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Biomedical subjects

J H Miller

Publications and source records attributed to J H Miller.

At least 163 records · Page 9Linked to original sources

Imported falciparum malaria in British troops returning from Kenya.

The objective of this study was to report on a breakthrough of Plasmodium falciparum infection following a military exercise in central Kenya and the treatment regimens used. A series of case reports are presented from the three UK hospitals involved. Among 150 British soldiers who had been on exercises for five weeks in central Kenya, taking proguanil/chloroquine anti-malarial prophylaxis, seven developed symptomatic falciparum malaria. Initial symptoms, which started between 2 and 10 days before their return to England, included faintness, sweating, shivering, diarrhoea, headache and myalgia. Diagnosis was delayed from between 5 and 13 days after the first symptom. One patient was severely ill with 50% parasitaemia: he required intensive care, exchange blood transfusion and haemofiltration for acute renal failure. Compliance with chemoprophylaxis was not measured and anti-mosquito measures were not generally practised. However, British Army policy was amended in June 1993 so that mefloquine will be used in future rather than proguanil/chloroquine. It was concluded therefore that even in an educated and motivated population simple preventive measures are not observed. Chemoprophylactic compliance could be improved by changing to a simpler regime. Falciparum malaria is a medical emergency that requires urgent admission for confirmation of diagnosis, supportive and curative treatment. Its presence should be suspected in any ill traveller.

Adolescent↗

Bone abnormalities detected with skeletal scintigraphy after bone marrow harvest in patients with childhood neuroblastoma.

PURPOSE: To illustrate abnormalities detected with radionuclide skeletal scintigraphy, computed tomography (CT), and radiography after bone marrow harvest in patients who are candidates for autologous bone marrow transplantation (ABMT) in treatment of neuroblastoma. MATERIALS AND METHODS: Twenty-four patients with neuroblastoma underwent ABMT and evaluation with conventional skeletal scintigraphy. Findings of abnormality on bone scans were correlated whenever possible with findings from CT and plain radiography. RESULTS: Skeletal scintigraphy revealed 36 sites of increased activity in the sacroiliac region, iliac crest, or both caused by bone marrow harvest in the 24 patients. In 10 patients, follow-up bone scans showed complete disappearance of abnormal activity at 18 sites. CONCLUSION: The harvesting of marrow for ABMT caused iatrogenic abnormalities on bone scans. It is important that these be recognized so that they will not be confused with progressive or new metastases.

Bone Marrow Transplantation↗

Na+ transport and pH in principal cells of frog skin: effect of antidiuretic hormone.

Intracellular pH (pHi), apical membrane potential (Va), and fractional apical membrane resistance (FRa) were measured in principal cells of isolated frog skin (Rana pipiens) with double-barreled microelectrodes under short-circuit conditions. Basolateral exposure to 10 mU/ml arginine vasotocin (AVT) depolarized Va by 30 mV, decreased FRa by 33%, increased short-circuit current (Isc) by 17 microA, and increased pHi by 0.17 pH units. The response of Va, Isc, and pHi occurred concurrently. Forskolin, theophylline, and 8-(4-chlorophenyl-thio)-adenosine 3',5'-cyclic monophosphate caused similar changes in Va, Isc, and pHi. The enhanced response of Isc, Va, and FRa to short pulses of apical amiloride applied during AVT or cAMP exposure suggests an increase in apical Na+ conductance. The presence of cAMP agonists also enhanced the response of pHi to amiloride. We conclude that the AVT- and cAMP-induced increase in Na+ transport across the apical cell membrane is associated with a change in pHi. These data are consistent with the hypothesis that changes in pHi may play a role in the second messenger cascade initiated by the antidiuretic hormone.

Amiloride↗

Starvation induces differential small bowel luminal amino acid transport.

