Immunogenicity of the mRNA-1273 and ChAdOx1 nCoV-19 vaccines in Asian patients with autoimmune rheumatic diseases under biologic and/or conventional immunosuppressant treatments.

OBJECTIVE: Nucleic acid-based vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are effective in the general population. However, it is unknown whether this is true in Asian patients with autoimmune rheumatic diseases (ARDs) who have received various combinations of disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We designed a large prospective observational study recruiting 228 patients with ARDs in a tertiary rheumatology centre in Taiwan. Altogether, 142 received biological or targeted synthetic DMARDs and 86 received only conventional synthetic (cs) DMARDs. Serum levels of immunoglobulin G antibody against SARS-CoV-2 spike proteins were measured 2-6 weeks after COVID-19 vaccination with mRNA-1273 (Moderna®) or ChAdOx1 nCoV-19 (Oxford/AstraZeneca®). The immunomodulatory therapies were not modified before or after vaccination. RESULTS: Overall, 194 patients (85.09%) exhibited antibodies (758.33 ± 808.43 ng/mL) but 34 patients did not (103.24 ± 41.08 ng/mL). Patients with systemic lupus erythematosus or rheumatoid arthritis had significantly lower humoral responses to COVID-19 vaccination than those with other ARDs (p < 0.05). There was no significant difference in immunogenicity among patients on different csDMARD treatments. Compared to patients treated with only csDMARDs, those on rituximab or abatacept therapy had significantly lower immune response to the vaccination (p = 0.008 and p = 0.035, respectively). Patients who were treated with anti-tumour necrosis factor-α or interleukin-6 inhibitor exhibited higher titres of vaccination antibodies than those treated with direct lymphocyte inhibitors. CONCLUSIONS: mRNA-1273 and ChAdOx1 nCoV-19 vaccines were immunogenic in the majority of ARD patients. Rituximab and abatacept were associated with significantly diminished COVID-19 vaccination immunogenicity.

Parathyroidectomy slows renal function decline in patients with primary hyperparathyroidism.

PURPOSE: Primary hyperparathyroidism has deleterious effects on health and causes nephrolithiasis and osteoporosis. However, it remains unclear whether parathyroidectomy benefits kidney function among patients with primary hyperparathyroidism. METHODS: In this retrospective study, patients with primary hyperparathyroidism receiving parathyroidectomy in a tertiary medical center between 2003 and 2017 were followed up until December 31 2017, death, or requiring renal replacement therapy. Impact of parathyroidectomy on kidney function was examined using longitudinal estimated glomerular filtration rate (eGFR) change scales: single, average, absolute difference, percent change, annual decline rate, and slope. We applied linear mixed-effect model to determine the effect of parathyroidectomy on kidney function. RESULTS: During study period, 167 patients with primary hyperparathyroidism were identified from 498 parathyroidectomized patients, and finally, 27 patients fulfilled our stringent criteria. Median follow-up duration was 1.50 years (interquartile range 1.05-1.81) before surgery and 2.47 years (1.37-6.43) after surgery. Although parathyroidectomy did not affect amount of proteinuria and distribution of eGFR, parathyroidectomy significantly slowed decline rate of eGFR compared with that before surgery (- 1.67 versus - 2.73 mL/min/1.73 m2/year, p < 0.001). More importantly, parathyroidectomy made more beneficial effects on kidney function in patients with age < 65 years and those without chronic kidney disease or hypertension. CONCLUSIONS: Our study showed that parathyroidectomy slows renal function decline irrespective of age or comorbidities, which offers novel insight into the revision of guidelines for surgical indications in primary hyperparathyroidism. Given small sample size, further large-scale controlled studies are warranted to confirm our findings.

Herb formula enhances treatment of impotent patients after penile venous stripping: a randomised clinical trials.

