Biomedical subjects
Publications and source records attributed to C Robertson.
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A series of 56 consecutive patients, referred for surgery to a specialized institute, had elective laparotomies with various surgical procedures aimed at curing locoregional colorectal cancer. Data defining patient and tumour-related preoperative, operative and postoperative variables, including costs, were collected. The study group was divided into two age groups (< 65 vs > or = 65 years), which were similar in terms of patient- and tumour-related variables. Differences were not statistically significant (Pounds 440; 95% exact CI; Pounds -50; 1800). There is no evidence to suggest that there are any total charge differences in treating the two age groups, as confirmed by the cost analysis.
The interpretation of time trends in disease rates can be facilitated using estimable contrasts from age-period-cohort models. Cohort and period trends in breast cancer incidence and mortality rates in Scotland were investigated using contrasts that measure the changes in the linear trends. These contrasts were compared with estimates obtained from mortality rates in the USA and Japan. A significant moderation of both breast cancer incidence and mortality rates was observed in Scotland, associated with cohorts of women born after the Second World War compared with women born between the two world wars. The moderation of breast cancer mortality among cohorts born after 1925 compared with cohorts born before 1925 that was observed in the USA and Japan was also observed in this study. This moderation is not present in the incidence rates. The relative decline in the risk of breast cancer seen in younger cohorts seems to be contradictory to the temporal pattern present among breast cancer risk factors. It may well be that the alteration of eating patterns as a result of rationing in the wartime and immediate post-war period, and the subsequent influence on certain breast cancer risk factors probably produced by such changes, may have had some influence on the development of healthier girls and women. Such speculation could be addressed in a well-designed epidemiological study. There have been no changes in the mortality rate trends with period in Scotland, although the changes in the incidence rate trends with period are consistent with an increase in registration coverage.
BACKGROUND: As part of the International Study of Asthma and Allergies in Childhood (ISAAC), prevalence surveys were conducted among representative samples of school children from locations in Europe, Asia, Africa, Australia, North and South America. SUBJECTS: 257,800 children aged 6-7 years from 91 centres in 38 countries, and 463,801 children aged 13-14 years from 155 centres in 56 countries. METHODS: Written symptom questionnaires were translated from English into the local language for self-completion by the 13-14-year-olds and completion by the parents of the 6-7-year-olds. Rhinitis was described as a problem with sneezing, or a runny, or blocked nose when you (your child) DID NOT have a cold or the flu. Additional questions were asked about rhinitis associated with itchy-watery eyes, interference with activities and a history of hay fever ever. RESULTS: The prevalence of rhinitis with itchy-watery eyes ("rhinoconjunctivitis") in the past year varied across centres from 0.8% to 14.9% in the 6-7-year-olds and from 1.4% to 39.7% in the 13-14-year-olds. Within each age group, the global pattern was broadly consistent across each of the symptom categories. In centres of higher prevalence there was great variability in the proportion of rhinoconjunctivitis labelled as hay fever. The lowest prevalences of rhinoconjunctivitis were found in parts of eastern Europe, south and central Asia. High prevalences were reported from centres in several regions. CONCLUSION: These results suggest substantial worldwide variations in the prevalence and labelling of symptoms of allergic rhinoconjunctivitis which require further study. These differences, if real, may offer important clues to environmental influences on allergy.
STUDY OBJECTIVE: To examine changes in regional variance in all cause mortality rates in Great Britain from 1931-91 using formal statistical modelling procedures, and to follow up the suggestion by Illsley and Le Grand that there has been a reduction over time in the regional variance in younger but not older age groups. DESIGN, SETTING, AND PARTICIPANTS: Data were the age and sex specific death rates around each census from 1931-91 for the British regions, reconstructed to make them comparable with the 1981 regional definitions. Regional variance was modelled using bootstrap simulation tests and by age-period and age-cohort models. MEASUREMENTS AND MAIN RESULTS: While there was some evidence of a decline and levelling off of the regional variance over time in older age groups (over 35), the decline in younger age groups was more marked. This broadly confirms previous findings. Parametrising the period effect into linear and quadratic components, with allowance for an increase in regional variance in the war years, gave broadly comparable fit to the data as a model with period as a factor. Models for the changes in regional variance which were based on period effects seemed to provide a better description of the observed variances than those based on birth cohort effects. In the younger (but not older) groups there was evidence of a rise in the regional variance between 1981 and 1991. CONCLUSIONS: The decline in regional variance is larger in younger than in older age groups when allowance is made for the increase in regional variance over the war years. Statistical modelling can provide insights into the data which are not always detected by descriptive analyses. Moreover, they provide a capacity for generalisation beyond the particular data; relationships found can form the basis for studies of replicability, for example, in other countries.
