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Biomedical subjects

P Clark

Publications and source records attributed to P Clark.

At least 73 records · Page 4Linked to original sources
PubMed2000

Injectable gold for rheumatoid arthritis.

OBJECTIVES: To estimate the short-term benefit and risk of side-effects of injectable gold for rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. SELECTION CRITERIA: Randomized clinical trials (RCT) comparing injectable gold against placebo in patients with rheumatoid arthritis were included. DATA COLLECTION AND ANALYSIS: Methodological quality of the RCTs was asessed by two reviewers (MS, BS) (kappa=1.0). Rheumatoid arthritis outcome measures were extracted by two reviewers from the publications for the 6 month endpoint. Sufficient data was obtained to conduct a pooled analysis of the number of swollen joints, physician global assessment, patient global assessment and erythrocyte sedimentation rate (ESR). Results were analyzed as standardized weighted mean differences for swollen joints and global assessments and weighted mean differences for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals. Heterogeneity was estimated using a chi-square test. Fixed effects models were used throughout. MAIN RESULTS: Four trials and 415 patients were included. A statistically significant benefit was observed for injectable gold when compared to placebo. The standardized weighted difference (effect size) between gold and placebo for the number of swollen joints was -0.5, translating into a percentage change of 30% in favour of gold adjusted for placebo. Statistically significant differences were also observed for ESR and patient and physician assessments. Twenty two percent of the treated patients withdrew from toxicity compared to 4% of controls (OR=3.9 - 95%Cl: 2.1 - 7.2). REVIEWER'S CONCLUSIONS: Although its use can be limited by the incidence of serious toxicity, injectable gold has an important clinically and statistically significant benefit in the short term treatment of patients with rheumatoid arthritis.

Antirheumatic Agents↗
PubMed2000

Syringe pressure irrigation of subdermic tissue after appendectomy to decrease the incidence of postoperative wound infection.

To evaluate syringe pressure irrigation of the surgical wound to decrease its infection after appendectomy, we designed a randomized control trial at the Emergency Department of Mexico City General Hospital, including 350 patients with acute abdomen suggestive of appendicitis, without any other infection clinically evident. The trial was randomized into 2 groups. Group I patients received prophylactic systemic antibiotics before surgery. Group II patients received the same prophylactic systemic antibiotics plus syringe pressure irrigation of the surgical wound with 300 ml of saline solution using a 20-ml syringe with 19-gauge intravenous (IV) catheter to measure the incidence of postoperative wound infection. In our results, 283 patients had appendicitis. Of these, 188 were uncomplicated (66.4%) and 95 (33.6%) were complicated. Of the complicated cases, 40 were assigned to group I, and of these, 29 (72. 5%) developed wound infection. In group II there were 55 patients and only 9 (16.3%) developed wound infection after syringe pressure irrigation [p = 0.000001; 95% confidence interval (CI) = 0.02-0.22]. We conclude that syringe pressure irrigation of the surgical wound after appendectomy contributes significantly to decrease the incidence of postoperative wound infection in complicated cases. It is a cheap, safe, and accessible method in any surgical room.

Adolescent↗
PubMed2000

Lipoprotein (a) levels in normal pregnancy and in pregnancy complicated with pre-eclampsia.

Lipoprotein (a) (Lp(a)) is recognised as a risk factor for arterial and venous thrombosis, a property which may relate to its structural similarity to plasminogen. Pregnancy is associated with a hypofibrinolytic state. Elevated Lp(a) may influence fibrinolysis and have an unfavourable role in pregnancy outcome. In this study alterations in plasma Lp(a) concentrations during normal pregnancy was examined, in a detailed longitudinal investigation, in ten women together with changes in other lipid parameters. In addition, Lp(a) concentrations were examined in subjects with pre-eclampsia (n=10) relative to matched controls (n=10), since it has recently been reported that a substantial increase in circulating Lp(a) occurs in this disorder. Lp(a) concentration increased steadily in normal pregnancy between 10 and 35 weeks with a doubling of the median value from 14.5 to 27.0 mg/dl (P=0.01). A significant increase in Lp(a) values was observed in all subjects with increasing gestation (median rise 190%, range 117-340%). This increase was intermediate to those seen in plasma triglyceride and cholesterol. No significant difference in Lp(a) values was observed in subjects with pre-eclampsia, compared with matched normal pregnancy controls (median 14 mg/dl [IQR 4.7-69.0] in pre-eclampsia vs 20 mg/dl [9.0-56. 3] in controls; P=0.57), at a median gestation of 32 weeks. In conclusion, there is a 2-fold increase in Lp(a) during normal pregnancy, which may influence fibrinolysis. Circulating Lp(a) is not significantly elevated in women with pre-eclampsia, and thus is unlikely to play a role in the pathophysiology of this disorder.

