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Biomedical subjects

A A Martin

Publications and source records attributed to A A Martin.

At least 19 recordsLinked to original sources

Combined effects of carbon dioxide laser and fluoride on demineralized primary enamel: an in vitro study.

This in vitro study aimed at evaluating the efficacy of a CO(2) laser (10.6 microm) alone or combined with acidulated phosphate fluoride (APF) on the inhibition of lesion progression in primary enamel. The specimens were treated with/without CO(2) laser and/or APF and submitted to pH cycling. Microhardness analysis was performed and the enamel mineral loss values were obtained. The groups treated with laser and/or APF presented lower mineral loss when compared to the control group (p < 0.05). Laser irradiation alone or combined with APF decreased lesion progression in primary enamel. However, the combined treatment did not show any significant additional effect.

Acidulated Phosphate Fluoride↗

Study of normal colorectal tissue by FT-Raman spectroscopy.

FT-Raman spectroscopy was employed to study normal human colorectal tissues in vitro with the aim of evaluating the spectral differences of the complex colon mucous in order to establish a characteristic Raman spectrum. The samples were collected from 39 patients, providing 144 spectra for the statistical analysis. The results enable one to establish three well-defined spectroscopic groups of non-altered colorectal tissues that were consistently checked by statistical (clustering) and biological (histopathology) analyses: group 1 is represented by samples with the presence of epithelial layer, connective tissue papillae, and smooth muscle tissue; group 2 comprises tissues with epithelial layer and connective tissue papillae; group 3 presented mostly fatty and slack conjunctive tissue. The study reveals the existence of an intrinsic spectral variability for each patient that must be considered when sampling tissues fragments to build a spectral database. This is the first step for future studies and applications of Raman spectroscopy to optical biopsy and diagnosis of colorectal cancer.

Adult↗

Using the laser-induced fluorescence spectroscopy in the differentiation between normal and neoplastichuman breast tissue.

This article reports results of the in vitro study for potential evaluation of the laser-induced fluorescence spectroscopy in the differentiation between normal and neoplastic human breast tissue. A coumarine dye laser pumped by nitrogen laser generated an excitation light centered at 458 nm. In order to collect the fluorescence signal was used an optical fiber catheter coupled to a spectrometer and CCD detector. Fluorescence spectra were recorded from normal and neoplastic (benign and malignant) human breast tissue, adding up 94 different areas. The discrimination between normal and neoplasm groups reach a sensitivity and specificity of 100%.

Breast Diseases↗

Comorbidity assessment using the Index of Coexistent Diseases in a multicenter clinical trial.

BACKGROUND: The Hemodialysis (HEMO) Study is a multicenter trial designed to determine whether hemodialysis dose and membrane flux affect survival. Comorbid conditions are also important determinants of survival, and thus, an accurate and reliable method to assess comorbidity was required. Comorbidity was being assessed at baseline and annually in the HEMO Study using the Index of Coexistent Disease (ICED). We describe the instrument, its implementation in the HEMO Study, and the results of comorbidity assessment in the first 1000 randomized patients in the trial. METHODS: The ICED aggregated the presence and severity of 19 medical conditions and 11 physical impairments within two scales: the Index of Disease Severity (IDS) and the Index of Physical Impairment (IPI). The final ICED score was determined by an algorithm combining the peak scores for the IDS and IPI. The range of the ICED was from 0 to 3, reflecting increasing severity. RESULTS: Study personnel at 15 clinical centers were trained to update and abstract data from the dialysis medical records. Availability of data, measures of construct validity, and measures of reliability were adequate; 99.8% and 60.6% of patients had comorbid conditions in at least one IDS or IPI category, respectively. The distribution of patients by ICED level was 0 (0.2%), 1 (34.9%), 2 (31.2%), and 3 (33.7%). In multivariable analysis, the following factors were significantly associated with more severe comorbidity: older age, diabetes and other causes of renal disease, a lower level of education, employment status (unemployed and retired), longer duration of dialysis, and lower serum creatinine. There was a significant variation in the severity of comorbidity among clinical centers after adjustment for other factors. The R2 of the model was 25.3%, indicating that a substantial proportion of the variation in the ICED was not explained by these factors. CONCLUSIONS: We conclude that comorbidity assessment using the ICED is feasible in multicenter clinical trials of dialysis patients. There is a large burden of comorbidity in dialysis patients, which is not well explained by the cause of renal disease, demographic, and socioeconomic factors and common clinical and laboratory measurements. These variables should not be considered substitutes for comorbid conditions in case-mix adjustment. Comorbidity assessment is useful to describe the sample population, to improve the precision of the treatment effect, and to use possibly as an outcome measurement.

