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Biomedical subjects

J Norman

Publications and source records attributed to J Norman.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

Non-invasive monitoring of cardiac output changes during aortic cross-clamping for infrarenal reconstruction--a new technique using suprasternal Doppler-derived cardiac output.

There is a significant morbidity and mortality associated with elective infrarenal aortic reconstruction. To examine the value of continuous cardiac output monitoring for predicting those at risk, 40 consecutive patients were monitored using Doppler-derived cardiac output. The anaesthetist was blind to all information from the monitor and managed the patients using standard techniques. In 28 patients there were no observed changes, while in seven, cardiac output rose after aortic cross-clamping. In five patients a fall in cardiac output occurred after cross-clamping. No cardiac events or cardiac deaths occurred in the 35 patients who showed a rise or no change in cardiac output. However, there were three cardiac events, including one cardiac death in the group of five patients in whom a fall in cardiac output was observed. It would appear that intraoperative non-invasive Doppler-derived cardiac output monitoring successfully predicts high-risk patients who would perhaps benefit from more intensive pre-, peri- and postoperative care.

Aged

Laparoscopy through an inguinal hernia for diagnosis of intraperitoneal pathology.

During the repair of an incarcerated inguinal hernia, a 68-year-old gentleman was found to have unsuspected ascites. Upon palpation of the peritoneal cavity through the hernial sac, superficial nodules could be appreciated, suggesting abnormal pathology. A laparoscope was placed through the hernia sac after establishing a pneumoperitoneum through the same approach. This allowed visualization of the entire peritoneal cavity and appropriate exploration of the abdominal viscera. Biopsies confirmed unsuspected metastatic renal cell carcinoma. The authors describe this technique and suggest possible indications for its use.

Aged

Comparison of atracurium-induced neuromuscular block in rectus abdominis and hand muscles of man.

We have compared neuromuscular block in the rectus abdominis and the hand muscles in 11 adult patients. Atracurium 0.5 mg kg-1 was administered by single bolus and anaesthesia maintained with isoflurane and nitrous oxide in oxygen. Train-of-four (TOF) stimulation was applied to the 10th intercostal space in the anterior axillary line and to the ulnar nerve at the wrist. Electromyographic (EMG) responses were recorded over the rectus abdominis and hypothenar muscles. Neuromuscular block had a significantly faster onset in the rectus abdominis (mean 1.6 (SEM 0.2) min) than in the hand (2.4 (0.3) min) (P less than 0.001). Recovery occurred more rapidly in the rectus abdominis: time to 25% TOF recovery was 39 (3) min at rectus abdominis and 51 (4) min at the hand (P less than 0.001). Time to 75% TOF recovery was 56 (4) min at rectus abdominis and 72 (6) min at the hand (P less than 0.001).

Abdominal Muscles

One-compartment kinetics.

The mathematical development of the equations needed to determine the plasma concentrations of drug in a one-compartment pharmacokinetic model are developed from first principles and are illustrated (with caution) by the use of morphine given by bolus or continuous i.v. injection or by a simulated i.m. injection. The equations allow the calculation of concentrations, given a knowledge of what drug is currently present, what are the sizes of the boluses by either i.m. or i.v. injection and what is the constant infusion rate. What happens when changes occur is also illustrated. The development illustrates the principles needed to apply to more complex models.

Humans

Lymphoscintigraphy in malignant melanoma.

The development and rationale for the use of lymphoscintigraphy in the preoperative evaluation of patients with malignant melanoma being considered for elective lymph node dissection is reviewed. This overview is updated by an analysis of 135 patients with early stage malignant melanoma involving the head, neck, shoulders, and trunk at Moffitt Cancer Center and Research Institute at the University of South Florida (Tampa, FL). High discordancy rates (overall, 41%) were seen between drainage patterns predicted from historical anatomical guidelines and those revealed by the lymphoscintigraphic examination. The high discordancy rate was most pronounced in the head (64%) and the neck (73%). Surgical management was changed in 33% of the patients, overall. A preoperative lymphoscintigram is recommended for all patients with melanoma with head, neck, and truncal lesions evaluated for elective lymph node dissection as the lymphatic drainage patterns are often unpredictable and variable.

Decision Making

Metastatic melanoma with an unknown primary.

An infrequent initial presentation for malignant melanoma is the diagnosis of metastatic disease without a history of an obvious primary lesion. Confusion exists in the literature concerning the workup, treatment, and prognosis of the unknown primary melanoma. A retrospective, computer-aided chart review of 580 consecutively registered patients with melanoma at the University Treatment Center (Tampa, FL), identified 18 patients with an unknown primary presentation. There were 10 males and 8 females with a mean age of 38.4 years. Ninety-four percent of the patients were diagnosed with metastatic disease in a nodal basin, whereas 1 patient had a resected isolated lung mass as the initial presentation. In the patients who presented after having a biopsy of a single positive node for diagnosis, more disease was recovered in the nodal basin with a formal node dissection in 59% of the patients. Actuarial survival curves were constructed for the group with unknown primary melanoma. As a control population, survival curves were constructed of the subpopulation of patients with melanoma who had a known primary and had stage III (regional nodal disease) at diagnosis. There was no difference in survival between those with known and unknown primary melanoma (p = 0.96).

Adolescent