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Biomedical subjects

L Jennings

Publications and source records attributed to L Jennings.

At least 19 recordsLinked to original sources
PubMed2006

Collagen degradation products modulate matrix metalloproteinase expression in cultured articular chondrocytes.

Destruction of collagen within osteoarthritic cartilage depends in part on collagen-degrading matrix metalloproteases (MMP). Degradative fragments of type II collagen (Col II) occur in normal and in osteoarthritic cartilage, and may contribute to regulation of matrix turnover by interfering with normal cell-matrix communication pathways. Therefore, the effects of different types of collagen fragments on mRNA and protein levels of MMP-2, MMP-3, MMP-9, and MMP-13 in cultured bovine articular knee chondrocytes and explants were examined. Primary chondrocytes and explants were incubated with fragments from whole cartilage collagen matrix (Colf) and from purified type II collagen (Col2f), or with a synthetic 29-mer peptide representing the amino-terminal domain of type II collagen (Ntelo). Gelatin zymography revealed increases of proMMP-2, a shift towards active MMP-2 and increases in proMMP-9, depending on the type of fragment. In situ hybridization of cartilage sections displayed MMP-3 mRNA in virtually all cells. Moderate to strong increases in MMP-2, MMP-3, MMP-9, and MMP-13 mRNA levels were detected by quantitative PCR. The results demonstrate stimulating effects of collagen fragments on both mRNA and/or protein from MMP -2, -3, -9, and -13, and suggest a novel mechanism of MMP induction and activation that includes a particular role for N-telo in controlling catabolic pathways of matrix turnover.

Amino Acid Sequence↗
PubMed2006

Radio-frequency ablation of hepatocellular carcinoma before liver transplantation: a histologic and 'TUNEL' study.

BACKGROUND: Radio-frequency ablation (RFA) is an increasingly used treatment modality for hepatocellular carcinoma (HCC) in patients awaiting liver transplantation (OLTX). The current study evaluates the effectiveness of RFA in this setting based on evaluation of total cell death in explanted native livers. DESIGN: We evaluated 36 tumors from 35 patients with RFA-treated HCC who underwent OLTX at our center between 1998 and 2002. Native livers from OLTX were extensively sampled for histologic evaluation. For each HCC, an estimate ratio of necrotic tumor areas was calculated based on hematoxylin and eosin (H&E) sections. In tumors with 10% or more residual viable areas, Tdt-mediated UTP nick-end labeling (TUNEL) was further performed to assess apoptosis in the morphologically 'viable' areas. A final 'tumor cell death' (TCD) ratio was recalculated for each HCC to include areas of apoptosis identified by TUNEL. RESULTS: Based on H&E evaluation, 22/36 (61.1%) HCC revealed > or = 90% necrosis including 12/36 HCC (33.3%) showing no evidence of residual viable tumor. The overall median tumor necrosis was 79%. When TUNEL findings were added, 26/36 (72.2%) HCC revealed > or = 90% TCD including 14/36 HCC (38.8%) showing complete TCD (median TCD of 88.4%). None of our patients died of HCC while awaiting OLTX. Longer RFA-to-transplant time appears to be associated with a higher TCD rate (median of 154.5 days in patients with less than 90% TCD vs 326 days for patients with > or = 90% TCD; P = 0.019). There was no significant correlation between tumor grade or pre-RFA size of the tumors and TCD rate in RFA-treated HCC (P = 0.11). CONCLUSION: Extensive TCD (88.4% median) can be obtained using RFA for HCC in patients awaiting OLTX. Our TUNEL findings suggest that RFA-induced cell injury could be associated with apoptosis.

Adult↗
PubMed2004

Community-acquired pneumonia: influence of management practices on length of hospital stay.

AIMS: To identify variation in the management of -community-acquired pneumonia between two New Zealand hospitals and the factors that may account for any differences. METHODS: A 12-month, prospective two-centre study was conducted. Between July 1999 and July 2000, 474 adult patients with community-acquired pneumonia were enrolled: 304 in Christchurch Hospital and 170 in Waikato Hospital. The patients were similar in age, sex, prior antibiotic use and comorbidity. There was no significant difference in the clinical outcomes for the patients at the two centres. RESULTS: The mean duration of i.v. antibiotic therapy was 1.7 versus 3.0 days (P < 0.001) and length of stay (LOS) was 3.0 versus 5.9 days (P < 0.001) for Waikato and Christchurch Hospitals, respectively. Using multivariate analysis, we could account for 61% of the observed variation in LOS. Duration of i.v. antibiotic therapy independently accounted for 16% of variation in LOS compared with age (2%), chronic obstructive pulmonary disease, duration of fever, intensive care unit admission and centre of admission (all <1%). For the duration of i.v. antibiotics, centre of admission, largely reflecting clinician practice at each centre, independently accounted for 13% of variation, compared with duration of fever (5%), admission to the Intensive Care Unit (4%), Pneumonia Severity Index score (3%) and bacteraemia (3%). CONCLUSION: Of the identifiable factors, variations in clinician behaviour outweighed the influence of patient factors on the duration of i.v. antibiotic therapy, which in turn was the major determinant of LOS for patients hospitalised with community-acquired pneumonia. An early switch from i.v. to oral antibiotic therapy in conjunction with early discharge planning may significantly reduce LOS without compromising patient outcomes.

