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Biomedical subjects

K A Miller

Publications and source records attributed to K A Miller.

At least 19 recordsLinked to original sources
PubMed2006

A remote and highly conserved enhancer supports amygdala specific expression of the gene encoding the anxiogenic neuropeptide substance-P.

The neuropeptide substance P (SP), encoded by the preprotachykinin-A (PPTA) gene, is expressed in the central and medial amygdaloid nucleus, where it plays a critical role in modulating fear and anxiety related behaviour. Determining the regulatory systems that support PPTA expression in the amygdala may provide important insights into the causes of depression and anxiety related disorders and will provide avenues for the development of novel therapies. In order to identify the tissue specific regulatory element responsible for supporting expression of the PPTA gene in the amygdala, we used long-range comparative genomics in combination with transgenic analysis and immunohistochemistry. By comparing human and chicken genomes, it was possible to detect and characterise a highly conserved long-range enhancer that supported tissue specific expression in SP expressing cells of the medial and central amygdaloid bodies (ECR1; 158.5 kb 5' of human PPTA ORF). Further bioinformatic analysis using the TRANSFAC database indicated that the ECR1 element contained multiple and highly conserved consensus binding sequences of transcription factors (TFs) such as MEIS1. The results of immunohistochemical analysis of transgenic lines were consistent with the hypothesis that the MEIS1 TF interacts with and maintains ECR1 activity in the central amygdala in vivo. The discovery of ECR1 and the in vivo functional relationship with MEIS1 inferred by our studies suggests a mechanism to the regulatory systems that control PPTA expression in the amygdala. Uncovering these mechanisms may play an important role in the future development of tissue specific therapies for the treatment of anxiety and depression.

Amygdala↗
PubMed2006

Differential effects of 4 types of environmental enrichment on aggressive pecking, feather pecking, feather loss, food wastage and productivity in Japanese quail.

1. We examined the effects of 4 types of environmental enrichment (foraging opportunities, structural complexity, sensory stimulation/novelty, and social companionship) on aggressive and feather pecking, feather condition, food wastage, body weight, feed conversion, and egg production in adult Japanese quail. Sex differences were examined where possible. 2. GLM analysis was used to evaluate the effects of enrichment and housing, while test-retest reliability and the stability of measures over 18 d were assessed using partial correlation. 3. Foraging enrichment reduced food wastage. 4. Body weight, feed conversion, and egg production were not affected by enrichment. Rates of aggressive and feather pecking were also not significantly affected, but these behaviours were observed very infrequently in this study. 5. Socially-housed birds had poorer feather condition, lower body weight and less efficient feed conversion than singly-housed birds. Social housing did not affect food wastage. 6. There were not sex differences in feather pecking, feather condition, food wastage, or feed conversion. 7. All measures except feather pecking were reliable over 24 h, but only feather condition and body weight were stable over 18 d. The instability f the behavioural measures over time suggest that enrichment effects may vary with age.

Aggression↗
PubMed2005

Total hip arthroplasty with cement and without acetabular bone graft for severe hip dysplasia. A concise follow-up, at a minimum of twenty years, of a previous report.

We previously evaluated a cohort of fifty-three patients with severe hip dysplasia (Crowe Type-II, III, or IV subluxation) who underwent a total of sixty-six Charnley total hip arthroplasties. The acetabular component was placed at the anatomic hip center, the superolateral defect was filled with cement, and no bone-grafting was used to supplement the acetabular wall. All but one patient, who was lost to follow-up, were followed until death or for a minimum of twenty years. Radiographic and functional follow-up data were collected prospectively. This retrospective review included twenty-four patients (thirty-four hips) who were alive at a minimum of twenty years following the surgery. Fourteen (22%) of the sixty-five hips underwent revision of a component, with eleven of the revisions performed because of aseptic loosening. Eight of those eleven hips underwent revision because of acetabular loosening alone; two, because of femoral loosening alone; and one, because of loosening of both components. The combined prevalence of revision because of aseptic loosening of the acetabular component and radiographic evidence of failure of the acetabular component was 28% (eighteen hips). With the numbers available, the need for acetabular revision was not associated with the percentage of cement coverage (p = 0.362) or the Crowe classification (p = 0.159). At a minimum of twenty years postoperatively, the survivorship of the acetabular component was 86% +/- 8% with revision because of aseptic loosening as the end point and 82% +/- 10% with revision because of aseptic loosening or radiographic evidence of loosening as the end point. The results that we evaluated at a minimum of twenty years after use of this technique can be compared with the results of other techniques in studies with similar long-term follow-up periods.

