Photochromic bis(thiophen-3-yl)maleimides studied with time-resolved spectroscopy.

The dynamics of the ring-closure reaction of three different bis(thiophen-3-yl)maleimides are investigated using ultrafast spectroscopy in the visible range. The structures of the molecules differ with respect to substitution of the thiophene ring and the maleimide. The experiments reveal reaction kinetics which point to the population of an excited electronic state for several nanoseconds. In the case of completely unsubstituted thiophene rings, a long excited-state lifetime (biexponential decay with 3 and 15 ns) can be observed. The remaining ultrafast absorption transients of this molecule are due to relaxational processes on the excited electronic potential energy surface. The ring-closure reaction has a small yield (<1%) and does not show up in the ultrafast absorption experiments. A dimethyl substitution of the thiophene ring results in completely different behavior: after transients related to relaxation in the excited electronic state, one finds pronounced absorption transients with tau = 16 ps which represent the partial decay of the excited electronic state and the formation of the ring-closed isomer. Another fraction of the emitting excited electronic state decays again on the few nanosecond time scale. The experiments suggest that the open isomer of the dimethyl-substituted imides exists in two conformations.

A probable cause of paradoxical thrombosis in zygomycosis.

Invasive zygomycoses (syn. mucormycoses) are rather rare but life-threatening diseases which often take a peracute course. Particularly endangered are diabetics and patients suffering from siderophilia. Zygomycosis is regularly complicated by thrombosis and subsequent necrosis. Usually it evolves from sinusitis in a rhinocerebral form. With the use of a clinical isolate (Rhizopus microsporus) and sera of the same female survivor, we investigated possible sources of the typical blood clotting. The results suggest that coagulation is probably initiated in a bimodal manner by an extracellular serine proteinase of the fungus and by elastase from the patients' leukocytes. The former causes a partial hydrolysis of fibrinogen, while the latter activates coagulation factor XIII (fibrin stabilizing factor). Both proteinases were present in the patient at the site of infection, and in vitro they jointly bring about regular clotting of fibrinogen.

Permanent pacemaker therapy before and after the reunification of Germany: 16 years of experience at an East German regional pacing center.

The reunification of Germany had a significant influence on the management of patients with bradyarrhythmias. The current study was performed in a regional pacing center located in the former German Democratic Republic. It compares the situation of patients with critical bradyarrhythmias before and after the reunification of Germany in 1990 focusing on (1) indication for pacemaker implantation, (2) pacemaker modalities and function, (3) type of leads, (4) frequency of reintervention, and (5) early and late complications. The study covers 9 years before and 7 years after the reunification. A total of 1,125 patients were included, and the database was formed by the patients' files and the protocols of implantation. The situation before reunification was characterized by a nonavailability of modern physiological pacing devices and insufficient diagnostic equipment. Between 1981 and 1990, 384 patients underwent pacemaker implantation solely receiving single chamber devices with no or only minimal feasibility of programming. Between 1990 and 1996, 741 patients were treated, and they all received modern pacemakers having the capability of multiprogramming and telemetry. Regarding complications of pacemaker therapy, lead related problems significantly decreased after the reunification (dislocation, 5.3% vs 1.7%, P < 0.05; exit block, 6.7% vs 1.4%, P < 0.05) opposite to pacemaker infections, which significantly increasing after dual chamber pacemakers were implanted (2.2% vs 6.0%, P < 0.05). The reunification of Germany dramatically improved the situation of patients with critical bradyarrhythmias leading to free access to high-tech pacing equipment within a few months. However, the abrupt change from antiquated to modern pacemaker therapy created some new problems, especially regarding application and handling of modern physiological pacing devices.

Electromyographic investigation of stretching: the effect of warm-up.

