Fosfomycin for the initial treatment of acute haematogenous osteomyelitis

Background and Aims: At our institution there has been a dichotomous antimicrobial treatment behaviour for acute haematogenous osteomyelitis (AHOM) since 1984. The surgical department favoured fosfomycin as initial choice and the medical department ß lactams. We aimed to compare the performance of both strategies. Methods: Data from patients discharged with the diagnosis of AHOM between January 1984 and January 1998 were gathered from the charts by means of a questionnaire. Patients receiving fosfomycin treatment (FT) were compared with those receiving fosfomycin plus other antimicrobials (FT+) and those receiving no fosfomycin treatment (NFT). Results: A total of 103 patients aged 0.1–15.5 years (mean 6.5, median 6.9) with AHOM received no surgical treatment initially. In 23 (22.3%) FT was instilled initially, in 47 (45.6%) FT+, and in 33 (32.0%) NFT. The pathogen was established in 30%, 36%, and 42% of FT, FT+, and NFT patients, respectively, Staphylococcus aureus being the predominant isolate. Mean C reactive protein levels and erythrocyte sedimentation rates normalised in all treatment groups after two and four weeks, respectively. The mean duration of intravenous antimicrobial treatment in FT patients was 2.5 weeks, in FT+ patients 3.1 weeks, and in NFT patients 3.8 weeks (p < 0.05), whereas the mean duration of intravenous plus oral treatment was comparable (7.1 v 6.8 v 6.5 weeks). Conclusions: The leucocyte penetrating fosfomycin performed similarly to extracellular ß lactams in the treatment of AHOM. Intravenous treatment for longer than 2.5 weeks offered no advantage.     

Preservative-free diclofenac sodium 0.1% for vernal keratoconjunctivitis

PURPOSE: The aim of this study is to evaluate the efficacy of prolonged treatment with preservative-free diclofenac sodium 0.1% eye drops in patients with vernal keratoconjunctivitis (VKC). METHODS: A prospective open study was performed in 22 patients with VKC treated with preservative-free diclofenac sodium 0.1% eye drops. Patients used the eye drops four times daily in both eyes for 120 days. Signs (papillae, hyperaemia and corneal lesions) and symptoms (itching, redness and photophobia) of the ocular surface were graded and statistically evaluated before and after treatment by a non-parametric test (Mann-Whitney U-test). RESULTS: Forty per cent of the patients showed an improvement in their symptoms at the end of the treatment. Total signs and symptoms scores were significantly decreased at the end of treatment compared with the baseline values (from 6.13+/-1.45 to 0.81+/-0.90 and from 5.40+/-1.18 to 2.63+/-0.95, respectively; P<0.001). Significant decreases in conjunctival redness (P<0.001), itching (P<0.001) and photophobia (P<0.001 ) were observed at the end of treatment. Conjunctival hyperaemia was significantly reduced (P<0.001) at the end of treatment, while no significant differences were observed for corneal lesions and for papillary size. No patient showed exacerbation of the disease during the treatment. CONCLUSION: VKC is a chronic disease that requires prolonged treatment to control the inflammatory process. Our preliminary study demonstrates the efficacy and safety of preservative-free diclofenac sodium 0.1% eye drops in controlling the signs and symptoms of VKC in prolonged treatment.     

Vascular damage and anti-angiogenic effects of tumor vessel-targeted liposomal chemotherapy

The poor selective toxicity of chemotherapeutic anticancer drugs leads to dose-limiting side effects that compromise clinical outcome. Solid tumors recruit new blood vessels to support tumor growth, and unique epitopes expressed on tumor endothelial cells can function as targets for the anti-angiogenic therapy of cancer. An NGR peptide that targets aminopeptidase N, a marker of angiogenic endothelial cells, was coupled to the surface of liposomal doxorubicin (NGR-SL[DXR]) and was used to treat orthotopic neuroblastoma (NB) xenografts in SCID mice. Pharmacokinetic studies indicated that liposomes coupled to NGR peptide had long-circulating profiles in blood. Their uptake into NB tumor was time dependent, being at least 10 times higher than that of nontargeted liposomes (SL[DXR]) after 24 h, with DXR spreading outside the blood vessels and into the tumors. No uptake was observed into tumors of mice treated with the mismatched peptide ARA-targeted SL[DXR]. Tumor-specific DXR uptake was completely blocked when mice were coinjected with a 50-fold molar excess of the soluble NGR peptide. Adrenal tumor-bearing mice treated with 2 mg/kg/week/x3 of NGR-SL[DXR] partly outlived the control mice (P < 0.001), whereas doses > 3 mg/kg/week/x3 were toxic. Histopathological analysis of cryosections taken from treated mice revealed pronounced destruction of the tumor vasculature with a marked decreased in vessel density. Double staining of tumors with terminal deoxynucleotidyl transferase-mediated nick end labeling and antifactor VIII antibody or antihuman NB demonstrated endothelial cell apoptosis in the vasculature, as well as increased tumor cell apoptosis. Moreover, mice injected with 3 mg/kg/week/x3 of NGR-SL[DXR] displayed rapid tumor regression, as well as inhibition of metastases growth (P = 0.0002). One day after the third treatment, four of six mice showed no evidence of tumors, and the two others showed a >80% reduction in tumor mass and a >90% suppression of blood vessel density (P < 0.01). In contrast, mice treated with ARA-SL[DXR] formed large well-vascularized tumors. Finally, a metronomic administration of NGR-SL[DXR] (1 mg/kg/every other 2 days x 9) induced complete tumor eradication in all animals (P < 0.0001). Our strategy markedly enhanced the therapeutic index of DXR and enabled metronomic administration of therapeutic doses. A dual mechanism of action is proposed: indirect tumor cell kill via the destruction of tumor endothelium by NGR-targeted liposomes and direct tumor cell kill via localization of liposomal DXR to the tumor interstitial space. This combined strategy has the potential to overcome some major limitations of conventional chemotherapy.     

