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Biomedical subjects

R E Kelly

Publications and source records attributed to R E Kelly.

At least 19 recordsLinked to original sources

Review and discussion of the complications of minimally invasive pectus excavatum repair.

PURPOSE: To review and discuss the complications of minimally invasive pectus excavatum repair. METHODS: 329 patients underwent minimally invasive pectus repair between January 1987 and August 2000, including 14 patients who recurred after previous Ravitch repairs, 10 failed Nuss repairs (eight done elsewhere) and two failed Leonard repairs. All patients received antibiotics and vigorous incentive spirometry to prevent atelectasis, pneumonia and bar infection. Epidural anesthesia was used for postoperative analgesia to keep patients comfortable and stable postoperatively and to prevent bar displacement. Thoracoscopy was used during bar insertion to minimize the risk of mediastinal injury and to select the best position for the bar. A new introducer was developed to elevate the sternum before bar insertion. A stabilizing bar was created to minimize bar displacement. The duration of sternal bracing has been increased from two years to three or four years in selected patients. COMPLICATIONS: There were no deaths, no cardiac perforations and no cases of thoracic chondrodystrophy. Pneumothorax with spontaneous resolution occurred in 52 % of the patients, with 1.2 % requiring simple aspiration and 1.5 % requiring chest tube drainage. This complication has essentially been eliminated by using a "water seal system". Pericarditis occurred in 2.4 % with good response to Indomethacin in six out of eight patients and two patients also required pericardial fluid aspiration. Pneumonia occurred in 0.9 %. Wound infection occurred in 2.6 % resulting in bar infection in three out of the seven patients. Long-term antibiotics were successful in curing the infection in one patient, whereas the other two required bar removal at 12 and 18 months, respectively. Bar displacement occurred in 8.8 % of patients. However, the introduction of stabilizers decreased the incidence from 15.7 % before the use of stabilizers to 5.4 % with stabilizers. Wiring the bar and stabilizer together has decreased the incidence even further. RESULTS: Long-term outcome after bar removal showed an excellent result in 71 %, good result in 21 % and recurrence in 7.8 %. CONCLUSION: The minimally invasive technique has a low complication rate with excellent long-term results.

Adolescent↗

Tripedal knuckle-walking: a proposal for the evolution of human locomotion and handedness.

A comparative morphological analysis of human and non-human hominoids was conducted in an attempt to determine the mode of locomotion of the protohominid. Although the generalized hominoid anatomy permits variation of locomotion: brachiation, knuckle-walking, etc., minor variations in structure determine which behavior is favored. Arboreal arm swinging requires a flexible forelimb while terrestrial fist or knuckle-walking demands more rigidity of the hand and wrist. It is demonstrated that the large human thumb accompanied by the strong adduction of the thenar, hypothenar, and palmar interosseous muscles offer powerful rigidity to the hand, while fusion of the os centrale with the scaphoid during gestation permits the formation of an arch of carpals which imbue the wrist with the stability necessary for weight bearing. Fascialization of the contrahentes and dorsiepitrochlearis muscles in the human as well as depilation of the middle phalanges; the webbing (syndactyly) of the palm; the direction of the fibers of the interosseous membrane of the forearm; the shape of the puerile annular ligament, and the direction of the human glenoid fossa strongly suggest that the ancestor of man used a knuckle-walking form of locomotion prior to becoming bipedal. A model is presented that suggests that bipedalism was attained through an intermediate stage of tripedalism. The model is based on the fact that man's anatomy is much more asymmetric than that of the great apes. A presumption is made that due to the absence of trees for climbing in the transition from forest to open plain, the protohominid needed to carry tools (stones) at all times for protection. Stones could be carried for long distances on the posterior iliac crest since the weight would be shifted posteriorly over the legs. Pick up, medial rotation and adduction of the stone would employ a two-muscle chain of biceps brachii and latissimus dorsi. On the iliac crest, the stone is posterior to the coronal plane of the glenohumeral joint, and with the contraction of this two-muscle chain, the shoulder on one side is moved posteriorly effecting a semi-erect posture. It is proposed that tripedalism of the protohominid may be an explanation for the handedness unique to hominids.

Animals↗

The effects of a pediatric unilateral inguinal hernia clinical pathway on quality and cost.

