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New agents directed against molecular targets have now been tested in large prospectively randomized clinical trials for patients with untreated advanced non-small cell lung cancer (NSCLC). The trials have included small molecule inhibitors of receptor tyrosine kinases (gefitinib and erlontinib), monoclonal antibodies directed against either the ligands (bevicizumab against vascular endothelial growth factor) or their receptors (trastuzumab against ErbB2) and antisense nucleotides directed against mRNA coding for molecular targets (ISIS 3521 against protein kinase C alpha). The largest mature trials have included agents directed against ErbB1 (epidermal growth factor receptor). Two different small molecule inhibitors of erbB1 (gefitinib and erlontinib) and have been tested in 4 large international randomized trials. Two trials treated patients with advanced NSCLC with either gemcitabine and cisplatin or the same chemotherapy drugs combined with two different doses of gefitinib or one dose of erlontinib (INTACT 1 and TALENT). The other two trials treated patients with advanced NSCLC with either paclitaxel and carboplatin or the same chemotherapy drugs combined with either one of two doses of gefitinib or a single dose of erlontinib (INTACT 2 or TRIBUTE respectively). The results of INTACT 1 and INTACT2 showed no significant difference in survival between those treated with conventional combination chemotherapy and those treated with the same chemotherapy plus gefitinib. The results of the TRIBUTE and TALENT studies showed their primary endpoints of improving overall survival were not met. The monoclonal antibody, bevacizumab, is being tested in an ongoing clinical trial. The trial will compare the outcome of patients with untreated advanced adenocarcinoma of the lung treated with paclitaxel plus carboplatin to those treated with the same chemotherapy drugs plus bevacizumab. The results are scheduled to be available in 2005–2006. Although the initial trials adding newly developed molecular targeted agents have not shown initial success when added to conventional combination chemotherapy, further clinical trials are needed to ultimately define their role in the treatment of non-small cell lung cancer.

This paper presents and applies a methodology for determining the optimal scale, type, and timing of IC manufacturing capacity additions when demand is uncertain. Using the methodology, six different 200-mm fab designs are evaluated, including standard 10 K- and 20 K-wafer start per month (ws/mo) facilities, a 5 K-ws/mo "minifab," and "sequentially deployable" or "expandable" 10 K- and 20 K-ws/mo facilities. The results suggest that in the presence of uncertainty, manufacturers should follow a conservative deployment policy (better late than early to avoid periods of costly underutilization). In addition, when optimally deployed, larger, more efficient facilities are economically more viable than smaller fabs, since they are capable of generating substantially larger profits with comparable risks of loss, Sequentially deployable large fabs are even more attractive since they offer the economies of scale of larger fabs but require a smaller initial capital outlay.

Spin polarized electron-energy-loss spectra have been obtained from Ag(100), Cu(100), Mo(110) and unmagnetized Co(110) and Fe(100) surfaces, in both specular and off-specular scattering geometries, by use of a low-energy polarized incident beam coupled with energy- and angle-resolved spin analysis of the scattered electrons. The data are interpreted in terms of a model that takes account of both dipole and impact scattering. Dipole scattering preserves the full polarization of the incident beam, whereas the scattered electron polarization is degraded by electron exchange in impact-scattering events that produce electron-hole pair excitation in the target. It is found that dipole scattering dominates at noble-metal surfaces but that the impact- and dipole-scattering rates are comparable for targets with incompletely filled d shells. The data also suggest that impact scattering, like dipole scattering, tends to be concentrated in the specular direction. {copyright} {ital 1997} {ital The American Physical Society}