Comorbidity↗

Plasminogen activator inhibitor type-1 and interleukin-6 in haemolytic uraemic syndrome.

OBJECTIVE: Because haemolytic uraemic syndrome (HUS) is an important cause of renal dysfunction in children, the availability of prognostic markers of disease severity could assist in identifying those at risk of developing long-term sequelae. The aim of this study was to test the hypothesis that plasma levels of plasminogen activator inhibitor type-1 (PAI-1) and interleukin-6 (IL-6) in children at the time of diagnosis of HUS would predict renal function outcome in terms of glomerular filtration rate (GFR). METHODOLOGY: Fourteen children suffering from diarrhoeal HUS were studied. Plasma samples were assayed for PAI-1 and IL-6, and GFR was measured at intervals after discharge from hospital. Twelve months following their recovery from HUS, the children were allocated to one of two outcome groups depending on whether GFR was above (Good Outcome, n = 9), or below (Poor Outcome, n = 5) 80 mL/min per 1.73 m2. RESULTS: Elevated concentrations of PAI-1 were found in 4 of 5 Poor Outcome and 4 of 9 Good Outcome children. At the same time, increased concentrations of IL-6 were observed in 3 of 5 Poor Outcome and 3 of 9 Good Outcome children. Renal function continued to be compromised in four Poor Outcome children 36 months after diagnosis. CONCLUSIONS: Our data show that PAI-1 and IL-6 are elevated in the plasma of some children at the time of diagnosis of HUS, but that neither is a definitive prognostic marker of poor outcome 3 years later.

Child↗

Factors associated with the prevalence of arteriovenous fistulas in hemodialysis patients in the HEMO study. Hemodialysis (HEMO) Study Group.

BACKGROUND: Arteriovenous (AV) fistulas are the vascular access of choice for hemodialysis patients, but only about 20% of hemodialysis patients in the United States dialyze with fistulas. There is little information known about the factors associated with this low prevalence of fistulas. METHODS: Multiple logistic regression analysis was used to evaluate the independent contribution of factors associated with AV fistula use among patients enrolled in the HEMO Study. The analysis was conducted in 1824 patients with fistulas or grafts at 45 dialysis units (15 clinical centers). RESULTS: Thirty-four percent of the patients had fistulas. The prevalence of fistulas varied markedly from 4 to 77% among the individual dialysis units (P < 0.001). Multiple regression analysis revealed five demographic and clinical factors that were each independently associated with a lower likelihood of having a fistula, even after adjustment for dialysis unit. Specifically, the prevalence of fistulas was lower in females than males [adjusted odds ratio (AOR) 0.37, 95% CI, 0.28 to 0.48], lower in patients with peripheral vascular disease than in those without (AOR 0.55, 95% CI, 0.38 to 0.79), lower in blacks than in non-blacks (AOR 0.64, 95% CI, 0.46 to 0.89), lower in obese patients (AOR per 5 kg/m(2) body mass index, 0.76, 95% CI, 0.65 to 0.87), and lower in older patients (AOR per 10 years, 0.85, 95% CI, 0.78 to 0.94). The differences in the prevalence of fistulas among the dialysis units remained statistically significant (P < 0.001) after adjustment for these demographic and clinical factors. Finally, there were substantial variations in the prevalence of fistulas even among dialysis units in a single metropolitan area. CONCLUSIONS: Future efforts to increase the prevalence of fistulas in hemodialysis patients should be directed at both hemodialysis units and patient subpopulations with a low fistula prevalence.

