Previous Corticosteroid Treatment Research Articles

Osteonecrosis asintomática de la cadera en los pacientes infectados por el virus de inmunodeficiencia humana

Osteonecrosis (ON) of the hip in human immunodeficiency virus (HIV)-infected patients has been related to corticosteroid use, dyslipidemia, alcoholism, lipodystrophy, antiretroviral drug use, and HIV infection, itself. The aim of this study was to evaluate the prevalence of silent ON of the hip in HIV-infected patients and its association with several risk factors. From a total of 1200 patients followed up at the HIV clinic of Xeral-Cies Hospital in Vigo (Spain), we selected those diagnosed with HIV infection before January 2006, aged 20-70 years, who came to the clinic during the period of March to May 2008. Patients with a diagnosis of ON of the hip and those with current symptoms were excluded. A magnetic resonance imaging (MRI) study of the hips was performed. Ninety-seven Caucasian patients (68 men) with a median age of 44 years were included. ON of the hip was detected in 4 patients (4.1%), with bilateral involvement in 2 patients. All 4 patients were men, with a median age of 44.5 years. Several risk factors for ON of the hip were recorded in each patient. CD4 lymphocyte nadir (P=0.034), percentage of patients with CDC stage C (P=0.039), and number of patients with previous corticosteroid treatment (P=0.042) were significantly different between patients with ON of the hip and those with normal MRI findings. The prevalence of asymptomatic ON of the hip in HIV-infected patients was 4.1%. The most important risk factors for developing this condition were corticosteroid treatment, lower CD4 lymphocyte nadir, and AIDS-defining disease. Antiretroviral treatment was not associated with osteonecrosis.

Intraocular Methotrexate in the Treatment of Uveitis and Uveitic Cystoid Macular Edema

A pilot study to evaluate the use of intravitreal methotrexate (MTX) for the treatment of uveitis and uveitic cystoid macular edema (CME). Prospective, consecutive, interventional case series. Fifteen eyes of 15 patients with a unilateral exacerbation of noninfectious intermediate, posterior uveitis, or panuveitis and/or CME such that visual acuity (VA) was 20/40 or worse, together with a history of increased intraocular pressure (IOP) in response to corticosteroid administration. Intravitreal injection of 400 microg in 0.1 ml MTX. The primary outcome measure was VA (using the Early Treatment Diabetic Retinopathy Study chart). Other outcome measures included ocular inflammation scores, time to relapse, levels of systemic corticosteroid and immunosuppressive therapy, and ocular coherence tomography. Potential complications of intravitreal MTX injection, including cataract progression, vitreous hemorrhage, retinal detachment, and corneal epitheliopathy, were assessed. VA improved at all time points and was statistically significant at the 3- and 6-month follow-up examinations. The mean visual improvement was 4 lines at 3 months and 4.5 lines at 6 months, with no statistical difference between the best VA obtained after MTX injection and after previous corticosteroid treatment, including intravitreal triamcinolone acetate injection. Five patients relapsed after a median of 4 months; a similar improvement was seen after re-injection. Ocular inflammation scores improved at all time points, and systemic immunosuppressive medication was reduced in 3 of 7 patients taking this at the start of the trial. In patients with uveitis and uveitic CME, intravitreal MTX can improve VA and reduce CME and, in some patients, allows the reduction of immunosuppressive therapy. Relapse occurs at a median of 4 months in some patients, but reinjection has similar efficacy.

Influence of Race and Nutritional Status on the Long Term Event Free Survival in Childhood Acute Lymphoblastic Leukemia (ALL): A 14-year Follow-up with a Reduced BFM-Based Treatment Protocol (GBTLI ALL-93)

