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PubMed2004

Plasmodium falciparum malaria disease manifestations in humans and transmission to Anopheles gambiae: a field study in Western Kenya.

Transmission of the malaria parasite Plasmodium is influenced by many different host, vector and parasite factors. Here we conducted a field study at Mbita, an area of endemic malaria in Western Kenya, to test whether parasite transmission to mosquitoes is influenced by the severity of malaria infection in its human host at the time when gametocytes, the transmission forms, are present in the peripheral blood. We examined the infectivity of 81 Plasmodium falciparum gametocyte carriers to mosquitoes. Of these, 21 were patients with fever and other malaria-related symptoms, and 60 were recruited among apparently healthy volunteers. Laboratory-reared Anopheles gambiae s.s. (local strain) were experimentally infected with blood from these gametocyte carriers by membrane-feeding. The severity of the clinical symptoms was greater in febrile patients. These symptomatic patients had higher asexual parasitaemia and lower gametocyte densities (P = 0.05) than healthy volunteers. Ookinete development occurred in only 6 out of the 21 symptomatic patients, of which only 33.3% successfully yielded oocysts. The oocyst prevalence was only 0.6% in the 546 mosquitoes that were fed on blood from this symptomatic group, with mean oocyst intensity of 0.2 (range 0-2) oocysts per mosquito. In contrast, a higher proportion (76.7%) of healthy gametocyte carriers yielded ookinetes, generating an oocyst rate of 12% in the 1332 mosquitoes that fed on them (mean intensity of 6.3, range: 1-105 oocysts per mosquito). Statistical analysis indicated that the increased infectivity of asymptomatic gametocyte carriers was not simply due to their greater gametocyte abundance, but also to the higher level of infectivity of their gametocytes, possibly due to lower parasite mortality within mosquitoes fed on blood from healthy hosts. These results suggest that blood factors and/or conditions correlated with illness reduce P. falciparum gametocyte infectivity.

Adolescent↗
PubMed2004

Surface-enhanced Raman spectroscopy for bacterial discrimination utilizing a scanning electron microscope with a Raman spectroscopy interface.

Surface-enhanced Raman scattering (SERS) utilizing colloidal silver has already been shown to provide a rapid means of generating "whole-organism fingerprints" for use in bacterial identification and discrimination. However, one of the main drawbacks of the technique for the analysis of microbiological samples with optical Raman microspectroscopy has been the inability to acquire pre-emptively a region of the sample matrix where both the SERS substrate and biomass are both present. In this study, we introduce a Raman interface for scanning electron microscopy (SEM) and demonstrate the application of this technology to the reproducible and targeted collection of bacterial SERS spectra. In secondary electron mode, the SEM images clearly reveal regions of the sample matrix where the sodium borohydride-reduced silver colloidal particles are present, Stokes spectra collected from these regions are rich in vibrational bands, whereas spectra taken from other areas of the sample elicit a strong fluorescence response. Replicate SERS spectra were collected from two bacterial strains and show excellent reproducibility both by visual inspection and as demonstrated by principal components analysis on the whole SERS spectra.

Bacillus subtilis↗
PubMed2006

IMS-IMS and IMS-IMS-IMS/MS for separating peptide and protein fragment ions.

Multidimensional ion mobility spectrometry (IMS-IMS and IMS-IMS-IMS) techniques have been combined with mass spectrometry (MS) and investigated as a means of generating and separating peptide and protein fragment ions. When fragments are generated inside a drift tube and then dispersed by IMS prior to MS analysis, it is possible to observe many features that are not apparent from MS analysis alone. The approach is demonstrated by examining fragmentation patterns arising from electrospray ion distributions of insulin chain B and ubiquitin. The multidimensional IMS approach makes it possible to select individual components for collisional activation and to disperse fragments based on differences in mobility prior to MS analysis. Such an approach makes it possible to observe many features not apparent by MS analysis alone.

Amino Acid Sequence↗
PubMed1998

Effect of different background lighting conditions on diagnostic performance of digital and film images.

