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A multi-center study was conducted to assess the clinical effectiveness and safety of high-strength capsaicin cream 0.25% in a lidocaine-containing vehicle for treatment of painful diabetic neuropathy (PDN) and postherpetic neuralgia (PHN). Eighty-three (83) patients with PDN (n = 56) or PHN (n = 27) who were already taking oral antiepileptics or tricyclic antidepressants with incomplete pain relief were enrolled. Capsaicin cream 0.25% in a lidocaine-containing vehicle was applied to painful areas three times daily for 6 weeks. Pain intensity was evaluated at Weeks 1, 3, and 6 using an Average Weekly Pain Score. At Week 6, improvement was also assessed with a Subject Global Evaluation (SGE), a Physician Global Evaluation (PGE), and a Functional Assessment Questionnaire. Following 1, 3, and 6 weeks of treatment, pain was reduced by 21%, 40%, and 50%, respectively, in patients with PDN, and by 24%, 39%, and 51%, respectively, in patients with PHN. On the SGE, 90% of patients with PDN were rated as Improved, with 58% rated as Much or Very Much Improved; 94% of patients with PHN were rated as Improved, with 56% rated as Much or Very Much Improved. On the PGE, 89% of patients with PDN were rated as Improved, with 63% rated as Much or Very Much Improved; 88% of patients with PHN were rated as Improved, with 63% rated as Much or Very Much Improved. Transient stinging/burning sensations at the application sites were the most commonly reported adverse events, while no serious adverse events related to study drug were observed. Capsaicin cream 0.25% in a lidocainecontaining vehicle was shown to be a safe, effective, and well tolerated adjunctive treatment for PDN and PHN in patients experiencing incomplete pain relief despite taking oral antiepileptics or tricyclic antidepressants. [ABSTRACT FROM AUTHOR]

Abstract Background Envenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists. Methods A geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm. Results A unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy. Conclusions Clinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.

Here's how to identify patient at risk for ventricular arrhythmias and sudden cardiac death. [ABSTRACT FROM AUTHOR]

Objective: To determine how neuropsychiatric comorbidity, modulatory indication, demographics, and other characteristics affect inpatient deep brain stimulation (DBS) outcomes., Methods: This is a retrospective study of 45 months' worth of data from the National Inpatient Sample. Patients were aged ≥ 18 years old and underwent DBS for Parkinson Disease (PD), essential tremor (ET), general dystonia and related disorders, other movement disorder (non-PD/ET), or obsessive-compulsive disorder (OCD) at a US hospital. Primary endpoints were prolonged length of stay (PLOS), high-end hospital charges (HEHCs), unfavorable disposition, and inpatient complications. Logistic models were constructed with odds ratios under 95% confidence intervals. A p-value of 0.05 determined significance., Results: Of 214,098 records, there were 27,956 eligible patients. Average age was 63.9 ± 11.2 years, 17,769 (63.6%) were male, and 10,182 (36.4%) patients were female. Most of the cohort was White (51.1%), Medicare payer (64.3%), and treated at a large-bed size (80.7%), private non-profit (76.9%), and metro-teaching (94.0%) hospital. Neuropsychiatric comorbidity prevalence ranged from 29.9% to 47.7% depending on indication. Compared with PD, odds of complications and unfavorable disposition were significantly higher with other movement disorders and dystonia, whereas OCD conferred greater risk for HEHCs (p < 0.05). Patients with ET had favorable outcomes. Neuropsychiatric comorbidity, Black race, and Charlson Comorbidity Index > 0 were significantly associated with unfavorable outcomes (p < 0.05)., Conclusion: The risk of adverse inpatient outcomes for DBS in the United States is independently correlated with non-PD/ET disorders, neuropsychiatric comorbidity, and non-White race, reflecting the heterogeneity and infancy of widespread DBS for these patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: As of the 2020 National Resident Matching Program (NRMP), nearly all applicants are evaluated together for graduate medical education (GME) candidacy. We set out to characterize US MD and DO Senior residency match performance in the single-accreditation GME era., Methods: A retrospective study was conducted in 2021 utilizing data collected from the 2018 and 2020 NRMP Charting Outcomes in the Match publications aggregated and subdivided into three groups based on competitiveness: low (LC), moderate (MC), and high (HC). Nonparametric analysis was performed using Chi square or Fisher exact tests if counts were less than five. Significance was determined at p < 0.05., Results: A total of 46,853 candidates were included, with 36,194 (77.3%) US MD and 10,659 (22.7%) DO Seniors. Match rates for US DO Seniors were lower than US MD Seniors across all competitiveness strata (p < 0.0001). Research item production, national licensing examination scores, and mean number of contiguous programs ranked were lower for matched US DO Seniors compared to matched US MD Seniors, with significant differences depending on competitiveness group., Conclusions: With recent changes to GME and its application process, understanding how various groups compare will be increasingly important. US DO Seniors have lower first-rank match rates for all specialty competitiveness levels. This may be due to lower research output or nuanced specialty selection. This study could aid GME stakeholders to more effectively allocate resources and better prepare residency candidates., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Kortz et al.)

