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Biomedical subjects

M Adams

Publications and source records attributed to M Adams.

At least 55 records · Page 3Linked to original sources

Potential risk factors associated with progressive renal damage in childhood urological diseases: the role of angiotensin-converting enzyme gene polymorphism.

PURPOSE: Experimental as well as human studies have established an important role for the renin-angiotensin system in the progressive deterioration of renal function. Recently genetic polymorphism in components of the renin-angiotensin system has been associated with several cardiovascular diseases, particularly variations in the angiotensin-converting enzyme gene that involve insertion (I) or deletion (D) of a 287 bp fragment. The D variant has been associated with myocardial infarction and cardiac hypertrophy. MATERIALS AND METHODS: To assess whether this genetic variant is associated with worse prognosis in renal disorders we evaluated 70 children with congenital urological abnormalities, since a substantial number have progressive renal deterioration even after early corrective intervention. Renal deterioration was assessed by the presence or absence of radiographic evidence of parenchymal damage and serum creatinine. RESULTS: Among patients with no radiographic renal parenchymal damage angiotensin-converting enzyme genotype distribution of II, ID and DD was 24, 67 and 9%, respectively. In contrast, a significantly different angiotensin-converting enzyme genotype distribution was observed in patients with evidence of parenchymal damage, that is 10, 49 and 41% for II, ID and DD, respectively (p < 0.05, chi-square 5.0). Mean serum creatinine plus or minus standard error in the former group was normal at 0.6 +/- 0.1 mg./dl., while in those with scarring it was elevated at 1.1 +/- 0.1 mg./dl., as expected. In patients with the DD genotype an overwhelming frequency of parenchymal damage was observed, that is of all 22 with that genotype 20 (91%) had parenchymal damage. CONCLUSIONS: Considered together, these studies suggest that there are differences in the distribution of angiotensin-converting enzyme gene polymorphism in patients with congenital urological abnormalities who have evidence of renal parenchymal damage versus those who do not have such damage. Given that this genetic variation activates the renin-angiotensin system and this activation may be particularly robust in the kidney, we propose that the genotype of an individual independent of other factors modifies the likelihood of parenchymal loss in this setting.

Adolescent

Predisposing factors for individuals' Lyme disease prevention practices: Connecticut, Maine, and Montana.

OBJECTIVES: This study examined factors that predispose individuals to protect against Lyme disease. METHODS: Knowledge, attitude, and practice questions concerning Lyme disease prevention were included in the Behavioral Risk Factor Surveillance surveys in Connecticut, Maine, and Montana. A total of 4246 persons were interviewed. RESULTS: Perceived risk of acquiring Lyme disease, knowing anyone with Lyme disease, knowledge about Lyme disease, and believing Lyme disease to be a common problem were significantly associated with prevention practices. CONCLUSIONS: Predisposing factors differ substantially between states and appear related to disease incidence. Personal risk, knowing someone with Lyme disease, and cognizance about Lyme disease and acting on this information are consistent with social learning theories.

Adult

Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass.

The haemostatic system and the use of heparin during cardiopulmonary bypass (CPB) have been studied extensively in adults but not in children. Results from adult trials cannot be extrapolated to children because of age-dependent physiologic differences in haemostasis. We studied 22 consecutive paediatric patients who underwent CPB at The Hospital for Sick Children, Toronto. Fibrinogen, factors II, V, VII, VIII, IX, XII, prekallikrein, protein C, protein S, antithrombin (AT), heparin cofactor II, alpha 2-macroglobulin, plasminogen, alpha 2-antiplasmin, tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin-AT complexes (TAT), D-dimer, heparin (by both anti-factor Xa assay and protamine titration) and activated clotting time (ACT) were assayed perioperatively. The timing of the sampling was: pre heparin, post heparin, after initiation of CPB, during hypothermia, post hypothermia, post protamine reversal and 24 h post CPB. Plasma concentrations of all haemostatic proteins decreased by an average of 56% immediately following the initiation of CPB due to haemodilution. During CPB, the majority of procoagulants, inhibitors and some components of the fibrinolytic system (plasminogen, alpha 2 AP) remained stable. However, plasma concentrations of TAT and D-dimers increased during CPB showing that significant activation of the coagulation and fibrinolytic systems occurred. Mechanisms responsible for the activation of haemostasis are likely complex. However, low plasma concentrations of heparin (< 2.0 units/ml in 45% of patients) during CPB were likely a major contributing etiology. ACT values showed a poor correlation (r = 0.38) with heparin concentrations likely due to concurrent haemodilution of haemostatic factors, activation of haemostatic system, hypothermia and activation of platelets. In conclusion, CPB in paediatric patients causes global decreases of components of the coagulation and fibrinolytic systems, primarily by haemodilution and secondarily by consumption.

