Clearance kinetics of parasites and pigment-containing leukocytes in severe malaria

In tropical areas, where unsupervised use of antimalarial drugs is common, patients with an illness consistent clinically with severe malaria but with negative blood smears pose a management dilemma. Malaria pigment is evident in peripheral blood leukocytes in greater than 90% of patients with severe malaria. To characterize the clearance kinetics of parasitized erythrocytes and malaria pigment-containing leukocytes, sequential peripheral blood and intradermal smears were assessed in 27 adult Vietnamese patients with severe falciparum malaria. The clearance of parasitized erythrocytes and pigment- containing monocytes (PCMs) followed first order kinetics. The elimination of pigment-containing neutrophils (PCNs) was first order initially, but deviated from this when counts were low. Clearance of peripheral blood PCMs (median clearance time, 216 hours; range, 84 to 492 hours) was significantly slower than that of parasitized erythrocytes (median, 96 hours; range, 36 to 168 hours) or PCNs (median, 72 hours; range, 0 to 168 hours; P < .0001). Intradermal PCM clearance times were the longest of all (median, 12 days; range, 6 to 23 days; significantly longer than peripheral blood PCM clearance, P < .001). Twenty-one (88%) patients still had signs, symptoms, or laboratory features of severe malaria after parasite clearance but before phagocyte pigment clearance. Sixteen of the 23 surviving patients (70%; 95% confidence interval, 50% to 87%) still had intraleukocytic malaria pigment on peripheral blood films 72 hours after parasite clearance. Thus, by determining the distribution of malaria pigment in peripheral blood and intradermal phagocytes, the time since effective antimalarial treatment started can be estimated. Microscopy for intraleukocytic pigment is valuable in the differential diagnosis of severe febrile illnesses in malarious areas where uncontrolled use of antimalarial drugs is widespread.     

Differences in the Management of Type 1 Diabetes Among Adults Under Excellent Control Compared With Those Under Poor Control in the T1D Exchange Clinic Registry

OBJECTIVE

Optimizing glycemic control in type 1 diabetes is important to minimize the risk of complications. We used the large T1D Exchange clinic registry database to identify characteristics and diabetes management techniques in adults with type 1 diabetes, differentiating those under excellent glycemic control from those with poorer control.

RESEARCH DESIGN AND METHODS

The cross-sectional analysis included 627 participants with HbA_1c <6.5% (excellent control) and 1,267 with HbA_1c ≥8.5% (fair/poor control) at enrollment who were ≥26 years of age (mean ± SD 45.9 ± 13.2 years), were not using continuous glucose monitoring, and had type 1 diabetes for ≥2 years (22.8 ± 13.0 years).

RESULTS

Compared with the fair/poor control group, participants in the excellent control group had higher socioeconomic status, were more likely to be older and married, were less likely to be overweight, were more likely to exercise frequently, and had lower total daily insulin dose per kilogram (P < 0.0001 for each). Excellent control was associated with more frequent self-monitoring of blood glucose (SMBG), giving mealtime boluses before a meal rather than at the time of or after a meal, performing SMBG before giving a bolus, and missing an insulin dose less frequently (P < 0.0001 for each). Frequency of severe hypoglycemia was similar between groups, whereas diabetic ketoacidosis was more common in the fair/poor control group.

CONCLUSIONS

Diabetes self-management related to insulin delivery, glucose monitoring, and lifestyle tends to differ among adults with type 1 diabetes under excellent control compared with those under poorer control. Future studies should focus on modifying diabetes management skills in adult type 1 diabetes patients with suboptimal glycemic control.The Diabetes Control and Complications Trial (DCCT) demonstrated that lowering average blood glucose levels leads to decreased microvascular and macrovascular complications (1,2). In the intervening years, much advancement has been made in an attempt to improve diabetes management through the development of insulin analogs, improvement of insulin infusion pumps, and development of continuous glucose monitoring (CGM) systems. Certified diabetes education programs provide evidence-based information to patients on ways to achieve optimal diabetes control, and in the current digital era, information about the carbohydrate content of food is at the fingertips of many patients. However, although some patients have excellent glycemic control on the basis of HbA_1c values, it is not always apparent how their diabetes management differs from patients who have poor diabetes control. The large T1D Exchange clinic registry database provides an opportunity to cross-sectionally analyze differences in patient characteristics as well as aspects of diabetes management in adult patients with HbA_1c values in the excellent range compared with those with values in the fair/poor range.     

Donation deferral criteria for human immunodeficiency virus positivity among blood donors in northern Thailand