Aged↗
PubMed2003

Total parenteral nutrition vs oral diet in autologous hematopoietic cell transplant recipients.

Autologous HCT patients often have poor oral intake for 2-4 weeks post transplant. To compare outcomes between patients provided prophylactic total parenteral nutrition (TPN) or an oral diet (OD), 55 well nourished breast cancer/ hematopoietic cell transplantation (HCT) patients were randomized to TPN (n=27), beginning day -1, or OD (n=28). Parameters studied include length of stay (LOS), engraftment, infections, survival, weight, anthropometrics, handgrip strength, and quality of life (QOL) In all, 50% of OD patients were given TPN due to poor oral intake for 10 consecutive days. No significant differences were found between the groups for any of the above parameters except weight and anthropometrics, which were better maintained in the TPN group than the OD group. Trends were seen for increased infections, more stable handgrip strength, and improved QOL in the TPN group vs the OD group. Prophylactic TPN did result in a more intact nutritional status and preservation of lean body mass post transplant but did not impact LOS or survival when compared to OD. For this reason, TPN should be reserved for autologous HCT patients with pretransplant nutritional depletion, complications post transplant, or prolonged poor oral intake. These results should not be extrapolated to allogeneic HCT patients but are likely applicable to other well nourished autologous HCT patients.

Adult↗
PubMed2001

Community-acquired pneumonia in Christchurch and Waikato 1999-2000: microbiology and epidemiology.

AIMS: To prospectively record current epidemiology and microbiology of community-acquired pneumonia in two New Zealand centres. METHODS: Between July 1999 and 2000 all adults admitted to Christchurch and Waikato Hospitals with community-acquired pneumonia were screened for study inclusion. All those enrolled had their medical history, clinical variables, inpatient management and clinical outcomes recorded and standardised microbial diagnostic testing carried out. RESULTS: 474 participants were enrolled with a mean age of 64 years and a microbial diagnosis was made in 197 cases (42%). Streptococcus pneumoniae (14%), Haemophilus influenzae (10%) and Influenza A virus (7%), Legionella spp (4%) and Mycoplasma pneumoniae (3%) were the most commonly isolated organisms. An 'atypical' organism was diagnosed in 8% of cases compared to 30% and 23% in previous Christchurch and Waikato studies respectively. Fourteen of the 67 S pneumoniae isolates (21%) had reduced susceptibility to penicillin, all with a MIC < or = 2 microg/mL, a level of reduced susceptibility not associated with worse patient outcomes. Clinical outcome included a mean hospital stay of 6.7 days and a 6 week mortality of 6%. CONCLUSION: Although S pneumoniae was the most commonly isolated organism in this study there have been significant changes in the prevalence of atypical organisms since previous surveys. Ongoing surveillance of antibiotic resistance and variations in the prevalence of organisms causing community-acquired pneumonia is required to guide clinicians' empiric antibiotic use.

Adult↗
PubMed2001

A redox-based mechanism for the contractile and relaxing effects of NO in the guinea-pig gall bladder.

