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Biomedical subjects

R Fisher

Publications and source records attributed to R Fisher.

At least 145 records · Page 8Linked to original sources
PubMed1991

Follow-up study on bone marrow reticulin fibrosis in AML.

Planimetric analysis of argyrophilic (reticulin) fibers of the bone marrow was performed on 17 patients (7 males, 10 females, median age 52 years) with acute myeloid leukemia (AML). Trephine biopsies were investigated at presentation and during the course of chemotherapy. Density of reticulin was determined by examining the total marrow area as well as the hematopoietic tissue. In about half of the patients with FAB-subtypes M4, M5 an increased amount of fibers was recognizable on admission in comparison with age-matched controls. Two to five bone marrow biopsies (total 81) of each patient were obtained at intervals ranging mostly between three and seven weeks after cytotoxic treatment. The following results could be demonstrated: in several patients with a normal or elevated fiber count at onset, partial and complete remission was characterized by an increase in reticulin in the regenerative hematopoietic tissue. On the other hand, a relapse was most frequently heralded by a reduction of the formerly increased amount of fibers. Because of the inverse relationship between the density of argyrophilic fibers and the amount of fat cells, these findings were observable only by considering the hematopoietic tissue and not the total marrow area, as has been done in previous studies. For this reason a significant decrease in reticulin fibers in the areas of regenerative hematopoiesis may be suggestive of an impending relapse of AML.

Adult↗
PubMed1991

Megakaryocytopoiesis in idiopathic thrombocytopenic purpura: a morphometric and immunohistochemical study on bone marrow biopsies with special emphasis on precursor cells.

A morphometric and immunohistochemical study was performed on trephine biopsies of the bone marrow in patients showing idiopathic thrombocytopenic purpura (ITP) and reactive thrombocytosis (RTH). Features of megakaryocytopoiesis were determined not only by using the periodic acid Schiff reaction (PAS), but also by immunostaining with the monoclonal antibody Y2/51, detecting a formalin-resistant epitope of glycoprotein IIIa (CD61). An increased number of megakaryocytes was observed in both ITP and in RTH as compared with a control group. Immunostaining revealed a predominance of small immature elements of this cell lineage, particularly in cases of ITP. Following previous experimental cell culture studies on megakaryocyte precursors and features derived from corresponding smear preparations, we characterized promegakaryoblasts immunomorphometrically. According to these calculations, ITP, as opposed to RTH, features a disproportionate expansion of the megakaryocyte precursor pool.

Antibodies, Monoclonal↗
PubMed1990

Bowel complications after radiotherapy for carcinoma of the prostate: the volume effect.

Late radiation-induced bowel complications were studied in 218 patients treated for localized carcinoma of the prostate by radical radiotherapy at the Prince of Wales Hospital between 1980 and 1986. Mild to moderate toxicity was seen in 38 cases, and severe toxicity requiring surgery occurred in 3 patients. The total actuarial complication rate (by 5 years) for all grades was 24% and for severe complications was 1.8%. Significant patient-related risk factors were older age at the time of radiotherapy (p = 0.035) and a previous history of abdominal operations (p = 0.028). Among treatment-related risk factors only inclusion of the whole pelvis in the irradiated volume had a significant association with this complication (p = 0.015). The risk of bowel complications was not related to the total radiation dose or to the use of interstitial implants as employed in this series.

Aged↗
PubMed1990

Preoperative versus postoperative irradiation in the prophylaxis of heterotopic bone formation in rats.

Irradiation treatment, commenced within 1-5 days post-surgery, reliably prophylaxes heterotopic bone formation but is painful and impairs desirable postop immobilization. To compare pre- versus post-op radiation, we bilaterally implanted bone matrix pellets into the thighs of 111 30-day-old Long Evans rats. Rats were randomized to time of radiation initiation (2 days pre-op, 1 hr pre-op, or 2 days post-op) and dose (300, 800, 1800, 2400, or 3000 cGy in 1 fraction). Pellets were removed on post-op day 16 or 48 and evaluated histologically and radiologically. Histologic analysis showed dose-related suppression in bone formation, that is, 40%, 27%, 6.8%, 2.5%, 6.4%, and 0.0% bone formed among sites receiving 0, 300, 800, 1800, 2400, and 3000 cGy, respectively. The difference in bone formation between control and irradiated implant sites was significant at every dose level in all treatment groups (p less than or equal to .03). There was no statistically significant difference in overall bone formation between post-op (7.1%) and 1 hr pre-op (5.3%) groups, whereas 2 day pre-op rats formed significantly more bone (12.6%). Stratified by dose, however, there were no significant differences between treatment groups except at 800 cGy. At this dose, 2 day pre-op rats formed more bone (10.6%) than 1 hr pre-op (6.6%) or post-op (3.3%) groups. Results suggest that a) radiation given shortly prior to a stimulus inducing proliferation among multipotential cells may inhibit subsequent proliferation and/or differentiation, and b) clinical formation of heterotopic bone may be preventable via modest doses of irradiation delivered shortly prior to surgery.

