Efficacy and adverse effects of intravenous lignocaine therapy in fibromyalgia syndrome

Background

To investigate the effects of intravenous lignocaine infusions (IV lignocaine) in fibromyalgia.

Methods

Prospective study of the adverse effects of IV lignocaine in 106 patients with fibromyalgia; retrospective questionnaire study of the efficacy of IV lignocaine in 50 patients with fibromyalgia.

Results

Prospective study: Two major (pulmonary oedema and supraventricular tachycardia) and 42 minor side-effects were reported. None had long-term sequelae. The commonest was hypotension (17 cases). Retrospective study: Pain and a range of psychosocial measures (on single 11-point scales) improved significantly after treatment. There was no effect of the treatment on work status. The average duration of pain relief after the 6-day course of treatment was 11.5 ± 6.5 weeks.

Conclusions

Intravenous lignocaine appears to be both safe and of benefit in improving pain and quality of life for patients with fibromyalgia. This needs to be confirmed in prospective randomised controlled trials.

     

Plant sterols: factors affecting their efficacy and safety as functional food ingredients

Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8–1.0 g of equivalents per day) and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL) cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status.     

GABA content in the retina of pigmented and albino rats

Reduction of the melanin precursor DOPA associated with albinism leads to spatiotemporal disturbances in retinal neurogenesis and thus seems to be responsible for numerous neuronal alterations found in albino retinae. To investigate whether these cellular alterations are reflected in retinal neurotransmitter concentrations we compared the levels of GABA and glutamate in the retina of adult pigmented Long Evans and albino Wistar rats using reversed phase-liquid chromatography (RP-HPLC). When normalized to retinal weight, GABA levels showed a statistically insignificant trend to be lower and glutamate values to be higher in albinos than in pigmented animals. The ratio of glutamate to GABA was significantly higher in albino than in pigmented retinae. As numerous studies have shown that the balance between GABA and glutamate plays a crucial role for establishing direction selectivity, these results are discussed in relation to direction selectivity and defects in the optokinetic system of albinos.     

GABA-immunoreactive starburst amacrine cells in pigmented and albino rats

In this study we tested whether the critical anatomical substrate for retinal direction selectivity is altered in albino mammals. We used dual immunostaining for GABA and choline acetyltransferase and quantitatively analyzed the number of double-labelled starburst amacrine cells in wild-type and albino rats. In albino rats, the percentage of ON-amacrine cells with high GABA content was significantly lower than in pigmented animals. OFF-amacrines did not significantly differ between the two rat strains. Thus, the decreased GABA content in ON-amacrine cells could reflect an altered neuronal substrate for retinal direction selectivity. These results are discussed in relation to the optokinetic deficits described in albino mammals.     

Evidence of 5-lipoxygenase overexpression in the skin of patients with systemic sclerosis: a newly identified pathway to skin inflammation in systemic sclerosis

OBJECTIVE: Leukotrienes are a family of arachidonic acid derivatives with potent proinflammatory and profibrotic properties, and 5-lipoxygenase (5-LOX) catalyzes two key steps in the leukotriene biosynthetic pathway. Since inflammatory cell infiltrates and excessive fibrosis are hallmarks of systemic sclerosis (SSc) skin lesions, we undertook the present study to investigate the expression of 5-LOX in skin biopsy specimens from patients with SSc. METHODS: Expression of 5-LOX in skin sections from 10 SSc patients and 8 healthy controls was examined by in situ hybridization with specific riboprobes and by immunohistochemistry analysis with 5-LOX monoclonal antibodies. Synthesis of 5-LOX by cultured dermal fibroblasts from 7 patients with SSc and 4 controls was measured by fluorescence-activated cell sorter analysis. In addition, concentrations of leukotriene B4 (LTB4) and LTE4 in fibroblast supernatants after stimulation were determined using enzyme immunoassays. RESULTS: Expression of 5-LOX was found in all skin sections from SSc patients as well as from controls. However, the number and percentage of 5-LOX-positive cells were significantly higher in SSc skin sections compared with control sections. Expression of 5-LOX was seen in cells within perivascular inflammatory infiltrates as well as in fibroblasts throughout the skin. The experiments with cultured skin fibroblasts revealed that 5-LOX was constitutively expressed in these cells, which resulted in the production of leukotrienes after cell stimulation. Whereas no difference was found for LTE4, SSc fibroblasts produced significantly higher amounts of LTB4 after stimulation, compared with healthy control fibroblasts. CONCLUSION: The results of this study suggest that the 5-LOX pathway may be of significance in the pathogenesis of SSc and may represent a target for new treatment strategies.     

Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity

For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.      

Early detection of abnormalities in partial epilepsy using magnetic resonance

The incidence of brain abnormalities determined by magnetic resonance in 30 consecutive children presenting with intractable complex partial seizures is reported. Images were optimised to visualise the hippocampus and cortical grey matter. Abnormalities of the hippocampus or temporal lobe were seen in all 19 children with clinical features of temporal lobe epilepsy and in six of the seven children with clinically unlocalised epilepsy. By contrast, in the four children with a clinical diagnosis of extratemporal epilepsy, no temporal or hippocampal abnormalities were seen. Generalised cortical abnormalities of uncertain significance were found in a total of 14 children from all groups. The identification of focal brain abnormalities using optimised magnetic resonance imaging enables early non-invasive assessment of children with intractable seizure disorders and the identification of patients for whom epilepsy surgery may be appropriate. It may also lead to a better understanding of the structural basis of intractable epilepsy, and thereby contribute to early treatment decisions.     

Calcium, phosphorus, and magnesium concentrations in plasma during first week of life and their relation to type of milk feed

Serial changes in plasma levels of calcium, phosphorus, magnesium, alkaline phosphatase, and total proteins have been investigated in 138 healthy, term Caucasian infants. Blood samples were obtained for each infant from cord blood and on day 1 and day 6. The infants were studied in three groups according to whether they were breast fed, received 'Ostermilk No. 1' or 'Cow and Gate V' formulas. Levels of calcium, phosphorus, magnesium, alkaline phosphatase, and total proteins did not differ between the groups at birth or on day 1. By day 6 calcium levels were higher and phosphorus levels lower in the breast-fed infants compared with either of the artificially-fed groups. Phosphorus levels were lower in the V Formula group compared with the Ostermilk group but the mean calcium levels of these two groups did not differ significantly. However, only 2-8% of the V Formula group developed hypocalcaemia compared with 18-2% of the Ostermilk group. The only infant developing clinical tetany belonged to the group fed Ostermilk. Evidence is also given which suggests that those infants with low calcium levels on day 1 who were fed the high-solute milk tended to show a fall in calcium by day 6. This did not apply to the two other groups. It is concluded that the use of adapted cows' milk preparations for infant feeding should lead to a reduction in the incidence of neonatal tetany.