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Biomedical subjects

R J Mullins

Publications and source records attributed to R J Mullins.

At least 73 records · Page 4Linked to original sources
PubMed1992

Serological response to purified mycobacterial phosphatidylinositol mannoside in healthy controls and in patients with tuberculosis and leprosy.

The serological response to a monoclonal antibody-defined phosphatidylinositol mannoside (L4-PIM) present in all mycobacteria was examined in patients with various mycobacterial diseases and healthy subjects from different populations. IgG but not IgM antibodies were detected in most patients with untreated lepromatous (84%) or borderline lepromatous (65%) leprosy, but in only a minority of those with disease at the tuberculoid end of the leprosy spectrum (< 17% positive). The response to L4-PIM was correlated with the IgM response to disaccharide octyl-bovine serum albumin (dBSA), and decreased with successful treatment. On the other hand, the test proved to be of little value in the diagnosis of untreated tuberculosis (4/15 positive) or atypical mycobacterial infection in patients with AIDS (0/11 positive). IgG antibodies to L4-PIM were also found in a significant proportion of healthy individuals, irrespective of their Mantoux status. These antibodies were shown to be specific for L4-PIM on immunoblotting, and their incidence increased with age in random donors from both urban Australia and rural Papua New Guinea. Despite the limited value of the assay in diagnosis of any particular mycobacterial disease, the presence of antibodies to L4-PIM appears to be a sensitive indicator of subclinical infection with environmental mycobacteria in subjects with an intact immune system.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Isolation and structural characteristics of a monoclonal antibody-defined cross-reactive phospholipid antigen from Mycobacterium tuberculosis and Mycobacterium leprae.

A low molecular weight antigen of Mycobacterium leprae and other mycobacteria was previously defined in our laboratory by means of IgG2a monoclonal antibody termed L4. The antigen had an apparent molecular mass of 4.5-6 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was assumed to be a glycoprotein on the basis of its staining with periodic acid Schiff and sensitivity to periodate treatment. In the present work, the cross-reactive and phospholipidic nature of the antigen, present in Mycobacterium tuberculosis as well as in M. leprae sonicates, was demonstrated and this enabled us to undertake its purification from crude M. tuberculosis phospholipidic extracts. The L4-reactive antigen from M. tuberculosis called L4-PIM, was purified by means of silicic acid high pressure liquid chromatography. Its characterization by gas chromatography and FAB-MS showed the antigen to be the common mycobacterial dimannosylated phosphatidylinositol (PIM2), the structure of which had been previously established by others (Lee, Y. C., and Ballou, C. E. (1964) J. Biol. Chem. 239, 1316-1327; Lee, Y. C., and Ballou, C. E. (1965) J. Biochem. (Tokyo) 4, 1395-1404). Delineation of the L4 epitope on M. tuberculosis L4-PIM revealed the involvement of the axial 2-hydroxyl of the alpha-D-mannosyl residues, without any detectable contribution from the myo-inositol. Consequently, L4 was shown to react with PIM5, the structure of which contains twice the number of epitopes as does PIM2. By using both immunostained thin layer chromatography and indirect enzyme-linked immunosorbent assay, similar L4-PIM epitopes were demonstrated in M. leprae sonicate, thereby explaining the cross-reactive nature of the L4-monoclonal antibody. Antibodies of IgG class directed against M. tuberculosis L4-PIM were detectable in sera from patients with leprosy, but no evidence of T cell reactivity to L4-PIM was obtained. The demonstration of a correlation of anti-L4-PIM IgG and anti-disacharide-conjugated bovine serum albumin IgM antibody titers in the sera of leprosy patients indicates that measurement of antibodies directed against L4-PIM may have the potential to be used as a complementary assay to the disaccharide-conjugated bovine serum albumin test for diagnosis and monitoring of patients undergoing leprosy therapy.

Antibodies, Monoclonal↗
PubMed1991

The sustained increase in permeability produced by bradykinin is dose related.