Adolescent

[Pre- and intraoperative localization of neuroendocrine tumors].

Previous studies of the intraoperative use of a hand-held gamma probe to localize metastases and primary tumors of colorectal cancer have shown improved assessment of tumor spread and changes in surgical management based on added information gained by radioimmunoguided surgery. Following the injection of 180 MBq [111In-DTPA-D-Phe1]-pentetreotide and/or 500 MBq 99mTc-dimercaptosuccinic acid (both for dual-radionuclide scintigraphy) preoperative somatostatin receptor imaging [11 patients with GEP tumors] and dual-radionuclide scintigraphy. (8 patients with relapsing medullary thyroid carcinomas) was performed. One patient with a metastasizing pheochromocytoma underwent 123]-MIBg scintigraphy. Results were combined with the information obtained from conventional imaging modalities. Intraoperative radiodetection was performed 24 hours after administration of [111In-DTPA-D-Phe1]-pentetreotide or 4 hours following the injection of 99mTc(V)DMSA using a hand-held gamma probe (Tec Probe 2000. Stratec, FRG). Intraoperative gamma counting localized 39 somatostatin receptor positive lesions of GEP tumors whereas preoperative receptor imaging visualized 81%, surgical palpation 41% and radiological imaging modalities localized only 31%. In 8 patients with recurrent medullary thyroid carcinoma the surgeon was successful in localizing and removing 18 tumor lesions by the help of the gamma probe. Dual-radionuclide scintigraphy revealed 77% (Octreoscan 5/18; 99mTc-V-DMSA 9/18), surgical palpation 55% and conventional imaging methods (CT, sonography) only 38% of all lesions detected intraoperatively by the hand-held gamma probe. In summary, this preliminary data show that intraoperative hand-held gamma probe detection of microscopic and occult endocrine tumors is feasible and more sensitive than external scintigraphy and conventional imaging.

Adrenal Gland Neoplasms

Practicing implant dentistry profitably.

The success of dental implants has opened up countless treatment possibilities for restorative dentists to offer to their patients. Just as our clinical paradigms have had to change because of this new technology, so too must our paradigms concerning the way we communicate with our patients change if we are to get them to say "yes" to treatment that we know that they need. Success in clinical treatment using implants requires a systematic approach. A systematic approach to communicating with your patients will allow you to have the same high degree of success with treatment acceptance that is possible with dental implants. The key to the systems we have discussed is Relationship Centered Care. A relationship is fostered and enhanced through a Comprehensive Examination Process, a structured Consultation Process utilizing the influencing process and Financial Arrangements that allow the patient to receive what they want while the office maintains the profitability that it needs. A system for calculating rational fees can be utilized that allows the practice to have control over an area that traditionally was controlled by anecdotal factors. The Pride Institute has developed this material and is presenting it to the profession so that restorative dentists can truly practice implant dentistry profitably.

Dental Implantation

A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer.

BACKGROUND: Human papillomavirus (HPV) infection, especially with type 16 or 18, is associated with cervical cancer. Two HPV proteins, E6 and E7, are consistently expressed in tumour cells. The objectives of the study were to examine the clinical and environmental safety and immunogenicity in the first clinical trial of a live recombinant vaccinia virus expressing the E6 and E7 proteins of HPV 16 and 18 (TA-HPV). METHODS: The study was an open label phase I/II trial in eight patients with late stage cervical cancer. The patients were vaccinated with a single dose of TA-HPV and kept in strict isolation to monitor local and systemic side-effects, environmental spread, and anti-E6/E7 immune responses. FINDINGS: Vaccination resulted in no significant clinical side-effects and there was no environmental contamination by live TA-HPV. Each patient mounted an antivaccinia antibody response and three of the eight patients developed an HPV-specific antibody response that could be ascribed to the vaccination. HPV-specific cytotoxic T lymphocytes, the effector mechanism most likely to be of therapeutic benefit, were detected in one of three evaluable patients. INTERPRETATION: Further studies to investigate the use ot TA-HPV for immunotherapy of cervical cancer are warranted.