In vitro function of cord blood platelets from 35 premature infants (gestational age 32 +/- 3.2 wk) was compared with that of 12 full-term infants and 14 adult control subjects. In comparison with adult platelets, preterm platelets showed impaired aggregation, in response to thrombin, collagen, ADP, and U46619 [a stable analog of thromboxane A2 (TxA2)], and impaired [14C]serotonin secretion in response to collagen and U46619. The production of TxB2 (the stable TxA2 metabolite) in response to collagen was reduced in preterm platelets (30.2 +/- 5.5 ng/mL) compared with full-term (52.7 +/- 12.6 ng/mL) or adult control platelets (132.3 +/- 38.7 ng/mL). The deficient TxB2 production and U46619 response prompted further investigation of TxA2 receptor number and binding characteristics. Immunoblotting using an anti-TxA2 receptor antibody (anti-P2) identified a single, identical 55-kD band in solubilized membranes of control, full-term, and preterm platelets. Flow cytometry using anti-P2 produced histograms that did not differ between adults and neonates. Ligand binding studies using [3H]U46619 were carried out on 10 samples from each group. Scatchard analysis yielded a single class of binding sites with no significant difference among the Kd values (85 +/- 16 versus 99 +/- 12 versus 100 +/- 12 nM) or number of binding sites per platelet (1876 +/- 460 versus 2450 +/- 478 versus 2777 +/- 536) for preterm and full-term infants and adults. Therefore platelets of preterm infants show impaired TxA2 production and response. The poor response is not related to altered binding characteristics of the TxA2 receptor but may lie in the postreceptor signal transduction pathway.
In two experiments, the capacity of Parkinson patients and normal controls to generate letters randomly was investigated using a dual task. The task was based on Baddeley's work (Baddeley, A. D., Quarterly Journal of experimental Psychology 18, 119-129, 1966) where participants vocalize letters of the alphabet in random order. The task was performed under two conditions where letters were (a) vocalized at a specified rate (0.5, 1, 2 and 4 sec); and (B) letters were vocalized at the same rates but with a secondary task of sorting cards into one, two, four and eight categories. The aim was to test the notion of non-specific slowing in response selection processing in Parkinson's disease. Results showed that randomness decreased as generation rate increased in both groups, but with the patient group significantly impaired in comparison to controls. The notion of a limited capacity response selector based on disruption to the Supervisory Attentional System is invoked to account for the impaired capacity of the patient group to generate information internally.
OBJECTIVE: This study compares laparoscopic versus open repair and suture versus sutureless repair of perforated duodenal and juxtapyloric ulcers. BACKGROUND DATA: The place of laparoscopic repair of perforated peptic ulcer followed by peritoneal toilet of the peritoneal cavity has been established. Whether repair of the perforated peptic ulcer by the laparoscopic approach is better than conventional open repair and whether sutured repair is better than sutureless repair are both undetermined. METHODS: One hundred three patients were randomly allocated to laparoscopic suture repair, laparoscopic sutureless repair, open suture repair, and open sutureless repair. RESULTS: Laparoscopic repair of perforated peptic ulcer (groups 1 and 2) took significantly longer than open repair (groups 3 and 4; 94.3 +/ 40.3 vs. 53.7 +/ 42.6 minutes: Student's test, p < 0.001), but the amount of analgesic required after laparoscopic repair was significantly less than in open surgery (median 1 dose vs. 3 doses) (Mann-Whitney U test, p = 0.03). There was no significant difference in the four groups of patients in terms of duration of nasogastric aspiration, duration of intravenous drip, total hospital stay, time to resume normal diet, visual analogue scale score for pain in the first 24 hours after surgery, morbidity, reoperation, and mortality rates. CONCLUSIONS: Laparoscopic repair of perforated peptic ulcer is a viable option. Sutureless repair is as safe as suture repair and it takes less time to perform.
