Tunable ligand emission of napthylsalophen triple-decker dinuclear lanthanide(iii) sandwich complexes.

The fluorescent ligand 1,1'-((1E,1'E)-(1,2-phenylenebis(azanylylidene))bis(methanylylidene)) bis(naphthalen-2-ol) (H2L) was used to prepare lanthanide(iii) metal complexes. These were found to self-assemble as triple decker sandwich complexes of the type (Ln2L3), where Ln = Pr(iii), Nd(iii), Sm(iii), Eu(iii), Gd(iii), Tb(iii), Dy(iii), Ho(iii), Er(iii), Yb(iii), or Lu(iii). The structures of the complexes Nd2L3, Gd2L3, Tb2L3, Dy2L3, Ho2L3, Yb2L3, and Lu2L3 are structurally characterized by single crystal X-ray diffraction. In the Nd2L3 complex, both metals are 8 coordinate. Yb2L3, Tb2L3, Dy2L3, and Lu2L3 are isostructural. In these, as in the Gd2L3 and Ho2L3 complexes, one metal is 8 coordinate, one 7 coordinate. The ligand was found to have tunable emission in the solid state across the lanthanide series with a maximum at 556 nm for the Sm2L3 complex to 617 nm for Er2L3. Of these, most demonstrate only ligand-centered fluorescence at room temperature. The ligand was found to have much greater fluorescence in the complex Lu2L3. Here, we describe these distinctive triple decker complexes and their absorption and emission properties as both solids and solutions.

Human exposure to selamectin from dogs treated with revolution: methodological consideration for selamectin isolation.

This study was undertaken to determine selamectin residue in dog's blood and in gloves worn while petting dogs after Revolution application. Revolution contains the active ingredient selamectin (a semisynthetic avermectin), which controls endoparasites and ectoparasites, including adult fleas, flea eggs, ticks, heartworms, ear mites, and sarcoptic mange in dogs, for 30 days. Revolution was applied topically on a group of six adult house hold dogs (240 mg selamectin/dog). The gloves worn for 5 min while petting the dogs were collected in glass jars and the blood samples (5 mL/dog) were collected in EDTA tubes at 0 h, 24 h, and 72 h, and at 1, 2, 3, 4, and 5 weeks post-Revolution application for selamectin residue determination. At no time during the study did the dogs show any signs of toxicity, weight loss, or change in body temperature. Extracts of the blood and the gloves were analyzed for selamectin residue using RP-HPLC coupled with a UV detector (246 nm). Selamectin standard used for peak identification and quantitation was purified from Revolution. Selamectin residue was detected in the blood (10.26 +/- 1.06 ng/mL) only at 72 h post-Revolution application, probably due to its poor dermal absorption and rapid elimination from the circulation. In the glove extracts, the highest concentration of selamectin (518.90 +/- 66.80 ppm) was detected 24 h after Revolution application. Transferable residue of selamectin in gloves from dog's coat was detected at a lesser magnitude after 1 week of Revolution application, and that was followed by a further descending trend during the second, third, and fourth weeks. No selamectin residue was detected in the glove extracts after the fifth week. In spite of selamectin's binding to the sebaceous glands of the skin, gloves contained significant transferable residue. Thus, these findings suggest that repeated exposure to selamectin can pose potential health risks, especially to veterinarians, veterinary technologists, dog trainers/handlers, and pet owners.

Human exposure to fipronil from dogs treated with frontline.

This investigation determined fipronil residues on gloves worn while petting dogs after Frontline application. Frontline contains 9.8% fipronil, which controls fleas and ticks on dogs for at least 30 d. Frontline (1.34 ml) was applied topically on adult household dogs and gloves worn for 5 min during pettingwere collected 24 hr and 1, 2, 3, 4 and 5 w post-Frontline application for fipronil residue determinations using GC/MS. The highest concentration of fipronil (589.3 +/- 205.7ppm) was detected 24 h after Frontline application and was undetectable in the gloves collected at 5w. Repeated exposure to such contamination can pose human health risks.

