Search

Objectives There have been very few longitudinal studies of dental caries in adolescents, and little study of the caries risk factors in this age group. The purpose of this study was to describe different caries trajectories and associated risk factors among members of the Iowa Fluoride Study (IFS) cohort. Methods The IFS recruited a birth cohort from 1992 to 1995, and has gathered dietary, fluoride and behavioural data at least twice yearly since recruitment. Examinations for dental caries were completed when participants were ages 5, 9, 13 and 17 years. For this study, only participants with decayed and filled surface (DFS) caries data at ages 9, 13 and 17 were included (N=396). The individual DFS counts at age 13 and the DFS increment from 13 to 17 were used to identify distinct caries trajectories using Ward's hierarchical clustering algorithm. A number of multinomial logistic regression models were developed to predict trajectory membership, using longitudinal dietary, fluoride and demographic/behavioural data from 9 to 17 years. Model selection was based on the akaike information criterion (AIC). Results Several different trajectory schemes were considered, and a three-trajectory scheme—no DFS at age 17 (n=142), low DFS (n=145) and high DFS (n=109)—was chosen to balance sample sizes and interpretability. The model selection process resulted in use of an arithmetic average for dietary variables across the period from 9 to 17 years. The multinomial logistic regression model with the best fit included the variables maternal education level, 100% juice consumption, brushing frequency and sex. Other favoured models also included water and milk consumption and home water fluoride concentration. The high caries cluster was most consistently associated with lower maternal education level, lower 100% juice consumption, lower brushing frequency and being female. Conclusions The use of a clustering algorithm and use of Akaike's Information Criterion (AIC) to determine the best representation of the data were useful means in presenting longitudinal caries data. Findings suggest that high caries incidence in adolescence is associated with lower maternal educational level, less frequent tooth brushing, lower 100% juice consumption and being female.

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.

Background: Peritoneal dialysis (PD) solutions with reduced sodium content may have advantages for hypertensive patients; however, they have lower osmolarity and solvent drag, so the achieved Kt/V-urea may be lower. Furthermore, the increased transperitoneal membrane sodium gradient can influence sodium balance with consequences for blood pressure (BP) control.Study Design: Prospective, randomized, double-blind clinical trial to prove the noninferiority of total weekly Kt/V-urea with low-sodium versus standard-sodium PD solution, with the lower confidence limit above the clinically accepted difference of 0.5. Setting & Participants: Hypertensive patients (1 antihypertensive drug, including diuretics, or office systolic BP 130 mm Hg) on continuous ambulatory PD therapy from 17 sites.Intervention: 108 patients were randomly assigned (1:1) to 6-month treatments with either low-sodium (125 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 338-491 mOsm/L) or standard-sodium (134 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 356-509 mOsm/L) PD solution.Outcomes: Primary end point: weekly total KtNurea; secondary outcomes: BP control, safety, and tolerability. Measurements: Total KtNurea was determined from 24-hour dialysate and urine collection; BP, by office measurement.Results: Total Kt/Vurea after 12 weeks was 2.53 +/- 0.89 in the low -sodium group (n = 40) and 2.97 +/- 1.58 in the control group (n = 42). The noninferiority of total KtNurea could not be confirmed. There was no difference for peritoneal KtNurea (1.70 +/- 0.38 with low sodium, 1.77 +/- 0.44 with standard sodium), but there was a difference in renal KtNurea (0.83 +/- 0.80 with low sodium, 1.20 +/- 1.54 with standard sodium). Mean daily sodium removal with dialysate at week 12 was 1.188 g higher in the low-sodium group (P Limitations: Broader variability of study population than anticipated, particularly regarding residual kidney function.Conclusions: The noninferiority of the low -sodium PD solution for total Kt/Vurea could not be proved; however, it showed beneficial clinical effects on sodium removal and BP. Am J Kidney Dis. 67(5):753-761. 2016 Fresenius Medical Care. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.orgIlicenses/by-nc-nd14.01).

Background Sugar-sweetened beverages (SSBs) have been associated with obesity in children and adults; however, associations between beverage patterns and obesity are not understood. Objective Our aim was to describe beverage patterns during adolescence and associations between adolescent beverage patterns and anthropometric measures at age 17 years. Design We conducted a cross-sectional analyses of longitudinally collected data. Participants/setting Data from participants in the longitudinal Iowa Fluoride Study having at least one beverage questionnaire completed between ages 13.0 and 14.0 years, having a second questionnaire completed between 16.0 and 17.0 years, and attending clinic examination for weight and height measurements at age 17 years (n=369) were included. Exposure Beverages were collapsed into four categories (ie, 100% juice, milk, water and other sugar-free beverages, and SSBs) for the purpose of clustering. Five beverage clusters were identified from standardized age 13 to 17 years mean daily beverage intakes and named by the authors for the dominant beverage: juice, milk, water/sugar-free beverages, neutral, and SSB. Outcomes Weight, height, and body mass index (BMI; calculated as kg/m 2 ) at age 17 years were analyzed. Statistical analyses We used Ward's method for clustering of beverage variables, one-way analysis of variance and χ 2 tests for bivariable associations, and γ-regression for associations of weight or BMI (outcomes) with beverage clusters and demographic variables. Linear regression was used for associations of height (outcome) with beverage clusters and demographic variables. Results Participants with family incomes P =0.070) and were heavier (2.0±0.7 BMI units; P =0.002) than participants with family incomes ≥$60,000/year. Adjusted mean weight, height, and BMI estimates differed by beverage cluster membership. For example, on average, male and female members of the neutral cluster were 4.5 cm ( P =0.010) and 4.2 cm ( P =0.034) shorter, respectively, than members of the milk cluster. For members of the juice cluster, mean BMI was lower than for members of the milk cluster (by 2.4 units), water/sugar-free beverage cluster (3.5 units), neutral cluster (2.2 units), and SSB cluster (3.2 units) (all P Conclusions Beverage patterns at ages 13 to 17 years were associated with anthropometric measures and BMI at age 17 years in this sample. Beverage patterns might be characteristic of overall food choices and dietary behaviors that influence growth.

