Gene/Protein Disease Symptom Drug Enzyme Compound
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Schistosomiasis is a chronic worm infection caused by a species of trematodes, the Schistosomes. We may distinguish a urinary form from Schistosomes haematobium and an intestinal-hepatosplenic form mainly from Schistosomes mansoni characterized by nausea, meteorism, abdominal pain, bloody diarrhea, rectal tenesmus, and hepatosplenomegaly. These infections represent a major health issue in Africa, Asia, and South America, but recently S mansoni has increased its prevalence in other continents, such as Europe countries and North America, due to international travelers and immigrants, with several diagnostic and prevention problems. We report a case of a 24-year-old patient without HIV infection, originated from Ghana, admitted for an afebrile dysenteric syndrome. All microbiologic studies were negative and colonoscopy revealed macroscopic lesions suggestive of a bowel inflammatory chronic disease. Since symptoms became worse, a therapy with mesalazine (2 g/d) was started, depending on the results of a bowel biopsy, but without any resolution. The therapy was stopped after 2 wk when the following result was available: a diagnosis of ""intestinal schistosomiasis" was done (two Schistosoma eggs were detected in the colonic mucosa) and this was confirmed by the detection of Schistosoma eggs in the feces. Therapy was therefore changed to praziquantel (40 mg/kg, single dose), a specific anti-parasitic agent, with complete recovery. Schistosomiasis shows some peculiar difficulties in terms of differential diagnosis from the bowel inflammatory chronic disease, as the two disorders may show similar colonoscopic patterns. Since this infection has recently increased its prevalence worldwide, it has to be considered in the differential diagnosis of our patients with gastrointestinal symptoms.
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PMID:A case of bowel schistosomiasis not adhering to endoscopic findings. 1643 15

Type 2 diabetes mellitus is a common chronic disease that causes significant morbidity and mortality worldwide. The primary goal of treatment is to target glycemic control by maintaining the glycosylated hemoglobin level near 6-7% without predisposing patients to hypoglycemia. Diabetes results from a combination of increased hepatic glucose production, decreased insulin secretion from beta cells, and insulin resistance in the peripheral tissues. Currently available antidiabetic agents work by different mechanisms to lower blood glucose levels. Unfortunately, each of them has its tolerability and safety concerns that limit its use and dose titration. Sitagliptin is the first antidiabetic agent from the class of dipeptidyl peptidase-4 enzyme inhibitors. It increases the amount of circulating incretins, which stimulate insulin secretion and inhibit glucose production. Sitagliptin was approved by the US Food and Drug Administration (FDA) for use with diet and exercise to improve glycemic control in adult patients with type 2 diabetes. It can be used alone or in combination with metformin or a thiazolidinedione (pioglitazone or rosiglitazone) when treatment with either drug alone provides inadequate glucose control. The usual adult dose is 100 mg once daily. A dose of 25-50 mg once daily is recommended for patients with moderate-to-severe renal impairment. In randomized, placebo-controlled trials that lasted for up to 6 months, sitagliptin lowered glycosylated hemoglobin levels by 0.5-0.8%. In a 52-week clinical trial, sitagliptin was shown to be noninferior to glipizide as an add-on agent in patients inadequately controlled on metformin alone. Sitagliptin was well tolerated with the most common side effects being gastrointestinal complaints (up to 16%), including abdominal pain, nausea and diarrhea; hypoglycemia and body weight gain occurred at similar rates compared with placebo. Overall, sitagliptin provides a treatment option for patients with type 2 diabetes as a monotherapy, or as an adjunct to metformin or a thiazolidinedione when patients achieve inadequate glycemic control while on either of the agents. It is also an alternative therapy for those patients who have contraindications or intolerability to other antidiabetic agents.
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PMID:Sitagliptin: a novel drug for the treatment of type 2 diabetes. 1770 Mar 85

