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PubMed2005

Alternatives to levodopa in the initial treatment of early Parkinson's disease.

Parkinson's disease (PD) is primarily a disease of elderly patients. This article reviews current knowledge and recent developments relating to drugs that can be used as alternatives to levodopa as initial treatment of PD. Synthetic orally acting dopamine agonists have found increasing favour as an option for early PD in relatively young patients. This strategy is based on evidence that this approach may delay the onset of motor fluctuations, at least during the first 5 years of treatment. Subcutaneous apomorphine infusions may attenuate motor fluctuations in late-stage disease, and transdermal rotigotine, a dopamine agonist in development, has also been shown to be efficacious. The greater proclivity for dopamine agonists to cause psychotoxicity has, however, limited their routine use in the elderly. Selective monoamine oxidase type B (MAO-B) inhibitors, used as monotherapy, delay the need for the introduction of levodopa by about 9 months. These agents appear to be less efficacious than dopamine agonists but are better tolerated. Concern has been expressed about the potential of the MAO-B inhibitor selegiline (deprenyl) to induce cardiovascular adverse effects (orthostatic hypotension), either directly or through its amphetamine catabolites. Rasagiline is a new MAO-B inhibitor that is not broken down to amphetamine derivatives and is indicated as both monotherapy in early PD and as adjunctive therapy in PD patients with motor fluctuations. Two older classes of agents have undergone a resurgence of interest in recent years. Amantadine, which enhances dopaminergic transmission and has antiglutamate activity, is occasionally used as monotherapy but has recently been widely used as an antidyskinetic agent in late-stage PD. Anticholinergic drugs, such as benztropine (benzatropine) and orphenadrine also provide control of symptoms when used as monotherapy, but their psychotoxic, cognitive and autonomic adverse events make them inappropriate for the treatment of the elderly. Effective therapy in PD should prevent disease progression and abolish motor and cognitive handicap. Currently, none of the existing drugs meets all these needs.

Aged↗
PubMed1984

The role of ionized calcium in the diagnosis of subtle hypercalcemia in symptomatic primary hyperparathyroidism.

This report details our continued study of the role of ionized calcium (CAI) in the diagnosis of symptomatic primary hyperparathyroidism (HPT) in patients with persistently normal total serum calcium (CAT) or fluctuating normal total serum calcium levels with elevated CAT. A patient was considered to have fluctuating CAT values if at least 40% of the CAT values were within the normal range. Our previous study demonstrated that CAI provided no additional diagnostic benefit in patients with HPT who had persistently elevated CAT levels. This retrospective study adds 15 additional patients to the four previously reported patients whose workup for HPT included normal or fluctuating normal total serum calcium with elevated CAT values. Eighteen of these 19 patients had complications or symptoms referable to HPT. Nine of these patients had renal calculi. CAT was measured by atomic absorption spectroscopy and CAI was measured by a calcium-selective ion flow-through electrode. One hundred fifty-one concurrent preoperative measurements of CAT and CAI from these 19 patients were used for analysis. Overall, 46 (30.5%) of the CAT values were elevated, whereas 134 (88.7%) of the concurrent CAI values were elevated (P less than 0.001). In three of these 19 patients all preoperative CAT values were within normal limits, however, 20 of the 21 (95%) concurrent CAI values were elevated. In the remaining 16 patients the CAT values fluctuated between normal and elevated. In all of these patients, at least 40% of the preoperative CAT values were normal, and in 15 of these 16 patients at least 50% of the preoperative CAT values were within the normal range. In this fluctuating category there were 130 concurrent values of CAT and CAI. Only 46 of these 130 (35.4%) CAT values were elevated, whereas 114 of the 130 (87.7%) CAI values were elevated (P less than 0.001). All patients underwent parathyroid operation; 15 patients had a parathyroid adenoma and four had hyperplasia. The CAI and CAT values returned to normal in all patients subsequent to operation. These data indicate that the measurement of serum ionized calcium appears to play an important role in the identification of symptomatic HPT in patients who have normal or fluctuating normal total serum calcium with elevated CAT values.

Adenoma↗
PubMed2002

Fluctuation of surface charge in membrane pores.

