Hippocampal adequacy versus functional reserve: predicting memory functions following temporal lobectomy.

While decrements in memory following temporal lobectomy for intractable epilepsy remain a major neurocognitive complication of surgical intervention, it has been difficult to identify patients who are most at risk for developing decrements in their memory functions following surgery. Two different models of hippocampal functioning have been posited to account for postsurgical memory losses: hippocampal reserve versus functional adequacy. This article briefly examines the basis of the traditional model of hippocampal reserve, which suggests that it is the reserve or capacity of the contralateral hippocampus to support memory after surgery that determines whether changes in memory function will be observed. A more in-depth review of emerging data from studies of function (baseline neuropsychological testing and intracarotid amytal procedure) and structure (histologic cell densities and MRI volumetrics) supporting a functional adequacy model of hippocampal functioning is then presented. Data from these latter studies provide strong convergent support for the view that the risk for memory decrements following mesial temporal lobe epilepsy surgery is inversely related to the functional adequacy of the tissue to be resected. Data reviewed here have broad implications for the field of neuropsychology. Not only do the data reported in this article challenge some of the basic tenets of our understanding of the role of the hippocampus in memory functioning, but they illustrate the importance of ongoing research, critical reevaluation of basic concepts, and the importance of self-scrutiny in light of new technologies.     

Cognitive functioning in children with sickle cell disease: a meta-analysis

OBJECTIVE: To establish whether sickle cell disease (SCD) affects cognitive functioning in children with no evidence of cerebral infarction. METHODS: We conducted a meta-analysis of studies of cognition in SCD to determine the size of any statistical difference between children with SCD and controls. Methodological factors were evaluated according to the size and frequency of group differences. RESULTS: There were small but reliable decrements in cognitive functioning on IQ measures (4.3-point difference overall). The most methodologically rigorous studies showed a highly similar pattern. Sampling issues associated with the effect size for IQ were identified. Measures of specific abilities appear more sensitive than IQ scores to cognitive decrements in SCD. CONCLUSIONS: SCD is associated with cognitive effects even in the absence of cerebral infarction. The causes of this cognitive decrement may include direct effects of SCD on brain function or indirect effects of chronic illness.     

Cognitive functioning in sydenham's chorea: Part 1. attentional processes

Ten patients with Sydenham's chorea, ages 7 to 15 years, were tested on a computerized battery of tasks assessing attentional processing. Relative to controls, the patients with Sydenham's chorea showed decrements in performance on tasks assessing response inhibition and divided attention. However, normal attentional functioning was observed on tasks assessing spatial attention, sustained attention, and shifts in attentional set These results are discussed in relation to deficits observed in patients of other basal ganglia disorders.     

Effects of 1,25 (OH)2D3 treatment on lipid levels in uremic hemodialysis patients.

The aim of this study was to evaluate the effect of 1,25 (OH)2D3 treatment on lipid levels in uremic hemodialysis (HD) patients. Thirty-one HD patients who had never been treated with vitamin D nor related drugs and 12 healthy subjects with normal renal functions were studied. Uremic HD patients were randomly divided into two groups. Sixteen uremic HD patients were treated with oral calcitriol (0.5 micrograms/day) for 8 weeks. 13 uremic HD patients and 12 healthy subjects were given placebo. In all these cases before and after 8 weeks of treatments; serum total lipid, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels were determined. After calcitriol treatment, triglyceride levels were significantly decreased. But total lipid, cholesterol, HDL-cholesterol and LDL-cholesterol levels did not significantly change. In the other two groups there were no significant changes. These results show that calcitriol treatment has a positive effect on triglyceride levels in uremic HD patients. This effect of mechanism of calcitriol treatment has not been known yet. But it could be due to regulation carbohydrates metabolism and normalization of parathormone (PTH) levels.     

Is lower ploidy of megakaryocytes another reason for uremic thrombocytopathy?