Herbs have been regarded as aphrodisiacs in treating impotence for many centuries despite little true scientific evidence. Our latest refined penile venous stripping (PVS) technique is effective in treating impotence, although this procedure remains controversial. A synergic effect of PVS and oral herbs was confirmed in our practice but lacked rigorous scientific proof. The objective of this report was to review our experience with this combination. From August 2010 to May 2014, 263 males underwent PVS. Among these, 67 unsatisfied men chose additional salvage therapy and were randomly assigned to oral herbs (n = 35) or placebo treatment (n = 32) which replaced herb eventually. All were evaluated with the international index of erectile function (IIEF-5) scoring and our dual pharmaco-cavernosography. The pre-op IIEF-5 score for the herb group was 9.7 ± 3.7, post-operative 13.9 ± 3.3 and post-herb 19.6 ± 3.4, while the control group scores were as follows: pre-op 9.3 ± 4.1, post-op 14.5 ± 3.6, post-placebo 15.1 ± 3.5 and post-herb 19.9 ± 3.2. Although there was no significant difference between the two groups pre-operatively, post-operatively and post-herb, a statistically significant difference was found post-salvage therapy (19.6 ± 3.4 versus 15.1 ± 3.6, P < 0.001). It appears that the combination of oral herbs and PVS treatment provides an enhanced outcome to impotent patients refractory to medicine and unsatisfied with PVS monotherapy alone.

Quantifying midbrain serotonin transporter in depression: a preliminary study of diagnosis and naturalistic treatment outcome.

INTRODUCTION: Serotonin may play an important role in the pathology of major depressive disorder (MDD). However, the relationship between serotonin transporter (SERT) availability and the medical outcome of antidepressant treatment is uncertain. METHODS: In this naturalistic study, SERT availability (expressed as the specific uptake ratio, SUR) in the midbrain of 17 drug-free patients with MDD and 17 controls matched for age and gender was measured using SPECT with [(123)I]ADAM. The severity of MDD was measured by the Hamilton Depression Rating Scale before, and after 6 weeks of non-standardized antidepressant treatment. RESULTS: A total of 12 patients completed the study. The SUR of the patients with MDD was significantly lower than that of the healthy controls. The SUR of SERT was not found to have a linear relationship with the treatment outcome; however, supplemental analysis found a curvilinear relationship between treatment outcome and the SUR of SERT. DISCUSSION: The findings indicate that the SUR of SERT is lower in patients with MDD; however it did not predict treatment outcome in a linear fashion. Studies with larger sample sizes are required.

Kefir improves fatty liver syndrome by inhibiting the lipogenesis pathway in leptin-deficient ob/ob knockout mice.

OBJECTIVE: Fatty liver disease is commonly associated with obesity, insulin resistance and diabetes. Severe fatty liver is sometimes accompanied by steatohepatitis and may lead to the development of hepatocellular carcinoma. At present, there is no effective treatment for non-alcoholic fatty liver disease (NAFLD); thus, recent investigations have focused on developing effective therapeutics to treat this condition. This study aimed to evaluate the effects of kefir on the hepatic lipid metabolism of ob/ob mice, which are commonly used to model fatty liver disease. RESULTS: In this study, we used leptin receptor-deficient ob/ob mice as an animal disease model of NAFLD. Six-week-old ob/ob mice were orally administered the dairy product kefir (140 mg kg(-1) of body weight (BW) per day) for 4 weeks. The data demonstrated that kefir improved fatty liver syndrome on BW, energy expenditure and basal metabolic rate by inhibiting serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities (P<0.05) and by decreasing the triglyceride (TG) and total cholesterol (TC) contents of the liver (P<0.05). Oral kefir administration also significantly reduced the macrovesicular fat quantity in liver tissue. In addition, kefir markedly decreased the expression of the genes sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) (P<0.05) but not the expression of peroxisome proliferator-activated receptor α (PPARα) or hepatic carnitine palmitoyltransferase-1α (CPT1α) in the livers of ob/ob mice. CONCLUSION: On the basis of these results, we conclude that kefir improves NAFLD on BW, energy expenditure and basal metabolic rate by inhibiting the lipogenesis pathway and that kefir may have the potential for clinical application to the prevention or treatment of NAFLD.

