Comprehensive case management of malaria: Operational research informing policy.

In 2013, the Odisha state Vector Borne Disease Control Programme led a five year operational research project, under programmatic conditions, in close collaboration with several partners. This Comprehensive Case Management Project covered a population of 900,000 across paired control and intervention blocks in four districts, each with different transmission intensities. Key gaps in access to malaria services were identified through household surveys and a detailed situation analysis. The interventions included ensuring adequate stocks of rapid diagnostic tests and antimalarial drugs at the village level, the capacity building of health workers and ASHAs, setting up microscopy centres at the primary health care level, and conducting mass screening and treatment in poorly accessible areas. The programme strengthened the routine health system, and improved malaria surveillance as well as the access to and quality of care. Initially, the programme led to increased case reporting due to improved detection, followed by a decline in malaria incidence. Lessons from the project were then scaled up statewide in the form of a new initiative-Durgama Anchalare Malaria Nirakaran (DAMaN).

Prediction equation estimates of creatinine clearance in the intensive care unit.

OBJECTIVE: To assess the accuracy of 4 mathematical equations used to estimate creatinine clearance versus the 24-h creatinine clearance in ICU patients. DESIGN: Prospective study of renal function prediction. SETTING: The general adult ICUs of 3 metropolitan hospitals. PATIENTS: 199 critically ill patients with indwelling foley catheters. INTERVENTION AND MEASUREMENTS: Routine 24 h creatinine clearances were evaluated only in patients whose urine volume recorded by the nurses was within 10% of the laboratory's measured volume. Four mathematical equations utilizing age, sex, body weight, height, and plasma creatinine were used as a comparison. There was no difference in estimated creatinine clearance by 3 published methods when the 24 h creatinine clearance exceeded 100 ml/min. When the 24 h creatinine clearance was less than 100 ml/min, however, one prediction equation adjusted for lean body weight (LBW), was the most accurate. This equation accurately predicted creatinine clearance in the range of 30-100 ml/min and slightly overestimated creatinine clearance at 0-30 ml/min (p < 0.01, ANOVA all groups, p < 0.05 Fisher and Scheffé post-hoc tests) with a mean difference +/- 95% confidence interval of -5 +/- 3.1 ml/min. CONCLUSION: An initial rapid estimate of creatinine clearance in critically ill ICU patients with reduced renal function can be determined by an equation adjusted for LBW.

Karyotype at relapse following allogeneic bone marrow transplantation for chronic myelogenous leukemia.

Eighty-four patients underwent allogeneic or syngeneic bone marrow transplantation as therapy for chronic myelogenous leukemia (CML) during a 5-year period at The Johns Hopkins Oncology Center. We describe the karyotype at relapse in 19 patients who were Ph chromosome positive (Ph+) at diagnosis. Eighty-four percent of patients demonstrated clonal and/or nonclonal chromosome abnormalities in addition to the t(9;22)(q34;q11) at first detection of relapse or later during relapse. These abnormalities included: Ph plus additional clonal abnormalities (three patients), Ph plus nonclonal abnormalities (five patients), Ph plus additional clonal and nonclonal abnormalities (eight patients). Three patients had only the original Ph+ clone. The additional chromosome abnormalities were primarily structural, and entirely different from those most frequently observed during karyotypic evolution in conventionally treated CML. Chromosome 1 was most frequently involved, with 1q32 being the location of three clonal and two nonclonal abnormalities. Other sites included 6p21-22 (the site of two clonal abnormalities), 7p21-22, and 10q21 (the site of two clonal and one nonclonal abnormality each). Chromosomes 5 and 7q, regions of frequent involvement in acute nonlymphocytic leukemia that follows chemotherapy for other malignancies, were infrequently involved. The clinical significance of these additional abnormalities remains undetermined at this time.

Chromosome abnormalities in patients treated with 4-hydroperoxycyclophosphamide-purged autologous bone marrow transplantation.

Autologous bone marrow transplantation (ABMT) offers potentially curative therapy for patients with acute leukemia and lymphoma, yet little information exists about the chromosome abnormalities observed in ABMT recipients. Clonal abnormalities of chromosome 1 were reported by van den Akker. We report the cytogenetic results of 55 patients who underwent ABMT between November 1987 and July 1990: acute nonlymphocytic leukemia (ANLL, 22), acute lymphocytic leukemia (ALL, eight), Hodgkin's disease (seven), lymphoma (16), other (two). ANLL patients received busulfan and cytoxan, and the others received cytoxan and total body irradiation as their preparative regimen before transplant. BM was purged ex vivo with 4-hydroperoxycyclophosphamide (4-HC) at 30-100 micrograms/ml before reinfusion to kill tumor cells. Cytogenetic analysis was performed before and after transplant. Between one and four posttransplant specimens of BM were analyzed per patient (range 36-921 days). Chromosome abnormalities were observed in 14 of 55 patients after transplant. Seven had clonal abnormalities; all were in leukemic relapse, and one karyotype had complex rearrangements. Clonal abnormalities of chromosome 1 were not observed. Seven patients had nonclonal changes, and three of these have had overt clinical relapse. Our data suggest that clonal abnormalities observed posttransplant are best explained by clinical relapse of tumor and that ex vivo marrow purging with 4-HC is not likely to induce clonal chromosome abnormalities in normal cells. Long-term observation of these patients will be required to answer that question definitively, however.

