Specific Therapeutic Effect Research Articles

Randomised clinical trial investigating the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction

Objective To investigate the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction. Patients and methods One hundred and sixty-two consecutive patients who had suffered from adhesive intestinal obstruction without clinical evidence of strangulation or gangrene were randomised into two groups, a control group (treated conservatively, n = 82) and a contrast group (treated with combined administration of octreotide and methylglucamine diatrizoate, n = 80). A laparotomy was performed in both the two groups if symptoms of strangulation developed or the obstruction did not resolve spontaneously after 72 h. Results Statistically significant rapid reduction in pain score, lower amount of nasogastric drainage, shorter hospital stay, lower operative rate and lower postoperative morbidity were observed in the contrast group. Among the non-operative patients, earlier passage of stool and gas, earlier first oral intake and shorter duration of nasogastric tube placement were significantly more frequently observed in the contrast group. No difference in the rate of readmission was found between the two groups. Conclusions Combined administration of octreotide and methylglucamine diatrizoate accelerates resolution of small bowel obstruction by a specific therapeutic effect and is safe for the older persons.

Une phénoménologie de la dépendance à l'alcool. Une expérience primordiale de la « nostrité »

The phenomenological approach to alcoholism interestingly focuses on specific dynamics of interpersonal relationships displaying the founding of the Self from a primary “us” and its original basis in the human feast. Priorities for treatment intervention recommend to involve social setting and relationships of the patients, reaching their active participation to a motivational and long term group treatment, underlying the specific therapeutic effect of world exchanges. Biopsychosocial determination of alcoholism could be primarily based on components of interpersonal relationships. Regarding social background, drinking is one of the most famous supports for the achievement of the feast, a founding marker of present time. Taking an existential point of view, the feast appears as the heart of mankind because it presents a primary “us”, a plural state which indicates the beginning and founding of the Self from the others. During the feast, we regularly have to reach our Self from the “us” while avoiding two main dangers, drunkenness, an increase in the dizziness of upright verticality, and addiction, an opposite vertical surrender to alcohol and falling into in the alcoholic relapse, both situations imply a spatial domination and the disappearance of others. Treatment programs of alcohol addicts need to integrate the necessity of reaching the existential basic trust from the support of a group to the appropriation of the community which can be defined as an original “usness”.

P60 - Maladie de Verneuil et zinc : une nouvelle approche thérapeutique

To study the specific therapeutic effect of zinc on spinal cord injury (SCI) and its specific protective mechanism.The effects of zinc ions on neuronal cells were examined in a mouse SCI model and in vitro. In vivo, neurological function was assessed by Basso Mouse Scaleat (BMS) at 1, 3, 5, 7, 10, 14, 21, and 28 days after spinal cord injury. The number of neurons and histomorphology were observed by nissl staining and hematoxylin-eosin staining (HE). The chromatin and mitochondrial structure of neurons were detected by transmission electron microscopy (TEM). The expression of nuclear factor erythroid 2 related factor 2 (Nrf2)-related antioxidant protein and NLRP3 inflammation-related protein were detected in vivo and in vitro by western blot (WB) and immunofluorescence (IF), respectively.Zinc treatment promoted motor function recovery on days 3, 5, 7, 14, 21 and 28 after SCI. In addition, zinc reduces the mitochondrial void rate in spinal neuronal cells and promotes neuronal recovery. At the same time, zinc reduced the levels of reactive oxygen species (ROS) and malondialdehyde in spinal cord tissue after SCI, while increasing superoxide dismutase activity and glutathione peroxidase production. Zinc treatment resulted in up-regulation of Nrf2/Ho-1 levels and down-regulation of nlrp3 inflammation-associated protein expression in vitro and in vivo.Zinc has a protective effect on spinal cord injury by inhibiting oxidative damage and nlrp3 inflammation. Potential mechanisms may include activation of the Nrf 2/Ho-1 pathway to inhibit nlrp3 inflammation following spinal cord injury. Zinc has the potential to treat SCI.

