The effects of preoperative alcohol, tobacco, and psychological stress on postoperative complications: a prospective observational study.

BACKGROUND: Postoperative complications occur frequently, despite progress in anesthetic pharmacology and surgical techniques. Although habits, such as alcohol and tobacco use, and mental health have been studied individually as modifying factors, few studies have examined the relationship between multiple lifestyle choices and postoperative complications in patients undergoing surgery. Hence, this study aimed to investigate the associations between unhealthy lifestyle choices and postoperative complications. METHODS: We included 730 patients who underwent surgery in our department between March 2015 and April 2016. Participants completed preoperative questionnaires, including the Alcohol Use Disorders Identification Test, Fagerström Test for Nicotine Dependence, and tests for psychological stress (6-item Kessler Psychological Distress Scale; Hospital Anxiety and Depression Scale). Multivariable logistic analysis was used to analyze the association of preoperative drug dependence and psychological stress with postoperative complications. RESULTS: Of the 721 cases analyzed, 461 (64%) were women. The median age of patients was 62 years (interquartile range: 48-71). At the time of surgical decision-making, 429 out of 710 respondents (60%) had a drinking habit, and 144 out of 693 respondents (21%) had a smoking habit during the preceding year. Seventy-nine patients had developed complications. Multivariable analysis revealed that old age (p = 0.020), psychological stress (p = 0.041), and longer anesthesia time (p < 0.001) were significantly associated with postoperative complications. Drinking or smoking variables were not associated with postoperative complications. CONCLUSIONS: Preoperative psychological stress, as evaluated with the 6-item Kessler Psychological Distress Scale, is associated with the risk of postoperative complications.

Gabapentin and pregabalin inhibit the itch-associated response induced by the repeated application of oxazolone in mice.

We investigated the effects of gabapentin and pregabalin on the itch-associated response in a mouse model of chronic dermatitis induced by the repeated application of 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (oxazolone). Challenging the mice with oxazolone-induced chronic dermatitis with the oxazolone evoked severe and transient scratching behavior until 1 h after the application of oxazolone. Thereafter, a more mild and continuous scratching behavior was also observed for at least 8 h. Both severe and continuous scratching behaviors were suppressed by systemic injection of gabapentin and pregabalin. This effect of these compounds was correlated with its affinity for the α2δ subunit of voltage-gated Ca²(+) channels. Intrathecal injection, but not peripheral treatment, with gabapentin inhibited the scratching behavior in this model. Gabapentin failed to suppress the scratching behavior induced by the intradermal injection of compound 48/80 in normal mice. The expression of the α2δ-1 subunit in dorsal root ganglion (DRG) from mice following repeated application of oxazolone was significantly higher than that from normal mice. These results suggest that gabapentin and pregabalin show an anti-pruritic activity through α2δ-subunit binding, and the up-regulation of the α2δ-1 subunit in DRG may therefore play an important role in its anti-pruritic activity.

Pharmacological characterization of itch-associated response induced by repeated application of oxazolone in mice.

We investigated pharmacological characteristics of the itch-associated response to chronic dermatitis induced by 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (oxazolone) repeated application in mice. Application of an oxazolone challenge to mice with oxazolone-induced chronic dermatitis evoked severe and transient scratching behavior for up to 1h. Thereafter, mild and continuous scratching behavior was observed for at least 8 h. Both severe and continuous scratching behaviors were suppressed by the opioid-receptor antagonist naltrexone, but not by the H(1) histamine-receptor antagonist fexofenadine, 5-hydroxytryptamine-2 (5-HT(2))-receptor antagonist methysergide, NK(1)-receptor antagonist LY303870, cyclooxygenase inhibitor indomethacin, or the platelet-activating factor-receptor antagonist YM264. The severe scratching behavior was suppressed by the 5-lipoxygenase inhibitor zileuton and leukotriene B(4)-receptor antagonist ONO-4057, but not by the cysteinyl leukotriene-receptor antagonist montelukast. The continuous scratching behavior was suppressed by pretreatment with the non-selective muscarinic acetylcholine-receptor antagonist atropine and M(3) muscarinic acetylcholine-receptor antagonist darifenacin. These results suggest that leukotriene B(4) receptor and M(3) muscarinic acetylcholine receptor are involved in the itch-associated response induced by repeated application of oxazolone in mice.

