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Biomedical subjects

T J Chen

Publications and source records attributed to T J Chen.

At least 19 recordsLinked to original sources

Involvement of apoptosis during deciduomal regression in pseudopregnant hamsters effect of progesterone.

We determined whether fragmentation of genomic DNA, apoptosis, occurs during deciduomal regression in pseudopregnant hamsters and the effect of progesterone on the apoptotic processes. Artificially induced deciduoma were obtained on different days of pseudopregnancy and separated into mesometrial and antimesometrial tissues. The deciduomal cell cycle progression and population profiles of both sides were compared by flow cytometry. The proportion of sub-G1 peak, which was correlated with the apoptotic cells, were about 10% on day 8 and reached to 40% in both tissues on day 10. Exogenous progesterone treatment by daily injection (2 mg; s.c.) on and after day 8 reduced the percentage of low molecular weight DNA in both tissues on day 10 and day 12 as compared to the nontreated control one, respectively. The appearance of DNA ladder was also delayed at least 24 h by progesterone administration. The intensity of DNA fragmentation was more pronounced in antimesometrial deciduoma. In situ 3'-end labeling of apoptotic cells further substantiated the apoptotic process. The apoptotic cells first appeared in the luminal region in antimesometrial deciduoma on day 8 and spreaded all over the entire deciduomal tissue on day 10. Progesterone treatment stimulated deciduomal proliferating cell nuclear antigen (PCNA) expression, maintained deciduoma until day 14 and retarded the differentiation and regeneration of the uterine epithelium.

Animals↗

Molecular genetics of glycogen-storage disease type 1a in Chinese patients of Taiwan.

The mutation spectrum of the glucose 6-phosphatase (G6Pase) gene in Chinese patients with type 1a glycogen-storage disease of Taiwan was studied by PCR/RFLP, temporal temperature gradient gel electrophoresis, and direct DNA sequencing methods. In addition to the two most prevalent mutations, 727G --> T (44.4%) and R83H (36.1%), that were detected by RFLP analysis, five other mutations, 341delG, 933insAA, Q104X, I341N, and H119L were identified. The frameshift mutations (341delG and 933insAA) and the nonsense mutation (Q104X) that produce truncated proteins are predicted to be disease-causing. The missense mutation, I341N, occurring in the last transmembrane domain of the ER-bound enzyme, retains a small amount of residual activity of approximately 10%. Except for R83H, the mutations have been described only in Asians. H119L, however, is of particular interest because of the essential role of the catalytic histidine of phosphohydrolase. This amino acid is believed to be involved in the formation of the phosphoryl-enzyme intermediate during catalysis. The patient who was compound heterozygous for 727G --> T and H119L mutations had essentially no G6Pase activity in her liver biopsy. This observation is consistent with the importance of H119L in catalysis.

Base Sequence↗

Left atrial and ventricular ball thrombi complicating rheumatic heart disease with combined mitral and aortic stenosis.

A 42-year-old woman with chronic mitral stenosis was admitted for progressive dyspnea, palpitation, and weakness of lower extremities. Echocardiography revealed rheumatic, thickened, and stenotic mitral and aortic valves, and two free-floating ball thrombi were detected in the left atrium and ventricle, respectively. She died suddenly the next day, probably due to mitral or aortic outflow obstruction by the ball thrombi. We believe that the occurrence of free-floating ball thrombi in both the left atrium and left ventricle concomitantly has never been reported.

Aged↗

Evaluating the protective role of the olivocochlear bundle against acoustic overexposure in rats by using Fos immunohistochemistry.

