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Biomedical subjects

J Norman

Publications and source records attributed to J Norman.

At least 109 records · Page 6Linked to original sources
PubMed1995

Prolonged evaluation of epinephrine and normal saline solution injections in an acute ulcer model with a single bleeding artery.

BACKGROUND: Animal studies of epinephrine or normal saline solution injection for bleeding ulcers do not consistently demonstrate local tamponade effect. METHODS: We studied the change of bleeding rates of 28 acute gastric ulcers with a single bleeding artery in 10 dogs. Four injections of 1 mL epinephrine 1:10000 at 1 mm from the spurting artery (n = 7) were compared to four injections of normal saline solution 1 to 5 mL (n = 12) and to four dry needle sticks (n = 9). Bleeding rates were measured at initial arterial incision and at minutes 1, 5, 10, 15, 20, 25, and 30 after treatment. RESULT: Reductions in early blood loss to 24.3% +/- .05 of baseline occurred with saline solution, to 17.7% +/- .03 with epinephrine, and to 66.0% +/- 1.8 in controls (p < .05 for epinephrine and saline solution vs control). A tendency for saline solution injected ulcers to resume bleeding was identified, with late blood loss increasing to 26.9% +/- .05 of baseline, (saline solution vs control) compared to 7.7% +/- .02 in epinephrine injected ulcers (p < .05 vs control). CONCLUSIONS: The early acute hemostatic effect of injection therapy depends on local tamponade. The prolonged hemostatic effect is a combination of tamponade and vasoconstriction, with advantage of epinephrine over saline solution.

Animals↗
PubMed1995

Interleukin-1 receptor antagonist decreases severity of experimental acute pancreatitis.

BACKGROUND: Fulminant acute pancreatitis is a disease of complex origin that results in activation of several of the proinflammatory cytokines. Because interleukin-1 (IL-1) is an integral early component of the acute inflammatory process, the use of an IL-1 receptor antagonist (IL-1ra) was investigated in experimental acute pancreatitis to determine the therapeutic potential of proximal cytokine blockade and to further establish the role of inflammatory cytokines in the pathogenesis of acute pancreatitis. METHODS: IL-1ra was administered in escalating doses either before or after acute edematous, necrotizing pancreatitis was induced in adult male mice by injection of cerulein. The severity of pancreatitis was quantified by serum amylase, lipase, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels, pancreatic wet weight, and blinded histologic grading. RESULTS: Administration of medium (10 mg/kg) and high (100 mg/kg) doses of IL-1ra either before or after the induction of pancreatitis significantly decreased the expected rise in pancreatic wet weight, lipase, IL-6, and TNF-alpha (all, p < 0.01). Serum amylase was significantly reduced when IL-1ra was administered in either dosage before (p < 0.05), but not after, induction of pancreatitis. Pancreatic edema, necrosis, and inflammatory cell infiltrate were significantly diminished (p < 0.05) by histologic grading in all animals receiving medium or high doses of IL-1ra. Low doses of IL-1ra (1.0 mg/kg) had modest effects if given before, but no effect if given after, induction of pancreatitis. CONCLUSIONS: The proinflammatory cytokines IL-6 and TNF-alpha are elevated during experimental acute pancreatitis and correlate well with the severity of local pancreatic destruction. Blockade of the cytokine cascade at the level of the IL-1 receptor before or soon after induction of pancreatitis significantly attenuates the rise in these cytokines and is associated with decreased severity of pancreatitis and reduced intrinsic pancreatic damage.

Acute Disease↗
PubMed1995

Cancer gene therapy using plasmid DNA: safety evaluation in rodents and non-human primates.

To evaluate the safety of a plasmid DNA-lipid complex, a series of good laboratory practice (GLP) safety studies were conducted with VCL-1005, a plasmid DNA expression vector containing both the human class I MHC HLA-B7 heavy-chain and the beta 2-microglobulin (beta 2m) light-chain genes formulated with the cationic lipid, DMRIE/DOPE. In mice, the repeated intravenous injection of VCL-1005 at plasmid DNA doses of 0.1, 1.0, or 10 micrograms for 14 days had only incidental effects on clinical chemistry and hematology, and did not result in any organ pathology. Repeated intrahepatic injections of VCL-1005 in mice did not result in significant liver histopathology or significant alterations in liver enzymes. In cynomolgus monkeys, the repeated intravenous administration of VCL-1005 at a cumulative dose of 720 micrograms of DNA had no effects on clinical chemistry, hematology, or organ pathology. Thus, systemic administration of a plasmid DNA expression vector containing the coding sequence for a foreign MHC class I molecule did not result in significant toxicity or a pathological immune response in animals. These results suggest that the direct transfer of VCL-1005, a plasmid DNA-lipid complex, could be used for the safe in vivo delivery of recombinant DNA for a cancer gene therapy trial.