Background: Different event-free survival rates (EFS) of childhood ALL treatment regarding race, were published in the literature. However, a better consensus exists considering the bad prognosis of undernutrition. Taking into account the social economic reality of a low-income country such as Brazil, the systematic evaluation of these variables is of utmost importance, while inserted in a modern ALL treatment protocol.Objective: To compare, prospectively, the long-term EFS rates of previously untreated children with ALL, according to race and nutritional status at diagnosis.Methods: Patients were classified as Low Risk and High Risk according to NCI Criteria.Treatment schedule: Low Risk group: Remission induction therapy with DEXA 6mg/m2/d × 28 days, VCR 1.5 mg/m2/wk × 4, Daunomycin 25 mg/m2/wk × 4, L-ASP 10.000 U/m2/dose × 8, Ara-C 75mg/m2/dose × 8 and TIT therapy (day 0,28 and 42). Intensification therapy with MTX 2g/m2/wk × 4, 24 h continuous infusion with LCV rescue 15mg/m2/dose × 4, 6MP-50mg/m2 d × 21days and TIT therapy (x 4). Re-induction therapy: Dexa 6mg/m2 d × 21days, VCR 1.5mg/m2/wk × 4, L-ASP 10.000 U/m2/d × 4, 6-MP 50mg/m2/d × 14days, Ara-C 75 mg/m2/d × 4 and TIT therapy (x3). Central randomization was done for maintenance therapy duration (130 vs 103 wk). Maintenance: 6-MP 50mg/m2/d, MTX 25mg/m2/wk and TIT therapy every 8 weeks during all treatment. No CNS radiation was done. For High Risk patients, an induction intensification with intermediate dose of AraC (750 mg/m2/d × 6) was introduced, as well as, a rotational maintenance therapy with different pair of drugs were proposed (AraC 750mg/m2 × 4/Asp 6 000 U; Dexa/VCR/wk × 3 and 6-MP 75 mg/m2/d × 21 days/MTX 40 mg/m2/wk × 3). Prophylatic CNS radiation(18Gy) was done at wks 19–21 of therapy.Statistical analysis: EFS is defined as the time from diagnosis till any failure, relapse, death, or the development of a second malignancy. Continuous complete remission duration (CCR) is defined as EFS, contingent upon induction of a complete remission. EFS and CCR rates have been estimated by Kaplan and Meier's method.Results: From October 1993 to September 1999, 867 patients were consecutively enrolled in the protocol GBTLI ALL-93. Fourteen pts were excluded (1.5%), due to wrong diagnosis or previous corticosteroid treatment. 853 pts were evaluated in this study. 447 pts were classified as Low Risk group (52%) and 406(48%) as High Risk. According to race, 226 pts (26.5%)were classified as black and 627 (73.5%) as white. Overall undernutrition was diagnosed among 7.0 % of the patients. In the black population 10.4% were undernourished, comparing with 5.7% in the white group. The 14yrs-EFS for all the study patients is 80% ± 2% and 55% ± 2.5% for the Low Risk and High Risk pts, respectively. Concerning race, the 14yrs-EFS is of 71.7% ± 4.5% for the black children, comparatively to 83% ± 2.1% for the white ones (p=0.01). According to the nutritional status, the EFS is of 70.2%± 1.7% and 53.0%± 6.8% for the nourished and undernourished children, respectively. Malnutrition had the worst desfavorable impact among the High Risk pts, with a 14yrs-EFS of 40.1% ± 8.7%, compared to those without malnutrition of 57.8% ± 2.7% (p = 0.05). Social and economical issues directly involved with treatment, were provided by means of free medical attention and drugs supplies. Treatment abandon was < 1%.Conclusion: The black race and undernutrition had significant adverse effect on the long-term EFS among the patients of this study.

Transcriptomic analysis of intestinal fibrosis-associated gene expression in response to medical therapy in Crohnʼs disease

Glucocorticoids and monoclonal antibodies to tumor necrosis factor reduce inflammation in Crohn's disease (CD). Rapid luminal healing, however, may promote intestinal stricture formation. The aim of this study was to examine fibrosis-associated gene expression in the intestine of patients with CD and correlate expression levels with prior medical therapies. In all, 37 patients with stricturing CD and 18 non-CD controls underwent a transmural biopsy at the time of elective intestinal resection. Quantitative real-time polymerase chain reaction (PCR) was conducted to determine differential mRNA expression of TGF-beta(1), Smad-7, CTGF, collagen-1alpha, fibronectin, BMP-7, and MIF. Intestinal fibroblasts were treated in vitro with dexamethasone. Relative to control, strictured CD intestinal tissue expressed increased TGF-beta(1), CTGF, collagen-1alpha, and BMP-7 (all P < 0.05). TGF-beta(1) gene expression positively correlated with the expression of its downstream targets (all P < 0.001). Preoperative infliximab exposure was not associated with increased expression in any of the target genes nor did the number of infliximab infusions correlate with gene expression. The number of cycles of corticosteroid treatment preoperatively was positively associated with CTGF (r = 0.486, P = 0.016) and MIF (r = 0.524, P = 0.009) expression. Intestinal fibroblasts treated in vitro with dexamethasone upregulated CTGF expression (P = 0.023). Exposure to infliximab does not appear to induce a profibrotic transcriptional response in the CD intestine. Previous corticosteroid treatment is associated with increased expression of CTGF and MIF. Treating intestinal fibroblasts in vitro with steroids upregulates CTGF expression.