Cytogenetic and FISH analysis of endometrial carcinoma.

Endometrial cancer is a common gynecologic tumor, yet reports of cytogenetic studies are few. We studied chromosomes from seven primary specimens of endometrial cancer. Six had abnormal chromosomes; five had a diploid-hyperdiploid modal number and one was triploid. One specimen had a normal karyotype. Chromosome 1 was frequently involved in abnormalities (five tumors) with i(1q) in two tumors, and one tumor each had der(7)t(1;7)(q12;p11) and +add (1)(p13). One additional tumor had trisomy 1 in the single cell which could be fully analyzed. Trisomy 7 was noted in two tumors, and trisomy 10 in one. Because trisomies of these chromosomes have been reported in other cases of endometrial cancer, we used fluorescent in situ hybridization (FISH) with centromere probes to determine the prevalence of trisomies 7 and 10 in these specimens. No additional tumors were found to have trisomies 7 or 10 by FISH. Our data, in combination with published literature, suggest that additional copies of 1q or portions of 1q constitute the primary change in this tumor. Extra copies of genes in this region may play an important role in tumorigenesis in endometrial carcinoma.

Intraoperative measurement of cerebral and tumor blood flow with laser-Doppler flowmetry.

A new technique, laser-Doppler flowmetry, has been used intraoperatively to measure blood flow responses in normal brain tissue and brain tumor to blood pressure and arterial blood gas alterations. We have observed that blood flow is reduced in most cerebral tumors, and that most tumors retain the normal response to changes in arterial blood gas; however, these responses are varied. One group of tumors in our study demonstrated an autoregulatory capacity; a second behaved passively--that is, blood flow changes followed blood pressure--while a third showed no response.

Influence of hydration on the internal dynamics of hen egg white lysozyme in the dry state.

Proteins exist in a predominantly aqueous solvent environment. Hydration of the protein surface significantly affects many aspects of the protein's structure and function; these effects may be related to the molecular dynamics of the protein. We have examined the influence of hydration on the internal dynamics of hen egg white lysozyme using room-temperature phosphorescence from the intrinsic tryptophan residues. Powders of lyophilized lysozyme were hydrated in a phosphorimeter using a flow system that allowed for continuous manipulation of relative humidity over the range 0-92%; this system allowed us to directly compare intensity differences that result from changes in hydration. Lysozyme phosphorescence intensity decreased as a function of hydration over the entire relative humidity range; the decrease was not linear but appeared to occur in distinct phases. The phosphorescence intensity decays were multiexponential over the hydration range studied, and hydration had the largest influence on the long lifetime component. These data suggest that the protein exists in multiple, static conformations in the dry state and that water binding to polar (as opposed to charged) sites on the protein surface induces local and/or global softening of the protein structure.

Stress dose steroids in renal transplant patients undergoing lymphocele surgery.

The requirement for perioperative stress dose steroids (SDS) in patients on long-term steroid therapy is controversial, but SDS are given during perioperative care. Studies focusing on surrogate outcomes like cortisol levels indicate a possible requirement for SDS, but clinical results are sparse. We retrospectively compared outcomes of renal or pancreas/kidney transplant patients undergoing surgical lymphocele drainage who did (n=20) or did not (n=38) receive SDS. Patients had similar demographic characteristics (P=NS). No patient developed hypotension (SBP < 80 mmHg), mental status change, unexplained arthralgias, or ileus. Impaired wound healing occurred in one patient in each group (P=NS), and lymphocele recurrence occurred in 25% of the SDS group and 10.5% of the other group (P=.25). SBP decreased from baseline in both groups (P <.001) but did not differ between groups, and maximum blood glucose was higher in the SDS group (P=.04). No difference was observed in other measured parameters. These data indicate that SDS increased the risk of hyperglycemia and provided no apparent benefit. A prospective study is warranted to confirm these findings.

Combined use of sirolimus and voriconazole in renal transplantation: a report of two cases.

Voriconazole is currently contraindicated for use with sirolimus. We report our experience with voriconazole/sirolimus in two renal transplant recipients. To our knowledge, this is the first experience with voriconazole/sirolimus. An interaction requiring a 75% to 87.5% sirolimus dose reduction was noted, but goal trough levels and clinical tolerability were achieved.

Effects of motion, ambient light, and hypoperfusion on pulse oximeter function.