OBJECTIVE: To assess the effect of guidelines for x ray requests on requests for cervical spine x rays. SETTING: Accident and emergency (A&E) department of tertiary referral centre. METHODS: Guidelines for all x ray requests were introduced in the (A&E) department of the Royal Infirmary of Edinburgh in February 1992. The effect of the guidelines on requests for cervical spine x rays was assessed by retrospective review of all such x rays taken over two 30 d periods, before and after the introduction of the guidelines. Junior staff had been in post for 3 months during both periods assessed. Films were reviewed for quality by a consultant radiologist. RESULTS: Guidelines reduced the number of inappropriate requests significantly; however, 26% of requests were still unnecessary. The standard of radiography improved but 49% of x rays remained inadequate, usually because the C7/T1 level was not demonstrated on the lateral view. The A&E doctors correctly interpretated the radiographs in 95% of examinations. CONCLUSIONS: Guidelines reduce inappropriate x ray requests. Further improvements can be expected with continued education.
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Lysosomal Associated Membrane Protein-2 (LAMP-2) is an inherent component of lysosomal granule membranes in diverse cell types, including platelets. We examined platelets for evidence of LAMP-2 in dense granule membranes as CD63 has previously been shown to be present in both lysosomal and dense granule membranes. Immunological techniques were used to examine the localization of LAMP-2 in control platelets and those from an individual with Hermansky-Pudlak syndrome (HPS), a condition characterised by platelet dense granule deficiency. Immunoblotting studies demonstrated that LAMP-2 was enriched in a dense granule preparation. Flow cytometry of thrombin-stimulated control platelets was consistent with biphasic surface expression of LAMP-2. The early expression was accompanied by dense granule, but minimal lysosomal granule, release. The late expression was accompanied by additional lysosomal granule release only. Thrombin stimulation of HPS platelets showed only late, lysosome-associated LAMP-2 expression. Immunoelectron microscopy indicated the presence of LAMP-2 in the membranes of serotonin-containing granules as identified by an anti-serotonin polyclonal antibody. These data indicate that LAMP-2 is present in the membranes of platelet dense granules in addition to lysosomal granules, and has a similar distribution to CD63.
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We have shown previously that treatment of rats bearing the Dunning R3327 MatLyLu prostatic tumor with human interleukin 2 (IL-2) gene-modified tumor cell preparations induces potent antitumor immunity in the animal. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of prostate cancer, we have explored the use of a simplified gene delivery system based on liposomes to introduce and express the IL-2 gene in the Dunning rat R3327 MatLyLu prostatic tumor cell line (MatLyLu) and in short-term cultures of primary human prostatic tumor cells. Liposome-DNA complexes containing the adeno-associated virus inverted terminal repeats exhibited 3-10-fold higher levels of gene transfer and IL-2 expression than did liposome complexes with non-adeno-associated virus containing plasmids. Single transfections resulted in IL-2 expression for an extended period of time that exceeded severalfold the amount of IL-2 secreted from retrovirally transduced MatLyLu cells. X-irradiation of cells (4000 rads) prior to transfection did not affect cytokine secretion, indicating that liposome-mediated gene transfer does not depend on cell proliferation. High levels of gene transfer and IL-2 expression were also achieved in short-term cultures of primary human prostatic tumor cells established from tumor specimens obtained following radical prostatectomy of cancer patients. Depending on the type of liposome used, IL-2 levels secreted from the human prostatic tumor cells were comparable to or exceeded the levels of IL-2 secreted from retrovirally transduced MatLyLu cells, which induced antitumor immunity in the rat model. The ability to culture and expand ex vivo human prostatic tumor cells, and the use of a simple and highly efficient gene transfer method to generate genetically modified tumor vaccines, set the stage for clinical exploration of gene-based immunotherapy of prostate cancer.
