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Induction of follicular development by direct single injection of vascular endothelial growth factor gene fragments into the ovary of miniature gilts.

Perifollicular angiogenesis is closely associated with ovarian follicular development. To investigate whether additional induction of perifollicular angiogenesis would support subsequent follicular development, we directly injected vascular endothelial growth factor (VEGF) gene fragments into the ovaries of miniature gilts, followed by gonadotroph treatment to stimulate follicle growth. In addition, to confirm extraexpression of the VEGF gene after injection, we assessed the expression of two isoforms of VEGF (VEGF 120 and VEGF 164) in granulosa cells and expression of fms-like tyrosine kinase (Flt-1), expression of fetal liver kinase (Flk-1), and density of capillary networks in theca cells. Direct injection of VEGF gene fragments into the ovaries was performed 7 days before eCG treatment. The ovaries in miniature gilts were removed 72 h after eCG treatment for histological examination. Granulosa cells and thecal tissues in the antral follicles (diameter, >4 mm) were collected to detect the mRNA expression of VEGF isoforms in the granulosa cells and of Flt-1 and Flk-1 in the thecal tissues by semiquantitative reverse transcription-polymerase chain reaction. The VEGF levels were measured in the follicular fluid by enzyme immunoassay. Injection of VEGF gene fragments increased the level of mRNA expression of VEGF 120 and 164 isoforms in the granulosa cells and VEGF protein contents in the follicular fluid. The number of preovulatory follicles and the capillary density in the theca interna increased significantly in the ovaries injected with VEGF gene fragments compared with those treated with eCG alone. The Flt-1, but not the Flk-1, mRNA expression show a tendency toward increasing in the thecal tissues of antral follicles in the ovaries injected with VEGF gene fragments. These results demonstrate that Flt-1 may be predominantly involved in the regulation of the capillary network in the theca interna during follicular development. Our data suggest that the regulation of perifollicular angiogenesis during follicular development is a very important factor in the development of ovulatory follicles. Our findings may offer an innovative technique for enhanced induction of follicular development in the ovary through gene and hormonal treatment, which may lead to prevention of infertility caused by ovarian dysfunction.

Animals↗

Echocardiographic monitoring during induction of general anesthesia with a miniaturized esophageal probe.

UNLABELLED: Standard transesophageal echocardiography (TEE) does not allow cardiac monitoring during the induction of anesthesia because standard probes would limit the oropharyngeal space and impair mask ventilation and tracheal intubation. We hypothesized that a prototype, miniaturized TEE probe could be safely introduced transnasally in awake patients and that mask ventilation and orotracheal intubation could be performed while continuously monitoring left ventricular (LV) function during the induction of anesthesia. Forty-five patients were studied prospectively. The transnasal TEE probe was introduced through one of the nares and advanced until a transverse plane image of the LV at the level of the papillary muscles was seen. Anesthesia was induced, and the patients were ventilated with a mask that had previously been threaded over the TEE probe via a central perforation. Probe insertion was successful in 12 patients under local anesthesia alone and in an additional 31 patients with a combination of local anesthesia and mild sedation. In two cases, probe placement was unsuccessful. Overall, hemodynamic variables did not change significantly during insertion. No case of significant mucosal bleeding was seen. In one patient, regurgitation of gastric contents occurred without affecting the perioperative outcome. The two-dimensional echocardiogram image quality of the LV during the induction of anesthesia was good or acceptable in 95% of patients. We conclude that transnasal TEE can effectively be used for cardiac monitoring during the induction of general anesthesia. IMPLICATIONS: This study demonstrates that it is feasible and generally safe to introduce a miniaturized transesophageal echocardiography probe transnasally in awake cardiac risk patients to monitor cardiac performance during the induction of general anesthesia.

Aged↗

Miniature postsynaptic currents depend on Ca2+ released from internal stores via PLC/IP3 pathway.

