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In recent years, successful assay miniaturization has enabled the exploration of synthesis scale reduction in pharmaceutical discovery. Miniaturization of pharmaceutical synthesis and purification allows a reduction in material consumption and shortens timelines, which ultimately reduces the cost per experiment without compromising data quality. Isolating and purifying the compounds of interest is a key step in the library synthesis process. In this manuscript we describe a high-throughput purification workflow in support of microscale (1–5 μmol or 0.5–2 mg) library synthesis. The optimized microscale purification system can routinely purify 384-well reaction plates with an analysis time of 4 min per sample. Instrument optimization, critical parameters such as column loading, delay time calibration, ultrafast pre- and post-purification analysis and library purification examples are provided.

Objectives(1) To develop an adaptation framework for MTM delivery for pharmacists (the MTM Adaptability Framework), (2) to examine the impact of an educational intervention informed by the MTM Adaptability Framework on MTM completion rates over a 2-year period, and (3) to explore pharmacists’ perceptions regarding knowledge and beliefs about MTM and MTM implementation self-efficacy pre- and post-intervention.MethodsThis study is a prospective, mixed-methods research study including a quasi-experimental, one-group pretest-posttest quantitative study with a sequential explanatory qualitative study arm featuring semi-structured key informant interviews. US supermarket pharmacy chain setting included 93 community pharmacy sites located in Tennessee, Kentucky, and Alabama. MTM completion rates are reported as percentage of completed comprehensive medication reviews (CMRs) and targeted medication reviews (TMRs) and pharmacist perceptions.ResultsAn 11.4% absolute increase in MTM completion rates was seen after the educational intervention targeting adaptation of MTM in the community pharmacy setting. This was found to be significant (46.92% vs. 58.3%;p< 0.001). Responses to the semi-structured interviews were mapped against CFIR and included themes: “knowledge and beliefs about MTM (pre-intervention),” “self-efficacy for MTM implementation (pre-intervention),” “knowledge and beliefs about MTM (post-intervention),” and “self-efficacy for MTM implementation (post-intervention).” Data convergence was found across these methodologies and suggested that targeting adaptability of MTM delivery increases MTM completion rates (quantitative data) and positively changes perceptions of MTM feasibility and self-efficacy (interviews).ConclusionThe use of an educational intervention about adaptation of MTM to influence adaptation of MTM to a chain community pharmacy setting part of an implementation strategy improved MTM completion rates significantly. Future research should investigate combined implementation strategies and their impact on MTM implementation success.

The objective of this study is to recover Active Pharmaceutical Ingredients (APIs) from tablets via green engineering technology to meet material requirements for downstream formulation development. A separation train, using water as the separation media, includes dissolution, centrifugal phase separation, diafiltration and reverse osmosis and has been developed based on the physical properties of the API and excipients. These properties include solubility, multiphase behaviors, particle densities, and size differences between API and excipients. The recovered API both meets purity specifications and contains no polymer. It is suitable for reuse in formulation process development. The recovery of the API from tablets is over 90%. A green engineering technology using water and separation methods is successfully developed and used to recover API from tablets.

Background: Cognitive pharmaceutical services (CPS) provided by pharmacists can improve patient adherence and industry standard performance measures. Community pharmacy technicians can aid in CPS support tasks on training, but it is unknown to what extent. Objective: To determine the effect of community pharmacy technicians on industry standard adherence performance measures after CPS training. Methods: Sixteen community pharmacy technicians within a supermarket chain division were chosen to participate in CPS training based on internal pharmacy benchmarking data. The training program consisted of 3 components: (1) classroom and (2) web-based training for medication therapy management platforms and (3) Hands-on in-pharmacy training. Researchers used pharmacy-specific EQuIPP reports of the proportion of days covered (PDC) for adherence related to diabetes, cholesterol, and hypertension to measure the primary outcome. September through October 2015 represented baseline data. November 2015 through March 2016 represented intervention data. Descriptive and inferential statistics were utilized for this retrospective analysis. The University of Tennessee Institutional Review Board classified the study exempt from review. Results: Overall, 100% of Cholesterol PDC 4-Star sites improved to a 5-Star score and 56% of sites improved in the Diabetes PDC score. All sites maintained a 5-Star score for RASA PDC postintervention. An average increase of 2.36% was observed for Cholesterol PDC across all sites. Possible lag time between the intervention and score improvements may limit relatability of results. Conclusions: This is the first study to report a positive trend between technician involvement in CPS and improvement in industry standard adherence performance measures. Further research capturing a longer time frame may be beneficial.

