Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura

High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000-790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3-4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2-10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.     

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.     

Neurotensin is an autocrine trophic factor stimulated by androgen withdrawal in human prostate cancer.

After therapeutic hormone deprivation, prostate cancer cells often develop androgen-insensitive growth through mechanisms thus far undefined. Neuropeptides have been previously implicated as growth factors in some prostate cancers. Here, we demonstrate that androgen-sensitive LNCaP human prostate cancer cells produce and secrete neurotensin following androgen withdrawal. We show that while LNCaP cells express the neurotensin receptor, only androgen-deprived cells exhibit a growth response to exogenous neurotensin. We further demonstrate that androgen-stimulated cells may be refractory to exogenous neurotensin due to androgen induction of a metalloprotease active toward neurotensin. Thus, prostate cancer cells deprived of androgen develop an alternative autocrine growth mechanism involving neurotensin.     

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.     

Lymphokine-induced phagocytosis in angiocentric immunoproliferative lesions (AIL) and malignant lymphoma arising in AIL

A factor that augmented the phagocytosis of IgG-coated ox red blood cells by the human monocyte/macrophage line U937 was identified in cell culture supernatants from two of two patients with angiocentric peripheral T cell lymphomas, three of three patients with angiocentric immunoproliferative lesions that were not frankly malignant, and one of two patients with T lymphoblastic malignancies. The factor was not present in supernatants derived from 14 nonangiocentric peripheral T cell lymphomas of other histologic types nor in ten cases of B cell lymphoma and two cases of Hodgkin's disease. A similar factor was present in the supernatants of concanavalin A (Con A)-stimulated normal peripheral blood mononuclear cells and in the supernatants of IL-2- dependent T cell lines derived from normal peripheral blood. The factor had an apparent mol wt of greater than 50,000 daltons, was heat labile (100 degrees C for two minutes), and stable at pH 2.0. Its stimulation of phagocytosis was independent of any increase in number of Fc receptors. Thus, this factor is probably not gamma-interferon. This factor may play a pathogenetic role in the hemophagocytic syndromes associated with certain T cell malignancies and immunodeficient states.     

Differential effects of nitric oxide on erythroid and myeloid colony growth from CD34+ human bone marrow cells

Nitric oxide (NO) is a reactive molecule with numerous physiologic and pathophysiologic roles affecting the nervous, cardiovascular, and immune systems. In previous work, we have demonstrated that NO inhibits the growth and induces the monocytic differentiation of cells of the HL- 60 cell line. We have also demonstrated that NO inhibits the growth of acute nonlymphocytic leukemia cells freshly isolated from untreated patients and increases monocytic differentiation antigens in some. In the present work, we studied the effect of NO on the growth and differentiation of normal human bone marrow cells in vitro. Mononuclear cells isolated from human bone marrow were cultured in semisolid media and treated with the NO-donating agents sodium nitroprusside (SNP) or S- nitroso-acetyl penicillamine (SNAP) (0.25 to 1 mmol/L). Both agents decreased colony-forming unit-erythroid (CFU-E) and colony-forming unit- granulocyte macrophage (CFU-GM) formation by 34% to 100%. When CD34+ cells were examined, we noted that these cells responded to SNP and SNAP differently than did the mononuclear cells. At a concentration range of 0.25 to 1 mmol/L, SNP inhibited the growth of CFU-E by 30% to 75%. However, at the same concentration range, SNP increased the number of CFU-GM by up to 94%. At concentrations of 0.25 to 1 mmol/L, SNAP inhibited the growth of CFU-E by 33% to 100%. At a concentration of 0.25 mmol/L, SNAP did not affect CFU-GM. At higher concentrations, SNAP inhibited the growth of CFU-GM. Although SNP increased intracellular levels of cGMP in bone marrow cells, increasing cGMP in cells by addition of 8-Br-cGMP (a membrane permeable cGMP analogue) did not reproduce the observed NO effects on bone marrow colonies. These results demonstrate that NO can influence the growth and differentiation of normal human bone marrow cells. NO (generated in the bone marrow microenvironment) may play an important role modulating the growth and differentiation of bone marrow cells in vivo.     

Influenza, pneumonia, tetanus: how effective is vaccination?

The rationale for immunizing older adults with influenza, pneumococcal, and tetanus-diphtheria vaccines is derived largely from epidemiological data indicating a heightened susceptibility to these illnesses within this population. The authors provide supportive information relevant to the routine use of these vaccines in adults aged 65 or older.     

Acute Stimulant Ingestion and Neurocognitive Performance in Healthy Participants

Context:

Concussion management has become an area of great concern in athletics, and neurocognitive tests, such as Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), are commonly used as management tools. Given the restrictive nature of current management plans, anecdotal concerns have been raised about athletes trying to cheat the assessments and return to participation sooner. Stimulants have been shown to improve neurocognitive measures similar to those used in ImPACT. Therefore, they could possibly improve performance during baseline and postinjury testing.

Objective:

To examine the effects of a supplement containing stimulants on ImPACT performance.

Design:

Crossover study.

Setting:

Research laboratory.

Patients or Other Participants:

A total of 5 men (age = 20.6 ± 1.5 years, height = 176.3 ± 9.6 cm, mass = 76.9 ± 18.6 kg) and 7 women (age = 20.6 ± 1.1 years, height = 162.9 ± 7.8 cm, mass = 60.9 ± 8.2 kg) with no histories of physician-diagnosed head injury, learning disability, or attention-deficit disorder.

