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Biomedical subjects

R McKenzie

Publications and source records attributed to R McKenzie.

At least 19 recordsLinked to original sources

Regulation of complement activity by vaccinia virus complement-control protein.

A major protein secreted by vaccinia virus-infected cells has structural similarity to the super-family of complement-control proteins. This vaccinia complement-control protein (VCP) was studied to determine how it regulates complement activation. VCP was bound by C4b and C3b and served as a cofactor with factor I in cleaving these two molecules. VCP inhibited the formation and accelerated the decay of the classical C3 convertase. It also accelerated decay of the alternative pathway convertase, although higher concentrations were apparently needed. In vitro, therefore, VCP interfered with the classical and alternative complement pathways at several steps. In vivo, this interference may increase the virulence of vaccinia virus by enabling it to escape attack by the host's complement system.

Complement Activation

Prophylactic intravenous ondansetron in female outpatients undergoing gynaecological surgery: a multicentre dose-comparison study.

The efficacy and safety of prophylactic intravenous ondansetron in preventing postoperative nausea and vomiting was investigated in a randomized, stratified, double-blind, placebo-controlled, dose-comparison study of 580 ASA physical class I and II female outpatients undergoing gynaecological surgery and receiving general anaesthesia. Patients received either ondansetron 1, 4 or 8 mg, or placebo i.v. immediately prior to a standardized technique for induction and maintenance of anaesthesia. All patients were intubated and received nitrous oxide and a narcotic. All doses of ondansetron were significantly more effective than placebo in preventing emesis over the 24 h postoperative period. Ondansetron significantly decreased nausea and emesis scores over 24 h postoperatively without causing sedation. No changes in laboratory parameters (haematology, blood chemistry, and liver enzymes) or vital signs (heart rate, blood pressure, and respiratory rate) were observed. Headache and dizziness were the most common side-effects; however, their incidence was the same as with placebo. Ondansetron was generally well tolerated, as evidenced by an adverse event, laboratory safety, and vital sign profile similar to placebo. Ondansetron 4 mg was found to be the optimal prophylactic i.v. dose for female outpatients over the entire 24 h postoperative period. Higher doses may offer an added benefit in some patients, such as those with a history of nausea and vomiting following general anaesthesia.

Adult

Side effects of morphine patient-controlled analgesia and meperidine patient-controlled analgesia: a follow-up of 500 patients.

Many physicians, Certified Registered Nurse Anesthetists (CRNAs), and registered nurses have the clinical impression that either morphine sulfate or meperidine hydrochloride is a better drug to control postoperative pain. In this study, we evaluated pain relief and side effects for these two drugs to assess their potential differences. CRNAs conducted a structured interview of 500 female patients 24 hours after major gynecologic, urologic, or breast surgery. Patients' responses on 4-point scales of none, mild, moderate, and severe were collected for pain intensity, degree of nausea, severity of vomiting and itchiness, and degree of sedation experienced since the operation. There were 91 patients who received morphine patient-controlled analgesia (PCA) and 409 patients administered meperidine PCA. No statistically significant differences for pain intensity, degree of nausea, severity and incidence of vomiting, or degree of sedation were found. However, a significant difference was found in the incidence rates of mild itchiness, which occurred more frequently in the morphine PCA group (P less than .001). Patients vomited more often after vaginal hysterectomy than patients having laparotomy, major oncology, or tuboplasty surgeries (P less than .05), and vaginal repair patients reported more vomiting than patients having major oncology or tuboplasty surgeries. Clinical impressions that either morphine or meperidine should be the preferred treatment for patients following gynecologic operations was not found by a 24-hour review of 500 patients for pain relief and side effects. Although mild itchiness occurred more frequently in the morphine PCA group, treatment was rarely necessary.

Adult

The causes of death in patients with human immunodeficiency virus infection: a clinical and pathologic study with emphasis on the role of pulmonary diseases.

