Fetal exposure to herpesviruses may be associated with pregnancy-induced hypertensive disorders and preterm birth in a Caucasian population.

OBJECTIVE: To investigate the role of fetal viral infection in the development of a range of adverse pregnancy outcomes (APOs), including pregnancy-induced hypertensive disorders (PIHD), antepartum haemorrhage (APH), birthweight <10th percentile (small for gestational age, SGA) and preterm birth (PTB). DESIGN: Population-based case-control study. SETTING: Laboratory-based study. POPULATION: The newborn screening cards of 717 adverse pregnancy cases and 609 controls. METHODS: Newborn screening cards were tested for RNA from enteroviruses and DNA from herpesviruses using polymerase chain reaction (PCR). The herpesviruses were detected using two PCRs, one detecting nucleic acids from herpes simplex virus (HSV)-1, HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus (HHV)-8, hereafter designated Herpes PCR group A viruses, and the other detecting nucleic acids from varicella-zoster virus (VZV), HHV-6 and HHV-7, hereafter designated Herpes PCR group B viruses. MAIN OUTCOME MEASURE: Odds ratios and 95% CIs for specific APOs. RESULTS: For both term and PTBs, the risk of developing PIHD was increased in the presence of DNA from Herpes PCR group B viruses (OR 3.57, 95% CI 1.10-11.70), CMV (OR 3.89, 95% CI 1.67-9.06), any herpesvirus (OR 5.70, 95% CI 1.85-17.57) and any virus (OR 5.17, 95% CI 1.68-15.94). The presence of CMV was associated with PTB (OR 1.61, 95% CI 1.14-2.27). No significant association was observed between SGA or APH and exposure to viral infection. CONCLUSIONS: Fetal exposure to herpesvirus infection was associated with PIHD for both term and PTBs in this exploratory study. Exposure to CMV may also be associated with PTB. These findings need confirmation in future studies.

Effect of clonidine on upper extremity tourniquet pain in healthy volunteers.

BACKGROUND AND OBJECTIVES: Tourniquet pain is often a limiting factor during intravenous regional anesthesia (IVRA). The purpose of this study was to evaluate the efficacy of 1 microg/kg of clonidine added to IVRA-lidocaine in decreasing the onset of severe tourniquet pain. METHODS: Upper extremity IVRA was performed in 15 volunteers with a double-cuffed tourniquet on 2 separate occasions at least 1 week apart. IVRA was established with either 40 mL 0.5% lidocaine (IVRA-L) or 40 mL 0.5% lidocaine with 1 microg/kg clonidine (IVRA-Cl). Verbal pain scores (VPS) from 0 to 10 were recorded every 5 minutes. When the VPS reached 6, the distal cuff was inflated, and the proximal cuff was deflated. This was defined as the first tourniquet time (T1). The study was terminated at a VPS of 10, or at 60 minutes, whichever occurred first. The time from distal cuff inflation to deflation was defined as the second tourniquet time (T2). Total tourniquet time (TT) was the sum of T1 and T2. RESULTS: T1 for IVRA-L (21.6 +/- 3.9) and IVRA-Cl (22.7 +/- 2.7) were not significantly different. T2 and TT were significantly longer (P < .0001; P < .0007, respectively) for IVRA-Cl (33.0 +/- 6.2; 55.6 +/- 6.6) than for IVRA-L (25.5 +/- 4.4; 47.1 +/- 5.2). CONCLUSION: This study shows that the addition of 1 microg/kg of clonidine to 40 mL of 0.5% IVRA-L delays the onset time of tourniquet pain in healthy, unsedated volunteers.

Use of clonidine in hernia patients: intramuscular versus surgical site.