Background: Health-related quality of life (HRQOL) assessment is an important health outcome for measuring the efficacy of treatments and interventions for coronary artery disease (CAD). HRQOL is known to improve over the first year after interventions for CAD, but there is limited knowledge of the changes in HRQOL beyond 1 year. We investigated heterogeneity in long-term trajectories of HRQOL in patients with CAD. Methods and Results: Data were obtained from 6226 patients identified from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease with at least 1-vessel CAD who underwent their first catheterization between 2006 and 2009. HRQOL was assessed using the Seattle Angina Questionnaire, a 19-item disease-specific measure of HRQOL for patients with CAD. Group-based trajectory analysis was used to identify various subgroups of Seattle Angina Questionnaire trajectories over time while adjusting for missing data through a longitudinal multiple imputation model. Multinomial logistic regression was used to identify the predictors of differences among the identified subgroups. Our analysis revealed significant improvements in HRQOL across all the 5 domains of Seattle Angina Questionnaire overtime for the whole data. Multitrajectory analyses revealed 4 HRQOL trajectory subgroups including high (25.1%), largely increased (32.3%), largely decreased (25.0%), and low (17.6%) trajectories. Age, sex, body mass index, diabetes mellitus, previous history of myocardial infarction, smoking, depression, anxiety, type of treatment received, and perceived social support were significant predictors of differences among these trajectory subgroups. Conclusions: This study highlights variations in longitudinal trajectories of HRQOL in patients with CAD. Despite overall improvements in HRQOL, about a quarter of our cohort experienced a significant decline in their HRQOL over the 5-year period. Understanding these HRQOL trajectories may help personalize prognostic information, identify patients and HRQOL domains on which clinical interventions are most beneficial, and support treatment decisions for patients with CAD.

Background— Sex and neighborhood socioeconomic status (nSES) may independently affect the care and outcomes of acute coronary syndrome, partly through barriers in timely access to cardiac catheterization. We sought to determine whether sex modifies the association between nSES and the receipt of cardiac catheterization and mortality after an acute coronary syndrome in a universal healthcare system. Methods and Results— We studied 14 012 patients with acute coronary syndrome admitted to cardiology services between April 18, 2004, and December 31, 2011, in Southern Alberta, Canada. We used multivariable logistic regression to compare the odds of cardiac catheterization within 2 and 30 days of admission and the odds of 30-day and 1-year mortality for men and women by quintile of neighborhood median household income. Significant relationships between nSES and the receipt of cardiac catheterization and mortality after acute coronary syndrome were detected for women but not men. When examined by nSES, each incremental decrease in neighborhood income quintile for women was associated with a 6% lower odds of receiving cardiac catheterization within 30 days ( P =0.01) and a 14% higher odds of 30-day mortality ( P =0.03). For men, each decrease in neighborhood income quintile was associated with a 2% lower odds of receiving catheterization within 30 days ( P =0.10) and a 5% higher odds of 30-day mortality ( P =0.36). Conclusions— Associations between nSES and receipt of cardiac catheterization and 30-day mortality were noted for women but not men in a universal healthcare system. Care protocols designed to improve equity of access to care and outcomes are required, especially for low-income women.

Background Metropolitan versus nonmetropolitan status and area median income may independently affect care for and outcomes of acute coronary syndromes. We sought to determine whether location of care modifies the association among area income, receipt of cardiac catheterization, and mortality following an acute coronary syndrome in a universal health care system. Methods and Results We studied a cohort of 14 012 acute coronary syndrome patients admitted to cardiology services between April 18, 2004, and December 31, 2011, in southern Alberta, Canada. We used multivariable logistic regression to determine the odds of cardiac catheterization within 1 day and 7 days of admission and the odds of 30‐day and 1‐year mortality according to area median household income quintile for patients presenting at metropolitan and nonmetropolitan hospitals. In models adjusting for area income, patients who presented at nonmetropolitan facilities had lower adjusted odds of receiving cardiac catheterization within 1 day of admission (odds ratio 0.22, 95% CI 0.11–0.46, P P P =0.008) but no significant difference for 1‐year mortality ( P =0.12). There were no differences in adjusted mortality among metropolitan patients. Conclusion Within a universal health care system, the association among area income and receipt of cardiac catheterization and 30‐day mortality differed depending on the location of initial medical care for acute coronary syndromes. Care protocols are required to improve access to care and outcomes in patients from low‐income nonmetropolitan communities.

