Carbon dioxide and pulsed dye laser treatment of angiofibromas in 29 patients with tuberous sclerosis.

BACKGROUND: Data on the benefits, adverse effects and appropriate types of laser treatment for angiofibromas (AF) in patients with tuberous sclerosis (TS) are limited. OBJECTIVES: To evaluate the efficacy and side-effect profile of carbon dioxide (CO2) 10,600 nm wavelength and flashlamp-pumped pulsed dye (FLPDL) 585 nm wavelength lasers in a retrospective study of 29 patients with TS aged 9-48 years. METHODS: Long-term results, based on clinical improvement of the vascular, fibrous or protuberant types of AF and the presence or absence of side-effects on follow-up visits, were classified as excellent, moderate or poor. RESULTS: Results were excellent in most patients with vascular-type AF treated with one or two sessions of FLPDL, but some required up to six treatment sessions. CO2 lasers produced excellent results with considerable long-term improvement in 10 of 13 (77%) patients with fibrous or protuberant AF, specifically in all (three of three) protuberant and 70% (seven of 10) of fibrous AF. Persistent hypertrophic scarring was seen in three of 13 (23%) patients with either fibrous or protuberant AF treated with the continuous wavelength CO2 laser. Treatment with both lasers used in four patients with combined vascular and non-vascular AF components was excellent in three of four (75%) patients. Significant relapse was seen in one patient treated with the CO2 laser. CONCLUSIONS: CO2 or FLPDL laser treatment should be considered as an effective treatment for patients with disfiguring TS. A combination of lasers may be required to achieve optimal results.

Structure-based design of caspase-1 inhibitor containing a diphenyl ether sulfonamide.

A series of compounds was designed and prepared as inhibitors of interleukin-1beta converting enzyme (ICE), also known as caspase-1. These inhibitors, which employ a diphenyl ether sulfonamide, were designed to improve potency by forming favorable interactions between the diphenyl ether rings and the prime side hydrophobic region. An X-ray crystal structure of a representative member of the diphenyl ether sulfonamide series bound to the active site of caspase-1 was obtained.

Specialist alcohol liaison services in general hospitals improve engagement in alcohol rehabilitation and treatment outcome.

OBJECTIVE: To examine the impact of providing a specialist addictions trained psychiatric nurse on outcome of alcohol treatment in patients presenting to general medical and surgical wards of a district general hospital. Before introducing the specialist alcohol liaison service, a range of staff including a consultant liaison psychiatrist, junior psychiatrists and community psychiatric nurses trained in liaison psychiatry assessed this patient group. METHOD: A retrospective review of all alcohol liaison referrals with ICD-10 defined alcohol misuse was performed for one year. Comparison data for the first 100 referrals to the specialist alcohol liaison service were obtained prospectively. Indicators included diagnosis at referral, and engagement in and completion of alcohol rehabilitation. RESULTS: The rates of completion of a four to six week period of alcohol rehabilitation were significantly better after introduction of the Specialist Alcohol Liaison Service. Of those who commenced alcohol rehabilitation, 88% completed, compared to 40% in the traditional assessment service (p < 0.0001). CONCLUSION: Specialist addictions trained staff in the assessment and management of alcohol dependent patients in medical and surgical wards produce a better immediate outcome than their non-specialist colleagues. This may have implications for service design.

Q-switched Alexandrite laser in the treatment of pigmented macules in Laugier-Hunziker syndrome.

We report clearance of pigmented macules on the lips of two subjects with Laugier-Hunziker syndrome using the Q-switched Alexandrite laser. Recurrence of two macules was noticed in one case 6 months after treatment and the lesions were successfully retreated. This report evaluates the efficacy and side-effect profile of the Q-switched Alexandrite laser in the treatment of lentigines in this syndrome.

The reliability of case register diagnoses: a birth cohort analysis.

BACKGROUND: Few studies assess the reliability of case register diagnoses, despite their widespread use in psychiatric research. This study investigates case register diagnostic reliability in comparison to casenote derived diagnoses in a birth cohort. METHODS: Diagnostic information from the case register and casenotes of 449 individuals was extracted. The incident and lifetime register diagnoses were compared with those derived from the casenotes. RESULTS: Inter-rater reliability was good (kappa = 0.71). Agreement between casenote and incident register diagnosis was moderate (kappa = 0.52), as was agreement between casenote and register lifetime diagnosis (kappa = 0.58). Case register diagnoses were insufficiently accurate to stand alone. Case register diagnoses for organic disorder, schizophrenia, alcoholism, learning disability, personality disorder and transient or no psychiatric disorder were reliable enough for the case register to act as a useful screening instrument. The case register was not acceptable, even as a screening instrument, for the diagnoses of neurotic or affective disorders. CONCLUSIONS: Studies relying only on case register diagnoses may be flawed if diagnoses are not independently verified. National statistics derived from case register data, especially for neurosis and affective disorder, may be unreliable.

Mohs micrographic surgery for the treatment of in situ nail apparatus melanoma: a case report.

Nail apparatus melanoma (or subungual melanoma) is rare and accounts for only 1.4% of all cutaneous melanomas in the United Kingdom. We report the use of fixed-tissue Mohs micrographic surgery to treat a biopsy-proven Clark level I in situ nail apparatus melanoma, presenting with diffuse longitudinal melanonychia.

Excision of selected skin tumours using Mohs' micrographic surgery with horizontal paraffin-embedded sections.