Adult↗
PubMed2004

Characterisation of a beta-tubulin gene from the monogenean parasite, Gyrodactylus salaris Malmberg, 1957.

The cDNA and two partial genomic sequences of beta-tubulin genes have been isolated from the monogenean parasite Gyrodactylus salaris. The cDNA sequence is not represented by either of the genomic sequences, implying that at least three isotypes of the gene exist in G. salaris. The sequences show regions of high homology with other helminth beta-tubulin genes. This represents the first isolation of a beta-tubulin gene from a monogenean and contributes to the overall characterisation of these genes within the helminths. This is an important area, as anthelmintic resistance is increasing against benzimidazole drugs that target the beta-tubulin gene. Benzimidazole drugs have been tested successfully against Gyrodactylus parasites, but their use is not widespread. Should it increase, analysis of the beta-tubulin gene may provide a tool for monitoring resistance development and improving management practises. Use of the beta-tubulin gene in the identification of Gyrodactylus species may prove complex due to the presence of different isotypes.

Amino Acid Sequence↗
PubMed2002

Experience with laparoscopic adrenalectomy in pediatric patients.

BACKGROUND: Laparoscopic adrenalectomy (LA) is now being recognized as the standard in the management of benign adrenal pathology in adult patients. Few reports have described the use of this technique in pediatric patients. This study combines experience from 2 institutions with lateral transperitoneal LA in children to analyze our results and the clinical and biochemical response to laparoscopic adrenalectomy in patients with hormonally active adrenal tumors. METHODS: A bi-institutional retrospective review of all patients undergoing LA between January 1997 and January 2001 was performed. Clinical and biochemical data were obtained during routine follow-up. RESULTS: Seventeen laparoscopic adrenalectomies were performed during this period. The average operating time was 120 minutes, mean estimated blood loss was 25 mL, the mean size of the adrenal lesion was 4.8 cm, and the mean length of hospitalization was 35 hours. Resolution of clinical and biochemical parameters of adrenal hyperfunction was accomplished in all patients with adrenocortical hyperplasia and pheochromocytoma in postoperative follow-up. CONCLUSIONS: Laparoscopic adrenalectomy can be performed safely and effectively with a short hospital stay, minimal blood loss, and excellent functional outcome in this age group. The authors believe laparoscopic adrenalectomy is an excellent approach for the management of benign pediatric adrenal pathology.

Adenoma↗
PubMed2002

Minimally invasive bar repair for 'redo' correction of pectus excavatum.

BACKGROUND/PURPOSE: A small percentage of patients who have undergone traditional, "Ravitch-type" pectus excavatum repair present with unsatisfactory results and require a second procedure for correction. Reoperative open surgery for pectus excavatum has been associated with extensive dissection and substantial blood loss. The minimally invasive (MIS) bar repair for the correction of pectus excavatum has been gaining acceptance. This study evaluates the authors results with patients who have undergone the MIS bar repair for redo correction of their pectus excavatum. METHODS: A retrospective chart review of all patients undergoing MIS bar repair between December 1997 and August 2001 was performed. Information about demographics, deformity, operative course, complications, and early outcome was recorded. RESULTS: Ninety-two patients underwent MIS repair during this period. Ten patients had redo MIS bar repair for unsatisfactory prior open correction. Operating time was 52 minutes for standard patients and 70 minutes for the redo patients (P <.001). Blood loss and postoperative hospitalization were similar between groups. CONCLUSION: The minimally invasive pectus repair can be performed safely with minimal blood loss and short operating time in patients who have undergone prior unsatisfactory open repair of pectus excavatum and can be an alternative approach to reoperative open repair in these patients.