Efferent inhibition on the cochlea is suggested as a possible function of the olivocochlear bundle (OCB). Substantial evidence supports the finding that the OCB may protect the inner ear from noise-induced damage. However, there is relatively less known about the effects of noise on the central auditory transmission compared to the effects on the periphery. In the present animal study, two experimental paradigms were designed to analyze the influence of OCB lesion on the central auditory transmission following acoustic overexposure. In order to evaluate the animal's auditory function, its hearing threshold and the tone-evoked Fos expression shown in auditory nuclei were examined. Fos is a protein product of proto-oncogene c-fos. Via appropriate acoustic stimulation, Fos expression reveals the activated neuronal elements along the ascending auditory pathway. Thus, in experiment 1, no exposure sound was introduced and therefore no significant differences were shown in hearing thresholds and Fos expression among all rats, regardless of the status of their OCB. This result indicates that, without acoustic overexposure, OCB lesion caused no significant effect on brainstem auditory transmission. In contrast, in experiment 2, rats were exposed to continuous 8 kHz tones at 85 dB sound pressure level (SPL). A significantly increasing threshold was observed in rats with OCB lesion following an exposure period of 5 or 10 days. In addition, Fos expression was invisible first in rats with OCB lesion following 5-day exposure and almost no Fos expression could be examined in all rats after 10-day exposure. Taken together, the present data demonstrate that damaging the OCB renders an animal more easily vulnerable to acoustic damage than that of rat with intact OCB, and then reduces its cochlear activities, which eventually leads to increasing difficulty to induce tone-evoked Fos expression along the ascending auditory pathway.

Animals↗

Impaired vascular dynamics in normotensive diabetic rats induced by streptozotocin: tapered T-tube model analysis.

This study is to explore the changes of arterial mechanical properties in streptozotocin (STZ)-diabetic rats, based on the exponentially tapered T-tube model. Rats given STZ 65 mg kg(-1)i.v. are compared with untreated weight- and age-matched controls. A high-fidelity pressure sensor and electromagnetic flow probe measured pulsatile pressure and flow waves in the ascending aorta, respectively. Diabetic rats exhibit isobaric vasodilatation that is characterized by an increase in cardiac output and no significant changes in aortic pressure. Total peripheral resistance of diabetic rats is lower than that of weight- and age-matched controls. Diabetic rats have higher total peripheral compliance (2.86+/-0.70 microl mm Hg(-1)) than do weight- (1.77+/-0.34 microl mm Hg(-1)) and age-matched (1.87+/-0.69 microl mm Hg(-1)) controls. Aortic characteristic impedance is reduced from 0.017+/-0.003 mm Hg min kg ml(-1)in weight- and 0.020+/-0.004 mm Hg min kg ml(-1)in age-matched controls to 0.010+/-0.004 mm Hg min kg ml(-1)in diabetic rats. Moreover, diabetic rats show shorter wave transit time in lower body circulation (17.86+/-1.91 ms) than do weight- (20.45+/-1.91) and age-matched (23.05+/-2.04 ms) controls. Under isobaric vasodilatation, the decreased resistance and increased compliance in peripheral circulation suggest that the contractile dysfunction of the smooth muscle cells may occur in resistance arterioles in diabetes. With unaltered aortic pressure, an impairment in aortic distensibility of STZ-diabetic rats is manifest on the reduced wave transit time rather than on the diminished aortic characteristic impedance.

Animals↗

High-resolution finite element models with tissue strength asymmetry accurately predict failure of trabecular bone.

The ability to predict trabecular failure using microstructure-based computational models would greatly facilitate study of trabecular structure-function relations, multiaxial strength, and tissue remodeling. We hypothesized that high-resolution finite element models of trabecular bone that include cortical-like strength asymmetry at the tissue level, could predict apparent level failure of trabecular bone for multiple loading modes. A bilinear constitutive model with asymmetric tissue yield strains in tension and compression was applied to simulate failure in high-resolution finite element models of seven bovine tibial specimens. Tissue modulus was reduced by 95% when tissue principal strains exceeded the tissue yield strains. Linear models were first calibrated for effective tissue modulus against specimen-specific experimental measures of apparent modulus, producing effective tissue moduli of (mean+/-S.D.) 18.7+/-3.4GPa. Next, a parameter study was performed on a single specimen to estimate the tissue level tensile and compressive yield strains. These values, 0.60% strain in tension and 1.01% strain in compression, were then used in non-linear analyses of all seven specimens to predict failure for apparent tensile, compressive, and shear loading. When compared to apparent yield properties previously measured for the same type of bone, the model predictions of both the stresses and strains at failure were not statistically different for any loading case (p>0.15). Use of symmetric tissue strengths could not match the experimental data. These findings establish that, once effective tissue modulus is calibrated and uniform but asymmetric tissue failure strains are used, the resulting models can capture the apparent strength behavior to an outstanding level of accuracy. As such, these computational models have reached a level of fidelity that qualifies them as surrogates for destructive mechanical testing of real specimens.

Animals↗

Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors.