Introduction Spontaneous intracerebral hemorrhage (ICH) results in significant morbidity and mortality. The pathogenesis of brain injury after ICH is thought to be due to mechanical damage followed by ischemic, cytotoxic, and inflammatory changes in the underlying and surrounding tissue. Various inflammatory and non-inflammatory biomarkers have been studied as predictors and potential therapeutic targets for intracerebral hemorrhage. Our prior study showed an association with low vascular endothelial growth factor (VEGF) levels and increased mortality. This current study looks to expand on our prior results and will look at the relationship between tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), VEGF, Homocysteine (Hcy), and CRP to albumin ratio (CAR) in predicting outcomes and severity in spontaneous intracerebral hemorrhage. Methods We conducted a retrospective chart review of patients with spontaneous intracerebral hemorrhage with TNFα, CRP, VEGF, Hcy levels drawn on admission. Albumin and CRP levels on admission were used to calculate CAR. Ninety-nine patients were included in the study. Primary outcomes included death, early neurologic decline (END), and hemorrhage size. Secondary outcomes included late neurologic decline (LND), Glasgow Coma Scale (GCS) on admission, GCS on discharge, ICH score, change in hemorrhage size, need for surgical intervention, and length of ICU stay. Results A total of 99 patients were included in this study, with 42% requiring surgical intervention and an overall mortality of 16%. Basal ganglia hemorrhage was seen in 41% of patients. Hcy and CAR were significantly correlated with ICH size in basal ganglia patients (r-=0.36, p=0.03; r=0.43, p=0.03, respectively). CAR was significantly correlated with ICH score (r=0.33, p=0.007874). Admission VEGF levels less than 45 pg/ml had 8.4-fold increase in mortality (odds ratio [OR] 8.4545, p=0.0488). Patients with TNFα levels greater than 1.40 pg/ml had a 4.1-fold increase in mortality (OR 4.1, p=0.04) Conclusion Our study demonstrated that low levels (<45 pg/ml) of VEGF were associated with an 8.4-fold increase in mortality, supporting the neuroprotective effect of this protein. Elevated Hcy and CAR levels were associated with an increase in hemorrhage size in patients with basal ganglia hemorrhages. TNFα levels greater than 1.40 pg/ml were associated with a 4.1-fold increase in mortality, and this together with CAR being correlated with increased hemorrhage size and ICH score further demonstrate the inflammatory consequences after intracerebral hemorrhage. Future studies directed at lowering CRP, TNFα, and Hcy and/or increasing VEGF in intracerebral hemorrhage patients are needed and may be beneficial., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Bernstein et al.)

