PubMed HealthSearch

Biomedical subjects

G R Dickson

Publications and source records attributed to G R Dickson.

18 recordsLinked to original sources

Serum c-reactive protein in patients with serious trauma.

Daily serum c-reactive protein (CRP) concentration was monitored in 98 patients (26 female) admitted to the Major Injuries Unit (MIU) at Birmingham Accident Hospital following serious trauma. The mean (SD) increase in CRP concentration for 79 survivors and 19 non-survivors between days 1 and 2 after trauma were 69.5 (74.6) and 111.8 (59.0) mg/l/24 h, respectively (P = < 0.001). By day 4 after trauma the mean serum CRP concentrations for survivors and non-survivors were 150.9 (76.9) and 233.4 (100.8) mg/l (P < 0.001), respectively. Injury severity data were available for 50 patients. The mean (range) injury severity score was 25.2 (4-50), Glasgow coma scale 10.4 (3-15), revised trauma score 6.5 (3.39-7.8) and predicted survival 0.78 (0.02-0.99). Univariate regression analysis of serum CRP on days 1-5 after injury against revised trauma score and injury severity score, revealed an inverse correlation between day 1 serum CRP and Glasgow Coma Score (r = -0.306, P < 0.05), but no correlation with injury severity score or predicted survival on any of the study days. The lack of correlation between serum CRP and injury severity or predicted survival, and the strong association with actual survival, suggests that the acute inflammatory response to serious trauma and subsequent complications, is an important determinant of outcome.

Adolescent

Rhabdomyolysis and acute renal failure following carbon monoxide poisoning: two case reports with muscle histopathology and enzyme activities.

Two patients with carbon monoxide poisoning are presented, both of whom suffered rhabdomyolysis complicated by acute renal failure. One patient, an attempted suicide, developed a compartment syndrome of the right thigh that required fasciotomy and recovered after a period of hemofiltration and hemodialysis. Muscle biopsy appearances were consistent with partial muscle infarction. The other patient, rescued from a smoke filled room, exhibited raised creatine kinase but no evidence of muscle swelling. He developed anuric renal failure and adult respiratory distress syndrome and died despite maximum intensive care. Muscle biopsy showed early evidence of muscle necrosis. In both cases there was a marked reduction of enzyme activities in the muscle biopsy consistent with metabolic derangement. Although there was a clinical compartment syndrome in the first case, there was no muscle swelling at the time of biopsy or subsequently in the second case. A direct toxic effect of carbon monoxide may thus have been an important mechanism contributing to the muscle necrosis in the second case, although local ischemia may have been an exacerbating factor in the first case.

Acute Kidney Injury

Early effects on the morphology of mouse small intestine of single or combined modality treatment with hyperthermia and X-irradiation.

This study describes the effects of hyperthermia and X-irradiation on the morphological appearance of normal, at risk tissues in the ileum of the mouse. The early morphological effects 1 day after a combined modality treatment are compared with those due to either hyperthermia or X-irradiation given alone. The response was assessed qualitatively and semiquantitatively using scanning electron microscopy and a villous scoring technique. Early post-irradiation effects on topography did not differ significantly from those observed after small intestine exteriorisation without treatment. The villous scores for the combined modality treatments reflected greater damage than would be expected from the sum of villous scores for each modality treatment on its own. This suggests that the combined modality treatment had a synergistic or enhancing effect. A 4 hour time interval between the two treatments did not seem to reduce the enhancing effect. Further studies are required to investigate the effects of fractionated combined treatment.

Animals

Injury scoring by TRISS and ISS/age.

Both the TRISS and ISS/Age methods have been used to assess the mortality results in a series of injured patients. Though observed survival was not significantly different from that expected using TRISS, the method seemed to place too great an emphasis on the initial clinical signs summarized in the RTS. In particular, early cardiovascular signs can be variable and misleading. The TRISS calculation also seems to make inadequate allowance for age effects in the elderly. The simpler ISS/Age method is free from these difficulties and with further development and a more up-to-date base series might become a better basis for overall survival estimates.

Adolescent

Familial expansile osteolysis: a morphological, histomorphometric and serological study.

