Effects Of Different Regimens Research Articles

Estrogen and nerve growth factor-related systems in brain. Effects on basal forebrain cholinergic neurons and implications for learning and memory processes and aging.

Estrogen replacement can significantly affect the expression of ChAT and NGF receptors in specific basal forebrain cholinergic neurons. The time-course of the effects is consistent with a direct up-regulation of ChAT followed by either direct or indirect down-regulation of p75NGFR and trkA NGF receptors, possibly due to increased cholinergic activity in the hippocampal formation and cortex and a decrease in hippocampal levels of NGF. Current evidence suggests ChAT, p75NGFR, trkA, and NGF all play a role in regulating cholinergic function in the hippocampal formation and cortex. In addition, all have been implicated in the maintenance of normal learning and memory processes as well as in changes in cognitive function associated with aging and with neurodegenerative disease. It is possible that estrogen may affect cognitive function via effects on NGF-related systems and basal forebrain cholinergic neurons. Effects of estrogen on cognitive function have been reported, as has some preliminary evidence for beneficial effects of estrogen in decreasing the prevalence of and reducing some cognitive deficits associated with Alzheimer's disease. Whether these effects are related to effects on NGF-related systems or basal forebrain cholinergic neurons is currently unknown. Indirect evidence suggests that estrogen interacts with NGF-related systems and that changes in circulating levels of estrogen can contribute to age-related changes in hippocampal levels of NGF. These findings have important implications for consideration of estrogen replacement therapy in pre- and post-menopausal women. Further studies examining effects of different regimens of estrogen replacement as well as estrogen combined with progesterone on NGF and basal forebrain cholinergic neurons in young and aged animals are required. Prospective studies correlating aging and estrogen replacement with numbers of basal forebrain cholinergic neurons and hippocampal and cortical levels of NGF also need to be performed to better assess the potential benefits of estrogen replacement in reducing age- and disease-related cognitive decline.

Clinical and economic considerations in the treatment of prostate cancer.

Prostate cancer is a growing health problem with considerable economic consequences. Despite progress in the management of this disease, few areas in medicine generate greater disagreement. The larger part of healthcare resources are allocated to 'halfway technologies' aimed at palliative intervention to prolong life, while a relatively small part goes to measures aimed at preventing or curing the disease. The aetiology of this cancer is multifactorial and no practical measures for primary prevention are known. The number of patients diagnosed with prostate cancer is increasing steadily. The age-adjusted mortality, however, has increased only slightly. In its early stages, prostate cancer is often asymptomatic and is usually not diagnosed until it has advanced. Programmes for the early detection of prostate cancer (screening) claimed to reduce morbidity and mortality are a matter of controversy. Furthermore, there has been much debate regarding optimal treatment in the early stages of the disease. Economic considerations have not as yet been integrated into studies concerning localised prostate cancer. The routine first-line treatment of advanced prostate cancer usually involves some type of endocrine treatment. The most straightforward technique is surgical castration. Oral estrogens are as effective as castration, but have significant cardiovascular adverse effects. These may possibly be prevented if estrogens are given parenterally. A third principal endocrine treatment is the administration of antiandrogens. Medical castration can be attained by the administration of recently developed synthetic peptides, gonadotrophin-releasing hormone {luteinising hormone-releasing hormone (LHRH)} (GnRH) analogue agonists which are given parenterally. The advantage of this type of medical castration is that the trauma of surgical castration and the adverse effects of oral estrogens are avoided. In an attempt to improve the results obtained with endocrine treatment, the concept of combining surgical or medical castration with antiandrogens was introduced. This combination could offer improved response rates and survival in a significant number of patients. However, this advantage must be weighed against the tolerability profiles and the high costs of antiandrogens and GnRH analogues. When using expensive drugs, the duration of treatment is a crucial factor in the total cost. As the length of treatment varies greatly between patients it is difficult to decide the most cost-effective alternative for a single individual. The patient's preference is an important factor when selecting treatment. When there is little or no difference in the effect of different regimens the total lifetime cost is important.(ABSTRACT TRUNCATED AT 400 WORDS)

