RESUMO
1. The influence of membrane cholesterol on some pharmacological properties of the GABA(A) receptor was investigated in acutely dissociated rat hippocampal neurones with whole cell patch clamp recording. The cholesterol levels were varied between 56% and 235% control using methyl-beta-cyclodextrin as the cholesterol carrier. 2. Enrichment of neurones with cholesterol increased the effects of the non-steroidal GABA potentiators propofol, flunitrazepam and pentobarbitone. A similar result was obtained after pre-incubation of neurones with epicholesterol, the 3alpha-hydroxy isomer of cholesterol. 3. In contrast, the effects of the steroidal GABA potentiators pregnanolone and alfaxalone were reduced by cholesterol enrichment, but not by epicholesterol. Depletion of membrane cholesterol increased the potentiation of GABA by pregnanolone and alfaxalone but did not affect the non-steroidal potentiators. 4. The steroidal antagonist of GABA, pregnenolone sulphate, reduced the maximum response to GABA. This effect, also, was diminished in cholesterol-enriched neurones and enhanced in cholesterol-depleted neurones. 5. The effects of the cholesterol manipulations that were selective for the steroidal modulators of GABA are suggested to arise from direct interactions between membrane cholesterol and the GABA(A) receptor. The separate effects on the non-steroidal potentiators of GABA of cholesterol-enrichment or addition of epicholesterol to the neurones are suggested to be due to changes in membrane fluidity. 6. In view of the likely physiological modulation of GABA(A) receptors by endogenous neuroactive steroids and evidence of the in vivo lability of membrane cholesterol, the present observations may have physiological as well as pharmacological relevance.
Assuntos
Colesterol/metabolismo , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Ácido gama-Aminobutírico/farmacologia , Animais , Membrana Celular/metabolismo , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Flunitrazepam/farmacologia , Hipocampo/metabolismo , Masculino , Potenciais da Membrana/efeitos dos fármacos , Neurônios/metabolismo , Técnicas de Patch-Clamp , Pentobarbital/farmacologia , Pregnanolona/farmacologia , Pregnenolona/farmacologia , Propofol/farmacologia , Ratos , Ratos Wistar , Receptores de GABA-A/metabolismoRESUMO
The effects of membrane cholesterol on the GABA(A) receptor were investigated in acutely dissociated rat hippocampal neurones, using the whole-cell patch clamp technique. Neuronal cholesterol was manipulated within the range 56-250% control by incubation with methyl-beta-cyclodextrin for depletion and a complex of cholesterol and methyl-beta-cyclodextrin for enrichment. Manipulation over a narrower range was achieved with cholesterol + phosphatidylcholine liposomes. A complex of epicholesterol and methyl-beta-cyclodextrin was used to insert epicholesterol. Cholesterol enrichment reduced the potency of GABA, as did cholesterol depletion, with increases in EC(50) of up to 4-fold. Cholesterol enrichment reduced the potency of the competitive antagonist bicuculline but did not affect that of the non-competitive antagonist picrotoxinin. Cholesterol depletion did not affect the potencies of either antagonist. Epicholesterol substituted functionally for cholesterol with respect to the effects of enrichment. In cholesterol-depleted neurones, however, only incubation with cholesterol was able to restore GABA potency to normal. These results suggest a specific requirement for cholesterol at control levels to maintain optimal GABA potency, which may involve specific binding of cholesterol to the GABA(A) receptor. The reduction in GABA potency by enrichment with cholesterol or epicholesterol is more likely to be due to reduced plasma membrane fluidity.
