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Results for “adjunct therapy”

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PubMed1999

Efficacy of anti-tumor necrosis factor-alpha antibody as an adjunctive therapy in experimental Escherichia coli meningitis in the newborn piglet.

This study was done to evaluate the efficacy of anti-tumor necrosis factor alpha (anti-TNF-alpha) antibody as an adjunctive therapy in neonatal bacterial meningitis. Newborn piglets were divided into three groups: 8 in the control group, 13 in the meningitis group (MG), and 10 in the meningitis with anti-TNF-alpha antibody group (AG). Meningitis was induced by intracisternal injection of 10(8) colony-forming units of Escherichia coli in 100 microl of saline. In the AG, 200 microl of anti-TNF-alpha antibody was also given intracisternally. In the AG, the elevated cerebrospinal fluid TNF-alpha level observed in the MG was completely abolished, and increased intracranial pressure, hypoglycorrhachia, and CSF pleocytosis observed in the MG were downmodulated. But blood, brain, and CSF lactate levels remained elevated in both MG and AG. Increased brain cell membrane lipid peroxidation products and decreased Na+,K+-ATPase activity observed in the MG were not attenuated in the AG. These results indicate that anti-TNF-alpha antibody was not particularly effective as an adjunctive therapy in attenuating acute inflammatory responses and ameliorating brain damage in neonatal bacterial meningitis.

Animals↗

PubMed1993

Hyperimmune human IgG or recombinant human granulocyte-macrophage colony-stimulating factor as adjunctive therapy for group B streptococcal sepsis in newborn rats.

Group B streptococcus (GBS) continues to cause considerable morbidity and death in newborn infants despite the use of antibiotics. We investigated the use of adjunctive therapies to be used with antibiotics in the treatment of neonatal sepsis, using a neonatal rat model of established GBS disease. After the development of GBS bacteremia, a human IgG preparation hyperimmune for GBS, administered with penicillin, decreased the mortality rate compared with the use of penicillin alone (14% vs 57%; p = 0.02). Similarly, recombinant human granulocyte-macrophage colony-stimulating factor, administered in a range of doses to animals with bacteremia, decreased mortality rates. The greatest effect was noted at a dose of 0.05 micrograms/kg (mortality rate 39% in combination with penicillin vs 76% for penicillin alone; p < 0.0001). Thus adjunctive therapies such as those studied here may have the potential to improve the outcome of neonatal sepsis.

Adjuvants, Immunologic↗

PubMed2004

In vitro transcorneal penetration of metronidazole and its potential use as adjunct therapy in Acanthamoeba keratitis.

PURPOSE: To investigate the in vitro permeation of metronidazole through rabbit and human corneas in the presence and absence of 0.01% benzalkonium chloride and to suggest its use as adjunct therapy in the treatment of Acanthamoeba keratitis. METHODS: Metronidazole permeation through rabbit and human corneas, the latter being unsuitable for transplantation, were used for all permeability experiments. Flux rates for metronidazole from 0.5% and 1.0% aqueous solutions in the presence and absence of 0.01% benzalkonium chloride (BZCL) were determined. ANOVA and the Duncan multiple range test were used to test for steady state and an unpaired t test with the Welch correction was used to test for differences between the mean flux values at each time point. A significance level of 5% was used for all the statistical tests. In the clinical cases described, 0.5% aqueous solution was used. RESULTS: Steady-state flux rates for metronidazole from 0.5% and 1.0% solutions across both rabbit and human corneas were achieved after 6 and 4 hours, respectively. No statistically significant differences were obtained in the presence and absence of 0.01% BZCl (P < 0.05) between the steady state flux values at both concentrations of metronidazole of human and rabbit corneas, except for 0.5% metronidazole across rabbit corneas. Flux rates of metronidazole across human corneas were 12%-33% higher than those across rabbit corneas. For both rabbit and human corneas, flux rates of metronidazole from 0.5% and 1.0% solutions were reduced by between 4% and 11%, respectively, in the presence of 0.01% benzalkonium chloride. CONCLUSIONS: Although statistically significant differences in flux values were obtained between human and rabbit corneas, the study supports the suitability of the in vitro rabbit cornea as a model for investigating permeation of drugs through human corneas. However, direct extrapolation of animal data to humans must be approached cautiously. The metronidazole from a 1% solution had a steady-state flux rate approximately double that from the 0.5% solution. Higher concentrations of up to 1% may be considered for clinical use for treating Acanthamoeba keratitis infections. It would appear to be prudent to omit benzalkonium chloride as a preservative from preparations of metronidazole formulated for topical ophthalmologic use. Early clinical experience with the topical solution as adjunct therapy in the treatment of Acanthamoeba keratitis is encouraging.