BACKGROUND/PURPOSE: The purpose of this study is to discover whether a pediatric inguinal hernia surgical clinical pathway (CP) reduces the frequency of wound infections, return visits, times associated with surgical repair, or costs. METHODS: A multidisciplinary team developed the inguinal hernia surgical clinical pathway. Healthy children greater than 50 weeks gestational age who required unilateral hernia repair were considered for the study. Two groups were formed: (1) an intervention group selected randomly (n = 46, CI = 95%, power = .80) from patients enrolled from November 1996 through April 1997, and (2) a retrospective cohort control group (n = 46) matched to each intervention patient by age, gender, and medical history. Analysis of variance and chi2 testing were used to test for significant differences between the 2 groups in postoperative wound infections, readmission and emergency department return visits within 72 hours, times associated with surgical repair, and costs. RESULTS: There were no significant differences in postoperative wound infections, times associated with surgical repair, or readmission rates within 72 hours. Total cost significantly decreased, by 10% (P< or = .05), for pathway patients ($982 v $880). CONCLUSION: These results show that the use of a pediatric inguinal hernia surgical clinical pathway is associated with reduced cost while maintaining quality of care.

Child, Preschool↗

Cervene (Nalmefene) in acute ischemic stroke : final results of a phase III efficacy study. The Cervene Stroke Study Investigators.

BACKGROUND AND PURPOSE: The goals of the present study were to assess the efficacy and safety of nalmefene (Cervene) in patients with acute (< or =6 hours) ischemic stroke and to investigate the safety of combined recombinant tissue plasminogen activator and nalmefene in a separate subset of patients. Nalmefene, an opioid antagonist with relative kappa receptor selectivity, has shown neuroprotective effects in multiple experimental central nervous system injury and ischemic models. Results from an earlier phase II study in patients with acute ischemic stroke suggested that nalmefene was safe and tolerable and may be effective for patients <70 years old. METHODS: This investigation was a phase III, placebo-controlled, double-blind, randomized study of a 24-hour infusion of nalmefene. Patients with acute ischemic stroke who had an onset of symptoms within 6 hours and a baseline score of > or =4 on the NIH Stroke Scale were randomized to receive either 60 mg nalmefene administered as a 10-mg bolus over 15 minutes and then a 50-mg infusion over 23.75 hours or placebo. The primary efficacy outcome was the proportion of patients achieving a score of > or =60 on the Barthel Index and a rating of "moderate disability" or better on the Glasgow Outcome Scale at 12 weeks. Assessments were performed at baseline (predose), hours 12 and 24, days 2 and 7, and week 12. RESULTS: A total of 368 patients were randomized at 42 centers, including 32 patients treated with recombinant tissue plasminogen activator and study drug. Nalmefene was well tolerated. Overall, there was no significant difference in 3-month functional outcome for nalmefene treatment compared with placebo on any of the planned analyses. A prospective secondary analysis also failed to find a treatment effect in patients <70 years old. CONCLUSIONS: Although nalmefene appears to be safe and well tolerated, this study failed to find any treatment benefit in stroke patients treated within 6 hours.

Acute Disease↗

Should central venous catheters be removed as soon as candidemia is detected in neonates?

BACKGROUND: Controversy exists regarding the most appropriate acute management of central venous catheters (CVCs) in neonates with candidemia, with up to two thirds of neonatologists preferring to attempt antifungal therapy without removing CVCs. OBJECTIVE: To determine whether CVCs should be removed as soon as candidemia is detected in neonates. Methods. A cohort study of candidemia and CVC was conducted in infants in a neonatal intensive care unit (NICU) over a 5-year period (1994-1998). RESULTS: Fifty infants had early-removal CVC (ER-CVC) within 3 days and 54 infants had late-removal CVC (LR-CVC) >3 days after the first positive blood culture for Candida species. All infants were treated with amphotericin B. There was no significant difference between infants in the ER-CVC and LR-CVC groups in terms of gender, ethnicity, birth weight, gestational age, age at candidemia, severity-of-illness scores, distribution of types of CVC, or in the distribution of Candida species causing candidemia. The ER-CVC group had significantly shorter duration of candidemia (median: 3 days; range: 1-14 days), compared with the LR-CVC group (median: 6 days; range: 1-24 days). The case fatality rate of Candida albicans candidemia was significantly affected by the timing of CVC removal: 0 of 21 (95% confidence interval [CI]: 0-14) infants died in the ER-CVC group in contrast to 9 of 23 (39%; 95% CI: 19-59) in the LR-CVC group. CONCLUSION: Failure to remove CVC as soon as candidemia was detected in neonates was associated with significantly increased mortality in C albicans candidemia and prolonged duration of candidemia regardless of Candida species.

Candida↗

Time-modulated convection with zero mean temperature gradient.