Summary Though it has been generally accepted that uremic serum contains substances which impair platelet function and inhibit erythropoiesis, the mechanism of uremic thrombocytopathy and bleeding tendency is still not clearly understood. By measuring the nuclear DNA content of the megakaryocytes of 20 patients with end-stage renal failure, we demonstrated that ploidy levels correlate with parameters of uremia. High creatinine and BUN levels as well as low hemoglobin or creatinine clearance values correlate with low average ploidy of megakaryocytes. In explaining this phenomenon, uremic inhibition of DNA replication seems to be more important than dialysis or the type of renal disease. As megakaryocytes of higher ploidy are thought to produce more reactive platelets than megakaryocytes of lower DNA content, this could be another reason for uremic thrombocytopathy and bleeding tendency.Abbreviations AU Arbitrary units - BUN Blood urea nitrogen     

1,25-Dihydroxyvitamin D-induced suppressor cells in uremic versus normal lymphocytes

1,25-Dihydroxyvitamin D3 (DHD) has been shown to suppress mitogen-induced blast transformation. This inhibition is abolished by prior elimination of adherent cells. Chronic renal failure is an immunodeficiency state on the one hand and is associated with abnormalities in vitamin D metabolism on the other. The effect of DHD on the induction of suppressor cells in uremic vs. normal peripheral blood mononuclear cells was investigated. Study groups included 16 chronically uremic patients and 16 age- and sex-matched controls. DHD induced suppressor cell activity in normal lymphocytes. However, no suppressor cell activity was observed in lymphocytes from the uremic patients preincubated with DHD. The origin of the responder cells (normal or uremic) did not affect the outcome. The results would suggest that monocyte-adherent suppressor cells from uremic subjects are either incapable of binding DHD or fail to mount a normal post-receptor intracellular chain of events culminating in suppressor activity.     

Synergism between immunosuppressive agents and uremia?

The susceptibility of uremic patients to infectious disease has been widely reported, but the host immune factors associated with the increased incidence of infection have not been clearly defined. In this study, the possibility of synergism between biologically active components that accumulate in uremia and immunosuppressive drugs used in the course of management was investigated. An animal model of chronic stable uremia was used in these experiments to assess the effect of cyclophosphamide, methotrexate, and azathioprine on antibody response in the uremic host. Chronic uremia did not affect the immunosuppressive activity of cyclophosphamide, methotrexate, or azathioprine, and synergism between these agents and uremic components is unlikely to complicate further the immune status of the host in renal failure.     

CAPD and bone marrow cell-cell interaction abnormality in end stage renal disease

In this research the early erythroid progenitor (BFU-E) growth has been observed in patients with chronic renal failure by studying in "in vitro" cultures the number of BFU-E developed per plate under various experimental conditions. Our results demonstrate that the BFU-E growth of uremic patients in the predialysis phase or on hemodialysis is suppressed both in basal conditions and with the addition of lympho-monocytes of normal subjects or CAPD patients to the "in vitro" cultures. In CAPD patients, on the contrary, the BFU-E growth appears near normal levels in basal conditions and is further more enhanced by adding the normal lympho-monocytes to the "in vitro" cultures. The above mentioned facts signify that in uremic patients both the abnormality of bone marrow and immunocompetent cells may be responsible for the suppressed BFU-E growth, while with CAPD the improvement of both systems allow a normalisation of erythropoiesis. Such a recovery with CAPD demonstrates the presence of an inhibitor material in uremia which is better depurated by this technique.     

Cognition in nephropathic cystinosis: pattern of expression in heterozygous carriers

Individuals with cystinosis exhibit specific cognitive deficits in visual spatial function. The purpose of the current study was to examine if obligate heterozygotes of the CTNS mutation have the same pattern of cognitive functioning seen in homozygotes, namely aberrant visual-spatial functioning against a background of relatively intact visual-perceptual functioning and overall cognitive ability. Study participants were 254 adults (100 heterozygotes and 154 controls), ages 17 years 10 months through 74 years 9 months. Tests of intelligence, visual perceptual, and visual spatial functioning were administered. Our results showed that cystinosis heterozygotes demonstrated intelligence within the normal range, and performed similarly to controls on tests of visual-perceptual ability. In contrast, the heterozygotes performed significantly more poorly on each of the visual-spatial tests when compared to controls. Obligate heterozygotes for the CTNS mutation display a similar pattern of visual processing decrements as do individuals with cystinosis. Namely, carriers demonstrate relative weaknesses in visual-spatial processing, while maintaining normal visual perceptual ability and intelligence in the normal range. The visual spatial decrements in heterozygotes were not as marked as those found in individuals with cystinosis, suggesting a gene dosing effect. This study provides an impetus for other studies of gene-behavior relationships in recessive disorders, and may stimulate further interest in the role of aberrant genes on "individual differences" in behavior.     

