Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Tachyphylaxis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 991 records · Page 55Linked to original sources
PubMed1980

Evidence that there are subcellular pools of norepinephrine and that there is flux of norepinephrine between these pools.

d-Amphetamine evokes blood pressure responses that are dose-dependent in magnitude and in shape. At a high dose, d-amphetamine evokes a response that decays biphasically. Response decay is not due to receptor desensitization or to decreasing plasma levels of drug. The first component of the biphasic decay (early, transient response) has an apparent peak of approximately 56 mm Hg and a rate constant for decay of approximately 0.043-min-1. The second component (late, relatively stable response) has an apparent peak of approximately 27 mm Hg and a rate constant for decay less than 0.0043-min-1. Chronic reserpine treatment diminishes the blood pressure response to a high dose of d-amphetamine, but it exerts a differential effect on the two components of the response. The ID50 for reducing the early, transient response is greater than 800 micrograms/kg; the ID50 for reducing the late, relatively stable response is approximately 100 micrograms/kg. Acute reserpine treatment enhances blood pressure responses to d-amphetamine, mainly by enhancing the early, transient response. In addition, acutely administered reserpine reverses the tachyphylactic effect of d-amphetamine. The data are used to construct a model for norepinephrine storage in postganglionic sympathetic nerves and to propose a model for d-amphetamine-induced tachyphylaxis.

Adrenalectomy↗
PubMed1993

Capsaicin-induced membrane currents in cultured sensory neurons of the rat.

Membrane currents induced by capsaicin (CAPS) in cultured sensory neurons from 1- to 2-day-old rats were studied. Responses to CAPS (10 microM) exceeding 1 nA at -50 mV were found in smaller, usually bipolar or tripolar neurons in which GABA (30 microM) induced small or no response. Large, unipolar neurons, which exhibited large responses to GABA, were completely insensitive to CAPS (10 microM). In contrast to GABA, responses to CAPS exhibited a slow rise and slow decay and a marked tachyphylaxis after repeated CAPS applications at high concentrations which made it difficult to study the concentration-response relationship. In partially run-down neurons, which exhibited quasi stable responses, the slope of the ascending phase was concentration-dependent with an apparent association rate constant K1 9 x 10(4) [M-1s-1]. The time constant of the decay was 3.5 s, and was concentration-independent. However, in 5 neurones the EC50 measured from the first series of CAPS applications at increasing concentrations was 0.31 +/- 0.5 microM with a Hill coefficient 1.66 +/- 0.35. The responses to CAPS reversed at +10.4 +/- 2.5 mV suggesting that the current is carried nonselectively by monovalent cations and Ca2+. The channel conductance of CAPS-gated channels at -50 mV calculated from the mean membrane current and variance of the current noise in outside-out patches or measured directly was 28 pS (n = 5). It is suggested that the CAPS-gated channels are either controlled by receptors with a very high affinity or that the channels are controlled by membrane-bound protein(s) which do not depend in their function on the supply of GTP or other intracellular metabolites.

Animals↗
PubMedDate not supplied

[The relationship between the isosorbide-5-mononitrate concentration and its antianginal effect following the administration of regular and prolonged-action drug forms in patients with stenocardia of effort].

Isosorbide-5-mononitrate (IMN) concentration-antianginal effect relationships were studied in 14 coronary heart diseases patients with stable exertion-induced angina after administration of Efox (Schwarz-Pharma) as two dosage forms: routinely acting tablets (20 mg) and long-acting capsules (50 mg). The antianginal effect index was an increase of treadmill exercise duration (sec) as compared with placebo, the concentration and effect were measured in points 0, 1, 3, and 7 hours after administration, in some patients, investigations were conducted 12 and 24 hours. The two formulations were found to be highly effective drugs whose action lasted 7 hours, by that time the effect of the tablets substantially decreased, which was associated with decreases in drug concentrations. The efficiency of the capsules at this point was significantly higher than that of the tablets. The use of the capsules resulted in tachyphylaxis--rapid decreasing responses to IMN. Following 7 hours of their administration there is a significant decrease in their effect with an increase in IMN concentrations.

