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SummaryBackground: Prospective studies on the incidence of thrombosis in asymptomatic individuals with hereditary protein C- or protein S deficiency have not been performed so far.Objective: We have carried out a prospective cohort study in 44 asymptomatic protein C- and protein S deficient subjects and in 49 asymptomatic non-deficient relatives (age at study entry > 14 years) of symptomatic deficient patients.Methods: 20 asymptomatic protein C deficient (median age 20 years) and 24 asymptomatic protein S deficient patients (median age 21.5 years) were prospectively followed and compared with 20 asymptomatic non-deficient relatives (median age 25 years) of protein C- and 29 (median age 27 years) of protein S deficient patients. The total observation period was 118.8 patient years for protein C deficient and 92.8 for protein S deficient patients. Patients were not on anticoagulants except for short duration in case of high risk situations.Results: Eight thromboembolic events (1 pulmonary embolism, 1 deep vein thrombosis + pulmonary embolism, 3 deep vein thrombosis, 1 caval vein thrombosis and 2 superficial vein thrombosis) occurred in 6 deficient patients. The incidence of thromboembolism was 2.5% per patient year for protein C deficient and 3.5% per patient year for protein S deficient patients. 4 events occurred spontaneously, in 2 patients thromboembolic events were triggered by high risk situations (caesarean section, minor trauma). In the controls no thromboembolic events occurred. The probability for thromboembolism was significantly higher in protein C and protein S deficient patients compared to the control group (Wilcoxon test, p = 0.002, log rank test, p = 0.001). One major and 5 minor uneventful surgeries were carried out in the deficient patients using heparin prophylaxis. 1/8 pregnancies was complicated by superficial vein thrombosis during the second trimester despite prophylactic heparin administration. The same pregnancy was complicated by pulmonary embolism 5 weeks after delivery after discontinuation of heparin.Conclusions: Asymptomatic deficient relatives of symptomatic patients with protein C or protein S deficiency are at an increased risk of thrombosis compared to nondeficient individuals. Prophylactic treatment seems to be highly effective in high risk situations.

The aim of this study was to assess the information needs of patients diagnosed with oesophageal and gastric cancer and to compare these with their perceived information needs in the opinion of junior doctors. One hundred patients and 100 doctors responded to a questionnaire regarding the information needs of cancer patients. Seventy-nine per cent of patients wanted as much information as possible about their diagnosis, but only 35% of doctors were willing to give all the available information (P < 0.0001). Seventy-seven per cent of patients wanted to receive their diagnosis from a consultant whereas only 5% of doctors believed that patients should receive their diagnoses from a consultant (P < 0.0001). Eighty-four per cent of doctors were willing to communicate a serious illness with a good prognosis, yet only 43% would communicate a diagnosis with a poor prognosis (P < 0.0001). All 100 doctors had received formal training in breaking bad news, but 20 considered this inadequate. Socio-economic deprivation was associated with poor access to supplementary Internet derived information (P < 0.001). The majority of patients with a diagnosis of oesophagogastric cancer want a great deal of information regarding their illness, which contrasts with doctors' perceptions. Adequate training in information disclosure may help address this issue.

Recombinant Cupriavidus necator H 16 with a novel metabolic pathway using a cobalamin-dependent mutase was exploited to produce 2-hydroxyisobutyric acid (2-HIBA) from renewable resources through microbial fermentation. 2-HIBA production capacities of different strains of C. necator H 16 deficient in the PHB synthase gene and genetically engineered to enable the production of 2-HIBA from the intracellular PHB precursor (R)-3-hydroxybutyryl-CoA were evaluated in 48 parallel milliliter-scale stirred tank bioreactors (V = 11 mL). The effects of media composition, limitations, pH, and feed rate were studied with respect to the overall process performances of the different recombinant strains. 2-HIBA production was at a maximum at nitrogen limiting conditions and if the pH was controlled between 6.8 and 7.2 under fed-batch operating conditions (intermittent fructose addition). The final concentration of 2-HIBA was 7.4 g L(-1) on a milliliter scale. Best reaction conditions identified on the milliliter scale were transferred to a laboratory-scale fed-batch process in a stirred tank bioreactor (V = 2 L). Two different process modes for the production of 2-HIBA, a single-phase and a dual-phase fermentation procedure, were evaluated and compared on a liter scale. The final concentration of 2-HIBA was 6.4 g L(-1) on a liter scale after 2 days of cultivation.

We report the characterization of the genetic defect in a family with hereditary type-II protein C (PC) deficiency. The propositus is a 28-year-old woman with a history of thrombosis. Her PC activity level (58%) and PC antigen level (115%) are compatible with the diagnosis of type-II PC deficiency. Her asymptomatic sister is also PC deficient. Analysis of the PC gene of the propositus revealed a point mutation (G to A) at nucleotide 8856, which results in the replacement of Gly381 by Ser in the heavy chain of PC. The amino acid change occurs close to the active-site serine at a residue which is highly conserved among the serine proteases. The mutation is also present in the PC gene of the propositus' sister. Her brother, who is asymptomatic, has a normal genotype with respect to the mutation at nucleotide 8856.