Propanil (3,4-dichloropropionanilide) particulate concentrations within and near the residences of families living adjacent to aerially sprayed rice fields.

Propanil is widely used as a postemergence herbicide in rice. Because it is typically applied aerially, there is a potential for propanil to drift into and around homes of those living adjacent to rice fields. Propanil has been shown to be immunotoxic in rodent models. The objective of this study was to measure the levels of propanil to which families living adjacent to aerially sprayed rice fields may be exposed. Air levels were sampled by actively and passively collecting propanil in and around the homes of volunteer families living in close proximity to rice fields sprayed with propanil. Homes ranged from 73 m to 113 m from treated rice fields. Sampling was conducted in the home, adjacent to the home (within 5 m of the home), 30 m from the home, and at the edge of the rice field. Concentrations were determined via gas chromatography/mass spectroscopy. Propanil levels adjacent to the homes ranged from nondetectable to 1,106.4 microg per 400 cm2 collection surface (2.0 microg detection limit). Wind direction and wind velocity were the primary determinants of propanil drift. At sites where the prevailing wind was blowing away from the home, no propanil was detected except at the edge of the field. Distance from the edge of the rice field also influenced the amount of drift with higher levels measured at 30 m from the house than adjacent to the house. No propanil vapor was detected on absorbent media sampled in and around the homes. The results indicate that individuals living adjacent to rice fields aerially sprayed with propanil are potentially exposed to variable amounts of propanil, and wind speed and direction are the most important factors that influence the concentration of aerially applied pesticide.

Mammographic pattern of microcalcifications in the preoperative diagnosis of comedo ductal carcinoma in situ: histopathologic correlation.

OBJECTIVE: The comedo subtype of ductal carcinoma in situ (DCIS) is more aggressive than noncomedo DCIS. Differentiating noncomedo DCIS from the more aggressive comedo subtypes on mammography would allow the surgeon to excise comedo DCIS with a wider margin. The mammographic features of microcalcifications associated with nonpalpable comedo DCIS, noncomedo DCIS and benign disease were compared to determine the usefulness of this finding in diagnosis of comedo DCIS. METHODS: The authors retrospectively and blindly reviewed the mammograms of 91 consecutive patients in whom DCIS was diagnosed by needle localization and surgical excision. An equal number of cases of benign microcalcifications were also reviewed. Microcalcifications were evaluated with respect to pattern, density, configuration and size. These results were correlated with the pathologic findings. RESULTS: All 16 cases (100%) of linear branching calcifications and 34 (80%) of the 43 cases of linear calcifications were associated with comedo DCIS (p < 0.001). The number of calcifications, the density and the size of clustering were not diagnostic of comedo DCIS. Granular calcifications occurred in noncomedo DCIS and in benign disease associated with noncalcifying DCIS. CONCLUSION: Comedo DCIS is suggested by the presence of linear and linear branching microcalcifications on mammography.

Anterior cervical discectomy without fusion: a comparison with Cloward's procedure.

The antero-medial microsurgical disc or osteophyte removal without formal interbody fusion is a surgical alternative in the treatment of cervical discs causing radicular compression or cervical myelopathy. In the past 20 years 379 patients underwent anterior surgery, including 240 microdiscectomies without graft and 139 Cloward's dowel procedures. The long-term results of both procedures are compared in patients suffering from radicular compression, dominant myelopathy and radiculo-myelopathy. We found no statistically significant differences between the two methods treating three different conditions. The improvement rate in patients with soft and sequestrated discs is generally better compared to those with hard discs and spondylotic changes. Functional stability of the cervical spine is present in 92% of cases treated without interbody fusion immediately after surgery. A complete osseous fusion after a period of 6-12 months was found in 90% of Cloward procedures and in 81% of discectomy without graft. No definite correlation was found between the clinical improvement and the radiological results. According to our experience the Cloward's fusion procedure has no long-term advantages over discectomy without graft except in cases of severe myelopathy caused by multilevel ventral compression due to osteophytes. No permanent postoperative complication was encountered. Most of the treated patients returned to their previous activities.

