Anticardiolipin antibodies in hemodialysis patients with hepatitis C and their role in fistula failure.

BACKGROUND/AIMS: Several conflicting results are presently reported regarding raised IgG and IgM-anticardiolipin antibodies (ACA) titers in hemodialysis (HD) patients and their role in vascular access dysfunction. We aimed to determine the prevalence of both IgM and IgG-ACA titers and to analyze retrospectively their role in primary and secondary arteriovenous fistula (AVF) failure in a homogeneous group of HD patients with chronic hepatitis C. METHODS: This study included 103 adults on maintenance hemodialysis with chronic hepatitis C infection. All participants had blood samples drawn predialysis and after an overnight fast. Analysis included biochemistry, IgG and IgM ACA, Anti-HCV, HBsAg, serum HCV RNA and HCV genotyping. RESULTS: The prevalence of IgG-ACA was 14.6% (15/103). No patient had a positive value of the IgM-ACA test. HCV replication was detected in 52 of 76 patients. The most common HCV genotype was genotype 1 (90%). The percentage of females was higher in ACA(+) group (p = 0.038). There were no significant differences between subjects with and without ACA-IgG regarding other parameters studied. No difference in regard to AVF survival was detected between ACA(+) and ACA(-) groups (p > 0.05). CONCLUSION: We found no significant differences in primary or secondary AVF failure between patients with elevated and normal ACA. Therefore, we conclude that AVFF may be caused by factors other than ACA in these patients. More prospective studies are needed to confirm this observation.

Does the direction of arterial needle in AV fistula cannulation affect dialysis adequacy?

AIM: The direction of arterial access needles in fistulas and grafts has been a subject of some controversy and there is no study comparing the results either direction of arterial needle placement in cannulation of arteriovenous fistula. We compared mean urea reduction rate (URR) and Kt/V in the same HD patients when dialyzed via antegrade or retrograde arterial needle cannulation. MATERIALS AND METHODS: This was a study involving 22 adults on maintenance hemodialysis for more than 6 months. Doppler US examinations of arteriovenous fistula were performed in all subjects. Pre-dialysis and post-dialysis blood samples were obtained at the patient's midweek HD treatment 4 times a month for each direction. Arterial needle was placed in retrograde direction for the first month. On the second month, the direction of arterial needle was converted to antegrade. Means were compared by paired t-test. RESULTS: Mean URR and eKt/Vof retrograde cannulation were 74.2+/-7.2% and 1.57+/-0.33. The results were indifferent statistically from those of antegrade cannulation (73.0+/-8.7% and 1.57+/-0.35 (p=0.123)). Mean fistula blood flow was 931 +/- 483 ml/min. No cannulation complication was observed during the study period for both directions. CONCLUSIONS: Both antegrade and retrograde arterial needle placement may be preferred according to center experience without concern of HD adequacy. Longterm outcomes of antegrade and retrograde arterial needle placement such as AVF failure, thrombosis, and stenosis warrant further studies.

Clinical significance of elevated antinuclear antibody test in patients with Hodgkin's and Non-Hodgkin's lymphoma: a single center experience.