BACKGROUND: The importance of small intestinal mucosa functions has been emphasized in recent years because gut metabolism becomes better defined. One of the major activities of the enterocyte is amino acid transport, which is important not only for the organism but also for the integrity of the mucosa. Bowel rest during the postoperative period is marked by decreased calorie and protein intake with atrophy of the brush border mucosa. We sought to determine whether active amino acid transport is altered during 72 hours of fasting. METHODS: New Zealand white rabbits were fed (control) or fasted for 72 hours. Brush border membrane vesicles were prepared from scraped jejunal mucosa, and their purity was assessed by marker enzyme enrichment (17- to 25-fold). Transport of tritiated glutamine, arginine, alanine, methylamino-isobutyric acid (MeAIB), and leucine into brush border membrane vesicles was measured by rapid mixing filtration. RESULTS: Fasted animals lost on average 138 +/- 51 gm of body weight. Glutamine and arginine transport were decreased in rabbits fasted for 72 hours compared with controls; alanine, MeAIB, and leucine transport were maintained. The decrease in Glutamine transport was due to a decrease in Vmax (545 +/- 22 versus 836 +/- 93 pmol/mg protein/10 sec; p < 0.05), consistent with a decrease in the number of functional transporter proteins. Km values were similar in both groups (644 +/- 25 versus 624 +/- 18 mumol/L), indicating no change in carrier affinity. CONCLUSION: Differential changes occur in brush border amino acid transport during a 3-day period of bowel rest. The apparent gut nutritive transporters for Glutamine and arginine are decreased, although the gluconeogenic transporters for alanine, MeAIB, and leucine are maintained. These adaptive changes may help explain the difficulties seen in postoperative and critically ill patients on prolonged bowel rest.

Amino Acids↗

Function of the zinc finger in Escherichia coli Fpg protein.

Fpg protein of Escherichia coli cleaves duplex DNA containing the oxidatively damaged base 8-oxo-7,8-dihydroguanine (Tchou, J., Kasai, H., Shibutani, S., Chung, M.-H., Laval, J., Grollman, A. P., and Nishimura, S. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 4690-4694). This DNA repair enzyme contains one zinc atom/protein molecule (Boiteux, S., O'Connor, T. R., Lederer, F., Gougette, A., and Laval, J. (1990) J. Biol. Chem. 265, 3916-3922); its N-glycosylase and apurinic/apyrimidinic lyase activities are physically associated. Amino acid sequence analysis reveals a putative single zinc finger motif of the CC/CC type located near the carboxyl terminus. A gel mobility shift assay was used to assay binding of Fpg protein to a noncleavable substrate analog, namely an oligodeoxynucleotide duplex containing a single tetrahydrofuran residue. High resolution hydroxyl radical DNA footprinting showed protection centered around the tetrahydrofuran residue. No footprint was observed on the complementary strand. To establish the role of COOH-terminal zinc finger in DNA binding and/or DNA cleavage, amino acid substitutions and an amber mutation were introduced at Cys-244 (C244S, C244H, C244A, and C244amber). In addition, a double amino acid substitution was generated at Cys-244 and Cys-247 (C244S/C247S). These mutant Fpg proteins lack DNA binding or cleavage activity, as tested in crude lysates of Escherichia coli. Wild type Fpg protein contains one zinc/protein molecule, whereas the mutant Fpg protein (C244S/C247S) lacks zinc, as measured by atomic absorption spectroscopy. This mutation did not significantly alter secondary structure, as assessed by circular dichroism spectroscopy. Our results suggest that Fpg protein utilizes its single COOH-terminal zinc finger motif in DNA binding.

Amino Acid Sequence↗

Studies of the hyperthermophile Thermotoga maritima by random sequencing of cDNA and genomic libraries. Identification and sequencing of the trpEG (D) operon.

Random sequencing of cDNA and genomic libraries has been used to study the genome of the hyperthermophile Thermotoga maritima. To date, 175 unique clones have been analyzed by comparing short sequence tags with known proteins in the PIR and GenBank databases. We find that a significant proportion of sequences can be matched to previously identified protein from non-Thermotoga sources. A high match rate was obtained from an oligo(dT)-primed cDNA library, where one-third of all unique sequences analyzed (21/65) shared high amino acid sequence similarity with proteins in the PIR and GenBank databases. Also, approximately one-third of the unique sequences from a second cDNA library (28/89), constructed with random oligo primers, could be matched to sequences in PIR and GenBank. Identification of genes from the oligo(dT)-primed cDNA library indicates that some Thermotoga mRNAs are polyadenylated. Genes have also been identified from a 1 to 2 kb genomic DNA library. Here, (3/21) of genomic sequences analyzed could be matched to protein in PIR and GenBank. One of the genomic clones had high sequence similarity to the tryptophan synthesis gene anthranilate synthase component I (trpE). Using this sequence tag, the Thermotoga trp operon was isolated and sequenced. The Thermotoga maritima trp operon is arranged with trpE forming an overlapping transcript with a second protein consisting of a fusion of anthranilate synthase component II (trpG) and anthranilate phosphoribosyltransferse (trpD). With regard to the fusion, the operon organization is similar to Escherichia coli and Salmonella typhimurium, but lacks the classic attenuation system of enteric bacteria. Amino acid sequence comparison with 19 trpE, 18 trpG and 14 trpD genes from other organisms suggest that the Thermotoga trp genes resemble corresponding genes from other thermophiles more closely than expected.

