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Biomedical subjects

J A Morris

Publications and source records attributed to J A Morris.

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

Electrolyte homeostasis in urothelial neoplasia: the effects of amiloride.

OBJECTIVE: To investigate the effect of amiloride preincubation on the intracellular electrolyte levels in neoplastic and non-neoplastic urothelium. MATERIALS AND METHODS: Samples of papillary transitional cell carcinomas (grades 1 and 2) and non-neoplastic human urothelium were either frozen immediately or after pre-incubation with Krebs saline alone or with Krebs saline containing amiloride. The frozen samples were planed in a cryo-ultramicrotome and then examined by low temperature scanning electron microscopy. Intracellular electrolyte levels were measured using X-ray microanalysis. RESULTS: In the cells frozen immediately the ratios K+/Na+, K+/P and K+/Cl- were significantly increased in neoplastic compared with non-neoplastic urothelial cells (P < 0.001). This difference was also found in the cells pre-incubated with Krebs saline alone but was not present in the cells pre-incubated with amiloride. CONCLUSIONS: These results were consistent with the concept that activation of the amiloride-sensitive Na+/H+ membrane exchanger is a primary event in neoplasia.

Aged↗
PubMed1995

Effects of nicotine on bacterial toxins associated with cot death.

Toxins produced by staphylococci and enterobacteria isolated from the nasopharynx of cases of sudden infant death syndrome (SIDS) have a lethal effect when injected into chick embryos. If the toxins are progressively diluted the lethal effect disappears, but certain combinations of toxins show synergy so that if sublethal doses are mixed a highly lethal effect is produced. In this paper it is shown that nicotine at very low concentrations (less than that produced in man by 0.05 cigarettes) potentiates the lethal action of certain SIDS associated bacterial toxins and markedly potentiates the lethal action of synergistic combinations of bacterial toxins. These results could explain, at least in part, why parental smoking increases the risk of SIDS. They also provide further support for the common bacterial toxin hypothesis of cot death.

Animals↗
PubMed1995

Lethal synergy between toxins of staphylococci and enterobacteria: implications for sudden infant death syndrome.

AIM: To test the hypothesis that lethal synergy occurs between toxin preparations of nasopharyngeal staphylococci and enterobacteria from sudden infant death syndrome (SIDS) victims and matched healthy infants. METHODS: SIDS and matched healthy babies were studied if both staphylococcal and enterobacterial strains were isolated from the nasopharynx. The lethality of toxin preparations from each bacterial isolate (separately and combined) was assessed over a range of dilutions using the chick embryo assay system. RESULTS: Staphylococci and enterobacteria were isolated together from the nasopharynx of seven SIDS babies but from only one normal healthy infant. Enterobacterial toxins were lethal at high dilutions. Staphylococcal toxins were less toxic. Simultaneous testing in the chick assay of staphylococcal and enterobacterial toxins, from each baby, at non-lethal concentrations enhanced lethality levels by 177 to 1011% compared with lethality expected by an additive effect alone. CONCLUSIONS: Synergy occurs between the toxins of nasopharyngeal staphylococci and enterobacteria. This combination of strains is more likely to occur in the nasopharynx of SIDS victims than that of healthy infants.

Case-Control Studies↗
PubMed1995

Aggressive use of ICP monitoring is safe and alters patient care.

OBJECTIVE: To identify complications and interventions resulting from fiberoptic ICP monitoring in a large series of patients with closed head injury (CHI). SETTING/DESIGN: Level I trauma center/Consecutive case series. METHODS: Of 11,962 consecutive trauma admissions from 1984-1991, 279 patients underwent fiberoptic ICP monitoring for CHI. We identified the last 100 consecutive blunt trauma patients who had received ICP monitoring. Ninety-eight of these patients had charts available and constitute the study group. We examined mortality, Glasgow Coma Score (GCS), and admission CT findings for the group. Indications, interventions, and complications (bleeding, meningitis, and wound infections) associated with ICP monitoring were identified. RESULTS: Mortality for the group was 24%. Reasons for ICP monitoring included GCS < or = 8 and/or abnormal CT findings; 83% had GCS < or = 8. Admission CT findings included subarachnoid hemorrhage (48%), intracerebral hemorrhage (47%), edema (31%), intraventricular hemorrhage (20%), subdural hematoma (18%), and epidural hematoma (9%). Eighty-one per cent of patients had interventions based on ICP monitoring: osmolar therapy (81%), emergency CT (22%), surgical decompression (3%), or pentobarbital coma (2%). No complications resulted from ICP monitoring. Mean duration of monitoring was 4 days (maximum 13 days). Twenty patients (20%) required two or more monitors. Reasons for placing a second monitor included duration > 5 days (50%), questionable accuracy (20%), and accidental removal of the first monitor (10%). CONCLUSIONS: 1) Fiberoptic intracranial pressure monitoring leads to specific interventions in the majority of patients. 2) The procedure is safe. 3) Prospective studies are needed to determine the impact of coagulopathy on the safety of fiberoptic intracranial pressure monitoring and to define those factors responsible for the low infection rate.