Animals↗
PubMed1995

Increased morbidity of appendicitis with advancing age.

The early diagnosis of acute appendicitis before progression to gangrene or abscess formation is recognized as important to minimize morbidity from this common disease process. As our population ages, the challenge for expedient diagnosis and intervention in older age groups will become more significant. Prompted by recent unexpected complications occurring in elderly patients, we reviewed 100 consecutive admissions with the diagnosis of appendicitis to a tertiary Veterans Administration hospital. All patients were males and were arbitrarily divided into three age groups: less than 50, 50-70, and greater than 70 years of age. There were no patients less than 20 years old. Operative findings were classified as simple acute appendicitis, ruptured or perforated appendicitis, appendicitis associated with intra-abdominal abscess, and finally other when the operative diagnosis differed from appendicitis. Of the 37 patients less than 50 years of age, 28 were found to have simple acute appendicitis, making this by far the most common finding in this age group (P < 0.05). Only two of the 18 patients aged 50-70 with appendicitis demonstrated simple acute appendicitis, with the remainder having progressed to perforation or abscess formation (P < 0.05). Patients greater than 70 years of age were significantly more likely than any other age group to manifest appendicitis associated with intra-abdominal abscess (10 of 19, P < 0.05). Eight patients died in this series, six of whom were more than 70 years of age. In most cases, mortality was directly attributable to infectious complications of perforated appendicitis. There were no deaths in the under 50 age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Abscess↗
PubMed1995

Occult vascular injuries following gunshot wounds resulting in long bone fractures of the extremities.

The routine use of arteriography following penetrating injuries to the extremities has declined in popularity in recent years. A careful physical examination coupled with Doppler-derived blood pressure has been shown to be sufficient to determine the presence of significant vascular injuries in most circumstances. Evaluating for occult vascular injuries in the presence of a complex wound involving the fracture of a long bone, however, seems to be an exception to this trend in management. This study was undertaken to ascertain the incidence of occult versus clinically apparent vascular injuries in patients suffering gun shot wounds (GSW) to the extremities that were associated with a long bone fracture. To address the value of invasive arteriographic evaluation, physical examination (pulse palpation, Doppler-derived limb blood pressure) was compared to arteriography in 75 consecutive patients following a GSW that resulted in fracture of the tibia/fibula (n = 28), femur (n = 19), humerus (n = 17), or radius/ulna (n = 11). Fourteen patients (19%) had an abnormal physical examination, with 13 (93%) of these also having an abnormal arteriogram. Of the 61 (81%) patients with a normal physical examination, an occult vascular injury was found on subsequent arteriography in 17 (28%). These occult injuries were classified as minor (intimal flap less than one-fourth the diameter of the vessel, segmental narrowing, noncritical branch vessel injury) or major (large intimal flap, occlusion, pseudoaneurysm, A-V fistula). The majority (83%) of occult injuries were minor and did not require operative intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Prolonged intragraft urokinase with a new infusion wire: improved short-term results.

Patients with aged saphenous vein grafts and recurrent symptoms of angina are being seen with increasing frequency [Bourassa: J Am Coll Cardiol 17:1081-1083, 1991]. The treatment of these patients remains a dilemma. Direct balloon angioplasty is frequently complicated by distal embolization and early restenosis [Aureran and Gruentzig: Am J Cardiol 53:953-954, 1984]. There is evidence that thrombus plays a significant role in this occlusive process [Hartmann et al.: J Am Coll Cardiol 18:1517-1523, 1991]. Prolonged intragraft urokinase infusion with a new multiside hole infusion catheter debulks thrombus and permits balloon angioplasty without the usual complications.