Assuntos
Colesterol/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Receptores de GABA-A/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Membrana Celular/metabolismo , Células Cultivadas , Colesterol/química , Hipocampo/citologia , Masculino , Técnicas de Patch-Clamp , Ratos , Ratos Wistar , EstereoisomerismoRESUMO
Breakthrough pain is defined as the transient exacerbation of pain occurring in a patient with otherwise stable, persistent pain. Breakthrough pain is relatively common among cancer patients, particularly those with moderate to severe background pain, and is one of the most difficult pain syndromes to treat. Breakthrough pain may be caused by patient movement (incident pain) or may be unrelated to patient action (spontaneous pain). Although breakthrough pain is usually managed pharmacologically with supplemental opioid medication, other means of treatment should also be considered. Primary antineoplastic therapies may alleviate the cause of some breakthrough pain, and other types of primary interventions may at least lessen this type of pain. Before a change in the around-the-clock analgesic dosage is implemented, the clinician should consider analgesic side effects, the number of episodes of breakthrough pain per day, and the best means for balancing side effects vs analgesia. The addition of pharmacologic agents to treat analgesic side effects may improve the overall side effect profile. Because breakthrough pain involves moderate to severe pain of rapid onset, use of a fast-acting, effective analgesic can be crucial to successful treatment.
Assuntos
Analgésicos Opioides/administração & dosagem , Antineoplásicos/uso terapêutico , Dor/tratamento farmacológico , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Humanos , Neoplasias/complicações , Dor/classificação , Dor/etiologia , Dor Intratável/tratamento farmacológico , Qualidade de VidaRESUMO
The effects of increased membrane cholesterol on the potentiation of GABA(A) currents by pregnanolone (5beta-pregnan-3alpha-ol-20-one), allopregnanolone (5alpha-pregnan-3alpha-ol-20-one), alphaxalone (5alpha-pregnan-3alpha-ol-11,20-dione) and propofol were investigated in acutely dissociated rat hippocampal neurones using the whole-cell patch clamp technique. Cholesterol enrichment of the neurones, isolated from 10 to 16-day-old Wistar rat brains, was achieved by incubation with cholesterol + phosphatidylcholine liposomes. Cholesterol enrichment (25.8+/-3.4%) reduced the potentiation of GABA(A) currents by pregnanolone (0.3 and 1 microM), allopregnanolone (1 microM) and alphaxalone (1 microM) but the potentiation of GABA(A) currents by propofol (5 microM) was not affected. Acute application of cholesterol (1 microM) did not significantly change the potentiation of GABA(A) currents by pregnanolone (1 microM). These results suggest that cholesterol within the neuronal membrane may compete with neurosteroids for their sites of action on the GABA(A) receptor or modulate the potentiating effect of the neurosteroids in some other ways.
Assuntos
Colesterol/metabolismo , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Esteroides/farmacologia , Membranas Sinápticas/metabolismo , Animais , Relação Dose-Resposta a Droga , Hipocampo/citologia , Hipocampo/fisiologia , Lipossomos , Potenciais da Membrana/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/fisiologia , Técnicas de Patch-Clamp , Pregnanodionas/farmacologia , Pregnanolona/farmacologia , Propofol/farmacologia , Ratos , Ratos Wistar , Receptores de GABA-A/metabolismo , Sinapses/efeitos dos fármacos , Ácido gama-Aminobutírico/farmacologiaRESUMO
1. Interactions were investigated between loreclezole, chlormethiazole and pentobarbitone as potentiators of depolarization responses mediated by gamma-aminobutyric acid(A) (GABA(A)) receptors on afferent nerve terminals in the rat cuneate nucleus in vitro. These drugs were also compared as modulators of [3H]-flunitrazepam (FNZ) binding to synaptic membranes prepared from rat whole brain homogenate. 2. In rat cuneate nucleus slices, the drugs shifted muscimol log dose response lines to the left in an approximately parallel fashion with the result that 200 microM chlormethiazole potentiated muscimol responses by 0.567 +/- 0.037 log unit (mean +/- s.e.mean, n = 4) while loreclezole gave a maximal potentiation at 10 microM of only 0.121 +/- 0.037 (n=6) log unit and 0.071 +/- 0.039 (n=22) at 50 microM. 3. While 50 microM chlormethiazole and 30 microM pentobarbitone showed no significant interactions between each other when potentiating muscimol responses in combination, 50 microM loreclezole in combination with either chlormethiazole or pentobarbitone attenuated their potentiating effects, possibly by inducing desensitization of GABA(A) receptors. 4. In the [3H]-FNZ binding studies on well-washed membranes, loreclezole enhanced binding to a maximum of 47.3 +/- 2.83% of control (mean +/- s.e.mean, n = 3) at 300 microM. Scatchard analysis revealed no change in Bmax but a decrease in K(D) for [3H]-FNZ from 3.9 +/- 0.29 nM to 2.7 +/- 0.10 nM (mean +/- s.e.mean, n=4) in the presence of 100 microM loreclezole. In contrast, 100 microM chlormethiazole caused no potentiation. A small component of the enhancement by loreclezole could be blocked by 100 microM bicuculline and could also be blocked by 100 microM chlormethiazole. It seems likely that the effects on [3H]-FNZ binding are due predominantly to direct actions of the drugs on the GABA(A) receptor and are separate from the GABA-potentiating effects. 5. The results indicate distinctly different profiles of action for loreclezole, chlormethiazole and pentobarbitone on GABA(A) receptors.