Background: The purpose of this study was to develop human immunodeficiency virus (HIV) infection donation deferral criteria for blood donors in an HIV-epidemic area of northern Thailand, where the predominant means of transmission of HIV is through heterosexual contact. Study Design and Methods: In a preliminary study, 2242 blood donors were interviewed, and their blood was tested for HIV antibodies between September 1993 and April 1994. The risk factors associated with HIV positivity were identified. Criteria to identify HIV-positive persons on the basis of a logistic equation were developed and applied to another group of 5769 prospective blood donors. Results: A multivariate analysis showed the following odds ratios (OR) for traits that were independently associated with HIV positivity: younger age (OR = 0.93 for each additional year of age), male gender (OR = 2.41), having no more than a primary school education (OR = 2.00), being in the military (OR = 1.78), being unsure of one's own blood safety (OR = 2.00), history of injecting drug use (OR = 5.36), diagnosis of syphilis or positive syphilis serologic test in the past 12 months (OR = 2.67), and genital ulcer in the past 12 months (OR = 4.56). On the basis of the model, with a limit of <10 percent loss of uninfected donors, predicted probabilities of HIV positivity alone or of markers of infection with HIV, hepatitis B virus, or Treponema pallidum were calculated. With a cutoff of 6.5-percent estimated probability of HIV infection, derived from the logistic equation, the donor deferral criteria have 33.6-percent sensitivity and 8.3-percent positive predictive value for HIV positivity and 15.5-percent sensitivity and 18.4-percent positive predictive value for markers of infection with one of the three pathogens. Conclusion: The proposed donor deferral system provides a more flexible, sensitive, and predictive tool for averting donation by those who, though HIV antibody-negative, are at a higher risk of being infected with HIV.     

Sickle erythrocytes adhere to polymorphonuclear neutrophils and activate the neutrophil respiratory burst

The vasoocclusive process in patients with sickle cell disease (SCD) is complex and involves interactions among sickle erythrocytes (SS-RBC), vascular endothelium, and plasma and cellular components. The role of neutrophils (PMN) in vasoocclusion has not been examined. Patients with SCD appear to have chronically activated PMN. Because the first step in PMN activation is particle recognition, we explored whether normal PMN recognize SS-RBC and whether this recognition results in PMN monolayers, significantly more SS-RBC adhered to the PMN than did normal erythrocytes (AA-RBC; P < .001). Preincubation of erythrocytes with autologous plasma significantly increased the adherence of SS-RBC to PMN but had no effect on AA-RBC (P < .001). When adhesion of density fractionated SS-RBC was performed, dense SS-RBC showed greater adherence to the PMN monolayers than did light SS-RBC (P < .001). To determine mechanisms of this adhesion, IgG and Arg-Gly-Asp-Ser (RGDS) receptor sites on PMN were saturated. IgG inhibited adherence of dense SS-RBC, whereas RGDS inhibited adherence in both fractions, although to a greater extent in the light fraction. We measured SS-RBC activation of PMN by incubating SS-RBC with 2', 7'-Dichloro-fluroescin Diacetate (DCF)-labeled PMN. Incubation of PMN with SS-RBC resulted in a significant increase in fluorescence compared to AA-RBC. We show here that PMN recognize SS-RBC through multiple mechanisms and that this recognition results in activation of PMN. These findings contribute to the understanding of vasoocclusive crisis in patients with SCD and may have therapeutic implications.     

Microsurgery of the hypothalamus with special reference to craniopharyngioma

Summary After a short survey of microanatomy, microtopography, neurophysiology and neuropathophysiology of the hypothalamus the surgical approaches to the hypothalamus with special reference to the craniopharyngiomas are described in detail. Based on 100 personal cases (1954–1979) the special procedure, depending on the site and extent of the tumour and its involvement of the hypothalamus, is discussed.Primary radical excision (19 cases) with a mortality rate of 10.5% seems to be the method of choice, as late mortality recurrences and secondary operations are frequent after non-radical procedures. Modern microsurgical technique promises to achieve primary radical excision more frequently and with less risk.     

The detection of an antibody against IgA allotype A2M 2 and a study of the Am genetic marker among the Han Chinese population

The serum of a woman was found by the Ouchterlony double-diffusion and the hemagglutination inhibition (HAI) methods to have immunoglobulin A (IgA) deficiency. Further investigation using the hemagglutination (HA) test with red cells coated with IgA myeloma proteins of different specificities showed that the serum agglutinated only IgA2-, A2M-1, and A2M 2-coated cells. The patterns of the HAI test with a reference panel confirmed the presence of two specificities. One was anti-IgA2 and the other was a rare antibody against the allotype A2M 2. The anti-A2M 2 was used for population studies. Testing of the Han Chinese population, including family studies, confirms that A2M.1 and A2M.2 have an autosomal dominant mode of inheritance and are controlled by a codominant allele. The distribution of the two Am genetic markers among the Han Chinese population demonstrated A2M.1 with a gene frequency of 0.553 and A2M.2 with a gene frequency of 0.447 (chi 2 = 0.145, 0.80 greater than p greater than 0.70).     

Capturing and missing the patient's story through outcome measures: A thematic comparison of patient‐generated items in PSYCHLOPS with CORE‐OM and PHQ‐9

Background

There is increasing interest in individualized patient‐reported outcome measures (I‐PROMS), where patients themselves indicate the specific problems they want to address in therapy and these problems are used as items within the outcome measurement tool.

Objective

This paper examined the extent to which 279 items reported in an I‐PROM (PSYCHLOPS) added qualitative information which was not captured by two well‐established outcome measures (CORE‐OM and PHQ‐9).

Design

Comparison of items was only conducted for patients scoring above the “caseness” threshold on the standardized measures.

Setting and patients

107 patients were participating in therapy within addiction and general psychiatric clinical settings.

Main results

Almost every patient (95%) reported at least one item whose content was not covered by PHQ‐9, and 71% reported at least one item not covered by CORE‐OM.

Discussion

Results demonstrate the relevance of individualized outcome assessment for capturing data describing the issues of greatest concern to patients, as nomothetic measures do not always seem to capture the whole story.