AIM: There is an increased risk of lymphoma subsequent to autoimmune conditions. Autoimmune disorders may occur in the course of lymphomas. In this study, the association of autoimmunity and related autoantibodies within non-Hodgkin's (NHL) and Hodgkin's lymphoma (HL) patients has been investigated. METHODS: The study enrolled 119 patients affected by NHL and 60 patients affected by HL for the presence of autoantibodies and autoimmune diseases. Afterwards, the results between the two lymphoma groups have been confronted. RESULTS: Autoimmune diseases were diagnosed in eight (6.7%) patients with NHL and three patients with HL (5%) (P=0.651). Thirty-four (28.5%) patients with NHL and 14 (23.3%) patients with HL displayed autoantibody positivity (P=0.083). As regards HL cases, antinuclear antibodies (ANA) were detected in 12 (20%) and anti PM-Scl in two patients (3.3%). None the patients had anti Jo-1, anti Scl-70, anti Sm, anti nRNP/Sm, anti single-stranded DNA (anti-ssDNA), anti double-stranded DNA (anti-dsDNA), antihistones, antinucleosomes, anti SS-A, anti SS-B or anti CENP-B autoantibodies. In patients affected by NHL ANA was detected in 16 (13.4%), anti SS-A and anti SS-B in two (1.7%), anti CENP-B in eight (6.7%) and anti PM-Scl in eight patients (6.7%). None of the patients had anti Jo-1, anti Scl-70, anti Sm, anti nRNP/Sm, anti ssDNA, antihistones or antinucleosome antibodies. There was a statistically significant difference between patients with HL and NHL in terms of anti CENP-B positivity (P=0.040). CONCLUSION: In conclusion, ANA and related autoantibodies can frequently be detected during lymphoma treatment. However, the majority of lymphoma patients with positive ANA did not display autoimmune diseases, demonstrating the lack of a strict correlation between the presence of ANA and autoimmune diseases.

Differences in the auxological characters of children with short stature - Differential diagnostic possibilities of hypothyreosis.

This study aimed to define the differences in growth characteristics in the three most frequent causes of growth retardation - growth hormone deficiency, hypothyreosis and constitutional delay of growth and development - in order to provide diagnostic means for distinguishing these disorders. The study included 166 children with growth disorders aged 4-18 years. The height for age, the bone age using the TW3 method, the predicted height as the target height and the current prediction using the TW3 method were studied. For bone age, the radius, ulna and short bones compartment (RUS) and carpal bones (CARP) were evaluated separately and the difference in their delay in relation to chronological age (ΔBA_RUS_CARP) was determined. The relationship of the studied variables with sex and the underlying diagnosis was tested and the relationship of hypothyreosis and growth data was estimated. The model was tested on the growth data of 104 randomly selected patients with a growth disorder. The largest significant distinction was demonstrated by the difference ΔBA_RUS_CARP in hypothyreosis. The created linear regression model was highly statistically significant (χ2 = 19.4, p < 0.0001) and showed high selectivity (0.609, 95% CI 0.409; 0.808) as well as high specificity (0.864, 95% CI 0.781; 0.946). The clinical validity of the model demonstrated a 61% predictive value for the detection and an 81% successful specification of hypothyreosis. The study demonstrated the possibility of distinguishing suspected hypothyreosis from other causes of growth retardation based on differences in severity of the ossification delay in skeletal compartments of the hand.

Atrophy in Neovascular Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report Number 15.

PURPOSE: To identify the development and progression of macular retinal pigment epithelial atrophy in eyes with neovascular (CNV) age-related macular degeneration (AMD) and to correlate with visual acuity (VA). DESIGN: Cohort study. PARTICIPANTS: Age-Related Eye Disease Study 2 (AREDS2) participants with intermediate AMD enrolled in a randomized controlled clinical trial of oral supplements. Analyses were conducted in the subset of AREDS2 participants who were also enrolled in the fundus autofluorescence ancillary (FAF) ancillary study. METHODS: Color photographs and FAF images were evaluated in eyes that developed CNV. Presence of geographic atrophy (GA) prior to the incidence of CNV and the development of macular atrophy following incident CNV were assessed. Areas of hypoautofluorescence representing atrophy were measured for area and macular involvement. Enlargement rate of atrophy and change in visual acuity over time were analyzed. MAIN OUTCOME MEASURES: incidence and enlargement rate of atrophy and VA changes in eyes with incident CNV. RESULTS: Incident CNV developed in 334 (9.2%) of eyes evaluated in the AREDS2 FAF substudy. Of these, 40% had macular atrophy at incidence of CNV with half of these attributable to pre-existing GA. Atrophy developed in 14.7 % of eyes over 4 years of follow-up. Mean area of atrophy was largest in eyes with pre-existing GA and CNV (5.17 mm2, p<0.001), and atrophy involved the center of the macula in > 65% of eyes. Mean VA letter score at the annual visit in which CNV was documented was similar in the three groups with atrophy; eyes with CNV and pre-existing GA, incident atrophy at the first visit with CNV, and atrophy during follow up (60 letters). Enlargement rate of atrophy was also similar in eyes in the three groups (1.23 - 1.86 mm2, p = 0.47). Eyes with macular atrophy lost more visual acuity compared to eyes without atrophy, particularly after 2 years of follow-up (-10.9 vs. - 3.6 letters, p = 0.07). CONCLUSION: Atrophy is commonly seen in neovascular AMD and often can be attributed to pre-existing GA. Macular atrophy and GA appear to be a continuum of the same disease process and are both associated with poor vision.

