Search PubMed⌕ Search

Biomedical subjects

H Alexander

Publications and source records attributed to H Alexander.

At least 73 records · Page 4Linked to original sources

[Risk assessment in ovarian hyperstimulation syndrome (OHS) using the machine learning system (Decision Master) in 155 in-vitro fertilisations and embryo-transfer (IVF/ET) cycles with a long stimulation protocol].

In 155 selected IVF/ET cycles stimulated with the long protocol 25 cycles with severe OHS are included which turned up later on (purposely overrepresented). An inductive machine learning program is described both in informatics and medical essentials. It is tested whether there exists an algorithm for ruling out the above-mentioned complication in the follicular phase of the same cycle already. By cross validation 89% of the OHS could be predicted and proven by practical rules using hormone and ultrasound values to avoid similar events in ongoing or further cycles.

Adult↗

An activated form of Notch influences the choice between CD4 and CD8 T cell lineages.

Notch is a transmembrane receptor that controls cell fate decisions in Drosophila and whose role in mammalian cell fate decisions is beginning to be explored. We are investigating the role of Notch in a well-studied mammalian cell fate decision: the choice between the CD8 and CD4 T cell lineages. Here we report that expression of an activated form of Notch1 in developing T cells of the mouse leads to both an increase in CD8 lineage T cells and a decrease in CD4 lineage T cells. Expression of activated Notch permits the development of mature CD8 lineage thymocytes even in the absence of class I major histocompatability complex (MHC) proteins, ligands that are normally required for the development of these cells. However, activated Notch is not sufficient to promote CD8 cell development when both class I and class II MHC are absent. These results implicate Notch as a participant in the CD4 versus CD8 lineage decision.

Animals↗

repE--the Dictyostelium homolog of the human xeroderma pigmentosum group E gene is developmentally regulated and contains a leucine zipper motif.

We have cloned and characterized the Dictyostelium discoideum repE gene, a homolog of the human xeroderma pigmentosum (XP) group E gene which encodes a UV-damaged DNA binding protein. The repE gene maps to chromosome 4 and it is the first gene identified in Dictyostelium that is homologous to those involved in nucleotide excision repair and their related XP diseases in humans. The predicted protein encodes a leucine zipper motif. The repE gene is not expressed by mitotically dividing cells, and repE mRNA is first detected during the aggregation phase of development when the cells have ceased dividing and replicating genomic DNA. The mRNA level plateaus by the time the developing cells have entered multicellular aggregates and remains at the same steady-state level for the remainder of development. In addition, we have demonstrated that the level of mRNA is very low in developing cells. These observations suggest that repE may play a regulatory role in development. The data indicate that potential developmental roles for XP-related genes can be profitably studied in this system.

Amino Acid Sequence↗

Canine bone response to tyrosine-derived polycarbonates and poly(L-lactic acid).

Tyrosine-derived polycarbonates are a new class of degradable polymers developed for orthopedic applications. In this study the long-term (48 week) in vivo degradation kinetics and host bone response to poly(DTE carbonate) and poly(DTH carbonate) were investigated using a canine bone chamber model. Poly(L-lactic acid) (PLA) served as a control material. Two chambers of each test material were retrieved at 6-, 12-, 24-, and 48-week time points. Tyrosine-derived polycarbonates were found to exhibit degradation kinetics comparable to PLA. Each test material lost approximately 50% of its initial molecular weight (Mw) over the 48-week test period. Poly(DTE carbonate) and poly(DTH carbonate) test chambers were characterized by sustained bone ingrowth throughout the 48 weeks. In contrast, bone ingrowth into the PLA chambers peaked at 24 weeks and dropped by half at the 48-week time point. A fibrous tissue layer was found surrounding the PLA implants at all time points. This fibrous tissue layer was notably absent at the interface between bone and the tyrosine-derived polycarbonates. Histologic sections revealed intimate contact between bone and tyrosine-derived polycarbonates. From a degradation-biocompatibility perspective, the tyrosine-derived polycarbonates appear to be comparable, if not superior, to PLA in this canine bone chamber model.

