Human choice in concurrent ratio-interval schedules of reinforcement

Seven undergraduates participated in a concurrent-choice experiment with monetary reinforcers. Response-independent analogues of variable-interval and variable-ratio schedules were used to assess whether subjects would maximize reinforcement rate. The optimal pattern of behavior, in terms of maximizing reinforcement rate, involved a large bias toward the ratio alternative, with only occasional sampling of the interval schedule. Most experiments with pigeons, however, demonstrate matching of response rates to reinforcement rates, with only slight biases for the ratio schedule. Although subjects in the present experiment allocated more time to the ratio alternative than required by matching, the magnitude of the bias did not approximate that predicted by a maximizing account. After exposure to clock stimuli correlated with the operation of each schedule, 1 subject's behavior did show a substantial level of bias, increasing the total number of reinforcers obtained, and lay at a point between the predictions of matching and maximizing. The other subjects, however, continued to respond less optimally. The present results can be accounted for by a view of matching that incorporates the effects of delayed reinforcement.     

Predicting realistic RBE values for clinically relevant radiotherapy schedules

To consider the therapeutic potential of radiation effect modifiers it is necessary to balance the modification of the injury in tumours with that in different types of normal tissue. It is especially important to ensure that the effects that have been demonstrated in preclinical experiments are both qualitatively and quantitatively relevant for the radiation doses that will be used in clinical schedules. Most radiobiology studies are initially performed with large single doses or a few large fractions, and from those results predictions have sometimes been made of the potential clinical benefit from a radiation modifier. In the clinic they will be used with many repeated small fractions of about 2 Gy over a period of several weeks. The effects will be quantitatively different in these two dose ranges for a variety of reasons. No modifiers of radiation effect are truly dose-modifying over the whole dose spectrum. They all have a differential effect on the type of damage inflicted at high and low dose levels, i.e. those described by the linear and quadratic terms in the LQ model. This means that every modifier has a dose or dose per fraction dependence on the magnitude of the sensitization or protection. The details of that dose dependence will vary with the alpha/beta ratio of the tissue under consideration. Furthermore all tissues and tumours contain a mixture of cells, with different proliferative, redox and other characteristics that influence their sensitivity to radiation and their susceptibility to the radiomodifier. The influence of different subsets of cells changes as a fractionated treatment progresses and the sensitive cells are eradicated, leaving more resistant survivors. The overall response to a fractionated schedule then depends critically on whether there is re-assortment of cells from the resistant phase into more sensitive or modifiable phases before the next fraction in the series. In addition, the magnitude of dose modification depends totally on the standard curve against which the comparison is made. The reference standard is different in preclinical laboratory studies and in conventional clinical experience. Those differences must be considered when moving from the laboratory to the clinic and back again. The effect of these different factors is considered using the linear quadratic model to dissect the components. Examples are provided to demonstrate the clinical relevance.     

Mathematical derivation of optimal treatment schedules for the radiotherapy of human tumours. Fractionated irradiation of exponentially growing tumours

A mathematical model is developed to allow derivation of optimal treatment schedules for the radiotherapy of exponentially-growing tumours. Preliminary calculations based on available data suggest that optimal schedules would (in general) be more protracted than conventional schedules and might achieve a significantly better tumour cell kill without causing excessive damage to normal connective tissue. The model is too simple, and the data inadequate, for the conclusions reached to be used as a guide to clinical practice at present. However, the analysis can be extended to more realistic models which may be of clinical benefit when the appropriate data can be obtained.     

The choice of the optimal schedules in the vaccination procedure against influenza in elderly subjects

The paper describes a clinical case of the cerebral hyperperfusion syndrome, a rare complication of carotid endarterectomy. The syndrome appeared as the generalized convulsive syndrome in the patient in the early postoperative period. In the context of clinical observation, the results of analysis of the literature are presented and the pathogenesis, diagnosis, therapy, and prevention of the cerebral hyperperfusion syndrome considered.     