Aseptic Osteonecrosis in Children and Adolescents Treated for Hemato-Oncologic Diseases

Aseptic osteonecrosis (AON) is a serious long-term complication of childhood cancer therapy. A retrospective study was undertaken to describe treatment and long-term follow-up of patients with AON. Between 1990 and 2003, 630 consecutive children with various malignancies were treated at the University Children's Hospital in Graz, Austria. In nine of these patients presenting with skeletal symptoms, MRI revealed AON. All nine had hematologic malignancies. The median age at diagnosis of malignancy was 15.8 years (range 13.7-18.6 years), and the median interval between diagnosis of malignancy and onset of osteonecrosis-related symptoms was 16 months (range 6-53 months). All patients had received previous corticosteroid therapy. Treatment of AON included restriction of weight-bearing, physiotherapy, and analgesics. Three patients were treated with hyperbaric oxygen therapy combined with the prostacyclin analog iloprost, and one patient also received pamidronate, a second-generation bisphosphonate. This conservative treatment resulted in alleviation of symptoms in all patients. One patient had to undergo bilateral hip replacement and two had to undergo arthrotomy with sequestrotomy due to subsequent deterioration of symptoms. Close monitoring for skeletal symptoms is mandatory during follow-up of patients with hematologic malignancies. Previous corticosteroid treatment and age older than 10 years seem to be major risk factors. Early detection of AON leading to prompt intervention may prevent more severe morbidity.

Pretreatment with corticosteroids attenuates the efficacy of colchicine in preventing recurrent pericarditis: a multi-centre all-case analysis

Effective prevention of recurrent pericarditis remains an important yet elusive goal. Corticosteroid therapy often needs to be continued for a prolonged period and causes severe side effects. We performed a multi-centre all-case analysis to investigate the efficacy of colchicine in preventing subsequent relapses of pericarditis, and addressed the hypothesis that pretreatment with corticosteroids may attenuate the beneficial effect of colchicine. One hundred and forty published and unpublished cases of patients treated with colchicine after at least two relapses of pericarditis were aggregated from European centres. Of those, 119 were included in the study group. Only 18% of the patients had relapses under colchicine therapy, and 30% after its discontinuation. There were significantly more relapses among male patients after colchicine treatment (36 vs. 17%, P=0.046), and those with previous corticosteroid treatment (43 vs. 13%, P=0.02). Multivariate logistic regression analysis identified previous corticosteroid therapy (OR 6.68, 95% CI: 1.65-27.02) and male gender (OR 4.20, 95% CI: 1.16-15.21) as independent risk factors for recurrence following colchicine therapy. Treatment with colchicine is highly effective in preventing recurrent pericarditis, while pretreatment with corticosteroids exacerbates and extends the course of recurrent pericarditis.

Long-term safety of once-daily budesonide in patients with early-onset mild persistent asthma: results of the Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study

The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study is a worldwide, randomized, prospective study to investigate early intervention with inhaled corticosteroids in recent-onset mild persistent asthma. To evaluate the safety and tolerability of long-term treatment with once-daily budesonide therapy in patients with mild persistent asthma. Patients aged 5 to 66 years with mild persistent asthma for fewer than 2 years and no previous regular corticosteroid treatment received budesonide or placebo once daily for 3 years, in addition to their usual asthma therapy. The daily budesonide dose was 200 microg for children younger than 11 years and 400 microg for those 11 years or older. Overall, 7,221 patients were included in the safety analysis, and a total of 21,520 adverse events were reported (10,850 in the budesonide group and 10,670 in the placebo group). The most commonly reported events included respiratory infections, rhinitis, pharyngitis, bronchitis, viral infections, and sinusitis. The number of deaths and serious adverse events were similar for children and adults in both treatment groups. Fewer asthma-related serious adverse events were reported with budesonide (162) compared with placebo (276). Oral candidiasis was reported more frequently with budesonide (1.2%) than with placebo (0.5%); the frequencies of other adverse effects previously reported to be associated with inhaled corticosteroids (psychiatric disorders, skin disorders, and allergic reactions) were similar. Three-year treatment with budesonide once daily (200 or 400 microg) is safe and well tolerated in children and adults with newly detected mild persistent asthma.

