The ineffectiveness of random donor platelet transfusion in splenectomized, alloimmunized recipients

The effect of splenectomy on the response to random donor platelet transfusion in 15 multitransfused thrombocytopenic patients is presented. Eight patients responded poorly, with low corrected platelet count increments at 1 and 24 hours posttransfusion. These eight patients were clinically alloimmunized and had lymphocytotoxic antibody ( LCTAb ) in their sera. They responded well to closely HLA-matched transfusions. In contrast, seven splenectomized patients responded well to random donor platelets. Five of these patients had no LCTAb and no other evidence of immunization. Two patients who responded well to random donor platelets had "weak" LCTAb , and one responded to platelets presplenectomy in the presence of this antibody. Splenectomy does not improve the response to random donor platelets in alloimmunized recipients.     

8a Liver transplantation: newer surgical approaches

The standard procedure for orthotopic liver transplantation remains transplantation of the whole organ together with resection of the vena cava and the use of venovenous bypass. In cases of severe mismatch of the donor and recipient vena cava, the piggyback technique, if necessary with vena cava plasty, is preferable. Furthermore, in all cases where venovenous bypass cannot be performed, the piggyback or other technique preserving the vena cava should be performed. In paediatric patients, reduced/size liver transplantation may be indicated because of the shortage of small livers. In the hands of experienced surgeons, the results of reduced-size liver transplantation in paediatric patients are similar to those of whole organ transplantation. Further innovative procedures to overcome the problem of organ shortage include split-liver and living related transplantation in children. Distinct advantages of living related transplantation can be seen in a well-functioning graft, lack of preservation injury, elective operation and optimal graft-size matching. The immunological advantage that has been claimed could not be demonstrated so far, and will need to be examined in the long-term follow-up. However, there remains a distinct disadvantage for living related transplantation with regard to the surgical technique. Pre-operative portal venous thrombosis should be carefully assessed, but is not a contraindication to liver transplantation if the confluence of the superior mesenteric vein and splenic vein is patent. Arterial reconstruction at the confluence of two arteries (hepatic and gastroduodenal or splenic artery) seems to be preferable to an end-to-end anastomosis because of improved inflow into the graft and a reduced risk of arterial stenosis and thrombosis. Where the common hepatic arteries are small, with reduced or reversed flow, and in patients with coeliac trunk stenosis, we recommend a direct approach to the suprarenal or infrarenal aorta. Bile duct anastomosis may preferably be performed with a side-to-side technique, to reduce early and late biliary complications.     

Prenatal stress in pigs: experimental approaches and field observations.

Prenatal stress can affect the offspring's behaviour, physiology, and immune parameters. This paper summarises and discusses experimental and field studies on prenatal maternal stress in pigs. Often, elevated maternal corticosteroid concentrations during gestation are used to model prenatal stress. We used prolonged oral administration of cortisol (hydrocortisone acetate, HCA) to pregnant sows, which resulted in elevated maternal plasma and salivary cortisol concentrations. This treatment induced elevated fetal basal and adrenocorticotropic hormone (ACTH)-induced plasma cortisol concentrations, as demonstrated by a pilot study. Postnatally, it reduced birth weight of the piglets, and resulted in more live born piglets and higher preweaning mortality. In addition, it reduced the female offspring's salivary cortisol response to ACTH, and it enhanced the piglets' novelty-induced locomotion and vocalisations, and the piglets were more aggressive in a social test. Some of these effects depended on the period of gestation during which maternal cortisol concentrations were elevated, and on the sex of the offspring. These results demonstrate that piglet physiology and behaviour can indeed be affected when the mother has elevated cortisol concentrations during gestation. Regular mixing of pregnant sows with unfamiliar sows during the last third of gestation did not affect maternal salivary cortisol concentrations. Also, it did not affect the piglets' performance, behaviour, adrenocortical response to ACTH, or wound healing. Regular mixing of pregnant sows during the last third of gestation did not affect the piglets' characteristics as studied in these experiments. However, performance and behaviour of piglets were highly influenced by the social rank of their mother during gestation. Our studies have demonstrated that piglets can be affected by elevated maternal cortisol concentrations during fetal development and by social rank of the pregnant sow during gestation.     