Randomized trial of peribulbar triamcinolone acetonide with and without focal photocoagulation for mild diabetic macular edema: a pilot study.

OBJECTIVE: To provide pilot data on the safety and efficacy of anterior and posterior sub-Tenon injections of triamcinolone either alone or in combination with focal photocoagulation in the treatment of mild diabetic macular edema (DME). DESIGN: Prospective, phase II, multicenter, randomized clinical trial. PARTICIPANTS: One hundred nine patients (129 eyes) with mild DME and visual acuity 20/40 or better. METHODS: The participants were assigned randomly to receive either focal photocoagulation (n = 38), a 20-mg anterior sub-Tenon injection of triamcinolone (n = 23), a 20-mg anterior sub-Tenon injection followed by focal photocoagulation after 4 weeks (n = 25), a 40-mg posterior sub-Tenon injection of triamcinolone (n = 21), or a 40-mg posterior sub-Tenon injection followed by focal photocoagulation after 4 weeks (n = 22). Follow-up visits were performed at 4, 8, 17, and 34 weeks. MAIN OUTCOME MEASURES: Change in visual acuity and retinal thickness measured with optical coherence tomography (OCT). RESULTS: At baseline, mean visual acuity in the study eyes was 20/25 and mean OCT central subfield thickness was 328 mum. Changes in retinal thickening and in visual acuity were not significantly different among the 5 groups at 34 weeks (P = 0.46 and P = 0.94, respectively). There was a suggestion of a greater proportion of eyes having a central subfield thickness less than 250 mum at 17 weeks when the peribulbar triamcinolone was combined with focal photocoagulation. Elevated intraocular pressure and ptosis were adverse effects attributable to the injections. CONCLUSIONS: In cases of DME with good visual acuity, peribulbar triamcinolone, with or without focal photocoagulation, is unlikely to be of substantial benefit. Based on these results, a phase III trial to evaluate the benefit of these treatments for mild DME is not warranted.

Metabotropic Glutamate 2/3 Receptors and Epigenetic Modifications in Psychotic Disorders: A Review.

Schizophrenia and Bipolar Disorder are chronic psychiatric disorders, both considered as "major psychosis"; they are thought to share some pathogenetic factors involving a dysfunctional gene x environment interaction. Alterations in the glutamatergic transmission have been suggested to be involved in the pathogenesis of psychosis. Our group developed an epigenetic model of schizophrenia originated by Prenatal Restraint Stress (PRS) paradigm in mice. PRS mice developed some behavioral alterations observed in schizophrenic patients and classic animal models of schizophrenia, i.e. deficits in social interaction, locomotor activity and prepulse inhibition. They also showed specific changes in promoter DNA methylation activity of genes related to schizophrenia such as reelin, BDNF and GAD67, and altered expression and function of mGlu2/3 receptors in the frontal cortex. Interestingly, behavioral and molecular alterations were reversed by treatment with mGlu2/3 agonists. Based on these findings, we speculate that pharmacological modulation of these receptors could have a great impact on early phase treatment of psychosis together with the possibility to modulate specific epigenetic key protein involved in the development of psychosis. In this review, we will discuss in more details the specific features of the PRS mice as a suitable epigenetic model for major psychosis. We will then focus on key proteins of chromatin remodeling machinery as potential target for new pharmacological treatment through the activation of metabotropic glutamate receptors.

