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Biomedical subjects

M Faulkner

Publications and source records attributed to M Faulkner.

At least 19 recordsLinked to original sources

The Rhnull phenotype in an English individual: haematological, serological and immunological studies.

We have characterized the first case of Rhnull phenotype to be identified in England. The red cells were serologically negative for C, c, Cw, D, E, e, f, hr B, Rh17, Lw a, Lw ab and Duclos, while the patient's serum contained anti-Rh29, which was subsequently boosted by transfusion. The Rh phenotype of the patient's son (R1r) confirmed that this was a regulator type of Rhnull in the patient. Follow up studies confirmed the presence of a mild chronic anaemia with stomatocytes and spherocytes; electron microscopy revealed the presence of cells with deep central indentations. Osmotic fragility was increased to a level intermediate between normal and hereditary spherocytic controls. The presence of ongoing haemolysis was indicated by a mild reticulocytosis and splenomegaly. The potent anti-Rh29 has made the provision of compatible blood difficult and autologous units have been frozen. The case illustrates the rare phenomenon of the Rhnull phenotype which not only causes problems for the transfusionist but should also be recognized as a cause of haemolytic anaemia secondary to a membrane defect. Blood film and Rh phenotyping are useful preliminary investigations in suspected cases.

Aged

Recruitment experience in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

Several approaches for recruitment of African American adults with renal insufficiency due to hypertension (glomerular filtration rate between 25 and 70 ml/min/1.73 m2) were explored in the Pilot Study for the African American Study of Kidney Disease and Hypertension (AASK). Over a period of 42 weeks, prescreening information was obtained on 2880 individuals, of whom 498 (17%) were evaluated at a screening visit. Two hundred and twenty-five (8%) had an 125I-iothalamate assessment of glomerular filtration rate. Ninety-four of 97 participants who met all the study eligibility criteria were enrolled in the trial. The most common reasons for ineligibility during screening were absence of renal insufficiency or hypertension, presence of diabetes mellitus, and a body mass index above the acceptable level. Overall, an average of 31 prescreen contacts and 8 screening visits were conducted for every randomization (3.3% yield from prescreening to randomization). Screening in clinical practice was the most efficient method for recruitment (12.6% yield from prescreen contact to randomization compared to 1.1% from mass mailing campaigns, 1.3% from mass media campaigns, and 1.7% from referrals by patients with end-stage renal disease). Randomization yields increased with progressively higher age ranges (2.4%, 3.3%, and 6.0% prescreen to randomization yields for those aged < or = 50, 51-60, and 61-70, respectively). A slight majority (51%) of the prescreen contacts were women, but 75% of the randomized participants were men. Our results suggest that clinic-based screening is an effective approach for recruitment of African Americans with hypertension and renal insufficiency into clinical trials. They also suggest that enrollment of African American women in such studies is a special challenge.

Adult

Effect of blood pressure control and antihypertensive drug regimen on quality of life: the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of carrying out a randomized, multicenter, 7-year clinical trial to determine the effects of two goal levels of blood pressure control and three antihypertensive drug regimens on decline in glomerular filtration rate in African Americans with clinically diagnosed hypertensive nephrosclerosis. Participants were randomized to either a usual mean arterial blood pressure (MAP) goal group (102-107 mm Hg) or a low-MAP goal group (< or = 92 mm Hg) and to a drug regimen (initial therapy with either atenolol, amlodipine, or enalapril). Quality of life was assessed by the Medical Outcomes Short-Form 36 (MOS SF-36) at baseline and the last follow-up visit for 84 of the 94 participants of the AASK Pilot Study. Symptoms were assessed at baseline and throughout the course of therapy by participant self-report. Mean SF-36 scores increased significantly on physical functioning (9.2), role limitations (physical) (19.0), social functioning (9.0), and vitality dimensions (5.6) from baseline to the last follow-up visit in the usual MAP goal group. Scores for the eight health dimensions assessed by the MOS SF-36 did not change significantly during the same time period either in the low-MAP goal group or in any of the drug regimens. The mean score for general health perception was significantly lower at the last follow-up visit in the enalapril drug regimen (49.9) compared to drug regimens with atenolol (65.4) or amlodipine (63.9). Physical functioning, role limitations (emotional), social functioning, mental health, vitality, and general health perception scores were negatively correlated with self-reported symptoms during treatment. We conclude that selected dimensions of quality of life improved during the AASK Pilot Study only in participants randomized to the usual MAP goal group. Significant differences between MAP goal groups and drug regimens at the end of follow-up were observed for only a few health dimensions.

