Chemoreceptor activity is normal in mice lacking the NK1 receptor

Substance P has been proposed to be an important neurotransmitter in the carotid body with the neurokinin 1 (NK1) receptor, mediating excitation between the glomus cells and afferent nerve endings. In order to better understand the role of substance P, this study examined chemoreceptor afferent activity, in vitro, and tissue catecholamine levels and release in adult, wild-type mice and mice lacking the gene for the NK1 receptor (NK1-KO). Groups did not differ significantly in body weight, carotid body dopamine content or carotid body norepinephrine content. In wild-type mice, single unit activity increased from 0.59 +/- 0.14 Hz to 19.78 +/- 2.27 Hz during superfusion with strong hypoxia (PO2 approximately 25 Torr). Chemoreceptor activity in NK1-KO mice, increased from 0.71 +/- 0.23 to 21.50 +/- 3.62 Hz, and neither baseline or peak frequencies were significantly different from the wild-type group. Less severe hypoxia (PO2 approximately 45 torr), evoked peak activities of 12.50 +/- 1.88 and 10.64 +/- 3.72 Hz in wild-type and NK1-KO mice, which were also not significantly different. In response to severe hypoxia, free-tissue catecholamine increased to 4.92 +/- 0.85 microm in wild-type mice and 4.26 +/- 0.63 microm in NK1-KO mice, which were also not significantly different. It may therefore be concluded that loss of NK1 receptors has little effect on chemoreceptor function in the mouse, and thus they play, at best, a minor role in the hypoxic chemoreception process.     

Tacrolimus ointment for the treatment of atopic dermatitis is not associated with an increase in cutaneous infections

OBJECTIVE: The purpose of this study was to evaluate the risk of cutaneous infection in patients with atopic dermatitis treated with tacrolimus ointment. METHODS: Data for 1554 patients with atopic dermatitis, treated with tacrolimus ointment in 5 clinical trials, were analyzed. RESULTS: In 3 controlled studies, the 12-week adjusted incidence of all cutaneous infections in patients treated with the vehicle, 0.03%, and 0.1% tacrolimus ointment, respectively, was 18.0%, 24.8%, and 17.7% for adult patients, and 20.9%, 19.6%, and 23.6% for pediatric patients. The incidence of any individual cutaneous infection was not significantly higher in the tacrolimus group than in the vehicle group, with the exception of folliculitis in adults. In two open-label studies, there was no evidence of an increased risk of cutaneous infections with long-term use of 0.1% tacrolimus ointment (up to 1 year), based on the incidence of adverse events, incidence by cumulative length of exposure, or hazard rates. CONCLUSION: Treatment with tacrolimus ointment (0.03% or 0.1%) does not increase the risk of cutaneous bacterial, viral, or fungal infections in patients with atopic dermatitis.     

Carnitine deficiency myopathy: a case of late diagnosis

Myopathies caused by lipidic metabolism alterations are very infrequent. Carnitine deficiency-associated myopathies are included in this group. Two main types of carnitine deficiency syndromes have been delineated: a predominantly myopathic form, with normal serum and low muscle carnitine levels, and a systemic form, with encephalopathy, hepatic dysfunction, muscle weakness and low muscle, liver and serum carnitine levels. Both types have typical lipid stores in muscle biopsy. We describe the case of a myopathic form of carnitine deficiency. Due to the age of the patient, this is an unusual case, with an unfavourable evolution. Therapeutic measures used in these patients have included prednisone, carnitine replacement and a low-fat with medium chain tryglycerides and high-carbohydrate diet. However, in none of the patients responding to therapy, a significative increase in muscle carnitine has been demonstrated.     

Gastroenteritis-associated Guillain-Barré syndrome on the Caribbean island Curaçao

BACKGROUND: The number of patients with Guillain-Barré syndrome (GBS) who have been observed in Cura?ao, the Netherlands Antilles, may be increasing. METHODS: Clinical and serologic data were obtained from records of patients admitted between 1987 and 1999 and fulfilling National Institute of Neurological and Communicative Disorders and Stroke criteria for GBS. When possible, serum and stool samples were collected. The results were compared with a large Dutch epidemiologic study. RESULTS: The authors identified 49 patients, an overall crude incidence rate (IR) in Cura?ao of 2.53/100,000 inhabitants (95% CI 1.87 to 3.35) (Dutch study 1.18, rate ratio (RR) of 2.14, p < 0.001). The IR in Cura?ao increased from 1.62 in 1987 to 1991 to 3.10 in 1992 to 1999, RR 5.22 (95% CI 2.48 to 10.2, p = 0.02). The IR showed a curvilinear shape within a year. In comparison with the Dutch group, patients from Cura?ao had a more severe course of the disease, with a mortality rate of 23% (3.4% in the Dutch group, p < 0.001), a higher percentage of preceding gastroenteritis (p < 0.001), and less sensory involvement (p < 0.001). In 8 of 10 serum samples, evidence was found for a recent infection with Campylobacter jejuni. CONCLUSIONS: The authors found a steady increase in incidence of GBS over the years in association with a more pronounced seasonal preponderance and a more severe course. The clinical characteristics suggest a role for C jejuni.     

