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Biomedical subjects

A R Jones

Publications and source records attributed to A R Jones.

At least 73 records · Page 4Linked to original sources

Relative biological effectiveness of tritium for induction of myeloid leukemia in CBA/H mice.

To help resolve uncertainties as to the most appropriate weighting factor for tritium beta rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium beta rays compared to X rays ranged from 1.0 +/- 0.5 to 1.3 +/- 0.3. A best estimate of the RBE for this experiment was about 1.2 +/- 0.3. A wR value of 1 would thus appear to be more appropriate than a wR of 2 for tritium beta rays.

Animals↗

Absolute versus proportional differential leucocyte counts.

Comparison of absolute (cells x 10(9)/l) leucocyte differential counts with proportional (percentage) counts from the same stained films demonstrates significant disparities between these two methods of reporting results. Within reference intervals the disparities are modest but become significant in specimens with distributional abnormalities. Although neither method of reporting is formally espoused in this communication, it is suggested that use of the absolute count is more likely to provide diagnostic support.

Diagnostic Errors↗

Reduction of angulated metacarpal fractures with a custom fracture-brace.

A thermoplastic fracture-brace was compared to closed reduction with ulnar gutter splinting in the treatment of 38 isolated fractures of the fifth metacarpal with angulation more than 40 degrees at the neck or 25 degrees in the diaphysis. Patient profiles, fracture patterns, compliance rates, and time to clinical union were similar in the two treatment groups. The two treatment methods improved fracture angulation by the same amount, to about one half of the initial angulation. At the time of splint or brace removal, there was more restriction of wrist, metacarpophalangeal, and proximal interphalangeal motion in the closed reduction/ulnar splint group, but this difference resolved by 3 months following injury. Serious skin problems were not encountered in either treatment group. Problems with fracture reduction occurred in two cases from each group; all involved oblique fractures. In laborers, the fracture-brace did not offer enough hand protection to allow them to resume heavy work before fracture union. The fracture-brace corrected fracture angulation as effectively as closed reduction with gutter splinting, and it restored motion to the fractured hand more quickly.

Adolescent↗

Primary peristalsis is the major acid clearance mechanism in reflux patients.

This study examined the clearance of gastric acid from the oesophagus in ambulant patients with gastro-oesophageal reflux. Eighteen patients with proved reflux disease were studied, nine with (group 1) and nine without (group 2) endoscopic oesophagitis. Oesophageal pressure and pH were recorded over 24 hours. Pressures were measured by a probe with five sensors: a 5 cm long sensor in the lower oesophageal sphincter, three sensors in the body of the oesophagus, and one at the pharynx to detect swallowing. Oesophageal pH was monitored 5 cm above the lower oesophageal sphincter. Manometric activities were classified as either peristaltic or ineffective. The latter included simultaneous, non-transmitted, and low amplitude peristaltic contractions. A reflux episode was defined as starting when pH fell to less than 4 and ending when the pH rose to 5. When the rise to pH 5 took place in three or more discrete steps after motor responses to gastro-oesophageal reflux, the pH steps were labelled as initial change (I), middle changes (M), and last change (L). A total of 595 episodes of gastro-oesophageal reflux and 1626 associated motor events were analysed. Of these, 1331 (81.9%) were classed as primary peristaltic activity, 174 (10.7%) as primary ineffective activity, 46 (2.8%) as secondary peristaltic activity, and 75 (4.6%) as secondary ineffective activity. There were no significant differences in initial change (p > 0.05), middle changes (p > 0.05), and last change (p > 0.05) between group 1 and group 2. In all patients, the successive changes of pH in response to motor activity were significantly different (p = 0.0001) between initial, middle, and last changes. Last change was significantly higher when compared with initial (p=0.001) and middle changes (p<0.001). Primary oesophageal peristalsis was the most frequent motor response to gastro-oesophageal reflux. The last motor activity during reflux showed the greatest change in pH.

Adult↗

Addition of low-dose folinic acid to a methotrexate/cyclosporin A regimen for prevention of acute graft-versus-host disease.

