Availability, preference, and consumption of indigenous forest foods in the Eastern Arc Mountains, Tanzania.

We investigated the availability, preference, and consumption of indigenous forest foods in Uluguru North (UNM) and West Usambara Mountains (WUM) of Tanzania. Data collection techniques involved focus group discussion, structured questionnaires, and botanical identification. Results revealed (1) there were 114 indigenous forest food plant species representing 57 families used by communities living adjacent to the two mountains; (2) sixty-seven species supplied edible fruits, nuts and seeds: 24 and 14 species came from WUM and UNM, respectively, while 29 came from both study areas; (3) of the 57 identified vegetable species, 22 were found in WUM only, 13 in UNM only, and 12 in both areas; (4) there were three species of edible mushrooms and five species of roots and tubers; (5) unlike the indigenous roots and tubers, the preference and consumption of indigenous vegetables, nuts, and seeds/oils was higher than exotic species in both study areas; and (6) UNM had more indigenous fruits compared to WUM, although preference and consumption was higher in WUM. We recommend increased research attention on forest foods to quantify their contribution to household food security and ensure their sustainability.

Different tropism of adenoviruses and adeno-associated viruses to corneal cells: implications for corneal gene therapy.

PURPOSE: Diseased corneas are potential targets for viral-based gene therapy to normalize (stimulate or inhibit) the expression of specific proteins. The choice of viral vectors is important to achieve optimal effect. The purpose of this study was to compare the tropism to different corneal cells of recombinant adenovirus (rAV) and recombinant adeno-associated virus (rAAV) constructs using live rabbit and organ-cultured human corneas. METHODS: rAV constructs harbored the green fluorescent protein (GFP) gene under the control of major immediate early cytomegalovirus (CMV) promoter. rAAV constructs from virus serotypes 1, 2 5, 7, and 8 had GFP under the chicken beta-actin promoter and CMV enhancer. For organ culture, 16 healthy and diabetic postmortem human corneas were used. Five or fifteen microl rAV at 10(7) plaque forming units per 1 microl were added for 2 days to culture medium of uninjured corneas that were further cultured for 5-32 days. rAAV were added at 1.2-7.8x10(10) vector genomes per cornea for 3 days to each cornea; the culture then continued for another 14-23 days. Corneal cryostat sections were examined by immunohistochemistry. Live rabbit corneas were used following excimer laser ablation of the corneal epithelium with preservation of the basal cell layer. Equal numbers of rAAV particles (2x10(11) vector genomes) were applied to the cornea for 10 min. After seven days to allow for corneal healing and gene expression the animals were euthanized, the corneas were excised, and sections analyzed by immunohistochemistry. RESULTS: By direct fluorescence microscopy of live organ-cultured human corneas GFP signal after rAV transduction was strong in the epithelium with dose-dependent intensity. On corneal sections, GFP was seen in all epithelial layers and some endothelial cells but most keratocytes were negative. In rAAV-transduced organ-cultured human corneas GFP signal could only be detected with anti-GFP antibody immunohistochemistry. GFP was observed in the epithelium, keratocytes, and endothelium, with more pronounced basal epithelial cell staining with rAAV1 than with other serotypes. No difference in the GFP expression patterns or levels between normal and diabetic corneas was noted. The rabbit corneas showed very similar patterns of GFP distribution to human corneas. With all rAAV serotype vectors, GFP staining in the epithelium was significantly (p=0.007) higher than the background staining in non-transduced corneas, with a trend for rAAV1 and rAAV8 to produce higher staining intensities than for rAAV2, rAAV5 (p=0.03; rAAV5 versus rAAV1), and rAAV7. rAAV serotype vectors also transduced stromal and endothelial cells in rabbit corneas to a different extent. CONCLUSIONS: rAAV appears to reach many more corneal cells than rAV, especially keratocytes, although GFP expression levels were lower compared to rAV. rAV may be more useful than rAAV for gene therapy applications requiring high protein expression levels, but rAAV may be superior for keratocyte targeting.

High tibial closing wedge osteotomy for medial compartment osteoarthrosis of knee.