Miniature postsynaptic currents (mPSCs) were examined on autaptic innervation of single rat retinal ganglion cells in low density cultures. Removal of Ca2+ from bath solution or blocking of Ca2+ channels by Cd2+ had no detectable effect on mPSC frequency or amplitude. Thapsigargin, an agent for mobilization of Ca2+ from internal stores, increased mPSC frequency 3-5-fold in control, Ca2+-free or Cd2+-containing solutions. The inositol 1,4,5-triphosphate (IP3) receptor antago- nist, heparin; the phospholipase C (PLC) inhibitor, U73122; and caffeine abolished mPSC or decreased mPSCs frequency. Calcium imaging showed that cytosolic Ca2+ was increased by thapsigargin and decreased by caffeine. These data demonstrate that internal store-released Ca2+ regulated by the PLC/IP3/IP3-receptor pathway has critical contribution to generation and control of miniature release in retinal ganglion cells.

Animals↗

Miniature circulatory support power transformer.

Direct power delivery to intracorporeal circulatory support devices risks infection. Electrical transformers spanning the integument (skin or mucosa) have long been attractive means of circumventing this risk. Yet all existing skin surface transformers leak substantial magnetic flux, with an intrinsic risk of battery draining cross-coupling by any nearby conductor, requiring strict control of surroundings. In a progression of designs, we have used the walls of a small pouch, surgically formed from ileum, rather than skin, as a barrier. Previously, we reported a torroidal design with complete magnetic circuits, having zero flux leakage and unmatched heat dissipation in a 2 week canine trial. This work was in three parts: (1) Devices were placed in eight dogs for 9-12 weeks to document performance of the existing design. (2) Based on these results, the device was further miniaturized. Iterative computational modeling was applied to material selection and design. Simultaneously, practical techniques for surgically constructing tiny accommodating ileal pouches were explored in cadavers, by using polymer "mock-ups" of potential designs. (3) The final design was tested by acute implantation in a live 52 kg goat and by in vitro testing of electrical transfer function. IN VIVO TRIALS: The earlier design demonstrated 97.2% AC/AC and 84.2% DC/DC efficiency with contiguous tissue warming of 0.1 degrees C. DESIGN AND PERFORMANCE: A transformer with a Square Permalloy torroidal core (6 cm3, 23 grams, both coils eight turns) was designed, by using human cadaver trials to optimize geometry. Input and output were 6 V, 12W at 9.2 kHz with AC-AC efficiency 96%. OPERATIVE PLACEMENT TRIAL: The primary coil easily fit into an isolated, vascularized, but otherwise disconnected "blind" ileal pouch < 2 cm long with a slender extension to a miniature stoma. With secondary turns, the pouch and transformer fit easily into the abdominal wall. This tiny system seems compatible with near "forgettable" power delivery allowing unprecedented freedom of environment and activity in circulatory support dependent people.

Animals↗

Miniature plates and screws in acute complex hand injury.

Thirty-six patients with 72 metacarpal and phalangeal fractures with associated injuries to the neurovascular bundle, tendon, soft tissue, or bone following acute complex hand injury were treated with miniature plates and screws and reconstruction of the disrupted and missing structures. The results were judged according to the criteria of the American Society for Surgery of the Hand. The overall results were good in 46.3%, fair in 32.2%, and poor in 21.5%. Although traditional wiring techniques are certainly useful in complex hand injuries, internal osteosynthesis with miniature plates and screws has definite indications in cases requiring stable and rigid internal fixation.

Adult↗

Transplantation in miniature swine. I. Fixation of the major histocompatibility complex.

Three strains of miniature swine, each homozygous for a different allele of the major histocompatibility locus (MHC), have been developed by a selective breeding scheme based on tissue typing of the offspring of each generation. Prior to breeding, the original parents were reciprocally immunized by skin grafts and lymphocyte injections to produce lymphocytotoxic antisera. These antisera were then used to assess the MHC genotype of the offspring by an analysis based on selective absorption of cytotoxicity. Offspring inheriting the same serologically determined genotype were then bred sequentially. Subsequent mixed lymphocyte cultures showed a pattern of reactivity consistent with the serological genotyping, further confirming the homology between the MHC of these miniature swine and those of man and mouse. In addition to their usefulness as a model for large animal surgical transplantation, these animals provide an abundant homozygous source of histocompatibility antigens and of antihistocompatibility antisera for use in chemical characterization of products of the MHC.