Treatment of advanced Hodgkin's lymphoma: standard and experimental approaches.

The introduction of polychemotherapy and improved radiation techniques has transformed Hodgkin's lymphoma from an incurable disease to a malignancy with one of the highest cure rates. Milestones were the development of the MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) regimens. Radiotherapy is commonly used, although its precise role has not been defined for patients with advanced-stage disease. More recently, dose-intensified schedules such as Stanford V (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone) were shown to be effective in this group of patients. In particular, the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), in both standard and escalated doses, has produced impressive results in a randomized three-arm study when compared with COPP (cyclophosphamide, vincristine, procarbazine, and prednisone)/ABVD. The significantly higher rates of complete remission (CR) and freedom from treatment failure (FFTF) suggest that the new BEACOPP regimen improves efficacy, but definitive conclusions require further years of follow-up evaluation. Interestingly, BEACOPP abrogates the impact of the newly described seven-factor prognostic scoring system that was reported for patients treated with MOPP/ABVD or similar regimens. The prognostic index includes factors such as serum albumin, hemoglobin, male sex, stage IV disease, age more than 45 years, white blood cell count, and lymphocyte count. Whereas patients with Hodgkin's lymphoma have a good prognosis on first diagnosis, those with relapsed or refractory disease face a poor outcome.     

Beta-lactam antibiotics: newer formulations and newer agents

beta-Lactam antibiotics share a common structure and mechanism of action, although they differ in their spectrum of antimicrobial activity and utility in treating different infections. The current classes include the penicillins, the penicillinase-resistant penicillins, the extended- spectrum penicillins, the cephalosporins, the carbapenems, and the monobactams. This article discusses some of the newest beta-lactams available for use in the United States: ertapenem, cefditoren, and cefepime. A new formulation of amoxicillin-clavulanate, which contains higher doses of amoxicillin, is also discussed.     

The newer macrolides: azithromycin and clarithromycin

Azithromycin and clarithromycin are two relatively new macrolide antimicrobial agents. Although azithromycin and clarithromycin are structural analogues of erythromycin, they offer distinct advantages in comparison. This article reviews the pharmacokinetics, antimicrobial activity, clinical use, and adverse affects of these antimicrobial agents.     

Haemovigilance: an effective tool for improving transfusion practice

Haemovigilance is a tool to improve the quality of the blood transfusion chain, primarily focusing on safety. In this review we discuss the history and present state of this relatively new branch of transfusion medicine as well as some developments that we foresee in the near future. The top 10 results and conclusions are: (1) Haemovigilance systems have shown that blood transfusion is relatively safe compared with the use of medicinal drugs and that at least in Europe blood components have reached a high safety standard. (2) The majority of the serious adverse reactions and events occur in the hospital. (3) The majority of preventable adverse reactions are due to clerical errors. (4) Some adverse reactions such as anaphylactic reactions often are not avoidable and therefore have to be considered as an inherent risk of blood transfusion. (5) Well-functioning haemovigilance systems have not only indicated how safety should be improved, but also documented the success of various measures. (6) The type of organisation of a haemovigilance system is of relative value, and different systems may have the same outcome. (7) International collaboration has been extremely useful. (8) Haemovigilance systems may be used for the vigilance and surveillance of alternatives for allogeneic blood transfusion such as cell savers. (9) Haemovigilance systems and officers may be used to improve the quality of aspects of blood transfusion other than safety, such as appropriate use. (10) Haemovigilance systems will be of benefit also for vigilance and surveillance of the treatment with other human products such as cells, tissues and organs.     

