A study of the antimicrobial activity of selected synthetic and naturally occurring quinolines.

The antimicrobial activities of 60 naturally occurring and synthetic quinolines were studied. The quinolines were organised into seven structural subgroups and, using an in-house microtitre assay, were tested against a range of gram-positive and gram-negative bacteria, including a hospital isolate of meticillin-resistant Staphylococcus aureus (MRSA). The quinolines exhibiting good bioactivity [i.e. low minimum inhibitory concentration (MIC)] against two S. aureus strains were then assessed for their antimicrobial activity against a range of eight clinically isolated MRSA strains. The study showed that 30 of the tested compounds displayed antimicrobial activity, mostly against gram-positive bacteria. The effects of substituent groups on the bioactivity of these quinolines have also been discussed. The quinoline 4-hydroxy-3-iodo-quinol-2-one (11) exhibited significant antimicrobial activity, being active against the MRSA clinical isolates with MIC values comparable with the antibiotic vancomycin used in the treatment of MRSA infections. In particular, 4-hydroxy-3-iodo-quinol-2-one (11) showed MIC values of 0.097 microg/mL against an Irish hospital MRSA-1 strain and 0.049 microg/mL against a distinct MRSA strain as well as a non-typeable MRSA strain.

Whites and African-Americans in headache specialty clinics respond equally well to treatment.

This study sought to determine if Whites and African-Americans respond similarly to headache treatment administered in 'real-world' headache specialty treatment clinics. Using a naturalistic, longitudinal design, 284 patients receiving treatment for headache disorders completed 30-day daily diaries that assessed headache frequency and severity at pretreatment and 6-month follow-up and also provided data on their headache disability and quality of life at pretreatment and 1-, 2- and 6-month follow-up. Controlling for socioeconomic status and psychiatric comorbidity, hierarchical linear models found that African-Americans and Whites reported significant reductions in headache frequency and disability and improvements in life quality over the 6-month treatment period. African-Americans, unlike Whites, also reported significant decreases in headache severity. Nevertheless, Africans-Americans had significantly more frequent and disabling headaches and lower quality of life after treatment relative to Whites. Although Whites and African Americans responded favourably to headache treatments, more efficacious treatments are needed given the elevated level of headache frequency that remained in both racial groups following treatment.

An investigation of bioactive phytochemicals in the leaves of Melicope vitiflora by electrospray ionisation ion trap mass spectrometry.

The ethyl acetate extract of the leaves of Melicope vitiflora was separated by column chromatography and the resulting fractions tested for their bioactivity towards methicillin-resistant-Staphylococcus aureus (MRSA) and Micrococcus luteus (ML). The bioactive column chromatography fractions were further separated by preparative TLC and dereplication was carried out on them by first subjecting them to electrospray ionisation-ion trap mass spectrometry (ESI-MS(n)). The resulting molecular masses, their fragmentation patterns in addition to the chemnet database (www.chemnetbase.com) were used to aid in the structural elucidation of some of the compounds by permitting comparison with known structures of natural origin. Some molecular masses and the corresponding fragmentations were found that did not correlate with any known compounds thus revealing potentially novel natural products that could be investigated on a larger scale and could ultimately find application as new drugs against MRSA and other multi drug resistant microorganisms. Structures are also proposed for known compounds that have not been previously reported for M. vitiflora.

Blindness and bias in a trial of antidepressant medication for chronic tension-type headache.

This study aimed to examine penetration of the blind in a randomized, placebo-controlled trial. Neurologists' ratings of improvement and medication side-effects, participants' ratings of improvement and daily diary recordings of headaches were assessed along with participants' and neurologists' guesses about treatment group placement in participants who completed at least 3 months of treatment (N = 169). Despite blinding, treating neurologists successfully identified the medication condition for 82% of participants receiving medication only; trial participants accurately identified their medication condition when receiving active medication (77% of participants), but not when receiving placebo. Concurrent stress-management therapy reduced, but did not eliminate penetration of the blind. Irrespective of drug condition, when participants were improved they were judged to be on active medication and when unimproved they were judged to be on placebo. However, neurologists' ratings of improvement, participants' reports of improvement and daily headache recordings yielded equivalent outcomes. Penetration of the blind needs to be assessed, not assumed in clinical trials in headache. However, penetration of the blind did not produce a prodrug bias as has been asserted by critics. Better methods of assessing and quantifying blindness are needed.