Evolution of oxidative stress and inflammation during hemodialysis and their contribution to cardiovascular disease

End-stage renal disease patients have increased cardiovascular morbidity and mortality. These patients have many unique risk factors, such as an accumulation of uremic toxins, electrolyte imbalances, metabolic disturbances, anemia, chronic inflammation, and thrombogenic disturbances. Oxidative stress has been implicated in many of these disturbances. This review will focus on some of the factors that may accelerate cardiovascular disease in uremic patients, with an emphasis on mechanisms and interactions of various components of oxidative stress and inflammation. Understanding the mechanisms of these pathways may be useful in developing effective prevention and treatment strategies.     

Acute hepatitis C in Brazil: results of a national survey

The incidence of acute hepatitis C has decreased in the world. However, new cases are still reported. The objective of this study was to obtain data of acute hepatitis C in Brazil and to identify risk factors of transmission, diagnostic criteria, clinical presentation, evolution, and treatment. A questionnaire was sent to all members of the Brazilian Society of Hepatology. Sixteen centers participated with a total of 170 cases between 2000 and 2008. Among them, 37 had chronic renal failure on hemodialysis and were evaluated separately. The main diagnostic criterion in non‐uremic patients was ALT (alanine aminotransferase) elevation associated with risk factors. In patients with chronic renal failure, anti‐hepatitis C virus (HCV) seroconversion was the most frequent criterion. Among the 133 non‐uremic patients the main risk factors were hospital procedures, whereas in hemodialysis patients, dialysis was the single risk factor in 95% of the cases. Jaundice was more frequent in non‐uremic patients (82% vs. 13%; P < 0.001) and ALT levels were higher in these individuals (P < 0.001). Spontaneous clearance was more frequent in non‐uremic patients (51% vs. 3%; P < 0.001). Sixty‐five patients were treated: 39 non‐uremic patients and 26 on dialysis. Sustained virological response rates were 60% for non‐uremic and 58% for uremic patients (P = 0.98). There was no association of these rates with the study variables. These findings show that cases of acute hepatitis C are still occurring and have been related predominantly to hospital procedures. Measures to prevent nosocomial transmission should be adopted rigorously and followed to minimize this important source of infection observed in this survey. J. Med. Virol. 83:1738–1743, 2011. © 2011 Wiley‐Liss, Inc.     

Altered monocyte function in uremia

Uremia appears to suppress immune function predisposing patients to infections. When the defect in cellular immunity was studied by exposing mononuclear cells (MNC) from uremic patients and controls to tetanus toxoid, diptheria toxoid, or Candida albicans antigen in vitro, the uremic cells were far less responsive. Monocytes and T cells, which are both involved in the proliferative response to soluble antigens, were isolated from MNC of uremic patients and HLA class II matched controls and incubated with tetanus toxoid. Tetanus toxoid-pulsed uremic monocytes were unable to stimulate the proliferation of HLA identical control T lymphocytes. Lymphocytes from uremic patients, however, were stimulated by tetanus toxoid-pulsed control monocytes. Therefore, the ability of monocytes to function as accessory cells is severely affected by uremia. The uremic monocytes were FcR+, produced IL-1 beta, and expressed levels of HLA class II antigens comparable to controls. Although the biochemical defect in uremic monocytes remains unknown, the abnormality could explain many of the immunological changes of uremia.     

