Laser Technology Advancements in the Treatment of Benign Prostatic Hypertrophy.

PURPOSE OF REVIEW: Lasers have had a significant impact on the treatment of benign prostatic hypertrophy. This article attempts to distill the advancements in laser technology for the treatment of benign prostatic hypertrophy (BPH) into key and understandable points to help make this topic more accessible to urologists. RECENT FINDINGS: The holmium:yttrium-aluminum-garnet (YAG) laser, one of the most significant lasers in the field of urology, has recently been improved with pulse modulating technology (Moses™ technology). New thulium:YAG technology allows both pulsed and continuous wave modes. The thulium fiber laser is one of the newer lasers to come to market and has been shown to have effective and safe outcomes. GreenLight™ lasers are predominantly used in photovaporization procedures and have also been studied extensively, although less in recent years. The modern urologist is fortunate to have many high-quality lasers and a wide variety of surgical techniques to choose from when treating BPH. Understanding the basic laser principles and applications will help urologists to select the best treatment options for their patients with BPH.

Comparison of Contemporary Surgical Outcomes Between Holmium Laser Enucleation of the Prostate and Robotic-Assisted Simple Prostatectomy.

PURPOSE OF REVIEW: This study reviews contemporary literature on RASP and HoLEP to evaluate perioperative outcomes, common complications, cost analytics, and future directions of both procedures. RECENT FINDINGS: RASP is indicated for prostates > 80 mL, while HoLEP is size-independent. No notable differences were found in operative time, PSA nadir (surrogate for enucleation volume), re-catheterization rates, or long-term durability. Prolonged incontinence and bladder neck contracture rates are low for both surgeries. Patients experience similar satisfaction outcomes and improvements in uroflowmetry and post-void residual volumes. HoLEP demonstrates shorter hospitalizations, lower transfusion rates, lower costs, and higher rates of same-day discharge. RASP offers a shorter learning curve and lower rates of early postoperative urinary incontinence. HoLEP is a size-independent surgery that offers advantages for patients seeking a minimally invasive procedure with the potential for catheter-free same-day discharge. Future directions with single-port simple prostatectomy may offer parity in same-day discharge, but further research is needed to determine broader feasibility.

Hematologic parameters are not predictors of upgrading or treatment in a racially diverse prospective study of men with prostate cancer on active surveillance.

INTRODUCTION: Neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) are useful clinical biomarkers for prognosis in several malignancies. Their predictive value has been less clearly demonstrated with prostate cancer (PCa), particularly, their utility within active surveillance (AS) protocols. We aim to evaluate NLR and PLR in AS patients. METHODS: We identified 98 patients who met inclusion criteria in our cohort of 274 men diagnosed with PCa on AS. Patients were then categorized into high and low NLR and PLR groups. RESULTS: The 2.5 and 5-year Gleason upgrading free probability for our high NLR cohort was 73.9%(CI 56.3% to 97.0%) and 46.2%(CI 22.4% to 95.1%) compared to 76.3%(CI 65.7% to 88.7%) and 61.7%(CI 47.7% to 80.0%) in the low NLR cohort(p = .73). The 2.5 and 5-year Gleason upgrading free probability for our High PLR cohort was 73.5%(CI 57.3% to 94.2%) and 60.1(CI 41.4% to 87.4%) compared to 76.8%(CI 65.8% to 89.65) and 58.1%(CI 42.2% to 80.1%) in our low PLR group(p = .41). A multivariant analysis demonstrated these groups were not significant predictors of upgrading or treatment. CONCLUSION: Despite their usefulness in many types of malignancy, NLR and PLR were not predictors of upgrading or treatment in men on AS for localized PCa in our cohort.

A large 'Active Magnetic Shield' for a high-precision experiment: nEDM collaboration.

We present a novel Active Magnetic Shield (AMS), designed and implemented for the n2EDM experiment at the Paul Scherrer Institute. The experiment will perform a high-sensitivity search for the electric dipole moment of the neutron. Magnetic-field stability and control is of key importance for n2EDM. A large, cubic, 5 m side length, magnetically shielded room (MSR) provides a passive, quasi-static shielding-factor of about 105 for its inner sensitive volume. The AMS consists of a system of eight complex, feedback-controlled compensation coils constructed on an irregular grid spanned on a volume of less than 1000 m3 around the MSR. The AMS is designed to provide a stable and uniform magnetic-field environment around the MSR, while being reasonably compact. The system can compensate static and variable magnetic fields up to ±50µT (homogeneous components) and ±5µT/m (first-order gradients), suppressing them to a few µT in the sub-Hertz frequency range. The presented design concept and implementation of the AMS fulfills the requirements of the n2EDM experiment and can be useful for other applications, where magnetically silent environments are important and spatial constraints inhibit simpler geometrical solutions.