BACKGROUND: Most patients of symptomatic osteoarthrosis of knee are associated with varus malalignment that is causative or contributory to painful arthrosis. It is rational to correct the malalignment to transfer the functional load to the unaffected or less affected compartment of the knee to relieve symptoms. We report the outcome of a simple technique of high tibial osteotomy in the medial compartment osteoarthrosis of the knee. MATERIALS AND METHODS: Between 1996 and 2004 we performed closing wedge osteotomy in 78 knees in 65 patients. The patients selected for osteotomy were symptomatic essentially due to medial compartment osteoarthrosis associated with moderate genu varum. Of the 19 patients who had bilateral symptomatic disease 11 opted for high tibial osteotomy of their second knee 1-3 years after the first operation. Preoperative grading of osteoarthrosis and postoperative function was assessed using Japanese Orthopaedic Association (JOA) rating scale. RESULTS: At a minimum follow-up of 2 years (range 2-9 years) 6-10 degrees of valgus correction at the site of osteotomy was maintained, there was significant relief of pain while walking, negotiating stairs, squatting and sitting cross-legged. Walking distance in all patients improved by two to four times their preoperative distance of 200-400 m. No patient lost any preoperative knee function. The mean JOA scoring improved from preoperative 54 (40-65) to 77 (55-85) at final follow-up. CONCLUSION: Closing wedge high tibial osteotomy performed by our technique can be undertaken in any setup with moderate facilities. Operation related complications are minimal and avoidable. Kirschner wire fixation is least likely to interfere with replacement surgery if it becomes necessary.

Tuberculosis of the spine: a historical review.

Almost all ancient civilizations described tuberculous bacilli in their old scripts, and these bacteria have been found in prehistoric skeletal remains. The clinical availability of specific antitubercular drugs was the most important breakthrough in managing spinal tuberculosis. Any attempt at surgical excision of the disease prior to the antitubercular era met with serious complications, dissemination of disease and high mortality (nearly 50%). Antitubercular drugs markedly improved the results of management by operative treatment. Excellent healing of disease was also observed in those patients who were treated nonoperatively. However, it took many years (1950-1970) for clinicians to appreciate the efficacy of antitubercular drugs. Operations for spinal tuberculosis are now indicated less for control of disease (5-10% of all cases) than for complications, including nonresponding neural deficit (nearly 40% of neural complications), prevention or correction of severe kyphotic deformity, and for tissue diagnosis (approximately 5% of all cases). For a classic spondylodiscitis when surgery is required for débridement and decompression, an anterior approach through an extrapleural anterolateral route or through transpleural route is recommended. Healthy posterior elements should not be jeopardized by surgery. The real control of tuberculous disease requires a serious and sustained global effort to eliminate immunocompromised states, poverty, malnutrition, and overcrowding.

The use of immunomodulators as an adjunct to antituberculous chemotherapy in non-responsive patients with osteo-articular tuberculosis.

We studied 51 patients with osteo-articular tuberculosis who were divided into two groups. Group I comprised 31 newly-diagnosed patients who were given first-line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol and pyrazinamide. Group II (non-responders) consisted of 20 patients with a history of clinical non-responsiveness to supervised uninterrupted antituberculous treatment for a minimum of three months or a recurrence of a previous lesion which on clinical observation had healed. No patient in either group was HIV-positive. Group II were treated with an immunomodulation regime of intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus vaccines as an adjunct for eight weeks in addition to antituberculous treatment. We gave antituberculous treatment for a total of 12 to 18 months in both groups and they were followed up for a mean of 30.2 months (24 to 49). A series of 20 healthy blood donors served as a control group.Twenty-nine (93.6%) of the 31 patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological healing response to treatment by five months. The CD4 cell count in both groups was depressed at the time of enrolment, with a greater degree of depression in the group-II patients (686 cells/mm(3) (sd 261) and 545 cells/mm(3) (sd 137), respectively; p < 0.05). After treatment for three months both groups showed significant elevation of the CD4 cell count, reaching a level comparable with the control group. However, the mean CD4 cell count of group II (945 cells/mm(3) (sd 343)) still remained lower than that of group I (1071 cells/mm(3) (sd 290)), but the difference was not significant. Our study has shown encouraging results after immunomodulation and antituberculous treatment in non-responsive patients. The pattern of change in the CD4 cell count in response to treatment may be a reliable clinical indicator.

Tibialization of the fibula: a viable option to salvage limbs with extensive scarring and gap nonunions of the tibia.