BACKGROUND AND OBJECTIVES: This study was designed to determine if administration of clonidine in hernia patients enhances analgesia. It was also designed to determine whether administration directly in the surgical site further improves the analgesia. METHODS: A randomized, double-blinded study was undertaken at a tertiary care hospital. Forty-five outpatients undergoing unilateral inguinal hernia repair by one of two surgeons (D.P. or M.A.) under local anesthesia with monitored anesthesia care were evaluated. Patients were invited to participate in this investigation at the time of the preoperative surgical visit. Patients who had a contraindication to the use of clonidine or who refused repair under local anesthesia with sedation were excluded. Patients were randomized to one of three groups: (a) clonidine 0.5 microg/kg intramuscularly and saline in the surgical site (mixed with the local anesthetic); (b) clonidine 0.5 microg/kg in the surgical site and saline intramuscularly; or (c) saline in both the surgical site and intramuscularly. The outcome measures included visual analog pain scores twice in the hospital, pain scores at rest and with movement 24 hours postoperatively, the time to first analgesic, and total analgesic requirement. RESULTS: The pain scores were lower in both clonidine groups at 2 hours postoperatively than in the control group (P < .03). No difference was observed with respect to the time to first analgesic, 24-hour analgesic use, or 24-hour pain scores among the groups. CONCLUSIONS: When clonidine is administered to patients undergoing hernia repair, the 2-hour pain scores are lowered. No difference was exhibited when clonidine was administered intramuscularly or directly into the hernia site.

Multiplexed, real-time PCR for quantitative detection of human adenovirus.

Adenovirus infection is becoming increasingly recognized as a cause of morbidity and mortality in the immunosuppressed patient population. While early detection and quantitation of adenovirus in peripheral blood has been suggested as a means of directing and monitoring antiviral therapy in these patients, few methods have been published, particularly with respect to viral quantitation. A multiplexed real-time PCR assay was developed that can quantitatively detect a wide range of known serotypes of human adenovirus, including all of subgroups A to C. This assay was compared to a qualitative, Southern blot-based PCR assay by using 45 peripheral blood specimens from 16 patients. There was 100% concordance between the two tests in terms of qualitative results. The real-time assay detected adenovirus in patient samples at levels from <200 to 266,681 copies/ml of blood. By using control viral samples, sensitivity was demonstrated to less than 10 copies of viral genome per reaction and quantitative linearity was demonstrated from 10 to 10(6) copies of input viral DNA. Equivalent sensitivity and linearity were demonstrated for 15 different reference serotypes of adenovirus. Eleven other viral serotypes have complete target region sequence homology to one or more of the strains tested. No cross-reactivity was noted with other commonly isolated viral species. Sequence analysis showed no significant homology with any other human pathogens (bacterial or viral). This assay allows rapid, sensitive, and specific quantitation of adenovirus and may have a significant impact on the care of immunocompromised patients at risk for disseminated viral infection.

Sumatriptan in patients with postdural puncture headache.

OBJECTIVE: To determine the efficacy of sumatriptan in the management of patients presenting for an epidural blood patch for the management of postdural puncture headache. BACKGROUND: Postdural puncture headache can be quite severe, requiring invasive therapy (ie, epidural blood patch). Sumatriptan has been used successfully in patients with postdural puncture headache, however, its use has not been investigated in a controlled fashion. METHODS: Ten patients with postdural puncture headache presenting for an epidural blood patch were given either saline or sumatriptan subcutaneously. The severity of the headache was evaluated at baseline and 1 hour following injection. If the headache remained severe, an epidural blood patch was performed. RESULTS: Only one patient in each group received relief from the injection. CONCLUSIONS: We do not recommend sumatriptan in patients who have exhausted conservative management of postdural puncture headache.

A dose-response study of intravenous regional anesthesia with meperidine.