Child↗
PubMed2001

Kruppel-like factor 4 regulates laminin alpha 3A expression in mammary epithelial cells.

Laminin-5, the major extracellular matrix protein produced by mammary epithelial cells, is composed of three chains (designated alpha3A, beta3, and gamma2), each encoded by a separate gene. Laminin-5 is markedly down-regulated in breast cancer cells. Little is known about the regulation of laminin gene transcription in normal breast cells, nor about the mechanism underlying the down-regulation seen in cancer. In the present study, we cloned the promoter of the gene for the human laminin alpha3A chain (LAMA3A) and investigated its regulation in functionally normal MCF10A breast epithelial cells and several breast cancer cell lines. Using site-directed mutagenesis of promoter-reporter constructs in transient transfection assays in MCF10A cells, we find that two binding sites for Kruppel-like factor 4 (KLF4/GKLF/EZF) are required for expression driven by the LAMA3A promoter. Electrophoretic mobility shift assays reveal absence of KLF4 binding activity in extracts from T47D, MDA-MB 231, ZR75-1, MDA-MB 436, and MCF7 breast cancer cells. Transient transfection of a plasmid expressing KLF4 activates transcription from the LAMA3A promoter in breast cancer cells. A reporter vector containing duplicate KLF4-binding sites in its promoter is expressed at high levels in MCF10A cells but at negligible levels in breast cancer cells. Thus, KLF4 is required for LAMA3A expression and absence of laminin alpha3A in breast cancer cells appears, at least in part, attributable to the lack of KLF4 activity.

Binding Sites↗
PubMed2001

Management of intestinal atresia in patients with gastroschisis.

BACKGROUND/PURPOSE: Intestinal atresia occurs in approximately 10% to 20% of children with gastroschisis and may be missed at the initial closure if a thick peel obscures the bowel. Some investigators have identified intestinal atresia as a significant contributor to morbidity and mortality. The authors reviewed their experience with gastroschisis and intestinal atresia in an attempt to answer the following questions. What is the incidence of this association? How often is the intestinal atresia unrecognized as a result of the peel? What is the optimal management for infants with atresia and gastroschisis, and does the atresia affect morbidity or mortality? METHODS: The hospital charts and medical records of all patients with gastroschisis treated at our institution from 1969 to present were reviewed thoroughly. Parameters analyzed included gestational age (GA), birth weight (BW), antenatal diagnosis, mode of delivery, type of closure, era of repair, presence of other major anomalies, and development of necrotizing enterocolitis. Morbidity and mortality rates were examined. Characteristics of patients with and without atresia were compared. Chi-squared was used for crosstabular analysis. Sample parameters were compared with Student's t test. P values of less than.05 were considered significant. RESULTS: A total of 199 babies had gastroschisis and 25 (12.6%) had intestinal atresia. Intestinal atresia was initially unrecognized in 3 patients. Most patients (80%) underwent primary closure of the abdominal wall. Initial stoma formation and delayed anastomosis was performed in 12 (48%) patients, none of whom required prosthetic material for abdominal wall closure. Initial stomas were avoided in 5 patients who required SILASTIC (Dow Corning, Midland, MI) silos. Skin closure alone was used in 2 babies. The level of the atresia was most commonly jejunoileal (20 of 25, 80%). Mean hospital stay was increased in babies with intestinal atresia, 36.2 versus 63.1 days (P <.001). CONCLUSIONS: Although patients with intestinal atresia did have feeding delays, an increased incidence of adhesive intestinal obstruction, and prolonged hospitalization, neither chi(2) nor logistic regression analysis showed any correlation with mortality. Intestinal repair at the first operation is sometimes possible and depends on the severity of the peel. Delayed repair of the atresia after a period of bowel decompression and parenteral nutrition is preferred, but in certain situations (colonic atresia, necrotic intestine, complicated atresia) may not be possible. The combination of stomas and prosthetic material can be avoided in almost all patients. A management algorithm for patients with atresia and gastroschisis is discussed.

Female↗
PubMed2001

Minimally invasive repair of pectus excavatum: a single institution's experience.

