Repair of soft tissue to bone using a biodegradable suture anchor

A decrease in blood androgen levels is well documented in women who experience natural or surgical menopause. This change may be associated with various negative effects on bone metabolism in addition to psychosocial and sexuality aspects of life. A review of published information on androgen replacement therapy shows that major benefits may be achieved; unfortunately, only minimal quality information is available to help clinicians make decisions about this type of therapy. In this review, we point out the potential benefits and risks to bone, lipid and carbohydrate metabolism, and sexuality; in addition, we discuss potential risks of neoplasms and virilizing somatic changes. Long-term, physiologic, and well-designed androgen replacement studies should be performed to obtain the knowledge needed to guide therapy in this important area.     

Deterioration of endocrine ophthalmology after radioiodine therapy in Graves' disease?

AIM: Our goal was to show the development of EO in RITH and compare it with the outcome of surgery or thyreostatic therapy. METHODS: In this study 103 cases of an RITH at 82 patients were performed. The EO findings were measured before RITH and several times afterwards by the same experienced researcher according to the following criteria: 1. subjective complaints, 2. NOSPECS-classification, 3. exophthalmometry, 4. by photo. The observation period was at least 12 months. The measured dosage to the thyroid gland was on average 210 +/- 80 Gy. In 57 cases no EO and in 46 cases an EO of grades I to IV before therapy occurred. RESULTS: In 11 cases there was an improvement and in 8 cases a worsening of the EO. In 84 cases the EO findings remained unchanged. Our data pointed towards the fact that with an achieved dosage to the thyroid of less than 200 Gy, a pretherapeutic thyroid gland volume greater than 55 ml, or implementation of RITH with preexisting EO without accompaning cortison therapy can worsen the EO findings. CONCLUSION: In comparison to surgical or thyreostatic therapy there was no increased risk of EO during or subsequent to RITH under cortison.     

Medical therapy of inflammatory bowel disease

In the past years the advances in therapy of IBD have been characterized mainly by the more widespread use of immunosuppression. Especially azathioprine is currently used in Crohn's disease with methotrexate as the second-line immunosuppressive drug. Cyclosporin may become a drug of choice to treat severe ulcerative colitis but its effect in the long term is probably insufficient. Topically acting glucocorticosteroids have emerged as a valuable safer alternative to standard glucocorticosteroids (GCS) in right ileocolonic Crohn's disease but GCS have no role in maintenance therapy. The most significant development in recent years is the introduction of immunomodulatory treatments using cytokines and anticytokines. The first data show that anti-TNF monoclonal antibodies, especially cA2, not only may result in rapid control of active Crohn's disease but also achieve rapid tissue healing. Repeated administration of cA2 maintains remission. Immunomodulation therapy creates great expectations since early reset of the immunostat might be able to control inflammation in the long term. Safety will be a key issue.     

Magnesium status in healthy free-living elderly Norwegians

With evidence on the important role of glycosaminoglycans (GAG) in the pathogenesis of endocrine ophthalmopathy (EO) having accumulated, the present study focused on the biochemical assessment of plasma GAG content in 37 EO patients as compared to 20 controls. Glycosaminoglycans were isolated from plasma samples by protein elimination, dialysis, and precipitation with ethanol and cetylpyridinium chloride. Patients (9.71, 5.09, 15.09 mg/100 ml; median, 25th, 75th percentile) exhibited significantly (p = 0.0021) higher plasma GAG levels than controls (4.6, 3.38, 6.8 mg/100 ml). Plasma GAG content was unrelated to age, sex, or antithyroid treatment. However, an even higher level of significance (p = 0.0001) was reached when discriminating between untreated patients with EO of recent onset (14.16, 10.35, 15.51 mg/100 ml) and controls. By contrast, steroid therapy of EO led to values (3.82, 1.85, 6.52 mg/100 ml) indistinguishable from those of the controls. Further statistical analysis of the results, based on a specificity of 95% for the control group, revealed a sensitivity of 91% for patients with untreated EO of recent onset, and a specificity of 100% for patients receiving steroid therapy. In comparison, plasma GAG content was determined in 8 untreated and in 6 treated EO patients by a second method already published. All untreated patients exhibited high GAG levels (median 2.23 mg/100 ml) whereas in treated EO patients normal plasma GAG values (0.17-0.34 mg/100 ml) were found. Follow-up determination of plasma GAG content in 7 patients undergoing steroid treatment unveiled a marked decrease of initially elevated values. These findings correlated well with clinical improvement of thyroid eye disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epithalamin effects on carbohydrate metabolism and cardiovascular system in patients with non-insulin dependent diabetes mellitus

Epithelamine made in Russia (Samson, St. Petersburg) was tried for effects on carbohydrate metabolism and cardiovascular system in 33 patients with non-insulin-dependent diabetes mellitus (NIDDM). Adjuvant use of epithelamine in combined treatment of NIDDM promoted a stable compensation of carbohydrate metabolism, lowering of glycosylated hemoglobin, immunoreactive insulin. There was also a moderate hypotensive effect and improvement of left ventricular diastolic function.     

