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G Malcolm

Publications and source records attributed to G Malcolm.

13 recordsLinked to original sources
PubMed2000

Spatio-logical processes in intracellular signalling.

Classical models of intracellular signalling describe how small changes in a cell's external environment can bring about major changes in cellular activity. Recent findings from experimental biology indicate that many intracellular signalling systems show a high level of spatial organisation. This permits the modification, by protein kinase or protein phosphatase action, of specific subsets of intracellular proteins - an attribute that is not addressed in classical signalling models. Here we use ideas and concepts from computer science to describe the information processing nature of intracellular signalling pathways and the impact of spatial heterogeneity of their components (e.g. protein kinases and protein phosphatases) on signalling activity. We argue that it is useful to view the signalling ecology as a vast parallel distributed processing network of agents operating in heterogeneous microenvironments, and we conclude with an overview of the mathematical and semantic methodologies that might help clarify this analogy between biological and computational systems.

Models, Biological↗
PubMed2000

The pandemic of Salmonella enteritidis phage type 4 reaches Utah: a complex investigation confirms the need for continuing rigorous control measures.

In 1995, Salmonella Enteritidis (SE) cases in the state of Utah increased fivefold. Isolates were identified as phage type 4 (PT4). Risk factors and sources of infection were investigated in two case-control studies, a traceback of implicated foods, and environmental testing. Forty-three patients with sporadic infections and 86 controls were included in a case-control study of risk factors for infection. A follow-up case-control study of 25 case and 19 control restaurants patronized by case and control patients examined risks associated with restaurant practices. In the first case-control study, restaurant dining was associated with illness (P = 0.002). In the follow-up case-control study, case restaurants were likelier to use > 2000 eggs per week (P < 0.02), to pool eggs (P < 0.05), and to use eggs from cooperative 'A' (P < 0.009). Eggs implicated in separately investigated SE PT4 outbreaks were traced to cooperative 'A', and SE PT4 was cultured from one of the cooperative's five local farms. We conclude that SE PT4 transmitted by infected eggs from a single farm caused a fivefold increase in human infections in Utah.

Adult↗
PubMed1999

Platinum distribution in malignant glioma following intraoperative intravenous infusion of carboplatin.

The objective of this paper was to determine the time course and extent of platinum uptake into human malignant glioma tissue. An intraoperative, intravenous infusion of carboplatin was given to nine patients (seven glioblastoma and two anaplastic glioma) undergoing tumour excision. Carboplatin dosage was calculated individually to achieve a target systemic free carboplatin exposure. Tumour and peritumoural tissue was harvested at timed intervals following carboplatin administration. Plasma and tumour platinum concentrations were measured by graphite furnace flameless atomic absorption spectrophotometry. Histological examination was also performed on a piece of each tissue sample. The mean carboplatin dose administered was 783, SEM 56 mg (range 485-903). Plasma pharmacokinetics showed a typical elimination curve. The mean peak plasma platinum concentration was 44, SEM 5 micrograms/ml (range 27-74). The mean total elemental plasma platinum area under the curve (AUC) was 9.0, SEM 1.4 mg/ml/min. Platinum was detected in 61 tumour samples, the mean peak concentration being 13 SEM 2 micrograms/g (range 5-21). Platinum was also detected in peritumoural brain and necrotic tumour. No correlation was apparent between the degree of necrosis in each tumour specimen and tumour platinum concentration. Platinum concentrations achieved in tumour were similar to levels that would be cytotoxic for glioma cells in vitro. The results of this study have implications for future studies using capillary permeability modifying agents as adjuncts to brain tumour chemotherapy.

Adult↗
PubMed1999

Identification of Bartonella species directly in clinical specimens by PCR-restriction fragment length polymorphism analysis of a 16S rRNA gene fragment.

