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Biomedical subjects

Michael Kaplan

Publications and source records attributed to Michael Kaplan.

At least 19 recordsLinked to original sources
PubMed2007

Evaluation of patterns of failure and subjective salivary function in patients treated with intensity modulated radiotherapy for head and neck squamous cell carcinoma.

BACKGROUND: Our aim was to correlate patterns of failure with target volume delineations in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiation therapy (IMRT) and to report subjective xerostomia outcomes after IMRT as compared with conventional radiation therapy (CRT). METHODS: Between January 2000 and April 2005, 69 patients with newly diagnosed nonmetastatic HNSCC underwent curative parotid-sparing IMRT at Stanford University. Sites included were oropharynx (n = 39), oral cavity (n = 8), larynx (n = 8), hypopharynx (n = 8), and unknown primary (n = 6). Forty-six patients received definitive IMRT (66 Gy, 2.2 Gy/fraction), and 23 patients received postoperative IMRT (60.2 Gy, 2.15 Gy/fraction). Fifty-one patients also received concomitant chemotherapy. Posttreatment salivary gland function was evaluated by a validated xerostomia questionnaire in 29 IMRT and 75 matched CRT patients >6 months after completing radiation treatment. RESULTS: At a median follow-up of 25 months for living patients (range, 10-60), 7 locoregional failures were observed, 5 in the gross target or high-risk postoperative volume, 1 in the clinical target volume, and 1 at the junction of the IMRT and supraclavicular fields. The 2-year Kaplan-Meier estimates for locoregional control and overall survival were 92% and 74% for definitive IMRT and 87% and 87% for postoperative IMRT patients, respectively. The mean total xerostomia questionnaire score was significantly better for IMRT than for CRT patients (p = .006). CONCLUSIONS: The predominant pattern of failure in IMRT-treated patients is in the gross tumor volume. Parotid sparing with IMRT resulted in less subjective xerostomia and may improve quality of life in irradiated HNSCC patients.

Carcinoma, Squamous Cell↗
PubMed2006

Neonatal hyperbilirubinemia in African American males: the importance of glucose-6-phosphate dehydrogenase deficiency.

OBJECTIVE: To perform risk factor analysis for the prediction of hyperbilirubinemia in an African American male neonatal cohort. STUDY DESIGN: A database of 500 previously published term and near-term African American male neonates was further analyzed to determine the role of risk factors for hyperbilirubinemia. Factors studied included birth weight >/=4.0 kg, gestational age </=37 weeks, breast-feeding, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, and predischarge bilirubin >/=75(th) percentile. Hyperbilirubinemia was defined as any bilirubin value >/=95(th) percentile on the hour-of-life-specific bilirubin nomogram. RESULTS: Forty-three (8.6%) neonates developed hyperbilirubinemia. At 48 +/- 12 hours, median transcutaneous bilirubin was 8.3 mg/dL, 75(th) percentile 10.0 mg/dL, and 95(th) percentile 12.6 mg/dL. Of the risk factors, only exclusive breast-feeding, G-6-PD deficiency and predischarge bilirubin >/=75(th) percentile were significant (Adjusted Odds Ratios [95% Confidence Intervals; CI] 3.15 [1.39-7.14], P = .006; 4.96 [2.28-10.80], P = .001; and 7.47 [3.50-15.94], P < .0001, respectively). G-6-PD-deficient neonates who were also premature and breast-feeding had the highest incidence of hyperbilirubinemia (60%). CONCLUSIONS: African American male neonates may be at higher risk for hyperbilirubinemia than previously thought. Screening for G-6-PD deficiency and predischarge bilirubin determination may be useful adjuncts in hyperbilirubinemia prediction in these newborns.

Bilirubin↗
PubMed2006

Immature sucking patterns in infants of mothers with diabetes.