Age Distribution↗

Haemolytic-uraemic syndrome outbreak caused by Escherichia coli O111:H-: clinical outcomes.

In South Australia in 1995, we treated 20 children with haemolytic-uraemic syndrome associated with Escherichia coli O111:H-. The source of the outbreak was contaminated locally produced semi-dry fermented sausage (mettwurst). One child died of multiple haemorrhagic cerebral infarcts. Eighteen children required renal dialysis (for a median of 14 days); 12 months after discharge five still had significant impairment of renal function. Other major complications included colonic necrosis (3), cerebral haemorrhage/infarction (3), convulsions (4), and glucose intolerance (2). Although E. coli O111:H- has been associated with sporadic cases of haemolytic-uraemic syndrome, this was the first large outbreak reported in Australia.

Animals↗

Effects of insulin-like growth factor-I and LR3IGF-I on regional blood flow in normal rats.

Two studies were conducted to investigate the haemodynamic effects of IGF-I and its analogue LR3IGF-I in normal anaesthetised rats. Infusion of IGF-I intravenously, at a dose of 125 micrograms/kg/h, for 20 min in the first study resulted in renal blood flow being significantly elevated by 35% above baseline. Mean arterial blood pressure (MABP) at this IGF-I dose fell by 18% of baseline, with LR3IGF-I also causing a significant decline in MABP (by 15%) at the dose of 125 micrograms/kg/h. In the second study the intravenous administration of IGF-I or LR3IGF-I, at a dose of 125 micrograms/kg/h, over a period of 60 min, resulted in MABP being significantly lowered by 25% of baseline values. Regional blood flow rates were determined using radioactive microspheres, 15 microns in diameter, injected systemically at the end of the peptide infusion period. The gastrocnemius, a representative skeletal muscle, was the only vascular region to show a significant increase in blood flow after IGF-I (by 58%) or LR3IGF-1 (by 308%) infusion. Vascular resistance in the brain was significantly reduced after infusion of IGF-I (by 60%) or LR3IGF-I (by 48%) as compared with vehicle. Skeletal muscle vascular resistance was also reduced by IGF-I (by 41%) and more particularly by LR3IGF-I (by 77%) in comparison to vehicle. These alterations to vascular tone produced by IGF infusion may be related to the central nervous system and systemic cardiovascular side-effects that have been reported during IGF-I administration in humans.

Animals↗

Effects of growth hormone on insulin-like growth factors and binding proteins before and after renal transplantation.

Three short children with severe chronic renal failure were treated with recombinant human growth hormone (rhGH) for 2 years. Each received a transplant in the 2nd year. Serum collected before and during rhGH therapy was analysed retrospectively by Western ligand blot and immunoblotting techniques. In addition, radioimmuno-assays for insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), acid-labile subunit (ALS) and IGFBP-1 were performed. IGFBPs in serum, detected by Western ligand blot, were identified as IGFBP-3, -2, -1 and -4 by immunoblot. The serum concentration of IGF-I in each child rose approximately fourfold with rhGH before transplantation and subsequently remained elevated. IGFBP-3 levels rose to double the pretreatment value, but dropped to normal levels following transplantation, while ALS rose with rhGH treatment and remained increased after transplantation. IGFBP-1 levels changed little with rhGH but fell following transplantation. A low molecular weight form of IGFBP-3 was noted at 30 kilodaltons on immunoblot which was not clearly seen on the ligand blot. IGFBP-2 was present as a distinct band on Western ligand blot before transplantation and appeared decreased in intensity subsequently. IGFBP-1, seen on immunoblot clearly before transplant, disappeared after the transplant. rhGH successfully improved growth in these children, in association with a fourfold increase in IGF-I levels, which was maintained following transplantation. The reduction in IGFBPs following transplantation suggests correction of impaired clearance by the diseased kidney.

