Correction of hallux valgus deformity with distal soft tissue realignment and proximal metatarsal osteotomy

Abstract Fifty moderate to severe hallux valgus deformities were corrected with a distal soft tissue realignment and proximal crescentic metatarsal osteotomy. With an average follow-up of 5.6 years, 40 feet (80%) were pain free and 42 (84%) caused no functional limitation. The average hallux valgus angle improved from 38.2° preoperatively to 12.4° at follow-up. The average intermetatarsal angle improved from 15.4° to 6.8°. The arch of motion of the first metatarsophalangeal joint was 75° preoperatively and 62° at follow-up. According to the AOFAS scoring system, 29 results (58%) were excellent, 14 (28%) good, 2 (4%) fair and 5 (10%) poor. The 5 poor results were attributed to recurrence of hallux valgus (2 cases), stiffness (1), hallux varus (1) and malunion of the osteotomy in dorsiflexion (1). The incidences of hallux varus and malunion in dorsiflexion were 8% and 14%, respectively. This technique is valuable in correction of moderate to severe hallux valgus deformities.     

Cyclic hormonal replacement therapy after the menopause: Transdermal versus oral treatment

Summary In an open, randomized, comparative, between-patient trial, 45 postmenopausal women were treated for 4 months with cyclical transdermal oestradiol 0.05 mg per day or oral conjugated equine oestrogens 0.625 mg per day, in both cases, plus, medroxyprogesterone acetate 10 mg per day on the last 8 days of each cycle. Similar relief from postmenopausal symptoms was obtained with both treatments. Post-treatment histological evaluation of the endometrium did not reveal neoplastic or hyperplastic change in any patient.Early follicular-phase plasma oestradiol levels were observed only after transdermal oestradiol. There was a significant reduction in serum total cholesterol and LDL cholesterol in both treatment groups, with no difference between treatments, whereas serum triglyceride levels were decreased only by transdermal oestradiol. Plasma calcium and phosphorus fell significantly and serum intact parathyroid hormone rose significantly, with no difference between the therapies. No significant changes were observed in clotting factors.Transdermal oestradiol appears to be an effective and safe hormonal replacement therapy, and this route of administration may be responsible for the more useful action of the drug on serum lipids and plasma oestradiol levels.     

Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications

Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.     

Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen.

BACKGROUND. Endocrine factors may affect the clinical course of malignant melanoma and the response to the treatment of this disease. The presence of estrogen receptors in melanomas has been suggested, and occasional responses to antiestrogen therapy have been reported. METHODS AND RESULTS. We randomly assigned 117 patients with metastatic malignant melanoma to treatment with dacarbazine alone or dacarbazine in combination with tamoxifen. The overall rate of response, measured objectively, was higher (28 percent vs. 12 percent, P = 0.03) and survival was longer (median, 48 vs. 29 weeks, P = 0.02) among the patients who received dacarbazine plus tamoxifen than among those who received dacarbazine alone. Among women, both the response rate (38 percent vs. 10 percent, P = 0.04) and the median survival (69 vs. 30 weeks, P = 0.008) were better with dacarbazine plus tamoxifen than with dacarbazine alone, whereas among men the differences were smaller and not statistically significant. Among the patients given dacarbazine alone, there were no significant differences between women and men in response rate (10 percent vs. 13 percent) or survival (30 vs. 27 weeks), whereas among those given dacarbazine plus tamoxifen, women had better outcomes, as indicated by both response rate (38 percent vs. 19 percent, P = 0.15) and survival (69 vs. 31 weeks, P = 0.02). When we analyzed the Quetelet body-mass index (the weight in kilograms divided by the square of the height in meters) as an indirect indicator of the levels of endogenous estrogens in postmenopausal women and in men, survival was not affected by the body-mass index in the group given dacarbazine alone, whereas in the group given dacarbazine plus tamoxifen, survival was longer among patients whose Quetelet index was above the median value than among those with a Quetelet index lower than the median value (60 vs. 26 weeks, P less than 0.001). CONCLUSIONS. In the treatment of metastatic malignant melanoma, dacarbazine plus tamoxifen is more effective than dacarbazine alone, as indicated by both the response rate and the median survival; the difference in efficacy is among women.     