OBJECTIVES Amplification is a core component of early intervention for children who are hard of hearing, but hearing aids (HAs) have unique effects that may be independent from other components of the early intervention process, such as caregiver training or speech and language intervention. The specific effects of amplification are rarely described in studies of developmental outcomes. The primary purpose of this article is to quantify aided speech audibility during the early childhood years and examine the factors that influence audibility with amplification for children in the Outcomes of Children with Hearing Loss study. DESIGN Participants were 288 children with permanent hearing loss who were followed as part of the Outcomes of Children with Hearing Loss study. All of the children in this analysis had bilateral hearing loss and wore air-conduction behind-the-ear HAs. At every study visit, hearing thresholds were measured using developmentally appropriate behavioral methods. Data were obtained for a total of 1043 audiometric evaluations across all subjects for the first four study visits. In addition, the aided audibility of speech through the HA was assessed using probe microphone measures. Hearing thresholds and aided audibility were analyzed. Repeated-measures analyses of variance were conducted to determine whether patterns of thresholds and aided audibility were significantly different between ears (left versus right) or across the first four study visits. Furthermore, a cluster analysis was performed based on the aided audibility at entry into the study, aided audibility at the child's final visit, and change in aided audibility between these two intervals to determine whether there were different patterns of longitudinal aided audibility within the sample. RESULTS Eighty-four percent of children in the study had stable audiometric thresholds during the study, defined as threshold changes

Objectives: Children who are hard of hearing (CHH) have restricted access to acoustic and linguistic information. Increased audibility provided by hearing aids (HAs) influences language outcomes, but the advantages of appropriately fit HAs can only be realized if children wear their devices on a consistent basis. The purpose of this article was to characterize long-term HA use in CHH, based on parent-report measures, and identify factors that influence longitudinal trends in HA use. Design: Participants were parents of 290 children with mild to severe hearing loss. At every visit, parents estimated the average amount of time the child used HAs per day during the week and on the weekends. Parent reports of daily HA use were analyzed to determine if different patterns of HA use were observed longitudinally during the study. Independent predictor variables were then related to longitudinal trends in HA use within three age groups (infant, preschool, school age). Results: On average across multiple visits, parents reported that their children wore their HAs for 10.63 hr per day (SD = 3.29). Data logging values were lower than parent-report measures (M = 8.44, SD = 4.06), suggesting that parents overestimated daily HA use. The majority of children in each age group wore HAs at least 8 hr per day from their first research testing interval to their last, based on parent-report measures. Maternal education level predicted longitudinal trends in HA use for infants and school-age CHH. Degree of hearing loss was related to trends in school-age children only. Conclusions: These results indicated that the majority of CHH increased HA use over time, but a sizable minority demonstrated a low level of use or decreased use in the time period studied. Maternal education level influenced longitudinal trends in daily HA use. Degree of hearing loss influenced trends in school-age children only. Audiologists and early intervention service providers might aid in improving HA use by providing regular hands-on training with the HAs and individualized problem-based strategies to address the challenges families experience with attaining a high level of use. Families may also benefit from practical demonstrations of the benefits of consistent HA use, such as hearing loss simulations, examples of listening in noise with and without HAs, or listening to malfunctioning HAs.

Summary Background Hydration to prevent contrast-induced acute kidney injury (CI-AKI) induces a diagnostic delay when performing computed tomography–pulmonary angiography (CTPA) in patients suspected of having acute pulmonary embolism. Aim To analyze whether withholding hydration is non-inferior to sodium bicarbonate hydration before CTPA in patients with chronic kidney disease (CKD). Methods We performed an open-label multicenter randomized trial between 2009 and 2013. One hundred thirty-nine CKD patients were randomized, of whom 138 were included in the intention-to-treat population: 67 were randomized to withholding hydration and 71 were randomized to 1-h 250 mL 1.4% sodium bicarbonate hydration before CTPA. Primary outcome was the increase in serum creatinine 48–96 h after CTPA. Secondary outcomes were the incidence of CI-AKI (creatinine increase > 25%/> 0.5 mg dL−1), recovery of renal function, and the need for dialysis within 2 months after CTPA. Withholding hydration was considered non-inferior if the mean relative creatinine increase was ≤ 15% compared with sodium bicarbonate. Results Mean relative creatinine increase was −0.14% (interquartile range −15.1% to 12.0%) for withholding hydration and −0.32% (interquartile range −9.7% to 10.1%) for sodium bicarbonate (mean difference 0.19%, 95% confidence interval −5.88% to 6.25%, P-value non-inferiority