Animals↗

Effects of growth-factor-enhanced culture on a chondrocyte-collagen implant for cartilage repair.

The effects of incubation and addition of growth factors to a chondrocyte-seeded collagen implant for cartilage repair were studied. Type I collagen matrices seeded with lapine articular chondrocytes and unseeded controls cultured in the presence and absence of fibroblast growth factor and insulin for 2, 6, and 9 weeks were subjected to biomechanical, biochemical, and histological analysis. Aggregate modulus of elasticity of seeded implants decreased by half at 6 weeks, then rose by a factor of 10 above initial values. Permeability of seeded implants and their controls decreased steadily. Glycosaminoglycan content peaked at 6 weeks, coinciding with the greatest number of chondrocytes and mitotic activity in seeded implants. Chondrocytes remained phenotypically stable and metabolically active; they incorporated glycosaminoglycan into the extracellular matrix, and formed an organized pericellular environment despite the predicted resorption of the collagen matrix. Adding fibroblast growth factor and insulin tripled the rate of cell turnover and doubled the glycosaminoglycan content of seeded implants, but had no effect on their material properties. In vitro incubation for 6 weeks in the presence of fibroblast growth factor and insulin creates a metabolically and mitotically active chondrocyte-collagen composite for implantation into articular cartilage defects.

Analysis of Variance↗

Risk of primary and recurrent acute myocardial infarction from lipoprotein(a) in men and women.

OBJECTIVES: This study sought to examine whether lipoprotein(a) concentrations were risk factors for a first acute and recurrent myocardial infarction. BACKGROUND: There is conflicting evidence concerning the risk of acute myocardial infarction from lipoprotein(a). No studies have examined the risk of recurrent acute myocardial infarction from lipoprotein(a), and few have addressed the risk in women. METHODS: This was a population-based case-control study of 893 men and women 35 to 69 years old participating in the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Project in Newcastle, Australia in 1993 to 1994. Case and control patients were classified into those with and without a previous myocardial infarction, and median lipoprotein(a) concentrations were compared after adjusting for other variables. Quintiles of lipoprotein(a) concentration were also examined. RESULTS: Compared with control subjects without a previous myocardial infarction, median lipoprotein(a) concentrations increased from case patients with a first myocardial infarction (15 mg/liter higher, 95% confidence interval [CI] -36 to 60) to control patients with a previous myocardial infarction (159 mg/ liter higher, 95% CI 40 to 278) and case patients with a previous myocardial infarction (60 mg/liter higher, 95% CI -16 to 136, p < 0.01, test for trend). Women had significantly higher lipoprotein(a) concentrations than men (median 71 mg/liter higher, 95% CI 23 to 118). The highest quintile of lipoprotein(a) (>550 mg/liter) was a significant risk factor for a first acute myocardial infarction (odds ratio [OR] 1.77, 95% CI 1.03 to 3.03); but in those with a previous myocardial infarction, the highest quintile was not associated with recurrent myocardial infarction (OR 0.84, 95% CI 0.30 to 2.37). CONCLUSIONS: High lipoprotein(a) concentrations may be a marker of vascular or tissue injury or may be associated with other genetic or environmental factors that cause acute myocardial infarction. Currently, lipoprotein(a) measurement cannot be recommended for assessment of risk for acute myocardial infarction.

Adult↗

Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion.