FINGERPRINTING OF HLA CLASS I GENES FOR IMPROVED SELECTION OF UNRELATED BONE MARROW DONORS

The degree of matching of HLA genes between the selected donor and recipient is an important aspect of the selection of unrelated donors for allogeneic bone marrow transplantation (UBMT). The most sensitive methods currently used are serological typing of HLA class I genes, mixed lymphocyte culture (MLC), IEF and molecular genotyping of HLA class II genes by direct sequencing of PCR products. Serological typing of class I antigenes (A, B and C) fails to detect minor differences demonstrated by direct sequencing of DNA polymorphic regions. Molecular genotyping of HLA class I genes by DNA analysis is costly and work-intensive. To improve compatibility between donor and recipient, we have set up a new rapid and non-radioisotopic application of the ‘fingerprinting PCR’ technique for the analysis of the polymorphic second exon of the HLA class I A, B and C genes. This technique is based on the formation of specific patterns (PCR fingerprints) of homoduplexes and heterodu-plexes between heterologous amplified DNA sequences. After an electrophoretic run on non-denaturing polyacrylamide gel, different HLA class I types give allele-specific banding patterns. HLA class I matching is performed, after the gel has been soaked in ethidium bromide or silver-stained, by visual comparison of patients’ fingerprints with those of donors. Identity can be confirmed by mixing donor and recipient DNAs in an amplification cross-match. To assess the technique, 10 normal samples, 22 related allogeneic bone marrow transplanted pairs and 10 unrelated HLA-A and HLA-B serologically matched patient-donor pairs were analysed for HLA class I polymorphic regions. In all the related pairs and in 1/10 unrelated pairs, matched donor-recipient patterns were identified. This new application of PCR fingerprinting may confirm the HLA class I serological selection of unrelated marrow donors.     

Ultrastructural evidence for neurogenically mediated changes in blood vessels of the rat dura mater and tongue following antidromic trigeminal stimulation.

We investigated the effects of unilateral electrical trigeminal ganglion stimulation (0.1 or 1.0 mA, 5 Hz, 5 ms, 5 min) on the morphology of blood vessels within the rat dura mater and tongue using light and transmission electron microscopy. Stimulation at both intensities caused changes which were confined to the ipsilateral post-capillary venules except in the tongue where arterioles were affected as well. Changes were more marked after 1.0 mA. Dramatic increases in the numbers of endothelial pinocytotic vesicles were found along the luminal and abluminal surfaces ipsilateral to the stimulation. Tight junctions remained largely intact, except that injected ferritin particles were occasionally trapped inside these junctions. Cytoplasmic microvilli and endothelial blebs were sometimes present as well. Approximately 80% of the examined dural post-capillary venules showed one or more of these endothelial changes. Horseradish peroxidase injected intravenously 5 min prior to stimulation was detected in the extracellular space surrounding dural blood vessels and within pinocytotic vesicles. Ferritin injected similarly, was also localized in post-capillary venule walls, interstitial spaces, intraendothelial vesicles and in vacuoles. Platelet accumulation and aggregation were present in approximately 10% of post-capillary venules in dura and tongue. These changes were associated with mast cell secretion, but neither vascular nor mast cell activation was observed in adult rats in whom C-fibers were destroyed during the neonatal period with capsaicin. The present observations provide morphological evidence which supports findings from previously reported albumin tracer studies suggesting enhanced transport and endothelial activation following electrical stimulation of small caliber afferent fibers.     

Coherent emission from surface Josephson plasmons in striped cuprates

The interplay between charge order and superconductivity remains one of the central themes of research in quantum materials. In the case of cuprates, the coupling between striped charge fluctuations and local electromagnetic fields is especially important, as it affects transport properties, coherence, and dimensionality of superconducting correlations. Here, we study the emission of coherent terahertz radiation in single-layer cuprates of the La_2-xBa_xCuO₄ family, for which this effect is expected to be forbidden by symmetry. We find that emission vanishes for compounds in which the stripes are quasi-static but is activated when c-axis inversion symmetry is broken by incommensurate or fluctuating charge stripes, such as in La_1.905Ba_0.095CuO₄ and in La_1.845Ba_0.155CuO₄. In this case, terahertz radiation is emitted by surface Josephson plasmons, which are generally dark modes, but couple to free space electromagnetic radiation because of the stripe modulation.