Introduction Dystonia can cause severe disability when left untreated. Once a patient has exhausted medical management, surgical intervention may be the only treatment option. Although not curative, deep brain stimulation has been shown to be beneficial for patients affected by this condition. Our study sought to review patients undergoing deep brain stimulation for medically refractory dystonia to assess outcomes. Methods Our institution's operative database was reviewed retrospectively for all patients undergoing deep brain stimulator placement over the last six years. These medical records were reviewed for the severity of dystonia preoperatively and followed postoperatively for 24 months, focusing on the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Patients with less than two-year postoperative follow-up were excluded from the study. The patients were further stratified by age into Group A, consisting of patients less than 40 years old, and Group B, patients greater than or equal to 40 years old. Other attributes such as age, sex, age of disease onset, disease duration at the time of surgery, genetic tests for dystonia-related genes, and any complication associated with surgery were also reviewed. Results Four hundred fifty-five operative cases for deep brain stimulator placement were reviewed, and 16 patients met inclusion criteria for the study. The mean age for our patient cohort was 43.75 years, with four males and 12 females. The average time from the age of disease onset to time of surgery was 9.7 years for Group A and 10.8 years for Group B; the overall average was 10.3 years. All patients had globus pallidus interna (GPi) as their surgical target. The first incidence of a statistically significant decrease in BFMDRS score was noted at three months postoperatively (p<0.001) when compared to preoperative values. Fourteen patients in our cohort underwent preoperative genetic testing for DYT gene mutations, out of which four were found to have a mutation. Conclusion Our review of outcomes for primary generalized dystonia at our institution found that deep brain stimulator targeting the GPi is safe and effective. We found an overall 88% response rate with younger patients (< 40-year-old) showing a better response at two years than older patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Ghanchi et al.)

Introduction Traumatic brain injury (TBI) results in primary and secondary brain injuries. Secondary brain injury can lead to cerebral edema resulting in increased intracranial pressure (ICP) secondary to the rigid encasement of the skull. Increased ICP leads to decreased cerebral perfusion pressure which leads to cerebral ischemia. Refractory intracranial hypertension (RICH) occurs when ICP remains elevated despite first-tier therapies such as head elevation, straightening of the neck, analgesia, sedation, paralytics, cerebrospinal fluid (CSF) drainage, mannitol and/or hypertonic saline administration. If unresponsive to these measures, second-tier therapies such as hypothermia, barbiturate infusion, and/or surgery are employed. Methods This was a retrospective review of patients admitted at Arrowhead Regional Medical Center from 2008 to 2019 for severe TBI who developed RICH requiring placement into a pentobarbital-induced coma with therapeutic hypothermia. Primary endpoints included mortality, good recovery which was designated at Glasgow outcome scale (GOS) of 4 or 5, and improvement in ICP (goal is <20 mmHg). Secondary endpoints included complications, length of intensive care unit (ICU) stay, length of hospital stay, length of pentobarbital coma, length of hypothermia, need for vasopressors, and decompressive surgery versus no decompressive surgery. Results Our study included 18 patients placed in pentobarbital coma with hypothermia for RICH. The overall mortality rate in our study was 50%; with 60% mortality in pentobarbital/hypothermia only group, and 46% mortality in surgery plus pentobarbital/hypothermia group. Maximum ICP prior to pentobarbital/hypothermia was significantly lower in patients who had a prior decompressive craniectomy than in patients who were placed into pentobarbital/hypothermia protocol first (28.3 vs 35.4, p<0.0238). ICP was significantly reduced at 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after pentobarbital and hypothermia treatment. Initial ICP and maximum ICP prior to pentobarbital/hypothermia was significantly correlated with mortality (p=0.022 and p=0.026). Patients with an ICP>25 mmHg prior to pentobarbital/hypothermia initiation had an increased risk of mortality (p=0.0455). There was no statistically significant difference in mean ICP after 24 hours after pentobarbital/hypothermia protocol in survivors vs non-survivors. Increased time to reach 33°C was associated with increased mortality (r=0.47, p=0.047); with a 10.5-fold increase in mortality for >7 hours (OR 10.5, p=0.039). Conclusion Prolonged cooling time >7 hours was associated with a 10.5-fold increase in mortality and ICP>25 mmHg prior to initiation of pentobarbital and hypothermia is suggestive of a poor response to treatment. We recommend patients with severe TBI who develop RICH should first undergo a 12 x 15 cm decompressive hemicraniectomy because they have better survival and are more likely to have ICP <25 mmHg as the highest elevation of ICP if the ICP were to become and stay elevated again. Pentobarbital and hypothermia should be initiated if the ICP becomes elevated and sustained above 20 mmHg with a prior decompressive hemicraniectomy and refractory to other medical therapies. However, our data suggests that patients are unlikely to survive if there ICP does not decrease to less than 15mmHg at 8 and 12 hours after pentobarbital/hypothermia and remain less than 20 mmHg within first 48 hours., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Bernstein et al.)