I retrospectively reviewed 21 patients who had tibialization of the fibula for infected nonunions with scarring of soft tissues. Most of the patients had unsuccessfully had other operations to restore continuity of the tibia before this treatment. The prerequisites were adequate vascularity, an intact sensate sole, and intact fibula. Proximal site tibiofibular synostosis was done in all patients. Three patients required a supplementary procedure at the proximal tibiofibular junction because of screws cutting out. Distal tibiofibular synostosis was done as a second-stage procedure in a majority of the patients 3 to 6 weeks after the proximal procedure. Protected weightbearing was recommended for 4 to 8 months. The transplanted fibula hypertrophied and approached the diameter of the tibia (or double the size of original fibula) in 2-3 years. Tibialization of the fibula is a safe, nondestructive, salvage procedure for treating difficult infected nonunions of the tibia. It is a simple technique that can be done in hospitals with a moderate infrastructure. Despite scarring, shortening, and limitation of knee and ankle motion, the patients were satisfied to be able to take part in normal daily activities on their own. After the success of synostosis, all patients engaged in activities of daily living and during the followup of 4-14 years none developed stress fracture of the tibialized fibula.

High-dose methylprednisolone for acute closed spinal cord injury--only a treatment option.

BACKGROUND: A systematic review of the evidence pertaining to methylprednisolone infusion following acute spinal cord injury was conducted in order to address the persistent confusion about the utility of this treatment. METHODS: A committee of neurosurgical and orthopedic spine specialists, emergency physicians and physiatrists engaged in active clinical practice conducted an electronic database search for articles about acute spinal cord injuries and steroids, from January 1, 1966 to April 2001, that was supplemented by a manual search of reference lists, requests for unpublished additional information, translations of foreign language references and study protocols from the author of a Cochrane systematic review and Pharmacia Inc. The evidence was graded and recommendations were developed by consensus. RESULTS: One hundred and fifty-seven citations that specifically addressed spinal cord injuries and methylprednisolone were retrieved and 64 reviewed. Recommendations were based on one Cochrane systematic review, six Level I clinical studies and seven Level II clinical studies that addressed changes in neurological function and complications following methylprednisolone therapy. CONCLUSIONS: There is insufficient evidence to support the use of high-dose methylprednisolone within eight hours following an acute closed spinal cord injury as a treatment standard or as a guideline for treatment. Methylprednisolone, prescribed as a bolus intravenous infusion of 30 mg per kilogram of body weight over fifteen minutes within eight hours of closed spinal cord injury, followed 45 minutes later by an infusion of 5.4 mg per kilogram of body weight per hour for 23 hours, is only a treatment option for which there is weak clinical evidence (Level I- to II-1). There is insufficient evidence to support extending methylprednisolone infusion beyond 23 hours if chosen as a treatment option.

p38 MAP kinase regulation of AP-2 binding in TGF-beta1-stimulated chondrogenesis of human trabecular bone-derived cells.

Collagenase-treated, explanted human trabecular-bone chips are an excellent source of osteoblast-like cells. We have recently shown the multiple differentiation potential of these cells; in addition to osteogenesis and adipogenesis, these cells also undergo chondrogenesis when maintained as high-density pellet cultures (250,000 cells/pellet) in a serum-free, chemically defined medium stimulated with TGF-beta1 (10 ng/mL). In this investigation, we have analyzed how transactivating nuclear transcription factors, specifically AP-2 and SP-1, may interact with common cis-acting elements found in the regulatory region of cartilage-specific genes as part of the signal transduction mechanism of TGF-beta1 and p38 during chondrogenesis of human trabecular bone-derived multipotential cells. Both TGF-beta1 stimulation and p38 MAP kinase activation affect the binding of AP-2 as well as SP-1 to oligonucleotides with sequence similarity to the overlapping AP-2/SP-1 sites found in the putative 52-bp immediate upstream regulatory region and the 5'-untranslated region of the human aggrecan gene. Electrophoretic mobility shift assays show that TGF-beta1 treatment of the bone-derived cells inhibits AP-2 DNA binding but enhances the DNA binding ability of SP-1. Additionally, treatment of these TGF-beta1-stimulated cells with p38 MAP kinase inhibitor, SB203580, rescued the AP-2 DNA binding but did not affect SP-1 DNA binding. These findings indicate that AP-2 DNA binding is the target of both TGF-beta1 and p38 MAP kinase signaling pathways and suggest a possible signal transduction cascade whereby TGF-beta1 induction of chondrogenesis involves the activation of p38 MAP kinase and the subsequent inhibition of DNA binding by AP-2, thereby preventing the transcriptional repression of the aggrecan gene.

