Effect of climate therapy at Gran Canaria on vitamin D production, blood glucose and lipids in patients with psoriasis

Background Climate therapy (heliotherapy) of psoriasis is an effective and natural treatment. Ultraviolet radiation (UVB) from the sun improves psoriasis and induces vitamin D₃ synthesis. Objective The aim of the study was to investigate the effect of climate therapy on vitamin D₃ synthesis, blood glucose, lipids and vitamin B12 in psoriasis patients. Methods Twenty Caucasian patients (6 women and 14 men; mean age, 47.2 years; range, 24–65) with moderate to severe psoriasis [mean Psoriasis Area and Severity Index (PASI) score 9.8; range, 3.8–18.8] received climate therapy at the Gran Canarias for 3 weeks. Blood samples were drawn before and after 15 days of sun exposure. In addition, the patients’ individual skin UV doses based on UV measurements were estimated. Results Sun exposure for 15 days lead to a 72.8% (± 18.0 SD) reduction in the PASI score in psoriasis patients. Although no direct correlation was observed between PASI score improvement and UVB dose, the sun exposure improved the vitamin D, lipid and carbohydrate status of the patients. The serum concentrations of 25‐hydroxyvitamin D [25(OH)D] increased from 57.2 ± 14.9 nmol/L before therapy to 104.5 ± 15.8 nmol/L (P < 0.0001) after 15 days of sun exposure; the serum levels of 1,25‐dihydroxyvitamin D [1,25(OH)₂D] increased from 146.5 ± 42.0 to 182.7 ± 59.1 pmol/L (P = 0.01); the ratio of low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol decreased from 2.4 to 1.9 (P < 0.001); and the haemoglobin A₁c (HbA₁c) levels decreased from 5.6 ± 1.7% to 5.1 ± 0.3% (P < 0.0001). Conclusion Climate therapy with sun exposure had a positive effect on psoriasis, vitamin D production, lipid and carbohydrate status.     

Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18

Platelets bound to thrombogenic surfaces have been shown to support activation-dependent firm adhesion of neutrophils in flow following selectin-mediated tethering and rolling. The specific receptor(s) responsible for mediating adhesion-strengthening interactions between neutrophils and platelets has not previously been identified. Furthermore, the ability of adherent platelets to support the migration of bound neutrophils has not been tested. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte binding in vascular shear flow and emigration at thrombogenic sites. Our results demonstrate that the beta 2-integrin Mac-1 (CD11b/CD18) is required for both firm attachment to and transmigration of neutrophils across surface-adherent platelets. In flow assays, neutrophils from patients with leukocyte adhesion deficiency-1 (LAD-I), which lack beta 2-integrin receptors, formed P-selectin-mediated rolling interactions, but were unable to develop firm adhesion to activated platelets, in contrast to healthy neutrophils, which developed firm adhesion within 5 to 30 seconds after initiation of rolling. Furthermore, the adhesion-strengthening interaction observed for healthy neutrophils could be specifically inhibited by monoclonal antibodies (mAbs) to Mac-1, but not to lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) or intercellular adhesion molecule-2 (ICAM-2; CD102). Further evidence for a beta 2-integrin-dependent neutrophil/platelet interaction is demonstrated by the complete inhibition of interleukin (IL)-8-induced neutrophil transmigration across platelets bound to fibronectin-coated polycarbonate filters by mAbs to Mac-1. Thus, Mac-1 is required for firm adhesion of neutrophils to activated, adherent platelets and may play an important role in promoting neutrophil accumulation on and migration across platelets deposited at sites of vascular injury.     

PRIMARY CEREBRAL MALIGNANT MELANOMA: AN UNUSUAL CAUSE OF DYSPRAXIA

SUMMARY Primary intracranial melanomas are rare and occur mainly in young adults. Originating from leptomeningeal melanoblasts and extending into the parenchyma, the tumours closely resemble meningiomas, from which they are radiologically difficult to distinguish despite progress in neuroimaging. Definitive diagnosis is usually made on histopathological examination, though confirmed only after post-mortem examination in some cases. Prolonged disease-free periods, and in rare cases long-term survival, are possible following successful total surgical excision. This case presented with typical clinical features but, at 79 years old, an unusual age.     