Cell adhesion molecules in the development of inflammatory infiltrates in giant cell arteritis: Inflammation-induced angiogenesis as the preferential site of leukocyte-endothelial cell interactions

To investigate the expression pattern of adhesion molecules involved in leukocyte-endothelial cell interactions in giant cell arteritis (GCA). Immunohistochemical analysis was performed on frozen temporal artery sections from 32 patients with biopsy-proven GCA and from 12 control patients with other diseases. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), very late activation antigen 4 (VLA-4), Mac-1 (CD18/CD11b), and gp 150,95 (CD18/CD11c). Clinical and biochemical parameters of inflammation in the patients, as well as the duration of previous corticosteroid treatment, were prospectively recorded. Constitutive (PECAM-1, ICAM-1, ICAM-2, and P-selectin) and inducible (E-selectin and VCAM-1) endothelial adhesion molecules for leukocytes were mainly expressed by adventitial microvessels and neovessels within inflammatory infiltrates. Concurrent analysis of leukocyte receptors indicated a preferential use of VLA-4/VCAM-1 and LFA-1/ICAM-1 at the adventitia and Mac-1/ICAM-1 at the intima-media junction. The intensity of inducible endothelial adhesion molecule expression (E-selectin and VCAM-1) correlated with the intensity of the systemic inflammatory response. Previous corticosteroid treatment reduced, but did not completely abrogate, the expression of the inducible endothelial adhesion molecules E-selectin and VCAM-1. Inflammation-induced angiogenesis is the main site of leukocyte-endothelial cell interactions leading to the development of inflammatory infiltrates in GCA. The distribution of leukocyte-endothelial cell ligand pairs suggests a heterogeneity in leukocyte-endothelial cell interactions used by different functional cell subsets at distinct areas of the temporal artery.

Skin coverage with Biobrane biomaterial for the treatment of patients with toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) is an exfoliative skin disorder that may involve a large body surface area and mucosal surfaces. The microscopic changes that occur with this condition are similar to those that occur with superficial dermal burns, such as dermal detachment from the underlying dermis. Complications of TEN are related to the loss of the epithelial skin barrier and include pain, fluid and electrolyte loss, and an increased risk of sepsis. The treatment of a patient with TEN is best accomplished in a burn unit, where expert treatment of these complications can be provided. Medical treatment includes the administration of immunosuppressive therapy and the discontinuation of any previous corticosteroid treatment. Surgical management includes the debridement of necrotic areas. In this article, the surgical management of 8 consecutive patients with TEN who were admitted to the intensive care burn unit at the Hospital Universitario de Getafe in Madrid, Spain, from 1996 to 1998 is described. These patients were treated with extensive early debridement of necrotic skin areas followed by wound coverage with Biobrane (Dow B. Hickam, Inc, Sugarland, Tex), a temporary semisynthetic skin substitute. Skin coverage with this material decreases pain and fluid loss, and it possibly facilitates epithelization and decreases the risk of sepsis, without adverse side effects. This semisynthetic material meets some standards of an ideal skin substitute: it is easy to use, provides several beneficial physiologic effects, and improves patients' comfort. In the 8 cases of patients with TEN that were studied, the use of Biobrane skin substitute for the coverage of massive areas of detached skin was found to be an important aspect of treatment.