BACKGROUND: The Nuss repair of pectus excavatum is a relatively new, minimally invasive surgical (MIS) alternative to the traditional open "Ravitch-type" operation. We have one of the larger single-center experiences to date, and we conducted this clinical study to evaluate our early experience, emphasizing initial outcome and technical modifications designed to minimize complications. METHODS: A retrospective chart review was performed on 112 patients who underwent 116 pectus excavatum repairs between January 1995 and January 2001. The Nuss procedure was performed in 80 patients, and open repair was performed in 32 patients. Information about demographics, deformity, operative course, complications, and early outcome was recorded. RESULTS: Operative duration was 143 minutes for the open group and 53 minutes for the Nuss MIS group (P <.001). Blood loss was 6 mL/kg for the open group and 0.5 mL/kg for the MIS group (P <.001). Postoperative hospitalization was 3.2 days for the open group versus 3.7 days for the MIS group (P<.05). CONCLUSIONS: The MIS pectus repair can be performed safely with minimal blood loss and reduced operative time. Short-term analysis of the quality of repair, including absence of preoperative symptoms, patient satisfaction, and cosmetic appearance are encouraging.

Adolescent↗
PubMed2001

1% lidocaine injection, EMLA cream, or "numby stuff" for topical analgesia associated with peripheral intravenous cannulation.

The purpose of this study was to assess patient's perception of pain associated with peripheral intravenous (i.v.) cannulation, using 3 methods of applying local anesthetics. A prospective, randomized, quasi-experimental study was conducted, using a convenience sample of men and women, ASA physical status I, II, or III, undergoing outpatient or same-day surgery. Group 1 received a subcutaneous injection of 1% lidocaine, group 2 received topical EMLA cream for 45 to 60 minutes, and group 3 received treatment with "Numby Stuff" for 40 mA minutes. After the intended analgesic treatment was complete, the patient was asked to rate the pain experienced during the skin-numbing process. An i.v. was then started using an 18-gauge i.v. catheter, and the patient again was asked to rate the amount of pain experienced with the catheter insertion. A visual analog scale was used as the tool of measurement for pain. Results of the study showed that group 1 experienced a higher treatment pain score than either group 2 or group 3, while group 2 experienced a higher pain score when the i.v. was started than either group 1 or group 3. Of the 3 methods tested, results seem to indicate that the Numby Stuff system using iontophoresis is the superior method for decreasing the pain associated with peripheral i.v. cannulation, and application of the analgesic method does not cause significant pain.

Analysis of Variance↗
PubMed2000

Relationship of MTT reduction to stimulants of muscle metabolism.

MTT, a positively charged tetrazolium salt, is widely used as an indicator of cell viability and metabolism and has potential for histochemical identification of tissue regions of hypermetabolism. In the present study, MTT was infused in the constant-flow perfused rat hindlimb to assess the effect of various agents and particularly vasoconstrictors that increase muscle metabolism. Reduction of MTT to the insoluble formazan in muscles assessed at the end of experiments was linear over a 30 min period and production rates were greater in red fibre types than white fibre types. The vasoconstrictors, norepinephrine (100 nM) and angiotensin (10 nM) decreased MTT formazan production in all muscles but increased hindlimb oxygen uptake and lactate efflux. Veratridine, a Na(+) channel opener that increases hindlimb oxygen uptake and lactate efflux without increases in perfusion pressure, also decreased MTT formazan production. Membrane stabilizing doses (100 microM) of (+/-)-propranolol reversed the inhibitory effects of angiotensin and veratridine on MTT formazan production. Muscle contractions elicited by stimulation of the sciatic nerve, reversed the norepinephrine-mediated inhibitory effects on MTT formazan production, even though oxygen consumption and lactate efflux were further stimulated. Stimulation of hindlimb muscle oxygen uptake by pentachlorophenol, a mitochondrial uncoupler, was not associated with alterations in MTT formazan production. It is concluded that apart from muscle contractions MTT formazan production does not increase with increased muscle metabolism. Since the vasoconstrictors angiotensin and norepinephrine as well as veratridine activate Na(+) channels and the Na(+)/K(+) pump, energy required for Na(+) pumping may be required for MTT reduction. It is unlikely that vasoconstrictors that stimulate oxygen uptake do so by uncoupling respiration.

