Immunization practices in children.

The resurgence of measles has highlighted concerns about U.S. programs for immunization in infants and children. In order to put the problems into perspective, this review will address such issues as the safety of pertussis vaccines; oral vs inactivated poliovirus vaccine; vaccines for measles-mumps-rubella, Hemophilus influenzae type B, and hepatitis B; and varicella vaccine.

The effect of local anesthetics on bacterial proliferation: TAC versus lidocaine.

We compared the effect of topical 0.5% tetracaine, 1:2,000 epinephrine, and 11.8% cocaine (TAC) with 1% lidocaine infiltration on bacterial proliferation in experimental lacerations. Forty-eight lacerations were made on the backs of Hampshire pigs, inoculated by injection with infectious doses of Staphylococcus aureus and randomly anesthetized with either topical TAC or lidocaine infiltration. Wounds were sutured, and quantitative cultures were obtained by excision after 48 hours. The mean log10 bacteria per gram of tissue for wounds anesthetized with TAC was 6.818 (95% confidence interval [CI], 6.07 to 7.54) compared with 6.820 (95% CI, 5.91 to 7.75) for those treated with lidocaine; this difference was not significant (P less than .05 by paired two-tailed t test). The probability of failing to detect an intergroup difference of 0.5 log10 bacteria per gram was less than .0001. TAC does not increase bacterial proliferation more than lidocaine infiltration in contaminated experimental porcine lacerations.

Mixing insulins in 1990.

Lente insulins can be mixed in any ratio at any time. Regular plus NPH insulins seem to be the preferred mixture of rapid- and intermediate-acting insulins because the effect of the combined insulins is the same as that of regular and NPH insulin injected separately. Mixing regular with lente insulins is more complex and needs further study. However, at the present time, if regular and lente insulins are going to be mixed, they should be either mixed and injected immediately, or they should be left to interact for up to 24 hours, in which case the resultant mixture does not have as rapid an action as the immediately injected mixture. Combinations of regular and protamine zinc insulins are rare and complicated by the fact that the resultant product is based upon the ratios of regular to PZI. Generally speaking, protamine zinc insulin is rarely used in humans. It is used by some veterinarians, especially to treat cats with diabetes. The Table summarizes information concerning the mixing of various insulins.

A comparison of the anti-hypertensive effectiveness of two triameterene/hydrochlorothiazide combinations: Maxzide versus Dyazide.

The hydrochlorothiazide component of Maxzide (Lederle Laboratories, Pearl River, NY) has been shown to be more bioavailable than the hydrochlorothiazide component of Dyazide (Smith, Kline and French Laboratories, Philadelphia, PA). The authors compared the antihypertensive effectiveness of a half-tablet of Maxzide (25 mg of hydrochlorothiazide and 37.5 mg of triamterene) to one capsule of Dyazide (25 mg of hydrochlorothiazide and 50 mg of triamterene) to determine if the difference in bioavailability would be reflected in differences in blood pressure control and metabolic changes. Thirty patients were studied in a randomized open-label crossover design study. There was a significant reduction in systolic blood pressure for both treatments although there was no difference in blood pressures at any time during the study between the two agents. There were no statistically significant differences between Maxzide and Dyazide in terms of metabolic changes for potassium, magnesium, glucose, cholesterol, triglycerides, uric acid, or calcium. Although the hydrochlorothiazide component of Maxzide is more bioavailable than that of Dyazide this did not translate into enhanced hypotensive efficacy.

New drugs for Parkinson's disease.

Parkinson's disease continues to be a tragic debilitator of close to half a million Americans. As more is learned about the disease, pharmacological treatment improves. Just recently, deprenyl became a part of our therapeutic armamentarium, and it appears that Sinemet CR will soon be following. It is hoped that these drugs will improve the quality and quantity of life for patients with PD until the disease can be cured.

Evidence that FMC7 is a human B cell differentiation antigen.

FMC7 is a 105-kDa B cell restricted antigen which is expressed on about 50% of adult human peripheral blood B cells. Seven to ten days following booster immunization with tetanus toxoid, peripheral blood contains a small population of B cell blasts with an increased density of FMC7. The majority of anti-tetanus toxoid antibody secreting cells (both IgM and IgG) are however found in FMC7- B cells. These data indicate that upon in vivo B cell activation FMC7 expression initially increases. B cells involved in antibody secretion have lost the FMC7 determinant.