Adult

Regional assignment and tissue expression of twenty-three expressed sequence tags (ESTs) from human chromosome 5.

Regional localization and expression patterns are reported for 19 expressed sequence tags (ESTs) from human chromosome 5, two of which were derived from the same transcript. Two of the ESTs correspond to genes not previously characterized in humans: a stress-activated protein kinase and nicotinamide nucleotide transhydrogenase. Expression was determined by three methods: Northern blots, PCR from tissue-specific cDNA libraries, and sequence sampling from EST sequencing projects. Six of the ESTs show no expression, and EST01986 appears to be expressed predominantly in the brain by all methods tested.

Chromosome Mapping

Mutation analysis in hereditary hemochromatosis.

The DNA of 147 patients of European origin clinically diagnosed with idiopathic hemochromatosis and 193 controls was examined for mutations of the HLA-H gene at nt 845 and nt 187. One hundred twenty-one (82.3%) of the hemochromatosis patients were homozygous and 10 (6.8%) heterozygous for the 845A (C282Y) mutation. All of the homozygous patients were also homozygous for nt 187C, and all 845A heterozygotes had at least one copy of 187C. Thus, the nt 845 and nt 187 mutations were in complete linkage disequilibrium; nt 187 was a C on all chromosomes with the 845A mutation. Eight of the 10 heterozygotes for 845A were heterozygous for 187G(H63D). The excess of heterozygotes at both nt 187 and nt 845 suggested either the presence of as yet undiscovered mutations existing in trans with 845A and in linkage disequilibrium with 187G, or that the 187G itself is a deleterious mutation, which in concert with the 845A can give rise to hemochromatosis. None of the 193 normal controls were homozygous for 845A and 29/193 (15%) were heterozygous for 845A. Although 47/193 (24.3%) of normal controls were heterozygous for the 187G mutation only two of these carried the 845A mutation. If the 187G mutation complemented the 845A mutation with high penetrance in causing hemochromatosis, then the population frequency of the two genes would require that a high proportion of patients with hemochromatosis be heterozygous for 845A and 187G. Instead, the frequency of homozygotes for the 845A mutation was much higher than that of the 845A/187G genotype. Based on our data, the penetrance of the 845A/187G genotype is only 1.5% and based on the data of Feder et al. only 0.5%. In contrast, the penetrance of the homozygous 845A/845A genotype seems to be very high. Thus, screening for this genotype should be very useful.

Alleles

Perioperative on-site haemoglobin determination: as accurate as laboratory values?

PURPOSE: This study assessed the accuracy of photometer based haemoglobin (Hb) determination technology (HemoCue) when used by different anaesthetists in situations of rapidly changing Hb values during anaesthesia. METHODS: (Part 1) In the laboratory, repeated measurements were done on 16 split samples of blood using both the Hematology Analyzer (CELL-DYN 3500 System, Abbot Laboratories, San Jose, California) and the photometer. (Part 2) Twelve patients had blood samples drawn from an arterial line for simultaneous Hb determination in the hospital laboratory and by the photometer. At the same time, capillary samples were taken from the patient's earlobe for Hb determination by the photometer. All sample collection and photometer measurements were done by the same operator. (Part 3) The Part 2 protocol was then repeated with different anaesthetists performing both the sampling and the photometer measurements. Statistical comparison was by ANOVA and a two-tailed paired t-test. RESULTS: (Part 1) Samples determined by the photometer and the laboratory were highly correlated (r2 = 1.0, P < 0.001). The average error of each method was similar ( < 4%). (Part 2) Using a 2-tailed paired t-test, the photometer arterial measurements were not different from the laboratory measurements, however the photometer capillary measurements were consistently approximately 8% higher (P = 0.003). (Part 3) When multiple operators performed the sampling there were no differences on arterial or capillary samples (r2 = 0.942, r2 = 0.851 respectively), although the variance was greater. CONCLUSIONS: The HemoCue haemoglobinometer has sufficient accuracy to support treatment decisions regarding blood transfusions.

Anesthesia