Search for Optimal Frequencies and Amplitudes of Therapeutic Electrical Carotid Sinus Nerve Stimulation by Application of the Evolution Strategy

In humans, electrical, bipolar, bilateral carotid sinus nerve stimulation (CSNS; impulse duration 0.35 ms) was applied, using frequencies between 10 and 110 Hz and voltages between individual thresholds and maximal amplitudes of stimulation. Ten anginal patients and two hypertensive patients were studied at an interval of up to 12 years after implantation of electrodes and a radiofrequency receiver for chronic therapeutic CSNS. In search of combinations of frequency and voltage of CSNS, eliciting largest ("optimal") depressor responses of blood pressure and heart rate in the individual patient, Rechenberg's evolution strategy was applied. This strategy simulates mutation and selection of biological evolution. In each patient and on each test stimulation, a value of quality was computed from actual heart rate and blood pressure values as a selection criterion for the strategy. Either responses to uninterrupted CSNS were investigated, while stimulation parameters were adjusted every 3 min, according to the strategy, or responses to 3 min of CSNS after a change in stimulation parameters were compared to intercalated 3-min control periods. In each patient, one or more combined settings of frequency and voltage elicited "optimal" responses. In principle, "optimal" CSNS frequencies ranged between 35 and 105 Hz with large interindividual differences. Due to chronic implantation of electrodes and technical features of radiofrequency transmitted stimulation energy, interindividually different voltages led to an optimal response to CSNS. Also according to the present results, the frequency of CSNS has to be determined individually. It is concluded that the evolution strategy was applied successfully, because voltage and frequency settings leading to "optimal" responses were found within 90-180 min, whereas intraindividual systematic investigations would not be feasible due to their necessarily very long duration. So far, only short-term responses have been evaluated. A broader use of the strategy in other applications is encouraged, as for example in pacemaker optimization and especially in functional electrostimulation.     

Suppression scotomas in primary microstrabismus — a perimetric artefact

Static perimetry with stereoscopic targets, stereo-perimetry, was performed on eight patients with primary microstrabismus to find out how strabismic subjects see under natural conditions, i.e. how they ordinarily make use of their squinting eye. In all cases, suppression scotomas were detectable using dissociating perimetric techniques. By means of stereoperimetry, however, the scotomas were not detectable. On the contrary, stereo-acuity was always best in the center of the suppression scotomas. This result indicates that suppression scotomas of the microstrabismic subjects examined here represented perimetric artefacts. In microstrabismic pateints, the cooperation of the deviated eye in the central visual field is probably much better than has previously been thought.     

Human recombinant neutralizing antibodies against hantaan virus G2 protein

Old world hantaviruses, causing hemorrhagic fever with renal syndrome (HFRS), still present a public health problem in Asia and Eastern Europe. The majority of cases has been recorded in China. The aim of our study was to generate human recombinant neutralizing antibodies to a hantavirus by phage display technology. To preserve the structural identity of viral protein, the panning procedure was performed on native Hantaan (HTN) (76-118) virus propagated in Vero-E6 cells. In total, five complete human recombinant IgG antibodies were produced in a baculovirus expression system. All of them were able to completely neutralize HTN, and Seoul (SEO) virus in a plaque reduction neutralization test (PRNT). Three of these antibodies could also completely neutralize Dobrava (DOB) virus but not Puumala (PUU) virus. All antibodies bind to Hantaan virus G2 protein localized in the virus envelope. The sequence areas within the HTN (76-118)-G2 protein detected by five selected antibodies were mapped using peptide scans. Two partial epitopes, 916-KVMATIDSF-924 and 954-LVTKDIDFD-963, were recognized, which presumably are of paramount importance for docking of the virus to host cell receptors. A consensus motif 916-KVXATIXSF-924 could be identified by mutational analysis. The neutralizing antibodies to the most widely distributed hantaviruses causing HFRS might be promising candidates for the development of an agent for prevention and treatment of HFRS in patients.     

The water jet as a new tool for endoprosthesis revision surgery--an in vitro study on human bone and bone cement

In revision surgeries of endoprostheses, the interface between implant and bone cement or bone must be loosened. Conventional tools have many disadvantages because of their size and limited range. Taking advantage of the selective and athermic cutting process, a plain water jet is already used in order to cut soft tissues. This study investigates the possibilities of both a plain and an abrasive water jet as cutting tools for revision surgery. Samples of the mid-diaphysis of human femora and bone cement (CMW3) were cut with a plain water jet (PWJ) and an abrasive water jet (AWJ) at two different jet-to-surface angles (30 degrees,90 degrees ) and at five different pressure levels (30, 40, 50, 60, 70 MPa). For a PWJ a selective pressure range was identified, where only bone cement was cut. Injecting a bio-compatible abrasive (lactose) to the jet stream resulted in significantly higher cut depths in both materials. Material removal in bone was significantly less at the smaller jet-to-surface angle for both techniques. No clear selectivity between bone and bone cement was observed for application of the AWJ. However, the material removal rate was significantly higher for bone cement than for bone at all pressure levels. The results indicate that an AWJ might be an alternative tool for cement removal. The possibility for localised cutting at interfaces could be an advantage for revision of a non-cemented prosthesis.     

