Dendritic processing of excitatory synaptic input in hypothalamic gonadotropin releasing-hormone neurons.

The activity of hypothalamic GnRH neurons results in the intermittent release of GnRH required for reproductive function. This intermittent neurosecretory activity has been proposed to reflect integration of intrinsic properties of and synaptic input to GnRH neurons. Determining the relative impact of synaptic inputs at different locations on the GnRH neuron is difficult, if not impossible, using only experimental approaches. Thus, we used electrophysiological recordings and neuronal reconstructions to generate computer models of GnRH neurons to examine the effects of synaptic inputs at varying distances from the soma along dendrites. The parameters of the models were adjusted to duplicate measured passive and active electrophysiology of cells from mouse brain slices. Our morphological findings reinforce the emerging picture of a complex dendritic structure of GnRH neurons. Furthermore, analysis of reduced morphology models indicated that this population of cells is unlikely to exhibit low-frequency tonic spiking in the absence of synaptic input. Finally, applying realistic patterns of synaptic input to modeled GnRH neurons indicates that synapses located more than about 30% of the average dendrite length from the soma cannot drive firing at frequencies consistent with neuropeptide release. Thus, processing of synaptic input to dendrites of GnRH neurons is probably more complex than simple summation.

Kinetics of reduction of the oxidized primary electron donor of photosystem II in spinach chloroplasts and in Chlorella cells in the microsecond and nanosecond time ranges following flash excitation.

Absorption changes (deltaA) at 820 nm, following laser flash excitation of spinach chloroplasts and Chlorella cells, were studied in order to obtain information on the reduction time of the photooxidized primary donor of Photosystem II at physiological temperatures. In the microsecond time range the difference spectrum of deltaA between 750 and 900 nm represents a peak at 820 nm, attributable to a radical-cation of chlorophyll a. In untreated dark-adapted material the signal can be attributed solely to P+-700; it decays in a polyphasic manner with half-times of 17 microseconds, 210 microseconds and over 1 ms. The oxidized primary donor of Photosystem II (P+II) is not detected with a time resolution of 3 microseconds. After treatment with 3--10 mM hydroxylamine, which inhibits the donor side of Photosystem II, P+II is observed and decays biphasically (a major phase with t1/2=20--40 microseconds, and a minor phase with t1/2 congruent to 200 microseconds), probably by reduction by an accessory electron donor. In the nanosecond range, which was made accessible by a new fast-response flash photometer operating at 820 nm, it was found the P+II is reduced with a half-time of 25--45 ns in untreated dark-adapted chloroplasts. It is assumed that the normal secondary electron donor is responsible for this fast reduction.

Reactions between primary and secondary acceptors of photosystem II in Chlorella pyrenoidosa under anaerobic conditions as studied by chlorophyll fluorescence.

The kinetics of the fluorescence yield phi of chlorophyll a in Chlorella pyrenoidosa were studied under anaerobic conditions in the time range from 50 mus to several minutes after short (t 1/2 = 30 ns or 5 mus) saturating flashes. The fluorescence yield "in the dark" increased from phi = 1 at the beginning to phi approximately 5 in about 3 h when single flashes separated by dark intervals of about 3 min were given. After one saturating flash, phi increased to a maximum value (4-5) at 50 mus, then phi decreased to about 3 with a half time of about 10 ms and to the initial value with a half time of about 2 s. When two flashes separated by 0.2 s were given, the first phase of the decrease after the second flash occurred within 2 ms. After one flash given at high initial fluorescence yield, the 10-ms decay was followed by a 10 s increase to the initial value. After the two flashes 0.2 s apart, the rapid decay was not followed by a slow increase. These and other experiments provided additional evidence for and extend an earlier hypothesis concerning the acceptor complex of Photosystem II (Bouges-Bocquet, B. (1973) Biochim. Biophys. Acta 314, 250-256; Velthuys, B. R. and Amesz. J. (1974) Biochim. Biophys. Acta 333, 85-94): reaction center 2 contains an acceptor complex QR consisting of an electron-transferring primary acceptor molecule Q, and a secondary electron acceptor R, which can accept two electrons in succession, but transfers two electrons simultaneously to a molecule of the tertiary acceptor pool, containing plastoquinone (A). Furthermore, the kinetics indicate that 2 reactions centers of System I, excited by a short flash, cooperate directly or indirectly in oxidizing a plastohydroquinone molecule (A2-). If initially all components between photoreaction 1 and 2 are in the reduced state the following sequence of reactions occurs after a flash has oxidised A2- via System I: Q-R2- + A leads to Q-R + A2- leads to QR- + A2-. During anaerobiosis two slow reactions manifest themselves: the reduction of R (and A) within 1 s, presumably by an endogenous electron donor D1, and the reduction of Q in about 10 s when R is in the state R- and A in the state A2-. An endogenous electron donor, D2, and Q- complete in reducing the photooxidized donor complex of System II in reactions with half times of the order of 1 s.

