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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 37 records · Page 2Linked to original sources

[Criteria for selection of patients for bariatric surgery].

Because of the high prevalence of co-morbid conditions and poor life expectancy a Body Mass Index (BMI) of 40 kg/m(2) or more is an indication for surgery in a fully informed, consenting adult in optimal medical condition to tolerate general anaesthesia. Patients with BMI of 35-40 kg/m(2) and the existence of one or more serious obesity-related conditions ameliorated by weight loss, such as hypertension, pulmonary insufficiency, non-insulin-dependent diabetes mellitus etc., are also candidates for surgical treatment. The bariatric surgeon should use these international criteria as guidelines only, not strict rules. Attempts on the part of internists and more frequently insurance carriers to require documented failure of previous non-operative treatment is not meaningful.

Body Mass Index↗

[Restrictive procedures in the treatment of morbid obesity -- vertical banded gastroplasty vs. adjustable gastric banding].

Vertical banded gastroplasty (VBG) has been in clinical use since 1979 and the adjustable gastric banding (AGB) since 1985. The aim of this study was to compare the outcome, short- and long-term complications of the two procedures. Within a period of 9 years (1992-2001) 1 011 gastric restrictive procedures were performed by two surgeons in the course of a prospective nonrandomized comparative trial. 563 VBG's via laparotomy and 448 laparoscopic AGB's were included into the study. The mean BMI of the patients was 46 kg/m 2 in both groups. The mean duration of follow up was 60 months (range 6 to 108 months). No statistical significant difference in outcome in terms of weight loss, reduction of co-morbidity and improvement in quality of life following ASGB or VBG was observed. The hospital mortality rate was 0.3 % (2 VBG, 1 AGB). The overall reintervention rate for long-term complications was 15.6 % for the VBG and 7 % for the AGB group (p < 0.0001). The AGB is entirely reversible and the less invasive procedure preserving an intact anatomy of the stomach. A trend in favour of the AGB is observed.

Adolescent↗

[Malabsorption methods in bariatric surgery].

In Europe, the incidence of morbid obesity amounts approximately 1% of a nation's population. At the time being, a surgical procedure represents the only effective long-term therapy of morbid obesity. In this regard, the gastric bypass is the most common surgical method in the USA, also gaining relevancy in Europe. The development, the basic principle and the actual operation technique are shown. The mode of functioning, complications, surgical alternatives, risks, results and outcome are discussed. Over the past years, bariatric procedures and techniques have been improved, which resulted in a reduction of the risk and in an improvement of the results. Long- term success can be achieved regarding weight reduction and decrease of comorbidities. The gastric bypass is a safe and effective surgical procedure in the treatment of morbid obesity.

Anastomosis, Roux-en-Y↗

[Intragastric stimulation (IGS) for treatment of morbid obesity].

The technique of implantable gastric stimulator (IGS(R)) placement for treatment of morbid obesity is described. There are three components of the IGS, the programming system, the lead and the electrical stimulator itself. It is placed in the anterior abdominal wall. It is connected to the bioplar lead that is positioned in the muscle wall of the stomach. The nominal parameters were: pulse width 208 micro sec 24 hours per day, pulse rate 40 Hertz and amplitude 6.2-10.0 mA. Fourty eight patients have been treated using techniques that were developed and refined around the world in a prospective open study. 32 and 7 patients, resp. were available for investigation after 6 and 15 months. Twenty-seven (56 %) intra-operative gastric penetrations occurred, as noted on operative gastroscopy, without any clinical sequelae. Six patients (12 %) showed lead dislodgements and a new procedure for lead replacement. There were no operative deaths. All procedures were successfully completed laparoscopically. Two connections required revision (4 %) because the leads were not fully inserted into the lead connector of the generator. No abscess formation or severe complication were noted. The excessive weight loss after 15 months ranged to 32 %. The operation for IGS placement is safe and simple to perform. Attention to technical details is essential for safe performance of the procedure.

Clinical Trials as Topic↗

Evaluation of safety and reliability in an infant reciprocal walking orthosis.

