Search

Summary Background The limitations of current treatments for postherpetic neuralgia (PHN) have led to the investigation of localised, non-systemic alternatives. NGX-4010, a high-concentration (8%) capsaicin dermal patch, was developed to treat patients with neuropathic pain. We report the results of a randomised, double blind, 12-week study of the efficacy and safety of one application of NGX-4010 in patients with PHN. Methods In this multicentre, double-blind, parallel-group trial, 402 patients were randomly assigned to one 60-min application of NGX-4010 (640 μg/cm 2 [8% capsaicin]) or a low-concentration capsaicin control patch (3·2 μg/cm 2 [0·04% capsaicin]). Patients were aged 18–90 years, had had postherpetic neuralgia for at least 6 months, and had an average baseline numeric pain rating scale (NPRS) score of 3 to 9. The primary efficacy endpoint was percentage change in NPRS score from baseline to weeks two to eight. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00115310. Findings Patients who were randomly assigned to NGX-4010 (n=206) had a significantly greater reduction in pain during weeks two to eight than did patients who had the control patch (n=196). The mean changes in NPRS score were −29·6% vs −19·9% (difference −9·7%, 95% CI −15·47 to −3·95; p=0·001). 87 (42%) patients who received NGX-4010 and 63 (32%) controls had a 30% or greater reduction in mean NPRS score (odds ratio [OR] 1·56, 95% CI 1·03 to 2·37; p=0·03). The patients who had NGX-4010 had significant improvements in pain during weeks two to 12 (mean change in NPRS score −29·9% vs −20·4%, difference −9·5, −15·39 to −3·61; p=0·002). Transient blood pressure changes associated with changes in pain level were recorded on the day of treatment, and short-lasting erythema and pain at the site of application were common, self-limited, and generally mild to moderate in the NGX-4010 group and less frequent and severe in the controls. Interpretation One 60-min application of NGX-4010 provided rapid and sustained pain relief in patients with postherpetic neuralgia. No adverse events were associated with treatment except for local reactions at the site of application and those related to treatment-associated pain. Funding NeurogesX.

Context Postherpetic neuralgia (PHN) and painful human immunodeficiency virus-associated distal sensory polyneuropathy (HIV-DSP) are peripheral neuropathic pain syndromes that are difficult to treat. Current treatment options are often limited by poor tolerability. Objectives The objective of the current open-label study was to assess the safety of repeated applications of NGX-4010, a high-concentration capsaicin patch (capsaicin 8%), over one year, in patients with moderate to severe PHN or HIV-DSP. Methods Patients had successfully completed a previous NGX-4010 study and had a pain level appropriate for further treatment. Eligible patients had not been treated with NGX-4010 within 12 weeks of study initiation. Patients received pretreatment with a topical local anesthetic (lidocaine 4%) for 60 minutes followed by either a 60-minute (PHN and HIV-DSP patients) or a 90-minute (HIV-DSP patients) treatment with NGX-4010. Patients could receive up to three additional treatments at intervals of ≥12 weeks. Regardless of the number of treatments received, all patients were followed up for 48 weeks except for those withdrawing early. Results A total of 106 patients were enrolled and received a total of 293 NGX-4010 treatments. The most frequently reported treatment-emergent adverse events were transient, mild-to-moderate application site erythema, pain, edema, and papules. Small, transient pain-related increases in blood pressure during and immediately after NGX-4010 application were observed. There was no evidence of an increased incidence of adverse events, dermal irritation, intolerability, or impaired neurological function with repeated treatments. Conclusion It is concluded that repeated treatments with NGX-4010 administered over a one-year period are generally safe and well tolerated.

DNA amplification is an important mechanism of tumor progression that allows cancer cells to up-regulate the expression of critical genes such as oncogenes and genes conferring drug resistance. Recent studies using comparative genomic hybridization (CGH) revealed increased DNA copies of 20q sequences in 7 melanoma cell lines and B archival metastatic melanoma lesions. To evaluate chromosome 20 abnormalities in more detail and to resolve discrepancies between karyotype and CGH findings, we performed FISH analysis of metaphase cells in 13 melanoma cell lines (including the 7 lines used for CGH) and 9 primary melanoma specimens by using a whole chromosome paint specific for chromosome 20. All 13 cell lines (100%) and 8/9 primary tumors (89%) showed extra copies of chromosome 20 relative to tumor ploidy. Additionally, 6/14 cell lines (43%) and 2/8 primary tumors (25%) showed translocated chromosome 20 material previously undetected by standard cytogenetics. Cytologic evidence for gene amplification was also found in one cell line, which contained an add(20)(p13), with additional DNA being derived from 20q sequences. These data suggest that overrepresentation of a gene or genes important for melanoma pathogenesis resides on the long arm of chromosome 20.

The remanent magnetization of samples spanning Zones I to III of the Hoxnian Interglacial at Hoxne has declination values that lie within 30° of the present-day declination, and inclination values that are not more than 10° steeper or 20° shallower than the present-day inclination.