Adolescent↗
PubMed1994

Saturation mutagenesis at dihydrofolate reductase codons 22 and 31. A variety of amino acid substitutions conferring methotrexate resistance.

Naturally occurring amino acid substitutions conferring resistance to methotrexate (MTX) have been reported previously at codon positions 22 (leu-->arg, phe) and 31 (phe-->ser, trp) of mammalian dihydrofolate reductases (DHFR). To explore the character of other substitutions, a polymerase chain reaction (PCR)-assisted saturation mutagenesis protocol was devised to introduce all possible codon sequences at positions 22 and 31 of the murine DHFR coding sequence in an expressible simian virus 40 (SV40)-regulated transcription unit. Nucleotide sequencing confirmed the presence of all four nucleotides at each of the three codon positions in the mutagenized material. Transfection of these "codon libraries" into DHFR-deficient Chinese hamster ovary cells resulted in an increased frequency of MTX-resistant colony formation in comparison with wild-type DHFR transfected cells. DHFR variants contained in different clones were characterized by PCR amplification and DNA sequencing, identifying six different amino acid substitutions at position 22 and seven substitutions at position 31. DHFR variants were extracted for determination of MTX inhibition character and catalytic activity, normalizing for the amount of DHFR protein by western blot analysis. A wide range of MTX sensitivities and catalytic activities were observed which is consistent with the role of these side chains in DHFR catalytic function. We observed that codon 22 variants were generally more resistant to MTX, but codon 31 variants retained substantially more catalytic activity (about 2.5-fold) at a given level of MTX resistance. This heterogeneity in catalytic and inhibition character has important implications for the function of different DHFR variants as mediators of drug resistance.

Animals↗
PubMed1994

Mortality factors in geriatric blunt trauma patients.

OBJECTIVE: To examine various clinical factors for their ability to predict mortality in geriatric patients following blunt trauma. DESIGN: In this retrospective study, trauma registries and medical records from three trauma centers were reviewed for patients 65 years and older who had sustained blunt trauma. The following variables were extracted and examined independently and in combination for their ability to predict death: age, gender, mechanism of injury, admission blood pressure, and Glasgow Coma Scale score, respiratory status, Trauma Score, Revised Trauma Score, and Injury Severity Score. SETTING: Three urban trauma centers. PATIENTS: Geriatric trauma patients entering three trauma centers (Stanford [Calif] University Hospital, Vanderbilt University Medical Center, Nashville, Tenn, and Maryland Institute for Emergency Medical Services Systems, Baltimore) following blunt trauma during a 7-year period (1982 to 1989). RESULTS: The Injury Severity Score was the single variable that correlated most significantly with mortality. Mortality rates were higher for men than for women and were significantly higher in patients 75 years and older. Admission variables associated with the highest relative risks of death included a Trauma Score less than 7; hypotension (systolic blood pressure, < 90 mm Hg); hypoventilation (respiratory rate, < 10 breaths per minute); or a Glasgow Coma Scale score equal to 3. CONCLUSIONS: Admission variables in geriatric trauma patients can be used to predict outcome and may also be useful in making decisions about triage, quality assurance, and use of intensive care unit beds.

Abbreviated Injury Scale↗
PubMed1994

The white blood cell response to splenectomy and bacteraemia.