A study of the analytical behaviour of selected synthetic and naturally occurring quinolines using electrospray ionisation ion trap mass spectrometry, liquid chromatography and gas chromatography and the construction of an appropriate database for quinoline characterisation.

Mass spectral fragmentation of quinoline alkaloids of significance in plants has been investigated using electrospray ionisation ion trap mass spectrometry (ESI-MS(n)) with a view to characterisation of molecules of unknown structure isolated from these natural sources. This investigation has led to the generation of an appropriate database incorporating data from ESI-MS(n) and also from gas liquid chromatography (GLC) and liquid chromatography (HPLC) for these low molecular mass quinolines. This has been put to practical application in the identification of quinoline alkaloids in a plant extract. Thus, an acid extraction of the leaves of Choisya ternata containing such tertiary alkaloids was analysed by liquid chromatography-electrospray ionisation mass spectrometry (HPLC-ESI-MS) and the resulting behaviour of the quinolines was compared with that of the quinoline alkaloids in the database.

Epidemiology and molecular characterization of co-circulating influenza A/H3N2 virus variants in children: Houston, Texas, 1997-8.

Co-circulating variants of influenza A/H3N2 viruses in children were studied in Houston, Texas between October 1997 and March 1998 to assess the effects of a new variant strain on the severity of clinical illness. Influenza A virus was isolated from the nasal wash or nasal aspirate specimens collected from children at two tertiary care hospitals, and 271 isolates were available for variant-specific subtyping using RT-PCR and restriction fragment length polymorphism (RFLP) analysis. We classified 124 (46%) influenza viruses as A/H3N2/Wuhan/359/95-like and 137 (50%) as A/H3N2/Sydney/05/97-like. Ten (4%) virus isolates could not be classified. Ill contacts in the household were reported more frequently in patients infected with A/Sydney-like viruses than in those infected with A/Wuhan-like viruses (85% vs. 71%, respectively, P=0.02). There were no differences in other demographic variables among children infected with these strains. This study found no increase in illness severity in children infected with a newly emerging strain.

A comparison of oral transmucosal fentanyl citrate and oral oxycodone for pediatric outpatient wound care.

Analgesia for pediatric burn wound care in the outpatient clinic is constrained by time, personnel, and/or monitoring capabilities, yet may improve patient satisfaction and comfort, clinic efficiency, and patient throughput. The ideal analgesic in this increasingly common setting should be palatable, provide potent, rapid, and brief analgesia, and require minimal appropriate monitoring. Using a placebo-controlled, double-blind design we compared oral transmucosal fentanyl citrate (OTFC, approximately 10 microg/kg) and oral oxycodone (0.2 mg/kg) in 22 pediatric outpatient wound care procedures (ages 5-14 years). Pulse oximetry, vital signs, side effects, patient pain scores, and observer scores for cooperation, anxiety, and sedation were recorded. OTFC and oral oxycodone resulted in similar outcome measures and vital signs, and no significant side effects. The taste of OTFC was preferred. We conclude that OTFC and oral oxycodone are safe and effective analgesics in the setting of monitored outpatient wound care in children, and that OTFC offers the advantage of improved palatability.

Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial.

CONTEXT: Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice. Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects. OBJECTIVE: To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches. DESIGN AND SETTING: Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio. PARTICIPANTS: Two hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo). INTERVENTIONS: Participants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53). MAIN OUTCOME MEASURES: Monthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating >/=5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group. RESULTS: Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity. Combined therapy was more likely to produce clinically significant (>/=50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P =.006), stress management therapy (35%; P =.003), or placebo (29%; P =.001). On other measures the combined therapy and its 2 component therapies produced similar outcomes. CONCLUSIONS: Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches. Combined therapy may improve outcome relative to monotherapy.

Age-associated risk of cancer among individuals with N-acetyltransferase 2 (NAT2) mutations and mutations in DNA mismatch repair genes.