Nonlinear terahertz (THz) spectroscopy has recently emerged as a new tool to study the microscopic properties of quantum materials, being susceptible to the symmetry of low-energy degrees of freedom and complementing already-existing nonlinear optical probes (1). For example, THz third-harmonic generation was shown to be a sensitive probe of superfluid stripes, which do not couple to light at linear order but participate in higher-order responses (2, 3). As such, the study of THz nonlinear optics in presence of frustrated couplings provides new opportunities to explore the symmetry of quantum materials. Here, we focus on THz emission from high-TC cuprates and demonstrate how this method is highly sensitive to the spatial arrangement of the superconducting state and its interaction with charge-stripe order.The emission of THz radiation from materials illuminated with femtosecond optical pulses (4–7) is generally enabled by two classes of mechanisms. The first mechanism, active in transparent noncentrosymmetric materials such as ZnTe or LiNbO₃, is based on optical rectification, where the second-order nonlinear optical susceptibility causes a time-dependent electrical polarization (8). The second mechanism relies on the excitation of time-dependent charge currents and is well documented for biased high-mobility semiconductors (8). A number of additional reports of coherent THz radiation have been made for complex quantum materials, typically related to the perturbation of electronic and magnetic interactions. THz emission in colossal magnetoresistance manganites (7, 9, 10), magnetic and multiferroic compounds (11–20), are some of the best-known examples.In the case of high-T_C superconductors, coherent THz emission has been reported only for situations in which time-dependent supercurrents, J˙s(t), are set in (8). These situations range from near-single-cycle THz pulses in biased antennae fabricated from YBa₂Cu₃O_7-δ or Bi₂Sr₂CaCu₂O_8+δ films (5, 21, 22), to multicycle narrowband emissions governed by the Josephson effect in the case of applied out-of-plane magnetic fields (23). It has also been shown that the use of Josephson junction stacks in mesa-type resonant structures allows orders of magnitude increase in THz emission efficiency, also providing narrow bandwidths and tuneable frequency (24–26).Here, we report anomalous THz emission in high-TC cuprates, observed for photoexcitation with femtosecond near-infrared pulses, in absence of external magnetic fields and current biases. The effect is detected only when superconductivity coexists with charge-stripe order in the Cu-O planes (27–30) and when these stripes are either incommensurate with the lattice or fluctuating.We studied cuprates belonging to the “214” family, with one Cu-O layer per unit cell. As a prototypical “homogeneous” cuprate, we considered optimally doped La_2-xSr_xCuO₄ (LSCO), with a critical temperature of 38 K (phase diagram in Fig. 1A). Although in the LSCO family fluctuating striped charge and spin orders have been reported in the underdoped region of the phase diagram (31), there is no evidence for stripes at optimal 0.16 doping (32). This sample was compared with the response of La_2-xBa_xCuO₄ (LBCO), for which superconductivity coexists with charge stripes (27). We focused on three LBCO compounds: La_1.885Ba_0.115CuO₄ (LBCO 11.5%, TC = 13 K), where the superconducting transition is highly depleted by a robust stripe phase below the charge ordering temperature TCO = 53 K, La_1.845Ba_0.155CuO₄ (LBCO 15.5%, TC = 30 K, TCO = 40 K), placed at the nominal optimal doping and characterized by weak, highly fluctuating stripes (27), and La_1.905Ba_0.095CuO₄ (LBCO 9.5%, TC = TCO = 33 K), for which the stripes have an intermediate intensity and correlation length compared with the other two compounds (27), but in contrast to them are here highly incommensurate (33, 34). The location of the three samples in the LBCO phase diagram is shown in Fig. 1 B–D.Open in a separate windowFig. 1.