Heart failure affects over 500,000 Canadians, and 50,000 new patients are diagnosed each year. The mortality remains staggering, with a five-year age-adjusted rate of 45%. Disease management programs for heart failure patients have been associated with improved outcomes, the use of evidence-based therapies, improved quality of care, and reduced costs, mortality and hospitalizations. Currently, national benchmarks and targets for access to care for cardiovascular procedures or office consultations do not exist. The present paper summarizes the currently available data, particularly focusing on the risk of adverse events as a function of waiting time, as well as on the identification of gaps in existing data on heart failure. Using best evidence and expert consensus, the present article also focuses on timely access to care for acute and chronic heart failure, including timely access to heart failure disease management programs and physician care (heart failure specialists, cardiologists, internists and general practitioners).

Background — Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for acute myocardial infarction (AMI) promotes the speed and magnitude of coronary artery recanalization and reduces reocclusion. Low-molecular-weight heparins offer practical and potential pharmacological advantages over UFH in multiple applications but have not been systematically studied as adjuncts to fibrinolysis in AMI. Methods and Results — Four hundred patients undergoing reperfusion therapy with an accelerated recombinant tissue plasminogen activator regimen and aspirin for AMI were randomly assigned to receive adjunctive therapy for at least 3 days with either enoxaparin or UFH. The study was designed to show noninferiority of enoxaparin versus UFH with regard to infarct-related artery patency. Ninety minutes after starting therapy, patency rates (thrombolysis in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1% in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days from TIMI grade 2 or 3 to TIMI 0 or 1 flow and TIMI grade 3 to TIMI 0 or 1 flow, respectively, occurred in 5.9% and 3.1% of the enoxaparin group versus 9.8% and 9.1% in the UFH group. Adverse events occurred with similar frequency in both treatment groups. Conclusions — Enoxaparin was at least as effective as UFH as an adjunct to thrombolysis, with a trend toward higher recanalization rates and less reocclusion at 5 to 7 days.

The purpose of the present study was to determine whether that which clinically appeared to be spasmus nutans could actually represent retinal sensory deficits diagnosable by electroretinography. Eight patients clinically thought to have spasmus nutans underwent electroretinography according to international standards. Five had normal electroretinograms and represented cases of true spasmus nutans. Three patients had abnormal electroretinograms, indicating that they did not have spasmus nutans. The clinical findings used to diagnose spasmus nutans can be simulated by retinal dystrophies. A normal electroretinogram is needed to confirm the diagnosis of spasmus nutans.

This paper argues that there has been a major change since the mid-1980s in the extent to which other workers involved in child protection recognize the value of the contribution of school nurses. Evidence for this is drawn from a longitudinal study in an English shire county using a vignette approach to explore workers' perceptions of the handling of child protection issues. While in part the greater recognition of the role of the school nurse can be attributed to the adoption of child protection procedures, this provides only a partial explanation. School nurses in the 1990s were better qualified and more experienced, while other workers such as school heads and social workers recognized the need to work with others, such as the school nurse, in order to meet their own objectives. The paper concludes that there is a case for more formal recognition of school nurses in child protection because, like health visitors, with whom they have a follow-on colleague relationship, they are often the most significant health workers for children who may be neglected or abused. Copyright © 2000 John Wiley & Sons, Ltd.