Introduction: Deep brain stimulation has emerged as an effective treatment for movement disorders such as Parkinson's disease, dystonia, and essential tremor with estimates of >100,000 deep brain stimulators (DBSs) implanted worldwide since 1980s. Infections rates vary widely in the literature with rates as high as 25%. Traditional management of infection after deep brain stimulation is systemic antibiotic therapy with wound incision and debridement (I&D) and removal of implanted DBS hardware. The aim of this study is to evaluate the infections occurring after DBS placement and implantable generator (IPG) placement in order to better prevent and manage these infections., Materials/methods: We conducted a retrospective review of 203 patients who underwent implantation of a DBS at a single institution. For initial electrode placement, patients underwent either unilateral or bilateral electrode placement with implantation of the IPG at the same surgery and IPG replacements occurred as necessary. For patients with unilateral electrodes, repeat surgery for placement of contralateral electrode was performed when desired. Preoperative preparation with ethyl alcohol occurred in all patients while use of intra-operative vancomycin powder was surgeon dependent. All patients received 24 hours of postoperative antibiotics. Primary endpoint was surgical wound infection or brain abscess located near the surgically implanted DBS leads. Infections were classified as early (<90 days) or late (>90 days). Infectious organisms were recorded based on intra-operative wound cultures. Number of lead implantations, IPG replacements and choice of presurgical, intra-operative, and postsurgical antibiotics were recorded and outcomes compared., Results: Two hundred and three patients underwent 391 electrode insertions and 244 IPG replacements. Fourteen patients developed an infection (10 early versus 4 late); 12 after implantation surgery (3%) and 2 after IPG replacement surgery (0.8%). No intracranial abscesses were found. Most common sites were the chest and connector. Staphylococcus aureus (MSSA) was the most common organism. Intra-operative vancomycin powder did not decrease infection risk. Vancomycin powder use was shown to increase risk of infection after electrode implantation surgery (Relative Risk 5.5080, p = 0.02063). Complete hardware removal occurred in eight patients, one patient had electrode only removal, three patients with I&D and no removal of hardware, and two patients with removal of IPG and extensor cables only. All patients were treated with postoperative intravenous antibiotics and no recurrent infections were found in patients with hardware left in place., Discussion/conclusion: Infections after DBS implantation and IPG replacement occurred in 3% and 0.8% of patients respectively in our study which is lower than reported historically. Early infections were more common. No intracranial infections were found. Intra-operative use of vancomycin was not shown to decrease risk of infection after electrode implantation surgery or IPG replacement. However, in our study it was shown to increase risk of infection after electrode implantation surgery. Treatment includes antibiotic therapy and debridement with or without removal of hardware. DBS hardware can be safely left in place in select patients who may have significant adverse effects if it is removed., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Bernstein et al.)