Acanthamoeba Keratitis↗

PubMed1995

Adjunctive therapy in the management of patients with acute myocardial infarction.

Adjunctive therapy for acute myocardial infarction should include aspirin, beta-adrenergic blocking agents, and, in most patients, consideration of the use of angiotensin-converting enzyme inhibitors, especially if left ventricular function is reduced. Heparin has an important adjunctive role in enhancing early vessel patency in patients who receive tissue-type plasminogen activator and in decreasing the frequency of reocclusion of an infarct-related artery during any thrombolytic therapy. Heparin must also be administered to all patients who undergo primary angioplasty. Intravenously administered nitroglycerin and orally administered nitrates are probably most effective in patients with symptomatic ischemia. Calcium channel blockers and prophylactic antiarrhythmic agents are not indicated for most patients with acute myocardial infarction. Currently, insufficient evidence is available to recommend the widespread use of intravenously administered magnesium sulfate in the setting of acute myocardial infarction. In patients with ischemic pain, judicious intravenous administration of morphine can provide relief. Use of warfarin sodium should be reserved for patients at risk for left ventricular mural thrombus. Although the use of lipid-lowering agents after myocardial infarction has been controversial, recent studies have demonstrated the importance of such therapy for secondary prevention of death and morbidity.

Acute Disease↗

PubMed1981

Imagery (self-hypnosis) as adjunct therapy in childhood cancer: clinical experience with 25 patients.

Clinical experience with 25 pediatric cancer patients referred by oncologists for imagery exercises (self-hypnosis) at Minneapolis Children's Health Center suggests that this modality is valuable adjunct therapy for symptom relief, such as reduction of pain and nausea, especially among those patients who begin these exercises at the time of their initial diagnosis. Twenty-one of these patients agreed to use the exercises and 19 demonstrated substantial symptom relief associated with their practice. This experience suggests the need for more research regarding the optimal use of this modality in children with cancer, and for better understanding of how psychological factors contribute, if at all to the development and course of malignancies. A 5-year prospective study of imagery as adjunct therapy in childhood cancer is now in process.

Adolescent↗

PubMed2026

Corticosteroids as adjunctive therapy to standard treatment in Kawasaki disease: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children in developed countries. While IVIG plus aspirin remains standard treatment, 10-20% of patients are IVIG-resistant and face an elevated risk of coronary artery abnormalities. Corticosteroids have been explored as adjunctive therapy, though evidence on their benefit remains inconsistent. To assess the efficacy and safety of adjunctive corticosteroids in Kawasaki disease across key clinical outcomes. This PRISMA 2020-compliant systematic review and meta-analysis included RCTs identified through database searches up to April 2026. Risk of bias was assessed using Cochrane RoB 2.0. Data were pooled using random-effects models to estimate risk ratios (RRs) and mean differences (MDs) with 95% CIs. Subgroup analyses, leave-one-out sensitivity analyses, and GRADE certainty appraisal were also performed. Eight studies (n = 4106) were included. No significant differences were found in coronary artery abnormalities (CAA) within 1 month (RR 0.49, 95% CI 0.17-1.42), after 1 month (RR 0.81, 95% CI 0.43-1.55), fever duration (MD - 1.75, 95% CI - 3.71 to 0.21), or adverse events (RR 1.08, 95% CI 0.57-2.07). Hospital stay was modestly shorter with corticosteroids (MD - 0.99, 95% CI - 1.86 to - 0.11). Exploratory subgroup analyses suggested potential benefits with prednisolone-based and prolonged corticosteroid regimens for selected outcomes; however, these findings should be interpreted cautiously given multiple subgroup comparisons. Overall certainty of evidence was very low. CONCLUSION:  Adjunctive corticosteroids did not significantly improve major outcomes in KD. Prednisolone-based regimens showed some promise, but high-quality trials are still needed before any firm conclusions can be drawn. WHAT IS KNOWN: • Corticosteroids have been studied as adjunctive therapy for Kawasaki disease, but their effects on coronary outcomes and other clinical outcomes remain inconsistent. WHAT IS NEW: • This meta-analysis found no significant improvement in major outcomes with adjunctive corticosteroids, although prednisolone-based and prolonged regimens may provide benefits for selected outcomes.

