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Biomedical subjects

K Mason

Publications and source records attributed to K Mason.

At least 73 records · Page 4Linked to original sources

The red cell distribution width in sickle cell disease--is it of clinical value?

The red cell distribution width (RDW) has been studied during the clinical steady state in 1121 patients with homozygous sickle cell (SS) disease, 344 with sickle cell-haemoglobin C (SC) disease, 68 with sickle cell-beta+ thalassaemia, 49 with sickle cell beta 0 thalassaemia and in 130 control subjects with a normal (AA) genotype. The mean RDW was moderately increased in S beta + thalassaemia and SC disease and markedly increased in S beta 0 thalassaemia and SS disease. In SS, SC and S beta 0 thalassaemia genotypes, lower RDW values occurred in females and with alpha thalassaemia. The RDW correlated negatively with total haemoglobin, mean cell haemoglobin concentration, mean cell volume, and fetal haemoglobin (HbF) and positively with reticulocyte count in SS disease. A low RDW was associated with higher weight and less frequent dactylitis, painful crisis, acute chest syndrome, acute splenic sequestration, and hospital admissions. A low RDW in SS disease is consistent with a high total haemoglobin, high HbF, low reticulocyte count, alpha thalassaemia, and a more mild clinical course.

Adolescent↗

Effect of interleukin 1, inflammation, and surgery on the incidence of adhesion formation and death after abdominal irradiation in mice.

There is clinical evidence that prior surgery and inflammation can increase the risk of the chronic complications of radiotherapy delivered to the pelvic/abdominal region. We have established a murine model to study this interaction using as end points mortality and late gut-associated peritoneal adhesion formation. A single dose of 16 Gy of total abdominal irradiation (TAI) was used. This gave no early deaths (less than 1 mo) and a relatively low mortality over the period 1 to 6 mo after TAI. The incidence of adhesions, which is the most serious complication 2 to 6 mo after TAI, was also low. Injection of lipopolysaccharide (50 micrograms, i.p.) or human recombinant interleukin 1 (IL-1) in doses as low as 100 units prior to TAI greatly enhanced both radiation-induced adhesion formation and death. Prior surgery also increased radiation-induced mortality, so much so that adhesions could not be accurately quantified. The timing of administration of lipopolysaccharide and IL-1 and of surgery relative to TAI was important in determining the outcome. For example, IL-1 enhanced adhesion formation and death if given from 3 days before to 1 day after, but not 4 days or 4 wk after, TAI. If given 20 h or less before TAI, there was a dramatic increase in early mortality 1 to 3 wk later, which was not seen if IL-1 was given at other times. These early deaths were not caused by bone marrow or gut stem cell depletion and may be a result of fluid leakage. We propose that surgery, bacterial invasion, or other inflammatory signals might act through a common mechanism of stimulating IL-1 production to enhance radiation-induced adhesion formation and the early and late morbidity and mortality associated with abdominal irradiation. If this is the case, blocking IL-1 production might inhibit the development of these late complications.

Abdomen↗

Fitting the linear-quadratic model using time of occurrence as the end-point for quantal response multifraction experiments.

A statistical technique is given for fitting the linear-quadratic model to experimental quantal response multifraction data using the time of the response as the end-point. The analysis used is based on the Cox Proportional Hazards model. The technique is useful for late effects where the time of occurrence of the response is dose dependent. The technique is compared to logistic regression analysis and the advantages and disadvantages are discussed. Both methods are applied to a lung pneumonitis experiment and a kidney experiment.

Animals↗

Cardiopulmonary complications after major surgery: a role for epidural analgesia?

Improvement in postoperative pulmonary mechanics with epidural analgesia has been described. Data on the hemodynamic effects of this technique are absent from the surgical literature. To provide such data we have evaluated two groups of patients undergoing aortic reconstruction: group I (n = 25), general anesthesia and group II (n = 6), general anesthesia with adjunctive epidural analgesia. The groups were comparable preoperatively as judged by the incidence of cardiac history, preoperative ejection fraction, and measured hemodynamic parameters. Postoperatively there were no significant differences in the pressure-related parameters; however, rate-related factors including heart rate and double product were significantly decreased in group II with no reduction in cardiac index. Postoperative increases in total body oxygen consumption were also markedly attenuated by epidural analgesia. Epidural analgesia reduces the hemodynamic demands on the heart after major surgery and is a useful adjunct, especially in patients with coronary artery disease.

