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Biomedical subjects

L M Adams

Publications and source records attributed to L M Adams.

At least 19 recordsLinked to original sources

Acute scrotum in Nigeria: an 18-year review.

One hundred and seventy-eight patients presenting with an acute scrotum during a period of 18 years (1978-1997) were reviewed retrospectively. Fifty per cent had testicular torsion, with a mean age of 23 years (range 3 weeks-55 years). Torsion was significantly more common in the cold harmattan season (October-early March). The salvage rate of torted testes was 52%. Inguinoscrotal hernia was the cause of testicular infarction in 10% and is an important contributor to male infertility. Twelve per cent of cases of suspected torsion were found to have epididymo-orchitis, at exploration. Twenty-three (13%) patients presented with scrotal gangrene (Fournier's gangrene) which did not result in testicular loss. There was significant morbidity following intervention by non-doctors, and misdiagnosis from unsuspecting physicians. The acute scrotum affecting young patients is a significant cause of male infertility and morbidity in Zaria. Early recognition, prompt treatment and re-education of those who may provide the first line care for such patients will reduce the morbidity and pathologic consequences following neglect.

Acute Disease↗

Differential effect of vinorelbine versus paclitaxel on ERK2 kinase activity during apoptosis in MCF-7 cells.

The effects of vinorelbine and paclitaxel on the activity of extracellular signal-regulated protein kinase2 (ERK2), a member of MAP kinase, and its role in the induction of bcl-2 phosphorylation and apoptosis were evaluated in MCF-7 cells. We demonstrated that ERK2 was activated rapidly by vinorelbine, and was inhibited by either paclitaxel or estramustine. A 3-fold increase of ERK2 kinase activity was observed within 30 min when MCF-7 cells were treated with 0.1 microM vinorelbine. In contrast, the same treatment with paclitaxel resulted in a significant decrease of ERK2 kinase activity. We also demonstrated that elevated bcl-2 phosphorylation induced by vinorelbine is paralleled by decrease of a complex formation between bcl-2 and bax, cleavage of poly (ADP) ribose polymerase (PARP) protein, activation of caspase-7, and apoptosis. The levels of bcl-2 phosphorylation, bax, and PARP were not significantly affected by 2'-amino-3'-methoxyflavone (PD 98059), an ERK kinase specific inhibitor. Thus, our data suggest that the apoptosis induced by vinorelbine in MCF-7 cells is mediated through the bcl-2 phosphorylation/bax/caspases pathways, and that activation of ERK2 by vinorelbine does not directly lead to the drug-mediated apoptosis. Since decrease of PARP occurred quickly following the treatment of MCF-7 cells with either 0.1 microM of vinorelbine or paclitaxel, this protein may serve as an early indicator of apoptosis induced not only by DNA damaging agents, but also by antimicrotubule drugs.

Antineoplastic Agents, Phytogenic↗

Reference ranges for thyroid function tests in premature infants beyond the first week of life.

OBJECTIVES: To establish reference ranges for the more sensitive assays of thyrotropin and the best available assays of free thyroxine in premature infants after the first week of life. STUDY DESIGN: Free thyroxine measurements by direct equilibrium dialysis and thyrotropin measurements by third generation immunometric assay were measured in 120 healthy premature infants 25 to 36 weeks' gestation at birth and every 3 weeks until hospital discharge. Infants were stratified by postconceptional age. Differences in free thyroxine and thyrotropin levels among groups were determined by ANOVA. Correlations between hormone measurements and gestational and postnatal ages were sought by linear regression analysis. Reference ranges were determined as arithmetic (free thyroxine) and geometric (thyrotropin) mean+/-2 SD ranges. RESULTS: From 120 infants, 164 samples were obtained and grouped by postconceptional age at sampling. Free thyroxine was not different among postconceptional age groups and did not correlate with gestational or postnatal age. The free thyroxine reference range based on these data was 10 to 33 pmol/l (0.8 to 2.6 ng/dl). Thyrotropin did not correlate with gestational age. There was a clinically trivial but statistically significant (r(2)=0.03, p<0.05) correlation of thyrotropin with postnatal age. The thyrotropin reference based on these data was 0.8 to 12 mU/l. CONCLUSIONS: Free thyroxine was closely regulated in these premature infants and levels were similar to those in older children and adults, once the natal surge in thyrotropin has subsided. After the first week of life a single range for each hormone appeared appropriate for all premature infants until 40 weeks postconceptional age.