Keeping Your Glass Half Full: Cognitive Strategy Intervention for Older Adults.

When older adults experience memory dysfunction it often compromises their confidence. Older adults' confidence in their memory can be improved through interventions designed to teach strategies for improving everyday memory functioning. The present study examines the efficacy of a five-session cognitive strategy program designed to be optimistic and inclusive for older adults living in a residential community. The memory self-efficacy of participants in the intervention group improved significantly relative to a control group. Additionally, participants' knowledge of memory strategies improved overall after completion of this program. Such findings highlight the benefits of practical cognitive-behavioral interventions for bolstering older adults' confidence and knowledge of memory strategies.

Effectiveness of interventions to reduce household air pollution from solid biomass fuels and improve maternal and child health outcomes in low- and middle-income countries: a systematic review protocol.

BACKGROUND: A variety of public health interventions have been undertaken in low- and middle-income countries (LMICs) to prevent morbidity and mortality associated with household air pollution (HAP) due to cooking, heating and lighting with solid biomass fuels. Pregnant women and children under five are particularly vulnerable to the effects of HAP, due to biological susceptibility and typically higher exposure levels. However, the relative health benefits of interventions to reduce HAP exposure among these groups remain unclear. This systematic review aims to assess, among pregnant women, infants and children (under 5 years) in LMIC settings, the effectiveness of interventions which aim to reduce household air pollutant emissions due to household solid biomass fuel combustion, compared to usual cooking practices, in terms of health outcomes associated with HAP exposure. METHODS: This protocol follows standard systematic review processes and abides by the PRISMA-P reporting guidelines. Searches will be undertaken in MEDLINE, EMBASE, CENTRAL, WHO International Clinical Trials Registry Platform (ICTRP), The Global Index Medicus (GIM), ClinicalTrials.gov and Greenfile, combining terms for pregnant women and children with interventions or policy approaches to reduce HAP from biomass fuels or HAP terms and LMIC countries. Included studies will be those reporting (i) pregnant women and children under 5 years; (ii) fuel transition, structural, educational or policy interventions; and (iii) health events associated with HAP exposure which occur among pregnant women or among children within the perinatal period, infancy and up to 5 years of age. A narrative synthesis will be undertaken for each population-intervention-outcome triad stratified by study design. Clinical and methodological homogeneity within each triad will be used to determine the feasibility for undertaking meta-analyses to give a summary estimate of the effect for each outcome. DISCUSSION: This systematic review will identify the effectiveness of existing HAP intervention measures in LMIC contexts, with discussion on the context of implementation and adoption, and summarise current literature of relevance to maternal and child health. This assessment reflects the need for HAP interventions which achieve measurable health benefits, which would need to be supported by policies that are socially and economically acceptable in LMIC settings worldwide. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020164998.

Investigating the Association between Wood and Charcoal Domestic Cooking, Respiratory Symptoms and Acute Respiratory Infections among Children Aged Under 5 Years in Uganda: A Cross-Sectional Analysis of the 2016 Demographic and Health Survey.

Background: Household air pollution associated with biomass (wood, dung, charcoal, and crop residue) burning for cooking is estimated to contribute to approximately 4 million deaths each year worldwide, with the greatest burden seen in low and middle-income countries. We investigated the relationship between solid fuel type and respiratory symptoms in Uganda, where 96% of households use biomass as the primary domestic fuel. Materials and Methods: Cross-sectional study of 15,405 pre-school aged children living in charcoal or wood-burning households in Uganda, using data from the 2016 Demographic and Health Survey. Multivariable logistic regression analysis was used to identify the associations between occurrence of a cough, shortness of breath, fever, acute respiratory infection (ARI) and severe ARI with cooking fuel type (wood, charcoal); with additional sub-analyses by contextual status (urban, rural). Results: After adjustment for household and individual level confounding factors, wood fuel use was associated with increased risk of shortness of breath (AOR: 1.33 [1.10-1.60]), fever (AOR: 1.26 [1.08-1.48]), cough (AOR: 1.15 [1.00-1.33]), ARI (AOR: 1.36 [1.11-1.66] and severe ARI (AOR: 1.41 [1.09-1.85]), compared to charcoal fuel. In urban areas, Shortness of breath (AOR: 1.84 [1.20-2.83]), ARI (AOR: 1.77 [1.10-2.79]) and in rural areas ARI (AOR: 1.23 [1.03-1.47]) and risk of fever (AOR: 1.23 [1.03-1.47]) were associated with wood fuel usage. Conclusions: Risk of respiratory symptoms was higher among children living in wood compared to charcoal fuel-burning households, with policy implications for mitigation of associated harmful health impacts.