In response to new demands for infant walking orthoses consideration was given to the development of a device for this category of patient. A specially developed hip joint with the required structural properties (Woollam et al., 2001) provided an opportunity for this development. Earlier structural assessment, and limited cyclic load testing of key elements of the orthosis (primarily the body brace), confirmed that a safe device for evaluation with patients could, theoretically, be produced. A provisional prototype was therefore designed and manufactured for initial structural testing of the complete infant orthosis (Stallard et al., 2001). Efficiency of walking is strongly influenced by the lateral rigidity of the orthosis. Monitoring the structural performance of the provisional infant design indicated it would equal or improve on the stiffness of that achieved in the adult specification. Additionally, relative strength was comparable with the adult version, which has proven to be safe and reliable in many years of routine prescription. This, together with the limited cyclic testing of the complete orthosis (Stallard et al., 2001), gave confidence that it was safe to proceed with controlled field evaluation of the infant design when supplied as a rehabilitation engineering device within the provisions of an ISO9001 and EN46001 QA System. This additional study of controlled patient use, and further representative cyclic load testing in parallel with the field evaluation, had established the long-term structural safety of the orthosis. Wider application is now to be introduced through completion of the EC (European Community) Medical Devices Directive formalities.

Humans↗

Quantification of the expression level of the gene encoding the catalytic subunit of telomerase in testicular tissue specimens predicts successful sperm recovery.

BACKGROUND: The objective of the present study was to evaluate the quantitative detection of human telomerase reverse transcriptase (hTERT) mRNA as a new molecular diagnostic parameter in the work-up of testicular tissue specimens from patients presenting with non-obstructive azoospermia. M ETHODS: hTERT mRNA expression was quantified in 49 cryopreserved testicular tissue specimens by fluorescence real-time RT-PCR in a LightCycler. This was paralleled by conventional histological work-up in all tissue specimens and additional semithin sectioning preparation in cases with maturation arrest (n = 20) and Sertoli cell-only syndrome (SCOS; n = 12). RESULTS: The average normalized hTERT expression (N(hTERT)) was 136.1 +/- 41.7 copies (mean +/- standard deviation) in tissue specimens with presence of haploid germs cells, N(hTERT) = 48.2 +/- 21.0 copies in those with maturation arrest and N(hTERT) = 2.7 +/- 2.8 copies in those with SCOS. The discriminant analysis showed that detection of N(hTERT) was able correctly to classify 89.0% of the investigated tissue specimens. CONCLUSIONS: Our results demonstrate that quantitative detection of hTERT mRNA expression in testicular tissue enables a molecular-diagnostic subclassification of spermatogenesis disorders. Quantitative detection of hTERT in testicular biopsies is thus well suited for predicting successful sperm recovery in patients with azoospermia and is a useful molecular diagnostic parameter for supplementing the histopathological evaluation.

Adult↗

Subtle developmental abnormalities in the inferior olive: an indicator of prenatal brainstem injury in the sudden infant death syndrome.

Subtle quantitative abnormalities in neuronal populations derived from the rhombic lip (i.e. arcuate nucleus at the ventral medullary surface, external granular layer of the cerebellum) have been reported in victims of the sudden infant death syndrome (SIDS). In this study, we examined the inferior olive, a major rhombic lip derivative, to determine if subtle rhombic lip abnormalities also involve this nucleus in SIDS. We analyzed the number and density of neurons and reactive astrocytes in the inferior olive in 29 SIDS cases and 29 controls. Computer-assisted cell counting procedures were used in sections stained with hematoxylin and eosin/Luxol fast blue. There was a significant difference in the postconceptionally age-adjusted mean for neuronal density between SIDS cases (7,687 +/- 255 neurons/mm(3)) and controls (8,889 +/- 255 neurons/mm(3)) (p = 0.002). The difference in age-adjusted mean neuronal number between SIDS cases (1,932 +/- 89 neurons/2 sections) and controls (2,172 +/- 89 neurons/2 sections) was marginally significant (p = 0.063). Reactive astrocytes were present in the inferior olive in SIDS cases, but their number, density, and developmental profile were not significantly different from that of control infants dying of diverse known causes. SIDS victims found dead in cribs, beds, and sofas, prone or supine had subtle olivary abnormalities, suggesting that affected infants are at risk in various sleeping situations. We propose that at least some SIDS victims experience intrauterine brainstem injury including the olivo-arcuato-cerebellar circuitry derived from the rhombic lip. These observations provide future directions for SIDS research concerning the role of early insults in pregnancy, the rhombic lip, and the interactions of the ventral medulla and cerebellum in cardioventilatory control.