Assuntos
Anticonvulsivantes/farmacologia , Clormetiazol/farmacologia , Pentobarbital/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Triazóis/farmacologia , Animais , Bicuculina/farmacologia , Flunitrazepam/metabolismo , Técnicas In Vitro , Masculino , Bulbo/efeitos dos fármacos , Bulbo/metabolismo , Ratos , Ratos WistarRESUMO
One of the most important concerns of patients with cancer, particularly those with metastatic disease, is "Will I be in constant pain?" This is a similar concern voiced by patients with late-stage human immunodeficiency virus infection. The management of chronic pain has enormous implications on a patient's ability to function and on his or her quality of life. In June 1996, Medical Interface convened a panel of experts in Chicago to discuss pain management therapies, guidelines, and how these issues will affect, and be affected by, the managed care environment.
Assuntos
Programas de Assistência Gerenciada/normas , Dor/tratamento farmacológico , Guias de Prática Clínica como Assunto , Síndrome da Imunodeficiência Adquirida/complicações , Algoritmos , Analgésicos/uso terapêutico , Capitação , Cuidadores , Administração de Caso/estatística & dados numéricos , Redes de Comunicação de Computadores/estatística & dados numéricos , Efeitos Psicossociais da Doença , Custos de Medicamentos , Planos de Assistência de Saúde para Empregados/estatística & dados numéricos , Humanos , Programas de Assistência Gerenciada/economia , Neoplasias/complicações , Dor/economia , Dor/etiologia , Cuidados Paliativos/normas , Padrões de Prática Médica , Qualidade de VidaRESUMO
1. Neurosteroids such as pregnanolone have been established as potent modulators of the GABAA receptor in both electrophysiological and binding studies. Since cholesterol is present in substantial amounts in the neuronal membranes, we have sought evidence for possible interactions of cholesterol with the neurosteroid site and more generally, with the GABAA channel. 2. Synaptosomal membranes were prepared from rat whole brain, cerebral cortex, cerebellum and spinal cord. These membranes were enriched with cholesterol to about double the original level by incubation with liposomes comprised of 50 phosphatidylcholine: 50 cholesterol in the presence of 1% BSA. The additional cholesterol formed a homogeneous mixture with the endogenous cholesterol. 3. The effects of cholesterol and modulatory drugs on the GABAA channel were assessed from the changes induced in [3H]-flunitrazepam (FNZ) binding. Cholesterol enrichment did not affect FNZ binding itself; however, the enhancement of [3H]-FNZ binding by pregnanolone was affected. In membranes from cerebral cortex, the potency of pregnanolone was reduced by a factor of 3.2 following cholesterol enrichment. By contrast, in membranes from spinal cord, the potency of pregnanolone was increased by a factor of 8.4 following cholesterol enrichment. In membranes from cerebellum, there was little overall change in pregnanolone potency although the effects of threshold concentrations were increased. 4. The enhancement of [3H]-FNZ binding by propofol in whole brain membranes was reduced in cholesterol-enriched membranes, similar to the effects of pregnanolone. Experiments with muscimol resulted in an increase in its potency as a potentiator of [3H]-FNZ binding, following cholesterol enrichment. 5. These results provide little evidence for a selective competition between cholesterol and pregnanolone at its binding site. Rather, they suggest an influence of membrane cholesterol on the functional coupling between the benzodiazepine site and the other specific drug sites on the GABAA channel. The detailed pattern of influence depended upon the region of CNS and may be related to the subunit composition of the GABAA channels present.