BACKGROUND AND PURPOSE: In past studies, cerebral outcome after normothermic cardiac arrest of 10 or 12.5 minutes in dogs was improved but not normalized by resuscitative (postarrest) treatment with either mild hypothermia or hypertension plus hemodilution. We hypothesized that a multifaceted combination treatment would achieve complete cerebral recovery. METHODS: With our established dog outcome model, normothermic ventricular fibrillation of 11 minutes (without blood flow) was followed by controlled reperfusion (with brief normothermic cardiopulmonary bypass simulating low flow and low PaO2 of external cardiopulmonary resuscitation) and defibrillation at < 2 minutes. Controlled ventilation was provided to 20 hours and intensive care to 96 hours. Control group 1 (n = 8) was kept normothermic (37.5 degrees C), normotensive, and hypocapnic throughout. Experimental group 2 (n = 8) received mild resuscitative hypothermia (34 degrees C) from about 10 minutes to 12 hours (by external and peritoneal cooling) plus cerebral blood flow promotion with induced moderate hypertension, mild hemodilution, and normocapnia. RESULTS: All 16 dogs in the protocol survived. At 96 hours, all 8 dogs in control group 1 achieved overall performance categories 3 (severe disability) or 4 (coma). In group 2, 6 of 8 dogs achieved overall performance category 1 (normal); 1 dog achieved category 2 (moderate disability), and 1 dog achieved category 3 (P < .001). Final neurological deficit scores (0% [normal] to 100% [brain death]) at 96 hours were 38 +/- 10% (22% to 45%) in group 1 versus 8 +/- 9% (0% to 27%) in group 2 (P < .001). Total brain histopathologic damage scores were 138 +/- 22 (110 to 176) in group 1 versus 43 +/- 9 (32 to 56) in group 2 (P < .001). Regional scores showed similar group differences. CONCLUSIONS: After normothermic cardiac arrest of 11 minutes in dogs, resuscitative mild hypothermia plus cerebral blood flow promotion can achieve functional recovery with the least histological brain damage yet observed with the same model and comparable insults.

Animals↗

Effect of annealing temperature on the degradation of reinforcing fibers for absorbable implants.

Calcium phosphate fibers designed for reinforcement of bioabsorbable fracture fixation devices were evaluated for their properties upon annealing. The composition of these fibers were 54% PO4, 27% Ca, 12% ZnO, 2.5% NaPO3, and 4.5% Fe2O3, and they were either not annealed, annealed at 250 degrees C, or annealed at 420 degrees C. Chemical degradation, mass loss, and morphology upon degradation were studied. Chemical degradation was performed in Tris-buffered HCl, while mass loss and morphologic studies were performed in both physiologic and nonphysiologic solutions. The results showed that degradation rates for fibers were inversely proportional to the annealing temperature. Mass loss analysis of fibers immersed in the two physiologic solutions (calf serum and simulated body fluid) revealed little change in fiber diameter up to 60 days. Morphologic examination revealed little change in fibers immersed in the two physiologic solutions until 60 days, after which thin shells were found to be peeling off the outer coating of the fiber. Samples in tris-buffered HCl revealed a dramatic difference in mode of degradation among the three fibers. Fibers not annealed and those annealed at lower temperatures underwent a delaminating type of degradation that appeared to destroy the overall integrity of the fiber, whereas fibers annealed at 420 degrees C underwent crater-like deterioration in which the overall alignment of the fiber remained intact. It is therefore concluded that annealing fibers at higher temperatures also undergo a mode of degradation that allows them to maintain their structural integrity. Although annealing fibers close to glass transition temperature may produce an initially weaker fiber, chemical and physical degradation occur much slower, making these fibers most suitable for reinforcement of biodegradable implants.

Absorption↗

Microcapsules through polymer complexation. Part 3: Encapsulation and culture of human Burkitt lymphoma cells in vitro.

Methacrylic acid (MAA) based polyelectrolytes were complexed with protonated or quaternized dimethylaminoethyl methacrylate (DMAEMA) containing polyelectrolytes to form microcapsules in vitro. Anchorage independent human Burkitt lymphoma (Raji) cells were successfully cultured in the presence of dissolved MAA containing polymer. Capsule morphology was investigated by light microscopy and by scanning electron microscopy (SEM). Capsules based on quaternized DMAEMA containing polymer were found to be more stable than capsules containing protonated DMAEMA functionality. Raji cells were successfully encapsulated in both systems and divided to confluence; thereafter sufficient pressure was exerted to burst open the capsules. Cells released from these capsules appeared to suffer no discernible trauma and were successfully isolated and subcultured to confluence.