Effect of orally administered KF66490, a phosphodiesterase 4 inhibitor, on dermatitis in mouse models.

Due to the broad anti-inflammatory and immunomodulatory actions of phosphodiesterase (PDE) 4 inhibitors, it has been proposed that PDE4 inhibitors might be efficacious for skin disorders such as atopic dermatitis. KF66490 is a newly developed PDE4 inhibitor that inhibits PDE4B (IC(50)=220 nM) and the production of tumor necrosis factor (TNF)-alpha by mouse peritoneal exudated cells stimulated with lipopolysaccharide (IC(50)=855 nM). To evaluate efficacy of KF66490 in atopic dermatitis (AD) models, on skin inflammation induced by repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) on ear in BALB/c mice and on spontaneously AD-like skin diseases in NC/Nga mice. BALB/c mice were sensitized with 0.3% w/v TNCB applied to the ear on day-7, followed by application three times a week from days 0 to 21. NC/Nga mice spontaneously developed dermatitis symptoms under conventional conditions. Test compounds were administered orally once daily during experiments. In the TNCB-induced dermatitis model, KF66490 significantly inhibited the increase in ear thickness and interleukin (IL)-4 and IL-1beta levels in the ear. Histopathological and immunohistochemical analysis revealed that KF66490 significantly inhibited the proliferation of fibroblasts and CD3-positive T cells infiltration into the ear. In addition, KF66490 significantly suppressed the development of dermatitis in NC/Nga mice on all observation days, except for 5 and 6 weeks after the first dose. Furthermore, KF66490 produced less potent emetic effects than the first generation PDE4 inhibitor, rolipram. The present results suggest that KF66490 has excellent potential as an oral medicine for the treatment of atopic dermatitis.

Differential effects of PDE4 inhibitors on cortical neurons and T-lymphocytes.

Inhibitors of PDE4 (cAMP-specific phosphodiesterase) induce side effects, including nausea and emesis, that limit their therapeutic potential. We investigated the function of two catalytically active conformations of PDE4 (a low-affinity conformer detected by conventional cAMP hydrolytic activity and a high-affinity conformer detected by [(3)H]rolipram binding) in neuronal cells. We assessed enhancement of beta-adrenoceptor-mediated cAMP accumulation in cortical neurons in vitro by eleven PDE4 inhibitors with diverse biochemical profiles. The compounds tested have a wide inhibition range of PDE4 catalytic activity and [(3)H]rolipram binding. Inhibition potency for PDE4 catalytic activity and [(3)H]rolipram binding for each compound was different. Potency in augmentation of cAMP correlated significantly with the inhibitory effect on [(3)H]rolipram binding, but not with that against PDE4 catalytic activity. On the other hand, the inhibitory effect on proliferation of T-lymphocytes of the same PDE4 inhibitors correlated both with inhibition of PDE4 catalytic activity and with inhibition of [(3)H]rolipram binding. These findings indicate that the high affinity PDE4 conformer exists at a high level in cortical neurons and is important in the regulation of cAMP. Furthermore, the relative contributions of the two PDE4 conformers in cell function may cause different PDE4 inhibitor effects on cortical neurons and T-lymphocytes.

Correlation between emetic effect of phosphodiesterase 4 inhibitors and their occupation of the high-affinity rolipram binding site in Suncus murinus brain.

