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Biomedical subjects

S Adler

Publications and source records attributed to S Adler.

At least 55 records · Page 3Linked to original sources
PubMed2000

Positive association between blood brain barrier disruption and osmotically-induced demyelination.

Rapid correction of chronic hyponatremia can cause osmotic brain demyelination in animals and humans. Why demyelination develops is unknown, but blood brain-barrier disruption might expose oligodendrocytes to substances normally excluded from the brain. To test this hypothesis, chronic hyponatremia was induced and corrected using a new, reproducible rat model for producing osmotic brain demyelination. Blood brain barrier integrity was assessed by NMR imaging at either 3, 16 or 24 h during the first day of correction. Demyelination was determined histopathologically 5 - 6 days later. Of 96 rats studied, demyelination developed 5 - 6 days later in 37 rats, 89% of whom showed barrier disruption. In the 59 rats who did not develop demyelination, 45 (76%) had no barrier disruption. Thus, blood-brain barrier disruption during the first 24 h of correction was associated with a 70% risk of developing demyelination. By contrast, the risk of developing subsequent demyelination was only 8% when the barrier was intact. This strong association between barrier disruption and subsequent demyelination provides new insights into the role of blood brain barrier function in demyelinative disorders such as the osmotic demyelination syndrome and by extension to other demyelinative disorders such as multiple sclerosis.

Animals↗
PubMed2000

Noninvasive measurement of total serum bilirubin in a multiracial predischarge newborn population to assess the risk of severe hyperbilirubinemia.

BACKGROUND: Jaundice in near-term and term newborns is a frequent diagnosis that may prompt hospital readmission in the first postnatal week. Hyperbilirubinemia, when excessive, can lead to potentially irreversible bilirubin-induced neurotoxicity. Predischarge risk assessment (at 24-72 hours of age) for subsequent excessive hyperbilirubinemia is feasible by a laboratory-based assay of total serum bilirubin (TSB). Hypothesis. Noninvasive, transcutaneous, point-of-care measurement of transcutaneous bilirubin (TcB) predischarge by multiwavelength spectral analysis, using a portable BiliCheck device (SpectRx Inc, Norcross, GA), is clinically equivalent to measurement of TSB in a diverse, multiracial term and near-term newborn population and predictive of subsequent hyperbilirubinemia. METHODOLOGY: We evaluated a hand-held device that uses multiwavelength spectral reflectance analysis to measure TcB (BiliCheck). The study population (490 term and near-term newborns) was racially diverse (59.1% white, 29.5% black, 3.46% Hispanic, 4.48% Asian, and 3.46% other) and was evaluated at 2 separate institutions using multiple (11) devices. The postnatal age ranged from 12 to 98 hours and the ranges of birth weights and gestational ages were 2000 to 5665 g and 35 to 42 weeks, respectively. All transcutaneous evaluations were performed contemporaneously and paired with a heelstick TSB measurement. All TSB assays were performed by high performance liquid chromatography, as well as by diazo dichlorophenyldiazonium tetrafluoroborate techniques. RESULTS: TSB values ranged from .2 to 18.2 mg/dL (mean +/- standard deviation: 7.65 +/- 3.35 mg/dL). The overall correlation of TSB (by high performance liquid chromatography technique) to TcB (by BiliCheck devices) was linear and statistically significant (r =.91; r(2) =.83; TcB =.84; TSB = +.75; standard error of regression line = 1.38; P <.001; n = 490 infants; 1788 samples). Similar regression statistics were evident in subset populations categorized by race (white: r =.91 [n = 289 infants]; black: r =.91 [n = 145 infants]) as well as by gestation (term: r =. 91 [n = 1625 samples]; near-term: r =.89 [n = 163 samples]). Intradevice precision was determined to be.59 mg/dL (2-3 measurements per infant with 1 device; n = 210 infants; 510 samples in a separate subset). Interdevice evaluation of 11 devices determined the precision to be.68 mg/dL (2-4 devices used for measurements per patient). In 23 of 419 of the study population infants who were in the 24- to 72-hour age range, the predischarge TSB values designated them to be at high risk for subsequent excessive hyperbilirubinemia (above the 95th percentile track on the hour-specific bilirubin nomogram). For these infants, the paired BiliCheck TcB values were all above the 75th percentile track (negative predictive value = 100%; positive predictive value = 32. 86%; sensitivity = 100%; specificity = 88.1%; likelihood ratio = 8. 43). CONCLUSIONS: Our data demonstrate the accuracy and reproducibility of the predischarge BiliCheck measurements in term and near-term newborn infants of diverse races and ethnicities. Infants with predischarge BiliCheck values above the 75th percentile of hour-specific TSB values on the bilirubin nomogram may be considered to be at high risk for subsequent excessive hyperbilirubinemia. Further studies are needed to assess the efficacy of this technique in preterm infants, those undergoing phototherapy, and those with TSB values of >/=15 mg/dL (>/=256 micromol/L).