Humans↗

PubMed2006

Adjunctive therapy with low-molecular-weight heparin in patients with chronic heart failure secondary to dilated cardiomyopathy: one-year follow-up results of the randomized trial.

BACKGROUND: Defective endothelial function has been shown in dilated cardiomyopathy. Therefore, improvement in endothelial function after low-molecular-weight heparin (LMWH) therapy may be clinically beneficial. Consequently, the effect of adjunct enoxaparin, a LMWH, on standard treatment of dilated cardiomyopathy was investigated. METHODS: This was a randomized, standard treatment-controlled, 2-center pilot trial of 102 patients (52 receiving adjunctive therapy with enoxaparin at a dosage of 1.5 mg/kg daily for 3 months and 50 receiving standard therapy with angiotensin-converting enzyme inhibitors, beta-blockers, and diuretics alone) with stable chronic heart failure secondary to dilated cardiomyopathy (New York Heart Association [NYHA] class II and III; left ventricular [LV] ejection fraction, < or = 40%). All patients underwent coronary angiography and endomyocardial biopsy and were clinically stable for at least 6 months before enrollment. The combined primary end point included mortality, urgent heart transplantation, and readmission to hospital due to heart failure progression. The secondary end point was to determine the severity of heart failure (serum level of N-terminal brain natriuretic peptide), cardiac function (LV ejection fraction by radionuclide ventriculography), LV diameters by echocardiography, exercise capacity (changes in NYHA class, changes in peak oxygen consumption), and changes in quality of life (Minnesota Living with Heart Failure questionnaire). The clinical outcome was assessed after 6 and 12 months of therapy. RESULTS: Baseline characteristics were comparable in both groups. Five patients dropped out during 12 months of the study. Twelve patients achieved primary end point (8 in the control group and 4 in the LMWH group). The free survival rate was 94% for the LMWH group and 90% for the controls (not statistically significant). After the 12-month period, in the LMWH group, N-terminal brain natriuretic peptide level and LV diameters decreased significantly (P < .001 and P = .006, respectively), whereas LV systolic function increased (P < .001). Changes in exercise capacity and subjective improvement did not differentiate the groups (nonsignificant). Adverse reactions to the enoxaparin therapy were minor and transient. CONCLUSIONS: In patients with chronic heart failure due to dilated cardiomyopathy, adjunct long-term enoxaparin therapy may offer additional clinical benefit without deleterious effects on major cardiac events.

Adult↗

PubMed1994

A pilot, early angiographic patency study using a direct thrombin inhibitor as adjunctive therapy to streptokinase in acute myocardial infarction.

BACKGROUND: The success of streptokinase in acute myocardial infarction is hampered by the high failure rate to achieve early reperfusion. This study evaluates the possible benefit of Hirulog (Biogen, Cambridge, Mass), a direct thrombin inhibitor, as adjunct therapy to streptokinase to enhance early patency and prevent rethrombosis. Heparin has been shown to be of very limited benefits in this setting. METHODS AND RESULTS: Forty-five patients were randomized to Hirulog or heparin (2:1 ratio). Coronary angiography documented a TIMI 2 or 3 flow after 90 minutes in 77% of the patients treated with Hirulog and streptokinase and in 47% of patients treated with heparin and streptokinase (P < .05) and after 120 minutes in 87% and 47% of patients, respectively (P < .01). TIMI 3 flow was established in 77% of patients with Hirulog compared with 40% with heparin (P < .02). The clinical outcome and the bleeding rate was also favorable to Hirulog; no reocclusion was observed at late angiography performed 4.7 days later. CONCLUSIONS: Hirulog in this pilot study significantly improved the early patency rate of the infarct-related artery with a favorable clinical profile. This new direct thrombin inhibitor exhibits promise as adjunctive therapy to thrombolysis.