Animals↗
PubMed1990

Survival following perforation of peptic ulcer.

Between 1979 and 1989, 92 patients were treated at St George Hospital, Kogarah, for perforated duodenal or prepyloric ulcer. Mortality rate at 28 days was 18%. Life table analysis showed 1-, 5- and 10-year survival rates for this group to be 78%, 60% and 46% respectively. During the second half of the study period, increasingly older females with a history of cardiovascular disease, arthropathy, chronic renal impairment and non-steroidal anti-inflammatory drugs (NSAIDS) intake were identified and found to be at greater risk of dying from their perforation. Age, cardiovascular disease and chronic renal impairment were demonstrated to be independent factors affecting survival. Patients treated by simple closure of the perforation had a long-term survival rate equivalent to that of patients treated in other ways, although the number of these latter patients is small. Implications for the administration of NSAIDS are considered in the light of these findings. These results suggest that orthodox simple closure of perforated peptic ulcer and administration of H2 blocking agents is the most appropriate treatment for patients presenting with perforated peptic ulcer.

Actuarial Analysis↗
PubMed1990

Regional localization of polymorphic markers on chromosome 10 by physical and genetic mapping.

The human vimentin gene and a random DNA segment (D10S39) were mapped to the short arm of human chromosome 10 by linkage analysis. A panel of somatic cell hybrids and monosomy cell-lines, which divide chromosome 10 into seven regions, was used to localize 10 polymorphic markers on this chromosome. The physical map locations obtained correlate well with linkage maps of chromosome 10. Two markers which have been shown to be closely linked to the gene for multiple endocrine neoplasia type 2A map distal to a translocation breakpoint in band 10q11.2.

Animals↗
PubMed1990

Differential modulation of single voltage-gated calcium channels by cholinergic and adrenergic agonists in adult hippocampal neurons.

1. Pharmacologic agents known to modulate long-term potentiation (LTP) at the mossy fiber-to-CA3 pyramidal neuron synapse were tested for their effects on the activity of single voltage-gated calcium channels in adult CA3 pyramidal neurons. 2. Single-channel current recordings of three types of voltage-gated calcium channels were made from acutely exposed CA3 pyramidal neurons of the adult guinea pig hippocampus. 3. The beta-adrenergic agonist isoproterenol (10 microM), which is known to enhance LTP, increased the activity of the two high-threshold calcium channels (N and L) with no striking effect on the low-threshold (T) channel. 4. The muscarinic agonists carbachol and muscarine (1-10 microM), the latter of which has been shown to inhibit LTP, decreased the probability of opening of L channels, increased the probability of opening of T channels, and had no effect on N channels. The effects were blocked by 0.1 microM atropine. 5. These results are consistent with the hypothesis that neuromodulation of mossy fiber LTP occurs, at least in part, through the modulation of postsynaptic, voltage-gated calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Resection of the epileptogenic area in critical cortex with the aid of a subdural electrode grid.

Electrode grids were implanted subdurally in 28 patients with epilepsy. In 16 of the 28 patients, an epileptogenic area was located in the speech-dominant left temporal lobe. Recordings made with the grid revealed that the epileptogenic areas in the patients varied widely in extent: the area was confined within the first 10 mm of the temporal lobe in some patients or it was scattered throughout the entire anterior to posterior 80-mm extend in others. Resection of the epileptogenic area was adjusted accordingly in each case. In 6 of 16 patients who were left-hemisphere-dominant for language, up to 55-80 mm from the tip of the temporal lobe was removed, a measure that exceeds the conventional limit of 50 mm from the tip of the dominant hemisphere. In the remaining 12 of the 28 patients, epileptogenic areas were located in a combination of several lobes. In 7 of these 12 patients, the epileptogenic area encompassed the rolandic area; it was removed without deficit in 4 patients and with expected deficit in 3. Of the latter 3 patients, 1 patient underwent hemispherectomy, and a large portion of the epileptogenic rolandic cortex in the frontal and parietal lobes was removed from the other 2. There were 2 cases of grid-related infection, which cleared with antibiotic treatment; there were no lasting complications of grid implantation in any patient. There was no mortality. Electroencephalographic recording and functional mapping using subdural electrode grids allow a tailored, maximal resection of epileptogenic tissue with minimal injury to critical cortex.

