Objective: The objective was to describe a novel ultrasound-assisted lumbar puncture (UALP) technique and to compare it to standard lumbar puncture (SLP) technique in infants.Methods: A prospective, randomized, controlled study in infants 60 days old and younger undergoing a lumbar puncture (LP) in a pediatric emergency department. Patients with a spinal anomaly or ventriculoperitoneal shunt were excluded. Eligible infants were randomized to UALP or SLP. A spinal sonogram was performed on all patients by an investigator not involved in performing the LP. Spinal landmarks and maximum safe depth were identified for the UALP providers. Providers in the SLP group were blinded to sonographic measurements. A successful LP was defined as the collection of cerebrospinal fluid (CSF) with a red blood cell count of less than 10,000 cells/mm 3 . Statistical analysis included chi-square, Mann-Whitney U-test, and number needed to treat (NNT).Results: Forty-three patients were enrolled, 21 in the UALP group and 22 in the SLP group. Prematurity, weight, length, provider experience, anesthesia use, stylet technique, and number of attempts were similar between groups. The median age in the UALP group was 38 days (interquartile range [IQR] = 33 days) versus 45 days (IQR = 19 days) in the SLP group (p = 0.02). CSF was obtained in all UALP subjects (100%) versus in 18 of 22 (82%) in the SLP group (p = 0.04); 20 (95%) UALP subjects versus 15 (68%) SLP subjects met our definition of success (p = 0.023). The odds ratio of successful LP using UALP technique was 9.33 (95% confidence interval [CI] = 1.034 to 84.026) and the NNT was 3.7 (95% CI = 2.02 to 24.18).
Conclusion:The UALP technique increases the rate of a successful LP in infants compared to standard technique.
Background: We investigated the combination of docetaxel
and cisplatin as first-line chemotherapy in patients
with metastatic esophageal cancer. Patients and
Methods: 16 chemotherapy-naïve patients with distant
metastases were included in the study (15 male, 1 female;
median age: 58.5 years (range 37-69); median
ECOG performance status: 1). 11 patients (69%) had
esophageal cancer, and 5 patients (31%) had cancer of
the gastroesophageal junction. Patients received docetaxel
75 mg/m2 and cisplatin 80 mg/m2 on day 1 every
3 weeks. A total of 55 chemotherapy cycles was administered.
The median number of cycles was 3 (range 1-6).
Results: The overall response rate was 31.3%. 4 out of
10 patients (40%) with squamous cell carcinoma and
1 out of 5 patients (20%) with adenocarcinoma responded
to chemotherapy. The median overall survival was
29.6 weeks, and the median progression-free survival
was 18.6 weeks. Hematological and non-hematological
toxicities were moderate (neutropenia WHO grade III/IV:
42.9%, alopecia grade II/III: 64.3%, nausea/vomiting
grade II/III: 57.2%, neurotoxicity grade II: 14.3%). Conclusion:
The combination of docetaxel and cisplatin is an
active regimen with moderate toxicity in the treatment
of patients with metastatic esophageal cancer. This pilot
study demonstrates the feasibility of a combination
treatment containing a taxane and cisplatin in metastatic
esophageal cancer.
In previous studies, we have shown that cerebral hypoxia results in increased activity of caspase-9, the initiator caspase, and caspase-3, in the cytosolic fraction of the cerebral cortex of newborn piglets. The present study examines the mechanism of caspase-9 activation during hypoxia and tests the hypothesis that the ATP and cytochrome c-dependent activation of caspase-9 increases in the cytosol of the cerebral cortex of newborn piglets. Newborn piglets were divided into normoxic (Nx, n=4), and hypoxic (Hx, n=4) groups. Anesthetized, ventilated animals were exposed to an FiO 2 of 0.21 (Nx) or 0.07 (Hx) for 60 min. Cerebral tissue hypoxia was documented biochemically by determining levels of ATP and phosphocreatine (PCr). Cytosolic fraction was isolated and passed through a G25-Sephadex column to remove endogenous ATP and cytochrome c. Fractions were collected and protein determined by UV spectrophotometry at 280 nm. Eluted high molecular weight samples from normoxic and hypoxic animals were divided into four subgroups: Subgroup 1 (control), incubated without added ATP and cytochrome c; Subgroup 2, incubated with added ATP; Subgroup 3, incubated with added cytochrome c; and Subgroup 4, incubated with added ATP and cytochrome c. The incubation was carried out at 37° C for 30 min. Following incubation, the protein was separated by 12% SDS PAGE and active caspase-9 was detected using specific active caspase-9 antibody. Protein bands were detected by enhanced chemilumenescence. Protein density was determined by imaging densitometry and expressed as absorbance (OD × mm 2 ). ATP (μmoles/g brain) level was 4.7±0.18 in normoxic, as compared to 1.53±0.16 in hypoxic (p<0.05 vs Nx). PCr (μmoles/g brain) level was 4.03±0.11 in the normoxic and 1.1±0.3 in the hypoxic brain (p<0.05 vs Nx). In the normoxic preparations, active caspase-9 density increased by 9%, 4% and 20% in the presence of ATP, cytochrome c and ATP + cytochrome c, respectively. In the hypoxic preparations, active caspase-9 density increased by 30%, 45% and 60% in the presence of ATP, cytochrome c, and ATP + cytochrome c, respectively. These results show that incubation with ATP, cytochrome c and ATP +cytochrome c result in a significantly increased activation of caspase-9 in the hypoxic group (p<0.05). We conclude that the ATP and cytochrome c dependent activation of caspase-9 is increased during hypoxia. We propose that the ATP and cytochrome c sites of apoptotic protease activating factor I that mediate caspase-9 activation are modified during hypoxia.
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