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1.  Effect of age on intraoperative cerebrovascular autoregulation and near-infrared spectroscopy-derived cerebral oxygenation 
BJA: British Journal of Anaesthesia  2011;107(5):742-748.
Age is an important risk factor for perioperative cerebral complications such as stroke, postoperative cognitive dysfunction, and delirium. We explored the hypothesis that intraoperative cerebrovascular autoregulation is less efficient and brain tissue oxygenation lower in elderly patients, thus, increasing the vulnerability of elderly brains to systemic insults such as hypotension.
We monitored intraoperative cerebral perfusion in 50 patients aged 18–40 and 77 patients >65 yr at two Swiss university hospitals. Mean arterial pressure (MAP) was measured continuously using a plethysmographic method. An index of cerebrovascular autoregulation (Mx) was calculated based on changes in transcranial Doppler flow velocity due to changes in MAP. Cerebral oxygenation was assessed by the tissue oxygenation index (TOI) using near-infrared spectroscopy. End-tidal CO2, O2, and sevoflurane concentrations and peripheral oxygen saturation were recorded continuously. Standardized anaesthesia was administered in all patients (thiopental, sevoflurane, fentanyl, atracurium).
Autoregulation was less efficient in patients aged >65 yr [by 0.10 (se 0.04; P=0.020)] in a multivariable linear regression analysis. This difference was not attributable to differences in MAP, end-tidal CO2, or higher doses of sevoflurane. TOI was not significantly associated with age, sevoflurane dose, or Mx but increased with increasing flow velocity [by 0.09 (se 0.04; P=0.028)] and increasing MAP [by 0.11 (se 0.05; P=0.043)].
Our results do not support the hypothesis that older patients' brains are more vulnerable to systemic insults. The difference of autoregulation between the two groups was small and most likely clinically insignificant.
PMCID: PMC3192482  PMID: 21835838
age groups; anaesthesia; cerebrovascular circulation
2.  Left ventricular remodelling, and systolic and diastolic function in young adults with β thalassaemia major: a Doppler echocardiographic assessment and correlation with haematological data 
Heart  2003;89(7):762-766.
Objective: To evaluate left ventricular morphology and function in a large population of patients with β thalassaemia.
Design: Echo Doppler assessment of left ventricular function and correlation of cardiovascular data with haematological data.
Setting: Thalassaemia unit in a tertiary referral centre.
Patients: 197 young adults with β thalassaemia, following an adequate transfusional and chelation treatment regimen, without clinical signs of cardiopulmonary involvement. The control group consisted of 213 healthy subjects.
Results: Left ventricular volumes, mass index, and mass/volume ratio were increased. Diastolic and systolic shapes were different, the left ventricle maintaining an ellipsoidal shape. The ejection fraction was reduced, and was < 50% in 33 patients. Stroke volume and cardiac index were increased, and systemic vascular resistance was decreased. Fractional shortening and mean velocity of circumferential shortening were decreased. Meridional end systolic and peak systolic stress were increased, as was circumferential end systolic stress. The contractile state was reduced while the functional preload index did not differ. Left ventricular diastolic function, evaluated from the mitral inflow, showed a slightly prolonged isovolumic relaxation time, increased flow velocity integrals, and an increased E/A ratio. Among the haematological data, only serum ferritin showed a weak negative correlation with left ventricular ejection fraction. The patients with the highest serum ferritin (> 2500 ng/ml) had the lowest ejection fraction.
Conclusions: Patients with β thalassaemia on an adequate transfusion and chelation treatment regimen show abnormal left ventricular remodelling with increased volumes, mass, and mass/volume ratio. Systolic chamber function and contractile state are reduced, with a slightly increased afterload. These findings seem mainly to be related to the increased cardiac output caused by chronic anaemia. Left ventricular performance is better preserved when chelation treatment is adjusted to maintain the serum ferritin concentration at < 1000 ng/ml.
PMCID: PMC1767731  PMID: 12807852
thalassaemia major; left ventricular dysfunction; Doppler echocardiography; iron toxicity
3.  Comparative Genomics of Two Leptospira interrogans Serovars Reveals Novel Insights into Physiology and Pathogenesis†  
Journal of Bacteriology  2004;186(7):2164-2172.
Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in accidental hosts, including humans. Complete genome sequencing of Leptospira interrogans serovar Copenhageni and comparative analysis with the available Leptospira interrogans serovar Lai genome reveal that despite overall genetic similarity there are significant structural differences, including a large chromosomal inversion and extensive variation in the number and distribution of insertion sequence elements. Genome sequence analysis elucidates many of the novel aspects of leptospiral physiology relating to energy metabolism, oxygen tolerance, two-component signal transduction systems, and mechanisms of pathogenesis. A broad array of transcriptional regulation proteins and two new families of afimbrial adhesins which contribute to host tissue colonization in the early steps of infection were identified. Differences in genes involved in the biosynthesis of lipopolysaccharide O side chains between the Copenhageni and Lai serovars were identified, offering an important starting point for the elucidation of the organism's complex polysaccharide surface antigens. Differences in adhesins and in lipopolysaccharide might be associated with the adaptation of serovars Copenhageni and Lai to different animal hosts. Hundreds of genes encoding surface-exposed lipoproteins and transmembrane outer membrane proteins were identified as candidates for development of vaccines for the prevention of leptospirosis.
PMCID: PMC374407  PMID: 15028702
4.  Retinoblastoma (RB1) gene product expression in breast carcinoma. Correlation with Ki-67 growth fraction and biopathological profile. 
Journal of Clinical Pathology  1998;51(11):818-824.
AIMS: To investigate the expression of retinoblastoma protein (pRb) in invasive breast tumours and compare its expression with the major biopathological prognostic indicators to identify more aggressive subgroups. MATERIAL: Archival paraffin embedded tissues from 153 consecutive primary breast carcinomas. METHODS: pRb, Ki-67, and oestrogen receptor/progesterone receptor proteins were identified by immunohistochemistry and score values were recorded by image cytometric analysis; p53 and EGFr expression was also evaluated. RESULTS: pRb scores correlated strongly with proliferation activity as determined by Ki-67 staining. Positive relations were also observed between pRb scores, tumour size, nuclear and histological grade, and oestrogen receptor/progesterone receptor content, while abnormal p53 accumulation was not associated with pRb expression. Among the high proliferating carcinomas it was possible to identify 13 cases with loss of pRb expression. CONCLUSIONS: pRb expression paralleled proliferative activity in the majority of breast carcinomas examined, suggesting that in these cases the protein behaves normally in regulating the cell cycle. Conversely in cases with loss of pRb immunostaining, the combined expression of specific highly aggressive factors (EGFr and p53 expression, oestrogen receptor/progesterone receptor negative status, and high K67) seems to characterise a more aggressive phenotype showing growth advantage and cellular "progression" rather than significant nodal involvement.
PMCID: PMC500975  PMID: 10193322
5.  Reproductive behaviour of families segregating for Cooley's anaemia before and after the availability of prenatal diagnosis. 
Journal of Medical Genetics  1991;28(8):523-529.
The reproductive behaviour of couples with heterozygous beta thalassaemia, with at least one affected child, was investigated for the period 1955 to 1984 and was compared to the behaviour of control couples matched for age, age at marriage, and presence of at least one child. The comparisons were made as a function of knowledge of the risk and availability of prenatal diagnosis and abortion. It was found that the couples segregating for Cooley's anaemia, before knowledge of the risk, had a higher reproductive rate than that of control couples. Knowledge of the genetic risk had a different effect on reproductive behaviour in the 1950s from that in later years. The difference was attributed both to the influence of cultural factors and to technical, therapeutic, and diagnostic advances.
PMCID: PMC1016980  PMID: 1920367
6.  Alpha and beta cell evaluation in patients with thalassaemia intermedia and iron overload. 
Postgraduate Medical Journal  1985;61(721):963-967.
Insulin and glucagon secretion were studied during an oral glucose tolerance test and arginine infusion in 11 patients with thalassaemia intermedia, who showed laboratory evidence of iron overload. Mean blood glucose concentrations in patients with thalassaemia intermedia were significantly higher than normal and 3 of 11 patients had impaired glucose tolerance. The principal abnormality appears to be a deficiency in insulin and glucagon from the pancreas in response to oral glucose tolerance and arginine stimulation tests. Several factors, such as iron overload, chronic hypoxia, zinc deficiency and increased catecholamine production secondary to anaemia, might play a part in the pathogenesis of these abnormalities. Each of these factors affect individual cases to a varied degree. Our data emphasize the mildness of carbohydrate defect as compared to the degree of insulinopenia and indicate the necessity for prescribing measures which prevent excessive iron deposition and improve iron excretion in thalassaemic patients with iron overload.
PMCID: PMC2418482  PMID: 3906615

Results 1-6 (6)