OBJECTIVE: To compare the fine wire electromyographic (EMG) firing patterns during static stretches in the biceps femoris, soleus, and gastrocnemius before and after warm-up as well as over time. DESIGN: Experimental single group pretest-posttest design. SETTING: Biomechanics research laboratory. PARTICIPANTS: Sixteen healthy volunteers 23 to 36 years of age with no history of lower extremity injury. INTERVENTION: Subjects performed one hamstring stretch and four calf stretches for 90 seconds, bicycled for 30 minutes as a warm-up, and stretched again. MAIN OUTCOME MEASURE: EMG was recorded at time 0, 30, 60, and 90 seconds during the stretches before and after warm-up. Recorded values were normalized to EMG during maximum manual muscle testing (MMT). A two-way analysis of variance with repeated measures (p < 0.05) was done to compare EMG activity during stretching before and after warm-up as well as over time. RESULTS: Low EMG activity was seen for all muscles (< 20% MMT). It was constant over the time of the stretch for all muscles, but it increased in the soleus during the bent knee stretch position. There was a statistically significant decrease in the EMG activity after the warm-up for the gastrocnemius using the traditional and heel off stretching positions and for the soleus using the heel off stretching position (p < 0.05). The biceps femoris EMG activity showed no significant differences before and after warm-up. CONCLUSIONS: EMG activity during static stretching was low. Overall, the EMG activity remained constant with time for a given stretch position. EMG of the soleus and gastrocnemius was significantly less after warm-up for some stretches, whereas the EMG activity of biceps femoris showed no differences before and after warm-up.

Steep central islands after myopic photorefractive keratectomy.

PURPOSE: To investigate the formation of steep central islands and their reduction under modified experimental conditions. SETTING: University Eye Hospital Münster and Schwind Co., Kleinostheim, Germany. METHODS: Corneas of enucleated intact bovine eyes were treated with the Schwind Keratom. All experimental conditions were repeated six times in six different corneas. Eight experimental groups were looked at. Fluence was 180 to 200 mJ/cm2. Ablation mode (phototherapeutic keratectomy ([PTK] and standard myopic photorefractive keratectomy [PRK]), internal repetition rate (3 to 30 Hz), and ablation diameter (5 to 8 mm) and depth (4 to 15 diopters [D] in PRK) were varied. Modifications to reduce or avoid steep central islands included blowing nitrogen gas and aerosol over the cornea, cleaning the cornea of fluid, and using an anti-central-island software program. RESULTS: In PTK, an increase in the internal repetition rate resulted in a decrease in the height of the steep central island. In standard PRK, increasing refractive correction up to -8.0 D and increasing the ablation diameter resulted in an increase in steep central island power. The anti-central-island program, blowing aerosol, and cleaning the cornea reduced the formation of steep central islands and blowing nitrogen gas eliminated them. CONCLUSION: Steep central islands are created by a wide-field ablation process and are probably caused by many factors. Both software and hardware modifications can be used to reduce their formation.

Human polyomavirus JC control region variants in persistently infected CNS and kidney tissue.

The question of a possible role for JC virus (JCV) genomic rearrangements in the pathogenesis of progressive multifocal leukoencephalopathy (PML) was addressed by analysis of the genomic complexity and the transcriptional control region (TCR) of the JCV DNA population in persistently infected CNS and kidney tissue. After cloning of full-length viral DNA, no extensive changes were detected in the coding regions of the JCV genome by restriction analysis suggesting an intact JCV DNA population. For further analysis of the distribution of JCV subtypes, the non-coding region was amplified by PCR. Molecular analysis revealed homogeneous JCV TCR populations in almost 50% of the individuals. Heterogeneity was found in two CNS samples with three and five different JCV subtypes, respectively, and in four kidney specimens with two TCR subtypes. Altogether, seven TCR subtypes were identified. One in each group represented single promoter element TCRs without duplication of sequences. The TCR of the major variant JCV-W1 was comparable in sequence and structure to that of the PML prototype JCV Mad-1 DNA. The identification of dominant PML-derived JCV TCR subtypes in most persistently infected individuals suggests that rearrangements of the JCV TCR can be associated with the persistent state of infection. However, it appears unlikely that PML-associated JCV subtypes are generated anew in each individual host in the course of persistence. The findings rather suggest that a limited number of stable JCV subtypes circulate in different geographical regions of the world.