On the use of T61 for euthanasia of domestic and laboratory animals; an ethical evaluation.

A number of experiments was carried out to determine the sequence of events leading to death following administration of the euthanizing agent T61. Simultaneous recordings of the EMG, EEG, ECG and end-tidal CO2 (dogs only) were obtained in acutely instrumented rabbits and dogs. Results show that following T61 administration the loss of consciousness and loss of muscle activity occurred simultaneously. Vocalization and increased muscle movement occurred in the initial phase of the injection in 3 of 8 dogs, injected with T61 or butyramide. From this study it was concluded that the presence of the muscle relaxant does not pose an ethical problem for the use of T61 as an euthanizing agent, but our results suggest that the use of T61 may have some emotionally unpleasant side-effects.

Comparative bioavailability characteristics of commercial quinidine polygalacturonate and sulfate tablets.

This study compared the relative bioavailability characteristics of quinidine polygalacturonate (QP) and quinidine sulfate (QS) after oral administration of commercial tablets and a liquid form prepared from crushed tablets in 13 healthy adult male volunteers. Each subject received the following four single-dose treatments in a randomized, crossover manner with a one-week washout period between treatments: 400 mg QS liquid, two 200-mg QS tablets, 550 mg QP liquid, and two 275-mg QP tablets. All four treatments were equivalent in terms of the dose of quinidine base. Multiple serum samples and two 24-hour urine specimens were collected over 24 and 48 hours, respectively, and assayed for quinidine with a specific HPLC assay method. For the absorption and disposition parameters measured (maximum serum concentration, time to reach maximum concentration, area under the concentration-time curve [0-48 hours], absorption and elimination rate constants, absorption and elimination half-lives, apparent total body clearance, apparent volume of distribution, and dose fraction excreted in the urine) no significant differences were observed for any of the parameters among the four treatments (p greater than 0.05). The results of the present investigation demonstrated that QP and QS produced identical serum quinidine concentration-time curves when given in the form of a tablet or liquid. The clinical implications of these observations with respect to the dosing of QP are discussed.

[The use of T61 for the humane killing of pets and laboratory animals]. / Het gebruik van T61 voor het verantwoord doden van gezelschaps- en laboratoriumdieren.

Experiments were carried out to determine the onset of loss of consciousness and muscle relaxation following administration of the euthanising agent T61. Simultaneous recordings of EMG, EEG, ECG and capnogram (dogs only) were obtained in acutely instrumented rabbits and dogs. The results showed that loss of consciousness and muscle activity occurred simultaneously following administration of T61. Vocalisation and increased muscle movement occurred both when T61 and butyramide were used in the initial phase of the injection in three out of eight dogs. From this study, it was concluded that the presence of the muscle relaxant does not pose an ethical problem for the use of T61 as euthanising agent, though the results suggested that the use of T61 may have some emotionally unpleasant side-effects.

The emergency department treatment of dyspepsia with antacids and oral lidocaine.

The treatment of dyspepsia in the emergency department often consists of antacid in combination with viscous lidocaine, even though the specific etiology of the pain is frequently unknown. The efficacy of lidocaine as a component of symptomatic therapy was evaluated in a randomized, patient-blinded protocol. Patients presenting to the ED with dyspeptic symptoms were randomized to receive 30 mL of antacid (Mylanta II), or 30 mL of antacid plus 15 mL of 2% viscous lidocaine (GI cocktail). Patients recorded their pain score on an 11-cm linear analog scale prior to and 30 minutes after treatment. Seventy-six patients were enrolled; three were excluded from analysis due to incomplete data. Thirty-four patients were randomized to receive antacid and 39 to receive GI cocktail. Patients rated their baseline pain at 6.4 +/- 2.8 cm in the antacid group and 6.7 +/- 2.7 cm in the cocktail group (P greater than .50). Improvement in pain score with treatment was 0.9 +/- 2.9 cm in the antacid group compared with 4.0 +/- 3.4 cm in the GI cocktail group (P less than .0001). Assessment of pain relief using a five-point rating scale also indicated greater relief with GI cocktail therapy compared with antacid alone (P = .004). No adverse effects were noted with either treatment. We conclude that a single dose of antacid and viscous lidocaine provides a significantly greater degree of immediate pain relief than antacid alone in patients with dyspepsia.