Trans to cis photoisomerization of epidermal urocanic acid (UCA) has been proposed as a primary event in UV-induced immunosuppression. 8-Methoxypsoralen (8-MOP) in combination with UVA radiation (PUVA) is used for photochemotherapy of several immunologicaly based skin disorders, and PUVA is known to cause immunosuppression. We examined the photointeraction of 8-MOP and other skin photosensitizing drugs (amiodarone, ciprofloxacin, doxycycline and ketoprofen) with trans-UCA in vitro. In oxic condition 8-MOP did not enhance the ability of radiation from standard PUVA fluorescent sources (0.2% radiation below 320 nm) to produce cis-UCA. When oxygen was removed, some 8-MOP photosensitization could be detected. 8-MOP, ciprofloxacin and ketoprofen also enhanced inefficient UCA photoisomerization by radiation from a filtered tungsten halogen source (0.2% radiation below 320 nm). 8-MOP photosensitization is essential for radiation from PUVA tubes to have a therapeutic or immunosuppressive effect. We have shown in vitro that 8-MOP does not enhance cis-UCA production by this source. Extrapolation of our data to the in vivo situation suggests that UCA may not be involved in either the therapeutic or the immunosuppressive effect of PUVA.

The new Philips TL01 narrow-band (311-313 nm) and conventional broad-band (e.g., Philips TL12; 270-350 nm) sources are effective for psoriasis phototherapy, for which treatment regimens are based on a predetermined minimal erythema dose. TL01 phototherapy treatment times are approximately half those with TL12 for psoriasis, whereas the cumulative exposure doses at clearing are similar. We compared the phototumorigenic potential of TL01 and TL12 radiation in mouse skin. Groups of albino Skh-1 hairless mice were exposed for 5 d/week at three dose levels. At each dose level, TL12 and TL01 doses were equally edematogenic. At each dose level, TL01 radiation was significantly more effective at producing first tumors of 1 mm in diameter and multiple tumors. At the lower two dose levels, TL01 radiation produced a significantly greater proportion of squamous cell carcinomas. This study demonstrates that TL01 radiation is more phototumorigenic than TL12 radiation at equally edematogenically weighted doses. This is in contrast with previous reports that edema production by polychromatic sources is predictive of their phototumorigenic effect in Skh-1 mice. The absolute cumulative TL12 dose needed to induce tumors was much less than that for TL01 radiation. The possibility of increased tumor risk with TL01 phototherapy should be considered but must be balanced against the high phototherapeutic efficacy of this source, short treatment times, and the low cumulative doses necessary for clearing of psoriasis.

Skin fibroblasts from certain patients with the photosensitivity dermatitis/actinic reticuloid syndrome show enhanced sensitivity to ultraviolet radiation compared to normal fibroblasts. To probe further the link between oxidative damage and this disease, we have obtained a more extensive set of cell lines from patients with a severe form of the disease and examined their sensitivity towards oxidative stress by measuring cell survival following UVA radiation (330-450 nm) or hydrogen peroxide treatment (0.1-2.4 mM). The activation of the stress gene, heme oxygenase, has also been assessed by measuring the accumulation of mRNA after hydrogen peroxide treatment. Our studies have confirmed that a slight ultraviolet sensitivity is a characteristic of photosensitivity dermatitis/actinic reticuloid syndrome cell strains and we further demonstrate that these cell lines are particularly sensitive to hydrogen peroxide with up to a three- to fourfold increased sensitivity as compared to normal controls. We also show that certain ataxia telangiectasia strains that are especially sensitive to hydrogen peroxide are also slightly sensitive to ultraviolet radiation. Hydrogen peroxide induces accumulation of mRNA for the oxidant-inducible stress protein, heme oxygenase, with similar kinetics (maximum mRNA accumulation 2-4 h following treatment) and with a similar range of magnitudes in both normal (6.6-20.6 times mRNA increase over basal levels) and photosensitivity dermatitis/actinic reticuloid (2.9-12.8 times) skin cells. Because cells from photosensitivity dermatitis/actinic reticuloid patients show increased sensitivity towards oxidative stress but show no significant change in oxidant activation of the heme oxygenase gene, we propose that the defect involves a late stage of processing of oxidative damage rather than a compromised free radical scavenging system.

