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Cancer therapies usually depend on cross-sectional imaging for the assessment of treatment response. This study was designed to evaluate the ability of MRI to predict zones of necrosis following the use of high-intensity focused ultrasound (HIFU) to treat liver metastases. Patients with liver metastases, who had been scheduled for elective surgical resection of their tumours, were recruited to this non-randomized Phase II study. In each case, a proportion of an index liver tumour target was ablated. The response to HIFU was assessed after 12 days using contrast-enhanced MRI and compared directly with histological analysis at the time of surgery. Eight patients were treated, of whom six were subsequently assessed with both MRI and histology. There were no major complications. MRI predicted complete ablation in three cases. In each case, histological analysis confirmed complete ablation. In one case, the region of ablation observed on MRI appeared smaller than predicted at the time of HIFU, but histology revealed complete ablation of the target region. The predominant characteristic of HIFU-ablated tissue was coagulative necrosis but heat fixation was evident in some areas. Heat-fixed cells appeared normal under haematoxylin and eosin staining, indicating that this is unreliable as an indicator of HIFU-induced cell death. This study demonstrates that HIFU is capable of achieving selective ablation of pre-defined regions of liver tumour targets, and that MRI evidence of complete ablation of the target region can be taken to infer histological success.

Objective: To assess the extent of scrotal pain in men before and after vasectomy, to produce accurate data for the benefit of men considering this procedure, and hence improved informed consent about the outcomes, as chronic scrotal pain after vasectomy is a poorly quantified clinical problem., Patients and Methods: Between November 2004 and January 2006 nine surgeons carried out vasectomies in 625 men (mean age 39.9 years, sd 5.6) under local anaesthesia. A questionnaire was devised to establish the presence of any scrotal or testicular pain, and to characterize this discomfort; 6 months after the procedure a modified version of the same questionnaire was administered., Results: In all, 593 (94.7%) men returned the preoperative questionnaires and were entered into the study; 488 (82.2%) of these completed the follow-up questionnaire, giving a mean (sd) follow-up of 6.8 (1.6) months. In all, 65 men reported new-onset scrotal pain at 7 months (14.7%). The mean visual analogue score for this pain was 3.4/10. Four men (0.9%) in the responding group described pain after vasectomy as 'quite severe and noticeably affecting their quality of life'., Conclusion: At 7 months after vasectomy about 15% of previously asymptomatic men have some degree of scrotal discomfort. These early data indicate that chronic scrotal pain after vasectomy is a genuine entity, but a longer-term follow-up in this group will be important to allow further evaluation of how this pain develops with time.

In recent years high intensity focused ultrasound (HIFU) has received increasing interest as a non-invasive modality for the treatment of tumours of solid organs. Surgeons continue their quest to find the optimal technique whereby a diseased organ can be treated with a minimum of damage to the patient, while providing a comprehensive treatment to produce either cure or resolution of symptoms. Two of the areas in which HIFU is beginning to establish itself as a real therapeutic alternative, are in the treatment of abdominal and gynaecological disease. In this paper, we will review the literature available regarding the use of HIFU in the treatment of various organs: liver, kidney, pancreas, bladder, uterus and vulva.

Objective: To propose a standard for the conduct of visually directed transrectal high-intensity focused ultrasound (HIFU) and to offer a formal description of the changes observed on B-mode ultrasonography (US) during this procedure. We describe our early experience of using two different treatment methods; algorithm-based HIFU and visually directed HIFU for the treatment of organ-confined prostate cancer., Patients and Methods: Between November 2004 and October 2005, 34 men were treated using the Sonablate-500 (Focus Surgery, Indianapolis, IN, USA) as primary therapy for T1 or T2 prostate cancer. None had had previous hormone therapy and all had > or = 3-month PSA nadirs recorded at the follow-up. Nine men were treated using an algorithm-based protocol (group 1) and 25 using visually directed therapy (group 2). The conduct of visually directed treatment was described and changes seen using B-mode US were categorized using three 'Uchida' grades. RESULTS The mean PSA nadir achieved in group 2 was 0.15 ng/mL, vs 1.51 ng/mL in group 1 (P < 0.005). In group 2, 21 of 25 men achieved PSA nadirs of < or = 0.2 ng/mL 3 months after treatment. Seven men achieved undetectable PSA values. The occurrence rate of treatment-related toxicity was similar in both groups., Conclusion: Visually directed, transrectal HIFU enables clinically important and statistically significantly lower PSA nadirs to be achieved than algorithm-based HIFU. This is the first reported experience of visually directed HIFU for the treatment of organ-confined prostate cancer. We think that this is the first attempt to standardize the conduct of therapy; such standardization facilitates teaching it, and makes it possible to derive quality standards. The standardization of the conduct of therapy is a key step in the process of health technology assessment.