Adult↗
PubMed2000

Haemophilia A in a litter of Siberian huskies.

AIM: To investigate haemorrhagic diathesis in several males in a litter of Siberian huskies. METHODS: Activated partial thromboplastin time, prothrombin time, and Factor VIII and Factor IX concentrations were measured in citrated whole blood samples. RESULTS: Males in the litter had decreased Factor VIII concentrations. CONCLUSIONS: Haemophilia A was diagnosed as the cause of haemorrhagic diathesis in several males in a litter of Siberian huskies.

Journal Article↗
PubMed2000

Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group. Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors.

PURPOSE: A phase III trial, Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors (CATAPULT I), was designed to determine the efficacy and safety of tirapazamine plus cisplatin for the treatment of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with previously untreated NSCLC were randomized to receive either tirapazamine (390 mg/m(2) infused over 2 hours) followed 1 hour later by cisplatin (75 mg/m(2) over 1 hour) or 75 mg/m(2) of cisplatin alone, every 3 weeks for a maximum of eight cycles. RESULTS: A total of 446 patients with NSCLC (17% with stage IIIB disease and pleural effusions; 83% with stage IV disease) were entered onto the study. Karnofsky performance status (KPS) was >/= 60 for all patients (for 10%, KPS = 60; for 90%, KPS = 70 to 100). Sixty patients (14%) had clinically stable brain metastases. The median survival was significantly longer (34.6 v 27. 7 weeks; P =.0078) and the response rate was significantly greater (27.5% v 13.7%; P <.001) for patients who received tirapazamine plus cisplatin (n = 218) than for those who received cisplatin alone (n = 219). The tirapazamine-plus-cisplatin regimen was associated with mild to moderate adverse events, including acute, reversible hearing loss, reversible, intermittent muscle cramping, diarrhea, skin rash, nausea, and vomiting. There were no incremental increases in myelosuppression, peripheral neuropathy, or renal, hepatic, or cardiac toxicity and no deaths related to tirapazamine. CONCLUSION: The CATAPULT I study shows that tirapazamine enhances the activity of cisplatin in patients with advanced NSCLC and confirms that hypoxia is an exploitable therapeutic target in human malignancies.

Adult↗
PubMed2000

Does being a woman make a difference in professional practice? A qualitative view to the practice of rheumatology.

OBJECTIVE: To explore to what extent female rheumatologists perceived that gender had an influence on their professional practice or on their choice of specialty. METHODS: We collected data from 29 female rheumatologists and used qualitative and quantitative methods to describe the findings. RESULTS: Three groups of respondents were identified (cluster analysis). Most of these rheumatologists perceived that gender influenced the way they practiced, although the specific weights of the topics were different in the 3 groups. Gender also influenced these physicians' choice of specialty field. CONCLUSION: The differences in practice style may have a potential effect on health systems as feminization of the medical profession increases.

Female↗
PubMed1999

Stem cell factor in combination with filgrastim after chemotherapy improves peripheral blood progenitor cell yield and reduces apheresis requirements in multiple myeloma patients: a randomized, controlled trial.