Background. Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e. g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates.Methods. Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions.Results. One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015).Conclusions. If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Chronic kidney disease (CKD) is associated with increased cardiovascular risk. Here we evaluate whether strict implementation of guidelines aimed at multiple targets with the aid of nurse practitioners (NP) improves management in patients with CKD.MASTER PLAN is a randomised controlled clinical trial, performed in nine Dutch hospitals. Patients with CKD (estimated glomerular filtration rate (eGFR) 20-70 ml÷min) were randomised to receive NP support (intervention group (IG)) or physician care (control group (CG)). Patients were followed for a median of five years. Presented data are an interim analysis on risk factor control at two-year follow-up.We included 788 patients (532 M, 256 F), (393 CG, 395 IG), mean (±SD ) age 59 (±13) years, eGFR 38 (±15) ml÷min÷1.73m(2), blood pressure (BP) 138 (±21)÷80 (±11) mmHg. At two years 698 patients (352 IG, 346 CG) could be analysed. IG as compared with CG had lower systolic (133 vs 135 mmHgsemi; p= 0.04) and diastolic BP (77 vs 80 mmHgsemi; p=0.007), LDL cholesterol (2.30 vs 2.45 mmol(-l); p= 0.03), and increased use of ACE inhibitors, statins, aspirin and vitamin D. The intervention had no effect on smoking cessation, body weight, physical activity or sodium excretion.In both groups, risk factor management improved. However, changes in BP control, lipid management and medication use were more pronounced in IG than in CG. Lifestyle interventions were not effective. Coaching by NPs thus benefits everyday care of CKD patients. Whether these changes translate into improvement in clinical endpoints remains to be established.

Blood pressure (BP) is the most important modifiable risk factor for cardiovascular (CV) disease and progression of kidney dysfunction in patients with chronic kidney disease. Despite extensive antihypertensive treatment possibilities, adequate control is notoriously hard to achieve. Several determinants have been identified which affect BP control. In the current analysis we evaluated differences in achieved BP and achievement of the BP goal between hospitals and explored possible explanations.At baseline, BP was measured in a supine position with an oscillometric device in 788 patients participating in the MASTER PLAN study. We also retrieved the last measured office BP from the patient records. Additional baseline characteristics were derived from the study database. Univariate and multivariate analyses were performed with general linear modelling using hospital as a random factor.In univariate analysis, hospital was a determinant of the level of systolic and diastolic BP at baseline. Adjustment for patient, kidney disease, treatment or hospital characteristics affected the relation. Yet, in a fully adjusted model, differences between centres persisted with a range of 15 mmHg for systolic BP and 11 mmHg for diastolic BP.Despite extensive adjustments, a clinically relevant, statistically significant difference between hospitals was found in standardised BP measurements at baseline of a randomised controlled study. We hypothesise that differences in the approach towards BP control exist at the physician level and that these explain the differences between hospitals.

We studied the effects of a single dose (100 mg orally) and repeated administration (100 mg o.d. for 7 days) of FK453, a novel adenosine-1 receptor antagonist, on renal sodium handling and blood pressure in eight patients with essential hypertension. Within 60 minutes after administration of FK453, sodium excretion increased threefold. This occurred in the absence of a change in renal hemodynamics, assessed from inulin and para-aminohippurate clearance, and was accompanied by increased fractional excretion of lithium, phosphate, and uric acid and by increased excretion of calcium and magnesium. Maximal free water clearance data showed an increase in maximal urine flow and distal delivery term and a decrease in the diluting segment reabsorption term. FK453 also decreased blood pressure and increased heart rate, but this did not occur until about 3 hours after ingestion, that is, when the natriuresis was already over. The natriuretic effect of FK453 was short-lasting, and continued use of FK453 was in fact accompanied by some net sodium retention. Blood pressure on the seventh day before FK453 treatment was not different from blood pressure before administration of the first dose of FK453. Again an acute natriuretic response followed, although less than after the first dose. Changes in intrarenal sodium handling parameters, blood pressure, and heart rate were similar to those seen after the first dose. The natriuretic and hypotensive effects of FK453 indicate that adenosine-1 receptor activity plays a role in the regulation of blood pressure and renal sodium handling in patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Maintenance treatment with prostaglandin synthesis inhibitors often causes some degree of hyper-kalemia, indicating impaired potassium (K) excretion. Hypoaldosteronism probably is a mediating factor, but it is unknown whether these drugs also impair renal K excretion directly. Indomethacin, for example, stimulates NaCl reabsorption in Henle's loop, and thus may impair K excretion by decreasing distal NaCl delivery. We therefore studied the effect of 1 day administration of indomethacin (50 mg tid) on the excretion of a single oral KC1 (1 mmol kg-1 body weight) in six healthy volunteers taking a 40 mmol sodium diet. To allow analysis of renal sodium handling, clearance studies were performed during water loading. In this acute setting, indomethacin had no effect on plasma K, and did not decrease plasma aldosterone. However, indomethacin clearly reduced NaCl excretion. Nonetheless, the excretion of the K load was entirely normal. Excretion of the K load was accompanied by increased clearance of phosphate and uric acid, and natriuresis. Data derived from the maximal free water clearance were compatible with increased delivery to and decreased reabsorption from the diluting segment. Occurrence of these effects was not prevented by indomethacin, although overall NaCl excretion remained less than observed without indomethacin. Indomethacin reduced prostaglandin E2 excretion substantially. Apparently, in normal man indomethacin does not impair K excretion directly, even though it greatly reduces NaCl excretion. Moreover, the effects of K on renal NaCl handling, probably contributing to the excretion of a K load, are not dependent on renal prostaglandins.