Surface charge in track-etched polyethylene terephthalate (PET) membranes with narrow pores has been probed with a fluorescent cationic dye (3,3'-diethyloxacarbocyanine iodide (diO-C2-(3))) using confocal microscopy. Staining of negatively charged PET membranes with diO-C2-(3) is a useful measure of surface charge for the following reasons: 1) the dye inhibits K(+) currents through the pores and reduces their selectivity for cations; 2) it inhibits [3H]-choline+ transport and promotes 36Cl- transport across the membrane in a pH- and ionic-strength-dependent fashion; and 3) staining of pores by diO-C2-(3) is reduced by low pH and by the presence of divalent cations such as Ca2+ and Zn2+. Measurement of the time dependence of cyanine staining of pores shows fluctuations of fluorescence intensity that occur on the same time scale as do fluctuations of ionic current in such pores. These data support our earlier proposal that fluctuations in ionic current across pores in synthetic and biological membranes reflect fluctuations in the surface charge of the pore walls in addition to molecular changes in pore proteins.

Biophysical Phenomena↗
PubMed1981

The mode of action of vasopressin: membrane microstructure and biological transport.

Vasopressin affects a variety of cell systems. This review is focused on permeability changes induced by vasopressin in tight epithelia such as the collecting duct of the mammalian kidney and the skin and the bladder of anurans. These vasopressin effects are discussed with reference to current concepts and models of the microstructure of the plasma membrane. The transport of three major chemical species--Na, urea and water--is analyzed. In each instance, the hormone appears to activate selective membrane pathways situated at the rat-limiting barrier of the epithelium, i.e., the apical membrane. Available data suggest that two intra-cellular messengers -- cAMP and calcium -- plan a key role in the coupling between stimulus (receptor occupancy) and biological effect (permeability change). The enhancement of Na transport (natriferic effect) depends on the opening and/or the insertion of Na channels, the biophysical and biochemical characteristics of which have been investigated by fluctuation analysis and by means of several chemical blockers of Na transport, particularly the amiloride molecule and its congeners. Likewise, the finding of inhibitors and activators of urea transport, which do not cause any appreciable change in Na or water permeability, led to the notion of selective urea channels or pores. Finally, the enhancement of water transport (hydrosmotic effect) possibly results from the insertion in the apical membrane of water channels already present in vesicular cytoplasmic structures. The restructuring of the apical membrane underlying the transition from a low to a higher state of water permeability is very likely related to the appearance of intramembrane particle aggregates detectable with the freeze-fracture technique in epithelia exposed to vasopressin. The putative water channels (or pores) appear to be so narrow that trans-apical water movement is constrained to single-file diffusion. Recent data also suggest that, in addition to cAMP, microtubules and microfilaments, the calmodulin-Ca complex is a major element in the hydrosmotic effect of vasopressin.

Amphibians↗
PubMedDate not supplied

Controlled release levodopa in Parkinson's disease: influence of selection criteria and conversion recommendations in the clinical outcome of 450 patients. STAR Study Group.

We present the results of an open, prospective, multicentric study including 450 patients with mild to moderate Parkinson's disease (PD) converted from standard Sinemet to Sinemet CR (controlled release; Dupont Pharma, Pavia, Italy). Patients with complex fluctuations and diphasic dyskinesias were excluded and the conversion was made after some recommendations, depending on the clinical problems and the daily dosage and administration schedule of standard (STD) Sinemet. The condition of more than 60% of the patients improved after the change and 80% of them preferred the CR formulation by the end of the study. We found a moderate, but significant, improvement in most of the efficacy parameters used, such as the Unified Parkinson's Disease Rating Scale (UPDRS), the Schawb and England scale, and dyskinesias and sleep questionnaires. Forty-five patients (10%) discontinued the study due to adverse effects (mainly gastrointestinal disturbances, functional deterioration, and dyskinesias). We conclude that Sinemet CR is a useful and safe therapeutic option in patients with mild and moderate PD. Selection of the patients is the most important outcome factor.

Aged↗
PubMed2003

[The fluctuation of anterior teeth colouration during the period of growth puberty in children and adolescents].