Assuntos
Encéfalo/metabolismo , Colesterol/metabolismo , Receptores de GABA-A/metabolismo , Medula Espinal/metabolismo , Membranas Sinápticas/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas , Flunitrazepam/metabolismo , GABAérgicos/farmacologia , Lipossomos , Masculino , Muscimol/farmacologia , Pregnanolona/farmacologia , Propofol/farmacologia , Ratos , Ratos Wistar , Receptores de GABA-A/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Membranas Sinápticas/efeitos dos fármacosRESUMO
The enhancement by pregnanolone (5 beta-pregnan-3 alpha-ol-20-one) and propofol (2,6-diisopropylphenol) of [3H]flunitrazepam (FNZ) binding to GABAA receptors in rat whole brain homogenate has been investigated. Two components in the concentration-effect relationship for pregnanolone were distinguished by the sensitivity of one component to antagonism by bicuculline and enhancement by muscimol, and the selective but weak antagonism of the bicuculline-insensitive component by 11-ketoprogesterone (4-pregnen-3,11,20-trione). Unlike pregnanolone, the enhancement by propofol of [3H]FNZ binding appeared to comprise a single component which was insensitive to 11-ketoprogesterone and was only slightly antagonised by bicuculline and slightly enhanced by muscimol. These results provide evidence for distinct GABA-dependent and GABA-independent components of the action of pregnanolone in the enhancement of [3H]FNZ binding, with the GABA-independent component being sensitive to 11-ketoprogesterone. The data also support the suggestion of different binding sites for pregnanolone and propofol.
Assuntos
Anestésicos Intravenosos/farmacologia , Flunitrazepam/metabolismo , Moduladores GABAérgicos/metabolismo , Pregnanolona/farmacologia , Propofol/farmacologia , Receptores de GABA-A/metabolismo , Animais , Bicuculina/farmacologia , Agonistas GABAérgicos/farmacologia , Técnicas In Vitro , Masculino , Muscimol/farmacologia , Progesterona/análogos & derivados , Progesterona/farmacologia , Ratos , Ratos Wistar , Receptores de GABA-A/efeitos dos fármacos , Membranas Sinápticas/efeitos dos fármacos , Membranas Sinápticas/metabolismoRESUMO
The first clinical experience in the United States of the transdermal therapeutic system (TTS) for delivery of fentanyl in cancer pain was a small study of five patients. Pain relief was established with intravenous (i.v.) fentanyl. A transdermal system was selected to deliver the same hourly dose while the i.v. infusion was tapered over 6 h. The transdermal system was changed every 24 h for a total duration of 3-156 days. A larger multicentre outpatient trial was conducted in 39 patients for a median of 84 days (range 5-365). The TTS fentanyl dose was established from a conversion table based on the dose of oral immediate-release morphine required to control pain. The TTS fentanyl patches were changed every 72 h. Immediate-release morphine was used on an as required basis for incident pain. The initial study demonstrated that steady-state plasma levels were linearly related to the TTS fentanyl dose. The multicentre trial further demonstrated that patients could be converted from oral morphine to an equianalgesic dose of TTS fentanyl and that pain relief could be maintained for a lengthy period of time on an outpatient basis. The systems were used throughout a variety of concomitant complications of the cancer process. This experience demonstrated the safety and clinical effectiveness of TTS fentanyl in the treatment of chronic cancer pain. TTS fentanyl has been used widely in the USA since it was approved for marketing in 1990.
