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Biomedical subjects

J J McNamara

Publications and source records attributed to J J McNamara.

At least 19 recordsLinked to original sources

Failure of mannitol to reduce myocardial infarct size in the baboon.

OBJECTIVE: The aim was to determine whether mannitol, previously shown to have several myocardial protective properties, could reduce the myocardial infarct size after coronary occlusion in the baboon. METHODS: Anaesthetised baboons underwent a 2 h transient coronary artery occlusion. Each was randomised into one of two groups receiving either mannitol (n = 6) or no adjunct (n = 8). Mannitol (20%) was given at a rate of 0.4 ml.min-1 x kg-1 starting at 105 min postocclusion until reperfusion was allowed at 2 h, and at a rate of 0.2 ml.min-1 x kg-1 thereafter, until a total of 500 ml had been delivered. Changes in the ST segments were recorded with epicardial wires. The animals were killed at 24 h postocclusion and the hearts excised. Silicone microvascular dye was injected into the previously occluded coronary artery to delineate the perfusion bed. The hearts were fixed in formalin, sliced, and mounted on slides. Using planimetry the ratios of the mean volume of infarct to the mean volume of the perfusion bed (VI/VPB) were calculated and compared. RESULTS: The VI/VPB for the mannitol treated group was 71.7(SEM 14.0)% and for the control group, 65.6(6.9)% (NS). No significant difference was noted in the mean summated ST segment elevations between the two groups. CONCLUSIONS: Mannitol does not reduce myocardial infarct size or ischaemia in the baboon.

Animals

Prolonged extracorporeal circulation for acute myocarditis.

Total circulatory support for acute reversible myocardial failure is rarely used in clinical situations outside the postoperative period following cardiac surgery. We treated an 8-year-old girl who suffered acute viral myocarditis and sustained cardiac arrest requiring cardiopulmonary bypass for resuscitation. This was accomplished with the use of the portable cardiopulmonary support system (CPS), which consists of a centrifugal pump and a membrane oxygenator. This patient was placed on CPS in Hawaii and transported after 3 days to San Diego (4200 km) for further mechanical support and possible heart transplantation. Adequate cardiac function returned and CPS was stopped after 6 days. She is alive and well, attending school two and a half years after the event. Prolonged use of CPS for acute myocardial failure outside the operating room, including long distance transportation, is effective and easily accomplished with currently and widely available equipment, and should be used in acute, reversible catastrophic heart disease.

Acute Disease

Fibrin glue reduces seroma formation in the rat after mastectomy.

Fibrin glue is a biologic tissue adhesive that has been found to be useful in several areas of surgical treatment. Little has been written in the English literature, however, on its use in preventing postoperative fluid collections. We performed a prospective randomized trial to determine if fibrin glue could reduce postoperative fluid collections after mastectomy in a rat. Bilateral mastectomies and axillary lymph node dissections were performed upon 42 rats, one-half of which were treated with fibrin glue and one-half of which served as controls. The rats were sacrificed after seven days and inspected for quantity of fluid and adhesion formation. The mean plus or minus standard error of the mean fluid collections were 0.71 +/- 0.26 milliliter and 3.75 +/- 0.65 milliliter for the rats treated with fibrin glue and control rats, respectively. This was statistically significant (p < 0.0001). Seventeen of 21 rats treated with fibrin glue and four of 21 control rats were found to have fluid collections of less than 1 milliliter, again statistically significant (p = 0.00006). Furthermore, greater adhesion formation between the skin flap and chest wall was noted in the rats treated with fibrin glue. The results support the use of fibrin glue in clinical investigations to reduce postoperative fluid collections and also support the need to develop a standard reproducible method of producing fibrin glue or a commercial product free of transmissible disease.

Animals

Elusive trypanosomes.

