Biomedical subjects

J S Jones

Publications and source records attributed to J S Jones.

At least 19 recordsLinked to original sources

PubMed1997

The maternal insulin-like growth factor (IGF) and IGF-binding protein response to trisomic pregnancy during the first trimester: a possible diagnostic tool for trisomy 18 pregnancies.

Many lines of evidence point to an important role for the insulin-like growth factors (IGFs) in embryonic and fetal growth in human pregnancy. The bioavailability of IGFs is modulated by IGF-binding proteins (IGFBP-1 to -6), whose permissive or inhibitory actions are regulated in part by posttranslational modification. In second and third trimester pregnancies, maternal IGFBP-1 is elevated in preeclampsia and intrauterine growth retardation. In the first trimester, trisomic pregnancies result in derangement of maternal serum levels of peptides, including hCG beta and pregnancy-associated plasma protein A. Trisomy 18 is characterized by growth failure in the first trimester, whereas trisomy 21 is not; thus, if maternal serum levels of IGFs and IGFBPs reflect fetal growth, changes specific to trisomy 18 may be expected. We report maternal serum levels of IGF-I, IGF-II, and IGFBP-1,-2, and -3; IGFBP-1 phosphorylation; and IGFBP-3 proteolysis in pregnancies (n = 139) complicated by trisomy 18 or trisomy 21 compared with those in normal controls. Maternal IGF-I, IGF-II, and IGFBP-3 showed no significant difference between fetuses with a normal karyotype and those with trisomy 18 or 21. The mean IGFBP-1 level was significantly higher and the mean IGFBP-2 level was lower in fetuses with trisomy 18 compared with normal fetuses [108.8 +/- 6.1 vs. 36.7 +/- 1.9 micrograms/L (P = 0.0001) and 81.2 +/- 5.5 vs. 206.1 +/- 10.2 micrograms/L (P = 0.0001), respectively]. There was no significant difference between the trisomy 21 and normal groups. The reduction in IGFBP-2 was confirmed by Western ligand and immunoblotting, and there was no evidence of variation in lower mol wt products to suggest differential proteolysis. IGFBP-1 phosphoforms and IGFBP-3 proteolysis were not significantly different between groups. The finding of altered maternal serum levels of IGFBP-1 and IGFBP-2 specific to pregnancies complicated by trisomy 18 suggests that these binding proteins may be important mediators of fetal growth in the first trimester, and the clear differences in the ratio of IGFBP-1 to -2 may serve as an additional diagnostic marker for trisomy 18 pregnancies.

Chromosomes, Human, Pair 18↗

PubMed1996

Pediatric injuries from cardiopulmonary resuscitation.

STUDY OBJECTIVE: To assess the type, rate, and severity of unanticipated complications of CPR (external cardiac compressions and ventilation) in a pediatric population. METHODS: A retrospective review was undertaken of the records from all deceased children ( < 12 years old) who had been given CPR during an 8-year period (1988 through 1995). Patients with historical or physical evidence of preceding trauma were excluded. Clinical and autopsy records were abstracted for patient demographics, clinical findings, duration of CPR, persons administering CPR, and medical examiner summaries. RESULTS: Two hundred eleven children (mean age, 19.0 months) met the inclusion criteria and were entered into the study. The most common cause of cardiac arrest was sudden infant death syndrome (56%), followed by drowning (8%), congenital heart disease (7%), and pneumonia (4%). Mean duration of CPR was 45 minutes (range, 3 to 180 minutes). Fifteen children (7%) had at least one injury as a result of CPR; 7 (3%) had injuries that were considered medically significant. These included retroperitoneal hemorrhage (n = 2), pneumothorax (n = 1), pulmonary hemorrhage (n = 1), epicardial hematoma (n = 1), and gastric perforation (n = 1); in spite of prolonged resuscitation performed with variable degrees of skill, only one patient was noted to have rib fractures. CONCLUSION: Significant iatrogenic injuries are rare in children who receive CPR; they occur in approximately 3% of cases. Recognizing the possibility of a complication may help in the management of children who survive cardiac arrest. Regardless of resuscitation history, abuse should be considered whenever traumatic injuries are encountered.