A study was performed to determine whether the addition of folinic acid to a combination of methotrexate (MTX) and cyclosporin A (CsA) after allogeneic bone marrow transplantation (BMT) could improve tolerance to the regimen without inhibiting its ability to prevent graft-versus-host disease (GVHD). Sixty-nine adult BMT patients received CsA plus MTX 15 mg/m2 on day 1 and 10 mg/m2 on days +3, +6 and +11. Folinic acid 5 mg was started 24 h after each MTX dose and continued 6 hourly until 12 h before the next dose of MTX. The median age of the group was 37 years and 13 patients (19%) received bone marrow from mismatched and/or unrelated donors. No MTX doses were omitted or modified. Grade II-IV acute GVHD occurred in 18 patients (29%) and chronic GVHD in 35 of 56 (64%) patients at risk. There were no cases of grade > or = III stomatitis. Transplant-related mortality was 7% before 100 days and 20% overall (9% for low risk leukaemia) with a median follow-up of 41 months (range 24-88 months). This regimen of folinic acid rescue may contribute to a well tolerated GVHD prophylaxis protocol with reasonably low BMT-related mortality. Our results suggest that the ability of MTX to prevent acute GVHD is not abrogated by folinic acid given in this way.

Acute Disease↗

A deep lateral femoral notch as a sign of acutely torn anterior cruciate ligament.

Anterior cruciate ligament (ACL) tears are frequently associated with abnormalities of the lateral femoral condyle as shown by magnetic resonance imaging. The mechanism of injury has been described as due to bone compression during knee trauma. This may lead to compression of the lateral condylopatellar notch (sulcus). It has been suggested that detection of a deep notch on the plain lateral radiograph is a useful indirect sign of ACL tear. Depth of this notch was measured in 34 consecutive prospective patients assessed as having acute ACL tear clinically and proven at arthroscopy. In no patient was the notch deep, suggesting that this is not a useful sign in acute tears of the anterior cruciate ligament.

Acute Disease↗

Allogeneic bone-marrow transplantation without protective isolation in adults with malignant disease.

Bone-marrow transplant (BMT) patients are severely immunocompromised immediately after the procedure and they are commonly nursed in strict protective isolation to reduce the risk of both infection and graft-versus-host disease (GvHD). We have studied a consecutive series of patients to see whether protective isolation is of benefit as prophylaxis against infectious complications of BMT. 50 consecutive patients who had malignant disease and received their first BMT from siblings or unrelated donors were nursed in standard single rooms with visitors instructed to wash their hands. A subset of 20 patients living locally spent a median of 25 days in hospital after BMT; they also spent some time at home on a median of 8 days before engraftment and 3 patients went home on more than 90% of their hospital days. 16 patients (32%) had positive bacterial cultures and/or focal infection. Gram-positive bacteraemia was found in 12 subjects (24%) but there were no gram-negative or deep fungal infections. Grade II or III acute GvHD developed in 17 patients (34%). There were no deaths from infection or acute GvHD. Transplant-related mortality was 6% in the first 100 days and 18% overall with a median follow-up of 22 months. Our mortality data compare favourably with those from institutions with strict isolation procedures. We conclude that BMT may be safely completed in some institutions without either protective isolation or the need to confine patients continuously in hospital.

Acute Disease↗

Case report: renal excretion of gastrografin following rectal administration.

Renal excretion of water soluble iodinated contrast media following oral administration has often been described but no reports describing renal excretion following rectal administration of such contrast have previously been described. We describe a case of renal excretion of diatrizoate methylglucamine (Gastrografin, Schering) following a diagnostic 'gastrografin enema' in a woman with caecal carcinoma.

Administration, Rectal↗

Metabolism of glycerol by mature boar spermatozoa.

Mature boar spermatozoa oxidized glycerol to carbon dioxide in the absence of any detectable activity of glycerol kinase. With triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase inhibited by the presence of 3-chloro-1-hydroxypropanone (CHOP), dihydroxyacetone phosphate accumulated in incubates when glycerol-3-phosphate was the substrate, but not when it was glycerol. Both dihydroxyacetone and glyceraldehyde could be used as substrates; in the presence of CHOP, dihydroxyacetone phosphate and fructose-1,6-bisphosphate accumulated when dihydroxyacetone was the substrate, but not when it was glyceraldehyde. The metabolic pathways glycerol----glyceraldehyde----glyceraldehyde 3-phosphate and dihydroxyacetone----dihydroxyacetone phosphate have been shown to operate in these cells.

Animals↗

The pericyte as a possible osteoblast progenitor cell.