The purpose of this study was to determine the effects of sodium nitroprusside (SNP), 2,2'-(hydroxynitrosohydrazino)bis-ethanamine (DETA/NO) and 3-morpholinosydnonimine (SIN-1), NO donors which yield different NO reactive species (NO+, NO* and peroxynitrite, respectively), as well as exogenous peroxynitrite, on gall bladder contractility. Under resting tone conditions, SNP induced a dose-dependent contraction with a maximal effect (10.3 +/- 0.7 mN, S.E.M.) at 1 mM. Consistent with these findings, SNP caused a concentration-dependent depolarization of gall bladder smooth muscle. The excitatory effects of SNP were dependent on extracellular calcium entry through L-type Ca2+ channels. Furthermore, the contraction and depolarization were sensitive to tyrosine kinase blockade, and an associated increase in tyrosine phosphorylation was detected in Western blot studies. DETA/NO induced dose-dependent relaxing effects. These relaxations were sensitive to the guanylyl cyclase inhibitor 1H-[1,2,4]oxidiazolo[4,3-a]quinoxaline-1-one (ODQ, 2 microM) but they were not altered by treatment with the potassium channel blockers tetraethylammoniun (TEA, 5 mM) and 4-aminopyridine (4-AP, 5 mM). When tested in a reducing environment (created by 2.5 mM 1,4-dithiothreitol, DTT), SNP caused a relaxation of gall bladder muscle strips. Similarly, the SNP-induced contraction was converted to a relaxation, and associated hyperpolarization, when DTT was added during the steady state of an SNP-induced response. SIN-1 (0.1 mM), which has been shown to release peroxynitrite, induced relaxing effects that were enhanced by superoxide dismutase (SOD, 50 U ml(-1)). The relaxations induced by either SIN-1 alone or SIN-1 in the presence of SOD were strengthened by catalase (1000 U ml(-1)) and abolished by ODQ pretreatment. However, exogenous peroxynitrite induced a concentration-dependent contraction, which was dependent on activation of leukotriene (LT) metabolism and extracellular calcium. The peroxynitrite-induced contraction was abolished in the presence of the peroxynitrite scavenger melatonin. These results suggest that SIN-1 behaves as an NO* rather than a peroxynitrite source. We conclude that, depending on the redox state, NO has opposing effects on the motility of the gall bladder, being a relaxing agent when in NO * form and a contracting agent when in NO+ or peroxynitrite redox species form. Knowledge of the contrasting effects of the different redox forms of NO can clarify our understanding of the effects of NO donors on gall bladder and other smooth muscle cell types.

Acetylcholine↗
PubMed2001

The effects of collagen fragments on the extracellular matrix metabolism of bovine and human chondrocytes.

Cartilage matrix degradation generates collagen type II fragments. The objective of this study is to explore the possibility that these collagen fragments may be part of an endogenous metabolic feedback. Initially, collagen fragments were extracted from normal or osteoarthritic cartilage, as part of a matrix fragment preparation. Later, collagen fragments were generated by digestion of bovine collagen type II with bacterial collagenase (col2f). These fragments were added to cultures of isolated chondrocytes (bovine and human) and cartilage explants (human). In a dose-dependent manner, col2f caused inhibition of cell attachment to collagen, inhibition of collagen synthesis, and induction of matrix degradation. In addition, when col2f were added to human cartilage explants, an induction of gelatinase activity was detected in the media. These data sets present first evidence that degradation products of collagen may be directly involved in the regulation of cartilage homeostasis.

Adult↗
PubMed2000

Influenza vaccination coverage in Canterbury rest homes.

AIMS: First, to investigate the effect on Canterbury rest home residents of national policy making influenza vaccination free for those aged 65 years and over. Second, to assess rest home staff influenza vaccination coverage. METHODS: A comparison of influenza vaccination coverage in Canterbury rest home residents during 1996 and 1997 was conducted. Subgroups of rest homes were formed in 1997 to minimise the bias introduced through conducting a coverage survey in 1996. Staff vaccination coverage was also assessed in 1997. RESULTS: Influenza vaccination coverage of Canterbury rest home residents was 74% in 1996 and 76% in 1997. Staff vaccination coverage was 21% in 1997. Significantly more staff were vaccinated in rest homes that offered free influenza vaccination to their staff. CONCLUSIONS: The free influenza vaccination policy had no measurable impact on Canterbury rest home residents' vaccination coverage. This may be due to a ceiling effect of previously high coverage. Coverage was low amongst rest home staff. Providing the vaccination free of charge might improve staff coverage.

Aged↗
PubMed2000

Oral oseltamivir in human experimental influenza B infection.

