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Biomedical subjects

J H Miller

Publications and source records attributed to J H Miller.

At least 91 records · Page 5Linked to original sources

Omental transfer to the brain: an experimental study in hydrocephalic rabbits.

Hydrocephalus is a common and potentially lethal condition in children that results from an imbalance between absorption and production of cerebral spinal fluid (CSF). Silastic shunts are inserted to drain excess CSF, but they are prone to a number of problems, and at times may be unreliable and ineffective. This study examines the physiological basis of a pedicled omental transfer to the brain as a functional conduit for CSF in an experimentally induced hydrocephalic rabbit model. The ability of the omentum to transport CSF from the subarachnoid space was tested using radioactive tracer substances: radio-iodinated serum albumin (125I-RISA), chromium 51-ethylenediaminetetraacetate (51Cr-EDTA), and technetium 99m (99mTc) glucoheptonate. Immediate ability of exteriorized omentum to transport artificial CSF, as well as transposed omental transport of subarachnoid CSF at 1 month, were examined. Nuclear scan measurements were correlated with clinical observation and a double-blind histological analysis with trichrome and hematoxylin-eosin stain. Exteriorized omentum rapidly absorbed 99mTc glucoheptonate-labeled artificial CSF, with a rapid appearance in the systemic circulatory and urinary systems. Transposed omentum to the brain in animals with artificially created hydrocephalus showed evidence of CSF-labeled 125I-RISA and 51Cr-EDTA absorption in those animals demonstrating histologically viable omentum.

Animals↗

Radiation effects on the native structure of proteins: fragmentation without dissociation.

Several proteins (avidin, carboxypeptidase B, glucose-6-phosphate dehydrogenase, glutamate dehydrogenase, maltase, and peroxidase) composed of one to six subunits were irradiated in the frozen state. Each irradiated protein was examined by size-exclusion chromatography (SEC) and by denaturing gel electrophoresis (SDS-PAGE). All these proteins eluted from SEC as a single peak even though SDS-PAGE showed cleavage of the polypeptide backbone of the monomers. Thus, fragmentation of the subunits did not result in dissociation of the oligomeric structure.

Carboxypeptidase B↗

Interlaboratory study of the analysis of benzylpenicillin by liquid chromatography.

A liquid chromatography method for analysis of benzylpenicillin was examined in a collaborative study involving seven laboratories. The method comprised an isocratic part, which is used in the assay. The isocratic part corresponds to the assay method for benzylpenicillin used by a manufacturer. When the isocratic part is combined with gradient elution, the method is suitable for purity control. Five samples of benzylpenicillin (sodium and potassium salts) were analysed. The main component and the impurities were determined. An analysis of variance proved the absence of consistent laboratory bias. The laboratory-sample interaction was not significant. Estimates for the repeatability and reproducibility of the method, expressed as standard deviations (S.D.) of the result of the determination of benzylpenicillin, were calculated to be 0.71 and 0.80, respectively.

Analysis of Variance↗

Manual vs robotically assisted laparoscopic surgery in the performance of basic manipulation and suturing tasks.

OBJECTIVE: To compare the surgical performance of manual and robotically assisted laparoscopic instruments on basic maneuvers and intracorporeal suturing in inanimate models. DESIGN: A set of laparoscopic tasks was used to evaluate basic endoscopic movements and intracorporeal suturing: positioning a cylinder on a Peg-Board, dropping beads into receptacles, running a 25-cm rope, and capping a hypodermic needle. Intracorporeal knot tying and running a suture through predetermined points were evaluated separately. The sutures used for these tasks were 2-0 and 4-0 silk and 6-0 and 7-0 polypropylene. PARTICIPANTS: Twenty surgeons completed the set of laparoscopic tasks manually and then with a robotically assisted system. None had used the robotic system before. MAIN OUTCOME MEASURES: Time required to complete the tasks and the precision in performing them. RESULTS: The robotic system accurately reproduced the movements of the surgeons and filtered their hand tremors efficiently. In the basic tasks, operative times were significantly longer for the robotic system (P<.001). In the suturing tasks, operative times were longer with the use of the robotic system for sutures sizes 2-0 and 4-0 (P<.001). However, time differences were not significant for suture sizes 6-0 and 7-0 (P> or =.07). Precision measurements were similar for all tasks using the manual instruments and the robotically assisted system. No significant differences were found between the performance of advanced laparoscopic surgeons and laparoscopic fellows. CONCLUSIONS: Laparoscopic maneuvering and suturing is faster and just as precise when performed manually as when performed with the prototype robotic system. These differences in speed are inversely proportional to the size of the suture. Future generations of the robotic system may eliminate these differences.