A one microsecond component of chlorophyll luminescence suggesting a primary acceptor of system II of photosynthesis different from Q.

The kinetics of the luminescence of chlorophyll a in Chlorella vulgaris were studied in the time range from 0.2 mus to 20 mus after a short saturating flash (t 1/2 = 25 ns) under various pretreatment including anaerobiosis, flashes, continuous illumination and various additions. A 1 mus luminescence component probably originating from System II was found of which the relative amplitude was maximum under anaerobic conditions for reaction centers in the state SPQ- before the flash, about one third for centers in the state S+PQ- or SPQ before the flash, and about one tenth for centers in the state S+PQ before the flash. S is the secondary donor complex with zero change; S+ is the secondary donor complex with 1 to 3 positive charges; P, the primary donor, is the photoactive chlorophyll a, P-680, of reaction center 2; Q- is the reduced acceptor of System II, Q. Under aerobic conditions, where an endogenous quencher presumably was active, the luminescence was reduced by a factor two. The 1 mus decay of the luminescence is probably caused by the disappearance of P+ formed in the laser flash according to the reaction ZP+ leads to Z+ in which Z is the molecule which donates an electron to P+ and which is part of S. After addition of hydroxylamine, the 1 mus luminescence component changed with the incubation time exponentially (tau = 27 s) into a 30 mus component; during the same time, the variable fluorescence yield, measured 9 mus after the laser flash, decreased by a factor 2 with the same time constant. Hereafter in a second much slower phase the fluorescence yield decreased as an exponential function of the incubation time to about the dark value; meanwhile the 30 mus luminescence increased about 50% with the same time constant (tau = 7 min). Heat treatment abolished both luminescence components. The 1 mus luminescence component saturated at about the same energy as the System II fluorescence yield 60 mus after the laser flash and as the slower luminescence components. From the observation that the amplutide is maximum if the laser flash is given when the fluorescence yield is high after prolonged anaerobic conditions (state SQ-), we conclude that the 1 mus luminescence is probably caused by the reaction PWQ- + hv leads to P*WQ- leads to P+W-Q- leads to P*WQ- leads to PWQ- + hv in which W is an acceptor different from Q. The presence of S+ reduced the luminescence amplitude to about one third. Two models are discussed, one with W as an intermediate between P and Q and another, which gives the best interpretation, with W on a side path.

Absorption changes of P-700 reversible in milliseconds at low temperature in Triton-solubilized photosystem I particles.

Triton-solubilized Photosystem I particles from spinach chloroplasts exhibit largely reversible P-700 absorption changes over the temperature range from 4.2 K to room temperature. For anaerobic samples treated with dithionite and neutral red at pH 10 and illuminated during cooling, a brief (1 microseconds) saturating flash produces absorption changes in the long wavelength region that decay in 0.95 +/- 0.2 ms from 4.2 to 50 K. Above 80 K a faster (100 +/- 30 microseconds) component dominates in the decay process, but this disappears again above about 180 K. The major decay at temperatures above 200 K occurs in about 1 ms. The difference spectrum of these absorption changes between 500 and 900 nm closely resembles that of P-700. Using ascorbate and 2.6-dichlorophenolindophenol as the reducing system with a sample of Photosystem I particles cooled in darkness to 4.2 K, a fully reversible signal is seen upon both the first and subsequent flashes. The decay time in this case is 0.9 +/- 0.3 ms.