Amino Acid Sequence↗

The role of radionuclide-labeled cells in the diagnosis of abdominal disease in children.

The use of radionuclide-labeled blood cells can provide diagnostic information concerning abdominal disease in children that may not be available by any other imaging method. The use of technetium-labeled red blood cells to identify bleeding sites in the gastrointestinal tract, to define mass lesions, or to localize the spleen offers a relatively quick and inexpensive method of evaluation. In the evaluation of Crohn's disease of the small bowel or involvement of the colon in inflammatory bowel disease, white blood cells labeled with either indium-111 or technetium-99m provide meaningful diagnostic information. There also may be a role for the use of labeled white cells in the evaluation of appendicitis. The individualized use of labeled blood cells provides the nuclear physician with a unique opportunity to contribute in a meaningful manner to the care of children using information that is critical in patient care.

Child↗

Femorocrural grafting and regrafting: does polytetrafluoroethylene have a role?

Between 1980 and 1988, 263 patients received 307 femorocrural bypass grafts. 180 were primary infrainguinal grafts, 106 secondary, 18 tertiary and three quaternary. Rest pain or tissue loss was the indication in 96% of cases. Outflow vessels were the tibioperoneal trunk (n = 34), posterior tibial artery (n = 115), peroneal artery (n = 89) and anterior tibial artery (n = 69). 88 primary vein grafts were completed. 201 polytetrafluoroethylene (PTFE) grafts were inserted (92 primary and 109 subsequent reconstructions). There were no direct PTFE to crural vessel anastomoses. A Miller cuff was used in the majority (n = 175). The three year primary patency for primary vein grafts (36%) was similar to primary PTFE grafts (29%), but significantly higher than subsequent PTFE grafts (20%) (p = 0.03). Three year foot salvage for primary vein grafts (65%) was similar to primary PTFE (64%), but significantly better than subsequent PTFE (42%) (p = 0.02). The results support both redo femorocrural grafting for critical ischaemia, as judged by foot salvage rates, and the use of PTFE with a distal vein cuff in primary and subsequent femorocrural reconstruction if autologous vein is not available.

Adult↗

Primary replacement of the fractured radial head with a metal prosthesis.

Compression testing of cadaver specimens showed that excision of the radial head allowed proximal radial displacement. The insertion of a metallic radial head restored normal mechanics, while a silicone rubber implant did not. We reviewed 31 of 36 comminuted fractures of the radial head, 21 associated with dislocation or ulnar fracture, which had been treated by primary replacement with a Vitallium prosthesis. At a mean follow-up of 4.5 years, there was reliable restoration of stability and prevention of proximal radial migration. There had been no dislocations or prosthetic failures, but two implants had been removed for loosening. The prosthesis is recommended for use as a spacer to stabilise the elbow after severe injuries while the soft tissues heal.

Adult↗

Effect of alcohol, neurohypophysectomy, and vasopressin antagonists on hemorrhage-induced bradycardia in the rat.

During initial stages of hemorrhage in the rat, cardiovascular compensation leads to a tachycardia (mean +/- SE, 5.2 +/- 0.7%; n = 23) that helps prevent a large fall in blood pressure. This compensatory phase is followed by a decompensatory phase in which mean arterial pressure and heart rate fall. A rise in arginine vasopressin (AVP) levels has been postulated as the cause of this hemorrhage-induced bradycardia (HIB). The object of the present study was to determine whether interference with AVP release by alcohol anesthesia or neurohypophysectomy or by blockade of AVP receptors in the plasma or cerebral spinal fluid could attenuate HIB. Male Wistar rats were anesthetized with pentobarbital, surgically prepared, and bled to maintain a blood pressure of 40-50 mm Hg. After hemorrhage, heart rate decreased 15 +/- 2% (n = 6) with alcohol anesthesia compared with 32 +/- 3% (n = 7) with pentobarbital. After neurohypophysectomy, however, HIB remained unchanged (-15 +/- 2%; n = 5) compared with sham-operated controls (-19 +/- 3%; n = 6). Peripheral administration of two nonselective V1/V2 antagonists and one V2 antagonist had no effect on HIB, whereas a V1 antagonist significantly attenuated the heart rate decrease (-15 +/- 4%; n = 6) compared with controls (-32 +/- 3%; n = 7). None of the AVP antagonists tested at one tenth the peripheral dose had any effect on HIB when administered into the lateral ventricle of the brain, although a mixed serotonin, dopamine, and catecholamine antagonist, spiperone, potentiated the response. It was concluded that although peripheral release of AVP may be partially involved in the heart rate response to hemorrhage, central AVP release and central AVP receptors were not involved in HIB.