(A–D) Temperature-doping phase diagrams of the four compounds investigated in the present study. TCO, TSO, and TC stand for the charge ordering, the spin ordering, and the superconducting critical temperature, respectively. (E–H) Time-dependent THz emission traces taken for a pump fluence of 2.5 mJ/cm² at the temperatures indicated by full circles in (A–D). Solid lines represent multicomponent fits to the data (SI Appendix). The vertical scales in the three panels are mutually calibrated. (I–L) Fourier transforms (circles) of selected time-domain traces in (E–H). Solid lines are multi-Gaussian fits. Insets: Experimental geometry. Near-infrared (NIR) pump pulses are shone at normal incidence onto an ac-oriented sample surface, with polarization parallel to the c axis. As a result of photoexcitation, c-polarized THz radiation is emitted. Ampl., amplitude.We note that LBCO is the same cuprate in which signatures of optically enhanced superconductivity have been measured (35–38) and attributed to the ultrafast perturbation of the stripe order (39, 40). In addition, a number of nonlinear optical effects, such as THz parametric amplification (41) and third-harmonic generation (2), related to the resonant driving of Josephson plasma waves, have also been measured.The main result of our experiment is summarized in Fig. 1 E–L, where the measured THz emission traces are reported for the four investigated compounds for selected temperatures, at a constant pump fluence of 2.5 mJ/cm². The experimental geometry is shown in the insets of the lower panels. We used the output of an amplified Ti:Sa laser as pump pulses, with a duration of 100 fs and photon energy of 1.55 eV (800 nm wavelength). These were focused at normal incidence onto an ac-oriented sample surface on an ∼ 500 μm spot. The emitted THz pulses were collimated with a parabolic mirror and refocused on a 1-mm-thick ZnTe crystal to perform electro-optic sampling directly yielding THz electric field traces in time domain.In optimally doped LSCO (Fig. 1E), the THz emission signal was measurable only in the superconducting state below TC and displayed a very small amplitude, just above the noise level. This effect consisted of a single-cycle trace, with a flat and featureless spectrum (Fig. 1I). A similar response was also found in LBCO 11.5% (Fig. 1 F and J), where charge stripes are robust, quasi-static, and quasi-commensurate. Here, a barely detectable emission signal was also found for T>TC.On the other hand, in LBCO 15.5% [weak, highly fluctuating, but quasi-commensurate stripes (33, 34) (Fig. 1 G and K)], the THz emission in the superconducting state acquired an appreciable amplitude, with oscillations at a frequency of ∼600 GHz (depending on temperature).In the compound with incommensurate, relatively strong stripes, i.e., LBCO 9.5%, the THz emission amplitude was even higher than LBCO 15.5% and greater by a factor of ∼5–10 compared with LSCO and LBCO 11.5%. Coherent multicycle oscillations were observed (Fig. 1H), corresponding to a narrow spectral peak (Fig. 1L). The frequency of these oscillations shifted to the red with increasing temperature, while also reducing in amplitude and disappearing at TC.The rest of the analysis in this paper is focused on LBCO 9.5%, which yielded the largest signal and highest coherence. We verified that the emission was entirely polarized along the out-of-plane crystallographic axis and could be induced only for a pump polarization aligned along the same direction (SI Appendix).Fig. 2A displays the pump fluence dependence measured at a constant temperature of 7 K. These experimental traces were modeled using fits in time domain (solid lines), for which we report the single components in the SI Appendix. These include a “single-cycle” pulse at early times, which was absent at the lowest fluences and grew quadratically with irradiation, and a quasi-monochromatic, long-lived oscillation, which grew linearly up to about 1 mJ/cm² and tended to saturate for higher excitation fluence (Fig. 2B). This linear trend of the main oscillation is compatible with the impulsive excitation of a coherent mode. In the fluence-dependent behavior of lifetime and oscillation frequency (Fig. 2 C and D), we identify a linear excitation regime where these quantities are weakly dependent on fluence and seem to stabilize at constant values of ∼4 ps and ∼0.45 THz, respectively. In this weak excitation regime, the driven mode parameters are well determined.Open in a separate windowFig. 2.Pump fluence-dependent THz emission in La_1.905Ba_0.095CuO₄ at T = 7 K. (A) Experimental traces taken for different pump fluences (full circles). Solid lines are multicomponents fits to the data, which include a quasi-monochromatic, long-lived oscillation and a “single-cycle” component around time 0 (SI Appendix). (B–D) Fluence-dependent parameters of the quasi-monochromatic oscillation extracted from the fits in (A). Ampl., amplitude; Freq., frequency.In Fig. 3, we report the temperature dependence of this effect. We show a comparison between the oscillation frequency in the THz emission signal in LBCO 9.5%, and the bulk Josephson plasma resonance measured at equilibrium with time-resolved THz spectroscopy in the same sample. In the inset of Fig. 3A, we show the experimental geometry in which we illuminated the sample with weak broadband THz pulses (generated in a 200-μm-thick GaP), polarized along the out-of-plane direction, that were then detected in another 200-μm-thick GaP crystal via electro-optic sampling after being reflected from the sample surface.Open in a separate windowFig. 