The interest of the business world in the use of geographical information systems (GIS) to support business decision-making is growing rapidly. This growth presents opportunities and challenges for geography educators. This study presents a literature-based examination of issues that help clarify the significance of business interest in GIS to academia, with the goal of providing a starting point for the eventual design of curricula that address business needs. These issues include how GIS is perceived by business users, how these perceptions influence pedagogical and content questions, who should be teaching GIS, and the challenges that may accompany business-related opportunities. Review of the literature suggests an incompletely defined business perception of GIS, a need for a curriculum that emphasizes education over training, and substantial precedent for the participation of geographers in the instruction of business GIS.

More than 7 million adolescents regularly compete in high school athletics each year in the United States.1 Most will undergo a limited, sports-oriented preparticipation evaluation before competition.2 This type of examination has been performed for many years to satisfy various legal, academic, and organizational requirements. However, the health care benefits to the teenagers themselves have not been analyzed objectively using direct comparison to the standard history and physical. At present, the value of the sports physical remains unproven and its efficacy has not been clearly established. In addition, the potential negative impact on delivery of comprehensive medical services to adolescents deserves further emphasis in the literature and, therefore, will be the focus of this commentary.

First published report of a child with an aneurysmal bone cyst (ABC) of the first cervical vertebrae treated successfully with intralesional injection of calcitonin and methylprednisolone.To describe a safe and effective nonsurgical treatment method for an ABC of the first cervical vertebrae.Aneurysmal bone cysts of the spine comprise from 3% to 20% of all such lesions. Upper cervical spine involvement is rare and these lesions are difficult to treat. Standard treatment with curettage and bone grafting or other alternatives such as radiation therapy or embolization may not be possible in this location. Percutaneous injection with a variety of agents has also been described. Methylprednisolone and calcitonin were selected in this case in an effort to combine the proposed angiostatic and fibroblastic inhibitory effects of steroid with the proposed osteoclastic inhibitory and promotion of new bony trabeculae formation effects of calcitonin.This case was described, and pertinent literature reviewed.Sclerosis and shrinkage of the lesion with concomitant symptom resolution occurred after two injections with calcitonin and methylprednisolone via computed tomography (CT) guidance. No complications occurred. The lesion remained quiescent at a 2-year 7-month follow-up.Percutaneous intralesional injection of an ABC of the first cervical vertebrae with calcitonin and methylprednisolone in a child via CT guidance was a safe and effective treatment. This is a promising treatment for surgically inaccessible aneurysmal bone cysts.

Summary. To evaluate the usefulness of the template bleeding time post-aspirin ingestion, this test was performed with other tests of haemostasis in 28 controls and 71 patients. The mean bleeding time (B. T.) in 24/28 true controls was 3.5+1 min (1 SD). Following the ingestion of 600 mg aspirin the B. T. was 6.3 + 1.4 min. Four out of 28 false ‘controls’with negative bleeding histories were documented to have asymptomatic von Willebrand's disease and abnormal post-aspirin B. T. Of the 71 patients studied, 22 had initial B. T. that were abnormal (16 with classical von Willebrand's disease and six with platelet dysfunction). Of the remaining 49 patients with initially normal B. T., 30 had abnormal post-aspirin B. T. Of these 30 patients 13 had von Willebrand's disease. In eight, initially the abnormal B. T. post-aspirin was the only abnormality demonstrable but later they were shown to have von Willebrand's disease. In four the abnormal post-aspirin B. T. was combined with abnormal Ristocetin aggregations and a positive family history. These patients were presumed to have a variant of von Willebrand's disease. The remaining five had platelet dysfunctional states. Of the 19 patients with normal initial post-aspirin B. T., 16 demonstrated no haemostatic abnormality, and three were proven to have von Willebrand's disease. The aspirin tolerance test raised the sensitivity of the B. T. as a screening test for haemostasis from 40% to 94% in the abnormal patient population.

Ftorafur, a furanyl analog of 5-fluorouracil (5-FU), is reported to be five to six times less toxic and possibly more effective in cancer of the breast and colon than 5-FU. The drug was synthesized, formulated, and utilized in toxicologic studies, and then in 24 patients with advanced incurable malignancies. When Ftorafur is given by intravenous push, it results in immediate flushing, dizziness, nausea, retching, and in some cases transient hypotension. These immediate side effects are largely eliminated by administering the drug slowly by infusion. In patients, 60 mg/kg of Ftorafur given i.v. daily for up to 10 days resulted in mild toxicity. However, 80 mg/kg given i.v. daily for 7 days resulted in severe toxicity, with nausea, vomiting, stomatitis, leukopenia, and thrombocytopenia. These studies confirm those of the Russian investigators as to toxicity and dosage, even with a different method of administration more convenient for therapy. Phase II studies are presently being carried out to compare the effectiveness of Ftorafur and 5-FU.

