A Comparison of Oral and Rectal Absorption of L-Dopa Esters in Rats and Mice

Short-chain alkyl esters of L-dopa were administered to rats and mice via oral and rectal routes. Plasma L-dopa esters and L-dopa were determined in the systemic and portal circulation by HPLC. A comparison of isopropyl, butyl, and 4-hydroxybutyl esters of L-dopa demonstrated significantly higher levels of the esters in both systemic and portal blood samples following rectal administration than following oral administration. In most cases, oral administration resulted in nondetectable (<0.01 µg/ml) levels of the esters in plasma. Correspondingly, the plasma levels of L-dopa itself were consistently higher following rectal administration. At very high oral doses (500 mg L-dopa equivalents/kg body weight), systemic plasma levels of the butyl ester could be detected (1.25 µg/ml at 10 min), which might indicate saturation of the esterase activity of the small intestine. These studies indicate that the systemic availability of L-dopa from short-chain alkyl esters of L-dopa may be best optimized by rectal administration, which avoids the relatively high esterase activity characteristic of the small intestine.     

A gestalt-experiential perspective on resistance.

The authors present background on the gestalt-experiential understanding of resistance, conceptualized to be either resistance to awareness or resistance to contact. The authors discuss why they do not use the term resistance and describe the phenomena as a client's self-protective attempt to avoid the anxiety necessitated by change. Such resistant behaviors occur outside a client's awareness and often result in an ambivalence or conflict about change. The authors also describe using in-session experiments as a way to engage with the client in exploring such a state of ambivalence or conflict. Finally, they respond to the case studies presented elsewhere in this issue and propose intervention strategies consistent with the gestalt-experiential perspective.     

Factors affecting breastfeeding among women of Mexican origin or descent in Los Angeles.

Data on breastfeeding intentions and behavior were collected in prenatal and postpartum interviews as part of a study on first birth among 518 women of Mexican origin or descent in two Los Angeles hospitals. The prenatal intentions of 82 per cent of the women to breastfeed were maintained postpartum in one hospital but dropped sharply in the other. A greater number of hours a day with the baby in the hospital and earlier initiation of breastfeeding were associated with the hospital where prenatal breastfeeding intentions were more likely to be carried out. The intention to work postpartum was associated both with the decision not to breastfeed at all and with shorter intended duration of breastfeeding.     

Family dynamics and emotional expression among patients with chronic pain and depression

Exploration of the relative roles of family dynamics and release of constrained, negative emotion in changing pain and depressive symptoms. Eighteen patients presenting mild to moderate depression and diagnoses of psychogenic pain disorder were randomly assigned to 1 of 2 treatment groups. One group was designed to facilitate the release of constrained and overcontrolled negative affect while the other was designed to provide information about pain and depression. Findings suggest that initial incongruity between patient's and significant other's ratings of family relationships retard changes in pain status and depressive symptoms. No significant differences were noted between patients who were taught to express negative feelings and those who were taught simply to understand those feelings. Results are discussed in terms of theories about family dynamics in the initiation and maintenance of pain conditions and in terms of the role of constrained affect as a precursor to both psychogenic pain and depression.     

Response to a diet low in total fat in women with postmenopausal breast cancer: a pilot study

A feasibility study was instituted to determine if women with postmenopausal breast cancer would follow a low-fat diet (20% of kcal) for at least four months. Nineteen women, whose baseline food intake was 1,504 +/- 420 kcal with 56 +/- 16 g of fat, reported a decrease in fat intake to 21 +/- 6 g after two months of dietary intervention. Serum concentrations of cholesterol, HDL cholesterol, and estradiol were significantly reduced by the fifth month on the diet. We conclude that self-selected patients can adhere to a low-fat diet, and that serum cholesterol may serve as an indicator of dietary compliance.     

Increased risk of necrotizing enterocolitis in premature infants with patent ductus arteriosus treated with indomethacin.