Forty-five patients with extensive chronic plaque or guttate psoriasis were treated with either narrowband (TL-01) phototherapy, etretinate TL-01 combination therapy (re-TL-01) or etretinate and PUVA (re-PUVA) (15 patients in each group). Re-PUVA was the most effective therapy with 100% satisfactory clearance rate. TL-01 monotherapy had an 80% success rate; the relapse rate compared favourably with re-PUVA (50% in remission after 6 months). In the etretinate-TL-01 group, there was a 93% success rate and a one-third reduction in the total irradiation dose (8.0 J/cm2 vs. 12.7 J/cm2) but the relapse rate was higher, only 33% remaining in remission after 6 months.

The stability of polysilicon sheet resistance was studied as a function of conventional furnace anneal (CFA) and rapid thermal anneal (RTA). Polysilicon films of 100, 200, and 300 nm thickness were doped with boron, borofluoride, arsenic, or phosphorus and subjected to a CFA anneal matrix simulating the thermal cycles of a digital base BiCMOS process. RTA was introduced at the beginning or the end of the CFA anneal cycle to study its effectiveness in stabilizing the sheet resistance. CFA temperature was varied from 550 to 900 degrees C, and RTA temperature from 900 to 1100 degrees C. Throughout this range, it was found that the resistance depends primarily on the final anneal temperature and duration. The resistance increases substantially when the samples are subjected to a final low temperature anneal cycle, and decreases dramatically when followed by high temperature RTA. This was observed for arsenic- phosphorus-, and boron-doped films. It is suggested that the duration of cooling plays an important role in determining the nominal film resistance, thus explaining the efficiency of RTA in reducing and stabilizing the resistance. The results are compared with available models on dopant redistribution and carrier transport in polysilicon films. >

Ciprofloxacin is one of the new series of broad-spectrum antibiotic quinolones, chemically related to nalidixic acid and which may, therefore, induce photosensitization of human skin. Three in vitro tests for phototoxicity: the destruction of histidine, killing of mouse peritoneal macrophages and inhibition of PHA-stimulated DNA synthesis in human lymphocytes have demonstrated this photosensitizing potential with UVA irradiation at an order of magnitude lower than that for nalidixic acid. The Candida albicans test and photohaemolysis were negative. Controlled irradiation monochromator phototesting of 12 subjects, before, during and after taking ciprofloxacin showed subclinical photosensitivity with significantly lowered minimal 24 h erythema doses at 335 +/- 30 nm, 365 +/- 30 nm and 400 +/- 30 nm but not at 305 +/- 5 nm or above 400 +/- 30 nm.

"Procurement options" provide manufacturers with guaranteed, reduced tool lead times in exchange for the assumption of liability for a portion of the capacity and material costs a tool supplier must incur to support this commitment. Appropriately constructed and managed portfolios of procurement options allow manufacturers to control capacity availability, cost, lead time and liability, making possible predictable operating and financial performance tailored to management's objectives. By managing customer relationships with procurement options, suppliers are similarly able to significantly improve both cost and efficiency of planning and execution, and reduce their operating and financial risk

This paper compares the cost structure, optimal deployment policies, expected values and financial risk of 200 mm and 300 mm IC manufacturing facilities. 300 mm facilities are shown to have significantly lower capital costs than 200 mm facilities of comparable size (measured by die output), but comparable fixed recurring costs, and measurably higher variable costs. Due to the dominant role of capital costs in IC manufacturing, 300 mm fabs are significantly more valuable than comparably sized 200 mm fabs. The manufacturer's optimal policy is to outsource production until demand reaches a level at which additional in-house capacity can be fully utilized with high probability, and then to add a large, sequentially deployable 300 mm facility.