Contains fulltext : 69499.pdf (Publisher’s version ) (Open Access) PURPOSE: To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal carcinomas. EXPERIMENTAL DESIGN: Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistochemical staining with two antibodies (HCA2 and HC10). RESULTS: Tumors were split into two groups: (1) tumors with >50% of tumor cells expressing HLA class I (high) and (2) tumors with < or =50% of tumor cells expressing HLA class I (low). No difference in distribution or prognosis of HLA class I expression was found between irradiated and non-irradiated patients. Patients with low expression of HLA class I (15% of all patients) showed an independent significantly worse prognosis with regard to overall survival and disease-free survival. HLA class I expression had no effect on cancer-specific survival or recurrence-free survival. CONCLUSIONS: Down-regulation of HLA class I in rectal cancer is associated with poor prognosis. In contrast to our results, previous reports on HLA class I expression in colorectal cancer described a large population of patients with HLA class I negative tumors, having a good prognosis. This difference might be explained by the fact that a large proportion of HLA negative colon tumors are microsatellite instable (MSI). MSI tumors are associated with a better prognosis than microsatellite stable (MSS). As rectal tumors are mainly MSS, our results suggest that it is both, oncogenic pathway and HLA class I expression, that dictates patient's prognosis in colorectal cancer. Therefore, to prevent confounding in future prognostic analysis on the impact of HLA expression in colorectal tumors, separate analysis of MSI and MSS tumors should be performed.

Plasmodium falciparum infection causes serious symptoms in the acute phase of the illness. Long-term sequelae are less common. In the following case report we describe a patient who developed hypopituitarism after a severe cerebral malaria infection, which was only recognized 17 years thereafter.

To examine the role of mineralocorticoid and glucocorticoid in potassium (K) tolerance in healthy humans, we studied the effects of canrenoate, a mineralocorticoid antagonist, and RU486, a glucocorticoid antagonist, on the excretion of a KCl load. Canrenoate (200 mg, iv) or RU486 (400 mg, orally) was administered 150 min before a KCl load (1 mmol/kg BW, orally) in seven healthy males undergoing maximal water diuresis. Clearance studies were extended for 5 h after the KCl load, and the data were compared with time control, KCl load alone, and canrenoate alone. KCl increased K excretion (from 18.8 +/- 2.4 to 63.3 +/- 3.9 mmol/5 h; P < 0.01) and sodium (Na) excretion (from 35.9 +/- 2.1 to 72.9 +/- 6.0 mmol/5 h; P < 0.01). Clearance calculations, based on maximal water diuresis, were compatible with increased distal Na and volume delivery. Canrenoate alone modestly increased basal cumulative NaCl excretion and had no effect on K excretion. However, canrenoate blunted the kaliuresis after the KCl load (51.9 +/- 4.4 mmol/5 h; P < 0.05 compared to KCl alone) and stimulated natriuresis in a complementary way. Clearance data were compatible with diminished distal Na reabsorption and K secretion in response to an undisturbed KCl-induced increase in distal Na delivery. RU486 did not influence the excretion of the KCl load or its effects on renal sodium handling parameters, although effective glucocorticoid receptor blockade was likely to be present in view of the increase in plasma cortisol. These data suggest that in healthy humans, mineralocorticoid activity, but not glucocorticoid activity, is involved in the elimination of a K load. The latter contrasts with data in adrenalectomized animals, in which situation glucocorticoid as well as aldosterone are indispensible for normal K tolerance.

1. Potassium salts increase sodium excretion in humans. To define the role of the potassium ion in this effect, we compared the effects of equimolar single oral loads of 100 mmol of NaCl and KCl on renal electrolyte excretion in seven healthy subjects. In a second group (n = 7), we infused equimolar loads of NaCl or KCl (0.75 mmol/kg in 2 h). 2. In both experiments the KCl load quickly increased plasma potassium and aldosterone concentrations and potassium and sodium excretion to a maximum by 2 h after the load, whereas the NaCl load had no such effect. 3. In a third group (n = 7) we compared the effects of single oral loads of KCl and KHCO3 (1 mmol/kg), to assess the role of the anion in the natriuretic effect of potassium salts. 4. KCl and KHCO3 transiently stimulated urinary excretion of potassium and sodium in an identical manner. 5. We also followed the changes in acid excretion over time. Whereas both KCl and KHCO3 loading decreased acid excretion, this effect was greater after KHCO3 loading. Interestingly, acid excretion did not decrease further after the first collection hour after the potassium load, although the plasma potassium concentration was still increasing. 6. From these data we conclude (1) that increased excretion of sodium, potassium and chloride and decreased excretion of protons after administration of potassium salts are the specific effects of the potassium component; (2) that potassium also appears to have secondary, indirect effects on proton excretion, the mechanism of which remains to be clarified.

Insulin increases sodium reabsorption in diluting segment in humans: Evidence for indirect mediation through hypokalemia. To examine the mechanism of renal sodium (Na) and potassium (K) retention during insulin infusion, seven healthy volunteers underwent clearance studies without (time control) and with insulin infusion (40mU bolus, followed by 1 mU/kg/min for 150 min). Maximal free water clearance and fractional lithium clearance (FELi) were used to analyze renal sodium handling. Insulin decreased Na excretion (from 189 ± 25 to 121 ± 19 µmol/min, P < 0.01) and K excretion (from 64± 8 to 19 ± 1 µmol/min, P < 0.01), but did not change in glomerular filtration rate. FELi increased from 29.8 ± 1.9 to 32.3 ± 1.9% (P < 0.05), minimal urine osmolality decreased from 59 ± 3 to 46 ± 3 mOsm/kg (P < 0.01), and the diluting segment reabsorption index increased from 88.0 ± 0.9 to 93.7 ± 0.9%, P < 0.01). Insulin also decreased plasma K, from 3.91 ± 0.08 to 3.28 ± 0.08 mmol/liter, P < 0.01. In a third clearance study KCl was infused simultaneously (3.75 µmol/kg/min) to prevent this fall in plasma K. In this study insulin had no effect on Na and K excretion and diluting segment reabsorption, but the rise in FELi remained. In a fourth clearance study NaCl (3.75 µmol/kg/min) instead of KCl was infused together with insulin. This manoever did not prevent the Na and K retaining effect of insulin, nor any of its effects on renal sodium handling parameters. These data suggest that Na and K retention during insulin infusion are largely secondary to hypokalemia, which causes increased reabsorption in the diluting segment.