Provider choice and continuity for the treatment of depression

The role of specialist versus generalist providers regularly surfaces in health-care reform debates about costs and quality of care. By changing incentives to seek and deliver care, different payments systems can affect both the probability of initial specialty care and the duration of this patient-provider relationship. The authors compare provider selection (psychiatrist, nonphysician mental-health specialist, general medical provider) and duration of this relationship among depressed patients in prepaid and fee-for-service plans. Regarding initial care, depressed patients in prepaid plans are significantly less likely to see a psychiatrist and more likely to see a nonphysician mental-health specialist than patients in fee-for-service plans. Although the mix of providers differs, patient demographic and clinical characteristics have similar effects on specialty in both payment systems, ie, there are no differences in who gets specialty care by type of payment, but in how many get specialty care. The average duration of a patient-provider relationship is significantly shorter in prepaid plans. Durations are significantly shorter for patients of both psychiatrists and general medical providers in prepaid plans, but do not differ by payments type for nonphysician therapists. In both payments systems, patients of nonphysician providers end the relationship sooner than patients of psychiatrists or general medical providers. Although the authors find provider switching to be associated significantly with discontinuing antidepressant medication, there is no significant direct effect on patient health outcomes.     

Oral treatment schedules for onychomycosis: a study of patient preference

BACKGROUND: An improved understanding of patients' attitudes to medication may help promote compliance with oral medications for onychomycosis. This study was performed to assess patients' preference between continuous and intermittent oral treatment schedules for onychomycosis and to determine the reasons underlying the selections made. METHODS: Patients were eligible for inclusion if they had current onychomycosis and were willing to take oral medication for this condition. In a 30-min, face-to-face interview, each patient answered questions about four possible treatment schedules for onychomycosis; regimen 1--continuous (daily regular intake) for 12 weeks; regimen 2--intermittent 1 week/month for 3 months (last week of therapy is week 9); regimen 3--intermittent once weekly for 21 weeks; regimen 4--intermittent 1 week/month for 4 months (last week of therapy is week 13). RESULTS: A total of 102 patients from Germany and Spain participated in the study. When asked to choose between regimens 1, 2, and 3, 46% of patients favored the 9-week intermittent schedule, 42% selected the 12-week continuous schedule, and 12% preferred the 21-week intermittent schedule. The preference for the 9-week intermittent schedule was more notable among younger patients (< 45 years), possibly because they are less used to taking regular medication, and among Spanish patients, an effect that could not be attributed to age because the average age of patients was similar in the participating countries (Germany 47.2 years; Spain 48.0 years). When the patients who preferred regimen 2 were asked to choose between regimens 1, 3, and 4 (both intermittent schedules longer than the continuous schedule), most (57%) favored the shortest treatment schedule (regimen 2). CONCLUSIONS: Overall, patients favored an intermittent schedule lasting 9 weeks. Treatment duration is the critical factor in determining patients' preference for treatment schedules for onychomycosis.     

Linguistic considerations in the treatment of bilinguals.

Language is intimately connected with most aspects of human development. Because of this pervasive quality, language is incorporated as part of the individual's coping mechanisms, and at times it may even serve a definite defensive role. This investigation examines research and clinical data regarding the language independence phenomenon as it relates to the treatment of bilingual patients. Attempts are made to describe the way the bilingual individuals mobilize (shift) their languages under anxiety-producing conditions and how this shifting of languages can be utilized by these individuals as part of their coping mechanisms. There can be both positive and negative implications for treatment. In this regard, the article illustrates how the linguistic shifting may further reinforce defenses such as intellectualization, splitting, and isolation of affect. Linguistic shifting can also be technically introduced by monolingual clinicians to advance the therapeutic process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Practical considerations in the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents one of the most common neoplasms worldwide. To date, curative treatment options include liver transplantation or resection. Unfortunately, most patients are detected with nonresectable or -transplantable HCC due to disease extension or comorbid factors, and are therefore candidates only for palliative treatments. Palliative medical treatments, including systemic chemotherapy, immunotherapy or hormonal manipulation, have a borderline activity on HCC and cannot be recommended outside clinical trials. A high response rate has been reported with local therapies such as transcatheter arterial embolisation, intra-arterial chemotherapy or percutaneous alcohol (ethanol) injection, but as there is no clear evidence of a survival advantage for these treatment modalities, further investigations are required. Multidisciplinary treatment, including preoperative cytoreduction or postoperative adjuvant therapy, is currently under investigation, with encouraging survival results. HCC patients should be evaluated within clinical trials, possibly randomised and with homogeneous prognostic factors, in order that we may find the answer to all these important questions.     