The clinical records and autopsy data of 75 patients dying with AIDS were reviewed to determine the frequency of individual diseases diagnosed premortem and postmortem, the significance of pulmonary processes found in the lungs at autopsy, and the clinical and pathologic causes of death. Cytomegalovirus (CMV) infection was identified histologically either premortem or postmortem in 81% of patients. The lungs and adrenal glands were infected most commonly. Only one-half of CMV infections were recognized premortem. Pneumocystis pneumonia and Kaposi sarcoma occurred in 68% and 59% of patients, respectively, but were not unsuspected premortem in any patient. Visceral involvement with Kaposi sarcoma, however, was frequently recognized only at autopsy. While disseminated M. avium-intracellulare infection was common (31% of patients), histologically documented pulmonary disease was uncommon (3% of patients). Cryptococcal infection, diagnosed in 10 patients, was confined to the central nervous system in only 1 patient. Toxoplasma, in contrast, infected the brain of only 6 patients. All 75 patients had one or more disease processes identified in their lungs or pleurae at autopsy. These processes included opportunistic infections in 76% of patients, neoplasms in 37% (Kaposi sarcoma in 36% and lymphoma in 3%), and other processes in 60%. The most prevalent pathogen, CMV was found in pulmonary tissue from 44 patients and caused significant disease in 21 patients. Five patients died due to CMV pneumonia. Pneumocystis carinii was found at autopsy in 24 patients. In spite of treatment, pneumocystis pneumonia was fatal in 11 patients. One patient died with concomitant CMV and pneumocystis pneumonia. Kaposi sarcoma, identified in the lungs of 23 patients, led to death in 5 patients via upper airway obstruction, hemorrhage, or parenchymal destruction. Other fatal pulmonary processes included bacterial pneumonia in 9 patients, idiopathic diffuse alveolar damage in 5, cryptococcosis in 2, and pulmonary hemorrhage in 1. Specific clinical criteria were used to determine the cause of death due to organ system failure. Fifty-one percent of patients died due to respiratory failure; 16% from neurologic disease; 17% from hypotension that was not caused by respiratory, neurologic, or cardiac disease; and 3% from cardiac dysfunction. Thirteen percent of deaths did not meet the clinical criteria defining these 4 categories. This clinical assessment was combined with autopsy data to identify specific diseases as causes of death.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Prevention of hypertension and vascular changes by captopril treatment.

Treatment of female spontaneously hypertensive rats (SHR) and control Wistar-Kyoto (WKY) rats with captopril was carried out by the addition of the drug in the drinking water throughout pregnancy and lactation and after weaning. At 28 weeks of age, average systolic blood pressure of treated SHR was 113 +/- 3 mm Hg, which was below that of control SHR (188 +/- 3 mm Hg) and WKY rats (124 +/- 3 mm Hg). Body weight and heart rate of the SHR were not affected by the treatment. Tissue level of catecholamines was increased by captopril treatment in the superior cervical ganglia but remained unchanged in the plasma, heart, mesenteric arteries, and the adrenal glands of both SHR and WKY rats. Left ventricular weight, wall thickness, and internal diameter of the left ventricle in the SHR were reduced by the treatment. Morphometric measurements of the mesenteric arteries showed that vascular alterations present in the control SHR were prevented by the treatment. In the superior mesenteric artery and large mesenteric artery, smaller lumen size at maximal relaxation found in the control SHR was normalized to the level of the WKY rats. Hypertrophy of the medial wall in the superior mesenteric, large and small mesenteric arteries, and an increase in the number of smooth muscle cell layers in the large mesenteric artery of the SHR were prevented by the treatment. Perfusion study of the mesenteric vascular bed showed that reactivity of these vessels to norepinephrine was reduced, and sensitivity to norepinephrine (as determined by the effective dose that causes 50% of maximal response) was increased in the SHR by captopril treatment. Sensitivity of the tail artery in response to norepinephrine was not altered by the treatment. We conclude that long-term treatment with captopril of SHR before and after birth prevented the development of hypertension, structural and functional alterations of the mesenteric arteries, and cardiac hypertrophy.

