Bisphosphonate therapy for postmenopausal osteoporosis.

Bisphosphonates are agents that are potentially useful for treatment of osteoporosis. They are antiresorptive agents, increasing bone mass by decreasing the frequency of osteoclast activation or the depth of osteoclast resorption, or both. Intermittent cyclical therapy with etidronate has been shown to be effective for postmenopausal osteoporosis in two controlled studies. Several second- and third- generation bisphosphonates are undergoing active clinical trials.     

Cellular distribution of the new growth factor Pleiotrophin (HB-GAM) mRNA in developing and adult rat tissues

Summary Pleiotrophin (PTN), also known as HBGAM, belongs to an emerging cytokine family unrelated to other growth factors. We report here the first comprehensive study using in situ hybridization on the cellular distribution of this new heparin-binding growth factor mRNA in rat tissues. PTN mRNA was developmentally expressed in many — but not all — neuroectodermal and mesodermal lineages, whilst no PTN mRNA was detected in endoderm, ectoderm and trophoblast. PTN mRNA was found in the nervous system throughout development, with a post-natal peak of expression. In the adult nervous system, significant expression persisted in hippocampal CA1 pyramidal neurons and in cortical neurons, but also in different non-neuronal cells types in various locations (olfactory nerve, cerebellar astrocytes, pituicytes, Schwann cells surrounding the neurons in sensory ganglia). PTN mRNA was also found during development in the mesenchyme of lung, gut, kidney and reproductive tract, in bone and cartilage progenitors, in dental pulp, in myoblasts, and in several other sites. Expression was differently regulated in each location, but usually faded around birth. In the adult, PTN mRNA was still present in the meninges, the iris, the Leydig cells of the testis and in the uterus. PTN mRNA was also strongly expressed in the basal layers of the tongue epithelium, which is the only epithelium and ectodermal derivative to express PTN mRNA, and this only after birth. PTN is known to be a growth factor for perinatal brain neurons and a mitogen for fibroblasts in vitro. Recently, trophic effects on epithelial cells and a role as a tumour growth factor have been reported. The mechanisms of regulation and the functions of PTN are however still uncertain. Its expression pattern during development suggests important roles in growth and differentiation. Moreover, the presence of PTN mRNA in several adult tissues and the up-regulation of PTN mRNA expression in the gravid uterus indicate that PTN also has physiological functions during adulthood.     

The hydration question. Hydration or dehydration of terminally ill patients.

Hydration of terminally ill patients is a controversial issue. This study assesses the reasons why doctors and nurses in hospital and hospice settings do or do not undertake this procedure.     

Autoregulation of beat frequency in respiratory ciliated cells. Demonstration by viscous loading

As opposed to the virtually constant load exerted by water on the cilia of ciliated protozoa, the hydrodynamic load on respiratory cilia can undergo broad variations because of changes in the rheologic properties of mucus. When water-rowing ciliated cells are exposed to increased viscosity (1 to 50 cP), their beat frequency decreases exponentially. According to Newton's fluid dynamic theory, this outcome is expected for an engine that generates constant force. However, the findings reported here indicate that when mucus-propelling respiratory ciliated cells are exposed to high viscous loads, ranging from 12 to 150 cP, the frequency of ciliary beat decreases only slightly, whereas the beat amplitude remains virtually constant. These observations suggest that ciliated cells of the respiratory tract have a functional reserve that allows them to autoregulate their mechanical output in response to the changes in viscosity to which they are normally exposed in the airway.     

A case of severe summer-type hypersensitivity pneumonitis treated with high-dose administration of steroid]

A 40-year-old man who lived in a wooden house built 30 years ago presented with complaints of fever, dry cough and dyspnea. Chest X-ray findings showed interstitial shadows throughout bilateral lung fields. After admission, high-dose administration of 3000 mg of methylprednisolone was performed because of deterioration of chest X-ray shadows and symptoms. In a week, clinical data and symptoms improved. Findings of BAL fluid on admission revealed a relative increase of lymphocytes, neutrophils and mast cells, and pathological findings of transbronchial lung biopsy revealed non-caseous granulation and alveolitis. Precipitating antibodies and indirect fluorescent antibodies against Trichosporon cutaneum and Cryptococcus neoformans had positive reactions and T. cutaneum was isolated and identified from the patient's house. A diagnosis of summer-type hypersensitivity pneumonitis was made according to the criteria advocated by Ando et al. This seemed to be a rare case of summer-type hypersensitivity pneumonitis prolonged after isolation from his normal living environment, successfully treated by high-dose administration of steroid.     

Respiratory symptoms and ventilatory capacity in swine confinement workers.

A group of 59 workers (41 men and 18 women) employed in swine confinement areas was studied to assess the presence of acute and chronic respiratory symptoms and the prevalence of abnormalities in ventilatory function. A control group of 46 (31 men and 15 women) unexposed workers was studied for the prevalence of chronic respiratory symptoms. For both male and female swine confinement workers complaints of chronic cough, dyspnoea, and chest tightness were significantly more frequent than among control workers. Male workers also complained more of chronic phlegm. Male swine confinement workers who were smokers had significantly higher prevalences of chronic cough, chronic phlegm, and chronic bronchitis than male non-smoking swine confinement workers. The frequency of acute symptoms associated with the workshift was high among the swine confinement workers with more than half of the workers complaining of cough and dyspnoea associated with work. Significant acute across shift reductions in lung function occurred in swine confinement workers, being largest for FEF25. All Monday preshift ventilatory capacity measurements in male confinement workers were significantly lower than predicted values; FVC and FEV1 were found to be lower than predicted values for women. The data indicate that exposure in swine confinement buildings is associated with the development of acute and chronic respiratory symptoms and impairment of lung function. Smoking appears to aggravate these changes.     

Usefulness of the determination of carcinoembryonic antigen (CEA) in the serum of patients with colorectal cancer in Albania.

In our work we have studied the value of the determination of serum CEA in patients with colorectal cancer. We have studied 56 patients with colorectal cancer aged 40 +/- 16 years of both sexes, 26 of whom have metastasis and 30 not. The positivity of serum CEA in the patients with colorectal cancer was 66% (37/56) in the patients without metastasis 53% (16/30) and in the patients with metastasis 80.7%. (21/26). The referent values of serum CEA were significantly lower than the values of serum CEA in the patients with colorectal cancer with and without metastasis (p1 < 0.001). Also we noticed that the values of serum CEA of the patients with colorectal cancer with metastasis were considerably higher than those without metastasis (p2 < 0.001). Analysing the values of serum CEA in the patients with colorectal cancer we noticed that all the patients of our work that had serum CEA value 20 ng/ml had metastasis. Relying on our data we conclude that the determination of serum CEA in the patients with colorectal cancer is very useful for the diagnosis and the prognosis of these patients.     

The biology of breast tumor progression. Acquisition of hormone independence and resistance to cytotoxic drugs.

Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCC1 cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.