Relation between dietary intake, serum concentrations, and retinal concentrations of lutein and zeaxanthin in adults in a Midwest population.

BACKGROUND: Information on concentrations of retinal carotenoids (macular pigment, or MP) is of particular interest because MP protects against age-related macular degeneration, the leading cause of irreversible blindness in the United States. OBJECTIVE: This study was designed to evaluate the relation between dietary intake, blood concentrations, and retinal concentrations of carotenoids in a large group of volunteers. DESIGN: Two hundred eighty volunteers in the Indianapolis area completed health and diet questionnaires, donated a blood sample, and participated in MP density assessment to determine retinal carotenoid status. Dietary intake was assessed by food-frequency questionnaire. Serum concentrations of lutein, zeaxanthin, and beta-carotene were measured by HPLC. MP optical density (MPOD) was determined psychophysically with a 460-nm, 1 degrees test stimulus. RESULTS: Average MPOD was 0.21 +/- 0.13. Average intakes of lutein + zeaxanthin and beta-carotene were 1101 +/- 838 and 2935 +/- 2698 microg/d, respectively. Although several key dietary intake variables (eg, lutein + zeaxanthin and beta-carotene) differed by sex, no significant sex differences were found in either serum concentrations of lutein and zeaxanthin or MPOD. Serum beta-carotene concentrations were significantly higher in women than in men. Serum lutein + zeaxanthin and dietary intake of lutein + zeaxanthin were significantly correlated and significantly related to variations in MPOD (r = 0.21, P < 0.001, and r = 0.25, P < 0.001, respectively). CONCLUSIONS: Retinal carotenoids can be measured in epidemiologic studies. In this study, MPOD was associated with lutein + zeaxanthin in the diet and the serum. Retinal concentrations, however, were influenced by other factors as well. To understand the effect of dietary lutein + zeaxanthin intake on the retina and risk of age-related eye disease, future studies should include measures of macular concentrations of these pigments.

Microvascular retinopathy in the Zucker diabetic fatty rat.

PURPOSE: To determine if quantifiable morphometric signs of retinopathy occur in the Zucker diabetic fatty rat (ZDF/Gmi-fa, formerly designated ZDF/Drt), a partially inbred strain in which the genetic propensity for diabetes is only expressed in obese males. METHODS: Retired diabetic (ZDF/Gmi-fa) and control lean Zucker (fa/+) breeder rats were examined for quantifiable evidence of microvascular changes of the retinal capillaries by gross examination, trypsin digestion of retinal vessels, and transmission electron microscopy. RESULTS: Gross examination of retinas and trypsin digestion of capillaries revealed no differences. Quantitative assessment of capillary cell nuclear density showed that diabetic retinas were hypercellular compared to lean rats (3.888 +/- 0.041 versus 3.304 +/- 0.046 nuclei per 100 microns (mean +/- SE), P = 0.0042). Transmission electron microscopic analysis of retinal capillary basement membrane thickness demonstrated thicker measurements in diabetic animals (mean thickness 21% greater in diabetic rats, P = 0.0307). CONCLUSIONS: This model may be useful for pharmacologic intervention studies because it is naturally and severely non-insulin-dependent diabetic, there are quantifiable retinal vascular changes, and same-sex litter mates can be used as controls.

HRP/trypsin technique for studies of the retinal vasculature.