Assuntos
Fentanila/administração & dosagem , Fentanila/farmacologia , Dor/tratamento farmacológico , Administração Cutânea , Administração Oral , Adulto , Idoso , Relação Dose-Resposta a Droga , Aprovação de Drogas , Sistemas de Liberação de Medicamentos/métodos , Feminino , Fentanila/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Morfina/farmacologia , Dor/classificação , Fatores de Tempo , Estados UnidosRESUMO
In rat brain membranes, the 3 alpha-hydroxy pregnane steroids, pregnanolone, allopregnanolone, alphaxalone and 5 beta-alphaxalone potentiated 1 nM [3H]flunitrazepam binding at the GABAA receptor, with maximal potentiations of 140-150% of control. The potencies of the 5 alpha isomers were greater than the 5 beta and the presence of an 11-keto group conferred lower potency. The potentiation produced by these steroids was antagonised by the 3 beta-OH isomers epipregnanolone, isopregnanolone and betaxalone (60 microM). The dose-effect curves for pregnanolone and allopregnanolone were shifted to the right, with no reduction in the maximal potentiation. In contrast, the maximal effect of alphaxalone and 5 beta-alphaxalone was reduced with no change in EC50. Alphaxalone (1 microM) caused an increase in the binding of [3H]flunitrazepam in the presence of maximal concentrations of pregnanolone or allopregnanolone. These results suggest multiple sites of action for neurosteroids in the brain.
Assuntos
Anestésicos/farmacologia , Flunitrazepam/farmacocinética , Pregnanodionas/antagonistas & inibidores , Pregnanolona/farmacologia , Receptores de GABA-A/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Técnicas In Vitro , Masculino , Membranas/efeitos dos fármacos , Membranas/metabolismo , Pregnanodionas/farmacologia , Ratos , Ratos Wistar , Receptores de GABA-A/efeitos dos fármacosRESUMO
Propofol (2,6-diisopropylphenol) robustly stimulated the binding of 1 nM [3H]flunitrazepam (FNZ) to rat brain membranes with an EC50 of 146 microM in chloride-free buffer and 23 microM in buffer containing 200 mM NaCl. NaCl showed an EC50 of 40 mM for its ability to increase the potency of propofol. The ability of a range of anions to potentiate propofol's interactions with the GABAA-benzodiazepine receptor was closely correlated with their permeabilities at this ion channel. Propofol, at a concentration of 300 microM, decreased the EC50 for the potentiation of FNZ binding by NaCl from 39 mM to 13 mM, with no change in the maximal potentiation. At a concentration of 30 microM, propofol significantly decreased the EC50 for potentiation of FNZ binding by the neurosteroid alphaxalone whilst increasing that for potentiation by pentobarbitone. We conclude that propofol is a potent barbiturate-like modulator of [3H]flunitrazepam binding.
Assuntos
Flunitrazepam/metabolismo , Propofol/farmacologia , Receptores de GABA-A/metabolismo , Animais , Ligação Competitiva , Sinergismo Farmacológico , Masculino , Pentobarbital/farmacologia , Pregnanodionas/farmacologia , Ratos , Ratos Wistar , TrítioRESUMO
The temperature dependence of [3H]flunitrazepam ([3H]FNZ) binding to rat brain membranes was examined in the presence of the anaesthetics, pentobarbitone, alphaxalone and propofol. Van't Hoff plots showed the binding of FNZ to be largely enthalpy driven. Alphaxalone and propofol increased the entropy of the binding reaction but not the enthalpy and therefore did not show temperature dependence in their efficacy. In contrast, pentobarbitone increased the enthalpy of FNZ binding and, therefore, is more efficacious at low temperatures. The EC50 values of all three modulators increased with temperature indicating that their interactions with the receptor may be enthalpy driven. The EC50 values of all three modulators were also anion dependent, showing a decrease in the presence of gamma-aminobutyric acid (GABAA)-channel permeant anions. The efficacies of alphaxalone and pentobarbitone, but not that of propofol, also increased with increasing chloride ion concentration. The results indicate that all three modulators interact with the GABAA receptor at distinct recognition sites.