Lumbar cerebrospinal fluid (CSF) norepinephrine concentrations determined by radioenzymatic assay in 9 patients with caudate atrophy associated with Huntington's disease were lower (p < 0.02) than those in 9 age- and sex-matched control patients. Preoperative lumbar CSF norepinephrine concentrations were determined in 5 patients undergoing stereotaxic thalamotomy. No significant alterations in prestimulation lumbar CSF norepinephrine levels were recorded 12 days after electrode installation and thalamic coagulation. Lumbar CSF norepinephrine concentrations were reduced (p < 0.03), however, 12 hours following intermittent selective electrical stimulation of the caudate nucleus. These data suggest that noradrenergic pathways in man are (1) impaired in Huntington's disease and (2) inhibited by direct caudate stimulation.

✓ The authors describe the use of temporal lobectomy following careful and repeated electroencephalogram (EEG) evaluation (with implanted electrodes in otherwise unresolvable cases) in the epileptic group characterized by automatisms (psychomotor seizures) with temporal epileptiform activity complicated by EEG foci in the opposite temporal lobe or by extratemporal activity. They found that this can render a significant number of patients (between 25% and 50%) either seizure-free or with significant and useful reduction in their seizure frequency. The cure and improvement rates of cases followed up after temporal resection with or without prior study with implanted electrodes were approximately equal. However, the implanted electrodes permitted surgical treatment of certain cases which would have been rejected on the basis of evidence derived from the scalp recordings alone. Of 28 of these 34 patients with persisting EEG epileptiform activity in the postoperative period, only one had such activity in a different location in a follow-up period of 6 years. No evidence of spreading epileptic activity or appearance of “mirror foci” was seen during a follow-up period averaging 8.2 years. Seizure remission up to 15 years with eventual recurrence of the original seizure type may occur following surgical therapy. Follow-up studies of surgical epileptic treatment of less than 3 to 5 years are of doubtful value.

In 1962, Chanceet al. demonstrated the feasibility of monitoring intramitochondrial NADH levelsin vivo. To extend this capability to the neurosurgical operating room on a practical basis, and to enable a comparison of metabolic changes in two different cortical areas a dual-beam long-focal-length fluorometer for the direct measurement of NADH fluorescence changes was designed.

After an “occipital lobectomy” that resulted in a severe dyslexia and a moderate dysgraphia-dyscalculia, anatomical study showed damage to the posterior extremity of the angular gyrus and degeneration in the posteroinferior pulvinar. This is in contrast to an earlier case that had degeneration in the anterosuperior pulvinar associated with a small anterior temporoparietal infarct and a well-documented receptive-expressive aphasia. However, the role of the pulvinar in speech function remains uncertain. The surgeon should be aware of the short distance between the angular gyrus and both the midline and the occipital pole because a lesion here during an “occipital lobectomy” produces a distressing and durable speech impairment.

Cancer involving the ethmoid and sphenoid frontal sinus complex can be successfully eradicated by a combined transcranial and transfacial surgical dissection. Survival rates of 44 to 58 percent with a 3 percent hospital mortality rate in patients whose previous surgery or radiotherapy was largely unsuccessful suggest that this cosmetically acceptable surgical endeavor should be used more often by the head and neck surgeon in treating paranasal sinus cancer. Utilizing the principles of antibiotic prophylaxis, strict attention to principles of tumor removal and surgical technique, and the talents of the combined surgical and neurosurgical team, this aggressive surgical approach to the paranasal sinuses can be safely and successfully carried out. The approach described herein has the following advantages: it allows accurate evaluation of intracranial tumor extension while protecting the intracranial contents, it essentially avoids cerebrospinal fistulization, it provides adequate exposure for hemostasis, facilitates en bloc tumor resection, selectively conserves the orbital contents, and provides patient survival rates up to 58 percent for paranasal cancer that involves the ethmoid and sphenoid frontal sinus complex.