3.Comparison with the equilibrium Josephson plasma resonance (JPR) in La_1.905Ba_0.095CuO₄. (A, Inset) Experimental geometry for the equilibrium THz time-domain characterization. A weak broadband THz pulse was shone at normal incidence onto the sample surface with polarization along the c direction. The electric field profile of the same THz pulse was then detected after reflection. (A) Reflectivity taken at two different temperatures in the superconducting state, normalized by the same quantity measured at T = 35 K > TC (full circles). The solid lines are fits to the data performed with a JPR model. (B) Temperature dependence of the equilibrium Josephson plasma frequency (gray circles), as determined from the fits in (A). The oscillation frequencies in the THz emission signal measured in the same sample are also reported for two different excitation fluences (legend). Error bars indicate uncertainties extracted from fits such as those in Fig. 2 (see also SI Appendix). Solid lines are guides to the eye.Fig. 3A displays examples of reflectivity ratios at two temperatures below TC, normalized by the same quantity measured in the normal state. These curves evidence a Josephson plasma resonance, the exact frequency of which was determined by fitting the experimental data with a Josephson plasma model (solid lines) (35, 38). The key result of this analysis is displayed in Fig. 3B, in which we show a comparison of the temperature dependence of the Josephson plasma frequency at equilibrium (gray) with the frequency of the emitted oscillations for two pump fluences. Notably, the emitted mode frequency hardens with decreasing fluence and approaches the equilibrium plasma frequency measured at the corresponding base temperature.In interpreting our results, we first note that in a centrosymmetric cuprate, impulsive excitation of Josephson plasmons is forbidden by symmetry. Josephson plasma modes are in fact symmetry-odd (infrared-active), while impulsive photoexcitation couples only to totally symmetric modes (42). As discussed in a related theory work (43), a prerequisite for the excitation of these modes is that charge order breaks inversion symmetry. However, this does not happen for commensurate quasi-static stripes as those expected for dopings x ≳1/8 (33, 34), which exhibit a twofold screw axis along the out-of-plane direction (see Fig. 4A) (44). A symmetry breaking is expected instead for incommensurate or highly fluctuating stripes, as in the case of LBCO 9.5% and LBCO 15.5%. Here, the charge order correlation length along the out-of-plane direction is of the order of one unit cell (27), resulting in a loss of the phase relation between stripes in next-nearest-neighboring planes (Fig. 4B).Open in a separate windowFig. 4.(A) Charge density pattern (gradual scale of blue) in three neighboring planes of a cuprate with commensurate stripes (red dashed lines are spaced by 4a, where a is the lattice constant). Stripes in next-nearest layers are off-phased by π (30). Here, inversion symmetry is preserved (black dot and vertical dashed line are an inversion center and a screw axis, respectively). (B) Once commensurability is lost, stripes are fluctuating, or there is no phase relation between next-nearest layers, inversion symmetry can be broken, and THz emission is enabled (43). (C, Left) In-plane dispersion of bulk Josephson plasma polaritons (red line). Emission from these modes (Right) is expected to be very broad, as it encompasses a wide range of in-plane momenta, qx (gray shading) (43). (D, Left) Out-of-plane dispersion of surface Josephson plasmons (solid blue line). These modes are localized at the surface and propagate along z (out-of-plane direction). As their dispersion lies below the light cone (red shading), they are not expected to radiate into vacuum. However, Bragg scattering off the stripe order induces a backfolding, defined by the stripe wave vector, Qstripes, into a reduced Brillouin zone (dashed horizontal line). Hence, these surface modes are redirected into the light cone and can radiate out at frequencies just below ωJPR(q=0). (Right) Calculated emission spectrum from surface Josephson plasmons in a striped superconductor (43). JPR, Josephson plasma resonance.Once inversion symmetry is broken, electromagnetic emission at a frequency ω≪ωpump can result from rectification of the optical pulse. We associate the optically rectified drive for plasma oscillations with the excitation of a shift current (43, 44) at the sample surface. This