Coronary Angiography↗

PubMed2002

A pilot study of N-acetylcysteine as adjunctive therapy for severe malaria.

BACKGROUND: The case fatality rate of severe malaria remains unacceptably high. N-acetylcysteine (NAC) is a safe compound that inhibits tumour necrosis factor (TNF) and impedes cytoadherence, both of which have been implicated in the pathogenesis of malaria complications. AIM: To evaluate NAC as adjunctive therapy in severe malaria. DESIGN: A placebo-controlled, double-blind prospective study, with serum lactate level as the principal objective measure of response. METHODS: Thirty adult males with severe, quinine-treated malaria received either 300 mg/kg of NAC or placebo, over 20 h. RESULTS: Serum lactate levels normalized twice as quickly after NAC (median 21 h, 95%CI 12-36 h) as after placebo (median 42 h, 95%CI 30-84 h; p=0.002, Mann-Whitney U test). Twenty-four hours after admission, 10/15 (67%) NAC-group patients but only 3/15 (20%) placebo-group patients had normal lactate concentrations (p=0.01, Fisher exact test). NAC-treated patients could be switched from intravenous to oral therapy earlier than individuals who received placebo (42 h vs. 51 h after admission) but the difference was not significant (p=0.28, Mann-Whitney U test). DISCUSSION: NAC's mechanism of action in malaria is unclear, since it did not markedly alter plasma cytokine profiles. Trials of NAC adjunctive therapy for complicated malaria, with mortality as an endpoint, appear to be warranted.

Acetylcysteine↗

PubMed1990

Sucralfate used as adjunctive therapy in patients with severe erosive peptic esophagitis resulting from gastroesophageal reflux.

A total of 36 patients with grade 2 or greater erosive esophagitis and an abnormal 24-h pH monitor study, were treated in a randomized, double-blind fashion to assess the efficacy of sucralfate suspension as adjunctive therapy to cimetidine for severe esophagitis secondary to gastroesophageal reflux. Treatment consisted of cimetidine, 300 mg qid and either sucralfate suspension (1 g/10 ml) or an identical placebo suspension, 10 ml after meals and 20 ml hs. Patients were treated for 12 wk unless endoscopic healing occurred earlier. Initial evaluation and monthly follow-up consisted of symptom monitoring, endoscopic evaluation and pre- and post-therapy esophageal manometry, Bernstein test, and 24-h pH monitoring. The combination of cimetidine and sucralfate suspension was superior to cimetidine alone in improving daytime heartburn symptoms (p less than 0.05) but not nighttime heartburn, dysphagia, or regurgitation. Sucralfate plus cimetidine improved the overall endoscopic outcome of esophagitis more than cimetidine alone (p less than 0.05). More patients exhibited endoscopic healing in the adjunctive sucralfate group than in the cimetidine-only group. Endoscopic healing, however, was not statistically different between groups. We conclude that sucralfate used as adjunctive therapy to cimetidine resulted in improvement of some of the symptoms of reflux, and probably increases the likelihood of complete healing of esophagitis, compared with cimetidine alone.

Cimetidine↗

PubMed2002

Pneumococcal meningitis in the rat: evaluation of peroxynitrite scavengers for adjunctive therapy.