Angina Pectoris↗
PubMedDate not supplied

Cardiovascular studies of phenylpropanolamine.

Phenylpropanolamine is found in a number of over-the-counter preparations commonly used for appetite control or as a cold remedy. Even though widely used, some questions still exist as to its effect on the cardiovascular system of man. Both anesthetized and unanesthetized adult beagle dogs were used in this study. In the unanesthetized conditioned dog, blood pressure and heart rate were measured using an inflatable tail cuff. In the first group, consisting of 12 dogs, phenylpropanolamine was given (0.0, 3.1, 6.25 and 12.5 mg/kg) via a stomach tube and the animals were followed for 300 minutes. Each dose of phenylpropanolamine was given to 4 groups made up of 3 dogs each. It produced dose-dependent increases in blood pressure and decreases of heart rate. Maximum changes were noted at 30 to 60 minutes, lasting for 3 to 5 hours. A second group of 9 unanesthetized dogs was given repeated oral doses of phenylpropanolamine (3 groups of 3 animals each). Doses of 3 mg/kg and 6 mg/kg, given orally, produced approximately the same increase in blood pressure and decrease of heart rate as previously observed. At 6 hours, these same doses of phenylpropanolamine produced little or no change in either parameter. At 24 hours after the first dose, however, the dogs responded in much the same manner as with the first administration of phenylpropanolamine. Control dogs given water did not exhibit any degree of tachyphylaxis. Dogs anesthetized with Na pentobarbital were given oral and intravenous doses of phenylpropanolamine (0.0-25 mg/kg). The overall response was like that observed in the unanesthetized preparation with the important exception that low doses (0.1-3 mg/kg) produced significant increases in both heart rate and blood pressure, while higher doses (6-25 mg/kg) resulted in a lesser overall effect. Six anesthetized animals were used to study the effects of phenylpropanolamine and norepinephrine on the cardiovascular function. Both the increase in blood pressure and left ventricular force of contraction, produced by the first dose of phenylpropanolamine, were markedly reduced or absent with the second administration of the drug. In addition, the classic blood pressure response to norepinephrine was likewise increased by prior administration of phenylpropanolamine.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Neurally mediated actions of leukotrienes on ion transport in guinea pig distal colon.

The effects of the sulfidopeptide leukotrienes (LT), LTC4, LTD4 and LTE4 on short-circuit current (Isc), a measure of active ion transport, were determined in muscle-stripped mucosa sheets from the guinea pig distal colon. LTC4 and D4, but not E4, evoked concentration-dependent increases in Isc. Auto- and cross-tachyphylaxis could be demonstrated in LT actions. LTD4 was more sensitive than LTC4 to inhibition by the LTD4 antagonist, 1-<2-hydroxy-3-propyl-4-<4-(1H-tetrazol-5-yl)butoxy>phenyl>etha none, and the intracellular Ca++ inhibitor, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester. Mucosal LT effects were reduced in tissues pretreated with bumetanide or bathed in HCO3(-)-free media. Measurements of transepithelial Na+ and Cl- fluxes revealed that LTC4 increased unidirectional and net secretory fluxes of Cl- but had no effect on Na+ transport. Tetrodotoxin, atropine and indomethacin inhibited mucosal responses to LTC4 and D4; in addition prazosin inhibited LTD4 effects. The results suggest that LTC4 and D4 evoke anion secretion by acting through distinct LT receptor populations. These effects are mediated in part by cholinergic and adrenergic submucosal neurons as well as by colonic prostanoids.

Adrenergic alpha-Antagonists↗
PubMed1993

Antitachyphylactic effects of progesterone and oxytocin on term human myometrial contractile activity in vitro.