Histological interpretation of frozen sections made during Mohs' micrographic surgery may be difficult, depending on the morphological and staining characteristics of the tumour and on the nature of the associated inflammatory infiltrate. We have employed an adaptation of micrographic surgery in which horizontal, formalin-fixed, paraffin-embedded sections were used to improve histological assessment in the excision of 18 non-melanoma skin tumours in which frozen sections had been or were likely to be unsatisfactory. We describe our experience of this method in the management of squamous cell carcinomas (11), extramammary Paget's disease (two), microcystic adnexal cell carcinomas (two), dermatofibrosarcoma protuberans (two), and primary cutaneous neuroendocrine carcinoma (Merkel cell carcinoma) (one). The use of horizontal paraffin-embedded sections lengthens the duration of the procedure but facilitates accurate assessment of histological sections in selected tumours.

Treatment of proliferative haemangiomas with the 585 nm pulsed dye laser.

Haemangiomas usually develop within the first few weeks of life, most regressing spontaneously before the age of 7 years. Some may ulcerate or compromise a vital function, in which case systemic corticosteroids, surgery or radiotherapy may be helpful. All of these treatment modalities are associated with significant morbidity. Treatment with the 585 nm flashlamp pulsed dye laser is safe and effective in the management of superficial vascular malformations. We report seven patients, under 12 months of age, who presented with proliferative haemangiomas, causing functional impairment. Ulcerated lesions were present in four patients. The patients were treated with the 585 nm pulsed dye laser (fluences 7.0-9.25 J/cm2), at intervals of 4-8 weeks. All of the lesions showed a significant reduction in size, together with improvement in the colour and integrity of the overlying skin. Treatment with the 585 nm pulsed dye laser should be considered in the management of infants with early proliferative haemangiomas, in whom intervention is indicated.

Basal cell carcinoma: rapid techniques using cytokeratin markers to assist treatment by micrographic (Mohs') surgery.

In micrographic (Mohs') surgery, routine haematoxylin and eosin stains may present difficulties in interpretation of infiltrative (morphoeic) basal cell carcinoma. To supplement these routine stains rapid immunoperoxidase and immunofluorescence techniques are described using cytokeratin markers Dako LP34, MNF 116 or Novocastra NCL-Pan CK on frozen sections to help in the histological evaluation of these tumours.

Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer.

Interleukin-1 beta-converting enzyme (ICE) proteolytically cleaves pro-IL-1 beta to its mature, active form. The crystal structure at 2.5 A resolution of a recombinant human ICE-tetrapeptide chloromethylketone complex reveals that the holoenzyme is a homodimer of catalytic domains, each of which contains a p20 and a p10 subunit. The spatial separation of the C-terminus of p20 and the N-terminus of p10 in each domain suggests two alternative pathways of assembly and activation in vivo. ICE is homologous to the C. elegans cell death gene product, CED-3, and these may represent a novel class of cytoplasmic cysteine proteases that are important in programmed cell death (apoptosis). Conservation among members of the ICE/CED-3 family of the amino acids that form the active site region of ICE supports the hypothesis that they share functional similarities.

Penile melanosis successfully treated with the Q-switched ruby laser.

Penile melanosis is an uncommon benign primary pigmentary disorder affecting the penile shaft and/or glans. We report the successful treatment of penile melanosis using the Q-switched ruby laser.

Micrographically controlled excision (Mohs' surgery) of basal cell carcinoma around the eye. Combined dermatological surgical clearance and oculoplastic surgical repair.

Periorbital infiltrative basal cell carcinomas are notoriously difficult to treat, particularly those around the medial canthus. Micrographically controlled excision with horizontal frozen sections (Mohs' surgery) allows for clearance of the tumour with minimal loss of normal tissue. Once the tumour has been completely removed, the defect can be repaired by the oculoplastic surgeon for the best functional and cosmetic result. This is the ideal treatment for tumours with a contiguous growth pattern that are liable to be seriously over or under treated by other modalities. The technique requires special training for both the operator and the Medical Laboratory Scientific Officer (MLSO). It is costly in time and manpower but in selected cases, where recurrent tumour is most dangerous and where tissue conservation is paramount, it may be invaluable. Close collaboration between dermatological and oculoplastic surgeons in such cases probably offers the patient the best treatment and outcome.

The use of Q-switched Nd:Yag laser for removal of permanent eyeliner tattoo.

We present the results of a pilot study of the use of Nd:Yag laser in the removal of permanent eyeliner tattoos. Fourteen eyelids were treated, and in all cases a reduction in pigmentation was achieved although responses were variable. The advantages of such therapy over existing techniques are described. The technique offers a useful reduction of permanent eyeliner pigmentation and is particularly suited to treatment of localized areas of imperfect application or pigment migration.

Methodology employed for the structure determination of tumour necrosis factor, a case of high non-crystallographic symmetry.

The structure of the protein tumour necrosis factor (TNF) was determined from crystals of space group P3(1)21 which contain six copies of the TNF monomer per crystallographic asymmetric unit [Jones, Stuart & Walker (1989). Nature (London), 338, 225-228]. The nature of these crystals (relatively high crystallographic symmetry coupled with multiple copies of the protein in the asymmetric unit) led to some peculiarly challenging problems at several points in the structure determination. In particular, (1) self-rotation function calculations failed to yield clearly interpretable solutions, (2) the analysis of difference Patterson maps for heavy-atom derivatives required the development of a Patterson search program suite GROPAT. The redundancy in the asymmetric unit allowed refinement of poor-quality isomorphous phases at 4 A resolution and phase extension from 4 to 2.9 A resolution using real-space symmetry averaging and solvent flattening in the absence of any isomorphous phase information. Despite further difficulties caused by structural differences between the six independent copies of the monomer the resultant electron density map was of high quality and proved to be easily interpretable.

Amelanotic lentigo malignant melanoma: a case report and review of the literature.

A patient with an amelanotic lentigo malignant melanoma is presented which manifested itself initially as an erythematous flare with the subsequent development of nodules. The diagnosis was only made histologically. A computer search of the literature revealed 6 previous cases, and a review of these rare tumours is presented.