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)

A cryptococcal primary pulmonary lymph node complex has been demonstrated at autopsy or after thoracotomy in 1% of the cases of cryptococcosis. Stepwise microscopic examination of hilar lymph nodes should reveal a more frequent incidence of this rare but now well-documented complex. Nine examples of the cryptococcal complex are extant, including three herewith reported from the files of the Armed Forces Institute of Pathology. Four of these complexes developed in apparently normal persons and five in those hypersusceptible to infection because of neutropenia, diabetes, renal insufficiency, or corticosteroid therapy. The complexes in the normal persons were circumscribed granulomas and represented first-infection cryptococcosis similar to first-infection tuberculosis. There was a chronic course and a good prognosis with surgical resection. The complexes in the compromised hosts were predominantly acute diffuse pneumonias and large diffuse lesions of the lymph nodes, and were interpreted as first-infection cryptococcosis with massive spread facilitated by the compromised state. All these compromised patients died within a few weeks.
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PMID:The primary pulmonary lymph node complex of crytptococcosis. 124 92

Etoposide is a schedule-dependent agent with greater activity against small cell lung cancer (SCLC) when a given dose is administered over several days compared with a 1-day administration of the same dose. In an attempt to capitalize on the schedule dependency of etoposide, 22 previously untreated extensive-stage SCLC patients were given cisplatin (100 mg/m2 on day 1) plus 21 days of low-dose, oral etoposide (50 mg/m2/d). Chemotherapy was repeated every 28 days for four cycles. Complete blood counts were monitored weekly, and etoposide was discontinued if either the leukocyte or platelet count dropped below 2000/microliters or 75,000/microliters, respectively. All 22 patients were evaluable for response; 18 had either a complete (9%) or partial response (73%), an overall response rate of 82% (95% confidence interval, 62% to 93%). The median response duration was 7 months, and the median survival was 9.9 months (range, 1 to 17+ months). Sixteen (73%) patients received all planned cycles of etoposide. In Cycle 1 of chemotherapy, the median leukocyte nadir was 2700/microliters (range, 100 to 6300/microliters), and median platelet nadir was 180,000/microliters (range, 51,000 to 397,000/microliters). Life-threatening leukopenia (less than 1000/microliters) was rare (3 of 74 cycles). There were three treatment-related deaths, only one of which was associated with neutropenia. One patient had mild renal insufficiency that resolved after discontinuation of therapy. Alopecia was observed in all patients, but other nonhematologic toxicities were uncommon. A randomized study is necessary to determine if this schedule of cisplatin and etoposide administration is superior to more standard methods. However, these data do not indicate a major survival benefit will be derived from increasing the duration of etoposide administration when used in combination with cisplatin given every 28 days.
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PMID:A phase II trial of cisplatin and prolonged administration of oral etoposide in extensive-stage small cell lung cancer. 130 32

To define the incidence and spectrum of pulmonary complications following autologous bone marrow transplantation (BMT), we retrospectively reviewed the course of 77 consecutive patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who failed conventional therapy and underwent autologous BMT. Forty-five percent of the 77 patients developed respiratory complications with a mortality from pulmonary causes of 26%. A total of 38 episodes of respiratory compromise occurred in 35 patients. Infections accounted for 15 episodes (39%) and included bacterial (16%), Aspergillus (8%) cytomegalovirus (8%), Herpes simplex (3%), and other (5%) pneumonias. The spectrum of infections was similar to that reported following allogeneic BMT, but cytomegalovirus pneumonia was not as frequent a problem in those with autologous transplant. Mortality from pulmonary infections was 33%. Noninfectious disorders accounted for 23 episodes (61%) and included recurrent HD (18%), radiation/drug toxicity (16%), and acute respiratory failure thought secondary to pulmonary alveolar hemorrhage (26%). This latter entity developed acutely within 2 wk following BMT and was associated with use of thoracic radiation for treatment of malignant disease in the chest just prior to BMT (p < 0.05). It was not associated with the age of the patient or presence of thrombocytopenia, coagulopathy, renal insufficiency or neutropenia (p NS). Mortality from noninfectious causes was 65%, but in those with pulmonary hemorrhage it was 100%. In conclusion, pulmonary complications are a major source of morbidity and mortality in patients with HD and NHL undergoing autologous BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary complications in lymphoma patients treated with high-dose therapy autologous bone marrow transplantation. 148 45