SummaryCommercial gravel working in the Devil's Wood Pit, Sproughton, situated in the flood plain of the River Gipping, has produced as chance finds two barbed points of bone and antler. Both came from the sand and gravel deposits which fill the buried channel of the Gipping. The points are discussed in relation to other barbed points found in England, particularly those which have associations which allow their dates to be assessed. Radiocarbon dates from organic material within the sands and gravels suggest that the barbed points were deposited during the latter part of pollen Zone III and the early part of Zone IV. A long blade industry has been recorded from the surface of the sands and gravels, and reference is given to further details of this industry.

Recent excavations have helped to clarify the cultural and stratigraphic sequences at Border Cave, and human skeletal remains recovered at this South African site may well be associated with a Middle Stone Age industry. A partial adult cranium is of particular interest, and this was originally described as quite different both from African Negro and from Bushman individuals. Eleven measurements were taken on the fossil, and these provide a basis for comparison of Border Cave with other crania drawn from extant African populations. Discriminant analysis shows clearly that the cranium lies close to the Hottentot male centroid and is within the range of modern African variation for the measurements employed. It is heavily constructed but not archaic in the fashion of Florisbad or Broken Hill. If the case for antiquity is regarded as firm, then the Border Cave skeleton suggests the presence of Homo sapiens sapiens in southern Africa before 50,000 B.P. and perhaps as early as 115,000 B.P. Hottentot or Bushman-...

This paper describes the context and nature of an assemblage of forty-four Palaeolithic hand-axes from a Roman religious site at Witham, Essex. The hand-axes are considered to have been derived from several sources, and it is suggested that the Romano-British occupants of the site deliberately selected them for their shape and placed them in the bottom of two large man-made depressions. In the light of stone axe finds on continental temple sites, and of classical Roman texts and traditions, the possibility arises that the Witham finds may have represented ‘thunderbolts’ in the worship of Jupiter or a local Celtic equivalent.

It is so rare for Palaeolithic artifacts to be found unequivocably stratified beneath glacial till, that the recent report by Alabaster and Straw (1976) of such an occurrence in Lincolnshire warrants some comments. Three hand-axes (fig. 1) were found between 1969 and 1973 in the quarry of Stephen Toulson and Son Ltd at Welton-le-Wold (TF 282884, 5 km west of Louth). They were found in association with fragmentary faunal remains of elephant, deer, horse and possibly Irish Giant Deer (see appendix by Boylan, in Alabaster and Straw 1976). Both artifacts and fauna came from a narrow zone in the Upper Division of the Welton Gravels underlying some 13 m of glacial till. This Upper Division, comprising silts, sands and flint gravels, is considered to have been deposited by periglacial aeolian and niveofluvial processes, whereas the Lower Division contains more water-bedded sands. The conclusion of the investigators was that as the animals represented could not have lived under the severe environmental conditions that prevailed during the accumulation of this Upper Division of the gravel, they had presumably been derived from an earlier temperate, interglacial deposit. The relative concentration of animal remains, the finding of two conjoinable elephant molars and the fairly fresh state of the artifacts suggests that they had not travelled far before coming to rest in the gravel. No sediment was traced in the quarry area which could have been a likely source.

The occurrence of submerged forests in places along the British coast has long attracted attention, and led to speculation on the relative displacement in land and sea levels that enabled such forests to grow. Many of these forest beds are only visible between high and low water of the spring tides; others, not so readily seen, are known to occur in beds to a depth 60 feet below present sea level. The melting of the ice sheets after the last glaciation and the consequent rise of sea level accounts for the submergence of many of these forest beds, although the actual height at which they are found, may be affected by displacement from the contemporary level by subsequent compaction of sediments and tectonic movement. The submerged forest at Westward Ho! rests on consolidated sediments and is not subject to change in level due to compaction. The tectonic factor is discussed in relation to analogous deposits of comparable age elsewhere in southern Britain.The presence of the submerged forest in Bideford Bay (Barnstaple Bay) at Westward Ho!, was recorded in a survey published by De la Beche in 1839, and in 1866 Ellis called attention to the presence of flints in the submerged forest bed. The peat was found in patches between a pebble ridge and low water mark and in places for about 200 yards along the beach.

The Iping Mesolithic site, found by Mr O. Knowles of Iping, lies on undulating Lower Greensand near the edge of a marsh which extends down to a pond and permanent spring (Sheet 181 O.S. 1″. 8485–2221). The site was totally excavated in 1960–61, by the West Sussex Excavation Group, following its accidental discovery. It consisted of a roughly circular area, about 25 feet across, of stained sand (Layer C) stratified between white sands (Layers B and D), all underlying the topmost deposit of heather on peat (Layer A). The white sand occurs as wind-blown material intermittently over the Lower Greensand of west Sussex, south Surrey and Hampshire. The darker stained layer was less than 6 inches thick and contained an abundant flint industry of cores, waste flakes and finished tools. The industry is of Maglemosian aspect and is important for its association with a well-preserved pollen which has yielded information about the contemporary environment.

Pleistocene macaque remains are uncommon in Great Britain. In addition to three specimens previously known from three sites, four teeth from Hoxne, Suffolk are recorded here. Closely resembling teeth of modern Macaca sylvanus (Barbary ape), they were recovered from a Middle Pleistocene stratum containing stone artifacts (including handaxes) and fauna including cold-climate lemmings.