Female↗

Contribution of plasmid-encoded fimbriae and intimin to capacity of rabbit-specific enteropathogenic Escherichia coli to attach to and colonize rabbit intestine.

Attachment to the intestinal mucosa is an essential step in the pathogenesis of diarrhea caused by enteropathogenic Escherichia coli (EPEC). Fimbriae and intimin, the outer membrane protein product of the chromosomal eae gene, contribute to this process, but their relative roles and the nature of their interaction are not known. The aim of this study was to determine the relative contribution of plasmid-encoded fimbriae, termed Ral, and intimin to the capacity of rabbit-specific EPEC (REPEC) to attach to the intestinal mucosa of rabbits. To achieve this, we constructed a series of mutants in REPEC strain 83/39 (O15:H-), in which the ralE and eae genes were insertionally inactivated. These strains were then inoculated into ligated loops of rabbit ileum, which were resected 18 h later and examined by light and electron microscopy. The results showed that intimin, but not Ral, is essential for the elicitation of attaching-effacing lesions by REPEC. Nevertheless, a delta eae Ral-bearing mutant adhered to the intestinal epithelium to the same extent as its eae-positive parent and far more extensively than an eae(+) delta ral strain. To examine the contribution of Ral and intimin to colonization of rabbit intestine, we fed these strains to weanling rabbits, which were killed 4 days later, so that the number of bacteria in various regions of the intestine could be determined. The results indicated that strain 83/39 requires both Ral and intimin to colonize the intestine successfully and that a delta eae delta ralE double mutant was incapable of colonizing the intestine. Taken together, these findings indicate that Ral and intimin act independently as adhesion factors of REPEC strain 83/39 and that this strain carries no other significant colonization factor. When both Ral and intimin are present, they appear to act cooperatively, with Ral-mediated adhesion preceding that mediated by intimin.

Adhesins, Bacterial↗

Colonization of the respiratory tract by a virulent strain of avian Escherichia coli requires carriage of a conjugative plasmid.

The E3 strain of E. coli was isolated in an outbreak of respiratory disease in broiler chickens, and experimental aerosol exposure of chickens to this strain induced disease similar to that seen in the field. In order to establish whether the virulent phenotype of this strain was associated with carriage of particular plasmids, four plasmid-cured derivatives, each lacking two or more of the plasmids carried by the wild-type strain, were assessed for virulence. Virulence was found to be associated with one large plasmid, pVM01. Plasmid pVM01 was marked by introduction of the transposon TnphoA, carrying kanamycin resistance, and was then cloned by transformation of E. coli strain DH5alpha. The cloned plasmid was then reintroduced by conjugation into an avirulent plasmid-cured derivative of strain E3 which lacked pVM01. The conjugant was shown to be as virulent as the wild-type strain E3, establishing that this plasmid is required for virulence following aerosol exposure. This virulence plasmid conferred expression of a hydroxamate siderophore, but not colicins, on both strain E3 and strain DH5alpha. Carriage of this plasmid was required for strain E3 to colonize the respiratory tracts of chickens but was not necessary for colonization of the gastrointestinal tract. However, the virulence plasmid did not confer virulence, or the capacity to colonize the respiratory tract, on strain DH5alpha. Thus, these studies have established that infection of chickens with E. coli strain E3 by the respiratory route is dependent on carriage of a conjugative virulence plasmid, which confers the capacity to colonize specifically the respiratory tract and which also carries genes for expression of a hydroxymate siderophore. These findings will facilitate identification of the specific genes required for virulence in these pathogens.

