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Meningothelial hamartomas are benign lesions of the scalp with a handful of case reports published. Usually thought to be congenital lesions, they have, on occasion, been seen in older adults. In this report, we describe the first ever reported case of a patient diagnosed with a meningothelial hamartoma overlying a prior craniotomy performed two decades prior. We also briefly describe the literature surrounding these rare lesions, as well as their management and differential diagnosis.

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.

Laboratory-based cadaveric training is essential for the development and refinement of neurosurgical technical skills in the operating room and has become an integral training component around the world. Postresidency fellowship—the first pillar of skull base surgery training—includes both hands-on clinical care and surgery supervised by an experienced skull base surgeon. Time is spent in a skull base laboratory practicing approaches and developing anatomic mastery. The second pillar includes formal skull-base courses—institutional dissection laboratories provide continuous anatomic and surgical education while complementary annual or semiannual cadaver courses gather recognized experts to share their knowledge and experience in an essential 2- to 3-day setting. In this paper, we present the history of the longest running annual skull-base cadaver microsurgical course, which was started by Dr. Ossama Al-Mefty: Annual Surgical Approaches to the Skull Base Course. At the Microscopic and Endoscopic Hands-on Cadaver Workshop, held in St. Louis, Missouri, we celebrated its 30th anniversary in April 2019. We also present the impact this course has had on neurosurgery and skull base surgery and on the professional and scientific developments of its participants in particular.

Petrous apex cholesterol granulomas are believed to result from blockage of the normal aeration of the petrous air cells, resulting in a repetitive cycle of mucosal engorgement, hemorrhage, and granuloma formation.1 The lesion usually progressively expands causing compressive symptoms. The thick granulomatous wall envelopes various ages of breakdown products, including a cholesterol-containing fluid, which is typically hyperintense on T1 and T2 weighted magnetic resonance imaging. Drainage procedures, regardless of the route (endoscopic, endonasal, or transtemporal), with or without stenting or marsupialization, will only temporarily drain this cholesterol-containing fluid, with consequently frequent recurrences.2-5 A total exoneration of the granuloma and obliteration of the cavity with vascularized tissue will assure a more durable outcome.1 The extradural zygomatic/middle fossa approach provides a short distance to the petrous apex and is purely extradural. By sectioning the zygoma, temporal lobe retraction is avoided.6 We present a case of a 29-yr-old male who presented in the year 2000 with progression of a left petrous apex cholesterol granuloma despite 2 previous drainage and stenting procedures. The patient consented for surgery and photo publication. Images in video at 2:41 © JNSPG, republished from Eisenberg et al1 with permission.

Objective: To evaluate the results of combined management of large vestibular schwannomas (VS) with initial subtotal resection (STR) followed by adjuvant stereotactic radiosurgery (SRS), with a particular emphasis on the timing and regimen of irradiation.

Giant and large pituitary adenomas (PA) constitute a specific subset of PAs, with gross total resection (GTR) rates frequently not exceeding 50%. Both an anatomical inaccessibility and an inadequate tumor visualization are thought to play a role. This study analyzes risk factors for postoperative residuals after endoscopic transsphenoidal pituitary surgery for large and giant pituitary adenomas. A retrospective analysis of patients with giant and large PA operated between 2015 and 2018 was performed. Forty patients (13 females, 27 males) were included in the analysis (30 large and 10 giant PAs). The mean MRI follow-up time was 5.9 ± 6.54 months. Overall, GTR was achieved in 29 patients (72.5%), subtotal resection in 9 (22.5%), and the inconclusive result was in 2 (5%). Unexpected residuals represented 7 (77.7%) of all 9 residual tumors. The most frequent intraoperative factor associated with unexpected residual tumors was improper identification of residual tumor due to obstruction of view in 2 (28.5%) cases and inability to distinguish normal tissue from tumor in the other two (28.5%). Sub-analysis based on tumor size revealed that with large PAs, GTR was achieved in 25 (83.3%), STR in 4 (13.3%), and inconclusive in 1 (3.3%) patient. In patients with giant PAs, GTR was achieved in 4 (40%), STR in 5 (50%), and inconclusive in 1 (10%). Analysis of preoperative factors showed a significant association of residual tumors with larger suprasellar AP distance (p = 0.041), retrosellar extension (p = 0.007), and higher Zurich Score (p = 0.029). Large and giant PAs are challenging lesions with high subtotal resection rates. Suprasellar AP distance, retrosellar extension, and higher Zurich Score seem to be significant predictors of degree of resection in these tumors. Improving the intraoperative ability to distinguish tumor from a normal tissue might further decrease the number of unexpected residuals.