Use of glue without graft replacement for type A dissections: a new surgical technique.

A new surgical technique for treating type A aortic dissections is described. It consists of the exclusive and extensive use of surgical glue without replacing a segment of the ascending aorta. Since 1984, 21 patients were operated on using this technique. No operative mortality occurred and one reoperation for redissection was required. The technique is simple and safe and yields excellent short-term and long-term results.

Spironolactone and altizide in systemic hypertension: ambulatory multicenter study.

A multicenter study was performed in 919 hypertensive patients, 780 of whom could be evaluated. Patients in group I (n = 482) were treated with Aldactazine alone (altizide + spironolactone, 2 tablets per day). The other 298 patients (group II) were treated with 1 or 2 tablets per day of Aldactazine plus a conventional antihypertensive agent, e.g., a beta blocker, alpha-methyldopa or clonidine. After 45 days of treatment with Aldactazine alone, mean systolic and diastolic blood pressure (BP) decreased by 15 and 14%, respectively, vs baseline values. The addition of the other antihypertensive agent decreased BP further; however, the best results were obtained with the combination of Aldactazine and clonidine. With this combination, systolic and diastolic BP decreased by 16.6 and 18%, respectively, vs baseline. In terms of adverse effects, a few cases of gastrointestinal disturbances and orthostatic hypotension were reported.

Radiosensitization of murine tumors by Fluosol-DA 20%.

The effect of perfluorochemicals in combination with carbogen breathing on the response of SCK tumors of mice to fractionated irradiation was investigated. The SCK tumors of A/J mice were irradiated twice a day at 3 Gy per fraction (6 Gy per day), with a total dose of 18 Gy over 3 days. When the host animals were treated with an intravenous (iv) injection of 12 ml/kg of Fluosol-DA 20% before the first daily tumor irradiation and carbogen breathing during every X irradiation with Fluosol-DA 20% injection without carbogen breathing. The hypoxic cell fraction, as determined by an in vivo-in vitro cloning assay, decreased significantly, and the intratumor pO2, as determined with microelectrodes, was markedly increased by Fluosol-DA 20% injection and carbogen breathing. It was concluded that oxygenation of hypoxic cells in SCK tumors during the course of fractionated irradiation was improved by the iv injection of Fluosol-DA 20% and carbogen breathing.

Toxicity of ototopical drugs: animal modeling.

It is important to be aware of the potential ototoxicity of any drug, vehicle, or antiseptic that is used in the middle ear. Frequently used ear drops (Cortisporin otic suspension, Coly-Mycin S Otic, and VoSoL otic solution) were studied for their ototoxicity. Compound action potentials were measured before and at 1, 2, and 24 hours following drug application on the round window membranes of chinchillas. Each drug was applied for 10 minutes and then was removed by rinsing. The sound pressure in decibels sound pressure level that produced a compound action potential amplitude of 10 microV was defined as the threshold. The change in threshold was interpreted as hearing loss. On the basis of the short-term results at 24 hours following drug application, the ototoxicity of Coly-Mycin was calculated to be twice that of Cortisporin, and the ototoxicity of VoSoL four times that of Cortisporin.

Disposition and toxicity of amphotericin-B in the hyperlipidemic Zucker rat model.