Angina Pectoris↗
PubMed1994

Functional glucocorticoid receptor modulates pancreatic carcinoma growth through an autocrine loop.

Several peptide hormones have been shown to influence growth and function in pancreatic carcinoma and have given evidence for an autocrine feedback loop governing the proliferation of these malignant cells. Conversely, steroid hormones including glucocorticoids have been shown to inhibit the growth of pancreatic cancer cells; however, the prevalence of the glucocorticoid receptor or its mechanism of growth suppression in these tumors is unknown. The ability of growth factors thought to be active in this autocrine loop to reverse the glucocorticoid-induced growth inhibition was studied in vitro in a human pancreatic adenocarcinoma (HPAC) cell line with a well-characterized glucocorticoid receptor (GR). The glucocorticoid dexamethasone (DEX) inhibited growth in a dose-dependent manner as measured by a [3H]thymidine incorporation assay as well as an MTT cell proliferation assay. Maximal effects were seen within 48 hr at a concentration of 100 nM DEX, suppressing growth to approximately 18% of control. When the maximally suppressed DEX-treated cells were exposed to exogenous growth factors, they rapidly attained or exceeded the growth rate of control cells: insulin-like growth factor = 106%, transforming growth factor-alpha = 134%, insulin = 151%, and epidermal growth factor = 187% (all P < 0.05, Student's t test). In order to determine the frequency of the GR in pancreatic cancer and the clinical relevance of our findings, immunohistochemical staining for the GR was performed on 20 human tumors. Twelve (60%) of all cancers, as well as all normal pancreatic tissues (n = 4), stained positively for cytoplasmic and/or nuclear GR with expression correlating highly with degree of tumor differentiation (Kruskal-Wallis test, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma↗
PubMed1994

Perineal reconstruction after surgical extirpation of pelvic malignancies using the transpelvic transverse rectus abdominal myocutaneous flap.

BACKGROUND: The nonhealing perineal wound is often a catastrophic complication after aggressive surgical extirpation of pelvic malignancies. METHODS: Eleven patients underwent perineal reconstruction using an inferiorly based transpelvic transverse rectus abdominal myocutaneous (TRAM) flap for large nonhealing postsurgical perineal wounds. After debridement of the perineum, the rectus muscles and their skin islands were mobilized, preserving their inferior epigastric blood supply. The flap was then taken through the midline abdominal incision transpelvically into the perineal defect. The study population was composed of three men and eight women ranging in age from 43 to 76 years (mean 59). The primary diagnosis was recurrent carcinoma of the rectum or anus (n = 5), recurrent squamous cell carcinoma of the vulva or cervix (n = 4), and recurrent sacral chordoma (n = 2). All patients had received adjuvant radiation therapy and all patients had undergone one to four previous attempts at perineal closure. The perineal defect ranged in size from 72 cm2 to 1,250 cm2 (mean 337). RESULTS: There were no perioperative deaths. Ten of the 11 patients (91%) had primary wound healing of the TRAM flap, perineal wound, and donor site. One patient with recurrent chordoma developed recurrent tumor at the suture line 4 months postoperatively. CONCLUSIONS: The inferiorly based transpelvic TRAM flap is a safe and effective reconstructive technique for recalcitrant nonhealing perineal wounds after extirpation of pelvic malignancies.

Adult↗
PubMed1994

The use of lymphoscintigraphy in melanoma of the head and neck.

Lymphoscintigraphy has been shown to be of assistance in defining the lymphatic drainage pattern of melanoma. In this study, lymphoscintigraphy was performed on 25 patients with primary melanoma (stages I and II at diagnosis) of the head and neck to determine whether the lymphatic drainage seen on lymphoscintigram was the same as the surgeon's expected lymphatic drainage. The lymphoscintigrams were discordant in 21 of the patients (84 percent) with drainage to a lymphatic basin not predicted clinically. Based on the discordant lymphoscintigram, a change in surgical therapy occurred in 13 of 21 patients (62 percent). Of the 25 patients, 18 underwent prophylactic node dissections and 7 did not. Of the nodal basins removed, 27 of 38 nodal bases (71 percent) were seen on lymphoscintigraphy. Melanoma metastatic to lymph nodes was removed from nodal basins identified by the lymphoscintigram, but not predicted clinically, in two patients (8 percent). Historical anatomical patterns of lymph drainage and the clinical impression of experienced surgeons cannot reliably predict the pattern of lymphatic drainage in patients with melanoma of the head and neck.

