Thalassaemia and malaria, revisited

Haldane's attractive hypothesis that the high gene frequencies for thalassaemia in the Mediterranean population may have resulted from heterozygote advantage in regions where Plasmodium falciparum malaria was common in the past has been extremely difficult to verify at the population or experimental level. However, the molecular era has provided some powerful new tools to attack this old problem. It is now clear that the thalassaemias are the commonest monogenic diseases in man, with a broad distribution throughout the Mediterranean, Middle East, Indian sub-continent and South-east Asia. All these populations have specific types of thalassaemia mutations which, presumably, have arisen locally and been expanded by selection together with drift and founder effect. Recent work indicates that alpha thalassaemia provides protection against severe malaria. Quite unexpectedly at least some of this protection may be mediated by rendering very young children more susceptible to both P. vivax and P. falciparum malaria; such early immunization may provide some protection against the disease in later life.     

Starches from A to C. Chlamydomonas reinhardtii as a model microbial system to investigate the biosynthesis of the plant amylopectin crystal

Wide-angle powder x-ray diffraction analysis was carried out on starch extracted from wild-type and mutant Chlamydomonas reinhardtii cells. Strains containing no defective starch synthases as well as mutants carrying a disrupted granule-bound starch synthase structural gene displayed the A type of diffraction pattern with a high degree of crystallinity. Mutants carrying a defect for the major soluble starch synthase (SSS), SSS II, were characterized by a switch to the B type of diffraction pattern with very low crystallinity. Mutant strains carrying SSS I as the only glucan elongation enzyme regained some of their crystallinity but switched to the C type of diffraction pattern. Differential scanning calorimetry analysis correlated tightly with the x-ray diffraction results. Together with the electron microscopy analyses, these results establish C. reinhardtii as a microbial model system displaying all aspects of cereal starch synthesis and structure. We further show that SSS II is the major enzyme involved in the synthesis of crystalline structures in starch and demonstrate that SSS I alone builds a new type of amylopectin structure.     

Anesthesia for patients with carcinoid syndrome

Carcinoid syndrome, although rare, can create serious problems to the anesthetist, both by the nature and variability of clinical manifestations and by the complications that can occur peroperatively. Recent research has led to a better understanding of the pathophysiology of the disease process. However, modern medicine is far from unraveling the precise nature and physiological effects of all the peptide mediators produced by these tumors. The severity of symptoms does not predict the severity of perioperative complications, so that patients with minor preoperative symptoms may have significant intraoperative complications. While urinary 5-HIAA levels provide a good indicator of disease progression, they cannot predict the degree or type of physiological response to intraoperative tumor manipulation. Indeed, urinary 5-HIAA may be normal both in the presence of a clinical diagnosis of carcinoid syndrome and in the face of a peroperative carcinoid crisis. The keys to successful anesthetic management of patients with carcinoid syndrome are good communication between endocrinologist, anesthetist, and surgeon and preoperative optimization of the patient. This includes appropriate investigation and treatment of the effects of carcinoid peptides and the prevention of their release from tumors. If possible, advice should be sought from centers with experience at managing this group of patients. Octreotide has largely replaced the use of other drugs both for symptomatic control and acute treatment of the symptoms associated with carcinoid syndrome. However, other drugs, such as aprotinin, still have a significant place in the symptomatic control and treatment of peroperative complications, as serotonin is only one of a large variety of peptides responsible for the clinical effects of this disease. Anesthetic technique should be aimed at minimizing carcinoid mediator release, in response to stress it induction of anesthesia and tracheal intubation and during tumor manipulation. It is equally important to prepare for carcinoid crisis by, for example, ordering drugs, which are otherwise uncommonly used in the theater setting, ahead of time. Cardiovascular instability, particularly hypotension, is common, so that full monitoring and vigilance is vital to predict its onset. The current surgical view of management is that, while curative resection of carcinoid tumors less than 2 cm in diameter with no evidence of invasion or metastatic spread is appropriate, patients with disseminated disease should be medically managed unless symptom control is poor. The exceptions to this are those patients with early and correctable carcinoid cardiac disease and those who require palliative procedures such as defunctioning obstructed bowel. Survival rates in patients following excision of gastric and appendical carcinoid tumors approach those of the general population as a whole and the chance of metastasis is extremely low. Only two series have been published in the anesthetic literature on anesthesia for patients with carcinoid syndrome, although there are many single-case reports. Despite the rarity of this syndrome, further formal studies into the anesthetic management of this condition should be encouraged.     

Systemic inflammatory response syndrome treatment by powdered sorbent pheresis: the BioLogic-Detoxification Plasma Filtration System

Systemic inflammatory response syndrome (SIRS) is one of the most common causes of death in intensive care unit patients. The detoxification plasma filtration (DTPF) system (HemoCleanse, Inc., West Lafayette, IN) combines the DT hemodiabsorption system in series with a push-pull pheresis PF system (a suspension of powdered sorbents surrounding 0.5 microm plasma filter membranes). Bidirectional plasma flow (at 80-100 ml/min) across the PF membranes provides direct contact between plasma proteins and powdered sorbents, as well as clearance of cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6) at a rate of 15-25 ml/min, without evidence of saturation for 90 minutes. In a U.S. Food and Drug Administration approved study we treated eight patients with SIRS and organ failure with a single DTPF treatment, using powdered charcoal as sorbent in four patients and powdered charcoal and silica in four patients. Treatments proceeded for 6 hours with proper heparin anticoagulation (activated clotting time 250-300 sec) and appeared safe. All patients improved during the treatments and each had increased blood pressure and decreased need for pressor agents. Plasma cytokine levels stabilized or decreased during treatment and were significantly lower the morning after treatment. Multiple organ dysfunction (MOD) and Acute Physiology Chronic Health Evaluation II scores and organ function gradually improved in most patients, and two patients survived for more than 28 days and two for more than 14 days. The DTPF System may prove beneficial in treatment of patients with sepsis.     

Delirium phenomenology illuminates pathophysiology, management, and course

The phenomenology of delirium has received little standardized longitudinal study but offers the prospect of valuable insights regarding clinical subtypes, differentiation from other neuropsychiatric disorders, identification of underlying pathophysiologies, management, and course. This review examines current approaches to the investigation of delirium phenomenology and how the findings to date illuminate our understanding of delirium. It concludes with recommendations for future investigations.