Lumbar Puncture Ordering and Results in the Pediatric Population: A Promising Data Source for Surveillance Systems

Background: The Centers for Disease Control and Prevention is incorporating laboratory data into real-time surveillance systems. When normal patterns of laboratory test orders and results are modeled, aberrations can be detected. Because many test orders are available electronically well before results, atypical patterns of test ordering may signal outbreaks.
Objectives: The authors sought to characterize baseline patterns in the ordering and early results of lumbar punctures, motivated by the possibility of using these data for real-time surveillance for early detection of meningitis or encephalitis outbreaks.
Methods: Retrospective cohorts of pediatric emergency department patients at a single hospital (1993–2003) and from the National Hospital and Ambulatory Medical Care Survey (1992–2000) were used for analysis.
Results: Test ordering exhibits seasonal patterns, with monthly peaks in January and August (p < 0.0001). For the hospital cohort, the rate of cerebrospinal fluid pleocytosis exhibits seasonal patterns (p < 0.0001), with a peak from August to October. This is strongly associated with the rate and pattern of clinical neurologic disease (p < 0.0001). A long-term secular decline in daily test ordering is evident, dropping from 5.3 to 2.9 in the hospital sample, and from 371.8 to 185.3 in the national sample (p < 0.001). The long-term rate of pleocytosis has declined (p < 0.0001), though the yield of testing for pleocytosis has improved (p = 0.0104).
Conclusions: Laboratory test patterns correspond with those of clinical disease and are a promising source of surveillance data. Using such data for real-time monitoring requires specific adjustments for patient age, periodicities, and secular trends.     

Applying the neoadjuvant paradigm to ductal carcinoma in situ

Local treatment options for ductal carcinoma in situ (DCIS) are virtually identical to those for early invasive breast cancer, despite the fact that the survival from this condition is much higher. Our ability to more appropriately tailor therapy for DCIS is hampered by a lack of understanding of the natural history of DCIS, our limited ability to predict the rate of progression to invasive cancer and the response to therapy, and the absence of tools to follow patients who have not had invasive treatments. Neoadjuvant therapy, which has been proven to be both safe and effective in tailoring treatments for invasive cancer, could be ideally suited to DCIS. However, neoadjuvant therapy requires that doctors and patients delay surgical treatment that has known benefits. In order to successfully introduce this approach into clinical practice, risk assessment and decision support tools will be needed to help physicians and patients feel comfortable that they are not being exposed to unnecessary or excessive risk. In addition, we need better imaging to track extent and progression of disease. Among the possible benefits of the neoadjuvant approach, we may discover that many lesions are responsive and some even reversible, leaving us with treatments that might be tailored to biology and with important clues for breast cancer prevention in high-risk women.     

Prevalence of knee abnormalities in patients with osteoarthritis and anterior cruciate ligament injury identified with peripheral magnetic resonance imaging: a pilot study.

OBJECTIVES: 1) To assess, with a peripheral magnetic resonance imaging system (pMRI), the prevalence of bony and soft tissue abnormalities in the knee joints of normal subjects, osteoarthritis (OA) patients, and individuals who have suffered an anterior cruciate ligament (ACL) rupture; and 2) to compare the prevalence among groups. METHODS: Magnetic resonance (MR) images of 28 healthy, 32 OA, and 26 ACL damaged knees were acquired with a 1.0-T pMRI system. Two radiologists graded the presence and severity of 9 MR image features: cartilage degeneration, osteophytes, subchondral cyst, bone marrow edema, meniscal abnormality, ligament integrity, loose bodies, popliteal cysts, and joint effusion. RESULTS: Ten of 28 healthy (35.7%), 24 of 26 ACL (92.3%), and all OA knees (100%) showed prevalent cartilage defects; 5 healthy (17.9%), 20 ACL (76.9%), and all OA knees (100%) had osteophytes; and 9 normal (32.1%), 21 ACL (80.8%), and 29 OA knees (90.6%) had meniscal abnormalities. One-half of the knees in the OA group (16 of 32, 50%) had subchondral cysts, and almost one-half had bone marrow edema (15 of 32, 46.9%). These features were not common in the ACL group (7.7%, and 11.5%, respectively) and were not observed in healthy knees. The OA group had the most severe cartilage defects, osteophytes, bone marrow edema, subchondral cysts, and meniscal abnormalities; the ACL group showed more severe cartilage defects, osteophytes, and meniscal abnormalities than did normal subjects. CONCLUSION: The results suggest that knees that have sustained ACL damage have OA-like reatures; most subjects (19 of 26, 73.1%) could be identified as in the early stage of OA. The prominent abnormalities present in ACL-damaged knees are cartilage defects, osteophytes, and meniscal abnormalities.     

Rapid Progression of Native Renal Artery Fibromuscular Dysplasia Following Kidney Donation

Fibromuscular dysplasia is the second commonest anatomical abnormality apart from multiple renal arteries in the potential live donors. Pretransplant evaluation of the donors may include an angiography to evaluate the renal arteries, and failure to recognize renal arterial stenosis, particularly fibromuscular dysplasia, by noninvasive methods may eventually lead to hypertension and ischemic renal failure. We report a case of fibromuscular dysplasia that was undetected by computed tomographic angiography prior to donation. One year after kidney donation, it rapidly progressed to severe symptomatic stenosis with hypertension and acute renal failure. Following renal artery angioplasty, her blood pressure normalized over a period of 2 weeks without any need for antihypertensive medications and the serum creatinine returned to her baseline. The acceptability of renal donors with fibromuscular dysplasia depends on the age, race and the availability of the other suitable donors. Mild fibromuscular dysplasia in a normotensive potential renal donor cannot be considered a benign condition. Such donors need regular follow-up postdonation for timely detection and treatment.     

