Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006.

BACKGROUND: Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. METHODS: In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. RESULTS: Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). CONCLUSIONS: For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.     

Deep venous thrombosis and pulmonary embolism. The importance of heightened awareness.

Left untreated, deep venous thrombosis and pulmonary embolism have a high rate of mortality and long-term morbidity. Physicians therefore must maintain a high index of suspicion for these conditions. Accurate diagnosis is facilitated by knowing the most common sites of thrombus formation, the likelihood of propagation, which patients are at greatest risk, signs and symptoms, and which tests to order. Prompt administration of anticoagulants and, in some cases, thrombolytic agents can minimize the consequences of these diseases. Interruption of the inferior vena cava, thrombectomy, and thromboembolectomy are other treatment options.     

Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

Pancreatic islet transplantation future prospects

There is good evidence that the long-term complications of diabetes are caused by poor control of blood sugar, even in patients where intensive glucose monitoring is used to control insulin therapy. Pancreatic transplantation offers the potential for normalisation of glucose metabolism, but at the cost of major surgery and immunosuppression. The possibility of separating the insulin-secreting tissue from the exocrine gland has many attractions. Isolated pancreatic islets are small enough to allow transplantation as free grafts by an injection technique. Furthermore, it may be possible to modify the graft in such a way as to prevent rejection with minimal or no immunosuppression. For pancreatic islet transplantation to become useful in clinical practice it will be necessary to develop efficient techniques for harvesting viable islet tissue in adequate quantities, identify a suitable site for transplantation and prevent rejection. Over the past 20 years experimental models of islet transplantation have proven the potential of this approach, but until recently it has not been possible to translate these experiments into clinical practice. Recently, there have been significant advances in the techniques available for separation of islets from the pancreas of large mammals and man, and recent clinical trials of islet transplantation have shown evidence of short-term function. However, significant problems remain, particularly those of rejection and the maintenance of long-term function, before introduction of clinical islet transplantation as standard therapy for diabetes can be expected.     

Adverse outcomes of planned and unplanned pregnancies among users of natural family planning: a prospective study.

OBJECTIVES: The purpose of this study was to determine prospectively whether unplanned pregnancies are associated with adverse pregnancy outcomes among users of natural family planning. METHODS: Women who became pregnant while using natural family planning were identified in five centers worldwide: there were 373 unplanned and 367 planned pregnancies in this cohort. The subjects were followed up at 16 and 32 weeks' gestation and after delivery. The risks of spontaneous abortion, low birth-weight, and preterm birth were estimated after adjustment by logistic regression. RESULTS: The women with unplanned pregnancies were more likely to be at the extremes of age, to report more medical problems before and during the index pregnancy, and to seek antenatal care later in gestation than the women with planned pregnancies. However, women with planned pregnancies reported a higher rate of spontaneous abortion in previous pregnancies (28.8%) than did women with unplanned pregnancies (12.9%). There were no significant differences in the rates of spontaneous abortion, low birthweight, or preterm birth between the two groups. CONCLUSIONS: No increased risk of adverse pregnancy outcomes was observed among women who experienced an unplanned pregnancy while using natural family planning.