Randomized controlled trial of Gastrografin in adhesive small bowel obstruction

Several previous studies have shown that Gastrografin can be utilized to triage patients with adhesive small bowel obstruction (ASBO) to an operative or a non-operative course. Previous studies assessing the therapeutic effect of Gastrografin have been confounded by post-administration radiology alerting the physician to the treatment group of the patient. Therefore the aim of the present paper was to test the hypothesis that Gastrografin hastens the non-operative resolution of (ASBO). Patients, diagnosed with ASBO on clinical and radiological grounds, were randomized to receive Gastrografin or placebo in a double-blinded fashion. Patients did not undergo further radiological investigation. If the patient required subsequent radiological intervention or surgical intervention they were excluded from the study. End-points were passage of time to resolution of ASBO (flatus and bowel motion), length of hospital stay and complications. Forty-five patients with ASBO were randomized to receive either Gastrografin or placebo. Two patients were excluded due to protocol violations. Four patients in each group required surgery. Eighteen of the remaining patients received Gastrografin and 17 received placebo. Patients who received Gastrografin had complete resolution of their ASBO significantly earlier than placebo patients (12 vs 21 h, P = 0.009) and this translated into a median of a 1-day saving in time in hospital (3 vs 4 days, P = 0.03). Gastrografin accelerates resolution of ASBO by a specific therapeutic effect.

A model for evaluating therapeutic response of combined cancer treatment modalities: applied to treatment of subcutaneously implanted brain tumors (N32 and N29) in Fischer rats with pulsed electric fields (PEF) and 60Co-gamma radiation (RT).

The aim of the present study is to develop a mathematical model for evaluating therapeutic response of combined treatment modalities. The study was performed in rats of the Fischer-344 strain with rat glioma N32 or N29 tumors implanted subcutaneously on the thigh of the hind leg. Pulsed electric fields, PEF, with 16 exponentially decaying pulses with a maximum electric field strength of 140 V/mm and t(1/e)= 1 ms were first applied to the tumors. Then within 5 min radiation therapy with (60)Co-gamma radiation, RT, was given in daily fractions of 5 Gy. The animals were arranged into one group of controls and 3 groups of different kind of treatments: PEF only, RT only or combination of PEF + RT. At about 4 weeks after inoculation, the tumors were given the treatment sessions during one week. In 2 experimental series with totally 52 rats with N32 tumors, of which 16 were controls, were given 4 sessions of PEF treatments and RT (totally 20 Gy). In a special experimental series with totally 56 rats with N32 tumors, of which 10 were controls, the different groups were given 1, 2, 3 or 4 treatment sessions respectively. Another strain of glioma tumor, N29 with 62 tumors of which 14 were controls was studied in 2 series given 4PEF + 4RT and 2PEF + 4RT respectively. Fitting the data obtained from consecutive measurements of tumor volume (TV) of each individual tumor to an exponential model TV = TV(0). exp[TGR.t] estimated the tumor growth rate (TGR % per day) after the first day of treatment (t = 0). The TGR of N32 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.0001), compared to RT alone (p < 0.0001) and compared to PEF alone (p < 0.001). The combined treatment of N32 gives significant effect on the tumor growth rate after 2, 3 and 4 treatment session while RT alone seems to be most efficient after one treatment of 5 Gy and PEF alone is most efficient after 2 treatments at 2 consecutive days. The TGR of N29 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.05) but the combination of 2PEF + 4RT was more effective (p < 0.005). The specific therapeutic effect STE is defined as the difference between the average tumor growth rates of controls and exposed tumors divided by the average tumor growth rate of the controls. With 4PEF treatments alone the average STE value was 0.32 for N32 tumors and 0 for N29; for 4RT alone the STE values were 0.29 and 0.42 respectively, and for combined treatments 4PEF + 4RT 0.67 and 0.17 respectively. For the N29 tumors treated with 2PEF + 4RT the STE value was 0.53. The therapeutic enhancement ratio, TER, value increase with the number of treatment sessions and the TER of the combined treatments is above 1 in two of the N32 series, which indicates a synergistic effect of 4PEF + 4RT. This work demonstrate the use of our model for analyzing the combination PEF + RT, but it can also be used for evaluation the therapeutic effects of combining RT with chemotherapy or immunogenetic therapy.

