Intranasal civamide for the acute treatment of migraine headache.

The objective of this study was to investigate the safety and efficacy of intranasal civamide for the acute treatment of migraine headache with or without aura. Civamide is a vanilloid receptor agonist and neuronal calcium channel blocker that inhibits the neuronal release of excitatory neurotransmitters (e.g. calcitonin gene-related peptide (CGRP) and substance P (SP)) and depletes the neurones of the trigeminal plexus of their neurotransmitter content. Applied intranasally, the release of neurotransmitters to meningeal and dural blood vessels should be decreased, along with the resultant vasodilatation, plasma extravasation, and histamine/serotonin release. Subsequent migraine headache pain may also be diminished. Thirty-four patients were enrolled into a double-blind study of intranasal civamide, and randomized to receive a single dose of either 20 microg or 150 microg of civamide, for the treatment of a single migraine headache, with or without aura, of moderate to severe pain. At 2 h post-dose, 55.6% of patients treated with either dose had a decrease in pain severity, with 22.2% of patients being pain-free. At 4 h post-dose, 72.7% of patients treated with either dose had a decrease in pain severity, with 33.0% of patients being pain-free. Adverse events were similar for both dosages, with 91.2% of patients experiencing nasal burning and 44.1% of patients experiencing lacrimation. No systemic side-effects were observed. Based upon the results of this study, intranasal civamide may be effective in the acute treatment of migraine headache. Given civamide's proposed mechanism of action, intranasal civamide should be substantially more effective for prophylaxis than acute treatment of migraine. A study evaluating its efficacy in prophylaxis of migraine is currently planned.

A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy.

An 8-week double-blind, multicenter, parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet. Two hundred thirty-five patients were randomized to treatment with either capsaicin cream or amitriptyline capsules. Capsaicin-treated patients received inactive capsules, and amitriptyline-treated patients applied vehicle cream. A visual analogue scale of pain intensity and measurements of interference by pain with functional activities were recorded at onset and at 2-week intervals. A visual analogue scale of pain relief and physicians' global evaluation assessed changes in pain status from baseline. Topical capsaicin and oral amitriptyline produced equal and statistically significant improvements in pain over the course of the study. By the end of week 8, 76% of patients in each group experienced less pain, with a mean reduction in intensity of more than 40%. By the end of the study, the interference with daily activities by pain had diminished significantly (P = .001) in both groups, including improvements in sleeping and walking. No systemic side effects were observed in patients treated with topical capsaicin. Most patients receiving amitriptyline experienced at least one systemic side effect, ranging from somnolence (46%) to neuromuscular (23%) and cardiovascular (9%) adverse effects. Topically applied capsaicin is an equally effective but considerably safer alternative to amitriptyline for relief of the pain of diabetic neuropathy.

Percutaneous cholecystostomy: does transhepatic puncture preclude a transperitoneal catheter route?

Percutaneous cholecystostomy is now commonly performed for the diagnosis and treatment of gallbladder and biliary disorders. The optimal method and route of percutaneous cholecystostomy catheter placement, however, remain controversial and may depend on the indication for the procedure. The ability to predict traversal of the extraperitoneal plane of fixation ("bare area") between the liver and gallbladder with a transhepatic approach was investigated. With sonographic guidance, 21 transhepatic catheterizations were attempted: 19 in cadavers and two in patients who subsequently underwent cholecystectomy. In all cases, 8-F or 5-F self-retaining catheters were used. At autopsy or surgery, the catheter course and gallbladder puncture site were evaluated. Of 21 punctures, 19 (90%) were transhepatic and two (10%) were transperitoneal. Among the 19 transhepatic punctures, eight catheters (42%) traversed the bare area, while 11 (58%) entered the free gallbladder wall adjacent to the serosal attachment. There were four instances of guide-wire dislodgment during catheter placement; all occurred following puncture of the free wall of the gallbladder. No guide-wire dislodgment occurred when the bare area was transversed. Transhepatic gallbladder puncture does not prevent puncture of the free gallbladder surface. However, the liver and bare area do seem to provide guide-wire stability during catheter placement.

Clinical evaluation of an after-pediculicide nit removal system.

A significant problem in the management of pediculosis is the removal of nits from the hair after pediculicide treatment. This study describes use of a nit removal system incorporating a cream rinse containing formic acid that loosens the bond between the nit and hair. Twenty-four children with pediculosis capitis, age 4 to 12 years, were evaluated. Sections of hair with equivalent numbers of nits were identified as control or test sites. Combining for 5 minutes after use of the formic acid rinse removed 93.5% of nits compared with a 27.6% reduction in the control section (p less than 0.0001). These results demonstrate that use of this nit removal system greatly facilitates nit removal.

