Healthy lungs tolerate repetitive collapse and reopening during short periods of mechanical ventilation

The possible occurrence of lung damage if alveolar units are allowed to collapse and reopen breath by breath during mechanical ventilation with normal tidal volumes was investigated. Anaesthetised, paralysed, open chest rabbits were subjected to either intrathoracic negative (NEEP; n=6) or positive (PEEP; n=6) end-expiratory pressure during volume controlled mechanical ventilation. Both experimental settings were preceded by a 30 min control period and followed by a 30 min recovery period during which a PEEP of 0.2 kPa was maintained. Pao₂ and pulmonary compliance deteriorated significantly in the NEEP group during the experimental period and compared to ventilation with PEEP. Partial restoration of lung mechanics and blood gases was achieved during the recovery period. After an alveolar recruitment manoeuvre, this recovery was complete. Lung clearance studied by depositing an aerosol of technetium-99m-labelled diethylenetriamine pentaacetate (^99mTc-DTPA) in the alveoli, was significantly faster during ventilation with NEEP compared to the PEEP group ( P =0.0002) as well as the control period ( P = 0.0029). It did not recover completely during the recovery period but remained significantly faster. light microscopic histology was normal in both groups with no evidence of inflammation or epithelial disruption. We conclude that previously healthy rabbit lungs show only a transient disturbance of lung mechanics and blood gases with repetitive collapse and re-expansion. The integrity of the alveolar rnicrostructure is preserved. The disturbance in the alveolo-capillary permeability persists and may indicate surfactant related alveolo-capillary barrier dysfunction.     

Comparative antitumor effects of hormonal ablation, estrogen agonist, estrogen cytotoxic derivative, and antiestrogen in the PAIII rat prostatic adenocarcinoma.

The effects of hormonal ablation, estrogen, estrogen-derived cytotoxic agent, and estrogen antagonist therapies used clinically were evaluated on in vitro colony formation, in vivo growth, and lymphatic and pulmonary metastasis of the PAIII tumor. Ventral prostatic and seminal vesicle weights were evaluated in the same animals to assess androgen-related responses. Estradiol, estramustine phosphate, and testosterone had no effects on PAIII colony formation in vitro. Castration, hypophysectomy, estradiol benzoate, and estramustine phosphate treatment of PAIII-bearing Lobund Wistar rats produced significant (P less than 0.05) regression of male accessory sex organs. Of these treatments, only hypophysectomy had significant (P less than 0.05) inhibitory effects on primary PAIII growth and lymphatic and pulmonary metastasis. LY117018 [6-hydroxy-2-(p-hydroxyphenyl)benzo(b)thien-3-yl-p-2-(l-pyrrolidin yl)ethoxy phenyl ketone] has antiestrogenic activity but produces no significant agonist responses. LY117018 had no effect upon PAIII colony formation in vitro. Following s.c. implantation of PAIII cells, LY117018 (2.0, 10.0, or 20.0 mg/kg s.c.) had no effect on primary tumor growth in the tail. In vitro LY117018 administration produced marked antimetastatic effects. In a dose-dependent manner, LY117018 inhibited PAIII metastasis to the gluteal (97%) and iliac lymph nodes (88%) (P less than 0.05 for both). LY117018 also maximally inhibited pulmonary metastasis by 86% (P less than 0.05). Maximal regression of 42% for ventral prostatic and 35% for seminal vesicle weights were also seen after LY117018 administration (P less than 0.05 for both). Co-administration of estradiol benzoate had no antagonistic effect upon the antitumor responses produced by LY117018. The mechanism of action of LY117018 is not known. The failure of estradiol benzoate to affect PAIII growth and metastasis supports the contention that the responses to LY117018 are not attributable to simple antagonism of estrogen action. LY117018 may be exerting its antitumor effects through autocrine, paracrine, or endocrine mechanisms. LY117018 represents a class of agents with potential utility in treating metastatic cancer of the prostate.     

Treatment of post herpetic neuralgia in the elderly

The incidence of acute herpes zoster and post herpetic neuralgia (PHN) increases with age. PHN resolves spontaneously within three months in approximately 50% of cases, although 22% experience discomfort for more than a year. There is little good evidence that treatment with antiviral agents, corticosteroids, local and regional anaesthesia, amantadine or levodopa in the acute stage can prevent the development of PHN. However, few studies have sufficient statistical power to allow firm conclusions to be drawn. Amitriptyline is beneficial in patients with established PHN and has an analgesic effect which is independent of its antidepressant action. Anticonvulsants and neuroleptics are of unproven efficacy and should be avoided in the elderly as side effects are common. Various local anaesthetic and surgical techniques may provide temporary relief in individual patients although none has been shown to produce consistent benefit. Transcutaneous electrical nerve stimulation (TENS) is free from adverse effects and appears to benefit some patients. Intractable pain often results in over-prescribing with the risk of adverse drug reactions. Drug therapy should be minimized with careful assessment of the risk/benefit ratio for any additional medication.     

Experimental studies on the comparative infectivity and pathogenicity of Streptococcus suis type 2. II. Porcine and human isolates in laboratory animals

Mice, rats, guinea-pigs and rabbits were inoculated with isolates of Streptococcus suis type 2. An isolate cultured from the tonsils of a healthy pig, produced disease in rabbits after intravenous inoculation but not in mice, rats or guinea-pigs. An isolate of S. suis type 2, that was pathogenic for pigs and had been cultured from a human patient with clinical disease, produced signs of neurological disease in mice, rats and rabbits following intravenous inoculation. There was an apparent dose response in mice with 31% of mice receiving more than 10(6) organisms developing clinical disease, whilst mice receiving less than this did not develop disease. There were no detectable histopathological lesions in the brains or meninges of mice with nervous signs. It is proposed that the disease in mice may mimic that reported in humans and that mice may be a useful indicator species for determining the virulence of isolates cultured from pigs.     

Cardiac abnormalities in the fragile X syndrome.

Twenty three patients with fragile X syndrome underwent cardiovascular assessment. Echocardiography showed dilatation of the aortic root in 12 (52%) and mitral valve prolapse in five (22%), four of whom had an apical mid-systolic click on auscultation. Patients with fragile X syndrome have cardiac defects similar to those seen in other disorders of connective tissue such as Marfan's syndrome and Ehlers-Danlos syndrome. These, and other somatic features, suggest an underlying connective tissue dysplasia.