Blotting, Western↗

Effects of chronic renal failure on plasma clearance of insulin-like growth factor I, des-(1-3)IGF-I, and LR3IGF-I.

Using a rat model of chronic renal failure (CRF), we examined insulin-like growth factor I (IGF-I) clearance, degradation, organ distribution, and IGF binding profiles in plasma. The effects of IGF-binding proteins (IGFBP) on IGF clearance and degradation in CRF were studied using the IGF-I analogues des-(1-3)IGF-I and LR3IGF-I, which bind poorly to IGFBP. Although total clearance of IGF-I was not significantly altered in CRF, half-life and area under the curve were increased in the rapid distribution phase and were reduced in the slow elimination phase. Total clearance of LR3IGF-I was significantly increased. Reduced binding of IGF-I in the 150-kDa complex and increased binding to smaller-molecular-weight IGFBP were observed in CRF. Increased degradation of both IGF-I and LR3IGF-I was associated with reduced IGF binding in the 150-kDa complex. The results suggest that the accumulation of lower-molecular-weight IGFBP with reduced IGF binding in the 150-kDa complex, associated with increased degradation of peptide, may explain, at least in part, the reduced bioactivity of IGF-I observed in CRF.

Animals↗

The effects of cage size and complexity on the behaviour of captive common marmosets, Callithrix jacchus jacchus.

Conditions of captivity of primates used in biomedical research may have deleterious effects on the welfare of the animals and consequently on the reliability of the research. We investigated the effects of cage size and cage complexity, two fundamental characteristics of captive conditions, on the behaviour of the common marmoset (Callithrix jacchus jacchus). We found an increase in the general level of activity and significant variation in the frequencies of specific behaviours with an increase in cage size and also with cage complexity. Stereotyped behaviours, which occurred in the small cages, were never exhibited in the large cages. The effect of the novelty of the changed conditions was also assessed and found to be significant for some behaviours. We also measured the time taken to capture an animal, a task frequently performed by the animal technician, under the various cage conditions. Capture time increased significantly in the larger cages, but the overall effect of the changes to the marmosets' housing conditions on the animal technician's work was not regarded as substantial. We conclude that the welfare of captive marmosets is enhanced by the provision of larger and more complex cages, and that such cages do not significantly affect the efficiency of the research laboratory.

Animal Welfare↗

Penile intracavernosal substance abuse.

A complete workup for a 36-year-old man with unexplained inguinal adenopathy and an indurated, enlarged penis and scrotum included urine cultures for bacteria, fungi, and acid-fast bacilli; scrotal ultrasound; computed tomography of the abdomen and groin; a retrograde urethrogram; a cystogram; duplex penile Doppler blood flow studies; and a surgical inguinal lymph node dissection. Pathologic examination of the excised lymph node revealed lipoid granulomatous lymphadenitis. After receiving definitive treatment for a psychotic condition, the patient acknowledged a 2-year history of intracavernosal injection of gelatinous vitamin E.

Adult↗

Morphometric and immunohistochemical characterization of human liver regeneration.