is expected to interact with modes at ω≃ωJPR, of which one finds at least two: 1) a bulk Josephson plasma polariton, sustained by tunneling supercurrents oriented in the z (out-of-plane) direction and propagating along the x (in-plane) direction; and 2) a surface Josephson plasmon, also sustained by plasma oscillations in the z direction, but localized at the surface of the material and propagating along z. The dispersion relations for these two modes are shown in Fig. 4 C and D, respectively (45).Radiation from bulk plasma polaritons (Fig. 4C), excited over a depth between ∼200 nm (skin depth of the pump) and ∼1 μm (46), would be expected to be broad in frequency and overdamped. This is because excitation by the near-infrared pump covers a wide range of in-plane momenta, qx, which in the first instance, is limited only by the envelope bandwidth of the pump pulse (gray shading in Fig. 4C). The spectrum of Josephson plasmons would, in this case, also be independent of the details of the stripe order and of its correlation lengths, as is instead observed. Moreover, one would expect radiation at frequencies ω≳ωJPR, in contrast to the experimental observation of a slightly redshifted emission with respect to the plasma frequency (Fig. 3B).Coherent narrowband emission by surface Josephson plasmons is instead more likely. Although the dispersion of these modes lies below the light cone and, hence, they are not expected to radiate into vacuum (Fig. 4D), we argue here that Bragg scattering off the stripe order induces a backfolding, defined by the stripe wave vector, into a reduced Brillouin zone (dashed horizontal line in Fig. 4D). For this reason, these surface modes can radiate, much like a situation in which a fabricated corrugation would be used to achieve the coupling (47–50).In the right panel of Fig. 4D, we report the emission spectrum calculated for a striped superconductor through the excitation of surface Josephson plasmons. As extensively discussed in our related theory work (43, 44), in the presence of stripes, the pump pulse is expected to give origin to an Umklapp shift current, JUcos(Qstripesz), that is modulated in space by the stripe wave vector, Qstripes. This naturally drives high-momenta surface plasmons, which can radiate out due to the aforementioned backfolding mechanism.In summary, we have reported the observation of coherent THz emission just below the Josephson plasma frequency in cuprates for which the superconducting state coexists with stripes. We assigned this effect to the excitation of surface Josephson plasmons, which become Raman active due to the breaking of inversion symmetry induced by the stripes and can radiate out thanks to the backfolding of their dispersion curve onto the light cone. Based on these findings, the characterization of coherent THz emission emerges as a sensitive method to unveil broken symmetry states, which may not be detectable with other conventional techniques. Moreover, the absence of THz emission in LBCO 11.5%, where the stripes are more robust and quasi-static, may suggest a qualitative difference in the nature of charge and spin order between compounds that are in the vicinity of the commensurate 1/8 doping and those that are far from it.     

Effects of different cigarette smoke yields on puffing and inhalation: is the measurement of inhalation volumes relevant for smoke absorption?

Puffing patterns (number of puffs, puff volume, puff duration, puff interval, peak pressure, peak flow, peak latency), respiratory smoke inhalation (postpuff inspiratory latency, volume and time and postpuff expiratory volume and time), and the pre- to postsmoking boost of tidal air CO concentration were analyzed in 117 regular smokers. They smoked both a cigarette of the habitual brand and a second cigarette of a brand with about 40 to 50% lower machine standard smoke yields and the most similar taste quality. The pre- to postsmoking CO boost remained unrelated to the smoke deliveries of the cigarettes in both comparisons (interindividual and switching). Estimated mouth intake of nicotine was strongly dependent on the smoke yield variables of the cigarettes but remained uncorrelated with CO absorption. The discrepancy between mouth smoke intake and alveolar smoke absorption could not be explained by the volumes or durations of the postpuff respiratory cycle. Multiple regression analyses suggested differential modes of control for the daily number of cigarettes smoked, for the patterns of puffing, for respiratory inhalation, and finally for alveolar CO absorption. The results are discussed in relation to the dynamics of puffing and inhalation and their possible relevance for tobacco-related diseases.