Cardiopulmonary Resuscitation↗

PubMed1996

Does warming local anesthetic reduce the pain of subcutaneous injection?

The most frequent complaint noted with the use of lidocaine (or other amide local anesthetic) is stinging or burning pain associated with subcutaneous infiltration. The purpose of this study was to evaluate the efficacy of warming buffered lidocaine for reducing the pain of infiltration. Forty adult volunteers were entered into a randomized, crossover study conducted at a community teaching hospital. Blinded subjects underwent 1-mL subcutaneous injections of the study agent through 27-gauge needles over 30 seconds. Following a crossover protocol, "room temperature" buffered lidocaine (20 degrees C) was injected into one midvolar forearm and "body temperature" buffered lidocaine (37 degrees C) into the opposite arm. The order and the handedness of the two injections were randomized; an independent observer prepared the anesthetic solutions. Pain was assessed using a 100-mm visual analog pain scale and subjects' comparison of pain on injection. Twenty subjects (50%) reported that 20 degrees C buffered lidocaine was more painful and 17 (42.5%) reported that the 37 degrees C solution was more painful (sign test, P = .74). Similarly, a median pain score difference of 5.0 mm favoring 37 degrees C lidocaine was not statistically significant (sign rank test, P = .42). The order or the initial side of the injection did not influence the pain scores. The study had a power of 80% to detect a 10-mm difference between the two solutions at alpha = .05. These results suggest that warming buffered lidocaine to body temperature (37 degrees C) does not reduce the pain of subcutaneous infiltration.

Adult↗

PubMed1996

Racemic epinephrine in the treatment of laryngotracheitis: can relapse be prevented?

Explore the source record for details and available documents.

Acute Disease↗

PubMed1996

Age as a risk factor for inadequate emergency department analgesia.

Inadequate treatment of pain, which has been termed as "oligoanalgesia", appears to be common in a number of practice settings, including the emergency department (ED). The purpose of this study was to determine whether elderly patients with isolated long-bone fractures are less likely to receive analgesics in the ED than a similar cohort of younger patients. Consecutive adult patients (aged 20 to 50 years or older than 70 years) presenting to the ED with isolated long-bone fractures were evaluated using a retrospective cohort study design. Patient demographics, ED treatment, and disposition were analyzed (t tests, chi2) to identify significant differences between the two age groups. Analgesic use was recorded as oral or parenteral, nonnarcotic or narcotic, and low or high dose (less than or at least the equivalent of 10 mg parenteral morphine sulfate, respectively). A total of 231 patients met the inclusion criteria, of whom 109 were elderly (mean age, 80.6 +/- 7.4 years) and 122 nonelderly (mean age 33.9 +/- 8.0 years). Nonelderly patients were more likely than the elderly to receive ED pain medication (80% vs 66%, P =.02) within a shorter period of time (mean 52 min vs 74 min, P = .02), and at a higher equivalent dose (44% vs 19%, P = .002). Younger patients also tended to receive more narcotic medications (98% vs 89%, P = .03). Inadequate use of analgesics in adult ED patients with acute fractures appears to be common. A chronologic basis for variability in analgesic practice needs to be further characterized.

Adult↗

PubMed1996

Informed consent for medical research: common discrepancies and readability.