An interferometer has been constructed with reflection optics and lamellar gratings to operate in the wavelength range of 175–400 μ. The gratings serve not only as beam splitters and recombiners but also as filters to separate out a narrow band of radiation. In this way a simple wide band Hg arc lamp can be used as the source. Because of the required response time for afterglow plasmas, a Putley detector measures the radiation. An application of the interferometer has been made to measure electron densities in repetitively pulsed plasma with λ = 200 μ and a time response of 3 μsec. The electron line density sensitivity is 3×1013 cm−2 and line densities have been measured up to 1015 cm−2, still substantially below the instrumental limit.

Fuel economy with experimental and commercial friction-modified engine oils has been measured in EPA 55/45 and road tests. Fuel economy improvements provided by the additives averaged 1.2 percent in road tests. Adding molybdenum disulfide to both the engine oil and rear axle lubricant improved EPA 55/45 test fuel economy 4.6 percent. Three commercial friction-modified engine oils were evaluated. In EPA and road tests, fuel economy with these oils improved an average 2.9 and 4.1 percent, respectively, over that obtained using the nonfriction-modified engine oils. Of these oils, the two containing soluble additives were most effective in improving fuel economy under warmed-up operation, whereas the graphite-containing oil was most effective during engine warm-up.

In an attempt to elucidate the usefulness of the Bleeding Time (BT) post Aspirin (ASA) ingestion this test was done with other tests of coagulation in 30 controls and 77 patients evaluated for a possible bleeding diathesis. Coagulation studies included PT, PTT, TT, VIII AHF & AGN, IX, XI, XIII platelet retention and aggregation, and modified Ivy BTs pre and 2 hrs. post 600 mgms ASA. The mean control BT in 25 normals was 3.6'±3.2' (3SD). Following ASA the BT was 6.4'±4.1' (3SD). 5/30 “controls” without bleeding histories had abnormal BTs post ASA. In this group, 4 were proven to have unrecognized von Willebrand’s disease (VWD) and one a platelet defect. Of the 74 patients studied, 28 had initial BTs that were abnormal (23 with VWD and 5 with platelet defects). Of the remaining 46 with initially normal BTs, 26 had abnormal BTs post ASA. 13/26 had VWD at their first evaluation. In 9/26, however, the abnormal BT post ASA was the only abnormality at initial evaluation. On repeated testing, these patients were also shown to have VWD. 4/26 with abnormal BTs post ASA were found to have platelet abnormalities. The remaining 20 patients had normal BTs pre and post ASA. 16/20 revealed no hemostatic abnormality. In 4 eventually proven to have VWD, the BT post ASA was normal. The use of the BT post ASA raised the sensitivity of the BT as a screening test from 48% to 93% in the abnormal patient population. VWD appears to be the most common symptomatic/ asymptomatic bleeding disorder. The BT post ASA is a valuable screen in the evaluation of hemostatic defects i.e., mainly VWD, as also the occasional patient with a thrombocytopathy.

Chronic ITP, unlike acute ITP, may be the result of an underlying immunologic disorder. To examine this possibility 3 children, and their families (totalling 13 members) were studied in an attempt to identify underlying abnormalities in cellular and humoral immunity. All 3 patients had their disease for more than 1 year. All had shortened platelet life spans. None were receiving drugs, and none had had their spleens removed. In these patients, 2 of 3 were found to have decreased numbers of T lymphocytes and PHA reactivity; 2 of 3 had dysgammaglobulinemias; 1 of 3 had decreased isohemagglutinins, and all 3 had abnormal reactivity to a variety of intradermal antigens. In the family members these same abnormalities were found with increased frequency. 6/13 were found to have decreased numbers of T lymphocytes and PHA reactivity; 6/13 dysgammaglobulinemias and 1/13 decreased isohemagglutinins. In addition, autoantibodies such as a biologically false positive serological test for syphilis, and antithyroid antibodies were also found. A parent of one of the propositi, and 2 asymptomatic siblings of another were also documented to have shortened platelet life spans in the presence of normal platelet counts. The HLA antigens, A3 and B7 were found in all 3 families. These 2 HLA antigens have previously been documented to occur with increased frequency in a variety of “auto-immune” disorders. These studies demonstrate that chronic ITP occurs in families with immunologic defects, and suggests that this disease has a genetic rather than an exclusively environmental basis.