Animals

Inhibition of the complement cascade by the major secretory protein of vaccinia virus.

The complement system contributes to host defenses against invasion by infectious agents. A 35-kilodalton protein, encoded by vaccinia virus and secreted from infected cells, has sequence similarities to members of a gene family that includes complement control proteins. Biochemical and genetic studies showed that the viral protein binds to derivatives of the fourth component of complement and inhibits the classical complement cascade, suggesting that it serves as a defense molecule to help the virus evade the consequences of complement activation.

Amino Acid Sequence

The dynamic distribution and quantification of DNA cruciforms in eukaryotic nuclei.

Cruciforms have been suggested as potential recognition structures at or near origins of DNA replication in eukaryotic cells. Monoclonal antibodies specific for cruciforms have been produced. The antibody binds to structural determinants at the base of the cruciform stem, the "elbow." Labeling of nuclei with anti-cruciform antibodies produces a nonuniform pattern of fluorescence in cells arrested at the G1/S boundary. This pattern of fluorescence changes when these cells are released from synchrony. Using fluorescence flow cytometry to quantify the number of DNA cruciform structures in cells throughout the cell cycle, we observed two major populations of nuclei with different numbers of cruciforms; the modal number of cruciforms in these populations was 0.6 x 10(5) and 3 x 10(5) cruciforms per nucleus. Synchronized cells (doubly arrested by serum starvation and aphidicolin) displayed a biphasic distribution of the number of cruciforms over the first 6 h after release from synchrony with maxima at 0 and 4 h after release.

Animals

Topical bupivacaine and etidocaine analgesia following fallopian tube banding.

The purpose of this study was to compare the effectiveness and safety of etidocaine and bupivacaine for postoperative analgesia after laparoscope sterilization. The study was performed in 22 healthy patients who received either one per cent etidocaine, 2 mg.kg-1, or bupivacaine 1.5 mg.kg-1 in a double-blind, randomized fashion. The local anaesthetic was dropped onto the fallopian tubes from uterus to fimbriae before tubal occlusion. To establish safety, blood concentrations of the parent drug and its metabolites were measured before application and at 1, 3, 6, 10, 15, 30, 60 and 120 min. The mean peak concentrations were 501.8 +/- 71.3 (SEM) for etidocaine with a range of 225 to 905 ng.ml-1. For bupivacaine, the mean peak concentration was 468 +/- 73.8 SEM with a range from 191 to 1005 ng.ml-1. The mean values are one eighth of the toxic convulsive dose for humans. Etidocaine was metabolized at a faster rate than bupivacaine with a rapid appearance of 2-amino-2'-butyroxylidide (ABX). The bupivacaine metabolite 2,6-pipecoloxylidide (PPX) was detected in low concentrations in the 60-minute samples. We conclude that the topical application of either etidocaine or bupivacaine is a safe procedure in the doses and concentrations used during general anaesthesia for laparoscopic tubal banding.

Abdominal Pain

Vascular changes associated with deoxycorticosterone-NaCl-induced hypertension.