The HRP/trypsin technique is a new histologic method for the light microscopic study of the retinal blood vessels. A two-stage procedure, the first step results in a retinal whole amount preparation which permits visualization of the three-dimensional architecture of perfused vessels and their relationship within the retina. This allows analysis of gross vessel morphology and differentiation of deep and superficial vascular beds. The second step involves digesting the whole mount with trypsin and staining with hematoxylin. This permits detailed evaluation of the density of retinal capillary endothelial cells and pericytes, recognition of basement membrane ghosts, microaneurysms, and other intraretinal microvascular abnormalities, with intravascular horseradish peroxidase as a perfusion marker. This technique has been employed with success in studies of the retinal vasculature in both normal and RCS rat retinas, and in a monkey model of branch retinal vein occlusion.

Inhibition of intraocular neovascularization caused by retinal ischemia in pigs by PKCbeta inhibition with LY333531.

OBJECTIVE: The authors tested the antiangiogenic properties of an orally administered protein kinase-Cbeta inhibitor, LY333531, in a pig model of preretinal neovascularization caused by retinal branch vein occlusion to determine the effectiveness of this therapy in preventing intraocular neovascularization from an ischemic stimulus. METHODS: In 20 eyes of 10 pigs, branch retinal vein occlusions were created in a standardized manner using photodynamic thrombosis with rose bengal dye and thermal burns from an argon laser with green light. Five animals received 1 mg/kg LY333531 daily in two oral doses, and five animals were untreated. The eyes were followed clinically for 12 weeks with ophthalmoscopy, fundus photography, and fluorescein angiography. A standardized grading system permitted masked assessment of disc proliferations using stereo fundus photographs. After the pigs were killed, all neovascularization was confirmed histopathologically in a masked fashion and a final grade was assigned to each eye. The Mann-Whitney test was used for statistical analysis of the median values of the unpaired data between the two eyes of each animal (data were rounded up). RESULTS: Significant inhibition of neovascularization was observed in eyes from animals treated with the study drug (P = 0.03). Although some of the treated eyes demonstrated no clinically evident new vessels, histopathologic and photographic analysis demonstrated fine new vessels on the optic disc in all eyes (mean grade 1.9). All the untreated eyes developed clinically evident neovascularization (mean grade 3.1). The oral drug was well tolerated, and no side effects were documented. CONCLUSIONS: A specific protein kinase-Cbeta inhibitor, LY333531, effectively inhibited preretinal and optic nerve head neovascularization in the pig model of branch retinal vein occlusion. This was consistent with the known pathways of signal transduction by growth factors in activated cells and suggested that inhibition of this key regulatory isozyme is effective in the treatment of ischemia-mediated neovascular diseases.

Transpupillary thermotherapy for subfoveal occult choroidal neovascularization: effect on ocular perfusion.

PURPOSE: To perform a descriptive analysis of the effects on ocular blood flow of transpupillary thermotherapy (TTT) for occult subfoveal choroidal neovascular membranes (CNVMs) in age-related macular degeneration (AMD). METHODS: Eleven subjects with occult subfoveal CNVM due to AMD were assessed in a masked fashion by color Doppler imaging (CDI) within 24 hours before, 24 hours after, and 1 month after undergoing TTT. RESULTS: In the posterior ciliary arteries (PCAs), there were no statistically significant changes observed in the peak systolic velocity (PSV), end diastolic velocity (EDV), or resistive index (RI) at 24 hours. At 1 month, the mean EDV decreased 36% (P = 0.0105) and the mean RI increased 3.8% (P = 0.0305) in the nasal PCA. Although there was a similar trend in the temporal PCA, the differences did not reach statistical significance. In the central retinal artery (CRA), the mean PSV decreased 16% (P = 0.0137), and the mean EDV decreased 21% (P = 0.0222) at 24 hours after treatment. There were no statistically significant differences in the CRA blood flow indices at 1 month after treatment. In the ophthalmic artery, there were no statistically significant differences observed in the mean PSV, EDV, or RI at 24 hours or 1 month after treatment. CONCLUSIONS: TTT is associated with transiently decreased volumetric blood flow in the retinal circulation 24 hours after treatment. In the posterior ciliary arteries that supply the choroid, there were no changes observed at 24 hours, but at 1 month, there was a decrease in the mean EDV and an increase in the RI in the nasal and temporal PCAs, reaching statistical significance in the nasal PCA only. This study suggests that TTT could lead to alterations in choroidal blood flow, as assessed by CDI. Further study is warranted.