We employed an ex vivo [(3)H]rolipram binding experiment to elucidate the mechanism of emetic activity of phosphodiesterase 4 inhibitors. In Suncus murinus (an insectivore used for evaluation of emesis), emetic potential as well as ability to occupy the high-affinity rolipram binding site in brain membrane fraction in vivo were determined for phosphodiesterase 4 inhibitors. In vitro, [(3)H]rolipram bound to the membrane fraction of S. murinus brain with high affinity and its value was comparable to that for rat brain (K(d)=3.6 nM and 3.5 nM, respectively). The test compounds included denbufylline, rolipram, piclamilast, CDP840 and KF19514, each of which possessed similar affinities for the rolipram binding sites in both S. murinus and rat brain. In S. murinus, these compounds induced emesis via intraperitoneal administration. Their ED(50) values were as follows: denbufylline (1.4 mg/kg), rolipram (0.16 mg/kg), piclamilast (1.8 mg/kg), CDP840 (20 mg/kg), and KF19514 (0.030 mg/kg). In addition, these compounds occupied the high-affinity rolipram binding site in vivo as detected by dose-dependent reduction in capacity of ex vivo [(3)H]rolipram binding in brain membrane fractions. A clear correlation was observed between dose required to induce emesis and that to occupy the high-affinity rolipram binding site for individual phosphodiesterase 4 inhibitors. We conclude that the emetic effect of phosphodiesterase 4 inhibitors is caused at least in part via binding to the high-affinity rolipram binding site in brain in vivo.

Administration of PDE4 inhibitors suppressed the pannus-like inflammation by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1beta, TNF-alpha, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-alpha and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

Effect of orally administered rolipram, a phosphodiesterase 4 inhibitor, on a mouse model of the dermatitis caused by 2,4,6-trinitro-1-chlorobenzene (TNCB)-repeated application.

The purpose of this study was to evaluate the efficacy of rolipram, a phosphodiesterase (PDE) 4 inhibitor, in a mouse model of dermatitis induced by repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB). BALB/c mice were sensitized with 0.3% w/v TNCB applied to the ear on day -7, followed by application three times a week from day 0. Rolipram, prednisolone and cyclosporine A were administered orally once daily from day 0 to 21. Rolipram at a dose of 10 mg/kg/day significantly inhibited the ear thickness and the increase in cytokine levels and enzyme activity in the ear. Interleukin (IL)-4 production was markedly decreased in cervical lymph node cells from animals treated with rolipram at a dose of 10 mg/kg/day. Prednisolone and cyclosporine A significantly reduced ear thickness. These compounds significantly decreased the total cell and lymphocyte number of the cervical lymph nodes. Furthermore, prednisolone markedly suppressed body weight gain, and cyclosporine A significantly increased the serum total IgE concentration compared with that in the vehicle-treated control. Rolipram, unlike prednisolone and cyclosporine A, did not influence body weight and the total IgE concentration in the serum. The present results suggest that the PDE4 inhibitor is a promising oral medicine for the treatment of chronic skin inflammatory diseases.

The effects of olopatadine hydrochloride on the number of scratching induced by repeated application of oxazolone in mice.

It is suggested that atopic dermatitis is a skin disease associated with itching as subjective symptoms, and histamine H(1) receptor antagonists are used in order to prevent the itching, and the deterioration for scratch by itching. Histamine H(1) receptor selective anti-histamine olopatadine hydrochloride (olopatadine; Allelock shows consistent efficacy and safety in the treatment of allergic disorders. We investigated the possible efficacy of olopatadine on the number of scratching induced by repeated application of oxazolone in BALB/c mice. The repeated treatment of olopatadine significantly inhibited the ear swelling and the increased number of scratching. It significantly inhibited the increased production of interleukin (IL)-4, IL-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lesioned ear. Moreover, it significantly inhibited the increased production of nerve growth factor (NGF) and substance P. On the other hand, loratadine, bepotastine and chlorpheniramine did not inhibit the ear swelling and the increased number of scratching. These results indicate that olopatadine inhibited not only the increased production of cytokines but also NGF and substance P unlike other histamine H(1) receptor antagonists. It was suggested that olopatadine suppressed the increased number of scratching by the anti-inflammatory effects. Therefore, olopatadine appears to exert additional biological effects besides its blockade of a histamine H(1) receptor.

Inhibitory effect of the 4-aminotetrahydroquinoline derivatives, selective chemoattractant receptor-homologous molecule expressed on T helper 2 cell antagonists, on eosinophil migration induced by prostaglandin D2.