We study numerically the onset of temporally modulated Rayleigh-Bénard convection with zero mean gradient for cases of antisymmetric and asymmetric boundary temperatures over a continuous range of nondimensional frequencies omega, from omega approximately O(10(-1)) to omega approximately O(10(3)). For omega below 1, the neutral curves for Pr=7 in both cases alternate between synchronous and subharmonic responses, with increasingly shorter intervals as omega becomes small. At large omega, the critical wave number k(c) asymptotes to omega(1/2) and the critical Rayleigh number R(c) asymptotes to omega(3/2), via a subharmonic response in both cases. A comparison with the experimental results of Niemela and Donnelly [Phys. Rev. Lett. 57, 583 (1986)] shows fairly reasonable agreement.

Journal Article↗

A 10-year review of a minimally invasive technique for the correction of pectus excavatum.

PURPOSE: The aim of this study was to assess the results of a 10-year experience with a minimally invasive operation that requires neither cartilage incision nor resection for correction of pectus excavatum. METHODS: From 1987 to 1996, 148 patients were evaluated for chest wall deformity. Fifty of 127 patients suffering from pectus excavatum were selected for surgical correction. Eight older patients underwent the Ravitch procedure, and 42 patients under age 15 were treated by the minimally invasive technique. A convex steel bar is inserted under the sternum through small bilateral thoracic incisions. The steel bar is inserted with the convexity facing posteriorly, and when it is in position, the bar is turned over, thereby correcting the deformity. After 2 years, when permanent remolding has occurred, the bar is removed in an outpatient procedure. RESULTS: Of 42 patients who had the minimally invasive procedure, 30 have undergone bar removal. Initial excellent results were maintained in 22, good results in four, fair in two, and poor in two, with mean follow-up since surgery of 4.6 years (range, 1 to 9.2 years). Mean follow-up since bar removal is 2.8 years (range, 6 months to 7 years). Average blood loss was 15 mL. Average length of hospital stay was 4.3 days. Patients returned to full activity after 1 month. Complications were pneumothorax in four patients, requiring thoracostomy in one patient; superficial wound infection in one patient; and displacement of the steel bar requiring revision in two patients. The fair and poor results occurred early in the series because (1) the bar was too soft (three patients), (2) the sternum was too soft in one of the patients with Marfan's syndrome, and (3) in one patient with complex thoracic anomalies, the bar was removed too soon. CONCLUSIONS: This minimally invasive technique, which requires neither cartilage incision nor resection, is effective. Since increasing the strength of the steel bar and inserting two bars where necessary, we have had excellent long-term results. The upper limits of age for this procedure require further evaluation.

Adolescent↗

Lymphadenopathy in children.

Lymphadenopathy is a common problem in children and adolescents. A detailed history and physical examination in addition to knowledge of lymph node anatomy is often adequate for diagnosis. The infectious and noninfectious causes of adenopathy are outlined according to location. Medical and surgical evaluation and treatment are discussed, with special attention given to mycobacterial infections, cat scratch disease, and lymphoma.

Adenoma↗

A comparison: the efficacy of sevoflurane-nitrous oxide or propofol-nitrous oxide for the induction and maintenance of general anesthesia.

STUDY OBJECTIVE: To compare sevoflurane-nitrous oxide with propofol-nitrous oxide for the induction and maintenance of anesthesia, and to determine the rates of recovery following each anesthetic. DESIGN: Randomized, controlled study. SETTING: Teaching hospital. PATIENTS: 50 ASA physical status I and II patients, ranging in age from 18 to 70 years. INTERVENTIONS: General anesthesia was induced with either sevoflurane or propofol and maintained with 60% to 70% nitrous oxide and either sevoflurane or a propofol infusion and supplemental fentanyl. At the conclusion of surgery, the oxygen flow was increased to 6 L/min and all anesthetics were discontinued simultaneously. Patients were monitored for the nature and speed of induction and emergency from anesthesia. MEASUREMENTS AND MAIN RESULTS: Induction of anesthesia was significantly slower in the sevoflurane group than in the propofol group (2.0 +/- 1.1 vs. 0.8 +/- 0.5 min, respectively). The ease of induction and the time required for emergence from anesthesia were the same in both study groups (eye opening: 9.0 +/- 4.4 min vs. 8.0 +/- 5.0 min; following commands: 11.2 +/- 5.0 min vs. 9.8 +/- 6.9 min; extubation: 9.1 +/- 4.5 min vs. 8.6 vs. 5.1 min in the sevoflurane and propofol groups, respectively). Patients in the sevoflurane group experienced nausea and vomiting more frequently than patients in the propofol group (13 and 5 patients vs. 3 and 0 patients in the sevoflurane and propofol groups, respectively), which were not related to the administration of neostigmine or intraoperative opioids. CONCLUSION: Sevoflurane allows for rapid inhalation induction of, and emergence from, general anesthesia.

