Smoking behaviour and compensation: a review of the literature

Rationale: Compensation or compensatory smoking, accurately defined, deals with the question of whether switching to cigarette brands with different smoke yields is associated with a change in smoke uptake proportional to the change in machine-derived yields. The issue of compensation is important because it bears on whether switching to ”lighter” brands means lower overall smoke intake or not. Objectives: The present review investigated whether and to what extend low yield cigarettes are smoked more intensively. In addition, published data on whether nicotine, ”tar”, or any other smoke constituent or property influence compensational smoking are summarized. Methods: The studies on compensation were classified as follows: (1) studies on smoking behaviour in relation to cigarette yields (with and without brand switching); (2) studies on compensation for nicotine (switching between cigarettes which differ ”only” in their nicotine yield, nicotine supplementation, manipulation of renal nicotine excretion, administration of nicotine agonists or antagonists); (3) studies on compensation for other factors (influence of tar, taste, irritation, draw resistance). In order to quantify the degree of compensation, an index is defined and applied to selected brand switching studies. This compensation index determines, in relative units, the degree to which a smoker responds to a change in smoke yields with a change in smoke uptake measured by suitable biomarkers. The role of vent blocking is also briefly discussed. Results: Most of the studies which compare the smoking behaviour when smoking cigarettes with different smoke yields supply evidence for ”partial” compensation, suggesting that cigarettes with lower yields are smoked more intensively than those with higher yields. These studies also show that a change in the daily number of cigarettes is not a common mechanism of compensation. Effective vent blocking during smoking is a rare event and can therefore also be regarded as an uncommon mechanism of compensation. Evaluation of a suitable subset of brand-switching studies revealed an average compensation of 50–60% of the nicotine yield. Compensation tended to be more complete when changing to cigarettes with higher yields than when changing to cigarettes with lower yields. In general, brand-switching studies do not supply information on the underlying causal factors responsible for compensatory smoking. Results of the nicotine supplementation studies are not conclusive: some report evidence of nicotine titration, others do not. A general problem with this type of investigation is that continuous nicotine application does not mimic the spike-wise application with cigarette smoking, and may lead to nicotine tolerance. There is limited evidence that cigarettes were smoked more intensively when the urinary clearance of nicotine was increased. A small number of studies provide some evidence that smoking intensity increased after smokers were administered a nicotine antagonist. Several reports indicate that tar, taste and sensory properties of the smoke as well as the draw resistance of the cigarette may play a role in compensatory smoking. Low-yield cigarettes usually have reduced pressure drops which smoke researchers have suggested leads to increased puff volume. This effect seems to be independent of the smoke yield of the cigarette. There is also some evidence that some smokers maintain a consistent pattern of smoking which works independent of any changes in nicotine or tar yields, taste or design features of the cigarette (”functional autonomy”). Conclusions: The available data suggest that smokers partially compensate for a different smoke yield. While the factors and their interaction responsible for compensational smoking are not fully understood, there are data suggesting that a subgroup of smokers may partially compensate for nicotine. Even in this subgroup of smokers, however, the relative importance of the pharmacological versus the sensory effects of nicotine in smoke remains to be determined. Received: 4 January 1999 / Final version: 22 March 1999     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

     

Limitations of flow detection by color Doppler: in vitro comparison to conventional Doppler

There is little awareness of the limitations of flow detection with the commercially available color Doppler flow mapping system. The influence of flow velocity, ultrasound attenuation, and penetration depth on flow detection in color Doppler (Toshiba SSH 65A) were therefore studied in vitro and compared with conventional Doppler. The flow model had physiological flow volumes and laminar flow with parabolic velocity profile in a horizontal tube of Lucite with less than 3 degrees of coincidence. Conventional Doppler flow velocity measurements correlated highly with laser Doppler anemometry results (r = 0.99, SEE = 3 cm/sec). Signal strength of color Doppler and pulsed Doppler was semi-quantitatively graded using a scale from 0 to 5. Scale 1 (sparse signals) was useless for any assessment in color Doppler but just allowed velocity measurement in pulsed Doppler. Using 19-dB attenuation, flow velocities greater than 100 cm/sec had good scores with moderate gain, 60-100 cm/sec needed increasing gain, and velocities less than 40 cm/sec were not detectable with color Doppler but readily so with pulsed Doppler. With increasing attenuation (1-29 dB) and also with increasing penetration depth, flow detection was reduced significantly (P less than 0.001) more in color Doppler than in the pulsed technique (P less than 0.01). In conclusion, low flow velocities, high attenuation, and greater than 8 cm penetration depth may hamper flow detection in color Doppler and, thus, diagnostic accuracy. Conventional Doppler with its superior accuracy and sensitivity should therefore consolidate diagnostic ultrasound assessment.     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

