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Biomedical subjects

G T Kovacs

Publications and source records attributed to G T Kovacs.

At least 19 recordsLinked to original sources

Multi-unit recording from regenerated bullfrog eighth nerve using implantable silicon-substrate microelectrodes.

Multi-microelectrode silicon devices were developed for extracellular recording from multiple axons in regenerated eighth cranial nerves of American bullfrogs. Each includes a photolithographically defined array of holes and adjacent metal microelectrodes. A device is implanted within a transected eighth nerve; regenerating fibers grow through the holes en route to the brainstem. Multiple spike trains were recorded from two animals at up to 21 weeks after implantation. Single units were tracked for over 8 h. Some responded to sound with tuning typical of fibers innervating the amphibian and basilar papillae. Units of vestibular origin also were recorded. Action potentials were 30-140 microV P-P amid noise of 5 10 microV RMS, an adequate signal-to-noise ratio for spike detection and sorting. Histology confirmed that bundles of myelinated fibers grew through holes near electrodes that recorded activity. The implantation success rate was low, due to surgical morbidity, device extrusion, and lack of nerve regeneration through some devices. Future designs will address these issues and incorporate transistor amplifiers on devices to increase signal-to-noise ratios. The potential of implanted silicon devices to simultaneously record from many axons offers an opportunity for multicellular studies of auditor, vestibular and seismic signal processing in the vertebrate inner ear.

Acoustic Stimulation

Assisted reproduction: a reassuring picture.

Many couples seek solutions to problems of infertility by using assisted reproduction techniques. Despite very different beginnings, children conceived after donor insemination, ovum donation, in-vitro fertilisation or gamete intrafallopian transfer show no adverse long term effects, either physically or psychosocially.

Fertilization in Vitro

A feedback controlled silicon microprobe for quantitative mechanical stimulation of nerve and tissue.

The ability to apply and control the force and force velocity of mechanical stimulation is essential for the study of mechanoelectric transduction and adaptation processes. Silicon micromachining technology was used to produce miniature (20-70 microns wide) mechanical microprobes. Passive polysilicon, piezoresistive, force sensing elements were deposited onto the boron-doped epitaxial silicon and the individual devices were chemically etched from the bulk wafer. These microprobes display a linear force versus output voltage relationship. Stimulation forces up to 2 mN can be generated with a measurement resolution of 1.5 microN. The probes were mounted onto circuit board holders and their output sent to a proportional-integral controller which drives an electromagnetic actuator. By using this force-feedback control circuit coupled to a PC it is possible to define any stimulus wave form pattern and independently control and measure the actual stimulus force and velocity. A computer controlled 3-axis stepper motor (0.025 micron step capability) manipulator is used to position the silicon microprobe-actuator assembly relative to the mechanoreceptive field. Sensor feedback control coupled to the 3-axis stepper motor manipulator allows automatic touchdown control and/or preloading of the probe prior to stimulation. Three-dimensional topographic manipulator feedback position control allows automated receptive field mapping.

Action Potentials

Force-sensing microprobe for precise stimulation of mechanosensitive tissues.

Quantitative study of the transduction mechanisms in mechanically sensitive nerve terminals has been impeded by the lack of instrumentation with which to generate precisely controlled, physically localized mechanical stimuli. We have developed high-resolution force sensing mechanical microprobes for use in the characterization of such nerve terminals. This paper describes their design, fabrication, and testing. A microprobe is comprised of a 0.5- to 2-mm long silicon cantilever beam projecting from a larger supporting silicon substrate. Acting as the variable leg of a Wheatstone bridge circuit, a piezoresistive polysilicon element located at the base of the beam is used to measure the stimulation force applied at the tip. The microprobes exhibit a stable, linear relationship between the stimulation force and the resulting output voltage signal. Stimulation forces up to 3 mN have been generated with a measurement resolution of 10 microN. These microprobes have been used as the force sensing element of a closed loop feedback-controlled stimulation system capable of stimulating the mechanoreceptive nerve terminals of the rabbit corneal epithelium.