Mutations in N-acetyltransferase 2 (NAT2), a highly polymorphic enzyme involved in the metabolism of xenobiotics and carcinogens, may affect risk for colorectal cancer (CRC), especially among individuals with germ-line mutations in DNA mismatch repair genes. We determined the NAT2 genotypes and allele frequencies for 86 individuals with CRC who had mutations in hMLH1, hMSH2, or hPMS1. No significant difference in time to onset was observed between rapid (NAT2*4) and slow (NAT2*5, NAT2*6, and NAT2*7) acetylators. However, when individuals were stratified separately by NAT2 polymorphism (NAT2*5, NAT2*6, and NAT2*7), those who were heterozygous at the mutant locus NAT2*7 after adjustment for the NAT2 mutant loci NAT2*5 and NAT2*6 had a significantly higher risk of CRC (hazard ratio, 2.96; P = 0.012) and all of the cancers (hazard ratio, 3.37; P = 0.00004) than individuals homozygous for wild type at the NAT2*7 allele. These findings suggest that NAT2 genotype may be an important factor in tumorigenesis of CRC and cancers related to hereditary nonpolyposis CRC among individuals with mismatch repair defects.

Exteroceptive suppression periods and pericranial muscle tenderness in chronic tension-type headache: effects of psychopathology, chronicity and disability.

We examined pericranial muscle tenderness and abnormalities in the second exteroceptive suppression period (ES2) of the temporalis muscle in chronic tension-type headache (CTTH; n = 245) utilizing a blind design and methods to standardize the elicitation and scoring of these variables. No ES2 variable differed significantly between CTTH sufferers and controls (all tests, P>0.05). We found no evidence that CTTH sufferers with daily or near daily headaches, a mood or an anxiety disorder, or high levels of disability exhibit abnormal ES2 responses (all tests, P>0.05). CTTH sufferers were significantly more likely than controls to exhibit pervasive tenderness in pericranial muscles examined with standardized (500 g force) manual palpation (P<0.005). Female CTTH sufferers exhibited higher levels of pericranial muscle tenderness than male CTTH sufferers at the same level of headache activity (P<0.0001). Elevated pericranial muscle tenderness was associated with a comorbid anxiety disorder. These findings provide further evidence of pericranial hyperalgesia in CTTH and suggest this phenomenon deserves further study. Basic research that better elucidates the biological significance of the ES2 response and the factors that influence ES2 assessments appears necessary before this measure can be of use in clinical research.

Laser trabeculodissection with a photopolishing scanning excimer laser.

A phase I study of nonpenetrating trabeculectomy (Zimmerman procedure) using a scanning excimer laser system was conducted to evaluate the ability of this laser system to achieve the deep dissection required to allow significant filtration without inadvertent penetration into the anterior chamber. A photopolishing, scanning 193 nm excimer laser system (LS 2000, LaserSight, Inc.) was used with a proprietary fluence, spot size, scanning pattern, and ablation shape to perform a trabeculodissection under a scleral flap with a limbal-based conjunctival flap in 8 cases of advanced glaucoma including 5 eyes that had a failed trabeculectomy. The laser trabeculodissection (LTD) was carried through Schlemm's canal and the juxtacanalicular trabecular meshwork, achieving vigorous aqueous outflow. No peripheral iridectomy was done. The scleral flap was closed loosely with a 10-0 suture. Mitomycin-C was used intraoperatively. In no case did inadvertent penetration into the anterior chamber occur. No peripheral iridectomy was performed. No intraoperative hyphema occurred. There was no postoperative iritis except minimal anterior chamber reaction in 1 eye with preoperative rubeosis. Postoperatively, a good filtering bleb was achieved in all 8 eyes with substantial reduction in the intraocular pressure without topical antiglaucoma therapy. No cases of postoperative shallowing (overfiltration) occurred. Gonioscopy, postoperatively, revealed no new peripheral anterior synechiae (PAS) to the filtration site and an intact inner trabecular meshwork. All eyes were followed for a minimum of 6 months. In this phase I study, laser trabeculodissection (LTD) with a 193 nm photopolishing, scanning system appears to be a promising alternative to full-thickness trabeculectomy, achieving significant filtration while perhaps avoiding much of the risk of filtration surgery. The laser system seemed to provide a more reliable, better-controlled dissection than a knife. The aqueous drainage seems to have acted as a self-regulating endpoint by absorbing UV energy, thus avoiding inadvertent penetration into the anterior chamber. More study is needed to establish the appropriate role of LTD in glaucoma therapy.

Perceived self-efficacy and headache-related disability.