Historical review of termite activity at forest service termiticide test sites from 1971 to 2004.

The U.S. Forest Service has a long history of providing termiticide efficacy data used for product registration and labeling. Four primary test sites (Arizona and Florida, Mississippi, and South Carolina [hereafter southeast]) have been used for this purpose. Various parameters of termite attack at water-only control plots were examined in this study to assess the relative pressures of termites at each site. Termiticide studies installed between 1971 and 2001 by using ground board (GB) and concrete slab (CS) test methods were included. GB control plots were attacked 85% of the time in the southeast, about twice the rate observed in Arizona (43%). CS plots were attacked 59-70% of the time in the southeast, significantly higher than in Arizona (43%). Termites were slower to initiate attack at control plots in Arizona compared with the southeast, and they were up to twice as slow at GB controls. Once initial attack began, GB plots were reattacked at higher percentages in the southeast (89-90%) than in Arizona (67%). Reattack at CS plots ranged from 65% in Arizona and South Carolina to 76% in Mississippi. Termites caused less damage to wooden blocks in control plots in Arizona than the southeast. Attack rates at controls generally declined during the 1990s, but these rates have rebounded since 2000, except at CS plots in Arizona and South Carolina. Statistical analysis of attacks at plots treated with chlorpyrifos, cypermethrin, fenvalerate, and permethrin also was undertaken. Time to initial termite attack (failure) of the organophosphate chlorpyrifos was generally shorter in Arizona than in the southeast, whereas time to initial attack in plots treated with one of three pyrethroids (cypermethrin, fenvalerate, and permethrin) was generally longer in Arizona.

Do varus or valgus outliers have higher forces in the medial or lateral compartments than those which are in-range after a kinematically aligned total knee arthroplasty? limb and joint line alignment after kinematically aligned total knee arthroplasty.

AIMS: The aims of this study were to determine the proportion of patients with outlier varus or valgus alignment in kinematically aligned total knee arthroplasty (TKA), whether those with outlier varus or valgus alignment have higher forces in the medial or lateral compartments of the knee than those with in-range alignment and whether measurements of the alignment of the limb, knee and components predict compartment forces. PATIENTS AND METHODS: The intra-operative forces in the medial and lateral compartments were measured with an instrumented tibial insert in 67 patients who underwent a kinematically aligned TKA during passive movement. The mean of the forces at full extension, 45° and 90° of flexion determined the force in the medial and lateral compartments. Measurements of the alignment of the limb and the components included the hip-knee-ankle (HKA) angle, proximal medial tibial angle (PMTA), and distal lateral femoral angle (DLFA). Measurements of the alignment of the knee and the components included the tibiofemoral angle (TFA), tibial component angle (TCA) and femoral component angle (FCA). Alignment was measured on post-operative, non-weight-bearing anteroposterior (AP) scanograms and categorised as varus or valgus outlier or in-range in relation to mechanically aligned criteria. RESULTS: The proportion of patients with outlier varus or valgus alignment was 16%/24% for the HKA angle, 55%/0% for the PMTA, 0%/57% for the DLFA, 25%/12% for the TFA, 100%/0% for the TCA, and 0%/64% for the FCA. In general, the forces in the medial and lateral compartments of those with outlier alignment were not different from those with in-range alignment except for the TFA, in which patients with outlier varus alignment had a mean paradoxical force which was 6 lb higher in the lateral compartment than those with in-range alignment. None of the measurements of alignment of the limb, knee and components predicted the force in the medial or lateral compartment. CONCLUSION: Although kinematically aligned TKA has a high proportion of varus or valgus outliers using mechanically aligned criteria, the intra-operative forces in the medial and lateral compartments of patients with outlier alignment were comparable with those with in-range alignment, with no evidence of overload of the medial or lateral compartment of the knee. Cite this article: Bone Joint J 2017;99-B:1319-28.

