Electrical responses of cultured thyroid cells to serotonin

Cultured porcine thyroid cells, maintained in the differentiated state by dibutyryl cyclic AMP, responded to serotonin (5-HT; 10 nmol/l to 1 mumol/l) with a depolarization of the membrane potential, but did not respond to histamine (100 mumol/l) or dopamine (1 mumol/l). The resting membrane potential of these cells was about -71 mV, maximal concentrations of 5-HT (1 mumol/l) inducing a depolarization to approximately -53 mV. Methysergide or phenoxybenzamine, but not propranolol, abolished the response to 5-HT. Sensitivity to 5-HT was reduced by previous exposure of cultures to TSH, the beta-adrenoceptor agonist salbutamol or 5-HT itself.     

Efficacy and safety of emergency non-invasive pelvic ring stabilisation

BackgroundUrgent non-invasive pelvic ring stabilisation (pelvic binding, PB) in shocked patients is recommended by state and institutional guidelines regardless of the fracture pattern. The purpose of this study was to determine the adherence to the guidelines, efficacy of the technique and identification of potential adverse effects associated with PB.Patients and methodsA 41-month retrospective analysis of the prospective pelvic fracture database was undertaken at a level 1 trauma centre. High-energy pelvic fractures were included in the analysis with exclusion of the A type injuries (AO/OTA classification) and patients who were dead on arrival. Collected data included patient demographics, injury severity score, fracture classification, application and timing of PB, associated injuries, physiological parameters, resuscitation fluids and outcomes. Pre and post-PB radiographs were reviewed. The potential effects of the PB on soft tissue (femoral vessel, bladder and rectal injury) complications were assessed by independent experts.Results115 patients with high-energy B and C type pelvic ring injuries were included. Thirty-six (31%) patients presented in haemorrhagic shock on arrival. A total of 43 pelvic bindings were performed, 18 of them on shocked patients. The adherence to the guidelines was 50% (18/36) overall. Analysing fracture types of shocked patients the adherence was: B1 80%, B2 20%, B3 20%, C1 66%, C2 86%, C3 33%. The alignment of the pelvis was improved or perfect on post-PB radiographs in 68% and had not changed in 21%. In some cases of B2 and B3 type injuries the PB increased the deformity after application (11%). There were 10 deaths (8.7%) in the study group, with 4 deaths attributed to acute pelvic bleeding. Two of these had PB applied and two were identified as potential for improvement. One femoral artery injury, four bladder injuries and three rectum injuries were identified in patients who had PB applied. Association between the PB and these injuries is unlikely.ConclusionThe adherence to the guidelines should be improved with further education and system development. The good effect of the technique was evident on radiographs. Although in some lateral compression fracture patterns the deformity increased, no hazards were associated with the use of PB.     

A comprehensive view of sex-specific issues related to cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of mortality in women. In fact, CVD is responsible for a third of all deaths of women worldwide and half of all deaths of women over 50 years of age in developing countries. The prevalence of CVD risk factor precursors is increasing in children. Retrospective analyses suggest that there are some clinically relevant differences between women and men in terms of prevalence, presentation, management and outcomes of the disease, but little is known about why CVD affects women and men differently. For instance, women with diabetes have a significantly higher CVD mortality rate than men with diabetes. Similarly, women with atrial fibrillation are at greater risk of stroke than men with atrial fibrillation. Historically, women have been underrepresented in clinical trials. The lack of good trial evidence concerning sex-specific outcomes has led to assumptions about CVD treatment in women, which in turn may have resulted in inadequate diagnoses and suboptimal management, greatly affecting outcomes. This knowledge gap may also explain why cardiovascular health in women is not improving as fast as that of men. Over the last decades, mortality rates in men have steadily declined, while those in women remained stable. It is also becoming increasingly evident that gender differences in cultural, behavioural, psychosocial and socioeconomic status are responsible, to various degrees, for the observed differences between women and men. However, the interaction between sex-and gender-related factors and CVD outcomes in women remains largely unknown.     

