The occurrence of obstructive vs absorptive hydrocephalus in newborns and infants: relevance to treatment choices

Background and objective The classification of hydrocephalus in newborns and in infants is different from the classification in adulthood. This difference exists due to disparity in the source pathologies that produce the hydrocephalus, and the practical distinctions in prognosis and treatment choices. The objective of this paper is to present the spectrum of obstructive-communicating hydrocephalus, which is more complex in the pediatric group, and to propose the relevance of this particular classification to treatment options. Materials and methods The authors categorized infants with active hydrocephalus at time of presentation into the following four groups along the spectrum of communicating vs obstructive HCP. Group 1: patients with a purely absorptive (communicating) HCP. In these patients, tetraventricular dilatation is usually observed with occasional extraaxial fluid accumulation. An extracranial CSF diversion (shunt) is the treatment of choice. Group 2: patients with an obstructive component together with a persistent absorptive component. In these patients, a technically successful endoscopic procedure will not prevent progression of clinical symptoms of HCP. An extracranial CSF diversion (shunt) should be the treatment of choice even though some of these patients are currently treated by endoscopy. Group 3: patients with an obstructive component together with a temporary absorptive component. In these patients, a technically successful ETV should be followed by temporary CSF drainage [via LP, continuous spinal drainage (CLD), or ventriculostomy] with or without supplemental medical treatment (i.e., Diamox) for several days. Such temporary drainage may decrease failure rate in this subgroup. Group 4: patients with a purely obstructive HCP. In these patients, an endoscopic procedure (ETV) is the treatment of choice. According to this spectrum classification, the authors classify different entities with representative cases and discuss relevancy to treatment options and prognosis. Results The data suggest that obstructive hydrocephalus in the very young population may be rather a combination of obstructive and absorptive problem. The outcome of the patient depends mainly not only on the basic pathology causing the hydrocephalus but also on the treatment that is chosen and its complications. While bleeding and infection represent the major causes for communicating hydrocephalus, patients with complex pathologies of congenital type and intra- or interventricular obstructions may reflect obstructive hydrocephalus. Treatment of these patients may be successful by shuntless procedures if the absorptive problem is not the major component. In transient absorptive hydrocephalus, temporary measures were effective in many cases leading to successful procedures of ETV and/or posterior-fossa decompression in selected cases. Conclusions Shuntless procedures are the dream of a pediatric neurosurgeon provided it solves the problem and does not imply unacceptable risk. However, the benefit has to be evaluated years after the procedure is performed, as only prospective multicenter studies will truly show which procedure may have the best overall results in the developing child. Until such studies are available, understanding the basic pathology or the combination of pathologies leading to hydrocephalus in a given child may open the window of opportunities for other than shunt surgery in many hydrocephalic children with major obstructive component.     

Utility of Major Leukocyte Subpopulations for Monitoring Secondary Cytomegalovirus Infections in Renal-Allograft Recipients by PCR

The feasibility of the major peripheral blood leukocyte (PBL) subsets for use in qualitative and quantitative PCR to monitor secondary cytomegalovirus (CMV) infection and ganciclovir therapy was assessed with 188 blood samples derived from 40 CMV immunoglobulin G-positive renal-allograft recipients. In pp65 antigen-positive patients all leukocyte fractions, but only 79.5% of plasma preparations, were PCR positive. In pp65 antigen-negative samples from patients after antiviral treatment only 7.3% of polymorphonuclear cell (PMNL) samples, but 81.8% of peripheral blood mononuclear cells (PBMC), and 10.9% of plasma samples remained PCR positive. Similarly, in patients with latent infections only 5.0% of PMNL, but 51.7% of PBMC preparations, and 8.0% of plasma samples were PCR positive. Regarding patients with active CMV infection, CMV DNA copy numbers in PMNL correlated significantly with pp65 antigen-positive cell counts before and after onset of ganciclovir therapy. Significant differences in CMV DNA copy numbers in PMNL and plasma were observed (i) between patients with symptomatic infection and those with asymptomatic infection and (ii) between patients with active infection and those with latent infection. In contrast, PBMC harbored equally low CMV DNA levels both in patients with active infection and those with latent infections, and no decline of CMV DNA load in PBMC was observed during antiviral treatment. We conclude that detection of CMV DNA in PMNL, not in PBMC, is associated with active infections and is more sensitive than detection of CMV DNA in plasma. Negative PCR results for PMNL after antiviral therapy indicate recovery, and fewer unwanted positive results occur compared to PBMC and plasma. Therefore, purified PMNL should be preferred for analysis by qualitative CMV PCR to avoid unwanted positive results. The CMV DNA load in PBMC compared with that in PMNL is negligible during active infection, so mixed PBL are sufficient for use in quantitative PCR.     