Equipment Design↗

MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily.

The DNA glycosylase MutY, which is a member of the Helix-hairpin-Helix (HhH) DNA glycosylase superfamily, excises adenine from mispairs with 8-oxoguanine and guanine. High-resolution crystal structures of the MutY catalytic core (cMutY), the complex with bound adenine, and designed mutants reveal the basis for adenine specificity and glycosyl bond cleavage chemistry. The two cMutY helical domains form a positively-charged groove with the adenine-specific pocket at their interface. The Watson-Crick hydrogen bond partners of the bound adenine are substituted by protein atoms, confirming a nucleotide flipping mechanism, and supporting a specific DNA binding orientation by MutY and structurally related DNA glycosylases.

Adenine↗

Long-term results of femorotibial bypass with vein or polytetrafluoroethylene.

BACKGROUND: This was a retrospective review of the long-term results of femorotibial bypass using autologous vein and polytetrafluoroethylene (PTFE) over 24 years. METHODS: Some 518 patients who underwent 635 femorotibial bypass grafts were studied. Outcome measures analysed included primary and secondary graft patency, limb salvage rates and death. RESULTS: Overall primary and secondary graft patencies were 62 and 67 per cent respectively at 12 months, and 44 and 48 per cent at 24 months. For vein grafts, the primary and secondary patencies were 63 and 66 per cent at 12 months, and 54 and 56 per cent at 24 months. For PTFE grafts, the primary and secondary patencies were 48 and 54 per cent at 12 months, and 31 and 37 per cent at 24 months. Limb salvage and patient survival rates were 81 and 84 per cent at 12 months, and 73 and 74 per cent at 24 months. Primary and secondary graft patencies for vein were significantly better than for PTFE (P = 0.0001). There was no difference in patency between reversed and in situ grafts. CONCLUSION: Femorotibial bypass can produce excellent long-term results. Vein remains the conduit of choice but in the absence of vein acceptable results can be achieved with PTFE.

Adult↗

Robotically assisted laparoscopic tubal anastomosis in a porcine model: a pilot study.

As with standard microsurgical procedures performed at laparotomy, laparoscopic tubal anastomosis requires great dexterity. Handling fine suture materials under magnification to anastomose tubal segments with lumens less than 3 mm in diameter while working with your hands at a distance from the tissue makes these fine movements even more difficult. This is exacerbated by the tremor induced by the fatigue caused by a prolonged laparoscopic procedure and the need for precise control. We conducted a pilot study to evaluate the feasibility of performing laparoscopic tubal anastomosis with robotic assistance in a live porcine model. Two anastomoses were performed on one uterine horn via each of the following techniques: laparoscopy, laparoscopy with robotic assistance, and open microsurgery. Immediate necropsy demonstrated all the anastomoses to be patent. There were no intraoperative complications. Laparoscopic tubal anastomosis was associated with surgeon fatigue and neck, shoulder, and back pain. The surgeons were more comfortable performing the procedure with robotic assistance. The device functioned well and without incident. This acute animal study suggests that robotic assistance in laparoscopic tubal anastomoses is safe and feasible. It enhances surgeons' dexterity and precision while reducing fatigue. It is promising for future use in chronic experimental studies.

Anastomosis, Surgical↗

An emergency multisystem screw removal module.

There are several practical indications for the removal of screws and plates from the reconstructive patient. For the craniomaxillofacial surgeon there exists a wide array of screw and plating systems available. As patients relocate, it is unlikely that individual hospitals have the full collection of rigid fixation systems in their inventory. Therefore, a universal screw removal system was designed to facilitate the elective and emergency removal of all existing craniomaxillofacial fixation hardware. This system is a self-contained module containing a single handle and 12 interchangeable screwdriver blades. The universal screw and plate removal system has been used successfully in several patients--children as well as adults--in whom hardware was removed.

Bone Screws↗

Examination of the role of DNA polymerase proofreading in the mutator effect of miscoding tRNAs.