OBJECTIVE: This study was designed to examine the fluctuation tendency of the anterior teeth coloration during the period of growth puberty. METHODS: One hundred children with average age of 13.3 years, and 100 adolescents with average age of 23.4 years were divided into two groups. The upper left incisors were selected for color matching using computerized spectrophotometery system (Shade-eye, Shofu). The measurements depicting color properties, including hue, value and chroma were quantitatively analyzed. Statistical evaluation was conducted for the comparison of the color measurements between the two groups. RESULTS: The following trends were indicated during the period of growth puberty: (1)The hue of the coloration changed from redness into mixture of redness and grayness. (2)The magnitude of value of the coloration was in decline. (3)The intensity of chroma increased significantly. CONCLUSIONS: The teeth coloration fluctuates within the period spanning the initial and final stages of growth puberty, characterized by a decrease in hue and value and an increase in chroma.

Adolescent↗
PubMed2002

Spatio-temporal patterns of neuronal activity: analysis of optical imaging data using geometric shape matching.

Optical imaging of neuronal network activity yields information of spatial dynamics which generally is analyzed visually. The transient appearance of spatial activity patterns is difficult to gauge in a quantifiable manner, or may even altogether escape detection. Here, we employ geometric shape matching using Fréchet distances or straight skeletons to search for pre-selected patterns in optical imaging data with adjustable degrees of tolerance. Data were sampled from fluorescence changes of a voltage-sensitive dye recorded with a 464-photodiode array. Fluorescence was monitored in a neuronal network in vitro. Neuronal activity prompting fluorescence fluctuations consisted of spontaneous epileptiform discharges in neocortical slices from patients undergoing epilepsy surgery. The experiments show that: (a) spatial activity patterns can be detected in optical imaging data; (b) shapes such as "mini-foci" appear in close correlation to bioelectric discharges monitored with field potential electrodes in a reproducible manner; (c) Fréchet distances yield more conservative matches regarding rectangular, and less conservative hits with respect to radially symmetric shapes than the straight skeleton approach; and (d) tolerances of 0.03-0.1 are suited to detect faithful images of pre-selected shapes, whereas values >0.8 will report matches with any polygonal pattern. In conclusion, the methods reported here are suited to detect and analyze spatial, geometric dynamics in optical imaging data.

Algorithms↗
PubMed1986

Na+ selective channels in the apical membrane of rabbit late proximal tubules (pars recta).

Using the patch-clamp technique, Na+ selective channels were observed in the luminal membrane of rabbit straight proximal tubule segments. In the cell-attached configuration (NaCl-Ringers in pipette and bath) influx of Na+ ions from the pipette into the cell through fluctuating channels was observed. The current-voltage curve of these Na+ channels yielded a zero-current potential of 84.3 +/- 30.9 mV (n = 10), reflecting the electrochemical driving force for Na+ influx under resting conditions. The single channel conductance was 12.0 +/- 2.1 pS (n = 13). In inside-out oriented cell-excised patches the single channel conductance was not significantly different with NaCl-Ringers on both sides. At clamp potentials ranging from +50 mV to -50 mV the single channel current was ohmic and channel kinetics were independent of the voltage. With KCl-Ringers on the bath side (corresponding to cell interior), the zero current potential was 62 +/- 19 mV (n = 4), indicating a high selectivity of Na+ over K+ ions. Addition of 10(-5) mol/l amiloride to the bathing solution decreased the mean channel open time slightly. This effect was more pronounced with 10(-4) mol/l amiloride, whereas the single channel conductance was unaffected by the diuretic. 10(-3) mol/l amiloride caused a complete block of the channel. It is concluded that amiloride sensitive Na+ channels, with similar properties to those observed in tight epithelia, contribute to Na+ reabsorbtion in the straight portion of proximal tubules.

Amiloride↗
PubMed2001

Engineering hepatocyte functional fate through growth factor dynamics: the role of cell morphologic priming.