OBJECTIVE: To determine whether progesterone causes any changes in the action of oxytocin on the contractile activity of term human myometrium in vitro. METHODS: Myometrial biopsies from 13 term pregnant women undergoing cesarean delivery were immediately immersed in Hepes buffer or buffer containing 5 micrograms/mL progesterone. In the laboratory under a stereomicroscope, the specimens were dissected into 1 x 7.5-mm muscle strips. These were mounted into six tissue baths and superfused with Hepes buffer and buffer containing 5 micrograms/mL progesterone, 5 micrograms/mL progesterone plus 10 microU/mL oxytocin, 5 micrograms/mL progesterone plus 100 microU/mL oxytocin, 10 microU/mL oxytocin, and 100 microU/mL oxytocin. Isometric tension was recorded constantly for at least 3 hours. RESULTS: The frequency of myometrial contractions and tonus increased by superfusion with progesterone, progesterone plus oxytocin, and oxytocin alone compared to buffer. In addition, a gradual decrease in frequency was observed after 60 minutes of contractions with oxytocin alone, whereas progesterone plus oxytocin had no such decrease. The activity area of contractions was greater with 10 microU/mL oxytocin and decreased with progesterone, progesterone plus both concentrations of oxytocin, and 100 microU/mL oxytocin alone, compared to buffer. CONCLUSIONS: Progesterone stimulated the frequency of contractions and tonus of strips from the lower uterine segment of term human myometrium. A lasting increase in the frequency of contractions was observed with superfusion of progesterone plus oxytocin, suggesting that progesterone counteracted the reaction of tachyphylaxis to oxytocin.

Dose-Response Relationship, Drug↗
PubMed1996

Desensitisation of substance P decreases the contractile effect of M15 and Gal (1-14)-(Abu 8) SCY-I on the rat gastric fundus.

Tachyphylaxis to SP decreased the effect of M15 and Gal(1-14)-[Abu8]SCY-I on gastric smooth muscles, without effect on the action of Gal. These findings support our initial hypothesis: the action of M15 and Gal(1-14)-[Abu8]SCY-I on the smooth muscles may not only be due to their agonist activity at Gal receptors, but may result from a subsequent stimulation of receptors for SP and perhaps for other tachykinins as well, however, a possibility that Gal analogues release endogenous SP can not be excluded. Further studies involving a tachykinin antagonist (spantide) are in progress at the moment. [1].

Animals↗
PubMed1999

Mechanisms and sites of action of endothelins 1 and 2 on the opossum internal anal sphincter smooth muscle tone in vitro.

Endothelins, localized in the enteric nervous system, may play important roles in the morphogenesis of the gastrointestinal (GI) tract and in the regulation of GI motility. However, the role of endothelins in the GI sphincters, including the internal anal sphincter (IAS) have not been examined. We examined the actions of endothelins on the basal tone of the opossum IAS circular smooth muscle strips before and after different neurohumoral antagonists or inhibitors. Endothelins 1 and 2 produced a concentration-dependent biphasic effect on the basal tone of the IAS, an initial brief fall followed by a sustained rise. The fall in the IAS smooth muscle tone was not modified by atropine, guanethidine, or tetrodotoxin but was significantly attenuated by the nitric oxide synthase inhibitor L-NNA, the specific neuronal nitric oxide synthase inhibitor, 1-(2-trifluoromethylphenyl)imidazole, the N-type neuronal Ca++-channel blocker omega-conotoxin GVIA, and by the calmodulin antagonist W-13. Endothelin-induced contraction of the IAS, on the other hand, was not affected by any of the neurohumoral antagonists but was significantly inhibited by the selective protein kinase C inhibitor H-7 or the calmodulin inhibitor W-13. The combination of H-7 and W-13 had no additive effect in attenuating the contractile action of endothelin 1. There was clear evidence of a cross-tachyphylaxis to the actions of endothelin 1 and endothelin 2. We conclude that the endothelins exert important neuromodulatory effects on the basal tone of the IAS. The contractile action occurs directly at the smooth muscle and the relaxant action by the activation of neuronal nitric oxide synthase at the nerve terminals. The contraction and relaxation of the smooth muscle caused by endothelins 1 and 2 may involve distinct receptors that are similar for both endothelins. The excitatory actions of endothelin 1 involve both the protein kinase C and the Ca++-calmodulin pathways that may lie in series.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1987

Intraocular pressure effects of multiple doses of drugs applied to glaucomatous monkey eyes.