Oseltamivir is the prodrug of Ro64-0802 (GS4071), a potent and selective inhibitor of influenza A and B virus neuraminidases. Three randomized, double-blind, placebo-controlled, parallel-group studies evaluated oral oseltamivir for early treatment (75 or 150 mg twice daily for 5 days) or prevention (75 mg once or twice daily for 7 days) of experimental influenza B virus infection in healthy susceptible adults. Treatment study A (n=60) demonstrated similar trends to treatment study B (n=117), in which 75 mg doses of oseltamivir introduced 24 h after inoculation reduced median area under curve (AUC) virus titre (oseltamivir, 22.7; placebo, 131.1 log10 TCID50 x h/ml; P=0.002) and duration of viral shedding (oseltamivir, 23.9 h; placebo, 95.8 h; P=0.0005). In prevention study C (n=58), oseltamivir did not reduce infection rates (85 versus 84%) but significantly reduced median AUC virus titre (10.0 versus 66.9 log10 TCID50 x h/ml; P=0.03) and duration of viral shedding (36 versus 84 h; P=0.03) compared with placebo. Oseltamivir was well tolerated. No emergence of drug-resistant variants was detected by testing last-day isolates (n=112) in neuraminidase inhibition assays. These results indicate that oseltamivir has significant antiviral activity in experimental human influenza B virus infection when used for prophylaxis or early treatment.

Acetamides↗
PubMed1999

Tramadol or fentanyl analgesia for ambulatory knee arthroscopy.

In a double-blind, randomized, controlled study, 61 patients who received a standardized anaesthetic for day case arthroscopic knee surgery were studied. Group T (n = 31) received tramadol 1.5 mg kg-1, and group F (n = 30) received fentanyl 1.5 micrograms kg-1 at the induction of anaesthesia. All patients also received 20 mL of intra-articular bupivacaine 0.5% at the end of surgery. Assessments were made of pain at rest and on movement, analgesic requirements and side-effects at hourly intervals up to 6 h and by means of a postal questionnaire at 24 h and 48 h post-operatively. Group F had higher pain scores than group T at 4 h only [VAS 3.3 (1.6-5.5) vs. 2.4 (1-4), P = 0.039, respectively; median (interquartile range)]. There were no other significant differences between the groups in terms of pain scores, supplemental analgesic requirements or incidence of side-effects. We conclude that tramadol offers little benefit clinically compared with fentanyl when used at induction of anaesthesia for day case arthroscopic knee surgery. Further studies are indicated in patients with more severe pain to determine the role of tramadol in post-operative analgesia.

Adolescent↗
PubMed1998

Futurespeak.

Explore the source record for details and available documents.

Communication↗
PubMed1997

The Mental Health Act and professional hostage taking.

Compulsory detention of psychiatric patients is seen as a necessary response to a perceived threat, against themselves or against others, and such detention is rationalized as humane, compassionate and benevolent. However, seen from the recipient's perspective such detention and enforced treatment may be viewed as malevolent. This paper is concerned with examining the role of compulsory detention of the mentally abnormal offender in respect of the 1983 Mental Health Act by analysis of the resultant ideas which underpin it. First, in terms of its role as a sanction against transgressors of a particular value system, who are spotlighted by the increased 'surveillance' in our society. Second, the issues of treatability and consent are discussed in relation to the neo-legalism that permeates our social world. In addition, the role of the 1983 Mental Health Act as a means of social control will be examined using the notion of a covert political 'policing' in the form of compulsory detention, resulting from the medico-legal confrontation of power bases which defines the patient as a 'professional hostage'. Quite clearly there is an overlap of themes which creates a difficulty in interpretation. However, with increasing legal facilities for detention and the increasing number of 'conditions' being drawn under the medical umbrella it is important to attempt to review the results of this legislation within those areas identified above and to understand how this may be interpreted for those held against their wishes.

Commitment of Persons with Psychiatric Disorders↗
PubMed1995

Quality of life improvements at one, two, and five years after liver transplantation.

We prospectively studied adult liver transplant (OLTX) recipients to evaluate the effect of OLTX on quality of life (QOL). Over an 8-year period, all adult patients undergoing OLTX at our institution were asked to complete a psychological questionnaire that probed broad facets of QOL. Patients seen for their 1, 2, and 5 or more-year post-OLTX visits were also asked to complete the form. Questions were then grouped by categories broadly highlighting self-image (SI), health perception (HP), ability to function (F), and ability to work (W). Questions ranged from demographic and occupational topics to symptom distress/frequency, activities of daily living, and the impact of health on daily life. Numerical scores were assigned to each question, and added to derive scores on SI, HP, and F. Higher scores reflect better QOL. Employment data (W) were also compared, though not amenable to scoring. A total of 573 forms were completed (210 pretransplant, 150 at 1 year, 131 at 2 years, 79 at 5 years). All posttransplant scores were significantly higher than pretransplant ones (P < or = .0001, ANOVA). Scores at posttransplant time points were not significantly different from each other. Subscores of SI and HP revealed less symptom frequency and distress following OLTX (P < or = .0003) continuing to beyond 5 years. Health limitations on activities decreased both at 1 year post-OLTX and again at 2 years (P < or = .0001) and were sustained to beyond 5 years. Fewer people were working for pay at 1 year post-compared with pre-OLTX, but pre-OLTX levels of employment had been regained by the second year, continuing to increase to beyond 5 years. OLTX leads to improved QOL by the end of the first posttransplant year, sustained through the 5th posttransplant year and beyond. Self-image, functioning ability, and perception of health status were significantly improved. Ill health interference in daily life continues to decrease as OLTX becomes more remote. Employment suffers early after OLTX, but recovers by the second post-OLTX year and continues to increase long-term.