Intestinal permeability in kwashiorkor

Intestinal permeability can be assessed non-invasively using the lactulose-rhamnose (L-R) test, which is a reliable measure of small intestinal integrity. AIMS: To determine risk factors for abnormal intestinal permeability in kwashiorkor, and to measure changes in L-R ratios with inpatient rehabilitation. DESIGN: A case-control study of 149 kwashiorkor cases and 45 hospital controls. The L-R test was adapted to study kwashiorkor in Malawi, with testing at weekly intervals during nutritional rehabilitation. Urine sugars were measured by thin layer chromatography in London. RESULTS: The initial geometric mean L-R ratios (x100) (with 95% confidence interval) in kwashiorkor were 17.3 (15.0 to 19.8) compared with 7.0 (5.6 to 8.7) for controls. Normal ratios are < 5, so the high ratios in controls indicate tropical enteropathy syndrome. Abnormal permeability in kwashiorkor was associated with death, oliguria, sepsis, diarrhoea, wasting and young age. Diarrhoea and death were associated with both decreased L-rhamnose absorption (diminished absorptive surface area) and increased lactulose permeation (impaired barrier function) whereas nutritional wasting affected only L-rhamnose absorption. Despite, clinical recovery, mean L-R ratios improved little on treatment, with mean weekly ratios of 16.3 (14.0 to 19.0), 13.3 (11.1 to 15.9) and 14.4 (11.0 to 18.8). CONCLUSION: Abnormal intestinal permeability in kwashiorkor correlates with disease severity, and improves only slowly with nutritional rehabilitation.     

Bacterial and mammalian DNA alkyltransferases sensitize Escherichia coli to the lethal and mutagenic effects of dibromoalkanes

Here we confirm and extend our previous studies demonstrating that the mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is markedly enhanced (not prevented) in bacteria expressing the O6- alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli ogt gene. We demonstrate that, in close parallel with mutagenesis, the Ogt ATase sensitizes the bacteria to the lethal effects of these carcinogens, suggesting that one or more of the potentially mutagenic lesions induced by DBE and DBM in the presence of Ogt has additional lethal capacity. We further demonstrate that the sensitization to both lethality and mutagenesis by DBE and DBM is a property shared by other DNA alkyltransferases. This objective was accomplished by quantifying the induction of mutations and lethal events in ogt- ada- E. coli expressing an exogenous bacterial or mammalian ATase from a multicopy plasmid. Mammalian recombinant ATases enhanced the lethal and mutagenic actions of DBE and suppressed the lack of sensitivity of the vector- transformed bacteria to DBM. In most cases the order of effectiveness of the ATases ranked: murine > human > Ogt > rat. Further comparisons included the full-length Ada ATase from E. coli and a truncated Ada version (T-ada) that retains the O6-methylguanine binding domain of the protein. The full-length Ada ATase was effective in enhancing the lethality but not the mutagenicity induced by DBE and DBM. The T-ada ATase provided less sensitization than Ada to lethality by DBE, but of the three bacterial ATases T-ada yielded the highest sensitization to mutagenesis by this compound. T-ada and Ada ATases were in general less effective than the mammalian versions, with the exception of the rat recombinant ATase. The effectiveness of the different mammalian and bacterial ATases in promoting the deleterious actions of dibromoalkanes was compared with the effectiveness of these proteins in suppressing the lethal and mutagenic effects induced by N-nitroso-N-methylurea. The ability to sensitize E. coli to the lethal and mutagenic effects of DBE and DBM seems restricted to DNA alkyltransferase, since overexpression of thioredoxin (Trx) or glutaredoxin (Grx1) in ogt- ada- cells showed no effect, in spite of the reported potential of bioactive dihaloethane- derived species to alkylate Trx.