The effects of multiple dosing with 0.5% timolol maleate, 2% epinephrine hydrochloride, 4% pilocarpine hydrochloride, 1% vanadate, 1% forskolin (nonproprietary name, colforsin), or 0.5% prostaglandin F2 alpha on intraocular pressure (IOP) were each tested on eight cynomolgus monkey eyes in which glaucoma was induced by photocoagulating the trabecular meshwork with the argon laser. The week prior to drug therapy, baseline IOP measurements were carried out at hourly intervals from 9:30 am to 3:30 pm on three days. One to two days later, therapy was initiated. Each drug was applied topically to both eyes of each monkey twice daily for at least four days. The IOP was measured with a calibrated pneumatonometer at the same hourly intervals on treatment days as on the baseline days. The IOP at each time of day on treatment days was compared with the average baseline IOP measured at the corresponding time of day. Topical application of timolol, epinephrine, pilocarpine, vanadate, and prostaglandin F2 alpha significantly reduced IOP without evidence of tolerance or tachyphylaxis during the course of therapy. Forskolin did not significantly decrease IOP after the second day of treatment.

Animals↗
PubMed1991

Effect of bunazosin hydrochloride on intraocular pressure and aqueous humor dynamics in normotensive human eyes.

We investigated the effects of topical administration of bunazosin hydrochloride, a new selective alpha 1-adrenergic antagonist, on intraocular pressure and aqueous humor dynamics in normal human eyes. In the single-dose study, all concentrations of bunazosin (0.025%, 0.05%, 0.1%, and 0.2%) significantly lowered intraocular pressure in a concentration-dependent manner. Administration of multiple doses of 0.1% bunazosin revealed no occurrence of tachyphylaxis after 1 week. Single application of 0.1% bunazosin had no significant influence on aqueous flow rate, tonographic outflow facility, or episcleral venous pressure, suggesting that bunazosin reduces intraocular pressure by increasing uveoscleral outflow. Aqueous protein concentration was found to be unaltered by bunazosin, indicating that blood-aqueous barrier permeability to protein molecules remained unchanged. We conclude that bunazosin may be a possible new antiglaucoma agent with a mechanism of action different from those currently in use for treating ocular hypertension.

Administration, Topical↗
PubMed1997

A 1-year study of brimonidine twice daily in glaucoma and ocular hypertension. A controlled, randomized, multicenter clinical trial. Chronic Brimonidine Study Group.

OBJECTIVE: Brimonidin tartrate is a highly selective alpha 2-agonist. This study investigates the safety and efficacy of 0.2% brimonidine administered twice daily for 1 year in patients with glaucoma or ocular hypertension. METHODS: The study design was a multicenter, double-masked, randomized, parallel-group, active-controlled comparison clinical trial. Subjects instilled 0.2% brimonidine or 0.5% timolol maleate twice daily for 12 months. Subjects were examined at baseline, week 1, and months 1, 2, 3, 6, 9, and 12. A subset of subjects was examined at week 2. RESULTS: Of 443 subjects enrolled in this study, 374 met the entry criteria; 186 received brimonidine and 188 received timolol. Brimonidine-treated subjects showed an overall mean peak reduction in intraocular pressure (IOP) of 6.5 mm Hg; timolol-treated subjects had a mean peak reduction in IOP of 6.1 mm Hg. Brimonidine lowered mean peak IOP significantly more than timolol at week 2 and month 3 (P < .03); no significant difference was observed between the groups for this variable at other visits throughout the 1-year course of the study. No evidence of tachyphylaxis was seen in either group. Allergy was seen in 9% of subjects treated with brimonidine. Dry mouth was more common in the brimonidine-treated group than in the timolol-treated group (33.0% vs 19.4%), but complaints of burning and stinging were more common in the timolol-treated group (41.9%) than in the brimonidine-treated patients (28.1%). Headache, fatigue, and drowsiness were similar in the 2 groups. In general, the tolerance to medication was acceptable. CONCLUSIONS: Brimonidine is safe and effective in lowering IOP in glaucomatous eyes. Brimonidine provides a sustained long-term ocular hypotensive effect, is well tolerated, and has a low rate of allergic response.

