Antibody-mediated in vitro growth inhibition of field isolates of Plasmodium falciparum from asymptomatic children in Burkina Faso

Antibody-mediated inhibition of Plasmodium falciparum parasites in vitro reflects the potential parasite-neutralizing activity of the antibodies in vivo. In this study, immunoglobulins and P. falciparum isolates were collected from children with asymptomatic malaria in Burkina Faso. We demonstrate a significantly lower in vitro growth inhibitory activity against the P. falciparum field isolates by autologous host immunoglobulin compared with that of immunoglobulin from other individuals. To gain further insight to possible mechanisms for the diverse sensitivity observed, analyses of consecutive isolates taken 14 days apart were performed with regard to polymerase chain reaction-based genotyping and sensitivity to growth inhibition in vitro. All the asymptomatic infections were composed of multiple, genotypically distinct parasite clones, and at least one new parasite clone appeared in most of the day 14 isolates compared with the corresponding day 0 isolates. Apparently persisting parasite clones, present in both the day 0 and day 14 isolates from the same person, were also frequently observed. The day 14 isolates were more effectively inhibited by autologous day 14 immunoglobulin than by the corresponding day 0 immunoglobulin in 57% of the cases. However, the frequent presence of persisting parasite clones in asymptomatic children indicates that the parasite may develop a relative resistance to neutralizing immune responses.     

Different response to Plasmodium falciparum malaria in West African sympatric ethnic groups

The comparison of malaria indicators among populations that have different genetic backgrounds and are uniformly exposed to the same parasite strains is one approach to the study of human heterogeneities in the response to the infection. We report the results of comparative surveys on three sympatric West African ethnic groups, Fulani, Mossi, and Rimaibé, living in the same conditions of hyperendemic transmission in a Sudan savanna area northeast of Ouagadougou, Burkina Faso. The Mossi and Rimaibé are Sudanese negroid populations with a long tradition of sedentary farming, while the Fulani are nomadic pastoralists, partly settled and characterized by non-negroid features of possible caucasoid origin. Parasitological, clinical, and immunological investigations showed consistent interethnic differences in Plasmodium falciparum infection rates, malaria morbidity, and prevalence and levels of antibodies to various P. falciparum antigens. The data point to a remarkably similar response to malaria in the Mossi and Rimaibé, while the Fulani are clearly less parasitized, less affected by the disease, and more responsive to all antigens tested. No difference in the use of malaria protective measures was demonstrated that could account for these findings, and sociocultural or environmental factors do not seem to be involved. Known genetic factors of resistance to malaria did not show higher frequencies in the Fulani. The differences in the immune response were not explained by the entomological observations, which indicated substantially uniform exposure to infective bites. The available data support the existence of unknown genetic factors, possibly related to humoral immune responses, determining interethnic differences in the susceptibility to malaria.     

Growth hormone treatment improves peripheral muscle oxygen extraction-utilization during exercise in patients with human immunodeficiency virus-associated wasting: a randomized controlled trial

The arteriovenous oxygen difference (a-vO(2) difference), a measure of peripheral muscle oxygen extraction-utilization during exercise, is reduced in antiretroviral-treated patients with human immunodeficiency virus (HIV), thus causing a shift in the cardiac output-oxygen consumption (Q-VO(2)) relationship. We investigated the impact of recombinant human GH (rhGH) treatment on a-vO(2) difference and the Q-VO(2) relationship during submaximal exercise by randomizing 12 HIV-infected patients (mean +/- sem: age, 43.3 +/- 1.5 yr; body mass, 69.5 +/- 2.9 kg; body mass index, 22.4 +/- 0.9 kg/m(2); maximum oxygen consumption, 33.6 +/- 1.5 ml/kg x min), with documented unintentional weight loss (>or=10% within the preceding 12 months) despite antiretroviral therapy, to receive 3 months of rhGH (6 mg/d) in a double-blind, placebo-controlled, cross-over trial. We assessed Q (determined noninvasively using CO(2) rebreathing), and subsequently a-vO(2) difference, from Q-VO(2) relationships. At study entry, the mean slope (8.1 +/- 1.0 liters/min x 1-liter increase in VO(2)) and intercept (3.1 +/- 1.3 liters/min), generated from each patient's Q-VO(2) relationship, were greater and lower, respectively, than those reported for healthy individuals (6.0 and 4.0, respectively), thereby indicating a deficit in the a-vO(2) difference. After 3 months of rhGH treatment, the slope decreased to 7.0, and the intercept increased to 3.5. After 1 month of rhGH treatment, the a-vO(2) difference (at a VO(2) of 1250 ml/min) significantly (P < 0.05) increased (17.1 +/- 8.9%) from baseline (9.92 +/- 0.51 ml/dl) and remained elevated (10.39 +/- 0.48 ml/dl) after 3 months of treatment. No significant changes were seen with placebo. Therefore, treatment with rhGH leads to an improvement in peripheral muscle oxygen extraction-utilization and the Q-VO(2) relationship during exercise in patients with HIV-associated wasting despite antiretroviral therapy.     

Role of left inferior prefrontal cortex in retrieval of semantic knowledge: A reevaluation

A number of neuroimaging findings have been interpreted as evidence that the left inferior frontal gyrus (IFG) subserves retrieval of semantic knowledge. We provide a fundamentally different interpretation, that it is not retrieval of semantic knowledge per se that is associated with left IFG activity but rather selection of information among competing alternatives from semantic memory. Selection demands were varied across three semantic tasks in a single group of subjects. Functional magnetic resonance imaging signal in overlapping regions of left IFG was dependent on selection demands in all three tasks. In addition, the degree of semantic processing was varied independently of selection demands in one of the tasks. The absence of left IFG activity for this comparison counters the argument that the effects of selection can be attributed solely to variations in degree of semantic retrieval. Our findings suggest that it is selection, not retrieval, of semantic knowledge that drives activity in the left IFG.     

Autoimmune Pankreatitis – Behandlung und Problematik der Diagnosestellung

Background

Autoimmune pancreatitis (AIP) was first classified as a defined disease entity in 1995. It accounts for approximately 2?% of cases of chronic pancreatitis (western world prevalence 36–41/100,000 inhabitants) and AIP is diagnosed in 2.4?% of pancreas resection specimens.

Objectives

Presentation of strategies for diagnosis and treatment with focus on differentiation of AIP and pancreatic carcinoma.

Methods

Selective literature research in PubMed regarding pathogenesis, diagnosis and treatment of AIP.

Results

Key characteristics of AIP are recurrent jaundice due to obstructed bile ducts, histological evidence of fibrosis, a lymphoplasmocytic or granulocytic infiltrate and the response to steroid therapy. There are two distinctive forms of AIP: type I or lymphoplasmocytic sclerosing pancreatitis and type II or idiopathic duct centric pancreatitis. The IgG4 positive AIP type I belongs to the group of IgG4-related systemic diseases. Diagnosis of AIP is established according to the international consensus diagnostic criteria (ICDC) or HISORt (mnemonic standing for histology, imaging, serology, other organ involvement and response to therapy) criteria. Differentiation from pancreatic adenocarcinoma can be challenging. The standard treatment consists of corticosteroids and in some cases azathioprine can be added. In refractory disease rituximab is a further option. Treatment is indicated in patients with jaundice, systemic manifestation or persistent pain.

Conclusion

Although AIP is increasingly being identified, the differentiation from pancreatic adenocarcinoma still remains difficult and in cases of a suspicion of neoplasia, resection should be favored. It can successfully be treated conservatively with steroids and rituximab.