Plasma tumor necrosis factor and mortality in critically ill septic patients

Tumor necrosis factor (TNF) cachectin has been implicated as an important host mediator responsible for shock and multiple organ failure (MOF) observed during sepsis. Using a sensitive enzyme-linked immunosorbent assay, we measured plasma TNF levels in 43 septic patients suffering from a broad range of diseases. Measurements were taken on the day that sepsis was diagnosed. Eleven patients had detectable TNF plasma levels ranging from 10 to 100 pg/ml (TNF-positive group); in 32 patients circulating TNF could not be detected (TNF-negative group). The groups did not differ significantly as to age, underlying disease, percentage positive bacteremia and bacteriologic profile, sepsis score, and extent of MOF. Eight (73%) of 11 TNF-positive patients died from sepsis during ICU stay, vs. 11 (34%) of 32 TNF-negative patients (p less than .05). This study demonstrates that sepsis is accompanied by detectable circulating TNF in 25% of the cases, and for these patients mortality is twice that for comparable TNF-negative patients.     

Pharmacokinetics of ethylenediaminemalonatoplatinum(II) (JM-40) during phase I trial

Pharmacokinetics of the cis-platin analog ethylenediaminemalonatoplatinum(II) (JM-410) was studied in 28 cycles of 19 patients during the phase I study of this drug. The drug was administered intravenously by short-term (10-60 min) infusion. Doses ranged from 20 to 1,200mg m-2. JM-40 was determined in plasma ultrafiltrate and urine by HPLC. Platinum (Pt) concentrations were determined in plasma, plasma ultrafiltrate, urine and red blood cells by atomic absorption spectrometry up to 5 days after administration of the drug. Ultrafilterable Pt could be determined up to 45 days after the infusion in one patient sampled over such a long period. Pharmacokinetics of JM-40 showed a linear behaviour. The final half-life of total Pt in plasma was 4.1 +/- 0.9 days. The disposition of JM-40 was similar to that of ultrafilterable Pt in respect to t1/2 alpha (10 and 13 min), t1/2 beta (44 and 57 min), volumes of distribution Vc (11 and 121) and Vss (17 and 201), systemic clearance (256 and 223 ml min-1), renal clearance (69 and 73 ml min-1) and metabolic clearance (183 and 154 ml min-1). During the first 6 h 27 +/- 9% of the administered dose was excreted as JM-40. Cumulative platinum excretion in the urine amounted to 29 +/- 13% and 60 +/- 13% over the first 6 h, 24 h and 5 days, respectively. The uptake of platinum in red blood cells was limited, comprising only 0.24 +/- 0.12% of the administered dose. Although JM-40 and carboplatin are structurally closely related, pharmocokinetics and toxicity of JM-40 were more similar to cis-platin than to carboplatin.     

The simultaneous determination of cerebrospinal fluid and plasma adenosine deaminase activity as a diagnostic aid in tuberculous meningitis

The simultaneous determination of cerebrospinal fluid (CSF) and plasma adenosine deaminase (ADA) activity was evaluated as a diagnostic aid in tuberculous meningitis (TBM). CSF and plasma ADA activity were determined in four groups of patients: (i) a 'no meningitis' group of 174 children investigated for possible meningitis, but found to be uninfected; (ii) an aseptic meningitis group of 40 children; (iii) a bacterial meningitis group of 31 children; and (iv) a TBM group of 27 patients (24 children and 3 adults). CSF ADA alone was determined in a further 23 children with aseptic meningitis, 19 with bacterial meningitis and 13 children and 7 adults with TBM. Both the CSF/plasma ADA ratio and the absolute CSF ADA activity were raised in TBM (mean values 0,24 and 12,61 U/I respectively) and bacterial meningitis (mean values 0,59 and 15,43 U/I respectively), but not in the aseptic meningitis group (mean values 0,06 and 2,00 U/I) or the 'no meningitis' group (mean values 0,04 and 1,51 U/I). Both values will distinguish TBM from aseptic meningitis, but do not appear to hold any marked advantages over conventional CSF criteria in the diagnosis of TBM.     

Behavior of acid secretion and clinical results following selective proximal vagotomy in uncomplicated duodenal ulcer

Reported in this paper are postoperative results recorded from 120 patients, 3 years after selective proximal vagotomy for uncomplicated duodenal ulcer. There was no intraoperative lethality and no recurrence in 96.7 per cent of all cases, while Visick grades I on II were recorded from 98.2 per cent. Radiologically and gastroscopically detected pathological processes receded soon. Average postoperative reduction in acid secretion was 66.2 per cent in BAO and 46.8 per cent in MAO. Acid values re-increased thereafter, and three years later reduction rates still amounted to 43.7 per cent in BAO and 28.6 per cent in MAO. Indications for proximal gastric vagotomy are discussed in some detail.     