Animals

Female sterilisation.

Adverse effects of female sterilisation are a popular subject for media focus; however, in reality modern techniques mean that the benefits outweigh the risks.

Female

Correlation of semen variables and pregnancy rates for donor insemination: a 15-year retrospective.

OBJECTIVE: To determine the validity of the criteria currently used to select fertile sperm donors. DESIGN: Retrospective study of the outcome of donor insemination treatment cycles over a 15-year period. SETTING: The Reproductive Medicine Clinic of Prince Henry's Institute of Medical Research (formerly Medical Research Centre, Prince Henry's Hospital, South Melbourne, Victoria, Australia). PATIENTS: Couples (1,299) presented with severe male factor infertility (azoospermia or severe oligozoospermia) and were treated by donor insemination (10,796 treatment cycles) using cryopreserved semen from 292 normal healthy men aged between 18 and 46 years as sperm donors. MAIN OUTCOME MEASURES: Semen characteristics, including volume, count, motility, motility index, normal morphology, live cells, and post-thaw motility, were analyzed by logistic regression analysis to determine which groups of factors were related independently and significantly to pregnancy rates. RESULTS: The pregnancy rate for donor insemination was 8.9% per cycle. By logistic regression count, normal morphology, post-thaw motility (%), and post-thaw motility index together explained 28% of the variance of the pregnancy rates. Other factors, including prethaw motility characteristics (percent motility and motility index), donor age, weight, LH, FSH, and T levels, were not significant. CONCLUSIONS: The standard parameters of sperm count, morphology, and post-thaw motility are the most important factors for the selection of highly fertile donors. As most of the variability in the pregnancy rates resulted from other undetermined factors related both to the donor and the recipient, it is suggested that the pragmatic approach of discarding donors after a reasonable number of treatment failures (20 to 50) should continue.

Cryopreservation

Relationship between stimulated hyperactivated motility of human spermatozoa and pregnancy rate in donor insemination: a preliminary report.

The proportion of spermatozoa exhibiting the vigorous motility behaviour termed 'hyperactivation' (HA) has been shown to be increased following removal of seminal plasma and stimulation with chemical agents such as pentoxifylline. The aim of this study was to examine the relationship between the proportion of HA in cryopreserved semen samples from sperm donors and the corresponding pregnancy rates achieved by donor insemination. Cryopreserved samples from 20 men were incubated in the presence or absence of 3 mM pentoxifylline for 1 h and the %HA determined in each sample. The relationship between pregnancy rate, the proportion of HA spermatozoa in control and pentoxifylline-treated groups and the change in %HA following pentoxifylline treatment (delta HA) as well as the mean semen characteristics for each donor [sperm count, motility (%), motility index, normal morphology (%), post-thaw motility (%) and post-thaw motility index] were examined by logistic regression of the occurrence of clinical pregnancy with each insemination. Both delta HA and mean post-thaw motility index were significantly related to pregnancy rates and together accounted for 64% of the observed variation in pregnancy rates.

Cryopreservation

Silicon-substrate microelectrode arrays for parallel recording of neural activity in peripheral and cranial nerves.

A new process for the fabrication of regeneration microelectrode arrays for peripheral and cranial nerve applications is presented. This type of array is implanted between the severed ends of nerves, the axons of which regenerate through via holes in the silicon and are thereafter held fixed with respect to the microelectrodes. The process described is designed for compatibility with industry-standard CMOS or BiCMOS processes (it does not involve high-temperature process steps nor heavily-doped etch-stop layers), and provides a thin membrane for the via holes, surrounded by a thick silicon supporting rim. Many basic questions remain regarding the optimum via hole and microelectrode geometries in terms of both biological and electrical performance of the implants, and therefore passive versions were fabricated as tools for addressing these issues in on-going work. Versions of the devices were implanted in the rat peroneal nerve and in the frog auditory nerve. In both cases, regeneration was verified histologically and it was observed that the regenerated nerves had reorganized into microfascicles containing both myelinated and unmyelinated axons and corresponding to the grid pattern of the via holes. These microelectrode arrays were shown to allow the recording of action potential signals in both the peripheral and cranial nerve setting, from several microelectrodes in parallel.