Electron acceptors associated with P-700 in Triton solubilized photosystem I particles from spinach chloroplasts.

Flash-induced absorption changes of Triton-solubilized Photosystem I particles from spinach were studied under reducing and/or illumination conditions that serve to alter the state of bound electron acceptors. By monitoring the decay of P-700 following each of a train of flashes, we found that P-430 or components resembling it can hold 2 equivalents of electrons transferred upon successive illuminations. This requires the presence of a good electron donor, reduced phenazine methosulfate or neutral red, otherwise the back reaction of P-700+ with P-430 occurs in about 30 ms. If the two P-430 sites, designated Centers A and B, are first reduced by preilluminating flashes or chemically by dithionite under anaerobic conditions, then subsequent laser flashes generate a 250 microseconds back reaction of P-700+, which we associate with a more primary electron acceptor A2. In turn, when A2 is reduced by background (continuous) illumination in presence of neutral red and under strongly reducing conditions, laser flashes then produce a much faster (3 microseconds) back reaction at wavelengths characteristic of P-700. We associate this with another more primary electron acceptor, A1, which functions very close to P-700. The organization of these components probably corresponds to the sequence P-700-A1-A2-P-430[AB]. The relation of the optical components to acceptor species detected by EPR, by electron-spin polarization or in terms of peptide components of Photosystem I is discussed. Preliminary experiments with broken chloroplasts suggest that an analogous situation occurs there, as well.

Lens transmission of blue-green light in diabetic patients as measured by autofluorophotometry.

Lens transmission for blue-green light (lambda = 490 nm and 530 nm) was assessed by means of fluorophotometry in 67 diabetic patients without cataracts and compared with that of 52 healthy controls. Lens transmission was determined from peak autofluorescence values in the anterior and posterior parts of the lens, assuming an about equal fluorescence peak quantum efficiency in both parts. The variation in lens transmission between individuals of about the same age was found to be larger in the diabetic patients than in the healthy controls. Decrease in lens transmission as a function of age occurred about 15 years earlier in patients with diabetes of more than 10 years' duration than in the healthy controls. The calculated average extra decrease of lens transmission in the diabetic group amounted to 0.5% for each year of diabetes.

The immediate effect of phenylephrine on aqueous flow in man.

Aqueous flow in normal human eyes was assessed at 1 hr intervals via fluorophotometric measurements, starting 4 hr after fluorescein instillation. The average coefficients of variation of the individual flow values were 5.3% and 8.4% for 1 hr and 1 week intervals, respectively. Aqueous flow was measured in 11 healthy volunteers after the instillation of phenylephrine. In the first hour the aqueous flow showed a significant increase: 131% +/- 72% (P less than 0.001) and in the second hour: 121% +/- 92% (P less than 0.002). Between 2 and 5 hr the average flow did not differ significantly from the flow in the untreated fellow eye. There was no marked effect of pupil dilation on aqueous flow.

Blood-retinal barrier dysfunction at the pigment epithelium induced by blue light.