Driving-related risks and outcomes of attention deficit hyperactivity disorder in adolescents and young adults: a 3- to 5-year follow-up survey.

OBJECTIVE: To determine whether teenagers and young adults with attention deficit hyperactivity disorder (ADHD) have more motor vehicle citations and crashes and are more careless drivers than their normal peers. DESIGN: A comparison of two groups of teenagers and young adults (ADHD and normal) followed up 3 to 5 years after original diagnosis. SETTING: A university medical center clinic for ADHD patients. PATIENTS: Thirty-five subjects with ADHD and 36 control subjects between 16 and 22 years of age, all of whom were licensed drivers. MAIN OUTCOME MEASURES: Parent ratings of current symptoms of ADHD, oppositional defiant disorder, and conduct disorder, a survey of various negative driving outcomes, and a rating scale of driving behavior. RESULTS: Subjects with ADHD used less sound driving habits. This deficiency was associated with greater driving-related negative outcomes in all categories surveyed. Subjects with ADHD were more likely than control subjects to have had auto crashes, to have had more such crashes, to have more bodily injuries associated with such crashes, and to be at fault for more crashes than control subjects. They were also more likely to have received traffic citations and received more such citations than control subjects, particularly for speeding. The sub-group of teenagers with ADHD having greater comorbid oppositional defiant disorder and conduct disorder symptoms were at highest risk for such deficient driving skills/habits and negative driving-related outcomes. CONCLUSIONS: ADHD, and especially its association with oppositional defiant disorder/conduct disorder, is associated with substantially increased risks for driving among teenagers and young adults and worthy of attention when clinicians counsel such patients and their parents.

Tolerance to cadmium hepatotoxicity by metallothionein and zinc: in vivo and in vitro studies with MT-null mice.

The protective role of metallothionein (MT) in Cd-mediated hepatotoxicity was investigated in vivo and in vitro. Following injection of Cd (2 mg/kg, intraperitoneal or subcutaneous) hepatoxicity was significantly greater at 20 h in metallothionein-null (MT-/-) mice, compared with controls (MT+/+). The decrease in the blood and liver glucose concentrations correlated with the extent of hepatotoxicity, with blood glucose 43% lower in MT-/- mice. Zinc (50 microM) and/or Dex (1 microM) were used in hepatocyte cultures to raise MT 2-5-fold. When Cd at 10 microM was co-treated with Zn and/or Dex, lactate dehydrogenase (LD) leakage in the MT+/+ and MT-/- hepatocytes was reduced only when Zn was present. Cellular glutathione (GSH) was the same in control MT+/+ and MT-/- cultures and was uninfluenced by Zn and Dex. After treatment with 5 and 10 microM Cd, GSH levels were lower in MT-/- than MT+/+ hepatocytes in the control and Dex groups. Higher GSH concentrations were maintained in Zn co-treated cultures from both genotypes, indicating that the superior protective effect of Zn may in part derive from its influence on cellular GSH. Pre-treatment with Zn and/or Dex provided no further protection than co-treatment. Tolerance to brief (15 min) Cd exposure was also investigated in the presence of MT inducers including progesterone (100 microM). Zn, Dex and progesterone treated hepatocytes had less LD leakage than controls with Zn giving the greatest protection (LD leakage 18% of controls at 100 microM Cd). Zn pre-treated cells had higher cytosolic/particulate ratios of Cd. These findings demonstrate that MT protects primary cultures of mouse hepatocytes from short-term exposure to Cd. Zn enhances the protection through MT and non-MT mechanisms.

Paracetamol hepatotoxicity in metallothionein-null mice.