Management of biliary obstruction in patients with unresectable carcinoma of the pancreas.

Clinical and pathologic data from 73 patients with unresectable carcinoma of the pancreas treated from 1980 to 1987 were reviewed to evaluate the efficacy of biliary enteric bypass and percutaneous transhepatic biliary drainage (PTBD) in the treatment of malignant biliary obstruction. Fifty-two patients underwent biliary enteric bypass with no operative deaths and with a 15% operative morbidity. These patients had a median postoperative hospitalization of 12 days. Four patients (8%) eventually developed recurrent jaundice, and three of these were successfully treated with PTBD. The median survival for these 52 patients was 7 months. Twenty-one patients underwent PTBD with an 81% technical-success rate. These patients had a 33% early complication rate and a 33% in-hospital mortality. The median hospitalization was 13 days postdrainage. Of the 14 patients surviving the initial hospitalization, 86% developed late complications requiring 16 hospital admissions and ten emergency room visits for a total of 155 days of hospitalization. The median survival for those patients undergoing PTBD was 4 months from the time of diagnosis and 2 months from the time of catheter drainage. Surgical bypass offers excellent palliation for malignant biliary obstruction with extremely low morbidity and mortality in properly selected patients; PTBD is useful in the treatment of those patients with extensive disease, who are poor surgical candidates, or who have failed previous surgical drainage. There is a role for both of these palliative procedures in the management of patients with biliary obstruction from pancreatic cancer.     

Late diagnosis of ectodermal dysplasia syndrome

This case study reports the clinical, skin biopsy and molecular findings in a 56‐year‐old Filipino man with the autosomal recessive ectodermal dysplasia disorder, Schöpf‐Schulz‐Passarge syndrome, the precise nature of which was established only after reading of a similar case in this journal. In addition to the late diagnosis, successful clinical management of his acral hyperkeratosis and ulceration has been difficult, with oral retinoids exacerbating the skin fragility.     

Optimizing dose and scheduling of filgrastim (granulocyte colony- stimulating factor) for mobilization and collection of peripheral blood progenitor cells in normal volunteers [see comments]

To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) for use in allogeneic transplantation, we evaluated the kinetics of mobilization by filgrastim (recombinant met- human granulocyte colony-stimulating factor [r-metHuG-CSF]) in normal volunteers. Filgrastim was injected subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10 micrograms/kg/d (n = 15). A subset of volunteers from each dose cohort underwent a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte-macrophage colony-forming cell (GM-CFC) numbers in the blood were maximal after 5 days of filgrastim; a broader peak was evident for CD34+ cells between days 4 and 6. The 95% confidence intervals (CI) for mean number of PBPC per milliliter of blood in the three dose cohorts overlapped on each study day. However, on the peak day, CD34+ cells were significantly higher in the 10 micrograms/kg/d cohort than in a pool of the 3 and 5 micrograms/kg/d cohorts. Mobilization was not significantly influenced by volunteer age or sex. Leukapheresis products obtained at the 10 micrograms/kg/d dose level contained a median GM-CFC number of 93 x 10(4)/kg (range, 50 x 10(4)/kg to 172 x 10(4)/kg). Collections from volunteers receiving lower doses of filgrastim contained a median GM- CFC number of 36 x 10(4)/kg (range, 5 x 10(4)/kg to 204 x 10(4)/kg). The measurement of CD34+ cells per milliliter of blood on the day of leukapheresis predicted the total yield of PBPC in the leukapheresis product (r = .87, P < .0001). Assuming a minimum GM-CFC requirement of 50 x 10(4)/kg (based on our experience with autologous PBPC transplantation), all seven leukapheresis products obtained at the 10 micrograms/kg/d dose level were potentially sufficient for allogeneic transplantation purposes. We conclude that in normal donors, filgrastim 10 micrograms/kg/d for 5 days with a single leukapheresis on the following day is a highly effective regimen for PBPC mobilization and collection. Further studies are required to determine whether PBPC collected with this regimen reliably produce rapid and sustained engraftment in allogeneic recipients.