Fluid therapy in burns

Abstract: The dissertation evaluates changes in transcapillary fluid and protein balance in the initial phase after extensive burns, comparing the effects of different regimens for post‐burn fluid resuscitation.Studies were performed in anaesthetized rats and sheep. Within 15 min after major thermal injury, cardiac output (CO) was reduced by 40–50%, mainly due to a reduced stroke volume. Mean arterial pressure (MAP) also dropped by 30–40 mmHg. Both lactated Ringer's and plasma improved this postburn circulatory impairment.Rapid bolus infusions of small volumes of very hypertonic saline, 7.5% NaCl (2 400 mosmol/1), have rapidly corrected the circulatory impairment in haemorrhagic shock. Following a rapid bolus infusion of 7.5% NaCl in 6% Dextran 70, CO and MAP were completely restored, but the effect only lasted 30–60 min. When administered by a slow infusion, 7.5% NaCl gave no circulatory improvement.The transcapillary colloid‐osmotic gradient was maintained in injured skin following infusion of plasma, whereas it was almost annihilated by infusion of lactated Ringer's. Plasma infusion thus induced a protein‐rich edema in injured skin, whereas lactated Ringer's resulted in a generalized edema.Increased interstitial fluid flux can mobilize the interstitial matrix protcoglycan hyaluronan. Following burn injury, plasma concentrations of hyaluronan increased up to ten times above baseline. This observation suggests that at least some of the degradation of structural connective tissue components in thermally injured skin is by lymphatic removal (and subsequent degradation in liver). Increased plasma concentrations of interstitial components have not previously been observed after thermal injury.

Graphic analysis of isobiological effectiveness for twice‐a‐day radiotherapy regimens and its application

AbstractThe effectiveness of twice‐a‐day (BID) hyperfractionated radiotherapy (RT) schedules has been demonstrated for carcinomas of the head and neck, the lung, and advanced stage breast cancers. Fractionation choices include identical or different doses of the two daily treatments referred to as equally split or unequally split BID doses, respectively. The choices of equally split, unequally split, or a mixture of both are based on the consideration of maximal tumor control or minimal late tissue effect. The comparison of biological effectiveness of different regimens is commonly done by computing the individual biological effective doses (BED) to tumor and late tissue. For this purpose, a different theoretical approach which adopts the concept of isobiological effectiveness may be more general and analytic than point dose computation. Taking advantage of the quadratic nature, a graphic analysis of isobiological effectiveness (GAIBE) was developed to analyze how to optimize the regimens for tumor killing effect and late tissue sparing effect. In this analysis, a Cartesian plot of two dose axes representing the two daily doses is used. The loci of isobiological effective dose (isoBED) regimens are circular on this plot. Thus, the effects of many regimens on tumor and late reacting tissue may be observed simultaneously by comparing the isoBED loci. Graphically, with GAIBE analysis and, mathematically, for a given isoBED to tumor, we have demonstrated that equally split hyperfractionation schedules will deliver the lowest biological effectiveness to late reacting tissues among all isoBED regimens to tumor. Situations when unequally split regimens are beneficial are also discussed. Another variable of clinical importance is the repopulation phenomenon which may counteract the biological effectiveness with increasing length of treatment course. The additive nature of BED from daily treatments allows GAIBE analysis to compensate for the repopulation phenomenon and aid the determination of the course length. Our analysis can also be used for the design of concomitant boost BID regimens. A subroutine in BASIC language has been developed and is available upon request. As a corollary of GAIBE analysis, for a chosen total dose, once‐daily treatment (QD) will result in the most tumor killing and the BID half‐dose exposures will have the least tumor killing. Other combinations of BID exposures with the sum of doses equal to QD exposure will have varying degrees of tumor killing which fall in between these two extremes. This concept from GAIBE analysis may be applied to determine α/β values for tumor cell lines using equally split exposures. © 1994 Wiley‐Liss, Inc.

The long-term effectiveness of different regimens of occlusion on recovery from early monocular deprivation in kittens

Although the behavioural effects of an early period of monocular deprivation imposed on kittens can be very severe, resembling an extreme form of the human clinical condition deprivation amblyopia, they are not necessarily irreversible. Considerable behavioural as well as physiological recovery can occur if normal visual input is restored to the deprived eye sufficiently early, particularly if the other (initially non-deprived) eye is occluded at the same time (reverse occlusion). However, past work has shown that in many situations the improvement in the vision of the initially deprived eye that occurs during reverse occlusion is not retained following the subsequent introduction of binocular visual input. Furthermore, the vision of the other eye is often reduced as well, with the result that the eventual outcome is a condition of bilateral amblyopia. This study first examines the consequences of several periods of reverse occlusion whose onset and duration would be thought to maximize the opportunity for good and long-standing recovery of vision in the initially deprived eye. However, only in a very restricted set of exposure conditions did animals acquire good vision in one or both eyes; in most situations the final outcome was one of bilateral amblyopia. A second set of experiments examined the consequences of various regimens of part-time reverse occlusion, where the initially non-deprived eye was occluded for only part of each day to allow a period of binocular visual exposure, on kittens that had been monocularly deprived until 6, 8, 10 or 12 weeks of age. Whereas short or long daily periods of occlusion of the initially non-deprived eye resulted eventually in amblyopia in one, or usually both, eyes, certain intermediate occlusion times (3.5 or 5 h each day) resulted in recovery of normal acuities, contrast sensitivity and vernier acuity in both eyes, in animals that had been monocularly deprived until 6, 8 or 10 weeks of age, but not in animals deprived for longer periods. Experiments were done to establish some of the factors that contributed to the successful outcome associated with certain of the regimens of part-time reverse occlusion. It was established that recovery was just as good in animals in which the visual axes were vertically misaligned by means of prisms during the daily period of binocular visual exposure, thereby indicating that the visual input to the two eyes need not be concordant. However, animals that received equivalent visual exposure of the two eyes each day, but successively rather than simultaneously, all developed very severe bilateral amblyopia.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of Different Regimens of Dietary Restriction on the Age‐Related Decline in Insulin Secretory Response of Isolated Rat Pancreatic Isletsa