Emotional regulatory function of receptor interacting protein 140 revealed in the ventromedial hypothalamus.

Receptor-interacting protein (RIP140) is a transcription co-regulator highly expressed in macrophages to regulate inflammatory and metabolic processes. However, its implication in neurological, cognitive and emotional conditions, and the cellular systems relevant to its biological activity within the central nervous system are currently less clear. A transgenic mouse line with macrophage-specific knockdown of RIP140 was generated (MΦRIPKD mice) and brain-region specific RIP140 knockdown efficiency evaluated. Mice were subjected to a battery of tests, designed to evaluate multiple behavioral domains at naïve or following site-specific RIP140 re-expression. Gene expression analysis assessed TNF-α, IL-1ß, TGF-1ß, IL1-RA and neuropeptide Y (NPY) expression, and in vitro studies examined the effects of macrophage's RIP140 on astrocytes' NPY production. We found that RIP140 expression was dramatically reduced in macrophages within the ventromedial hypothalamus (VMH) and the cingulate cortex of MΦRIPKD mice. These animals exhibited increased anxiety- and depressive-like behaviors. VMH-targeted RIP140 re-expression in MΦRIPKD mice reversed its depressive- but not its anxiety-like phenotype. Analysis of specific neurochemical changes revealed reduced astrocytic-NPY expression within the hypothalamus of MΦRIPKD mice, and in vitro analysis confirmed that conditioned medium of RIP140-silnenced macrophage culture could no longer stimulate NPY production from astrocytes. The current study revealed an emotional regulatory function of macrophage-derived RIP140 in the VMH, and secondary dysregulation of NPY within hypothalamic astrocyte population, which might be associated with the observed behavioral phenotype of MΦRIPKD mice. This study highlights RIP140 as a novel target for the development of potential therapeutic and intervention strategies for emotional regulation disorders.

Inhibition of cyclooxygenase 2 expression by diallyl sulfide on joint inflammation induced by urate crystal and IL-1beta.

OBJECTIVE: Investigation of the effects of diallyl sulfide (DAS), a garlic sulfur compound, on joint tissue inflammatory responses induced by monosodium urate (MSU) crystals and interleukin-1beta (IL-1beta). DESIGN: The HIG-82 synovial cell line was used to establish the experimental model and DAS regime. Primary cultures of articular chondrocytes and synovial fibroblasts obtained from patients undergoing joint replacement for osteoarthritis were used in experimental studies. Cyclooxygenase (COX) expression following MSU crystal and IL-1beta stimulation with/without DAS co-incubation was assessed by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunocytochemistry and nuclear factor-kappa B (NF-kappaB) activation determined by electrophoretic mobility shift assay. Prostaglandin E2 (PGE(2)) production was measured by enzyme-linked immunosorbent assay (ELISA). DAS effects on COX gene expression in an MSU crystal-induced acute arthritis in rats were assessed by RT-PCR. RESULTS: MSU crystals upregulated COX-2 expression in HIG-82 cells and this was inhibited by co-incubation with DAS. DAS inhibited MSU crystal and IL-1beta induced elevation of COX-2 expression in primary synovial cells and chondrocytes. Production of PGE(2) induced by crystals was suppressed by DAS and celecoxib. MSU crystals had no effect on expression of COX-1 in synovial cells. NF-kappaB was activated by MSU crystals and this was blocked by DAS. Increased expression of COX-2 in synovium following intraarticular injection of MSU crystals in a rat model was inhibited by co-administration of DAS. CONCLUSIONS: DAS prevents IL-1beta and MSU crystal induced COX-2 upregulation in synovial cells and chondrocytes and ameliorates crystal induced synovitis potentially through a mechanism involving NF-kappaB. Anti-inflammatory actions of DAS may be of value in treatment of joint inflammation.

High prevalence of latent tuberculosis infection in patients in end-stage renal disease on hemodialysis: Comparison of QuantiFERON-TB GOLD, ELISPOT, and tuberculin skin test.