The epidemiology and clinical aspects of the hemolytic uremic syndrome in Minnesota

BACKGROUND. The frequency of the hemolytic uremic syndrome, characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, is increasing. Although Escherichia coli serotype O157:H7 has been implicated as a causative agent, more information is needed about the basic epidemiology and clinical aspects of this syndrome. METHODS. We conducted a retrospective population-based study of hemolytic uremic syndrome in Minnesota residents less than 18 years of age from 1979 through 1988 to assess trends in disease occurrence, describe the clinical illness, and identify predictors of disease severity and outcome. We also conducted a case-control study of patients with onsets of illness from 1986 through 1988 to examine risk factors. RESULTS. One hundred seventeen patients were identified. The mean annual incidence increased from 0.5 case per 100,000 child-years among children less than 18 in 1979 (6 cases) to 2.0 cases per 100,000 in 1988 (26 cases) (P = 0.000004). E. coli O157:H7 was isolated from 13 of 28 patients (46 percent) who had stool specimens submitted for testing. For those who presented with typical hemolytic uremic syndrome, an elevated polymorphonuclear-leukocyte count on hospital admission, a shorter duration of prodrome, and the presence of bloody diarrhea were predictive of severe disease. In the case-control study, the patients were more likely to attend large daycare centers (more than 50 children) than were the controls (odds ratio, 10.2; P = 0.03), suggesting that day-care attendance may be a risk factor. On the basis of the population-attributable risk, however, this factor could account for no more than 16 percent of the cases. CONCLUSIONS. This study provides evidence for an increase in the incidence of hemolytic uremic syndrome, which is probably related to an increased incidence of E. coli O157:H7 infections. Hemolytic uremic syndrome has become an important pediatric and public health problem.     

Platelet thromboxane formation and BTG levels after intensive charcoal HP in uremics or regular hemodialytic treatment (RHT)

Vascular tissues from uremic patients show increased prostaglandin synthesizing capacity while uremic platelets have decreased thromboxane synthesis. It has been suggested that the platelet defects in uremia are partially corrected by hemodialysis and a correlation with the levels of guanidinsuccinic acid, phenolic acid, creatinine or urea has been demonstrated. In our study 6 patients with end-stage renal disease on RHT, underwent, daily and for ten days, two-hours hemoperfusion, in order to obtain lower levels of toxic metabolites such as creatinine (less than 6 mg/dl.). Before and after this intensive treatment we have evaluated BTG plasmatic levels and thromboxane formation by platelets after thrombin and arachidonic acid stimulation. The thromboxane formation was not increased following this treatment, whereas BTG plasmatic levels were significantly diminished.     

Search for the uremic toxin. Decreased motor-nerve conduction velocity and elevated parathyroid hormone in uremia.

In a retrospective analysis to determine whether secondary hyperparathyroidism in uremia has a role in uremic peripheral neuropathy, we simultaneously measured motor-nerve conduction velocity and serum parathormone level in 42 uremic patients. We compared age-matched groups of nondiabetic uremic patients, divided into three groups according to serum parathyroid hormone, for degree of impairment of motor-nerve conduction velocity, and 12 diabetic patients with uremia. The group with highest levels had a significantly (P less than 0.01) lower conduction velocity (25.3 +/- 4.9 m per second) than the group with normal or slightly elevated parathyroid hormone, who had only mild depression of nerve conduction (45.1 +/- 1.3 m per second). Mean serum calcium and creatinine were not significantly different between groups. Nerve conduction velocity was similarly depressed in 17 patients on additional dialysis studied prospectively and divided into groups according to parathyroid hormone levels. These results suggest a relation between high parathormone levels and uremic neuropathy and implicate parathyroid hormone as a uremic toxin.     

The dialysis encephalopathy syndrome. Possible aluminum intoxication.

The aluminum content of muscle, bone and brain was measured in control subjects and in uremic patients on dialysis who had been maintained on phosphate-binding aluminum gels. The mean muscle aluminum was 14.8 ppm, and the trabecular-bone aluminum 98.5 ppm in the patients on dialysis, as compared with 1.2 and 2.4 in control subjects (P less than 0.05). Brain gray-matter aluminum values in a group of uremic patients on dialysis who died of a neurologic syndrome of unknown cause were 25 ppm as compared with 6.5 ppm in a group of uremic patients on dialysis who died of other causes and 2.2 ppm in control subjects. The fact that brain gray-matter aluminum was higher in all patients with the dialysis-associated encephalopathy syndrome than any of the control subjects or other uremic patients on dialysis suggests that this syndrome may be due to aluminum in intoxication.     

