Biodistribution of radiolabeled lipid-DNA complexes and DNA in mice

The tissue biodistribution and expression of [33P]DNA-1-[2-[9-(Z)-octadecenoyloxy]ethyl]]-2-[8](Z)-heptadece nyl]-3 -[hydroxyethyl]imidazolinium chloride (DOTIM):cholesterol complexes and 33P-radiolabeled DNA expressing chloramphenicol acetyl transferase (CAT; 4.7 kB) were studied after intravenous (iv) injection in ICR mice. Mice were injected with 200 microL of complex containing DNA at 3 mg/kg or DNA alone. One group received 8 microCi of radioactivity and were sacrificed at 5 and 20 min, and 1, 2, 4 and 24 h post-dose (n = 4/time point). A second group received the equivalent of 3.9 microCi of radioactivity and were sacrificed at 20 min, and 2 and 24 h for subsequent whole body autoradiographic analysis (WBA; n = 2/time point). The tissue distribution of intact DNA was assessed by Southern blot at 24 h post-dose, whereas the integrity of complexes and DNA incubated in heparinized whole blood was studied separately. In further studies, the time course of expression in lung tissue over a 48-h period was examined, and the relative lung-expression of purified open circular (OC) versus supercoiled (SC) DNA at 24 h was evaluated. Approximately 42% of the radioactivity was found in the lungs 5 min after injection and about half this percentage was found in the liver. By 2 h, only 5% remained in the lungs, but 48% was present in the liver. No other tissue accumulated >5% of the dose throughout the duration of the study. WBA radiograms confirmed the tissue distribution results and highlighted significant accumulation of radioactivity in bone over time. Southern Blot analysis demonstrated intact DNA in many tissues 24 h after dosing. In contrast, the majority of DNA incubated in blood was degraded within 2 h, although the complexes afforded some protection relative to DNA alone. The OC DNA expressed equivalently to SC DNA in lung tissue (OC = 1035 +/- 183 pg; SC = 856 +/- 257 pg/mg soluble protein, n = 6, mean +/- SEM) at 24 h, and detectable levels of CAT were present within 2 h of dosing (21.3 +/- 7.2 pg, n >/= 8, mean +/- SD). The results confirm that DNA-DOTIM:cholesterol complexes are initially deposited in the lungs after iv administration.     

Ectopic pregnancy associated with the intrauterine device: a study of seventy cases

Seventy cases of ectopic pregnancy associated with an IUD comprised 10% of all ectopics in a 9 year period. This increased to 15% in the last 19 months as more IUD's were in use. In two thirds of the ectopics the IUD had been in situ more than 1 year. Unusual bleeding and cramping attributed to the IUD obscured the diagnosis and resulted in removal or replacement of the IUD in over one half the cases 1 to 8 weeks before surgery. The episodic nature of the abdominal hemorrhage in two thirds of all ectopics resulted in surgery on day 44 average gestational age. The IUD is probably not causal in ectopic pregnancy but does not protect the predisposed patient from ectopic pregnancy which should be suspected in any patient with an IUD who has irregular bleeding and abdominal pain.     

Inflammation of the tail in swine. Slaughter-house findings during 1972, 1973, and 1974 (author's transl)

In the Public Salughter-House of Utrecht, a percentage increase in the number of pigs with inflammation of the tail, which had or had not healed, was observed during the period from 1972 to 1974 inclusive. The most common secondary symptoms of inflammation consisted in embolic pneumonia, osteomyelitis of the vertebrae and abscess formation in other parts of the body, particularly the semimebranosus muscles. Osteomyelitis was found to be the most common complication in pigs in which the inflammation of the tail had healed, whereas this usually consisted in embolic pneumonia in those cases in which the inflammation of the tail had not healed. The bacteriological examination carried out in accordance with the Meat Inspection Regulations was positive in 21.7 per cent, 13.5 per cent of the cases respectively in 1972, 1973 and 1974. Micro-organisms were isolated much more frequently from the kidney than they were from the spleen and meat. There was no relationship between the presence of inflammation of the tail and climatological conditions during the fattening period. The losses at slaughter from inflammation of the tail in the Netherlands are estimated at 3-4 million guilders per annum.     

A multifactorial study of patients with asthma. Part 2: air pollution, animal dander and asthma symptoms

As part of a multifactorial computer-assisted study of patients with asthma, the relationship between air pollution, animal dander and asthma symptoms was evaluated. No association was found between four major air pollutants (carbon monoxide, ozone, nitrogen oxides and sulfur dioxide) and asthma symptoms. Patients who owned cats and dogs reported more severe asthma symptoms (p less than .01) than patients who did not own cats and dogs. The evaluations completed to date indicate that daily exposure to cats and dogs accounts for more of the asthma symptoms differences between patients than daily exposure to air pollutants.