Assuntos
Química Encefálica , Flunitrazepam/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Animais , Ânions , Ligação Competitiva , Interações Medicamentosas , Flunitrazepam/metabolismo , Masculino , Pentobarbital/farmacologia , Pregnanodionas/farmacologia , Propofol/farmacologia , Ratos , Ratos Wistar , Receptores de GABA-A/metabolismo , TemperaturaRESUMO
Alternative routes of drug delivery have particular relevance for use in chronic pain. When the pain experience is constant or nearly constant, a continuous infusion of drug is an ideal way to achieve effective pain relief. Early experience with the transdermal application of fentanyl in chronic cancer pain suggests that it is a safe, noninvasive, effective method of managing pain. The first experience with the use of transdermal fentanyl in cancer pain was reported by Miser and colleagues in 5 patients. They demonstrated that steady-state blood concentrations of fentanyl were linearly related to the transdermal fentanyl dose. The terminal elimination half-life was approximately 34 hr. Zech and colleagues studied 13 patients with chronic cancer pain. Pain relief was obtained and was correlated with plasma fentanyl levels. The largest experience so far was reported in 39 patients in a multicenter trial conducted by Simmonds and colleagues. The median fentanyl dose was 100 micrograms/hr (range, 25-525 micrograms/hr). The initial dose of fentanyl from morphine conversion (6:1) was adequate in 50% of patients and titrated upward by 72 hr for the remaining 50%. Patients wore the system for a median of 84 days (range, 5-365 days). Median supplementary daily dose of morphine was 105 mg/day (range, 0-720 mg/day). The system was able to be maintained through a variety of concomitant events. This experience demonstrated the safety and clinical effectiveness of transdermal fentanyl. The transdermal therapeutic system (fentanyl) is a promising advance in achieving noninvasive, continuous drug administration for the management of chronic cancer pain.
Assuntos
Fentanila/uso terapêutico , Neoplasias/fisiopatologia , Dor/tratamento farmacológico , Administração Cutânea , Doença Crônica , Ensaios Clínicos como Assunto , Fentanila/administração & dosagem , Humanos , Dor/etiologiaRESUMO
Electrophysiological responses to glycine (0.25-5 mM) were obtained on preparations of rat optic nerve. The log dose-response curve for glycine was shifted to the left by a factor of 2 by 1 microM 20 alpha-dihydrocortisol and by a factor of about 1.5 by 1 microM alpha-cortol and 10 microM hydrocortisone. A similar effect was obtained with 100 microM chlormethiazole but the GABA-potentiating steroid alphaxalone (1 microM) was ineffective on responses to glycine. 20 alpha-Dihydrocortisol and chlormethiazole also appeared to increase the antagonistic potency of strychnine against glycine. These observations suggest that the active steroids and chlormethiazole increase the functional interaction of both glycine and strychnine with the glycine-gated chloride channel.
Assuntos
Receptores de Neurotransmissores/efeitos dos fármacos , Esteroides/farmacologia , Estricnina/farmacologia , Animais , Clormetiazol/farmacologia , Eletrofisiologia , Hidrocortisona/análogos & derivados , Hidrocortisona/farmacologia , Técnicas In Vitro , Masculino , Muscimol/farmacologia , Nervo Óptico/fisiologia , Ratos , Ratos Endogâmicos , Receptores de GABA-A/efeitos dos fármacos , Receptores de GlicinaRESUMO
Studies were made on the potentiation of [3H]flunitrazepam binding to rat brain membranes by gamma-aminobutyric acid (GABA), pentobarbitone and pregnanolone (5 beta-pregnan-3 alpha-ol-20-one). Epipregnanolone, the 3 beta isomer of pregnanolone, inhibited competitively the potentiation by pregnanolone with a Ki of 10.5 microM without affecting that of GABA. The potentiation by pentobarbitone was slightly enhanced. Epipregnanolone alone showed only slight potentiation of benzodiazepine binding. These findings demonstrate that epipregnanolone is a specific antagonist of the neurosteroid site of the GABAA receptor and raise the possibility of a physiological role for 3 beta-hydroxysteroids in modulating this receptor.