Thrombolysis during cardiopulmonary resuscitation

Between 40 and 90 cardiopulmonary resuscitations are performed per 100,000 inhabitants each year in western industrialised nations. In 50-70% of these patients, either fulminant pulmonary embolism or acute myocardial infarction is the underlying cause of cardiac arrest. Based on this fact, thrombolysis may represent a new and effective causal therapeutic strategy in patients suffering from cardiac arrest due to acute myocardial infarction or fulminant pulmonary embolism. In the past, thrombolysis was contraindicated during cardiopulmonary resuscitation due to great fears of severe bleeding complications (resuscitation-mediated or lysis-induced intracerebral bleeding). For a long time, only clinical case reports or small clinical case series were reported in the literature, however, recently, the first clinical studies focusing on the safety and efficacy of thrombolytic therapy during out-of-hospital cardiopulmonary resuscitation have been published. Besides a specific therapeutic causal effect on pulmonary artery emboli and coronary artery thrombosis, experimental data strongly indicate that thrombolysis might also have an impact on cerebral microcirculatory reperfusion during and after cardiopulmonary resuscitation. This effect might be responsible for the exceptionally good neurological outcome observed in patients treated with thrombolytic agents during cardiopulmonary resuscitation and might be a result of the proven imbalance of the endogenous coagulation system in patients suffering from cardiac arrest. This coagulation imbalance is thought to be responsible for postresuscitation cerebral microcirculatory reperfusion disorders in patients after cardiac arrest and cardiopulmonary resuscitation. In summary, recent clinical and experimental data focusing on thrombolysis during cardiopulmonary resuscitation strongly indicate, that thrombolysis may represent a new and relatively safe therapeutic option during resuscitation after cardiac arrest due to acute myocardial infarction or fulminant pulmonary embolism. If the results of an international randomised, controlled clinical multicentre trial presently underway confirm the previous clinical findings, thrombolysis during cardiopulmonary resuscitation could become an important part of future cardiopulmonary resuscitation algorithms.

Rehabilitation of very severe unilateral neglect by visuo-spatio-motor cueing: Two single case studies

Robertson, North, and Geggie (1992) have suggested that the voluntary activation of the left upper limb in the left hemispace (spatio-motor cueing) could reduce unilateral neglect. This study assesses the efficacy of visuo-spatio-motor cueing, and particularly the generalisation to daily-life activities, in two patients with very severe neglect who had failed to improve with scanning training. The patients were included in the trial 4 and 7 months after a severe unilateral right hemispheric stroke. They both suffered from disabling unilateral neglect despite intensive conventional therapy. A single-case experimental ABAB design was used (A = baseline with conventional treatment; B = visuo-spatio-motor cueing; each period = 2 weeks). A randomisation test was used to assess the presence of a specific therapeutic effect. In both cases, there was a statistically significant treatment-related improvement on a line bisection test. A parallel improvement was found on neglect behaviourin daily life, as assessed by the Catherine Bergego Scale (Azouvi et al., 1996). The therapeutic effect was maintained at 1-month follow up. These results suggest that visuo-spatio-motor cueing may be efficient in very severe neglect and may help in obtaining generalisation to daily-life activities.

RETROPERITONEAL HEMATOMA DUE TO RUPTURE OF A PSEUDOANEURYSM CAUSED BY ACUPUNCTURE THERAPY

Acupuncture, an ancient technique using needle insertion at specific points on the body for a specific therapeutic effect, has now become a major alternative treatment. Approrrimately 1 million patients visited an acupuncture professional in the United States in 1994.' However, several complications have been reported, including spinal cord injury, needle migration in the medulla oblongata, fatal cardiac tamponade, pneumothorax, spinal epidural hematoma and subcutaneous pseudoaneurysm.'Z3 To our knowledge we report the first case of retroperitoneal hematoma caused by acupuncture therapy. CASE REPORT A 72-year-old Japanese woman with essential hypertension underwent acupuncture therapy performed by a physician for relief of persistent lumbago. Several needles were inserted into the right loin region, followed by electroacupuncture stimulation. Four hours later the patient visited another hospital complaining of nausea and right flank pain. Abdominal computerized tomography (CT) demonstrated a large retroperitoneal mass around the right kidney (fig. 1, A). The patient was referred to our hospital due to hypotension with tachycardia. Selective right renal arteriography revealed 3 sections of pseudoaneurysm with rupture, presumably caused by acupuncture therapy (fig. 2). Subsequent selective arterial embolization by metallic coil resulted in good function of the affected kidney (fig. 1, B). DISCUSSION Various complications due to acupuncture therapy have been reported, including spinal cord injury (acute transverse myelopathy), perineal nerve palsy, embedded type needle migration in the medulla oblongata, fatal cardiac tamponade, pneumothorax, spinal epidural hematoma and pseudaneury~m.~,~ A huge retroperitoneal hematoma requiring a subsequent hemostatic procedure is a rare and serious complication of acupuncture therapy. The diagnosis is easy to establish in cases of embedded needle, since the needle may be identified on radiography. However, a detailed patient