Analysis of Variance↗
PubMed2000

Suppression of telomerase activity and cytokine messenger RNA levels in acute myelogenous leukemia cells in vivo in patients by amifostine and interleukin 4.

High levels of telomerase activity and high rates of cell proliferation are associated with a poor prognosis in acute myelogenous leukemia. Furthermore, cytokine production by leukemia cells is believed to play an important role in determining the proliferative characteristics of leukemia. The in vivo effects of two noncytotoxic agents on these parameters were determined in 33 acute myelogenous leukemia patients. Three daily doses of interleukin (IL) 4 or a single dose of amifostine reduced telomerase activity in the leukemia marrow cells in 7 of 9 and 11 of 13 patients, respectively. The administration of a single dose of amifostine resulted in a reduction in tumor necrosis factor alpha and IL-6 transcript levels in the marrow cells of 10 of 13 and 12 of 13 patients in which these transcripts were present. The administration of only three doses of IL-4 or a single dose of amifostine has a significant effect on leukemia cell parameters, which are believed to have a significant impact on the in vivo biology of the disease and on its response to remission induction therapy.

Adult↗
PubMed2000

Safety and success of early laparoscopic cholecystectomy for acute cholecystitis.

Although elective laparoscopic cholecystectomy is today's gold standard for the treatment of symptomatic cholelithiasis, its safety and effectiveness for acute cholecystitis remain controversial. The authors present a retrospective study comparing laparoscopic cholecystectomy in the acute versus the elective setting. A total of 605 patients were treated surgically for gallstone disease between August 1991 and January 1999. A total of 269 patients (44.5%) underwent surgery for acute cholecystitis as soon as possible after diagnosis, and elective cholecystectomy was performed on 336 patients (55.5%) for symptomatic gallstones. Initial open cholecystectomy was performed on 52 (19.3%) of the acute patients and 16 (4.8%) of the elective patients. Laparoscopic cholecystectomy was attempted on 217 of the acute patients (80.7%), with 11 cases (5.1%) converted to open cholecystectomy, and on 320 (95.2%) of the elective patients, with 6 cases (1.9%) converted to open cholecystectomy. The mean (+/-SD) operative time for the acute and elective patients was 105 (+/-38) and 85 (+/-21) minutes, respectively (P < 0.05). There was no perioperative mortality in either laparoscopic group. Surgical complications related to laparoscopic cholecystectomy in the acute and elective groups occurred in six (2.9%) and eight (2.5%) cases, respectively (P = NS). The current study shows that early laparoscopic cholecystectomy for acute cholecystitis is safe and efficient. Low conversion rates can be maintained with strict guidelines for appropriate patient selection, adequate experience, and proper laparoscopic technique.

Acute Disease↗
PubMed1999

Thrombospondin peptides are potent inhibitors of mesangial and glomerular endothelial cell proliferation in vitro and in vivo.