Assuntos
Antagonistas de Receptores de GABA-A , Pregnanolona/farmacologia , Animais , Benzodiazepinas/metabolismo , Ligação Competitiva/efeitos dos fármacos , Flunitrazepam/farmacologia , Técnicas In Vitro , Masculino , Pentobarbital/farmacologia , Ratos , Ratos Endogâmicos , Ácido gama-Aminobutírico/farmacologiaRESUMO
The Pennsylvania Cancer Registry was used to contact breast cancer patients and, through them, their adult sisters and daughters. The sisters and daughters were counseled concerning their higher than average risks for breast cancer and their need for mammography and breast self-examination. Results showed a 9 percent increase in mammography and a 10 percent increase in breast self-examination rates for the counseled over control group. Costs were $49 per counseled sister or daughter indicating a need to increase cost effectiveness before implementation is practical.
Assuntos
Neoplasias da Mama/psicologia , Família , Neoplasias da Mama/diagnóstico , Aconselhamento , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Palpação , Pennsylvania , Sistema de RegistrosRESUMO
This paper reviews evidence on the kinds of information needed by family members of cancer patients, discusses why families frequently lack needed information, and suggests strategies for meeting their information needs. Studies reviewed show that families' needs for information are substantial and that a large percentage of family members feel that these needs have not been adequately met by health care providers. This lack of needed information negatively affects the patient's care as well as the physical, psychological, and social well-being of family members. Strategies for addressing this problem include wider distribution of generic information about cancer and treatments to family members as well as developing standard professional procedures for making information about a patient's clinical condition available to family members.
Assuntos
Família , Educação em Saúde/normas , Necessidades e Demandas de Serviços de Saúde , Neoplasias , Comportamento do Consumidor , Educação em Saúde/métodos , Humanos , Materiais de Ensino/normasRESUMO
Newly developed somatostatin analogues may be useful agents in the treatment of breast and prostate cancer. Potential mechanisms of antitumor action include suppression of circulating levels of trophic hormones and growth factors as well as direct effects at the tumor level, potentially involving autocrine/paracrine mechanisms. Pilot clinical trials conducted in heavily pretreated women with advanced breast cancer indicate that SMS 201-995 (Sandostatin R) has minimal toxicity and moderately suppresses stimulated growth hormone secretion and basal somatomedin-C level. Somatostatin analogues have also been found to retard the growth of experimental prostate cancer, particularly when used in combination with LHRH analogues. The therapeutic efficacy of these compounds used alone or in combination with other agents in the treatment of breast and prostate cancer remains to be established in larger clinical trials involving less heavily pretreated patients.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Somatostatina/uso terapêutico , Substâncias de Crescimento/metabolismo , Humanos , Masculino , Somatostatina/análogos & derivadosRESUMO
In this pilot clinical trial conducted in 10 postmenopausal women with advanced breast cancer, we evaluated the endocrine effects and toxicity of combined somatostatin analog and dopaminergic therapy in the attempt to suppress both growth hormone (GH) and prolactin (PRL) secretion. The patients' mean age was 63 years (range: 54-77) and the average number of previous treatments was 4.8 +/- 2 (SD). All patients were treated with the somatostatin analog SMS 201-995 (100-200 micrograms s.c. in a.m. and h.s.) and bromocriptine (2.5 mg orally twice a day). During treatment, GH levels following provocative testing (either L-DOPA or insulin-induced hypoglycemia) were suppressed in 7/9 patients. Basal somatomedin-S (Sm-C) levels declined in 6/9 women. Both GH and Sm-C levels decreased in 4 patients, while in the remaining 5 only one of the two parameters was lowered on treatment. PRL secretion (during provocative TRH testing) was almost totally abolished in 8/9 patients. The treatment did not affect circulating levels of FSH, LH, E1, E2, E1-S, T4, T3RU, or cortisol. Seven patients experienced no side effects. Nausea occurred in 3, but was severe enough in only one to require discontinuation of therapy. One patient experienced disease stabilization consisting of less than 50% regression of skin nodules and pleural effusion, a decline in CEA titer, and an improved performance status lasting 7 months. We conclude that combined SMS 201-995 and bromocriptine therapy is safe and frequently suppresses GH and PRL secretion. Its role in the treatment of metastatic breast cancer should be tested in patients with less advanced disease.