Adolescent↗

Deficiency of retinoblastoma protein leads to inappropriate S-phase entry, activation of E2F-responsive genes, and apoptosis.

The retinoblastoma susceptibility gene (Rb) participates in controlling the G1/S-phase transition, presumably by binding and inactivating E2F transcription activator family members. Mouse embryonic fibroblasts (MEFs) with no, one, or two inactivated Rb genes were used to determine the specific contributions of Rb protein to cell cycle progression and gene expression. MEFs lacking both Rb alleles (Rb-/-) entered S phase in the presence of the dihydrofolate reductase inhibitor methotrexate. Two E2F target genes, dihydrofolate reductase and thymidylate synthase, displayed elevated mRNA and protein levels in Rb- MEFs. Since absence of functional Rb protein in MEFs is sufficient for S-phase entry under growth-limiting conditions, these data indicate that the E2F complexes containing Rb protein, and not the Rb-related proteins p107 and p130, may be rate limiting for the G1/S transition. Antineoplastic drugs caused accumulation of p53 in the nuclei of both Rb+/+ and Rb-/- MEFs. While p53 induction led to apoptosis in Rb-/- MEFs, Rb+/- and Rb+/+ MEFs underwent cell cycle arrest without apoptosis. These results reveal that diverse growth signals work through Rb to regulate entry into S phase, and they indicate that absence of Rb protein produces a constitutive DNA replication signal capable of activating a p53-associated apoptotic response.

Animals↗

Identification of an origin of bidirectional DNA replication in the ubiquitously expressed mammalian CAD gene.

Most DNA replication origins in eukaryotes localize to nontranscribed regions, and there are no reports of origins within constitutively expressed genes. This observation has led to the proposal that there may be an incompatibility between origin function and location within a ubiquitously expressed gene. The biochemical and functional evidence presented here demonstrates that an origin of bidirectional replication (OBR) resides within the constitutively expressed housekeeping gene CAD, which encodes the first three reactions of de novo uridine biosynthesis (carbamoyl-phosphate synthetase, aspartate carbamoyltransferase, and dihydroorotase). The OBR was localized to a 5-kb region near the center of the Syrian hamster CAD transcriptional unit. DNA replication initiates within this region in the single-copy CAD gene in Syrian baby hamster kidney cells and in the large chromosomal amplicons that were generated after selection with N-phosphonacetyl-L-aspartate, a specific inhibitor of CAD. DNA synthesis also initiates within this OBR in autonomously replicating extrachromosomal amplicons (CAD episomes) located in an N-phosphonacetyl-L-aspartate-resistant clone (5P20) of CHOK1 cells. CAD episomes consist entirely of a multimer of Syrian hamster CAD cosmid sequences (cCAD1). These data limit the functional unit of replication initiation and timing control to the 42 kb of Syrian hamster sequences contained in cCAD1. In addition, the data indicate that the origin recognition machinery is conserved across species, since the same OBR region functions in both Syrian and Chinese hamster cells. Importantly, while cCAD1 exhibits characteristics of a complete replicon, we have not detected autonomous replication directly following transfection. Since the CAD episome was generated after excision of chromosomally integrated transfected cCAD1 sequences, we propose that prior localization within a chromosome may be necessary to "license" some biochemically defined OBRs to render them functional.

Animals↗

Succinylcholine increases intraocular pressure in the human eye with the extraocular muscles detached.

BACKGROUND: The increase in intraocular pressure in the human eye that is associated with the use of intravenous succinylcholine has long been ascribed to contraction of the extraocular muscles leading to compression of the globe. This created concern that such contraction would extrude global contents in the patient with an open globe, and led clinicians to avoid the use of succinylcholine in these patients. METHODS: The authors studied 15 patients undergoing elective enucleation, and compared the intraocular pressure change after the administration of succinylcholine in the diseased eye after all the extraocular muscles had been detached to that of the normal eye that had the extraocular muscles attached. RESULTS: The authors found no difference in baseline intraocular pressure (mmHg) between eyes (15.1 vs. 16.1) or at peak intraocular pressure (25.2 vs. 24.7), but did observe a significant difference in pressure in both eyes when baseline was compared with peak pressure. CONCLUSIONS: The authors concluded that extraocular muscle contraction does not contribute to the increase in intraocular pressure after succinylcholine.