Studies of populations with chronic cancer pain have shown a high prevalence of breakthrough pain (BTP), defined as transitory, severe flares of pain that occur on a background of otherwise controlled, persistent pain. High BTP prevalence rates have also been reported in patients with chronic noncancer pain, although data in these patient populations are more limited. The incidence of BTP appears to be associated with progression of chronic disease, with more than 80% of patients reporting BTP with far-advanced, end-stage cancer and noncancer terminal conditions (1). The most widely accepted therapeutic approach for the management of BTP involves use of short-acting opioids taken as needed in addition to the around-the-clock opioid regimen being used for the continuous component of the persistent pain syndrome. For some patients, an optimal treatment outcome for BTP may be unattainable because of a mismatch between the time course of the BTP episode and the onset of analgesia of short-acting opioids. Breakthrough pain typically reaches peak intensity within a few minutes, whereas the onset of analgesia with traditional, orally administered short-acting opioids is between 30 and 60 minutes (2-7). Consequently, treatment outcomes for BTP are likely to be improved with agents that have a more rapid onset of analgesia. Fentanyl buccal tablet (FBT) is a new formulation of fentanyl indicated for the management of BTP in patients with cancer who are already receiving, and who are tolerant to, opioid therapy for their underlying persistent cancer pain. The FBT formulation uses OraVescent (Cephalon, Inc., Frazer, PA, USA) drug delivery technology to provide rapid absorption of fentanyl through the buccal mucosa. In pharmacokinetic studies in healthy volunteers, FBT demonstrated high, early systemic absorption. In addition, FBT delivered a larger proportion of the fentanyl dose transmucosally and produced a greater early systemic exposure than oral transmucosal fentanyl citrate (OTFC), which is also indicated for the management of BTP in opioid-tolerant cancer patients. A number of short-term studies have evaluated the efficacy, safety and tolerability of FBT in the management of BTP in opioid-tolerant patients with chronic pain. All these studies included an open-label dose-titration phase prior to randomized, placebo-controlled, double-blind treatment. Pain Intensity of a BTP episode was measured using an 11-point scale (0 = no pain, 10 = worst pain), and the primary outcome measure was the Summed Pain Intensity Difference (SPID) at a specified time point. Secondary efficacy measures included Pain Relief, Pain Intensity Differences, and the proportion of BTP episodes demonstrating >or=33% and >or=50% improvement in Pain Intensity scores at each time point postdose, and the proportion of BTP episodes requiring supplemental medication. In a pivotal study of opioid-tolerant patients with cancer-related chronic pain and BTP, the primary outcome measure, SPID at 30 minutes (SPID(30)), significantly favored FBT compared with placebo (mean +/- SE: 3.0 +/- 0.12 vs. 1.8 +/- 0.18, p<0.0001). Better efficacy was also observed with FBT compared with placebo for pain relief, Pain Intensity Differences, and the proportion of episodes showing >or=33% and >or=50% improvement in Pain Intensity Scores. Treatment with FBT was generally well tolerated. Most adverse events were mild to moderate in severity and typical of those associated with opioid use (e.g., nausea, dizziness) (8). Similar results have been observed in studies of opioid-tolerant patients with BTP in association with noncancer-related chronic pain. In a study of patients with chronic low back pain, the primary outcome measure, SPID(60), significantly favored FBT over placebo (mean +/- SE: 8.3 +/- 0.66 vs. 3.6 +/- 0.57, p <0.0001). All secondary efficacy measures were similarly improved, with Pain Intensity Differences and Pain Relief scores showing significant differences versus placebo as early as 10 and 15 minutes, respectively. As in the study of cancer patients, treatment with FBT was well tolerated (9). Across all studies, there was no simple linear relationship between the effective dose of FBT and the dose of the around-the-clock opioid regimen or the previous supplemental opioid, indicating that doses of FBT should be individually titrated to effectiveness rather than calculated as a percentage of existing opioid regimens. This monograph summarizes current data on the clinical pharmacology, efficacy, safety and tolerability of FBT relating to the management of opioid-tolerant patients with BTP in association with chronic pain.
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PMID:Fentanyl buccal tablet. 1830 3

Gastroparesis is a chronic disorder of gastric motility that is characterized by delayed emptying of either solids or liquids from the stomach in the absence of any mechanical obstruction. Nausea, vomiting, early satiety and bloating are some of the manifestations of gastroparesis. Idiopathic, diabetes mellitus and postsurgical states account for the majority of cases. Gastroparesis is a difficult condition to treat. Prokinetic drugs like metoclopramide and erythromycin form the mainstay of therapy but are less than ideal. Some patients may benefit from endoscopic botolinium toxin injection. Gastric electrical stimulation, though promising, is not ready for prime time yet.
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PMID:Treatment of gastroparesis: an update. 1909 43

