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Biomedical subjects

D Denham

Publications and source records attributed to D Denham.

At least 19 recordsLinked to original sources
PubMed2000

Liposome-mediated, nonviral gene transfer induces a systemic inflammatory response which can exacerbate pre-existing inflammation.

Cationic liposome and plasmid-mediated gene transfer has emerged as a novel technique for the targeted delivery of protein-based therapies in acute inflammatory diseases. However, concerns have arisen that cationic liposomes and plasmid DNA have inherent proinflammatory properties which could exacerbate pre-existing inflammatory processes. In healthy mice, intraperitoneal administration of cationic liposomes (200 nmol) complexed to plasmid DNA (100 microg) induced a proinflammatory response characterized by the induction of tumor necrosis factor alpha and interleukin-1beta mRNA expression. The plasma concentrations of the hepatic acute phase proteins interleukin-6, amyloid A, amyloid P, and seromucoid were also increased (P<0.05), and this response was seen in endotoxin-resistant (C3H/HeJ) mice. The inflammatory response associated with gene transfer increased the mortality and severity of experimentally induced sterile inflammation (pancreatitis). We conclude that systemic administration of cationic liposomes and plasmid DNA is associated with induction of the innate immune response which may exacerbate pre-existing inflammatory processes.

Amyloid↗
PubMed1998

TNF but not IL-1 decreases pancreatic acinar cell survival without affecting exocrine function: a study in the perfused human pancreas.

Substantial quantities of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are produced within the pancreatic parenchyma during acute pancreatitis. Recent evidence suggests that IL-1 beta and TNF-alpha propagate acute pancreatitis and intensify the resulting pancreatic acinar cell death. This study examines the direct effect of IL-1 beta and TNF-alpha on pancreatic acinar cells. Human pancreata (n = 6), harvested during organ procurement, were perfused ex vivo through the splenic artery using a sterile, oxygenated colloid solution. Each pancreas was perfused with either recombinant human IL-1 beta or TNF-alpha for 2 h and subsequently with the cholecystokinin analogue caerulein (positive control). Venous effluent was collected continuously and amylase and lipase were determined at 15-min intervals. Pancreatic histology was graded at baseline and following cytokine and caerulein perfusion. To examine the long-term effects of these cytokines on acinar cell viability, additional in vitro studies utilized the AR42J acinar cell line which was exposed to either IL-1 beta or TNF-alpha with survival determined daily by MTT assay. Perfusion of the human pancreas with either IL-1 beta or TNF-alpha did not alter amylase, lipase, or histology. Caerulein did induce pancreatitis as measured by increased amylase, lipase, and pancreatic histology. Survival of pancreatic acinar cells decreased when they were incubated with TNF-alpha but not IL-1 beta. Although present in large amounts within the pancreas during acute pancreatitis, IL-1 beta and TNF-alpha have no direct effect on acinar cell viability or exocrine function acutely nor do they induce pancreatitis. When present for more than 24 h, however, TNF-alpha but not IL-1 beta has a dramatic effect on acinar cell survival.

Acute Disease↗
PubMed1998

Minimally invasive radioguided parathyroidectomy in the reoperative neck.

BACKGROUND: Operations for hyperparathyroidism (HPT) in a previously operated neck present a significant challenge and carry much higher morbidity rates than first-time operations. Our extensive experience with minimally invasive radioguided parathyroidectomy (MIRP) for first-time surgery for HPT has shown this method to be a directed approach to the offending adenoma, suggesting that the technique could be used to minimize reoperative neck surgery as well. METHODS: Over an 11-month period 24 consecutive patients with primary HPT who had undergone at least one previous neck operation were referred for re-exploration. All patients underwent preoperative sestamibi scanning; 21 localized sufficiently to undergo MIRP. RESULTS: All patients were cured after reoperation. Eighteen patients underwent MIRP under local anesthesia as outpatients; 3 MIRPs were done under general anesthesia. Average total operative time was 44 minutes, average incision length was 3.0 cm +/- 0.2 cm. Nineteen of the procedures were completed without any frozen sections. There were no complications. CONCLUSION: MIRP is extremely effective in patients with HPT who have undergone previous neck exploration for parathyroid or thyroid disease. The technique allows for such a directed dissection that smaller incisions and local anesthesia in an outpatient setting are routine.

Adenoma↗
PubMed1998

Transient human gene therapy: a novel cytokine regulatory strategy for experimental pancreatitis.