Animals↗

Biocompatibility of the Ex-PRESS miniature glaucoma drainage implant.

PURPOSE: Based on lessons learned from earlier attempts, a novel miniature glaucoma implant, Ex-PRESS, was developed in 1998. The current study summarizes the histopathologic evaluation of this device implanted in the eyes of rabbits. METHODS: The device was implanted into the anterior chamber at the corneoscleral junction in 1 eye each of 8 white New Zealand rabbits, while the contralateral eye served as control. Three and 6 months after implantation, the rabbits were killed and their eyes were enucleated and processed histologically, leaving the device in situ when sectioning. RESULTS: Three and 6 months postoperatively, the local tissue reaction typically consisted of an enveloping, thin, mature, fibrotic capsule (thickness <0.04 mm), devoid of inflammatory cells. This capsule surrounded approximately 25% of the implant surface area present in the sections. The lumina of the devices were devoid of inflammatory exudates or other obstructions in all specimens examined, suggesting free flow of fluid. CONCLUSIONS: The implantation of the Ex-PRESS miniature glaucoma shunt resulted in minimal capsular reaction. Considering the high reactivity of the rabbit eye, it is possible that this implant will induce a smaller cellular inflammatory reaction in the human eye.

Animals↗

Total hip arthroplasty using the miniature Anatomic Medullary Locking stem.

We report the outcome of a prospective consecutive series of 52 primary total hip arthroplasties using the miniature porous-coated Anatomic Medullary Locking stem in patients with small anatomic proportions because of hip dysplasia or juvenile chronic arthritis. The mean age of the patients at the time of surgery was 28.7 years (range 14-56 years). The average body weight and height of the patients were 51.8 kg (range 38.5-78.3 kg) and 157.1 cm (range 142.2-183 cm), respectively. The stem was cementless in 40 hips and cemented in 12 hips because of poor bone stock. A cementless acetabular cup with screw was used in all hips. The average followup was 7.1 years (range, 3-15.6 years). The Harris hip scores improved from an average of 31.2 points (range, 3.1-68.8 points)preoperatively to 82.8 points (range, 61.1-96.6 points) at latest followup. Three of 12 (25%) cemented and two of 40 (5%) cementless stem were revised. Four of seven 42-44-mm cups were revised. The miniature Anatomic Medullary Locking cementless femoral stem provides a satisfactory outcome in patients with small anatomic proportions. However, wear and osteolysis with the use of a small cementless polyethylene liner remain challenges.

Adult↗

Comparison of trabeculectomy with Ex-PRESS miniature glaucoma device implanted under scleral flap.

PURPOSE: To evaluate the Ex-PRESS miniature implant (Model R 50) placed under partial-thickness scleral flap compared with standard trabeculectomy. METHODS: In this retrospective comparative series of 100 eyes, we compared 50 eyes in 49 patients treated with the Ex-PRESS miniature glaucoma implant under a scleral flap with 50 matched control eyes in 47 patients treated with trabeculectomy. Success was defined as intraocular pressure (IOP) > or =5 mm Hg and < or =21 mm Hg, with or without glaucoma medications, without further glaucoma surgery or removal of implant. Early postoperative hypotony was defined as IOP <5 mm Hg during the first postoperative week. RESULTS: The average follow-up was 10.8 months (range 3.5 to 18) for the Ex-PRESS group and 11.2 months (range 3 to 15) for the trabeculectomy group. Although the mean IOP was significantly higher in the early postoperative period in the Ex-PRESS group compared with the trabeculectomy group, the reduction of IOP was similar in both groups after 3 months. The number of postoperative glaucoma medications in both groups was not significantly different. Kaplan-Meier survival curve analysis showed no significant difference in success between the 2 groups (P=0.594). Early postoperative hypotony and choroidal effusion were significantly more frequent after trabeculectomy compared with Ex-PRESS implant under scleral flap (P<0.001). CONCLUSIONS: The Ex-PRESS implant under a scleral flap had similar IOP-lowering efficacy with a lower rate of early hypotony compared with trabeculectomy.