Background and purpose The pathogenesis of brain injury after intracerebral hemorrhage is thought to be due to mechanical damage followed by ischemic, cytotoxic, and inflammatory changes in the underlying and surrounding tissue.In recent years, there has been a greater research interest into the various inflammatory biomarkers and growth factors that are secreted during intracerebral hemorrhage. The biomarkers investigated in this study are tumor necrosis factor alpha (TNF alpha), C-reactive protein (CRP), homocysteine (Hcy), and vascular endothelial growth factor (VEGF). The aim of this study was to further investigate the effects of these biomarkers in predicting the acute severity outcome of intracerebral hemorrhage (ICH). Methods We conducted a retrospective chart review of patients with spontaneous ICH with TNF alpha, CRP, VEGF, and Hcy levels drawn on admission. Forty-two patients with spontaneous ICH with at least one of the above labs were included in the study. Primary outcomes included death, Glasgow Coma Scale (GCS) on admission, early neurologic decline (END), and hemorrhage size. Secondary outcomes included GCS on discharge, ICH score, functional outcome risk stratification scale of intracerebral hemorrhage (FUNC score), change in hemorrhage size, need for surgical intervention, and length of intensive care unit (ICU) stay. Results Forty-two patients with spontaneous intracerebral hemorrhage (ICH) were analyzed, 12 patients (28.5%) required surgical intervention, and four patients (9.5%) died. Only low VEGF serum values were found to predict mortality. TNF alpha, CRP, Hcy, and VEGF levels in our patients with ICH were not found to predict early neurologic decline and were not correlated with GCS on admission, initial hemorrhage size, change in hemorrhage size, need for surgical intervention, ICH score, FUNC score, midline shift, and length of ICU stay. CRP and Hcy were elevated in 58% and 31% of patients tested, respectively. GCS on admission and ICH score were significantly associated with mortality. Conclusion After careful statistical review of the data obtained from this patient population, only low VEGF values were found to be a significant predictor of mortality. However, elevated CRP and Hcy levels were associated with a non-significant trend in hemorrhage size and mortality suggesting that CRP and Hcy-lowering therapies may decrease hemorrhagic stroke risk and severity., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the safety and efficacy of civamide cream 0.075% for the treatment of osteoarthritis (OA) of the knee., Methods: We conducted a 12-week, multicenter, randomized, double-blind study with a 52-week open-label extension. Patients with OA of the knee received either civamide cream 0.075% or a lower dose of civamide cream, 0.01%, as the control. The 3 co-primary endpoints in the double-blind study were the time-weighted average (TWA) of change from baseline to Day 84 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, the WOMAC physical function subscale, and the Subject Global Evaluation (SGE). In the 52-week open-label extension study, the Osteoarthritis Pain Score and SGE were assessed., Results: A total of 695 patients were randomized to receive civamide cream 0.075% (n = 351) or civamide cream 0.01% (control; n = 344) in the double-blind study. Significance in favor of civamide cream 0.075% was achieved for the TWA for all 3 co-primary efficacy variables: WOMAC pain (p = 0.009), WOMAC physical function (p < 0.001), and SGE (p = 0.008); and at Day 84 for these 3 variables (p = 0.013, p < 0.001, and p = 0.049, respectively). These analyses accounted for significant baseline-by-treatment interactions. In the 52-week open-label extension, efficacy was maintained. Civamide cream 0.075% was well tolerated throughout the studies., Conclusion: These studies demonstrate the efficacy of civamide cream for up to 1 year of continuous use. Civamide cream, with its lack of systemic absorption, does not have the potential for serious systemic toxicity, in contrast to several other OA treatments.