Flow dynamics of extrusion needle vacuuming in a closed vitrectomy system.

The dynamics of pressure, flow, and ocular volume relationships were examined with respect to extrusion needle use in simulated vitrectomy. Glass-stoppered bottles used with infusion lines with drip chambers lowered the intraocular pressure 4 to 7 inches below the fluid level in the bottle, varying with the amount of fluid in the bottle. Compared with flow rates using the regular tip needle with the steel infusion cannula, the disposable infusion cannula lowered the flow rate by about 25% and the tapered tip extrusion needle decreased outflow by 40% to 50%. Tracer dilution rates were decreased by the use of the disposable infusion port or the aphakic model eye; however, 2 minutes of infusion at a 30-inch bottle height dilution was still sufficient to wash out the tracer to less than 5% of the original concentration.

Preretinal and optic nerve head neovascularization induced by photodynamic venous thrombosis in domestic pigs.

OBJECTIVE: To develop a reliable model of ischemic preretinal and optic nerve head neovascularization in young male domestic pigs. METHODS: Using laser-induced branch retinal venous obstruction assisted by photodynamic thrombosis with rose bengal, 15 of 15 treated eyes developed neovascularization of the optic nerve head and retina. All cases of neovascularization were followed up clinically for up to 12 weeks. RESULTS: Clinical, fluorescein angiographic, and histopathologic features were consistent with neovascular proliferation into the vitreous. CONCLUSIONS: Further evaluation of the long-term natural history, role of the degree of ischemia, and the effect of interventions for various types of ischemic retinopathy (eg, panretinal photocoagulation) is warranted. This model is simple and relatively inexpensive and allows easy clinical assessment.

Intravitreal triamcinolone acetonide inhibits choroidal neovascularization in a laser-treated rat model.

OBJECTIVE: To determine if intravitreal triamcinolone acetonide (TAAC) inhibits experimental choroidal neovascular membranes induced by laser trauma in a rat model. METHODS: Nineteen anesthetized male Brown Norway rats received a series of 8 krypton red laser lesions per eye (647 nm, 0.05 seconds, 50 microm, and 150 mW in 17 rats, and 200 mW in 2 rats). One eye received an intravitreal injection of triamcinolone acetonide (20 microL, 0.8 mg) and the other eye received an injection of isotonic sodium chloride solution. Fundus and fluorescein angiography examinations occurred just before euthanasia and tissue processing for histopathology on day(s) 0, 1, 3, 7, 14, 21, 28, and 35. RESULTS: From the control eyes that underwent photocoagulation at 150 mW, 57 discrete lesions with definitive fibrovascular proliferations were observed at 21, 28, and 35 days, arising from a total of 72 spots placed (79% yield). From the control eyes that underwent photocoagulation at 200 mW, 11 discrete lesions with definitive fibrovascular proliferations were observed at 28 days, arising from a total of 16 spots placed (69% yield). In the TAAC-treated group, no fibrovascular proliferations were observed in the 72 lesions and in the 16 lesions created with 150 mW and 200 mW, respectively. CONCLUSION: Intravitreal TAAC is a potent inhibitor of fibrovascular proliferations in a rat model of choroidal neovascular membranes induced by laser trauma. CLINICAL RELEVANCE: This study corroborates previous investigations that propose TAAC as a potential treatment for choroidal neovascular membranes in humans.

Purulent pericarditis in children.