Aged↗

Propagation of cold atoms along a miniature magnetic guide

A cloud of laser-cooled 85Rb atoms is coupled through a magnetic funnel into a miniature waveguide formed by four current-carrying wires embedded in a silica fiber. The atom cloud has a approximately 100 &mgr;m radius within the fiber and propagates over cm distances. We study the coupling, propagation, and transverse distribution of atoms in the fiber, and find good agreement with theory. This prototype demonstrates the feasibility of miniature guides as a tool in the new field of integrated atom optics, leading to single-mode propagation of de Broglie waves and the possible preparation of 1D atom clouds.

Journal Article↗

Applications of SPICE for modeling miniaturized biomedical sensor systems.

This paper proposes a model for a miniaturized signal conditioning system for biopotential and ion-selective electrode arrays. The system consists of three main components: sensors, interconnections, and signal conditioning chip. The model for this system is based on SPICE. Transmission-line based equivalent circuits are used to represent the sensors, lumped resistance-capacitance circuits describe the interconnections, and a model for the signal conditioning chip is extracted from its layout. A system for measurements of biopotentials and ionic activities can be miniaturized and optimized for cardiovascular applications based on the development of an integrated SPICE system model of its electrochemical, interconnection, and electronic components.

Electric Impedance↗

Miniature acoustic guidance system for endotracheal tubes.

Ensuring that the distal end of an endotracheal tube (ETT) is properly located within the trachea, and that the tube is not obstructed by mucus deposition, is a major clinical concern in patients that require mechanical ventilation. A novel acoustic system was developed to allow for the continuous monitoring of ETT position and patency. A miniature sound source and two sensing microphones are placed in-line between the ventilator hose and the proximal end of the ETT. Reflections of an acoustic pulse emitted into the ETT lumen and the airways are digitally analyzed to estimate the location and degree of lumen obstruction, as well as the position of the distal end of the tube in the airway. The system was evaluated through in vitro studies and in a rabbit model. The system noninvasively estimated tube position in vivo to within roughly 4.5 mm, and differentiated between proper tracheal, and erroneous bronchial or esophageal intubation in all cases. In addition, the system estimated the area and location of lumen obstructions in vitro to within 14% and 3.5 mm, respectively. These findings indicate that this miniature technology could improve the quality of care provided to the ventilated adult and infant.

Acoustics↗

Distortion cancellation performance of miniature delay filters for feed-forward linear power amplifiers.

The technique of feed-forward amplitude control has been widely used in the linearization of power amplifiers for wireless communication systems. In this technique, an error signal due to third order intermodulation distortion (IMD) is extracted, amplified, and used to correct the delayed main line distorted signal. For example, a miniature prototype base station for the Global System for Mobile Communications/Code Division Multiple Access (GSM/CDMA) cellular system uses feed-forward amplifiers with bulky and expensive coaxial cables, about 20 feet in length, to provide about 25 ns of delay. This paper shows alternate space-saving approaches of achieving these delays using three different types of delay filters: electromagnetic interdigital/lumped (<2.5"), ceramic (<1.8"), and ladder-type surface acoustic wave (SAW) (0.15"). The delay lines introduce phase and amplitude imbalance and delay mismatch in the linearization loop due to fabrication tolerances. These adversely affect the IMD cancellation. Using an RF system simulation tool, this paper critically compares the IMD cancellation performance achieved using the three technologies. Simulation results show that the optimization of delay mismatch can achieve the desired cancellation more easily than other parameters. It is shown that, if the critical system parameter (phase deviation from linearity), is maintained at <2.5 degrees peak-to-peak over a 20 MHz bandwidth in the frequency range 855 MHz to 875 MHz, one can achieve 25 dB of IMD cancellation performance. This paper concludes with the suggestion of a set of realistic specifications for a miniature delay filter for the low power loop of the feed-forward amplifier.

Amplifiers, Electronic↗

Enhancement of phagocytosis and bactericidal activity of neutrophils in miniature pigs by dihydroheptaprenol, a synthetic polyprenol derivative.

