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Biomedical subjects

A Lucas

Publications and source records attributed to A Lucas.

At least 19 recordsLinked to original sources

Breast milk and subsequent intelligence quotient in children born preterm.

There is considerable controversy over whether nutrition in early life has a long-term influence on neurodevelopment. We have shown previously that, in preterm infants, mother's choice to provide breast milk was associated with higher developmental scores at 18 months. We now report data on intelligence quotient (IQ) in the same children seen at 7 1/2-8 years. IQ was assessed in 300 children with an abbreviated version of the Weschler Intelligence Scale for Children (revised Anglicised). Children who had consumed mother's milk in the early weeks of life had a significantly higher IQ at 7 1/2-8 years than did those who received no maternal milk. An 8.3 point advantage (over half a standard deviation) in IQ remained even after adjustment for differences between groups in mother's education and social class (p less than 0.0001). This advantage was associated with being fed mother's milk by tube rather than with the process of breastfeeding. There was a dose-response relation between the proportion of mother's milk in the diet and subsequent IQ. Children whose mothers chose to provide milk but failed to do so had the same IQ as those whose mothers elected not to provide breast milk. Although these results could be explained by differences between groups in parenting skills or genetic potential (even after adjustment for social and educational factors), our data point to a beneficial effect of human milk on neurodevelopment.

Age Factors

Plasma folate levels in preterm infants, with and without a 1 mg daily folate supplement.

One hundred and four preterm infants were studied during the first few months of life in the Special Care Baby Unit of Addenbrooke's Hospital, Cambridge, United Kingdom. Previously, it had been the daily practice within the Unit to give a 1 mg oral supplement of folate (in the form of pteroylglutamic acid), once the infants had commenced full enteral feeding. At least one blood sample was obtained from 70 infants before oral folate supplementation was started. In these, the plasma folate levels fell progressively from a median value of 45 micrograms/l to a median of 12 micrograms/l, by the 2nd-3rd week of life. Once started on the oral supplement, 83 of the infants provided at least one blood sample. The plasma folate level of these infants rose immediately to a median value of 300 micrograms/l and a maximum of 1000 micrograms/l. Within individuals, these plasma folate levels decreased progressively following the introduction of the supplement, despite continuing daily supplementation. In a typical baby this decrease appeared to be explained by an increase in body-size, i.e. dilution of the folate into a larger pool. The implications of this level of supplementation are discussed, and in the light of our observations we suggest that daily supplementation in the range, 0.05-0.2 mg folate may be preferable for well preterm infants.

Dose-Response Relationship, Drug

High folate intakes related to zinc status in preterm infants.

The former practice of giving 1 mg (2.27 mumoles) oral folic acid daily to premature infants receiving enteral feeds was assessed with respect to zinc status in Cambridge, United Kingdom. A group of 60 preterm infants, 80% of whom were receiving 1 mg oral folic acid daily, were studied for up to the first 16 weeks of life. Plasma folate and plasma zinc were measured for each subject. A significant inverse relationship was found between the maximum attained serum folate level and the minimum attained serum zinc level, (t = 5.0, 58 df, P less than 0.0001). This remained significant after corrections had been made for gestational age at birth, fetal growth retardation, birth weight, sex, diet, assisted ventilation and length of time to full enteral feeding. The hypothesis that very high folate intakes may adversely affect serum zinc levels and, by inference, zinc status in preterm infants could not be rejected. Caution is therefore advised when prescribing such very high folate doses daily for small preterm infants.

Dose-Response Relationship, Drug

A prospective analysis of vascular access device-related infections in children.