Prostaglandin (PG) D2, a major cyclooxygenase metabolite generated from immunologically stimulated mast cells, is known to induce activation and chemotaxis in eosinophils, basophils, and T helper 2 (Th2) lymphocytes via a newly identified PGD2 receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). CRTH2 is hypothesized to play an important role in the outcome of allergic responses. However, the absence of selective CRTH2 antagonists has prevented the elucidation of the role of CRTH2 in pathogenesis of allergic diseases. We now report compounds discovered as selective CRTH2 antagonists, (2R*,4S*)-N-(1-benzoyl-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)-N-phenylisobutyramide (K117) and (2R*,4S*)-N-(1-benzoyl-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)-N-phenylcyclopropanecarboxamide (K604). K117 and K604 have inhibitory effects on human CRTH2 with Ki values of 5.5 and 11 nM, respectively. The effect of these compounds is CRTH2-specific with no cross-reactivity against 15 other receptors and four arachidonic acid-metabolizing enzymes. K117 and K604 has no effect on the basal Ca2+ level and inhibited the Ca2+ response induced by PGD2 in 293EBNA cells expressing human CRTH2. Also, K117 and K604 inhibit PGD2-induced human eosinophil chemotaxis with IC50 values of 7.8 and 42.2 nM, respectively, but they do not inhibit the CC-chemokine receptor 3 agonist eotaxin-induced chemotaxis. These results indicate that K117 and K604 are highly potent and selective antagonists for human CRTH2. These compounds have possibilities to become useful tools to explore CRTH2 functions in allergic diseases.

Analyses of a mouse model of the dermatitis caused by 2,4,6-trinitro-1-chlorobenzene (TNCB)-repeated application.

BACKGROUND: The model of chronic dermatitis caused by repeated application of hapten is frequently used as a tool for assessment of the efficacy of a compound or the elucidation of chronic dermatitis. OBJECTIVE: The purpose of this study is to provide more detailed analysis of the model of chronic dermatitis caused by repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB). METHODS: BALB/c mice were sensitized with TNCB on day -7 to the ear, and then TNCB was repeatedly applied to the same ear three times per week, through days 0-21. RESULTS: The repeated application of TNCB induced an increase of ear thickness, and a relatively steep increment of ear thickness from days 7 to 9 was observed. This increment reached almost a plateau at day 9. The peaks of ear swelling on days 7, 14 and 21 were approximately two times higher than that on day 0. Regarding cytokines in the ear, the highest production of IL-1 beta, 4, 6 and 18 were observed on day 7. The peak production of IL-1 beta, 4 and 6 on day 7 was found within 24 h after the challenge, while that of IL-18 was found at 0 h. The inflammatory cell infiltration into epidermis and dermis was observed and increased in day 7, then reached almost a plateau on day 9. CONCLUSION: The indices such as thickness, swelling and inflammatory cell infiltration in the lesional skin was increased and maintained by repeated application, however, the protein levels of some cytokines were not always consistent with the reactions.

Optimum pain relief with continuous epidural infusion of local anesthetics shortens the duration of zoster-associated pain.

OBJECTIVE: To investigate effects of continuous epidural infusion (CEI) of 0.5% bupivacaine added to intermittent epidural boluses (IEB) on the duration of zoster-associated pain (ZAP), as compared with continuous infusion of normal saline placebo added to IEB. DESIGN: A prospective, double-blind, randomized, placebo-controlled study. SETTING: A university hospital and an affiliated clinic in Japan from 1996 through 1999. PATIENTS: 56 immunocompetent herpes zoster (HZ) patients, 50 years or older, within 10 days of rash onset and with severe pain and eruption. INTERVENTIONS: Patients were hospitalized and randomly allocated into 2 groups. CEI group given CEI of 0.5% bupivacaine (0.5-1.0 mL/h) plus IEB of 0.5% bupivacaine 4 times daily (n = 29). IEB group given normal saline infusion plus IEB of 0.5% bupivacaine 4 times daily (n = 27). All patients received oral acyclovir 800 mg, 5 times daily, for 7 days. OUTCOME MEASURES: The number of days required for complete cessation of ZAP and the proportion of subjects with allodynia beyond 30 days. RESULTS: The median time to cessation of ZAP was significantly shorter in the CEI group than in the IEB group (29 days vs. 40 days, P = 0.002). The number of patients whose allodynia persisted beyond 30 days of treatment was significantly lower in the CEI group than in the IEB group (10% vs. 37%, P = 0.027). CONCLUSIONS: CEI of 0.5% bupivacaine plus IEB was associated with a shorter duration of ZAP and fewer patients with allodynia beyond 30 days, compared with IEB plus normal saline infusion. Patients at high risk for developing postherpetic neuralgia (PHN) can be managed with intensive therapies at the early stage of disease, such as CEI, which maintains effective analgesia and may reduce the burden of PHN.

