Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti-cancer drug treatment.

Therapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport. It is with anti-cancer drugs that major progress has been made in the study of partition between the largest cellular blood compartment, i.e., erythrocytes, and the plasma compartment. The aim of the present review is to detail the progress made in predicting what a drug does in the body, i.e., pharmacodynamics including toxicity and plasma and/or red blood cell concentration monitoring. Furthermore, techniques generally used in anti-cancer drug monitoring are highlighted. Data for complex Bayesian statistical approaches and population kinetics studies are beyond the scope of this review, since this is generally limited to the plasma compartment only.     

Treatment of facial spasm with botulin A toxin

The authors use injections of botulinum A toxin in treatment of facial spasms. 105 patients (70 patients with blepharospasm, 35 patients with hemispasm) were treated during 4 years. The toxin Wisconsin relieved spasms for an average of 10 weeks. Local complications such as ptosis and diplopia appeared in less than 1/5 of the cases. No general complications were observed. Repeated treatments are necessary. The authors noted a decrease of lacrimal secretion on the treated side in hemifacial spasm and concluded that botulinum A toxin injections could be used as a treatment of epiphora.     

First evidence of fatal hantavirus nephropathy in India, mimicking leptospirosis.

Sir, In a recent Indian serosurvey [1], it was announced that ‘noreports of hantavirus infections in humans from India existed[before 2005]’. We wish to point out that serologicaland clinical evidence of hantavirus infection in India was alreadywell documented before 2005. From 1998 on, we screened leptospirosis-suspected cases in Indiafor the only known cosmopolitan hantavirus serotype, Seoul virus(SEOV). Wild rats are the reservoir     

Indications and role of surgery in painful dysfunction syndromes of the masticatory apparatus]

Among the numerous causes of facial neuralgias, the painful dysfunction syndrome of the manducatory apparatus corresponds to a frequent etiology whose thorough study carried out by a multidisciplinary team over about 500 cases allowed their splitting into several evolutive clinical forms. At present, a number of these forms which are particularly painful, require a disk surgery (dislocation reduction, perforation suture, etc.) and if necessary an articular facet surgery (modelling condylectomy, surfacing, etc.). This study specifies the indications and prognosis for these surgical operations.     

Childhood precursors of age at first intercourse for females

Age at first intercourse for a sample of adult white women using variables measured during childhood is predicted. Childhood predictors were measured at birth, and ages 5 and 9–11, using existing public-use data on the women. Median age at first intercourse for the sample was 17.5 years. Early family predictors, early developmental characteristics, and temperamental characteristics during childhood together could predict about a fourth of the variance in age at first intercourse. The strongest predictors were motor skills and nightmares at age 5, church attendance with family at age 9, and domineering and mature personality at age 9.This research was supported by grants R01-HD23454 and P30-HD05798 from the National Institute of Child Health and Human Development. An earlier version of this paper was presented at the annual meetings of the Population Association of America, Denver, Colorado, April 30–May 2, 1992.     

Erythromycin prophylaxis for Legionnaire's disease in immunosuppressed patients in a contaminated hospital environment

Between January 1 and June 30, 1983, immunosuppressive drugs were administered in 20 renal transplant recipients undergoing 23 rejection episodes and in 3 patients with renal failure secondary to systemic disease. Legionella pneumophila, serogroup 1, pneumonia was diagnosed on 12/26 (47%) occasions. In an attempt to decrease this high rate, a program of erythromycin prophylaxis was instituted for every new patient who received immunosuppressive chemotherapy until eradication of the organism from the water supply could be realized. From July 1, 1983 to April 30, 1984, erythromycin prophylaxis (1.5-3 g/day by mouth) was administered during 39 episodes of high-dose immunosuppression (20 kidney graft recipients and 4 patients with systemic diseases); no cases of Legionnaire's disease were recorded. During the same period, erythromycin prophylaxis was withheld from 9 other high-dose immunosuppression episodes (7 kidney graft recipients and one patient with sarcoidosis); 5 cases of Legionnaire's disease occurred (56%) in this group. We conclude that erythromycin effectively protects immunocompromised patients in an environment contaminated with L pneumophila.     

Natural history of parathyroid function and calcium metabolism after kidney transplantation: a single-centre study.