The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms. The net effect of neurotransmitter interaction at the mesolimbic brain region induces "reward" when dopamine (DA) is released from the neuron at the nucleus accumbens and interacts with a dopamine D2 receptor. "The reward cascade" involves the release of serotonin, which in turn at the hypothalmus stimulates enkephalin, which in turn inhibits GABA at the substania nigra, which in turn fine tunes the amount of DA released at the nucleus accumbens or "reward site." It is well known that under normal conditions in the reward site DA works to maintain our normal drives. In fact, DA has become to be known as the "pleasure molecule" and/or the "antistress molecule." When DA is released into the synapse, it stimulates a number a DA receptors (D1-D5) which results in increased feelings of well-being and stress reduction. A consensus of the literature suggests that when there is a dysfunction in the brain reward cascade, which could be caused by certain genetic variants (polygenic), especially in the DA system causing a hypodopaminergic trait, the brain of that person requires a DA fix to feel good. This trait leads to multiple drug-seeking behavior. This is so because alcohol, cocaine, heroin, marijuana, nicotine, and glucose all cause activation and neuronal release of brain DA, which could heal the abnormal cravings. Certainly after ten years of study we could say with confidence that carriers of the DAD2 receptor A1 allele have compromised D2 receptors. Therefore lack of D2 receptors causes individuals to have a high risk for multiple addictive, impulsive and compulsive behavioral propensities, such as severe alcoholism, cocaine, heroin, marijuana and nicotine use, glucose bingeing, pathological gambling, sex addiction, ADHD, Tourette's Syndrome, autism, chronic violence, posttraumatic stress disorder, schizoid/avoidant cluster, conduct disorder and antisocial behavior. In order to explain the breakdown of the reward cascade due to both multiple genes and environmental stimuli (pleiotropism) and resultant aberrant behaviors, Blum united this hypodopaminergic trait under the rubric of a reward deficiency syndrome.

Behavior, Addictive↗

Kinetics of germanium dioxide in rats.

The kinetics of germanium dioxide (GeO2) in single dose and repeated exposures were investigated in male Wistar rats. In the single dose GeO2 (100 mg/kg BW, p.o.) exposure study, values of several kinetic parameters were shown as follows, a maximum concentration in serum of 15.5+/-0.7 microg/ml (mean +/- S.E.M.), an absorption half-life of 0.7+/-0.1 h (mean +/- S.E.M.), an elimination half-life of 2.3+/-0.5 h (mean +/- S.E.M.), a distribution of the central compartment Vp (3.1+/-0.3 1, mean +/- S.E.M.), and the apparent volume of distribution of the tissue compartment Vt (8.5+/-2.9 1, mean +/- S.E.M.). In the repeated exposure study, 730+/-92 mg GeO2 in 1 1 double-distilled H2O ( = 100 mg/kg/day) was given daily to rats for 4 weeks (p.o.). After sacrificing the rats, the analysis of tissue distribution showed that GeO2 was accumulated in some important organs or tissues in the body, especially the peripheral nerves and kidney. These results indicate that GeO2 could be absorbed rapidly but had a longer elimination half-life in rats. In addition, GeO2 was accumulated especially in the nerves and kidney following long-term exposure.

Animals↗

Effects of food restriction on mechanical properties of arterial system in adult and middle-aged rats.

The effects of food restriction on the mechanical properties of the vasculature were determined in Long-Evans male rats with different ages. Rats that began food restriction at the ages of 6 months and 12 months were fed on alternate days for 6 months. Rats at the ages of 12 and 18 months were referred to as adult and middle-aged rats and were anesthetized and thoracotomized. The exponentially tapered T-tube model was employed to relate pulsatile pressure and flow signals measured in the ascending aorta. In each age group, food restriction elicited a decrease in body weight as well as basal heart rate but showed no significant change in cardiac output. Arterial blood pressure, total peripheral resistance, and aortic characteristic impedance were not affected by food restriction in middle-aged rats. However, adult food-restricted rats exhibited lower mean arterial blood pressure (99.1 +/- 3.1 mmHg) than did adult ad libitum-fed rats (110.7 +/- 3.0 mmHg). Total peripheral resistance was reduced from 0.645 +/- 0.045 mmHg-min-kg/ml in adult ad libitum-fed rats to 0.492 +/- 0.030 mmHg-min-kg/ml in adult food-restricted rats. Moreover, aortic characteristic impedance of adult food-restricted rats (0.014 +/- 0.001 mmHg-min-kg/ml) was lower than that of adult ad libitum-fed rats (0.024 +/- 0.002 mmHg-min-kg/ml). Neither age nor diet exerted effects on wave transit time and produced no changes in aortic distensibility. In conclusion, food restriction may elicit significant changes in the mechanical properties of both Windkessel vessels and resistance arterioles in adult rats, but not in middle-aged rats.