Objective: To evaluate the safety and efficacy of intranasal civamide solution for preventive treatment during an episodic cluster headache period., Subjects and Methods: This was a multicenter, double-blind, randomized, vehicle-controlled study with a 7-day treatment period and a 20-day posttreatment period performed at 14 headache/neurology centers in the United States. Twenty-eight subjects were randomized to receive civamide or its vehicle in a 2:1 ratio; 18 received civamide and 10 received the vehicle. Subjects received 100 microL of 0.025% civamide (25 microg) or 100 microL of the vehicle to each nostril via dropper once daily for 7 days. The total daily dose of civamide was 50 microg., Main Outcome Measures: The number of cluster headaches per week during the treatment and posttreatment periods, pain intensity, presence of associated symptoms, and the incidence of adverse events were assessed., Results: Subjects in the civamide group had a significantly greater percent decrease in the number of headaches from baseline to posttreatment during days 1 through 7 (-55.5% vs -25.9%; P =.03) and a trend toward significance during days 8 through 14 (-66.9% vs -32.3%; P =.07) and days 15 through 20 (-70.6% vs -34.9%; P =.07), as well as a near-significant decrease during the entire posttreatment period (days 1 through 20 [P =.054]) compared with the vehicle group. There were larger decreases in the number of headaches per week during the posttreatment period in the civamide-treated group, with trends toward significance during posttreatment days 8 through 14 (-8.6 vs -3.6; P =.09) and days 15 through 20 (-8.9 vs -3.6; P =.07). There were no significant differences between groups in cluster headache pain intensity, number of severe headaches, or associated symptoms. The most common adverse events included nasal burning (14 of 18 civamide-treated subjects, 1 of 10 vehicle-treated subjects; P =.001) and lacrimation (9 of 18 civamide-treated subjects, 0 of 10 vehicle-treated subjects; P =.01)., Conclusion: Intranasal civamide solution at a dose of 50 microg may be modestly effective in the preventive treatment of episodic cluster headache.

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 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.

A subcorneal pustular dermatosis and a vesicobullous eruption with the clinical ad histologic features of localized bullous pemphigoid(BP) were observed in a 44-year-old woman with morphea and a recent history of phenytoin sodium-induced toxic epidermal necrolysis. Localized BP is rare and has been previously described in association with other cutaneous disorders. The coexistence of localized BP, morphea, and subcorneal pustulosis suggests that immunologic factors may play a role in all three conditions.

We evaluated the effectiveness of 2% erythromycin and its alcohol/propylene glycol vehicle in the treatment of three hundred forty-eight patients with inflammatory acne vulgaris. A significantly greater reduction was noted in the papulopustule count for the erythromycin-treated group compared to the vehicle-treated group. Additionally, clinical improvement, as measured by physician global ratings, was significantly greater in the erythromycin-treated group. A lower adverse reaction rate observed in the erythromycin-treated patients may result from previously demonstrated anti-inflammatory properties of this antibiotic.

We report herein the concurrent appearance of childhood pemphigus foliaceus and Graves' disease in a 14-year-old girl who was initially seen with crusted and hyperpigmented plaques on her chest, back, abdomen, and legs. The diagnosis of pemphigus foliaceus was confirmed by biopsy and immunofluorescent microscopic studies while the diagnosis of Graves' disease was based on clinical and laboratory findings. The coexistence of these two immune-mediated diseases in a single patient suggest that some persons may bear a unique predisposition to the development of two or more autoimmune-type disorders that may affect diverse organ systems.

Angioimmunoblastic lymphadenopathy (AIL) is an uncommon immunoproliferative disorder with a presentation similar to malignant lymphoma but with a benign histopathologic picture. We report a case of a 49-year-old woman with AIL who manifested a pruritic maculopapular eruption as her presenting complaint and whose disease pursued an aggressive clinical course. Forty-four percent of patients with AIL experience a nonspecific dermatitis that in general is maculopapular and precedes other clinical symptoms by at least several weeks. AIL should be included in the differential diagnosis of any maculopapular eruption of unknown etiology accompanied by lymphadenopathy.

We evaluated the roles of endogenous opioid peptides and histamine in the pathophysiology of alcohol-induced facial flushing in rosacea. Non-diabetic patients with rosacea ingested 360 ml of 6% ethanol after receiving either subcutaneous naloxone hydrochloride or oral chloropheniramine maleate. Only pretreatment with naloxone blocked the alcohol-induced rosacea flushing (AIRF), suggesting an active role of endogenous enkephalin and/or endorphin in this vascular reactivity. In this respect, AIRF is similar to chlorpropamide alcohol flushing and menopausal flushing.