Effects of Different Regimens of Dietary Restriction on the Age‐Related Decline in Insulin Secretory Response of Isolated Rat Pancreatic Islets^a

Sequential methotrexate (MTX) and 5-fluorouracil (FU) in human tumor xenografts.

Human and animal tumor-lines heterotransplanted in nude mice were treated with MTX and FU sequentially. In order to investigate the relationship between tumor response and drug toxicity sequence, time and dose of both MTX and FU were varied. Pretreatment with MTX followed by FU with intervals of 3 or 24 h produced superior therapeutic results when compared to single administration of MTX or FU, simultaneous treatment, or the reverse sequence. In the MTX followed by FU regimen, dose reduction of either MTX or FU tended to decrease the anti-tumor effect. To investigate the toxic effects of different regimens, tumor-free nude mice were treated with MTX and FU the same way as the tumor-bearing animals. In this case, toxicity (weight loss, leukopenia) was more pronounced in those schedules with the best therapeutic results. However, toxicity appears to be more clearly related to the applied FU-dose.

Effectiveness of oral hygiene techniques on plaque and gingivitis in patients placed in intermaxillary fixation

Twenty-one patients undergoing reconstructive maxillofacial surgery volunteered to learn and practice specific oral hygiene techniques while in intermaxillary fixation in order to compare the effectiveness of different regimens. Oral irrigation was taught to all subjects; one third of the subjects were also instructed in the use of the sulcus brush, and another third were instructed in the use of the Perio-Aid. Scoring was done every 2 weeks for a 6-week period, with measurements taken of the amount of plaque and the amount of inflammation present in papillary, marginal, and attached gingiva. Results show that the group employing only the Water Pik had less inflammation in the attached gingiva than the group using the Perio-Aid and less plaque accumulation and papillary inflammation than the group using the sulcus brush. While more research is necessary to confirm these results, the simplest home care regimen, use of the Water Pik only, appears to offer the best way for intermaxillary fixation patients to remove plaque and minimize inflammation during convalescence.

A regimen for low-dose aspirin?

The effects of different regimens of 40 mg aspirin on platelet thromboxane A2 synthesis and vascular prostacyclin synthesis were determined in patients who were undergoing elective surgery for removal of varicose veins. Aspirin 40 mg taken at intervals of 48 hours consistently reduced platelet thromboxane A2 synthesis to a level at which it failed to support platelet aggregation and the associated release reaction. This effect lasted for at least 36 hours. In contrast, aspirin 40 mg every 72 hours did not have the same consistent effect. Both dose regimens led to a reduction in vascular prostacyclin synthesis 12 hours after the last dose, but 36 or 72 hours after the last dose prostacyclin synthesis was not reduced; thus the inhibition of prostacyclin synthesis was short lived. If the balance between platelet thromboxane A2 and vascular prostacyclin synthesis is important in thrombosis 40 mg aspirin every 48 hours may have the maximum antithrombotic effect.

Effect of different regimens of early malnutrition on behavioural development and adult avoidance learning in Swiss white mice.

1. The effects of perinatal malnutrition on behavioural development and adult shuttle-box avoidance performance were studied in Swiss white mice. 2. Mice were malnourished (a) from the 7th day of gestation until birth, (b) from birth until weaning, or (c) during both gestation and the sucking period. 3. Pups born of protein-restricted mothers had reduced birth weights, retarded development and poor adult avoidance performance, even if reared from birth by well-nourished mothers. 4. Postnatal malnutrition, induced either by restricting maternal diet or by rearing in large litters, retarded development during the second half of lactation and lowered subsequent adult avoidance performance.

The therapeutic significance of the dose response curve for antilymphocytic serum.

SUMMARY In mice treated with antilymphocyte serum (ALS), the curve relating dose of serum to number of antibody-forming cells or graft-rejecting cells is hyperbolic, i.e., log cell number is inversely related to log dose. As a consequence, it is shown on theoretical grounds that, if a fixed total amount of serum is administered over a fixed total period, regimens of small frequent doses should be, within limits, more effective than regimens of large, infrequent doses. This prediction has been confirmed by comparing the effects of different regimens of ALS on the formation of hemolytic plaque-forming cells (PFC) in the mouse spleen after injection of sheep red cells and on rejection of skin grafts.