Action Potentials

A thermal signal generator probe for the study of neural thermal transduction.

The study of thermal transduction in neural tissues has been impeded by the lack of instrumentation able to generate complex, focal temperature variations. Specifically, we are interested in the study of neural thermal transduction within the cornea, with its homogeneous thermal conductivity and avascularity. We present a thermal signal generator probe that is capable of producing arbitrarily shaped bipolar (heating or cooling) thermal swings in a small volume of corneal tissue with which it is in contact. Heating and cooling of the probe tip are achieved by means of a Peltier effect thermoelectric device. The probe temperature, measured directly at the tip, is controlled using closed-loop control circuitry and waveform generation software on a host computer. Response characteristics of thermally sensitive C-fibers were investigated in an in vitro preparation of the rabbit cornea.

Action Potentials

A case of successful use of reproductive technology for a couple with subfertility due to retrograde ejaculation, where artificial insemination had failed.

A case history of a couple where the infertility was due to retrograde ejaculation is presented; when conventional treatment with artificial insemination using sperm isolated from postejaculatory urine failed, IVF and GIFT technology was applied. This resulted in a pregnancy which unfortunately failed at 3 months, unrelated to the method of conception. This case report highlights the possible use of IVF/GIFT for yet another type of male subfertility.

Adult

The use of gamete intra-fallopian transfer with donor spermatozoa after failed donor insemination.

The objective of this study was to assess the efficacy of gamete intra-Fallopian transfer (GIFT) in couples who had failed to conceive by donor insemination. The study was designed as a retrospective analysis of couples who entered the GIFT programme after 12 failed cycles of donor insemination. It took place in a comprehensive reproductive clinic with large donor insemination and in-vitro fertilization/GIFT programmes. A total of 197 patients received a total of 350 treatments from 1985 until 1992. Couples entered the GIFT programme with the routine stimulation and monitoring. The only difference was that frozen spermatozoa were used for the insemination. The main outcome measure was pregnancy, defined as a positive beta-human chorionic gonadotrophin (> 30 IU/l) at 16 days after replacement of gametes. The overall pregnancy rate achieved was 31% per cycle. Life table analysis showed a cumulative pregnancy rate of 75.4 +/- 5.7% after four cycles and 96.0 +/- 2.7% after eight cycles. It was concluded that the use of GIFT with donor spermatozoa is a highly effective treatment and should be offered to all couples who fail to conceive with donor insemination.

Cryopreservation

Survey of general practitioner instructions to oral contraceptive users.

The study indicates that this group of metropolitan general practitioners is generally well informed about the increased risk that missed pills, malabsorption or antibiotics causes. Nevertheless, there is considerable confusion about the effect on contraception efficacy and few respondents use the Family Planning Movement's '7 day rule'. The authors would like to recommend that the pharmaceutical companies and family planners put more effort into advertising this simple set of instructions for women who miss pills, have diarrhoea or vomiting or use antibiotics. There is also merit in inviting patients who have concerns to contact their doctor, practice nurse or pharmacist for advice. There are occasions when the '7 day rule' may not be necessary, such as transient vomiting or diarrhoea, or both, of less than 12 hours when the patient can be advised to take an extra active tablet from a spare pack and continue with the rest of the pack as usual. Consultations involving prescriptions for oral contraception represent an excellent opportunity for health promotion and preventive medicine.

Adult

The likelihood of pregnancy with IVF and GIFT in Australia and New Zealand.