Staphylococcus aureus peptidoglycan stimulates granulocyte macrophage colony-stimulating factor production from human epidermal keratinocytes via mitogen-activated protein kinases.

Epidermal keratinocytes with atopic dermatitis (AD) overproduce mediators such as granulocyte macrophage colony-stimulating factor (GM-CSF), which are associated with pathology of AD. We found that peptidoglycan (PGN) of Staphylococcus aureus, which is frequently observed in lesion with AD, induced the production of numerous mediators such as GM-CSF and regulated on activation, normal T-cell expressed and secreted. Moreover, PGN phosphorylated extracellular-signal-regulated kinases and p38 mitogen-activated protein kinase, which were involved in the induction of GM-CSF expression. These results suggested that PGN of S. aureus directly exacerbates inflammation of inflammatory skin disease.

[Recent development of new drugs for the treatment of allergic diseases].

Due to the prevalence of allergic diseases such as bronchial asthma, allergic rhinoconjunctivitis and dermallergosis, efforts at the discovery of novel and effective medications for prevention and treatment of these conditions have been reinforced. Recently, it has been recognized that these allergic diseases are a chronic inflammatory disorder of the lower and upper airways and skin. In this article, we reviewed the recent development of the following new antiallergic therapies: anti-Th2 cytokine antibodies, decoy receptors, receptor antibodies, anti-IgE antibodies, anti-cell adhesion molecules antibodies, antisense oligonucleotides, keratinocyte modulators, inhibitors of phosphodiesterase 4, tachykinin receptor antagonists, and anti-histaminic drugs. Most of these new agents are aimed to inhibit various components of allergic inflammation. The future use of allergic disease therapies hold great promise and excitement.

Severity of skin lesions of herpes zoster at the worst phase rather than age and involved region most influences the duration of acute herpetic pain.

Duration of acute herpetic pain (AHP) in 1431 patients for whom treatment was begun within 14 days after the onset of herpes zoster (HZ) was analyzed with respect to age, involved region, and severity of skin lesions. All patients were treated with repeated sympathetic nerve blocks until their pain was almost nil. Severity of the skin lesions at the worst phase was defined as mild when they covered less than one-quarter of the primary dermatome, as severe when they covered more than three-quarters of the primary dermatome, and moderate if they were between mild and severe. Without taking into account the severity of skin lesions, the duration of AHP for those aged 60 years or over and for those with trigeminal involvement was significantly longer than for patients aged under 40 years (P < 0.01 and P < 0.001) and for patients with thoracic (P < 0.001) and lumbosacral (P < 0.01) involvement, respectively. However, duration of AHP was significantly longer with increase in the severity of skin lesions in all age groups (the mild group versus the moderate group, P < 0.01 and P < 0.001; the moderate group versus the severe group, P < 0.01 and P < 0.001). The mean duration of AHP for patients aged 60 years or over with mild skin lesions ranged from 17.4 to 22.9 days, while that for patients aged 30-59 years with severe skin lesions ranged from 37.2 to 50.1 days. In addition, duration of AHP was significantly longer with increase in the severity of skin lesions in all regions (the mild group versus the moderate group, P < 0.01 and P < 0.001; the moderate group versus the severe group, P < 0.05 and P < 0.001). The mean duration of AHP for those with trigeminal involvement with mild skin lesions was 19.5 days, while the range was from 51.3 to 55.0 days for patients with severe skin lesions involving regions other than the trigeminal area. The frequency of severe skin lesions was significantly higher (P < 0.001) in patients aged 60 years or over and in those with trigeminal involvement. Multiple stepwise regression analysis revealed that the most important factors influencing the duration of AHP were the severity of skin lesions of HZ at the worst phase (r = 0.412), age (r = 0.277) and the involved region (r = -0.101). Thus, AHP in the elderly and in cases of trigeminal involvement is longer because of higher frequencies of severe HZ in the elderly and in trigeminal involvement rather than "being aged' and "trigeminal involvement' itself. We propose that one needs to analyze the results of treatment of AHP with respect to the severity of skin lesions at the worst phase.