BACKGROUND: Individuals with end-stage renal disease (ESRD) are 10- to 25-fold more likely than immunocompetent people to develop active tuberculosis (TB) and are candidates for being treated for latent TB infection (LTBI). However, diagnosis using the tuberculin skin test (TST) is doubly difficult due to cutaneous anergy and cross-reactions with Bacille-Calmette-Guérin (BCG) vaccination. MATERIALS AND METHODS: This was a prospective, doublematched, cohort study in which 32 ESRD patients and 32 age-matched, healthy controls were enrolled. The TST and two new interferon-gamma blood tests, QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB (ELISPOT), were performed. The subjects were followed up 2 years for active TB disease. ELISPOT was done in ESRD patients only. RESULTS: Compared to the healthy controls, a high prevalence of LTBI was found in the ESRD patients by TST (62.5%, 95% confidence interval [CI] 43.7-78.9), QFT-G (40.0%, 95% CI 22.7-59.4), and ELISPOT (46.9%, 95% CI 29.1-65.3). Agreement was moderate (kappa [kappa] = 0.53) for QFT-G and ELISPOT but only slight between TST and QFT-G (kappa = 0.25) and fair between TST and ELISPOT (kappa = 0.32). ESRD (p = 0.03) and diabetes mellitus (p = 0.04) were significant risk factors for QFT-G positivity on the multivariable analysis. The overall rate of active TB was 1.66 cases per 100 person-years (pys), with the rate higher in patients with ESRD (3.53 per 100 pys) and those with positive (3.40 per 100 pys) and indeterminate QFT results (30.16 per 100 pys), although the difference was not statistically significant. Sensitivity, specificity, and positive and negative predictive values of QFT-G for active TB was 100%, 62.1%, 8.3% and 100%. CONCLUSION: This pilot study is the first to compare QFT-G, ELISPOT, and TST in ESRD patients on hemodialysis and demonstrates a high prevalence of LTBI in this population. In our study, the QFT-G was the more accurate method for identifying those truly infected with Mycobacterium tuberculosis, even in BCG-vaccinated individuals.

Heparin-induced thrombocytopenia associated with intra-tumour haemorrhage in cavernous sinus after cardiac myxoma surgery.

Heparin-induced thrombocytopenia (HIT) is a life-threatening disorder that is associated with heparin exposure. The incidence of HIT in patients undergoing cardiac surgery is relatively rare. We present a case of intratumor haemorrhage in the cavernous sinus 1 week after cardiac surgery. The pathogenesis may be venous thrombosis and haemorrhagic infarct caused by HIT following cardiopulmonary bypass surgery. This is a rare case and has not been reported previously.

Selective COX2 inhibition improves whole body and muscular insulin resistance in fructose-fed rats.

BACKGROUND: The effects of cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX2) inhibition on insulin resistance in subjects with the metabolic syndrome remain elusive. Aims of this study were to examine the effects of COX1 and COX2 inhibitors on whole body and muscular insulin resistance in fructose-fed rats, an animal model of the metabolic syndrome. MATERIALS AND METHODS: The rats on regular or 60% fructose-enriched diets for 6 weeks were further divided into rats combined with or without piroxicam (a selective COX1 inhibitor) or celecoxib (a selective COX2 inhibitor) treatment for an additional 2 weeks. Euglycaemic hyperinsulinaemic clamp (EHC) with a tracer dilution method was performed at the end of the study. RESULTS: The present result showed that fructose-induced increases in systolic blood pressure and fasting plasma insulin levels were significantly suppressed in rats treated with celecoxib but not piroxicam. In the EHC period, celecoxib significantly reversed fructose-induced decreases in whole body glucose uptake, mainly by glucose storage. Hepatic glucose production and whole body glycolysis were not significantly changed among groups. Celecoxib but not piroxicam significantly reversed fructose-induced decreases in glycogen synthase activities in red and white quadriceps muscles and insulin-stimulated membrane GLUT4 recruitment in soleus muscles. Celecoxib and piroxicam both significantly diminished fructose-induced increases in plasma thromboxane B2 and 6-keto prostaglandin (PG) F1alpha; but only celecoxib treatment significantly attenuated a fructose-induced increase in 8-isoprostane levels. Plasma PGE metabolites were not different among groups. CONCLUSIONS: This study demonstrates that a therapeutic dose of celecoxib, but not piroxicam, could significantly attenuate fructose-induced whole body and muscular insulin resistance in rats.