Stem cell factor (SCF) has been shown to synergize with filgrastim to mobilize CD34(+) cells into the peripheral blood. To determine if addition of SCF to chemotherapy and filgrastim reduces the number of leukaphereses required to achieve a target yield of 5 x 10(6) CD34(+) cells/kg, 102 patients with multiple myeloma were randomized to receive mobilization chemotherapy with cyclophosphamide (4 g/m(2)) and either SCF (20 micrograms/kg/d) combined with filgrastim (5 micrograms/kg/d) or filgrastim alone (5 micrograms/kg/d), administered daily until leukaphereses were completed. After collection, patients were treated with myeloablative therapy supported by autologous peripheral blood progenitor cell (PBPC) infusion and filgrastim (5 micrograms/kg/d). There was a significant difference between the treatment groups in the number of leukaphereses required to collect 5 x 10(6) CD34(+) cells/kg (median of 1 v 2 for SCF + filgrastim and filgrastim alone, respectively, P =.008). Patients receiving the combination of SCF plus filgrastim had a 3-fold greater chance of reaching 5 x 10(6) CD34(+) cells/kg in a single leukapheresis compared with patients mobilized with filgrastim alone. The median CD34(+) cell yield was significantly increased for the SCF group in the first leukapheresis (11.3 v 4.0 x 10(6)/kg, P =.003) and all leukaphereses (12.4 v 8.2 x 10(6)/kg, P =.007). Total colony-forming unit-granulocyte-macrophage (CFU-GM) and mononuclear cell counts were also significantly higher in the SCF group in the first leukapheresis and in all leukaphereses. As expected for patients mobilized to an optimal CD34(+) cell yield, the time to engraftment was similar between the 2 treatment groups. Cells mobilized with the combination of SCF plus filgrastim were thus considered effective and safe for achieving rapid engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate injection site reactions being the most frequently reported adverse events. There were no serious allergic-like reactions to SCF. The addition of SCF to filgrastim after cyclophosphamide for PBPC mobilization resulted in a significant increase in CD34(+) cell yield and a concomitant reduction in the number of leukaphereses required to collect an optimal harvest of 5 x 10(6) CD34(+) cells/kg.

Adult↗
PubMed1999

Calcium oxalate crystalluria in a goat.

As part of a routine health evaluation of an 8-month-old female Nubian goat, serum biochemical analyses and urinalysis were performed. Most serum biochemical values including concentrations of blood calcium and indicators of urinary system dysfunction, such as blood urea nitrogen, creatinine, and phosphorous concentrations, were within reference ranges. An aliquot of voided urine was hypersthenuric and acidic and contained numerous typical cuboidal-bipyramidal calcium oxalate dihydrate crystals and unique rectangular parallelepiped crystals that were confirmed by energy dispersive X-ray microanalysis as being of calcium oxalate dihydrate composition. We hypothesize that the calcium oxalate crystals resulted from a diet containing calcium and oxalic acid. Treatment was not administered, and the goat remained healthy during the ensuing year.

Animals↗
PubMed1999

Curvature of dinucleotide poised for formation of trinucleotide in transcription with Escherichia coli RNA polymerase.

A frequently used schematic model of transcriptional elongation shows an RNA polymerase molecule moving along a linear DNA. This model is of course highly idealized and not compatible with promoter sequences [Gralla, J. D. (1991) Cell 66, 415-418; Schleif, R. (1992) Annu. Rev. Biochem. 61, 199-223] and regulatory proteins [Koleske, A. J., and Young, R. A. (1995) Trends Biochem. Sci. 20, 113-116; Dunaway, M., and Dröge, P. (1989) Nature 341, 657-659; Müller, H. P., Sogo, J. M., and Schaffner, W. (1989) Cell 58, 767-777] located some distance away from the point of transcription initiation [Karsten, R., von Hippel, P. H., and Langowski, J. (1995) Trends Biochem. Sci. 20, 500-506]. These circumstances lead to the expectation of curvature along the DNA strand and require looping between sometimes distant points. We have now shown curvature in a dinucleotide formed at the very onset of transcription when it is poised for reaction with a mononucleotide to form a trinucleotide. The curvature became evident from the demonstration that a metal ion bound with a mononucleotide in the i+1 (elongation) site is approximately equidistant from bases at the 5' end (i-1 site) and 3' end (i site) of the dinucleotide. Similar results were obtained with three different dinucleotides and four mononucleotides. Curvature of the RNA initiate may reflect curvature of the DNA to which it is bound. These studies show curvature to be a significant feature in the interaction between DNA template and RNA elongate even at the very beginning of transcription.

Adenosine Triphosphate↗
PubMed1999

Relative potency of controlled-release oxycodone and controlled-release morphine in a postoperative pain model.