The class of immunoglobulin (Ig) deposited at the dermal-epidermal junction (DEJ) of the skin in patients with systemic lupus erythematosus (SLE) has been proposed to have prognostic implications. The authors studied disease activity in 51 SLE patients with a positive lupus band. Patients with cutaneous IgM deposits had significantly more severe disease than those with only IgG or with mixed immunoglobulin deposits. While their data suggest an association between IgM deposits, severe disease and a poor prognosis, they urge caution in utilizing Ig deposits as a prognostic indicator.

Central elicitation of itch by morphine may result from binding to opiate receptors, mimicking the physiological binding of endorphins and enkephalins to these receptors. Pretreatment of normal subjects with naloxone hydrochloride resulted in diminution or abolition of histamine-provoked itch. These results suggest an important role for central opioid peptides as mediators of the itch sensation.

The association of acanthosis nigricans with pituitary tumors and insulin-resistant diabetes suggests that a pituitary peptide may promote papillomatosis and acanthosis characteristic of acanthosis nigricans. Although such a peptide has not been isolated, it may derive by sequential cleavage from the 31,000-dalton precursor peptide to ACTH and beta-lipotropin (beta-LPH). In order to evaluate the role of pituitary peptides in the pathogenesis of acanthosis nigricans, we compared plasma levels of beta-endorphin (beta-EP) and ACTH in plasma of 8 fasting patients with obesity-associated benign acanthosis nigricans and 7 fasting normal controls utilizing sensitive radioimmunoassay procedures. Mean plasma beta-EP levels for the acanthosis nigricans and control subjects were not significantly different (90 pg/ml vs. 140 pg/ml), nor was any significant difference observed between plasma ACTH levels of the 2 groups (42.3 and 31.2 pg/ml, respectively.) Our data indicate that plasma levels of the pituitary-derived peptides ACTH and beta-EP are not increased in obesity-associated benign acanthosis nigricans, and suggest that its proposed hormonal mediator might originate independently from the large peptide precursor of ACTH, beta-LPH and their fragments.

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.

Although most deformities in front of the tragi are limited abnormalities, they may be signs of certain associated congenital syndromes that result from maldevelopment of the mandibular arch.

Malignant melanoma derives from melanocytic cells that possess the special biochemical pathway for the conversion of levodopa to melanin. Levodopa is widely employed in the treatment of Parkinson's disease, and several patients receiving levodopa have been observed to have acquired melanomas, raising concern about a possible relationship between this drug and the tumor. We encountered a 74-year-old woman in whom three distinct primary melanomas developed after she had been receiving long-term therapy with levodopa and a decarboxylase inhibitor. These lesions could be distinguished histologically from epidermotropic metastatic melanoma. Although the association between levodopa and melanoma is tenuous, careful monitoring of pigmentary changes in patients receiving levodopa is advised.

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.

Skin necrosis is a rare complication of heparin administration that is usually localized to injection sites. A 32-year-old insulin-dependent diabetic patient, receiving intravenous (IV) and low-dose heparin sodium therapy, had cutaneous necrosis in areas distant to the sites of injection. Prior to the onset of cutaneous lesions, thrombocytopenia develop]ed in the patient that may have been heparin induced. Heparin may induce the production of platelet aggregating immunoglobulins that predispose persons who are sensitive to the drug to thrombocytopenia, skin necrosis, and thrombotic events. Obesity, diabetes, and treatment with broad-spectrum antibiotics seem to increase the risk of such complications. Cutaneous necrosis secondary to heparin administration may serve as a warning of the potentially lethal complications of IV use. In patients in whom skin necrosis or thrombocytopenia develops, heparin therapy should be discontinued and anticoagulation with an oral agent should be considered.

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.