The authors describe and analyze two capacitors which are incorporated in a baseline BiCMOS technology without added process complexity. The first capacitor is formed between degenerated doped polysilicon and silicon. The second is formed between two degenerately doped polysilicon layers. In both structures, the insulator is a deposited or grown oxide. The sensitivity of the capacitor voltage coefficient to oxide thickness and surface dopant concentration is discussed theoretically and compared to measured data. The two capacitors are optimized to exhibit very low voltage coefficients. >

The phototoxic potential of several non-steroidal anti-inflammatory drugs and quinolone antibiotics was assessed using the photohaemolysis assay. In this system, human erythrocytes are irradiated (UVA radiation 320-400 nm) from below in the presence of suspected photosensitizers. Photohaemolysis with ketoprofen, tiaprofenic acid or nalidixic acid was initially concentration dependent, but photohaemolysis apparently decreased at higher drug concentrations. As erythrocytes were irradiated from below any optical screening at high drug concentrations was discounted. Other phototoxic drugs can oxidize haemoglobin to methaemoglobin resulting in a decrease in absorption and an artificially lowered photohaemolysis level. However, in the present experiments, the use of Drabkin's solution overcame this effect as haemoglobin and most of its oxidized derivatives were converted into a single derivative, namely cyanmethaemoglobin. Further possibilities are that photosensitized damage to haemoglobin results in the formation of intracellular Heinz bodies and/or bleaching of released haemoglobin. The latter hypothesis was tested by irradiating free haemoglobin in the presence of drugs. The results suggested that certain phototoxic agents cause 'bleaching' of the haemoglobin and formation of a derivative that fails to react with Drabkin's solution. If only high concentrations of these drugs are used in the photohaemolysis assay, this increases the risk of false negative results. It is therefore suggested that both photohaemolysis and photosensitized 'bleaching' of haemoglobin should be investigated when using this assay for screening drug phototoxicity.

Twenty-five patients suffering from severe polymorphic light eruption (PLE) were randomized to either photochemotherapy (PUVA) or narrow-band phototherapy (TL-01 UVB) treatment in early spring; patients receiving UVB were given placebo tablets to achieve a matching therapy procedure. During the 4 months following treatment, patient exposure to solar UVB was monitored with polysulphone badges. PLE occurrence, severity, and restriction of outdoor activity were recorded, using weekly diary-sheets. Analysis of covariance on this data, using the logarithm of UVB exposure as the explanatory variable, showed no significant differences between the treatments. TL-01 UVB is an effective alternative to PUVA in the management of PLE.

The Philips TL01 narrow-band (311-313 nm) fluorescent lamp provides effective phototherapy for psoriasis and atopic eczema while emitting less erythemogenic radiation than conventional broad-band (e.g. Philips TL12; 270-350 nm) sources. We studied the potency of TL01 and TL12 radiation to induce edema and sunburn cells (SBC) and to photoisomerize naturally occurring trans-urocanic acid (UCA) to cis-UCA in hairless mouse skin. Cis-UCA has immunosuppressive properties and is a putative mediator of UV-induced suppression of immune responses. For each source, there was UV dose dependence for all three responses. Within the dose ranges used, the potency ratio of TL12:TL01 radiation to induce equivalent edema and SBC was about 6:1. However, the potency ratio to induce cis-UCA was less than 2.3:1. Therefore, at a given level of edema or SBC induction, TL01 was more efficient than TL12 at UCA photoisomerization. The TL01 induction of immunomodulating cis-UCA, while causing minimal skin injury, may relate to the therapeutic efficacy of this source in skin conditions with an immunological component.

Cutaneous photosensitivity reactions are a consistent although uncommon feature of the fluoroquinolone group of antibiotics, which are related to nalidixic acid. Objective laboratory and clinical data are now routinely required by regulatory bodies for new drugs suspected of being photosensitizers, but no clear recommendations exist. A series of in vitro tests ranging in complexity revealed a UVA-dependent phototoxic potential for the fluoroquinolone norfloxacin similar to that for ciprofloxacin, and less than that of nalidixic acid. Controlled monochromator phototesting, designed to reveal the clinical characteristics, wavelength dependence and severity of cutaneous reactions in normal subjects showed both norfloxacin and ciprofloxacin to have a weak phototoxic potential which clears within 4 weeks of stopping the drug. UVA wavelengths (335 +/- 30 nm; 365 +/- 30 nm) appear most responsible for producing an asymptomatic erythema which is maximal at 24 h. The clinical study differs from those used previously in being blind, containing positive and negative controls, and phototesting after cessation of drug intake. The methodology has the anticipated limitation of failing to detect idiosyncratic photosensitivity responses.