OBJECTIVE: The relative analgesic potency of single doses of oral controlled-release oxycodone and oral controlled-release morphine were compared in a randomized, double-blind trial using a postoperative pain model. METHODS: Women (n = 169) with moderate to severe pain following abdominal hysterectomy received single oral doses of controlled-release oxycodone, 20 mg or 40 mg, or controlled-release morphine, 45 mg or 90 mg. Assessments were made at 30 min, 60 min, then hourly after dosing for 12 h or until remedication. RESULTS: The most precise estimates of relative potency showed that controlled-release oxycodone was 1.8 times more potent than controlled-release morphine for total effect (95% confidence limits 1.09-2.42; lambda 0.44) and 2.2 times more potent for peak effect (95% confidence limits 0.96-4.59; lambda 0.71). Controlled-release oxycodone at doses of 20 mg or 40 mg was comparable with controlled-release morphine at doses of 45 mg or 90 mg, respectively, for total and peak analgesic effects. For the two higher doses, time to peak relief was approximately 1 h shorter with controlled-release oxycodone than with controlled-release morphine. Most patients reported onset of analgesia within 1 h with all doses. Side effects were similar with the two opioids. CONCLUSION: Oral controlled-release oxycodone was twice as potent as oral controlled-release morphine in this single-dose, relative potency assay. When converting patients from oral morphine to oral oxycodone, an initial oral oxycodone dose of one-half the oral morphine dose is recommended.

Administration, Oral↗
PubMed1999

Maternal and neonatal infection rates with three different protocols for prevention of group B streptococcal disease.

OBJECTIVES: We compared maternal and neonatal infection rates under 3 different group B streptococcal prevention strategies and also evaluated reasons for each protocol's failures in preventing neonatal disease. STUDY DESIGN: Women who were delivered at our center from August 1, 1991, through April 30, 1998, were managed by 1 of 3 protocols for prevention of early-onset neonatal group B streptococcal infection: a selective screening protocol, The American College of Obstetricians and Gynecologists protocol, and the Centers for Disease Control and Prevention-recommended universal screening strategy. We compared maternal infection rates and neonatal group B streptococcal infection rates under each protocol. We also compared reasons for each protocol's failures in preventing neonatal infection. RESULTS: Clinical chorioamnionitis rates were 7.4% with selective screening, 7.7% under The American College of Obstetricians and Gynecologists' protocol, and 5.2% with universal screening (relative risk 0.7, 95% confidence interval 0.6-0.8). Endometritis rates were 4.0% with selective screening, 4.6% with The American College of Obstetricians and Gynecologists protocol, and 2. 8% with universal screening (relative risk 0.7, 95% confidence interval 0.6-0.8). Overall neonatal group B streptococcal infection rates were lower under the 2 more recent strategies, but not significantly so. Despite the ability of universal screening to find more women at risk for group B streptococcal transmission, half of the neonatal infections under this protocol occurred when the mothers were not considered candidates for prophylaxis. CONCLUSIONS: The Centers for Disease Control and Prevention-endorsed universal screening strategy for group B streptococcal infection prevention was associated with significantly lower rates of clinical chorioamnionitis and endometritis than were the other strategies. We were unable to document statistically significant improvement in neonatal outcome under the universal screening protocol.

Anti-Bacterial Agents↗
PubMed1999

Amniotic fluid matrix metalloproteinase-9 levels in women with preterm labor and suspected intra-amniotic infection.

OBJECTIVE: To determine the accuracy of amniotic fluid (AF) matrix metalloproteinase-9 measurements for diagnosing intra-amniotic infection in women with preterm labor. METHODS: We performed amniocenteses in 44 women between 22 and 35 weeks' gestation who presented to our center with preterm labor and clinical suspicion of intra-amniotic infection. Each sample was analyzed by glucose measurement, Gram stain, and culture for aerobes, anaerobes, and mycoplasmas. We tested the AF for matrix metalloproteinase-9 using gelatin zymography and a commercial enzyme-linked immunosorbent assay (ELISA) system. We calculated accuracy and confidence intervals (CIs) for AF matrix metalloproteinase-9, glucose, and Gram stain for diagnosing intra-amniotic infection, using culture as the criterion standard. RESULTS: All patients who had matrix metalloproteinase-9 detectable by ELISA also demonstrated matrix metalloproteinase-9 by zymography. Six cases of intra-amniotic infection were confirmed by culture (prevalence 14%). The performance statistics of AF matrix metalloproteinase-9 for diagnosing intra-amniotic infection were: sensitivity 83% (95% CI 53, 99), specificity 95% (95% CI 88, 99), positive predictive value 71% (95% CI 37, 99), and negative predictive value 97% (95% CI 92, 99). Two women had false-positive results; one had gram-negative rods on the AF Gram stain and developed clinical signs and symptoms of chorioamnionitis several hours after amniocentesis and the other had a purulent vaginal discharge and an AF glucose level less than 15 mg/dL. Both delivered within 24 hours of amniocentesis. CONCLUSION: Measuring matrix metalloproteinase-9 in the AF appeared to be reliable for diagnosing intra-amniotic infection. An elevated matrix metalloproteinase-9 concentration in the AF at a preterm gestational age may portend imminent delivery regardless of microbiologic confirmation of intra-amniotic infection.