It is now established that two species of Bartonella, namely, Bartonella henselae and B. quintana, cause bacillary angiomatosis in human immunodeficiency virus-infected patients. In addition, B. henselae causes cat scratch disease and B. quintana, B. henselae, and B. elizabethae can cause bacteremia and endocarditis in immunocompetent persons. We have developed a PCR-restriction fragment length polymorphism-based assay for direct detection and identification to species level of Bartonella in clinical specimens. This is accomplished by PCR amplification of Bartonella DNA using primers derived from conserved regions of the gene carrying the 16S ribosomal DNA, followed by restriction analysis using DdeI and MseI restriction endonucleases. We amplified a Bartonella genus-specific 296-bp fragment from 25 clinical samples obtained from 25 different individuals. Restriction analysis of amplicons showed that identical patterns were seen from digestion of B. henselae and B. quintana amplicons with DdeI, whereas a different unique pattern was seen by using the same enzyme with B. vinsonii and B. elizabethae. With MseI digestion, B. henselae and B. vinsonii gave nearly identical patterns while B. quintana and B. elizabethae gave a different pattern. By combining the restriction analysis data generated with MseI and DdeI, unique "signature" restriction patterns characteristic for each species were obtained. These patterns were useful in identifying the Bartonella species associated with each tissue specimen.

Angiomatosis, Bacillary↗
PubMed1998

An outbreak of salmonellosis among children attending a reptile exhibit at a zoo.

OBJECTIVE: In January 1996, an outbreak of diarrhea caused by Salmonella Enteritidis occurred in children attending a Komodo dragon exhibit at a metropolitan zoo. We sought to determine the extent of the outbreak and mode of transmission. STUDY DESIGN: A case-control study was conducted. Controls were randomly selected from zoo membership lists and matched to patients by age group and date of exhibit visit. RESULTS: Of 65 patients identified, 39 had confirmed and 26 had suspected cases. The median age was 7 years (range, 3 months to 48 years); 55% were enrolled in the case-control study. No patients and two (4%) controls reported touching a dragon; however, 83% of patients but only 52% of controls touched the wooden barrier that surrounded the dragon pen (odds ratio = 4.0, 95% CI 1.2 to 13.9). Washing hands at the zoo after visiting the dragons was highly protective (OR = 0.14, 95% CI 0.03 to 0.7). Cultures from the patients, one dragon, and the exhibit barriers yielded Salmonella Enteritidis, phage type 8. On the basis of an attack rate of 4.3% among exhibit attendees under 13 years old on whom data were collected, we estimate that 315 additional cases of salmonellosis occurred among visitors in this age group. CONCLUSION: This large outbreak demonstrates the importance of environmental contamination in the transmission of Salmonella from reptiles, and the protective value of hand washing. Recommendations regarding reptile exhibits and reptilian pets should emphasize this indirect route.

Adolescent↗
PubMed1997

A comparison of the ventilatory response of sleeping newborn lambs to step and progressive hypoxaemia.

1. Slight variations in the rate at which hypoxaemia develops may significantly alter the ventilatory response (VR) elicited. Here we have developed a technique to compare the VRs elicited from sleeping newborn lambs by specific (step versus progressive), short-duration (< or = 5 min) episodes of hypoxaemia. The results may help us understand the limitations of using tests which deliver poorly defined stimuli to evaluate the postnatal development of the oxygen chemoreflex. 2. The VRs of five lambs elicited by a 5 min step or progressive reduction in the arterial oxygen saturation (Sa,O2) during quiet sleep were compared. Minute ventilation (V1, face mask) and Sa,O2 (pulse oximeter) were measured continuously. Alternate step (Sa,O2 reduced to 80-85% within 60 s and maintained for a further 4 min) and progressive tests (progressive reduction in Sa,O2 to 80% over 5 min) were administered daily between postnatal days 2-14. 3. There was a significant difference between the mean VR to step versus progressive hypoxaemia. The VR to a step challenge was biphasic (delta Vi = +32 +/- 5% at 1 min and -1 +/- 4% at 5 min; mean +/- S.E.M.). Progressive hypoxaemia elicited a more subdued but sustained hyperpnoea (delta Vi = +11 +/- 2% at 1 min and +11 +/- 4% at 5 min). The difference between these two response profiles was statistically significant (P < 0.001). 4. Mean responses of lambs aged < or = 5 days (4 +/- 0.2 days) and > or = 9 days (10 +/- 0.3 days) were also compared. There was an upward shift in the position of step and progressive response curves of older lambs, reflecting primarily the increased vigour of the initial hyperpnoea elicited by step (delta Vi at 1 min = +20 +/- 4% at 4 days vs. +40 +/- 11% at 10 days) as well as progressive (delta Vi at 1 min = +6 +/- 2% at 4 days vs. +17 +/- 5% at 10 days) hypoxaemia. 5. Qualitatively different VRs may be elicited from the newborn, depending upon the specific hypoxaemic profile administered. Therefore, to evaluate the significance of VRs elicited in response to classical, steady-state hypoxia at different postnatal ages properly, the stimulus must be accurately described.

