A randomized, controlled trial of a eutectic mixture of local anesthetic cream (lidocaine and prilocaine) versus penile nerve block for pain relief during circumcision.

OBJECTIVE: We set out to compare a eutectic mixture of local anesthetic cream (lidocaine and prilocaine) to dorsal penile nerve block with lidocaine for anesthesia during circumcision. STUDY DESIGN: In a double-blind study, term newborns were randomized to local anesthetic cream and sodium chloride solution dorsal penile nerve block (n = 31) or to placebo cream and lidocaine dorsal penile nerve block (n = 29). Pain was assessed by determination of heart rate, respiratory rate, and behavioral distress scoring. Group differences were evaluated with repeat-measures analyses of variance. RESULTS: Distress scores and heart rates were significantly higher in the eutectic mixture group than in the lidocaine group. Respiratory rates were higher in the eutectic mixture group but did not reach statistical significance. CONCLUSIONS: Distress scores and heart rates were significantly higher in infants treated with the anesthetic mixture than in infants treated with lidocaine. Dorsal penile nerve block with lidocaine is a more efficacious means of providing anesthesia for neonatal circumcision than the mixture of local anesthetics.

A randomized, placebo-controlled comparison of EMLA() and dorsal penile nerve block for pain relief during neonatal circumcision.

Objective: To evaluate the relative efficacies of eutetic mixture of local anesthetics (EMLA()) cream and dorsal penile nerve block (DPNB) for pain relief during neonatal circumcision.Methods: After parental informed consent, appropriate-for-gestational age, term, healthy newborns were randomized to receive either EMLA cream and placebo saline DPNB or placebo cream and 1% lidocaine DPNB. Placebo and EMLA cream were prepared by the pharmacy and applied by study nurses. Preloaded syringes of saline or 1% lidocaine were also prepared by the pharmacy for the DPNB injections. This ensured blinding of the surgeons and assistants at the time of circumcisions. Circumcisions were performed with the Gomco clamp technique by one of three obstetrics and gynecology residents. Pain levels were assessed by measuring pulse and respiratory rates and determining Brazelton states at each step of the circumcision. Videotapes were made of each procedure to allow later scoring by a single blinded observer for Brazelton states. Brazelton state scores increase with increased infant pain and distress, as do heart and respiratory rates. Means were compared by t test and proportions by chi(2). A P value of.05 was considered statistically significant.Results: A total of 60 infants were randomized, 29 to DPNB and 31 to EMLA. Preoperative Brazelton state scores, heart rates, and respiratory rates were similar in both groups. Brazelton state scores were lower in the DPNB group at each step of the procedure-injection, dissection of the foreskin, clamp placement, and clamp removal-and postoperatively and overall, but the differences only reached statistical significance during dissection and clamp removal. Heart and respiratory rates also were lower at all surgical steps in the DPNB group but only reached statistical significance during postoperative observation.Conclusions: Although both EMLA and DPNB have been shown in other studies to decrease pain during neonatal circumcisions, DPNB has greater effectiveness in relieving the pain of circumcision.

Modulation of cholecystokinin activity by albumin.

We found that a variety of cholecystokinin (CCK) receptor ligands bind to bovine serum albumin (BSA). This binding was rapid, fully reversible, temperature independent, of low affinity, and specific for BSA; it depended on the concentration of BSA, the chemical structure of the ligand, and the chemical composition of the incubation medium. BSA also decreased the binding of 125I-labeled CCK octapeptide (125I-CCK-8) to CCK receptors on pancreatic acini and membranes but increased the potency with which CCK-8 inhibited binding of 125I-CCK-8. These counterintuitive findings appeared to result from BSA altering the affinities of CCK-8 for different affinity states of the pancreatic CCK receptor. An alternate hypothesis is that BSA increased the efficacy of CCK-8 such that it bound to receptors and also caused biochemical changes in other receptors that reduced their ability to bind 125I-CCK-8. BSA enhanced the ability of CCK-8 to stimulate amylase secretion from pancreatic acini and to cause contraction of dispersed gastric smooth muscle cells. Thus, CCK can bind to BSA, and the BSA-CCK complex has substantially different activities from the free, uncomplexed hormone.

Characterization of the three different states of the cholecystokinin (CCK) receptor in pancreatic acini.