BACKGROUND: Headache-specific self-efficacy refers to patients' confidence that they can take actions that prevent headache episodes or manage headache-related pain and disability. According to social cognitive theory, perceptions of self-efficacy influence an individual's adaptation to persistent headaches by influencing cognitive, affective, and physiological responses to headache episodes as well as the initiation and persistence of efforts to prevent headache episodes. OBJECTIVE: The objective of the present study was to construct and validate a brief measure of headache specific self-efficacy and to examine the relationship between self-efficacy and headache-related disability. METHODS: A sample of 329 patients seeking treatment for benign headache disorders completed the Headache Management Self-Efficacy Scale and measures of headache-specific locus of control, coping, psychological distress, and headache-related disability. A subset of 262 patients also completed 4 weeks of daily headache recordings. RESULTS: As predicted, patients who were confident they could prevent and manage their headaches also believed that the factors influencing their headaches were potentially within their control. In addition, self-efficacy scores were positively associated with the use of positive psychological coping strategies to both prevent and manage headache episodes and negatively associated with anxiety. Multiple regression analyses revealed that headache severity, locus-of-control beliefs, and self-efficacy beliefs each explained independent variance in headache-related disability.

Survey of migraineurs referred to headache specialists: care, satisfaction, and outcomes.

The authors report a survey of 281 migraineurs recently referred to headache specialists by primary care physicians. Compared with care before referral, specialists spent substantially more time with patients and were more likely to ask patients to take a prophylactic drug and to keep a headache diary, to discuss migraine triggers, and to prescribe 5-hydroxytryptamine1B/1D agonists (triptans). After referral, patients reported improved satisfaction with care and significant decreases in frequency, duration, and severity of attacks.

Psychosocial correlates and impact of chronic tension-type headaches.

OBJECTIVES: To examine the psychosocial correlates of chronic tension-type headache and the impact of chronic tension-type headache on work, social functioning, and well-being. METHODS: Two hundred forty-five patients (mean age = 37.0 years) with chronic tension-type headache as a primary presenting problem completed an assessment protocol as part of a larger treatment outcome study. The assessment included a structured diagnostic interview, the Medical Outcomes Study Short Form, Disability Days/Impairment Ratings, Recurrent Illness Impact Profile, Beck Depression Inventory, State-Trait Anxiety Inventory-Trait Form, Primary Care Evaluation for Mental Disorders, and the Hassles Scale Short Form. Comparisons were made with matched controls (N = 89) and, secondarily, with Medical Outcomes Study data for the general population, arthritis, and back problem samples. RESULTS: About two thirds of those with chronic tension-type headache recorded daily or near daily (> or =25 days per month) headaches with few (12%) recording headaches on less than 20 days per month. Despite the fact that patients reported that their headaches had occurred at approximately the present frequency for an average of 7 years, chronic tension-type headache sufferers were largely lapsed consulters (54% of subjects) or current consulters in primary care (81% of consulters). Significant impairments in functioning and well-being were evident in chronic tension-type headache and were captured by each of the assessment devices. Although headache-related disability days were reported by 74% of patients (mean = 7 days in previous 6 months), work or social functioning was severely impaired in only a small minority of patients. Sleep, energy level, and emotional well-being were frequently impaired with about one third of patients recording impairments in these areas on 10 or more days per month. Most patients with chronic tension-type headache continued to carry out daily life responsibilities when in pain, although role performance at times was clearly impaired by headaches and well-being was frequently impaired. Chronic tension-type headache sufferers were 3 to 15 times more likely than matched controls to receive a diagnosis of an anxiety or mood disorder with almost half of the patients exhibiting clinically significant levels of anxiety or depression. Affective distress and severity of headaches (Headache Index) were important determinants of headache impact/impairment. CONCLUSIONS: Chronic tension-type headache has a greater impact on individuals' lives than has generally been realized, with affective distress being an important correlate of impairment. If treatment is to remedy impairment in functioning, affective distress, as well as pain, thus needs to be addressed.

Comparison of a new neuraminidase detection assay with an enzyme immunoassay, immunofluorescence, and culture for rapid detection of influenza A and B viruses in nasal wash specimens.