Adult

Participant satisfaction in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

Seventy-one of the 94 eligible participants of the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study completed a self-administered questionnaire at the end of the study to determine their satisfaction with the study, difficulties encountered during participation, and willingness to join a similar study in the future. Nearly all of the participants (97%) believed that they would directly benefit from the study; treatment and information from physicians (94%), and more knowledge (92%) and closer monitoring (90%) of their physical condition were often cited as the ways in which the AASK Pilot Study helped. The two most commonly reported problems in the study were side effects from antihypertensive drugs (27%) and travel to and from the clinic (25%). Eighty-two percent of those who completed the survey indicated that they would volunteer for a similar study in the future. We conclude that AASK Pilot Study participants believed that they would benefit directly from the trial and that medical aspects of the trial were of major importance. Side effects from antihypertensive drugs and difficulties in travel to and from the clinic were commonly encountered problems and may hinder long-term participation in the AASK Full-Scale Trial.

Adult

Immunogenicity of influenza and HSV-1 mixed antigen ISCOMs in mice.

Immunostimulating complexes (ISCOMs) were prepared with mixtures of antigens from influenza A virus (A/PR/8/34 or A/Sichuan/2/87) and herpes simplex virus type 1 (HSV-1), and were characterised by enzyme linked immunosorbent assay (ELISA) and electron microscopy using double-labelling immunogold techniques employing monoclonal antibodies to influenza or HSV-1 glycoproteins. The immunogenicity of the mixed antigen ISCOMs was evaluated in mice, following administration by the subcutaneous route, by measuring the total and subclass IgG antibody responses. Protection of these animals against challenge with live influenza A/Sichuan virus or live HSV-1, was compared with that induced by immunization with aqueous mixed antigen preparations. It was found that relatively high humoral responses to both influenza and HSV antigens, and increased levels of protection to both influenza and HSV viruses were elicited in mice receiving the mixed antigen ISCOM preparation compared to those observed in animals receiving the mixed aqueous subunit preparation. The findings also indicate that antigens from more than one virus can be used in an ISCOM formulation to produce immunity and protection.

Animals

Severe anemia: a risk factor for glomerular injury in sickle cell disease.

Approximately 15% to 20% of patients with sickle cell disease have proteinuria. Proteinuria, particularly albuminuria, is the hallmark of glomerular injury. This study examines risk factors for glomerular injury as indicated by urinary albumin excretion (UAE) 30 microgram/minute, directly related to sickle cell disease. A total of seven patients were enrolled between September 1992 and March 1993. Fasting blood chemistries, complete blood cell count, 24-hour urine for protein and creatinine clearance, and glomerular filtration rate determined by 125 I-iothalamate were obtained for each patient. The results indicated that the lower the hematocrit, the higher the UAE rate. Low hematocrits have served as a protective mechanism in sickle cell disease by reducing blood viscosity and thus decreasing the number of vaso-occlusive crises. However, severe anemia appears to have an indirect adverse effect on the kidney in sickle cell disease.

Adult

The pituitary in cirrhosis: ultrastructure, growth hormone, and prolactin concentrations.

Micronodular cirrhosis was induced in male SUAH substrain Wistar rats by combined phenobarbitone and carbon tetrachloride treatment. Both pituitary and serum concentrations of growth hormone were significantly reduced in cirrhotic rats compared with age-related untreated rats or those treated only with phenobarbitone. Ultrastructurally growth hormone-secreting cells (somatotrophs) of pituitaries of cirrhotic rats appeared relatively inactive, having few hormone-containing granules, sparse rough endoplasmic reticulum, and small nuclei with areas of condensed chromatin. The cells themselves were smaller than similar cells of untreated rats with a reduced cytoplasmic area. In addition immunocytochemistry of pituitaries at light microscope level, using sheep anti-rat growth hormone antibody, showed that somatotrophs of cirrhotic rats were more heteromorphic and disorganized than those in controls. There was marked development of the folliculo-stellate cell system in pituitaries of cirrhotic rats, the cells were enlarged with distinct golgi, and numerous microvilli were projecting into dilated follicular lumena.

Animals

The application of sodium dodecyl sulphate-polyacrylamide gel electrophoresis to the taxonomic identification of the total body protein band profiles of Diplostomum spp. metacercariae (Digenea), parasites of fish eyes.