BACKGROUND: Thrombospondin 1 (TSP1), a multifunctional, matricellular glycoprotein, is expressed de novo in many inflammatory disease processes, including glomerular disease. Short peptide fragments derived from the type I properdin repeats of the TSP1 molecule mimic anti-angiogenic and/or transforming growth factor-beta (TGF-beta)-activating properties of the whole TSP1 glycoprotein. We investigated the effects of D-reverse peptides derived from the type I domain of TSP1 in experimental mesangial proliferative glomerulonephritis in the rat (anti-Thy1 model), as well as their effects on cultured mesangial and glomerular endothelial cells. METHODS: Effects of TSP peptides on proliferation of mesangial or glomerular endothelial cells in culture after growth arrest or growth factor stimulation (fibroblast growth factor-2, platelet-derived growth factor-BB, 10% fetal calf serum) were measured by [3H]thymidine incorporation assay. Adhesion of rat mesangial cells (MCs) to a TSP-peptide matrix was assayed using an attachment-hexosaminidase assay. TSP peptides were intraperitoneally injected daily in rats that had received an intravenous injection of polyclonal anti-Thy1 antibody to induce mesangial proliferative glomerulonephritis. On biopsies from days 2, 5, and 8 of anti-Thy1 disease, mesangial and glomerular endothelial proliferation, matrix expansion, mesangial activation, and microaneurysm formation were assessed. Functional parameters such as blood pressure and proteinuria were also measured. RESULTS: An 18-amino acid peptide (type I peptide) with anti-angiogenic and TGF-beta-activating sequences decreased mesangial and glomerular endothelial cell proliferation in vitro and in vivo and reduced microaneurysm formation and proteinuria in experimental glomerulonephritis. Analogues lacking the TGF-beta-activating sequence mimicked most effects of the type I peptide. The mechanism of action of these peptides may include antagonism of fibroblast growth factor-2 and alteration of MC adhesion. The TGF-beta-activating sequence alone did not have significant effects on mesangial or glomerular endothelial cells in vitro or in experimental kidney disease in vivo. CONCLUSION: Peptides from TSP1 may be promising therapeutics in treating glomerular disease with mesangial and endothelial cell injury.

Amino Acid Sequence↗
PubMed1999

A statewide system to track medical students' careers: the Pennsylvania model.

In 1994 the Commonwealth of Pennsylvania announced a statewide Generalist Physician Initiative (GPI) modeled after The Robert Wood Johnson Foundation's GPI. Three-year grants totaling more than $9 million were awarded to seven of Pennsylvania's medical schools, including two that had already received GPI grants from the foundation. Stimulated by these initiatives, the state's six allopathic and two osteopathic medical schools decided to work together to develop a collaborative longitudinal tracking system to follow the careers of all their students from matriculation into their professional careers. This statewide data system, which includes information for more than 18,000 students and graduates beginning with the entering class of 1982, can be used to evaluate the impact of the Pennsylvania GPI, and it also yielded a local longitudinal tracking system for each medical school. This paper outlines the concept of the system, its technical implementation, and the corresponding implications for other medical schools considering the development of similar outcomes assessment systems.

Career Choice↗
PubMed1999

Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD.

Central to the bone-sparing effect of estrogen (E(2)) is its ability to block the monocytic production of the osteoclastogenic cytokine TNF-alpha (TNF). However, the mechanism by which E(2) downregulates TNF production is presently unknown. Transient transfection studies in HeLa cells, an E(2) receptor-negative line, suggest that E(2) inhibits TNF gene expression through an effect mediated by estrogen receptor beta (ERbeta). We also report that in RAW 264.7 cells, an E(2) receptor-positive murine monocytic line, E(2) downregulates cytokine-induced TNF gene expression by decreasing the activity of the Jun NH(2)-terminal kinase (JNK). The resulting diminished phosphorylation of c-Jun and JunD at their NH(2)-termini decreases the ability of these nuclear proteins to autostimulate the expression of the c-Jun and JunD genes, thus leading to lower production of c-Jun and JunD. The consequent decrease in the nuclear levels of c-Jun and JunD leads to diminished binding of c-Jun/c-Fos and JunD/c-Fos heterodimers to the AP-1 consensus sequence in the TNF promoter and, thus, to decreased transactivation of the TNF gene.

Base Sequence↗
PubMed1999

A requirement for the POU transcription factor, Brn-2, in corticotropin-releasing hormone expression in a neuronal cell line.

The expression of the endogenous CRF gene was examined in the human neuroblastoma cell line, BE(2)-M17. In this cell line, treatment with retinoic acid induces CRF mRNA transcription. We examined the requirement for the POU transcription factor, Bm-2, for this response. We confirmed that Bm-2 is expressed in retinoic acid-induced BE(2)-M17 cells. Expression of antisense Bm-2 message aborted the retinoic acid-mediated induction of CRF transcription. However, overexpression of Bm-2 was not sufficient for CRF expression in the absence of retinoic acid. These experiments support the hypothesis that Bm-2 is an intermediary for retinoic acid-induced CRF expression.

Binding Sites↗
PubMed1998

Granulocytes in the subarachnoid space of humans and rabbits with bacterial meningitis undergo apoptosis and are eliminated by macrophages.