We evaluated the effect of different peroxynitrite scavengers for adjunctive therapy of experimental bacterial meningitis. Twenty hours after intracisternal injection of Streptococcus pneumoniae, rats were treated with ceftriaxone [100 mg/kg intraperitoneal (i.p.)] and either urate (300 mg/kg i.p.), Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP, 15 mg/kg i.p.), ascorbate (100 mg/kg i.p.), or urate (300 mg/kg i.p.) + ascorbate (100 mg/kg i.p.). Six hours after initiation of treatment, the cerebrospinal fluid (CSF) pleocytosis was significantly (p<0.05) reduced by urate (8697 +/- 1526 cells/microl) and MnTBAP (8542 +/- 4059 cells/microl) vs. ceftriaxone alone (15,793 +/- 3202 cells/microl). Brain concentrations of proinflammatory cytokines [interleukin-1beta (IL-beta), interleukin-6 (IL-6), and macrophage inflammatory protein-2 (MIP-2)] were also reduced by urate and MnTBAP. The intracranial hypertension was significantly reduced by MnTBAP (14.0 +/- 5.4 mm Hg), but not by urate (25.5 +/- 7.1 mm Hg) vs. ceftriaxone alone (22.5 +/- 5.9 mm Hg). Ascorbate alone had no effect on CSF pleocytosis (15,775 +/- 7058 cells/microl), intracranial pressure (25.6 +/- 8.8 mm Hg), and brain cytokine concentrations. However, the combination of urate and ascorbate was as effective as MnTBAP (CSF pleocytosis: 5392 +/- 4232 cells/microl, intracranial pressure: 13.3 +/- 6.9 mm Hg).

Animals↗

PubMed2004

Nutritional supplements as adjunctive therapy for children with chronic/recurrent sinusitis: pilot research.

OBJECTIVE: Inflammation and edema of the sinonasal mucosa are important in the pathophysiology of sinusitis. Based on the similarities between otitis media (OM) and sinusitis, and our previous research on OM, we hypothesized that nutritional supplements would be effective adjunctive therapy for the treatment of children with chronic/recurrent sinusitis. METHODS: We performed a 4 month, open-label, dose-titration study; subjects were enrolled from late January to early March 2003. Each subject served as his own control. Study supplements were a lemon-flavored cod liver oil and a children's multivitamin-mineral with selenium, prescribed in escalating doses; at higher doses, fish oil was substituted for cod liver oil. Subjects were private pediatric otolaryngology outpatients with a clinical diagnosis of chronic/recurrent sinusitis, whose symptoms were refractory to treatment with antibiotics. RESULTS: Our four subjects were Caucasian males, ranging in age from 4.2 to 9.8 years, with chronic/recurrent sinusitis for at least 3 years prior to entry in the study. Three subjects had a positive response; one subject dropped out for administrative reasons. Four, six, and eight weeks after beginning study supplements, the responders had decreased sinus symptoms, fewer episodes of acute sinusitis, and fewer doctor visits for acute illnesses. Their parents reported that they had begun to recover from upper respiratory illnesses without complications, which was unusual for these children, as was improvement in springtime; their improvement had previously been limited to the summer months or periods of home-schooling. CONCLUSIONS: Use of flavored cod liver oil and a multivitamin-mineral with selenium as adjunctive therapy for children with chronic/recurrent sinusitis is an inexpensive, non-invasive intervention that clinicians can use for selected patients, pending the performance of definitive, large, well-controlled studies.

Child↗

PubMed2002

Safety of unoprostone isopropyl as mono- or adjunctive therapy in patients with primary open-angle glaucoma or ocular hypertension.

This review summarises the safety of unoprostone isopropyl (both at the 0.12 and 0.15% concentrations) instilled twice daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). For unoprostone 0.15%, combined data from two 12-month comparative monotherapy studies are reported, as well as data from three adjunctive therapy studies and two special population studies. With unoprostone monotherapy, most adverse events were mild or moderate and transient in nature. Less than 7% of unoprostone-treated patients discontinued therapy due to an adverse event. The most common adverse events associated with unoprostone were burning/stinging, burning/stinging directly upon drug instillation, ocular itching, and conjunctival hyperaemia. Unoprostone had no clinically notable effects on vital signs, laboratory profiles, or comprehensive ophthalmic examinations. One of 659 unoprostone 0.15%-treated patients had a change in iris colour after 12 months of monotherapy. Except for a higher incidence of burning/stinging and burning/stinging upon instillation, unoprostone was comparable to timolol 0.5% twice daily and betaxolol 0.5% twice daily. No safety concerns were raised with use of unoprostone as adjunctive therapy. Unoprostone had no significant effect on exercise-induced heart rate in healthy subjects or on pulmonary function in patients with mild-to-moderate asthma. The safety profile of unoprostone 0.15% was consistent with published information on the 0.12% formulation. In conclusion, unoprostone has an excellent safety profile in patients with POAG or OH.

