Validity of the Patient Health Questionnaire-9 to screen for depression in a high-HIV burden primary healthcare clinic in Johannesburg, South Africa.

BACKGROUND: Integration of depression screening into primary care may increase access to mental health services in sub-Saharan Africa, but this approach requires validated screening instruments. We sought to validate the Patient Health Questionnaire-9 (PHQ-9) as a depression screening tool at a high HIV-burden primary care clinic in Johannesburg, South Africa. METHODS: We conducted a validation study of an interviewer-administered PHQ-9 among 397 patients. Sensitivity and specificity of the PHQ-9 were calculated with the Mini International Neuropsychiatric Interview (MINI) as the reference standard; receiver operating characteristic (ROC) curve analyses were performed. RESULTS: The prevalence of depression was 11.8%. One-third of participants tested positive for HIV. HIV-infected patients were more likely to be depressed (15%) than uninfected patients (9%; p=0.08). Using the standard cutoff score of ≥10, the PHQ-9 had a sensitivity of 78.7% (95% CI: 64.3-89.3) and specificity of 83.4% (95% CI: 79.1-87.2). The area under the ROC curve was 0.88 (95% CI: 0.83-0.92). Test performance did not vary by HIV status or language. In sensitivity analyses, reference test bias associated with the MINI appeared unlikely. LIMITATIONS: We were unable to conduct qualitative work to adapt the PHQ-9 to this cultural context. CONCLUSION: This is the first validation study of the PHQ-9 in a primary care clinic in sub-Saharan Africa. It highlights the potential for using primary care as an access point for identifying depressive symptoms during routine HIV testing. The PHQ-9 showed reasonable accuracy in classifying cases of depression, was easily implemented by lay health workers, and is a useful screening tool in this setting.

Abundant nuclear copies of mitochondrial origin (NUMTs) in the Aedes aegypti genome.

A portion of the Aedes aegypti mitochondrial NADH dehydrogenase subunit 4 gene (ND4) was amplified using PCR with a 42 degrees C annealing temperature. Amplified fragments from individual mosquitoes were similar to ND4 but contained multiple segregating sites. We suspected that nuclear copies of mitochondrial origin (NUMTs) exist in the Ae. aegypti genome. A BlastN search in VectorBase with the entire Ae. aegypti mitochondrial genome identified 233 NUMTs comprising 110 178 bp in 145 supercontigs. At a density of 0.080 bp/kb, this represents the second highest density of NUMTs in an insect genome and the highest in Diptera. Analyses of flanking sequences suggested that Ae. aegypti NUMTs arise through mtDNA leakage from damaged mitochondria followed by breakage and nonhomologous recombination, rather than through duplicative processes such as transposition or molecular drive.

Evidence of multiple chromosomal inversions in Aedes aegypti formosus from Senegal.

Chromosomal inversions are prevalent in mosquito species but polytene chromosomes are difficult to prepare and visualize in members of the tribe Aedinii and thus there exists only indirect evidence of inversions. We constructed an F(1) intercross family using a P(1) female from a laboratory strain of Aedes aegypti aegypti (Aaa) and a P(1) male Aedes aegypti formosus (Aaf) from a strain collected from south-eastern Senegal. Recombination rates in the F(2) offspring were severely reduced and genotype ratios suggested a deleterious recessive allele on chromosome 3. The F(2) linkage map was incongruent in most respects with the established map for Aaa. Furthermore, no increased recombination was detected in F(5) offspring. Recombination rates and gene order were consistent with the presence in Aaf of at least four large inversions on chromosome 1, a single small inversion on chromosome 2 and three inversions on chromosome 3.

Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: A dose escalating phase I/II study.