CMV retinitis and the controversies associated with highly active antiretroviral therapy and the immune recovery hypothesis.

The aggressive multidrug regimen of highly active antiretroviral therapy (HAART) has offered some degree of promise of immune reconstitution in AIDS patients, a phenomenon that theoretically would impact positively on the incidence and severity of opportunistic infections. Some studies already have noted complete regression of cytomegalovirus (CMV) retinitis without specific use of anti-CMV agents in patients undergoing HAART. However, the role of HAART in CMV retinitis remains controversial among investigators. This review of the salient details regarding the controversies associated with CMV retinitis and the immune recovery hypothesis is meant to shed light on current and future therapeutic issues concerns. Early data seem to predict a decline in CMV retinitis. However, some investigators have noted that increased CD4 T-lymphocyte counts may not protect against CMV retinitis; therefore, the diagnosis cannot be excluded based on count alone. There is also the question of whether CMV retinitis progression in any way represents failure of HAART in those patients receiving this type of combination therapy. HAART is seen as an encouraging development in the treatment of AIDS and opportunistic infection, but its more specific therapeutic effect on CMV retinitis requires further research with controlled prospective clinical trials.

Ekbom&amp;rsquo;s Syndrome: Delusional Disorder, Somatic Type, Treatment with Trifluoperazine

Since Ekbom’s classical description was first published in 1938, numerous case reports of Ekbom’s syndrome have been reported. Claims have been made that pimozide exerts a specific therapeutic effect

Cholinergic deficits in aged rat brain are corrected with nicergoline

Choline acetyltransferase (CAT) and muscarinic cholinergic receptor (MCR) activities are markedly reduced in aged as compared with young-adult rat brain. Nicergoline was found to correct these reduced activities in most regions of the brain, especially in the cerebral cortex and hippocampus. Chronic administration of nicergoline had no effect on CAT activity or MCR binding in young-adult rat brain. Nicergoline thus appears to have a specific therapeutic effect on cholinergic functions in aged rat brain, where it acts both pre-synaptically and post-synaptically.

The efficacy of laser therapy for musculoskeletal and skin disorders: a criteria-based meta-analysis of randomized clinical trials.

The efficacy of laser therapy for musculoskeletal and skin disorders has been assessed on the basis of the results of 36 randomized clinical trials (RCTs) involving 1,704 patients. For this purpose, a criteria-based meta-analysis that took into account the methodological quality of the individual trials was used. The studies with a positive outcome were generally of a better quality than the studies with a negative outcome. No clear relationship could be demonstrated between the laser dosage applied and the efficacy of laser therapy, or between the dosage and the methodological score. In general, the methodological quality of these studies appeared to be rather low. Consequently, no definite conclusions can be drawn about the efficacy of laser therapy for skin disorders. The efficacy of laser therapy for musculoskeletal disorders seems, on average, to be larger than the efficacy of a placebo treatment. More specifically, for rheumatoid arthritis, posttraumatic joint disorders, and myofascial pain, laser therapy seems to have a substantial specific therapeutic effect. Further RCTs, avoiding the most prevalent methodological errors, are needed in order to enable the benefits of laser therapy to be more precisely and validly evaluated.