To identify significant predictors of device-related infections, we performed a prospective, nonrandomized analysis of our experience with vascular access devices over a 2-year period in a pediatric oncology population. Variables analyzed included: (1) age at placement, (2) sex, (3) underlying disease, (4) type of device used (catheter v port), and (5) total white blood cell count at placement. Quantitative microbiologic criteria were used for diagnosis of bacteremia while clinical and microbiologic criteria were used in diagnosis of tunnel/port/site infections. During the study period a total of 351 devices, comprising 78,159 days in situ, were placed and data for univariate and multivariate analysis were available on 271 (77%). The mean age at placement was 7.2 +/- 4.7 years for catheters and 9.5 +/- 4.8 years for implantable devices (P less than or equal to .01). Significant predictors of device-related infections in univariate analysis were type of device (P less than or equal to .0001) and age (P less than or equal to .002). External catheters and age less than or equal to 7 years were associated with increased risk of infection. Underlying disease had a marginal effect on the infection rate (P = .08). In multivariate analysis, device type (P less than or equal to .0001) and age (P less than or equal to .002) continued to affect infections, whereas underlying disease demonstrated only a borderline effect (P = .14). We conclude that device type and age significantly affect the rate of device-related infections. These data support increased use of implantable devices in pediatric oncology patients.

Catheters, Indwelling

Comparative effects of captopril versus nifedipine on proteinuria and renal function of type 2 diabetic patients.

Our study compared the effects of an angiotensin-converting enzyme inhibitor (captopril) versus a calcium antagonist (nifedipine) on proteinuria and renal function in patients with diabetic nephropathy. A randomized follow-up study was designed. Type 2 diabetic patients, with established diabetic nephropathy (proteinuria greater than 0.5 g/24 h), were treated with nifedipine (10 patients, group A) or captopril (10 patients, group B) for 6 months. Arterial blood pressure, metabolic parameters, proteinuria and renal function were measured and compared. Mean percentage differences for glomerular filtration rate, renal plasma flow and filtration fraction between the two groups were calculated. No significant differences were observed in serum glucose, glycosylated hemoglobin (hemoglobin A1c), Na+, K+ or albumin in either group or between groups. Blood pressure decreased significantly with both treatments and mean blood pressure was significantly lower in group A compared with group B at 6 months (Mann-Whitney U-test, P = 0.03). Proteinuria was similar in both groups at randomization, but after 3 and 6 months of treatment significant reductions were observed only in the group treated with captopril (P less than 0.01). A significant decrease in filtration fraction was observed in group B with an increase in group A (Mann-Whitney U-test, P = 0.03). Multiple regression analysis identified the therapeutic agent administered as an independent variable for decrease in proteinuria. It is concluded that antihypertensive treatment with captopril, but not with nifedipine, reduced proteinuria in patients with diabetic nephropathy, although a better mean blood pressure was obtained with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose

Suppressive therapy with levothyroxine for solitary thyroid nodules.

OBJECTIVE: To evaluate the effect of treatment with TSH suppressive dose of levothyroxine in patients with benign thyroid nodules. DESIGN: Prospective randomized study. Group A (n = 20) patients received levothyroxine and group B (n = 20) patients did not. The dose of levothyroxine was adjusted to obtain an effective suppression of TSH. A clinical, analytical and morphological (with ultrasound) review was performed every 3 months. The mean +/- SD follow-up period was 10.6 +/- 2.2 months. PATIENTS: Forty euthyroid women with solitary thyroid nodule on palpation, cold on scintigraphy and cytologically benign without contraindication participated. MEASUREMENTS: At entry: biochemical and hormonal parameters, thyroid scintigraphy and thyroid ultrasonography. Every 3 months additional determinations of thyroid hormones and TSH levels were carried out, if necessary, to verify effective TSH suppression. Every 6 months thyroid ultrasound imaging was performed. RESULTS: Patients were euthyroid at entry into the study. The mean dose of levothyroxine necessary to obtain TSH suppression was 2.82 +/- 0.6 micrograms/kg/day. No significant modification in the thyroid nodule diameter (mean +/- SD 2.6 +/- 1.2 vs 2.5 +/- 1.2 cm) or in the thyroid nodule volume (10.3 +/- 11.9 vs 10.1 +/- 12.2 ml) were observed in group A. In group B the results were similar (2.8 +/- 0.9 vs 2.7 +/- 1.8 cm and 9.2 +/- 6.4 vs 9.2 +/- 9.5 ml, respectively). No differences were found in either group in the number of nodules that reduced significantly their volume (four and three, respectively). CONCLUSIONS: The suppressive therapy with levothyroxine was not effective in reducing nodule sizes in patients with solitary benign thyroid nodules.