UNLABELLED: Intravenous regional anesthesia (IVRA) with meperidine in doses > or = 100 mg provides effective postoperative analgesia. However, this technique is associated with excessive opioid-related side effects, which limit its clinical usefulness. The minimal dose of meperidine that is effective for IVRA has yet to be established. We added 0, 10, 20, 30, 40, or 50 mg of meperidine to 0.5% lidocaine IVRA for either carpal tunnel or tenolysis surgery. Pain and sedation scores and the incidence of side effects were assessed in the postanesthesia care unit. The duration of analgesia, defined as the time to first request for pain medications, and use of acetaminophen/codeine (T3) tablets were measured. The duration of analgesia increased, in a dose-dependent manner, in the groups that received 0, 10, 20, and 30 mg of meperidine. There was no significant difference in the duration of analgesia for patients receiving > or = 30 mg of meperidine. T3 use was similar in the groups that received 0, 10, and 20 mg of meperidine and in the groups that received 30, 40, and 50 mg. T3 use was significantly lower in the larger dose groups. The incidence of sedation and of all other side effects was significantly higher in the groups that received 30-50 mg of meperidine compared with those that received smaller doses. We conclude that doses of meperidine large enough to produce the most effective postoperative analgesia with IVRA lidocaine causes a significant incidence of side effects, thus limiting its clinical usefulness. IMPLICATIONS: Meperidine may be a useful addition to 0.5% lidocaine for i.v. regional anesthesia. We showed that 30 mg is the optimal dose of meperidine with respect to postoperative analgesia. However, this dose caused a significant incidence of sedation, dizziness, and postoperative nausea and vomiting.

Dose-response of ketorolac as an adjunct to patient-controlled analgesia morphine in patients after spinal fusion surgery.

UNLABELLED: This randomized, blind study was designed to determine the appropriate dose of ketorolac (a drug used as a supplement to opioids) to administer to patients who have undergone spinal stabilization surgery. The ketorolac was administered every 6 h, in addition to patient-controlled analgesia (PCA) with morphine, to 70 inpatients undergoing spine stabilization by one surgeon. The study was performed to determine the analgesic efficacy and incidence of side effects with different doses of ketorolac. The patients were divided into seven groups. They were given either i.v. saline (control group) or i.v. ketorolac (5, 7.5, 10, 12.5, 15, or 30 mg) every 6 h. The outcomes measured included pain scores, 24-h morphine usage, level of sedation, and side effect profile six times during the first 24 h postoperatively. The total dose of morphine was significantly larger in the control and 5 mg ketorolac groups than in the other five groups. Morphine consumption was similar in all groups receiving > or = 7.5 mg of ketorolac. The pain scores were significantly higher in the control group than in some of the larger dose groups at three of the study intervals. The 5 mg group had higher pain scores than the other groups at most of the time intervals studied. There were no significant differences in pain scores among the other five groups. Sedation scores were higher (i.e., patients were more sedated) in the control group than in the other six groups at three of the time periods. We conclude that the administration of ketorolac 7.5 mg every 6 h has a morphine-sparing effect equivalent to that of larger doses in patients undergoing spine stabilization surgery. Using larger doses of ketorolac did not result in less somnolence, lower morphine use, or less pain. We recommend that ketorolac 7.5 mg be given every 6 h to patients undergoing spinal fusion surgery in addition to PCA morphine. IMPLICATIONS: Using smaller doses of ketorolac (e.g., 7.5 mg every 6 h) as a supplement to morphine patient-controlled analgesia is as effective as larger doses in patients who have undergone spine stabilization surgery.

Intraarticular morphine in the multimodal analgesic management of postoperative pain after ambulatory anterior cruciate ligament repair.