Aging↗

Detection of mitochondrial DNA mutations by temporal temperature gradient gel electrophoresis.

BACKGROUND: A unique requirement for the molecular diagnosis of mitochondrial DNA (mtDNA) disorders is the ability to detect heteroplasmic mtDNA mutations and to distinguish them from homoplasmic sequence variations before further testing (e.g., sequencing) is performed. We evaluated the potential utility of temporal temperature gradient gel electrophoresis (TTGE) for these purposes in patients with suspected mtDNA mutations. METHODS: DNA samples were selected from patients with known mtDNA mutations and patients suspected of mtDNA disorders without detectable mutations by routine analysis. Six regions of mtDNA were PCR amplified and analyzed by TTGE. Electrophoresis was carried out at 145 V with a constant temperature increment of 1.2 degrees C/h. Mutations were identified by direct sequencing of the PCR products and confirmed by PCR/allele-specific oligonucleotide or PCR/restriction fragment length polymorphism analysis. RESULTS: In the experiments using patient samples containing various amounts of mutant mtDNA, TTGE detected as little as 4% mutant heteroplasmy and identified heteroplasmy in the presence of a homoplasmic polymorphism. In 109 specimens with 15 different known mutations, TTGE detected the presence of all mutations and distinguished heteroplasmic mutations from homoplasmic polymorphisms. When 11% of the mtDNA genome was analyzed by TTGE in 104 patients with clinically suspected mitochondrial disorders, 7 cases of heteroplasmy ( approximately 7%) were detected. CONCLUSIONS: TTGE distinguishes heteroplasmic mutation from homoplasmic polymorphisms and appears to be a sensitive tool for detection of sequence variations and heteroplasmy in patients suspected of having mtDNA disorders.

Alleles↗

Atypical central neurocytoma: report of a case.

Central neurocytomas are rare, relatively benign intraventricular neoplasms composed of uniform round cells with neuronal differentiation. The majority of previously reported central neurocytomas did not recurr after tumor removal and the patients had favorable postoperative outcomes. Only a few cases with malignant histopathology or malignant behavior have been noted. Atypical central neurocytoma is a new entity that was first described in the literature in 1997. The tumors have been noted to exhibit a Ki-67 labeling index of 2% or more, or vascular proliferation, mitoses, and necrosis, or both. Atypical histologic findings are usually associated with a somewhat less favorable clinical course and requires postoperative radiotherapy. We report a unique case of a 33-year-old man with a large intraventricular central neurocytoma. The characteristic histopathologic picture, the immunoreactivity for both synaptophysin and neuron-specific enolase, and the ultrastructural features of neuronal differentiation distinguished it from ependymoma and oligodendroglioma. The mitotic activity (up to 3 mitoses/10 high power field) and the high percentage of Ki-67-staining tumor cells (labeling index, 5.0%) in our case were consistent with the atypical variant of central neurocytoma. The patient underwent craniotomy and partial resection of the tumor. Unfortunately, he died of hydrocephalus and brain edema, the next day.

Adult↗

Variations of prostaglandin E2 receptors in hamster's ovary and endometrium during estrous cycle.