Evidence indicates that the neurotrophin nerve growth factor (NGF) is a mediator of cutaneous inflammatory responses. Cellular responses to NGF are facilitated by two receptors called trk A and p75 neurotrophin receptor (p75NTR). In the current study we have investigated the expression of these receptors in lesional and non-lesional skin from patients with plaque psoriasis and in normal skin exposed to three times the minimal erythema dose of ultraviolet (UV) B radiation. Trk A immunostaining was confined to the basal keratinocytes in normal skin. There was a significant reduction in trk A immunostaining in both non-lesional and lesional psoriatic skin compared with control skin. In UVB-irradiated normal skin, there was a significant reduction in trk A immunostaining at 4 h after irradiation, which was still evident at 48 h. In normal skin, p75NTR immunopositive fine nerve fibres were present throughout the dermis and occasionally seen in the epidermis. Thick nerve fibres were evident in the deep dermis and in the middle region of the dermis. p75NTR immunopositive basal keratinocytes were occasionally seen. There was a statistically significant loss of p75NTR immunopositive fine nerve fibres in the epidermis of lesional psoriatic skin and a statistically significant loss of p75NTR immunopositive fine nerve fibres in the dermis in both non-lesional and lesional psoriatic skin. p75NTR immunopositive thick nerve fibres were reduced in lesional psoriatic skin compared with normal skin. UVB irradiation of normal skin led to a statistically significant decrease in the p75NTR immunopositive fine nerve fibres in the epidermis at 48 h after irradiation. There was no significant reduction in the dermal p75NTR immunoreactivity. These results demonstrated that expression of both NGF receptors is decreased following an acute inflammatory stimulus and also in association with a chronic inflammatory dermatosis.

It has been argued that the digital cutaneous microvasculature is the site of the anomaly which causes Raynaud's phenomenon (RP). Both endothelin-1 (ET-1), a potent vasoconstrictor peptide present in the digital cutaneous microvasculature, and calcitonin gene-related peptide (CGRP), a powerful vasodilator present in digital cutaneous perivascular nerves, have been implicated in the pathogenesis of RP. Circulating ET-1 levels are raised, and there is a diminution of CGRP-containing perivascular nerves in finger skin in RP. We undertook a pharmacological study to investigate the sensitivity of the digital cutaneous microvasculature to intradermal ET-1 and CGRP. Differences were found in RP compared with normal digital skin, supporting the idea that the digital cutaneous microvasculature is actively involved in the pathogenesis of RP. In RP, the erythematous response to ET-1 was diminished at both 20 and 5 degrees C (a low temperature at which RP classically occurs) providing pharmacological support for the morphological evidence that in RP there is a deficiency of CGRP-containing nerves in the distal digital skin.

The aim of this study was to investigate in human skin in vivo the role of nitric oxide in maintaining resting vascular tone, in the vasodilatation caused by local warming and by ultraviolet B light exposure, and in the response to exogenous calcitonin gene-related peptide (CGRP). Cutaneous blood flow was assessed by planimetry of the visible erythema or pallor and by laser Doppler flowmetry. Intradermal injection of the inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol), into forearm skin produced a visible pallor and a reduction of blood flow at a controlled ambient temperature of 21 degrees C. The control, NG-nitro-D-arginine methyl ester (D-NAME; 25 nmol) or NG-monomethyl-L-arginine (L-NMMA; 25 nmol) did not cause pallor or reduce blood flow. L-NAME and L-NMMA caused dose- and time-dependent increases in pallor, and reductions in cutaneous blood flow in skin that had been locally warmed by immersion in water at 45 degrees C and in skin that had been exposed to ultraviolet B light. D-NAME and D-NMMA at comparable concentrations did not have the effects on skin blood flow observed with the L forms. L-NAME and L-NMMA both inhibited the increased blood flow in human skin caused by the intradermal injection of CGRP (12.5 or 25 pmol). The reduction of CGRP-induced increase of blood flow by L-NAME was reversed by L-arginine. Neither D-NAME nor D-NMMA inhibited the increase in blood flow caused by CGRP. Neither L-NAME nor L-NMMA inhibited the increase in blood flow in human skin caused by the intradermal injection of prostaglandin E2 (63 pmol). The data show that nitric oxide is involved in the maintenance of resting blood flow in human skin and also in the cutaneous vasodilator responses to local warming, ultraviolet B irradiation, or injection of CGRP.