By measuring binding of [125I]CCK-8 and [3H]L-364,718 to rat pancreatic acini we demonstrated directly that the pancreatic CCK receptor can exist in three different affinity states with respect to CCK--high affinity, low affinity and very low affinity. Binding of [125I]CCK-8 reflects interaction of the tracer with the high and low affinity states, whereas binding of [3H]L-364,718 reflects interaction of the tracer with the low and very low affinity states. Treating acini with carbachol abolished the high affinity state of the CCK receptor and converted approximately 25% of the low affinity receptors to the very low affinity state. Carbachol treatment was particularly useful in establishing the values of Kd for the high and low affinity states for different CCK receptor agonists and antagonists. Of the various CCK receptor agonists tested, CCK-8 had the highest affinity for the high affinity state (Kd approximately 1 nM), whereas CCK-JMV-180 had the highest affinity for the low (Kd 7 nM) and very low affinity (Kd 200 nM) states. Gastrin and de(SO4)CCK-8 had affinities for the high and low affinity states of the receptor that were 100- to 400-fold less than those of CCK-8 but had affinities for the very low affinity state that were only 3- to 10-fold less than that of CCK-8. CCK receptor antagonists showed several patterns in interacting with the different states of the CCK receptor. L-364,718 had the same affinity for each state of the CCK receptor. CR1409 and Bt2cGMP each had similar affinities for the high and low affinity states and lower affinity for the very low affinity state. L-365,260 and CCK-JMV-179 had the highest affinity for the low affinity state and lower affinities for the high and very low affinity states. Different CCK receptor agonists caused the same maximal stimulation of amylase secretion but showed different degrees of amplification in terms of the relationship between their abilities to stimulate amylase secretion and their abilities to occupy the low affinity state of the CCK receptor. When amplification was expressed quantitatively as the value of Kd for the low affinity state divided by the corresponding EC50 for stimulating amylase secretion the values were CCK-8 (1000), de(SO)CCK-8 (1500), gastrin (100) and CCK-JMV-180 (Menozzi, D., Vinayek, R., Jensen, R.T. and Gardner, J.D. (1991) J. Biol. Chem. 266, 10385-1091).(ABSTRACT TRUNCATED AT 400 WORDS)

Multiple affinity states of different cholecystokinin receptors.

We transfected COS cells with cDNA for rat cholecystokinin-A (CCK-A) and different CCK-B receptors and measured binding of 125I-CCK-8, [3H]L-364,718 and [3H]L-365,260 to characterize the different affinity states for each type of CCK receptor. Rat CCK-A and CCK-B receptors, canine CCK-B receptors and canine mutant CCK-B (M-CCK-B) receptors in which the leucine in position 355 was replaced by valine each existed in three different affinity states for CCK-8, high affinity, low affinity, and very low affinity. In rat CCK-A and probably CCK-B receptors, most were in the very low affinity state, whereas with canine CCK-B and M-CCK-B receptors, most were in the low affinity state. Studies with CCK receptor agonists, CCK-8, gastrin, and CCK-JMV-180, in conjunction with CCK receptor antagonists, L-364,718 and L-365,260, showed a different pattern of affinities for these ligands at the different CCK receptors. Thus, each transfected CCK receptor can exist in three different affinity states for CCK-8 and has a characteristic pattern of interaction with different ligands. This ability to exist in multiple affinity states is an intrinsic property of the CCK receptor molecule itself.

Direct demonstration of three different states of the pancreatic cholecystokinin receptor.

We used rat pancreatic acini as well as COS-7 cells transfected with the cloned pancreatic cholecystokinin (CCK) receptor and measured the abilities of CCK octapeptide (CCK-8) and L-364,718 (a CCK receptor antagonist) to inhibit binding of 125I-labeled CCK-8 (125I-CCK-8) and [3H]L-364,718. With pancreatic acini 125I-CCK-8 bound to two different states of the CCK receptor. The high-affinity state (1% of the receptors) had a Kd for CCK-8 of 985 pM and the low-affinity state (19% of the receptors) had a Kd for CCK-8 of 30 nM. [3H]L-364,718 bound to low-affinity receptors and to a previously unrecognized very-low-affinity state (80% of the receptors) having a Kd for CCK-8 of 13 microM. L-364,718 had the same affinity (Kd 3 nM) for each of the three different states of the CCK receptor. Similar measurements using transfected COS cells also identified three different states of the CCK receptor, with the very-low-affinity state being the most abundant. Thus, the ability of the CCK receptor to exist in three different states is an intrinsic property of the CCK receptor molecule itself.

Correlation of Doppler US tumor signals with neovascular morphologic features.

Abnormal Doppler ultrasound signals were detected in 44 of 47 patients with primary malignant tumors of the liver, kidney, adrenal gland, or pancreas (94%). Two different signal types were noted: a high-velocity signal (n = 38) with Doppler shifts exceeding 3 kHz (at an insonating frequency of 3 MHz) and a very low-impedance signal (n = 9) demonstrating little systolic-diastolic variation. In three patients, both types were present. In 19 patients, histologic (n = 12) and/or angiographic (n = 16) correlation was available. Among 13 patients with angiographic studies and signals over 3 kHz, arteriovenous shunting was demonstrated in six. The ratio of the systolic to diastolic Doppler shift is a function of vascular impedance. This systolic/diastolic index was less than 3 in eight patients with histologic correlation. All eight had prominent vascular spaces, and the flow in such thin-walled, endothelium-lined spaces would account for the low-impedance signals. Of nine patients with systolic/diastolic indexes of 3 or less and angiographic correlation, three had marked and four had moderate tumor staining.