Rats were injected with deoxycorticosterone (DOC) and salt was added to the drinking water (DOC/NaCl) for 3 weeks. Approximately half of the animals became hypertensive (DOC-H), whereas the remainder showed no increase in blood pressure (DOC-N) compared to age-matched, untreated controls. Morphometric analysis of the alterations in the arteries of the mesenteric bed was carried out in vessels fixed at maximum relaxation. Alterations were observed in the arteries, some of which were related to hypertension, but not to treatment, and some were due to treatment alone. The alterations within the arteries of the mesenteric bed depended in part on the type of artery, i.e. elastic, muscular or arteriolar. An increase in lumen area, in intimal area, and in the area of the media was seen in all types of arteries from DOC-H, but not in either group of normotensive animals. The medial hypertrophy was positively correlated with the increase in blood pressure; and was due to an increase in the number of smooth muscle cell layers in the elastic and muscular arteries, and probably to smooth muscle cell hypertrophy in the arterioles. The adventitial area was increased only in the elastic and muscular arteries. Endothelial injury, degeneration of the basement membrane, loss of heparan sulfate proteoglycan and intimal edema was observed in all the DOC/NaCl-treated animals, but was more severe in those which were also hypertensive. Hypertrophy of the heart and kidneys were observed in both normotensive and hypertensive DOC/NaCl-treated animals. These data indicate that changes in the rat cardiovascular system can be induced by DOC/NaCl treatment in the absence of hypertension, but also that hypertension is associated with specific arterial structural alterations, which vary according to the type of artery.

Animals

Ludwig's angina. Report of a case and review of the literature.

In the preantibiotic era, Ludwig's angina frequently caused asphyxiation and death. Recognized less often today, this rapidly progressive submaxillary cellulitis may still be fatal. A case associated with Haemophilus influenzae bacteremia in an adult is presented. Twelve additional cases of cellulitis of the neck in adults with H influenzae bacteremia are summarized. One hundred forty-one cases of Ludwig's angina reported since 1945 are reviewed and compared with 315 earlier cases. In the cases reported in the antibiotic era, the mean age of the patients was 29 years. Most patients were previously healthy but had evidence of dental disease. Submandibular swelling, elevation of the tongue, fever, dysphagia, and trismus were each present in more than one half of patients. Streptococci and anaerobes were most frequently isolated from soft-tissue cultures. Untreated, this illness is fatal in one half of patients. Early recognition is therefore essential. Appropriate therapy includes maintenance of the airway, antibiotics, and surgical drainage when indicated.

Adult

Ultrastructure and morphometric measurements of mesenteric arteries from newborn spontaneously hypertensive rats.

A morphometric and ultrastructural study of superior mesenteric arteries and large mesenteric arteries from newborn spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) was carried out. Morphometric measurements showed that in both vessel types, cross-sectional areas of the lumen and vessel wall components (e.g., media, adventitia) were similar between SHR and WKY. There was also no ultrastructural difference between SHR and WKY in the two types of arteries. We therefore conclude that vascular alterations found in older SHR take place after birth.

Animals

Peptide-containing nerves around blood vessels of stroke-prone spontaneously hypertensive rats.

The distribution and density of nerves containing vasoactive intestinal polypeptide, substance P, and neuropeptide Y around the cerebral and peripheral blood vessels of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were studied using an indirect immunofluorescence technique. Neonatal sympathectomy of SHRSP with anti-nerve growth factor and guanethidine was also carried out to study the effect of sympathectomy on the distribution of these nerves. Vasoactive intestinal polypeptide nerve density was higher in the veins and superior mesenteric artery of SHRSP than of WKY and lower in the cerebral arteries of SHRSP than of WKY, but no difference was found in the muscular mesenteric arteries. Sympathectomy reduced the density of these nerves in all the peripheral vessels but had little effect on the cerebral arteries. Density of substance P nerves was similar between SHRSP and WKY in the peripheral vessels but higher in the cerebral arteries of WKY than of SHRSP. Sympathectomy reduced the density of these nerves in the peripheral vessels but increased the density in some cerebral arteries of SHRSP. Neuropeptide Y nerve density was higher in the peripheral blood vessels of SHRSP than of WKY, and no difference was found in the cerebral arteries. Sympathectomy almost completely removed these nerves in the peripheral vessels but had no effect on the cerebral arteries. We suggest that some of the differences in nerve density between SHRSP and WKY, especially those in the peripheral blood vessels, may be related to the development of hypertension in the SHRSP.

Animals

Low back pain.

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Back Pain