Neuropsychological correlates of homocysteine levels in euthymic bipolar patients

BACKGROUND: We have previously reported that homocysteine levels are elevated in euthymic bipolar patients with functional deterioration. The current study was designed to extend this finding by examining the relationship between neuropsychological functioning and homocysteine levels in euthymic bipolar patients. METHODS: Fifty-seven euthymic bipolar outpatients were assessed for serum levels of homocysteine, folic acid, and vitamin B-12 and administered a battery of neuropsychological tests. RESULTS: We found that male bipolar subjects showed higher average homocysteine levels than a comparison group of normal subjects, that poorer functioning on a task of executive function (Wisconsin Card Sort) was related to higher homocysteine levels, and that folic acid or vitamin B-12 levels did not significantly affect neuropsychological functioning. LIMITATIONS: These results, while suggesting some relationship between higher homocysteine levels, bipolar illness, and impairment in cognitive function do not establish any causative effects. CONCLUSIONS: The findings of this study confirm that in euthymic bipolar patients, higher homocysteine levels are associated with poorer performance in some neuropsychological tests. Treatment trials will be required before it will be known if the putative decrements in the executive function of bipolar patients can be reversed, or at least retarded, if homocysteine levels are reduced (as, for example, by dietary addition of B vitamin supplements).     

Cellular immune function in uremia: altered cytotoxic and suppressor cell responses to an immunomodulating heptapeptide

Hemodialysates of uremic patients have been shown by T. Abiko, M. Kumikawa, and H. Sekimo (Biochem. Biophys. Res. Commun. 86, 945, 1979) to contain a heptapeptide which inhibits E-rosette formation by human T cells. This heptapeptide also corresponds to a fragment of beta 2-microglobulin and may play an immunoregulatory role in uremia. We investigated the potential for induction of cytotoxic and suppressor cells by the synthetic heptapeptide (HP) in blood lymphocytes of normal donors and uremic patients. Cytotoxic activity of normal lymphocytes was significantly enhanced by low concentrations of HP while high concentrations depressed it. Two patterns of responsiveness were observed among uremic patients: a high responder group reacted similarly to normals, whereas a low responder group showed little reactivity to HP. Removal of the NH2-terminal histidine of the heptapeptide strongly diminished its enhancing activity on normal cytotoxic cells while maintaining activity on uremic lymphocytes. When HP and des-His-HP were studied as possible inducers of suppressor cell activity, only the latter was found to be active on normal cells. Lymphocytes from uremic patients failed to respond to either HP or des-His-HP in suppressor cell generation. It is suggested that continuous interaction between lymphocytes and high concentrations of HP or des-His-HP in uremia may have altered their sensitivity to the immunomodulatory effects of the peptides and may be instrumental in the immune deficiency associated with renal failure.     

PTH and bone metabolism in chronic dialysis patients

The abnormal metabolism of calcium and bone is one of the most common complications seen in chronic dialysis patients. The activity of PTH has been mainly assessed by intact PTH assay; however, recent data suggest that this assay may overestimate PTH activity by detecting 7-84 PTH fragments in addition to 1-84 PTH molecules(whole PTH). Another issue in this field is that higher levels of PTH are needed to maintain normal bone turnover in uremic patients. Accumulated osteoprotegerin in uremic serum may be responsible for this skeletal resistance to PTH.     

Disturbed cognitive functions after nasal provocation in patients with seasonal allergic rhinitis

Background Allergic rhinitis (AR) reduces quality of life as a result of impaired psychological well-being and perceived impaired cognitive functioning. Few studies have measured cognitive functions objectively and it remains uncertain whether AR leads to an objective reduction in cognitive functions.
Objective The present study investigated whether AR is associated with a decrement in several aspects of cognitive functioning. Furthermore, the study investigated whether AR patients invest more 'mental effort' in order to achieve the same cognitive performances as healthy controls.
Methods Twenty five patients with seasonal allergic rhinitis (SAR) and 26 healthy controls, matched for age, education and sex, were tested on a battery of time-demanding and strenuous objective cognitive tests and subjective questionnaires, both before and after nasal provocation (NP). The cognitive functions assessed were sustained attention, short- and long-term memory and speed of information processing. Mental effort was assessed using visual rating scales.
Results Sustained but not short cognitive performance was impaired in patients after NP. Patients showed an increased effort on short cognitive tests.
Conclusion SAR patients suffer from cognitive performance decrements that can be compensated by additional mental effort for short tasks only.