The pharmacokinetics and toxicity of the lipophilic antifungal agent, amphotericin-B (AmpB), were studied in the hyperlipidemic obese rat model and compared with lean litter-mates. Serial blood samples were obtained for 36 h following a single intravenous infusion of AmpB (1.2 mg/kg) with pre- and post-drug measurements of renal function. Although triglyceride, cholesterol, HDL-cholesterol and LDL + VLDL-cholesterol levels were elevated in the obese compared with lean rats, protein: lipoprotein ratios were similar. There was a 2-fold increase in the area under the serum concentration-time curve of AmpB in obese rats compared to lean litter-mates (15,600 +/- 6900 v. 7800 +/- 2900 ng. h/ml; P less than 0.05); no differences in elimination rate constants were found between groups. Weight-corrected volume of distribution and total body clearance were significantly lower in obese compared with lean rats; no differences were found in absolute clearance or volume. Kidney levels of AmpB were markedly increased in obese versus lean rats. Similarly, kidney to serum ratios of AmpB were greater in obese compared with lean rats (152 +/- 113 v. 41 +/- 23; P less than 0.001). There was a significant decline in the creatinine clearance from baseline in the obese rats coupled with a rise in serum creatinine; no differences were found in lean rats. Similarities in absolute pharmacokinetic variables and protein: lipoprotein ratios suggest differences in AmpB disposition and toxicity are a result of differences in lipoprotein-mediated transport mechanisms between obese and lean rats.

Classification of antineoplastic treatments by their differential toxicity toward putative oxygenated and hypoxic tumor subpopulations in vivo in the FSaIIC murine fibrosarcoma.

In order to investigate the effect of environmentally determined conditions on the cytotoxicity of anticancer treatments, Hoechst 33342 dye selected tumor subpopulations were separated after in vivo treatment and plated for single cell colony survival. The 10% brightest cells were assayed as putative normally oxygenated cells and the 20% dimmest as putative hypoxic cells. At single therapeutic doses, cyclophosphamide treatment resulted in the largest differential killing between bright and dim cells (6.3-fold bright greater than dim); 1,3-bis(2-chloroethyl)-1-nitrosourea was 3.2-fold more cytotoxic toward bright cells and carboplatin was 2.4-fold more toxic toward bright cells. Both radiation (10 Gy) and melphalan were 2.2-fold more toxic to bright cells, while cis-diamminedichloroplatinum(II) was 1.8-fold, thiotepa was 1.2-fold and procarbazine was 1.3-fold more toxic to bright cells. Actinomycin D was 3.4-fold more toxic to bright cells. Adriamycin was 2.2-fold, vincristine was 2.1-fold, and etoposide was 1.6-fold more toxic to bright cells. Bleomycin and 5-fluorouracil were also tested and were 1.5- and 2.3-fold more toxic to bright cells, respectively. Only four treatments were more toxic to dim cells: mitomycin C (3.5-fold), misonidazole (1.5-fold), etanidazole (3.5-fold), and 43 degrees C, 30 min local hyperthermia (2.6-fold). In an attempt to shift the pattern of dim cell sparing, Fluosol-DA plus carbogen (95% O2/5% CO2) breathing was added to treatment with radiation (10 Gy), melphalan, cis-diamminedichloroplatinum(II), and etoposide. Although each of these treatments became significantly more toxic with the addition of Fluosol-DA/carbogen, only with melphalan did the combination overcome the sparing of dim cells. These results indicate that cells located distally from the tumor vasculature are significantly less affected by most anticancer drugs and suggest that successful therapeutic strategies against solid tumors will involve greater use of the few treatments which are more toxic toward this tumor subpopulation.

Plasma concentrations of lidocaine and prilocaine and analgesic effect after dermal application of EMLA cream 5% for surgical removal of mollusca in children.

The plasma concentrations of lidocaine and prilocaine after dermal application of EMLA cream 5% were determined in two clinical studies. The cream (10-16 g) was applied to a total surface area of 100-160 cm2. Each area was covered by a Tegaderm dressing (3M) in order to obtain occlusion. An application time of 2 hours was used. Two age groups of ten children were studied: 2-3 years and 6-8 years. In both groups venous blood samples were drawn prior to application and at 2, 3, 4 and 5 hours. In addition, in one of the studies, the cream was used during the surgical removal of mollusca in order to study the analgesic effect of the cream. The absorption of the local anaesthetics as indicated by plasma concentrations was far below toxic levels. The highest individual concentration of lidocaine was 315 ng/ml and of prilocaine 215 ng/ml. The analgesic effect was sufficient--eight out of ten patients experienced no or slight pain. Transient local reactions (paleness, redness) were frequently observed. In one patient with eczema present at the application site prior to the application, a reaction persisted for one week. Dermal analgesia provided by EMLA is a safe and effective method for alleviation of pain from removal of mollusca and the plasma concentrations are innocuous.