OBJECTIVE: The purpose of this study was to evaluate the ability to transfect a murine pancreas with a human cytokine regulatory gene (interleukin-10 [IL-10]) and examine the duration of transgene expression, its effect on the normal pancreas, and its antiinflammatory effect during acute pancreatitis. SUMMARY BACKGROUND DATA: Interleukin-1beta and tumor necrosis factor-alpha are known detrimental mediators during the progression of acute pancreatitis, and blockade of either cytokine results in decreased severity of pancreatitis and improved survival. Although gene therapy has been proposed as a method to deliver protein-based therapy during a number of conditions, no means of effectively transfecting the pancreas without inducing injury has been developed. METHODS: A plasmid-human IL-10 construct (pMP6-hIL-10) complexed with cationic liposomes was administered by single intraperitoneal injection to healthy mice. Effective transfection (reverse transcriptase-polymerase chain reaction for hIL-10 mRNA), transfected cell type (in situ polymerase chain reaction for hIL-10 DNA), and the effect on the normal pancreas were determined. Additional animals were transfected to determine the effects of this regulatory gene on the severity of pancreatitis. RESULTS: Nearly 80% of all pancreatic cells expressed human DNA that was subsequently transcribed into mRNA through day 14. The transfection event had no effect on amylase, lipase, or pancreatic histologic appearance. Successful transfection could attenuate subsequently induced pancreatitis (all parameters p < 0.05). CONCLUSIONS: Transient transfection of a human IL-10 gene can be accomplished into all cell types of murine pancreata using a plasmid/ liposome vector. The DNA is effectively transcribed into intact mRNA and does not cause inflammation or acinar cell damage. Transfer of this cytokine regulatory gene decreases the severity of pancreatitis, demonstrating a benefit of gene therapy during this acute inflammatory process.

Amylases↗
PubMed1998

[Keratoprosthesis by posterior fixation and mechanical biocompatibility: determination of intraocular pressure provoking aqueous humor leak and/or extrusion].

The effect of a sudden increase in intraocular pressure (IOP) on Eye Bank eyes implanted with a posterior fixation keratoprosthesis PCL5 type (Lacombe) is evaluated. The IOP was artificially increased at a rate close to that observed in direct eye trauma. The critical pressure values causing aqueous humor leak and/or keratoprosthesis extrusion were compared to those found to blow up unoperated eyes. No statistical difference was found between operated and control eyes (6 pairs of eyes). This KPro type showed its efficacy for keratoprosthesis fixation.

Aqueous Humor↗
PubMed1997

Ablation rate of PMMA and human cornea with a frequency-quintupled Nd:YAG laser (213 nm).

BACKGROUND AND OBJECTIVE: As an alternative to the standard excimer laser used for PRK, we investigated the ablation rate at 213 nm of PMMA, and human corneas under controlled hydration. STUDY DESIGN/MATERIALS AND METHODS: The output of a frequency-quintupled Nd:YAG laser (213 nm) was transformed into a quasi-Gaussian beam. PMMA and corneal lenticules maintained under controlled hydration were ablated until perforation was detected. RESULTS: The ablation rate of PMMA and cornea at 213 nm were similar to that at 193 nm when radiant exposure was below 200 mJ/cm2 and increased gradually between one and two times faster than that at 193 nm when radiant exposure was > 200 mJ/ cm2. CONCLUSIONS: PMMA and cornea ablation at 213 nm are similar to that at 193 nm and are different from that at 248 nm. The difference between PMMA and cornea ablation rates should be considered when using PMMA to test ablated diopter and smoothness for photorefractive surgery.

Cornea↗
PubMed1997

HLA and elephantiasis revisited.

A recent case-control study in Indonesia suggested that the course of Brugian filariasis and in particular resistance to the development of elephantiasis was associated with certain HLA class II alleles. In order to see whether these data could be confirmed we conducted a similar study in another Indonesian population from South Sulawesi. We could not confirm our earlier results and therefore concluded that HLA-DR and -DQ alleles are at least not strongly associated with progression to elephantiasis in Brugian filariasis. The complete data are presented also for anthropological reference purposes.

Alleles↗
PubMed1997

Gene targeting demonstrates additive detrimental effects of interleukin 1 and tumor necrosis factor during pancreatitis.