In HCI research, the user experience (UX) in response to interactive public installations, media facades and displays is frequently evaluated using the AttrakDiff questionnaire. The latent assumption is that its result is invariant to changes over time, environment and context. While previous research analyzed the impact of time as single variable, studies have not yet investigated environment or context. At the same time, researchers and practitioners appear to have the intuitive assumption that interaction with any media facade is best experienced from the middle at a distance which is 'convenient' to watch. We investigated the temporal, spatial and contextual impact on AttrakDiff's user rated pragmatic and hedonic qualities and attractiveness. Analysis revealed that interacting from different positions in close vicinity (

Background: Both subjective cognitive decline (SCD) and a family history of Alzheimer's disease (AD) portend risk of brain abnormalities and progression to dementia. Posterior default mode network (pDMN) connectivity is altered early in the course of AD. It is unclear whether SCD predicts similar outcomes in cognitively normal individuals with a family history of AD. Methods: We studied 124 asymptomatic individuals with a family history of AD (age 64 ± 5 years). Participants were categorized as having SCD if they reported that their memory was becoming worse (SCD+). We used extensive neuropsychological assessment to investigate five different cognitive domain performances at baseline (n = 124) and 1 year later (n = 59). We assessed interconnectivity among three a priori defined ROIs: pDMN, anterior ventral DMN, medial temporal memory system (MTMS), and the connectivity of each with the rest of brain. Results: Sixty-eight (55%) participants reported SCD. Baseline cognitive performance was comparable between groups (all false discovery rate-adjusted p values >.05). At follow-up, immediate and delayed memory improved across groups, but the improvement in immediate memory was reduced in SCD+ compared with SCD− (all false discovery rate–adjusted p values −, SCD+ subjects showed increased pDMN–MTMS connectivity (false discovery rate–adjusted p

The Goethe-Schiller monument at the centre of Weimar's Theatre Square is a tourist attraction that embodies German national cultural heritage. In summer 2016, an interactive participatory live projection mapping lent refugees in Weimar a voice by projecting them onto the statues of German poets Goethe and Schiller and to engage Weimar citizens in a dialogue.

The surgical correction of functional mitral regurgitation (MR) remains challenging and controversial. The study aim was to systematically review the outcomes of surgical mitral valve repair (MVRpr) and mitral valve replacement (MVR) in patients with significant functional MR and left ventricular (LV) dysfunction.A meta-analysis was performed of published data acquired from patients with moderate to severe functional MR and LV ejection fraction (LVEF)40% who underwent surgical MVRpr or MVR. The data were meta-analyzed across studies using Bayesian hierarchical models when feasible.The search yielded 36 observational studies. The pooled proportion of operative mortality following MVRpr was 5% (33 studies; 2,231 patients; 95% credible interval (CrI) 4-7%), while that following MVR was 10% (10 studies; 389 patients; 95% CrI 5-18%). For patients undergoing MVRpr, pooled proportions of postoperative cerebrovascular accidents and renal failure were 2% (11 studies; 750 patients; 95% CrI 1-3%) and 9% (11 studies; 756 patients; 95% CrI 5-16%), respectively. The five-year actuarial survival rates following MVRpr across 12 studies ranged from 47% to 78% (median 66%).In selected patients with significant functional MR and LV dysfunction, surgical MVRpr and MVR can be performed with acceptable intermediate operative mortality risks.

In the context of an escalating opioid epidemic, infectious disease clinicians increasingly treat the infectious complications of injection drug use. In this learning unit, we review the history, pharmacology, and clinical use of buprenorphine as maintenance therapy for opioid use disorder, and we describe the process by which clinicians can obtain a buprenorphine waiver.

Studies of skin graft behaviour in rodent excisional wound models are limited by the dominance of wound contracture and graft sloughing as primary healing responses. To slow skin contraction, polytetrafluoroethylene (Teflon) rings were inserted into dorso-lateral full-thickness wounds in SCID mice. Cultured skin substitutes (OrCel), composed of cultured human keratinocytes and fibroblasts in a bovine collagen sponge, were implanted within the rings. Examination and histology of grafts 14 days later showed graft take in four of six recipients, with 90% epithelialization and wound contraction of 31-47%. Immunohistochemical studies, using human-specific antisera to distinguish graft from host tissues, showed that regenerated tissue was predominantly human. Staining with anticytokeratin, revealed a multilayered, stratified neoepidermis. HBG were identified in keratinocytes in all epidermal layers. Langerhans cells were absent. Antihuman vimentin, used as a fibroblast marker, confirmed that cells of the neodermis were primarily of human origin. Neoepidermal keratinocytes, primarily in the basal and suprabasal layers, were also stained. Results suggest that the poly(tetrafluoroethylene) ring inhibited graft sloughing and provided a more favourable environment for the skin substitute to regenerate a substantially normal human skin.