Effects of reducing engine oil and rear axle lubricant viscosities on fuel economy were determined in EPA combined City and Highway (EPA 55/45) tests and in road tests, using four different sized cars. In EPA 55/45 tests, fuel economy rating improvements averaged about 1.5 percent; warmed-up and cold-start road test fuel economy improvements averaged about 4 and 8 percent, respectively. /GMRL/

"Not since Rachel Carson's 'Silent Spring' has so urgent a clarion call been sounded. 'The Dragon Hunters' shows us the way to ecological survival." So says author and commentator Roger Caras on the front of the jacket of "The Dragon Hunters." Les Line, editor of Audubon magazine, comments on the back of the jacket, "Rachel Carson's 1962 shocker, 'Silent Spring,' warned us of the devastating results of pesticide abuse. Now, while there's still time to curb the chemical countdown, Frank Graham Jr. narrates tales of the environmental scientists around us who are tracking down nature's hidden ways of nonpolluting pest control. 'The Dragon Hunters' is a timely, profoundly important, and fascinating book." To call "The Dragon Hunters" an "urgent clarion call" is a bit much, although it may sell books. To call "The Dragon Hunters" a series of "tales of the environmental scientists around us who are tracking down nature's hidden ways of nonpolluting pest ...

• The association of consumptive coagulopathy and malignancy is thought to be rare in pediatrics. In one patient with Ewing's sarcoma and in two with rhabdomyosarcoma consumptive coagulopathy developed in the presence of either diffuse metastatic disease or an extensive primary tumor. The coagulopathy was a major clinical problem, developing within five days of the onset of chemotherapy. Resolution coincided with the clinical response of the tumor. ( Am J Dis Child 132:870-872, 1978)

This study examines the role of labor-intensive manufacturing, particularly the textile and apparel industries, in the postwar industrial development of the Southeast. It is argued that this role continued to take the form of an early or pioneer involvement in the spread of industrial development, an involvement that has produced important but often overlooked changes in the postwar industrial geography of the area. Correlation matrices were used to examine the position of labor-intensive industry in this evolutionary process and to identify any differences in the types of labor markets sought by the textile and apparel industries that could have affected their pioneer roles. It was found that these industries could indeed be fit into a process of evolutionary change in the Southeast, that they continued to perform a pioneer function, and that this pioneer function led to expansion into less industrialized areas off the Piedmont. The apparel industry led in this expansion.

In an attempt to elucidate the usefulness of the BT poat ASA ingeation, this test was done with other tests of coagulation in 30 controls and 77 patients evaluated for a possible bleeding diathesis. Coagulation studies included FT, PTT, TT, VIII AHF & AGN, IX, XI, XIII, platelet retention and aggregation, and nodified Ivy BTs pre and 2 hrs. post 600 mgma ASA. The mean control BT in 25 normals was 3.6′ ± 3.2′ (3 SD). Following ASA the BT was 6.4′ ± 4.1′ (3 SD). 5/30 “controla” without bleeding histories had abnormal BTs poat ASA. In thla group, 4 were proven to have unrecognized von Willebrand's disease (VWD) and one a platelet defect. Of the 77 patients studied, 23 had initial BTs that were abnormal (21 with VWD and 2 with platelet defects). Of the remaining 54 with initially normal BTs, 32 had abnormal BTs post ASA. 18/32 had VWD at their first evaluation. In 8/32, however, the abnormal BT poat ASA waa the only abnormality at initial evaluation. On repeated teating, these patients were also shown to have VWD. 6/32 with abnormal BTs poat ASA were found to have platelet abnormalities. The remaining 22 patients had normal BTs pre and poat ASA. 17/22 revealed no hemoatatic abnormality. In 5 eventually proven to have VWD, the BT poat ASA was normal. The uae of the BT poat ASA ralaed the aenaltivity of the BT as a screening test from 35% to 92% in the abnormal patient population. We conclude that the BT poat ASA is a valuable screen in the evaluation of possible hemoatatic defects.