Adolescent↗
PubMed1994

Paroxysmal nocturnal haemoglobinuria and pregnancy.

A woman with paroxysmal nocturnal haemoglobinuria (PNH) who was successfully delivered of 3 healthy infants after 4 pregnancies is reported. The obstetric literature of women with PNH is reviewed and the consequent view presented that judicious advice should not preclude pregnancy in such women.

Administration, Oral↗
PubMed1994

Endothelin-1 and angiotensin-II stimulate delayed mitogenesis in cultured rat aortic smooth muscle cells: evidence for common signaling mechanisms.

The vasoactive peptides endothelin-1 (ET-1) and angiotensin-II (AII) have been implicated in chronic hypertension and may play important roles in related vascular diseases such as restenosis and atherosclerosis. Using a rat aortic smooth muscle (RASM) cell model, both ET-1 and AII induced concentration-dependent delayed increases in DNA synthesis relative to that in the serum-deprived controls. Stimulation of DNA synthesis was maximal at 100 nM for each peptide. All treatment of RASM cells resulted in a greater mitogenic effect (4- to 7-fold) than that observed for ET-1 (3-fold). When added in the presence of AII, ET-1 had a supplemental effect on DNA synthesis (5- to 10-fold above control). Although RASM cells expressed both ETA and AT1 receptors, radioligand binding experiments indicated that approximately 10-fold as many AT1 receptors as ETA receptors were present. In signal transduction studies, ET-1 and AII each elicited concentration-dependent increases in the intracellular Ca2+ concentration. ET-1 and AII also stimulated phosphoinositide metabolism and phosphorylation of a specific substrate for protein kinase-C. The release of total inositol phosphates in response to ET-1 and AII was concentration dependent and inhibited by the ETA receptor-selective antagonist BQ-123 and the AT1 receptor-selective antagonist losartan, respectively. In addition, tyrosine phosphorylation of 120- and 75-kilodalton proteins as well as the mitogen-activated protein kinases p44mapk and p42mapk was observed within 5 min of the addition of either ET-1 or AII. Taken together, these data indicate that ET-1 and AII may promote smooth muscle cell growth through common intracellular signaling mechanisms.

Angiotensin II↗
PubMed1994

Flow cytometry data analysis: comparing large multivariate data sets using classification trees.

This paper describes a method to compare flow cytometry data sets, which typically contain 50,000 six-parameter measurements each. By this method, the data points in two such data sets are divided into subpopulations using a binary classification tree generated from the data. The chi 2 test is then used to establish the homogeneity of the two data sets based on how their data are distributed across these subpopulations. Preliminary results indicate that this comparison method is sufficiently sensitive to detect differences between flow cytometry data sets that are too subtle for human investigators to notice.

Animals↗
PubMed1994

The role of emergent arteriography in penetrating limb trauma.

Routine arteriographic evaluation of patients with penetrating trauma in proximity to major limb arteries has been declining in popularity. Although some controversy still exists, management based on clinical examination alone has been advocated for those without overt signs of vascular injury. To better identify the need for invasive radiologic intervention, 453 limbs (394 patients) sustaining gunshot, shotgun, and stab wounds (331, 28, and 94, respectively) in proximity to a major artery underwent angiography from 1984 through 1990. An arterial injury was demonstrated in 37 (9.4%) of 394 limbs, with a normal vascular examination, but only eight (2.0%) were deemed to require operative intervention. By comparison, 45 (76%) of 59 patients with an abnormal vascular examination (diminished/absent peripheral pulses or decreased Doppler-derived limb blood pressures) had an arterial injury demonstrated by arteriography, with 33 (55.9%) undergoing operative repair. The presence of an associated long bone fracture increased the incidence of angiographically demonstrated vascular injury, but operative intervention was only increased for those with an abnormal vascular exam. A detailed physical examination including Doppler-derived limb blood pressures is essential. In the presence of a normal vascular exam, routine arteriography for proximity of injury is unnecessary. Arteriography should be reserved to identify those few patients with an abnormal vascular examination and an unclear injury who may require vascular repair.