Animals↗

Synergism of cytotoxic effects of vinorelbine and paclitaxel in vitro.

Empiric combinations of vinca alkaloids with taxanes have been recently used in clinical oncology. To enhance the activity of these two classes of agents, we evaluated the sequence and duration of exposure, looking for synergistic effects. Cell lines DU 145, PC 3, LnCaP, LL 86, MCF7wt, and MCF7/ADR (NCI/ADR-RES) were incubated with varying concentrations of paclitaxel or vinorelbine. Cytotoxicity was evaluated by a semiautomated MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) method. Synergism or antagonism of these two agents either sequentially or in combination was determined by median effect analysis. Prolonged exposure of cells to either drug enhanced cytotoxic effect. Synergism or antagonism with vinorelbine and paclitaxel were both sequence dependent and cell line specific. In the case of MCF7wt, synergism was seen when a 48-hr exposure to vinorelbine preceded paclitaxel, whereas antagonism was noted when both agents were applied simultaneously or when the sequence was reversed. Concurrent vinorelbine and paclitaxel were synergistic in four of six cell lines when the exposure was extended to 96 hr but not for shorter durations of exposure. Sequential exposure of vinorelbine preceding paclitaxel or prolonged exposure to both agents concurrently needs to be tested clinically to determine whether the antitumor activity of this combination can be enhanced. In addition, these studies suggest concurrent administration of these two agents may lead to a less than optimal cytotoxic result.

Antineoplastic Agents, Phytogenic↗

Infusional vinorelbine in relapsed or refractory lymphomas.

Vinorelbine (Navelbine is a semisynthetic vinca alkaloid devoid of serious neurotoxicity. When given weekly vinorelbine has documented activity against many tumors, including lymphomas. Since weekly schedules cannot be easily incorporated in combination regimens, we tested an infusional schedule of vinorelbine given every 21 days in adults with relapsed or refractory lymphoma. Patients with inadequate organ or bone marrow reserve, HIV or other serious infection, central nervous system disease, or prior stem cell or bone marrow transplantation were ineligible. In the phase I part, patients received a constant intravenous bolus of 8 mg/m(2), followed by intravenous continuous infusion over 24 hours daily for four days increasing from 10, 12, to 14 mg/m(2) /d in successive three-patient cohorts. Cycles were repeated every 21 days, and the daily continuous infusion dose was adjusted for toxicity. Dose-limiting mucositis and neutropenia were reached at the continuous dose of 14 mg/m(2) /d. Consequently, for the Phase II trial the starting continuous infusion dose was 12 mg/m(2) /d. After the first 19 patients were entered in the phase II study, the starting infusion dose was reduced to 10 mg/m(2) /d because of frequent grade (3/4) myelosuppression and mucositis. Forty-four patients were entered in the phase II study, of whom 41 are evaluable. Median age was 61 years, 23 were males, with clinically aggressive non-Hodgkin's lymphoma (NHL) in 22, indolent NHL in 18, and Hodgkin's Disease in one patient. The median number of prior regimens was 3 (range 1-11). The lymphoma was refractory to the initial regimen in nine patients, and to the regimen immediately before vinorelbine in 20 patients. Serum LDH was high in 2(1/4)1, and serum beta(2) -microglobulin > 3.0 mg / L in 16/31 patients. Responses were observed in four of 22 patients with aggressive NHL (18%, 95% confidence interval 5%-40%), and in six of 18 with indolent NHL (33%, 95% confidence interval 13%-59%). Median progression-free survival was 6 months for responders. During the Phase II trial 114 vinorelbine courses were administered. Neutrophil nadir was < 1000/microl in 65% and < 100/microl in 35% of courses, respectively. Platelet nadir was < 100,000/microl in 30% and < 20,000/microl in 8% of courses, respectively. Grade (3/4) mucositis was seen in 18% of courses, and neutropenic fever in 13%, and was complicated by death in one patient. We conclude that this dosage and schedule of vinorelbine has modest activity in patients with relapsed or refractory NHL. Myelosuppression is frequent but reversible, but there is no significant neurotoxicity. The role of vinorelbine in combination regimens for patients with relapsed lymphomas, particularly those of indolent histology, should be further investigated.