Angiotensin II↗
PubMed2000

Anterior submucous laryngeal cleft.

Upper airway obstruction in the newborn is frequently due to congenital laryngeal anomalies. One of these, the posterior laryngeal cleft, is often associated with subglottic stenosis and respiratory difficulty. This discussion of the anterior laryngeal cleft reports findings in an infant who required intubation immediately after birth and survived only 3 days. The anterior cricoid cleft was associated with severe congenital anomalies including congenital tracheal stenosis.

Abnormalities, Multiple↗
PubMed2000

Inhibition of laminin-5 production in breast epithelial cells by overexpression of p300.

The transcriptional coactivator p300 is essential for normal embryonic development and cellular differentiation. We have been studying the role of p300 in the transcription of a variety of genes, and we became interested in the role of this coactivator in the transcription of genes important in breast epithelial cell biology. From MCF-10A cells (spontaneously immortalized, nontransformed human breast epithelial cells), we developed cell lines that stably overexpress p300. These p300-overexpressing cells displayed reduced adhesion to culture dishes and were found to secrete an extracellular matrix deficient in laminin-5. Laminin-5 is the major extracellular matrix component produced by breast epithelium. Immunofluorescence studies, as well as experiments using normal matrix, confirmed that the decreased adhesion of p300-overexpressing cells is due to laminin-5-deficient extracellular matrix and not due to loss of laminin-5 receptors. Northern blots revealed markedly decreased levels of expression of two of the genes (designated LAMA3 and LAMC2) encoding the alpha3 and gamma2 chains of the laminin-5 heterotrimer in the cells that overexpress p300, whereas LAMB3 mRNA, encoding the third or beta3 chain of laminin-5, was not markedly reduced. Transient transfection experiments with a vector containing a murine LAMA3 promoter demonstrate that overexpressing p300 down-regulates the LAMA3 promoter. In summary, overexpression of p300 leads to down-regulation of laminin-5 production in breast epithelial cells, resulting in decreased adhesion.

Breast↗
PubMed2000

Pharmacological and behavioral characterization of cocaine-kindled seizures in mice.

RATIONALE: Convulsions associated with cocaine toxicity are a serious aspect of cocaine-related emergency room incidents. Seizures can result from a single high dose of cocaine, and evidence is accumulating that correlates repetitive administration of sub-convulsive doses of cocaine with a decreased seizure threshold, a phenomenon known as pharmacological kindling. A murine model of cocaine kindling has not been characterized. OBJECTIVES: To determine the necessary and sufficient conditions for generating increased sensitivity to the convulsive and lethal effects of cocaine and to characterize some of the basic pharmacological and behavioral consequences of this phenomenon in mice. METHODS: Male, Swiss-Webster mice were given repeated injections of cocaine. RESULTS: Daily administration of 60 mg/kg cocaine produced robust kindling; significant leftward shifts in the dose-effect curves for seizures were observed in cocaine-kindled mice. Cocaine kindling was enduring as these left shifts persisted for at least 20 days, indicating possible permanent synaptic changes. Induction of convulsions per se, utilizing 75 mg/kg cocaine, was not sufficient to engender kindling with a non-optimal dose (40 mg/kg). However, administration of a non-kindling dose of cocaine (40 mg/kg) for as few as four occasions produced increased seizure sensitivity to a 60-mg/kg cocaine challenge. The lethal potencies of cocaine and methamphetamine were significantly increased in cocaine-kindled mice. The baseline locomotor activity of kindled mice was not different from that of non-kindled mice. However, challenge doses of cocaine revealed significant differences in the vertically directed activity of kindled versus non-kindled mice. CONCLUSIONS: Overall, this study provides a description of important parameters for a model of cocaine kindling in mice that may be useful for the elucidation of mechanisms responsible for the long-term changes in sensitivity to cocaine and the discovery of novel pharmacological treatments.