OBJECTIVE: To identify common discrepancies and average reading grade levels for informed consent forms (ICFs) as submitted to institutional review boards (IRBs) by medical researchers. METHODS: A retrospective evaluation of ICFs as submitted to IRBs of 3 university-affiliated hospitals during a 1-year period. ICF content was evaluated using a checklist of 23 requirements specified in the federal regulations governing human research. Documents then were computer-analyzed to determine the readability scores using 2 common indexes of comprehension. A discrepancy was defined as any instance in which an ICF did not address an applicable requirement in the Code of Federal Regulations. RESULTS: Eighty-two ICFs representing 16 medical specialties were evaluated; 8 (10%) were from emergency medicine. Eighteen ICFs (22%) were conspicuously incomplete, lacking > or = 9 federal requirements. The mean number of discrepancies was 4.7 (95% CI, 3.9-5.5) Common omissions included: a statement about who is doing the research, number of subjects in the study, circumstances when a subject's participation may be terminated, disclosure of alternative procedures, and notice to subjects regarding new findings. The mean Flesch grade level required to read all ICFs was 13.8 (95% CI, 13.5-14.2), implying that the majority of the U.S. adult population would be unable to comprehend these forms. CONCLUSION: Designing a consent form to meet all of the federal requirements while maintaining a level of reading comprehension suitable for the general population is a difficult task for investigators.

Adult↗

PubMed1996

Structure and practice of institutional review boards in the United States.

OBJECTIVE: The institutional review board (IRB) is a critical element in the protection of patients' and subjects' rights with regard to their participation in research protocols. The purpose of this study was to describe the structure and current practices of IRBs in the United States. METHODS: A self-administered questionnaire was mailed to the IRB chair of each U.S. hospital with a capacity of at least 400 beds (n = 907). The survey contained 21 questions outlining committee size and structure, review of research proposals, and policies concerning scientific misconduct. Chairs also were asked what advice they would offer a young investigator preparing a proposal for submission. RESULTS: A total of 488 surveys (54%) were returned; 447 of the responding institutions had an IRB committee. Committees had an average of 14 members, representing 27 medical specialties. Orthopedics had the least IRB representation (10% of committees), followed by emergency medicine (12%) and ophthalmology (15%). The majority of research proposals go through 5 specific steps once submitted for review. Common reasons for proposal rejection were improperly designed consent form (54%), poor study design (44%), unacceptable risk to subjects (34%), ethical or legal reasons (24%), and scientific merit (14%). When a research proposal is rejected, 86% of the responding IRBs assist the investigator in making appropriate revisions. Although a number of IRBs (17%) have dealt with scientific misconduct allegations, only 58% have a written policy regarding research integrity. CONCLUSION: Despite variations in committee structure and representation, IRBs have similar procedures for governing research. Investigators should be familiar with these procedures and are encouraged to discuss their proposal with an IRB representative prior to formal review.

Ethics, Institutional↗

PubMed1996

Sequential changes in insulin-like growth factor I (IGF-I) and IGF-binding proteins in children with end-stage liver disease before and after successful orthotopic liver transplantation.