Severe anoxia with and without concomitant brain atrophy and neuropsychological impairments

Significant anoxia may cause a variety of neuropathologic changes as well as cognitive deficits. We have recently seen 3 patients who have suffered severe anoxic episodes all with initial Glasgow Coma Scores (GCS) of 3 with sustained coma for 10-14 d. All 3 patients had extended hospitalizations and rehabilitation therapy. A neuropsychological test battery was administered and volumetric analyses of MRI scans were carried out in each case at least 6 mo postinjury. Two of the patients display distinct residual cognitive and neuropathologic changes while 1 patient made a remarkable recovery without evidence of significant morphological abnormality. These three cases demonstrate, that even with similar admission GCS, the outcome is variable and the degree of neuropsychological impairment appears to match the degree of morphologic abnormalities demonstrated by quantitative MR image analysis. An important finding of this study is that even though subjects with an anoxic insult exhibit severe cognitive and memory impairments along with concomitant morphologic changes, their attention/concentration abilities appear to be preserved. MR morphometry provides an excellent means by which neural structural changes can be quantified and compared to neuropsychological and behavioral outcomes.     

Quantitative cerebral blood flow and metabolism determination in the first 48 hours after severe head injury with a new dynamic SPECT device

OBJECTIVE: To determine cerebral blood flow (CBF) and metabolism in the acute phase after severe head injury by a new dynamic SPECT device using 133Xenon and to evaluate a possible role of CBF and metabolism in the determination of prognosis. DESIGN: Prospective study. SETTING: General intensive care unit in a universitary teaching hospital. SUBJECTS: 23 severely head injured patients having CT scan and CBF determination, intracranial pressure (ICP) and jugular bulb oxygen saturation monitoring in the first 48 hours. MEASUREMENTS AND MAIN RESULTS: CBF varied from 18.0 to 60.0 ml/100 g/min. No correlation was found between early CBF and severity of trauma evaluated with the Glasgow Coma Score (GCS) (F = 2.151, p = 0.142) and between CBF and prognosis at 6 months evaluated with Glasgow outcome score (GOS) (F = 0.491, p = 0.622: rs = 0.251, p = 0.246). CMRO2 was depressed in relation to the severity of injury, specifically ranging from 0.9 +/- 0.5 ml/100 g/min in patients with GCS 3 to 1.7 +/- 0.8 ml/100 g/min in patients with GCS 6-7. In no patient with CMRO2 less than 0.8 ml/100 g/min was a good outcome observed. A significant correlation was found between GCS and GOS (rs = 0.699, p = 0.0002), between CMRO2 and GOS (F = 4.303, p = 0.031; rs = 0.525, p = 0.013) and between AJDO2 and GOS (F = 3.602, p = 0.046; rs = 0.491, p = 0.017). Fronto-occipital ratio (F/O) of CBF distribution was significantly lower than normal values (chi 2 = 18.658, p = 0.001) but did not correlate either with prognosis (chi 2 = 1.626, p = 0.443) or with severity (chi 2 = 1.913, p = 0.384). CONCLUSIONS: CBF in the first 48 hours after trauma varies within a large range of values and is not correlated with severity and prognosis. Clinical evaluation with GCS and CMRO2 are much more reliable indicators of severity of head trauma and have a significant role in the determination of prognosis. F/O ration is significantly altered from normal values confirming "post-traumatic hypofrontalism" but does not correlate with severity and prognosis.     

Deletion of the p16 gene and microsatellite instability in carcinoma arising in pleomorphic adenoma of the parotid gland

Dogs and cats with cancer have significant alterations in carbohydrate, protein, and fat metabolism, which can result in cancer cachexia and subsequently can decrease quality of life, reduce response to therapy, and shorten survival time. Nutritional modulation may be beneficial in the treatment of cancer patients to reverse these metabolic alterations. There is evidence that foods relatively low in simple carbohydrates with moderate amounts of high-quality protein, fiber, and fat (especially fats of the omega-3 fatty acid series) are beneficial for pets with cancer. In addition, certain supplemental nutrients may have potential to reduce the risk of developing cancer, or the growth and metastases of established malignant disease. Nutritional intervention can be a powerful tool for controlling malignant disease and for reducing toxicity associated with chemotherapy and radiation therapy.     