Association of humoral markers of inflammation and dehydroepiandrosterone sulfate or cortisol serum levels in patients with chronic inflammatory bowel disease

Objectives: Dehydroepiandrosterone sulfate (DHEAS) and cortisol are multifunctional adrenal hormones with immunomodulating properties. DHEAS levels were found to be very low in chronic inflammatory diseases. This study aimed to shed more light on the interrelation between DHEAS and cortisol (and humoral markers of inflammation) in chronic inflammatory bowel disease. Methods: DHEAS and cortisol serum levels were measured by ELISA in the serum of 66 normal subjects, 115 patients with Crohn’s disease (CD) and 64 patients with ulcerative colitis (UC). Humoral markers of inflammation and disease activity scores were assessed by standard techniques. Results: DHEAS was lower in patients with CD ( p < 0.005) and UC ( p < 0.005) than in controls, which was, in part, dependent on previous corticosteroid treatment ( p < 0.01). In CD patients, z-normalized DHEAS was inversely correlated with blood sedimentation rate ( p = 0.017). Z-normalized DHEAS was negatively correlated with interleukin-6 (IL-6) in the form of a trend ( p = 0.068), and z-normalized DHEAS was significantly positively correlated with hemoglobin ( p = 0.001) but not with the Crohn’s disease activity index. Cortisol, however, was positively correlated with blood sedimentation rate ( p = 0.034) and C-reactive protein ( p = 0.006). In contrast, in UC patients no such correlation of z-normalized DHEAS or cortisol and parameters of humoral inflammatory activity or Rachmilewitz index exist. Conclusions: DHEAS as a marker of inflammation was low in CD and UC. In CD patients, low DHEAS and high cortisol serum levels were associated with higher humoral inflammatory activity. With respect to humoral inflammatory activity in CD patients, DHEAS and cortisol seem to be inversely regulated, which may have an impact on several immune functions, such as IL-6 secretion.

Association of humoral markers of inflammation and dehydroepiandrosterone sulfate or cortisol serum levels in patients with chronic inflammatory bowel disease.

Dehydroepiandrosterone sulfate (DHEAS) and cortisol are multifunctional adrenal hormones with immunomodulating properties. DHEAS levels were found to be very low in chronic inflammatory diseases. This study aimed to shed more light on the interrelation between DHEAS and cortisol (and humoral markers of inflammation) in chronic inflammatory bowel disease. DHEAS and cortisol serum levels were measured by ELISA in the serum of 66 normal subjects, 115 patients with Crohn's disease (CD) and 64 patients with ulcerative colitis (UC). Humoral markers of inflammation and disease activity scores were assessed by standard techniques. DHEAS was lower in patients with CD (p < 0.005) and UC (p < 0.005) than in controls, which was, in part, dependent on previous corticosteroid treatment (p < 0.01). In CD patients, z-normalized DHEAS was inversely correlated with blood sedimentation rate (p = 0.017). Z-normalized DHEAS was negatively correlated with interleukin-6 (IL-6) in the form of a trend (p = 0.068), and z-normalized DHEAS was significantly positively correlated with hemoglobin (p = 0.001) but not with the Crohn's disease activity index. Cortisol, however, was positively correlated with blood sedimentation rate (p = 0.034) and C-reactive protein (p = 0.006). In contrast, in UC patients no such correlation of z-normalized DHEAS or cortisol and parameters of humoral inflammatory activity or Rachmilewitz index exist. DHEAS as a marker of inflammation was low in CD and UC. In CD patients, low DHEAS and high cortisol serum levels were associated with higher humoral inflammatory activity. With respect to humoral inflammatory activity in CD patients, DHEAS and cortisol seem to be inversely regulated, which may have an impact on several immune functions, such as IL-6 secretion.

Dynamic pattern of endothelial cell adhesion molecule expression in muscle and perineural vessels from patients with classic polyarteritis nodosa