Biopsies from the diseased bones of patients with familial expansile osteolysis (FEO) were examined by light and electron microscopy. Focal concentrations of multinuclear osteoclasts were present, and these contained viral-like microcylindrical inclusions which appeared exclusive to their nuclei. No consistent relationship was found between osteoclast size and the number of osteoclast nuclei containing microcylindrical inclusions. Quantitative histomorphometry showed evidence of increased bone remodelling with high bone cell densities and a decrease of the reversal period in bone remodelling. The lesions contained prominent woven bone and fibrovascular tissue, together with mononuclear cells and adipocytes. Little bone was found in the most radiolucent lesions, which were almost totally occupied by adipocytes and fibrovascular tissue. Serology did not reveal any significant differences between the viral antibody titres of patients and their age- and sex-matched controls. The present study suggests that intranuclear viral-like microcylindrical inclusions of osteoclasts are not a specific feature of Paget's disease, and are found in other disorders of osteoclast function, including pycnodysostosis, osteopetrosis, giant cell tumours, and familial expansile osteolysis.

Adult

An investigation of vanishing bone disease.

Vanishing bone disease is a rare condition producing local deformity and instability. Fibrovascular tissue replaces bone completely but the mechanism of bone destruction and resorption is unknown and there is controversy regarding the presence or absence of osteoclasts in the disease. Radiography, clinical chemistry, light microscopy, transmission electron microscopy (TEM) and cytochemistry were used to investigate the condition of a young woman presenting early in the disease process. We detected atypical ultrastructure in osteoblasts and endothelial cells. The rare osteoclasts, numerous mononuclear phagocytes and vascular endothelium found in the condition reacted positively for the enzyme acid phosphatase. Aggressive local excision of diseased tissue and insertion of a free vascularized bone graft at an advanced stage of the disease, accompanied by subsequent radiotherapy for residual disease only were successful in rehabilitating the affected forearm and hand.

Adult

Characterisation of a tamoxifen-resistant variant of the ZR-75-1 human breast cancer cell line (ZR-75-9a1) and ability of the resistant phenotype.

A 6-month exposure of ZR-75-1 human breast cancer cells to tamoxifen (1 microM rising to 2 microM). resulted in a fall in oestrogen receptor (ER) levels from 225 fmol mg protein-1 to 56 fmol mg protein-1 while progesterone receptor (PGR) concentration fell from 63 fmol mg protein-1 to undetectable levels. Sensitivity to the anti-proliferative effects of tamoxifen was unchanged. A further 6 months' exposure to 4 microM tamoxifen resulted in loss of detectable ER and PGR and development of resistance to tamoxifen. Resistant cells, designated ZR-75-9a1, displayed morphological changes consistent with the acquisition of a less well differentiated phenotype. Flow cytometric studies demonstrated that the cell cycle distribution pattern of the resistant variant growing in the presence of 8 microM tamoxifen was identical to that of the untreated parent line, which showed marked accumulation of cells in G0/G1 when exposed to 8 microM tamoxifen. The resistant phenotype was not stable if cells were transferred to complete drug-free medium, but remained stable for at least 3 months in the presence of medium lacking oestrogenic activity. ZR-75-9a1 cells differ from previously reported tamoxifen-resistant variants of the MCF-7 line which retain ER and may prove a valuable model for the study of the development and stability of tamoxifen resistance in human breast cancer.

Breast Neoplasms

Examination of mucosal surfaces by scanning electron microscopy before and after removal of debris.

A rapid method is described whereby gastrointestinal biopsy specimen surfaces can be examined by scanning electron microscopy with overlying tract contents (debris) intact, and also re-examined after cleaning to determine the structure of the underlying mucosal surface. The conductive coating of gold is removed using mercury, a non-wetting agent. The specimen surface is suitably cleaned of debris after a brief ultrasonication in absolute ethanol which mixes with the transitional fluid (CO2) used for critical point drying.

Animals

Familial expansile osteolysis. A new dysplasia.

We report 40 cases in one family of an autosomal dominant bone dysplasia, which, though similar in some aspects to Paget's disease, seems unique in some features and in its natural history. The disease shows both general and focal skeletal changes, the latter being mainly in the limbs with an onset from the second decade. Progressive osteoclastic resorption is accompanied by medullary expansion which leads to pain, severe deformity and a tendency to pathological fracture. The serum alkaline phosphatase and urinary hydroxyproline are variably elevated, while other biochemical indices are normal. Most patients had an associated deafness of early onset and loss of dentition. No previous description of this disease has been found in the literature.

Deafness

Cytochemical localization of alkaline and acid phosphatase in human vanishing bone disease.

