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Biomedical subjects

R Hall

Publications and source records attributed to R Hall.

At least 217 records · Page 12Linked to original sources

Papilloedema and cranial nerve palsies complicating apparent benign aseptic meningitis.

Three patients who presented with apparently uncomplicated aseptic meningitis subsequently developed papilloedema and sixth cranial nerve palsies between 11 and 16 days after the onset of the illness. All three patients recovered completely without treatment. Raised intracranial pressure is a poorly recognized complication of aseptic meningitis that may represent a post-infective or 'allergic' response to an enteroviral infection. While clinicians should be aware of this possible complication of aseptic meningitis, differentiation from tuberculous meningitis may be difficult necessitating empirical treatment with anti-TB drugs.

Abducens Nerve↗

The measurement of complement fixation by autoantibodies directed against thyroid membrane antigens.

This paper describes the use of sensitized sheep red blood cells for the detection and titration of complement fixation by autoantibodies directed against human thyroid membranes in the serum of patients with autoimmune thyroid disease. Patients with elevated circulating levels of TPO antibodies and diagnosed as having autoimmune hypothyroidism (including Hashimoto's disease) or autoimmune hyperthyroidism (Graves' disease) were studied. Complement fixation titres were highest in those patients with autoimmune hypothyroidism compared with the autoimmune hyperthyroid group. Serum samples obtained from a group of patients with thyroid neoplasia and from normal healthy volunteers were negative in this test. The TPO antibody activity when "corrected" for its CF potency suggests that the autoantibodies found in autoimmune hypothyroidism are potentially more destructive than those found in the non-destructive autoimmune thyroid diseases.

Analysis of Variance↗

Endogenous N-nitrosation and cancer of the biliary tract.

Evidence is presented that N-nitroso compounds occur in bile from patients who have undergone surgery for gallstones or had gastrectomy and from unoperated persons. It is unlikely, therefore, that local formation of nitrosamines can account for the excess risk for gallbladder cancer in the first two groups. Gastric formation remains the likeliest hypothesis.

Bile↗

Interference in thyroid-function tests in postpartum thyroiditis.

Three women are described from a study of patients with postpartum thyroiditis whose sera gave spuriously increased concentrations of free thyroid hormone because of antibody binding of radiolabeled thyroxin (T4) and triiodothyronine (T3) analogs. All of the women showed increased serum concentrations of thyroid autoantibodies. The antibody binding of radiolabeled analogs and its effect on free T4 and free T3 assays disappeared by 48 weeks postpartum. Postpartum women who develop thyroid autoantibodies have approximately 2% prevalence of increased binding of radiolabeled analogs, which can result in an interference in thyroid hormone assays involving T4 and T3 analogs.

Autoantibodies↗

Current status of bioassay procedures to detect and quantify previous exposures to radioactive materials. Bioassay Procedures Working Group.

This report was prepared by a working group established by the Oak Ridge Associated Universities (ORAU) for the purpose of assessing the current capabilities of bioassay methods that can be used to determine the occurrence and magnitude of a previous internal deposition of one or more radionuclides. The first five sections discuss general features of the use of in-vitro bioassay samples to achieve this purpose. The remainder of the report is focused on the possible use of urine bioassay procedures to detect and quantify internal depositions of radionuclides that may have occurred in United States occupation troops in Hiroshima or Nagasaki, Japan, prior to 1 July 1946, or to personnel who participated in atmospheric nuclear weapons tests conducted between 1945 and 1962. Theoretical calculations were made to estimate the quantities of various radionuclides produced in a 20-kiloton (kt) nuclear detonation that might still be present in measurable quantities in people today if they were exposed 25 to 40 y ago. Two radionuclides that emerged as good choices for this type of bioassay analysis were 90Sr, which emits beta particles, and 239,240Pu, which emits alpha particles. The current status and future prospects of chemical procedures for analyzing in-vitro urine bioassay samples for these two radionuclides were examined to determine the minimum amounts that could be detected with current methods and how much one might expect the sensitivity of detection to improve in the near future. Most routine 239,240Pu bioassay analyses involve detection by alpha spectrometry. The current minimum detectable amount (MDA) is about 0.74 mBq L-1 (20 fCi L-1), but this could be lowered to 74 muBq L-1 (2 fCi L-1). An MDA of 0.74 mBq L-1 (20 fCi L-1) is adequate for routine bioassay analyses but is too high to detect most uptakes of 239,240Pu that may have occurred 25 to 40 y ago. Methods under development that are or can be much more sensitive and have lower MDAs than alpha spectrometry for 239Pu are fission track analysis and mass spectrometry. Currently, the fission track analysis method has an MDA of about 19 muBq L-1), and this may eventually be lowered to 1.9 muBq L-1 (0.005 fCi L-1). The current MDA for 239Pu by mass spectrometry is about 7.4 mBq L-1 (200 fCi L-1), but the potential exists that it could be lowered to a value of about 0.37 muBq L-1 (0.01 fCi L-1).(ABSTRACT TRUNCATED AT 400 WORDS)

