Eight-month repellency and efficacy of an imidacloprid/flumethrin (Seresto® ) collar against the eastern paralysis tick (Ixodes holocyclus) on cats.

OBJECTIVE: The objective of this study was to determine the repellency and efficacy of a 10% imidacloprid/4.5% flumethrin (Seresto® , Elanco) collar over an 8-month period against the eastern paralysis tick (Ixodes holocyclus) on cats. METHODS: Two non-blinded, open gender, randomised, placebo-controlled pen studies were conducted, with 26 cats enrolled in each study. Prior to inclusion, cats were immunised with I. holocyclus holocyclotoxin. Cats were treated on Day 0 with either an imidacloprid/flumethrin or placebo collar. Tick infestations with 20 unfed adult female eastern paralysis ticks commenced on Day 7, and were repeated monthly for 8 months. Repellency was determined by comparing the mean number of attached ticks on imidacloprid/flumethrin treated cats, to placebo collar treated cats at 6 and 24 h post infestation. Efficacy was determined by comparing the mean number of live ticks on imidacloprid/flumethrin collar treated cats to placebo collar treated cats at 72 h post infestation. RESULTS: Efficacy was 100% (P < 0.001) at 72 h, and repellency was greater than 96% (P < 0.001) at 24 h for every tick challenge in each of the two studies, from Day 7 to the final infestation at 8 months for imidacloprid/flumethrin collar treated cats. CONCLUSIONS: In two pen studies, an imidacloprid/flumethrin collar controlled and repelled the eastern paralysis tick (I. holocyclus) on cats for 8-months. The marked repellency effect in addition to controlling tick paralysis would be beneficial in preventing tick bites and their sequelae.

Orofacial granulomatosis: three case reports illustrating the spectrum of disease and overlap with Crohn's disease.

We report three cases of orofacial granulomatosis (OFG) to illustrate the spectrum of this disease, and to discuss the appropriate management steps, consider its overlap with Crohn's disease (CD) and raise its awareness among paediatric dermatologists. The term 'orofacial granulomatosis' was first used in 1985 to describe granulomas in the orofacial region in the absence of any recognized systemic condition. It is uncommon but becoming increasingly recognized in children. The clinical features of the disease may vary greatly, and often present with subtle changes that can be missed. There is a debate about whether OFG exists as a separate condition or whether it is an oral feature of CD, as some patients go on to develop CD several years later. Identifying those most at risk is important, as ongoing investigations may be necessary. The three cases presented in this series illustrate the range of disease signs and symptoms, and the investigations required.

Nicorandil: do the dermatological and gastrointestinal risks outweigh the benefits?

BACKGROUND: Nicorandil has been available in the U.K. since 1994 for the prophylaxis and treatment of angina. Since the first reported case of nicorandil-associated oral ulceration in 1997 complications elsewhere in the gastrointestinal tract have been reported. OBJECTIVES: Our case series highlights this serious drug complication. METHODS: We reviewed the records of all patients referred to our specialist stoma dermatology clinic who had stoma surgery for diverticular disease and all patients referred with persistent parastomal or perianal ulceration that was not attributable to Crohn's disease or pyoderma gangrenosum. Patient demographics, nicorandil ingestion, bowel involvement, stoma type, cutaneous ulceration and outcome were recorded. RESULTS: A total of 36 patients had stoma surgery performed as a consequence of diverticular disease. The proportion of patients taking nicorandil (in all cases at a dose of 40 mg or more daily) was one third, higher than expected. There was a higher incidence of enteric fistula formation and bowel perforation among those taking nicorandil, 92% (11/12) and 50% (6/12), respectively, compared with those not on the drug, 0% and 21% (5/24), respectively. In addition, parastomal ulceration was seen more often in those taking nicorandil, 100% (12/12), compared with those not, 8% (2/24). Even without a history of diverticular disease we observed a high incidence of bowel perforation and parastomal and/or perianal ulceration among patients taking nicorandil. In the vast majority of cases ulceration healed upon cessation of nicorandil. CONCLUSIONS: For those with diverticular disease taking nicorandil is strongly associated with fistula formation or bowel perforation; as such the risk-benefit equation for nicorandil needs careful consideration given that other nitrates are available.

Calciphylaxis with normal renal function: treated with intravenous sodium thiosulfate.