Intracranial aneurysms and autosomal dominant polycystic kidney disease

Three women aged 55, 47 and 40 years with polycystic kidney disease had several relatives with cystic kidneys, some of whom had died or been crippled after (presumably) a subarachnoid haemorrhage. Two of these patients had a haemorrhage from an aneurysm of a cerebral artery; after clipping of the vessel they recovered without sequelae. The third patient had magnetic resonance (MR) angiography performed, which revealed no aneurysm. The prevalence of intracranial, saccular aneurysms in patients with autosomal dominant polycystic kidney disease (ADPKD) is about 10%. ADPKD patients with questions about the risk of a subarachnoid haemorrhage should be informed about the need of blood pressure control and the possibility of screening by MR angiography. Diagnosed aneurysms can be treated neurosurgically or endovascularly. Since aneurysms develop in the course of life, screening as a rule is only necessary from the age of 20 years, and its repetition every 5 years should be considered.     

Effect of induced uterine retroversion on bone mass in rats

OBJECTIVE: To evaluate the effect of surgical uterine retroversion on bone mass in rats. STUDY DESIGN: Forty-five female Wistar rats were assigned randomly to three groups: 15 unmanipulated rats, 15 rats that underwent uterine retroversion, and 15 rats that underwent sham uterine retroversion (exposure of the uterus to air followed by closure of the abdominal cavity). Sixty days later the rats were killed and their femurs were dissected. Femurs were weighed and measured, and femoral bone mineral content (BMC) and bone mineral density (BMD) were determined by dual energy X-ray absorptiometry. RESULTS: In the group of rats that underwent uterine retroversion, BMC, BMD, and BMC corrected for final body weight were significantly lower (P<0.001) than in the unmanipulated control and sham uterine retroversion groups. CONCLUSION: Our findings indicate that uterine retroversion induced a loss of bone mass. We could not determine the mechanism of bone loss; in our opinion, these problem merits further investigations, which currently occupy our interest.     

Crush fracture syndrome in senile osteoporosis: a nutritional consequence?

Osteoporosis is a very important age-related health problem. The body's composition changes with age, and these changes are a true reflection of aging and of the individuals's nutritional status. Mineral content changes have been reported in vertebral osteoporosis. Interestingly, enough, there have not been reports on concomitant water, fat, and fat-free mass changes associated with this condition. In this report, changes in the latter parameters are compared between patients with osteoporosis and controls. The four components (water, mineral, fat, and fat-free mass) were found significantly reduced (p less than 0.001) in osteoporosis. Serum albumin and protein mass were also reduced (p less than 0.001).     

Toxicité à long terme du cadmium administré à très faible dose chez le rat: Répartition du cadmium,du zinc,et du cuivre

Urinary cadmium elimination and tissue distribution as well as that of zinc and copper were studied in groups of rats receiving 0 or 2.5 ppm Cd in water for 3, 6, or 12 months. By 3 months, cadmium ingestion induced only increases in urinary and kidney cadmium concentrations, after which urinary cadmium remained stable as a reflection of daily food intake. On the other hand, kidney cadmium accumulated reflecting total cadmium ingestion. In the livers and kidneys of animals observed during 3 and 6 months, cadmium accumulation was more marked in females, whether receiving cadmium or not. In other organs (liver, pancreas, ovary, testicle) cadmium concentrations were not higher in animals receiving cadmium. Kidney fixation of cadmium was associated with a slight decrease of hepatic copper after 3 months and a decrease in zinc as well after 12 months. These results attest that cadmium ingested at very low doses selectively accumulates in the kidney. They suggest either a mechanism unrelated to metallothionein synthesis or an early kidney induction.     

Gamma glutamyl transferase and cancer (author's transl)

Attention has been drawn in recent years to the diagnostic interest offered by increases in serum gamma GT in the detection of liver metastases and various cancers in man. Although this analysis is not specific and presents a few false positive and negative results, it seems however profitable to include it either in detection or in supervision tests. Furthermore, in the rat and mouse, this enzyme practically absent from the adult liver, reappears during liver cancer Whatever the cause: this onco-foetal character may be useful to exploit in studies of experimental carcinogenesis, but does not seem to be a valid model for the increases observed in man.