The aim of this study was to determine the relationship of the white blood cell (WBC) count to bacteraemia, and the risk of bacteraemia after splenectomy. The case series study was carried out at the Vanderbilt University Level I Trauma Center, and included 11,870 consecutive trauma admissions: 258 required a splenectomy (191) or splenorrhaphy (67). Bacteraemia was defined as the presence of a positive blood culture. Statistical analysis included ANOVA, the non-parametric Kruskal-Wallis test and logistical regression. Forty-two (22 per cent) of the splenectomy patients had positive blood cultures, while only six (9 per cent) of the splenorrhaphy patients had positive cultures. For the group of patients requiring a splenectomy, the mean WBC count was higher and more persistent in patients with bacteraemia. Logistical regression demonstrated that the type of surgery does not significantly correlate with bacteraemia after accounting for severity of injury (TRISS). The study conclusions were as follows (1) for the group of patients with bacteraemia after splenectomy, the peak WBC count was higher and more persistent than that which occurred in the group of patients without bacteraemia after splenectomy; (2) the WBC count cannot be used to predict bacteraemia for an individual patient, but a WBC count greater than 20,000 after 10 days should initiate a vigorous search for infection; (3) the severity of injury (and not splenectomy/splenorrhaphy) accounted for the increased risk of bacteraemia in population studied.

Adolescent↗
PubMed1994

Information and clonal concepts in ageing.

A model based on information theory and one based on somatic mutation in an expanding pool of cells are combined to give a theory of ageing. A mathematical formula, based on concepts from information theory, gives a close fit to the age incidence of mortality and disease in middle and old age. The basic concept is that biological systems process information and make decisions to maintain their integrity. But the decision process is fallible and significant errors could lead to disease or death. Decay in the components of the system will lead to a rising error rate with age and the form of the curve will be influenced by redundancy which is a fundamental property of information systems. In addition it is suggested that an important part of the decay in the decision process is due to a subset of mutant stem cells which have a proliferative advantage and slowly expand in number throughout life. This idea is derived from application of a model of somatic mutation in expanding cells to data in cancer and on the increase of dominant mutations with paternal age. This composite view explains why ageing is less subject to the vagaries of the extrauterine environment than suggested by the simple information model and points to a significant role for the intrauterine environment in the ageing process.

Aging↗
PubMed1994

Psychological influences in disease: a decision theory model.

The integrity of living organisms depends on analyzing information from an uncertain and hostile world and responding appropriately to it. Statistical decision theory indicates that an optimum decision strategy takes into account information, probability and subjective values ascribed to correct and incorrect responses. It follows that decisions at all levels, including the molecular level, can be strongly influenced by psychological and emotional states which influence subjective evaluation. This concept provides a framework within which psychological influences in disease can be analyzed.

Decision Making↗
PubMed1994

Outcome of cardiovascular collapse in pediatric blunt trauma.

STUDY OBJECTIVES: To determine the survival and functional outcome of pediatric blunt trauma victims demonstrating cardiovascular collapse, including pulseless cardiopulmonary arrest or severe hypotension, on initial presentation in an emergency department. DESIGN: Seven-year consecutive case-control series. SETTING: Level I trauma center and university teaching hospital. PARTICIPANTS: Two thousand one hundred twenty consecutive pediatric victims of blunt trauma less than 16 years old admitted to a Level I trauma center from August 1984 through December 1991 had a mortality of 5.2%. Thirty-eight patients (1.8%) demonstrated pulseless cardiac arrest or severe hypotension (systolic blood pressure of 50 mm Hg or less) on initial presentation in the ED. INTERVENTIONS: All patients received basic and advanced life support consistent with guidelines published by the American Heart Association, American Academy of Pediatrics, and American College of Surgeons. MEASUREMENTS AND MAIN RESULTS: Survival, functional outcome, and donor status were reviewed. Outcome of ED resuscitation (death or reanimation), post-ED destination (morgue, operating room, or pediatric ICU) length of hospitalization, functional outcome after hospital discharge, time to death (time from admission to ED to declaration of death), cause of death, total hospital costs, total hospital charges, and organ donation were reviewed. There were no functional survivors among 38 pediatric victims of blunt trauma who presented to the ED in pulseless cardiac arrest or with severe hypotension. Eleven of the 12 patients who were transferred to the pediatric ICU died; the single survivor demonstrated profound neurologic impairment six years after hospitalization. Six of these 12 patients were eligible potential donors and resulted in four multiorgan donors during the seven-year study. The mean hospital unreimbursed care for the 38 study patients was $3,514 per patient. CONCLUSION: No child who presented with pulseless cardiac arrest or severe hypotension following blunt trauma achieved functional survival. Reimbursed care for pediatric victims of blunt trauma demonstrating cardiovascular collapse is disproportionately poor compared with that for pediatric patients who maintain hemodynamic integrity in the ED. Half of all patients who were stabilized sufficiently for transfer to the pediatric ICU were eligible potential organ donors. Therefore aggressive resuscitation of these patients may be justified if organ donation is seriously contemplated and aggressively pursued.