Antihypertensive Agents↗

PubMed2004

Short term efficacy and safety in glaucoma patients changed to the latanoprost 0.005%/timolol maleate 0.5% fixed combination from monotherapies and adjunctive therapies.

AIMS: To evaluate efficacy and safety in patients with ocular hypertension or open angle glaucoma changed to latanoprost/timolol fixed combination (LTFC). METHODS: A prospective, multicentre, historical control in which qualified patients had their previous therapy substituted by LTFC and were followed for at least 2 months. RESULTS: In 1676 patients LTFC was continued in 93% throughout the observation period. In all patients LTFC reduced the intraocular pressure (IOP) from 20.6 (SD 3.8) to 17.7 (3.0) mm Hg (p<0.001) compared to previous monotherapies including latanoprost, timolol, alpha agonists or carbonic anhydrase inhibitors (CAI). LTFC provided more efficacy after changing from adjunctive therapies including: a beta blocker added to either CAI, alpha agonist, or pilocarpine, or CAI added to an alpha agonist, or latanoprost added to either CAI, alpha agonist, or beta blocker (unfixed combination), and travoprost added to timolol (p<0.007). LTFC was as effective as latanoprost used with dorzolamide/timolol fixed combination (-0.9 mm Hg, p = 0.1792). The most common reason to discontinue therapy was lack of efficacy (n = 70, 4%) and adverse event (n = 17, 1%). CONCLUSION: In a clinical setting, patients who have their monotherapy or adjunctive therapy substituted with LTFC may experience reduced IOP, good tolerability, and continuation of therapy for the first 2-3 months of treatment.

Aged↗

PubMed2001

Randomized prospective controlled trial of recombinant granulocyte colony-stimulating factor as adjunctive therapy for limb-threatening diabetic foot infection.

Adult diabetic patients admitted to our Diabetes Center from September 1996 to January 1998 for severe, limb-threatening foot infection were consecutively enrolled in a prospective, randomized, controlled clinical study aimed at assessing the safety and efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) (lenograstim) as an adjunctive therapy for the standard treatment of diabetic foot infection. Forty patients, all of whom displayed evidence of osteomyelitis and long-standing ulcer infection, were randomized 1:1 to receive either conventional treatment (i.e., antimicrobial therapy plus local treatment) or conventional therapy plus 263 microg of G-CSF subcutaneously daily for 21 days. The empiric antibiotic treatment (a combination of ciprofloxacin plus clindamycin) was further adjusted, when necessary, according to the results of cultures and sensitivity testing. Microbiologic assessment of foot ulcers was performed by both deep-tissue biopsy and swab cultures, performed at enrollment and on days 7 and 21 thereafter. Patients were monitored for 6 months; the major endpoints (i.e., cure, improvement, failure, and amputation) were blindly assessed at weeks 3 and 9. At enrollment, both patient groups were comparable in terms of both demographic and clinical data. None of the G-CSF-treated patients experienced either local or systemic adverse effects. At the 3- and 9-week assessments, no significant differences between the two groups could be observed concerning the number of patients either cured or improved, the number of patients displaying therapeutic failure, or the species and number of microorganisms previously yielded from cultures at day 7 and day 21. Conversely, among this small series of patients the cumulative number of amputations observed after 9 weeks of treatment appeared to be lower in the G-CSF arm; in fact, only three patients (15%) in this group had required amputation, whereas nine patients (45%) in the other group had required amputation (P = 0.038). In conclusion, the administration of G-CSF for 3 weeks as an adjunctive therapy for limb-threatening diabetic foot infection was associated with a lower rate of amputation within 9 weeks after the commencement of standard treatment. Further clinical studies aimed at precisely defining the role of this approach to this serious complication of diabetes mellitus appear to be justified.