Regeneration in human liver is characterized in part by the formation of ductular structures, so-called ductular hepatocytes in massive hepatic necrosis and bile ductules in mechanical biliary obstruction. In an attempt to characterize the liver regenerative process, we performed image analysis and immunohistochemical staining of the ductular structures in these well defined human liver disorders, 13 cases of massive hepatic necrosis and 9 cases of mechanical biliary obstruction. The proliferation index was determined and the expression of several antigens was localized by immunohistochemical staining using antibodies to alpha-fetoprotein, alpha-1-antitrypsin, albumin, and cytokeratin 19. The ductular structures in adult human liver were compared with the developing ductal plates in 11 fetal livers, ranging in age from 9 to 36 weeks of gestation. Image analysis demonstrated that the mean total area, mean nuclear area, and mean cell size of ductular hepatocytes were significantly larger than those of bile ductules (p < 0.05). The proliferation index of ductular hepatocytes and bile ductules was significantly higher than that of hepatocytes of normal livers (p < 0.02). Bile ducts, bile ductules in mechanical biliary obstruction, ductular hepatocytes in massive hepatic necrosis, and the ductal plate cells in fetal liver showed strong staining for cytokeratin 19, which characterizes intermediate filaments associated with bile duct epithelial cells. Albumin, a liver-specific protein, and alpha-1-antitrypsin, a protease inhibitor, were strongly expressed in ductal plate cells of fetal liver, hepatocytes, and ductular hepatocytes, whereas bile duct cells and bile ductules were negative for albumin. In summary, ductular hepatocytes demonstrate morphometric and immunophenotypic features of both hepatocytes and biliary epithelial cells, whereas bile ductules share characteristics primarily with fetal ductal plates and mature bile ducts. These findings suggest that ductular hepatocytes in massive hepatic necrosis may serve as bipotential progenitor cells, and bile ductules in mechanical biliary obstruction are related to ductal plates of fetal liver.

Aging↗

Carcinoma in situ of the urinary bladder. Clues to host involvement in human carcinogenesis.

BACKGROUND: Carcinoma in situ (CIS) of the urinary bladder is a neoplasm of uncertain biologic behavior. It rarely occurs as the primary disease and exists most often in association with high grade, invasive tumors. The unfavorable prognosis ascribed to CIS may not be due to tumor-related factors but to low host resistance or to host-tumor relationships established for previous or co-incident invasive cancers. The scant available evidence indicates that a large proportion of patients with primary CIS have a low frequency of muscle invasion and death from disease. METHODS: Of 2000 patients with bladder neoplasms in our pathology files and tumor registry, 102 had CIS confirmed on histologic review. There were 29 cases of primary CIS and 73 cases of secondary CIS. These cases were compared, with an emphasis on patient outcome. RESULTS: The data indicate that primary and secondary CIS are histologically identical lesions whose effect on patients is related mainly to the presence of multifocal disease, often associated with previous or coincident invasive cancers. Progression or death from disease is unusual among patients presenting with primary CIS but common among individuals with CIS associated with other bladder cancers. CONCLUSION: The authors suggest that the appearance of urothelial CIS identifies patients with at least localized resistance to the development of invasive bladder cancer. The degree of patient resistance to carcinogenic events leading to bladder carcinoma is manifested by the type, grade, and stage of their initial neoplasms.

Adult↗

Enhanced body growth in uremic rats treated with IGF-I and growth hormone in combination.

The efficacy of seven days treatment with IGF-I (1.7 mg/kg/day), growth hormone (GH) (2 mg/kg/day), IGF-I+GH (1.7 mg/kg/day + 2 mg/kg/day) or vehicle, in promoting growth was investigated in female Sprague-Dawley rats with 5/6 nephrectomies (N = 8 per group). Treatment commenced after chronic renal failure had been present for seven weeks. Significant increases in body weight gain were found in all groups versus control, with IGF-I+GH causing the greatest response, and increased body weight gains correlating with increased nitrogen retention. GH treatment alone significantly stimulated food intake. IGF-I+GH resulted in close to additive increases in food conversion efficiency (18.8%, 21.5% and 39.6% increases with IGF-I, GH and IGF-I+GH, respectively, over control levels) and longitudinal bone growth (39%, 37% and 67% increases with IGF-I, GH and IGF-I+GH, respectively, vs. control). Serum insulin and cholesterol levels significantly decreased with IGF-I and IGF-I+GH treatment. Creatinine clearance did not change, suggesting there were no effects of treatment on kidney function. Although IGF-I at the doses used did not result in a greater anabolic response than GH, IGF-I+GH caused significantly enhanced growth while reducing serum insulin and cholesterol levels.