Female↗
PubMed1994

HLA compatibility and liver transplant outcome. Improved patient survival by HLA and cross-matching.

In liver transplantation (LTx), numerous studies have failed to demonstrate an adverse effect of HLA-A,B,DR incompatibility or of donor-specific positive cross-match on survival of the recipients. In this study, we examined the effect of antidonor cytotoxic antibody and HLA compatibility in 800 LTx recipients with CsA-based immunosuppression. Thirty-four of 482 (7%) recipients were transplanted across a positive donor-specific T cell cross-match. Four-year patient and graft survival was 71% and 67%, respectively, in negative cross-match recipients and 53% and 50%, respectively, in positive cross-match recipients (P = 0.0051 and P = 0.023). Neither B cell-positive cross-match nor the presence of panel reactive antibody (PRA) had an adverse impact on the liver allograft outcome. Interestingly, 21/58 (36.2%) patients with PRA > or = 10% had a positive T cell cross-match, whereas only 7/382 (1.8%) patients with PRA < 10% did (P < 0.0001). This indicates the predictive value of PRA cross-match results. B lymphocyte cross-match results also were strongly correlated with the presence of PRA, as 26/57 (45.6%) of the patients with PRA > or = 10% had a positive cross-match, whereas only 22/394 (5.6%) with PRA < 10% did (P < 0.0001). Analysis of HLA compatibility demonstrated a significant impact on patient's survival, comparing only 0-2 vs. 6 HLA-A+B+DR mismatches and 0 vs. 1 vs. 2 HLA-DR mismatches. Four-year patient survival rate for 0 to 2 antigen mismatches was 86%, whereas for 6 antigen mismatches it was 62% (P = 0.025). Overall actuarial 4-year patient survival rate in HLA-DR-mismatched groups (0 vs. 1 vs. 2) was 84%, 73%, and 64%, respectively (P = 0.033). In no mismatched category was graft survival rate significantly different. Sepsis or rejection was the cause of graft loss in 1/10 (10%), 21/75 (28%), and 34/85 (40%) patients with 0, 1, and 2 HLA-DR mismatches, respectively. The difference between patient and graft survival was accounted for by survival after retransplantation, which was lower in patients with more HLA-DR mismatches in primary transplants. The latter group received intensive immunosuppressive therapy during the first month after primary transplantation, as compared with those with fewer HLA-DR mismatches (P = 0.04). The above data suggest that prospective cross-match should be performed in patients with > or = 10% PRA if it is logistically feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1994

A three-dimensional kinematic method for determining the effectiveness of arm segment rotations in producing racquet-head speed.

The contribution that a segment's anatomical rotations make to racquet-head speed depends on both the segment's angular velocity and the instantaneous position of the head of the racquet with respect to the segment's axes of rotation. Any analysis of racquet swing technique that does not consider both of these factors simultaneously is, at best, incomplete. With this in mind, a three-dimensional kinematic method was developed to determine the effectiveness of the anatomical rotations of the upper arm, forearm, and hand in producing racquet-head speed. The method entailed developing a system of vector equations for three-dimensional upper limb rotations that used displacement histories of 10 selected landmarks as input. The required three-dimensional displacement histories were obtained using three cine cameras and the DLT approach. To test the diagnostic capabilities of the method, a tennis serve was selected for analysis. For the player and serve analyzed, the greatest contribution to racquet-head speed at impact was produced by internal rotation of the upper arm (8 m s-1). Forearm pronation, although exhibiting the fastest rotation at impact (24 rad s-1), ranked only fourth in terms of its contribution (4 m s-1) to racquet-head speed. To test the performance of the method, a comparison was made between the racquet-head speed measured directly from film and the racquet-head speed computed by summing all of the individual segment contributions to speed commencing at the start of forward swing and ending at ball contact. The results indicate that the method can successfully determine the individual contributions that the different anatomical rotational velocities of the arm segments make to the measured instantaneous racquet-head speed.

Algorithms↗