Intrathecal narcotics for labor using combined spinal epidural technique: an attractive option for solo anesthesia providers.

A 31-year-old primigravida woman presenting with term pregnancy was admitted for labor and delivery. After approximately 10 hours of labor, which included an oxytocin infusion, she requested anesthesia intervention. A combined spinal/epidural (CSE) block was administered featuring a 3 1/2-in, 18-gauge Hustead epidural needle into the epidural space, through which was placed a 4 11/16-in, 27-gauge Whitacre spinal needle into the subarachnoid space. Fifty micrograms of fentanyl, 0.25 mg of morphine, 0.2 mg of epinephrine, and 2 mL of perservative-free normal saline were given intrathecally, the spinal needle was withdrawn, and a catheter placed into the epidural space. Profound analgesia without motor impairment was achieved. After the patient failed to progress, 2% lidocaine was administered epidurally to provide anesthesia to a T4 level, and a cesarean section was performed. The CSE technique provides a safe, flexible choice of anesthesia for labor and delivery. Monitoring of the patient by the anesthetist is necessary for only the initial 30 minutes after block administration. This, coupled with the advantage of having an epidural catheter as a backup, makes it an especially attractive alternative for the solo anesthetist.

Interval changes in nonpalpable breast lesions as an indication of malignancy.

OBJECTIVE: To determine whether the patterns of interval changes in nonpalpable breast lesions can be used to determine malignancy. PATIENTS AND METHODS: The authors reviewed the records for 128 nonpalpable breast lesions detected by mammography between March 1990 and May 1992 for which previous imaging studies were available. Changes in size, density and contour of the 59 masses and changes in size, number, configuration and pattern for the 69 cases involving microcalcifications were determined from comparison of the current mammograms with the earlier imaging studies, obtained 6 to 42 months previously. These findings were correlated with the pathological diagnosis based on needle localization and excisional biopsy. RESULTS: Twelve (55%) of the 22 new masses and 15 (48%) of the 31 masses that changed were malignant, but none of the 6 masses that did not change were malignant (chi 2 test, p < 0.01). All of the 31 masses that changed increased in size (and of these, 15 [48%] were malignant). In addition, 14 (45%) of the masses that changed exhibited increased density (and of these 9 [64%] were malignant), and 11 (35%) became irregular (and all of these were malignant). Eight (47%) of the 17 cases of new calcifications, 18 (43%) of the 42 cases of calcifications that changed and none of the 10 cases of unchanged calcifications were malignant (chi 2 test, p < 0.01). Twelve (44%) of the 27 calcifications that changed in area and 14 (40%) of the 35 that changed in number were malignant. Fifteen (60%) of the 25 calcifications that changed from scattered to grouped and 8 (53%) of the 15 that changed from punctate to linear were malignant. CONCLUSION: A change in the density or contour of a mass is a fairly definite sign of malignancy. The authors conclude that interval observation is a good method of detecting malignancy in breast masses but is less reliable for detecting malignancy in calcifications.

Eutectic mixture of local anesthetic cream--topical anesthesia for extracorporeal shock wave lithotripsy.

A 44-year-old man presented with a history of sudden onset left flank pain, accompanied by nausea and microhematuria. The diagnosis of ureteropelvic junction calculus was made and the patient was scheduled for extracorporeal shock wave lithotripsy (ESWL). ESWL uses an electrical spark to generate a shock wave that is focused on a stone in the ureter or kidney. The shock waves mechanically stress and crush the stone, eliminating the need for manipulation or open procedure. The pain of ESWL is caused by skin sensation. Eutectic mixture of local anesthetics (EMLA) cream (2.5% lidocaine and 2.5% prilocaine) has been used as a topical anesthetic on intact skin for various minor procedures. Studies have shown that it is effective in dramatically decreasing or eliminating the pain of ESWL. The use of topical EMLA as an anesthetic management technique for a patient undergoing ESWL is described.