Detection of neovascular signals in a 3 day Walker 256 rat carcinoma by CW Doppler ultrasound.

An animal model was used to study tumor blood flow by the Doppler CW technique. The objective was to determine when neovascularity could be detected as a function of tumor size and time since transplantation. A Walker 256 carcinosarcoma tumor was inoculated into the flank of 17 Sprague-Dawley rats. Doppler examinations, using a 9 MHz CW probe, were performed daily from day 0 to day 7. The contralateral flank was used as a control. No signals were detected from the control side nor from the inoculated side until day 3. By day 3, Doppler signals could be easily detected in all tumor implants with a minimum weight of only 50 mg. These signals showed a mean systolic frequency shift of 3.3 +/- 0.47 kHz at 3 days and 3.46 +/- 0.58 kHz at 7 days. The diastolic Doppler shifted frequency was 1.78 +/- 0.31 kHz at 3 days and 1.88 +/- 0.23 kHz at 7 days giving a Pourcelot index of 0.47 +/- 0.1 at 3 days and 0.46 +/- 0.09 at day 7. These figures indicate the presence of low impedance vessels with high velocity flow such as has been reported in many human tumors. The vascular morphology was further evaluated by digital angiography which demonstrated coincidence between the site of the high velocity Doppler signals and the presence of arteriovenous anastomoses manifested by simultaneous arterial and venous filling. Further infusion techniques using India ink or Microfil showed the chaotic arrangement of tumor vessels located around the growing edge of the tumor implant. The development of such vascularity is a well-recognized prerequisite for tumor growth and invasion.(ABSTRACT TRUNCATED AT 250 WORDS)

Focal liver masses: differential diagnosis with pulsed Doppler US.

Duplex Doppler ultrasound (US) was used in 68 consecutive patients with focal liver lesions, including 12 hepatocellular carcinomas, one cholangiocarcinoma, 37 metastases, 15 hemangiomas, one hemangioendothelioma, and two focal nodular hyperplasias. Of the hepatocellular carcinomas, six were diffusely hyperechoic, two were hypoechoic, two were single hyperechoic lesions, and two were multifocal and hyperechoic. All ten tumors with Doppler shifts of 5 kHz or above proved to be hepatocellular carcinomas. The other two hepatocellular carcinomas showed Doppler shifts of 3 kHz. In contrast, no hemangioma showed shifts above 0.7 kHz, and ten of the 15 gave no detectable signal. Of the metastases, 20 gave no signal and 17 had signals of up to 4 kHz. Three-kilohertz signals were also obtained from a cholangiocarcinoma, a hemangioendothelioma, and focal nodular hyperplasia. Correlation with angiographic findings suggested that the high-velocity Doppler signals were associated with large pressure gradients due to arteriovenous shunting. Duplex Doppler US can therefore aid in the differential diagnosis of diffuse and focal liver lesions.

Transformation of a plasmid encoding an adhesin of Staphylococcus aureus into a nonadherent staphylococcal strain.

Plasmid DNA was isolated and purified from a strain of Staphylococcus aureus demonstrating adherence to human epithelial cells, as determined by an assay quantitating adherence of radiolabeled S. aureus to HeLa cells in tissue culture. Other phenotypic characteristics of the donor strain are resistance to ampicillin and absence of hemolysis. A 23.5-kb (kilobase) plasmid was transformed into a nonadherent, ampicillin-sensitive, beta-hemolytic recipient of S. aureus, rendering it both ampicillin-resistant and adherent to a degree approaching that of the donor strain. Plasmid analysis of the donor and transformant strains revealed three identical EcoRI fragments of 7.6 kb, 6.5 kb, and 2.2 kb, together with a 3.6-kb EcoRI fragment in the transformant that demonstrated homology with the last 7.2-kb fragment in the donor. We conclude that an adhesin of S. aureus is encoded by this 23.5-kb penicillinase-encoding plasmid and that techniques of molecular genetics may be utilized to clarify the mechanisms of adherence of S. aureus.

Vancomycin pharmacokinetics in small, seriously ill infants.

Twenty vancomycin pharmacokinetic studies were performed on 17 small infants who were receiving the antibiotic for treatment of documented infections. Fourteen patients were less than or equal to 41 weeks' postconception. In this group there was no statistical difference in mean elimination rate, volume of distribution, or clearance between neonates and infants 4 to 8 weeks of age. However, they had significantly lower clearance and prolonged mean beta-half-life than infants who were 3 to 6 months old (greater than 43 weeks' postconception). Vancomycin clearance was directly related to postconceptional age by linear regression analysis. beta-Half-life was influenced by the weight of the patient, volume of distribution, and gestational age. In view of the interpatient variability observed in the prematurely born infants, pharmacokinetic studies should be performed to determine the appropriate dose and intervals in vancomycin therapy.