OBJECTIVE: To compare the performance of a photostimulable phosphor (PSP) imaging system with radiographic film for the detection of approximal lesions under two background lighting conditions. METHODS: Bitewing exposures were made of the extracted human teeth with artificial approximal lesions using D-speed and E-speed radiographic film and a PSP imaging plate. Eight dentists rated 12 approximal surfaces in each image on a 5-point scale. Images were viewed with overhead fluorescent room lighting on and off. ROC curves were generated for each image receptor and lighting condition. Repeated measures analysis of variance ANOVA tested differences between observers, lesion size, image receptor, lighting condition. RESULTS: Mean ROC curve areas for D-speed film viewed in full ambient light scored highest (0.8030) followed by E-speed film using dark conditions (0.7386). The lowest mean curve area was found when PSP (enhanced mode) images were viewed in a dark room (0.6726). Significant differences were found between observers, lesion size, image receptor and image receptor-lesion size interaction. No significant difference was found with background lighting. CONCLUSIONS: Background lighting does not appear to effect the ability to detect artificial approximal lesions.

Analysis of Variance↗
PubMed1996

Use of proficiency tests to assess the comparative performance of analytical methods: the determination of fat in foodstuffs.

The determination of fat in foodstuffs is a common analytical task. Hitherto there has been no authoritative comparative exercise to assess the available methods by means of results from a large number of laboratories. In this paper four different empirical methods of analysis for fat are compared using the results generated from a proficiency testing scheme. The results show significant bias between some of the different methods, confirming the empirical nature of the determination.

Animals↗
PubMed2003

Statistical analysis of the physico-chemical data on the coastal waters of Cochin.

Measurements of temperature, salinity, dissolved oxygen, nitrogen as ammonia, nitrate and nitrite, and phosphate along with chlorophyll were carried out at three stations on the coastal waters of Cochin, south west India, at two-levels of the water column over a period of five years. The data set has been factorised using principal component analysis (PCA) for extracting linear relationships existing among a set of variables. A graphical display of the scores generated from the PCA was done by means of boxplots and biplots, which helped in the interpretation of the data. The major factors conditioning the system are related to the input of fresh water from the estuary of the Periyar river and the high organic load of the bottom sediment in the coastal area which results in a reducing environment, as reflected in the parameters of dissolved oxygen, ammoniacal-nitrogen and nitrite-nitrogen. Another factor which contributes to the variation in the system is related to the unloading activity in the port area. The present approach presents a logical way to interpret the complex data of the physico-chemical measurements.

Ammonia↗
PubMed2003

Analysis of red cell and platelet morphology using an imaging-combined flow cytometer.

Laser-based flow cytometry and aperture-impedance methods are still the dominant technologies used for cell analysis in haematology, but both are limited to areas such as morphological analysis of red cell shape and high-sensitivity detection of platelet agglutinates and aggregates. Flow cytometry alone does not provide precise measurement of red cell volume without chemical pretreatment before detection and aperture-impedance is still considered the gold standard in the field of particle volume analysis. In the present study, an experimental prototype instrument called the imaging-combined flow cytometer (IFC) was evaluated. The IFC is equipped with an imaging device consisting of a pulse laser, lens units and a charge-coupled device (CCD) camera in addition to the flow-cytometric optical set-up. A personal computer was attached to the instrument to handle images derived from the imaging device. Laser illumination was triggered so that the image of an object was captured for each exposure of the CCD camera. Objects in the images were used to calculate size and shape information and to compute fractal texture features by image processing after each measurement. The advantage of the IFC is that it can capture images of selected cells of interest at the same time as flow-cytometric detection. Estimation of red cell volume, discrimination of red cells and platelets, and detection of platelet agglutinates and aggregates were attempted using the IFC in combination with image processing, It was found that image analysis on the IFC could provide a substitutional function for mean corpuscular volume (MCV) estimation and detection of platelet agglutinates and aggregates. The additional information generated by the IFC may be useful in diagnostic haematology.

Autoanalysis↗
PubMed2002

Prenatal ultrasound findings in a fetus with congenital contractural arachnodactyly.

Congenital contractural arachnodactyly (CCA) or Beals-Hecht syndrome is an autosomal dominant disorder caused by mutations in the fibrillin-2 (FBN2) gene. The principal features of CCA are a marfanoid habitus, multiple congenital contractures, camptodactyly, arachnodactyly, kyphoscoliosis, muscular hypoplasia, and external ear malformations. Our case is the first that shows typical sonographic signs in a fetus at 25 weeks' gestation with molecular genetically verified CCA in a large family with many members affected over four generations. This demonstrates that CCA can be detected prenatally by non-invasive ultrasonography. The importance of confirmation of CCA by means of DNA sequence analysis of the FBN2 gene is stressed.

Adult↗
PubMed2002

Pasteurella multocida meningitis: case report and review of the last 11 y.