Effect of lithium citrate on adrenocortical activity in manic-depressive illness

Twelve manic-depressive patients were treated with lithium citrate on a research ward where fluid and electrolyte intake was controlled. The following findings were noted: Four of the five depressed patients became symptom free as did all seven manic patients. The substitution of placebo during the symptom-free period was associated within 24–48 hr with recurrence of depressive or manic symptomatology in three manic and two depressed patients. In addition to its well established effect upon mania, lithium, in these cases, had a specific therapeutic effect upon depression as well. The introduction of lithium was associated with a temporary increase in 17-OHCS excretion along with an increased excretion of water, sodium, and potassium. These effects were not sustained, in some instances, beyond 24 hr. The substitution of placebo for lithium during the course of treatment resulted in changes in excretion which were in the opposite direction. The direction of the changes in steroid excretion suggests that lithium's effect upon electrolyte metabolism is not secondary to its action upon the adrenal cortex. Manic patients whowed a tendency to retain lithium while symptomatic and to excrete amounts in excess of that administered after becoming symptom-free. This retention of lithium tended to differentiate the manic from the depressed patients. Manic patients treated with lithium showed a higher rate of 17-OHCS excretion after they had become symptom-free than before administration of lithium. This increase may have been secondary to clinical improvement or to retention of lithium. The depressed patients did not show this trend towards increased steroid excretion.

Metabolic balance studies on the effect of lithium salts in manic-depressive psychosis.

The specific therapeutic effect of lithium salts in the treatment of the manic phases of manicdepressive psychosis was first reported by Cade (1949) and has been confirmed in a number of studies since (Schou, Juel-Nielson, Strömgren and Voldby, 1954; Maggs, 1963; Hartigan, 1963). In view of the claims made by Baastrup (1964) and more recendy by Baastrup and Schou (1967) that lithium also has a prophylactic action against both manic and depressive phases of manic-depressive psychosis it is likely that lithium salts will be used increasingly by psychiatrists.

The need for drug monitoring in psychiatric practice.

The national cost of prescriptions for drugs for use in medical practice in the United Kingdome has risen progressively from £35,000,000 in 1949 to well over £100,000,000 a year now (Dunlop, 1965). The number of drugs taken by patients is vast, and the variety of drugs available for prescription is considerable. Prescribed in order to produce a specific therapeutic effect, few drugs, if any, are wholly free from the potential of producing undesirable side-effects. These vary from the trivial to the lethal, from the transient to the permanent. Methods for their accurate detection, qualitative evaluation and risk identification are vital prerequisites to therapeutic safety and refinement. Experimental techniques, using detailed observation on large samples of patients being treated by drugs, have been developed recently. A monitoring system which scans for side-effects of drugs represents a means whereby prospective and cumulative data on the frequency of occurrence and nature of these side-effects can accrue. This is referred to as drug monitoring.

Lithium as a prophylactic agents. Its effect against recurrent depressions and manic-depressive psychosis.

THE SPECIFIC therapeutic effect of lithium in manic phases of the manicdepressive psychosis was first observed in 1949 1 and was confirmed later in controlled studies, 2,3 as well as in a number of uncontrolled ones. A prophylactic action of the drug against both the manic and depressive phases of the illness could be noted in a few of the patients described by Schou et al. 2 More systematic and detailed observations of this effect were made independently by Hartigan 4 and Baastrup, 5 and the term normothymotics was proposed for drugs with a specific action against manic-depressive psychosis. 6 In order to demonstrate prophylactic drug action in a disorder such as manicdepressive psychosis, which is characterized by a capricious and largely unpredictable course, one must study a large number of patients who have a sufficiently high risk of relapse and who are observed for

4 Diuretic Drugs

Publisher Summary This chapter discusses diuretic drugs. It also discusses renal mechanisms that are affected by diuretic drugs. The chapter describes the evaluation of diuretic drugs. One essential step is the determination of the over-all toxicity of the new compound both in acute and in chronic experiments; another is the evaluation of its specific therapeutic effect, either in absolute terms or in comparison with a compound acting similarly. Toxicity tests of diuretics in animals are carried out according to well-established methods. The scheme adopted for the classification of diuretic drugs has taken into account the fact that individual diuretics may produce their effect in several ways. Moreover, diuretic drugs may act differently in the healthy and in the diseased subject. Diuretics fall into one of three main classes: (1) there are those that reduce sodium ion reabsorption by direct tubular action, (2) there are compounds that affect tubular sodium ion reabsorption indirectly, (3) and there are drugs that increase the filtered load of sodium chloride.