The purpose of this study was to determine concurrent ovarian and endometrial prostaglandin E2 (PGE2) receptor concentrations throughout the hamster estrous cycle. The effect of progesterone (P4) on PGE2 receptor in these two tissues was also investigated during in vitro culture. Estrous cycles of mature female hamsters were monitored according to the appearance of the vaginal discharge on cycle day 1 (D1). Ovaries and uteri were removed from cyclic hamsters at 10:00 a.m. on each day of the cycle and at 6:00 p.m. on D4 (proestrus). Ovarian and endometrial cell membranes were collected and assayed for the specific PGE2 binding by Scatchard plot analysis, using seven different concentrations of 3H-PGE2 (0.72-9.1 nM) with or without the presence of unlabelled PGE2 (9.1 microM). Ovarian and endometrial tissues of the cyclic hamsters were shown to contain a saturable, specific binding site with KD=4.69+/-0.55, and 5.7+/-0.4 nM for ovary and endometrium, respectively. Relative binding activity of PGE1 for the PGE2 binding site was about 28%. PGF2alpha and PGA1 did not compete for the PGE2 binding site. In ovaries, the PGE2 receptor levels started to increase sharply in the evening of D4 and reached maximum in the morning of D1. A precipitous drop of PGE2 receptor was observed on D2 followed by gradual decreases on D3 and D4. The PGE2 receptor concentrations in endometrium were the lowest in the morning of D4, and increased thereafter until a maximal level was reached on D2. Progesterone (10 nM) augmented PGE2 receptors in ovarian but not in endometrial tissue during 24-h in vitro incubation.

Animals↗

Effect of olivocochlear bundle lesion on locomotor activity in rats.

This study was conducted to investigate the effect of olivocochlear bundle (OCB) lesion on spontaneous locomotor activity in Wistar rats. The OCB is an auditory efferent pathway which originates from the superior olivary complex in the brainstem and terminates within the cochlea. It has an inhibitory effect on the auditory end organs. In the present study, the OCB was damaged at the floor of the fourth ventricle using radiofrequency current. The rats' locomotor activities were then monitored weekly for 2 months using an automated Digiscan activity monitor system. Six behavioral variables were collected and analyzed: horizontal activity (HA), total distance (TD), movement time (MT), vertical activity (VA), stereotypy count (SC), and margin time (MGT). Significant time-dependent increases were noted for HA, TD, VA, and SC following OCB lesion. These results of increasing exploratory and stereotyped behaviors may be caused by the rat experiencing more auditory stimulation than before due to OCB dysfunction and may cause the rat to become more curious to explore its surroundings.

Animals↗

Development of recombinant human prolactin receptor antagonists by molecular mimicry of the phosphorylated hormone.

Previous studies have demonstrated that naturally phosphorylated PRL antagonizes the growth-promoting effects of unmodified PRL in two different PRL-responsive cell lines. In this study our aim was to produce a molecular mimic of phosphorylated PRL by substituting a fairly bulky, negatively charged amino acid (glutamate or aspartate) for the normally phosphorylated serine [serine 179 in human PRL (hPRL)]. In addition, because of the marked effect of phosphorylation on biological activity, we investigated the importance of the unmodified serine in the growth-promoting activity of PRL. hPRL complementary DNA was obtained from the American Type Culture Collection and subcloned into pT7-SCII after site-directed mutagenesis using the deoxyuridine approach. Proteins were expressed in Escherichia coli BL21 (DE3) and were primarily found in inclusion bodies. Agonist and antagonist activities of each serine 179 mutant were assessed using the Nb2 bioassay. Compared with standard hPRL, the recombinant wild-type was more active in the Nb2 assay, attesting to both the absence, or low level, of endotoxin contamination in preparations from these cells and the appropriate folding of the molecule. The aspartate and glutamate mutants had no intrinsic agonist activity, but both antagonized the growth-promoting activity of wild-type PRL, with the aspartate mutant proving to be a very effective antagonist. Two hundred picograms per ml of the aspartate mutant negated 75% of the growth response to 400 pg/ml wild-type PRL. When serine 179 was mutated to alanine or valine, mutant PRLs with 0% and 14% of the biological activity of wild-type PRL, respectively, were produced. These results demonstrate 1) that molecular mimicry of the phosphorylated hormone does produce a PRL antagonist, and 2) that the serine at position 179 is crucial to the growth-promoting activity of PRL. The aspartate mutant can now be used to study many aspects of the physiology of PRL.

Amino Acid Sequence↗

Successful resection of sigmoid colon cancer in a patient with factor XI deficiency.