Adjuvants, Immunologic↗

PubMed2006

SIRS and group-B streptococcal sepsis in newborns: pathogenesis and perspectives in adjunctive therapy.

Clinical signs of systemic inflammation and suspected systemic infection are common in neonatal medicine. Yet, causative infectious organisms can only infrequently be isolated. In previously healthy infants at low risk of sepsis, group B streptococcus (GBS) is the most common isolate. In vitro and in vivo data suggest that immune cells from newborn infants have impaired antimicrobial properties against GBS. In contrast large amounts of inflammatory mediators are formed upon GBS challenge and Toll-like receptors (TLR) are critical host molecules in this context. Thus, the immune balance tilts towards inflammation, SIRS and sepsis. Adjunctive therapy of neonatal sepsis needs to adjust the inflammatory response without further impairing bacterial clearance. This article summarises the pathophysiological events leading to sepsis and suggests molecular targets for adjunctive therapy.

Animals↗

PubMed1989

Thrombolysis and its sequelae. Calcium antagonists as potential adjunctive therapy.

Randomized, placebo-controlled trials have documented that both streptokinase and rt-PA given early are associated with limitation of infarct size, improved ventricular function, and reduced mortality. Other concerns, however, documented experimentally include myocardial hemorrhage, the "no-reflow" phenomenon, myocardial "stunning," reperfusion-induced injury, and clinically, rethrombosis that occurs at a rate of 20% and reinfarction at 8-10%. Thus, even with the ideal thrombolytic agent, adjunctive therapy to prevent rethrombosis will remain a requisite to obtaining long-term benefit. Calcium blockers in association with reperfusion have been shown experimentally to be protective, resulting in limitation of infarct size and improved ventricular function. There is no data on the role of calcium blockers in conjunction with thrombolysis in patients. Results are available from two randomized trials with the calcium blocker, diltiazem, in patients with non-Q wave infarction. In the short-term trial involving 576 patients with non-Q wave infarction, the incidence of early reinfarction was reduced by 50%, and in the long-term study (non-Q wave infarction, n = 634), reinfarction and death were reduced by 40% after 1 year and by 34% after 4.5 years. Non-Q wave infarction is believed to undergo early spontaneous reperfusion based on the following: small infarct size, contracture necrosis at postmortem, early peaking of plasma CK, coronary patency on angiography, residual ischemia, and a high incidence of reinfarction. Thus, thrombolysis occurring spontaneously or induced therapeutically is associated with a high incidence of reinfarction. The implications of these clinical studies together with the experimental data suggests that the hypothesis of a calcium blocker being important adjunctive therapy following thrombolysis is worthy of clinical evaluation.

Animals↗

PubMed1976

Primary carcinoma of the gallbladder. The role of adjunctive therapy in its treatment.

Of forty-three patients with carcinoma of the gallbladder discovered ih a twenty-five year period (during which 10,349 patients were diagnosed as having cholelithiasis), eighteen patients (42 per cent) had no obvious tumor outside of the gallbladder at the time of operation, nineteen patients (44 per cent) had local spread of the disease, and six patients (14 per cent) had abdominal carcinomatosis or distant metastasis. In the twenty-one patients who underwent surgical therapy for cure of their disease, the five year survival rate was 33 per cent. The more extensive surgical procedures (other than cholecystectomy alone) did not significantly increase survival. Neither the duration of the symptoms nor the pathologic type of the tumor altered the eventual outcome. No patients with tumor outside the gallbladder at the time of operation survived longer than two years. Compared to those who did not receive it, the fifteen patients treated postoperatively with adjunctive therapy (radiation therapy or chemotherapy or both) lived longer and also were significantly better palliated when tumor outside of the gallbladder was found at the time of operation. From these findings, the routine use of adjunctive therapy is recommended in all patients with disease outside of the gallbladder and serious consideration should be given to its use in all patients found to have carcinoma of the gallbladder.

Adenocarcinoma↗