The role of metallothionein (MT) in protecting the liver against paracetamol (PCT) toxicity was investigated in vivo and in vitro in mice lacking expression of MT-1 and MT-2 genes (MT -/-). In the fed, glycogen replete state, hepatotoxicity (PCT 300 mg/kg i.p.) at 6 h was significantly greater in MT -/- than MT +/+ mice. Plasma lactate dehydrogenase (LD) and alanine aminotransferase (ALT) were 5- and 13-fold greater respectively than in MT +/+ mice. Liver glycogen, glucose and zinc levels were significantly lower in MT -/- mice at this time. In contrast, hepatotoxicity (PCT 135 mg/kg i.p.) at 6 h was similar in both MT +/+ and MT -/- mice fasted 24 h, despite a doubling in liver MT in MT +/+ mice. No differences were found between MT -/- and MT +/+ mice in cytochrome P450 activity. Liver glutathione levels were the same in both groups of mice prior to fasting and were decreased to a similar extent (55-65%) following PCT treatment. Investigation of lower PCT doses (< or = 120 mg/kg) in fasted mice over 24 h demonstrated a greater susceptibility in female MT -/- mice with plasma LD, 2.4-fold and ALT, 7.5-fold greater than in MT +/+ mice at 120 mg/kg PCT. In male MT -/- mice, there was only a trend towards greater susceptibility at 110 mg/kg PCT compared to male MT +/+ mice, and at 120 mg/kg, both male genotypes were equally affected. Investigations with cultured hepatocytes supported the in vivo findings in that there was a trend towards greater toxicity (PCT at 1 and 5 mM for 24 h) in hepatocytes from fed MT -/- mice, with the difference diminished in association with greater hepatotoxicity in hepatocytes from fasted mice. Use of dexamethasone (Dex) to increase MT in the MT +/+ mouse hepatocytes protected from PCT toxicity. Zn alone was not protective. Zn plus Dex offered no protection despite higher MT levels. Generation of apo-MT with Dex may offer more protection than Zn-MT. In conclusion, MT -/- mice were more susceptible than MT +/+ mice to PCT toxicity in the fed state, but the increased susceptibility was much smaller, but still significant, when the effects of glycogen were minimised by fasting.

Parent training for attention-deficit hyperactivity disorder: its impact on parent functioning.

This study examined changes in parent functioning resulting from parental participation in a behavioral parent training (PT) program specifically designed for school-aged children with attention-deficit hyperactivity disorder (ADHD). Relative to wait list controls, subjects who completed the nine-session PT program showed significant posttreatment gains in both child and parent functioning, which were maintained 2 months after treatment. In particular, there were PT-induced reductions in parenting stress and increases in parenting self-esteem, which accompanied parent-reported improvements in the overall severity of their child's ADHD symptoms. In addition to their statistical importance, these findings are discussed in terms of their clinical significance, utilizing methods developed by Jacobson and Truax (1991).

Parenting stress among families of children with attention deficit hyperactivity disorder.

Prior research has shown that parenting stress levels can be quite high among families of children with attention deficit hyperactivity disorder (ADHD). This study investigated the degree to which such stress was related not only to the child's ADHD, but also to various other child, parent, and family-environment circumstances. Multimethod assessments were conducted on 104 clinic-referred children with ADHD. Data collected from these subjects were entered into hierarchical multiple-regression analyses, utilizing the Parenting Stress Index as the criterion. The results showed that the child and parent characteristics accounted for a substantial portion of the variance in overall parenting stress. The child's oppositional-defiant behavior and maternal psychopathology were especially potent predictors. The severity of the child's ADHD, the child's health status, and maternal health status also emerged as significant predictors. These findings are discussed in terms of their impact upon the clinical management of children with ADHD.

Multimethod psychoeducational intervention for preschool children with disruptive behavior: two-year post-treatment follow-up.

This paper describes the 2-year post-treatment follow-up of preschool children identified as having high levels of disruptive behavior at kindergarten entry. They were assigned to four treatment conditions: A no-treatment group, parent-training only, treatment classroom only, and the combination of parent training with the treatment classroom. Interventions lasted the entire kindergarten academic year. Initial post-treatment results reported previously indicated no effects for the parent-training program but some efficacy for the classroom intervention program. For this report, the disruptive behavior (DB) children were subdivided into those who did (n = 74) and did not (n = 77) receive the treatment classroom. Two-year post-treatment follow-up results indicated no differences between the classroom treated and untreated DB groups. These groups also failed to differ in the percentage of children using available treatments across the follow-up period. The DB children in both groups had significantly more symptoms of ADHD and ODD than a community control group (N = 47) at follow-up. They also received higher ratings of externalizing problems on the parent Child Behavior Checklist, more severe ratings of behavior problems at home, and ratings of more pervasive behavior problems at school, and had poorer academic skills. Results suggested that early intervention classrooms for DB children may not produce enduring effects once treatment is withdrawn, and that better approaches are needed for identifying those DB children at greatest risk for later maladjustment.

Psychiatric and psychological morbidity as a function of adaptive disability in preschool children with aggressive and hyperactive-impulsive-inattentive behavior.