This report is the first cytochemical investigation of vanishing bone disease "Gorham's Disease" (Gorham and Stout 1955). The ultrastructural localization of non-specific alkaline phosphatase and of specific and non-specific acid phosphatase activity was studied in slices of tissue removed from a patient with this rare disorder. Sodium beta-glycerophosphate and phosphorylcholine chloride were used as substrates. Alkaline phosphatase was present around the plasma membranes of osteoblasts and associated with extracellular matrix vesicles in new woven bone. This is consistent with the proposed role for this enzyme (Robison 1923) and for matrix vesicles (Bonucci 1967) in the mineralization of bone (Bernard and Marvaso 1981). Concentrations of specific secretory acid phosphatase reaction product in the cytoplasm of degenerating osteoblasts may contribute to the imbalance between bone formation and resorption. Osteoclasts, while few in number, showed non-specific and specific acid phosphatase activity. The Golgi apparatus and heterophagic lysosomes of mononuclear phagocytes were rich in non-specific acid phosphatase. This was also present in the Golgi lamellae and lysosomes of endothelial cells. Acid phosphatase cytochemistry suggests that mononuclear phagocytes, multinuclear osteoclasts and the vascular endothelium are involved in bone resorption in this disease.

Acid Phosphatase

The effects of Mg2+ ions or EDTA on nuclear integrity and apparent subcellular distribution of unoccupied oestrogen receptors in breast cancer cells.

Homogenisation and fractionation of cells in the presence of Mg2+ or EDTA resulted in unoccupied oestrogen receptor being recovered in the particulate fraction. Nuclei were partially purified by pelleting at 100,000 g through 41% and 44% (w/w) sucrose (in buffer containing Mg2+ or EDTA), plasma membranes being collected from the top of the 41% barrier. In Mg2+-prepared fractions, both 5'-nucleotidase and unoccupied receptor were distributed between plasma membrane, partially-pure nuclei and mitochondrial/microsomal pellets. Lactate dehydrogenase was not a significant contaminant of particulate fractions. In EDTA fractions, the majority of binding activity was in the partially-pure nuclei (which were extensively disrupted) and mitochondrial/microsomal pellets. Little or no binding was found in the EDTA-prepared plasma membranes which were amorphous in appearance. Mg2+-prepared nuclei, freed of membranous contamination by pelleting through 1.8 M sucrose, were intact by electron microscopy but had no 5'-nucleotidase or unoccupied receptor. These data suggest that recovery of receptor in partially-pure nuclei during fractionation is not caused by trapping of cytosolic protein but rather by redistributed nuclear receptor having become bound to adhering plasma membrane fragments during homogenisation. Implications for the study of cell-free systems are discussed.

Breast Neoplasms

Meptazinol--a cause of respiratory depression in general anaesthesia.

The respiratory effects of meptazinol 1 mg kg-1 have been compared with those of pethidine 0.5 mg kg-1 and 1 mg kg-1 in a double-blind trial in 30 patients undergoing arthroscopic meniscectomy under general anaesthesia. Respiratory depression was seen in all treatment groups. Pethidine 1 mg kg-1 produced respiratory depression which was greater than that produced by meptazinol 1 mg kg-1. The least depressant respiratory effects were seen in the group receiving pethidine 0.5 mg kg-1. We submit that the measurement of tidal volume enhances the assessment of the respiratory effects of analgesic drugs during anaesthesia.

Adult

A little known cell in the gastrointestinal tract.

A little known cell in the gastrointestinal tract has been described. The confusion over terminology is discussed. The question of the undifferentiated cell type is also considered. Although well recognised by gastroenterologists they remain little known in general. Their function is unknown. The various possibilities are summarized.

Animals

Ultrastructural localization of alkaline phosphatase in the hypertrophic chondrocyte of the frog.

The ultrastructural localization of alkaline phosphatase was studied in the hypertrophic chondrocyte of the frog (Rana temporaria) by incubating sections of glutaraldehyde fixed tissue in a medium containing sodium beta glycerophosphate and calcium chloride. Control specimens were incubated in substrate free medium. Alkaline phosphatase (orthophosphoric monoester phosphohydrolase) is a high molecular weight glycoprotein that hydrolyses phosphorylated metabolites much as acid phosphatase does except that its action is optimal at an alkaline pH. The results of this investigation showed that alkaline phosphatase activity was present within the cytoplasm and around the plasma membrane of frog hypertrophic chondrocytes. Although only a small proportion of frog hypertrophic chondrocytes demonstrated enzyme activity, there was evidence that this was concentrated within Golgi lamellae and vesicles leaving other organelles unreactive. The finding of alkaline phosphatase activity within Golgi lamellae of hypertrophic chondrocytes is regarded as unusual although postitive reactions within chondrocyte lysosomes have previously been reported (Doty and Schofield, 1976).

Alkaline Phosphatase