Sodium dodecyl sulphate-polyacrylamide gel electrophoresis has been used to determine the metacercariae (Mc) total body protein band profiles of different Diplostomum spp. Four species of fish were investigated, roach (Rutilus rutilus) infected with D. spathaceum Mc, gywniad (Coregonus laveratus) infected with D. coregonus Mc, ruff (Gymnocephalus cernua) infected with a Diplostomum species related to D. gasterostei Mc, and perch (Perca fluviatilis) infected with D. gasterostei Mc. The four species of Diplostomum Mc were distinguished by three different bands of molecular weight, Mr 55,500, 53,500 and 52,000. A homology of polypeptide component distribution was evident for D. gasterostei Mc, from P. fluviatilis, and D. coregonus Mc, from C. laveratus, the latter showing reduced protein concentrations between bands Mr 32,000-40,000. Critical analysis of Mc polypeptide patterns showed no evidence of contamination with lens, retina or vitreous humour host eye protein. Gross morphological data for the parasites was also considered in relation to different band profiles obtained for the Diplostomum spp. Mc. Band profile analysis in conjunction with other taxonomic tests proved to be a useful tool in the identification of unknown species.

Animals

Sexual, seasonal and tissue variation in the encystment of Cotylurus variegatus metacercariae in perch, Perca fluviatilis.

All of the 267 perch sampled from Lough Neagh between 1981 and 1983 were infected with the metacercarial cysts of Cotylurus variegatus. Sites of infection were the swim-bladder, pericardium, septum transversum and, to a lesser extent, the visceral cavity. The swim-bladder, particularly the anterior portion, was the site of heaviest infection. Visceral cysts were found chiefly in female fish and this may be related to reduced immunological defence and/or thinner body wall during the breeding season. The number of cysts recorded was not related to host length, suggesting that further parasite invasion is offset by cyst mortality possibly as a result of the host immunological response to the parasite. Highest mean worm burden was recorded between May and June. This corresponded to increased water temperature necessary for development of eggs and the breeding season (April-June) of the perch.

Animals

Acute renal failure following cocaine abuse.

Three healthy adult males developed acute renal failure following cocaine abuse. Muscle pain, tenderness, elevated levels of serum muscle enzymes, heme-positive urine and the presence of pigmented granular casts in urine all indicated occurrence of rhabdomyolysis. One of them developed acute compartmental syndrome of the left leg and required emergency fasciotomy. The course of renal failure and fast recovery were suggestive of acute tubular necrosis in all 3 patients. A possible role of cocaine in the aggravation of renal and/or muscle ischemia has been speculated.

Acute Kidney Injury

Hypersensitivity angiitis associated with naproxen.

A 52-year-old male developed cutaneous necrotizing vasculitis, renal failure, massive proteinuria, and elevated serum IgE levels following oral naproxen therapy. Renal biopsy specimen revealed cellular crescents in more than 40% of the glomeruli and a rare arteriole displayed thickening and eosinophilia of intima. Electron microscopic examination showed fusion of epithelial foot processes. Discontinuation of naproxen therapy was associated with disappearance of cutaneous lesions and improvement of renal function.

Drug Hypersensitivity

Polypeptide patterns obtained by polyacrylamide gel electrophoresis of thylakoid membranes isolated from light and dark grown strains of Chlorogloea fritschii.

Sodium dodecyl sulphate-polyacrylamide gel electrophoresis has been used to determine the difference between thylakoid polypeptide patterns of light and dark grown strains of the cyanobacterium Chlorogloea fritschii. There were only 2 prominent bands present in the dark grown strains, polypeptide Mr50,000 and polypeptide Mr90,000, also five fainter bands in the Mr range 45,000-66,200 corresponding to photosystem one, compared with the 32 bands present in the light grown strains. There was no obvious indication of the Mr 33,000 3-(3,4-chlorophenyl)-1,1-dimethyl-urea binding protein. In addition the progressive daily development of the various photosystem components in the light and their relationship in photosynthesis was determined. It was observed that the increase of the relative concentrations of the photosystem two and phycocyanin components indicated their developments are mutually synchronized. The effect of light to dark and dark to light transfer on established strains was investigated. Appreciable loss of photosystem two components and the presence of an additional band Mr22,500 of unknown function in the light to dark transfer, and little reactivation of the photosynthetic capabilities in the dark to light transfer was observed.

Cell Membrane

Pneumocystis carinii pneumonia following 5-fluorouracil administration.

A 54-year-old man who had been treated with monthly courses of 5-fluorouracil for one year developed Pneumocystis carinii pneumonia. No evidence of significant, permanent, immunologic impairment was evident one year after the patient became infected. An infection associated with 5-fluorouracil treatment is implicated.

Fluorouracil