Administration, Topical↗
PubMed1995

Effect of dopamine on renal blood flow and cardiac output.

OBJECTIVE: To characterize the relationship between changes in renal blood flow and cardiac output induced by dopamine, hypothesizing that at low doses renal blood flow changes more than cardiac output. DESIGN: Anesthetized swine had renal blood flow and cardiac output measured during either continuous dopamine infusions (2 to 8 micrograms/kg per minute) or bolus dosing (1 to 16 micrograms/kg), and increases in both were compared. Two different fluid protocols were compared using constant dopamine infusions. In the constant pulmonary capillary wedge pressure protocol, intravenous fluids were titrated to keep this parameter constant. In the other protocol, fluid therapy was held constant at 10 mL/kg per hour. RESULTS: With infusions, mean increases in renal blood flow and cardiac output were relatively equal. The maximum increase was 35% at 8 micrograms/kg per minute under the constant pulmonary capillary wedge pressure protocol, with no significant differences (P > .1) found between the change in renal blood flow and cardiac output at any dose in either protocol. With bolus dosing, renal blood flow increased significantly more than cardiac output at 1, 4, and 8 micrograms/kg (P < .05). CONCLUSION: Disproportionate increases in renal blood flow compared with cardiac output at low bolus doses show initial renal responses to be independent of cardiac output. The infusion data suggest that renal responses exhibit tachyphylaxis or that cardiac output slowly accommodates to decreased total peripheral resistance.

Animals↗
PubMed1988

Combination antiemetics for cisplatin chemotherapy.

Nausea and vomiting occur in a majority of patients receiving cisplatin chemotherapy despite prophylactic single agent antiemetic therapy. Three potent antiemetics, metoclopramide, droperidol and dexamethasone, and diphenhydramine to prevent potential extrapyramidal reactions, were combined in prophylaxis of 67 patients receiving cisplatin chemotherapy. Of the patients studied, 76.1% experienced complete protection from both nausea and vomiting in their first course and 62.7% in all their courses of treatment. In 73.3% of 161 evaluable courses, there was neither nausea nor vomiting. Vomiting did not occur in 79.5% of courses. There was no evidence to suggest tachyphylaxis. The efficacy in preventing nausea and vomiting was independent of primary disease site, age, sex, performance status, prior chemotherapy, and prior vomiting. Toxicities were mild and infrequent. Reversible transient extrapyramidal reactions, sweating or twitches occurred in 5.6% of courses. The combination of metoclopramide, diphenhydramine, droperidol and dexamethasone was highly efficacious in preventing nausea and vomiting in moderate or high-dose cisplatin chemotherapy with little toxicity.

Antiemetics↗
PubMed1980

Prostaglandin receptors in the airways.