ALIGNANT tumors of the paranasal sinuses account for but a small percentage of human neoplastic disease. This amounts to about 3 % of all cancer of the upper respiratory and alimentary tracts or approximately 0.2 % of all human cancers. TM Watson TM found an incidence of 0.44 % of cancer of the paranasal sinuses in a total of 26,062 patients admitted for malignant disease at Memorial Hospital. Nevertheless, serious study of these patients is merited not only because of the peculiarly unpleasant suffering these patients undergo in the terminal period but because it has been found practical to eradicate the disease in a relatively high proportion of patients. It should be re-emphasized that only histologically malignant tumors are under present consideration. From a statistical point of view, several features suggest that radical therapy should provide a high cure rate. Some 80 % of tumors of the paranasal sinuses are estimated to arise in the maxillary sinus which has long been considered a surgically accessible site. 1 The tumors, appearing as they most commonly do in the fifth to seventh decade, are predominantly carcinomas or adenocarcinomas and frequently of slow-growing type. 8 Certainly one of the greatest difficulties in treatment is diagnosis of the tumor in an early stage. Often, many months of symptomatic treatment is prescribed for the protean symptoms of nasal obstruction, local pain, and epistaxis before a definitive diagnosis of malignancy is made. Despite the late diagnosis, metastases are relatively uncommon. Of 68 patients with cancer of the nasal cavity, MacComb and Martin ~x found that 12 % had metastases on admission and only 17% had metastases later in their course. This incidence is approximately the same as that of Ashley Received for publication July 13, 1967. and Schwartz I who noted at autopsy that only 25 % of maxillary carcinomas spread beyond the local area. Metastases usually appeared in the retropharyngeal and superior cervical lymph nodes if the primary tumor was in the superior and medial portion of the antrum. Tumors involving the floor and lateral wall were more prone to show metastases in the submandibular lymph nodes. Taken together, these features encourage surgical attack upon the local lesion. Unfortunately, hopes of an en bloc resection through a facial approach can only be realized in the cases with very small lesions, since tumors, even if primary in the antrum, seldom remain there. The common extension of tumor into the ethmoidal sinus and the impossibility of removing this sinus en bloc through a facial approach is a particular deterrent to resection, since even as late as 1963, FrazeU and Lewis 6 warned that "the entire cribriform plate can rarely be resected without creating cerebral complications .... "

Clinical neurologists and neurosurgeons are beginning to realize the usefulness of quantitative testing batteries to augment the qualitative measurements of the standard neurological examination in evaluating treatments for neurological diseases. This paper briefly reviews the literature on the subject, defines what is meant by a clinical quantitative neurological test, discusses the advantages of quantitative testing, considers some essential ingredients in constructing a quantitative testing system, and describes the battery of tests which is being used currently by the authors. A sample of patients from a recent study of the efficacy of thalamotomy in Parkinson’s disease is used to develop an example illustrating the usefulness of quantitative testing.

Summary The combined intracranial transfacial approach to the ethmoid, sphenoid, and frontal sinuses has been satisfactory in performing en bloc resection of cancer arising in or involving these anatomic areas. Fifty-four patients have been treated with this procedure, using the combined expertise of the neurosurgeon and the surgeon interested in the head and neck area. Two postoperative deaths have occurred, both attributed to meningitis. The long range postoperative morbidity is negligible, except as it relates to loss of the palate in all but eight patients and the orbital contents in thirty patients. The cumulative five year survival in this series of patients, forty-two of whom had failure of previous treatment, is 56 per cent. If the procedure is carried out with rigid attention to good surgical technic and the principles of en bloc tumor removal, this combined procedure has the following advantages: (1) allows accurate evaluation of the intracranial tumor extension, (2) protects the brain, (3) avoids cerebrospinal fistulization, (4) provides adequate hemostasis, (5) facilitates en bloc tumor resection, and (6) selectively conserves the orbital contents.

A stereotaxic radiotherapy technique that permits accurate delivery of highly localized dose to a small intracranial target has been developed. The technique facilitates precise integration of the diagnostic and therapeutic procedures including target localization, treatment planning, simulation, repetitive patient irradiation, and daily treatment verification. A conventional linear accelerator and computed tomography scanner as well as special diagnostic and therapeutic guides are used. A suitable dosimetric distribution is achieved using arc therapy with small radiation fields and 10-MV x rays.

