Characterization of rearranged Y chromosomes in human testicular tumor cell lines

Cytogenetic analysis of four cell lines established from two different human testicular tumors revealed rearranged or missing Y chromosomes. Southern blot analysis and in situ hybridization with different Y-derived human DNA sequences revealed the existence of Y chromosomal material even in a line without a cytogenetically visible Y chromosome and clarified the composition of Y marker chromosomes.     

Untersuchungen zur Regulation der Ammoniumassimilation von Candida maltosa

Activities of ammonia-metabolizing enzymes from Candida maltosa were measured. The synthesis of glutamate and glutamine involves three primary enzymes: glutamate dehydrogenase (GDH), glutamine synthetase (GS), and glutamate synthase (GOGAT). This yeast has two distinct GDH, the first responsible for glutamate catabolism, and the second solely biosynthetic. The GS is derepressed during growth on low ammonia or on a variety of alternative nitrogen sources, whereas the catabolic GDH (NAD) is repressed under this conditions. Ammonia limitation did not significantly affect GOGAT as well as biosynthetic GDH (NADP) levels. The relatively low K_m-value for ammonia suggest that the GS is catalytically active during cell growth on low concentrations of ammonia. It seems that under N-limitation ammonia assimilation is achieved via GS/GOGAT and under N-excess via GDH/GS.     

Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.     

Distinguishing characteristics of a new neuroblastoma cell line

The characteristics of a new neuroblastoma cell line (MC-NB-1) established from the bone marrow of a 2-year-old male are described. Morphologically, the cells appear as flattened and epithelial-like or as small and spherical. Electron microscopy demonstrated microtubules and dense core secretory granules. The doubling time was approximately 35 hr. Isoenzyme patterns and catecholamine secretion indicated a human line of neuronal origin. The soft agar tumor colony forming system demonstrated drug resistance in vitro comparable to in vivo nonresponsiveness. The stemline karyotype of MC-NB-1 is 44,Y,del(1) (p22:), -4, -7, +del(7)(q22:), -16, +t(7;16)(16pter leads to 16q24::7q22 leads to 7q32), -17. Additionally, double-minute bodies were observed. However, no evidence of homogeneous staining regions (HSRs) were detected.     

Evaluation of cerebrospinal fluid mononuclear cells obtained from children with acute lymphocytic leukemia: advantages of combining cytomorphology and terminal deoxynucleotidyl transferase

Sixty cerebrospinal fluid (CSF) samples were obtained from 28 children with terminal deoxynucleotidyl transferase (TdT) positive acute lymphocytic leukemia (ALL). Cell morphology was evaluated using Wright's stained cytocentrifugation prepared slides. The presence of nuclear TdT was detected by an immunofluorescent (IF) assay. Evaluation of CSF mononuclear cells using these two methods simultaneously allowed us to differentiate between leukemic and nonleukemic pleocytosis. Agreement between cytomorphology and TdT in identifying CNS lymphoblasts was found in 55 of 60 samples. Seventy-two per cent of the TdT-positive samples were obtained from children with CSF cell counts less than 10 WBC/mm3. We recommend that these two methods be used in conjunction when evaluating CSF mononuclear cells from children with TdT positive ALL.     

Somatic symptoms in primary affective disorder. Presence and relationship to the classification of depression

The incidence and severity of somatic symptoms were determined in 132 patients with major depressive disorder and 80 normal controls. The role of somatic symptoms was analyzed in relation to the unipolar-bipolar division, Research Diagnostic Criteria (RDC) subtypes, hypersomnia, and appetite increase. The data suggest that the rate and level of somatic symptoms increased with the severity of depression and age, only appetite loss differentiated unipolar from bipolar patients, and the classic somatic symptoms of depression were present in most RDC subtypes and not exclusively associated with the "endogenous" subtype. Hypersomnia or increased appetite identified two overlapping depressive subgroups; patients in both groups were young and characterized by high interpersonal sensitivity. Hypersomniac depressed patients were less anxious and agitated; patients with increased appetite were more hostile and showed a greater decrease in libido than age-matched and sex-matched patients with neither symptom.     