Adult↗
PubMed1999

The contribution of the intrinsic muscles to grip and pinch strength.

Profound deficiencies occur in the intrinsic minus hand with loss of the interossei, thenar, hypothenar, and adductor pollicis muscles. The purpose of this study was to define the load-generating deficiencies of grip and pinch after simulated low median and/or low ulnar nerve lesions. Twenty-one healthy volunteers underwent median and ulnar nerve blocks at the wrist level with mepivacaine HCI injection. Key pinch and grip data were recorded before injection and after each nerve block was determined to be effective. A computerized dynamometer that simultaneously recorded individual force data from each digit and cumulative grip was used to record grip strength. Grip strength data showed a significant decrease in total grasp at all 3 handle sizes after initial median or ulnar nerve block. The average decrease in grip strength was 38% after ulnar nerve block and 32% after median nerve block. The total grip loss after both injections averaged 49% compared with the preinjection strength. After ulnar or median nerve block there was a significant decrease in the force production of the long, ring, and small fingers but not the index finger. Pinch data revealed a significant decrease in key pinch of 77% after ulnar block and 60% after median block with a further significant change after combined block to decrease pinch 85%.

Adult↗
PubMed1999

Interaction of the protein C/protein S anticoagulant system, the endothelium and pregnancy.

Normal pregnancy is associated with significant changes in haemostasis, lipid metabolism and endothelial function. This suggests that maternal adaptation in these systems is required for successful pregnancy outcome. A number of acquired and heritable prothrombotic abnormalities are associated with complications in pregnancy. A common feature of these abnormalities is their ability to alter endothelial function or the protein C/protein S system and increase thrombin generation. In this review the normal function of the endothelium and the protein C/protein S system is detailed. The changes which characterize normal and complicated pregnancies are outlined and the evidence for the impact of heritable and acquired disorders of the protein C/protein S system on pre-eclampsia and fetal loss are discussed.

Anticoagulants↗
PubMed1999

Prediction of over-response to ovarian stimulation in an intrauterine insemination programme.

Prediction of poor-response is of equal importance to prediction of over-response in intrauterine insemination programmes. The gonadotrophin-releasing hormone agonist (GnRHa) stimulation test (GAST) was assessed as a predictor of over-response to ovarian stimulation in 81 patients. Blood samples were taken on cycle day 2 (before and 24 h after starting the GnRHa). Day 2 and 3 samples were assayed for oestradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Linear and logistic regression analyses were used to assess age, day 2 FSH, day 2 FSH/LH, oestradiol ratio (oestradiol on day 3/oestradiol on day 2) and FSH ratio (FSH on day 3/FSH on day 2) as predictors of the number of follicles (total and > or = 14 mm), oestradiol on HCG day, and clinical pregnancy rate as appropriate. Several parameters were also compared between the patients who produced < or = 3 (> or = 14 mm) follicles (group A) and those who produced >3 (> or = 14 mm) follicles (group B). The mean +/- SEM age of the patients in the study was 32 +/- 0.4 years. The mean total dose of recombinant FSH was 800 +/- 20 IU and the mean duration of stimulation was 7.6 +/- 0.2 days. Nine (11%) and 12 (15%) patients were cancelled for poor and over-response respectively. The oestradiol ratio was significantly positively correlated with oestradiol on HCG day (P < 0.001), and with the number of mature follicles (> or = 14 mm) (P = 0.01). Age, day 2 FSH and FSH ratio were not significantly correlated with oestradiol on HCG day, total follicles and follicles > or = 14 mm. None of the above-mentioned variables was correlated with clinical pregnancy rate. Group A had significantly lower oestradiol ratio (P = 0.007), longer duration of stimulation (P = 0.002), higher total FSH dose (P = 0.001), and lower oestradiol on HCG day (P = 0.001). GAST is therefore useful in predicting the high responders to gonadotrophin stimulation.

Adult↗