Multiple pregnancy rate and embryo number transferred during in vitro fertilization.

OBJECTIVE: Our goal was to achieve a good pregnancy rate after in vitro fertilization; more than one embryo, if available, is transferred to the uterine cavity. This is a recognition of the low implantation rates of embryos from in vitro fertilization. A consequence of this can be high-order multiple implantation with obstetric complications. STUDY DESIGN: Retrospectively, we reviewed 42 months' in vitro fertilization experience; we related the number of embryos transferred and the pregnancy outcome. During this period 2173 fresh and frozen-thawed embryo transfers were performed. One to six embryos were transferred to women whose average age was 34.4 years (range 21 to 49). RESULTS: A total of 734 delivered pregnancies (33.8% per embryo transfer) was analyzed according to whether they were single or multiple, and this was related to the original number of embryos transferred. The overall multiple pregnancy rate was 31.3% (24.7% twins, 5.8% triplets, 0.8% quadruplets). CONCLUSIONS: There was a trend toward a higher pregnancy rate with more embryos transferred. The embryonic implantation rate, which reflects the number of embryos that implant per total transferred, was not significantly different in any one group, except in older women in whom more than one embryo was transferred. Whereas greater numbers of embryos (more than three) were transferred in couples with a poorer prognosis for successful in vitro fertilization (e.g., older women [> 36 years old], previous failure of in vitro fertilization, poor embryo quality, or severe male factor causing infertility), there still remained a significant trend toward a higher pregnancy rate when more embryos were transferred. The embryonic implantation rate did not decline in the poorer-prognosis groups (more than three embryos transferred), yet the multiple pregnancy rate was increased. Technologic procedures such as embryo biopsy for aneuploidy screening are proposed as one means to reduce embryo numbers transferred without decreasing the overall pregnancy rate.

Enhancement of outcome from intracytoplasmic sperm injection: does co-culture or assisted hatching improve implantation rates?

In two separate prospectively randomized trials, intracytoplasmic sperm injection (ICSI) cycles were studied in a controlled manner to monitor the effects of either bovine oviductal epithelial cell co-culture (n = 119) or assisted hatching by zona drilling (n = 100). In the first study, immediately following ICSI, all eggs were placed directly either onto partial monolayers of bovine oviductal cells or into regular culture medium. Although the embryo developmental rate was apparently compromised in part by the presence of the co-culture cells, ultimately there were no significant differences in either the viable pregnancy rate (31.6% co-culture versus 29.0% control) or the embryonic implantation rate (11.4% co-culture versus 13.6% control). Assisted hatching also had no significant impact on ICSI cycle outcome in terms of either the viable pregnancy rate (30.0% assisted hatching versus 32.0% control) or the embryonic implantation rate (8.5% assisted hatching versus 13.5% control). However, in female patients aged > or = 35 years, assisted hatching appeared to convey a marginally significant benefit in terms of both the viable pregnancy rate (35.5% assisted hatching versus 11.1% control) and the embryonic implantation rate (10.3% assisted hatching versus 3.1% control). It seems that the overall improvement of ICSI cycle outcome cannot be achieved by the general application of either co-culture or assisted hatching. Nevertheless, it is possible that there remain specific patient groups that might benefit from selected use of either of these modalities.

Heparinized saline versus normal saline in maintaining patency of the radial artery catheter.