Factors Affecting Cardiac Catheterization Rates in Elders with Acute Coronary Syndromes

Background: Elder patients with acute coronary syndromes (ACS) are less likely to receive cardiac catheterization. The reasons for this are unclear.
Objectives: To assess whether elder patients who had a documented history of dementia, lived in extended care facilities, or had do not intubate–do not resuscitate (DNR-DNI) advance directives were less likely to receive cardiac catheterization, despite having ACS with high-risk features.
Methods: This was a medical record review conducted at an urban teaching hospital. DNR-DNI status before hospitalization, extended care facility (nursing home or assisted living) residence, and a previous diagnosis of dementia were obtained from the medical record. Patients 65 years and older who presented to the emergency department with acute myocardial infarction or with unstable angina with ST segment deviation were included. Univariate and multivariate logistic regression were performed, and odds ratios (ORs) were reported with their 95% confidence intervals (CIs).
Results: Of the 201 eligible patients, 66 (32.8%) patients did not undergo cardiac catheterization. In the univariate analysis, patients who had dementia, resided in extended care facilities, or were DNR-DNI were less likely to receive cardiac catheterization. Only extended care facility residence (OR, 0.18; 95% CI = 0.04 to 0.83) and DNR-DNI status (OR, 0.19; 95% CI = 0.04 to 0.92) remained significantly associated with decreased cardiac catheterization in the multivariate analysis.
Conclusions: Elder patients with ACS residing in extended care facilities or who are DNR-DNI are less likely to receive cardiac catheterization. Future studies concerning the quality of ACS care for elders should take these variables into account.     

Effects of trichostatins on differentiation of murine erythroleukemia cells

The fungistatic antibiotics trichostatins (TS) A and C were isolated from culture broth of Streptomyces platensis No. 145 and were found to be potent inducers of differentiation in murine erythroleukemia (Friend and RV133) cells at concentrations of 1.5 X 10(-8) M for TSA and 5 X 10(-7) M for TSC. Differentiation induced by TS was cooperatively enhanced by UV irradiation but not by treatment with dimethyl sulfoxide. This enhanced activity was completely inhibited by adding cycloheximide to the culture medium 2 h after exposure to TS, suggesting that TS are dimethyl sulfoxide-type inducers of erythroid differentiation. No inhibitory effect of TS was observed on macromolecular synthesis in cultured cells.     

Probable pre- and postsynaptic modifications by 5-hydroxytryptamine of contractile responses to electrical stimulation of isolated guinea-pig vas deferens

Two kinds of electrical stimulation, low frequency stimulation (5 Hz, 1 msec, 5 pulses, every 20 sec) and high frequency stimulation (30 Hz, 0.05-0.1 msec, 10 pulses, every 20 sec), produced contractions in the isolated guinea-pig vas deferens. These responses were blocked by tetrodotoxin but not hexamethonium. Phentolamine potentiated the contractions produced by low frequency stimulation, while it reduced the contractions produced by high frequency stimulation. Diametrically, 5-hydroxytryptamine reduced the contractions produced by low frequency stimulation, while it potentiated the contractions produced by high frequency stimulation. These inhibitory and potentiating actions of 5-hydroxytryptamine were reversed by cyproheptadine and 2-bromolysergic acid diethylamide. Moreover, that 5-hydroxytryptamine produced a depolarization of the smooth muscle membrane was shown by the sucrose gap technique. The results suggest that a 5-hydroxytryptamine receptor exists pre- and postsynaptically in the neuroeffector transmission of the guinea-pig vas deferens, that the stimulation of the presynaptic receptor by 5-hydroxytryptamine inhibits the release of a transmitter from noradrenergic nerves, and that the stimulation of the postsynaptic receptor by a high concentration of 5-hydroxytryptamine produces a depolarization of the smooth muscle membrane, and this relates to the potentiation of contractile responses.     

Cytosolic aldehyde dehydrogenase (ALDH1) variants found in alcohol flushers

Although mitochondrial aldehyde dehydrogenase (ALDH2) has been thought to play a major role in acetaldehyde detoxification, and the high incidence of 'alcohol flushing' among Orientals is attributed to the inherited deficiency of ALDH2, the role of cytosolic aldehyde dehydrogenase (ALDH1) cannot be ignored. On the premise that alcohol flushing in Caucasians could be related to ALDH1 abnormalities, we examined the enzyme properties and electrophoretic mobilities of ALDH1 partially purified from red blood cells of nine unrelated alcohol flushers. One exhibited very low activity (10–20% of control level), and another exhibited moderately low activity (60%) and altered kinetic properties. The electrophoretic mobilities of these two samples were also distinguishable from the control samples. Immunological quantitation indicated that the amounts of ALDH1 protein in these two samples were not reduced in parallel with their enzyme deficiency. In the first case, the two characteristics, i.e. very low enzyme activity and alcohol flushing, were inherited by her daughter.