OBJECTIVE: To evaluate immaturity of sucking patterns of infants of mothers with diabetes. STUDY DESIGN: Term infants born to mothers with gestational diabetes mellitus (16 mothers managed with insulin and 31 with diet alone) were compared with 55 matched healthy infants (control group). Sucking patterns were recorded and analyzed for number of sucks and bursts and averages maximum suck pressure, number of sucks per burst, suck width, and time between bursts. The measurements were made for feedings of 5 minutes duration with Kron's Nutritive Sucking Apparatus on the third day of life. RESULTS: Relative to the control group, newborns of the insulin-treated mothers averaged 5.2 fewer bursts and 42 fewer sucks (P = .013 and P = .04, respectively). No differences were noted for other variables tested. There were no differences in sucking patterns between newborns of diet-managed mothers and control newborns. CONCLUSION: Poorer sucking patterns were found among infants of insulin-managed mothers with diabetes. The present findings indicate some degree of neurologic immaturity during the early neonatal period.

Bottle Feeding↗
PubMed2006

Probiotics and neonatal intestinal infection.

PURPOSE OF REVIEW: Necrotizing enterocolitis remains an enigmatic and potentially devastating condition with high morbidity and mortality. This review explores ways in which bacterial pathogens, together with gut microflora, influence the pathophysiology of necrotizing enterocolitis. Specifically, it examines the role of gut microbial colonization and its 'normalization' with probiotics vis a vis its contribution to intestinal bacterial invasion. RECENT FINDINGS: Recent studies have demonstrated that prophylactic administration of probiotics to preterm neonates decreases both the incidence and severity of subsequent necrotizing enterocolitis. SUMMARY: Probiotics represent a therapeutic effort to bolster natural host defenses via the 'normalization' of abnormal gut microflora of the premature infant at risk, thereby reducing the subsequent threat of necrotizing enterocolitis. The appeal of probiotics in neonatology is threefold. First, their safety record renders them an attractive alternative to many of the more aggressive therapeutic options; second, they represent a simple, noninvasive attempt to recreate a natural or normal flora rather than a disruption of nature. Third, probiotics are used mainly for disease prevention and are naturally occurring. As such, they are not considered to be drugs, but rather food supplements. To date, very few other strategies have been proven definitively to be efficacious in decreasing the incidence of necrotizing enterocolitis.

Enterocolitis, Necrotizing↗
PubMed2006

Dose-dependent effect of pitavastatin on VEGF and angiogenesis in a mouse model of choroidal neovascularization.

PURPOSE: To evaluate the relation between statin therapy, vascular endothelial growth factor (VEGF) expression, vascular leakage, and CNV size in experimentally induced choroidal neovascularization (CNV). METHODS: Wild-type (C57 Bl/6J) mice received pitavastatin 0.18 mg/kg per day (group 1), 1.8 mg/kg per day (group 2) or 18 mg/kg per day (group 3) for 3 days before laser-induced CNV and continued to receive the drug for 14 days. Serum total cholesterol levels were measured by spectrophotometry. Fluorescein angiograms were graded by masked observers. VEGF protein levels from retinal lysates were measured and CNV area was assessed by histology. RESULTS: Pitavastatin did not reduce total serum cholesterol at any of the doses used. The incidence rate ratios for development of clinically significant CNV leakage was 0.62 (95% CI, 0.46-0.84) for group 1, 0.56 (95% CI, 0.28-1.10) for group 2, and 1.22 (95% CI, 1.01-1.48) for group 3 (P=0.002, 0.09, and 0.04, respectively). Mean CNV area increased by 13%, 22%, and 95% in groups 1, 2, and 3, respectively (P>0.05). Normalized VEGF levels did not mirror the observed changes in fluorescein leakage and CNV area in histologic examination. CONCLUSIONS: Pitavastatin therapy for experimental CNV in wild-type mice resulted in reduced fluorescein leakage at a dose of 0.18 mg/kg per day. The higher dose of 18 mg/kg per day resulted in increased fluorescein leakage and a trend toward an increase in CNV size, indicating a potentiating effect in choroidal neovascular disease.

Animals↗
PubMed2005

Studies in hemolysis in glucose-6-phosphate dehydrogenase-deficient African American neonates.