Feces↗

O6-alkyltransferase activity in normal human gastric mucosa.

The spectrum of activity of the DNA repair enzyme O6-alkyltransferase has been studied in a large series of normal stomachs in order to establish the baseline range of values for this enzyme. Sixty-eight patients with histologically normal stomachs were biopsied during the course of upper gastrointestinal endoscopy and the biopsies assayed for O6-alkyl-transferase activity. A wide spectrum of activity was found with values ranging from 38 fmol O6-guanine extracted/mg protein to over 400 fmol/mg. This suggests that there may be wide inter-individual differences in susceptibility to alkylating actions in the human gastric mucosa.

Adult↗

Characterisation of an extrachromosomal DNA element from Theileria annulata.

Extrachromosomal nucleic acid elements are found in all organisms, commonly as organelle, viral or plasmid genomes. In this paper we describe the initial characterisation of a novel 6.5-kb linear, double-stranded extrachromosomal element from Theileria annulata, and a 2.6-kb RNA species. The DNA element is present in different stages of the life cycle and in different stocks of the parasite. Northern blots of total RNA isolated from different stages of the parasite, probed with the purified element, detect three major transcripts, of 1.45, 1.05 and 0.24 kb, present in all life-cycle stages examined. The possible origin and function of this element is discussed, together with its possible use as a transfection vector for the introduction of genes into protozoan cells.

Animals↗

A clinical update on hypothalamic-pituitary control.

There is at present an accumulation of data which indicate the importance of stimulatory and inhibitory growth factors in the paracrine, and perhaps autocrine, regulation of anterior pituitary cell growth and function. There may well be several more specific pituitary growth factors which will be identified in the near future. Preliminary data are also emerging concerning the pattern of oncogene expression in human pituitary tumours. It is now necessary to relate growth factor production, oncogene expression and hypothalamic regulation to specific anterior pituitary cell populations and human pituitary adenomas. In the midst of these studies it should not be forgotten that coordinated vascular and supporting tissue growth is also crucial to the normal development and maintenance of anterior pituitary structure and function.

Adrenocorticotropic Hormone↗

Brain protection: physiological and pharmacological considerations. Part I: The physiology of brain injury.

Ischaemia, whether focal or global in nature, produces a sequence of intracellular events leading to increased cell permeability to water and ions including Ca++. There is a loss of cellular integrity and function, with increased production of prostaglandins, free radicals, and acidosis with lactate accumulation. These events may be exacerbated by glucose administration. Pharmacological agents aimed at alleviating ischaemic injury could be directed at decreasing cerebral metabolic requirements for oxygen, improving flow to ischaemic areas, preventing Ca+(+)-induced injury, inhibition of free radical formation, lactate removal, inhibition of prostaglandin synthesis, and prevention of complement-mediated leukocyte aggregation. Part I of this paper describes some of the pathophysiological events leading to ischaemic brain injury. Part 2 of this paper will consider the current agents available for brain protection.

Anesthesia↗

Brain protection: physiological and pharmacological considerations. Part II: The pharmacology of brain protection.