Fixed-time schedules attenuate extinction-induced phenomena in the treatment of severe aberrant behavior

We compared the effects of extinction (EXT) and fixed-time (FT) schedules as treatment for severe problem behavior displayed by 3 individuals with developmental disabilities. First, functional analyses identified the reinforcers maintaining aberrant behavior for all 3 individuals. Next, EXT and FT schedules were compared using a multielement design. During EXT, the reinforcer maintaining problem behavior was withheld. During FT, the reinforcers were presented response independently at preset intervals. Results showed that FT schedules were generally more effective than EXT schedules in reducing aberrant behavior. FT schedules may be used in situations when extinction-induced phenomena are problematic.     

Time-related differential effects of epidural morphine on the neuraxis

To clarify the site and potency of the analgesic and anesthetic action of epidurally administered morphine, we investigated the effects of epidurally and intravenously administered morphine (100 micrograms/kg) on change in the pressure pain threshold (PPT) and the minimum alveolar concentration (MAC) of halothane. Epidural morphine (EM) increased PPT significantly (P < 0.01) at the points around the surgical incision by 40% and 60% from baseline compared with intravenous morphine (IM) with which PPT remained at baseline 1 and 2 h after administration, respectively. Duration of analgesia was much longer in EM than in IM (18 h vs 1.7 h). EM increased PPT from preoperative value at the forehead and the points around the surgical incision by 9.9% and -24.9% at 1 h, by 10.9% and 3.8% at 4 h, and by -19.5% and -50.4% at 12 h after administration at mean values, respectively. Halothane MAC in EM and IM were 0.54% and 0.57%, respectively, 40 min after administration. Halothane MAC in EM at 4 h and 12 h after administration were 0.45% and 0.70%, respectively. The results suggest that EM provides long-lasting analgesia by its time-related differential effects on the neuraxis.     

A technique for fractionated stereotactic radiotherapy in the treatment of intracranial tumors

PURPOSE: The excellent treatment results obtained with traditional radiosurgery have stimulated attempts to broaden the range of intracranial disorders treated with radiosurgical techniques. For major users of radiosurgery this resulted in a gradual shift from treating vascular diseases in a single session to treating small, well delineated primary tumors on a fractionated basis. In this paper we present the technique currently used in Montreal for the fractionated stereotactic radiotherapy of selected intracranial lesions. METHODS AND MATERIALS: The regimen of six fractions given every other day has been in use for "fractionated stereotactic radiotherapy" in our center for the past 5 years. Our current irradiation technique, however, evolved from our initial method of using the stereotactic frame for target localization and first treatment, and a "halo-ring" with tattoo skin marks for the subsequent treatments. Recently, we developed a more precise irradiation technique, based on an in-house-built stereotactic frame which is left attached to the patient's skull for the duration of the fractionated regimen. Patients are treated with the stereotactic dynamic rotation technique on a 10 MV linear accelerator (linac). RESULTS: In preparation for the first treatment, the stereotactic frame is attached to the patient's skull and the coordinates of the target center are determined. The dose distribution is then calculated, the target coordinates are marked onto a Lucite target localization box, and the patient is placed into the treatment position on the linac with the help of laser positioning devices. The Lucite target localization box is then removed, the target information is tattooed on the patient's skin, and the patient is given the first treatment. The tattoo marks in conjunction with the target information on the Lucite target localization box are used for patient set-up on the linac for the subsequent 5 treatments. The location of the target center is marked with radio-opaque markers on the target localization box and verified with a computerized tomography scanner prior to the second treatment. The same verification is done prior to other treatments when the target center indicated by the target localization box disagrees with that indicated by the tattoo marks. The new position of the target center is then determined and used for treatment positioning. CONCLUSION: The in-house-built frame is inexpensive and easily left attached to the patient's skull for the 12 day duration of the fractionated regimen. Positioning with the Lucite target localization box verified with tattoo marks ensures a high level of precision for individual fractionated treatments.     

The choice of the method for the surgical treatment of bladder exstrophy

129 children with exstrophy of the bladder underwent primary surgical reconstruction according to G. A. Bairov. Morphofunctional findings in these children gave grounds for determination of three degrees of the bladder congenital defects. 39 patients had defect of the 1st degree, 53 of the 2nd and 37 of the 3d degree. The results of plastic reconstruction of the bladder with local tissue support the validity of such procedure only for patients with the congenital defect degree I. For degree II the benefit is relative. In degree III plastic surgery in contraindicated.     