Pediatric end-stage liver disease (ESLD) leads to poor linear growth and wasting. After orthotopic liver transplantation (OLT), catch-up growth occurs unpredictably and with a delay. The bulk of circulating insulin-like growth factor I (IGF-I) and its major circulating binding protein, IGF-binding protein-3 (IGFBP-3), is derived from the liver. We hypothesized that growth failure in ESLD, both before and after OLT, may result from abnormalities in the IGF-IGFBP axis. Serum IGF-I, IGFBP-1, and insulin were measured by RIA, and IGFBP-3 was determined by immunoradiometric assay in 26 children with ESLD (mean of 3.7 samples pre-OLT and 4.2 samples post-OLT per patient) and 30 age-matched controls. In addition, serum IGFBPs were visualized by Western ligand blotting. IGFBP-3 and IGFBP-2 were also observed by immunoblotting with specific antisera. IGFBP-3 protease activity was determined by protease gels using recombinant human IGFBP-3 label as substrate. Anthropometric measurements were performed according to standard techniques. Pre-OLT, IGF-I (32.7 +/- 4.8 micrograms/L), and IGFBP-3 (1.11 +/- 0.10 mg/L) were significantly lower than control values [IGF-I, 168.3 +/- 16.5 micrograms/L (P = 0.0001); IGFBP-3, 2.57 +/- 0.17 mg/L (P = 0.0001)]. Post-OLT, IGF-I (179.2 +/- 19.7 micrograms/L; P = NS) rose to control levels, whereas IGFBP-3 (3.49 +/- 0.14 mg/L; P = 0.002) became significantly greater than the control value. IGFBP-1 was significantly higher pre-OLT (78.9 +/- 9.6 micrograms/L; P = 0.0001) than post-OLT (45.7 +/- 6.9 micrograms/L), and both were significantly higher than control values (18.5 +/- 2.5 micrograms/L; P = 0.0001 vs. pre-OLT and P = 0.0002 vs. post-OLT). There was a trend toward higher insulin levels both pre-OLT (15.5 +/- 1.8 mU/L) and post-OLT (12.5 +/- 1.4 mU/L) compared with control values (9.7 +/- 1.1 mU/L; P = 0.06 vs. pre-OLT). IGFBP-1 was negatively correlated with serum insulin post-OLT (P = 0.008), but there was no correlation pre-OLT. Western ligand blotting confirmed the changes in IGFBP-3 pre- and post-OLT. Immunoblotting demonstrated a reduction in all mol wt forms of IGFVBP-3 pre-OLT. Protease assays demonstrated the appearance of IGFBP-3 proteolysis only at a time coincidental with the operative stress of OLT; overall, there was no difference in protease activity pre- and post-OLT. IGFBP-2 was unchanged post-OLT compared with pre-OLT, although levels were higher than control values. Mid-upper arm circumference and triceps skin fold thickness SD score 3 months post-OLT and weight SD score 1 yr post-OLT were significantly higher than those at OLT. In conclusion, IGF-I and IGFBP-3 are reduced, and IGFBP-1 and IGFBP-2 are increased in children with ESLD. After OLT, IGF-I levels return to normal, but marked abnormalities in IGFBPs remain. These changes may help to explain at least in part the growth failure seen in pediatric ESLD both before and after successful OLT.

Adolescent↗

PubMed1996

Differential effects of malnutrition, bile duct ligation and galactosamine injection in young rats on serum levels and gene expression of IGF-binding proteins.

Hepatic gene expression and circulating levels of IGF-binding proteins (IGFBP)-1 to -4 were examined in two rat models of liver disease employing acute hepatitis or chronic structural damage. The study comprised four groups: group 1 (n = 6) was injected intraperitoneally with saline and food was available ad libitum (AL), group 2 (n = 6) underwent bile duct ligation (BDL), group 3 (n = 6) was injected with 400 mg galactosamine (GAL), group 4 (n = 6) was sham-operated and pair-fed to group 2 (PF). All were killed by decapitation at day 7. Serum IGF-I, by RIA, was significantly (P < 0.05) lower in the BDL group (458 +/- 37 micrograms/l) and PF group (451 +/- 51 micrograms/l) compared with the AL group (643 +/- 77 micrograms/l) and GAL group (720 +/- 67 micrograms/l). Immunoblotting showed raised IGFBP-2 levels in all groups compared with AL (BDL, 167 +/- 14% of AL; GAL, 173 +/- 13%; PF, 149 +/- 9%). IGFBP-3 was decreased in the GAL (56 +/- 11%) and PF groups (66 +/- 5%) but increased in the BDL group (154 +/- 29%). IGFBP-4 was decreased in the GAL (76 +/- 11%) and PF groups (47 +/- 5%) but unchanged in the BDL group (90 +/- 10%). By Northern analysis, IGFBP-1 mRNA expression was increased in the GAL (321 +/- 51%) and PF groups (263 +/- 12%) but reduced in the BDL group (68 +/- 8%). IGFBP-2 expression increased in all groups (PF, 836 +/- 19%; BDL, 683 +/- 121%; GAL, 372 +/- 68%) and was highest in the BDL and PF groups. IGFBP-3 expression was reduced in all groups (BDL, 57 +/- 16%; GAL, 52 +/- 12% PF, 51 +/- 13%). IGFBP-4 expression was reduced in the GAL (30 +/- 4%) and PF (28 +/- 5%) groups but unchanged in the BDL group (76 +/- 9%). Marked changes in gene expression of IGFBPs occurred in both models of liver disease, together with serum changes, which were different from each other and from malnutrition alone.

Animals↗

PubMed1996