Age Factors↗

HER-2/neu expression in germ cell tumours.

AIMS: To determine the rate of HER-2/neu positivity of germ cell tumours by immunohistochemistry (IHC) and by fluorescence in situ hybridisation (FISH). PATIENTS/METHODS: Ninety six archival, paraffin wax embedded pathology specimens were chosen from four groups of germ cell tumours. IHC for HER-2/neu was performed with the HercepTest kit; FISH analysis was performed with the INFORM assay and confirmed with a centromere 17 probe. RESULTS: Twenty two of 96 specimens overexpressed the HER-2/neu protein when measured by IHC. Only three specimens showed HER-2/neu gene amplification by FISH. There was no correlation between the results obtained by IHC and FISH. CONCLUSIONS: The lack of concordance between IHC and FISH makes it unlikely that overexpression of the HER-2/neu protein in germ cell tumours is of prognostic or therapeutic relevance. Because of the low rate of HER-2/neu gene amplification in germ cell tumours, a clinical trial of trastuzumab treatment in patients with germ cell tumours is not warranted.

Gene Expression↗

Transvaginal bone anchors in female stress urinary incontinence: poor results.

OBJECTIVE: This study evaluates the results of a minimally invasive technique for correcting female stress urinary incontinence by transvaginal implantation of pubic bone anchors. PATIENTS AND METHODS: Female stress urinary incontinence was treated by fixing a gelatin-coated Dacron sling between two miniature titanium anchors with Prolene sutures. RESULTS: A total of 26 patients (median age 57.2 years) underwent the sling procedure. The follow-up examination was performed after 11.4 months on average. Stress incontinence showed a median improvement from grade 2 to grade 0.5 (p = 0.01), although only 16 of the 26 patients were completely continent. Urethral pressure and functional length were not significantly influenced. Impaired vaginal wound healing was seen in 14 of the 26 patients (53.8%), and 13 of them underwent revision. All patients affected (15/26, 57.7%) as well as 1 with uneventful healing showed sensory urge symptoms or detrusor instability (7/26, 26.9%). The correlation between impaired wound healing and detrusor instability was highly significant (p < 0.003). 17 of the 26 patients (65.3%) were dissatisfied or very dissatisfied with the intervention. The unfavorable results did not significantly correlate with the patients' age, the number of previous operations, or the surgeon's skill. CONCLUSION: In view of the poor vaginal wound healing and the resultant irritative symptoms, transvaginal bone anchoring with fixation of a Dacron sling must be regarded as an unsuitable technique.

Bone Screws↗

Structural design and performance of a rear support walking frame.

Rear support walking frames provide predetermined vertical support for patients with dysfunctional lower limbs that have limited active control; the support is provided through a spring-loaded boom hinged on an upright stanchion mounted at the rear of a wheeled frame within which the patient ambulates. The application of these frames for total-body-involved cerebral palsy patients, in combination with a walking orthosis, has highlighted a number of practical problems that need to be addressed for the system to become fully viable. A composite material prototype walking frame has been developed that permits the patient to be transferred by a single carer without the need to use inappropriate manual handling techniques. The frame has improved structural properties, with stiffness in the sagittal and coronal planes increasing by between 50 and 100 per cent. Evaluation with patients showed that the greater structural stiffness permitted the objective of improved continuity of walking to be achieved. The strength of the frame is such that it can accommodate patients of up to 80 kg, more than twice that possible in the earlier system. Since the structural yield point is approximately twice the maximum working load, the device should not be prone to unacceptable fatigue characteristics. Despite the use of carbon composite materials (which have brittle failure characteristics), the mode of failure is of progressive collapse and is therefore inherently safe. The successful outcome of prototype testing has justified production development. Work is now proceeding on a design that incorporates further improvements in structural performance and ease of manufacture.

Biomechanical Phenomena↗

Multidose flurbiprofen 8.75 mg lozenges in the treatment of sore throat: a randomised, double-blind, placebo-controlled study in UK general practice centres.