Efficacy of point-of-entry copper--silver ionisation system in eradicating Legionella pneumophila in a tropical tertiary care hospital: implications for hospitals contaminated with Legionella in both hot and cold water.

A medical centre in Southern Taiwan experienced an outbreak of nosocomial Legionnaires' disease, with the water distribution system thought to be the source of the infection. Even after two superheats and flush, the rate of Legionella positivity in distal sites in hospital wards and intensive care units (ICUs) was 14% and 66%, respectively. Copper-silver ionisation was therefore implemented in an attempt to control Legionella colonisation in both hot- and cold-water systems. Environmental cultures and ion concentration testing were performed to evaluate the efficacy of ionisation. When the system was activated, no significant change in rate of Legionella positivity in the hospital wards (20% vs baseline of 30%) and ICUs (28% vs baseline of 34%) of the test buildings over a three-month period was found, although all Legionella positivity rates were below 30%, an arbitrary target for Legionnaires' disease prevention. When ion concentrations were increased from month 4 to month 7, however, the rate of Legionella positivity decreased significantly to 5% (mean) in hospital wards (P=0.037) and 16% (mean) in ICUs (P=0.037). Legionella positivity was further reduced to 0% in hospital wards and 5% (mean) in ICUs while 50% sites were still positive for Legionella in a control building. Although Legionella was not completely eradicated during the study period, no culture- or urine-confirmed hospital-acquired Legionnaires' disease was reported. Ionisation was effective in controlling Legionella for both hot and cold water, and may be an attractive alternative as a point-of-entry systematic disinfection solution for Legionella.

Parathyroidectomy reduces 25-hydroxyvitamin D3-1 alpha-hydroxylase activity in the hypocalcemic vitamin D-deficient chick.

To test the hypothesis that in the vitamin D-deficient state the activity of 25-hydroxyvitamin D3-1 alpha-hydroxylase (25-OHD3-1 alpha-hydroxylase) is modulated by parathyroid hormone and the plasma concentration of phosphate only in the presence of small amounts of 1,25-dihydroxyvitamin D3 (or some other metabolite of vitamin D), we measured the activity of this enzyme 24 h after parathyroidectomy (PTX) in frankly hypocalcemic, vitamin D-deficient chicks that were not supplemented with vitamin D or one of its metabolites. The otherwise predictable complications of PTX in this metabolic setting (hypocalcemia of increasing severity, tetany, moribundity, and death) were prevented by continuous intravenous administration of calcium (as a solution of calcium chloride/calcium gluconate 1:1) through a catheter in the external jugular vein placed at the time of PTX. The findings were as follows: (a) The activity of 25-OHD3-1 alpha-hydroxylase was significantly less in the parathyroidectomized group than in the sham-operated control chicks (P less than 0.001). (b) The reductive effect of PTX on the activity of this enzyme was significantly attenuated when hypophosphatemia was increased in severity by administration of glucose. (c) In the post-PTX state the activity of 25-OHD3-1 alpha-hydroxylase and plasma concentration of phosphate were significantly, inversely related (P less than 0.001). (d) In the sham-operated control group the activity of this enzyme and the plasma concentration of phosphate were not significantly correlated. These findings indicate that in the vitamin D-deficient state, both circulating parathyroid hormone and the plasma concentration of phosphate can significantly modulate the activity of 25-OHD3-1 alpha-hydroxylase in the absence of vitamin D or its metabolites. The findings also suggest that in the vitamin D-deficient state the plasma concentration of phosphate modulates the activity of this enzyme only when the concentration of circulating parathyroid hormone is not increased.