UNLABELLED: Reconstruction of the anterior cruciate ligament (ACL) is associated with a considerable degree of postoperative pain. Our customary multimodal approach to postoperative analgesia after ambulatory ACL surgery includes perioperative nonsteroidal antiinflammatory drugs, pre- and postincisional intraarticular (I.A.) bupivacaine (B), and postoperative cryotherapy using an external cooling system. This study was designed to determine whether the addition of I.A. morphine (MS) provides improved postoperative analgesia. One hundred patients scheduled for elective ambulatory ACL repair received our standard multimodal therapy. After surgery, patients were randomized to one of four study groups. Group 1 received 30 mL of 0.25% B I.A. Group 2 received 30 mL of normal saline I.A. and 5 mg of MS I.A. Group 3 received 30 mL of 0.25% bupivacaine I.A. and 5 mg of MS I.V.. Group 4 received 30 mL of 0.25% B I.A. and 5 mg of MS I.A. The addition of I.A. B postoperatively provided prolonged analgesia and decreased postoperative pain and analgesic requirements. The addition of MS to I.A. B did not provide additional postoperative analgesia. We conclude that patients undergoing ambulatory ACL repair using our standard multimodal analgesic regimen failed to receive additional postoperative analgesia when MS was added to the I.A. B. IMPLICATIONS: Patients receiving a multimodal analgesic regimen of perioperative nonsteroidal antiinflammatory drugs, intraarticular bupivacaine, and external cooling did not receive any additional analgesia from intraarticular morphine.

Gastric contents in children presenting for upper endoscopy.

UNLABELLED: Previous studies of gastric contents in children presenting for surgery specifically excluded those with gastrointestinal disorders. Because these children often need sedation or anesthesia for procedures such as upper endoscopy, it is important to determine the gastric fluid volume and pH in this group to better characterize their risk of aspiration. We therefore analyzed the gastric fluid volume and pH of children with a variety of gastrointestinal symptoms presenting for upper endoscopy. After obtaining institutional review board approval, the stomach contents of 248 children (aged 2 mo to 18 yr) presenting for upper endoscopy were prospectively measured under direct endoscopic vision. Children were fasted for both solids and liquids for at least 6 h (<6 mo) or 8 h (>6 mo). Gastric fluid pH was measured using pH paper. Children received either deep sedation or general anesthesia and were grouped according to their presenting diagnosis. Results were analyzed by using analysis of variance, Kruskal-Wallis, and correlation (P value < 0.05). The mean gastric fluid volume was 0.35 +/- 0.45 mL/kg (range 0-3.14 mL/kg), and the mean gastric fluid pH was 1.37 +/- 1.6 (range 1-7). Of the children, 33% had gastric fluid volumes >0.4 mL/kg, 87% had gastric fluid pH <2.5, and 30% had gastric fluid volume >0.4 mL/kg and pH <2.5. Children with the presenting complaint of abdominal pain had the largest gastric fluid volumes. These data are not appreciably different from historical controls (healthy children fasted for an equivalent period of time who did not have gastrointestinal symptoms). IMPLICATIONS: When fasted for at least 6-8 h, children with a history of gastrointestinal symptoms presenting for upper endoscopy did not have gastric contents with increased volume and acidity compared with previously published groups of children without gastric symptoms who were fasted the same length of time. These results do not support the argument that children with gastrointestinal symptoms pose an increased anesthetic risk for aspiration.

Apolipoprotein A-I Milano: sex-related differences in the concentration and composition of apoA-I- and apoB-containing lipoprotein particles.