Multivariate analysis of roentgenologic characteristics and risk factors for nonpalpable carcinoma of the breast.

Screening mammography improves carcinoma of the breast survival through early detection and treatment of nonpalpable, often noninvasive, carcinomas. Consideration of the roentgenologic characteristics of mammographic masses and calcifications in combination with risk factors of patients may improve the yield of spot localization breast biopsy. Risk factors solicited by questionnaire were correlated with the roentgenologic appearance and histopathologic factors of 482 specimens from spot localization breast biopsies (39 percent malignant). Masses with irregular contour (p < 0.001) and high density (p < 0.005) were associated with malignant tumors. Packed, coarse and round calcifications were associated with benignity (p < 0.001), whereas scattered, fine and mixed calcifications were associated with malignant tumors (p < 0.05). Malignant masses with smooth contour were significantly more likely to be associated with noninvasive histology. Patients found to have malignant tumors were significantly older than patients with benign lesions (58 versus 52 years, p < 0.001). Stepwise logistic regression was used to evaluate the relative usefulness of demographics and roentgenologic features in predicting benign and malignant pathology among masses and calcifications. Age and irregular contour were independent significant predictors of malignancy for masses. Age, round, coarse, packed or scattered calcifications were significant independent predictors of benignity among calcifications. The radiologist correctly predicted malignant pathology in 60 percent of the patients and benign pathology in 78 percent. Parity, age at menarche, age at first pregnancy, age at menopause, history of benign breast disease, history of carcinoma of the breast, family history of carcinoma of the breast, birth control pill exposure and smoking were not significantly associated with the diagnosis of malignant tumor. These results suggest that risk factors for carcinoma of the breast are insignificant for nonpalpable lesions because patients referred for needle localization are already selected for high risk. Roentgenologic patterns of masses are useful for predicting which lesions are invasive.

Immunochemical detection of oxidized proteins.

An immunochemical assay was developed to detect carbonyl moieties that result from oxidative damage to proteins. Bovine serum albumin was reacted with hydroxyl radicals generated via a Fenton-like mechanism or by a radiolysis mechanism. The resulting albumin-derived carbonyls were reacted with 2,4-dinitrophenylhydrazine, giving the corresponding hydrazones, which were detected by Western blot using anti-dinitrophenyl antisera. The immunoblot demonstrated a concentration-dependent increase in carbonyl formation, as well as fragmentation of the albumin into two distinct bands with molecular masses of 51 and 45 kDa when oxidized with the Fenton-like mechanism, and 62 and 46 kDa when oxidized by radiolysis. Analysis of the immunoblot using laser densitometry indicated a linear relationship between carbonyl groups and increasing treatment from radiolysis. This immunochemical assay was approximately 3 orders of magnitude more sensitive than the spectrophotometric method and was able to determine the molecular mass of carbonyl-modified polypeptides in the detection of oxidative damage.

Insulin prophylaxis in individuals at high risk of type I diabetes.

Prevention of type I diabetes is now a practical goal thanks to the ability to define confidently a high-risk group and the success of preventive strategies in animal models. We describe here a pilot trial of low-dose insulin to prevent diabetes in relatives of patients with type I diabetes.

Nonpalpable ductal carcinoma in situ versus infiltrating carcinoma of the breast--can they be differentiated by mammography?

The radiologic patterns of 193 consecutive women with nonpalpable breast carcinoma were evaluated. The results were correlated with patient age and with the histopathologic diagnosis. Of the 193 women in the study, 135 (70%) were older than 50 years; 102 women had ductal carcinoma in situ, and 67 (62%) of them were over age 50; the remaining 91 women had infiltrating carcinoma, and 73 (80%) of these patients were older than 50 years. Of the 58% of women who presented with microcalcifications, 75% had ductal carcinoma in situ and 25% infiltrating carcinoma. Of the 36% of patients who presented with a mass, 87% had infiltrating carcinoma and 90% were over age 50. Six percent presented with a mass with microcalcifications; 75% of these masses were found to be infiltrating carcinoma. Most of the masses were infiltrating carcinoma, and of these 90% were high-density masses. The small number of masses representing ductal carcinoma in situ were proportionately of low density.