Vitamin D status regulates 25-hydroxyvitamin D3-1 alpha-hydroxylase and its responsiveness to parathyroid hormone in the chick.

We asked this question: Under normal or near-normal metabolic conditions, does the prevailing normal or near-normal vitamin D status dampen the activity of 25-hydroxyvitamin-D3-1 alpha-hydroxylase (1 alpha-hydroxylase) such that it determines not only its "basal" activity but also its responsiveness to stimulation by increased circulating concentrations of parathyroid hormone (PTH)? To answer this question, we measured the activity of 1 alpha-hydroxylase in chicks, with and without administration of PTH, immediately before and during deprivation of vitamin D. Before deprivation of vitamin D, 1 alpha-hydroxylase activity increased only slightly with administration of PTH. With deprivation of vitamin D for 5 and 10 d, while the plasma concentrations of calcium and phosphorus persisted normal and unchanged, 1 alpha-hydroxylase activity not only increased progressively but also became sharply and increasingly responsive to stimulation by administration of PTH. But after 15 d of vitamin D deprivation, and the supervention of hypocalcemia, 1 alpha-hydroxylase activity was not further increased by the administration of PTH. With deprivation of vitamin D, the progressive increase in 1 alpha-hydroxylase correlated inversely with circulating levels of 1,25-dihydroxyvitamin D (1,25-[OH]2D), and the decreasing calcemic response to PTH correlated inversely with the responsiveness of 1 alpha-hydroxylase to PTH (in chicks deprived of vitamin D for 1-10 d). These results demonstrate that: under normal metabolic conditions, the normal vitamin D status regulates the activity of 1 alpha-hydroxylase so as to dampen both its "basal" activity and its responsiveness to stimulation by PTH; and vitamin D deprivation insufficient to cause hypocalcemia enhances both the "basal" activity of 1 alpha-hydroxylase and its responsiveness to stimulation by PTH. The results suggest that the normal dampening of 1 alpha-hydroxylase and both of the demonstrated enhancements of its activity are mediated by normal and reduced levels of circulating 1,25-(OH)2D, respectively. The finding that PTH fails to further stimulate 1 alpha-hydroxylase when vitamin D deprivation is sufficient in duration to cause hypocalcemia confirms the findings of other investigators and again demonstrates that observations made during abnormal metabolic circumstances may bear little on the physiologic regulation of 1 alpha-hydroxylase under normal or near-normal metabolic circumstances.

Accelerated neutrophil apoptosis in the acquired immunodeficiency syndrome.

Neutrophil (PMNL) function defects occur as a consequence of HIV infection. This study examined PMNL apoptosis in patients with the acquired immunodeficiency syndrome (AIDS) to determine if accelerated apoptosis contributes to impaired function. PMNL were isolated from 10 HIV-infected patients with CD4+ lymphocyte counts < 200/mm3 without signs of active infection and 7 healthy volunteers. PMNL were stained with acridine orange and ethidium bromide after 0, 3, 6, and 18 h in culture, and examined for the morphologic changes of apoptosis and viability by fluorescent microscopy. Apoptosis was also demonstrated by electron microscopy, flow cytometry, and DNA gel electrophoresis. Apoptosis was minimal at 0 h, but PMNL from AIDS patients exhibited significantly greater apoptosis than controls at 3 h (22.5+/-11.5 vs. 8.9+/-6.9%, P = 0.015), 6 h (38.1+/-14.2 vs. 18.1+/-4.5%, P = 0.003), and 18 h (71.3+/-19.0 vs. 38.8+/-16.7%, P = 0.002). Viabilities were > or = 88.0% for both groups from 0-6 h, but by 18 h viability was significantly decreased for the HIV group (58.8+/-12.4 vs. 83.5+/-10.4%, P = 0.001) due to an increase in non-viable apoptotic cells. Incubation with serum from AIDS patients had no effect on control PMNL, and incubation with control serum did not reduce the rate of apoptosis of PMNL from AIDS patients. Incubation with granulocyte colony-stimulating factor (G-CSF) in vitro significantly decreased apoptosis for PMNL from AIDS patients. PMNL from patients with AIDS exhibit markedly accelerated apoptosis ex vivo. In vivo, apoptosis and functional impairment of PMNL may contribute to the risk of secondary infections, and cytokine therapy may be of potential clinical benefit in this circumstance.