Exposure to low-intensity white light can induce dysfunction of the blood-retinal barrier (BRB) at the retinal pigment epithelium (RPE). To determine whether the shorter wavelengths white light are responsible for this dysfunction, rabbit retinas were exposed to blue light (400-520 nm) or yellow light (510-740 nm). The permeability of the BRB, a parameter for the integrity of the barrier, was quantified with vitreous fluorophotometry. Morphologically, the barrier at the RPE was visualized on light and electron microscopy using horseradish peroxidase (HRP) as a tracer. Seventeen pigmented rabbits were exposed to blue light and 11 were exposed to yellow light. Vitreous fluorescein leakage increased with the exposure energy according to a power function (correlation coefficient > 0.79). The threshold energy for an increase in BRB permeability was 50 J/cm2 (0.014 W/cm2 for 1 hr) after blue and 1600 J/cm2 after yellow light. HRP tracing demonstrated that after blue light exposure, a significant fluorescein leakage on fluorophotometry corresponded to the presence of HRP in the RPE cells and in the subretinal space. After yellow light exposures of < 3700 J/cm2 and in rabbits with no significant fluorescein leakage, the HRP was limited to the choroidal capillaries and Bruch's membrane. These results demonstrate that the blue component of white light causes dysfunction of the BRB at the RPE 30 times more effectively than the longer wavelength fraction of white light. As a result, a blue light blocking filter should be used in ocular surgery on humans when an operating microscope is being used (light power 0.1-0.9 W/cm2).

Basal tear turnover and topical timolol in glaucoma patients and healthy controls by fluorophotometry.

To assess the effect of glaucoma and timolol on tear secretion, basal tear turnover was measured with fluorophotometry in 13 open-angle glaucoma patients not using any ophthalmic medication, 24 patients using timolol medication daily, and 41 healthy control subjects. Basal tear turnover is defined as the tear turnover at the lowest level of reflex lacrimation possible under physiologic conditions. Tear turnover was calculated from the decay of the tear fluorescence after instillation of fluorescein. Minimal influence of reflex lacrimation was obtained by instilling 1 microliter of 2% fluorescein without touching the eye and by discarding measurements performed in the first 5 min. Minimization was confirmed by a monophasic decay of tear fluorescence. The values of patients who used timolol and those who did not use timolol were significantly lower than those of healthy control subjects (mean values in percent/minute +/- standard deviation: 10.1 +/- 3.2, 12.3 +/- 4.1, and 15.6 +/- 5.4, respectively; Student's t-test: P < 0.02). The values of patients who used timolol were significantly lower compared to those of patients who did not use timolol (P = 0.03). The tear film break up time values of patients who used timolol were significantly shorter than those of patients who did not use timolol and healthy control subjects (Fisher exact test: P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Corneal epithelial barrier function after oxybuprocaine provocation in diabetics.

Corneal epithelial permeability for fluorescein was determined after provocation by a local anesthetic in 18 non-insulin-dependent diabetes mellitus (NIDDM) patients, 23 insulin-dependent diabetes mellitus (IDDM) patients, and 22 healthy controls to evaluate the corneal epithelial barrier function in diabetes. All volunteers had Oxybuprocaine instilled into one eye and saline into the other eye. The epithelial permeability values were determined by fluorophotometry, and the ratio between both eyes was calculated for each individual. The mean permeability values of the saline-instilled eyes in the diabetic patients did not differ significantly from those in the healthy controls (P greater than 0.2). The individual ratios between Oxybuprocaine- and saline-instilled eyes in the NIDDM and IDDM patients differed significantly from those in the healthy controls (mean ratios: 2.6, 1.9, and 1.0, respectively; P less than 0.002). The permeability ratios and the percentage glycosylated hemoglobin (HbAlc) were linearly correlated in the NIDDM patients but not in the IDDM patients (r = 0.73, P less than 0.001, and r = 0.09, P greater than 0.68, respectively). The results showed that the corneal epithelial barrier function in the diabetic patients was not impaired compared with that in the healthy controls. After provocation by a local anesthetic, the barrier function was impaired in the diabetic patients only.

Corneal autofluorescence: an indicator of diabetic retinopathy.