Objective To investigate endothelial cell adhesion molecule expression in vessels from patients with classic polyarteritis nodosa (PAN). Methods Frozen sections of 21 muscle and 16 nerve samples from 30 patients with biopsy-proven PAN and 12 histologically normal muscle and 2 histologically normal nerve samples from 12 controls were studied immunohistochemically, using specific monoclonal antibodies (MAb) that recognize adhesion molecules. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), and very late activation antigen 4 (VLA-4). Neutrophils were identified with a MAb recognizing neutrophil elastase. Endothelial cells were identified with the lectin ulex europaeus. Results In early lesions, expression of PECAM-1, ICAM-1, ICAM-2, and P-selectin was similar to that in control samples, and VCAM-1 and E-selectin were induced in vascular endothelium. In advanced lesions, immunostaining for adhesion molecules diminished or disappeared in luminal endothelium, whereas these molecules were clearly expressed in microvessels within and surrounding inflamed vessels. Staining in endothelia from vessels in a healing stage tended to be negative. A high proportion of infiltrating leukocytes expressed LFA-1 and VLA-4, and only a minority expressed L-selectin. No relationship between the expression pattern of adhesion molecules and clinical features, disease duration, or previous corticosteroid treatment was observed. Conclusion Endothelial adhesion molecule expression in PAN is a dynamic process that varies according to the histopathologic stage of the vascular lesions. The preferential expression of constitutive and inducible adhesion molecules in microvessels suggests that angiogenesis contributes to the persistence of inflammatory infiltration in PAN.

Dynamic pattern of endothelial cell adhesion molecule expression in muscle and perineural vessels from patients with classic polyarteritis nodosa.

To investigate endothelial cell adhesion molecule expression in vessels from patients with classic polyarteritis nodosa (PAN). Frozen sections of 21 muscle and 16 nerve samples from 30 patients with biopsy-proven PAN and 12 histologically normal muscle and 2 histologically normal nerve samples from 12 controls were studied immunohistochemically, using specific monoclonal antibodies (MAb) that recognize adhesion molecules. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), and very late activation antigen 4 (VLA-4). Neutrophils were identified with a MAb recognizing neutrophil elastase. Endothelial cells were identified with the lectin ulex europaeus. In early lesions, expression of PECAM-1, ICAM-1, ICAM-2, and P-selectin was similar to that in control samples, and VCAM-1 and E-selectin were induced in vascular endothelium. In advanced lesions, immunostaining for adhesion molecules diminished or disappeared in luminal endothelium, whereas these molecules were clearly expressed in microvessels within and surrounding inflamed vessels. Staining in endothelia from vessels in a healing stage tended to be negative. A high proportion of infiltrating leukocytes expressed LFA-1 and VLA-4, and only a minority expressed L-selectin. No relationship between the expression pattern of adhesion molecules and clinical features, disease duration, or previous corticosteroid treatment was observed. Endothelial adhesion molecule expression in PAN is a dynamic process that varies according to the histopathologic stage of the vascular lesions. The preferential expression of constitutive and inducible adhesion molecules in microvessels suggests that angiogenesis contributes to the persistence of inflammatory infiltration in PAN.

Doxorubicin alone or in combination with asparaginase, followed by cyclophosphamide, vincristine, and prednisone for treatment of multicentric lymphoma in dogs: 121 cases (1987-1995)

Objective To determine response rate and remission as well as survival times for dogs with multicentric lymphoma treated first with doxorubicin alone or in combination with asparaginase and then with cyclophosphamide, vincristine sulfate, and prednisone (CVP) and to identify prevalence of toxicoses associated with this protocol and factors associated with prognosis. Design Retrospective case series. Animals 121 dogs. Procedure Variables evaluated for prognostic value were initial response rate to chemotherapy, age, breed, sex, body weight, histologic grade, clinical stage and substage, previous corticosteroid treatment, and serum calcium concentration. Results Median overall remission and survival times for all 121 dogs were 205 and 237 days, respectively. Response rate (complete or partial response) was 88%. Ten dogs were hospitalized because of toxicoses associated with doxorubicin, and 19 dogs were hospitalized because of toxicoses associated with CVP. Asparaginase favorably influenced the initial response rate, but did not significantly influence overall remission or survival times. Initial response rate to chemotherapy, body weight. clinical substage, and serum calcium concentration was found to have prognostic value. Clinical Implications For dogs with multicentric lymphoma, treatment with doxorubicin alone or in combination with asparaginase and then with CVP resulted in an acceptable response rate and low prevalence of toxicoses. (J Am Vet Med Assoc 1997;210:512–516)

Inflammatory infiltrates in sural nerve biopsies in Guillain-Barre syndrome and chronic inflammatory demyelinating neuropathy.