Adult↗

A phase I study of sequential vinorelbine followed by paclitaxel.

BACKGROUND: In vitro experiments suggest that administration of vinorelbine preceding paclitaxel results in synergistic cytotoxic effects. A phase I dose escalation trial of vinorelbine daily x 3 with paclitaxel on day 3 repeated every 28 days in metastatic breast cancer patients was completed. PATIENTS AND METHODS: Female patients, PS 0-2, without evidence of CNS disease or prior neuropathies were treated with vinorelbine at dose levels 7, 10, 13 mg/m2 per day and paclitaxel over three hours at dose levels of 135, 175, and 200 mg/m2. RESULTS: Twenty-eight patients with six dose levels were studied. At dose level 1, patients developed intolerable but reversible neutropenia. Subsequent dose levels required filgrastim. Dose limiting toxicities were myalgia and fatigue at vinorelbine 13 mg/m2/day and paclitaxel 200 mg/m2. Neuropathy was minor. Twelve of twenty-five patients with measurable disease had a rapid response which did not correlate with dose level. CONCLUSIONS: Sequential administration of these two agents demonstrates activity in breast cancer patients. Phase II dosing on this schedule should be vinorelbine 13 mg/m2/day x 3 and paclitaxel 175 mg/m2. With proper selection of patients, concern about neurologic toxicity should not impede future trials of vinorelbine with paclitaxel.

Adult↗

Orbital teratoma.

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Calcinosis↗

Selective early elimination of luteal support in assisted reproduction cycles using a gonadotropin-releasing hormone agonist during ovarian stimulation.

OBJECTIVE: To determine if women undergoing GnRH agonist-hMG stimulated IVF cycles can undergo successful discontinuation of luteal phase support. DESIGN: A protocol for selective discontinuation of luteal phase support was evaluated prospectively in women undergoing assisted reproduction cycles. SETTING: A tertiary care institutional-based assisted reproduction program. PATIENT(S): One hundred eighty-eight women who conceived after an IVF or zygote intrafallopian transfer cycle including a GnRH agonist between January 1994 and June 1997. INTERVENTION(S): Women with serum progesterone levels of > or = 60 ng/mL at 4 weeks' gestation were selected for discontinuation of their luteal phase support. MAIN OUTCOME MEASURE(S): Delivery rate. RESULT(S): Sixty-three women (62.4%) met the criteria for discontinuation of luteal phase support. There were no differences in the mean age, peak E2 levels, number of follicles, number of embryos transferred, or delivery rates (85.7% versus 78.9%) between the women who did and those who did not have discontinuation of their progesterone supplementation. CONCLUSION(S): These data reveal that luteal phase support can be discontinued successfully for selective women undergoing IVF who are receiving a GnRH agonist.

Adult↗

Apoptosis in a neonatal rat model of cerebral hypoxia-ischemia.

BACKGROUND AND PURPOSE: The mechanisms of excitotoxic cell death in cerebral ischemia are poorly understood. In addition to necrosis, apoptotic cell death may occur. The purpose of this study was to determine whether an established model of cerebral hypoxia-ischemia in the neonatal rat demonstrates any features of apoptosis. METHODS: Seven-day-old neonatal rats underwent bilateral, permanent carotid ligation followed by 1 hour of hypoxia, and their brains were examined 1, 3, and 4 days after hypoxia-ischemia. The severity of ischemic damage was assessed in the dentate gyrus and frontotemporal cortex by light microscopy. Immunocytochemistry was performed to detect the cleavage of actin by caspases, a family of enzymes activated in apoptosis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) reactivity was examined in the cortical infarction bed and dentate gyrus. Neonatal rat brain DNA was run on agarose gel electrophoresis to detect DNA fragmentation. Ethidium bromide-staining and electron microscopy were used to determine whether apoptotic bodies, 1 of the hallmarks of apoptosis, were present. RESULTS: The frontotemporal cortex displayed evidence of infarction, and in most rats the dentate gyrus showed selective, delayed neuronal death. Immunocytochemistry demonstrated caspase-related cleavage of actin. TUNEL and DNA electrophoresis provided evidence of DNA fragmentation. Ethidium bromide-staining and electron microscopy confirmed the presence of chromatin condensation and apoptotic bodies. CONCLUSIONS: Features of apoptosis are present in the described model of cerebral hypoxia-ischemia. Apoptosis may represent a mode of ischemic cell death that could be the target of novel treatments that could potentially expand the therapeutic window for stroke.