Neuroprotective agents may exert their effect by reducing cerebral oxygen demand (CMRO2), increasing cerebral oxygen delivery, or by altering ongoing pathological processes. Barbiturates provide neuroprotection by reducing the CMRO2 necessary for synaptic transmission while leaving the component necessary for cellular metabolism intact. Isoflurane may exert a neuroprotective effect by a similar mechanism but its efficacy is likely less than that of barbiturates due to adverse effects on cerebral blood flow. Lidocaine reduces CMRO2 by affecting both cellular metabolic processes and synaptic transmission and thus resembles hypothermia in its mechanism of action. Benzodiazepines reduce CMRO2 by reducing synaptic transmission and their use as neuroprotectants produces less haemodynamic compromise than barbiturates. The mechanism of protection by calcium entry blocking agents appears to be due to improved blood flow as opposed to altering abnormal Ca++ fluxes. In contrast, agents such as ketamine and MK-801 may prevent abnormal Ca++ fluxes through their competitive interaction with N-methyl-D-aspartate receptors. Phenytoin prevents K(+)-mediated ischaemic events from progressing. Agents worthy of further investigation include corticosteroids, free radical scavengers, prostaglandin inhibitors and iron chelators.

Anesthetics↗

DQA2 U allele: a genetic marker for relapse of Graves' disease.

The association of HLA-DR3 with Graves' disease in Caucasoids is well established but its significance is unclear and its clinical value as a predictive parameter for relapse after a course of antithyroid drug therapy is controversial. We have further investigated the predictive value at the genomic level in 51 patients with Graves' disease who were treated with a 6-month course of carbimazole and followed up for 2 years. Using DNA-restriction fragment length polymorphism (DNA-RFLP) allogenotyping, (i) complete concordance of HLA-DR assignment was observed between serological and DNA-RFLP analysis of all but one of 51 patients with Graves' disease; (ii) the DR beta 17(1)-DQ alpha 2-DQ beta 2a (a DNA-RFLP allogenotype of the classical Northern European haplotype of HLA-B8 DR3) was significantly (corrected P = Pcorr less than 0.02) associated with Graves' disease particularly in patients who relapsed (Pcorr less than 0.005); (iii) HLA-DR3 was highly associated with DQA2 U allele (chi 2 = 18.53, d.f.2, P less than 0.0005); (iv) a strong correlation between the DQA2 U allele and the outcome of the disease was observed. Relapse occurred in 91% (10/11) of the patients who were homozygous for the DQA2 U allele whilst only 65% (15/23) and 41% (7/17) of patients who were hetero or homo-zygous for the DQA2 L allele (DQA2 U/L and DQA2 L/L) relapsed within the same period of follow-up (chi 2 = 7.18, d.f.2, P less than 0.05). Though the relapse rate in patients with the DQA2 U/U genotype was not significantly higher than the relapse rate in patients with the DQA2 U/L genotype, it was significantly higher than the relapse rate in patients with DQA2 L/L genotype (P less than 0.0001) with a relative risk of 14.3.

Alleles↗

A long-term follow-up of postpartum thyroiditis.

To investigate the long-term outcome of postpartum thyroiditis (PPT), 43 patients with PPT and 171 control women were evaluated 3.5 (range 2-4) years postpartum. Ten (23%) PPT patients were hypothyroid compared to none of the controls (P less than 0.001). Factors associated with the development of hypothyroidism were high antimicrosomal antibody titre measured at 16 weeks gestation (P less than 0.01), severity of hypothyroid phase of PPT, multiparity, and a previous history of spontaneous abortion. The presence of microsomal antibody but no PPT in one pregnancy did not prevent the occurrence of PPT in the next pregnancy in two patients and a further five patients had PPT in two successive pregnancies. There was no association between HLA haplotype, family history of thyroid disease, smoking or frequency of oral contraception, and the development of long-term hypothyroidism after PPT. It is concluded that permanent hypothyroidism is an important sequel to PPT and patients with PPT should be followed up appropriately.

Adult↗

Postpartum thyroid dysfunction and HLA status.