Calciphylaxis is a rare and potentially life-threatening condition. It is thought to result from arterial calcification causing complete vascular occlusion and subsequent cutaneous infarction. Most often, it is a complication of end-stage renal failure or hyperparathyroidism; without either of these associated conditions, it is extremely rare. We report a case of calciphylaxis in a 58-year-old white British man, who had received long-term oral prednisolone for asthma control, with prophylactic calcium supplementation. There was no history of renal failure, and the patient's parathyroid function was normal. He was found to be heterozygous for the Factor V Leiden mutation. The acute presentation was seemingly precipitated by an episode of trauma and subsequent compression bandaging. The patient responded promptly to intravenous sodium thiosulfate. To our knowledge, this is the first case with no history of renal failure and normal parathyroid function, precipitated by compression bandaging and with an associated Factor V Leiden mutation.

Serotonergic potentiation of photic phase shifts: examination of receptor contributions and early biochemical/molecular events.

The 5-HT mixed agonist/antagonist 1-(2-methoxyphenyl)4-[4-(phthalimido)butyl]-piperazine hydrobromide (NAN-190) has been shown to greatly potentiate photic phase shifts in hamsters. The mechanism of this potentiation has yet to be determined. NAN-190 is believed to act primarily through the 5-HT(1A) receptor, but also binds to several other receptors, making it uncertain as to which receptor underlies its potentiation of photic phase shifts. Also uncertain are the intracellular changes in the suprachiasmatic nucleus (SCN) which are associated with such enhanced phase shifting. Here we examine the role of the 5-HT(1A) receptor as well as the physiological underpinnings, in terms of both gene expression and biochemical activation, in the behavioral responses to photic stimuli following pretreatment with NAN-190. Administration of NAN-190 to wildtype mice significantly potentiated late subjective night photic phase shifts, while mice lacking the 5-HT(1A) receptor (knockouts) exhibited an attenuated behavioral response to light when pretreated with NAN-190. In wildtype mice, the protein product of the immediate-early gene c-fos, induced following photic stimulation, was found to be significantly decreased with NAN-190 pretreatment. Similarly, the levels of phosphorylated CREB protein, involved in a biochemical pathway leading to gene transcription, were also attenuated by NAN-190 in the wildtype mice. However, activation of the extracellular signal-regulated kinase I/II (ERK) pathway in wildtype mice, following the light pulse, was not affected by NAN-190 pretreatment, nor was the expression of the circadian clock components Period1 and Period2. These findings suggest that the 5-HT(1A) receptor plays a critical role in the potentiation effect observed with NAN-190, and that NAN-190 may potentiate photic phase shifts at least partly by down-regulating the activity of some (but not all) genes and biochemical pathways involved in coupling the light signal to the output of the circadian clock.

Altered photic and non-photic phase shifts in 5-HT(1A) receptor knockout mice.

The mammalian circadian clock located in the suprachiasmatic nucleus (SCN) is thought to be modulated by 5-HT. 5-HT is though to inhibit photic phase shifts by inhibiting the release of glutamate from retinal terminals, as well as by decreasing the responsiveness of retinorecipient cells in the SCN. Furthermore, there is also evidence that 5-HT may underlie, in part, non-photic phase shifts of the circadian system. Understanding the mechanism by which 5-HT accomplishes these goals is complicated by the wide variety of 5-HT receptors found in the SCN, the heterogeneous organization of both the circadian clock and the location of 5-HT receptors, and by a lack of sufficiently selective pharmacological agents for the 5-HT receptors of interest. Genetically modified animals engineered to lack a specific 5-HT receptor present an alternative avenue of investigation to understand how 5-HT regulates the circadian system. Here we examine behavioral and molecular responses to both photic and non-photic stimuli in mice lacking the 5-HT(1A) receptor. When compared with wild-type controls, these mice exhibit larger phase advances to a short late-night light pulse and larger delays to long 12 h light pulses that span the whole subjective night. Fos and mPer1 expression in the retinorecipient SCN is significantly attenuated following late-night light pulses in the 5-HT(1A) knockout animals. Finally, non-photic phase shifts to (+/-)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) are lost in the knockout animals, while attenuation of the phase shift to the long light pulse due to rebound activity following a wheel lock is unaffected. These findings suggest that the 5-HT(1A) receptor plays an inhibitory role in behavioral phase shifts, a facilitatory role in light-induced gene expression, a necessary role in phase shifts to 8-OH-DPAT, and is not necessary for activity-induced phase advances that oppose photic phase shifts to long light pulses.

Evaluation of the ZEBRA 2000 (Z-10) Breger Vision bifocal contact lens.