Urocanic acid (UCA) is a major UV chromophore in the upper layers of the skin where it is found predominantly as the trans isomer. UV irradiation induces photoisomerisation of trans-UCA to cis-UCA which has been shown to mimic some of the immunosuppressive properties of UV exposure. We examined the wavelength dependence for trans-UCA to cis-UCA photoisomerisation in vitro and in mouse skin in vivo over the spectral range 270-340 nm. The resulting action spectra were very similar with maximal effectiveness at 300-315 nm and equal activity at 270 nm and 325-330 nm, demonstrating that UVA-II radiation (320-340 nm) is efficient at UCA photoisomerisation. These action spectra differed markedly from the trans-UCA absorption spectrum in vitro and also the reported action spectrum for UV suppression of contact hypersensitivity in mice. These findings suggest that the relationship between cis-UCA formation in skin and UV-induced immunosuppression may be complex.

Anecdotal reports suggest that the dihydropyridine calcium antagonist, nifedipine (NIF), may be phototoxic in human skin. We have studied NIF phototoxicity in vitro using UVA fluorescent tubes (Sylvania PUVA). NIF was phototoxic to Candida albicans and induced photohaemolysis both with NIF present during irradiation and with pre-irradiated drug. In V79 hamster fibroblasts, NIF (10 micrograms ml-1) was phototoxic MTT assay) 24 h after irradiation (0-112 kJ m-2); at 7.5 kJ m-2, about 70% of cells were damaged whilst at 37.5 kJ m-2, only about 45% of cells were damaged. A similar pattern was seen with pre-irradiated NIF. Absorption spectroscopy showed that the NIF absorption maximum (Amax approximately 340 nm) blue-shifted to 314 nm at low UVA doses (7.5 kJ m-2 or less) and red-shifted to 345 nm at higher doses (isosbestic point, 325 nm). Thin layer chromatography of irradiated NIF showed a single photoproduct (PP1; Amax approximately 314 nm) formed at 7.5 kJ m-2 or less which disappeared at higher UVA doses to give further photoproducts. PP1 was highly dark toxic to V79 cells (50% damage at about 5 micrograms ml-1) but PP1 pre-irradiated with UVA was non-toxic. Preliminary gas chromatography-mass spectroscopy studies suggest that PP1 is the nitroso derivative of NIF. These results indicate that NIF phototoxicity in vitro is partially mediated by initial formation of a toxic photoproduct (PP1) but, paradoxically, subsequent UVA irradiation may reduce phototoxicity. The NIF concentrations required to induce in vitro phototoxicity are much greater than therapeutic plasma levels. Unless there is skin accumulation of NIF or PP1, our in vitro results suggest that NIF may not be an important skin-photosensitizing agent in vivo.

The Dundee experimental bald rat (DEBR) is reported as a model for human alopecia areata. Parallels with human alopecia areata were observed in relation to the gradual and patchy loss of hair and the penetration of both pelage and vibrissa follicles by mononuclear cells. In particular, the apparent disruption of the follicles within the precortical region of the epidermal component and consequent alterations of normal geometrical relationships between dermal and epidermal components relate directly to similar studies on human alopecia areata. In comparison with other previously described hypotrichotic rodent mutants, the DEBR rat exhibits a unique mechanism of hair loss which may provide important information regarding the pathomechanism of human alopecia areata.

Solutions of ciprofloxacin were irradiated with different wavebands of ultraviolet and visible radiation and the antibiotic activity of the drug was determined against Escherichia coli. A wavelength dependent loss of antibiotic activity was found with maximal effect around 320 nm; no effect occurred with visible irradiation. The degree of the decrease in activity with longer wavelength ultraviolet (UVA) radiation was sufficient to indicate that human exposure to sunlight through window glass (greater than 320 nm) or UVA from tanning sunbeds may result in a significant reduction in both cutaneous and circulating levels of ciprofloxacin.