STUDY OBJECTIVE: To compare the performance of five pulse oximeters during hypoperfusion, probe motion, and exposure to ambient light interference. DESIGN: Prospective study. SETTING: Laboratory facility at a university medical center. PATIENTS: 8 unanesthetized, ASA physical status I volunteers. INTERVENTIONS: We evaluated five common pulse oximeters with respect to three scenarios: (1) an operating room light was shone on oximeter probes, (2) a motion generator was used to generate 2 Hz and 4 Hz hand motion, and (3) a pneumatic compression device overlying the brachial artery was used to simulate hypoperfusion. Electrocardiographic (ECG) and arterial blood gas values were considered gold standards for heart rate (HR) and oxygen saturation (SpO2) respectively. SpO2 nondisplay and values greater than 4% from simultaneous arterial SaO2-oximeter values were defined as errors. Nondisplay of HR, or HR greater than 5% from ECG values, were also considered errors. MEASUREMENTS AND MAIN RESULTS: The Ohmeda and Nellcor N200 with finger probe had the highest total failure rates with respect to both SpO2 and HR due to ambient light interference (p < 0.05). The Nellcor N200 with finger probe and N200 with C lock were the most accurate with regard to SpO2 during 2 Hz and 4 Hz motion (p < 0.05). However, all oximeters failed dramatically during 4 Hz motion when measuring HR. In the hypoperfusion model, the Nellcor N200 with finger probe and the Nellcor C Lock oximeters performed significantly better than all others in terms of both HR and SpO2 (P < 0.05), while the Criticare oximeter failed 100% of the time. CONCLUSION: There are significant differences in the accuracy of commercially available pulse oximeters during nonideal circumstances, with failure rates varying from approximately 5% to 50% depending on the oximeter and source of interference. Furthermore, no single oximeter performed the best under all conditions.

Pulse oximeter performance during desaturation and resaturation: a comparison of seven models.

STUDY OBJECTIVE: To compare pulse oximeter performance during induced hypoxemia. DESIGN: Prospective investigation in human volunteers. SETTING: Laboratory facility at a university medical center. PATIENTS: 8 unanesthetized, healthy ASA physical status I volunteers. INTERVENTIONS: We evaluated the accuracy and response times of seven popular pulse oximeters during induced hypoxemia. Arterial blood fractional oxygen saturation (SaO2) measurements were performed simultaneously and considered a gold standard. MEASUREMENTS AND MAIN RESULTS: All oximeters were accurate (+/-2%) while subjects were breathing room air. During maximal hypoxemia (induced by breathing a FIO2 = 10% in nitrogen), large differences were noted between oxygen saturation as measured by pulse oximetry (SpO2) and SaO2 values, with pulse oximeters consistently underreporting SpO2 when actual SaO2 values were 75% or less. The Ohmeda 3740 (Ohmeda, Boulder, CO) using an ear probe was the first to detect desaturation (change in SpO2 > 3%) in 4 of 8 subjects (p < 0.05), and the Nellcor N200 reflectance oximeter (Nellcor, Inc., Pleasanton, CA) was first in 3 of 8 subjects (p < 0.05). During resaturation (after administering 100% oxygen), the Novametrix Oxypleth (Novametrix, Wallingford, CT) was significantly faster than other oximeters (p < 0.05) to return to baseline (SpO2 = 98%). CONCLUSION: Most models of oximeters tested performed well when hemoglobin oxygen saturation was high, but all were inaccurate when SaO2 was approximately 75%. During induced hypoxemia, there were significant differences in the response times of oximeters tested, with no model demonstrably superior to others in all measures of performance.

Spontaneous left ventricle cavity thrombus in a patient of systemic lupus erythematosus.

A 32 year old female with systemic lupus erythematosus having circulating lupus anticoagulant developed a thrombus in the left ventricle cavity, an unusual site. She responded to standard anticoagulant regime.

Clinical spectrum of HIV infection.

OBJECTIVE: To study the modes of transmission of pediatric HIV infection, to categorize clinical manifestations and to compare clinical spectrum of perinatal with transfusion acquired HIV infection. DESIGN: Case series study. SETTING: Hospital based pediatric HIV clinic. METHODS: Children confirmed to have HIV infection were evaluated and relevant details recorded. RESULTS: 55 children were enrolled of whom 41 (74.5%) had perinatal transmission of HIV, 12 (21.8%) were infected through blood transfusions and 2 (3.6%) through other routes. Thirty-seven (90.2%) of the 41 perinatally infected children were symptomatic. Tuberculosis was seen in 25 (67.5%) of these children and failure to thrive in 18 (48.6%). Nonspecific features such as recurrent bacterial infection, oral candidiasis and chronic diarrhea were other manifestations. Eight (26.3%) of the 30 children available for follow up for a median period of 9 months died at the median age of 8.5 months. Amongst the transfusion acquired HIV infection, 11 (91.6%) of the 12 were asymptomatic at presentation. Six (50%) of these children died at the median age of 3 years and the remaining 6 had no major symptoms at a median follow up of 3.5 years. CONCLUSION: Perinatal route is the major route of HIV transmission in children and clinical manifestations are different from those of adults.