General principles of osteoarticular tuberculosis.

Since approximately 1985, with the pandemic of the human immunodeficiency virus and with the increase in the number of people who are immunocompromised, there is a resurgence of tuberculosis worldwide. The diagnosis in endemic areas generally can be made on clinical and radiologic examinations. However, whenever there is doubt because of an atypical clinical presentation or lack of clinical exposure, tissue diagnosis is mandatory. If osteoarticular tuberculosis is diagnosed and treated at an early stage, approximately 90% to 95% of patients would achieve healing with near normal function. The mainstay of treatment is multidrug antituberculous chemotherapy (for 12 to 18 months) and active - assisted non-weightbearing exercises of the involved joint throughout the period of healing. Operative intervention is required when the patient is not responding after 4 to 5 months of chemotherapy (synovectomy and debridement), the therapeutic outcome is not satisfactory (excisional arthroplasty for the hip or the elbow), or the healed status has resulted in a painful ankylosis (arthrodesis for the ankle, the wrist, or the knee). Joint replacement may be considered if the disease has remained inactive for 10 years or more. Multidrug resistance should be suspected if the activity of disease does not subside after 4 to 6 months of uninterrupted multidrug therapy. Such patients (5% to 10%) present a desperate therapeutic challenge. Second-line and potential antitubercular drugs, and possible immunomodulations may control such a disease.

Delayed suprachoroidal hemorrhage after glaucoma filtration procedures.

OBJECTIVES: To determine the incidence of, risk factors for, and outcomes of delayed suprachoroidal hemorrhage (DSCH) after glaucoma filtration surgery. DESIGN: Retrospective case-control study. PARTICIPANTS: All patients undergoing glaucoma filtration procedures between 1986 and 2000 at Indiana University who were diagnosed postoperatively with suprachoroidal hemorrhage. A total of 66 patients with DSCH were identified. These were compared with a randomly selected group of patients who underwent similar procedures but did not have suprachoroidal hemorrhage. METHODS: Total cases of DSCH were initially compared with the total number of glaucoma surgeries to determine the overall incidence and the incidence in the different procedures. Subsequently, a case-control study was performed comparing the group with hemorrhage to the control group to identify risk factors. Finally, outcomes and prognostic factors were determined by comparing vision preoperatively and postoperatively and parameters of patients with good and poor outcomes. MAIN OUTCOME MEASURES: Incidence of DSCH, risk factors associated with its occurrence, visual outcomes, and factors important for prognosis. RESULTS: Of a total of 2285 glaucoma filtration procedures, 66 (2.9%) cases of DSCH were identified. It developed in 9 of 615 (1.5%) trabeculectomies without antimetabolite, 30 of 1248 (2.4%) trabeculectomies with antimetabolite, 2 of 72 (2.8%) valved tube shunt implantations, and 25 of 350 (7.1%) nonvalved tube shunt implantations. The increased incidence of DSCH after tube shunts compared with trabeculectomy-associated DSCH was significant (P < 0.0001) with an odds ratio of 3.2. The risk factors for DSCH after glaucoma surgery include white race (P = 0.012), anticoagulation (P = 0.034), severe postoperative hypotony (P = 0.033), and aphakia/anterior chamber intraocular lens (P = 0.002). The visual outcomes of patients with hemorrhage were poor, with a decrease in logarithm of the minimum angle of resolution visual acuity from 0.72 to 1.36, which was statistically significant compared with the controls (P < 0.009). CONCLUSIONS: Delayed suprachoroidal hemorrhage occurs more frequently after tube shunt implantation than after trabeculectomy. Caution should be exercised when operating on patients with known risk factors, because the visual outcomes after DSCH are poor.

Long-term survival of allogeneic donor cell-derived corneal epithelium in limbal deficient rabbits.