We have reported previously that cellular stimulation induced by variable mechanochemical properties of the extracellular microenvironment can significantly alter liver-specific function in cultured hepatocytes (Semler et al., Biotech Bioeng 69:359-369, 2000). Cell activation via time-invariant presentation of biochemical growth factors was found to either enhance or repress cellular differentiation of cultured hepatocytes depending on the mechanical properties of the underlying substrate. In this work, we investigated the effects of dynamic growth factor stimulation on the cell growth and differentiation behavior of hepatocytes cultured on either compliant or rigid substrates. Specifically, hepatotrophic growth factors (epidermal and hepatocyte) were either temporally added or withdrawn from hepatocyte cultures on Matrigel that was crosslinked to yield differential degrees of mechanical compliance. We determined that the functional responsiveness of hepatocytes to fluctuations in GF stimulation is substrate specific but only in conditions in which the initial mechanochemical environment induced significant cell morphogenesis. Our studies indicate that in conditions under which hepatocytes adopted a "rounded" phenotype, they exhibited increased levels of differentiated function upon soluble stimulation and markedly decreased function upon the depletion of GF stimulation. In contrast, hepatocytes that assumed a "spread" phenotype exhibited slightly increased function upon the depletion of GF stimulation. By examining the functional responsiveness of hepatocytes of differential morphology to varied fluctuations in GF activation, insights into the ability of cell shape to "prime" hepatocyte behavior in dynamic microenvironments were elucidated. We report on the possibility of uncoupling and, thus, selectively manipulating, the concerted contributions of GF-induced cellular activation and substrate- and GF-induced cell morphogenesis toward induction of cell function.

Animals↗
PubMed1999

Dopamine agonists: what is the place of the newer compounds in the treatment of Parkinson's disease?

Three new dopamine agonists (cabergoline, pramipexole, ropinirole) have been put on to the market within the past months to treat patients with Parkinson's disease. Like any marketed dopamine agonists, the new compounds bind to the D2-like receptors. Pramipexole and ropinirole appear to be quite close drugs. Both are selective non ergot D2 (and preferentially D3) agonists, with an elimination half-life of 5 to 10 hours. Conversely, cabergoline is an ergot derivative, less selective for the D2 receptors, with a much longer elimination half-life (60 hours or more). In moderately advanced levodopa treated patients with Parkinson's disease and motor fluctuations, cabergoline, pramipexole and ropinirole all do significantly better than placebo in reducing UPDRS motor examination scores, time spent off and daily dose of levodopa. None of the 3 newer agonists proved to do significantly better than bromocriptine in this indication, at the cost of very similar adverse effects. In de novo levodopa naive patients, pramipexole and ropinirole did significantly better than placebo in short-term (few months) follow-up trials, at the cost again of classical dopaminergic adverse effects. Ropinirole was marginally more effective than bromocriptine, while its use induced the same risk of psychosis than the "old" reference agonist. Early treatment with cabergoline, compared with levodopa, in a long-term (5 year) study reduced the relative risk of developping motor complication by more than 50%. A similar study is presently on-going to compare ropinirole and levodopa. Clinical trials to assess putative neuroprotective effects are also on going with ropinirole and pramipexole. Up to now, the available clinical controlled data suggest that the newer dopamine agonists have very similar clinical effects with only minor superiority, if any, versus bromocriptine.

Dopamine Agonists↗
PubMed1981

In vitro effect of some mutagens/carcinogens on cultured fish cells.

Fibroblast cells derived from juvenile bluegill sunfish were tested for their response the effects of known mutagens/carcinogens. The cells grew well and cloned in Eagle's minimal essential medium which contained fetal bovine serum. Growth rate was temperature dependent and increased steadily as temperature was raised from 15 to 33 degrees C. Direct mutagens and promutagens were toxic to the cells, and fluorescence spectroscopy revealed the capability of metabolizing at least one promutagen, benzo(a)pyrene, to water-soluble intermediates. Ouabain resistant mutants were produced by exposing the cells to N-methyl-N-nitro-nitrosoguanidine (MNNG) or to benzo(a)pyrene (B(a)P). The mutant clones were resistant to 100-fold increases in concentration of the selective agent ouabain, over that which was lethal to wild type cells. Spontaneous mutation frequency to ouabain in mass cultures averaged 1.2 X 10(-6) for all experiments. A fluctuation test confirmed an expected random occurrence of spontaneous mutations. Visible crystals formed within the cells when high concentrations of B(a)P (greater than 5 micrograms/ml were added to the tissue culture medium. Crystal formation resulted in no apparent cell damage but did reduce the growth rate of the cultures. The crystals were rhombic, resembling those described for pure native B(a)P, and gradually disappeared when the cells were exposed to mutagen-free medium which contained serum.

Animals↗
PubMed1988

Segmental autotransplantation of the pancreas after total pancreatectomy for advanced periampullary carcinoma--a case report.