A four-hour topotecan infusion achieves cytotoxic exposure throughout the neuraxis in the nonhuman primate model: implications for treatment of children with metastatic medulloblastoma

The purpose of this study was to define the length of topotecan (TPT) i.v. infusion necessary to attain a cytotoxic exposure for medulloblastoma cells throughout the neuraxis. In vitro studies of human medulloblastoma cell lines (Daoy, SJ-Med3) were used to estimate the length and extent of TPT systemic exposure associated with inhibition of tumor cell growth or the exposure duration threshold (EDT). We evaluated TPT systemic and cerebrospinal fluid (CSF) disposition in six male rhesus monkeys (8-12 kg) that received TPT 2.0 mg/m2 i.v. as a 30-min or 4-h infusion. Plasma and CSF samples were assayed for TPT lactone by high-performance liquid chromatography, and the CSF exposures were compared with the estimated EDT. Results of the in vitro studies defined an EDT as a TPT lactone concentration of > 1 ng/ml for 8 h (IC99) daily for 5 days. The mean +/- SD for systemic clearance (CL(SYS)), penetration into fourth ventricle (%CSF(4th)), and penetration into lumbar space (%CSF(LUM)) were similar for the 30-min and the 4-h infusions. At a TPT lactone systemic exposure (AUC(PL)) of 56.7 +/- 19.9 ng/ml x h, time above 1 ng/ml in the fourth ventricle was 1.4-fold greater for a 4-h infusion compared with a 30-min infusion. At a TPT lactone AUC(PL) of 140 ng/ml x h, the 4-h infusion achieved the desired TPT exposure throughout the neuraxis (lateral and fourth ventricles and lumbar space), whereas the 30-min infusion failed to achieve it in the lumbar space. In conclusion, prolonging TPT i.v. infusion from 30-min to 4-h at a targeted AUC(PL) achieves the EDT throughout the neuraxis and represents an alternative method of TPT administration that will be tested prospectively in patients with high-risk medulloblastoma.     

Herbal medicine for the treatment of cardiovascular disease: clinical considerations

Herbs have been used as medical treatments since the beginning of civilization and some derivatives (eg, aspirin, reserpine, and digitalis) have become mainstays of human pharmacotherapy. For cardiovascular diseases, herbal treatments have been used in patients with congestive heart failure, systolic hypertension, angina pectoris, atherosclerosis, cerebral insufficiency, venous insufficiency, and arrhythmia. However, many herbal remedies used today have not undergone careful scientific assessment, and some have the potential to cause serious toxic effects and major drug-to-drug interactions. With the high prevalence of herbal use in the United States today, clinicians must inquire about such health practices for cardiac disease and be informed about the potential for benefit and harm. Continuing research is necessary to elucidate the pharmacological activities of the many herbal remedies now being used to treat cardiovascular diseases.     

Tumor enucleation as the conservative treatment of choice for renal carcinoma

BACKGROUND: The coexistence of other psychiatric disorders in patients with bulimia nervosa is of major clinical and theoretical interest. We therefore studied a group of consecutively evaluated bulimic patients. METHOD: The Structured Clinical Interview for DSM-III-R (SCID) was administered to a sample of 59 female patients with DSM-III-R-defined bulimia nervosa. RESULTS: The following frequencies of lifetime Axis I comorbid diagnoses were found (in decreasing frequency): any affective disorder (75%), major depressive disorder (63%), any anxiety disorder (36%), any substance abuse disorder (20%), social phobia (17%), generalized anxiety disorder (12%), and panic disorder (10%). In the 44 cases with an affective disorder, 27 (61%) had the onset of affective disorder, 27 (61%) had the onset of their affective disorder prior to the onset of their bulimia, 15 (34%) afterward, and 2 (5%) concurrently. In the 21 cases with any anxiety disorder, 15 (71%) had the onset of their anxiety disorder prior to the onset of their bulimia, 4 (19%) afterward, and 2 (10%) concurrently. CONCLUSION: These data confirm previous reports of a strong association between bulimia nervosa and affective illness, which in most cases precedes the eating disorder. In addition, a high frequency of anxiety disorders, particularly social phobia, is seen in bulimic patients.