Adolescent↗
PubMed1993

Exogenous epidermal growth factor fails to accelerate functional recovery in the autotransplanted ischemic pig kidney.

The reversibility of ischemic renal injury is dependent on epithelial cell regeneration and repopulation of the nephron. Renal cells produce and respond to many growth factors. In the rat, epidermal growth factor (EGF) is mitogenic for tubular cells and accelerates renal recovery after ischemia. We used a pig renal autotransplant model to evaluate the effect of exogenous EGF on renal recovery in a large animal more analogous to man. Group 1 animals underwent left autotransplant after 120 minutes of warm ischemia and received either a single intra-arterial dose of recombinant human EGF (EGF, 10(-7) M.) (N = 11) or vehicle alone (N = 6). Group 2 animals underwent left autotransplant after 72 hours of cold preservation with Collins' solution and received a similar intra-arterial dose plus a subcutaneous dose of EGF (0.5 ml. of 10(-3) M.) (N = 8) or vehicle alone (N = 6). Contralateral nephrectomy was performed in all animals. Daily creatinine measurements revealed no beneficial effect from EGF on recovery of renal function in Group 1 or 2 animals. Studies of EGF on pig proximal tubular cells demonstrated in vitro mitogenesis; autoradiography with 125I-EGF revealed binding of EGF throughout the kidney. Immunohistochemistry showed significant tubular cell proliferation in response to ischemic injury, without further enhancement from EGF. Thus, although exogenous EGF bound to pig kidney cells and stimulated cell proliferation, we were unable to demonstrate a clinically significant acceleration of recovery from ischemic injury.

Animals↗
PubMed1993

Glycosylation of active human renin is necessary for secretion: effect of targeted modifications of Asn-5 and Asn-75.

Renin is a mammalian aspartic protease that is rate-limiting in the renin-angiotensin cascade. Preprorenin is the translational product of the human renin gene and is secreted as prorenin, an inactive zymogen, primarily from the juxtaglomerular cells of the kidney. It has previously been shown that the 46-amino-acid pro domain is not necessary for the secretion of fully active or mature renin from mammalian cells. Additionally, previous reports indicated that glycosylation of Asn-5 and Asn-75, the two potential sites of N-glycosylation in renin, is not necessary for the secretion of prorenin from mammalian cells. In the present study, the role of N-glycosylation in the secretion of mature renin was examined. Asn to Ser mutations at one or both of the glycosylation sites of mature renin were made and the expression of these constructs was examined in COS, CHO, and Sf9 insect cells. In the absence of the pro sequence, N-glycoylation at Asn-75 was essential for the secretion of active renin protein from all three cell types. The mutation at Asn-75 caused a more dramatic reduction in renin secretion than the mutation at Asn-5. This is in contrast to results previously reported for prorenin.

Animals↗
PubMed1993

An easy approach to laparoscopic cholangiography.

Laparoscopic cholecystectomy has become the procedure of choice for surgical removal of the gallbladder. Intraoperative cholangiography is often needed to define ductal anatomy and to detect choledocholithiasis, a procedure which often proves more difficult than its open counterpart. Several newer cholangiocatheters have been introduced which have made laparoscopic cholangiography easier, however, the standard approach through an existing operating port will usually place the catheter at an odd angle, making catheterization of the cystic duct all but impossible in some cases. To avoid this acute angle between the catheter and the cystic duct, the authors have begun using a standard central line introducer as the port through which the catheter is inserted. When placed in the proper position through the lateral abdominal wall, this approach allows the catheter to be inserted parallel and in line with the cystic duct for much easier and faster cannulation.

Catheterization↗
PubMed1993

Resistance to vecuronium.

A 19-year-old epileptic patient taking carbamazepine was anaesthetised for a sigmoid colectomy. Such patients are reported to show a resistance to the actions of competitive neuromuscular blocking drugs, and a conventional dose of vecuronium (0.1 mg.kg-1) produced relaxation for only 18 min. Subsequently she received vecuronium 6.7 mg.h-1 which kept the first twitch of the train-of-four response at 30% of the control value. Antagonism with neostigmine 1.25 mg produced a rapid and full recovery. The report illustrates the usefulness of monitoring neuromuscular transmission whenever there is an anticipation of an altered response.

Adult↗