Professor Kershaw's encouragement of the development of anion-exchange separation of African trypanosomes from blood led to two decades of activity when, for the first time, considerable progress was made in the intrinsic characterization of these parasites. Such characterization depended on establishing high infections in laboratory rodents. However, the collection of samples from the field was restricted by the failure of certain trypanosomes either to infect, or to multiply adequately in, rodents. More recently, in vitro culture has come to play an increasingly important role in producing material. By obtaining procyclic forms directly from wild tsetse flies, or by transforming low numbers of bloodstream forms in field samples to the procyclic phase in experimental tsetse, trypanosomes of poor or nil infectivity to rodents were readily cultured in the large amounts required for biochemical characterization. A number of specimens of a new kind of Nannomonas, of Trypanosoma simiae, of T. grayi, and of an antigenically distinct T. brucei gambiense were found. Evidence is presented that many other kinds of trypanosome may be eluding isolation by their inability to infect rodents.

Animals

Improved identification of Nannomonas infections in tsetse flies from The Gambia.

Trypanosomes from 36 midgut infections were isolated in procyclic culture from Glossina morsitans submorsitans and G. palpalis gambiensis in The Gambia. Twenty-eight stocks (78%) were identified using DNA probes specific for: (a) Trypanosoma (Nannomonas) congolense savannah type, (b) T. (N.) congolense riverine-forest type, (c) T. (N.) simiae and (d) Trypanozoon, T. simiae and savannah type T. congolense were found only in G.m. submorsitans while the riverine-forest type T. congolense was restricted to populations of G.p. gambiensis from two isolated areas of relict forest: one Trypanozoon stock was isolated from G.m. submorsitans. T. congolense accounted for only 17% of all Nannomonas infections, as identified by dissection, in G.m. submorsitans. This re-emphasises the importance of differentiating infections below the subgeneric level when estimating challenge to domestic animals. T. simiae could not be distinguished from T. congolense by the arrangement of trypanosomes in the fly proboscis. The 8 stocks which were not identified by DNA probes were separated into two groups on the basis of hybridization with total DNA probes and the cycle of development in experimental tsetse. One group of four isolates, all from G.m. submorsitans, was a new kind of Nannomonas which appeared to be common and widespread in The Gambia. The second group, which was found only in G.p. gambiensis, had a stercorarian cycle of development, maturing in the hindgut, and was morphologically similar to insect forms of the crocodile parasite T. grayi.

Animals

Isolation and cultivation in vitro to the infective, metacyclic stage of Trypanosoma (Nannomonas) simiae from Glossina morsitans submorsitans.

Two separate trypanosome isolations were made from a single Nannomonas-infected Glossina morsitans submorsitans from The Gambia. Inoculation of a piglet with the infected hypopharynx produced an infection with Trypanosoma simiae. DNA was isolated from the bloodstream forms to prepare a probe specific for this species. Trypanosomes isolated from the fly midgut were frozen in liquid nitrogen and then cultivated in vitro. Amplification of this population and elimination of a yeast contaminant were achieved by two passages through laboratory G. m. morsitans. Further cultivation in vitro resulted in the production of epimastigotes and, later, metacyclic forms. Two pigs inoculated with cultivated metacyclic forms developed infections with atypical, relapsing parasitaemias and extended survival time. Neither the metacyclic forms, nor bloodstream forms derived from them, infected calves. The identity of various stages of the in vitro cultivated, procyclic-derived stock was confirmed morphologically and with the T. simiae-specific DNA probe.

Animals

Effect of cystic fibrosis on inhaled aerosol boluses.

An aerosol bolus undergoes changes in shape between its inspiration and expiration. In comparison with the inhaled bolus, the exhaled bolus is more spread because of convective mixing, may have a shift in the location of the mode caused by asymmetries of filling and emptying of lung units, and contains fewer particles because of particle deposition. We hypothesized that the extent of these changes is related to lung health. To examine this, 11 patients with cystic fibrosis (CF) and 11 healthy subjects inhaled 70 cm3 boluses containing 1 micron monodisperse particles that were inspired to volumetric penetrations (Vp) of 100 to 700 cm3. As each bolus was expired, we measured spreading (volumetric width at one-half aerosol concentration peak height), modal shift, and particle deposition. Patients with CF exhaled boluses that were broader than those exhaled by normal subjects at all penetrations examined. At a Vp of 600 cm3, patients had a mean bolus half-width that was 68% greater than that of healthy subjects (p less than 0.0001), and they exhaled the bolus mode 20% earlier (p less than 0.0002). Particle deposition was increased compared with that in normal subjects at all Vp. For example, mean deposition at a Vp of 600 cm3 was 46.2 +/- 2.6% (SE) for the patients versus 25.8 +/- 1.6% for the normal subjects (p less than 0.0001). Among the patients with CF, pulmonary function parameters indicating obstruction were significantly correlated with bolus spreading and aerosol deposition: the percent predicted FEV1/FVC was inversely correlated with spreading (r = -0.88, p less than 0.0004) and deposition (r = -0.84, p less than 0.0008).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols

Antiserum to endotoxin in hemorrhagic shock.

Antiserum to Escherichia coli J5, a mutant endotoxin (LPS) which contains only core determinants, has proven effective in reducing mortality from endotoxic shock due to a wide variety of gram-negative bacteria. Twenty New Zealand white rabbits with coliforms in the gut were subjected to hemorrhagic shock of 36 mm Hg for 3 hr. Treated rabbits were resuscitated with 15 cc of rabbit J5 antiserum (hemagglutinating antibody titer against J5 lipopolysaccharide of 1:1024), remaining shed blood, and lactated Ringer's to achieve a mean arterial blood pressure (MABP) within 20% of baseline. The control group was similarly resuscitated but received 15 cc normal rabbit serum (titer 1:2). Catheters were removed and rabbits were returned to their cages until death or 5 days of survival. Hemodynamic parameters (heart rate, MABP, cardiac output, and total peripheral resistance) did not differ significantly between groups. However, six treated rabbits survived 5 days (60%) and no control rabbit lived past the third postexperimental day (P less than 0.019). Our data suggest that systemic endotoxemia may contribute to morbidity and mortality in severe hemorrhagic shock.

Alanine Transaminase

Air embolism and the radial arterial line.

A clinical case of apparent air embolism through a radial artery line served as the impetus to conduct a study in primates to investigate the possibility of air embolism from the radial artery into the cerebral circulation. Using 133Xe cerebral scanning, we demonstrated that greater than 2 ml of air in the radial artery would result in retrograde passage of air into the vertebral system and then into the brain.

Animals

Why not your pediatrician's office? A study of weekday pediatric emergency department use for minor illness care in a community hospital.

To determine the rationale for using a community hospital's emergency department for minor illness care on weekdays, we surveyed 150 parents of children 15 years of age or younger. Fifty (33.3%) participants had no identified source of routine pediatric care, and 31 (20.7%) had pediatric providers not locally available. For participants with local providers, major reasons for use of the emergency department included economic factors, parental knowledge, parent/provider communication, convenience, and insurance coverage. The results of this study demonstrate that the utilization pattern and sociodemographic profile of children seen in our emergency department on weekdays is more characteristic of an inner-city hospital than of a non-metropolitan setting. There are a number of feasible measures which could improve access to routine pediatric care for low socioeconomic families and reduce unnecessary emergency department utilization.

Adolescent

Lung inflation does not increase maximal expiratory flow during induced obstruction in the dog.

A deep inflation (DI) reverses induced bronchoconstriction in normal human subjects whether assessed by airway resistance before and after a DI or by isovolumic maximal expiratory flows (Vmax) from partial expiratory flow-volume (PEFV) vs. maximum expiratory flow-volume (MEFV) maneuvers. These observations suggest that with induced constriction the hysteresis of airways exceeds that of the parenchyma. In contrast with humans, a previous study of ours on dogs indicated that induced increases in airway resistance were unaffected by DI, suggesting that hysteresis of airways and parenchyma were equal. We hypothesized therefore that in constricted dog lungs, any differences that might arise in isovolumic Vmax between PEFV and MEFV maneuvers would not be due to changes in airway caliber but rather would be wholly determined by isovolumic differences in deflational recoil pressures. Recoil pressures were dynamically measured using six separate alveolar capsules in each of six dogs. At base line there were no significant differences between isovolumic recoil pressures or maximal flows with volume history, suggesting equal degrees of airway and parenchymal hysteresis. After histamine-induced constriction there were also no isovolumic differences in flows, but due to striking nonhomogeneities in dynamic recoil pressure among alveolar capsules, it was not possible to express a single meaningful recoil pressure pertinent to the lungs as a whole. These findings are consistent with the idea that isovolumic comparisons of Vmax serve as a reasonable indicator of changes in the relative degree of airway and parenchymal hysteresis.