BACKGROUND: The role of hemolysis in the mechanism and prediction of hyperbilirubinemia was contrasted between glucose-6-phosphate dehydrogenase (G-6-PD)-deficient and -normal African American neonates. METHODS: Corrected end tidal carbon monoxide (ETCOc) values from the subset of male neonates born to non-smoking African American mothers, drawn from a previously published study, were analyzed. The relationship between ETCOc and bilirubin values, the latter represented as percentiles on the hour of life specific bilirubin nomogram, was determined. Hyperbilirubinemia was defined as any bilirubin value > or =95th percentile for hour of life. RESULTS: 18.6% of 59 G-6-PD-deficient neonates developed hyperbilirubinemia, compared with 7.5% of 362 controls (relative risk 2.50, 95% confidence interval 1.31 to 4.76). As reported, ETCOc values (median, interquartile range) were significantly higher among G-6-PD-deficient neonates than controls (2.4 [2.0-2.9] vs. 2.1 [1.7-2.5] ppm, p<0.001. However, higher ETCOc values were limited to those G-6-PD-deficient neonates with lower bilirubin percentiles: among those whose bilirubin value did not exceed the 95th percentile ETCOc was 2.30 [2.00-2.85] vs. 2.00 [1.70-2.40] ppm in controls, p=0.001. In contrast, among the hyperbilirubinemic neonates ETCOc values were similar between G-6-PD-deficient neonates and controls: 2.7 [2.03-3.33] vs. 2.6 [2.33-3.45] ppm, p=0.9. In the G-6-PD-deficient neonates ETCOc > or =75th percentile contributed no additional predictive value for hyperbilirubinemia (likelihood ratio 1.8). CONCLUSIONS: G-6-PD-deficient African American neonates have increased hemolysis and increased rate of hyperbilirubinemia, but the hemolysis is neither a predominant factor in the pathogenesis of hyperbilirubinemia nor is it predictive of hyperbilirubinemia, over and above the already increased risk conferred by G-6-PD deficiency.

Black People↗
PubMed2005

Understanding severe hyperbilirubinemia and preventing kernicterus: adjuncts in the interpretation of neonatal serum bilirubin.

The serum total bilirubin concentration at any point in time represents the amount of bilirubin being produced minus that being excreted. Hyperbilirubinemia develops when bilirubin production exceeds the body's capacity to excrete it, primarily by conjugation. When extreme, hyperbilirubinemia may lead to the development of free bilirubin, that form of bilirubin which may cross the blood-brain barrier and enter and damage the basal nuclei of the brain. This rare, though devastating complication, may result in irreversible bilirubin induced brain damage termed kernicterus. In this paper, adjuncts to the interpretation of the serum total bilirubin are discussed, with the purpose of singling out those few neonates in real danger of bilirubin encephalopathy. Interpretation of the serum total bilirubin should be performed in conjunction with factors unique to the particular infant being evaluated. Understanding the mechanisms and dangers of severe neonatal hyperbilirubinemia should facilitate recognition of an emergency situation and optimize the speed with which bilirubin testing is performed and blood for exchange transfusion prepared. Hyperbilirubinemia is a condition of major importance and a source of concern to all involved in the management of the newborn. Its prevention and management should be based on the recently revised American Academy of Pediatric guidelines, with special attention paid to neonates manifesting risk factors for kernicterus. Close cooperation between the clinical laboratory and the medical team managing the newborn is an essential component in the management of a hyperbilirubinemic baby.

Bilirubin↗
PubMed2005

Glucose-6-phosphate dehydrogenase activity in term and near-term, male African American neonates.