OBJECTIVE: To compare the ability of normal versus heparinized saline infusion to maintain patency of the radial artery catheter used for monitoring or multiple blood sampling. DESIGN: Randomized double-blind trial. SETTING: A university-affiliated hospital. PATIENTS: All 108 patients admitted to the surgical intensive care unit who required radial arterial line catheters. Excluded were patients who required emergency admission, those who refused to give consent, those who needed anticoagulants, thrombolytic or platelet therapy, those whose cannulation site was other than the radial artery, inadvertent discontinuation of the arterial line or incomplete data collection. This resulted in a sample of 78 adults, randomized according to date of admission. INTERVENTIONS: Forty patients admitted on odd-numbered dates received heparinized normal saline (2 units/mL), and 38 patients admitted on even dates received normal saline, both as continuous flush solutions. MAIN OUTCOME MEASURES: Measurement of radial artery flow and pressure before and after cannulation, and catheter patency during cannulation. RESULTS: The type of flush solution did not adversely affect the radial artery or the hand in any measurable way. Catheter blockage occurred in three patients receiving heparinized saline and seven patients receiving normal saline as the flush solution (p = 0.06). At 96 hours of cannulation, 92% of the catheters in the heparinized saline group were patent compared with 74% in the normal saline group. Intra-arterial blood pressure was inaccurate compared with the brachial cuff pressure in 6 patients in the heparinized saline group compared with 14 patients in the normal saline group (p < 0.03). CONCLUSIONS: There is no significant difference between flushing with normal saline and heparinized saline in the maintenance of radial arterial line patency. However, the use of a continuous heparinized flush solution in pressurized arterial lines is beneficial in that it results in greater accuracy of blood pressure monitoring than normal saline infusion.

A roadmap for the novice researcher.

This article outlines the research process as it applies to nurses in clinical practice. While the topic seems intimidating at first, by questioning clinical practice and maintaining an open mine, nurses can generate the enthusiasm and commitment necessary to conduct their own research. First, a nursing research issue worthy of investigation needs to be identified and thoroughly reviewed in the literature. The nurse next needs to bring together an appropriate research team and develop a formal research proposal. The team then submits the proposal through the organizational structure that grants approval and provides funding. Once the study has been implemented and the data collection is complete, the research team must decide on the best method of disseminating the research findings to nursing colleagues. This last important step helps to expand and build nursing's professional body of knowledge, and ensures that current nursing practice is based on valid research findings.

Evidence of human polyomavirus BK and JC infection in normal brain tissue.

Infection with the polyomaviruses JC and BK is ubiquitous in the human population and JCV is the only virus associated with the central nervous system disease progressive multifocal leukoencephalopathy. In the attempt to analyze the pathogenesis of polyomavirus infections we asked whether human polyomaviruses invade the brain during persistence. Brain autopsy material from 67 individuals with disorders other than PML was examined for the presence of polyomavirus DNA. Southern blot analysis demonstrated JCV-specific full-length virus genomes in healthy brain tissue in about 20% of the patients. Type-specific analysis with polymerase chain reaction and sequencing confirmed these data. Additionally, the presence of BKV DNA sequences covering an early gene fragment and the control region with flanking early and late protein coding sequences was detected. Cloning of the complete BKV genome from two cases supported the assumption that not only full-length JCV DNA was present in those tissue specimens but also BKV genomes. The data obtained demonstrate that dual infection of the brain with the polyomaviruses JCV and BKV is a common event and give strong evidence that both viruses frequently establish a latent CNS infection.

Poor implantation of cryopreserved reinsemination-fertilized human embryos.

