectively. Bovine SMCs in culture were found to produce alpha 1(XI) mRNA. However, alpha 2(XI) and alpha 1(II) collagen RNA were not detectable; therefore, SMCs cannot synthesize the same type XI collagen as found in cartilage. Since type XI collagen is structurally related to type V collagen, the expression of alpha 1(XI) and alpha 2(V) collagen mRNA in SMCs was characterized. Levels of alpha 1(XI) and alpha 2(V) collagen mRNAs were low in exponentially growing SMCs and increased 3-4-fold as cells became confluent. Increased mRNA levels were also observed when exponentially growing subconfluent SMCs were incubated in medium containing 0.5% fetal bovine serum for 24 h, similar to the effects of serum deprivation on the expression of types I and III collagen genes (Kindy, M. S., Chang, C.-J., and Sonenshein, G. E. (1988) J. Biol. Chem. 263, 11426-11430). However, as cell density increased, serum deprivation resulted in very different responses for these collagen genes. Serum deprivation caused a decrease in expression of alpha 1(XI) and alpha 2(V) collagen mRNAs in cultures as they approached confluence. In contrast, at confluence alpha 1(I) and alpha 2(I) mRNA levels no longer responded to serum concentration whereas expression of alpha 1(III) mRNA remained inducible by serum deprivation. These results suggest concerted regulation of alpha 1(XI) and alpha 2(V) collagen gene expression, which is distinct from that for the chains of type I and type III collagen with respect to cell density and serum.

Amino Acid Sequence↗

Site of action of grayanotoxins in mad honey in rats.

Grayanotoxins are known to occur in honey produced from the nectar of Rhododendrons of the family Ericaceae. Grayanotoxins extracted from honey sample obtained from a patient who experienced severe bradycardia and hypotension after ingesting two tablespoonfuls corresponded to Rhododendron ponticum tetrades. Anaesthetized albino rats were injected with honey extract intracerebroventricularly or intraperitoneally. The intracerebroventricular dose was equivalent to 50 mg honey and i.p. doses were equivalent to 50 mg, 1 mg kg-1 and 5 g kg-1 honey. Marked bradycardia and respiratory rate depression were observed in rats injected with extract equivalent to 1 and 5 g kg-1 honey i.p. and in rats injected with 50 mg i.c.v., but not in rats given 50 mg i.p. In bilaterally vagotomized animals, grayanotoxin-contaminated honey extract was not bradycardic. These results suggest that the sites of cardiac and respiratory actions are within the central nervous system, and that the bradycardic effect of grayanotoxin is mediated by vagal stimulation at the periphery.

Animals↗

Disseminated fungal infections in children infected with human immunodeficiency virus.

A retrospective review of charts of 156 human immunodeficiency virus-infected children cared for during a 7.5-year period revealed 11 episodes of disseminateed candidiasis (DC) occurring in 11 patients (7%). All 11 patients developed the fungal infection in the context of advanced human immunodeficiency virus infection. All but one were hospital-acquired, occurring at a mean of 2.3 months after admission. Ten patients had been febrile for more than 14 days before diagnosis. Previous oral thrush and central venous catheters (73 and 82% of patients) represented major predisposing factors for development of DC. Neutropenia (2 of 11 patients) did not represent a major risk factor for DC. Candida albicans was isolated in 9 patients, Rhodotorula minuta in 1 patient and 1 fungal isolate could not be identified. Sources of isolation were blood (8 of 11 patients), central venous catheters (3 of 11) and urine (2 of 11). Lungs (6 of 11 patients), esophagus (5 of 11) and brain, heart and kidneys (3 patients each) were the organs most often involved in DC. Antemortem diagnosis was achieved in only 7 (64%) patients; none of the 4 patients with DC diagnosed postmortem had been treated before death. Seven patients were treated with amphotericin B; 6 of them died but only 3 were treated for more than 7 days of therapy. The overall mortality was 90% (10 of 11 patients). In all 20% of the 50 human immunodeficiency virus-infected children who died at our hospital during the study period had an episode of DC in close proximity to their death. DC was considered the direct cause of death in 4 of 10 children.

Child↗

Mad honey poisoning in man and rat.