Steroids have been found to be effective in treating symptomatic oral lichen planus (OLP) by reducing pain and inflammation. In fact, systemic corticosteroids should be reserved for acute exacerbation, and multiple or widespread lesions. They may be indicated in patients whose condition is unresponsive to topical steroids. However, various potent topical steroids have been reported to be effective in the treatment of symptomatic OLP. They can be used as the first line drugs in the treatment of OLP with no serious side-effects. During the therapy, candidiasis was commonly found and in addition, bad taste, nausea, dry mouth, sore throat and swollen mouth may occur as minor side-effects from some topical steroids. Because OLP is a chronic disorder that requires long-term treatment, topical steroids are recommended for the treatment OLP because of minimal side-effects and the cost benefit. This manuscript reviews the use of steroids, especially its topical application, in the treatment of OLP.
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PMID:Steriods in the treatment of lichen planus: a review. 1910 64

Anxiety disorders are persistent impairing diseases, with often chronic course and suffering from symptoms throughout a life-span. The medication with the most evidence of efficacy is the benzodiazepines having a low incidence of side effects but may cause physical dependence, withdrawal and sedation. The use of these drugs should be limited to the acute treatments during the first several weeks in combination with an SSRI or and SNRI for the treatment of the acute phase. After three to four weeks, when antidepressants become effective, benzodiazepine dose should be tapered over a one week period. Among the antidepressants, the SSRI and the SNRI are considered a first-line therapy because of their favourable side effect spectrum compared to tricyclic antidepressants. However, the association with side effects such as nausea, sweating, sexual dysfunction and gastrointestinal problems and insomnia may be intolerable for a number of patients. Combining antidepressants and benzodiazepine therapy or medication treatment and psychotherapy may lead to an increase in improvement in patients not responding to one treatment approach alone. The most effective treatment for managing the recurrent symptoms of this chronic disorder are still unknown and other studies and approaches are in need as remission rates are still only about 40%.
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PMID:[Treatment strategies in anxiety disorders--an update]. 1949 38

The aim of this study was to compare the efficacy, safety, and tolerability of sertraline and clomipramine in the treatment of obsessive-compulsive disorder (OCD). Outpatients with DSM-III-R defined OCD for 1 year or longer and scores of >/=20 on the YaleBrown Obsessive Compulsive Scale (Y-BOCS), >/=7 on the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH-OC), >/=4 on the Clinical Global Impression Severity of Illness Scale (CGI-S) and </=17 on the Hamilton Depression Scale (17 item HAMD) were randomized to sertraline (n = 86) or clomipramine (n = 82) once daily for 16 weeks. Initial daily doses of sertraline and clomipramine were 50 mg. After a minimum of 4 weeks, these doses could be increased by 50 mg increments every 2 weeks to a maximum of 200 mg daily if the response was thought inadequate. Efficacy was assessed at the end of 1, 2, 4, 6, 8, 12 and 16 weeks of therapy using the Y-BOCS, NIMH-OC, CGI-S, CGI Improvement Scale (CGI-I) and Clinical Anxiety Scale (CAS). One hundred sixty-eight patients were randomized and received at least one dose of double-blind medication; 86 received sertraline and 82 clomipramine. Mean final daily doses at final visit were clomipramine 90 mg (efficacy evaluable patients 101 mg, completers 110 mg), and sertraline 129 mg (efficacy evaluable patients 132 mg, completers 136 mg). Mean baseline Y-BOCS, NIMH-OC and CGI-S totals were 27.7, 10.1 and 5.5, respectively, for sertraline and 27.4, 9.9 and 5.5, respectively, for clomipramine. Sertraline demonstrated greater efficacy than clomipramine in the intent-to-treat patient group: mean baseline to final visit changes were 50.8% (Y-BOCS), 41.9% (NIMH-OC) and 37.7% (CGI-S) for sertraline and 42.9% (Y-BOCS), 33.8% (NIMH-OC) and 30.0% (CGI-S) for clomipramine (P < 0.05). The number of patients withdrawing because of adverse events was substantially greater for clomipramine (26%) than sertraline (11%) (P < 0.05). The most frequent adverse events for clomipramine were dry mouth (20%), anxiety (17%), constipation (16%), nausea (15%) and somnolence (11%), and for sertraline, diarrhea (12%) and nausea (12%). In this study, sertraline was more effective than clomipramine in the intent-to-treat analysis. The difference in efficacy between the treatments is almost wholly accounted for by a greater number of clomipramine withdrawals due to the poor patient acceptance of clomipramine. The superior tolerability of sertraline and the lower rate of premature treatment withdrawal relative to clomipramine may offer considerable quality of life and compliance benefits in the long-term management of a chronic disorder such as OCD.
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PMID:A double-blind comparison of sertraline and clomipramine in outpatients with obsessive-compulsive disorder. 1969 11