Long-term fear memory in the medaka fish (Oryzias latipes) regains transient sensitivity to a consolidation blocker immediately after memory reactivation in retrieval ('reconsolidation'). Here we show that reconsolidation occurs in fresh long-term memories but not in remote memories, and that the apparent amnesia induced by blockade of reconsolidation can be reinstated by an unpaired reinforcer, a procedure that has no effect on amnesia induced by blockade of consolidation. Extinction memory also undergoes post-reactivation reconsolidation, the blockade of which exposes the previously acquired fear. Hence in medaka, the process manifested in reconsolidation seems itself to consolidate; moreover, even when the post-reactivation application of the consolidation blocker is still able to disrupt the memory, the conditioned fear does not seem to go away permanently.

Memory consolidation refers to the progressive stabilization of items in long-term memory as well as to the memory phase(s) during which this stabilization takes place. The textbook account is that, for each item in memory, consolidation starts and ends just once. In recent years, however, the notion that memories reconsolidate upon their reactivation and hence regain sensitivity to amnestic agents has been revitalized. This issue is of marked theoretical and clinical interest. Here we review the recent literature on reconsolidation and infer, on the basis of the majority of the data, that blockade of reconsolidation does not induce permanent amnesia. Further, in several systems, reconsolidation occurs only in relatively fresh memories. We propose a framework model, which interprets reconsolidation as a manifestation of lingering consolidation, rather than recapitulation of a process that had already come to a closure. This model reflects on the nature of consolidation in general and makes predictions that could guide further research.

In memory consolidation, the memory trace stabilizes and becomes resistant to certain amnesic agents. The textbook account is that for any memorized item, consolidation starts and ends just once. However, evidence has accumulated that upon activation in retrieval, the trace may reconsolidate. Whereas some authors reported transient renewed susceptibility of retrieved memories to consolidation blockers, others could not detect it. Here, we report that in both conditioned taste aversion in the rat and fear conditioning in the medaka fish, the stability of retrieved memory is inversely correlated with the control of behavior by that memory. This result may explain some conflicting findings on reconsolidation of activated memories.

Major bleeding was recently identified as an independent predictor of adverse clinical outcomes in patients with acute coronary syndromes. We sought to determine the impact of major bleeding on in-hospital mortality in patients with ST-elevation myocardial infarction (STEMI) and the clinical characteristics associated with major bleeding. AMI-QUEBEC was a retrospective cohort study of consecutive STEMI patients admitted to 17 selected acute-care hospitals in the Province of Quebec (Canada) in 2003. Research coordinators identified major bleeding complications according to the Thrombolysis In Myocardial Infarction (TIMI) classification. The cohort included 1,655 patients. Thirty-eight percent (38%) of patients were treated with fibrinolysis, 51% with primary percutaneous coronary intervention (PCI) (65% femoral approach) and 12% received no reperfusion therapy. Twenty-eight percent (28%) of patients were females, mean age was 62.3 years, mean weight was 77.5 kg, 5.1% had prior stroke, and baseline serum creatinine was 104 μmol/L. Concomitant medications included clopidogrel loading in 32%, glycoprotein IIb/IIIa inhibitor 24%, unfractionated heparin 82% and low molecular weight heparin 9%. TIMI major bleeding occurred in 7.3% of patients. Overall in-hospital mortality was 11.6%. Independent predictors of mortality were major bleeding (OR 4.36 [2.48 –7.68]) and age (OR 1.06 [1.03–1.08] per year increase). Independent predictors of TIMI major bleeding were femoral approach (OR 11.2 [3.9 –32.1]) female gender (OR 2.8 [1.5–5.1]) and peak creatinine (OR1.02 [1.01–1.03] per 1μmol/L increase). Age, weight, blood pressure, mode of reperfusion, clopidogrel, aspirin, anticoagulant, clopidogrel load, glycoprotein IIb/IIIa inhibitors, PCI within 24 hours post-fibrinolysis were not independent predictors of major bleeding. TIMI major bleeding conferred a greater than four-fold increase in risk of short-term mortality in an unselected STEMI population. The use of the femoral approach for vascular access was the most powerful predictor of major bleeding in this patient population, highlighting the impact of vascular access site selection.