Eosinophilic meningitis caused by Angiostrongylus cantonensis: report of 17 cases.

PURPOSE: To describe two outbreaks of Angiostrongylus cantonensis infection that occurred in Kaohsiung, Taiwan, during 1998 and 1999, and to characterize the source of the outbreaks and the clinical manifestations of the disease. SUBJECTS AND METHODS: We performed a retrospective cohort study among Thai laborers with eosinophilic meningitis who ate raw snails (Ampullarium canaliculatus), as well as an environmental surveillance of larvae in snails. RESULTS: We enrolled 17 Thai laborers in whom severe headache and eosinophilia developed within 4 to 23 days after eating raw snails. Twelve (71%) developed eosinophilic meningitis. Third-stage larvae were found in the cerebrospinal fluids of 2 patients and in all 12 tested snails. Specific antibodies to A. cantonensis were detected in serum from 16 of the patients and in cerebrospinal fluid from 5 of the patients. Central nervous system manifestations included headache (n = 17 [100%]), fever (n = 11 [65%]), Brudzinski's sign/stiff neck (n = 11 [65%]), hyperesthesia (n = 3 [18%]), cranial nerve palsy (n = 2 [12%]), diplopia (n = 2 [12%]), and ataxia (n = 1 [6%]). Laboratory findings included peripheral eosinophilia (n = 15 [88%]) and cerebrospinal fluid eosinophilia (n = 12 [71%]); elevated immunoglobulin (Ig) E levels (n = 13 [100%]); and transient increases in white blood cell count (n = 7 [41%]) and in serum levels of creatine kinase (n = 7 [41%]), transaminase (n = 3 [18%]), and lactate dehydrogenase (n = 2 [12%]). The severity of illness and eosinophilia were correlated with the number of ingested snails. Meningeal and basal ganglion enhancement was noted on magnetic resonance imaging in several patients. Treatment with mebendazole combined with glucocorticosteroids appeared to shorten the course of the infection, but not the number of relapses. The eosinophil count fell to normal within 3 months, but IgE levels remained elevated for as long as 6 months. All patients recovered with minimal neurologic sequelae. CONCLUSION: Eosinophilic meningitis caused by A. cantonensis should be considered in patients who have headache or central nervous system manifestations after eating raw snails.

Pigmentary abnormalities of the macula in rhesus monkeys: clinical observations.

In a survey of 546 rhesus monkeys of various ages, 6.1% of the animals showed ophthalmoscopically visible hypopigmented spots in their maculas. There was a statistically significant correlation between the age of the animal and the degree of hypopigmentation. Electroretinographic responses and visually evoked potentials were evaluated in a selected group of monkeys with and without hypopigmented macular spots. No significant change in retinal function as a result of the macular abnormalities could be detected.

Metabolic acidosis in the vitamin D-deficient chick.

In vitamin D-deficient chicks raised from age 1 day on a vitamin D-deficient diet, hyperchloremic metabolic acidosis accurred at 3 wk and persisted. Within 24 hr of administration of vitamin D, the acidosis and hypocalcemia were attentuated; during the subsequent 72 hr the severity of the metabolic acidosis but not that of the hypocalcemia was further attenuated. That further attenuation occurred despite hypocalcemia of unchanging severity and presumed continuing secondary hyperparathyroidism suggests the possibility that vitamin D deficiency may be a requirement for the expression of metabolic acidosis. Since in vitro and in vivo studies suggest that subphysiologic values of media and blood pH, respectively, are attended by reduced production of 1,25-(OH2D3, the most biologically active vitamin D metabolite known, the occurrence of acidosis in vitamin D deficiency may compound its metabolic consequences. The possible effects of acidosis must be considered in interpreting results of investigations of vitamin D metabolism in vitamin-D-deficient chicks.