Animals↗

Cerebral perfusion abnormalities in children with central nervous system manifestations of lupus detected by single photon emission computed tomography.

OBJECTIVE: Central nervous system (CNS) abnormalities have been reported in 30-60% of children with systemic lupus erythematosus (SLE) during the course of the disease. Unlike most other manifestations of childhood lupus, few laboratory studies and imaging modalities aid in the documentation of CNS lupus. Single photon emission computed tomography (SPECT) provides a means of assessing cerebral blood flow and may reveal subtle areas of decreased perfusion or loss of functioning brain parenchyma. METHODS: We evaluated 5 children with clinical signs of CNS lupus using SPECT, lumbar puncture, electroencephalogram (EEG), computerized tomogram (CT) and magnetic resonance imaging (MRI), as well as autoantibody and complement serologic testing. All patients fulfilled classification criteria for SLE and within one year of onset presented with the following CNS manifestations: grand mal seizures with encephalopathy or psychosis (2) and transverse myelitis (1), focal seizure and depression (1), and severe headache and ophthalmitis (1). RESULTS: Four patients had anticardiolipin (aCL) antibodies. One girl with positive aCL had a concurrent ischemic event involving both parietal lobes and another had a CNS bleed. Both of these children had abnormal EEG, CT and MRI scans. All children had normal cerebral spinal fluid analyses. No correlation was found between serologic variables and CNS disease. All 5 children had abnormal SPECT perfusion studies. CT and MRI failed to demonstrate abnormalities in 3 children. Although CT and MRI documented parietal lobe infarcts in one child and focal hemorrhage in another, poor perfusion found with SPECT extended beyond these abnormalities and into areas which appeared intact using the conventional imaging techniques. All children improved clinically and 4/5 had additional SPECT studies. In all 4, the perfusion abnormalities improved but did not resolve. One of these patients had a recurrence of hallucinations and worsening of SPECT findings which improved again after the patient stabilized. CONCLUSIONS: We conclude that the cerebral perfusion SPECT scan is a sensitive tool and may prove useful in the documentation of CNS lupus in children.

Adolescent↗

Intraoperative fluorescein angiography.

BACKGROUND: Fluorescein angiography is often beneficial in the evaluation and management of many retinal vascular diseases. However, vitreous blood or opacities may prevent fluorescein studies before pars plana vitrectomy. After vitrectomy, fluorescein angiography may be delayed, creating uncertainty over differentiation of preoperative, intraoperative, and postoperative findings. METHODS: The authors have modified an intraocular light source and operating microscope to perform intraoperative fluorescein angiography easily. Twenty-five patients underwent fluorescein angiography during pars plana vitrectomy. All studies were recorded using a microscope-mounted video camera for intraoperative and postoperative evaluation. RESULTS: In all cases, intraoperative angiography was performed without complication. Indications for intraoperative studies included confirmation of macular edema, delineation of avascular retina, and localization of retinal and choroidal neovascularization. All videotape recordings of procedures were of high quality, allowing easy review and interpretation. CONCLUSION: Intraoperative fluorescein angiography is an easily performed adjunctive diagnostic procedure that can aid intraoperative evaluation and treatment of selected retinal vascular disorders.

Adult↗

Pharmacological characterization of the rat hippocampal muscarinic autoreceptor.