In the developing hypothalamus, a variety of neurons are generated adjacent to each other in a highly coordinated, but poorly understood process. A critical question that remains unanswered is how coordinated development of multiple neuronal types is achieved in this relatively narrow anatomical region. We focus on dopaminergic (DA) and oxytocinergic (OT) neurons as a paradigm for development of two prominent hypothalamic cell types. We report that the development of DA and OT-like neurons in the zebrafish is orchestrated by two novel pathways that regulate the expression of the homeodomain-containing protein Orthopedia (Otp), a key determinant of hypothalamic neural differentiation. Genetic analysis showed that the G-protein-coupled receptor PAC1 and the zinc finger-containing transcription factor Fezl act upstream to Otp. In vivo and in vitro experiments demonstrated that Fezl and PAC1 regulate Otp at the transcriptional and the post-transcriptional levels, respectively. Our data reveal a new genetic network controlling the specification of hypothalamic neurons in vertebrates,and places Otp as a critical determinant underlying Fezl- and PAC1-mediated differentiation.

PURPOSE Offi ce-based treatment of opioid addiction with a combination of buprenorphine and naloxone was approved in 2002. Effi cacy of this treatment in nonresearch clinical settings has not been studied. We examined the effi cacy and practicality of buprenorphine-naloxone treatment in primary care settings. METHODS We studied a cohort of 99 consecutive patients enrolled in buprenor- phine-naloxone treatment for opioid dependence at 2 urban primary care practices: a hospital-based primary care clinic, and a primary care practice in a free-stand- ing neighborhood health center. The primary outcome measure was sobriety at 6 months as judged by the treating physician based on periodic urine drug tests, as well as frequent physical examinations and questioning of the patients about substance use. RESULTS Fifty-four percent of patients were sober at 6 months. There was no sig- nifi cant correlation between sobriety and site of care, drug of choice, neighbor- hood poverty level, or dose of buprenorphine-naloxone. Sobriety was correlated with private insurance status, older age, length of treatment, and attending self- help meetings. CONCLUSIONS Opioid-addicted patients can be safely and effectively treated in nonresearch primary care settings with limited on-site resources. Our fi ndings suggest that greater numbers of patients should have access to buprenorphine- naloxone treatment in nonspecialized settings. Ann Fam Med 2007;5:146-150. DOI: 10.1370/afm.665.

Memory consolidation refers to the progressive stabilization of items in long-term memory as well as to the memory phase(s) during which this stabilization takes place. The textbook account is that, for each item in memory, consolidation starts and ends just once. In recent years, however, the notion that memories reconsolidate upon their reactivation and hence regain sensitivity to amnestic agents has been revitalized. This issue is of marked theoretical and clinical interest. Here we review the recent literature on reconsolidation and infer, on the basis of the majority of the data, that blockade of reconsolidation does not induce permanent amnesia. Further, in several systems, reconsolidation occurs only in relatively fresh memories. We propose a framework model, which interprets reconsolidation as a manifestation of lingering consolidation, rather than recapitulation of a process that had already come to a closure. This model reflects on the nature of consolidation in general and makes predictions that could guide further research.

Hiccups occurring secondary to high-doses of corticosteroids are a well-recognized problem in the field of neurosurgery. Numerous reports of oral, intravenous and intraarticular corticosteroids inducing hiccups exist in the literature. To date, there is only one case of anabolic steroids inducing hiccups. We now present a case of a patient who underwent a suboccipital craniotomy for resection of a cerebellar pontine angle meningioma. Postoperatively the patient was on high doses of Decadron and Oxandrin, an anabolic-anticatabolic agent used to combat the deleterious effects of corticosteroids. The patient suffered intractable hiccups postoperative day one, resistant to Thorazine. Oxandrin was discontinued to assess the possibility of a anabolic steroid-induced singultus. The hiccups resolved within 24 hours. This report validates the previous report on anabolic steroids inducing hiccups and exemplifies the ability for steroids as a class, due to there backbone structural homology, to induce function even as competitive inhibitors.

