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Background Severe acne vulgaris has limited therapeutic options. Objectives To evaluate photodynamic therapy ( PDT) using topical methyl aminolaevulinate ( MAL, 80 mg g −1) as the photosensitizer in severe facial acne. Methods A double-blind, randomized, vehicle-controlled multicentre trial in 153 patients (aged 12-35 years) with severe facial acne [Investigator's Global Assessment ( IGA) score 4; 25-75 inflammatory lesions with ≤ 3 nodules; 20-100 noninflammatory lesions]. Treatment (four treatments 2 weeks apart) involved incubation with MAL ( n = 100) or vehicle cream ( n = 53) for 1·5 h under occlusion, then illumination (635-nm red light, total dose 37 J cm −2). IGA assessment and standardized lesion counts were performed before each treatment and 12 weeks after the first treatment. Treatment success was defined as improvement from baseline in IGA by ≥ 2 grades at 12 weeks. Safety assessments were for pain (10-cm visual analogue scale, immediately after illumination), erythema (four-point rating scale) and adverse events. Results At 12 weeks, PDT using MAL 80 mg g −1 reduced inflammatory lesions vs. vehicle PDT (mean change −15·6 vs. −7·8, P = 0·006; mean percentage change −37·3% vs. −16·2%, P = 0·003). However, noninflammatory lesions did not decrease significantly (mean change −11·8 vs. −10·7, P = 0·85; mean percentage change −28·6% vs. −24·9%, P = 0·72). Treatment success rates were greater with MAL- PDT 80 mg g−1 (44% vs. 26%, P = 0·013). Pain was low and manageable by briefly pausing illumination. There was similar pain or erythema with successive treatments. Conclusions PDT using topical MAL 80 mg g−1 and red light may offer promise for severe acne vulgaris. [ABSTRACT FROM AUTHOR]

Postmortem brain studies have shown deficits in the cortical?-aminobutyric acid (GABA) system in schizophrenic individuals. Expression studies have shown a decrease in the major GABA-synthesizing enzyme (glutamic acid decarboxylase (GAD67) mRNA levels in neurons in dorsolateral prefrontal cortex in schizophrenics relative to controls. In the present study, SNPs in and around the GAD1 gene, which encodes the protein GAD67, were tested on a rare, severely ill group of children and adolescents with childhood-onset schizophrenia (COS) (n=72), in a family-based association analysis. Compared to adult-onset samples, the COS sample has evidence for more salient familial, and perhaps genetic, risk factors for schizophrenia, as well as evidence for frontal cortical hypofunction, and greater decline in cortical gray matter volume on anatomic brain MRI scans during adolescence. We performed family-based TDT and haplotype association analyses of the clinical phenotype, as well as association analyses with endophenotypes using the QTDT program. Three adjacent SNPs in the 5'upstream region of GAD1 showed a positive pairwise association with illness in these families (P=0.022-0.057). Significant transmission distortion of 4-SNP haplotypes was also observed (P=0.003-0.008). Quantitative trait TDT analyses showed an intriguing association between several SNPs and increased rate of frontal gray matter loss. These observations, when taken together with the positive results reported recently in two independent adult-onset schizophrenia pedigree samples, suggest that the gene encoding GAD67 may be a common risk factor for schizophrenia.Molecular Psychiatry (2005) 10, 581-588. doi:10.1038/sj.mp.4001599 Published online 26 October 2004 [ABSTRACT FROM AUTHOR]