Cancer and its treatment can induce subjective and objective evidence of diminished functional capacity encompassing physical fatigue and cognitive impairment. Dexmethylphenidate (D-MPH; the D-isomer of methylphenidate) was evaluated for treatment of chemotherapy-related fatigue and cognitive impairment. A randomized, double-blind, placebo-controlled, parallel-group study evaluated the potential therapeutic effect and safety of D-MPH in the treatment of patients with chemotherapy-related fatigue. Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-F) total score at Week 8 was the primary outcome measure. One hundred fifty-four patients (predominantly with breast and ovarian cancers) were randomized and treated. Compared with placebo, D-MPH-treated subjects demonstrated a significant improvement in fatigue symptoms at Week 8 in the FACIT-F (P=0.02) and the Clinical Global Impression-Severity scores (P=0.02), without clinically relevant changes in hemoglobin levels. Cognitive function was not significantly improved. There was a higher rate of study drug-related adverse events (AEs) (48 of 76 [63%] vs. 22 of 78 [28%]) and a higher discontinuation rate because of AEs (8 of 76 [11%] vs. 1 of 78 [1.3%]) in D-MPH-treated subjects compared with placebo-treated subjects. The most commonly reported AEs independent of study drug relationship in D-MPH-treated subjects were headache, nausea, and dry mouth, and in placebo-treated subjects were headache, diarrhea, and insomnia. D-MPH produced significant improvement in fatigue in subjects previously treated with cytotoxic chemotherapy. Further studies with D-MPH or other agents to explore treatment response in chemotherapy-associated fatigue should be considered.
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PMID:Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. 1989 71

Gastroparesis is a chronic disorder of gastric motility characterized by delayed gastric empting in the absence of mechanical obstruction, which can lead to symptoms of nausea, vomiting, bloating, abdominal pain, postprandial fullness and weight loss. Although there are many etiologies, the primary causes are diabetes or are idiopathic. The mainstay of treatment is dietary and drug therapies. However, many patients will continue to suffer intractable symptoms despite these treatments. Gastric neurostimulation with the Enterra Therapy system has been approved for use under the Humanitarian Device Exemption by the US FDA. The device produces pulses of electrical stimulation that are delivered to the stomach continuously. One randomized clinical trial and multiple nonrandomized unblinded clinical trials and case series have documented improvement of symptoms in intractable diabetic and idiopathic gastroparesis. The purpose of this article is to introduce the Enterra Therapy gastric neurostimulator. Gastroparesis and its pathophysiology will be discussed in this clinical context to enhance the understanding of the device and its development. We will analyze the device in detail, its placement and the results of studies evaluating its efficacy.
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PMID:Enterra Therapy: gastric neurostimulator for gastroparesis. 2042 May 55

Anticholinergic effects of medications are factors in autonomic control of the lower esophageal sphincter function. Changes in sphincter control often lead to gastroesophageal reflux disease (GERD), a chronic disease with a prevalence of up to 25% for adults. This effect is a consideration in the treatment of depression, the fourth-leading disease burden. Lower esophageal-sphincter changes are well documented in association with tricyclic antidepressants. The newer medications, selective serotonin-reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, are often used as first-line agents. This case report reviews the emergence of GERD in association with the use of newer agents. The patient, a 55-year-old woman, presented to her primary care physician with complaints of low energy, dysphoric mood, and anhedonia of several months' duration. Trials of citalopram and escitalopram were associated with reports of persistent nausea and gastric reflux unresolved by changes in dosing schedule or positioning. Over-the-counter omeprazole on an as-needed basis was added. Ultimately, the patient was successfully managed with desvenlafaxine for dysphoric mood and low energy and scheduled administration of omeprazole for GERD. The adverse drug reaction was evaluated using the Naranjo Adverse Drug Reaction Probability Scale. This methodology indicated a probable relationship (score of 7 out of 12) between initiation of antidepressant therapy and the presentation of GERD symptoms. When evaluating patient response to medication, inquiring about new-onset symptoms may help assess pharmacotherapy, identify potential medication-related effects such as the anticholinergic profile, evaluate the need to add an antisecretory/antispasmodic agent, or consider an alternative treatment strategy.
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PMID:Antidepressant-mediated gastroesophageal reflux disease. 2148 38


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