Adult

Randomised trial of nutrition for preterm infants after discharge.

In a randomised double blind trial, the effect on growth and clinical status of a nutrient enriched 'post-discharge' milk formula versus a standard term formula, was compared in 32 exclusively bottle fed preterm infants. The formulas were used as the sole milk intake up to a postnatal age of 9 months. Significant increases in linear growth and weight gain were observed in the infants who received the enriched diet. There were no differences in vomiting, posseting, or bowel habit between the groups. Formula volumes ingested were similar between diet groups, indicating that the difference in formula composition did not affect the infants' regulation of intake. These preliminary data suggest that there is a role for specially designed formulas for preterm infants after discharge from hospital.

Animals

Postdischarge formula consumption in infants born preterm.

In 31 infants born preterm and formula fed ad libitum, all milk intake was weighed from hospital discharge to nine months post-term. Mean daily milk intake was high, reaching 230 g/kg before four weeks post-term and was still over 150 g/kg beyond six months. Five of the 31 infants (16%) consumed 300-350 g/kg; 50% 'voluntarily' consumed more than upper recommended limits for energy intake and 35% did so for protein intake.

Body Weight

Randomised trial of a ready-to-feed compared with powdered formula.

Forty three infants were assigned randomly to a ready-to-feed infant formula or a standard formula that required reconstitution from powder. Despite similar nutrient composition of the two formulas those fed the powdered formula had significantly increased body weight and skinfold thickness gains, and became significantly heavier than a further group of 20 breast fed infants by 3 and 6 months. Of those fed the powdered formula 6/19 had become overweight (above the 90th or 97th centile) by 6 months, whereas 1/19 fed the ready-to-feed product was overweight at this age. While differences in fat absorption might have been contributory, our data suggest that errors in reconstitution of formula from powder might be the main cause for the growth differences observed. If it is appropriate to take the breast fed infant as a model, infants fed ready-to-feed formula in this study showed a more physiological pattern of growth than those fed a standard formula reconstituted from powder. These results require replication using other formulas as the findings have potentially important implications for infant feeding.

Body Weight

Clinical usefulness of urinary growth hormone measurements in normal and short children according to different expressions of urinary growth hormone data.

To assess the clinical usefulness of urinary growth hormone (UGH) measurements, a UGH determination technique, including dialysis, ultrafiltration, and measurement by polyclonal-coated tube RIA, was established. Sixty-three short children were studied: 56 idiopathic growth retarded (37 prepubertal and 19 pubertal) and seven prepubertal with classic GH (growth hormone) deficiency. Forty-two healthy children (32 prepubertal and 10 pubertal) served as controls. Two groups of adults were studied: eight with active acromegaly and 11 healthy controls. UGH was measured in 24-h urine samples from all patients and controls. Mean +/- SD UGH excretion expressed as ng/24 h was significantly lower in the GH-deficient group compared with prepubertal growth-retarded and control children (p less than 0.01). No differences were found between UGH excreted by controls and by the growth-retarded groups. Pubertal children excreted significantly higher amounts of GH when UGH was expressed as ng/24 h (p less than 0.02 and p less than 0.03, respectively), but this difference disappeared when UGH was expressed as ng/g creatinine. UGH was significantly higher in acromegalic patients compared with adult controls (p less than 0.001). Differences between day, night, and 24-h UGH were studied in 23 children. UGH in night urine was significantly lower whether expressed as the total amount or as ng/g creatinine. The effect of recombinant hGH administration on UGH was studied in 13 children after 6 and 12 mo of treatment. UGH increased significantly under recombinant hGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly

Reevaluation of autoantibodies to islet cell membrane in IDDM. Failure to detect islet cell surface antibodies using human islet cells as substrate.