The purpose of this experiment was to determine in skin microvasculature the dose response to bradykinin (BRADY). Over a range 0, 0.2, 0.4, and 0.8 microgram/kg/min BRADY was infused into the femoral artery of anesthetized dogs while lymph was collected from the hind paw. After 4 hours of continuous BRADY, venous pressure was increased 20 to 30 mm Hg by tightening a tourniquet around the thigh to further increase lymph flow and achieve a filtration-independent lymph-plasma ratio, for albumin (R Alb), immunoglobulin G (R IgG), and immunoglobulin M (R IgM). These proteins were measured with immunoelectrophoresis and immunodiffusion. MEAN +/- SD, * p less than 0.05, ANOVA, DIFFERENT FROM LOWER DOSE. [Formula: see text] BRADY caused a dose-related increase in microvascular permeability up to 0.4 microgram/kg/min. The increase in the lymph-plasma ratio for the large plasma proteins (IgM, molecular radius 110 A) is of the same magnitude as for albumin, (molecular radius 36 A), and this suggests BRADY increased the number but not the size of "large pores" in the microvascular membrane.

Animals↗
PubMed1991

Effect of fluid resuscitation from endotoxin shock on lung transvascular fluid and protein exchange.

The hypothesis that volume expansion during septic shock produces a greater transvascular protein flux than volume expansion alone was tested in anesthetized sheep by giving a high dose of endotoxin (40 micrograms/kg) intravenously. After 0.5 h of systemic hypotension, Ringer lactate, equivalent to 8% body wt, was infused followed by an additional 4 h of lymph collection. The results were compared with those from control animals receiving only Ringer lactate. The changes in plasma total protein with time were similar between groups. The increases in lymph flow and lymph protein flux were greater in the endotoxin-challenged group compared with the control group receiving Ringer lactate during the first 2 h but were similar thereafter. The interstitial volume was greater in the endotoxin-challenged animals compared with controls. The extravascular masses or apparent tissue concentrations for albumin or immunoglobulin G did not change in either group receiving Ringer lactate. The pulmonary edema following resuscitation from septic shock with Ringer lactate could be accounted for by either the pulmonary hypertensive effects of endotoxin or an initial, transient increase in microvascular protein permeability but not a sustained increase in microvascular permeability.

Animals↗
PubMed1990

Samuel D. Gross: pioneer academic trauma surgeon of 19th century America.

It is appropriate on the 50th anniversary of the American Association for the Surgery of Trauma to recall the most influential trauma surgeon in 19th century America: Samuel D. Gross. Gross was an innovative surgeon whose 50-year career as a surgeon caring for injured patients encompassed orthopedics, thoracic surgery, abdominal surgery, and ophthalmology. The dominant influence of Gross over contemporary surgical doctrine was a consequence of his prolific scholarship which included six superbly written texts that passed through a combined total of 15 editions. Gross was a teacher, occupying for 42 years Chairs of Surgery at three medical schools. Gross wore the mantle of political leadership, founding medical societies that continue today as forums for the presentation and review of new treatments for injured patients. Modern academic trauma surgeons could do no better than to emulate the career of Samuel David Gross, the Patriarch of American trauma surgeons.

General Surgery↗
PubMed1990

The management of penetrating pelvic trauma.

Eighty-nine patients with penetrating pelvic trauma were treated during a three-year period. Sixty-three of 72 patients who had mandatory exploration had findings at operation. The negative laparotomy rate was higher for patients with posterior penetrations (40%). Diagnostic peritoneal lavage, sigmoidoscopy, and intravenous pyelography were useful adjunctive tests to confirm the lack of need for exploration in patients with negative physical findings. This protocol of tests was particularly useful for patients with posterior sites of injury. Patients with injury to multiple organ systems had a higher rate of infectious complications (48%) than those with single system injury (11% complication rate). Primary repair of colon, urologic and vascular injuries was safe even in patients with injury to multiple organ systems.

Adolescent↗
PubMed1989

Nasal histamine challenges in symptomatic allergic rhinitis.

Twenty subjects (seven with perennial allergic rhinitis, seven with symptomatic seasonal allergic rhinitis, and six normal control subjects) underwent assessment of nasal sensitivity to histamine. Nasal resistance was measured by posterior rhinometry under control conditions and after log incremental doses of histamine solution pipetted into the nose (0.5 to 5000 micrograms). Allergic subjects exhibited a twofold rise of nasal resistance with doses of 0.5, 5, or 50 micrograms of histamine, whereas the nasal resistance in normal subjects remained unchanged until 500 or 5000 micrograms of histamine had been administered. Nasal reactivity to histamine was not correlated with symptoms on the day of testing but was correlated with the number of positive wheals to skin prick testing. It was concluded that nasal resistance is more sensitive to histamine in subjects with allergic rhinitis than in normal control subjects and that this difference may be used as the basis of a diagnostic test.