Dihydroheptaprenol (DHP), a synthetic polyprenol derivative, markedly stimulated the generation of peripheral blood neutrophils after intramuscular injection in miniature pigs. The generated neutrophils exhibited enhanced phagocytic activity against latex particles and also enhanced killing activity against Escherichia coli. The effective dose in miniature pigs (1.4 mg/kg) was markedly less than that required in mice (100 mg/kg). These results indicate that DHP induces resistance to some bacterial infections in pigs, suggesting the applicability of DHP for humans.

Animals↗

An evaluation of the Universal PAC and Oxford Miniature Vaporizers for paediatric field anaesthesia.

A laboratory study has demonstrated that the Universal PAC and Oxford Miniature Vaporizers can be used for paediatric anaesthesia in drawover mode at varying ambient temperatures. Changes in tidal volume have minimal effect on the delivered concentration of halothane from either vaporizer but varying ambient temperature significantly affects the output of the Oxford Miniature Vaporizer. The Oxford performs well in continuous flow mode, which is of particular use for T-piece anaesthesia, whereas the Universal PAC does not perform adequately in this way.

Anesthesia, General↗

Blood groups and serum protein polymorphisms in the Pitman-Moore and Ohmini strains of miniature pigs.

The variations of blood groups and biochemical polymorphisms in the populations of the two miniature pig strains reared in Japan were investigated in this report. The variations in eight blood group systems were investigated by using serological techniques, and five serum protein systems by using starch gel electrophoresis. The Pitman-Moore strain showed no variations in K, O, Tf, Cp and Am systems, but showed plymorphisms in A,E,F,G,H,L,Pa and Hpx systems. The Ohmini strain showd no or little variations in E,F,G,Tf,Pa and Cp systems, but showed polymorphisms in A,H,K,L,O,Hpx and Am systems. From the results of investigation of genetic similarities among nine pig populations including various breeds, it was made clear that the two miniature pig strains were very different genetically, and the Pitman-Moore strain was genetically closer to European large pig breeds than to East Asian native pigs, while the Ohmini strain was close to Thai and Philippine natives.

Animals↗

Developmental assessment: 18 months to 4 1/2 years. The miniature toys test.

A modified version of the miniature toys test, originally designed by Sheridan (1975), has been standardized on a sample of 425 children in the age range 18 months to 4 1/2 years. The distinctive features are the assessment of symbolic play and the understanding of prepositions when used in verbal instructions. The acquisition of expressive verbal labels for miniature household objects and transport, and comprehension of questions relating to them have been explored. Responses in some of these areas are not always clear-cut or are ambiguous. The test will be more suited to the needs of the developmental paediatrician for assessment of children with developmental delay, than for doctors of primary care and health visitors in screening apparently healthy children.

Child, Preschool↗

Absence of hyaline cartilage in the tongue of 'Caspian miniature horse'.

Histology of the tongue, including apex, root and body, in four adult Caspian miniature horses was examined. Serial sections with 6 mum thickness were stained with haematoxylin-eosin and Masson trichrome and studied under light microscope. The tongue was covered by stratified squamous epithelium. It was thick and keratinized bearing numerous lingual papillae on the dorsum, mostly filiform with a very fine keratinized thread projecting above the surface and bending backward. The fungiform papillae were sparsely scattered among the filiform papillae and covered with keratinized squamous epithelium. Few taste buds were detected on it. The two very large vallate papillae were detected on the dorsum, just rostral to the root, which were covered with stratified squamous epithelium with relatively high amounts of taste buds in the epithelium of the surrounding grooves. The foliate papillae were present near the palatoglossal arch and had a few taste buds. The epithelium covering the ventral surface of the tongue was thin and keratinized. The lingual muscle core consisted of transverse, longitudinal and perpendicular bundles of skeletal muscle fibres. Clusters of minor salivary glands were present between the muscle fibres and lamia propria. Most of the lingual glands were mucous and most of the gustatory ones were serous type. The mid-dorsal special structure of the tongue (dorsal lingual cartilage) contained sparse skeletal muscle fibres and was rich in white adipose tissue. Hyaline cartilage, routinely observed in this structure in the horses, was not detected in Caspian miniature horse.

Animals↗