We previously described Escherichia coli mutator tRNAs that insert glycine in place of aspartic acid and postulated that the elevated mutation rate results from generating a mutator polymerase. We suggested that the proofreading subunit of polymerase III, epsilon, is a likely target for the aspartic acid-to-glycine change that leads to a lowered fidelity of replication, since the altered epsilon subunits resulting from this substitution (approximately 1% of the time) are sufficient to create a mutator effect, based on several observations of mutD alleles. In the present work, we extended the study of specific mutD alleles and constructed 16 altered mutD genes by replacing each aspartic acid codon, in series, with a glycine codon in the dnaQ gene that encodes epsilon. We show that three of these genes confer a strong mutator effect. We have also looked for new mutator tRNAs and have found one: a glycine tRNA that inserts glycine at histidine codons. We then replaced each of the seven histidine codons in the mutD gene with glycine codons and found that in two cases, a strong mutator phenotype results. These findings are consistent with the epsilon subunit playing a major role in the mutator effect of misreading tRNAs.

Amino Acid Sequence↗

Fluoride distribution in sound and carious root tissues of human teeth.

Proton probe analysis has been used to provide for the first time quantitative F concentration data in carious root tissues from subjects consuming water containing 1 ppm F. In small lesions at the neck of the tooth with minimal tissue loss the F concentration was significantly higher at the outer lesion edge than at the outer edge of adjacent sound root tissue. In one sample with high F values the lesion edge had 19,000 ppm F and the adjacent sound root surface 5,400 ppm F microg F/g apatite). In large lesions with extensive cavitation F was again concentrated in the outer edge of the lesion and was significantly higher (1,800-4,100 ppm) than in adjacent sound inner dentine (190-290 ppm). Fluoride concentrations varied markedly along the outer edge of both normal and carious root tissues. Fluoride increase at the lesion edge is not an effect of tissue shrinkage but probably a result of remineralisation events during caries. This additional F may be expected to increase tissue resistance to further acid attacks.

Acids↗

Extraskeletal uptake of technetium-99m-MDP in sites of heparin administration.

A 19-yr-old woman with juvenile diabetes and protein C deficiency was referred for a bone scan to rule out osteomyelitis of the right tibia. The bone scan did not reveal evidence of osteomyelitis. There was, however, extraskeletal uptake of the 99mTc bone tracer in the anterior abdominal wall confined to the sites of subcutaneous heparin administration. This case is presented because of its interesting scintigraphic findings and to discuss the association of protein C deficiency and heparin administration as a cause of extraskeletal 99mTc bone tracer accumulation.

Abdominal Muscles↗

Scintigraphic findings of fibular donor sites.

Vascularized fibulas are used for reconstruction of bony defects after surgical removal of malignant skeletal tumors. Here, we describe scintigraphic findings at fibular donor sites in three patients who underwent limb salvage procedures for primary malignant bone tumors.

Adolescent↗

Intestinal adaptation and amino acid transport following massive enterectomy.

Morphological and physiological adaptation in residual small intestine occurs after massive enterectomy and is influenced significantly by different growth factors and hormones. The mechanism of adaptation occurs through hypertrophy and hyperplasia as well as nutrient transporter changes. These transporters are classified into different classes dependent on its biological properties. The adaptation process evolves over time and different nutrient absorption profiles occur at different postoperative stages. There is an initial decrease in amino acid transport after resection followed by a return to approximately normal levels. Glucose also follows a similar pattern of changes but returns to normal later than amino acids. The time course of these changes are different for different animals with rat adaptation being much faster than rabbit. Growth hormone (GH) induces increased amino acid transport during this adaptation period, however, appears not to affect small intestine hypertrophy or hyperplasia. The increase in transport occurs via an increase in transport numbers rather than affinity. Epidermal growth factor (EGF) also increases amino acid transport in postoperative animals. Its advantage is it is orally stable when given with a protease inhibitor. EGF also reverses the down-regulating effects of the somatostatin analogue Octreotide (SMS) post resection. EGF in combination with GH has additive effects. However, the effects of the growth factors are site specific. GH and EGF combination therapy significantly increased alanine and arginine transport in distal small bowel after 70 % enterectomy but not in the proximal small bowel. The same combination increases leucine and glutamine transport in the proximal small intestine only. Understanding the specific changes that occur with these therapies may improve quality of life for patients and also reduce that need for total parenteral nutrition.

Absorption↗

Calculated distortions of duplex DNA by a cis, syn cyclobutane thymine dimer are unaffected by a 3' TpA step.