The presence of apolipoprotein (apo) A-IMilano (A-IM) mutant of apoA-I has a marked effect on plasma lipoproteins of A-IM carriers including variable hypertriglyceridemia, increased levels of very low density lipoproteins (VLDL), slightly elevated levels of triglyceride-enriched low density lipoproteins (LDL) and greatly reduced levels of high density lipoproteins (HDL). To gain further insight into this dyslipoproteinemic syndrome characterized clinically by the absence of coronary artery disease, we have determined the concentration and composition of apoA- and apoB-containing lipoprotein families in four male and four female carriers and corresponding normal controls. Results have shown that A-IM carriers have significantly reduced levels of lipoprotein (LP) A-I (45%), LP-A-I:A-II (60%), and LP-A-II (70%) and significantly increased levels of cholesterol-rich LP-B (67%) and triglyceride-rich LP-B:C, LP-B:C:E, and LP-A-II:B:C:D:E (65%) particles compared to controls. However, there were significant sex-related differences in the levels of apoA-and apoB-containing lipoproteins. Female carriers had significantly higher concentrations of LP-A-I (39 +/- 10 vs. 12 +/- 6 mg/dl) and LP-A-I:A-II (48 +/- 11 vs. 30 +/- 6 mg/dl) than male carriers. Furthermore, female carriers had higher levels of LP-B:C (23 +/- 18 vs. 6 +/- 5 mg/dl) and LP-A-II:B:C:D:E (13 +/- 6 vs. 2.3 +/- 0.8 mg/dl) but lower concentrations of LP-B (103 +/- 52 vs. 152 +/- 54 mg/dl) and LP-B:C:E (5 +/- 2.5 vs. 13 +/- 8 mg/dl) than male carriers. In general, the levels of LP-A-I and LP-A-I:A-II particles correlated positively with the levels of all three types of triglyceride-rich lipoproteins (LP-Bc) and negatively with the levels of LP-B particles. A comparative study of lipoprotein families in several dyslipoproteinemic states characterized by low levels of HDL has indicated that the characteristic lipoprotein particle profile of A-IM carriers results most probably from the selective effect of apoA-IM mutant rather than a general reduction in HDL levels. It appears that increased levels of LP-A-II:B:C:D:E particles, an inefficient substrate for lipoprotein lipase, and structurally defective LP-A-I:A-II particles, the normal acceptors of minor apolipoproteins released during lipolysis of triglyceride-rich lipoproteins, may be the main contributing factors to moderate hypertriglyceridemia characteristic of A-IM carriers.

Characterization of apoA- and apoB-containing lipoprotein particles in a variant of familial apoA-I deficiency with planar xanthoma: the metabolic significance of LP-A-II particles.

This study describes a variant of familial apoA-I deficiency associated with a moderate risk for premature coronary artery disease. The proband, a 25-year-old man of Philippine origin, and his 62-year-old maternal aunt had peripheral corneal opacification, xanthelasma, and planar xanthoma; the aunt had coronary artery bypass surgery at 61 years of age. Proband's parents and three brothers were asymptomatic and apparently healthy. The characteristic apolipoprotein features of affected patients were the immunochemically and chemically undetectable apoA-I, reduced levels of apoA-II, apoC-II, apoC-III, and apoD, and normal levels of apoB and apoE; except for negligible levels of high density lipoprotein (HDL)-cholesterol (2-3 mg/dl), their plasma lipid profile was normal. The apoA-I levels in all five unaffected relatives were more than one SD below the normal mean values for their age and sex; the HDL-cholesterol levels of proband's unaffected brothers were below the 10th percentile of normal control values. Patient's very low density lipoprotein (VLDL), low density lipoprotein (LDL), and HDL contained 1.4, 80.4, and 18.1%, whereas those of control subjects contained 2.7, 28.8, and 68.1% of the total apolipoprotein mass, respectively. In unaffected relatives, the levels of LP-A-I, but not LP-A-I:A-II, were significantly lower than in controls. Neither of the two patients had detectable concentrations of LP-A-I or LP-A-I:A-II. Their HDL only consisted of LP-A-II particles, the levels of which (7-13 mg/dl) were similar to those of unaffected relatives or controls. There was no difference in the lipid composition of LP-A-II between patients and their relatives. However, LP-A-II from patients contained substantial amounts of apoC-peptides and apoE (0.40-0.98 mg/mg apoA-II), whereas those from unaffected relatives were free of these minor apolipoproteins. In patients, among all four major apoB-containing lipoproteins, only the levels of LP-B and LP-B:C were slightly higher than those in controls. Results of this study suggest a genetic cause for this variant of apoA-I deficiency characterized most probably by autosomal recessive inheritance. It appears that patients are likely to be homozygous for a gene present in single dose in the parents and brothers of the affected proband.(ABSTRACT TRUNCATED AT 400 WORDS)