A 42-year-old-women with sigmoid colon adenocarcinoma was found to have isolated prolonged activated partial thromboplastin time (aPTT 102.5 s, normal range 24-36 s) preoperatively. Her medical history included an episode of prolonged postdelivery uterine bleeding 16 years previously. A mixed aPTT test showed immediate correction of the prolonged aPTT, indicating a coagulation factor deficiency in the intrinsic pathway. Factor assays showed factor XI was below 1% of average normal value whereas factor VIII, IX and XII activities were normal. Family screening revealed one sister among the three siblings also had isolated prolonged aPTT. The patient was transfused with four units (5mL/kg) of fresh frozen plasma the day before surgery, then with two units during surgery. The operation was uneventful with no bleeding problems. The patient recovered smoothly and is currently undergoing adjuvant chemotherapy. This is the first formal report of a patient with factor XI deficiency undergoing major surgery in Taiwan. Careful monitoring of aPTT, with fresh frozen plasma transfusion, when needed, may safely overcome bleeding problems during surgery.

Adenocarcinoma↗

Dimethylformamide-induced occupational liver injury--a case report.

Dimethylformamide(DMF), a widely used industrial solvent, has been reported to induce subtle to clinically overt hepatotoxicity. Liver injury due to occupational exposure through inhalation and skin contact have been sporadically reported. We reported a 42-year-old male Taiwanese who developed progressive, intermittent abdominal pain for 6 months after working in a synthetic leather factory. Acute hepatitis episode occurred after working in an enclosed and poorly-ventilated workplace for one day. Based on occupational history, pathological examination and serial liver function examinations, the case was compatible with DMF-induced acute chemical hepatitis.

Adult↗

The suppressive effect of the olivocochlear bundle in rats studied by brainstem auditory evoked potentials following brainstem lesion.

The olivocochlear bundle (OCB) stems from the superior olivary complex in the brainstem and projects to the ipsilateral and contralateral cochlea. Several studies have suggested that the OCB has a suppressive effect on the inner ear by inhibiting the responses of the primary afferent fibers. To evaluate the action of OCB by more available measurement, radiofrequency lesion was applied to 30 Wistar rats which were divided into four groups, a sham group and another three groups with different OCB lesion sites. Consequent changes following OCB lesion were evaluated by measuring the brainstem auditory evoked potentials (BAEPs), which are considered to reflect the auditory brainstem afferent conduction. The amplitudes and latencies did not change significantly after sham treatment. However, although the BAEP peak latencies were not significantly altered after damaging the OCB, the amplitudes of the BAEP waves I to III were augmented significantly. These results indicate that increased neural activities were presented in the auditory nerves, cochlear nucleus and the superior olivary complex upon disinhibition of the OCB. Unilateral OCB lesions predominantly augmented BAEP waveform which was recorded ipsilaterally to the lesion side. Upon lesion of the midline OCB, BAEP recordings on either side showed significant increments in the amplitudes of waves I to III. These findings are compatible with those observed in the cat model and other rodents, and thus confirm that (1) OCB lesion leads to increased amplitudes in some BAEP peaks which were evoked by certain hyperactive auditory nuclei and tracts; and (2) BAEP measurment is a convenient and useful tool for assessing the OCB function.

Animals↗

A study of the referral patterns of obstetric clinics and the performance of receiving neonatal intensive care units in Taiwan.

To study the referral patterns of obstetric clinics, and the performance of receiving intensive care units measured by the survival of transported neonates, transport records were collected prospectively between July, 1991 and June, 1992. Two hundred and fifty-four transported neonates born in 51 obstetric clinics (level I units) in Tainan City and County, in southern Taiwan, were enrolled in this study. Nineteen percent of the transported neonates were very low birthweight infants (< 1500 g). Nearly equal numbers of them were transported to eight district hospitals (level II units) and to a tertiary center (level III unit), but these infants were 1.5 times more likely to die in a level II unit than a level III unit. In addition, equal numbers of infants assisted by mechanical ventilators were transported to level II and III units, but these infants were three times more likely to die in a level II unit than a level III unit (P = 0.006). Seventy-seven percent of the normal birthweight infants (> or = 2500 g) were transported to level II units, and the mortality in this group was 12.3% compared with 0% in those transported to the level III unit. Approximately 56% of these normal birthweight infants in level II units died of severe birth asphyxia. The referral patterns of level 1 units had an unfavorable effect on the survival of neonates requiring mechanical ventilation. Enhancing the skills of the staff in level I units to recognize and stabilize such infants, elevating the capability of level II units in treating some of these cases, and increasing the hospital beds for level III care are necessary to increase their chance of survival.

Health Services Research↗