STUDIES ON BILIARY DYSKINESIA

In 35 patients with the so-called gall duct syndrome, in whom no stone was roentgenologically detected in the biliary system and neither inflammatory findings, gall sand, nor bacillus (by 48 h. culture in blood agar) was observed in the duodenal fluid, roentgenography with Biligrafin was made to examine the bladder and duct as an entity. The appearance of these organs was roentgenographically classified into three types: tonic, flaccid and normal. Next in each type the therapeutic effects of various agents were examined and the improvement in the treatment was attempted. The results obtained were as follows:1. The most frequent abnormality was the prolongation of the common duct visible time accompanied with the dysfunction of the gall bladder contraction which was found in 34% of the patients. Other abnormalities were, in the order of the frequencies: dilatations of the hepatic duct (29%), gall bladder (26%), and common duct (23%), insufficient cholecystography (17%), and abnormally shaped (14%), contracted (9%) and ptosed gall bladder (3%).2. There was a parallelism between the dilatation of the hepatic duct and that of the common duct. However, the prolongation of the common duct visible time did not always parallel its dilatation. In no case with the dilated gall bladder the prolongation of the common duct visible time was observed. No correlation was found either between the dilatation of the common duct and that of the gall bladder or between the disturbance of the contracting function or morphological abnormality of the gall bladder and the density of its shadow on the roentgenogram.3. With special reference to the chronological change in the density of the roentgenographical shadow of the common duct, dyskinesia was classified. The frequencies were: tonic 34%, flaccid 26%, and normal 40%.4. Therapeutic effects. A cholagogue (magnesium sulfate solution) and choleretic (dehydrocholic acid) were effective both in the tonic and flaccid types, especially in the latter. No effect was observed in the normal type. Antibiotics (Mycilin, Chloromycetin) were not effective in any type. Autonomic nervous system blockades (Buscopan, atropin) were effective only in the tonic type. Chlorpromazine or meprobamate was effective in the normal type and not so effective in the tonic and flaccid types. Grelan and barbiturates showed no specific therapeutic effect in any type.

The effect of isoniazid on depressive states.

Isonicotinyl Hydrazide or Isoniazid has for some years now been used in conjunction with other compounds in the treatment of pulmonary tuberculosis. During this treatment certain workers (Robitzek et al., 1952) noted the development of a state of euphoria in their patients. Since Isoniazid was known to exert toxic effects on nervous tissue (Gammen et al., 1953) the hypothesis was made that the substance might be capable of producing an elevation of mood by direct action on the central nervous system. Acting on this hypothesis, Salzer and Lurie (1953) treated a group of patients suffering from various depressive conditions with Isoniazid given orally in the dosage of 50 mgm. t.d.s. for one week. If no toxic effects occurred the dosage was raised to 100 mgm. t.d.s. for a further two weeks, while in a few cases only higher doses were given. These workers maintained this level of dosage in order to avoid the advent of toxic side effects. Their results, which will be discussed later in this paper, led them to the conclusion that isoniazid had a specific therapeutic effect upon certain depressive disorders.The object of this study, arising out of the work mentioned, was to carry out an initial survey of the effects of isoniazid on the affective component of various depressive states. If any demonstrable therapeutic action had been noted a larger, controlled, and more systematic study would have been undertaken but in view of the results obtained this further project has now been abandoned.

An investigation of carbon dioxide as an adjunct to psychotherapy in some neuroses.

1. A total of 100 patients were treated for anxiety or neurotic depression with carbon dioxide combined with psychotherapy or with psychotherapy alone. 2. Of 50 patients treated with carbon dioxide, two-thirds showed no change, one-third improved, none could be classified as having recovered socially. 3. Of 50 control patients treated with psychotherapy alone, three-fourths showed improvement or social recovery and one-fourth showed no change. 4. Patients treated by psychotherapy alone showed improvement on fewer treatments. 5. The explosive abreaction following administration of carbon dioxide could not be integrated into the patients' defense mechanisms. 6. The use of carbon dioxide therapy in our hands added no specific therapeutic effect but did add problems of transference and resistance that retarded or prevented recovery. 7. Treatment of patients with symptoms of anxiety or neurotic depression was best accomplished by psychotherapy alone.