The interactions of both agonists and antagonists with the hippocampal presynaptic muscarinic autoreceptor were studied in a release assay with mechanically dissociated tissue. Muscarinic agonists inhibited potassium-ion-evoked release of [3H]acetylcholine maximally by 30 to 40%. Using partial receptor alkylation, the Kd value for oxotremorine-M was determined to be 2.5 microM, whereas the EC50 for this agonist was 0.43 microM; the Kd/EC50 ratio (5.8) indicates that a modest degree of "spare receptors" exist for this response. The relative intrinsic efficacies of partial agonists (pilocarpine, [(4-hydroxy-2-butynyl)trimethyl ammonium chloride] and bethanechol) were compatible with the involvement of a mixture of the M2 and the M4 receptor subtypes. With Schild analysis, pirenzepine was shown to block with low potency (Ki = 370 nM), which indicated that the M1 muscarinic receptor was not involved in this response. The potencies of the cardioselective drugs (11-[[2-(diethylamino)methyl]-1-piperdinyl] acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one] and methoctramine (111 and 61 nM, respectively) were somewhat too low to definitely indicate the involvement of an M2 receptor subtype. The Ki values for the smooth muscle/glandular-selective drugs, 4-diphenylacetoxy-N-methylpiperidine methbromide and hexahydrosiladifenidol (2.5 and 87 nM, respectively), were similar to values for these drugs at the M4 subtype, but their potencies did not clearly distinguish this receptor from the M3 subtype. However, the Kd value for himbacine at this receptor (8.6 nM) ruled out involvement of the M3 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Partial replacement of an infected arterial graft by a new prosthetic polytetrafluoroethylene segment: a new therapeutic option.

PURPOSE: As the title suggests, this is an account of treating infected arterial grafts other than by the accepted methods of complete graft removal and revascularization with autogenous material or extraanatomic bypass. METHODS: Since 1973, 42 patients with infected arterial grafts (n = 35) or autogenous reconstructions (n = 7) were seen with false aneurysm, hemorrhage, or perigraft or perianastomotic pus and were treated by removal of the infected graft and immediate adjacent or in situ revascularization by polytetrafluoroethylene (PTFE) in 39 cases and Dacron in three cases. Management plan included (1) removal of only the obviously infected part of the original graft, (2) obliteration of the infected anastomotic site, and (3) placement of the new PTFE graft in an adjacent clean or debrided route. So treated were 15 aortic Dacron grafts, 20 PTFE grafts (2 iliofemoral, 3 femorofemoral, and 15 femorodistal), and 7 autogenous reconstructions with bleeding. Partial graft salvage was attempted in 10 of 15 Dacron and 19 of 20 PTFE grafts. RESULTS: Four patients required further removal of the original infected graft (three Dacron, one PTFE), giving an ultimate success rate of 7 of 15 Dacron and 18 of 20 PTFE grafts; two patients required further obliteration of the original adjacent infected arterial segment because of rebleeding. An additional PTFE segment was joined successfully to incorporated PTFE in all six repeat operations. Initial failure did not prejudice the outcome; direct arterial flow to at least midthigh level was preserved in 37 of the 42 patients for a mean period of 40 months (range 9 to 130 months). Three of the new PTFE grafts occluded and became infected, which led to amputation and one death at a secondary operation. Visceral complications caused the only two other deaths in the aortic group. Five late amputations (four below the knee and one above the knee) were required because of femorodistal graft occlusion. CONCLUSIONS: Partial removal of infected grafts with adjacent or in situ replacement by PTFE is possible, simplifies management, and permits maintenance of distal circulation with low morbidity and mortality rates.

Aortic Aneurysm, Abdominal↗

A repair system for 8-oxo-7,8-dihydrodeoxyguanine.

Active oxygen species can damage DNA and may play a role in aging and carcinogenesis. We have tested MutY glycosylase for activity on undamaged mispairs as well as mispairs formed with the oxidatively damaged substrates, 8-oxo-7,8-dihydrodeoxyguanine (GO) or 8-oxo-7,8-dihydrodeoxyadenine (AO). MutY acts as a glycosylase on four of the heteroduplexes tested, A/G, A/GO, A/C, and A/AO, removing the undamaged adenine from each substrate. Genetic data suggest that the primary substrate for MutY glycosylase in vivo is the A/GO mispair. We present biochemical evidence demonstrating that MutY glycosylase is an important part of a repair system that includes the MutM and MutT proteins. The GO repair system is dedicated to the repair of the oxidatively damaged guanine and the mutations it can induce.

8-Hydroxy-2'-Deoxyguanosine↗