Animals↗

Effects of insulin-like growth factor-I peptides in rats with acute renal failure.

The effect of insulin-like growth factor-I (IGF-I) administration on body weight gain and the rate of recovery of renal function was investigated in rats following an acute episode of renal ischaemia. Since the des(1-3)IGF-I and LR3IGF-I variant forms of IGF-I have been shown to be more potent than IGF-I, their effects were also examined. Acute renal failure was produced in male Sprague-Dawley rats by clamping both renal arteries for 45 min. Treatment was commenced at the time of renal artery occlusion with vehicle (0.1 mol acetic acid/l; control group), IGF-I (2.0 mg/kg per day), des(1-3)IGF-I (2.0 mg/kg per day) or LR3IGF-I (1.5 mg/kg per day) by s.c. osmotic pump, and continued for 7 days, with rats being held in metabolism cages. Glomerular filtration rate (GFR) was estimated by the use of 51Cr-EDTA continuously infused i.p. via osmotic pump. Following the episode of renal ischaemia, body weight gain and nitrogen retention were significantly improved in all three peptide-treated groups, and serum urea concentrations were reduced in the groups treated with IGF-I and des(1-3)IGF-I. However, there was no evidence of the variants having any increased potency over the growth effects of IGF-I itself. GFR was significantly reduced, urine output was increased and urinary concentrating ability was reduced in all groups compared with normal rats, with no significant effect of the IGF peptides being apparent. A closer examination of the acute effects of LR3IGF-I on renal function was undertaken by measuring GFR for 3 days before and 3 days after renal ischaemia in two groups of rats, treated for the latter 3 days with either vehicle (controls) or LR3IGF-I (1.5 mg/kg per day). LR3IGF-I treatment following renal ischaemia resulted in a significantly greater fall in GFR than in controls, urinary osmolality was also significantly reduced, and fractional excretion of sodium was increased. In addition, there was histological evidence of a greater degree of tubular epithelial calcification in the kidneys of the rats treated with LR3IGF-I. This study showed that administration of IGF peptides at doses sufficient to cause significant improvement in anabolic status did not improve renal function in rats following an acute episode of renal ischaemia. Indeed the LR3IGF-I variant of IGF-I had a deleterious effect on renal function in the early stage of the recovery period.

Acute Kidney Injury↗

Rapid changes in plasma concentrations of insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding proteins during anaesthesia in young sheep.

Halothane anaesthesia in young sheep results in greatly increased plasma binding capacity for radiolabelled insulin-like growth factor (IGF), as demonstrated using size-exclusion chromatography. Most of the increased binding was at an estimated molecular mass range of 30-50 kDa, with a smaller increase evident at 130-150 kDa. These changes were not evident in control animals which had food withheld for the same period. The progressive increase in plasma radioligand binding during anaesthesia was the net result of a rise in circulating levels of a 29-31 kDa IGF-binding protein (IGFBP), as shown by ligand blotting, and declining plasma concentrations of IGF-I and IGF-II. Recovery from anaesthesia was accompanied by the restoration of plasma IGFs and the IGFBP towards pre-anaesthesia concentrations. The induced IGFBP was provisionally identified as IGFBP-1 because it bound anti-IGFBP-1 antiserum but not antibodies against IGFBP-2, IGFBP-3 or IGFBP-4. The elevation of plasma IGFBP-1 immunoreactivity was associated with reduced concentrations of glucose and insulin, the regulators of IGFBP-1 in humans and rats. These results suggest that IGF experiments that require anaesthesia but assume that the anaesthetised state is representative of conscious sheep should be reassessed. A similar situation may occur with other mammalian species.

Anesthesia↗