Molecular dynamics simulations were performed on the duplex DNA dodecamers d(CGCGAA TT CGCG): d(CGCGAATTCGCG) and d(GCACGAA TT AAG): d(CTTAATTCGTGC), where TT denotes a cis, syn cyclobutane thymine dimer. The constant temperature and pressure algorithm of the AMBER 4.1 molecular-modeling package was used with explicit water and counterions, periodic boundary conditions and electrostatic interactions evaluated by the particle-mesh Ewald method. Results were analyzed by the CURVES algorithm and its implementation in DIALS and WINDOWS. Calculated distortions of DNA structure by the thymine dimer were qualitatively and quantitatively similar for the two sequences. Despite the enhanced flexibility of the native TpA dinucleotide step, major deviations from the B-DNA values of helicoidal parameters were found only at the Ap and p dinucleotide steps in both sequences. Only the AT base pairs of the two sequences that contain the 5' thymine of the dimers exhibited weakened Watson-Crick hydrogen bonds and anomalous stretching. Hence, we conclude that the pattern of structural perturbations responsible for recognition of cis, syn thymine dimers by repair enzymes is not sensitive to their sequence context.

Algorithms↗

Human growth hormone induces system B transport in short bowel syndrome.

BACKGROUND: After massive enterectomy, remnant intestine undergoes compensatory adaptation. A combination of human growth hormone (hGH) and a glutamine-enriched modified diet induces further adaptation in patients with short bowel syndrome (SBS) on long-term total parenteral nutrition. The specific actions of each component, however, are not well-defined. METHODS: New Zealand White rabbits were randomized to control, sham operation, or SBS (70% midjejunoileal resection) groups and treated with either hGH or saline. Sodium-dependent uptake of glucose, glutamine, alanine, leucine, and arginine into brush border membrane vesicles was quantitated. Serum insulin-like growth factor-I (IGF-I) levels were determined by immunoradiometric assay. Mucosal mRNA expression of IGF-I and IGF binding protein 4 (IGFBP-4) was evaluated by northern blot analysis using rat cDNA probes. RESULTS: Glutamine and leucine transports were 33 and 39% greater, respectively, in the hGH-treated versus saline-treated SBS group (P < 0.05), supporting induction of system B amino acid transport. This upregulation was due, in part, to an 88% increase in glutamine carrier capacity (Vmax) with no change in carrier affinity (Km). Both hGH treatment and SBS increased serum IGF-I levels without direct correlation with increased nutrient transport. IGFBP-4 mRNA expression in small bowel mucosa of saline-treated SBS animals was significantly greater than saline-treated unoperated control values. Mucosal IGFBP-4 mRNA was not significantly altered from control in the other study groups. IGF-I mRNA expression was not detected in mucosa, but weak hybridization was noted in rabbit liver. CONCLUSIONS: Human growth hormone accelerates early adaptation in SBS by upregulation of system B carrier capacity. Serum IGF-I levels and mucosal IGF-I and IGFBP-4 mRNA expression did not directly correlate with this enhanced nutrient transport, suggesting that hGH might exert its adaptive effects by mechanisms that are independent from the IGF system in this model.

Amino Acids↗

A fosmid-based genomic map and identification of 474 genes of the hyperthermophilic archaeon Pyrobaculum aerophilum.

We have constructed a physical map of the approximately 1.7-Mb genome of the hyperthermophilic archaeon Pyrobaculum aerophilum. Derived from a 12x coverage genomic fosmid library with an average insert size of 36 Kb, the map consists of a single circular contig of 96 overlapping fosmid clones with 211 markers ordered along them. One hundred of the sequence markers have strong similarities to known genes. Many overlaps were also checked using restriction fingerprint analysis. This map is an important step in the elucidation of the sequence of the entire genome of Pyrobaculum aerophilum. To this end we have determined more than 95% of the genome with 15,000 random sequences. Each sequence has been screened against the public sequence databases to identify similarities to known genes. We report here a list of the 474 putative genes we have identified.

Animals↗

Congenital cervical atresia: report of seven cases and review of the literature.

OBJECTIVE: Our aim was to evaluate the clinical course and management of congenital cervical atresia. STUDY DESIGN: This retrospective analysis included 7 patients referred to our clinic and a review of the medical literature. RESULTS: Including this case series, 58 cases of congenital cervical atresia have been reported in the literature. Forty-eight percent of patients had isolated congenital cervical atresia with a normal vagina whereas the remainder had either complete or partial vaginal atresia ("shortened blind vaginal pouches"). Surgical management has included abdominal hysterectomy or uterovaginal cannulation with or without vaginoplasty. In 59% of patients who underwent uterovaginal canalization procedures (23/39), normal menstrual bleeding was achieved. Four of these patients subsequently became pregnant and were delivered at term. CONCLUSION: Surgical canalization in selected patients with congenital cervical atresia can be successfully performed to provide patients an opportunity for conservative management, resulting in normal menstrual bleeding, resolution of cyclic pelvic pain, and some potential (albeit limited) for fertility.

Abnormalities, Multiple↗