Tissue plasminogen activator using a rapid-infusion low-dose regimen for unstable angina.

The clinical effect of a low-dose rapid-infusion intravenous regimen was assessed using human recombinant tissue-type plasminogen activator (rt-PA) in unstable angina. Fifty patients with unstable angina pectoris were randomly assigned to blinded treatment with either placebo (24 patients) or low-dose (20 mg bolus, 30 mg infusion over 1 hour) intravenous rt-PA (26 patients). Before randomization, all patients were treated with aspirin, twice-daily subcutaneous heparin, and maximally tolerated antianginal therapy. Of the 50 patients assigned, 26 received rt-PA and the outcome was successful in 15 (58%) (angina settled, no myocardial infarction or urgent intervention) compared with 9 (38%) successful outcomes in the 24 who received placebo (0.5 greater than p greater than 0.1). Angina remained refractory in 8 (31%) of the rt-PA group and in 13 (54%) of the placebo group (0.1 greater than p greater than 0.05). Urgent interventions were required in 6 patients (23%) who received rt-PA and in 11 patients (46%) who received placebo. Three patients in each group sustained a myocardial infarction within 72 hours of entering the trial and there were 3 deaths (1 in the active treatment group, 2 in placebo group) within 2 weeks of the trial (p = not significant). Administration of intravenous rt-PA was not associated with any complications. Low-dose rt-PA administration in patients with unstable angina was associated with a tendency to stabilization of anginal symptoms and a reduction in the need for urgent intervention. However, these trends did not achieve statistical significance.     

Negative polysomnogram in patients with obstructive sleep apnea syndrome.

We evaluated the possibility that in some patients with obstructive sleep apnea, the initial polysomnogram may be negative. We reviewed polysomnograms performed at the Medical College of Georgia from 1984 to 1990 and found nine patients whose initial polysomnogram was negative but whose repeat polysomnogram confirmed obstructive sleep apnea. All nine patients (five women and four men; average age, 44.2 years) had an apnea index of less than 5 (fewer than five apneic episodes per hour) and had a total of fewer than 20 apneic episodes during the initial overnight polysomnogram. The change in average weight was not significant. Three patients had received short-term oxygen therapy, and two of these three received nasal continuous positive airway pressure prior to the initial study. The time that patients spent supine increased from 101 min in the initial study to 180 min in the second, but this was not significant (p = 0.12). Comparison of the initial and diagnostic polysomnograms showed significantly reduced total sleep time (from 3.75 +/- 1.84 h to 5.32 +/- 1.11 h; p = 0.04) and reduced rapid eye movement (REM) sleep time (from 0.27 +/- 0.27 h to 0.75 +/- 0.58 h; p = 0.037) in the initial study. We conclude that in a small subset of patients with obstructive sleep apnea, the initial polysomnogram may be falsely negative, which could be due to previous therapy, a reduction in total sleep time and REM sleep, or other unidentified factors.     

Global warming is causing a more pronounced dip in marine species richness around the equator

The latitudinal gradient in species richness, with more species in the tropics and richness declining with latitude, is widely known and has been assumed to be stable over recent centuries. We analyzed data on 48,661 marine animal species since 1955, accounting for sampling variation, to assess whether the global latitudinal gradient in species richness is being impacted by climate change. We confirm recent studies that show a slight dip in species richness at the equator. Moreover, richness across latitudinal bands was sensitive to temperature, reaching a plateau or declining above a mean annual sea surface temperature of 20 °C for most taxa. In response, since the 1970s, species richness has declined at the equator relative to an increase at midlatitudes and has shifted north in the northern hemisphere, particularly among pelagic species. This pattern is consistent with the hypothesis that climate change is impacting the latitudinal gradient in marine biodiversity at a global scale. The intensification of the dip in species richness at the equator, especially for pelagic species, suggests that it is already too warm there for some species to survive.

The latitudinal gradient in species richness is a striking biogeographic pattern in both terrestrial and marine realms that is likely to reflect evolutionary history and current environmental conditions (1–4). It is strongly correlated with temperature (5–8) (SI Appendix, Table S1) and may thus serve as a natural laboratory to study the impact of climate change (9). A unimodal latitudinal gradient in species richness peaking at the equator had been assumed to be the general pattern for most taxa (10–15). However, the majority of global studies have been limited to a specific taxonomic group, and multitaxon studies have been regional, making generalizations difficult. Recently, in a review of 27 studies and a dataset of 65,000 species, Chaudhary et al. (10, 16) suggested that the distribution of marine diversity was bimodal, with a dip at the equator, and that all marine taxa followed this pattern, with the possible exception of planktonic radiolarians (17), which are found deeper in tropical waters (the so-called “tropical submergence”) (18). Species distribution models forced by Earth system models predict that the leading (cool) edge of species’ distributions will move away from the equator in the future (19), which could further depress equatorial richness relative to midlatitudes. This begs the question: Is climate change already altering the global latitudinal gradient in species richness? Here, we analyze the latitudinal pattern in species richness for a suite of taxonomic groups based on 48,661 marine species to assess whether there was a consistent dip in species richness at the equator and what role ocean warming might play as a driver of changing latitudinal distribution of marine biodiversity.     