Management of pediatric pontine gliomas

We present 36 consecutive patients with intrinsic glioma of the pons. Tumors with exophytic expansion were excluded. There were 16 females and 20 males, ranging in age from 2 to 13 years, median 6 years. The most common presenting symptoms were cranial nerve dysfunction. unsteadiness of gait, and hemiparesis. Computed tomography (CT) showed a hypodense (17/21) or isodense (4/21) expansion of the pons. Five tumors had areas of contrast enhancement. Following information about prognosis and possible types of management, parents decided for or against radiation therapy: twentyfour children underwent irradiation and 12 did not. Median survival among children receiving a full course of irradiation was 280 days, compared to 140 days in an equivalent group of non-irradiated children. Hemiparesis presenting without cranial nerve symptoms and contrast enhancement on CT scan were poor prognostic factors, whereas sex, age, and duration of symptoms at diagnosis were unrelated to prognosis.     

Manifestation of malignant lymphoma of the head and neck with special reference to the salivary glands

We found that thirteen per cent of all head and neck malignomas are malignant lymphomas. In 75% of these cases the Non-Hodgkin type could be found. The major salivary glands were involved by the lymphoma in 55% out of 104 patients. Paraglandular lymph nodes of the parotid gland were affected as well as intraglandular lymph nodes and the lymphoid tissue within the gland proper. The submandibular gland normally shows an involvement only with its paraglandular lymph nodes. Two thirds of the Non-Hodgkin lymphomas located in the salivary glands were low-grade. In case of clinical suspicion of a malignant lymphoma, fine needle biopsy is required for cytological diagnosis. However, surgery is mandatory for histological diagnosis, not as a therapeutic measure.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (I)

Occupational diseases Nos. 2108 and 2110 correspond to intervertebral disc-related diseases of the lumbar spine from many years of carrying or lifting heavy loads, occupations in extreme postures of full flexion or oscillation of the whole body when seated, and which compel the cessation of all activities which are or could be the cause for the origin, exacerbation or recurrence of the disease. These occupational diseases came into force at the start of 1993, but there have been considerable problems in their implementation. The present Part I of the contribution is the result of the work of an interdisciplinary study group and contains medical criteria for the assessment of possibly strain-related clinical characteristics and the evaluation of other possible causes. Part II is to be published in Volume 4/2005 and will deal with questions related to forced cessation and to the assessment of the loss of earning ability. Agreement was reached in many areas related to the assessment of occupational claims. This should allow for evidence-based decision making in the future for the occupational diseases Nos. 2108 and 2110.     

Lipid nanoparticles for skin penetration enhancement-correlation to drug localization within the particle matrix as determined by fluorescence and parelectric spectroscopy.

With topical treatment of skin diseases, the requirement of a high and reproducible drug uptake often still is not met. Moreover, drug targeting to specific skin strata may improve the use of agents which are prone to cause local unwanted effects. Recent investigations have indicated that improved uptake and skin targeting may become feasible by means of nanoparticular systems such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Here we describe techniques to characterize drug loading to carrier systems and skin penetration profiles by using the lipophilic dye nile red as a model agent. Since the mode of drug association with the particle matrix may strongly influence the efficiency of skin targeting, parelectric spectroscopy (PS) was used to differentiate between matrix incorporation and attachment to the particle surface and fluorescence spectroscopy (FS) to solve dye distribution within NLC particles. Nile red was incorporated into the lipid matrix or the covering tensed shell, respectively, of SLN and NLC with all the lipids studied (Compritol, Precirol, oleic acid, Miglyol). In NLC, the dye was enriched in the liquid phase. Next, nile red concentrations were followed by image analysis of vertical sections of pigskin treated with dye-loaded nanoparticular dispersions and an oil-in-water cream for 4 and 8 h in vitro. Following the SLN dispersions, dye penetration increased about fourfold over the uptake obtained following the cream. NLC turned out less potent (相似文献   

The influence of protein solubilisation, conformation and size on the burst release from poly(lactide-co-glycolide) microspheres.

Encapsulation of proteins in poly(lactide-co-glycolide) microspheres via emulsion is known to cause insoluble protein aggregates. Following protein emulsification and encapsulation in PLGA microspheres, we used circular dichroism to show that the recoverable soluble protein fraction also suffers subtle conformational changes. For a panel of proteins selected on the basis of molecular size and structural class, conformational stability measured by chemical denaturation was not indicative of stability during emulsion-encapsulation. Partial loss of structure was observed for alpha-helical proteins released from freeze-dried microspheres in aqueous buffer, with dramatic loss of structure for a beta-sandwich protein. The addition of sucrose (a lyoprotectant) did not prevent the loss of protein conformation upon encapsulation. Therefore, the conformational changes seen for the released soluble protein fraction originates during emulsification rather than microsphere freeze-drying. Analysis of the burst release for all proteins in buffer containing denaturant or surfactant showed that the degree of protein solubilisation was the dominant factor in determining the initial rate and extent of release. Our data for protein release into increasing concentrations of denaturing buffer suggest that the emulsion-denatured protein fraction remains insoluble; this fraction may represent the protein loss encountered upon comparison of protein encapsulated versus protein released.