The contribution of leukocyte apoptosis to the resolution of meningeal inflammation in bacterial meningitis was studied in the cerebrospinal fluid (CSF) and in meningeal infiltrates of humans and rabbits by in situ tailing, flow cytometry, agarose gel electrophoresis, and electron microscopy. In humans, the rate of apoptotic granulocytes was 21.0+/-20.8% (n=11) in cytocentrifuge preparations and 3.3+/-3.4 (n=14) in putrid infiltrates of autopsy cases (P=0.02). In rabbits, CSF pleocytosis peaked 8 h after the initiation of antibiotic treatment (5311+/-3122/microl). At this time, the rate of apoptotic granulocytes was 15.2+/-7.3% in CSF and 1.8+/-1.4% in the meningeal infiltrates (each group n=6, P=0.007). Thereafter, the rate of apoptotic granulocytes in CSF declined below 10%. In humans and rabbits, bands representing internucleosomal fragments of approximately 180 base pairs and multiples thereof were documented on agarose gels. Phagocytosis of apoptotic granulocytes by macrophages was visualized by light and electron microscopy. In conclusion, during resolution of subarachnoid space inflammation in bacterial meningitis, a substantial fraction of granulocytes undergoes apoptosis. These granulocytes are removed by phagocytosis by macrophages. Apoptosis is more frequent in granulocytes floating in the CSF than in adherent cells.

Animals↗
PubMed1998

Induction of T cell response by bluetongue virus core-like particles expressing a T cell epitope of the M1 protein of influenza A virus.

A CD4+ T cell epitope of the influenza virus matrix protein corresponding to the C terminus (QAYQKRMGVQMQRFK) was inserted into the VP7 gene of bluetongue virus (BTV). The chimeric protein was expressed by a dual recombinant Autographa californica polyhedrosis virus (AcNPV), which encodes the two inner capsid proteins VP3 and VP7 of BTV. When Spodoptera fRugiperda cells (Sf9 cells) were infected with this recombinant BTV, core-like particles (CLPs) were formed as demonstrated by electron microscopy. To study the immunogenicity of a foreign epitope deprived of its natural flanking sequences in vitro, purified CLPs expressing the T cell epitope were used to stimulate two different MHC class II-restricted CD4+ human T cell clones. One of these T cell clones, ALF 3.7 was specific for the inserted epitope, whereas the other T cell clone ALF 4.4 recognized shorter derivates of the given epitope. CLPs with the inserted epitope were presented as efficiently as purified influenza virus matrix protein to the clone ALF 3.7, whereas clone ALF 4.4 showed no proliferative response.

Baculoviridae↗
PubMed1998

Costs of low-temperature plasma sterilization compared with other sterilization methods.

Plasma sterilization is a new technique for decontaminating thermolabile products without the severe drawbacks associated with gas sterilization methods (residues, environment compatibility). The actual costs, per sterilization unit, of three sterilization techniques--plasma, ethylene oxide and formaldehyde--were compared. As plasma sterilization is an alternative to steam sterilization for sterilizing thermostable but easily corroding products or electronic instruments, costs for steam sterilization were calculated and compared as well. If one considers only the cost of the sterilization procedure itself, without taking into account the time-saving element of plasma sterilization, then ethylene oxide sterilization proves to be the most expensive procedure, followed by plasma sterilization; sterilization with formaldehyde was the least expensive. Inclusion of the time required to sterilize an instruments, however, altered the relative costs of the three methods. Because plasma sterilization takes less time to perform than either ethylene oxide or formaldehyde sterilization, fewer instruments need be procured. In order to measure and compare the time-saving advantage that plasma sterilization affords, five groups of instruments were assembled and the total cost of sterilizing an instrument of each group was calculated. The five groups included (1) disposable, (2) electronic, (3) endoscopic, (4) sharp and (5) standard instruments. In all cases, ethylene oxide sterilization was the most expensive method. Formaldehyde sterilization was, in four out of five cases, more expensive than plasma sterilization. Steam sterilization proved to be the cheapest method of sterilizing a laparoscopic set, even when costs due to damage inflicted on the optical instruments were calculated. In the case of a vitrectome, however, plasma sterilization costs were nearly the same as steam sterilization when the lower rate of damage by plasma sterilization was taken into account.

Costs and Cost Analysis↗