Since their demonstration in 1975, ICSAs have been proposed as serological markers and pathogenic elements in IDDM. ICSAs are detected in the sera of most newly diagnosed IDDM patients by indirect IFL that uses viable preparations of rat islet or insulinoma cells as substrate, but they also can be detected by using human insulinoma or fetal islet cells. We have tried to demonstrate ICSAs in the sera of 31 newly diagnosed diabetic patients, including 6 positive samples on human fetal islet cells, which used their natural target for the first time: normal human islet cells. In spite of using different types of preparations of these cells (i.e., freshly dispersed cell suspensions, monolayer cultures, or dispersed islets after culture), ICSAs could not be detected by IFL under the UV microscope, nor by flow cytometry. In contrast, 9 of 29 of the sera gave a positive staining on the RIN rat insulinoma cells. In an attempt to establish whether the putative ICSA autoantigen is present in the surface of human islet cells in the diabetic pancreas, the insulitis microenvironment was emulated by exposing the islets to three types of stress: 1) cytokines (IFN-gamma and TNF-alpha); 2) heat shock; and 3) hyperglycemia. However, diabetic sera failed again to recognize membrane antigens on the islet cells after either of these treatments. Neither were islet cells from a newly diagnosed diabetic patient stained by its autologous serum (ICA titer > 80 JDF U). These results suggest that ICSA autoantigen is not expressed in the membrane of human islet cells and therefore raises doubts about their proposed pathogenic role.

Adolescent

Mechanism of action of maternal serum on the interleukin2 receptor expression.

Neoplastic Jurkat cells were submitted to a PHA stimulation test after a preincubation in maternal or nulliparous serum (10% dilution). The Il2R expression was significantly downregulated among maternal serum treated cells. Retroplacental serum was significantly more inhibitive than peripheral maternal serum (P less than 0.01). The maternal IgG fractions and mostly the retroplacental IgG fraction proved to contain a factor mainly responsible for the Il2R expression inhibitive property. The molecular mechanism of this phenomenon was further studied. It was shown that H7 (acting as a protein kinase inhibitor) could not influence the Il2R modulation. E.G.T.A., a calcium chelator, was not able to interfere with the inhibitive influence of maternal serum. It was suggested that the maternal serum mediated inhibition of the IL2R expression is not influenced by the hydrolysis of membrane bound phosphatidyl inositol. In contrast, pertussis toxin markedly enhanced, in a dose dependent way, the suppressive influence of maternal serum as compared to nulliparous serum. At low concentrations, pertussis toxin lost its stimulating property and retained its ability to ADP ribosylate the alpha subunit of G proteins inducing a release of adenylcyclase mediating cAMP synthesis. This mechanism has been further studied by the addition of dbc AMP or dbc GMP to Jurkat cells preparations stimulated by PHA. dbc AMP, in a dose-related way, induced a downregulation of the IL2R expression of stimulated neoplastic cells preincubated in nulliparous or maternal serum. dbc GMP did not influence the IL2R expression in the same experimental conditions. The maternal serum mediated cells showed the most pronounced IL2R inhibition. Finally, it was shown that the cAMP synthesis by PHA stimulated Jurkat cells was upregulated in a dose dependent way, after a previous cellular incubation in progressive concentrations of maternal serum. In contrast, among nulliparous serum pretreated cells, cAMP synthesis remained significantly lower, after a lectin stimulation, as compared to the cAMP production derived from retroplacental serum treated and stimulated cells. Taken together, these experiments suggest that the maternal serum dependent suppression of the IL2R expression is related to a protein G stimulation followed by an enhanced cAMP synthesis.