Peripheral inflammation induced in adult rats by an intraplantar injection of complete Freund's adjuvant results in a rapid (6 h) increase in the expression of the messenger RNAs for the neuronal growth-associated protein 43 and for preprotachykinin A, the precursor for substance P, in dorsal root ganglion sensory neurons innervating the inflamed area. This increase peaks at 48 h and then declines by five days. The changes are present in the dorsal root ganglion cells innervating the inflamed skin (lumbar 4 or 5) but no elevation was found in the third lumbar dorsal root ganglion which innervates neighbouring non-inflamed skin. The increased growth-associated protein 43 messenger RNA in the dorsal root ganglion is followed by a marked increase in growth-associated protein 43-like immunoreactive fibres in the epidermis of the inflamed skin. Systemic administration of neutralizing anti-nerve growth factor antibodies immediately prior to the inflammation prevents the increase in growth-associated protein 43 and preprotachykinin A messenger RNAs in the sensory neurons. A subcutaneous injection of nerve growth factor (200 ng) into the hindpaw elevates preprotachykinin A but not growth-associated protein 43 messenger RNA in the fourth lumbar dorsal root ganglion 48 h post-injection and this could be prevented by co-administration of the anti-nerve growth factor serum. The production of nerve growth factor in inflamed target tissues leads to alterations in the phenotype of responsive adult primary sensory neurons which include a change in the levels of a growth-related protein and a peptide neuromodulator.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a 55-year-old woman with acrodermatitis chronica atrophicans (ACA) and a peripheral sensory neuropathy. ACA is an uncommon late cutaneous manifestation of Lyme disease, which follows disseminated Borrelia burgdorferi infection. This is the second published case from the U.K. since serological diagnosis has been available. In this patient the diagnosis was confirmed by serology using a sensitive enzyme-linked immunosorbent assay and immunoblotting techniques. B. burgdorferi DNA was demonstrated in the affected skin using the polymerase chain reaction, although staining and cultures for the organism were negative. Recommended treatment of ACA is with oral doxycycline 100 mg twice daily for 28 days, but our patient did not respond well to this regimen. She was therefore treated with ceftriaxone intravenously for 21 days, which resulted in a rapid symptomatic and clinical response.

Vibration white finger or hand-arm vibration syndrome is the episodic blanching of the fingers in response to cold occurring in those who work with hand held vibrating tools. Clinically the condition differs from primary Raynaud's phenomenon as persistent paraesthesiae and pain are common in the hands and arms and these occur independently from the 'white attacks'. Symptoms can become severe enough to warrant a change of occupation. Industrial compensation may be awarded for vibration white finger but, at present, no simple or reliable objective diagnostic test is available. Calcitonin gene-related peptide (CGRP) is a neuropeptide with powerful vasodilator properties. A deficiency of immunoreactive CGRP nerve fibres has been previously demonstrated in the digital cutaneous microvasculature of patients with primary and secondary Raynaud's phenomenon with the distribution and quantity of other types of nerve fibres not being significantly altered. To determine if the innervation of the cutaneous microvasculature in vibration white finger was also abnormal skin biopsy samples from the fingers of 15 patients with vibration white finger, six healthy age matched controls who worked with vibrating machinery and 26 healthy age matched controls who were heavy manual workers without exposure to vibrating machinery were examined by immunohistochemistry. To try to correlate any histological abnormalities with clinical neurological deficit sensory nerve conduction studies have so far been performed in six patients with vibration white finger.(ABSTRACT TRUNCATED AT 250 WORDS)

Malignant atrophic papulosis (Degos disease) is a rare disorder characterized by a vasculopathy of unknown origin. The cutaneous manifestations comprise erythematous papules, which heal to leave scars with a pathognomonic central porcelain-white atrophic area and a peripheral telangiectatic rim. There is usually involvement of the gastrointestinal tract but other organ systems can also be affected, the central nervous system being involved in 20% of cases. It is frequently fatal within 2 or 3 years from onset of systemic involvement, the cause of death usually being intestinal perforation. Our patient is of interest as she has survived an unusually long time despite florid cutaneous and neurological manifestations.