An analysis of the effects of some natural prostaglandins and of synthetic analogues with more selective actions points to the existence of several receptors for prostaglandins in the airways. Three effects have been studied: the contraction and relaxation of bronchial smooth muscle in vitro and the cough elicited by inhalation of prostaglandin aerosols by the conscious cat. From the rank orders of potency of a group of prostaglandins and analogues, from tachyphylaxis induced by continued exposure to a single species and from antagonism by indomethacin or mefenamic acid, three prostaglandin receptors have been distinguished: (1) for contraction (chi receptor) and (2) for relaxation (psi receptor) of bronchial smooth muscle, and (3) for cough (omega receptor). The natural prostaglandins tested stimulated to different extents each of these three receptors; but synthetic analogues with selective actions on only one or two receptors were identified. It seems likely that (1) prostaglandins or thromboxanes not yet tested will interact with these receptors, (2) other receptors for these substances may be distinguished in the airways, (3) the receptors so far distinguished may also be found in other sites, and (4) the receptor categories described may be subdivisible.

Animals↗
PubMed2002

Somatostatin analogs and radiopeptides in cancer therapy.

Since the discovery of somatostatin (sst) in 1973, numerous chemical and biological studies have been carried out to develop sst analogs with enhanced resistance to proteases and prolonged activity. Three highly potent sst analogs-octreotide, lanreotide, and vapreotide-are now available in the clinic, and demonstrate efficacy in the treatment of tumors of the pituitary and the gastroenteropancreatic tract. The most striking effect is the control of hormone hypersecretion associated with these tumors. Available data on growth suppression in patients indicate a limited antiproliferative action, tumor shrinkage is observed in 10-20% patients, and tumor stabilization in about half of the patients for duration of 8-16 months. Eventually, however, all patients escape from sst analog therapy with regard to both hormone hypersecretion and tumor growth, the only exception being observed in acromegalic patients who do not experience tachyphylaxis even after more than 10 years of daily octreotide injection. The mechanism underlying the escape phenomenon is not yet clarified. Regarding the molecular mechanisms involved in sst antineoplastic activity, both indirect and direct effects via specific somatostatin receptors (SSTRs) expressed in the target cells have be described. Direct action may result from blockade of mitogenic growth signal or induction of apoptosis following interaction with SSTRs. Indirect effects may be the result of reduced or inhibited secretion of growth-promoting hormones and growth factors that stimulate the growth of various types of cancer; also, inhibition of angiogenesis or influence on the immune system are important factors. Five SSTR subtypes have been identified so far, which are variably expressed in a variety of tumors such as gastroenteropancreatic (GEP) tumors, pituitary tumors, and carcinoid tumors. Although all five SSTR subtypes are linked to adenylate cyclase, they are now known to affect multiple other cellular signaling systems and hence they differentially participate in the regulation of the various cellular processes. The finding of several laboratories that SSTR-expressing tumors frequently contain two or more SSTR subtypes, and the recent discovery that SSTR subtypes might form homo/heterodimers to create a novel receptor with different functional characteristics, expand the array of selective SSTR activation pathways and subsequent intracellular signaling cascades. This may lead to improved clinical protocols that take into account possible synergistic interactions between the SSTR subtypes present on the same cancer cell. Radiolabeled sst analogs, such as [(111)In]-[diethylenetriamine pentaacetic acid (DTPA)-D-Phe(1)]-octreotide (OcreoScan), have proved to be very useful for tumor scintigraphy and internal radiotherapy of SSTR overexpressing tumors. The recent introduction of the metal chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) considerably improved the stability of the radioconjugates, making possible the incorporation of a variety of radionuclides, such as (90)Y for receptor-mediated radionuclide therapy or (68)Ga for positron emission tomography (PET). Another promising area is the development of sst conjugates incorporating cytotoxic anticancer drugs.

Amino Acid Sequence↗
PubMed1986

Randomized study of Corynebacterium parvum adjuvant therapy following surgery for (stage II) malignant melanoma.