Isolation of the furocoumarins (psoralens) bergapten, isobergapten, sphondin, isopimpinellin and pimpinellin from the Umbilliferous plant Heracleum laciniatum was carried out by column chromatography, and the structure and absorption spectra for the 5 furocoumarins isolated are described. Photoepicutaneous testing showed the strongest phototoxic effects from bergapten, marked effects from pimpinellin, weak effects from sphondin and none from the others. These in vivo findings were confirmed by the in vitro Candida test. Action spectrum studies demonstrated peak photosensitivity in the range 330-335 nm, bergapten being more than twice as phototoxic as pimpinellin.

A quantitative study of 8-methoxypsoralen plasma profiles in patients with psoriasis undergoing photochemotherapy shows that a poor response to the treatment may be explained in terms of abnormal pharmacokinetic behaviour. However, not all 'poor responders' exhibit an abnormal pattern and for these an alternative explanation is required.

The question of which C ∗ -algebras have only inner derivations has been considered by a number of authors for 25 years. The separable case is completely solved, so this paper deals only with the non-separable case. In particular, we show that the C ∗ -tensor product of a von Neumann algebra and an abelian C ∗ -algebra has only inner derivations. Other special types of C ∗ -algebras are shown to have only inner derivations as well such as the C ∗ -tensor product of L ( H ) (all bounded operators on separable Hilbert space) and any separable C ∗ -algebra having only inner derivations. Derivations from a smaller C ∗ -algebra into a larger one are also considered, and this concept is generalized to include derivations between C ∗ -algebras connected by a ∗ -homomorphism. Finally, we consider the general problem of a sequence of linear functionals on a C ∗ -algebra which converges to zero (in norm) when restricted to any abelian C ∗ -subalgebra. Does such a sequence converge to zero in norm? The answer is “yes” for normal functionals on L ( H ), but unknown in general.

These studies of lung cancer suggest that a number of molecular mechanisms may be important in the pathogenesis of lung cancer, especially SCLC. An inherited predisposition to develop SCLC may correlate with a nonfunctional, recessive allele for a gene (McKusick #18228, McKusick 1986) that maps to chromosome region 3p(14-23). Individuals at risk would be heterozygous for this allele in their germ line, carrying one copy of a normal functional gene and one mutant, recessive allele. Exposure to carcinogens, in particular cigarette smoke, can produce somatic genetic changes such as chromosomal deletion or gene mutation in the functional allele of this gene, unmasking the nonfunctional allele. Loss of this normal gene may alter the regulation of cell growth, perhaps by allowing the deregulated expression of proto-oncogenes of the myc family, or autocrine growth factors such as GRP and/or its receptor. Alternatively, loss of this gene may result in the cell returning to a less differentiated developmental state where growth regulation is less stringent. Persons with this mutant gene should be at increased risk to develop SCLC, and further RFLP analysis of the 3p region in SCLC may allow identification of specific haplotypes with increased risk of developing lung cancer. If this notion is correct, one might expect to find an increased frequency of second tumors in lung cancer patients and the presence of similar chromosomal deletions in second tumors arising in SCLC patients. In this regard, cured lung cancer patients, including those with SCLC, have a tenfold increased risk of developing a second lung cancer (Fontana 1977; Cortese et al. 1983; Johnson et al. 1986b). In fact, a chromosome 3p deletion along with other chromosomal abnormalities was identified in acute erythroleukemia cells arising in a long-term survivor of SCLC (Bradley et al. 1982), implicating this same region in the pathogenesis of both tumors. Other predictions include the correction of at least a portion of the defect by introducing a normal chromosome 3 into SCLC cells. While c-myc is expressed in many fetal and adult tissues, high-level expression of N- and L-myc is very restricted as to tissue and stage in the developing mouse, with N-myc expressed in the fetal but not adult lung, whereas the lung was the only adult tissue where L-myc expression was detected (Zimmerman et al. 1986). Could these patterns provide a clue to the differential expression of c-, N-, and L-myc found in different lung cancers (Nau et al. 1986)?(ABSTRACT TRUNCATED AT 400 WORDS)

Synopsis This paper reviews current ideas concerning the reactions involved in sunburn, suntanning, premature ageing and carcinogenesis due to acute or chronic exposure to sunlight. The physiological mechanisms of protection involving melanin pigmentation, thickening of the epidermal horny layer and urocanic acid are briefly discussed. The importance of wavelengths from 290-315 nm (UV-B) for these reactions is emphasized as is the need to investigate further the involvement of longer wavelength (UV-A, 315-400 nm).