Multinutrient Biofortification of Maize (Zea mays L.) in Africa: Current Status,Opportunities and Limitations

Macro and micronutrient deficiencies pose serious health challenges globally, with the largest impact in developing regions such as subSaharan Africa (SSA), Latin America and South Asia. Maize is a good source of calories but contains low concentrations of essential nutrients. Major limiting nutrients in maize-based diets are essential amino acids such as lysine and tryptophan, and micronutrients such as vitamin A, zinc (Zn) and iron (Fe). Responding to these challenges, separate maize biofortification programs have been designed worldwide, resulting in several cultivars with high levels of provitamin A, lysine, tryptophan, Zn and Fe being commercialized. This strategy of developing single-nutrient biofortified cultivars does not address the nutrient deficiency challenges in SSA in an integrated manner. Hence, development of maize with multinutritional attributes can be a sustainable and cost-effective strategy for addressing the problem of nutrient deficiencies in SSA. This review provides a synopsis of the health challenges associated with Zn, provitamin A and tryptophan deficiencies and link these to vulnerable societies; a synthesis of past and present intervention measures for addressing nutrient deficiencies in SSA; and a discussion on the possibility of developing maize with multinutritional quality attributes, but also with adaptation to stress conditions in SSA.     

What Are the Frequency,Related Mortality,and Factors Associated with Bone Cement Implantation Syndrome in Arthroplasty Surgery?

BackgroundBone cement implantation syndrome (BCIS) is characterized by hypoxia, hypotension, and the loss of consciousness during cemented arthroplasty; it may result in death. Its incidence has only been explored for hemiarthroplasty and THA after fracture or cancer. To our knowledge, there are no studies that comprehensively explore and compare the incidence of BCIS in other arthroplasty procedures.Questions/purposes(1) To report the incidence of BCIS in TKA, unicondylar knee arthroplasty, hip hemiarthroplasty, THA, shoulder arthroplasty, TKA, and revision THA and TKA; (2) to determine whether severe BCIS is associated with an increased risk of death within 30 days of surgery; and (3) to identify factors associated with the development of severe BCIS.MethodsAll patients undergoing cemented arthroplasty for any reason (TKA [11% cemented, 766 of 7293], unicondylar knee arthroplasty [100% cemented, 562 procedures], hip hemiarthroplasty for femur fractures [100% cemented, 969 procedures], THA [8% cemented, 683 of 8447], shoulder arthroplasty [84% cemented, 185 of 219], and revision arthroplasty of the hip and knee [36% cemented, 240 of 660]) between January 2008 and August 2019 were considered for inclusion in the current retrospective observational study. Fixation choice was dependent on surgeon preference (THA and TKA), prosthesis design (shoulder arthroplasty), or bone quality (revision arthroplasty). The following procedures were excluded because of insufficient data: < 1% (1 of 766) of TKAs, 1% (4 of 562) of unicondylar knee arthroplasties, 6% (54 of 969) of hip hemiarthroplasties, 1% (6 of 683) of THAs, 6% (12 of 185) of shoulder arthroplasties, and 14% (34 of 240) of revision procedures. This resulted in a final inclusion of 3294 procedures (765 TKAs [23%], 558 unicondylar knee arthroplasties [17%], 915 hip hemiarthroplasties [28%], 677 THA [21%], 173 shoulder arthroplasties [5%], and 206 revision arthroplasties [6%]), of which 28% (930 of 3294) had an emergent indication for surgery. Of the patients, 68% (2240 of 3294) were females, with a mean age of 75 ± 11 years. All anesthetic records were extracted from our hospital’s database, and the severity of BCIS was retrospectively scored (Grade 0 [no BCIS], Grade 1 [O₂% < 94% or fall in systolic blood pressure of 20% to 40%], Grade 2 [O₂% < 88% or fall in systolic blood pressure of > 40%], and Grade 3 [cardiovascular collapse requiring CPR]). Procedures were dichotomized into no or moderate BCIS (Grades 0 and 1) and severe BCIS (Grades 2 and 3). The adjusted 30-day mortality of patients with severe BCIS was assessed with a multivariate Cox regression analysis. A multivariate logistic regression analysis was performed to identify factors associated with the development of severe BCIS.ResultsBCIS occurred in 26% (845 of 3294) of arthoplasty procedures. The incidence was 31% (282 of 915) in hip hemiarthroplasty, 28% (210 of 765) in TKA, 24% (165 of 677) in THA, 23% (47 of 206) in revision arthroplasty, 20% (113 of 558) in unicondylar knee arthroplasty, and 16% (28 of 173) in shoulder arthroplasty. Patients with severe BCIS were more likely (hazard ratio 3.46 [95% confidence interval 2.07 to 5.77]; p < 0.001) to die within 30 days of the index procedure than were patients with less severe or no BCIS. Factors independently associated with the development of severe BCIS were age older than 75 years (odds ratio 1.57 [95% CI 1.09 to 2.27]; p = 0.02), American Society of Anesthesiologists Class III or IV (OR 1.58 [95% CI 1.09 to 2.30]; p = 0.02), and renal impairment (OR 3.32 [95% CI 1.45 to 7.46]; p = 0.004).ConclusionBCIS is common during cemented arthroplasty; severe BCIS is uncommon, but it is associated with an increased risk of death within 30 days of surgery. Medically complex patients undergoing hip hemiarthroplasty may be at particular risk. Patients at high risk for severe BCIS (renal impairment, ASA III/IV, and age older than 75 years) should be identified and preventive measures such as medullary lavage before cementation, femoral venting, and avoidance of excessive pressurization of implants should be taken to reduce the likelihood and consequences of BCIS. Because of the increased risk of periprosthetic fractures in uncemented hip stems, factors associated with the development of BCIS should be weighed against the risk factors for sustaining periprosthetic fractures (poor bone quality, female sex) to balance the risks of fixation method against those of BCIS for each patient.Level of EvidenceLevel III, therapeutic study.     

Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility

BACKGROUND: Adding clomiphene citrate (CC) to FSH for controlled ovarian stimulation (COS) decreases FSH dose required for optimum stimulation. However, because of its anti-estrogenic effects, CC may be associated with lower pregnancy rates offsetting the FSH-dose reduction benefit. Previously, we reported the success of aromatase inhibition in inducing ovulation without antiestrogenic effects. METHODS: A prospective pilot study that included women with unexplained infertility undergoing COS and intrauterine insemination. Thirty-six women received the aromatase inhibitor letrozole + FSH, 18 women received CC + FSH and 56 women received FSH only. Each woman received one treatment regimen in one treatment cycle. All patients were given recombinant or highly purified FSH (50-150 IU/day) starting on day 3 to 7 until day of hCG. RESULTS: The FSH dose needed was significantly lower in letrozole + FSH and CC + FSH groups compared with FSH-only without a difference in number of follicles >1.8 cm. Pregnancy rate was 19.1% in the letrozole + FSH group, 10.5% in the CC + FSH group and 18.7% in the FSH-only group. Both pregnancy rate and endometrial thickness were significantly lower in CC + FSH group compared with the other two groups. Estradiol (E2) levels were significantly lower in the letrozole + FSH group compared with the other two groups. CONCLUSIONS: Similar to CC, aromatase inhibition with letrozole reduces FSH dose required for COS without the undesirable antiestrogenic effects sometimes seen with CC.     

An indirect method for the estimation of osteoporotic fractures from injury and fracture profiles

Summary Study objective was to develop a valid epidemiological method for the estimation of osteoporotic fracture risk, using administrative databases and accounting for variable baseline risks of injury. Design is the secondary analysis of inpatient and outpatient utilization data. A baseline injury risk was estimated by the incidence of primary utilization of medical services for soft tissue injuries (ICD-9 diagnostic codes 910–929), and the risk profile was compared after normalization with the overall primary utilization rate for fractures (ICD-9 diagnostic codes 800–829). The setting is a county with approximately 100,000 inhabitants in the former East Germany. Participants were all inhabitants of the county who had a physician contact (inpatient or outpatient) during 1987–1988, as well as hospital inpatients for all of Germany in 1989. The number of fractures increased with age, especially in women, when compared to the number of fractures expected from the incidence of soft tissue injury. Similar patterns were identified in hospitalization data from East and West Germany. Estimating the prevalence of osteoporosis directly from certain osteoporotic fracture types associated with higher age is potentially biased, since it neglects the underlying risk of injury. Our model distinguished the osteoporotic fracture risk as the excess risk over an expected injury-related fracture risk for a given age and sex, and may allow a more valid quantification of osteoporotic fractures in different populations.