Pasteurella multocida meningitis is a rare clinical occurrence. We report a new case and review the 28 other cases described in the English literature. A history of recent animal contact remains strongly associated with P. multocida meningitis (noted in 89% of all cases), with licking of mucus surfaces or injured skin being most common. Bacteremia was present in 63% of all patients. Spread from an adjacent site of infection continues to be an important factor, with otitis media being documented or strongly suspected in 24% of all cases. The presenting signs and symptoms were characteristic of bacterial meningitis, with fever, headache, nucal rigidity and an altered level of consciousness being present in most patients. Cerebrospinal fluid analysis was typical for bacterial meningitis. Penicillin G or ampicillin was the most common definitive treatment; however, third-generation cephalosporins have been successful. The mean duration of treatment was 14 d. Neurologic complications were present in 17% of patients overall and mortality remains substantial at 25%. Although not statistically significant, there is a trend toward decreased neurologic complications and mortality during the last 11 y.

Adult↗
PubMed1999

Statistical analysis of array expression data as applied to the problem of tamoxifen resistance.

BACKGROUND: Although the emerging complementary DNA (cDNA) array technology holds great promise to discern complex patterns of gene expression, its novelty means that there are no well-established standards to guide analysis and interpretation of the data that it produces. We have used preliminary data generated with the CLONTECH Atlas human cDNA array to develop a practical approach to the statistical analysis of these data by studying changes in gene expression during the development of acquired tamoxifen resistance in breast cancer. METHODS: For hybridization to the array, we prepared RNA from MCF-7 human breast cell tumors, isolated from our athymic nude mouse xenograft model of acquired tamoxifen resistance during estrogen-stimulated, tamoxifen-sensitive, and tamoxifen-resistant growth. Principal components analysis was used to identify genes with altered expression. RESULTS AND CONCLUSIONS: Principal components analysis yielded three principal components that are interpreted as 1) the average level of gene expression, 2) the difference between estrogen-stimulated gene expression and the average of tamoxifen-sensitive and tamoxifen-resistant gene expression, and 3) the difference between tamoxifen-sensitive and tamoxifen-resistant gene expression. A bivariate (second and third principal components) 99% prediction region was used to identify outlier genes that exhibit altered expression. Two representative outlier genes, erk-2 and HSF-1 (heat shock transcription factor-1), were chosen for confirmatory study, and their predicted relative expression levels were confirmed in western blot analysis, suggesting that semiquantitative estimates are possible with array technology. IMPLICATIONS: Principal components analysis provides a useful and practical method to analyze gene expression data from a cDNA array. The method can identify broad patterns of expression alteration and, based on a small simulation study, will likely provide reasonable power to detect moderate-sized alterations in clinically relevant genes.

Animals↗
PubMed1992

Different patterns of myometrial activity and 24-h rhythms in myometrial contractility in the gravid baboon during the second half of pregnancy.

Two clearly distinct epochs of myometrial contractility were observed in 13 pregnant baboons when recorded either as intraamniotic pressure (IAP) or myometrial electromyogram (EMG). Contractures, epochs lasting longer than 3 min, were the characteristic form of myometrial activity throughout pregnancy. Contractures generated only small increases in IAP. Short-lived contractions, generating larger increases in IAP, were characteristic of labor and delivery. Power spectral analysis of IAP and myometrial EMG activity proved to be an effective means whereby periods when the myometrium was in the contractures or contractions mode could be easily distinguished. Concomitantly recorded maternal intraabdominal temperature showed significant 24-h variations. When myometrial activity switched from low-amplitude, long-lasting regular contractures of pregnancy to contractions, the switch always occurred around the onset of darkness. Five baboons went into spontaneous labor, 3 prematurely and 2 at term. In these animals the switch from contractures to contractions occurred for several nights before delivery. The recurrence and timing of the switch from contractures to contractions for several nights before delivery were similar to the pattern we and others have observed in the pregnant rhesus monkey. The presence of 24-h periodicity in the patterns of specific types of myometrial activity in another nonhuman primate lends support to the view that similar 24-h patterns of myometrial activity may occur in pregnant women.

Animals↗
PubMedDate not supplied

[Displaced women's opinion of the impact of forced displacement on their health].