Summary Drug therapy of epidermolysis bullosa dystrophica (E.B.D.) for the past forty years is reviewed. A reproducible method for the direct extraction of collagenase and collagen peptidase from skin homogenates is described. Markedly elevated collagenase and collagen peptidase activity is demonstrated in skin of dystrophic E.B. patients. Diphenylhydantoin in pharmacological doses is shown to cause significant inhibition of the collagenolytic system both in vitro and in vivo. Diphenylhydantoin was used parenterally in two children with proven E.B.D. and was found to have a beneficial effect on skin fragility.

The reaction of chymase, a chymotryptic proteinase from human skin, and bovine pancreatic chymotrypsin with a number of time-dependent inhibitors has been studied. An integrated equation, relating product formation with time, has been derived for the reaction of enzymes with time-dependent inhibitors in the presence of substrate. This is based on a two-step model in which a rapidly reversible, non-covalent complex (EI) is formed prior to a tighter, less readily reversible complex (EI)*). The equation depends on the simplifying assumption [I] much greater than [E], but is applicable to reversible and irreversible slow-binding and tight-binding inhibitors whether or not they show saturation kinetics. The method has been applied to the reaction of chymase and chymotrypsin with the tetrapeptide aldehyde, chymostatin, basic pancreatic trypsin inhibitor and Ala-Ala-Phe-chloromethylketone (AAPCK). The irreversible inhibitor, AAPCK, showed the expected saturation kinetics for both enzymes and the apparent first-order rate constants (k2) and dissociation constants (Ki) for the non-covalent complexes were determined. Chymostatin was a much more potent inhibitor which failed to show a saturation effect. The second-order rate constant of inactivation (k2/Ki), the first-order reactivation rate constant (k-2), and the dissociation constant of the covalent complex (Ki*) were determined. Basic pancreatic trypsin inhibitor, a potent inhibitor of chymotrypsin, had similar kinetics to chymostatin but failed to inhibit chymase. The applicability of the two-step model and the integrated equation to slow- and tight-binding inhibitors is discussed in relation to a number of examples from the literature.

A rapid full-spectrum recording spectrophotometer was used to analyze the nucleotide composition of a yeast cell extract by high-performance liquid chromatography. Throughout the run, which lasted 47 min, a UV spectrum with 1-nm resolution was transmitted to a minicomputer every 2.5 sec. The recorded data were later evaluated by several computer programs. One program (HPMAX) plots the position of the absorption maximum for each time point. Another program (HPSPEC) displays three spectra at any chosen time points and enables their normalization (allowing comparison with standards and analysis of the purity of peaks) and the display of the logarithm of the ratio of the values (used to determine the best wavelength for integration of overlapping peaks). A third program (HPEAK) displays the absorption at any desired wavelength against time, allows cursor positioning to mark the position of a slanting baseline as well as the beginning and end of a peak, and the integration of the peak. The components in overlapping peaks can be separately integrated. The method is generally applicable to all compounds that are detectable by spectrophotometric means.

A 1-year course of methadone maintenance and psychotherapy in an outpatient VA Drug Dependence Treatment Center was shown to enable a significant proportion of patients (55%) to reduce their opiate drug use by at least half. A large majority (85%) were able to reduce their nonopiate drug use by half during the same period. Methadone was felt by the authors to be a moderately effective therapeutic modality which, when combined with psychotherapy and other measures, can effect a significant reduction of illicit drug use in a substantial number of patients.

Hydrocolloid dressing (HCD), a new oxygen impermeable occlusive dressing, was studied in a controlled clinical trial of three pediatric patients with dystrophic epidermolysis bullosa (RDEB). Advantages of this material over such dressings as paraffin gauze (PG) or the perforated plastic film (TELFA), include considerably faster re-epithelialization, pain free movement of the injured part and fewer dressing changes. The most significant advantage of HCD for RDEB patients has been in the reduction of scar tissue formation, because in this disease, wounds heal with scarring that causes mutilating deformities.

The chymotrypic proteinase "chymase" has been purified to apparent homogeneity from human skin. Our procedure differs from previously published partial purifications in that it does not involve affinity chromatography, most of the steps are carried out in 2 M KCl which stabilizes the enzyme, detergent is used to protect the enzyme in low-ionic-strength media, and troublesome concentration steps are avoided by using very small columns of high-capacity exchangers. The high-salt skin extract is applied successively to columns of hydroxyapatite, copper chelate Sepharose, and Sephadex G-100 in 2 M KCl. After dialysis against a zwitterionic detergent, the enzyme is adsorbed onto a 0.4-ml column of CM-Sepharose. An alkaline wash removes the remaining contaminants from the highly cationic enzyme, which is then eluted with 1 M KCl in a final volume of 2 ml. Sodium dodecyl sulfate electrophoresis reveals a single diffuse band of Mr 30,000. Recoveries range from 20 to 40% with yields of 0.2 to 0.4 mg of enzyme from 200 g of skin. Specific activities vary from 600 to 1400 units/mg for the hydrolysis of acetyltyrosine ethyl ester.