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Zusammenfassung Studienziel war die Entwicklung einer validen Methode zur Abschätzung des osteoporotischen Frakturrisikos unter Verwendung administrativer Daten und unter Berücksichtigung eines variablen Hintergrundrisikos für Unfälle. Studiendesign ist die sekundäre Analyse von Daten zur stationären und ambulanten Inanspruchnahme. Das Hintergrundrisiko für Unfälle wurde aus der Inzidenz der primären Inanspruchnahme der medizinischen Versorgung für Weichteilverletzungen (ICD-9 Kodierungen 910–929) geschätzt, und das Risikoprofil nach Normalisierung mit der allgemeinen primären Inanspruchnahme wegen Frakturen (ICD-9 Kodierungen 800–829) verglichen. Studienort war ein Landkreis mit etwa 100 000 Einwohnern in der ehemaligen DDR. Studienteilnehmer waren alle Einwohner des Kreises, welche 1987–1988 einen ambulanten oder stationären Arztkontakt hatten, sowie Krankenhausfälle in beiden deutschen Staaten im Jahr 1989. Die Anzahl der Knochenbrüche nahm mit dem Lebensalter zu, vor allem bei Frauen, verglichen mit der Anzahl, welche aus der Inzidenz der Weichteilverletzungen zu erwarten gewesen wäre. Ein ähnliches Muster war bei den Krankenhausfällen in Ost- und Westdeutschland zu beobachten. Die direkte Schätzung der Prävalenz der Osteoporose aus bestimmten osteoporotischen Frakturtypen, welche mit dem höheren Lebensalter verbunden sind, enthält potentiell einen systematischen Fehler, da ein Hintergrundrisiko für Unfälle vernachlässigt wird. Unser Modell identifiziert ein osteoporotisches Frakturrisiko als überschiessendes Risiko über ein nach Alter und Geschlecht zu erwartendes unfallbedingtes Frakturrisiko, und erlaubt potentiell eine validere Quantifizierung osteoporotischer Frakturen in verschiedenen Populationen.

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Résumé L'objective de la recherche était le développement d'une méthode valide pour l'estimation du risque d'une fracture ostéoporotique, utilisant données administratives et tenant compte des risques basales variables concernant les accidents. Le désigne de l'étude est l'analyse secondaire des données hospitalières et ambulatoires. Le risque basale des accidents fut estimé par l'incidence de l'utilisation première des services médicaux pour des blessures non-skeletals (ICD-9 codes 910–929) et cette risque fut comparé après normalisation avec la rate d'utilisation pour des fractures (ICD-9 codes 800–829). La recherche se concentrait sur un département de l'Allemagne de l'Est avec a peu près 100000 habitants. Les participants étaient tous les habitants du département qui avaient un contact avec un médecin (a l'hôpital ou ambulatoire) pendant les années 1987–1988, ainsi que tous les cas hospitalisés dans toute l'Allemagne en 1989. Le nombre de fractures augmentait avec l'âge, en particulier parmi les femmes, comparé avec le nombre attendu de l'incidence des blessures. Des profils de risque pareils ont pu être observés parmi les cas hospitalisés de l'Allemagne de l'Ouest et de l'Est. L'estimation directe de la prévalence de l'ostéoporose a la base de certains types «ostéoporotiques» des fractures, associés avec le troisième âge, peut être incorrecte, parce qu'il néglige le risque basale pour les accidents. Notre modèle distingue le risque ostéoporotique de fracture comme un risque plus haut que le risque de l'accident attendu pour un certain âge et gendre, et permet une quantification plus valide des fractures ostéoporotiques parmi des populations différentes.