Airway Obstruction

Effects of sympathectomy on heart size and function in aortic-constricted rats.

Effects of chemical sympathectomy with 6-hydroxydopamine on left ventricular mass, norepinephrine content, and performance in aortic-constricted and sham-constricted rats were examined. Sympathectomy did not affect mean arterial pressure but it led to lower final body weights in aortic-constricted rats. Of the hypertensive aortic-constricted rats, those that had also been sympathectomized showed greater increases in left ventricular weight-to-body weight, right ventricular weight-to-body weight, and lung weight-to-body weight ratios. Left ventricular norepinephrine content was depressed by either sympathectomy or aortic constriction and was severely depleted by their combination. Sympathectomy had no effect on maximal cardiac output or left ventricular stroke work during rapid saline infusion. In aortic-constricted rats, however, it lowered heart rate during the infusion and increased left ventricular end-diastolic pressure at peak stroke work. This evidence suggests that elimination of the adrenergic nervous system's chronotropic influence promotes greater left ventricular filling, and the resultant increase in preload may importantly contribute to the stimulation of cardiac hypertrophy.

Animals

Heterogeneous lung emptying during forced expiration.

Several lines of evidence suggest that the healthy mammalian lung empties homogeneously during a maximally forced deflation. Nonetheless, such behavior would appear to be implausible if for no other reason than that airway structure is known to be substantially heterogeneous among parallel pathways of gas conduction. To resolve this paradox we reexamined the degree to which lung emptying is homogeneous, and considered mechanisms that might control differential regional emptying. Twelve excised canine lungs were studied. Regional alveolar pressure relative to pleural pressure was used as an index of regional lung volume. By use of a capsule technique, alveolar pressure was measured simultaneously in each of six regions during flow-limited deflations; flow from the lung was measured plethysmographically. The standard deviation of interregional pressure differences, which was taken as an index of nonuniformity, was 0.0, 0.74, 0.64, and 0.90 cmH2O at mean recoil pressures of 30, 8.4, 4.5, and 2.1 cmH2O (0, 25, 50, and 75% expired vital capacity), indicating that interregional pressure differences increased more rapidly earlier in the deflation. When we examined the time rate of change of regional alveolar pressure as an index of regional flow, we observed an intricate pattern of differential regional behavior that was inapparent in the maximum expiratory flow-volume (MEFV) curve. The most plausible interpretation of these findings is that regions of the healthy excised canine lung empty heterogeneously to a small degree, but in an interdependent compensatory pattern that is inapparent in the configuration of the maximum expiratory flow-volume curve.

Animals

Humoral factors in primate endotoxin shock.

Many biologically active substances are released from the cell in endotoxic shock and thought to contribute to morbidity and mortality. Whether or not these substances are independently toxic or require endotoxin as a catalyst is uncertain; 20 mg/kg E. coli endotoxin was infused into seven rhesus (R) macaca monkeys (toxin donor). Seven R macaques received an equivalent volume of normal saline (control donor). Animals were monitored for 12 h and lactated Ringer's was infused to maintain a minimum MABP of 40 mmHg. Donor animals were exsanguinated; plasma was extracted and a Limulus lysate assay (LAL) was utilized to determine the approximate amount of endotoxin present in toxin donor plasma. This volume of endotoxin (0.125 mg/kg) was added to control donor plasma. Plasma was infused into seven toxin receivers and six control receivers. Receiver animals were monitored for 24 h and killed after 3 d. Lungs were evaluated histologically for evidence of acute injury. Five of the seven toxin receivers and no control receivers died within 3 d (P less than .005). Significantly more hemorrhage occurred in toxin receivers (P less than .01). Our data suggest a humoral factor present in the plasma of toxin donor capable of promoting tissue injury and death of recipient animals independent of endotoxin.

Animals