Increased serum levels of macrophage colony-stimulating factor (M-CSF) in alpha- and beta-thalassaemia syndromes: correlation with anaemia and monocyte activation

The Glasgow Coma Scale (GCS) is routinely used in the acute care setting after traumatic brain injury (TBI) to guide decisions in triage, based on its ability to predict morbidity and mortality. Although the GCS has been previously demonstrated to predict mortality, efficacy in prediction of functional outcome has not been established. The purpose of this study was to assess the value of the acute GCS in predicting functional outcome in survivors of TBI. This study used the Multicenter National Institute on Disability and Rehabilitation Research TBI Model Systems database of 501 patients who had received acute medical care and inpatient rehabilitation within a coordinated neurotrauma program for treatment of TBI. Initial and lowest 24 hr GCS scores were correlated with the following outcome measures: the Disability Rating Scale (DRS), Rancho Los Amigos Levels of Cognitive Functioning Scale (LCFS), and cognitive and motor components of the Functional Independence Measure (FIM(SM)-COG and FIM(SM)-M). Outcome data were collected at admission to and discharge from the inpatient TBI rehabilitation unit. Correlation analysis revealed only modest, but statistically significant, relationships between initial and lowest GCS scores and outcome variables. Initial and lowest GCS score comparison with outcome demonstrated the following correlation coefficients: admission DRS, -0.25 and -0.28; discharge DRS, -0.24 and -0.24; admission LCFS, 0.31 and 0.33; discharge LCFS, 0.27 and 0.25; admission FIM-COG, 0.36 and 0.37; discharge FIM-COG, 0.23 and 0.23; admission FIM-M, 0.31 and 0.31; discharge FIM-M, 0.25 and 0.21. The GCS as a single variable may have limited value as a predictor of functional outcome.     

The characteristics of disorders in carbohydrate metabolism and insulin and C-peptide secretion in patients with chronic glomerulonephritis in developing chronic kidney failure

The authors studied hormonal regulation of carbohydrate metabolism by secretion of insulin, C-peptide in 86 patients with chronic glomerulonephritis with different functional condition of the kidneys. There was a decrease in glucose tolerance, basal and reactive hyperinsulinemia, elevated level of C-peptide (relative insulin insufficiency). Mechanism of arising changes in the carbohydrate and insulin metabolism is complex and multicomponent. This includes renal lesion and consequent inhibition of hormone metabolism. Intensification of glomerular filtration is associated with inhibition of filtration of insulin and C-peptide derivants. Accumulation of nitrogen metabolism products results in changed response of pancreatic beta-cells to glucose. General disturbances of metabolism are accompanied by increasing levels of hormonal and nonhormonal contrainsular substances.     

Phase I pharmacokinetics and limited sampling strategies for the bioreductive alkylating drug EO9. EORTC Early Clinical Trials Group

EO9 is a synthetic indoloquinone which was designed to undergo redox cycling and formation of alkylating intermediates under bioreductive conditions. As part of a phase I clinical trial, EO9 plasma disposition was evaluated in 20 patients receiving 2.7-15 mg/m2i.v. weekly for 3 weeks. Pharmacokinetic studies were performed with the first and third dose of therapy and nine blood samples were obtained over 30 min postinfusion. Plasma EO9 was detected using HPLC UV and the disposition described by a two-compartment model. Wide variability in EO9 pharmacokinetics was observed. EO9 was rapidly eliminated from plasma with a median systemic clearance of 3.5 l/min/m2 (range 1.2-9.8), apparent volume of distribution of 6.2 l/m2 (1.0-34.9) and t 1/2 beta of 10.1 min (2.2-63.0). Substantial intrapatient variability was observed for all pharmacokinetic parameters. Linear regression and Bayesian methods were developed and validated for estimation of EO9 plasma AUC using up to three samples postinfusion. The use of two or three plasma samples provided precise estimation with acceptable prediction bias. In addition, a Bayesian algorithm offered more robust estimation of AUC and is preferable to linear regression models for future EO9 population pharmacokinetic analysis.     