Burkitt Lymphoma↗

Peritoneal cooling for mild cerebral hypothermia after cardiac arrest in dogs.

After normothermic cardiac arrest in dogs, we found that mild hypothermia (34 degrees C) of 1-2 h reduced brain damage, providing that hypothermia was achieved within 15 min of reperfusion. A clinically feasible rapid brain-cooling method is needed. As head-neck surface cooling alone in dogs was found to be too slow (0.1 degrees C/min), we reviewed peritoneal cooling in the Introduction and Discussion sections. PRELIMINARY EXPERIMENTS WITHOUT CARDIAC ARREST: In 5 dogs with spontaneous circulation and IPPV, 2 L of Ringer's solution at 10 degrees C were instilled into the peritoneal cavity, left for 5 min, and drained. Brain (tympanic membrane) temperature (Tty) decreased by a mean of 0.3 degrees C/min (12 min to 34 degrees C). Core (pulmonary artery) temperature (Tpa) decreased by a mean of 0.8 degrees C/min (5 min to 34 degrees C). COOLING AFTER CARDIAC ARREST: In our reproducible dog model of normothermic ventricular fibrillation cardiac arrest of 11 min (no flow), brief low-flow normothermic cardiopulmonary bypass (CPB) was used for reperfusion and restoration of spontaneous circulation (ROSC) within 2 min. In 24 dogs, mild hypothermia was induced by head-neck surface cooling with ice bags, starting with reperfusion, plus peritoneal lavage as above, starting with ROSC. All 24 dogs were resuscitated. Initial head-neck surface cooling alone over 2 min decreased Tty by only 0.15 degrees C/min. Subsequent additional peritoneal lavage decreased Tty by a mean of 0.3 degrees C/min (11 min to 34 degrees C); and Tpa 0.6 degrees C/min (7 min to 34 degrees C). There were no significant physiologic effects. We conclude that peritoneal instillation of cold Ringer's solution is more rapidly effective than other non-intravascular cooling methods reported previously. Peritoneal cooling should be tried in patients during CPR.

Animals↗

[Overview of the development of laparoscopic surgery at the gynecologic clinic of the Leipzig University 1989-1993].

This paper reports on the trend in pelviscopy at the women's Hospital of the University of Leipzig during the period from 1989 to 1993. There were 1989 operations performed. Most of them (50.2%) were of diagnostic nature, followed by tubal sterilization (39.8%). Endoscopic surgery was represented with 9.9% of pelviscopy. Complication rate was at 0.6%. Mortality rate was at 0.05%. Since tubal sterilization has been introduced in 1990, a number of 792 patients have been sterilized by endocoagulation according to the method of Semm. Sterilization failure was at 0.38%.

Female↗

Materials and design concepts for an intervertebral disc spacer. I. fiber-reinforced composite design.

The intervertebral disc is a complex joint anatomically and functionally. It may be displaced or damaged due to trauma or a disease process. To alleviate this condition, it may be necessary to remove the involved disc surgically and fuse the two adjacent vertebrae. Fusion is one option; however, replacing the damaged disc (or part thereof) with a suitable synthetic equivalent to allow near normal joint motion is more desirable. Unfortunately, the complex mechanical properties of the lumbar disc cannot be duplicated with homogeneous synthetic materials (polymers). To overcome this fundamental problem we have developed rational designs utilizing biocompatible thermoplastic elastomers of various stiffnesses (durometers) with and without fiber reinforcements. Our design consisted of three components analogous to the natural end plates, annulus, and nucleus. In this study only the fiber-reinforced design is considered. The variables examined in the present study included orientation of the fiber layers, number of fiber layers, and order of the reinforcing layers. The results of mechanical testing of the fiber reinforced disc spacer indicate that the range of compressive and torsional properties can be achieved. The results further demonstrate that properly developed, this design results in properties similar to the natural disc. Designs developed provided adequate compression and compression torsion properties for a synthetic spine disc spacer.

Biocompatible Materials↗