Active compression-decompression cardiopulmonary resuscitation (ACD-CPR) has been evaluated in animal cardiac arrest models and in human outcome studies. Blood flow to the brain and heart is significantly increased during ACD-CPR compared to standard CPR. Transoesophageal Doppler analysis indicates that ACD-CPR increases left ventricular blood volume, velocity of blood flow through the mitral valve (82-140%), and stroke volume (85%). Pressures, such as coronary perfusion-, systolic-, mean-, and diastolic aortic pressures, ETCO2, and tidal volume generated by chest compression and decompression, increase during ACD-CPR compared to standard CPR. Prehospital outcome studies have shown both positive and no extra benefit of ACD-CPR on return of spontaneous circulation, hospital admission, and discharge rates. The ACD-CPR method should be evaluated in patients with witnessed arrest receiving bystander CPR who are found in ventricular fibrillation and do not respond to the three initial DC shocks. There is no evidence that ACD-CPR is worse than standard CPR. Appropriate ACD-CPR training using a standardized curriculum must preceed its implementation. Long-term neurologic outcome studies are needed.
A randomized, double-blind, placebo-controlled trial was performed in 13 hospitals in Canada to assess whether two rescue doses of a synthetic surfactant (Exosurf Neonatal) would reduce mortality and morbidity rates in neonates with respiratory distress syndrome who weighed from 750 to 1249 gm. As part of the original trial design, double-blind follow-up evaluations were performed at 1-year adjusted age. A total of 118 patients who received air placebo and 114 patients who received synthetic surfactant were evaluated at 1 year. Growth and development in the two groups were equivalent. Scores on the Bayley Scales of Infant Development were within the normal range for both groups (mental development index, 90 +/- 22 vs 92 +/- 22; psychomotor development index, 81 +/- 19 vs 87 +/- 22 for the air placebo and synthetic surfactant groups, respectively). However, in both groups the proportion of infants with any impairment (air placebo group, 43 of 118 (36%); synthetic surfactant group, 41 of 114 (36%) and severe impairment (air placebo group, 29 of 118 (25%); synthetic surfactant group, 21 of 114 (18%)) was substantial. We conclude that two rescue doses of synthetic surfactant in infants with RDS who weighed 750 to 1249 gm had no detrimental effect on developmental outcome or late morbidity. No long-term benefits to 12-months corrected age were observed with the use of surfactant in this weight class. Larger studies or meta-analyses of existing trials will be required to determine if there are any late outcome advantages associated with rescue use of synthetic surfactant in infants weighing 700 to 1249 gm.
This study determined outcomes at 12-months adjusted age of 957 infants weighing more than 1250 gm at birth who were subjects in a randomized, double-blind, controlled trial of synthetic surfactant or air placebo administered in a rescue trial at 23 hospitals in the United States and 13 hospitals in Canada. Follow-up results were available for 475 of 563 surviving infants who received air placebo (84%) and 482 of 571 infants who received synthetic surfactant (84%). Developmental outcome was equivalent in the two groups. Morbidity was less in the synthetic surfactant group as assessed by the need for medication for chronic lung disease (52 of 475 (11%) for the air placebo group vs 32 of 482 (7%) for the synthetic surfactant group) or respiratory support (10 of 475 (2%) for the air placebo group vs 1 of 482 (< 1%) for the synthetic surfactant group) at 1-year adjusted age. Bayley Scales of Infant Development (mental development Index: 102 for both the air placebo and synthetic surfactant groups; psychomotor development index: 95 for the air placebo group vs 94 for the synthetic surfactant group) and impairment rates (94 of 475 (20%) for the air placebo group vs 86 of 482 (18%) for the synthetic surfactant group) were similar in the two groups. Infants weighing more than 1250 gm who have respiratory distress syndrome have previously been shown to have improved survival rates and lower neonatal morbidity after treatment with synthetic surfactant. These follow-up data confirm that developmental outcome as determined at 12-months adjusted age is at least as good in those receiving synthetic surfactant.