OBJECTIVE: To determine the likelihood of pregnancy for couples entering the New Reproductive Technology (NRT) programs in Australia and New Zealand, by combining the data from nearly all the practising units. DESIGN: All units practising in-vitro fertilisation (IVF) and/or gamete intrafallopian transfer (GIFT) were contacted and asked to provide data on patients treated and pregnancy rates. These figures were then combined to produce life tables to determine the likelihood of pregnancy with repeated attempts. SETTING: IVF/GIFT units in five States of Australia, the Australian Capital Territory and New Zealand. Eighteen of the 22 units provided data to be analysed. PATIENTS: Data were available for analysis on 18,089 cycles of IVF resulting in 3034 clinical pregnancies, and 6308 cycles of GIFT resulting in 1724 clinical pregnancies. MAIN OUTCOME MEASURES: This was either "clinical pregnancy" (the presence of products of conception on ultrasound examination), or "viable pregnancy" (a pregnancy developing to at least 20 weeks of gestation). RESULTS: After four attempts at IVF, half the couples achieved a pregnancy, whereas four attempts at GIFT resulted in two-thirds of the couples achieving pregnancy. CONCLUSION: Both IVF and GIFT are effective and successful options for infertile or subfertile couples. New Reproductive Technology should be readily available in every advanced clinic dealing with subfertile couples in the 1990s.

Australia

Age and follicular phase estradiol are better predictors of pregnancy outcome than luteinizing hormone in menotropin ovulation induction for anovulatory polycystic ovarian syndrome.

OBJECTIVE: To examine the relationship of baseline and preovulatory serum E2, P, and LH levels and age with pregnancy outcome in polycystic ovarian syndrome (PCOS) patients undergoing hMG ovulation induction. DESIGN: Retrospective analysis of all available data over 2 years. SETTING: Tertiary referral ovulation induction clinic. SUBJECTS: Forty-four anovulatory PCOS patients with 25 ovulatory nonconception and 50 conception cycles after hMG ovulation induction. MAIN OUTCOME MEASURES: Ovulation (midluteal serum P > 25 nmol/L [7.86 ng/mL]); pregnancy (serum beta-hCG > 30 mIU/mL 16 days after ovulating injection); pregnancy outcome: pregnancy termination < 20 weeks' or > or = 20 weeks' amenorrhea. RESULTS: Of the endocrine parameters considered, none was significantly different in nonconceptive and conceptive ovulatory cycles. Miscarriage was associated with low basal serum E2: median value for pregnancies ending < 20 weeks, 105 pmol/L (28.6 pg/mL) and for > or = 20 weeks 150 pmol/L (40.9 pg/mL). It was also significantly associated with age. For patients > 29.5 years of age, (29.5 years, population mean age) a baseline E2 < or = 140 pmol/L (38.2 pg/mL) had sensitivity 92%, specificity 54%, positive predictive value 65%, and negative predictive value 87% for the prediction of miscarriage. The nature of the previous cycle, the day of the cycle on which therapy commenced, and a past history of miscarriage were not related either to pregnancy outcome or to basal serum E2.

Abortion, Spontaneous

A controlled study of the psycho-social development of children conceived following insemination with donor semen.

Although donor insemination has been used to produce pregnancies for many years, there has been little information on how children conceived in this unusual manner develop psycho-socially. We have therefore carried out a controlled quantitative assessment comparing children who were conceived by donor insemination to adoptees and naturally conceived children who were matched for age and sex. We conclude that the psycho-social development of donor insemination children was no different from the two control groups.

Adoption

A prospective randomized study comparing the clinical effects of a norethisterone and a levonorgestrel containing low dose oestrogen oral contraceptive pills.

The two types of low dose oral contraceptives one containing levonorgestrel the other containing norethisterone have been compared in a randomized prospective study. We have found that cycle control was much poorer with the norethisterone pill and would therefore recommend that if the norethisterone-containing pill needs to be prescribed then either the 1 mg or the 'synphasic' preparation should be considered.

Adolescent