Calcium

[Restoration of colonic continuity after Hartmann's operation].

A retrospective analysis of data from 69 patients treated by Hartmann's operation between 1981 and 1991 determined prognostic factors for colon continuity re-establishment and the mortality of this second intervention. The 15 patients who died during the first month after the Hartmann's operation were excluded from the study, the 54 survivors including 32 men and 22 women, mean age 68 +/- 12 years (range 19 to 87 years). The initial indication for surgery was: complicated sigmoid diverticulis (n = 26), cancer of colon (n = 14) or other site (n = 14). Colon continuity was re-established in 23 patients (42.6%), including 15 men and 8 women, mean age 60 +/- 10 years (range 38 to 78 years). In this latter group, 82.6% of the patients were under 70 years of age, indicative of a significant effect of age (p < 0.001) on re-establishment of continuity. Secondary anastomosis was obtained in 65.4% of cases of complicated sigmoid diverticulitis, whereas re-establishment of continuity was possible in only 7.1% of colon cancer patients (p < 0.001). The mean duration prior to re-establishment was 4.8 +/- 1.6 months (range 2.5 to 9 months). Morbidity was high (47.8%) and mortality 4.3% (1 patient). Hartmann's operation remains indicated for stages III and IV of complicated sigmoid diverticulosis, as well as for other benign affections (volvulus of sigmoid, perforation of sigmoid following injury), although it must be recognized that the possibilities of re-establishment are limited more in elderly patients and that fewer patients with colon cancer can benefit from the procedure. A period of 3 to 4 months appears sufficient to allow healing of the inflammatory phenomena of the initial operation, without the development of excessive retraction of the rectal stump.

Adult

Long-term vascular access via the inferior vena cava.

A prospective evaluation of long-term venous access catheters placed via the inferior vena cava was performed to determine their efficacy as well as short- and long-term morbidity. From June 1987 to May 1989, 31 catheters were placed in 26 patients, for a total of 3,503 catheter use days. All catheters were placed via an infraumbilical approach when the more conventional supraumbilical route was technically difficult, dangerous, or impossible to be used. There were a total of 14 complications in 12 episodes (one in every 701 catheter use days), six episodes of catheter occlusion or vessel thrombosis (one in every 583 catheter use days), one catheter malfunction, one episode of cuff erosion through the skin, and one catheter that migrated through the inferior vena cava into the retroperitoneum. These results compared favorably with our experience with long-term catheters of a similar type placed via a supraumbilical approach into the superior vena cava. We conclude that the infraumbilical route for long-term central venous access is safe and technically easy and should be strongly considered in patients in whom venous access via the supraumbilical approach will be technically difficult or have a high likelihood of failure.

Adolescent

Laser-induced fluorescence emission: I. The spectroscopic identification of fibrotic endocardium and myocardium.

UNLABELLED: Laser-induced fluorescence has been developed as a guidance system for laser angioplasty. Laser ablation has been used for resection of arrhythmogenic ventricular scar. We have investigated the use of laser-induced fluorescence for the detection of fibrotic and ischemic changes in endocardium and myocardium. Fluorescence emission spectra from human necropsy specimens were correlated with histologic examination. Normalized fluorescence intensity detected from both the endocardial and the myocardial surfaces of the fibrotic ventricular specimens was significantly higher than that of corresponding normal specimens at 440 to 475 nm. Fibrotic endocardium could be identified by a fluorescence emission intensity ratio less than 1.5 for wavelength ratio 375/450nm. Acutely infarcted endocardium was recognizable by a ratio of 1.5 to 2.0. The specificity and sensitivity of detection of scarred endocardium was 70 and 100%, respectively. Fibrotic myocardium was also consistently identified by fluorescence spectroscopy. CONCLUSION: Fluorescence emission spectroscopy can differentiate normal and fibrotic endocardium and myocardium, in vitro. This technique may be useful for guidance during laser ablation of arrhythmogenic ventricular scar.

Capillaries