Bovine capillary and microvessel pericytes were grown in monolayer in standard tissue culture medium supplemented with 10% newborn calf serum at various oxygen tensions for up to ten weeks. The pericytes synthesized alkaline phosphatase and formed colonies that mineralized. Energy dispersive X-ray spectrometry revealed the presence of calcium and phosphate, showed positive staining for collagen and glycosaminoglycan, and, most importantly, demonstrated the synthesis of osteocalcin. Cell proliferation, hydroxyproline production, and alkaline phosphatase synthesis were greatest in 3% oxygen, whereas osteocalcin production was least in 3% oxygen. These findings demonstrate that the capillary or microvessel pericyte exhibits phenotypic expressions in vitro that are similar to that of in vitro bone cells, and these expressions may be somewhat oxygen dependent. It is suggested from these findings that the capillary or microvessel pericyte may be an osteoblast precursor cell.

Alkaline Phosphatase↗

The male antifertility activity of 6-chloro-6-deoxyglucose.

6-Chloro-6-deoxy[U-14C]glucose is not metabolised by mature boar spermatozoa nor has it any specific inhibitory action on their metabolic activity in vitro. The compound is metabolised by the male rat and the identification of two urinary metabolites as alpha-chlorohydrin and 3-chlorolactate confirmed that (S)-3-chlorolactaldehyde is produced by this species in vivo. A tissue distribution study revealed that radioactivity from 6-chloro-6-deoxy[U-14C]glucose was more concentrated in rat caudal spermatozoa than in any other of the major tissues.

Animals↗

Metabolism of fructose-1,6-bisphosphate by mature boar spermatozoa.

Mature epididymal boar spermatozoa converted glucose and fructose to carbon dioxide and lactate and maintained high concentrations of ATP. In the presence of (S)-alpha-chlorohydrin these processes were inhibited and there was an accumulation of fructose-1,6-bisphosphate and dihydroxyacetone phosphate. With fructose-1,6-bisphosphate as the substrate, the concentration of ATP was maintained, carbon dioxide was evolved and dihydroxyacetone phosphate accumulated. Cells pre-incubated with (S)-alpha-chlorohydrin did not maintain ATP levels, evolved less carbon dioxide and produced dihydroxyacetone phosphate. Assays of incubates in which fructose-1,6-bisphosphate was used as the substrate showed the presence of equilibrium quantities of fructose-6-phosphate and glucose-6-phosphate which were not detected when either fructose or glucose were used as substrates. [14C]Fructose and [14C]glucose were not produced from [14C]fructose-1,6-bisphosphate in spermatozoal incubates which had or had not been pre-incubated with (S)-alpha-chlorohydrin. Evidence is presented that a high concentration of fructose-1,6-bisphosphate leads to the formation of fructose-6-phosphate and glucose-6-phosphate but not of fructose and/or glucose.

Adenosine Diphosphate↗

Granulocytic sarcoma of the ovary. An unusual case presentation.

We report an unusual occurrence of granulocytic sarcoma presenting as an ovarian mass in a 46-year-old woman with a history of dysplastic nevus syndrome. During workup of the ovarian mass, the diagnosis of acute myelogenous leukemia was made. A fine-needle aspirate of the ovarian mass showed granulocytic sarcoma. The patient died of complications of the acute leukemia a short time later. A postmortem examination was performed, which confirmed the nature of the ovarian mass as a granulocytic sarcoma. Material was obtained for flow cytometry, immunohistochemical and histochemical studies, and electron microscopy. Ploidy analysis of the tumor showed it to be diploid with an S phase of 4.8% and a G2 + M ratio of 0.5%. To our knowledge, there is only one previous report of a primary ovarian presentation of granulocytic sarcoma, and only four cases in which granulocytic sarcoma was diagnosed by fine-needle aspiration cytology. The association between dysplastic nevus syndrome and acute myeloid leukemia in this case is discussed with reference to a review of the metachronous association between melanoma and leukemia as described in the literature.

Biopsy, Needle↗

Double autologous bone marrow transplantation for acute myelogenous leukemia in a patient treated for Hodgkin's disease.

A 30-year-old man developed acute myelogenous leukemia nearly 3 years after treatment of Hodgkin's disease with radiation and three chemotherapy combinations. Remission was induced with one cycle of high-dose Ara-C therapy. Three cycles of consolidation chemotherapy were given. The patient then had two autologous bone marrow transplants, the first after conditioning with 5 Gy total body irradiation, the second after Melphalan 140 mg/m2. The procedures were well tolerated, although hematological reconstitution was very slow after the second autotransplant. The patient has been disease-free for over 4 years. Such patients may be more vulnerable to transplant-related complications because of their previous exposure to chemotherapy and radiation, which may damage several organs including the bone marrow. This report demonstrates that patients with secondary acute myelogenous leukemia may tolerate a double autotransplant procedure and achieve durable remissions.

Adult↗