SUMMARY A study of the abnormal sunlight response seen in nine patients taking benoxaprofen showed that the action spectrum was between 310 and 325 nm, which is similar to the drug's absorption spectrum. In vitro studies using three separate methods indicated that benoxaprofen has a powerful phototoxic action which may be directed mainly against cellular membranes.

SUMMARY Of sixty-nine examples of the photosensitivity dermatitis and actinic reticuloid syndrome, nine were found to be allergically sensitive to chrysanthemum oleoresin extract. Although this extract showed evidence in vitro of a phototoxic action we were unable with in vivo studies to explain the connection between the contact allergic sensitivity and the photosensitivity. The fractions responsible for the in vitro phototoxicity appear to be different from those involved in the in vivo contact allergic sensitivity. This study provides further support for the view that in the photosensitivity dermatitis and actinic reticuloid syndrome contact allergic sensitivity is of importance.

Abnormal cutaneous photosensitivity is included among a number of more common side effects of tretinoin (Fig. 1; al l trans-ret inoic acid) (Pedace and Stoughton, 1971; Papa et al., 1975). The related synthetic retinoids, etretinate (Tigason) and isotretinoin (Roaccutane) (Fig. 1) may well produce a similar photosensitization. While photosensitivity is frequently listed as an adverse effect of isotretinoin, reports in the literature are contradictory. An increased susceptibility to sunburn reactions has been stated to occur in 5-12% of patients (Angel, 1983; Strauss et al., 1984) but the work of others has failed to detect this problem (Diffey et al., 1985). A single case report of clinical photosensitivity by McCormack and Turner (1983) described burning erythema of sun-exposed sites which was thought to be phototoxic in origin. Phototesting a group of subjects taking isotretinoin proved negative (Diffey et al., 1985). Etretinate has also been reported as causing sunburn reactions in 7-9% of patients (Grekin et al., 1984). Two early studies failed to produce evidence of an abnormal response to sunlight in subjects taking the drug (Ippen et al., 1978; Goerz and Orfanos, 1978) but case reports continue to appear in the literature (Collins et al., 1986).

SUMMARY This article describes the satisfactory clinical improvement obtained in the majority of a group of 72 patients with psoriasis of various types as a result of the oral and/or topical administration of 8–methoxypsoralen followed by long wavelength ultraviolet irradiation. The irradiation source used was that of conventional longwave UV fluorescent tubes mounted in a specially constructed cubicle. Until such time as the long term effect of this form of photochemotherapy on the cell has been evaluated and the most appropriate regime worked out, it would seem to be important to restrict the amount of irradiation used to that required to produce acceptable maintained clinical improvement.

Osteomalacia due to vitamin D deficiency is common in elderly women. It has been suggested that ultraviolet light may have a place in its prevention but our studies with Vita-Lite fluorescent tubes have given no support to the view that these can play a useful role in the promotion of vitamin D synthesis.

Contact allergic sensitivity to allergens such as plants of the Compositae family is a feature of the chronic skin reaction seen in the photosensitivity dermatitis with actinic reticuloid syndrome. In fifty patients with this syndrome an increased incidence of contact allergic sensitivity to some common fragrance materials was demonstrated. Evidence is also presented, both by in vitro and in vivo studies, which indicates that a phototoxic mechanism is involved. The relevance of continued exposure to common allergens and their involvement in photosensitization mechanisms is discussed in an attempt to explain the state of 'persistent light reaction'.