Administration, Intranasal↗
PubMed1989

Fractional change in blood volume following normal saline infusion in high-risk patients before noncardiac surgery.

Patients with multiple-system disease were considered to be at high-risk to develop cardiac complications when undergoing an elective noncardiac surgical procedure. Their operative risk was prospectively assessed by a protocol that included recording the presence of established clinical risk factors and measuring the hemodynamic response to an intravenous infusion of up to 2 L of normal saline given over a two-hour period. The day prior to their operations, 126 patients were admitted to the Surgical Intensive Care Unit, where pulmonary artery catheters were inserted without serious complications. One hundred and eleven patients tolerated the entire 2-L infusion. The hemoglobin concentration of blood was measured before and after the infusion. The fractional change in blood volume (BV after/BV before) calculated with hemoglobin data was 1.06 +/- 0.06 (mean +/- SD). A multivarient discriminant analysis showed that the fractional change in blood volume was a covariant with a higher correlation rank than the hemodynamic data in identifying patients at risk for an adverse outcome.

Aged↗
PubMed1989

Isoproterenol inhibits the increase in microvascular membrane permeability produced by bradykinin.

Bradykinin (BRADY) is hypothesized to cause the "capillary leak" syndrome in patients with sepsis, trauma, and burns. Our purpose was to determine if isoproterenol (ISO) reversed a BRADY-produced accelerated loss of intravascular fluid and protein into the interstitium of skin. An increase in microvascular permeability in canine hind paw skin was sustained by a continuous femoral artery infusion of BRADY (0.2 micrograms/kg/min). After 2 hours of BRADY, skin lymph flow (LYM FLOW microliters/min) increased nine-fold and skin lymph-to-plasma total protein concentration ratio (RTP) was substantially increased. Mean blood flow in the femoral arteries was increased four-fold by the BRADY infusion. After 2 hours of BRADY-induced increased permeability, five of the ten dogs were started on intravenous ISO (2 micrograms/min continuously) which increased heart rate from 182 +/- 15 to 222 +/- 11 beats/min. ISO reversed the increase in RTP produced by the BRADY. After 8 hours of BRADY, there was less tissue albumin in the dogs given ISO (14.5 +/- 2.0 vs. 29.5 +/- 6.6 mg/gram dry wgt, p less than 0.05 unpaired t-test). ISO can reverse the sustained increase in skin microvascular permeability produced by BRADY.

Animals↗
PubMed1989

Proximal gastric vagotomy for duodenal ulcer disease.

Proximal gastric vagotomy is a useful operation for duodenal ulcer disease that is intractable to medical management. It is also useful in selected patients with acute duodenal ulcer perforation. We present an overview of the indications for proximal gastric vagotomy, along with its results. The major benefits of proximal gastric vagotomy are low operative mortality and a low incidence of late complications.

Acute Disease↗
PubMed1989

Inhibition of human lymphoproliferative responses by mycobacterial phenolic glycolipids.

The effect of mycobacterial phenolic glycolipids from Mycobacterium leprae, M. bovis BCG, and M. kansasii on in vitro proliferative responses by human blood mononuclear cells from healthy BCG vaccinees was investigated. All three phenolic glycolipids inhibited proliferation in a concentration-dependent manner. Inhibition was independent of the stimulus used and involved neither antigen-presenting cells nor antigen-specific CD8+ suppressor T cells. It was concluded that the phenomenon may be a general property of mycobacterial phenolic glycolipids, perhaps analogous to the growth-modulating properties of gangliosides. Despite the lack of specificity of inhibition in vitro, de facto specificity may occur in vivo by virtue of the localization of glycolipid in the leprosy lesions.

Antigen-Presenting Cells↗
PubMed1989

Effect of preincubation on the proliferative response to antigen by cells from leprosy patients and healthy controls.