We conducted a randomized, double-blind, placebo-controlled trial of two forms of topical interferon therapy for condyloma acuminata in women. Gel containing 10(6) IU of leukocyte interferon/g, with or without nonoxynol-9, was compared with treatment with gel base alone. Eighty-nine patients applied the gel three times a day for four weeks and were studied for at least 16 w. Side effects were generally mild and limited to the site of application for all three drugs. Although a transient, statistically significant therapeutic effect was noted early in the course of treatment with both interferon gels as compared with placebo, this effect was lost by the end of the follow-up period, possibly because of a generally high response rate in patients receiving placebo. Hence, there was no overall difference in the number of patients with a partial or complete response to any of the agents by the end of therapy or by the end of the study.

Summary Latent and active collagenase were demonstrated following direct extraction from normal skin homogenates with 0.1M calcium chloride at 60°C. 83 % of the collagenase activity was in latent form and could be maximally activated with trypsin. Partial activation of the latent enzyme could also be demonstrated by incubation of the skin extract without added trysin. This endogenous activation was inhibited by the addition of soya bean trypsin inhibitor, trasylol, di-isopropylphosphofluoridate and phenylmethanesulphonylfluoride, none of which inhibited collagenase directly. This suggests that the skin extracts contain a collagenase activating enzyme with the inhibition profile of a serine proteinase. A chymotryptic proteinase with a similar inhibition profile was extracted from normal human skin and partially purified. This enzyme activated fibroblast procollagenase derived from tissue culture of normal skin. The procollagenase was also partially activated by plasmin and chymotrypsin. This is the first demonstration of a collagenase activating enzyme in human skin and raises the possibility that collagenase activation by this mechanism may be responsible for collagen degradation in some disease processes.

Nearly a half century has passed since the modern antimicrobial era began with the introduction of sulphanilamide in 1936. Since that time a vast array of antibiotic agents have been discovered which have improved our therapeutic armamenterium against microbes. Yet, it has only been in the past decade that real progress has been made in the development of specific antiviral therapy.

Study objective To determine the efficacy of adenine arabinoside monophosphate (Ara-AMP vidarabine phosphate) with or without human leukocyte interferon in chronic hepatitis B. Study design Randomized, double-blinded, placebo-controlled trial with 6-month treatment and an 18-month follow-up. Setting Referral-based liver-disease clinics at three university medical centers. Patients Twenty-five patients with chronic active hepatitis or cirrhosis and 39 with chronic persistent hepatitis. Interventions Thirteen patients received intramuscular Ara-AMP, 2.5 mg/kg body weight, twice daily, alternated monthly for 6 months with subcutaneous human leukocyte interferon, 5 million units, twice daily. Painful paresthesia of the legs necessitated dosage reduction and early discontinuation of enrollment. Twenty-four patients received intramuscular Ara-AMP, 2.5 mg/kg, twice daily, alternated monthly for 6 months with a matching placebo given subcutaneously twice daily. Twenty-seven patients received placebo by intramuscular and subcutaneous injections twice daily for 6 months. Measurements and main results Of the 64 patients, 95% had symptomatic and virologic data available and 64% had biopsies at 12 months; at 24 months, 77% had data available and 56% had repeat biopsies. The highest dropout rate was seen in the group receiving Ara-AMP. The group receiving the placebo was less symptomatic (Karnofsky score of 96% compared with 91% in the group receiving Ara-AMP/placebo and 92% in the group receiving Ara-AMP/human leukocyte interferon, p = 0.02) at 12 but not at 24 months. Loss of DNA polymerase, the hepatitis B e antigen, and the serum hepatitis B virus DNA was similar in all three groups. Histologically, erosion of the limiting plate and lobular activity favored Ara-AMP at 12 but not at 24 months and these differences did not result in differences in the histologic diagnosis. Conclusion These results do not support the use of Ara-AMP and human leukocyte interferon in chronic persistent or chronic active hepatitis B.