Aged↗

Alpha thalassemia and the hematology of homozygous sickle cell disease in childhood.

alpha Thalassemia modifies the hematologic expression of homozygous sickle cell (SS) disease, resulting in increased total hemoglobin and HbA2 and decreased HbF, mean cell volume, reticulocytes, irreversibly sickled cells, and bilirubin levels. The age at which these changes develop in children with SS disease is unknown. Ascertainment of globin gene status in a large representative sample of children with SS disease has afforded an opportunity to study the hematologic indices in nine children homozygous for alpha thalassemia 2 (two-gene group), 90 children heterozygous for alpha thalassemia 2 (three-gene group), and 167 children with a normal alpha globin gene complement (four-gene group). The two-gene group had significantly lower mean cell volumes from birth, higher red cell counts from one month, lower reticulocytes from three months, and higher HbA2 levels from one year, as compared with the four-gene group. Children with three genes had intermediate indices but resembled more closely the four-gene group. Differences in total hemoglobin or in fetal hemoglobin between the groups were not apparent by eight years of age. The most characteristic differences of the two-gene group were the raised proportional HbA2 level and low mean cell volume, the latter having some predictive value for alpha thalassemia status at birth.

Age Factors↗

The pharmacodynamic properties of lorazepam and methylphenidate drugs on event-related potentials and power spectral analysis in normal subjects.

The effect of lorazepam and methylphenidate on the ERPs and power spectral analysis was studied. Lorazepam caused prolonged latency and decreased amplitude of N200 and P300. This result suggests that lorazepam affects the neural processing of cognitive function. The drowsiness induced by lorazepam correlated inversely with alpha frequency power, but had no direct correlation with fast activity. On the contrary, when methylphenidate was given, there was no change in ERPs. There was an increase in percent alpha frequency correlated with the alertness of the subjects. An analysis of variance involving the factors of drug and time of rating showed that subjects showed a significant (p less than 0.0001) decrease in alertness over time while receiving lorazepam, and a significant (p less than 0.05) increase in alertness over time while receiving methylphenidate.

Adolescent↗

The haematology of steady state homozygous sickle cell disease: frequency distributions, variation with age and sex, longitudinal observations.

The steady state haematological characteristics observed in 1071 patients with homozygous sickle cell (SS) disease aged 5-66 years are presented. Cross sectional studies indicated that HbA2 levels were consistently higher in males but no age related change was apparent. Fetal haemoglobin levels were consistently higher in females and fell significantly in males between the 5-9 and 10-14 year age groups. Total haemoglobin was significantly higher in females before age 15 and higher in males after 20 years, a dramatic age related rise occurring in males between the 10-14 and 25-29 year age groups, and a fall in patients aged 40 years and over. The mean cell volume was consistently greater in females after 15 years and a marked age related rise occurred in both sexes between the 5-9 and 25-29 year age groups. Counts of irreversibly sickled cells were consistently higher in males. Reticulocytes fell significantly with age, while platelets and total bilirubin fell significantly after the age of 15 years. Longitudinal studies confirmed the increase in total haemoglobin levels in males over the ages 10-14 years, and a significant fall in males after the age of 30 years. Such studies also confirmed the fall in HbF in males aged 5-14 years, the increase in MCV in both sexes aged 5-29 years, and the fall in platelet counts in both sexes over the age of 20 years. These observations provide 'normal' values for patients seen elsewhere and also contribute to an understanding of factors determining the haemoglobin indices in SS disease.

Adolescent↗

Haematological change in sickle cell-haemoglobin C disease and in sickle cell-beta thalassaemia: a cohort study from birth.

The haematological changes in early years following neonatal diagnosis have been observed in representative groups of children with sickle cell-haemoglobin C (SC) disease, sickle cell-beta(+) thalassaemia, and in sickle cell-beta(0) thalassaemia. Most haematological indices in SC disease were intermediate between previously published values in SS disease and in AA controls, generally being closer to values in normal children. Exceptions were microcytosis which may be genetically determined and a striking elevation of mean cell haemoglobin concentration from age 2 months to 4 years. The combination of a raised MCHC and a lowered MCV is unusual and may be characteristic of SC disease. Features in sickle cell-beta thalassaemia generally differed according to the type of beta thalassaemia gene. Sickle cell-beta(0) thalassaemia had lower levels of haemoglobin, MCHC, red cell count, MCV, and higher reticulocytes, most differences being significant before 1 year. No differences between S beta(0) thalassaemia and S beta(+) thalassaemia were apparent in HbF levels (which resembled those in SS disease) or in HbA2 levels (which exceeded those in SS disease by 1 year of age).

Anemia, Sickle Cell↗

Alpha thalassaemia and the haematology of normal Jamaican children.