Grayanotoxins are known to occur in the honey produced from the nectar of Rhododendron ponticum growing on the mountains of the eastern Black Sea region of Turkey and also in Japan, Nepal, Brazil, and some parts of North America and Europe. Two cases of honey intoxication are presented here. Both of the patients experienced severe bradycardia and hypotension after ingestion of honey which was brought from Trabzon, Turkey. Microscopical examination showed Rhododendron ponticum pollen tetrades. Anesthetized albino rats were injected intraperitoneally with toxic honey extract doses equivalent to 1 or 5 g honey/kg. Dose-dependent hypotension, bradycardia and respiratory rate depression were observed. When marked bradycardia (approximately 75% of control value) was reached, rats were given atropine sulfate (2 mg/kg, i.p.) or AF-DX 116 (20 mg/kg, i.p.). Atropine sulfate improved both bradycardia and respiratory rate depression. AF-DX 116, which is a selective M2-muscarinic receptor antagonist, restored only heart rate, but not the respiratory rate depression. These results suggest that M2-muscarinic receptors are involved in cardiotoxicity of grayanotoxin.

Aged↗

Hypotension associated with methylmethacrylate in partial hip arthroplasties. The role of femoral canal size.

The relationship between a decrease in systolic blood pressure following methylmethacrylate cement insertion in femoral head replacement and femoral canal diameter was investigated in 33 patients. A positive, significant correlation was demonstrated in all patients, especially among the female subgroup. Femoral canal diameters of 21 mm or more were associated with a significantly greater risk of intraoperative hypotension than were diameters of 20 mm or less. This relationship between femoral canal diameter and hypotension appears to be primary and unrelated to the patient's sex or age. In clinical terms, the femoral canal diameter may be easily measured prior to arthroplasty, and a diameter of 21 mm or more indicates an increased risk of hypotension following insertion of cement into the femoral canal.

Aged↗

Brugia pahangi in rats: increasing the number of infective larvae inoculated increases the percentage of microfilaremic rats.

One hundred Brugia pahangi infective larvae (L3) caused microfilaremic (mf + ve) infection in 56% of inbred PVG rats. Adult worms were recovered consistently from infected rats but worm recovery was very low, only 1-3% of L3 inoculated survived to adulthood and the worms were dispersed in a wide range of anatomical sites. This suggested that lack of microfilaremia may be due to the low probability of male and female worms meeting in the same site and thus may be numerically and topographically based. When the number of infective larvae inoculated was increased to 500, the percentage of mf + ve infections in rats also increased to 94%, corroborating the hypothesis that lack of mf was not due to an immune response. In a further experiment all infected rats had lost both mf and adult worms by day 420. It has yet to be established whether final rejection of the parasite is due to immunity.

Animals↗

Demonstration of blood flow patterns in human soft tissue sarcomas using 99mTc-labelled hexamethyl propyleneamineoxime.

Blood flow patterns have been studied in 28 patients with soft tissue sarcoma (29 tumours) using 99mTc-labelled hexamethyl propyleneamineoxime with planar views of the tumour-bearing region. Tumour:background ratios ranged from 1.13 to 6.60 (mean 2.74) and maximum:minimum tumour ratios (between peripheries and centres of tumours) ranged from 1.34 to 32.0 (mean 4.70). In eight of 29 tumours (seven of which were involving the trunk) the tumour could not be identified. This study demonstrates that the blood supply to soft tissue sarcomas is generally greater than that to adjacent normal tissues and that tumour centres are relatively underperfused compared with the tumour periphery. In this heterogeneous series there was no clear-cut relationship between blood flow and histological grade or type.

Adult↗

The use of caesium iodide mini scintillation counters for dual isotope pulmonary capillary permeability studies.

A commercially available system of caesium iodide crystal mini-detectors (Oakfield Instruments, Oxon, UK) was modified so that it was suitable for dual isotopic measurement of the plasma protein accumulation index (PPA)- a measure of pulmonary endothelial permeability. Using this modified system the mean PPA x 10(-3) min-1 +/- (S.E.M.) recorded in 11 normal subjects (22 lungs) was 0.18 (0.08) and in 6 patients (9 lungs) with the adult respiratory distress syndrome was 2.88 (0.63) (P less than 0.02). These values for PPA concur with those found by other groups using larger sodium iodide detectors. We conclude that with simple modification caesium iodide mini-detectors may be used successfully for the measurement of PPA in the intensive care setting.

Capillary Permeability↗