The metabolic disorder in diabetics often results in progressive retinopathy with severe visual impairment. Changes in metabolism can influence corneal autofluorescence. This has led to speculation that diabetic retinopathy might be associated with changes in corneal autofluorescence. Corneal autofluorescence of both eyes was determined by fluorophotometry in 94 insulin-dependent diabetes mellitus patients and in 46 healthy controls to evaluate its correlation with diabetic retinopathy. The modified Airlie House classification was used for grading diabetic retinopathy: (1) no or negligible retinopathy; (2) minimal background retinopathy; (3) background retinopathy; and (4) (pre-) proliferative retinopathy. The corneal autofluorescence values of grade 1 retinopathy patients did not differ significantly from those of the healthy controls (mean +/- standard deviation in ng equivalent fluorescein/ml: 11.6 +/- 3.0 and 11.4 +/- 2.8, respectively; P = 0.8). The means of grade 2, 3, and 4 retinopathy patients (mean +/- standard deviation in ngEq fluorescein/ml: 16.2 +/- 4.4, 16.7 +/- 4.3, 20.9 +/- 5.4, respectively) were significantly higher than the means of grade 1 patients and healthy controls (P less than 0.004). The mean values of patients with grade 4 were significantly higher than those of patients with grades 2 and 3 (P less than 0.01). The sensitivity and specificity of corneal autofluorescence as a screening test for diabetic retinopathy were 80% and 76%, respectively; the positive predictive value for the presence of retinopathy was 90%. The values for screening on (pre-) proliferative diabetic retinopathy were 68%, 72%, and 58%, respectively. These data show corneal autofluorescence to be an adequate indicator of diabetic retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Inward permeability of the blood-retinal barrier by fluorophotometry.

A method for assessing the inward permeability of the blood-retinal barrier by fluorophotometry is presented. The permeability value is calculated with the fluorophotometer computer from fluorophotometric scan values in vitreous and non-protein-bound fluorescein concentration values in plasma. No diffusion coefficient of fluorescein in vitreous was required in the calculations. Corrections were performed for lens transmission, corneal transmission, and the spatial resolution of the apparatus. The method was applied to 58 healthy volunteers, aged 13-72 yr. An insignificant average increase of permeability values was found from 4.8 nm/s at 10 yr, up to 6.1 nm/s at 70 yr (P = 0.14; standard deviation: 1.8 nm/s). Permeability values showed an average increase of 10% between 30 min and 60 min after injection (P less than 0.001).

Reflex lacrimation in patients with glaucoma and healthy control subjects by fluorophotometry.

PURPOSE: Steady state tear turnover (TTO), defined as TTO under normal physiological conditions, is significantly lower in patients with untreated glaucoma than in healthy control subjects. To obtain more information on the effect of glaucoma on lacrimation, a method for quantification of reflex lacrimation was developed and applied to patients with glaucoma or ocular hypertension and healthy control subjects. METHODS: After instillation of 2 microl of fluorescein (2%), the decay of fluorescein concentration in tears was measured by fluorophotometry over 10 minutes to determine steady state TTO. Then, reflex lacrimation was induced by stimulating the trigeminal nerve with ethanol vapor via the nostrils. Thereafter, the decay of fluorescein and corresponding steady state TTO were determined again. An index of reflex lacrimation, defined as the percentage decrease in fluorescein concentration as a result of stimulation, was calculated by forward and backward extrapolation of the steady state decay of the fluorescein concentration in tears, relative to the time of stimulation. RESULTS: The index of reflex lacrimation was determined in 16 patients with newly discovered but not yet treated glaucoma, 16 patients with untreated ocular hypertension, and 16 healthy control subjects. The values did not differ between groups (mean +/- SD, 67.0%+/-17.7%, 63.5%+/-21.3%, and 70.4%+/-19.6%, respectively; ANOVA, P>0.25). Surprisingly, the steady state TTO after stimulation was lower than that before stimulation in each group (ratio, 0.62+/-0.46; paired t-test, P<0.04). CONCLUSIONS: The method developed is appropriate for the quantification of reflex lacrimation. Reflex lacrimation is not influenced significantly by glaucoma or ocular hypertension. The decreased steady state TTO after reflex stimulation may be caused by exhaustion of the lacrimal glands after excessive reflex lacrimation, indicating that normal lacrimation probably also contains reflex tears.

Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry.

Autofluorescence (lambda = 530 nm) of the human lens was determined as a function of age by fluorophotometry in insulin-dependent diabetics and in healthy controls. Statistical analysis revealed a significant linear age dependency for both groups (7.98 ng eq X ml-1 y-1 for diabetic patients, P less than 0.001 and 6.36 ng eq X ml-1 y-1 for healthy controls, P less than 0.001) and a significant dependency on diabetes duration (8.78 ng eq X ml-1 per year of diabetes duration, P less than 0.001). The increase with age was found from about zero value at early childhood.

Bacteriochlorin a, a new photosensitizer in photodynamic therapy. In vivo results.

The photosensitizing properties of bacteriochlorin a (BCA), a nontoxic derivative of bacteriochlorophyll a, were investigated in vivo. BCA has an absorption band at a wavelength at which tissue penetration is optimal (760 nm), and it shows preferential tumor retention in Greene melanoma implanted in the anterior chamber of rabbit eyes. A dose of 20 mg/kg BCA was administered IV at 4-7 mm tumor diameter; 24 hr later the tumor was irradiated with near-infrared light (30 min, 760 nm, 150-280 J/cm2). On the day after the irradiation it appeared that tumor growth had stopped: fluorescein angiography showed nonperfusion of the tumor. Histopathology after enucleation showed subtotal tumor necrosis with occasionally small clusters of viable cells around a blood vessel and at the tumor periphery. Neither BCA nor light alone had any effect on the eye or melanoma.

Regulation of tyrosine hydroxylase gene expression by the m1 muscarinic acetylcholine receptor in rat pheochromocytoma cells.

Tyrosine hydroxylase (TH) gene transcription rate is increased in rat adrenal medulla after administration of muscarinic agonists. In order to study this muscarinic regulation of TH gene expression in more detail, we have generated a rat pheochromocytoma PC18 cell line that stably expresses the mouse m1 muscarinic acetylcholine receptor. Treatment of this cell line, designated PC18/m1-13, with carbachol leads to rapid increases in phosphatidylinositol turnover and intracellular [Ca2+]i; these increases are totally blocked by the muscarinic antagonist atropine. Carbachol produces no changes in cAMP levels or protein kinase A activity in PC18/m1-13 cells. TH mRNA levels in PC18/m1-13 cells increase approximately 3-fold after 6 h of treatment with carbachol. This induction of TH mRNA is also completely inhibited by simultaneous treatment with atropine. Transient transfection assays using a TH gene promoter-chloramphenicol acetyltransferase (TH-CAT) construct demonstrate that sequences within the most proximal 272 bp of the TH gene 5'-flanking region are responsive to carbachol in PC18/m1-13 cells. Studies using TH-CAT constructs with site-directed mutations within the TH gene promoter indicate that the responsiveness of the promoter to carbachol is mediated primarily by the cAMP response element; however, the AP1 site also participates to a lesser extent in this response. The carbachol-mediated stimulation of TH gene promoter activity is partially inhibited by down-regulation of protein kinase C (PKC) or by treatment with the Ca2+/calmodulin-dependent protein kinase inhibitor, KN62. These results are consistent with the hypothesis that agonist occupation of m1 muscarinic receptors stimulates the TH gene via signal transduction pathways that are initiated by activation of PKC and Ca2+/calmodulin-dependent protein kinase, leading to activation of transcription factors that interact with the TH CRE and AP1 sites.

Function and morphology of the retinal pigment epithelium after light-induced damage.