Brain Diseases↗
PubMed1990

Longitudinal study of thyroid function in acutely ill elderly patients using a sensitive TSH assay-defer testing until recovery.

A prospective longitudinal study of thyroid function was conducted in 180 consecutive admissions to an acute geriatric unit. The rest strategy included assay of TSH and TRH testing when appropriate. On admission TSH was suppressed (less than 0.1 mU/l) in 17 patients (9.4%) and elevated (greater than 4.0 mU/l) in 8 (4.4%). Follow-up of these initial abnormalities showed resolution in almost all cases. Our findings suggest that acute illness may interfere with the hypothalamic-pituitary-thyroid axis, causing either temporary suppression or stimulation of TSH release. Although no new cases of thyroid disease were diagnosed, the prevalence of established dysfunction was 3.3% (2.7% hypothyroid; 0.6% hyperthyroid). To avoid misleading results, testing of thyroid dysfunction should be delayed until recovery from illness.

Acute Disease↗
PubMed1990

Growth and development of brain of artificially reared hypoketonemic rat pups.

Three groups of rats were reared: mother-reared controls; artificially reared controls (AR-c), which were fed a milk substitute with the same composition of macro-nutrients as natural rat's milk; and an artificially reared test group (AR-h), which was fed a milk substitute identical to that fed AR-c pups except that the component of fat containing medium chain length fatty acids was omitted (medium chain triglyceride deficient) and replaced on an isocaloric basis with carbohydrate. The AR rats were fed the milk substitute from postnatal Day 5 until Day 17 by fitting them with gastric cannulas through which the milk could be infused automatically. The nutritional impact of the milk substitutes on growth and the integrity of the brain was assessed by a comparison of morphologic and biochemical markers. Pups in the AR-h group were hypoketonemic. Animals in all groups attained the same body weight by Day 17 and there was no difference in the morphologic markers among the groups with one exception: the vibrissal "barrel fields" of the somatosensory cortex of rat pups in both AR groups were reduced in size but not in number of distribution from those of the mother-reared groups. Furthermore, the brains of the rat pups in the AR groups were not different in weight, but they weighed less than brains of mother-reared controls. Our data show that although there are many similarities in the status of AR rat pups when compared with mother-reared controls, distinctive differences associated with artificial rearing are evident. We conclude that medium chain fatty acids in milk fat and the circulating ketone bodies are not mandatory substrates for growth and the development of the brain. Mechanisms must exist whereby alternative substrates are used to compensate when these metabolites are diminished in supply.

Animal Nutritional Physiological Phenomena↗
PubMed1989

Neutral selection of transfected mammalian cells using tissue plasminogen activator gene expression.

The gene that produces the proteolytic enzyme, tissue plasminogen activator (tPA), was used as a selectable marker for transfection. Cells that were successfully transfected with plasmids containing a gene for tPA (tpa) produce plaques in the caseinolysis assay. Two tpa-containing plasmids were constructed and used to transfect a variety of cell types. One plasmid contained the promoter region of simian virus 40 and the other contained the Moloney murine leukemia virus promoter. No significant difference in transfection frequencies was found for the two plasmids. However, 80% of the cell types tested produced plaques. This system allows for the identification and isolation of transfected cells under conditions that are not lethal to nontransfected cells.

Animals↗
PubMed1989

Rabbit F(ab')2 antihuman IgE is a universal skin test reagent in the evaluation of skin mast cell degranulation in vivo.

