Graded responses of human neutrophils induced by serum-treated zymosan

A modified zymosan preparation was used to probe the interaction of particulate stimuli with human neutrophils (PMNs). After extraction with alkali and detergent, the zymosan particles retained their ability to be opsonized in serum and to stimulate PMNs. Serum-treated zymosan (STZ) induced dose-dependent superoxide (O2-) production and membrane potential depolarization in the range of 1 to 10 mg/mL of STZ. The rate and extent of secretion of lysozyme and beta-glucuronidase were also dose-dependent in the range of 1 to 10 mg/mL of STZ. Cytochemical studies using nitroblue tetrazolium, however, showed that 92% of PMNs were stimulated to produce O2- at 0.1 mg/mL of STZ. The dose response of O2- production induced by STZ is therefore due to increasing O2- production by individual PMNs and not to the stimulation of more PMNs to produce O2-. Evidence for O2- production was found only in the area of PMN-zymosan contact, suggesting a mechanism for the graded responses of PMNs treated with particulate stimuli. In order to determine the nature of the dose dependence of depolarization (a measure of PMN activation), PMNs equilibrated with the fluorescent probe 3,3'- dipentyloxacarbocyanine were analyzed by flow cytometry. The results demonstrate that STZ induces a dose-dependent depolarization of the membrane potential of individual PMNs. These results also demonstrate that increasing concentrations of STZ can induce increasing PMN responses even when all of the PMNs have been activated. These results are consistent with the hypothesis that receptor-mediated particulate stimulation of PMNs is a phenomenon that results in graded PMN responses.     

Acupuncture and transcutaneous electric nerve stimulation in the treatment of pain associated with chronic pancreatitis. A randomized study

In 23 patients with pancreatitis, daily pain for at least 3 months, and no abuse of alcohol, the pain-relieving effect of electroacupuncture (13 patients) or transcutaneous electric nerve stimulation (TENS) (16 patients) was studied. In two prospective studies with a cross-over design, active acupuncture was compared with sham acupuncture, and TENS of the segmental points of the pancreas with sham treatment. Neither electroacupuncture nor TENS brought about pain relief that could substitute for or supplement medical treatment.     

Benzodiazepine/gamma-aminobutyric acid receptor deficit in the midbrain of the seizure-susceptible gerbil.

The density of benzodiazepine/gamma-aminobutyric acid receptor binding sites was lower in the midbrain of seizure-susceptible gerbils compared to control seizure-resistant gerbils. Binding of [3H]diazepam to high-affinity brain-specific sites in membrane homogenates of gerbil brain showed a 20-30% lower binding in midbrain (but not other regions) in adult seizure-susceptible gerbils than in controls. This binding deficit was localized by tissue slice autoradiography with [3H]flunitrazepam to the substantia nigra and mesencephalic periaqueductal gray regions, while higher binding was observed in the interpeduncular nucleus. These differences were also seen in animals sacrificed immediately after a seizure. A parallel deficit of [3H]bicuculline methochloride binding to low-affinity gamma-aminobutyric acid receptors also was seen in the same midbrain regions. Scatchard plot analysis showed that the benzodiazepine binding deficit in the nigra was due to a lower number of binding sites with not significant difference in affinity. Lower [3H]flunitrazepam binding was likewise seen in younger animals (29% lower at 30 days of age, 38% at 60 days, and 21% at 90 days), indicating that the midbrain receptor deficit is present in the seizure-susceptible gerbil prior to the age of onset of seizures at 50-100 days. Therefore, these changes are not likely to result from seizures but reflect genetically determined biochemical differences that could play a role in the expression of seizure susceptibility. The deficit in midbrain benzodiazepine/gamma-aminobutyric acid receptors in the seizure-susceptible gerbil would be consistent with the hypothesis that a deficit of gamma-aminobutyric acid-mediated inhibition might contribute to some kinds of epilepsy.     

In vivo studies of intestinal carnitine absorption in rats

We have studied small intestinal absorption of carnitine in vivo using a combination of segmental perfusion techniques and bolus intraluminal injection. We found evidence of a partially saturable absorption process (with Km values of 1035 and 1267 microM for jejunum and ileum calculated for the saturable component) that appeared to be separate from the imino acid transport system. Absorption was characterized by slow mucosal uptake, prolonged mucosal retention, and a very slow mucosal exit process with blood levels of [3H] carnitine still rising 8 h after intraluminal administration. We have also demonstrated the presence of carnitine acetyltransferase in intestinal mucosa and have shown that the intestine forms significant amounts of acetylcarnitine from exogenous carnitine.     

Tissue hypoxaemia causes oedema, inflammation and fibrosis in porcine bronchial transsection

Abstract Objectives. Bronchial artery revascularization in lung transplantation is disputed. This study examined the physiological consequences of porcine bronchial transsection and reanastomosis with and without bronchial artery blood supply with relation to lung transplantation. Design. Translational, controlled animal study. Twelve pigs were operated through a left lateral thoracotomy. The left bronchus was transsected and reanastomosed. In the control group (n =?6), the bronchial arteries were preserved and in the study group (n =?6) they were severed. Bronchial mucosa blood flow (BMBF) was measured with laser-Doppler velocimetry and bronchial mucosa haemoglobin saturation and concentration with diffuse reflectance spectrophotometry. Measurements were made preoperatively, postoperatively and after 1 week. Results. In the study group, left postoperative BMBF was significantly lower than preoperatively (115 vs. 210 PU/s, p =?0.0001) and lower than in the control group (115 vs. 205 PU/s, p =?0.002). Repeated measurement ANOVA showed a significant treatment effect depending on time (p =?0.0034). The left mucosal haemoglobin saturation in the study group was significantly reduced postoperatively, 92% versus 61%, with a treatment effect depending on time (p =?0.0080). The reduction in left/right ratio of the mucosal haemoglobin concentration 1 week postoperatively in the study group was insignificant. Conclusion. Bronchial transsection and reanastomosis without bronchial artery blood supply was followed by significant decrease in mucosal blood flow and saturation postoperatively, and also in tissue haemoglobin concentration at section, and provides a physiologic explanation of histological changes.     