PURPOSE: To investigate the capability of cultivated allogeneic epithelial stem cells to restore a functional ocular surface in a limbal deficient cornea; to verify the long term survival of epithelial allograft; and to examine the host immune response to heterologous cell transplant in a rabbit model. METHODS: Limbal deficiency was established by performing limbectomy on rabbits (n = 100). Corneal epithelial stem cells were obtained from the limbus and replicated in vitro without a supporting layer. The cell (3 x 10(5)) suspension was then transplanted via topical application as eye drops. Animals were divided into allograft, autograft, and control groups. Females were used as recipients and males as donors for the allograft. Corneas were collected at 7, 14, 21, 40 days as well as 2, 3, 7 and 8 months after cell transplantation. Experimental corneas were evaluated by histology, immunofluorescence, immunohistochemistry and Y chromosome analysis. RESULTS: A well-differentiated corneal epithelium was recognized at 14 to 40 days after cell transfer overlying an infiltrated corneal stroma. Corneal re-epitheliazation was confirmed in 31 of 36 allograft corneas. No significant immune rejection was noted. Stromal abnormality caused by previous limbal deficiency was mostly resolved three months after the regeneration of corneal epithelium. CONCLUSIONS: Transplanted corneal epithelial stem cells were able to differentiate into normal corneal epithelium in vivo without the use of membrane scaffolding. This non-autologous donor cell-derived corneal epithelium survived up to 8 months without immunosuppression and was able to reverse the stromal scarring. Thus, cultivated epithelial stem cells have great potential as an alternative to multiple-surgical procedures in the treatment of limbal deficiency states.

Molecular characterization of prostate carcinoma tumor antigen-1, PCTA-1, a human galectin-8 related gene.

The galectin family of proteins has been associated with several diverse cellular processes. More than 30 years since the discovery of the first member, precise biological functions for the family as a whole, or for individual members has proven elusive. The isolation of Prostate Carcinoma Tumor Antigen-1 (PCTA-1), a cDNA closely related to rat and human Galectin-8, as a surface marker associated with prostate cancer was achieved using a previously described immunological subtraction approach, Surface Epitope Masking (SEM) approach, in combination with expression screening. It appears that PCTA-1 expression is almost ubiquitous in normal human tissues and could alter in specific contexts such as transformation or metastasis. Multiple expression isoforms of PCTA-1 at the mRNA level are observed. PCTA-1 maps to 1q42-43, a locus associated with predisposition to prostate cancer. We have determined the genomic structure of PCTA-1 to account for the several observed isoforms, performed expression analysis to determine distribution in normal and transformed contexts at the RNA and protein level and conducted over-expression studies to determine effects on cellular phenotype.

Risk factors for repeated cerebrospinal shunt failures in pediatric patients with hydrocephalus.

OBJECT: Repeated cerebrospinal fluid (CSF) shunt failures in pediatric patients are common, and they are a significant cause of morbidity and, occasionally, of death. To date, the risk factors for repeated failure have not been established. By performing survival analysis for repeated events, the authors examined the effects of patient characteristics, shunt hardware, and surgical details in a large cohort of patients. METHODS: During a 10-year period all pediatric patients with hydrocephalus requiring CSF diversion procedures were included in a prospective single-institution observational study. Patient characteristics were defined as age, gender, weight, head circumference, American Society of Anesthesiology class, and cause of hydrocephalus. Surgical details included whether the procedure was performed on an emergency or nonemergency basis, use of antibiotic agents, concurrent surgical procedures, and duration of the surgical procedure. Details on shunt hardware included: the type of shunt, the valve system, whether the shunt system included multiple or complex components, the type of distal catheter, the site of the shunt, and the side on which the shunt was placed. Repeated shunt failures were assessed using multivariable time-to-event analysis (by using the Cox regression model). Conditional models (as established by Prentice, et al.) were formulated for gap times (that is, times between successive shunt failures). There were 1183 shunt failures in 839 patients. Failure time from the first shunt procedure was an important predictor for the second and third episodes of failure, thus establishing an association between the times to failure within individual patients. An age younger than 40 weeks gestation at the time of the first shunt implantation carried a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.68-3.68) for the first failure, which remained high for subsequent episodes of failure. An age from 40 weeks gestation to 1 year (at the time of the initial surgery) also proved to be an important predictor of first shunt malfunctions (HR 1.77, 95% CI 1.29-2.44). The cause of hydrocephalus was significantly associated with the risk of initial failure and, to a lesser extent, later failures. Concurrent other surgical procedures were associated with an increased risk of failure. CONCLUSIONS: The patient's age at the time of initial shunt placement and the time interval since previous surgical revision are important predictors of repeated shunt failures in the multivariable model. Even after adjusting for age at first shunt insertion as well as the cause of hydrocephalus, there is significant association between repeated failure times for individual patients.