Giant cell tumors of bone: treatment with radiation therapy

Records of 15 patients with giant cell tumor of bone treated with radiation therapy over a 35-year period were reviewed; ten patients for whom follow-up information was available constituted the study group. One patient was treated by means of orthovoltage equipment only, a second, by both orthovoltage and megavoltage equipment (cobalt 60). The remaining eight were all treated with megavoltage to doses of 40-52 Gy in 24-30 fractions. Seven patients are alive without disease, with an average survival of 192 months (range, 48-360 months). Three patients died of uncontrolled local and distant disease (average survival, 52 months; range, 23-99 months): one with metastasis in the lungs at time of treatment and two after treatment. Although incidence of lung metastasis appears high, it may be due to patient selection because chemotherapy had failed in all three. Complications from irradiation in one surviving patient required surgical closure of a dural fistula 19 years after treatment. No radiation-induced sarcomatous transformations of controlled tumors were noted. These data suggest that giant cell tumor of bone can be well controlled by radiation therapy. Megavoltage irradiation should be considered in treating local disease not easily controlled by surgery in the axial skeleton. Complications are minimal, and normal function can be preserved in the treated areas.     

Resistance to 6-thioguanine in mismatch repair-deficient human cancer cell lines correlates with an increase in induced mutations at the HPRT locus

Although the resistance to the cytotoxic response of certain DNA damaging agents has been well characterized in cells deficient in mismatch repair, little is known about how such resistance affects mutagenesis. Using human cancer cell lines defective in mismatch repair (MMR) and complementary cell lines in which the MMR defects were corrected by chromosome transfer, we present the cytotoxic effect and the mutagenic response at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus following exposure to the chemotherapeutic agent, 6-thioguanine (6-TG). Upon exposure to 6-TG, there was a differential cytotoxic response. The MMR-deficient cells were resistant to 6-TG exposure up to 5 microM, whereas the MMR-proficient cell lines were significantly more sensitive at the same levels of exposure. Furthermore, the mutagenic response at HPRT induced by 6-TG was substantially increased in the MMR-deficient lines relative to the MMR- proficient cell lines. These findings support the notion that cytotoxicity to 6-TG is mediated through functional MMR and that resistance to the cytotoxic effects of 6-TG is directly associated with an increase in induced mutations in MMR-defective cells. These data suggest that the use of 6-TG as a chemotherapeutic agent may result in the selection of MMR-defective cells, thereby predisposing the patient to an increased risk for developing secondary tumors.      

Cefazolin as empiric therapy in hemodialysis-related infections: efficacy and blood concentrations

Concern about the increasing incidence of vancomycin-resistant organisms has tempered the enthusiasm for indiscriminate vancomycin use. Cefazolin has an antibacterial activity profile similar to vancomycin against most pathogens encountered in the hemodialysis (HD) population. We evaluated the clinical efficacy and serum concentrations that were achieved during empiric cefazolin use. Fifteen consecutive HD patients (five, conventional HD; five, high-efficiency HD; and five, high-flux HD) with suspected or documented infections warranting antibiotic intervention, including access-related, respiratory tract, urinary tract, or wound infections, were enrolled. Each patient received intravenous cefazolin (20 mg/kg actual body weight rounded to the nearest 500-mg increment [range, 1 to 2 g]) after each dialysis treatment for at least three doses. Cefazolin concentrations were obtained before and immediately after the next three consecutive dialysis treatments. Thirteen patients were evaluated for efficacy and all 15 were evaluated for toxicity and cefazolin blood concentrations. All patients showed at least a short-term (3-week) clinical resolution of infection with cefazolin treatment. No central nervous system toxicities were noted and no other adverse events were expressed by the patients during the course of cefazolin treatment. Predialysis cefazolin concentrations, as determined by high-performance liquid chromatography, were 70.2 +/- 42.7 (conventional HD), 45.6 +/- 18.9 (high-efficiency HD), and 41.6 +/- 23.9 mg/L (high-flux HD) over the three dialysis sessions. Cefazolin at doses of approximately 20 mg/kg administered post-HD appears to be a safe and effective empiric therapy and yields predialysis cefazolin concentrations of 2.5 times or greater than those considered to be the minimum inhibitory concentration breakpoint (16 mg/L) for susceptible organisms. These data support the broader use of cefazolin for empiric treatment in the HD population, allowing vancomycin to be reserved for confirmed resistant organisms.     