Glycaemic control for patients with severe acute brain injury: Protocol for a systematic review

Background

Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury.

Methods

We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/ , http://www.clinicaltrials.gov/ , www.eudraCT.com , http://centerwatch.com/ , The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Discussion

The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.     

Primary Extracranial Meningiomas: An Analysis of 146 Cases

Primary extracranial meningiomas are rare neoplasms, frequently misdiagnosed, resulting in inappropriate clinical management. To date, a large clinicopathologic study has not been reported. One hundred and forty-six cases diagnosed between 1970 and 1999 were retrieved from the files of the Armed Forces Institute of Pathology. Histologic features were reviewed, immunohistochemistry analysis was performed (n = 85), and patient follow-up was obtained (n = 110). The patients included 74 (50.7%) females and 72 (49.3%) males. Tumors of the skin were much more common in males than females (1.7:1). There was an overall mean age at presentation of 42.4 years, with a range of 0.3–88 years. The overall mean age at presentation was significantly younger for skin primaries (36.2 years) than for ear (50.1 years) and nasal cavity (47.1 years) primaries. Symptoms were in general non-specific and reflected the anatomic site of involvement, affecting the following areas in order of frequency: scalp skin (40.4%), ear and temporal bone (26%), and sinonasal tract (24%). The tumors ranged in size from 0.5 up to 8 cm, with a mean size of 2.3 cm. Histologically, the majority of tumors were meningothelial (77.4%), followed by atypical (7.5%), psammomatous (4.1%) and anaplastic (2.7%). Psammoma bodies were present in 45 tumors (30.8%), and bone invasion in 31 (21.2%) of tumors. The vast majority were WHO Grade I tumors (87.7%), followed by Grade II (9.6%) and Grade III (2.7%) tumors. Immunohistochemically, the tumor cells labeled for EMA (76%; 61/80), S-100 protein (19%; 15/78), CK 7 (22%; 12/55), and while there was ki-67 labeling in 27% (21/78), <3% of cells were positive. The differential diagnosis included a number of mesenchymal and epithelial tumors (paraganglioma, schwannoma, carcinoma, melanoma, neuroendocrine adenoma of the middle ear), depending on the anatomic site of involvement. Treatment and follow-up was available in 110 patients: Biopsy, local excision, or wide excision was employed. Follow-up time ranged from 1 month to 32 years, with an average of 14.5 years. Recurrences were noted in 26 (23.6%) patients, who were further managed by additional surgery. At last follow-up, recurrent disease was persistent in 15 patients (mean, 7.7 years): 13 patients were dead (died with disease) and two were alive; the remaining patients were disease free (alive 60, mean 19.0 years, dead 35, mean 9.6 years). There is no statistically significant difference in 5-year survival rates by site: ear and temporal bone: 83.3%; nasal cavity: 81.8%; scalp skin: 78.5%; other sites: 65.5% (P = 0.155). Meningiomas can present in a wide variety of sites, especially within the head and neck region. They behave as slow-growing neoplasms with a good prognosis, with longest survival associated with younger age, and complete resection. Awareness of this diagnosis in an unexpected location will help to avoid potential difficulties associated with the diagnosis and management of these tumors.     

Oral administration of antioxidants improves skin wound healing in diabetic mice

Oxidative stress aggravates several long‐term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan‐induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post‐wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b⁺ and Ly6G⁺ cells) and reduced levels of KC, TNF‐α, IL‐1β, and IL‐12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG⁺/CD206^? macrophages whereas CD206⁺/MIG^? macrophages were decreased. Cytokines IL‐12p40, TNF‐α, IL‐1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia.     

The natural history of functional morbidity in hospitalized older patients

This study provides data on changes in the functional status of older patients that are associated with acute hospitalization. Seventy-one patients over the age of 74 admitted to the medical service of Stanford University Hospital between February and May 1987 received functional assessments covering seven domains: mobility, transfer, toileting, incontinence, feeding, grooming, and mental status. Assessments were obtained by report from the patient's caregiver (or the patient when he or she lived alone) for 2 weeks before admission; from the patient's nurse on day 2 of hospitalization and on the day before discharge; and again from the caregiver (or patient) 1 week after discharge. The sample had a mean age of 84, covered 37 Diagnostic Related Groups, and had a median length of stay of 8 days. Between baseline and day 2, statistically significant deteriorations occurred for the overall functional score and for the individual scores for mobility, transfer, toileting, feeding, and grooming. None of these scores improved significantly by discharge. In the case of mobility, 65% of the patients experienced a decline in score between baseline and day 2. Between day 2 and discharge, 67% showed no improvement, and another 10% deteriorated further. These data suggest that older patients may experience a burden of new and worsened functional impairment during hospitalization that improves at a much slower rate than the acute illness. An awareness of delayed functional recovery should influence discharge planning for older patients. Greater efforts to prevent functional decline in the hospitalized older patient may be warranted.