The physician compliance of red blood cell transfusion by computerized transfusion decision support system

“When should we trigger a transfusion?” is always a critical question between the patient’s benefits and risks in red blood cell (RBC) transfusion. A computerized transfusion decision support system (CTDSS) has been used since September 2004 in an academic medical center with 1400 beds. In this study, the factors affecting RBC transfusion were investigated. In total 20,551 RBC-transfusion episodes between January and December 2008 were reviewed. The nearest hemoglobin concentration before transfusion is defined as the transfusion trigger. The physician compliance, the factors associated with the transfusion triggers and posttransfusion hemoglobin increment were investigated. The physician compliance is 83.1%. The transfusion trigger is 8.32 ± 1.84 (mean ± standard deviation) g/dL. The transfusion triggers are statistically significant in terms of both different order sources and disease types (p < 0.05).The posttransfusion hemoglobin level increased in two-thirds of the episodes. The percentages of hemoglobin increments after transfusion are dependent on the transfusion triggers. Appropriate transfusion practice may reduce the overuse of blood components and improve transfusion quality. CTDSS should be more powerful to intervene in the appropriateness of transfusion practice.     

Current and newer approaches in the drug treatment of congestive heart failure

Summary Most patients with chronic congestive heart failure (CHF) are subjected to symptomatic treatment, predominantly with drugs. Over the years, it has become clear that treatment with unloading drugs is probably more beneficial than treatment with inotropic agents. In addition, it has been widely recognized that the neuroendocrine compensatory changes associated with CHF afford an important target for drug treatment. This may also hold for some of the changes in receptor density, such as the downregulation of cardiac beta-adrenoceptors. The present and clearly changing insights into the backgrounds of drugs for the treatment of CHF are critically discussed. Apart from the changing views and appreciation of the currently used drugs (diuretics, ACE inhibitors, digoxin, beta-adrenoceptor agonists), the following new approaches are discussed: beta-blockers, angiotensin II receptor antagonists, ibopamine, calcium antagonists, inhibitors of ANP degradation, vasopressin antagonist, vesnarinone, and calcium sensitizers.     

Erythrocyte aggregation: experimental approaches and clinical implications

From a clinical point of view, quantitative studies of erythrocyte aggregation or rouleau formation is of great interest. However, in order to approach the phenomenon, structural parameters (rouleau shape), kinetic parameters (rouleau formation and dissociation velocity) and rheological parameters (dissociation thresholds) must be determined. At present, optical dynamic methods are available for use in clinical hemorheology. They involve optical measurements in a viscometer. The first method consists of a study of the light intensity transmitted through the measuring chamber of a cone plan viscometer. A device calculates and index I, which provides a whole approach to the aggregation kinetics. On the other hand, a systemic which also involves a cone-plain viscometer and an inverted microscope (Rheoscope) allows to collect data by means of microphotographs, microcinematography or numerical image processing. In that case, an adimensional K index typical of the morphology of the aggregates can be determined. The second method involves the analysis of the light intensity backscattered by the red blood cells sheared in a Couette flow. An automatic system has been developed and aggregation times, orientation and structure index, total and partial disaggregation thresholds can be determined on the basis of the curves of variations of backscattered light.     

Vulvodynia--new and more effective approaches to therapy

Two cases are described of treatment-resistant vulvodynia that responded well to gabapentin. Gabapentin, an anti-epileptic drug, has been used in the treatment of neuropathic pain such as diabetic neuropathy and post-herpetic neuralgia. However, there has been little experience of its use in the relief of symptoms in vulvodynia and we add our observations to the one report of its use in these circumstances that has been published so far.     

From blood transfusion to patient blood management: a new paradigm for patient care and cost assessment of blood transfusion practice

The ageing population in developed countries, including Australia, is putting increasing demands on blood transfusion services. With a falling donor pool there is likely to be a shortage of blood and blood products in the next 20 to 30 years unless there are significant changes in medical practice. The National Health and Medical Research Council/Australasian Society of Blood Transfusion Clinical Practice Guidelines on the Use of Blood Components from 2001 are being redeveloped by the National Health and Medical Research Council/Australian and New Zealand Society of Blood Transfusion as evidence-based patient-focused Patient Blood Management guidelines with the aim of improving patient outcomes by reducing inappropriate blood and blood product use and targeting therapies for improving the management of anaemia and coagulopathies.     