Adolescent↗
PubMed1994

Safety of the blood supply. Surrogate testing and transmission of hepatitis C in patients after massive transfusion.

OBJECTIVE: To define a risk profile for post-transfusion hepatitis C in patients receiving massive transfusion. SUMMARY BACKGROUND DATA: Hepatitis C accounts for more than 90% of post-transfusion hepatitis. METHODS: Two-hundred twenty-one of 8,765 consecutive trauma admissions to a Level I trauma center received more than 20 units of erythrocytes. Sixty-nine survivors had positive viral serologic tests at least 1 year after transfusion. Surrogate testing for hepatitis C using alanine aminotransferase (ALT) levels and antibodies to hepatitis B core antigen (Core) began in October 1986 and January 1987, respectively. Donor blood for group 1 (pre-ALT/Core) was transfused before surrogate screening was introduced. Donor blood for group 2 (post-ALT/Core) was transfused after surrogate screening. RESULTS: Sixty-nine patients received blood products from 4,987 donors (mean, 72.3 units of exposure). No patient tested positive for antibodies to hepatitis B surface antigen, human immunodeficiency virus, or human T-lymphotrophic virus type 1. However 23.2% tested positive for hepatitis C virus (HCV) as measured by a second-generation enzyme immunoassay (HCV 2.0) and a recombinant immunoblot assay (RIBA), and 21.7% tested positive by HCV 1.0. Antibodies to Core were found in 8.7% of patients. The risk for post-transfusion hepatitis C per unit of exposure is estimated to be 1.52% group 1 (pre-ALT/Core) and 0.239% for group 2 (post-ALT/Core). CONCLUSIONS: The introduction of ALT/Core donor screening by a blood bank reduced the incidence of post-transfusion hepatitis C by 84%. The risk for post-transfusion hepatitis C depends on units of exposure, screening techniques, and prevalence of hepatitis C in the donor population. In our community, the risk for post-transfusion hepatitis C is less than 0.2% per unit of exposure. The population of massively transfused patients may serve as our effective resource for monitoring the safety of the blood supply.

Adult↗
PubMed1994

The spectrum of blunt injury to the carotid artery: a multicenter perspective.

The relative infrequency of blunt carotid artery trauma prompted a multicenter review to determine the spectrum of injuries, treatment strategies, and neurologic outcome. During a six-year period, 60 carotid artery injuries from blunt mechanisms in 49 patients were treated at 11 institutions. There were 11 bilateral injuries. Injury mechanisms were diverse but involved motor vehicles in 35 (72%) patients. In 14 (29%) patients, significant neurologic deficits developed more than 12 hours after a normal admission neurologic examination. The diagnosis was confirmed by angiography in 42 (86%). Duplex ultrasound accurately demonstrated the arterial injury in 12 (86%) of 14 patients. Documented injuries included arterial thrombosis in 20 arteries, arterial dissection alone in 19, dissection with pseudoaneurysm in six, pseudoaneurysm alone in five, frank arterial disruption in seven, and carotid-cavernous fistula in three. Arterial dissection was managed nonsurgically in 15 (79%) of 19 cases, the majority with systemic anticoagulation. Arterial thrombosis was managed with supportive therapy alone for 16 (80%) of 20 arteries; most associated with fixed neurologic deficits. Pseudoaneurysm repair was performed for six (55%) injuries. Carotid-cavernous fistulas were treated in all three instances with balloon occlusion. Overall mortality was 16 of 49 patients (43%). Good neurologic outcome was achieved in 22 (45%) patients. We conclude that: (1) Neurologic symptoms may develop in a delayed fashion; prior clinical suspicion and diagnostic testing are essential; (2) arterial dissection without complete occlusion may effectively be managed by anticoagulation; (3) pseudoaneurysms in accessible anatomic locations can be repaired with good results; and (4) injuries with complete arterial thrombosis are associated with high mortality and poor neurologic outcome in proportion to the initial degree of neurologic impairment.

Adolescent↗
PubMed1994

Gastric tonometry supplements information provided by systemic indicators of oxygen transport.