Patients with inoperable pancreatic cancer have a dismal prognosis with a mean life expectancy of 3-6 months. New treatment modalities are thus urgently needed. Telomerase is expressed in 85-90% of pancreas cancer, and immunogenic telomerase peptides have been characterised. A phase I/II study was conducted to investigate the safety, tolerability, and immunogenecity of telomerase peptide vaccination. Survival of the patients was also recorded. Forty-eight patients with non-resectable pancreatic cancer received intradermal injections of the telomerase peptide GV1001 at three dose levels, in combination with granulocyte-macrophage colony-stimulating factor. The treatment period was 10 weeks. Monthly booster vaccinations were offered as follow-up treatment. Immune responses were measured as delayed-type hypersensitivity skin reaction and in vitro T-cell proliferation. GV1001 was well tolerated. Immune responses were observed in 24 of 38 evaluable patients, with the highest ratio (75%) in the intermediate dose group. Twenty-seven evaluable patients completed the study. Median survival for the intermediate dose-group was 8.6 months, significantly longer for the low- (P = 0.006) and high-dose groups (P = 0.05). One-year survival for the evaluable patients in the intermediate dose group was 25%. The results demonstrate that GV1001 is immunogenic and safe to use. The survival data indicate that induction of an immune response is correlated with prolonged survival, and the vaccine may offer a new treatment option for pancreatic cancer patients, encouraging further clinical studies.

Changes in IP3 and cytosolic Ca2+ in response to sugars and non-sugar sweeteners in transduction of sweet taste in the rat.

1. The transduction pathways of sweet-sensitive cells in rat circumvallate (CV) taste buds were investigated with assays for inositol 1,4,5-trisphosphate (IP3) and with Ca2+ imaging. Stimulation with the non-sugar sweeteners SC-45647 and saccharin rapidly increased the cellular content of IP3 by 400 pmol (mg protein)-1, while sucrose had a much smaller effect on IP3. As shown previously, sucrose, but not saccharin, increased the content of cyclic adenosine monophosphate (cAMP) of this preparation. 2. Stimulation of isolated CV taste buds with SC-45647 increased the cytosolic Ca2+ concentration ([Ca2+]i) by 56.7 +/- 3.2 nM (n = 181). Due to the non-confocality of the measuring system, these concentrations are underestimates. The increase in [Ca2+]i did not require the presence of extracellular Ca2+, suggesting that the Ca2+ release was from intracellular stores. 3. Individual cells responding to the non-sugar sweeteners with Ca2+ release also responded to sucrose and to forskolin with an increase in [Ca2+]i. Such cells did not respond to the bitter tastant denatonium chloride. 4. Responses to sucrose were abolished by lowering the Ca2+ concentration of the stimulus solution, indicating Ca2+ uptake from the extracellular medium. 5. The responses of sweet-sensitive cells to forskolin were also abolished when Ca2+ ions were omitted from the stimulus solution. They were partially inhibited by the presence of Co2+, Ni2+, D600 (methoxyverapamil) and amiloride, indicating multiple pathways of Ca2+ uptake activated by cAMP. 6. In conclusion, a sweet-sensitive cell of the rat responds to sucrose with an increase in cAMP and Ca2+ uptake, but to non-sugar sweeteners with an increase in IP3 and Ca2+ release. The increase in [Ca2+]i, common to both pathways, is presumably required for synaptic exocytosis and for signal termination.

Usefulness of duplex ultrasound in evaluating vertebral arteries.

A criticism of duplex scanning of the carotid vessels is that the study is limited to evaluation of the carotid bifurcations, whereas with other vascular imaging studies the vertebral vessels can also be seen. We have prospectively collected data on our ability to evaluate the vertebral vessels on all patients who are sent for carotid evaluations. We have scanned 677 patients and have identified flow in one or both vertebral arteries in nearly 90% of these patients. Therefore, we urge that evaluation of vertebral vessels be made a routine part of the standard carotid duplex ultrasound examination.

Establishment and characterization of a human glioblastoma cell line with a stable karyotype and nullisomy 13.