CSF shunts 50 years on--past, present and future.

Cerebrospinal fluid (CSF) shunts were invented almost 50 years ago. While their introduction revolutionized the treatment of hydrocephalus, their complications have become legendary, and the focus of much investigation and development of new devices. New devices have been based upon improved understanding of the pathophysiology of hydrocephalus or shunt complications. Despite the rational, or frequently "more physiological," functioning of these devices, all too often unexpected complications have ensued, and the initial enthusiasm for the devices has waned. Assessing the efficacy of the devices has been difficult, owing to the lack of properly conducted studies. Nevertheless, the overall impact of shunt design improvements has seemed very limited. A recent randomized trial of CSF shunt design, examining the failure rates of two new and widely used valves (the Cordis Orbis Sigma and the Medtronic PS Medical Delta valves) failed to find any advantage of these over standard valve designs, many of which have been used almost since the inception of CSF shunts. A search for risk factors for failure, in a post hoc analysis of the data, indicated only that the etiology of the hydrocephalus and the position and local environment of the ventricular catheter tip were probably important. Remarkably, the rate of change in the size of the ventricles and the final ventricular size were not different despite the substantial differences in flow characteristics of the two new valves. Shunt failure rates of less than 5% at 1 year, with infection rates of less than 1%, seem like reasonable goals for the next decade in the new millenium. This can be achieved through basic research into the pathophysiology of shunt failure with improved mathematical models, and perhaps animal models of shunt failure. Efficacy of new devices or treatments must be scrutinized scientifically so as not to waste valuable resources and time on unproven treatments. Uncontrolled series and testimonial assertions about new treatments or devices, especially from proponents with a vested interest, should be regarded with great skepticism. Nevertheless, our best efforts are likely to result in a major advance in the management of pediatric hydrocephalus, which now seems tantalizingly close.

Change in ventricular size and effect of ventricular catheter placement in pediatric patients with shunted hydrocephalus.

OBJECTIVE: The multicenter, randomized pediatric cerebrospinal fluid shunt valve design trial found no difference in the rate of shunt failure between a standard valve, a siphon-reducing valve (Delta; Medtronic PS Medical, Goleta, CA), and a flow-limiting valve (Orbis Sigma; Cordis, Miami, FL); however, the valves were expected to have different effects on ultimate ventricular size. Also, the catheter position or local environment of the ventricular catheter tip might have affected shunt failure. Therefore, we performed a post hoc analysis to understand what factors, other than valve design, affected shunt failure and to identify strategies that might be developed to reduce shunt failure. METHODS: Ventricular size was measured at as many as six different intervals, using a modified Evans' ratio (with incorporation of the frontal and occipital dimensions), in 344 patients. Ventricular catheter location was defined as being in the frontal horn, occipital horn, body of the lateral ventricle, third ventricle, embedded in brain, or unknown. The ventricular catheter tip was described as surrounded by cerebrospinal fluid, touching brain, or surrounded by brain parenchyma within the ventricle (slit ventricle). Repeated measures analysis of variance for unbalanced data was used to analyze ventricular size. A Cox model (with incorporation of time-dependent covariates) was used to evaluate the contribution of age, etiology, shunt design, ventricular size, ventricular catheter location, and environment among the cases. RESULTS: Ventricular volume decreased in an exponential fashion, forming a plateau at 14 months, and was similar for the three valves (P = 0.4). Frontal and occipital ventricular catheter tip locations were associated with a reduced risk of shunt failure (hazard ratios, 0.60 [P = 0.02] and 0.45 [P = 0.001], respectively). Ventricular catheter tips surrounded by cerebrospinal fluid or touching the brain were associated with a reduced risk of failure (hazard ratios, 0.21 and 0.33, respectively; P = 0.0001). Patients with myelomeningocele or large ventricles had increased risk of malfunction (hazard ratios, 1.78 [P = 0.006] and 2.33 [P = 0.03], respectively). CONCLUSION: Decline of ventricular size over time is not affected by these different shunt valve designs. This suggests that the mechanical models of hydrocephalus on which the designs were based are inadequate. Ventricular catheter tip location and ventricular catheter environment are important. Techniques to accurately place ventricular catheters and new valve designs that effectively control ventricular size might reduce shunt malfunction.