Prompted by observations in experimental autoimmune neuritis we reanalyzed immunohistochemically the inflammatory infiltrates in sural nerve biopsies of 22 cases with Guillain-Barre syndrome (GBS) and 13 cases with chronic inflammatory demyelinating polyneuropathy (CIDP). Endoneurial infiltration of CD3+ T cells was found in 20 cases of GBS (median 5.5 cells/mm(2)) and in 10 cases of CIDP (5 cells). Epineurial T cells were present in all GBS cases (19.5 cells) and in 11 CIDP cases (21 cells). CD68+ macrophages were abundant in these neuropathies and often occurred in endoneurial perivascular clusters. In GBS subgroups the number of endoneurial T cells was significantly higher in patients with hypoesthesia and abnormal electrophysiological findings in the sural nerve. In CIDP hypoesthesia was associated with significantly higher numbers of macrophages. Our study also indicates that other factors including the time point of biopsy or previous corticosteroid treatment may influence the inflammatory cell profile. Quantifying cell infiltration may aid in establishing the diagnosis of an immunoneuropathy in patients with mild and noncharacteristic pathology.

Pneumocystis carinii Pneumonia in Patients Without AIDS, 1980 Through 1993

Pneumocystis carinii pneumonia (PCP) occurs in immunocompromised patients without the acquired immunodeficiency syndrome (AIDS). There has been an increasing yearly number of cases of PCP in our patients without AIDS. To determine the nature of the underlying disorder and previous immunosuppressive treatment in patients with PCP without AIDS. A study of the charts of 78 such patients admitted to our hospital from 1980 through 1993. The number of PCP cases per year increased during the period studied. All patients had an underlying disorder, either hematologic malignancy (49%), solid organ tumor (4%), vasculitis or other immunologic disorder (22%), or they had undergone renal transplantation (17%) or bone marrow transplantation (9%). Previous immunosuppressive medication consisted of prednisone or other corticosteroids in 72 (92%) of 78 patients, cytotoxic drugs in 55 (71%) of 78 patients, both in 50 (64%) of 78 patients, and none in one patient. Quantification of previous corticosteroid treatment showed a large variability among patients. The overall mortality rate for patients was 35% (27/78). Mortality was significantly higher in patients with a concomitant pulmonary infection (P = .01), an underlying disorder other than that which resulted in renal transplantation (P = .03), mechanical ventilation (P < .001), previous chemotherapy (P = .04), as well as previous cyclophosphamide treatment (P = .01). A trend toward a higher mortality in patients with previous corticosteroid use was detected (P = .06). Pneumocystis carinii pneumonia may complicate a variety of immunocompromised states, with considerable mortality. Pneumocystis carinii pneumonia occurred at all levels of immunosuppression; no threshold level could be defined.

How does previous corticosteroid treatment affect the biopsy findings in giant cell (temporal) arteritis?

To determine the effect of previous corticosteroid treatment on the results of temporal artery biopsy. Consecutive case series. Tertiary care center. A consecutive cohort of 535 patients who had temporal artery biopsies at Mayo Clinic, Rochester, Minnesota, between 1 January 1988 and 31 December 1991. The dose and duration of corticosteroid treatment received before temporal artery biopsy and detailed clinical and laboratory data were obtained from the patients' medical records. All temporal artery biopsy slides were re-evaluated by a pathologist blinded to clinical data, previous corticosteroid treatment information, and the original pathologic diagnosis. Biopsy specimens were classified as negative for arteritis, positive for typical temporal arteritis, or positive for atypical temporal arteritis. Biopsy results were positive for 31% of patients (89 of 286) who did not receive corticosteroids before biopsy and for 35% of those (86 of 249) who did receive corticosteroids before biopsy (P = 0.4; 95% confidence interval for the difference, -4.7% to 11.5%). Patients who received corticosteroids before biopsy tended to have clinical features more suggestive of arteritis. A multiple logistic regression analysis model, controlling for these differences in clinical and laboratory features, showed that the biopsy positivity rate was unrelated to previous corticosteroid treatment. Although these results do not prove that histologic features are unaffected by corticosteroids, they show that, in this large, consecutive sample, the positivity rates of temporal artery biopsy were similar in untreated and corticosteroid-treated patients. Temporal artery biopsy may show arteritis even after more than 14 days of corticosteroid therapy in the presence of clinical indications of active disease.