Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of cytomegalovirus (CMV) disease met with limited success until the development of ganciclovir. Favorable clinical responses to ganciclovir have been reported in approximately 80% of immunocompromised patients with CMV retinitis or gastrointestinal disease. CMV pneumonia is more difficult to treat, with therapy benefiting 10%-72% of patients. Ganciclovir must be given parenterally; the dose-limiting adverse event is neutropenia. Patients with AIDS frequently experience relapse and require maintenance therapy. Foscarnet is an attractive anti-CMV drug but must be given parenterally and is completely dependent on renal clearance for elimination. Prevention of CMV disease with antiviral drugs may be possible. Five weeks of intravenous acyclovir (500 mg/m2 three times a day) significantly reduced the risk of CMV infection and disease in seropositive allogeneic bone marrow transplant recipients. The prophylactic benefit of acyclovir has recently been confirmed and extended by a placebo-controlled trial in renal allograft recipients at the University of Minnesota. A 12-week course of high doses of oral acyclovir (3,200 mg/d) was safe and significantly reduced the incidence of CMV infection and disease.
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PMID:Management of cytomegalovirus disease with antiviral drugs. 217 14

Experience with ganciclovir treatment of life- or sight-threatening cytomegalovirus (CMV) infections in 22 heart and heart-lung transplant recipients at six medical centers was reviewed. All six heart-lung recipients and six of 16 heart recipients had CMV pneumonitis; five heart recipients had CMV gastrointestinal disease, three had retinitis, and two had infections in more than one organ system. Of the 18 patients (82%) surviving initial ganciclovir therapy, 16 improved, one stabilized, and one showed no change in clinical status. All cultures positive for CMV before treatment became negative during therapy. Six patients (33% of survivors) had recurrent episodes and received additional therapy. Four patients (18%) died during initial therapy; death was believed to be related to CMV infection in only two cases and to ganciclovir treatment in no case. Adverse reactions possibly attributable to ganciclovir included neutropenia (four patients), impaired renal function (one), thrombocytopenia (one), decreased blood pressure (one), and seizure (one). Ganciclovir appears to be well tolerated and to alter favorably the outcome of serious CMV infection in this patient population.
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PMID:Ganciclovir treatment of serious cytomegalovirus infection in heart and heart-lung transplant recipients. 284 94

Of 760 AIDS patients seen at San Francisco General Hospital in 1986, 5.7 per cent had retinitis and 2.2 per cent had gastrointestinal disease caused by cytomegalovirus. We reviewed the records of 44 patients treated with ganciclovir for culture-confirmed cytomegalovirus retinal (31 patients) or gastrointestinal disease (17 patients) or both (four patients) in 1986. Retinitis stabilized or improved during initial treatment with ganciclovir in 22 of 27 (81.5 per cent) patients. Following a median 10-day induction course, 16 patients with retinitis continued to have serial ophthalmologic assessments: eight patients were maintained on treatment and eight had maintenance treatment deferred. Before treatment, the two groups were comparable in age, Karnofsky scores, hematologic assessment, visual acuity, and history with respect to Pneumocystis carinii pneumonia. Retinitis did not progress for a median 53.8 days in the immediate maintenance group compared to 18.8 days for the deferred maintenance group (p = 0.01). In 17 patients with CMV gastrointestinal disease, nine of 14 (64 per cent) had resolution of pain and eight of 11 (73 per cent) had resolution of diarrhea when treated initially with ganciclovir. In both retinitis and gastrointestinal disease patients, ganciclovir decreased recovery of CMV from urine and blood markedly. Ganciclovir also caused a decrease in mean absolute neutrophil counts to about half of baseline values; decreases in mean platelet count and hemoglobin were also noted but were less than 25 per cent. Neutropenia severe enough to require dose adjustment (less than 800 cells/microliters) occurred in 31 per cent of patients receiving maintenance ganciclovir.
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PMID:Retinal and gastrointestinal disease due to cytomegalovirus in patients with the acquired immune deficiency syndrome: prevalence, natural history, and response to ganciclovir therapy. 285 94