BACKGROUND & AIMS: During severe pancreatitis, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha are produced in large quantities. The aim of this study was to determine whether either one plays a more dominant role and if their detrimental effects are additive. METHODS: Necrotizing pancreatitis was induced in transgenic (-/-) knockout mice deficient in either IL-1 type 1 receptors, TNF type 1 receptors, or both IL-1 and TNF type 1 receptors. Wild-type mice served as controls. Mortality was assessed for 10 days. Additional animals were killed on days 0, 1, 2, 3, and 4 for determination of pancreatitis severity. RESULTS: All three knockout groups showed decreased amylase and lipase, histological score, serum IL-6, and mortality compared with wild-type groups. Animals devoid of receptors for both cytokines showed improved survival and decreased IL-6 levels compared with those devoid of either IL-1 or TNF receptors individually, yet they failed to show a further decrease in pancreatitis severity. CONCLUSIONS: Preventing the activity of IL-1beta or TNF-alpha has a nearly identical beneficial effect on the severity and mortality of acute pancreatitis. Preventing the activity of both cytokines concurrently has no additional effect on pancreatitis severity but further attenuates the systemic stress response and is associated with an additional but modest decrease in mortality.

Amylases↗
PubMed1992

Photogrammetric analysis of corneal trephination.

We used a high-magnification shadow photogrammetric system to evaluate corneal buttons trephined from human donor globes. Whole eyes were trephined with one of five instruments: nonguarded blades held by hand or placed on a handle, Barraquer-Mateus motorized trephine, Hessberg-Barron suction trephine, or Hanna microkeratotrephine. Corneoscleral buttons were punched with one of three punches: Cottingham, Katena Lieberman guillotine, or a modified Lieberman guillotine with an increased impact force (BPEI 2). The precision (how closely buttons approximated the trephine diameter), accuracy (repeatability), acircularity (deviation from roundness), and straightness (verticality of edges) of cut were calculated from the diameter and edge profile angle measurements of buttons cut by the different instruments. These results were statistically compared. The Hanna microkeratotrephine instrument had the greatest precision and accuracy, least acircularity, and straightest edges. Of the corneal punches evaluated, the Cottingham instrument had the greatest precision; however, the BPEI 2 punch cut with the greatest accuracy and the straightest edges.

Cornea↗
PubMed1989

Shadow photogrammetric apparatus for the quantitative evaluation of corneal buttons.

We have developed a technique for the accurate, quantitative, geometric evaluation of trephined and punched corneal buttons. A magnified shadow of the frontal and edge views of a corneal button mounted on the rotary stage of a modified optical comparator is projected onto the screen of the comparator and photographed. This process takes approximately three minutes. The diameters and edge profile at any meridian photographed can subsequently be analyzed from the film. The precision in measuring the diameters of well cut corneal buttons is +/- 23 microns, and in measuring the angle of the edge profile is +/- 1 degree. Statistical analysis of inter observer variability indicated excellent reproducibility of measurements. Shadow photogrammetry offers a standardized, accurate, and reproducible method for analysis of corneal trephination.

Calibration↗
PubMed1988

A suction trephine block for marking donor corneal buttons.

We describe a technique to accurately align the circumferences of the donor button and host cornea during penetrating keratoplasty. The donor cornea is trephined on a block into which four narrow, intersecting, equally spaced radial cuts are made. Suction is applied to the donor cornea through the four cuts, resulting in four radial marks in the donor corneal epithelium. Four radial marks are also made in the host cornea before trephination, using a radial keratotomy marker. When the donor button is placed within the recipient opening, the radial marks are aligned and used as guides for the cardinal sutures. This simple technique allows for matching of the donor and host circumferences, even if there is some collapse of the peripheral host cornea and sclera at surgery, and should minimize astigmatism resulting from donor/host misalignment.

Astigmatism↗
PubMed1975

A light and electron microscopic study of the changes in the duodenal mucosa induced by sustained pentagastrin stimulation of gastic acid secretion in young rats.

The histological and electron microscopic changes in the duodenal mucosa have been studied over an 8-week experimental period in rats whose gastric acid secretion was stimulated by pentagastrin in a medium of beeswax and mineral oil, and in controls that received injections of beeswax and mineral oil only. The changes leading of final disintegration of the epithelium are described in detail. The main aim of the experiment--to induce mucous change in the duodenal mucosa--was not realized.

Animals↗
PubMed1974

Mucous change in the human duodenum: a light and electron microscopic study and correlation with disease and gastric acid secretion.

The significance of mucous change in the human duodenum in a series of patients with peptic ulcer disease has been appraised. No specific correlation was demonstrated with the acid output of the stomach if the extent of the change is considered, but it was shown to be more common in the higher acid states. Electron microscopic studies confirmed the specific structure of the mucous cells of the duodenum and suggest that they arise either by transformation of Brunner's gland cells or as a distinctive population in the crypts. It is suggested that the mucous change is a protective mechanism involved in some way as yet unknown with the healing of ulcers.

Biopsy↗