Chronic intracerebroventricular administration of morphine down-regulates spinal adenosine A1 receptors in rats.

Previous studies from our laboratory have shown that systemic chronic morphine treatment causes down-regulation of spinal adenosine A1 receptors in rats. In this study, we further investigated whether supraspinal morphine treatment causes this effect. Adult male Sprague-Dawley rats were rendered tolerant to morphine by multiple intracerebroventricular (i.c.v.) injections for 2 or 4 days. Adenosine A1 receptor binding activities were measured with [3H]cyclohexyladenosine in the spinal cord and midbrain. A significant decrease in [3H]cyclohexyladenosine binding was found in the spinal cord but not in the midbrain region after 2 or 4 days of chronic i.c.v. morphine treatment. A decrease in the number of binding sites (Bmax) with no change in the affinity (Kd) of the ligand for the adenosine A1 receptor was observed. These results suggest that supraspinal morphine administration could cause the down-regulation of spinal adenosine A1 receptors and this may play a role in the mechanism of morphine tolerance.

Comparative study of the efficacy and safety of valaciclovir versus acyclovir in the treatment of herpes zoster.

Acyclovir, a specific and selective inhibitor of the replication of Herpesviridae family, has well-documented efficacy and tolerability in the treatment of herpes zoster. Its limited oral bioavailability and short half-life, however, necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, could be rapidly converted to acyclovir after oral administration, resulting in a three- to five-fold increase in acyclovir bioavailability compared with oral acyclovir in humans. Valaciclovir allows less frequent dosing and maintains the safety profiles of the parent drug. During the period from October 1996 through May 1998, a randomized, prospective study was performed in the Kaohsiung Veterans General Hospital to compare the safety and efficacy of valaciclovir with acyclovir in the treatment of herpes zoster in Taiwanese patients. Patients presenting with herpes zoster within 72 h after the onset of rash were enrolled and randomized to receive one of the following treatments: 1000 mg valaciclovir three times daily for 7 days or acyclovir 800 mg five times daily for 7 days. Patients were followed up for 29 days beginning with the start of therapy. A total of 57 patients were enrolled and randomized to receive valaciclovir (n = 32) or acyclovir (n = 25). Five patients in the valaciclovir group and three in the acyclovir group did not complete the study. The intent-to-treat analysis (57 patients) showed that valaciclovir significantly accelerated the resolution of herpes zoster-associated pain compared with acyclovir; on day 29, the valaciclovir group was 23% superior to the acyclovir group. There was no clinically significant difference in the nature, frequency or severity of adverse events between these two groups, although one and three adverse events were reported in the acyclovir and valaciclovir group, respectively. Thus, we conclude that in the management of herpes zoster, valaciclovir accelerates the resolution of pain and offers a simpler dosing, and maintains the favorable safety profile of acyclovir.

Radiation-induced hearing impairment in patients treated for malignant parotid tumor.

Radiation-induced hearing loss was evaluated in 21 patients with unilateral malignant parotid tumors treated with surgery and radiotherapy. The contralateral ear was used as a control. Eight patients (38%) were found to have a reduction in static compliance of the tympanic membrane (type B tympanogram) in the irradiated ear. By audiometry, significant hearing loss was found in 9 patients (43%). These hearing losses were mainly sensorineural, as shown by a similar reduction in both air and bone conduction, although mixed-type hearing loss existed in some patients. A statistically significant difference in incidence of 67% versus 0% (p = .0085) was noted for patients with a cochlear dose of greater than or equal to 60 Gy, in comparison to those receiving doses of less than 60 Gy. A type B tympanogram was also found to be a prognostic factor for significant sensorineural hearing loss. Patients with type B tympanograms had a much higher incidence of significant sensorineural hearing loss than those with type A tympanograms (88% versus 15%, p = .02). This study clearly shows that radiotherapy can induce significant hearing impairment, especially when the cochlear doses are higher than 60 Gy.