Animals↗

Role of a general surgeon in obstetrics and gynaecology in a rural setting.

In a rural hospital in northern Nigeria, general surgeons performed 217 obstetric and gynaecologic operations over a five-year period. These operations were responsible for 23% of all operations at the hospital. Emergency operations were most frequent with caesarean section accounting for 90%. Eighty five per cent of the caesarean sections were performed for cephalopelvic dysproportion. The complications encountered were mostly septic complications, predominantly in patients who had caesarean section for obstructed labour. The overall mortality was 5.1% and neonatal mortality from caesarean section was 4.8%. It is concluded that in the abscence of an obstetrician and gynaecologist general surgery experience is required to manage obstetric and gynaecologic problems in rural areas. Such experience should be considered when recruiting doctors for rural hospitals in developing countries.

Cesarean Section↗

Morphometry of human lumbar apophyseal joints. A novel technique.

STUDY DESIGN: The anatomy of cadaveric lumbar apophyseal joints was examined as part of a study of possible correlations between lumbar apophyseal morphology, arthrosis, and cartilage thickness and stiffness. OBJECTIVES: To establish the morphometry of human upper lumbar apophyseal joints using an objective technique. SUMMARY OF BACKGROUND DATA: The apophyseal joints of 30 unfixed lumbar motion segments, all from different cadavers (24 male, five female, and one unknown, mean age 35 years, range 16-78 years) were exposed by dissection and disarticulation. Twenty-five motion segments were L1-L2, three were L2-L3, and two were L3-L4. The extent of fibrillation and linear dimensions of 29 of these specimens were examined, whereas the vertebrae and joints of 22 of them (18 being L1-L2) were cast in araldite resin. METHODS: The casts of the vertebrae were sectioned cephalocaudally at 1-mm intervals. Image processing of photographic slides of the sections established the orientations and dimensions of the lumbar apophyseal joints and their shapes using Fourier analysis. RESULTS: Apophyseal joint surface area was 158 +/- 43 mm2, cephalocaudal length 15.2 +/- 2.7 mm, and straight line length between anterior and posterior borders was 13.2 +/- 1.9 mm. The joints were orientated at 62.5 +/- 11.8 degrees to the coronal plane. Average maximum depth of concavity was 1.8 +/- 0.7 mm. The posterior edges of two joint pairs twisted inward toward the midsagittal plane in a cephalocaudal direction; thus, some apophyseal joints bear part of the axial spinal load. The right inferior surfaces were more elongated cephalocaudally (but not longer) than their contralateral partners. Inferior apophyses were significantly more elongated cephalocaudally (but not longer) than their ipsilateral articulating superior surfaces. CONCLUSIONS: In theory, Fourier analysis of joint surfaces was objective, but it dictated the criterion by which joints were grouped; care must be exercised so that measurement methods do not categorize joints artificially. "Symmetry" is too subjective to be applied to contralateral apophyseal joints; correlation coefficients should be quoted for areas and orientations. The morphology of contralateral lumbar apophyseal joint pairs was significantly correlated in all respects, as was the morphology of articulating lumbar apophyseal surfaces.

Adolescent↗

Inhibition of leukotriene B4 (LTB4) in human neutrophils by L-threo-dihydrosphingosine.