Spectrophotometric and ESR evidence for vanadium(IV) deferoxamine complexes.

Complexes of vanadium(IV), vanadyl, are reported to be formed with the trihydroxamic acid deferoxamine (H3DF+). One complex exhibits a reddish-violet color, with a major absorbance peak at 386 nm and a smaller peak at 520 nm. This complex is potentially useful for the microdetermination of vanadyl. The apparent molar absorptivity is 3.91 mM-1 cm-1, and the complex obeys Beer's law in the concentration range of 0.6-63 ppm. Electron spin resonance studies indicate the formation of two vanadyl complexes that are 1:1 in vanadyl and deferoxamine, but have two or three bound hydroxamate groups. ESR and spectrophotometric evidence indicate that the red, low pH form, involves an octahedral vanadium (4+) ion coordinated by three hydroxamate ligands. One of these hydroxamates is displaced by an oxygen at pH greater than 2.8 according to the following equilibria: VO2+ + H3DF+ in equilibrium with VIV(DF)2+ + H3O+, VIV(DF)2+ + H2O in equilibrium with VO(HDF)+ + H+, where pk2 = 2.8.

Mechanism of acetaminophen-stimulated NADPH oxidation catalyzed by the peroxidase-H2O2 system.

The oxidation of NADPH catalyzed by horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) is markedly increased by the presence of acetaminophen in a concentration-dependent manner. The oxidation follows pseudo-first order kinetics with respect to acetaminophen concentration. The product of the oxidation is enzymatically active NADP+. The stoichiometry of the reaction shows that 1.4 mol of NADPH are oxidized per mole of H2O2 added, and the addition of superoxide dismutase to the reaction mixture increases the ratio of NADPH oxidized:H2O2 consumed, which suggests formation of superoxide as a product. Monitoring cytochrome c reduction in the presence and absence of superoxide dismutase further suggests formation of superoxide. These results indicate that the HRP-H2O2 system oxidizes acetaminophen to the phenoxyl radical, N-acetyl-p-benzosemiquinone imime, which undergoes a rapid electron transfer reaction with NADPH. The NADP thus formed reacts with molecular oxygen to produce superoxide.

Glucose therapy for glycogenosis type 1 in infants: comparison of intermittent uncooked cornstarch and continuous overnight glucose feedings.

This study was undertaken to test the glycemic response of five infants with glycogen storage disease type 1, aged 0.7 to 1.5 years, to uncooked cornstarch under various dietary conditions, and to evaluate the long-term effects of a dietary regimen consisting of uncooked cornstarch in milk every 4 hours, in addition to three meals daily, on biochemical values and physical growth. The results were compared with previous experience in treating six infants with continuous overnight glucose infusion via gastrostomy plus multiple daily feedings containing an adequate source of glucose. A test dose of cornstarch (1.6 to 1.8 gm/kg) providing four times the calculated hourly glucose production rate, when given in water 15 to 30 minutes after a continuous overnight intragastric glucose infusion was stopped, did not maintain normoglycemia. When the same dose was given in 2% cow milk 4 hours later, mean blood glucose levels remained greater than 68 mg/dl (3.8 mmol/L) for up to 4 hours. A regimen of uncooked cornstarch in 2% cow milk at 4-hour intervals in addition to three meals daily prevented hypoglycemia, and maintained blood lactate at nearly normal levels and serum uric acid and cholesterol within the normal range; triglyceride levels were increased only modestly. Overnight blood glucose levels were comparable to those achieved with continuous intragastric glucose infusion. With this regimen the five infants have maintained linear growth rates normal for their age and genetic potential; the mean percentage of ideal body weight for length percentile did not change significantly, although two of the five patients were overweight (123% and 124% of ideal body weight respectively) after 3 years of treatment. We conclude that a trial of uncooked cornstarch in feedings of milk every 4 hours should be attempted as soon as a more frequent feeding schedule with dextrose-containing formulas proves ineffective, because the former has the potential to provide the continuous glucose required by infants with glycogen storage disease type 1 in a safer and less invasive fashion than continuous intragastric glucose infusion.

