Covalent Binding of Inhaled Formaldehyde to DNA in the Respiratory Tract of Rhesus Monkeys: Pharmacokinetics, Rat-to-Monkey Interspecies Scaling, and Extrapolation to Man

Covalent Bindingoflnhaled Formaldehyde to DNA in the RespiratoryTractofRhesus Monkeys: Pharmacokinetics, Rat-to-Monkey InterspeciesScaling, and Extrapolation to Man. CASANOVA, M., MORGAN, K.T., STEINHAGEN, W. H., EVERITT, J. I., POPP, J. A., AND HECK,H. D'A. (1991). Fundam. Appl Toxicol 17, 409–428. DNA-proteincross-links were formed in the respiratory tract of rhesus monkeysexposed to [¹⁴C]formaldehyde (0.7, 2, or 6 ppm; 6 hr). Concentrationsof cross-links (pmol/mg DNA) were highest in the mucosa of themiddle turbmates; lower concentrations were produced in theanterior lateral wall/septum and nasopharynx. Very low concentrationswere found in the larynx/trachea/carina and in the proximalportions of the major bronchi of some monkeys exposed to 6 ppmbut not to 0.7 ppm. No cross-links were detected in the maxillarysinuses or lung parenchyma. The pharrnacokinetics of cross-linkformation in the nose were interpreted using a model in whichthe rate of formation is proportional to the tissue concentrationof formaldehyde. The model includes both saturable and nonsaturableelimination pathways and describes regional differences in DNAbinding as having an anatomical rather than a biochemical basis.Using this model, the concentration of cross-links formed incorrespondmg tissues of different spacies can be predicted byscaling the pharmacokinetic parameter that depends on minutevolume () and quantity of nasal mucosal DNA (M_DNA). The concentration-response curve for the average rateof cross-link formation in the turbinates lateral wall, andseptum of rhesus monkeys was predicted from that of F-344 ratsexposed under similar conditions. There was significant overlapbetween predicted and fitted curves, implying that V and M_DNAare major determinants of the rate of cross-link formation inthe nasal mucosa of different species. Concentrations of cross-linksthat may be produced in the nasal mucosa of adult men were predictedbased on experimental data in rats and monkeys. The resultssuggest that formaldehyde would generate lower concentrationsof cross-links in the nasal mucosa of humans than of monkeys,and much lower concentrations in humans than in rats. The rateof formation of DNA-protein cross-links can be regarded as asurrogate for the delivered concentration of formaldehyde. Useof this surrogate should decrease the uncertainty of human cancerrisk estimates derived by interspecies extrapolation by providinga more realistic measure of the delivered concenmtion at criticaltarget sites.     

Fat gram target to achieve high energy intake in cystic fibrosis

Higher fat and energy intakes confer a survival advantage in cystic fibrosis (CF). There is a need to develop effective nutrition programmes that ensure optimal energy intake in CF.

Methodology:

A cross-sectional measurement of clinical characteristics and energy and fat intakes in patients attending the CF outpatients clinic of the John Hunter Hospital, Newcastle was undertaken. Twenty-nine subjects, mean age 12 years (range 4.3–20.2), completed weighed food records to determine the contribution of fat to the percentage of the recommended energy intake obtained and to document use of pancreatic enzyme replacement therapy.

Results:

Diets with a high percentage of energy derived from fat did not guarantee that individuals with CF met their energy requirements. Subjects with total fat intakes of 100 g per day or greater, however, achieved in excess of 110% recommended daily intake (RDI) for energy. Up to 47% of subjects consumed more pancreatic enzyme replacement capsules than shown to give maximum effectiveness.

Conclusion:

Setting a 100 g daily fat target is a realistic way of ensuring high energy intakes in CF. Fat ready reckoners would identify the fat content of food and prescribe specific numbers of pancreatic enzyme replacement capsules to be consumed with each meal or food item.     

Ventricular Tachycardia/Ventricular Fibrillation Ablation in the Setting of Ischemic Heart Disease

Recurrent ventricular tachycardia (VT) in the setting of coronary artery disease is frequently a life-threatening electrophysiologic emergency. Even in patients with an implantable defibrillator, recurrent VT is frequently accompanied by repeated and disabling shock therapy. Catheter ablative therapy offers the ability to provide immediate control of recurrent VT. Long-term elimination of VT should be anticipated in most patients. This article reviews the strategies, tools, techniques, and expected outcome for catheter ablation of stable and unstable ventricular arrhythmias in the setting ischemic heart disease.     

Comparison of preservative-free and preservative-containing ipratropium bromide

Abstract A double-blind crossover study was performed on 33 children with asthma to compare the effectiveness of nebulized solutions of preservative-containing and preservative-free ipratropium bromide. Both solutions produced bronchodilation. No significant differences were found between the two solutions at any time after nebulization in minimum and maximum changes from baseline value or in the areas under the lung function time curves. The presently formulated preservative-containing ipratropium bromide solution was not shown to be inferior to a preservative-free compound.     

Chest radiograph appearances after head and neck flap reconstructive surgery

The chest radiographs of 17 patients who had undergone pectoralis major myocutaneous flap (PMMF) reconstruction for head and neck cancers were reviewed. Surgical procedure correlated well with radiographic findings, which consisted of the following signs: abnormal axillary and supraclavicular folds, replacement of normal vertical neck fold by an oblique fold, soft tissue mass and loss of facial plane at base of the neck. Unilateral radiolucent hemithorax was present in 41% of cases. In females, loss of breast shadow simulating the post-mastectomy appearance was present.