One of the postulated mechanisms contributing to the selective T-cell hyporesponsiveness in patients with leprosy is receptor blockade, the characteristic feature of which is reversibility following preincubation of cells in vitro. To test this hypothesis, peripheral blood mononuclear cells (PBMC) obtained from 17 leprosy patients and 10 healthy Mantoux-positive and -negative controls were cultured freshly or after a period of preincubation in serum-containing medium, and the proliferative responses to Mycobacterium leprae, BCG, and streptokinase-streptodornase (SKSD) were measured. On the basis of the response to M. leprae, the leprosy patients could be divided into low, intermediate and high responders. Preincubation for 2-16 hr resulted in enhanced proliferation by cells from moderate responders, but not from low or high responders. Although the effect was serum dependent, it was neither antigen specific nor was it confined to cells from leprosy patients. Thus, an increase in response to both the crossreactive and unrelated antigens BCG and SKSD occurred, and the same trend was observed when cells from healthy controls were preincubated in serum-containing medium. Furthermore, cells from different individuals displayed varying responses to different antigens following preincubation, suggesting that the effect of this step was neither confined to isolated individuals nor to particular antigens. The addition of pronase to the preincubation step did not further enhance the response to antigen over and above that obtained with preincubation alone. It was therefore concluded that the enhanced proliferative response to antigen following preincubation was an in vitro phenomenon dependent upon the culture conditions employed, was not specific to leprosy, and was not related to receptor blockade.

Antigens, Bacterial↗
PubMed1988

Multiple adenocarcinomas of the colon and rectum. An analysis of incidences and current trends.

Three hundred forty-five colorectal cancers were identified in 320 patients over a nine-year period. Twenty-one patients (7 percent) had synchronous cancers. Metachronous cancers were identified in five patients (2 percent). Thirteen of the synchronous cancers were foci of invasive adenocarcinoma in polyps with elements of benign neoplastic tissue. There was a trend for younger patients to have multiple colon cancers. Fifteen percent of the synchronous colon cancer patients were less than 50 years of age. The mean age of patients who presented with metachronous cancer was 54, and 11 years was the average time interval between the diagnosis of the initial and the metachronous tumor. Colonoscopy proved to be more reliable than barium-enema examinations in identifying synchronous cancers. It is concluded from this review that before elective resections, colonoscopy should be used to effectively screen patients for synchronous cancers, and following curative resection, the residual colon should be periodically examined for the remainder of the patient's life.

Adenocarcinoma↗
PubMed1988

Experimental methods in the pathogenesis of limb ischemia.

Ischemia of extremities is responsible for considerable morbidity and mortality and the pathophysiology of this condition warrants further study. The purpose of this review is to discuss techniques used in the evaluation of limb ischemia and reperfusion. It is of critical importance to study limb blood flow distribution to the microcirculation where nutritive exchange occurs. Skeletal muscle ischemia progresses to infarction when critical deficits of cellular metabolites develop, which mandates that studies be focused at the cellular level. It is clear that the adverse effects of ischemia can be exacerbated by a reperfusion injury to the endothelium of the microvasculature. Investigators wishing to study limb ischemia have a wide spectrum of methodology and established models available to use in improving the understanding of the complex events of ischemic injury.

Animals↗
PubMed1988

Controversies in the management of pancreatic pseudocysts.

Review of the diagnosis and treatment of patients with pancreatic pseudocysts over the past 8 years has led us to three conclusions regarding controversial aspects of their treatment. We found that patients who present with chronic pseudocysts can be identified with the help of computerized axial tomography and promptly undergo successful internal drainage, whereas patients with acute peripancreatic fluid secondary to pancreatitis can be observed expectantly with a 43 percent frequency of spontaneous resolution. Patients with infected pancreatic pseudocysts can be safely drained internally. The most common cause of extrahepatic biliary obstruction in this group of patients with pancreatic pseudocysts was stricture due to pancreatitis and fibrosis, not extrinsic compression.

Adult↗
PubMed1988

AIDS and the heart.

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Acquired Immunodeficiency Syndrome↗
PubMed1988

Management of recurrent duodenal ulcer disease.

The purpose of this project was to evaluate the medical and surgical treatment of patients with recurrent peptic ulcer disease and to determine whether the addition of cimetidine has altered the treatment outcome. The authors studied 42 patients with recurrent ulcers after duodenal ulcer surgery. Four patients underwent emergency operation for ulcer-related complications, while 38 patients received medical therapy including cimetidine as initial treatment. Medical therapy achieved good results in 18 of 38 patients (47%). The remaining 20 patients either were treated surgically (14) or are still symptomatic. Four of the 18 patients managed operatively had a second recurrent ulcer (22%). There were no deaths. Thirty-two of the original 42 patients (76%) were helped by the treatment. It was concluded that cimetidine has improved medical therapy compared with historical controls but that operative treatment is indicated in about one-half of patients with recurrent peptic ulcer disease.

Anti-Ulcer Agents↗