SUMMARY Four patients with seizures of presumed temporal lobe origin are presented in whom a definite focal ictal onset in the orbitofrontal cortex was revealed during recording, either by chronically implanted electrodes or ECoG. In three cases automatisms occurred concomitantly with orbitofrontal activation without spread of paroxysmal activity into the temporal structures monitored. With eight additional cases of possible orbitofrontal epilepsy found on reviewing the literature, two subgroups emerge: (1) patients with primarily psychomotor-type fits, and (2) patients with loss of consciousness, head and eye deviation, and generalized convulsions. Scalp EEGs, in patients on whom we have available data, manifested bilaterally synchronous, paroxysmal discharges which were bifrontal, frontopolar, or maximal in one anterior quadrant, with or without evidence of additional temporal lobe involvement. On the basis of anatomic and physiological studies, as well as our own electrographic data, it is felt that a posterior orbitofrontal and temporo-limbic, or mesial orbitofrontal and parasagittal-limbic relationship exists, within which autonomous epileptogenic zones may develop, with the ability to discharge directly and independently to subcortical centers, while eliciting similar clinical patterns. RESUME On a etudie 4 malades ayant des crises supposees ďorigine temporale, dans lesquelles un debut critique focal bien precis dans le cortex orbito-frontal etait revele pendant Ľenregistrement, soit par des electrodes implantees chroniques, soit par ECoG. Dans 3 cas, des automatismes se manifestaient simultanement a une activation orbitofrontale, sans que Ľactivite paroxystique s'etende aux structures temporales enregistrees. Avec 8 cas en plus ďeventuelle epilepsie orbitofrontale, decouverts en revoyant la litterature, on peut distinguer 2 sous-groupes: (1) les malades presentant essentiellement des crises temporales (2) et les malades ayant des pertes de conscience, deviation de la tete et des yeux, et convulsions generalisees. Les enregistrements EEG chez les malades pour qui nous avons des donnees valables, montraient des decharges paroxystiques synchrones et bilaterales qui etaient bifrontales, frontopolaires ou maximum dans une region anterieure avec ou sans participation additionnelle evidente du lobe temporal. En se basant sur des etudes anatomiques, et physiologiques aussi bien que sur nos propres donnees electrographiques, on pense qu'il existe une relation entre la region orbitofrontale posterieure et temporale limbique ou orbitofrontale mesiale et limbique parasagittale, dans lesquelles des zones epileptogeniques pourraient se developer, avec la possiblite de decharges directement et independamment vers les centres subcorticaux, en provoquant des manifestations cliniques semblables. RESUMEN Se han presentado 4 pacientes con ataques de presumible origen temporal, en los que se encontro un claro comienzo focal del ataque en la corteza orbitofrontal, durante el registro mediante electrodos implantados permanentemente o electrocorticograma. En tres de estos enfermos los automatismos ocurrieron simultaneamente con activacion orbitofrontal sin propagacion de la actividad paroxistica a los lobulos temporales, tambien monitorizados. Tras el estudio de ocho casos adicionales de posible epilepsia orbito-frontal, registrados en la literatura, se pueden extraer los siguientes subgrupos: (1) enfermos que presentan, princi-palmente, ataques psicomotores, y (2) enfermos con perdida de conocimiento, rotacion de cabeza y ojos y convulsiones generalizadas. En enfermos en los que hemos recogido information, los EEGs habituates mostraron descargas paroxisticas, bilaterales y sincronas de presentation bifrontal, frontopolar o dominando en uno de los cuadrantes anteriores, con o sin evidencia de afectacion adicional de uno de los lobulos temporales. Basandose en los estudios anatomicos y fisiologicos, unidos a nuestra information electroencefalografica, es possible aceptar una relation entre las regiones orbitofrontal posterior y limbico-temporal o entre las regiones orbitofrontal medial y parasagital limbica, con capacidad epileptogenica autonoma en cada una de dichas zonas y la posibilidad de descargar directa e indepen-dientemente sobre centros subcorticales dis-tintos con manifestaciones clfnicas semejantes. jantes. ZUSAMMENFASSUNG Vier Patienten werden besprochen, bei denen Temporallappen-Anfalle vermutet wurden. Die Ableitungen mit chronisch im-plantierten Elektroden bzw. Des Elektro-corticogramms liessen eindeutig den fokalen Anfallsbeginn im orbitofrontalen Cortex erkennen. Bei drei Patienten zeigten sich Auto-matismen gleichzeitig mit der orbitofrontalen Aktivierung, ohne dass eine Ausbreitung der paroxysmalen Aktivitat in die temporalen Strukturen erkennbar war. Unter Beruck-sichtigung von 8 zusatzlichen Patienten mit vermuteter orbitofrontaler Epilepsie aus der Literatur, lassen sich zwei Untergruppen unterscheiden: (1) Patienten mit Anfallen primar vom psychomotorischen Typ und (2) Patienten mit Bewusstseinsverlust, Deviation von Kopf und Augen und generalisierten Krampfen. Soweit Oberflachen-EEGs dieser Patienten verfugbar sind, zeigen sich bilateral synchrone, paroxysmale Entladungen bifrontal, frontopolar oder mit Betonung in einem vorderen Quadranten mit oder ohne Hinweise auf zusatzliche Einbeziehung des Temporallappens. Aufgrund anatomischer und physiologischer Untersuchungen sowie unserer eigenen elektro-graphischen Daten werden hintere orbitofrontale und temporal-limbische oder mesiale orbitofrontale und parasagittal-limbische Ver-bindungen angenommen innerhalb derer auto-nome epileptogene Zonen sich entwickeln konnen. Sie haben die Fahigkeit, direkt und unabhangig nach subcortikalen Zentren sich zu entladen, und dabei ahnliche klinische Muster auszulosen.

✓ This series included five patients who had suffered 8 to 23 years of severe, medically intractable seizures without remission, severe socioeconomic handicaps, and an average of over one seizure a day on hospital observation and by history. All had combinations of partial and general seizures with focal and/or bilaterally synchronous epileptiform activity consistently on multiple electroencephalograms (EEG's). One patient had nearly continuous myoclonic activity. Serum levels of phenytoin, primidone, and phenobarbital were adjusted to therapeutic ranges. Three patients had additional medication (diazepam, ethosuximide). Cerebellar biopsy in three patients showed reduction in Purkinje cells. After implantation of cerebellar stimulators, seizure frequency was evaluated in hospital during three or four admissions for 4- to 6-week periods over the ensuing 15 to 21 months. No slow trends toward improvement or deterioration were noted. No significant differences in seizure frequency were found when comparing intervals of about 7 days of on-and-off stimulation both in the double-blind and unblinded conditions. No changes in EEG or Intelligence or Memory Quotients occurred unaccounted for by variations in serum levels of antiepileptic drugs. Despite the lack of objective improvement, patient and family acceptance of cerebellar stimulation was positive to enthusiastic. A rise in CSF norepinephrine and a fall in gamma aminobutyric acid (GABA) accompanied cerebellar stimulation and may be related to the results.

This study is based on 28 patients with intractable seizures in whom exclusively extratemporal or a combination of temporal and extratemporal electrodes were chronically implanted for the localization of the epileptogenic process and possible surgical treatment. Clinical and electrographic data are briefly summarized, the indications for the use of implanted electrodes are outlined, and the number and position of the electrodes and the findings in each individual case are given. Four illustrative examples are described in greater detail. Mainly on the basis of data derived from this particular technique of investigation, surgical treatment was eventually carried out in 14 patients. It is concluded that the use of implanted electrodes in seizure disorders of probable extratemporal origin can be of real diagnostic benefit in certain specific situations. In most instances, however, this technique simply serves to demonstrate the complexity of an apparently simple case or, of greater clinical consequence, might tend to oversimplify cases that are actually very complex. Indeed, many data in this study raise some doubts about the validity of the classic concepts of “focal” epilepsy.