Children with high levels of aggressive-hyperactive-impulsive-inattentive behavior (AHII; n = 154) were subdivided into those with (n = 38) and without (n = 116) adaptive disability (+AD/-AD) defined as a discrepancy between expected versus actual adaptive functioning. They were compared to each other and a control group of 47 normal children. Both AHII groups were more likely to have attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder than control children; more symptoms of general psychopathology; greater social skills deficits; more parental problems; and lower levels of academic achievement skills. Compared to AHII - AD children, AHII + AD children had (1) more conduct disorder; (2) greater inattention and aggression symptoms; (3) more social problems, less academic competence, and poorer self-control at school; (4) more severe and pervasive behavior problems across multiple home and school settings; and (5) parents with poorer child management practices. Thus, adaptive disability has utility as a marker for more severe and pervasive impairments in AHII children.

Fine-needle aspiration cytology of a case of oncocytic adrenocortical carcinoma.

We report on the results of fine-needle aspiration cytology of a case of oncocytic adrenocortical carcinoma in a 39-yr-old man. The tumor invaded the inferior vena cava and extended up to the right atrium. Aspirate smears were very cellular and showed a monomorphic population of large polyhedral cells with abundant granular cytoplasm, predominantly distributed singly. Mitotic activity was inconspicuous, and there was no necrosis. Immunohistochemically, the tumor cells were positive for vimentin, cytokeratin, and p53, and negative for synaptophysin, chromogranin, inhibin, and S-100. Ultrastructurally, the cytoplasm of the tumor cells was packed with mitochondria. The patient underwent left radical nephrectomy as well as a combined cardiopulmonary bypass, with atriotomy and resection of the tumor from the right atrium and inferior vena cava. Three months of postoperative follow-up were uneventful.

Light microscopic and scanning electron microscopic analyses of dental implants retrieved from humans.

This paper reports analyses obtained from 51 implant cases retrieved from humans and submitted to the AAIDRF-MCG Implant Retrieval Center. The undecalcified samples were embedded in PMMA and examined with scanning electron microscopy and with routine light or Nomarski microscopy. Cases included individual implants as well as 2 mandibles obtained at autopsy. Retrieved implants were sometimes shown to be encapsulated with connective tissue (CT), whereas other implants were apposed by bone, with only minimal CT association. In the latter cases, the implants were apposed by substantial amounts of viable bone. Nomarski microscopy disclosed the orientation and close apposition of the collagen bundles comprising the interfacial bone. In these cases where close bone apposition was observed to the implants, implant fracture was often the cause of failure. Periodontal lesions were reported around some implants showing a marked degree of inflammatory cell infiltrate (ICI). This study underscores the need for evaluation of failed human dental implants. Failure of implants placed longer than 10 years ago (perhaps loaded immediately) may be due to loss of bone support, CT encapsulation, and ICI (i.e., biological failure). Failure of more recently placed implants could also be due to this scenario, but failure was more often ascribed to biomaterial failure.

Excerpts from family-centered care for children needing specialized health and developmental services.

In 1994, Family-Centered Care for Children Needing Specialized Health and Developmental Services was published. This monograph is the third revision of the 1987 landmark publication titled Family-Centered Care for Children with Special Health Care Needs. The revision incorporates several changes: the key elements of family-centered care are reworded for clarity; the order in which the elements are presented is changed to better illustrate their inter-relationships; new understandings about family-centered care are integrated; program examples are updated; and research findings are incorporated. The revised key elements of family-centered care are listed and described here in material excerpted from the 1994 monograph.

Lactate transport and receptor actions in cerebral malaria.

Cerebral malaria (CM), caused by Plasmodium falciparum infection, is a prevalent neurological disorder in the tropics. Most of the patients are children, typically with intractable seizures and high mortality. Current treatment is unsatisfactory. Understanding the pathogenesis of CM is required in order to identify therapeutic targets. Here, we argue that cerebral energy metabolic defects are probable etiological factors in CM pathogenesis, because malaria parasites consume large amounts of glucose metabolized mostly to lactate. Monocarboxylate transporters (MCTs) mediate facilitated transfer, which serves to equalize lactate concentrations across cell membranes in the direction of the concentration gradient. The equalizing action of MCTs is the basis for lactate's role as a volume transmitter of metabolic signals in the brain. Lactate binds to the lactate receptor GPR81, recently discovered on brain cells and cerebral blood vessels, causing inhibition of adenylyl cyclase. High levels of lactate delivered by the parasite at the vascular endothelium may damage the blood-brain barrier, disrupt lactate homeostasis in the brain, and imply MCTs and the lactate receptor as novel therapeutic targets in CM.