BACKGROUND: We determined values for glucose-6-phosphate dehydrogenase (G-6-PD) activity in African American neonates. METHODS: G-6-PD activity was measured on umbilical cord blood from term and near-term healthy, male neonates. Neonates were stratified according to the number of neonates for each numerical unit of G-6-PD activity. Corrected end tidal carbon monoxide (ETCOc), a non-invasive index of hemolysis, was performed on each neonate. At least one predischarge transcutaneous bilirubin determination was performed. RESULTS: Five hundred neonates were studied. Two subpopulations were apparent, with no overlap between the subgroups. Mean value for the 64 (12.8%) infants with the lower values (G-6-PD deficient) was 2.7+/-1.1 U/g Hb, range 0.4-6.6 U/g Hb, while that for the 436 neonates with the higher values (G-6-PD normal) was 21.8+/-2.9 U/g Hb, range 14.5-33.8 U/g Hb. No significant differences in activity were noted between those neonates <37 weeks gestational age and those >37 weeks. Enzyme activity in the lower range in both groups was not related to the development of hyperbilirubinemia. G-6-PD enzyme activity did not correlate with ETCOc values either for the entire cohort or for the individual subsets. CONCLUSIONS: G-6-PD-deficient neonates formed a separate subgroup from those with normal enzyme activity. The data supplied should facilitate interpretation of G-6-PD test results.

Black or African American↗
PubMed2005

Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates.

OBJECTIVE: To test the hypothesis that normalizing the intestinal flora by administration of prophylactic probiotics would provide a natural defense, thereby reducing both the incidence and severity of necrotizing enterocolitis (NEC) in preterm neonates. STUDY DESIGN: Neonates < or =1500 g birth weight were randomized to either receive a daily feeding supplementation with a probiotic mixture (Bifidobacteria infantis, Streptococcus thermophilus, and Bifidobacteria bifidus; Solgar, Israel) of 10(9) colony forming units (CFU)/day or to not receive feed supplements. NEC was graded according to Bell's criteria. RESULTS: For 72 study and 73 control infants, respectively, birth weight (1152 +/- 262 g vs 1111 +/- 278 g), gestational age (30 +/- 3 weeks vs 29 +/- 4 weeks), and time to reach full feeds (14.6 +/- 8.7 days vs 17.5 +/- 13.6 days) were not different. The incidence of NEC was reduced in the study group (4% vs 16.4%; P=.03). NEC was less severe in the probiotic-supplemented infants (Bell's criteria 2.3 +/- 0.5 vs 1.3 +/- 0.5; P=.005). Three of 15 babies who developed NEC died, and all NEC-related deaths occurred in control infants. CONCLUSION: Probiotic supplementation reduced both the incidence and severity of NEC in our premature neonatal population.

Administration, Oral↗
PubMed2005

Comparison of sucking patterns at introduction of oral feeding and at term in Israeli and American preterm infants.

BACKGROUND: It has been hypothesized that early initiation of oral feeding in premature infants may enhance the maturation of sucking patterns. AIM: To compare preterm infant sucking characteristics in urban level III neonatal care units in the USA and Israel. The two hospitals have different practices regarding the introduction of oral feeding. METHODS: Infants were assessed at 34-35 wk postconceptional age (PCA) and at term. Sucking parameters were assessed with the Kron's Nutritive Sucking Apparatus. RESULTS: 70 infants (38 Americans and 32 Israelis) participated in the study. Oral feedings were initiated earlier (32.6 +/- 4.3 vs 34.5 +/- 1.8 wk PCA, p < 0.01) and full oral feedings were reached earlier (35.4 +/- 2.8 vs 36.5 +/- 2.5 wk PCA, p < 0.05) in the USA infants. American preterm infants produced significantly more sucks (p < 0.001), had a higher suck rate (p < 0.001), more sucks per burst (p < 0.05), and a shorter interburst width (p < 0.01) at 34 wk PCA than Israeli infants. At term, American infants produced significant more sucks (p < 0.001), higher suck rate (p < 0.001), shorter intersuck width (p < 0.001), and a shorter interburst width (p < 0.05) than the Israeli infants of the same PCA. CONCLUSION: Different practices in the care of preterm infants, such as postconceptional age at introduction of oral feeding, may play a role in the development of feeding and feeding organization at term.

Age Factors↗
PubMed2004

Phototherapy and photo-oxidation in premature neonates.