The flurbiprofen 8.75 mg lozenge is a novel formulation that combines a demulcent effect with the analgesic activity of a non-steroidal anti-inflammatory drug. Previous controlled clinical studies have demonstrated the single- and multi-dose efficacy of these lozenges over placebo. The current study reflected the treatment of sore throat in general practice, investigating multiple dose efficacy where patients also had access to concomitant antibiotics and rescue medication. The efficacy of flurbiprofen 8.75 mg lozenge over placebo was confirmed: there was a significant difference in pain relief obtained from flurbiprofen 8.75 mg versus placebo, along with a significant reduction of difficulty in swallowing from the time of first assessment and significantly greater reductions in throat soreness and difficulty in swallowing throughout the study period. Additionally, significant benefit over placebo was demonstrated where concomitant antibiotic use was introduced, indicating that flurbiprofen 8.75 mg lozenges can be co-administered when antibiotic therapy is appropriate. No significant safety issues were identified.

Adult↗

Response of saccadic eye movements to alcohol in African American and non-Hispanic white college students.

BACKGROUND: The primary goal of this study was to evaluate how race and sex interact with the effects of a moderate dose of alcohol on different ocular control subsystems in African American (AA) and non-Hispanic white American (WA) college students. METHODS: Horizontal visually guided (VG) saccades and antisaccades (AS) of 80 young adult, healthy, AA and WA college students were recorded with an infrared system. Subjects ingested 10 aliquots of ethanol at 3 min intervals, with the aggregate dose precalculated to yield a peak breath alcohol concentration (BrAC) of 80 mg%. Data from the measures performed at baseline and the ascending and descending limbs of the BrAC at approximately 65 mg% were compared across race and sex by multivariate analysis of variance. A no-alcohol control session, performed in 20 of the subjects, documented test-retest reliability of the VG and AS measurements. RESULTS: Both AA and WA groups demonstrated slowing of AS and VG saccades after alcohol administration, but there was no significant effect of 65 mg% alcohol on VG accuracy or AS errors. AS latency recovered toward baseline values, whereas the slowing of VG latency/velocity progressed, during alcohol exposure. There were significant differences between AA and WA groups in the time course of VG latency after alcohol but not in most other dependent measures. No significant effects for sex were observed in any of the saccade measures. The faster disappearance of alcohol in WA compared with AA was replicated, and some measures demonstrated a significant, albeit small, negative correlation between the alcohol disappearance rate and impairing effects of alcohol on saccades. CONCLUSIONS: Prolonged latencies and unchanged percentage of errors reflect a differential effect of alcohol on neural function in specific areas (parietal eye field, superior colliculus, and frontal eye areas). Race may interact with the effect of ethanol on saccadic eye movements in a college student population.

Adult↗

Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET(A) receptor antagonism.

Endothelin-1 (ET-1) is a vasoconstrictor peptide which stimulates proliferation in vitro in different cell types, including colorectal cancer cells. Raised ET-1 levels have been detected both on tissue specimens and in the plasma of patients with cancers. To investigate the role of ET-1 in colorectal cancer: (i) ET-1 plasma levels in patients with colorectal cancer were measured by radioimmunoassay: group 1 = controls (n = 22), group 2 = primary colorectal cancer only (n = 39), group 3 = liver metastases only (n = 26); (ii) ET-1 expression in primary colorectal cancer specimens (n =10) was determined immunohistochemically and (iii) the effect of intraportally infused antagonists to the two ET-1 receptors, ET(A) and ET(B), on the growth of liver metastases in a rat model was assessed. ET-1 plasma levels were significantly increased in both patients with primary tumour and patients with metastases, compared to controls (P < 0.01, 3.9 +/- 1.4, 4.5 +/- 1.5, vs. 2.75 +/- 1.37 pg/ml, respectively). Immunohistochemically, strong expression of ET-1 was found in the cytoplasm, stroma and blood vessels of cancers, unlike the normal colon where only the apical layer of the epithelium, vascular endothelial cells and surrounding stroma were positively stained. In the rat model, there was significant reduction in liver tumour weights compared to controls, following treatment with the ET(A) antagonist (BQ123) 30 min after the intraportal inoculation of tumour cells (P < 0.05). These results suggest ET-1 is produced by colorectal cancers and may play a role in the growth of colorectal cancer acting through ET(A) receptors. ET(A) antagonists are indicated as potential anti-cancer agents.

Adult↗

Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity.

Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC(50) = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of 1a led to 1c, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of 1c with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC(50) of 1.2 nM in the Src enzymatic assay, an IC(50) of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

Animals↗