A permanent cell line (HeRo) with a stable karyotype (80-84,XXYY) and with defined numerical and structural chromosome aberrations was established from a human glioblastoma, a highly malignant brain tumor. Transformation of these cells with SV40 led to a second permanent cell line (HeRo-SV) with a reduced, but also stable, karyotype (72-74,XXYY). The morphological appearance of the glioblastoma line was similar to the main component of the original tumor tissue. The transformed cells differed from their counterparts in accelerated growth, enhanced growth in soft agar, reduced growth conditions, expression of SV40 T antigen, and altered epitheloid morphology. Both cell lines have been grown in continuous culture for more than 2 years. The stability of both the biologic properties and the karyotypic changes induced by SV40 is quite remarkable. Both lines show a nullisomy 13.

Comparative hemodynamic study of IS-5-MN and ISDN in man--which are equieffective doses?

In a crossover study, the hemodynamic effects of 40 mg sustained release isosorbide dinitrate were compared with those of 40 mg isosorbide-5-mononitrate in 10 patients after myocardial infarction. No differences between both drugs were seen in the magnitude of their effects on cardiac preload. The onset of the effect, however, was faster after IS-5-MN and reached its nadir earlier than after sustained release ISDN. Thus, both drugs are hemodynamically equieffective in equal doses, but their effects show different time courses.

Combined silver staining of the nucleolus organizing regions and Giemsa banding in human chromosomes.

A combination of the silver-staining method of the nucleolus organizer regions (NORs) with a Giemsa-banding method is described. This double staining allows a rapid identification of the NOR-bearing chromosomes.

[Combinations of routine laboratory tests in diagnosis of malignomas (author's transl)]. / Kombinationen unspezifischer Laboruntersuchungen in der Tumordiagnostik

The question if combined routine-laboratory-tests could improve the search for malignomas in man was checked by comparison of 519 patients with carcinoma and 460 patients with other diseases. In order to do so a combination of four (erythrocyte sedimentation rate, alkaline phosphatase, red blood-picture, relative alpha-2-globuline-increase) and five (additionally alpha-1-globuline-increase) was put up. For either group the found constellations - consisting of normal and pathological items - and their sensibility and specificity were set up. To find out their diagnostical value the likelihood-ratio was determined. Those combinations with exclusively pathological results of all four respectively five laboratory reports and the linked symptoms "anemia - relative alpha-2-globuline-increase" showed to be of high differential diagnostical value. In these groups the probability of malignoma was found to be 4,6:1, 8:1, 3,2:1. The serum protein dispersion of a group of patients with benigne and maligne diseases of the digestive tract was additionally checked by means of the paper-electrophoresis. Those changes that showed a relative increase of all globuline-fractions combined with a decrease of serum albumins under 45% was almost exclusively found in patients with malignomas. All-together this paper shows that certain pathological laboratory-tests--if found together in one patient--give a grave indication for the presence of malignoma.

Carbamoyl phosphate compartmentation in Neurospora: histochemical localization of aspartate and ornithine transcarbamoylases.

Carbamoyl phosphate is required for arginine and pyrimidine synthesis. In the arginine pathway, it is used in the ornithine transcarbamoylase (EC 2.1.2.1) reaction; in the pyrimidine pathway, it is used in the aspartate transcarbamoylase (EC 2.1.3.2) reaction. In Neurospora crassa, two pathway-specific enzymes catalyze the synthesis of carbamoyl phosphate, and two path-specific pools of carbamoyl phosphate are maintained. Histochemical studies show that ornithine transcarbamoylase is located in mitochondria, and, with less certainty, that aspartate transcarbamoylase is confined largely to nuclei. The enzymes that form carbamoyl phosphate are associated with the respective transcarbamoylases in the cell. Therefore, the segregation of carbamoyl phosphate pools could be accounted for by one or both organellar membranes, which demarcate two separate sites of carbamoyl phosphate metabolism in Neurospora. The alternative possibility that the enzyme complex that produces and consumes carbamoyl phosphate in the pyrimidine pathway could explain the channelling of carbamoyl phosphate, wholly or in part, is discussed.