The antidyslipoproteinemic activity of ufibrate in patients with non-insulin-dependent diabetes mellitus

Ufibrate (150 mg daily) was found to have a beneficial effect on main parameters characterizing lipid metabolism, with no effect being exerted on carbohydrate metabolism, as evidenced by three months' follow-up of 24 patients aged 42 to 65 presenting with insulin-nondependent type II diabetes mellitus and hyperlipidemia. Ufibrate appeared to be a most efficacious long-term drug treatment option, particularly so in those patients presenting with initially high blood levels of a great many of lipid fractions.     

Changes in glycolysis and glycogenolysis in tissues and level of certain hormones in blood and urine from rats with varying lengths of cold adaptation

The production phase changes of adaptive hormones and the activity of key glycolytic and glycogenolytic enzymes were studied in Wistar rats exposed to a long-term (1-49 day) cold (+5 degrees C) exposure. The allosteric mechanisms responsible for regulating carbohydrate metabolism were shown to interact with endocrine ones and to modulate their effects. In cold acclimation, activation of the sympathoadrenal system aimed not only at increasing carbohydrate metabolism, but at enhancing the metabolism of fats and calorigenic effects.     

The effect of oral ritodrine on maternal and fetal carbohydrate metabolism

The reported growth-promoting effects of the beta-sympathomimetic compound, ritodrine, have been investigated. The carbohydrate tolerance of eight pregnant women was found to be unaffected by treatment with oral ritodrine over a ten-week period. A further observation that the carbohydrate metabolism of the newborn infants of these women was within normal limits tends to discount possibility that any growth-promoting action ritodrine may have on the fetus is mediated through a diabetogenic effect on the mother.     

Association of benign prostatic hyperplasia with male pattern baldness

OBJECTIVE: To determine whether crude extracts of ginseng saponin (GCS), containing the active ingredients from Panax ginseng and used as an aphrodisiac in oriental countries, relax corpus cavernosal smooth muscle in the rabbit. MATERIALS AND METHODS: Corpus cavernosal strips were prepared from rabbit penises. Isometric tension changes, recorded with a pressure transducer, in response to various drugs and electrical stimulation were assessed in an organ chamber, after active muscle tone had been induced by 10 micromol/L phenylephrine. RESULTS: GCS (0.2-8.0 mg) relaxed the smooth muscle of rabbit corpus cavernosum (SMRCC) pre-contracted with phenylephrine in a dose-dependent manner. GCS at 0.75 mg significantly enhanced the relaxation of SMRCC induced by electrical field stimulation. The relaxation induced by 0.2-8.0 mg GCS was significantly attenuated by atropine (1 micromol/L), methylene blue (100 micromol/L) and N-omega-nitro-L-arginine methyl ester (L-NAME, 10 micromol/L). However, there was no significant difference in the attenuation of GCS-induced relaxation of SMRCC by adding vasoactive intestinal peptide antagonists or indomethacin. In addition, the decreasing rate of GCS-induced relaxation of SMRCC by methylene blue and L-NAME was greater than that by atropine. L-arginine (10 mmol/L) reversed the inhibitory effect induced by L-NAME (1 mmol/L) on the attenuation of GCS-induced relaxation. CONCLUSIONS: These data suggest that GCS, as a nitric oxide donor, induces the relaxation of SMRCC through the L-arginine/nitric oxide pathway. For the clinical application of ginseng saponin, further studies are required to clarify the active subfraction(s) of GCS.     

Reduction of the indoloquinone anticancer drug EO9 by purified DT-diaphorase: a detailed kinetic study and analysis of metabolites

DT-diaphorase has been implicated in the activation and mechanism of cytotoxicity of the investigational indoloquinone anticancer drug EO9. Here, we have used a highly purified DT-diaphorase isolated from rat Walker tumour cells to provide unambiguous evidence for the ability of this enzyme to catalyze reduction of EO9 and to provide a more detailed characterization of the reaction. Under the conditions used hypoxia had no effect on the initial rate of this reduction but did effect the nature and stability of metabolites formed. Electron spin resonance (ESR) spectrometry studies showed that DT-diaphorase reduced EO9 to a highly oxygen-sensitive metabolite that is probably the hydroquinone. In the presence of air, this metabolite is auto-oxidized to generate both drug- and oxygen-based radicals. Comproportionation:disproportionation reactions may also be involved in the generation of these radical species. The identification of these metabolites may contribute to the understanding of the molecular mechanism of DNA damage and cytotoxicity exerted by EO9.     