Antihuman IgE is often used to study basophil- and mast cell-mediator release in vitro but is infrequently used in vivo. To evaluate in vivo skin reactivity to anti-IgE, an affinity-purified rabbit F(ab')2 fragment of antihuman IgE was injected intradermally in 22 nonallergic and 27 allergic subjects. All 49 subjects (including a subject with less than 1 ng/ml of total serum IgE) had positive immediate cutaneous reactions to anti-IgE. Although total serum IgE level was weakly correlated (r = -0.51; p less than 0.005) with in vivo skin reactivity to anti-IgE for the entire population, allergic subjects did not have significantly increased skin reactivity compared to nonallergic subjects (p = 0.18), despite having higher total serum IgE levels (p less than 0.002). A late-phase cutaneous response (LPR) to anti-IgE occurred in 60% of the allergic and in 50% of the nonallergic subjects. Subjects with an LPR required approximately tenfold higher concentrations of anti-IgE to produce an immediate wheal of 10 mm compared to subjects who did not develop an LPR (p = 0.02), suggesting that the concentration of the stimulus injected is more important for the development of a LPR than the size of the immediate cutaneous response. Skin reactivity to codeine phosphate (a non-IgE-dependent secretagogue) was correlated with skin reactivity to anti-IgE (r = 0.47; p less than 0.05), suggesting that in vivo skin mast cell degranulation is partially a function of mast cell releasability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Central nervous system toxicity of cyclosporine in a rat model.

The central nervous system toxicity of cyclosporine, which is known to be neurotoxic clinically, was investigated in a rat model. Munich-Wistar rats were divided into 3 groups for a 2-week protocol. After baseline EEG and behavioral testing, group 1 (control) received a weight-adjusted volume of parenteral cyclosporine vehicle i.p., group 2 (low-dose) received 5 or 10 mg/kg/day i.p., and group 3 (high-dose) received 20 mg/kg/day i.p. Spontaneous behavior was observed, simple sensorimotor testing performed daily, and awake EEG's recorded 3 times per week. Four of 12 high-dose animals died during study, one after a witnessed tonic-clonic seizure, and two after recording of frankly epileptiform EEG's; there were no deaths in control or low-dose animals. Significant EEG abnormalities developed only at high-dose, with frankly epileptiform EEG's and/or seizures seen in 58 +/- 15% of these rats (P = 0.005, different from controls by life-table analysis). Although some high-dose animals demonstrated hyperirritability and dystonic posturing, behavioral changes were subtle, and animals were often still or rocking slightly during recording of frankly epileptiform EEG's. Walking latency and alley escape behaviors were delayed in high-dose rats, the latter correlating with abnormal EEG's. Serum urea nitrogens were mildly elevated in high-dose animals, but serum creatinine, electrolytes, bilirubin, body magnesium stores, and blood pressure remained normal in all groups. Kidneys showed only mild vacuolation histologically. The brain showed only very focal cortical injury sites related to electrode placement, which did not correlate with EEG changes or mortality. These results suggest that there may be a direct effect of cyclosporine on the central nervous system. This model system should prove useful in defining mechanisms of cyclosporine-related neurotoxicity.

Animals↗
PubMed1989

Invasive bladder cancer. Prognostic factors and results of radiotherapy with and without cystectomy.

We report the results and complications of treatment in 205 patients with nonmetastatic invasive bladder cancer. Between 1977 and 1982 there were 3 treatment groups: palliative radiotherapy, radical radiotherapy, and pre-operative radiotherapy followed by total cystectomy. Data were complete on each patient until the end of 1985 (minimum follow-up 3 years, median 5.6), when 48 patients were alive without evidence of bladder cancer and 28 had died of intercurrent illness (without clinical evidence of bladder cancer). The overall actuarial 5-year survival rate (death from any cause) was 24%. The 5-year survival rates were 13% for group 1, 25% for group 2 and 38% for group 3. Group 1 patients had a significantly shorter survival. The difference between groups 2 and 3 was not statistically significant. The prognostic factors of significance for survival were clinical stage and ureteric obstruction. Factors such as age, tumour grade and multiplicity were significant when examined singly but not in a multivariate analysis which included stage and ureteric obstruction. The actuarial incidence of all radiotherapy complications in bladder and bowel was 9.4 and 10.5% respectively.

Adult↗
PubMed1988

Sequence structure and expression of a cloned beta-glucosidase gene from an extreme thermophile.

The gene for a beta-glucosidase from the extremely thermophilic bacterium Caldocellum saccharolyticum has been isolated from a genomic library and sequenced. An open reading frame identified by computer analysis of the sequence could encode a protein of Mr 54,400, which is close to the size of the polypeptide experimentally determined using maxicells. Analysis of the amino-terminal residues of the protein produced in Escherichia coli suggests that it is processed by a methionine aminopeptidase. A sequence within C. saccharolyticum DNA upstream of the beta-glucosidase gene was found to act as a promoter for expression of the thermophile gene in E. coli. The protein has been overproduced in E. coli and Bacillus subtilis where it retains its enzymatic activity and heat stability. There appears to be a single copy of the gene in Caldocellum DNA.

Amino Acid Sequence↗