The prognostic value of 36 clinical and analytical parameters at diagnosis in patients with drug-induced agranulocytosis was analysed in an adult population. This multicentre, retrospective study examined possible prognostic factors by multiple logistic regression analysis in a series of 168 clinical episodes. The overall mortality was 16%. Renal insufficiency at diagnosis and the development of bacteraemia were associated with a poor prognosis. Advanced age, decreased leucocyte count, lymphocytopenia, bone marrow myeloid hypoplasia, increased percentage of bone marrow plasma cells and shock were found to be associated with a poor prognosis only in the univariate analysis. An independent analysis of the myeloid cellularity at diagnosis showed an inverse correlation with the time to recovery of the granulocyte counts (r = -0.43; P = 0.001). Our data indicate that despite some important clinical differences (higher incidence of infections of the oropharynx, shorter period of neutropenia and almost exclusive presence of gram-negative organisms), the infections complicating the treatment of cancer patients have the same prognostic features than those seen in patients with acute agranulocytosis. Therefore the established therapeutic guidelines for neutropenia after cancer chemotherapeutic agents are applicable to patients with acute agranulocytosis.
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PMID:Drug-induced agranulocytosis: prognostic factors in a series of 168 episodes. 175 64

We undertook a phase I trial using fixed-dose cisplatin, escalating doses of etoposide, and reinfusion of previously obtained autologous bone marrow in 29 relapsed or refractory small cell and non-small-cell lung cancer patients. Median age was 59 years (range of 38-68 years). Three patients had small-cell and 26 patients had non-small-cell lung cancer. Patients received i.v. cisplatin 200 mg/m2 over 5 days and i.v. etoposide 600 mg/m2/day for 3 days (total of 1,800 mg/m2) that was escalated to 800, 1,000, 1,200, 1,400, and 1,600 mg/m2/day for 3 days (total of 2,400-4,800 mg/m2). Cryopreserved autologous bone marrow was thawed and reinfused through a central venous catheter the second day after the completion of chemotherapy. Toxicities included nausea, vomiting, alopecia, high-tone hearing loss, mucositis, diarrhea, renal insufficiency, metabolic acidosis, and severe myelosuppression. The duration of neutropenia (less than 500 neutrophils/microliter) ranged from 5 to 22 days (median of 11 days) and the duration of severe thrombocytopenia (platelets of less than 20,000/microliters untransfused) ranged from 2 to 19 days (median of 9 days). Reversible renal insufficiency (peak serum creatinines of 6.7, 6.6, 4.3, and 3.5 mg/dl) occurred in four patients who completed the therapy. In three patients, death occurred within 4 weeks of chemotherapy and marrow reinfusion. Three complete and 12 partial remissions (range of 1+(-)22+ months, median of 3 months) were observed. No response was noted in eight patients and tumor progression within 1 month of transplant occurred in two patients. The maximally tolerated dose of etoposide was 1,400 mg/m2/day (total of 4,200 mg/m2), since two of three patients developed life-threatening diarrhea at the 1,600 mg/m2/day (total of 4,800 mg/m2) dose. The encouraging antitumor effects of this regimen suggest that this approach may be useful therapy for lung cancer and other tumors sensitive to VP-16 and cisplatin.
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PMID:Phase I trial of high-dose etoposide, high-dose cisplatin, and reinfusion of autologous bone marrow for lung cancer. 215 15

Cytomegalovirus (CMV) retinitis is the major cause of visual loss in acquired immune deficiency syndrome (AIDS). Thirty-one patients with active CMV retinitis were treated with the new antiviral drug, Foscarnet (trisodium phosphonoformate). After a 3-week course of induction therapy, the retinitis improved in 29 of 31 patients (93.5%). Complete resolution of the retinitis was seen in 19 cases (61.3%). Ten patients had partial resolution (32.2%) and two (6.5%) failed to respond. After induction therapy, six patients were put on a low-dose maintenance regimen. All patients without maintenance therapy relapsed within 3 weeks after discontinuation of Foscarnet. The rate of relapse on maintenance therapy was 50% (3/6) within the first 5 weeks. The three other patients of Foscarnet maintenance did not relapse after a follow-up period of 12 weeks. In contrast to ganciclovir, Foscarnet did not induce neutropenia but it produced kidney toxicity that led to reversible renal insufficiency in three cases. Thus, Foscarnet appears to be a useful alternative to ganciclovir, particularly when combined with bone marrow toxic drugs, such as zidovudine (azidothymidine).
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PMID:Foscarnet in the treatment of cytomegalovirus retinitis in acquired immune deficiency syndrome. 254 40

Iproplatin (CHIP) was administered to 35 previously treated women with metastatic adenocarcinoma of the breast. The drug was given at a dose of 45 mg/m2 intravenously for 5 consecutive days and was repeated every 28 days. In this trial, there was one partial response and two patients with stable disease out of 29 evaluable patients. The median duration of response in patients with either a partial response or stable disease was 4.8 months. Myelosuppression was the major toxicity, 11 patients had severe thrombocytopenia and 3 severe neutropenia. Mild renal insufficiency, anemia, and nausea and vomiting were also noted. Iproplatin has limited activity in heavily pretreated women with advanced breast carcinoma; further studies in patients less heavily treated may show an improved response rate.
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PMID:A phase II trial of iproplatin (CHIP) in previously treated advanced breast cancer. 270 2