Vibration white finger (VWF) is an ischemic condition of the hands that is associated with long-term exposure to hand-held vibration tools. The pathophysiology of VWF remains unknown. The aim of this study was to assess the hemorheologic effect of acute hand-transmitted vibration. This study investigated 52 men divided into two groups: VWF=29, mean age 46.9 years (range twenty-two to sixty-six); Controls=23, mean age 42.8 years (range twenty to sixty-four). Each subject gripped a vibrating handle for seven minutes thirty seconds at a vibration frequency of 120 Hz with an amplitude of displacement of 0.25 mm. Venous blood was analyzed before and after acute vibration to determine the hematocrit, the plasma hemoglobin concentration, plasma viscosity, and red cell deformability, expressed as red cell transit time (RCTT). At rest, there was no significant difference in RCTT, plasma viscosity, hematocrit, and plasma hemoglobin concentration between the VWF group and controls. Acute vibration did, however, significantly increase the red cell transit time in the VWF group but not in the control group. In both groups vibration resulted in a significant increase in plasma viscosity, hematocrit, and plasma hemoglobin concentration in hand venous blood. Moreover, in each group there was a highly significant correlation between the change in plasma viscosity and the change in the hemoglobin concentration and the hematocrit. The authors conclude that hand-transmitted vibration is associated with hemoconcentration. [ABSTRACT FROM AUTHOR]

Fluctuations in female sex hormones may be responsible for the high prevalence of Raynaud's phenomenon (RP) observed in premenopausal women. These hormones are known to act on central and peripheral thermoreceptors. In an attempt to establish whether cold sensitivity is altered during the menstrual cycle 50 premenopausal women were investigated. Of these, 26 had primary RP and 24 acted as controls. Each subject was exposed to environmental heating and cooling at three stages of the menstrual cycle to coincide with peaks and troughs in hormone levels. These stages were menstruation, periovulation, and during the midluteal phase. Finger hemodynamics was assessed by means of venous occlusion strain gauge plethysmography and fingertip temperature. Core temperature was assessed with an oral thermocouple. The results show that cold sensitivity was altered during the menstrual cycle in both groups with the fastest finger rewarming pattern during menstruation. Moreover, a significant difference was observed in core temperature between the two groups during the midluteal phase. As a group, subjects with RP failed to show a significant rise in core temperature following ovulation. The authors conclude that the menstrual cycle is associated with changes in the effect of cold on digital blood flow. [ABSTRACT FROM AUTHOR]

In an attempt to examine the role of the thermoregulatory apparatus in the etiology of Raynaud's phenomenon (RP), the authors exposed 15 women with RP and 12 controls to central body cooling and central body warming. Subjects were placed in an environmental chamber at 25°C. Their right hand was placed in an annex of the chamber, which was insulated from the main chamber and maintained at a constant temperature of 25°C throughout the experiment. Blood flow was measured in the digits of the right hand by venous occlusion strain gauge plethysmography and skin thermometry. Body temperature was measured with an oral thermometer. The temperature of the chamber was then increased to 35°C and then reduced to 13°C for twenty-five minutes with measurements repeated. Following this period patients were rewarmed in an ambient temperature of 35°C for twenty minutes. Results: subjects with RP had significantly lower blood flow at all stages of the test; moreover, their digital rewarming response following central cooling was considerably prolonged when compared with controls. Body temperature was lower and dropped significantly more in the RP group following the cold challenge. The authors conclude that subjects with RP have an impaired thermoregulatory mechanism. This may partially explain cold sensitivity. [ABSTRACT FROM AUTHOR]

Vibration white finger (VWF) is an occupational disorder associated with long-term exposure to hand-transmitted vibration. The condition exhibits features of secondary Raynaud's phenomenon. The etiology is unknown. The aim of this study was to examine the role of leukocyte rheology in the pathogenesis of VWF. Fifty-two male subjects divided into two groups were exposed to controlled acute band-transmitted vibration. One group consisted of 29 workers who have all bad occupational exposure to handheld vibration and all suffered from VWF (mean age 46.9 years, range 22–66). The second group consisted of 23 controls. Venous blood was analyzed from the dorsum of the band before and after vibration to determine granulocyte deformability, granulocyte morphology, and white blood cell count with differential. There was a subpopulation of bard and poorly deformable granulocytes in the VWF group when compared with controls (p <0.05). Acute band-transmitted vibration had no in vitro effect on leukocyte rheology in either group. Leukocyte rheology may play a role in the pathogenesis of microvascular disease and tissue ischemia in VWF, although whether this is a cause or an effect of the disorder is not clear. [ABSTRACT FROM AUTHOR]