Cellular immunity to human insulin in individuals at high risk for the development of type I diabetes mellitus.

In order to investigate the role of insulin as a potential target autoantigen of cellular immunity in the prediabetic period, proliferative responses of T lymphocytes to human insulin were studied in nine islet-cell antibody (ICA) + first-degree relatives of patients with Type I diabetes (individuals at high risk for the development of Type I diabetes, or the 'prediabetic' group, which was never treated with insulin) and in 12 control individuals. Insulin autoantibodies were present in 6/9 (67%) of the prediabetic subjects and none of the controls. Peripheral blood lymphocytes were collected on Ficoll and incubated with human insulin, control antigens, or media alone for 5-6-day and 9-10-day incubation periods. Cells were pulsed with 3H-thymidine, harvested, and analysed in a scintillation counter. Results are expressed as stimulation index (SI = cpm with antigen/cpm without antigen), with a SI greater than or equal to 1.5 considered a positive response. Eight of nine (89%) prediabetic individuals responded positively to insulin after a 9-10-day incubation period, in contrast to four of 12 (33%) control subjects, P less than 0.05. The mean proliferative response to insulin after 9-10 days' incubation was 2.1 +/- 0.4 and 1.2 +/- 0.1, for the prediabetic and control groups, respectively. The proliferative response to insulin was not directly correlated with levels of insulin autoantibodies (r = -0.05, NS). These data suggest that most individuals at high risk for the development of Type I diabetes display a cellular immune response to insulin, and a subset of these individuals does not display a concomitant humoral immune response to insulin based on the presence or absence of insulin autoantibodies.

Nonpalpable breast masses: radiologic predictability of malignancy.

Of 568 nonpalpable breast lesions detected by screening mammography 242 proved to be noncalcified masses; biopsy showed 165 to be benign and 77 malignant. The lesions were evaluated with respect to contour, radiographic density and size. Of the malignant lesions 90% were infiltrating carcinomas, 88% of which had an indistinct contour and were of moderate to high density. Of the benign lesions 40% of those with an indistinct contour demonstrated high radiographic density. Low-density, distinct masses were all benign. There was no correlation between the size of the lesion and whether it was malignant.

Oxidation of NADH by vanadium compounds in the presence of thiols.

The nonenzymatic oxidation of NADH was studied spectrophotometrically in the presence of two vanadium compounds, sodium orthovanadate and vanadyl sulfate. At physiological pH 7.4, in 25 mM sodium phosphate buffer, addition of the synthetic thiol, dithioerythritol (DTE) results in a marked increase of NADH oxidation in the presence of sodium orthovanadate, but not in the presence of vanadyl sulfate. Other reductants, such as dithiothreitol and cysteine, can also increase NADH oxidation, whereas glutathione and ascorbate cannot. In all reactions, superoxide dismutase and catalase completely inhibit the vanadium-stimulated oxidation of NADH. Inhibition occurs in a concentration-dependent manner, and the boiled enzymes do not inhibit the thiol reaction. The hydroxyl radical scavenger, thiourea, inhibits the reaction, whereas urea cannot. ESR studies show that the ability of the thiol to reduce vanadate can be correlated with the degree of NADH oxidation. Using spin trapping techniques, hydroxyl radicals are detected during the course of the reaction. Addition of hydrogen peroxide to vanadyl in the presence of DTE greatly increases NADH oxidation; however, no NADH oxidation occurs when hydrogen peroxide is added to vanadyl and ascorbic acid. These results provide a partial explanation for the ability of vanadium compounds to both decrease cellular reducing equivalents and promote lipid peroxidation.