Urine test strips: reliability of semi-quantitative findings under tropical conditions

Semi-quantitative urinalysis with urine reagent strips (URS) for erythrocyturia (EU), leucocyturia (LU) and proteinuria (PU) was performed in Congolese and Sudanese school children withSchistosoma haematobium and/orS.mansoni infection. Quantitative urinalysis was performed on the same specimen using microscopy and a Neubauer counting chamber for EU and LU and the Coomassie blue dye-binding assay for PU. Microscopically detectable EU of more than 10 cells/l was found in 63% of all samples and LU of more than 20 cells/l was found in 60% of all samples. With the Coomassie blue method, PU of more than 150 mg/l was detected in 51% of all samples. URS gave positive results of grade 1–3 for EU in 69% of all samples, for LU in 63% of all samples and for PU in 66% of all samples. The sensitivity and specificity of URS compared with standard reference methods were as follows: EU 95% and 75%, LU 81% and 81% and PU 90% and 56%. When the results of all three test were combined, URS differentiated abnormal from normal urine specimens with a sensitivity of 94% and a specificity of 70%. Median quantitative results showed a good correlation with semiquantitative URS readings for all parameters, but there was a wide range of URS scores.We concluded that URS sensitively detect urinary abnormalities and thus may be used as a general screening method under field conditions when more specific methods cannot be performed. In the hospital laboratory,urine microscopy with a counting chamber would be preferred to URS as a sole method for EU and LU detection; URS is useful for the detection of PU in the tropical hospital laboratory where an appropriate quantitative method with a better specificity may not be available.     

Primary position vertical nystagmus: ‘Directional preponderance’ of the pursuit system?

Summary The essential disturbance in five patients with vertical nystagmus was an inability to generate smooth pursuit eye movements in the direction of the quick phase of their nystagmus. As the cause of this behavior, the authors suggest an asymmetric impairment of the visual input to the pursuit system. This defect causes a directional preponderance of the pursuit system detectable as a continuous drift off target. The drift is interrupted by refoveating saccades, thus resulting in a vertical nystagmus.

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Zusammenfassung Fünf Patienten mit Vertikalnystagmus zeigten als wesentliche Störung eine Unfähigkeit, gleitende Folgebewegungen in Richtung der raschen Nystagmusphase auszuführen. Als Ursache dieser Störung nehmen Verff. eine asymmetrische Unterbrechung visueller Zuflüsse zum Folgesystem an. Durch diese Unterbrechung wird das normalerweise bestehende Gleichgewicht im Folgesystem gestört. Es entsteht ein Richtungsüberwiegen im Folgesystem, das sich in einem Abtreiben der Gesichtslinie vom ruhenden Fixierpunkt auswirkt. Dieses Abtreiben wird immer wieder durch Sakkaden korrigiert, so daß ein Nystagmus entsteht.

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Supported by the Deutsche Forschungsgemeinschaft, SFB 70, B 4     

Direct gamete uterine transfer in patients with tubal absence or occlusion

Purpose: Our aim was to examine the potential of the uterine cavity to affect fertilization and early embryo development. Design: A prospective IRB-approved protocol for patients fulfilling study eligibility criteria was used. Methods: Patients studied included those with primary or secondary infertility, aged less than 38 years, with no history of severe male-factor infertility, and with hysterosalpingogram-and laparoscopic-confirmed bilateral proximal tubal occlusion. Superovulation induction was accomplished with a combination of GnRH agonist and menotropins, with serum hormonal and sonographic monitoring. Within 24 hr prior to, and again at the time of, ovulatory hCG administration, progesterone (P4) was given. Sonographic-guided transvaginal retrieval was performed 35 hr after hCG. Between four and six oocytes were returned to the uterine cavity, admixed with sperm, immediately following retrieval. Luteal support consisted of daily P4 administration. Results: Of the 20 patients recruited for the study, all completed the retrieval and transfer procedure. A total of four clinical pregnancies was achieved, with one early first-trimester loss, one late first-trimester loss (Trisomy 14), and two healthy term infants delivered. IVF of surplus oocytes demonstrated a 82.5% fertilization rate and 66.7% cleavage following cryopreservation. Conclusions: Human fertilization can be achieved through direct uterine transfer of gametes. Furthermore, administration of P4 prior to the ovulatory dose of hCG is compatible with in vitro or in vivo fertilization and implantation.