Internet patient decision support: a randomized controlled trial comparing alternative approaches for men considering prostate cancer screening

BACKGROUND: We conducted a randomized controlled trial to evaluate the effects of patient decision support Web sites on decision quality for men considering prostate cancer screening. METHODS: Men older than 50 years (N = 611) were randomly assigned to 1 of 4 Internet conditions: traditional didactic decision aid providing information about prostate-specific antigen (PSA) screening options and outcomes; chronic disease trajectory model for prostate cancer followed by a time-trade-off exercise; both the didactic decision aid and the chronic disease trajectory model; or links to public prostate cancer-specific Web sites from credible sources (control condition). Participants completed questionnaires at baseline and after their physical examination. Primary outcome measures were PSA test choice, prostate cancer treatment preferences, knowledge and concern about prostate cancer, and decisional conflict. RESULTS: Participants assigned to view public Web sites were less likely to review information (116 participants [76.8%] reviewed) than those assigned to experimental groups (399 [86.7%] reviewed; P = .004). Greater reductions in PSA screening from pretest to posttest were observed among participants assigned to the traditional decision aid (-9.1%) or chronic disease trajectory model (-8.7%), compared with participants assigned to the combination (-5.3%) or control (-3.3%) groups (P = .047). Preferences for watchful waiting increased significantly in all 4 groups (baseline, 219 [35.8%]; follow-up, 303 [66.2%]; P < .001). Knowledge scores were lowest for those assigned to public Web sites (mean [SD] score, 7.49 [0.19] of questions correct) and highest for the traditional decision aid (8.65 [0.18] of questions correct; P = .005). CONCLUSION: Public Web sites about prostate cancer provide less effective decision support than a specially designed Internet decision aid.     

The role of newer antibiotics in gastroenterology.

The past decade has seen the introduction of a number of new potent antimicrobial agents, including broad-spectrum beta-lactam compounds such as the ureidopenicillins, third-generation cephalosporins, carbapenems, and monobactams; combinations of penicillins with inhibitors of beta-lactamase; and the quinolones. Most of these agents have excellent activity against enteric gram-negative rods and some are active against anaerobic organisms, the two bacterial groups most likely to be encountered in gastrointestinal infections. Despite the potency and wide spectrum of many of these new agents, there are currently relatively few clinical situations in which any of the newer antimicrobials are the first-line agents for therapy or prophylaxis of gastrointestinal diseases. Reluctance to use these agents as first-line therapy is based on concerns about the selection and spread of resistant organisms, superinfection syndromes, and the high cost of many of the newer agents. Specific clinical settings in which these agents may be given preference are as follows: 1. use of a third-generation cephalosporin (cefotaxime or ceftriaxone) in the treatment of spontaneous bacterial peritonitis. 2. use of broad-spectrum beta-lactam compounds to provide gram-negative coverage in patients who should not receive aminoglycosides 3. use of a third-generation cephalosporin (ceftriaxone) in the treatment of central nervous system relapses of Whipple's disease 4. use of quinolones for the empiric treatment of suspected bacterial diarrhea in patients sufficiently ill to require empiric initiation of antibiotics. 5. use of quinolones for the treatment of chronic carriers of Salmonella typhi 6. use of norfloxacin for prophylaxis against SBP. As further experience with these new antimicrobial agents is obtained and as more bacteria develop resistance to current first-line agents, there can be little doubt that these new antibiotics will play an increasing role in the prevention and treatment of gastrointestinal disease.     

The importance of nutritional support for the geriatric surgical patient.

An appropriately designed program of nutritional support will allow the geriatric patient to undergo necessary surgical therapy with fewer risks and improved results. The selection of the route of administration and the specific agent(s) will depend on the functional status of the gastrointestinal tract as well as the patient's protein and calorie requirements. Table 6 summarizes our recommendations in the delection process. Our obvious preference is the gastrointestinal tract route if possible. When this optimum method of nutritional management is not available, sequential or concurrent supplemented feedings or intravenous hyperalimentation may be required to achieve adequate protein calorie intake. Regardless of the route chosen, careful monitoring of the geriatric patient's response to nutritional therapy is required. Only through careful planning and execution of nutritional therapy can optimum results be achieved in this group of patients.