A case is reported here in which segmental autotransplantation of the pancreas was performed after total pancreatectomy for advanced periampullary carcinoma in an attempt to preserve pancreatic endocrine function. The postoperative course was uneventful. The requirement of insulin decreased after the operation and the daily profile examination, done 5 months following surgery, showed a permissive fluctuation of blood sugar levels without insulin injection. Thus, segmental autotransplantation of the pancreas offers a method of preserving pancreatic endocrine function after total pancreatectomy for periampullary carcinoma in selected patients.

Carcinoma↗
PubMed2003

Winter warming facilitates range expansion: cold tolerance of the butterfly Atalopedes campestris.

Our ability to predict ecological and evolutionary responses to climate change requires an understanding of the mechanistic links between climate and range limits. The warming trend over the past half-century has generated numerous opportunities to develop much-needed case studies of these links. Species that are only limited by climatic factors are likely to shift range quickly during periods of warming. Such species directly impact recipient communities and indicate trends that will become more widespread. Because minimum temperature (T (min)) is rising at twice the rate of maximum temperature, species with this range-limiting factor may be especially responsive to global warming. In this study, I test the hypothesis that rising T (min) has directly affected the range of a skipper butterfly. Atalopedes campestris has moved northward rapidly this century, recently colonizing eastern Washington where January T (min) has risen 3 degrees C in 50 years. The results show that: 1. A. campestris' range lies completely within the -4 degrees C January average minimum isotherm, and that recently colonized areas were below this threshold earlier this century. 2. In acute cold stress experiments, -4 to -7 degrees C proved to be a critical thermal limit: median supercooling point was -6.3 degrees C, and minimum lethal temperature (LT50 with 12-h exposure) was -5.7 degrees C. 3. In chronic cold stress experiments, survivorship declined sharply in diurnally fluctuating thermal regimes typical of the current range edge. High mortality occurred under constant 0 degrees C conditions as well as in fluctuating regimes, implying that thermal insulation from snow would not protect A. campestris. 4. There was no evidence of evolution in cold tolerance at the range margin, despite strong selection. Thus, winter warming was apparently a prerequisite for the range expansion. Characteristics of this species that seem to be associated with its rapid response are that it is an opportunistic species, it is not habitat or dispersal limited, and it is constrained by T (min).

Acclimatization↗
PubMed1983

Immunologic and respiratory responses to airway challenges of dogs with toluene diisocyanate.

Dogs received biweekly or monthly aerosol immunization with single doses of toluene diisocyanate (TDI) that were cumulative doses analogous to human chronic exposure at 0.02 ppm. The three dogs developed systemic immune responses to TDI-dog serum albumin (DSA). The immune responses included IgG, IgA, and IgM antibody responses and development of lymphocyte reactivity. IgA titers approached IgG titers and both were persistent, whereas IgM titers were low and of short duration. IgE antibody titers demonstrated by endpoint cutaneous titration appeared but fluctuated and became negative in spite of continued aerosol exposure of TDI. Immediate-type airway responses occurred after TDI aerosolization. Some limited responses that showed only abnormalities of selected pulmonary function parameters were clearly not immunologically mediated because they occurred with initial exposure. Other immediate-type airway responses occurred that qualitatively simulated IgE-mediated, antigen-induced airway responses in dogs. There was a statistically significant correlation (p = 0.0268) between these latter airway responses and immediate-type skin reactivity. This study demonstrates that this dog model simulates the complexity of airway responses to TDI in man but may provide a laboratory system for evaluation of immunologic or other proposed mechanisms of TDI asthma.

Animals↗
PubMed1998

Taking the laboratory to the skies: ambulatory assessment of self-report, autonomic, and respiratory responses in flying phobia.

We evaluated the feasibility of recording multiple physiological anxiety measures during a flight and how well they could distinguish flight phobics from controls. Benefits of baseline adjustment and transformation for all variables and adjustment of heart rate by ventilation to give additional heart rate were calculated. Effect size, one measure of the power to discriminate groups, was between 1.1 and 1.7 for heart rate measures. Although respiratory rate and minute ventilation, indicators of hyperventilation, did not differ between groups, phobics paused more during inspiration than did controls. Phobics also showed more skin conductance fluctuations and less respiratory sinus arrhythmia. Self-reported anxiety was a more powerful discriminator than physiological measures, a result that may be partially explained by how phobics were selected. These results indicate that monitoring of multiple physiological systems outside the laboratory is practical and informative. Physiological measures of psychological importance can be quantified accurately in a noisy, changing, unsupervised ambulatory setting.