Aging↗
PubMed1997

Ventilatory response of the newborn infant to mild hypoxia.

The transition from an immature (biphasic) to a mature (sustained hyperpneic) response to a brief period of sustained hypoxia is believed to be well advanced by postnatal day 10 for newborn infants. However, a review of the supporting evidence convinced us that this issue warranted further, more systematic investigation. Seven healthy term infants aged 2 days to 8 weeks were studied. The ventilatory response (VR) elicited by 5 min breathing of 15% O2 was measured during quiet sleep. Arterial SaO2 (pulse oximeter) and minute ventilation (expressed as a change from control, delta V'i) were measured continuously. Infants were wrapped in their usual bedding and slept in open cots at room temperature (23 degrees-25 degrees). Infants aged 2-3 days exhibited predominantely a sustained hypopnea during the period of hypoxia (delta V'i = -2% at 1 min, -13% at 5 min). At 8 weeks of age, the mean response was typically biphasic (delta V'i = +9% at 1 min, -4% at 5 min). This age-related difference between responses was statistically significant (two-way ANOVA by time and age-group; interaction P < 0.05). These data reveal that term infants studied under ambient conditions during defined quiet sleep may exhibit an immature VR to mild, sustained hypoxia for at least 2 months after birth. This suggests that postnatal development of the O2 chemoreflex is slower than previously thought.

Aging↗
PubMed1994

Carbon dioxide concentrations in the environment of sleeping infants.

In 22 infants continuous measurements were made of the concentration of carbon dioxide (CO2) in inspired air during sleep. Evidence was found of CO2 enrichment of inspired air in certain environmental conditions. The levels achieved were not sufficiently high to acutely endanger an infant. Carbon dioxide concentrations as high as 2-3% were observed in the prone position when the infant's head was under a blanket and when the lower face was obscured by bedding. Sleeping prone on a sheepskin also resulted in an increased concentration of CO2 but to a lesser extent than being under a blanket. In awake infants the presence of a pacifier also promoted an excess of CO2 in the inspired air, both in the prone and supine positions. The physiological and clinical implications of these findings, in relation to the Sudden Infant Death Syndrome (SIDS), are unknown and warrant investigation.

Air↗
PubMed1991

Amniocentesis in the management of preterm premature rupture of the membranes.

A retrospective analysis has been performed of perinatal outcome in 81 pregnancies in which preterm premature rupture of membranes (PPROM) was managed using amniocentesis to diagnose intrauterine infection and lung maturity. Ten patients (13%) had a positive Gram stain on microscopy whilst 29 (37%) had a positive culture. Forty-one patients (58%) had a mature lecithin:sphingomyelin ratio. There was evidence of sepsis in 13 neonates (16%), with a further 16 (20%) being colonized. Both Gram stain and amniotic fluid culture were relatively poor predictors of neonatal sepsis. For Gram stain the sensitivity was low at only 15%. Although the sensitivity for culture was higher (69%), the specificity (71%) was too low to be clinically useful. It is recommended that a randomized controlled trial of amniocentesis in PPROM is needed to define the role of this diagnostic test.

Amniocentesis↗
PubMed1991

Absent or reversed end diastolic flow velocity in the umbilical artery and necrotising enterocolitis.

Absent or reversed end diastolic flow (AREDF) velocities in the umbilical artery were identified in 25 high risk pregnancies. In six pregnancies the fetus was abnormal and all but one of these ended in perinatal death. Of the 19 morphologically normal fetuses, three died in utero and there were four neonatal or infant deaths. The mortality rate was 48% for all pregnancies and 37% for those with morphologically normal fetuses. There was a highly significant increased risk for the development of necrotising enterocolitis in these morphologically normal fetuses with AREDF (53%) compared with controls (6%) who did have umbilical artery end diastolic flow velocities in fetal life. There were no significant differences between the matched pairs for parameters of neonatal outcome chosen to reflect neonatal morbidity. These findings demonstrate the close association between AREDF and necrotising enterocolitis that appears to be independent of other variables such as degree of growth retardation, prematurity, and perinatal asphyxia.

Blood Flow Velocity↗