Adult↗

Early and long-term effects of colectomy and endorectal pullthrough on bile acid profile.

OBJECTIVE: Although total colectomy with mucosal proctectomy and endorectal pullthrough affects two sites critical to the enterohepatic circulation of bile acids, little information is available regarding the manner in which normal digestive physiology is altered by these procedures. This study defines the early and long-term effects of colectomy and endorectal pullthrough on bile acid profile and the long-term effects on biliary lipid metabolism. SUMMARY BACKGROUND DATA: Specific changes in bile acid absorption have been reported in patients after ileal resection. Recent studies from our laboratory indicate that in the early postoperative period, colectomy with endorectal pullthrough causes a significant decrease in gallbladder bile concentrations of total bile acids, cholesterol, phospholipids, and calcium. The observation by several authors that the pouch undergoes morphologic and perhaps functional adaptation suggest that these changes may be transient and perhaps reversible. METHODS: These studies were done in an awake, unanesthetized canine model that allows periodic sampling of gallbladder bile without creation of an external biliary fistula and its associated sequelae. Animals were ultimately randomly assigned to either laparotomy and gallbladder cannulation (N = 6), or gallbladder cannulation with total colectomy and ileorectal anastomosis (N = 7), or biliary cannulation, colectomy, mucosal proctectomy and endorectal pullthrough with ileal reservoir (N = 5). RESULTS: Six weeks after operation, colectomy and ileorectal anastomosis were associated with a significant alteration in the relative composition of bile acids in gallbladder bile. These early changes were manifested by a significant (p < 0.05) increase in taurocholic acid and a concomitant decrease in taurodeoxycholic acid. These changes became even more pronounced in the ileorectal anastomosis group 12 weeks after colectomy and ileorectostomy. Although similar changes in the relative concentrations of individual bile acids occurred in the 6-week endorectal animals, bile acid profile was restored to normal by 12 weeks. CONCLUSIONS: Colectomy with ileorectal anastomosis leads to early and significant changes in bile acid profile, which persist and become even more pronounced with time. In contrast, the construction of an ileal reservoir after colectomy facilitates restoration of a normal bile acid profile. We propose that these alterations in bile acid metabolism result from adaptation of the ileal reservoir as its mucosa assumes functional characteristics of normal colon.

Adaptation, Physiological↗

The effect of lumbar disc surgery on postoperative pulmonary function and temperature. A comparison study of microsurgical lumbar discectomy with standard lumbar discectomy.

Preoperative and postoperative pulmonary function and body temperature were measured prospectively in 15 patients undergoing either microlumbar discectomy or standard lumbar laminectomy and discectomy for herniated nucleus pulposus. In these otherwise comparable groups patients undergoing standard lumbar laminectomy and discectomy had significant depression in pulmonary function in the first 20 hours postsurgery and febrile temperatures for as long as 48 hours postsurgery. No alteration in pulmonary function or body temperature was observed in those operated on by the microlumbar discectomy technique. We conclude that patients undergoing microlumbar discectomy for lumbar disc herniation have less postsurgical pulmonary morbidity and temperature elevation than those treated by lumbar laminectomy and discectomy.

Adult↗

Localization of a bidirectional DNA replication origin in the native locus and in episomally amplified murine adenosine deaminase loci.

Gene amplification is frequently mediated by the initial production of acentric, autonomously replicating extrachromosomal elements. The 4,000 extrachromosomal copies of the mouse adenosine deaminase (ADA) amplicon in B-1/50 cells initiate their replication remarkably synchronously in early S phase and at approximately the same time as the single-copy chromosomal locus from which they were derived. The abundance of ADA sequences and favorable replication timing characteristics in this system led us to determine whether DNA replication initiates in ADA episomes within a preferred region and whether this region is the same as that used at the corresponding chromosomal locus prior to amplification. This study reports the detection and localization of a discrete set of DNA fragments in the ADA amplicon which label soon after release of synchronized B-1/50 cells into S phase. A switch in template strand complementarity of Okazaki fragments, indicative of the initiation of bidirectional DNA replication, was found to lie within the same region. This putative replication origin is located approximately 28.5 kbp upstream of the 5' end of the ADA gene. The same region initiated DNA replication in the single-copy ADA locus of the parental cells. These analyses provide the first evidence that the replication of episomal intermediates involved in gene amplification initiates within a preferred region and that the same region is used to initiate DNA synthesis within the native locus.

Adenosine Deaminase↗