Clinical implications of positive tests for antibodies to human immunodeficiency virus type 1 in asymptomatic blood donors

Of 693,000 volunteer blood donors in Washington, D.C., who were screened for infection with human immunodeficiency virus type 1 (HIV-1) from July 1985 through December 1988, 284 tested positive on both enzyme immunoassay and Western blot assay. To determine the clinical importance of confirmed positive test results in asymptomatic blood donors, we followed 156 donors with positive Western blot assays and 80 donors with positive enzyme immunoassays but negative or indeterminate Western blots at 6-month intervals for a mean of 28 months. As compared with Western blot-negative persons, those with positive Western blots were significantly more likely to be black, male, and first-time donors and to have a history of venereal disease, generalized lymphadenopathy on examination, CD4-cell counts lower than 0.4 x 10(9) per liter, IgG levels higher than 18 g per liter, and antibody to hepatitis B core antigen on initial evaluation. In 17 (11 percent) of the Western blot-positive donors, the disease progressed to Class IV (symptomatic disease), according to the Centers for Disease Control system. CD4 counts below 0.2 x 10(9) per liter, IgA levels above 4 g per liter, abnormal proliferative responses to tetanus toxoid, and positive viral cultures were the strongest predictors of disease progression. Among the 80 donors with repeatedly reactive assay results but either negative or indeterminate Western blot assays, there was no evidence of HIV exposure in their histories, physical examinations, or laboratory evaluations, and manifestations of HIV infection developed in none of them. We conclude that a small number of persons with HIV infection continue to donate blood, despite attempts to exclude them, but that donors who test positive on enzyme immunoassay but persistently negative or indeterminate on Western blot assay probably do not represent a risk for the transmission of HIV.     

Developmental expression of FOG-1/CPEB protein and its control in the Caenorhabditis elegans hermaphrodite germ line.

The specification of a germ cell as sperm or oocyte and determination of cell number remain unsolved questions in developmental biology. This paper examines Caenorhabditis elegans FOG-1, a CPEB-related RNA-binding protein that controls the sperm fate. We find that abundant FOG-1 protein is observed transiently in germ cells just prior to their expression of an early sperm-differentiation marker. As the germline tissue elongates, abundant FOG-1 appears more and more distally as sperm become specified, but disappears when the germ line switches to oogenesis. This dynamic pattern is controlled by both globally acting and germline-specific sex-determining regulators. Importantly, the extent of FOG-1 expression corresponds roughly to sperm number in wild-type and mutants, altering sperm number. By contrast, three other key regulators of the sperm/oocyte decision do not similarly correspond to sperm number. We suggest that FOG-1 is precisely modulated in both time and space to specify sperm fate and control sperm number.     

An association study of the cholesteryl ester transfer protein TaqI B polymorphism with late onset Alzheimer's disease

Cholesteryl ester transfer protein (CETP) is reportedly able to affect the amount of cholesterol available for deposition and/or removal from peripheral tissues, in its capacity to mediate the transfer of cholesterol from high density lipoprotein (HDL) to very low density lipoprotein, in exchange for triacylglycerols from the latter. The TaqI B polymorphism of the human CETP gene has been associated with decreased CETP mass and an increase in HDL-cholesterol. While many studies have addressed the atherogenic or anti-atherogenic potential of this polymorphism, little is known about its effect on neurodegeneration, despite the fact that CETP is expressed in the brain and the disturbance of cholesterol homeostasis appears to be an important factor in the pathogenesis of Alzheimer's disease (AD). In this report, we have compared the distribution of the TaqI B polymorphism in an independent population of 102 clinically diagnosed late onset AD patients and a spousal control group of 97 individuals. We have also examined the possible interaction between this polymorphism and two other polymorphisms suspected of affecting cholesterol flux, namely apolipoprotein E APOE epsilon4, and lipoprotein lipase LPLS447X. No statistically significant differences have emerged with respect to either genotype or allele frequencies between the AD and control populations. CETP TaqI B did not interact significantly with either APOE epsilon4 or LPLS447X, in this study.     