Adult↗
PubMed1996

Dissociation in prefrontal cortex of affective and attentional shifts.

The prefrontal cortex is implicated in such human characteristics as volition, planning, abstract reasoning and affect. Frontal-lobe damage can cause disinhibition such that the behaviour of a subject is guided by previously acquired responses that are inappropriate to the current situation. Here we demonstrate that disinhibition, or a loss of inhibitory control, can be selective for particular cognitive functions and that different regions of the prefrontal cortex provide inhibitory control in different aspects of cognitive processing. Thus, whereas damage to the lateral prefrontal cortex (Brodmann's area 9) in monkeys causes a loss of inhibitory control in attentional selection, damage to the orbito-frontal cortex in monkeys causes a loss of inhibitory control in 'affective' processing, thereby impairing the ability to alter behaviour in response to fluctuations in the emotional significance of stimuli. These findings not only support the view that the prefrontal cortex has multiple functions, but also provide evidence for the distribution of different cognitive functions within specific regions of prefrontal cortex.

Affect↗
PubMed1999

Semiquantitative analysis of residual disease in patients treated for adult T-cell leukaemia/lymphoma (ATLL).

Many adult T-cell leukaemia/lymphoma (ATLL) patients who respond to induction treatment, then relapse. Knowing the clonality pattern of residual tumourous clones during treatment could help understand disease evolution and aid therapeutic decisions. We developed a sensitive and semi-quantitative molecular analysis of these clones in ATLL patients. DNA samples from PBMCs derived from eight ATLL patients were studied over time by quadruplicate linker mediated PCR (LMPCR) amplification of HTLV-1 integration sites. Patients were treated with combination chemotherapy, zidovudine-interferon-alpha and/or by peripheral stem cell transplantation or allogeneic bone marrow transplantation. Persistence of tumourous clones at a high frequency (>1/300 PBMCs) was frequently observed, even in complete responders, and was invariably correlated with relapse and/or poor outcome. Fluctuation in the frequency of some tumourous clones was observed with evidence for clonal change under treatment in one patient, indicating that treatment of ATLL can result in the selection of resistant clones. Finally, allogeneic bone marrow transplantation (BMT) using an HTLV-1 infected sibling as donor was found to be associated with long-lasting disappearance of tumourous clones and a possible cure of the disease. Long-term persistent clonal expansion of circulating HTLV-1 bearing T cells which derived from the donor bone marrow was evidenced in this patient. In conclusion, variable success in treatment of ATLL is probably due to the clonal heterogeneity which results in the selection of resistant clones. Semi-quantitative assessment of residual disease (RD) through LMPCR may predict treatment failure. Accordingly, additional therapy may be tailored to the clonality pattern observed after first-line therapy.

Adult↗
PubMed1991

The relationship of neonatal alimentation practices to the occurrence of endemic necrotizing enterocolitis.

Enteric alimentation has been one of several factors implicated in the development of necrotizing enterocolitis (NEC). To examine this relationship further, the alimentation records of 19 patients who developed NEC were each compared with two matched patients controlled for birthweight and time of admission to the intensive care nursery. Parameters compared included total fluids provided, rate of enteral feed volume advancement, milk selection, and medications given. In addition, because there were no marked day-to-day differences between the mean values of most parameters and because we noted a marked fluctuation of formula intake and volume increments, we analyzed the maximum differences between the two groups. Maximum total fluids intake occurred on day 5 of life for the NEC patients and was 180.7 +/- 44 ml/kg. The control group on this same day received 149.7 +/- 35 ml/kg (p less than 0.01). Maximum enteral intake occurred on day 8 for the NEC patients at 124.3 +/- 5.7 ml/kg, whereas the control group had consumed only 83.5 +/- 60 ml/kg (p less than 0.05) on this matched day. The feed increment rate from initiation of feeds to day of maximum feeds was 27.8 +/- 16 ml/kg/day for the NEC patients and 16.8 +/- 11 for the control patients (p less than 0.0005). Furthermore, during the entire study period patients who developed NEC had the greatest 1 day increment compared with the controls (56.7 +/- 19.4 vs 44.6 +/- 26.2 ml/kg, p less than 0.05). Very rapid advancement of enteral feedings and excessive fluid volumes may predispose premature infants to the development of NEC and should be discouraged.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