The sphingosine analog L-threo-dihydrosphingosine has been shown to inhibit protein kinase C (PKC) isoenzymes in mixed micelle and vesicle assays. This compound also inhibited the reactive oxygen intermediates (ROI) released from isolated neutrophils (IC50 approximately 2 microM) and phorbol ester-induced edema and neutrophil influx in the mouse ear model (ED50 approximately 11 mg/kg). Based on the anti-inflammatory activity of this compound, studies were done to determine its effect on arachidonate metabolism by the lipoxygenase pathway. Neutrophils were preincubated with test agents or vehicle for one minute and then incubated with 1 microM calcium ionophore A23187 for two minutes. Supernatants were assayed for LTB4 using a radioimmunoassay. The reference lipoxygenase inhibitor nordihydroguaiaretic acid exhibited 98.3% inhibition at 1 microM (n = 2) and prevented ROI production (IC50 approximately 6 microM). In contrast, the potent PKC inhibitor staurosporine was inactive against LTB4 in these studies (< 23% inhibition at 10 microM, n = 2), but inhibited ROI formation (IC50 approximately 3nM). L-threo-dihydrosphingosine inhibited LTB4 production 96.9 +/- 1.3%, at 10 microM (IC50 = 6 microM, n = 2). These data suggest that L-threo-dihydrosphingosine blocks the release of LTB4 from human neutrophils via a mechanism independent of PKC.

Animals↗

Identification and characterization of a K88- and CS31A-like operon of a rabbit enteropathogenic Escherichia coli strain which encodes fimbriae involved in the colonization of rabbit intestine.

Initiation of attaching-effacing lesions, which characterize infections with rabbit enteropathogenic Escherichia coli (REPEC), requires bacteria to adhere to the intestinal epithelium. This adherence is reflected in vitro by the affinity of these E. coli strains for various types of eukaryotic cells. TnphoA mutants of REPEC 83/39 (O15:H-) which had lost the ability to adhere to HEp-2 epithelial cells, guinea pig ileal brush borders, and mouse erythrocytes were generated. DNA sequencing of the region surrounding the inactivating transposon insertions within a 95-kb plasmid, designated pRAP for REPEC adherence plasmid, revealed extensive homology between that region and the structural genes of enterotoxigenic E. coli operons encoding the K88 and CS31A fimbrial adhesins and the genes for the afr2 adhesin from REPEC B10 (O103:H2). Seven genes of the ral operon (for REPEC adherence locus), including three putative minor fimbrial subunit genes (ralC, ralF, and ralH), a major fimbrial subunit gene (ralG), a gene of unknown function (ralI), and genes for two fimbrial subunit chaperones (ralD and ralE), were sequenced. When inoculated perorally into weanling rabbits, a mutant with a TnphoA insertion in the ralE gene showed a 10-fold reduction in colonizing ability, with only 1 of 10 rabbits excreting bacteria compared to all 5 of those infected with the wild-type parent strain (P = 0.002). The severity of the diarrheal illness caused by the mutant strain was also reduced. Western blotting of surface protein extracts of strain 83/39 with hyperimmune anti-83/39 antiserum, adsorbed with the ralE mutant, revealed a 32-kDa protein which was absent from protein extracts of two nonadherent mutants. The adsorbed antiserum also bound to the surface of strain 83/39 but not to nonadherent mutants, as detected by immunogold labeling. These results indicate that the ral operon of REPEC 83/39 contains genes necessary for the biosynthesis of fine fimbriae which are responsible for in vitro adherence of the bacteria and play a role in their colonization of, and hence virulence for, rabbits. The putative major fimbrial subunit is a protein with an observed molecular size of approximately 32 kDa which, when assembled, appears to form a capsule of fimbriae surrounding the bacterium similar to that described for CS31A.

Amino Acid Sequence↗

Blunt traumatic injury of the gallbladder in childhood.