Assessment of MUSASHI 1 and MUSASHI 2 expression in spermatozoa and testicular tissue

MUSASHI (MSI) family plays the main role in the spermatogenesis process. The purpose of this study was the assessment of sperm MSI1 and MSI2, and sperm functional tests in infertile men (n = 30) with varicocele and fertile men (n = 30). Furthermore, MSI1 and MSI2 proteins were assessed in testicular tissue of azoospermic men (n = 9) as well as epididymal spermatozoa and testis of mice. Expression of MSI1 and MSI2 was assessed at RNA and protein levels in human spermatozoa. Sperm concentration and motility were significantly lower, while abnormal sperm morphology, lipid peroxidation, DNA fragmentation and protamine deficiency were significantly higher in men with varicocele compared to fertile individuals. Any significant difference was not observed in the expression of MSI1 and MSI2 mRNA between the two groups. Unlike MSI1 protein that was not detectable in humans, the relative expression of MSI2 protein was similar in varicocele and fertile individuals. The expression level of both Msi1 and Msi2 proteins was also observable in mouse spermatozoa. No significant relationship was observed between sperm functional parameters with expression of these genes. The data of this study demonstrated that although MSI1 and MSI2 play important roles during spermatogenesis, their relative expression in spermatozoa was not affected by varicocele.     

Frailty,Race/Ethnicity,Functional Status,and Adverse Outcomes After Total Hip/Knee Arthroplasty: A Moderation Analysis

BackgroundAlthough frailty has been shown to be associated with adverse outcomes in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), prior studies have not examined how race/ethnicity might moderate these associations. We aimed to assess race/ethnicity as a potential moderator of the associations of frailty and functional status with arthroplasty outcomes.MethodsThe National Surgical Quality Improvement Program was queried for patients who underwent THA or TKA from 2011 to 2017. Frailty was assessed using the modified frailty index. Regression analyses were conducted to examine associations connecting frailty/functional status with 30-day readmission, adverse discharge, and length of stay (LOS). Further analyses were conducted to investigate race/ethnicity as a potential moderator of these relationships.ResultsWe identified 219,143 TKA and 130,022 THA patients. Frailty and nonindependent functional status were positively associated with all outcomes (P < .001). Compared to White non-Hispanic patients, Black non-Hispanic patients had higher odds for all outcomes after TKA (P < .001) and for adverse discharge/longer LOS after THA (P < .001). Similar associations were observed for Hispanics for the adverse discharge/LOS outcomes. Race/ethnicity moderated the effects of frailty in TKA for all outcomes and in THA for adverse discharge/LOS. Race/ethnicity moderated the effects of nonindependent function in TKA for adverse discharge/LOS and on LOS alone for THA.ConclusionDisparities for Black non-Hispanic and Hispanic patients persist for readmission, adverse discharge, and LOS. However, the effects of increasing frailty and nonindependent functional status on these outcomes were the most pronounced among White non-Hispanic patients.     

An exploration of relative health stock in advanced cancer patients.

OBJECTIVE: The authors sought to empirically test whether relative health stock, a measure of patients' sense of loss in their health due to illness, influences the treatment decisions of patients facing life-threatening conditions. Specifically, they estimated the effect of relative health stock on advanced cancer patients' decisions to participate in phase I clinical trials. METHOD: A multicenter study was conducted to survey 328 advanced cancer patients who were offered the opportunity to participate in phase I trials. The authors asked patients to estimate the probabilities of therapeutic benefits and toxicity, their relative health stock, risk preference, and the importance of quality of life. RESULTS: Controlling for health-related quality of life, an increase in relative health stock by 10 percentage points reduced the odds of choosing to participate in a phase I trial by 16% (odds ratio = 0.84, 95% confidence interval = 0.72, 0.97). CONCLUSION: Relative health stock affects advanced cancer patients' treatment decisions.