Nine-hundred-and-one women presenting in an antenatal clinic at the 60th week of pregnancy were tested for antithyroid antibodies. A group of 113 antibody-positive women and 108 antibody-negative age-matched controls were HLA typed and followed prospectively at 6-weekly intervals through pregnancy and for 12 months postpartum. Forty-five of the women developed biochemical evidence of postpartum thyroid dysfunction (PPTD) of whom 36 were antibody positive. Compared with a local control population (n = 600), and using multiplex analysis, there was a significant increase in the combinations HLA B8, DR3 and HLA A1, B8, DR3 from 22.5% to 40.0% (P less than 0.02) and from 18.6% to 35.6% (P less than 0.01) respectively in the women who developed PPTD. The well-recognized association of these haplotypes with other organ-specific autoimmune diseases provides further support for autoimmune events being implicated in the development of PPTD.

Autoantibodies↗

Identification of lambda gt11 clones encoding the major antigenic determinants expressed by Theileria parva sporozoites.

An antiserum, C16, was raised in cattle against freeze-thawed extracts of sporozoites of Theileria parva (Muguga). This antiserum, which neutralizes sporozoite infectivity in vitro, identified theileria-specific antigens having approximate molecular masses of 105, 90, 85, 69, 67, 52, 47, and 43 kilodaltons (kDa) on Western blots (immunoblots) of infected tick salivary gland extracts. The antiserum was used to screen an expression library of T. parva (Muguga) genomic DNA fragments. Three recombinant bacteriophage clones carrying different theileria DNA inserts were studied. The expressed gene product from each clone was used to affinity purify antibodies from C16 antiserum for use in probing Western blots of uninfected and infected tick salivary gland extracts. The population of antibodies selected by each clone specifically recognized a subset of the antigens identified by C16 antiserum. The antigens fell into three distinct groups as defined by their reactivity with each set of selected antibodies. One group included antigens of 105, 90, 85, and 35 kDa, a second group included antigens of 69, 67, 52, 47, and 43 kDa, and the third group included an apparently distinct pair of antigens of 47 and 43 kDa. Thus, antibodies that reacted with determinants encoded by the three recombinant phage clones recognized all of the major antigens seen on Western blots probed with whole C16 antiserum. These results suggest that there may be only three immunodominant antigens expressed in T. parva (Muguga) sporozoites. Additionally, monoclonal antibodies have been raised which neutralize sporozoite infectivity in vitro. These antibodies react with epitopes of the antigens with Mrs of 69,000, 67,000, 52,000, 47,000, and 43,000 which are encoded in clone pgT-42 and have been used to localize these epitopes on the sporozoite surface.

Animals↗

Post-partum thyroiditis can be painful.

A patient with post-partum thyroiditis is described. She was a 22 year old with a negative family history of autoimmune thyroid disease who was noted to have a high titre of antithyroid microsomal antibody during pregnancy. She developed mild hyperthyroidism 8 weeks post-partum but at 12 weeks she had a mildly painful enlarged thyroid gland. At 20 weeks post-partum she had severe thyroidal pain with dysphagia. The thyroid was exquisitely tender to palpation. She was treated with L-thyroxine and the pain resolved within 4 weeks. This is the first report documenting pain in the thyroid as a feature of post-partum thyroiditis.

Adult↗

Long-term treatment of acromegaly with octreotide (Sandostatin).

Sixteen patients with acromegaly have been treated with octreotide [100 micrograms twice daily to 200 micrograms 3 times daily according to growth hormone (GH) response] for between 3 and 44 months. The mean serum GH concentrations fell from 39.3 mU/l before treatment to 10.5 mU/l on day 1 of treatment and, with continued treatment (and higher doses in 8 of 16 patients), to 7.9 mU/l. In 2 patients there was no GH suppression. GH suppression after the first administration of octreotide appeared to predict long-term response. Pre-treatment serum insulin-like growth factor 1 levels were elevated in 11 of 12 patients investigated, but were normalized on continued octreotide therapy in 10 of 12. Octreotide suppressed prolactin secretion in all 6 hyperprolactinaemic patients. Steatorrhoea occurred in 15 of 16 patients at initiation of treatment, but resolved in all within 7 days. Two patients developed gallstones. In summary, octreotide is a safe and effective treatment for acromegaly, producing clinical and biochemical improvement in up to 90% of patients. Octreotide is a valuable adjunctive treatment where surgery has failed and also in those with contra-indications to surgery.

Acromegaly↗