A 75-year-old woman presented with painful recurrent venous ulcers (VU) continuously for the past 33 months on a background of frequent intermittent problems for the last 16 years. She had previously been treated with varicose vein surgery and trials of compression bandaging. Subsequently, she underwent endovenous laser ablation (EVLA) targeting the distal incompetent remnant of her great and small saphenous veins. This resulted in complete healing of her ulcers within four weeks. The dramatic response demonstrated in this case suggests that EVLA may represent an effective intervention in the management of postsurgery refractory VU. [ABSTRACT FROM AUTHOR]

Abstract Correction to Rao J S, Kim H W, Kellom M, Greenstein D, Chen M, Kraft A D, Harry G J, Rapoport S I, Basselin M. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats. Journal of Neuroinflammation 8:101.

Abstract Background Cognitive impairment has been reported in human immune deficiency virus-1- (HIV-1-) infected patients as well as in HIV-1 transgenic (Tg) rats. This impairment has been linked to neuroinflammation, disturbed brain arachidonic acid (AA) metabolism, and synapto-dendritic injury. We recently reported upregulated brain AA metabolism in 7- to 9-month-old HIV-1 Tg rats. We hypothesized that these HIV-1 Tg rats also would show upregulated brain inflammatory and AA cascade markers and a deficit of synaptic proteins. Methods We measured protein and mRNA levels of markers of neuroinflammation and the AA cascade, as well as pro-apoptotic factors and synaptic proteins, in brains from 7- to 9-month-old HIV-1 Tg and control rats. Results Compared with control brain, HIV-1 Tg rat brain showed immunoreactivity to glycoprotein 120 and tat HIV-1 viral proteins, and significantly higher protein and mRNA levels of (1) the inflammatory cytokines interleukin-1β and tumor necrosis factor α, (2) the activated microglial/macrophage marker CD11b, (3) AA cascade enzymes: AA-selective Ca2+-dependent cytosolic phospholipase A2 (cPLA2)-IVA, secretory sPLA2-IIA, cyclooxygenase (COX)-2, membrane prostaglandin E2 synthase, 5-lipoxygenase (LOX) and 15-LOX, cytochrome p450 epoxygenase, and (4) transcription factor NF-κBp50 DNA binding activity. HIV-1 Tg rat brain also exhibited signs of cell injury, including significantly decreased levels of brain-derived neurotrophic factor (BDNF) and drebrin, a marker of post-synaptic excitatory dendritic spines. Expression of Ca2+-independent iPLA2-VIA and COX-1 was unchanged. Conclusions HIV-1 Tg rats show elevated brain markers of neuroinflammation and AA metabolism, with a deficit in several synaptic proteins. These changes are associated with viral proteins and may contribute to cognitive impairment. The HIV-1 Tg rat may be a useful model for understanding progression and treatment of cognitive impairment in HIV-1 patients.

Objective: Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to "normalize" by age 17 years. Here we present a replication with nonoverlapping groups of healthy full siblings and healthy controls.Method: Using an automated measure and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in nonpsychotic full siblings (n = 43, 68 scans; ages 5 through 26 years) of patients with COS, contrasting them with age-, gender-, and scan interval-matched healthy controls (n = 86, 136 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons.Results: As in our previous study, young nonpsychotic siblings (<17 years) showed significant GM deficits in bilateral prefrontal and left temporal cortices and, in addition, smaller deficits in the parietal and right inferior temporal cortices. These deficits in nonpsychotic siblings normalized with age with minimal abnormalities remaining by age 17.Conclusions: Our results support previous findings showing nonpsychotic siblings of COS probands to have early GM deficits that ameliorate with time. At early ages, prefrontal and/or temporal loss may serve as a familial/trait marker for COS. Late adolescence appears to be a critical period for greatest localization of deficits in probands or normalization in nonpsychotic siblings. [ABSTRACT FROM AUTHOR]