Haematological indices were studied from birth to 9 years in a representative sample of 195 children with a normal haemoglobin (AA) genotype subdivided according to the number of alpha globin genes. These were 5 homozygotes for alpha-thalassaemia 2 (two-gene group), 60 heterozygotes for alpha-thalassaemia 2 (three-gene group), and 130 with a normal alpha globin gene complement (four-gene group). HbF and HbA2 showed no differences between the groups. Compared to the four-gene group, the three-gene group tended to have significantly lower levels of total haemoglobin, MCHC, MCV, and MCH, and higher levels of red cell count. These differences became apparent with increasing age in the order of MCV, RBC, MCHC, and total haemoglobin. The data suggested that haematological differences were more marked in the two-gene group but with the small numbers available, the differences were not significant.

Child↗

Multifraction radiation response of mouse lung.

The response of mouse lung to repeated doses of 60Co gamma-rays of as low as 115 cGy per fraction was measured using death from pneumonitis between 80 and 120 days after irradiation as the endpoint. A fractionation interval of 3 h was maintained for most regimens but in the longer experiments some 12 h intervals were introduced for logistic reasons. The longest overall duration (for a 43 fraction regimen) was 8 days. The total doses required to produce 50 per cent mortality increased continuously as dose/fraction was decreased, even from 160 to 115 cGy per fraction. Of clinical relevance, the steepness of the isoeffect curve over the dose range 115-500 cGy indicates that the lung shows greater sparing from dose fractionation than is characteristic of more rapidly-responding normal tissues, resembling, in this respect, other more slowly-responding tissues such as spinal cord. The plot of the reciprocal of the LD50 values as a function of dose per fraction was non-linear, suggesting that a linear quadratic dose response model may not be appropriate or that repair of cellular injury in lung is not complete in 3 h, or both.

Animals↗

Purification and analysis of isoforms of soluble immune response suppressor (SIRS).

Soluble immune response suppressor (SIRS) isolated from the T cell hybrid 393D2.6 was originally reported to exist as at least two m.w. forms and to migrate on reverse-phase high-performance liquid chromatography columns as three separate species. In experiments presented here, a further analysis of the different chromatographic forms of SIRS has been carried out. SIRS-alpha elutes from C-18 reverse-phase columns in 20% propanol. When SIRS-alpha is subjected to isoelectric focusing, three biologically active species are isolated at approximately pH7, approximately pH6, and approximately pH5 (SIRS-alpha 7, SIRS-alpha 6, and SIRS-alpha 5, respectively). SIRS-beta elutes in 30% propanol, and on isoelectric focusing the biologic activity is found only at approximately pH7 (SIRS-beta 7). Both the alpha and beta forms of SIRS have nearly identical m.w. when subjected to molecular sieve chromatography and migrate with a m.w. of 11,000. The molecular basis for these isoforms is not yet clear but is consistent with earlier studies showing two separate messenger RNA species coding for SIRS.

Animals↗

Factors affecting the prevalence of tinnitus.

The prevalence of tinnitus was studied in a large population of noise-exposed workers. It was found that 6.6% had tinnitus which was more than momentary. Results of two other studies were compared. Factors possibly relating to the prevalence of tinnitus were studied. The single most important factor found to be related to tinnitus is hearing level. The higher the hearing level, the faster the rate of increase in the prevalence of tinnitus. Other factors such as sex, age, laterality, smoking and shooting do not seem to have a significant, direct relationship with tinnitus, but they are related to the prevalence of tinnitus indirectly through the influence they have on hearing loss.

Adolescent↗

A trial of folate supplementation in children with homozygous sickle cell disease.

A double blind controlled trial of supplementation with folic acid has been performed in 117 children with homozygous sickle cell (SS) disease aged 6 months to 4 years over a 1 year period. No megaloblastic change was observed in either group. At the end of the study period the folate supplemented group showed no significant differences in haemoglobin, growth characteristics, or in the proportion of children affected by major or minor infections, acute splenic sequestration, dactylitis or episodes of bone or abdominal pain. However, the folate supplemented group showed a significantly lower mean cell volume and the placebo group contained a significant excess of children experiencing multiple episodes of dactylitis. The results are compatible with mild folate deficiency in some patients in the placebo group but the absence of striking effects on haematology or growth suggest that the policy of regular folate supplementation in children with SS disease should be critically reviewed.

Anemia, Sickle Cell↗

The ear effect as a function of age and hearing loss.

Many studies have shown that the right ear statistically is slightly more sensitive than the left ear, particularly in the male adult population. In this study, we examined the lateral difference in hearing sensitivity, termed the ear effect here, in an industrial noise-exposed, nonshooting population, by sex, age, and hearing level. It was found that the male population had a larger ear effect (right ear being more sensitive) than the female population. The magnitude of the ear effect was found to be significantly related to the hearing threshold level. The ear effect was highest when the threshold was between 30- and 40-dB HL. Several possible causes for the ear effect are discussed.

Adult↗