OBJECTIVE: To analyze the adaptation process of women internally displaced to the city and the relationship between displacement and their self-perceived main health problems. METHODS: A qualitative, exploratory, descriptive study was carried out by means of semi-structured individual interviews with a maximum variation sample of 25 internally displaced women. A narrative content analysis was conducted with mixed generation of categories and data segmentation by age and themes. The area under study consisted of five localities in the city of Bogotá (Colombia). RESULTS: According to the interviewed women's discourses, their adaptation to city life depended on the new socioeconomic and environmental conditions and the psychosocial impact of displacement on the family. Precarious economic conditions forced them to live in an unhealthy environment and, occasionally, to adopt the role of head of household. In this role, many of these women, particularly young women, faced great difficulties in ensuring that the family's needs were met. Young women and teenagers reported behavioral changes due to displacement, including reproduction of violence in the home. The main self-perceived health problems among displaced women were mental health, access to food, infections and gynecological alterations. Displaced women identified the main factors hindering their access to health services as their economic situation and home responsibilities. CONCLUSIONS: Displaced women face new environmental and family challenges that negatively affect their health and access to healthcare. Specific interventions aimed at displaced women are required to foster better health through access to work and long -term socioeconomic stability.

Colombia↗
PubMed1999

Functional outcome and gait analysis after triple or double arthrodesis.

Thirteen patients who had undergone unilateral triple or double arthrodesis were studied an average of 5.2 years after surgery. Patients with a neuromuscular disorder; inflammatory arthritis; or any other focus of lower extremity arthritis, deformity, or joint dysfunction were excluded from the study. Clinical and radiological assessment of the patients was performed in addition to three-dimensional kinematic and kinetic gait analysis. Objective clinical outcome based on the American Orthopaedic Ankle and Foot Society score was rated as good or excellent for 10 patients, fair for 2, and poor for 1. Two patients developed radiological evidence of arthrosis affecting other tarsal joints that was not apparent on preoperative radiographs. Two other patients had some progression of radiological arthrosis that was identified before the index surgery. The presence of radiological ankle or tarsal arthritis did not correlate with the level of the patient's pain or functional disability. Gait analysis demonstrated a 13% increase in range of flexion of the ipsilateral knee during the third rocker period of stance. At the ankle, range of motion during the same period of stance was reduced by 33%. This was mostly the result of a 6 degrees (53%) loss of plantarflexion at toe-off. Analysis of the ankle kinetic data identified a mean 13% reduction in the peak external ankle dorsiflexion moment and a 45% reduction in mean maximum power generation at the ankle in comparison to the normal side. Unilateral triple or double arthrodesis was shown to predictably result in decreased pain and increased function in otherwise normal individuals.

Adult↗
PubMed2005

Lithium alters brain activation in bipolar disorder in a task- and state-dependent manner: an fMRI study.

BACKGROUND: It is unknown if medications used to treat bipolar disorder have effects on brain activation, and whether or not any such changes are mood-independent. METHODS: Patients with bipolar disorder who were depressed (n = 5) or euthymic (n = 5) were examined using fMRI before, and 14 days after, being started on lithium (as monotherapy in 6 of these patients). Patients were examined using a word generation task and verbal memory task, both of which have been shown to be sensitive to change in previous fMRI studies. Differences in blood oxygenated level dependent (BOLD) magnitude between the pre- and post-lithium results were determined in previously defined regions of interest. Severity of mood was determined by the Hamilton Depression Scale for Depression (HAM-D) and the Young mania rating scale (YMRS). RESULTS: The mean HAM-D score at baseline in the depressed group was 15.4 +/- 0.7, and after 2 weeks of lithium it was 11.0 +/- 2.6. In the euthymic group it was 7.6 +/- 1.4 and 3.2 +/- 1.3 respectively. At baseline mean BOLD signal magnitude in the regions of interest for the euthymic and depressed patients were similar in both the word generation task (1.56 +/- 0.10 and 1.49 +/- 0.10 respectively) and working memory task (1.02 +/- 0.04 and 1.12 +/- 0.06 respectively). However, after lithium the mean BOLD signal decreased significantly in the euthymic group in the word generation task only (1.56 +/- 0.10 to 1.00 +/- 0.07, p < 0.001). Post-hoc analysis showed that these differences were statistically significant in Broca's area, the left pre-central gyrus, and the supplemental motor area. CONCLUSION: This is the first study to examine the effects of lithium on brain activation in bipolar patients. The results suggest that lithium has an effect on euthymic patients very similar to that seen in healthy volunteers. The same effects are not seen in depressed bipolar patients, although it is uncertain if this lack of change is linked to the lack of major improvements in mood in this group of patients. In conclusion, this study suggests that lithium may have effects on brain activation that are task- and state-dependent. Given the small study size and the mildness of the patient's depression these results require replication.