The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterol

OBJECTIVES: To investigate the relationship between low cholesterol and mortality in older persons to identify, using information collected at a single point in time, subgroups of persons with low and high mortality risk. DESIGN: Prospective cohort study with a median follow-up period of 4.9 years. SETTINGS: East Boston, Massachusetts; New Haven, Connecticut; and Iowa and Washington counties, Iowa. PARTICIPANTS: Four thousand one hundred twenty-eight participants (64% women) age 70 and older at baseline (mean 78.7 years, range 70-103); 393 (9.5%) had low cholesterol, defined as < or =160 mg/dl. MEASUREMENTS: All-cause mortality and mortality not related to coronary heart disease and ischemic stroke. RESULTS: During the follow-up period there were 1,117 deaths. After adjustment for age and gender, persons with low cholesterol had significantly higher mortality than those with normal and high cholesterol. Among subjects with low cholesterol, those with albumin> 38 g/L had a significant risk reduction compared with those with albumin < or =38 g/L (relative risk (RR) = 0.57; 95% confidence interval (CI) = 0.41-0.79). Within the higher albumin group, high-density lipoprotein cholesterol (HDL-C) level further identified two subgroups of subjects with different risks; participants with HDL-C <47 mg/dl had a 32% risk reduction (RR = 0.68; 95% CI = 0.47-0.99) and those with HDL-C > or =47 mg/dl had a 62% risk reduction (RR = 0.38; 95% CI = 0.20-0.68), compared with the reference category; those with albumin < or =38 g/L and HDL-C <47 mg/dl. CONCLUSIONS: Older persons with low cholesterol constitute a heterogeneous group with regard to health characteristics and mortality risk. Serum albumin and HDL-C can be routinely used in older patients with low cholesterol to distinguish three subgroups with different prognoses: (1) high risk (low albumin), (2) intermediate risk (high albumin and low HDL-C), and (3) low risk (high albumin and high HDL-C).     

Antibiotic resistance in community-acquired pulmonary pathogens

Among infectious diseases, pneumonia is still the ;;captain of the men of death.' Etiologic diagnosis is often unreliable; consequently, clinicians must know epidemiology of community-acquired pneumonia for optimizing empiric antibiotic therapy. In recent years, all major pulmonary pathogens have become more and more resistant to conventional antibiotics. Penicillin-resistant and even multiresistant pneumococci have spread worldwide, but primarily in the United States, some European countries, South Africa, and the Far East. A similar trend is evidenced by ampicillin-resistant Hemophilus influenzae, whereas Moraxella catarrhalis almost invariably produces beta-lactamases. The widening of methicillin-resistant Staphylococcus aureus from hospitals to the community may be the new reality of the 1990s. Increasing erythromycin resistance of Streptococcus pyogenes requires beta-lactam therapy. The spread of both cromosomally and plasmid-mediated beta-lactamases makes treatment of infections caused by gram-negative enterobacilli more difficult. Bacterial resistance creates a challenge for clinicians from the viewpoint of correct and successful management of patients with community-acquired pneumonia.     

AIDS and Chagas' disease

Chagas' disease can reactivate in patients with AIDS and present as a brain mass lesion or an acute diffuse meningoencephalitis indistinguishable from other opportunistic infections or neoplastic processes, such as toxoplasma encephalitis or central nervous system (CNS) primary lymphoma. The CNS tumor-like lesion is the most common manifestation of Chagas' disease reactivation in AIDS patients. The prognosis of untreated cases is grim and underscore the need for safe and effective therapeutic agents.     

Autoimmune thyroiditis following interleukin-2 and LAK cell therapy for metastatic renal cell carcinoma: correlation with tumor regression.

A 63-year-old woman receiving recombinant interleukin-2 (rIL-2) + lymphokine activated killer cells for metastatic renal cell carcinoma developed autoimmune thyroiditis with clinical hypothyroidism and high titer anti-thyroglobulin and anti-microsomal antibodies. The onset of thyroid dysfunction was associated with tumor regression and resulted in complete response at the end of the treatment. Cytologic and cytofluorimetric studies on thyroid tissue showed two distinct populations, mainly consisting of small lymphocytes and large thyrocytes, and the latter expressed MHC class II antigens. After completion of rIL-2 treatment, hypothyroidism gradually decreased until resolution; complete tumor remission lasted 18 months. Mechanisms underlying the association between autoimmune thyroiditis and cancer regression are discussed.     

Cáncer evanescente de la próstata. Presentación clínica y revisión histológica

The impossibility to identify cancer in the final surgical specimen has been reported in some patients with prostate cancer undergoing radical prostatectomy. This has been attributed to either a wrong diagnosis or pathological technique, or to spontaneous or biopsy-induced cure of the tumor. This study assessed the incidence of vanishing prostate cancer in our department for 12 years, the clinical characteristics of patients, and their follow-up. The initial puncture biopsies were also re-evaluated using inmunohistochemical stains.Prostate cancer could not be confirmed in the surgical specimen in six out of 346 operated patients (1.73%) receiving no neoadjuvant therapy. When the initial biopsies were reviewed, cancer was only confirmed in three patients. Incidence of vanishing cancer at our department in the 12-year period considered was 0.86% (3/346). No tumor relapse occurred during 4.5 years of follow-up.