Animals↗
PubMed2000

Benzodiazepines protect hippocampal neurons from degeneration after transient cerebral ischemia: an ultrastructural study.

The ability of full and partial benzodiazepine receptor agonists to prevent DNA fragmentation and neuronal death after transient cerebral ischemia was investigated in the Mongolian gerbil. Diazepam (10mg/kg, i.p.) or the partial agonist imidazenil (3mg/kg, i.p.) was administered 30 and 90min after transient forebrain ischemia produced by occlusion of the carotid arteries for 5min. Treatment with diazepam completely protected CA1b hippocampal pyramidal neurons in 94% of the animals and partially protected pyramidal neurons in 6% of the animals, as assessed with a standard Nissl stain three and four days after ischemia. DNA fragmentation was examined by the terminal dUTP nick-end labeling (TUNEL) reaction. Prior to cell death, there were no TUNEL-positive neurons in area CA1b. By three days after ischemia, when neuronal degeneration was nearly complete, 14 out of 16 gerbils exhibited a positive TUNEL reaction throughout area CA1b stratum pyramidale. In 13 out of 14 gerbils treated with diazepam, no TUNEL-positive neurons were observed in this region. Imidazenil was less effective than diazepam with respect to both neuroprotection and prevention of DNA fragmentation. Three days after ischemia, six out of eight gerbils treated with imidazenil showed partial to complete neuroprotection. Imidazenil completely prevented DNA fragmentation in only one of the animals; varying degrees of TUNEL reaction persisted in the remainder. To determine whether the neurons protected by diazepam had a normal ultrastructure, gerbils were killed two to 30 days after ischemia and the hippocampal neurons in area CA1b were examined by electron microscopy. Within the first 48h after ischemia, early cytoplasmic changes of varying degrees (e.g., vacuolation, rough endoplasmic reticulum stacking, swollen mitochondria) and electron-dense dendrites were observed in gerbils not treated with diazepam. Degeneration was nearly complete by three days after ischemia. In contrast, pyramidal neuron ultrastructure appeared normal in gerbils that exhibited complete area CA1b neuroprotection (defined at the light microscope level) by diazepam when studied two, seven or 30 days after ischemia. In gerbils with partial protection of area CA1b, most of the remaining neurons exhibited varying degrees of necrosis when studied 30 days after ischemia. No apoptotic bodies were observed. We conclude that: (i) diazepam can fully protect CA1 pyramidal cells from the toxic effects of transient cerebral ischemia; (ii) when diazepam affords only partial neuroprotection, the residual CA1 pyramidal cells exhibit ultrastructural abnormalities consistent with necrotic damage; and (iii) diazepam is a more efficacious neuroprotectant than the partial benzodiazepine receptor agonist, imidazenil.

Animals↗
PubMed2000

Evaluation of health status and quality of life after bariatric surgery: comparison of standard Roux-en-Y gastric bypass, vertical banded gastroplasty and laparoscopic adjustable silicone gastric banding.

BACKGROUND: This study is a trial to compare the effects and outcomes of three different bariatric procedures performed in two centers. Standard Roux-en-Y gastric bypass was performed by Dr. Norman Samuels in Fort Lauderdale (Florida); vertical banded gastroplasty and laparoscopic adjustable silicone gastric banding were done in Hallein (Salzburg) by Dr. Emanuel Hell and Dr. Karl Miller. METHODS: In a prospective comparative study 30 matched patients from each group were followed to assess post-operative improvement in health status and quality of life, to compare the three different techniques. The Bariatric Analysis and Reporting Outcome System (BAROS) as described by Oria and Moorehead has been used for evaluation. RESULTS: The observation time was at least 3 years (3 to 8 years) in each individual case. A significant increase in quality of life and health status in 75% of the surgically-treated patients was observed when compared with a non-operated control group of morbidly obese patients. CONCLUSIONS: By utilizing BAROS it has been found possible to compare the results of different procedures done by different surgeons with different techniques, utilizing patients from different cultures and with different languages. The results of this comparative study favor the standard gastric bypass for the treatment of morbid obesity. This operation is superior to purely gastric restrictive procedures in weight loss and improvement of quality of life.

Adult↗