The drug 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (DHPG) was used to treat serious cytomegalovirus infections in 26 patients with underlying immunodeficiency (including 22 with the acquired immunodeficiency syndrome). In 17 of 22 patients in whom cytomegalovirus was virologically confirmed, clinical status improved or stabilized, although in 4 of them the status of some affected organs deteriorated or did not improve. Fourteen of 18 patients with adequate viral-culture data had clearing of cytomegalovirus from all cultured sites. Patients with cytomegalovirus pneumonia often responded poorly; four of seven died before completing 14 days of DHPG therapy. The condition of 11 of 13 patients with cytomegalovirus retinitis and 5 of 8 with gastrointestinal disease stabilized or improved. However, clinical and virologic relapses occurred in 11 of 14 patients (79 percent) when DHPG was discontinued. Neutropenia was the most frequent adverse reaction. We conclude that DHPG offers promise for the therapy of severe cytomegalovirus infections in some immunodeficient patients, but further study will be necessary to establish its efficacy and safety.
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PMID:Treatment of serious cytomegalovirus infections with 9-(1,3-dihydroxy-2-propoxymethyl)guanine in patients with AIDS and other immunodeficiencies. 300 61

9-(1,3-dihydroxy-2-propoxymethyl) guanine (ganciclovir) was used to treat 41 patients (median age, 37 years) with the acquired immunodeficiency syndrome and cytomegalovirus gastrointestinal infection. Sites of infection were the colon in 31, the esophagus in 5, the rectum in 4, and the small bowel in 1. Patients received ganciclovir, 5 mg/kg body weight, intravenously every 12 hours for 14 days. Clinical improvement was seen in 30 patients and virologic response in 32. Mainly hematologic toxicity occurred: moderate leukopenia (1000 to 1900/mm3) was seen in 7 patients and severe (less than 1000/mm3) in 1, and moderate neutropenia (500 to 1000/mm3) in 5 and severe (less than 500/mm3) in 1. A cutaneous rash developed in 2 patients. Median overall survival was 16 weeks (range, 2 to 56). Cytomegalovirus recurred in 13 patients; median time to recurrence was 9 weeks from the start of treatment. Ganciclovir may be effective in treating cytomegalovirus gastrointestinal disease in patients with the acquired immunodeficiency syndrome.
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PMID:9-(1,3-Dihydroxy-2-propoxymethyl)guanine (ganciclovir) in the treatment of cytomegalovirus gastrointestinal disease with the acquired immunodeficiency syndrome. 303 60

Ninety-one congenitally immunodeficient patients treated from 1972 to 1981 were reviewed to assess the incidence and nature of gastrointestinal complications. Thirty-three of these patients (36%) developed 59 complications. Patients with immunodeficiencies characterized by neutrophil dysfunction--chronic granulomatous disease (20 patients) and cyclic neutropenia (eight patients)--developed 22 surgical infections, 22 of which required operation. In patients with neutrophil defects, postoperative morbidity was frequent and severe. Gastrointestinal symptoms were common in patients with isolated defects of B or T lymphocytes. Ten of forty-one patients with congenital hypogammaglobulinemia developed gastrointestinal complications, as did one of four patients with DiGeorge Syndrome, and the single patient with secretory IgA deficiency. However, operation was not required for these patients with isolated disorders of lymphocyte function. Patients with combined B and T cell disorders developed gastrointestinal disease, requiring operative therapy at intermediate rates. Gastrointestinal symptoms developed in four of nine patients with severe combined immunodeficiency and three of eight with Wiskott-Aldrich syndrome. Operative therapy was required in two of these seven symptomatic patients.
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PMID:Gastrointestinal complications of congenital immunodeficiency states. The surgeon's role. 660 28

Clostridium tertium bacteremia is unusual, seen most often with gastrointestinal disease and/or neutropenia. Two cases are described. The first was a 19-yr-old female with acute leukemia, who developed gastrointestinal symptoms and C. tertium bacteremia while neutropenic. The second was a 57-yr-old female with quiescent ulcerative colitis, who presented with fever, rigors and epigastric pain. Four organisms including C. tertium were isolated from blood cultures. This patient responded to broad spectrum antimicrobial therapy, whereas the first patient required the addition of specific agents to recover. C. tertium is aerotolerant and thus can be misidentified as a Bacillus or Corynebacterium spp. Our isolates had a distinctive Gram stain morphology, were catalase negative and failed to sporulate aerobically--this aided in the recognition of this significant Gram-positive bacillus.
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PMID:Clostridium tertium bacteremia: 2 cases and review. 871 77