BACKGROUND: The natural history of parathyroid function after successful renal transplantation (RT) and the factors predisposing to persistent hyperparathyroidism (HPT) are not well established. A better knowledge of these data may be helpful in the development of algorithms for optimal surveillance and treatment of HPT after successful RT. Our aim was to evaluate the post-transplant natural history of parathyroid function and calcium metabolism in patients with a functional renal graft and to identify risk factors for persistent HPT. METHODS: Charts of 1165 allograft kidney recipients transplanted between 1989 and 2000 were reviewed. Patients with an intact parathyroid hormone (iPTH) level available at the time of transplantation were identified. The charts of the latter patients were checked for a variety of demographic and clinical data, and all determinations of the iPTH concentration available since transplantation were recorded. Serum levels of calcium, phosphorus, alkaline phosphatases and creatinine, concurrently determined, were also registered. RESULTS: After an initial fall, iPTH levels showed a slow but steady decline towards the upper normal limit. The prevalence of persistent HPT, defined as an iPTH level > or =2.5 times the upper normal limit or the need for parathyroidectomy following transplantation, remained stable at approximately 17% up to 4 years after transplantation. Patients with persistent HPT had significantly elevated serum levels of iPTH, calcium and phosphorus at the time of RT, and had spent a longer time on dialysis. Post-transplant iPTH levels correlated significantly with transplant kidney function. CONCLUSION: Kidney transplant recipients with a high iPTH and calcium x phosphate product at the time of transplantation are at risk for persistent HPT especially when renal function is suboptimal. Therapy for persistent HPT, if considered, should be initiated 3 months post-transplantation since further spontaneous improvement of parathyroid function thereafter is limited.     

Disturbances in dexamethasone suppression test and lower availability of L-tryptophan and tyrosine in early puerperium and in women under contraceptive therapy.

This study investigates the function of the hypothalamic-pituitary-adrenal (HPA)-axis and the availability of L-tryptophan and tyrosine to the brain in postpartum women and in women taking long-term oral contraceptives. To this end, we have measured the following parameters in 50 women (i.e. 9 normal controls, 10 women taking oral contraceptives, and 31 postpartum females): plasma cortisol, L-tryptophan, tyrosine and the amino acids (CAA) known to compete with them for transport through the blood-brain barrier. We have determined the effects of 1 mg of dexamethasone on the above-mentioned biological markers in postpartum females. Plasma cortisol and tyrosine were significantly higher and lower, respectively, in puerperium and in women under contraceptive therapy as opposed to normal controls. L-Tryptophan was significantly lower in postpartum females, whilst the L-tryptophan/CAA ratio did not differ across the three study groups. Postpartum females revealed a significant negative relationship between the availability of L-tryptophan to the brain and postpartum mood, as measured by Zung's Depression and Anxiety Scales and State Anxiety Inventory. Dexamethasone had a significant suppressive effect on L-tryptophan/CAA and tyrosine/CAA ratios, with cortisol nonsuppression appearing in 82% of the postpartum females.     

Pharmacodynamics and pharmacokinetics of intravesical mitomycin C upon different dwelling times.

The schedule in dosing of intravesical chemotherapy has thus far received little attention. Correlation of optimal contact time with bladder toxicity, as well as maximal chemotherapeutic effect for one of the drugs of first choice for intravesical instillation, i.e. mitomycin C (MMC), is a particularly important question. In a randomized study, we treated bladder cancer patients with intravesical MMC using 30-min and 60-min dwelling times. There were 28 evaluable patients in each of the 2 groups. The groups were comparable with respect to mean age, sex ratio and distribution of primary or recurrent and single or multiple tumors. Stages and grades of tumors were also comparable over both treatment groups. Pharmacokinetics of MMC and degradation/metabolism were monitored during the first 4 cycles and the last (8th) cycle using HPLC and mass spectrometry. Recurrence was significantly lower in the 60-min treatment group (35.7% vs. 14.3%, chi 2 test; 0.01 less than p less than 0.05). No recurrences were found in patients with Ta and T1 tumors when the 60-min dwelling time was used. Toxicity was mild and transient; the incidence was, surprisingly, lower in the 60-min group but the difference failed to reach the level of significance. Pharmacokinetics of systemic MMC and recovery in the urine was comparable over both groups and systemic absorption was calculated to be in the range of 1-5%.