OBJECTIVE: To investigate whether a poor rate of implantation after in vitro fertilization (IVF) was due to poor embryonic/endometrial synchrony during the original IVF cycle, we have cryopreserved reinseminated-fertilized embryos for later more synchronous replacement after thawing. The chance of implantation of fresh reinseminated fertilized human oocytes is approximately one tenth that of timely fertilized embryos. STUDY DESIGN AND DATA: Retrospective study of 35 original oocyte collections in which initial normal fertilization was 47.3% (129/273 oocytes), with 49.6% fertilization (67/135) upon reinsemination. Of these, 70 initially fertilized and 67 reinsemination-fertilized embryos were cryopreserved, and 50 initially fertilized and all 67 reinsemination-fertilized embryos were subsequently thawed with 72% and 63% cryosurvival, respectively, (not significant). SETTING: Private infertility clinic. RESULTS: In 11 cycles, 23 thawed initially fertilized embryos (group A) were replaced with a 21.7% implantation rate per embryo; in 10 cycles, 13 initially fertilized and 12 reinsemination-fertilized embryos (group B) were replaced together with an 8% implantation rate; finally, in 16 cycles, 30 reinsemination-fertilized embryos (group C) were replaced with a 3.3% implantation rate (group A versus group C: P = 0.076). Comparison of clinical pregnancies between these groups was significantly different (6/11 versus 1/16; P = 0.0427). CONCLUSION: Reinsemination-fertilized embryos survive freezing as well as initially fertilized embryos, but better embryonic/endometrial synchrony does not improve chances of their implantation.

Immunosuppression supports implantation of zona pellucida dissected human embryos.

The effect of low dose immunosuppression with methylprednisolone during the first 4 days after oocyte retrieval on potential immune cell invasion of partially zona dissected embryos in utero was investigated in alternate in vitro fertilization patients (n = 32). The incidence of pregnancy was significantly higher in patients receiving methylprednisolone (7 of 18, 39%) than in control patients (1 of 14, 7%). Twenty-eight percent (11 of 39) of the embryos replaced in the corticosteroid treated patients implanted, whereas only 7% (2 of 31) of embryos in control patients had a fetal heart beat. There were no side effects reported in any of the patients receiving corticosteroids. It can be concluded that methylprednisolone supports implantation of embryos with small holes in their zonae. However, the actual mechanisms of corticosteroid support on the interaction between immune cells and micromanipulated embryos are not well understood.

Observations on the morphology of pronuclei and nucleoli in human zygotes and implications for cryopreservation.

The effects of cryopreservation on human zygotes at various stages between the appearance of pronuclei and their close association were investigated. Pronuclear zygotes (n = 233) from 101 patients were frozen using propanediol 21-35 h following egg collection. The incidence of implantation of thawed pronuclear zygotes frozen 29-35 h following oocyte collection was significantly higher than that of younger pronuclear zygotes (28 versus 10%, respectively). Zygote age did not affect cell survival following cryostorage. The diameter and association of pronuclei and the number and distribution of nucleoli were determined from video tape recordings of 140 fresh zygotes. Pronuclear migration continued after pronuclear enlargement. The number of nucleoli remained constant during pronuclear migration, but their random distribution within the pronucleus diminished. Strongly adhered pronuclei had significantly more aligned nucleoli on adjacent sides than pronuclei which were still visually separated by ooplasm. This equatorial distribution of nucleoli was noted in the majority of zygotes older than 26 h. The findings suggest that zygote cryopreservation should be initiated when pronuclear migration is completed. This moment can be determined accurately by studying pronuclear association and nucleolar alignment.

Cryopreserved zygotes and embryos and endocrinologic factors in the replacement cycle.

Several parameters relating to features of replacement cycles in 88 patients were found to influence implantation of cryopreserved zygotes and early cleaved embryos. Cryopreserved embryos were replaced in 47 patients with a natural cycle, resulting in 12 (25%) clinical pregnancies. Patients who had anovulation or irregular cycles received either 50 mg clomiphene citrate on days 5 to 9 or 100 mg on days 2 to 6; the incidence of clinical pregnancy was 7 of 23 (30%) and 2 of 18 (11%), respectively. Neither a rise in follicular phase estradiol (E2) nor absolute levels of E2 predicted implantation. The length of the follicular phase during the replacement cycle correlated well with previous menstrual cycles in 43 (54%) of the patients, and 16 (37%) of these patients became pregnant. The follicular phase was either longer or shorter than anticipated in 39 patients, and only 5 (13%) became pregnant: a detrimental effect was especially apparent when the follicular phase was shortened.