Human cytomegalovirus, HCMV, infects most of the population by adulthood; The primary infection is often accompanied by transient neutropenia and thrombocytopenia, and is followed by a period asymtomatic viral latency. In the setting of bone marrow transplantation, however, the immunosuppressed state of the recipient enables HCMV to re-activate or to infect the individual and cause serious sequelae. These range from hepatitis and gastrointestinal disease to interstitial pneumonia and hematologic abnormalities, which are more common in the allograft. Little is currently known about the mechanisms by which HCMV causes these hematologic abnormalities. In this review, we discuss experimental models which are helping investigators understand the immunology and pathology of CMV infection. We also summarize the vivo studies of the effects of HCMV on human hematopoiesis. Several possible mechanisms that could explain the deleterious effect of HCMV on human hematopoietic function include: 1) alteration of accessory cell function by inducing the production of inhibitory cytokines; 2) perturbation of stromal cell function resulting in a decreased production of hematopoietic factors or by altering cell surface adhesion molecule expression; 3) by direct infection of the hematopoietic stem or progenitor cells. It is likely that the pathogenesis of this syndrome is multifactorial therefore requiring a broad therapeutic approach. This would include the use of the antiviral agents, hematopoietic growth factors and donor derived HCMV specific cytolytic cells.
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PMID:Cytomegalovirus as a cause of pancytopenia. 872 2

A 23-year-old Thoroughbred gelding was referred for the evaluation of acute onset of ataxia and depression, and a 2-day history of fever. On physical examination, the gelding was profoundly depressed and 10-12% dehydrated. The horse appeared very unstable, with a wide-based stance in the hind limbs, severe symmetric ataxia in all 4 limbs, and proprioceptive deficits in both hind limbs. Nasogastric intubation produced 4 L of brown, fetid reflux, and rectal examination revealed mild small intestinal and cecal distention. Hematologic abnormalities included neutropenia with toxic change, compatible with acute inflammation and endotoxemia, and prolonged coagulation times. Serum biochemical abnormalities included prerenal azotemia. metabolic acidosis, and electrolyte abnormalities consistent with enteritis. Blood ammonia concentration was markedly increased (406 micromol/L; reference interval 4-49 micromol/L), however, serum bile acids concentration and hepatic enzyme activities were within reference intervals. Histopathologic examination of a liver biopsy revealed no abnormalities and results of tests for several infectious agents were negative. Clinical signs resolved with correction of the dehydration and electrolyte abnormalities and with antibiotic therapy. The horse was diagnosed with hyperammonemic neuropathy associated with gastrointestinal disease. In such cases, hyperammonemia is caused by increased production of ammonia by organisms in the gastrointestinal tract in combination with increased gut permeability that facilitates ammonia absorption.
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PMID:Neurologic signs and hyperammonemia in a horse with colic. 1678 25

Enterococcus is an important cause of bacteraemia. Previous epidemiological studies examining risk factors for enterococcal bacteraemia have used traditional case-control study designs, which can be potentially biased. This case-case-control study examining risk factors for enterococcal bacteraemia was conducted over 10 years (January 2000 to December 2009) in a tertiary, university-affiliated hospital. There were 440 episodes of enterococcal bacteraemia, 80 of which were caused by vancomycin-resistant Enterococcus (VRE). Two multivariable models were generated, comparing VRE and vancomycin-susceptible Enterococcus (VSE) with the same control group. VRE bacteraemia was associated with central venous catheter use (OR 11.6, 95% CI 2.6-51.5), neutropenia (OR 16.9, 95% CI 2.4-120.2), and allogenic bone marrow transplantation (OR 18.0, 95% CI 2.4-133.4). In contrast, VSE bacteraemia risk factors included: age (OR 1.0, 95% CI 1.0-1.1), exposure to metronidazole (OR 8.7, 95% CI 1.7-43.5), and gastrointestinal disease (OR 6.4, 95% CI 1.2-34.5). Meropenem use decreased the risk of VSE bacteraemia (OR 0.3, 95% CI 0.1-0.9). Hypoalbuminaemia was the only factor identified in both models (VRE, OR 6.0, 95% CI 1.7-21.1; VSE, OR 3.3, 95% CI 1.4-7.7). The absence of substantial overlap of risk factors for VRE and VSE argues in favour of differences in pathogenesis. These data suggest that environmental sources are more important in VRE bacteraemia. Endogenous sources, particularly the gastrointestinal tract, play a pivotal role in VSE bacteraemia. This study highlights the importance of infection control protocols to reduce the risk of VRE bacteraemia.
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PMID:Differing risk factors for vancomycin-resistant and vancomycin-sensitive enterococcal bacteraemia. 2184 77


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