Ceftazidime versus ceftazidime plus tobramycin in febrile neutropenic children

Summary Although the effectiveness of antibiotic monotherapy in febrile neutropenic patients remains unproven, ceftazidime has been shown previously to be effective monotherapy for the empiric treatment of selective patients. The efficacy and safety of ceftazidime versus ceftazidime plus tobramycin was evaluated in the treatment of febrile children (range 8 months to 18 years) with neutropenia secondary to cancer chemotherapeutic agents. Of the evaluable 89 patients, 45 received ceftazidime and 44 received ceftazidime plus tobramycin for 5 to 10 days. At the end of therapy, 30 (67%) of the 45 ceftazidime-treated patients were clinically cured compared with 38 (86%) of 44 combination-treated patients. Thirteen (29%) of the patients treated with ceftazidime failed to respond clinically to treatment, versus four (9%) of the patients treated with ceftazidime/tobramycin (p=0.046). This study suggests that ceftazidime as monotherapy in febrile neutropenic children may be inferior to combination therapy for optimal clinical response in these patients.

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Ceftazidim im Vergleich zu Ceftazidim plus Tobramycin bei neutropenischen Kindern mit Fieber

Zusammenfassung Ceftazidim hat sich in Monotherapie bei ausgewählten Patienten in der empirischen Behandlung von febriler Neutropenie als wirksam erwiesen, dennoch muß die Effizienz einer Antibiotika-Monotherapie bei neutropenischen Patienten mit Fieber nach wie vor als unbewiesen angesehen werden. Bei neutropenischen Kindern im Alter von 8 Monaten bis 18 Jahren, die eine Krebs-Chemotherapie durchmachten, wurde wegen Fieber eine Behandlung mit Ceftazidim allein oder in Kombination mit Tobramycin durchgeführt. Die Wirksamkeit und Sicherheit dieser beiden Therapieformen wurde verglichen. Von den 89 auswertbaren Patienten erhielten 45 Ceftazidim allein und 44 in Kombination mit Tobramycin. Die Behandlungsdauer lag zwischen 5 und 10 Tagen. Am Ende der Behandlung waren 30 der 45 mit Ceftazidim allein behandelten Patienten (67%) geheilt, in der mit Ceftazidim plus Tobramycin behandelten Gruppe 38 von 44 (86%). 13 der mit Ceftazidim behandelten Patienten (29%) sprachen klinisch nicht auf die Therapie an, in der Ceftazidim/Tobramycin-Gruppe waren 4 Therapieversager (9%) festzustellen (p=0,046). Aus dieser Studie läßt sich ableiten, daß Ceftazidim bei Kindern mit Neutropenie und Fieber in Monotherapie nicht in gleichem Ausmaß optimale Therapieergebnisse erzielen kann wie die Kombination Ceftazidim plus Tobramycin.

     

Association of a genetic risk score with prevalent and incident myocardial infarction in subjects undergoing coronary angiography

Background- Genome-wide association studies have identified multiple variants associating with coronary artery disease (CAD) and myocardial infarction (MI). Whether a combined genetic risk score (GRS) is associated with prevalent and incident MI in high-risk subjects remains to be established. Methods and Results- In subjects undergoing cardiac catheterization (n=2597), we identified cases with a history of MI onset at age <70 years and controls ≥70 years without prior MI and followed them for incident MI and death. Genotyping was performed for 11 established CAD/MI variants, and a GRS was calculated based on average number of risk alleles carried at each locus weighted by effect size. Replication of association findings was sought in an independent angiographic cohort (n=2702). The GRS was significantly associated with prevalent MI, occurring before age 70, compared with older controls (≥70 years of age) with no history of MI (P<0.001). This association was successfully replicated in a second cohort, yielding a pooled P value of <0.001. The GRS modestly improved the area-under-the-curve statistic in models of prevalent MI with traditional risk factors; however, the association was not statistically significant when elderly controls without MI but with s\ angiographic CAD were examined (pooled P=0.11). Finally, during a median 2.5-year follow-up, only a nonsignificant trend was noted between the GRS and incident events, which was also not significant in the replication cohort. Conclusions- A GRS of 11 CAD/MI variants is associated with prevalent MI but not near-term incident adverse events in 2 independent angiographic cohorts. These findings have implications for understanding the clinical use of genetic risk scores for secondary as opposed to primary risk prediction.     

Intratumoral acetic acid injection eradicates human prostate cancer tumors in a murine model

Introduction

To treat localized prostate cancer without substantial morbidity, an ideal treatment would be an effective local therapy with minimal morbidity. Direct injections have been used to treat benign prostatic hyperplasia without major complications, but in limited cases. We evaluated the local oncotoxic effects of acetic acid in a prostate cancer xenograft murine model.

Materials and methods

PC3 and LNCaP human prostate cancer cell lines were used to grow subcutaneous tumors in SCID mice. For each cell line, 14 mice underwent intratumor injection with 25 % acetic acid (0.05 ml/100 cm³ of tumor) after the tumor was >300 mm³. Post-treatment one mouse/group was euthanized after 2 h, 24 h, 1 and 2 weeks; remaining mice (n = 10) were killed at 120 days. Control mice (8/group) were euthanized after they met the humane criteria for tumor burden and overall health.

Results

Tumor necrosis was noted immediately post-injection; by 24 h, ulceration and crusting of overlying skin were noted, which healed into scars by 23 ± 5 days. Histological examination showed tumor degeneration and necrosis with blood vessel obstruction. Ten treated mice in both groups survived for 120 days, which was much longer than the mean survival of PC3 (40 ± 9 days) and LNCaP (56 ± 10) control mice.

Conclusions

Direct injection of acetic acid successfully eradicated both tumors. This treatment option could potentially be used in humans for treatment of early localized prostate cancer and nonoperative management of locally advanced cases. This is the first report of successful local chemical therapy for prostate cancer.