OBJECTIVE: To illustrate blunt traumatic injury of the gallbladder in childhood. DESIGN: A case report. SETTING: Hospital. SUBJECT: An eight year old boy. MAIN OUTCOME MEASURE: Incidence, history, treatment. RESULT: The gallbladder was ruptured at the neck necessitating a cholecystectomy. The child has remained well at three months follow up. CONCLUSIONS: Blunt traumatic injury of the gallbladder, though rare, does occur usually as a consequence of direct abdominal injury especially in children during sporting activities and fights. Minor injuries can be repaired but cholecystectomy is necessary in more extensive injuries or injury to the cystic duct and neck. A comprehensive history taking including direct questioning regarding trauma and a high index of suspicion are important for early diagnosis and prompt treatment.

Child↗

Felbamate protects CA1 neurons from apoptosis in a gerbil model of global ischemia.

BACKGROUND AND PURPOSE: Felbamate, a novel anticonvulsant that binds to the glycine site of the N-methyl-D-aspartate receptor, has been shown to have neuroprotective properties in vitro and in vivo. In a rat pup model of hypoxia-ischemia, felbamate selectively reduced delayed death in hippocampal granule cells. The present study explores its neuroprotective potential in a gerbil model of global ischemia, in which good evidence exists that ischemia triggers apoptosis of CA1. METHODS: Gerbils were subjected to bilateral carotid occlusion for 5 minutes and then treated with felbamate (100 or 200 mg/kg IV) or vehicle. They were killed 3 days later, and the numbers of live and dead neurons in the CA1 sector of the hippocampus were counted at sterotaxically defined levels. RESULTS: Felbamate (200 mg/kg IV) administered after the release of carotid clamping did not change brain temperature but reduced neuronal death in CA1 from 332 +/- 60 cells per section of dorsal hippocampus in unmedicated gerbils to 62 +/- 12 cells in felbamate-treated animals (P<.001). A lower dose of felbamate (100 mg/kg post hoc) showed only a nonsignificant reduction of neuronal death. In the 200-mg/kg group, felbamate serum concentrations peaked at 162 microg/mL and were above 100 microg/mL for at least 3 hours, and brain levels reached 150 microg/mL at 1 hour. In the 100-mg/kg group, blood serum levels were well below 100 microg/mL. CONCLUSIONS: These results suggest that felbamate given post hoc is remarkably effective in preventing delayed apoptosis secondary to global ischemia but that effective neuroprotection requires doses higher than those used for anticonvulsant treatment.

Animals↗

Reference ranges for newer thyroid function tests in premature infants.

OBJECTIVE: To establish reference ranges for recently developed assays of thyroid function in premature infants. METHODS: We measured serum free thyroxine (T4) by direct equilibrium dialysis and serum thyrotropin by a sensitive immunometric method in 104 preterm infants (25 to 36 weeks of gestational age) during the first week of life. RESULTS: The free T4 level correlated positively with gestational age (p < 0.0001; r2 = 0.09) and differed significantly between adjacent gestational age groups (p < 0.05). Free T4 concentrations (mean +/- SD) for the 25- to 27-, 28-to 30-, 31- to 33-, and 34- to 36-week groups were 18.0 +/- 5.2, 25.7 +/- 9.0, 30.9 +/- 9.0, 36.0 +/- 10.3 pmol/L (1.4 +/- 0.4, 2.0 +/- 0.7, 2.8 +/- 0.8 ng/dl), respectively. Two reference ranges for free T4 were determined, one for 25 to 30 weeks (6.4 to 42.5 pmol/L (0.5 to 3.3 ng/dl) and one for 31 to 36 weeks (16.7 to 60.5 pmol/L (1.3 to 4.7 ng/dl)). The logarithm of the value for thyrotropin correlated positively with gestational age (p < 0.001; r2 = 0.08); one reference range of 0.5 to 29 mU/L was determined for thyrotropin. CONCLUSION: This study extends information on thyroid function of preterm infants and establishes reference ranges for this population.

Gestational Age↗