One hundred and fifteen patients with histologically proven primary cutaneous melanoma were entered into a randomized prospective study following surgical removal of clinically obvious regional metastases. The study started in 1977 and was completed in June 1982. Fifty-eight patients (10 with regional skin metastases and 48 with regional node metastases) were in the control group and 57 (15 regional skin, and 42 regional node metastases) received adjuvant C. parvum. Other clinical features were well balanced for each group. C. parvum, 2 mg/m2 IV was repeated eight times at three weekly intervals. The schedule was based on previous work which indicated significant increase in killer cell activity. There was no serious toxicity and 22 patients exhibited tachyphylaxis. Seventeen patients in the control group (11 tumour free) are alive at 24-80 months, and 20 patients in the C. parvum group (12 tumour free) are alive 24-76 months from randomization. No statistically significant difference (P greater than 0.05) was observed between the two patient groups for overall survival (median 26 months) or relapse free survival (median 8 months) from the date of randomization. Nor was the overall survival from the date of primary surgery (median 52 months, range 4-237) or the relapse free survival, median 28 months, range 2-225, significantly different between the two groups of patients. The relapse pattern in the two groups, and survival after relapse were no different though the response rate to actinomycin D and DTIC chemotherapy was significantly higher in the control (48 per cent) than in the C. parvum (23 per cent) group. Toxicity to chemotherapy was not significantly affected by previous C. parvum treatment. Although there were trends for better survival, in the C. parvum patient group, statistically significant activity has not been noted in this study.

Adjuvants, Immunologic↗
PubMed1996

Topical glyceryl trinitrate in the treatment of chronic anal fissure.

The aetiology of anal fissure is unclear, but there is an association with high maximum resting pressure (MRP). Internal sphincterotomy reduces MRP and heals fissure through an increase in local blood supply. Glyceryl trinitrate (GTN) is a nitric oxide donor which contributes to internal anal sphincter relaxation via a non-adrenergic non-cholinergic pathway. GTN ointment was applied topically in different concentration to the anal margin in patients with chronic anal fissure to monitor its effect primarily on MRP and secondarily on fissure healing. Nineteen patients with chronic anal fissure were treated with ointment containing increasing concentrations of GTN (0.2-0.8 per cent) to produce a reduction in MRP of greater than 25 per cent. The actual dose of GTN varied as no standard delivery system has been developed, but a 'typical amount' of GTN ointment weighed about 200 mg. In 15 of 19 patients, a concentration greater than 0.2 per cent was required to lower the MRP by at least 25 per cent. The minimum concentration of GTN that reduced the resting pressure by at least 25 per cent was prescribed and local application was carried out by the patient twice daily for 6 weeks. At 6 weeks, nine patients had healed, six required sphincterotomy and four were lost to follow-up. Eight of the nine patients with healed fistula required a GTN concentration of 0.3 per cent or more. Sixteen patients were resistant to the usually effective does of 0.2 per cent GTN. In three there was tachyphylaxis and the duration of action of GTN was less than the 12 h described previously in control patients. Two patients did not fulfil the study because of headache.

Administration, Topical↗
PubMed1987

Management of cancer patients receiving interferon alfa-2a.

This is a review of the data on the safety and tolerance of interferon alfa-2a in the treatment of cancer patients and is particularly aimed at patient care. Since 1981, interferon alfa-2a prepared from human sources has been administered to over 2500 cancer patients and 2500 patients with viral diseases. Adverse effects have been invariably produced following parenteral injections of greater than 3 X 10(6) IU. These were mainly flu-like symptoms (greater than 90%), fatigue (90%), gastrointestinal (85%), central nervous system (65%) and musculoskeletal (60%) disorders. Laboratory abnormalities, though common (greater than 75%) were rarely dose limiting. Their severity can be reduced by using dose schedules which promote tachyphylaxis, co-medication with paracetamol and evening administration. Fatigue is best controlled by careful dose attenuation and occasional therapy rest periods. At dosages of 3 X 10(6)-18 X 10(6) IU/injection, interferon alfa-2a therapy can be safely managed on an out-patient basis, requiring minimal or no hospitalization. The frequency and low titre of antibody development to interferon alfa-2a indicates that it is a weak antigen and is suitable for long-term therapeutic application.

Adolescent↗