The performance of a new, rapid, easy-to-perform assay based on neuraminidase enzyme activity for detection of influenza virus types A and B was compared to detection by culture, indirect immunofluorescence, and enzyme immunoassay in 479 nasal wash specimens from children with respiratory infections. Compared to isolation of influenza virus by culture, the neuraminidase assay had a sensitivity of 70.1%, specificity of 92.4%, positive predictive value of 76.3%, and negative predictive value of 89.9%. There was a higher sensitivity for the detection of influenza A virus (76.4%) than for influenza B virus (40.9%). Indirect immunofluorescence showed a sensitivity of 59.8% and specificity of 97% compared to culture isolation for detection of influenza A and B viruses. Enzyme immunoassay showed a sensitivity of 89.7% and specificity of 98.1% for the detection of influenza A alone. The quality of the nasal wash specimen had a significant effect on the detection of influenza virus by all of the assays. A strong response of the neuraminidase assay was more likely to represent a culture-confirmed influenza infection. This new rapid neuraminidase assay was useful for the detection of influenza A and B viruses in nasal wash specimens.

Laser treatment of solar elastosis with epithelial preservation.

BACKGROUND AND OBJECTIVE: Laser resurfacing has gained wide acceptance for the treatment of actinic facial skin. However, postoperative care of the face is reasonably complicated and prolonged erythema is common. To simplify the postoperative care and to possibly reduce the duration of the erythema, we investigated a laser treatment that spares the epithelium. STUDY DESIGN/MATERIALS AND METHODS: A 980 nm diode laser was used with a spherical optic handpiece to focus the light in the dermis. We treated in vitro breast and facial skin and measured the tissue shrinkage and the histological changes. We also treated two patients and harvested the tissue after 6 and 21 days of wound healing. RESULTS: The diode laser treatment does not ablate the epidermis. The tissue shows shrinkage (16% at 8W) similar to three passes of the scanned carbon dioxide laser treatment (15%). Thermal damage in the dermis is similar to the residual damage left after laser resurfacing with the scanned carbon dioxide laser. After 21 days the tissue shows new collagen and an abundance of young elastin fibers. CONCLUSIONS: These investigations indicate that solar elastosis in skin can be treated with the 980 nm diode laser while preserving the epithelial layer.

Ablation smoothness as a function of excimer laser delivery system.

OBJECTIVE: To quantitatively study and compare the ablation profiles of three kinds of excimer laser delivery systems to identify which technology provides the smoothest ablation profile. SETTING: Three private practices, one in Canada and two in the United States. METHODS: Excimer laser myopic ablations were performed on poly(methyl methacrylate) (PMMA) test blanks in 3.00 diopter increments using a 5 mm optical zone with three kinds of excimer laser delivery systems: (1) iris diaphragm without beam-homogenizing technology (ExciMed, Summit Technologies, Inc.); (2) iris diaphragm with beam homogenizer (20/20, VISX, Inc.); (3) galvanometric scanning (Mini-Excimer, LaserSight, Inc.). We used a scanning white-light interferometer (NewView 100, Zygo Corp.) to study three measures of surface smoothness: peak to valley, root mean square average deviation height (RMS), and the arithmetic average deviation from the center line of the data. RESULTS: Using RMS as a measure of surface smoothness in an optical system, the galvanometric scanning delivery system produced ablations approximately three times smoother than the iris diaphragm with beam homogenizer (P = .01), which in turn produced ablations about twice as smooth as the iris diaphragm without beam homogenizer (P = .03). CONCLUSIONS: Galvanometric scanning delivery systems provide a significantly smoother ablation profile than iris-diaphragm (variable aperture) systems.

Surface roughness in PMMA is linearly related to the amount of excimer laser ablation.

OBJECTIVE: To determine if surface roughness after excimer laser ablation is a function of the amount of ablation and to identify a standard unit for ablation roughness. METHODS: We used a VISX 20/20 excimer laser to perform a series of single zone 6-mm diameter ablations (photorefractive keratectomy [PRK]) in polymethylmethacrylate (PMMA). Corrections ranged from -1.00 diopter (D) to -15.00 D. A scanning white light interferometry microscope (Zygo Corp, Middlefield, Conn) was used to quantify the surface roughness at the center of each ablation. RESULTS: We found a linear increase in surface roughness as the refractive correction increased. Each diopter increment resulted in an approximately 300 nm increased peak-to-valley measurement. This represented an increase of 25 nm roughness per micron of ablation in PMMA. CONCLUSIONS: Surface irregularities in PMMA increase with ablation depth. We propose a unit of measure of roughness, the "ablation," expressed as the peak-to-valley distance in nm/divided by m of ablation.