Intervention(s):

Participants were assessed under supplement (5.5 g of Jacked 3D, which contains caffeine and 1,3-dimethylamylamine), placebo, and control conditions separated by 1 week.

Main Outcome Measure(s):

I compared ImPACT composite scores for verbal and visual memory, visual motor speed, reaction time, impulse control, and a cognitive-efficiency index under each of the 3 conditions and assessed them 30 minutes after ingestion.

Results:

I observed a difference when comparing reaction times, as the participants reacted faster during the supplement condition (0.53 ± 0.03 seconds) than during the placebo (0.55 ± 0.03 seconds) and control (0.55 ± 0.03 seconds) conditions (F_2,22 = 4.31, P = .03). A difference also was observed for the cognitive-efficiency index, as participants scored higher during the supplement condition (0.49 ± 0.09) than during the placebo (0.41 ± 0.10) and control (0.41 ± 0.12) conditions (F_2,22 = 4.07, P = .03).

Conclusions:

Stimulant ingestion 30 minutes before testing resulted in improved memory, visual processing speed, and reaction time. However, the improvements were relatively nominal, and the question of clinical importance remains. Thus, it is unclear if stimulant ingestion would affect the return-to-participation progression.Key Words: ImPACT, caffeine, 1,3-dimethylamylamine, reaction time, processing speed

Key Points

• Acute ingestion of a nutritional supplement containing caffeine and 1,3-dimethylamylamine improved neurocognitive performance compared with the control and placebo conditions and could threaten Immediate Post-Concussion Assessment and Cognitive Testing validity.
• Clinicians should standardize and control test conditions, including controlling for caffeine and stimulant use before and during testing, to increase the validity of Immediate Post-Concussion Assessment and Cognitive Testing during baseline and postinjury testing.
• Comparing postinjury neurocognitive performance with baseline data accurately identifies cognitive changes only if both the baseline and postinjury tests are valid.

The management of mild traumatic brain injury, typically referred to in the United States as a concussion, has become an area of great concern and controversy in the athletic setting. Numerous states have adopted or are in the process of adopting legislation that mandates evaluation procedures and return-to-participation criteria for interscholastic athletics, and many sport governing bodies have adopted similar policies. Concussions are typically diagnosed after several clinical domains are assessed, including self-reported symptoms, physical signs, and cognitive functioning. Current strategies for injury management suggest that abnormalities in any 1 or more of these domains should exclude an athlete from training and competition.Many clinicians use neurocognitive tests, such as Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT; ImPACT Applications, Inc, Pittsburgh, PA), as assessment and management tools. These tests are usually administered before the sport season to obtain baseline data. If an athlete is concussed, serial evaluations are conducted postinjury to determine when neurocognitive deficits and clinical symptoms are no longer present. Researchers¹ have recommended that neurocognitive performance must revert to baseline or better before the patient returns to participation to reduce the possibility of a more serious, cumulative injury during the vulnerable recovery period.The restrictive nature of many current management plans has resulted in a longer recovery period and a delay in return to participation compared with older management plans and has created controversy. Authors^2–4 of several peer-reviewed publications have reported that athletes ranging from the high school to the professional level have stated that they have hidden or would hide the symptoms of a concussion from a health care professional or a coach primarily because they feared missing participation time or status. Similarly, anecdotal concerns have been raised about athletes trying to cheat the assessment and return to participation sooner than they should.Various stimulants, including caffeine, have been shown to improve working memory, visual information processing, and reaction time (RT), which are similar to the skills used during ImPACT.^5–7 Thus, stimulant use could possibly improve performance during neurocognitive concussion testing. However, no researchers have examined the effects of stimulant use on ImPACT or any other type of computerized neurocognitive testing. Therefore, the purpose of my study was to determine if acute stimulant ingestion would improve performance during ImPACT. I hypothesized that memory, processing speed (PS), and RT would improve after stimulant ingestion.     

Validity and Reliability of Stillbirth Data Using Linked Self-Reported and Administrative Datasets

Background

A high rate of stillbirth was previously observed in the Australian Longitudinal Study of Women’s Health (ALSWH). Our primary objective was to test the validity and reliability of self-reported stillbirth data linked to state-based administrative datasets.

Methods

Self-reported data, collected as part of the ALSWH cohort born in 1973–1978, were linked to three administrative datasets for women in New South Wales, Australia (n = 4374): the Midwives Data Collection; Admitted Patient Data Collection; and Perinatal Death Review Database. Linkages were obtained from the Centre for Health Record Linkage for the period 1996–2009. True cases of stillbirth were defined by being consistently recorded in two or more independent data sources. Sensitivity, specificity, positive predictive value, negative predictive value, percent agreement, and kappa statistics were calculated for each dataset.

Results

Forty-nine women reported 53 stillbirths. No dataset was 100% accurate. The administrative datasets performed better than self-reported data, with high accuracy and agreement. Self-reported data showed high sensitivity (100%) but low specificity (30%), meaning women who had a stillbirth always reported it, but there was also over-reporting of stillbirths. About half of the misreported cases in the ALSWH were able to be removed by identifying inconsistencies in longitudinal data.

Conclusions

Data linkage provides great opportunity to assess the validity and reliability of self-reported study data. Conversely, self-reported study data can help to resolve inconsistencies in administrative datasets. Quantifying the strengths and limitations of both self-reported and administrative data can improve epidemiological research, especially by guiding methods and interpretation of findings.Key words: data, kappa, linkage, reliability, self-report, sensitivity, specificity, stillbirth, validity