Gianotti-Crosti syndrome associated with cytomegalovirus antigenemia after bone marrow transplantation

Gianotti-Crosti syndrome (GCS) is characterized by a distinctive self-limiting acral papular or papulovesicular eruption associated with an underlying viral illness. It has not been previously reported in patients post-bone marrow transplantation. We report a 6-year-old Japanese boy who underwent allogeneic bone marrow transplantation from an unrelated donor for acute lymphoblastic leukemia (ALL) in second remission. He had clinical and histopathologic findings characteristic of GCS and evidence of subclinical infection with cytomegalovirus (CMV) detected by CMV antigenemia assay. It is likely that CMV is the causative agent for the GCS in this case.     

Histochemical detection of lymphatic drainage pathways in the middle nasal meatus

AIM: Assessment of the antihypertensive effect of doxazosin, alpha-1 blocker, as well as its action on lipid and carbohydrate metabolism, microcirculation and platelet function in patients with non-insulin-dependent diabetes mellitus (NIDDM). MATERIALS AND METHODS: Doxazosin (tonocardin) treatment was given for 11 weeks to 33 NIDDM patients with concomitant hypertension. The clinical examination comprised evaluation of central hemodynamics, vessels of the fundus of eye, lipid and carbohydrate metabolism, renal function, platelet aggregation. RESULTS: Tonocardin produced a fall in the systolic blood pressure (BP) by 14%, in the diastolic BP--by 17%. The 24-h profile of BP, lipid and purine metabolism, microcirculation of the vessels of the fundus of eye also improved. Total peripheral vascular resistance, left ventricular myocardial mass and platelet aggregation. Carbohydrate metabolism remained unchanged. CONCLUSION: Monotherapy with tonocardin (2-8 mg/day) is effective and safe in the treatment of arterial hypertension in NIDDM patients.     

Rapid assay of plasma acetate by gas chromatography: evaluation and comparison with two other methods

Human plasma acetate is derived from colonic fermentation of fiber and endogenous metabolism of dextrose and fatty acids. Acetate may have regulatory functions in hepatic carbohydrate metabolism. Intake of dietary fiber is associated with several beneficial effects on carbohydrates and lipids metabolisms. To study theses effects a valid and automated method for routine analysis of acetate in plasma is necessary. After oral administration of lactulose to healthy human volunteers, the concentration of plasma acetate was measured by head space gas chromatography (HS-GC), vacuum distillation gas chromatography (VD-GC) and enzymatic spectrometric method (ES). The method HS-GC was linear to 0.5 mmol.l-1 (n = 5, r = 0.998), the detection limit is 0.005 mmol.l-1. Within-day variation (CV) was 3.60% and day-to-day variation was 4.5% (0.1 mmol.l-1). The coefficients of correlation between CG-ET/CG-DsV and CG-ET/E-M are 0.903 (p = 0.0001) and 0.54 (p = 0.006) respectively, the mean square errors are respectively 0.118 and 0.138 mmol.l-1. The variation curves of plasma acetate measured by GC versus time show peak concentration of 0.323 to 0.380 mmol.l-1 at 120 min.     

In vivo bioavailability and metabolism of topical diclofenac lotion in human volunteers

OBJECTIVE: To characterize the long-term impact of four hormone therapy regimens on insulin and glucose concentrations measured during a standard oral glucose tolerance test. RESEARCH DESIGN AND METHODS: The Postmenopausal Estrogen/Progestin Intervention Study was a 3-year placebo-controlled randomized trial to assess effects of four hormone regimens on cardiovascular risk factors. This efficacy analysis describes glucose and insulin concentrations from 788 adherent women at baseline and at 1 and 3 years' postrandomization. RESULTS: When compared with women taking placebo, those taking conjugated equine estrogen (CEE) at 0.625 mg/day with or without a progestational agent had mean fasting insulin levels that were 16.1% lower, mean fasting glucose levels 2.2 mg/dl lower, and mean 2-h glucose levels 6.4 mg/dl higher (each nominal P < 0.05). No significant differences were apparent between women taking CEE only versus the three progestin regimens: medroxyprogesterone acetate (MPA) at 2.5 mg daily (continuous MPA), MPA at 10 mg on days 1-12 (cyclical MPA), and micronized progesterone (MP) (cyclical) at 200 mg on days 1-12. The impact of hormone therapy on insulin and glucose depended on baseline levels of fasting insulin and 1-h glucose (P < 0.05). However, the treatment effects on carbohydrate metabolism appeared to be consistent across participant subgroups formed by lifestyle, clinical, and demographic characteristics. CONCLUSIONS: Oral hormone therapy involving 0.625 mg/day of CEE may modestly decrease fasting levels of insulin and glucose. Postchallenge glucose concentrations are increased, however, which may indicate delayed glucose clearance.