T-lymphocyte subsets in otherwise healthy patients with herpes zoster and relationships to the duration of acute herpetic pain.

T-lymphocyte subsets (CD3, CD4, and CD8 lymphocytes) in peripheral blood, parameters of cell-mediated immunity, were serially measured in 62 otherwise healthy Japanese patients with herpes zoster (HZ), and the findings were compared with those of 20 age-matched healthy controls who had had varicella but not HZ. Our objective was to elucidate whether there were changes in cell-mediated immunity, even in immunocompetent patients with HZ, and to investigate relationships between these variables and the duration of acute herpetic pain (AHP). All the patients underwent repeated sympathetic nerve blocks until pain was relieved. As compared with controls, there were slight increases in the percentages of CD4 lymphocytes (helper/inducer) and highly significant increases in the percentages of CD8 lymphocytes (suppressor/cytotoxic), resulting in marked decreases in CD4/CD8 ratios in the acute phase of HZ. The percentages of CD3 lymphocytes (pan-T lymphocytes) did not differ significantly. The duration of AHP was analyzed in 49 patients in whom T-lymphocyte subsets were measured more than twice. There was a weak but statistically significant positive linear correlation between age and the duration of AHP (r = 0.43, P < 0.01). There were statistically highly significant positive linear correlations between the number of days on which percentages of CD3 (r = 0.72, P < 10(-8)) and CD4 lymphocytes (r = 0.60, P < 10(-5)), and CD4/CD8 ratios (r = 0.62, P < 10(-5)) reached the maximum values after the onset of HZ and the duration of AHP. These correlation coefficients were higher than that between age and the duration of AHP.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors influencing the duration of treatment of acute herpetic pain with sympathetic nerve block: importance of severity of herpes zoster assessed by the maximum antibody titers to varicella-zoster virus in otherwise healthy patients.

Antibody responses to varicella-zoster virus (VZV) were serially investigated by the complement-fixation test in 72 Japanese of both sexes, suffering from herpes zoster (HZ), but otherwise healthy. Our objective was to elucidate whether there were mutual relationships among severities of skin lesion, maximum antibody titers to VZV, and duration of treatment for acute herpetic pain (AHP). Patients were divided into 3 groups: mild group (n = 26), moderate group (n = 26) and severe group (n = 20), according to the severity of the skin lesions. The 3 groups did not differ significantly with respect to age (P greater than 0.6). All patients were treated with regional sympathetic nerve blocks (SNBs) until pain relief was achieved. The durations of treatment for AHP became significantly longer as HZ increased in severity; the mean log10 durations of treatment (+/- S.E.) for the mild, moderate, and severe groups were 1.383 +/- 0.037, 1.616 +/- 0.055, and 1.888 +/- 0.069 days, respectively (P less than 0.01 for the mild group vs. the moderate group, and P less than 0.001 for the moderate group vs. the severe group). Irrespective of age, the maximum antibody titers closely paralleled the severities of the skin lesion of HZ; the mean maximum log2 antibody titers (+/- S.E.) for the mild, moderate, and severe groups were 5.12 +/- 0.24, 6.73 +/- 0.20, and 8.00 +/- 0.18, respectively (P less than 0.001 for the mild group vs. the moderate group and for the moderate group vs. the severe group).(ABSTRACT TRUNCATED AT 250 WORDS)