Acute purulent pericarditis was treated successfully in five children between the ages of 27 months and 11 1/2 years during the past 5 years. The responsible organism was Hemophilus influenzae, type b, in two cases and Meningococcus, Pneumococcus, and coagulase-positive Staphylococcus aureus in one case each. No primary source of infection could be identified in two patients. A high index of suspicion, combined with immediate echocardiograms and pericardiocentesis, led to the diagnosis. Immediate antibiotic therapy was instituted on the basis of the gram stain of the pericardial fluid. All five patients had a pericardial window established--four through subxyphoid approach and the fifth, because of a left pleural effusion, through a left thoracotomy. When the subxyphoid approach was used, sump drains were left for postoperative suction and irrigation. All five patients survived without sequalae during follow-up periods of from 18 months to 5 years. We advocate an aggressive approach to the diagnosis and treatment of this problem. This report documents the safety, ease, and effectiveness of the subxyphoid approach as a means of drainage.

Age-related macular degeneration: a review of experimental treatments.

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the USA. Laser photocoagulation of choroidal neovascular membranes (CNVMs) in exudative AMD is currently the only well-studied and widely accepted treatment modality. It is beneficial for only a small minority of patients who show well-demarcated "classic" CNVMs, and it destroys normal retinal tissue, creates a scotoma, and is associated with an unacceptably high CNVM persistence and recurrence rate. Consequently, investigators have attempted to develop new modalities for treatment of CNVMs. These treatment modalities can be grouped into four major categories: photodynamic therapy; pharmacologic inhibition of CNVM formation with antiangiogenic agents; surgical intervention, including excision of subfoveal CNVMs; and radiation therapy. All of these experimental treatment modalities are directed toward destroyiing CNVMs, the end result of the exudative process, and all have limitations. The ideal treatment of the future must be based on the pathogenesis of the disease at a stage well before CNVMs develop. Investigations in nonexudative AMD are currently focusing on several major areas. Epidemiologic factors, such as genetics, sunlight, and nutrition, are being evaluated in several large studies, including the Age-Related Eye Disease Study, with the possibility of ultimately limiting the risk of AMD through behavior modification. Laser treatment of drusen is being evaluated as a means of limiting the risk of CNVM formation, although mixed results have been reported in the small number of studies to date. Choroidal perfusion abnormalities have been described in AMD, and some investigators postulate that altering blood flow may limit the risk of CNVM formation. No perfusion-treatment trials have been completed to date.

Nesidioblastosis in children.

Three cases in which seizure disorder was first noticed were examined in the last seven years; low fasting glucose and high serum insulin levels then led to the diagnosis of severe hypoglycemia secondary to nesidioblastosis. Hypoglycemic episodes were uncontrolled by frequent oral feedings and intravenous administration of dextrose, glucagon, and diazoxide. Within three weeks after diagnosis, all three patients underwent subtotal pancreatectomy; all three survived and have been followed-up for two to seven years. Two remain euglycemic and have no evidence of CNS damage. The third has occasional fasting hypoglycemia that is treated with diazoxide; he continues to have a seizure disorder and is mentally retarded. Neonatal hypoglycemia secondary to hyperinsulinism requires prompt recognition and aggressive treatment to avoid irreversible CNS damage. Subtotal pancreatectomy safely and effectively restores the euglycemic state.

Management of severe gastroesophageal reflux in children.

To evaluate response to fundoplication, clinical results for 66 consecutive pediatric patients operated on for gastroesophageal reflux were retrospectively reviewed. Indications for operation were gastroesophageal reflux with apnea, repeated emesis, recurrent pneumonia, failure to thrive, stricture, and esophagitis. All patients had preoperative documentation of significant gastroesophageal reflux by either cinefluoroscopic reflux esophagogram or reflux nuclear scan. Fundoplication was effective in 56 (87%) of 64 patients. None of the patients considered to be operative failures had persistent gastroesophageal reflux. Operative failures occurred primarily in patients with gastroesophageal reflux and apnea or recurrent pneumonia. More advanced diagnostic tests, such as pH monitoring, may help to select patients whose symptoms of apnea and recurrent pneumonia are truly due to reflux. Gastroesophageal reflux produces significant morbidity in pediatric patients and is well treated operatively by fundoplication.