OBJECTIVE: The authors evaluated the risk of necrotizing enterocolitis (NEC) in very low birth weight infants receiving indomethacin (INDO) to close patent ductus arteriosus (PDA). BACKGROUND DATA: Controversy exists regarding the best method of managing very low birth weight infants with PDA and whether to employ medical management using INDO or surgical ligation of the ductus. METHODS: Two hundred fifty-two premature infants with symptomatic PDA were given intravenously INDO 0.2 mg/kg every 12 hours x 3 in an attempt to close the ductus. Patients were evaluated for sex, birth weight, gestational age, ductus closure, occurrence of NEC, bowel perforation, and mortality. RESULTS: There were 135 boys and 117 girls. The PDA closed or became asymptomatic in 224 cases (89%), whereas 28 (11%) required surgical ligation. Ninety infants (35%) developed evidence of NEC after INDO therapy. Fifty-six were managed medically; surgical intervention was required in 34 of 90 cases (37.8%) or 13% of the entire PDA/INDO study group. Bowel perforation was noted in 27 cases (30%). Factors associated with the onset of NEC included gestational age < 28 weeks, birth weight < 1 kg, and prolonged ventilator support. The overall mortality rate was 25.5%, but was higher in infants with NEC versus those without. The highest mortality was noted in perforated NEC cases. The PDA/INDO patients were compared with a control group of 764 infants with similar sex distribution, birth weights, and gestational ages without PDA who did not receive INDO. Necrotizing enterocolitis occurred in 105 of 764 control patients (13.7%), including 13 (12.3%) with perforation. The overall mortality rate of controls was 25%, which was similar to the overall 25.5% mortality rate in the PDA/INDO study group. CONCLUSION: These data indicate that there is increased risk of NEC and bowel perforation in premature infants with PDA receiving INDO. Mortality was higher in the PDA/INDO group with NEC than those PDA/INDO infants without NEC.     

Quantitative Characterization of Epicardial Wave Fronts During Regional Ischemia and Elevated Extracellular Potassium Ion Concentration

This study applied zero-delay wave number spectral estimation as a means of quantifying the changes in activation and recovery sequences of propagating plane waves on the epicardial surface of in situ porcine hearts during regional hyperkalemia and ischemia. Unipolar electrograms (104) were recorded from the left ventricular surface of nine hearts using a plaque electrode array with 1 mm spatial sampling intervals. The objectives were (1) to define a set of parameters capable of quantifying the spatial and temporal changes in measured extracellular potentials associated with localized ischemia prior to the onset of conduction block; (2) to elevate regional levels of extracellular potassium ion concentration and quantify potential changes due to this known physiologic manipulation; and (3) to use quantitative parameters to make statistical comparisons in order to distinguish wave fronts during normal, ischemic and hyperkalemic conditions. Results showed that the parameters of wave number and average temporal frequency and the associated power, as determined from the wave number spectrum, provided statistically significant (p < 0.05) quantification of changes in wave front features during normal and ischemic or hyperkalemic conditions. The results were consistent with results obtained from conventional time–space domain methods like isochronal mapping and electrograms, with the advantage of a quantitative result enabling simple comparisons and trend analysis for large numbers of heart beats. © 1998 Biomedical Engineering Society. PAC98: 8759Wc, 8722Fy, 8780+s     

Phenotype delineation of ZNF462 related syndrome

Zinc finger protein 462 (ZNF462) is a relatively newly discovered vertebrate specific protein with known critical roles in embryonic development in animal models. Two case reports and a case series study have described the phenotype of 10 individuals with ZNF462 loss of function variants. Herein, we present 14 new individuals with loss of function variants to the previous studies to delineate the syndrome of loss of function in ZNF462. Collectively, these 24 individuals present with recurring phenotypes that define a multiple congenital anomaly syndrome. Most have some form of developmental delay (79%) and a minority has autism spectrum disorder (33%). Characteristic facial features include ptosis (83%), down slanting palpebral fissures (58%), exaggerated Cupid's bow/wide philtrum (54%), and arched eyebrows (50%). Metopic ridging or craniosynostosis was found in a third of study participants and feeding problems in half. Other phenotype characteristics include dysgenesis of the corpus callosum in 25% of individuals, hypotonia in half, and structural heart defects in 21%. Using facial analysis technology, a computer algorithm applying deep learning was able to accurately differentiate individuals with ZNF462 loss of function variants from individuals with Noonan syndrome and healthy controls. In summary, we describe a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features.     

Phosphatemic action of 1,25-dihydroxyvitamin D3.

The action of a single intraperitoneal injection of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was investigated in thyroparathyroidectomized (TPTX) vitamin D-deficient phosphate-depleted rats. After 14 h, plasma inorganic phosphorus (Pi) was significantly greater in animals receiving 1,25(OH)2D3 than in D-deficient controls, but urinary Pi excretion was very low in both groups and not significantly different in the rats given 1,25(OH)2D3. Clearance studies indicated that the D-deficient controls reabsorbed more than 99% of their filtered Pi. Avid Pi reabsorption continued even after the infusion of sufficient phosphate to raise the plasma and filtered Pi to approximately 3 times normal. Fractional calcium excretion (FECa) exceeded fractional sodium excretion (FENa) by severalfold, but FECa decreased strikingly during phosphate infusion. In animals that manifested a substantial elevation of plasma Pi after 1,25(OH)2D3, FECa was significantly less than in D-deficient controls. Therefore, the increase in plasma Pi following 1,25(OH)2D3 administration occurs independently of any effect on renal Pi reabsorption and may be responsible, at least in part, for the amelioration of hypercalciuria after 1,25(OH)2D3 treatment.