Newborn tongue-tie: prevalence and effect on breast-feeding

OBJECTIVE: The purposes of this study were: (1) to determine whether breast-fed infants with tongue-tie have decreased rates of breast-feeding at 1 week and 1 month of age, (2) to determine the prevalence of tongue-tie, and (3) to test the usefulness of the Assessment Tool for Lingual Frenulum Function (ATLFF) in assessing the severity of tongue-tie in breast-feeding newborns. METHODS: A case-control design was used. All infants in the Regions Hospital newborn nursery were examined for tongue-tie. Tongue-tied babies were examined using the ATLFF. Two breast-feeding babies with normal tongues were identified and matched for each case. Mothers were interviewed when the babies were 1 week and 1 month old. RESULTS: The prevalence of tongue-tie was 4.2%. Forty-nine tongue-tied and 98 control infants were enrolled. Tongue-tied babies were 3 times as likely as control babies to be bottle fed only at 1 week [risk ratio (RR), 3.11; 95% confidence interval (CI), 1.21, 8.03) By 1 month, tongue-tied babies were as likely as controls to be bottle fed only. (RR, 1.00; 95% CI, 0.55, 1.82) Twelve of the tongue-tied infants had ATLFF scores of "Perfect," none had scores of "Acceptable," and 6 had scores of "Function Impaired." The remaining 31 infants had scores that fell into none of these categories. CONCLUSIONS: Tongue-tie is a relatively common condition in newborns. Affected infants are significantly more likely to be exclusively bottle-fed by 1 week of age. The ATLFF was not a useful tool to identify which tongue-tied infants are at risk for breast-feeding problems.     

Maternal postpartum health care utilization and the effect of Minnesota early discharge legislation

PURPOSE: To describe maternal postdischarge follow-up and health care utilization in the context of Minnesota's early discharge legislation, which mandates coverage for a home visit for a mother and baby who voluntarily leave the hospital early. METHODS: Claims data from a large managed care organization were used to identify 22,944 women giving birth from January 1995 through February 1999. Study variables included home or clinic visits within 1 week of discharge (early follow-up), readmissions within 1 month of discharge, and urgent care or emergency department visits within 2 months of discharge. RESULTS: After enactment of Minnesota's legislation, the percentage of mothers with short stays decreased from 52% to 16% for vaginal births and from 87% to 63% for cesarean births (P =.001). Overall, 33% of mothers with vaginal births and 40% with cesarean births had early home or clinic follow-up (P =.001). Mothers who stayed 0 or 1 hospital days after vaginal births were more likely to have early follow-up than those with longer stays (37% vs 32%, P =.01). However, mothers who stayed 2 or 3 days after cesarean birth were no more likely to have early follow-up than mothers who stayed 4 or more days (39% vs 42%, P =.08). Rates of early follow-up were significantly higher after enactment of Minnesota's legislation, regardless of length of stay. CONCLUSIONS: Implementation of Minnesota's early discharge legislation corresponded with significantly increased lengths of stay and an increase in the percentage of mothers who received early follow-up visits. However the majority of mothers with short stays continued to lack early follow-up.     

ATG plus corticosteroid therapy for acute graft-versus-host disease: predictors of response and survival

 Innovative treatment strategies for acute graft-versus-host disease (aGVHD) have not replaced corticosteroids as the primary therapy. We retrospectively reviewed 74 patients who received equine antithymocyte globulin (ATG) in addition to corticosteroids as therapy for GVHD, 21 who received primary therapy and 53 who received ATG after progressing or failing to improve with corticosteroids alone. The groups were comparable in clinical characteristics and in timing and severity of GVHD. After primary therapy with ATG 67% of patients' GVHD symptoms were stable or improved by 28 days versus 56% in those receiving secondary ATG (p=0.57). In univariate analysis the absence of multiple organ, GI, and liver aGVHD and a clinical stage score ≤4 were predictive of a favorable response, while in a multivariate logistic regression model only a clinical stage score ≤4 was independently associated with a favorable response (odds ratio 0.08, 95% CI 0.02–0.32, p=0.003). ATG response rates and 6-month survival (38 vs. 40%, p=0.89) were similar following primary and secondary ATG. Patients stable or improved 28 days after ATG therapy had a significantly better 6-month survival than those whose aGVHD had progressed (50 vs. 30%, p=0.02). Further study is required to assess whether some initial presentations of aGVHD would predictably fail corticosteroid therapy and may thus suggest a role for ATG in the primary management of aGVHD. For this determination, formal prospective comparative trials are needed. Received: 11 March 1997/Accepted: 16 June 1997     

Wilms tumor in children: abdominal CT and US evaluation

Computed tomographic (CT) scans and sonograms of 13 children with Wilms tumor were reviewed to determine the ability of each imaging test to characterize the tumor and determine its extent. The findings of this review were correlated with diagnoses based on surgical and pathologic evidence. Tumor necrosis and a pseudocapsule were detected more often using CT scans than sonograms. CT scanning also was more sensitive in assessing perinephric extension, lymph node involvement, and bilateral tumors. Overall, CT scans allowed better determination of the extent of a suspected tumor, enabling correct diagnosis in 77% of patients, while US study was correct in only 23%.