Chronic ITP, unlike acute ITP, may be the result of an underlying, immunolgic disorder. To examine this possibility 3 children, and their families, were studied in an attempt to identify underlying abnormalities in cellular and humoral immunity. All 3 patients had their disease for more than 1 year. All had shortened platelet life spans. None were receiving drugs, and none had had their spleens removed. In these patients, 2 of 3 were found to have decreased numbers of T lymphocytes and PHA reactivity; 2 of 3 had dysgammaglobulinemias: 1 of 3 had decreased isohemagglutinins, and all 3 had abnormal reactivity to a variety of intradermal antigens. In the family members these same abnormalities were found with increased frequcncy. In addition, autoantibodies such as a biologically false positive serologicnl test for syphilis, and anti-thyroid antibodies were also found. One parent and 2 asymptomatic siblings of one of the propositi were also documented to have shortened platelet life spans in the presence of normal platelet counts. The HLA antigens, A3 and B7 were found in all 3 families. These 2 HLA antigens have previously been documented to occur with increased frequency in a variety of “auto-immune” disorders. These studien demonstrate that chronic ITP occurs in families with immunologic defects, and suggests that this disease has a genetic rather than an exclusively environmental basis.

We studied three children with chronic idiopathic thrombocytopenic purpura (ITP) and their immediate families. All three patients and 10/13 family members manifested at least one immunologic defect, eg, decreased numbers of T lymphocytes (1/3, 5/13), diminished in vitro response to phytohemagglutinin (2/3, 6/13), dysgammaglobulinemia (2/3, 4/13), altered autoantibodies (1/3, 5/13), and decreased serum properdin levels (3/3,2/13). In addition, one parent and two asymptomatic siblings of two of the propositi had shortened platelet life spans with normal platelet counts. The HLA antigens A 3 and B 7 were identified in all three families. There also appeared to be an association between a familial haplotype and the immunologic defects. Chronic ITP appears to occur in families with underlying immunologic defects, which are genetically related. ( JAMA 239:939-942, 1978)

The use of Central Nervous System (CNS) prophylaxis with intrathecal chemotherapy is now considered an important early measure in the treatment of acute lymphoblastic leukemia and lyraphomas. It has been suggested that epidural or subdural extravasation at the time of lumbar puncture occurs frequently (NEJM 293:161, 1975). In order to determine the frequency of inadequately administered chemotherapy as well as its distribution within the CNS, Tc-99m labeled inulin complex was admixed with chemotherapy and injected intrathecally during 75 procedures. Gamma cisternograms were performed within 2 hours of drug instillation, obtaining 4 position images of the head and an image of the injection site. In 59 studies (79%) the radiopharmaceutical was seen at the basal cisterns and over the cortical subarachnoid spaces with no extravasation at the injection site. In 13 studies (17%) there was slight extravasation with the bulk of the radiopharmaceutical normally distributed. In 3 studies there was epidural or subdural localization with no subarachnoid distribution, a 4% failure rate. In these 3 procedures, there was free flow of fluid prior to injection. Inadequacy of therapy would not have been realized without cisternography. These studies demonstrate that intrathecally administered chemotherapeutic agents distribute widely within the CNS and that gamma cisternography is a valuable means of monitoring the adequacy of administration.

• A 3-year-old girl had pancytopenia and bone marrow erythroid hypoplasia. The pancytopenia resolved without therapy, but the erythroid hypoplasia persisted for four months in spite of a five-week course of corticosteroid therapy. She responded briefly when androgens were added to the corticosteroid regimen, but within three weeks of stopping therapy she developed acute lymphocytic leukemia. The differential diagnosis of RBC aplasia in childhood is discussed. To our knowledge, this is the first case reported with erythroid hypoplasia as a prodrome of acute lymphocytic leukemia of childhood. ( Am J Dis Child 132:763-764, 1978)