PURPOSE: Evaluate the ZEBRA 2000 (Z-10) bifocal contact lens on presbyopic and aphakic patients. METHODS: Thirty-eight patients, 37 presbyopes and one aphake, were fit in the Z-10 and evaluated for 6 months. RESULTS: Twenty patients (53%) completed 6 months of contact lens wear. Ten (26%) discontinued due to lens related problems, three (8%) discontinued due to other health problems, and five (13%) were lost to follow-up. Average refits per eye were 1.75. Average distance visual acuity was 20/25; average near visual acuity was J1.6; average wear time, 11 hours. Patient satisfaction was rated good in comfort and vision and fair in nighttime glare by patients' subjective evaluation. CONCLUSIONS: The ZEBRA 2000 (Z-10) can be a useful addition in fitting the general presbyopic patient population.

Achieving additional myopic correction in undercorrected radial keratotomy eyes using the Lexington RK splint design.

PURPOSE: To reshape or flatten the corneas of post-radial keratotomy (RK) patients with residual myopia to improve uncorrected vision. METHODS: Twenty-one eyes (12 patients) with undercorrected RK results were fit with the Lexington RK splint, a multicurve plateau concept RGP contact lens. RESULTS: After wearing the lens an average of 6.1 months, undercorrected visual acuity improved an average 3.4 lines; change in spherical equivalent averaged 0.77 D; and flat K change averaged 0.75 D. Seventeen of 21 eyes (81%) demonstrated improved uncorrected vision. Nine eyes (43%) subsequently had a decrease in vision after discontinuing lens wear. Patients fit within 7 months of their last RK procedure were more likely to achieve optimal results. Sixty-two percent of this group did not require glasses or contact lenses (range: 4 to 21 months). CONCLUSIONS: A well-designed and fit plateau RGP contact lens can manipulate the healing post-RK cornea.

Corneal topography, arcuate keratotomy, and compression sutures for astigmatism after penetrating keratoplasty.

BACKGROUND: Twenty (20) patients with post-penetrating keratoplasty (PKP) (21 eyes) and excessive corneal astigmatism were studied using corneal topography to determine placement of arcuate incisions and compression sutures for astigmatism reduction. METHODS: Keratoplasty wounds and compression sutures were placed asymmetrically based on corneal topography only. Incisions were at the donor-host junction at a depth of 500 microns. RESULTS: A 56% reduction in corneal astigmatism was accomplished with an average cylinder reduction of 5.3 D. Keratometry readings were reduced in 18 of 20 (90%) of eyes and refractive cylinder was reduced in 15 of 20 (75%) of eyes. Corrected visual acuity improved in 15 of 20 (75%) declined in 15%, and did not change in 10%. CONCLUSION: Visual acuity can be improved by manipulating the astigmatism after penetrating keratoplasty using corneal topography maps to determine placement of arcuate incisions and compression sutures.

GATA-3 dominant negative mutant. Functional redundancy of the T cell receptor alpha and beta enhancers.

The GATA family of transcription factors regulates a wide variety of genes, including those involved in differentiation of erythrocytes and T lymphocytes. We report here the creation of a dominant negative mutant of GATA-3, KRR, which effectively blocks wild-type GATA-1, GATA-2, and GATA-3 transactivation when co-expressed in transient assays. KRR was generated by site-directed mutagenesis while investigating a putative activation domain of GATA-3, located between its two zinc fingers. The GATA-3 KRR mutation does not affect expression, nuclear translocation, or the ability to bind to a consensus GATA sequence. KRR can suppress the activity of the minimal T cell receptor (TCR) alpha and beta enhancers by 12- and 3.4-fold, respectively. However, KRR did not have a significant effect on the activity of larger TCR-alpha and -beta enhancer fragments. Thus, functional redundancy in the TCR-alpha and -beta enhancers can compensate for the loss of GATA-3 activity.

A new contact lens design for post-keratoplasty patients.

We conducted a study of 25 post-penetrating keratoplasty (PK) patients (28 eyes) fit with Quintasphere PK rigid gas permeable contact lenses. Using the Quintasphere PK trial set, 96% of patients were successfully wearing the lens at 6 months; at 1 year 93% were successfully wearing the lens. Eighty-two percent of eyes fit achieved at least 20/40 visual acuity, and 93% achieved at least 20/50. The average number of lenses fit per eye was 1.29. The design basis of the Quintasphere PK lens was predicated on a plateau-shaped corneal graft.