Topical capsaicin treatment of chronic postherpetic neuralgia.

Uncontrolled studies have indicated that topically applied capsaicin may be a safe and effective treatment for postherpetic neuralgia. In a double-blind study 32 elderly patients with chronic postherpetic neuralgia were treated with either capsaicin cream or its vehicle for a 6-week period. Response to treatment was evaluated by visual analogue scales of pain and of pain relief, together with changes in a categoric pain scale and in a physician's global evaluation. Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables. After 6 weeks almost 80% of capsaicin-treated patients experienced some relief from their pain. Because capsaicin avoids problems with drug interactions and systemic toxicity, we suggest that topical capsaicin be considered for initial management of postherpetic neuralgia.

Treatment of chronic postherpetic neuralgia with topical capsaicin. A preliminary study.

Continuing pain following herpes zoster is common in patients 60 years of age or older. Current treatments are generally unsatisfactory. The endogenous neuropeptide substance P is an important chemomediator of nociceptive impulses from the periphery to the central nervous system and has been demonstrated in high levels in sensory nerves supplying sites of chronic inflammation. In an attempt to alleviate the pain of 14 patients with postherpetic neuralgia, capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), known to deplete substance P, was applied topically to painful areas of skin for 4 weeks. Of the 12 patients completing this preliminary study, 9 (75%) experienced substantial relief of their pain. The only adverse reaction was an intermittent, localized burning sensation experienced by one patient with application of capsaicin. Although these results are preliminary, they suggest that topical application of capsaicin may provide a useful approach for alleviating postherpetic neuralgia and other syndromes characterized by severe localized pain.

Capsaicin in the treatment of dermatologic disease.

Capsaicin cream is the first of a class of neuropeptide active agents to be introduced into dermatologic therapy. Capsaicin's effects appear primarily related to its ability to deplete the neuropeptide substance P from local sensory terminals in the skin. The use of capsaicin cream in the treatment of postherpetic neuralgia and psoriasis is discussed. I believe that capsaicin and other neuropeptide active agents may become important therapeutic modalities for the dermatologist in the near future.

Effects of topically applied capsaicin on moderate and severe psoriasis vulgaris.

Alterations in the cutaneous vascular system are prominent in psoriasis and may play an important role in the pathogenesis of this disorder. We evaluated the effects of topically applied capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a known inhibitor of cutaneous vasodilatation, on moderate and severe psoriasis. Under a double-blind paradigm, forty-four patients with symmetrically distributed psoriatic lesions applied topical capsaicin to one side of their body and identical-appearing vehicle to the other side for 6 weeks. After 3 and 6 weeks of treatment, we performed ratings on changes in scaling and erythema, as well as overall improvement of the psoriasis. Over the course of the study, significantly greater overall improvement was observed on sides treated with capsaicin compared to sides treated with vehicle. Similarly, significantly greater reductions in scaling and erythema accompanied capsaicin application. Burning, stinging, itching, and redness of the skin were noted by nearly half of the patients on initial applications of study medication but diminished or vanished upon continued application. These results suggest that topical application of capsaicin may be a useful new approach in the treatment of psoriasis.

Cutaneous immunofluorescence studies in adult rheumatoid arthritis in sun-exposed and non-sun-exposed areas.

The incidence and significance of positive cutaneous immunofluorescence findings were assessed in biopsy specimens of both sun-exposed and non-sun-exposed skin of 34 adult patients with rheumatoid arthritis (RA) who were not receiving systemic corticosteroids. The incidence of lupus erythematosus (LE)-band was low (8.6%) in both groups. Twenty-eight percent of the patients had perivascular IgM and/or C3 deposits, and 74% had cytoid bodies in the papillary dermis. These studies indicate that the incidence of LE band is low in RA and that the detection of such a band in normal skin warrants close follow-up of RA patients for possible development of LE.

Reduced threshold to suction-induced blister formation in insulin-dependent diabetics.

Diabetics may have an increased susceptibility to cutaneous blister formation clinically manifest as the bullous eruption of diabetes. We evaluated the mechanical force necessary to induce suction blisters in fifteen insulin-dependent diabetics and twenty age-matched normal controls. The mean suction blister threshold for the diabetics was 31.9 minutes versus 68.0 minutes for the controls, a highly significant difference (p less than 0.01). Histologic appearance of suction blisters was similar in diabetic and normal skin, under both light and electron microscopic examination, with a noninflammatory subepidermal separation in the lamina lucida between the cell membrane and the basal lamina. These results demonstrate that insulin-dependent diabetics have a marked reduction in suction blister threshold as compared to age-matched controls.