HYPOTHESIS: Assessment of splanchnic perfusion by gastric intramucosal pH (pHi) adds to the information provided by systemic indicators of oxygen transport. SETTING: University Hospital level I trauma center. DESIGN: Prospective study in 20 critically ill trauma patients comparing pHi with base deficit, lactate, oxygen delivery, and oxygen consumption (indexed to body surface area), mixed venous oxygen saturation (Svo2), oxygen utilization coefficient, and arterial pH. All measurements were obtained at admission, 1, 2, 4, 8, 16, and 24 hours, or at death. MAIN OUTCOME MEASURES: Correlation of pHi with the measured systemic variables, prediction of organ dysfunction, development of multiple organ dysfunction syndrome, and mortality. RESULTS: There was a poor correlation between pHi and the systemic hemodynamic and oxygen transport variables. Patients with a low pHi (< 7.32) on admission who did not correct within the initial 24 hours had a higher mortality (50% vs. 0.0%, p = 0.03) and incidence of organ dysfunction (2.6 organs/patient vs. 0.62 organs/patient, p = 0.02) than those who did. Using logistic regression analysis, only pHi, base deficit, and Svo2 were significantly associated with mortality during the study period. At 24 hours, only pHi was different between patients who developed multiple organ dysfunction syndrome and those who did not. There was a threshold value for pHi (7.10) which identified those patients who would go on to develop multiple organ dysfunction syndrome. CONCLUSIONS: Uncorrected splanchnic malperfusion is associated with a higher incidence of organ dysfunction and mortality. Gastric tonometry supplements information provided by systemic indicators of oxygen transport during resuscitation of critically ill trauma patients.

Acid-Base Equilibrium↗
PubMed1994

Childhood cancer around nuclear installations.

There is an increased incidence of childhood cancer, particularly lymphocytic neoplasia, in children who live close to nuclear installations. Possible causes are radiation-induced germ line mutations in occupationally exposed parents, or radiation-induced somatic mutation in the developing cells of the fetus or child due to increased environmental exposure. An alternative possibility is that the socioeconomic characteristics of the communities lead to an altered response to infection in childhood and this increases the risk of lymphocytic neoplasia in particular. For sites other than Sellafield in the UK, the evidence linking childhood cancer to radiation is unconvincing and it is possible that the increase is entirely due to the social characteristics of the communities. In Seascale, a village close to Sellafield, however, the increase is more marked and it is unlikely that social factors alone can explain the change. Furthermore, the environmental discharges from Sellafield are much higher than from other sites, and approach levels which could have a measurable effect on cancer incidence. In spite of a great deal of epidemiological investigation, no clear answer is available. It is argued that in order to solve the problem we must use new knowledge from molecular genetics and measure the rate of somatic mutation in those who work in the nuclear industry and in those who live nearby.

Child↗
PubMed1994

Information and observer disagreement in histopathology.

Concepts from information theory are used to assess the process of ordinal classification of histopathological continua such as degree of dysplasia or degree of differentiation. A working model is used to show that reducing the number of categories leads to an increase in inter-observer agreement, as measured by kappa statistics, but a decrease in information transmitted. It is argued that the prime role of histopathologists is to pass information, obtained from visual patterns, to the clinician and therefore more categories, rather than fewer, should be used. It is suggested that judgements of continua should be made on 100 point scales and quoted together with 95% confidence limits; and that the judgements of different observers should be averaged to form a reference range.

Humans↗
PubMed1994

Antibodies to endotoxin core in sudden infant death syndrome.

To assess the possible role of endotoxaemia in the pathogenesis of sudden infant death syndrome (SIDS), antibodies to endotoxin core (EndoCAb), which have previously been shown to be depressed by systemic endotoxaemia, were measured. IgG and IgM EndoCAb and total serum IgG and IgM were measured in serum samples from 25 children who had died from SIDS and 164 control children under 1 year of age. Twelve (48%) of the 25 children who had died from SIDS had no detectable IgG EndoCAb compared with 28 (17%) of the 164 control children, and this difference was concentrated in children aged less than 3 months. There was no significant difference between the two groups in the percentage of children with no IgM EndoCAb, nor in the total IgG and IgM concentrations. For IgM EndoCAb, the younger children who had died from SIDS had higher concentrations than the controls. These results suggest that, in children who have died from SIDS, due to either unusually early or severe exposure to endotoxin, maternal IgG EndoCAb have been depleted and early IgM EndoCAb triggered.

Aging↗