Lumbar cerebrospinal fluid norepinephrine concentrations were determined by radioenzymatic assay in five epileptic patients receiving double-blind cerebellar stimulation and in three epileptic patients with subdural cerebral surface electrodes. Mean CSF norepinephrine levels were significantly elevated by chronic cerebellar stimulation and significantly depressed after intermittent cerebral cortical stimulation. Lumbar CSF cyclic adenosine monophosphate levels determined by radioimmunoassay were not significantly altered by either cerebellar or cerebral surface stimulation. Our study suggests that (1) electrical stimulation of the anterodorsal cerebellum in man evokes alterations in noradrenergic metabolism. Cerebellar stimulation-induced elevations in norepinephrine may inhibit cerebellar, cerebral, and spinal neuronal activity. In addition, (2) noradrenergic responses to brain surface stimulation may exhibit regional specificity, and (3) noradrenergic alterations evoked by cerebral surface stimulation may not mimic those induced in isolated brain preparations.

Mechanisms for perception and memory were probed by electrical stimulation via chronic electrodes in the human thalamus. Stimulation within the left pulvinar nucleus induced transient dysphasia and a retrograde loss in recent memory for verbal memoranda. In contrast, comparable stimulation of the right pulvinar failed to disrupt verbal behavior and, instead, disabled the mechanism for discrimination and recognition of complex visual patterns. The findings suggest that an asymmetry in the functional organization of linguistic and nonverbal processes appears to exist at the level of the lateral thalamus. The hypothesis is advanced that the pulvinar scans incoming sensory traces and searches long-term memory registers for appropriate cues and labels.

In 14 patients operated upon for focal cerebral seizures under local anesthesia, cortical electrical activity was compared with the levels of nicotinamide adenine dinucleotide (NADH) observed fluorometrically. NADH levels fell 3 to 15% in response to 5-second intervals of cortical stimulation in 42 of 70 observations. Although a rough correlation was seen between the quantity of current delivered (milliamperes X seconds) and the NADH decrease, this varied from case to case. The presence of cortical afterdischarge often, but not invariably, corresponded to a greater percentage of change in the NADH levels. Averaging the NADH response to sporadic interictal epileptiform discharges failed to demonstrate concomitant NADH reductions. A similar lack of change was seen in four patients in whom low frequency spike foci were induced by topically applied penicillin in cortex destined for excision. Preliminary studies of the topography of spread of NADH change after cortical stimulation indicate that this is usually asymmetrical in human epileptogenic cortex. Under experimental conditions in cats, it seemed possible to differentiate primary from projected epileptiform activity, in that the projected activity had little or no concomitant fall in the NADH level after the electrographic spike. Pathological examination of the excised sites of NADH recording showed, with one exception, fibrous astrocytic transformation of the central cortex layers.

Cerebellar biopsy specimens were obtained at the time of cerebellar electrode installation in three epileptic patients. Cerebellar autopsy specimens also were examined from four epileptic patients and from five patients without epilepsy or neurologic disease. All specimens from seizure patients showed isomorphic gliosis of the cerebellar cortices. Significantly lower Purkinje cell densities were found in epileptic patients as compared with nonepileptic control patients. Our two epileptic patients showing marked Purkinje cell loss before cerebellar stimualtaion appeared to have better seizure control during stimulation than the patient who had only mild reduction in Purkinje cell density. These data suggest that augmentation of Purkinje cell inhibitory discharges in not the dominant mechanism for seizure suppression during cerebellar stimulation. Comparison of cerebellar specimens obtained during electrode installation with those obtained later during electrode revisions may have been prognostic significance.

BECAUSE of its accessibility and the myriad responses induced by its stimulation, the cerebral cortex has intrigued many investigators since Fritsch and Hitzig 1 demonstrated its electrical excitability, in 1870. Spencer's 2 careful work, published in 1894, showed that autonomic, as well as somatic, functions were represented at the cortical level. Since the work of these pioneers much has been added to our knowledge, and this knowledge has increasingly been applied to clinical problems. The present paper is a summary of the results of a series of experiments on dogs, presented with the hope that it may serve as a guide to a better understanding of the mechanism of action of the human cerebral cortex in relation to autonomic functions. The term "feeding pattern" is intended to imply the actions of the most rostral part of the digestive tract during the ingestion of food. Specifically, our observations dealt with tongue

A patient, suffering from syringomyelia for 34 years and syringobulbia for 27 years, has been under our care for the past 10 years. The symptoms and neurological signs were typical, both developed or rapidly became worse after a minor injury. On three occasions the patient was almost completely disable because of sensory and motor dysfunctions; and, without exceptions, his misery was relieved by surgical drainage of the syrinx.

THE PRESENT studies were made on a group of 50 patients studied in collaboration with the Branch of Endocrinology of the National Cancer Institute over a period of approximately two years. Nearly all of the patients were undertaken for the palliation of metastatic breast carcinoma. They were accepted only after oophorectomy in the premenopausal women who had reached their maximum benefit from palliative x-rays and endocrine therapy. In addition, a number of patients had had chemotherapy for their metastatic disease. It became evident rather early in the series that a beneficial response from oophorectomy or endocrine therapy was a rather uncertain indicator of the outcome of the pituitary ablation. Although many patients who had previously responded favorably to the treatment also responded favorably to pituitary ablation, others did not; and, it was soon found that certain patients who had not responded favorably before would respond with remission to pituitary ablation.