OBJECTIVE: The potential for photo-oxidation during phototherapy in premature neonates was assessed by measuring parameters reflective of photo-oxidation. METHODS: Blood was sampled from premature neonates prior to, and after 4 and 24 h of phototherapy, respectively. Total plasma bilirubin (TPB), blood carboxyhemoglobin corrected for inspired carbon monoxide (COHbc) (a sensitive index of heme catabolism), blood thiobarbituric acid reacting substances (TBARS) (a measure of lipid peroxidation), and plasma protein carbonyls (representative of protein oxidation) were determined. Study measurements were compared with baseline values both for the entire study group, and also individually for subgroups < and > or = 1.5 kg birthweight, respectively. The percentage difference (%delta) between baseline and the 24-hour measurement was calculated for each parameter. RESULTS: Forty-one premature neonates (mean [+/- SD] gestational age 30.5 +/- 2.7 weeks and birthweight 1,499 +/- 448 g) were studied. Mean TPB values decreased from a baseline of 9.1 +/- 2.3 to one of 7.2 +/- 2.8 mg/dl, p < 0.01, during the first 24 h of phototherapy. For the entire patient sample, neither COHbc, TBARS or protein carbonyl values increased significantly over baseline measurements: COHbc: 0.90 +/- 0.26% vs. 0.92 +/- 0.32%; TBARS: 19.0 +/- 5.6 vs. 18.0 +/- 4.5 nmol/ml, and protein carbonyls 7.73 +/- 3.78 vs. 7.63 +/- 3.56 U/ml (baseline and 24-hour samples only are shown in the abstract). Similarly, for the entire group, %delta (mean, interquartile range) were not significantly different between COHbc [-3.77 (-15.89-17.65)%], TBARS [-7.47 (-17.37-7.38)%], and protein carbonyls [-1.47 (-28.51-43.48)%], respectively. For subgroup analysis of neonates < or > or = 1.5 kg birthweight, respectively, no significant increases in COHbc, TBARS or protein carbonyls were documented. A significant increase in %delta for COHbc in the <1.5 kg birthweight subgroup compared with those > or =1.5 kg, possibly indicative of hemolysis, was not matched by similar changes in %delta for TBARS or protein carbonyls, and may therefore not be a result of photo-oxidation. CONCLUSIONS: Except for changes in %delta in COHbc alone and in the smallest babies only, overall, short term phototherapy in premature infants was effective in reducing TPB concentrations without associated evidence reflective of photo-oxidation.

Bilirubin↗
PubMed2004

Comparative effects of two phototherapy delivery systems on cerebral blood flow velocity in term neonates.

BACKGROUND: Phototherapy is an effective and generally safe method of treating neonatal hyperbilirubinemia. However, there is some concern that it may affect cerebral blood flow velocity (CBFV) in newborns with fragile cerebral vasculature. OBJECTIVES: To measure and compare the effects of two different phototherapy units, delivering similar irradiance, on CBFVs. METHODS: Doppler flow velocities were measured in term infants under fluorescent overhead and fluorescent BiliBed phototherapy units, respectively, at baseline, 4 and 24 h of therapy. RESULTS: Peak systolic CBFV increased during treatment in infants treated under overhead phototherapy (n = 18) but not in those treated in BiliBeds (n = 12). CONCLUSIONS: Different phototherapy delivery modalities can have differential effects on CBFV in term neonates.

Blood Flow Velocity↗
PubMed2004

Germ warfare: probiotics in defense of the premature gut.

The potential benefits of a predominantly lactic acid bacterial flora include an improved balance of gut microbial ecology and decreased susceptibility of the gut mucosa to bacterial translocation via adherence to the intestinal mucosa, strengthening mucosal barrier function. These properties should be especially beneficial to the premature neonate with (1) delayed establishment of nor-mal flora, increasing the potential for proliferation of pathogenic bacteria and (2) immature development of the intestinal mucosa, rendering it more susceptible to the translocation of these pathogenic bacteria and leading to extra-intestinal spread and systemic disease. Early probiotic supplementation in preterm infants is theoretically sound and associated with minimal risk. Clinical data remain preliminary but are supportive of a reduction in feeding intolerance and NEC in this high-risk group.

Animals↗