Adverse effects of converting enzyme inhibitors are either substance-specific (neutropenia, proteinuria, skin rashes, taste disturbances) or due to the converting enzyme inhibition (hypotension, functional renal insufficiency, hyperkalemia, cough, angioedema). They are rare nowadays because of better knowledge of the pharmacokinetics and -dynamics of the converting enzyme inhibitors, resulting in lower dosage, and because of identifying patients at high risk. The dosage must be adjusted according to renal function, in order to prevent accumulation and toxicity. In addition to patients with renal insufficiency, patients at high risk are those with a stimulated renin-angiotensin-aldosterone system, i.e. patients with renovascular hypertension or heart failure. Patients with collagen vascular disease, for example, systemic lupus erythematosus or scleroderma, should not be considered for long-term therapy with converting enzyme inhibitors because of the increased risk of neutropenia. Life-threatening angioedema may develop, mainly during the first few hours after drug administration.
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PMID:[Angiotensin-converting enzyme inhibition: side effects and risks]. 285 Jun 87

The pharmacokinetics of the antiviral drug 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine (DHPG) were examined in six patients receiving 2.5 or 5.0 mg/kg every 8 or 12 hours for human cytomegalovirus (HCMV) pneumonitis or retinitis. Biexponential decay with a mean distribution t1/2 of 0.23 hours and terminal t1/2 of 2.53 hours was observed. Total clearance correlated well with and exceeded creatinine clearance by a factor of 2.4. Mean volume of the central compartment was 15.26 L/1.73 m2 and the volume of distribution at steady state was 32.8 L/1.73 m2. Peak (model predicted) and trough plasma concentrations were 4.75 to 6.20 micrograms/ml and less than 0.25 to 0.63 microgram/ml, respectively, in patients receiving 2.5 mg/kg. Peak concentrations are well above those needed to inhibit HCMV at the 50% level (ID50) and troughs are near this ID50. Cerebrospinal fluid concentrations of DHPG indicate a penetration of 24% to 67%. No accumulation of DHPG was apparent in these patients. However, dosage reduction is necessary in renal insufficiency. Neutropenia occurred in one patient. The plasma concentration profile of DHPG suggests potential beneficial activity against HCMV.
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PMID:Human pharmacokinetics of the antiviral drug DHPG. 301 30

Numerous trials have shown the efficacy of ACE-inhibitors in moderate and severe essential hypertension. Their use must be regarded as very promising. They lower peripheral vascular resistance without influencing cardiac index and heart rate. Additionally, they maintain serum potassium and do not effect plasma lipids or provoke diabetes mellitus or gout. In 20-30% of hypertensive patients ACE-inhibitors have to be combined with diuretics and/or calcium antagonists. The addition of beta-blockers is useful in patients with resting tachycardia. In mild hypertension the use of ACE-inhibitors as first-line drugs is indicated in patients with adverse reactions to beta-blockers or diuretics. In bilateral renovascular hypertension, ACE-inhibitors may induce a strong blood pressure fall; in bilateral stenosis they contribute to a deterioration of renal function with reversible renal insufficiency. In renoparenchymal hypertension, ACE-inhibitors may attenuate the progression of renal insufficiency; in addition, proteinuria is lowered. In systolic hypertension in the elderly, one must be aware of a marked first-dose hypotensive effect. ACE-inhibitors decrease exaggerated exercise-induced elevation of blood pressure and heart rate and therefore lower myocardial oxygen consumption. In patients with hypertension and diabetes mellitus, antihypertensive treatment should be initiated for blood pressure levels above 140/90 mmHg, to attenuate the progression of vascular damage in the kidney. In patients with severe left ventricular hypertrophy, ACE-inhibitors reduce left ventricular mass within three months by about 30%. In hypertension and coronary heart disease, recent studies report benefits of ACE-inhibitors on coronary circulation. Presently available ACE-inhibitors and those in preparation do not differ in pharmacodynamic, but in pharmacokinetic properties, concerning the beginning and duration of blood pressure lowering. A hypotensive first-dose effect can be observed in diuretic pretreated patients, in severe (malignant) and renovascular hypertension. ACE-inhibitors should not be used during pregnancy or in patients with autoimmune diseases or those undergoing treatment with immunosuppressive drugs, due to the side effects of neutropenia and proteinuria, which are more often seen under these conditions. Results from long-term studies on the influence of ACE-inhibitor treatment on cardiovascular risk in mild hypertension have not been available until now. In the decision to treat mild hypertension with ACE-inhibitors as first-line drug therapy, the costs of therapy in comparison to cheaper antihypertensives must be taken into account.
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PMID:[The value of angiotensin-converting enzyme inhibitors in the treatment of hypertension]. 306 60


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