Journal Article↗
PubMed2004

Citalopram concentrations and response in obsessive-compulsive disorder. Preliminary results.

OBJECTIVE: Citalopram, a highly potent SSRI, is effective in the treatment of depressive disorders and obsessive-compulsive disorder (OCD); however, very few studies have reported concentration-effect relationships for SSRIs. The aim of this study was to investigate the relationship between citalopram concentrations and clinical response in patients with OCD. METHODS AND STUDY DESIGN: Fifteen patients (aged 18-65 years) with a DSM-IV diagnosis of OCD were included in this open-label, single-blind study. Citalopram was started at a dosage of 20 mg/day; the dosage was increased to a maximum of 60 mg/day by the third week, on the basis of clinical need and tolerability. The dosage then remained unchanged until the end of the 10-week study. Clinical assessments were made at baseline, weekly for the first four weeks and then at weeks 6, 8 and 10. The assessment scales used were the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Clinical Global Impression Scale (CGI) and the Hamilton Depression Rating Scale (HDRS). Plasma citalopram concentrations were determined using a high performance liquid chromatography method after solid phase extraction. RESULTS: One patient was withdrawn from the study because of poor compliance. Of the 14 patients who completed the study, nine did not meet the treatment response criterion of an improvement of >25% from the baseline total Y-BOCS score and a score of < or =3 for the global improvement item of the CGI (these patients were termed non-responders), while five did (responders). There were no differences in the main demographic and baseline clinical variables between responders and non-responders. Steady-state citalopram concentrations were similar in the two groups, suggesting that the anti-obsessional effects of citalopram were not related to pharmacokinetic differences between responders and non-responders. There was no linear relationship between steady-state citalopram concentrations and response. The citalopram concentrations and Y-BOCS scores of individual responders obtained at baseline and various study timepoints showed a sigmoid relationship when analysed using the E(max) (maximum change in Y-BOCS score) model, with a mean EC(50) value (drug concentration that elicits 50% of the E(max)) of 152 microg/L, whereas a similar analysis of the non-responders generated a flat line. CONCLUSION: The results of this preliminary study suggest that plasma citalopram concentrations may be related to the clinical response in responders, but do not seem to account for the lack of clinical effect in non-responders. These data, as well as the usefulness of the model in relating plasma concentrations to response, even after repeated administration, need to be validated by further investigations.

Adolescent↗
PubMed1991

Localization and characterization of substance P binding sites in rat and rabbit eyes.

Specific and high-affinity binding sites for Substance P (SP) were found in eyes from albino rabbits and rats using an in vitro autoradiographic method with 125I-Bolton Hunter SP (BHSP). autoradiograms were generated by apposing 10-20 microns-thick cryostat eye sections to 3H-Hyperfilm or liquid emulsion and quantified by means of image-analysis procedures. Kinetic studies showed that equilibrium was reached after a 75-min incubation at room temperature. In rat retina, specific binding corresponding to approximately 90% of total binding, was reversible, of high affinity (dissociation constant [Kd], 0.13 +/- 0.02 nM). Half-time for dissociation of 125I-BHSP was about 15 min. Unlabeled SP and the two neurokinins (NK) A and B competed in a concentration-dependent manner for retinal sites labeled by 125I-BHSP with the following order of potencies: SP greater than NKA greater than NKB, in agreement with a pharmacologic profile of a SP receptor site. In both species, specific binding was found in the iris sphincter muscle, choroid, and retina. In rats, detectable amounts of SP-binding sites were also expressed in the corneal epithelium and iridial stroma. Quantitative analysis of the autoradiograms revealed that the highest densities of 125I-BHSP binding sites were localized in the iris sphincter muscle in rabbits and the inner retina in rats.

Animals↗
PubMed1981

The "iron screen": modification of standard laboratory practice with data analysis.

Multivariate analysis was applied to iron deficiency anemia to generate an efficient sequence of diagnostic laboratory tests. A three step diagnostic system--serum ferritin level and mean corpuscular volume as a screen in all patients, followed by serum iron level and total iron binding capacity in some patients, and by erythrocyte sedimentation rate in a few patients--was constructed using a previously validated data reduction system. When compared to bone marrow iron stores, this system was found to have 96 per cent accuracy. In one year of clinical trial the "iron screen" classified 396 of 416 patients in a hospital setting. This sequential strategy shows how clinical laboratory data can be utilized to render diagnoses of defined probability.

Anemia, Hypochromic↗