The purpose of this study was to determine the threshold energy for light-induced functional damage of the retinal pigment epithelium at various wavelengths. Retinas of 58 pigmented and 21 albino rabbits were exposed to low intensity broadband blue light (400-520 nm), yellow light (510-740 nm), and narrowband blue light (408, 417, 439, 455, 485, 501 nm, respectively; deltalambda = 10-13 nm). The intensity values were 50, 280, and 5 mW x cm (-2), respectively, and the illumination time was 0.5 up to 5 h. The cumulative dose of light energy was calculated from these data (J x cm(-2)). The blood-retinal barrier dysfunction was evaluated in vivo using fluorophotometry to measure the leakage of fluorescein into the vitreous after intravenous injection and in vitro using light and electron microscopy after an in vivo intraarterial injection of horseradish peroxidase (HRP). The threshold energy for fluorescein leakage was 50 J x cm (-2) for blue light and 1,600 J x cm(-2) for yellow light. After broadband blue light exposure, the HRP reaction product was seen in the cytoplasm of the retinal pigment epithelium (RPE) cells and in the subretinal space but only if fluorescein leakage had been observed. Threshold energy and fluorescein leakage as a function of light energy were similar for albino and pigmented rabbits (P > 0.5). Only after yellow light exposure in excess of 3,700 J x cm(-2) was fluorescein leakage found. In that case complete disruption of the RPE was seen, but no HRP was observed in the RPE cytoplasm. Of the narrow-band blue light exposures, only that at lambda = 418 nm caused a significant increase in fluorescein leakage; the threshold energy was 18 J x cm(- 2). Blue light was found to be at least 30 times more efficient than yellow light in causing dysfunction of the blood-retinal barrier. The most efficient wavelength was 418 nm, corresponding with the absorption spectrum of cytochrome c oxidase. Melanin seemed to play no role. The presence or absence of melanin in the RPE appeared to have no influence on the threshold energy.

Patients' perspectives of a physician-delivered smoking cessation intervention.

Forty-three patients--recipients of a highly structured, physician-delivered smoking cessation intervention--were interviewed using ethnographic (anthropological) research methods. We conducted interviews with patients after visits with the physician, then audiotaped and transcribed them. Discourse analysis of interview texts identified features and components of the physician maneuver most effective from the patients' point of view. Patients discussed two general areas of physicians' preventive activities: an interventionistic component (in which professional, diagnostic, and authoritative features were emphasized) and a personalistic component (in which physicians were experienced as equals, supportive, caring, empowering, and challenging). From the perspective of patients, the personalistic component of the physician-delivered smoking cessation maneuver appeared most effective. We conclude that, in clinical preventive medicine generally, patients (1) evaluate the kind of support they receive from their physician (e.g., degree of empathy, encouragement, and sincerity), (2) respond favorably to positive imagery in the challenge to alter their lifestyle, (3) look for a balance in the relationship established with their physician (negotiation, respect, mutual understanding, and rapport), and (4) remember the consistency and regularity of their physician's health promotion messages.

A family physician smoking cessation program: an evaluation of the role of follow-up visits.

Our purpose in this randomized clinical trial was to compare a two-visit smoking cessation intervention by family physicians with the same intervention supplemented by additional follow-ups. Forty-one southern Ontario family physicians volunteered for the study and subsequently participated in a four-hour training program on smoking cessation techniques. Physicians advised patients who smoked and indicated an interest in attempting to quit with the help of their physician to stop smoking at the end of a regularly scheduled visit. Physicians instructed patients to make a specific appointment for an evaluation of their smoking habits. Six hundred forty-seven patients returned for that assessment and were than randomized into either the two-visit intervention group (with risk assessment, support, the setting of a cessation date, self-help literature, and a prescription for nicotine gum, where appropriate) or into the other intervention group (with the same maneuvers as well as the offer of four more supportive follow-up visits). We found no statistically significant difference in one-year, biochemically validated, sustained cessation rates between the group offered the long-term follow-up visits (12.5%) and the group given the brief intervention (10.2%). The 95% confidence interval on the difference between the groups was 2.8% in favor of the brief intervention group to 7.3% in favor of the group offered follow-up. The results do not support the value of long-term follow-up visits for smokers.