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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 73 records · Page 4Linked to original sources

Toxicological and chemical assessment of ordinance compounds in marine sediments and porewaters.

Toxicological and chemical studies were performed with a silty and a sandy marine sediment spiked with 2,6-dinitrotoluene (2,6-DNT), 2,4,6-trinitrophenylmethylnitramine (tetryl), or 2,4,6-trinitrophenol (picric acid). Whole sediment toxicity was analyzed by the 10-day survival test with the amphipod Ampelisca abdita, and porewater toxicity tests assessed macro-algae (Ulva fasciata) zoospore germination and germling growth, sea urchin (Arbacia punctulata) embryological development, and polychaete (Dinophilus gyrociliatus) survival and reproduction. Whole sediments spiked with 2,6-DNT were not toxic to amphipods. The fine-grained sediment spiked with tetryl was also not acutely toxic. The tetryl and picric acid LC50 values in the sandy sediment were 3.24 and 144 mg/kg dry weight, respectively. The fine-grained sediment spiked with picric acid generated a U-shaped concentration-response curve in the amphipod test, with increased survival both in the lowest and highest concentration. Grain-size distribution and organic carbon content strongly influenced the behavior of ordnance compounds in spiked sediments. Very low concentrations were measured in some of the treatments and irreversible binding and biodegradation are suggested as the processes responsible for the low measurements. Porewater toxicity varied with its sedimentary origin and with ordnance compound. The sea urchin embryological development test tended to be the least sensitive. Tetryl was the most toxic chemical in all porewater tests, and picric acid the least toxic. Samples spiked with 2,6-DNT contained a degradation product identified as 2-methyl-3-nitroaniline (also known as 2-amino-6-nitrotoluene), and unidentified peaks, possibly degradation products, were also seen in some of the picric acid- and tetryl-spiked samples. Degradation products may have played a role in observed toxicity.

Amphipoda↗

Optimizing local anesthesia during 10-core biopsy of the prostate.

OBJECTIVES: To examine, in a prospective, randomized study, the effect of different anesthetic techniques versus no anesthesia in a 10-core prostate biopsy. Reports thus far have shown a high variability in assessing the pain intensity of prostate biopsies and the effectiveness of anesthesia. METHODS: Ultrasound-guided 10-core prostate biopsy was performed. Patients were prospectively randomized into four groups: no local anesthesia (group 1); anesthetic block of the prostatic plexus (group 2); local anesthesia onto the capsula of the apex (group 3); and a combination of the anesthesia used for groups 2 and 3 (group 4). The degree of pain was recorded using the visual analog scale/numeric analog scale (VAS/NAS) score. RESULTS: The study included 187 patients. Results were assessed in 170 patients: 44 in group 1, 44 in group 2, 40 in group 3, and 42 in group 4. In group 1 (no anesthesia), 2 (4.5%) of 44 patients had no pain during biopsy (VAS/NAS = 0); the pain was mild (VAS/NAS of 1 to 4) in 38 (86.4%), moderate (VAS/NAS of 4 to 7) in 3 (6.8%), and severe (VAS/NAS of greater than 7) in 1 (2.3%) of 44 patients. The mean pain scores were 2.33 in group 1, 1.68 in group 2 (P = 0.05), 1.07 in group 3 (P <0.001), and 1.23 in group 4 (P <0.001). Pain caused by the local anesthesia itself was 0 in group 1, 1.52 in group 2 (P = 0.001), 1.05 in group 3 (P = 0.001), and 1.79 in group 4 (P = 0.001). CONCLUSIONS: Local anesthesia significantly reduces pain. An injection onto the capsule at the apex was the most effective technique. It is technically easier to perform than an anesthetic block of the prostatic plexus and can be recommended.

Aged↗

Quantification of telomerase activity, porphobilinogen deaminase and human telomerase reverse transcriptase mRNA in testicular tissue - new parameters for a molecular diagnostic classification of spermatogenesis disorders.

The aim of the study was to evaluate the quantitative detection of human telomerase reverse transcriptase (hTERT) mRNA and telomerase activity as new molecular diagnostic parameters for a subclassification of spermatogenesis disorders. Telomerase activity was detected by a quantitative telomerase PCR ELISA, and hTERT mRNA expression was quantified by fluorescence real-time RT-PCR in a LightCycler in cryopreserved testicular tissue specimens. This was paralleled by a histological workup. The discriminant analysis showed that detection of normalized hTERT expression was able to correctly classify 89.0% of the investigated tissue specimens into the subgroups of full spermatogenesis, maturation arrest or Sertoli-cell-only syndrome. In contrast, discriminant analysis revealed an only 58% accuracy of telomerase activity for the investigated tissue specimens. This study shows that the quantification of hTERT expression in testicular tissue by real-time fluorescence RT-PCR is well suited for correctly classifying spermatogenesis disorders and proved to be markedly superior to the determination of telomerase activity.

Biopsy↗

Intestinal and renal handling of oxalate in magnesium-deficient rats. Evaluation of intestinal in vivo 14C-oxalate perfusion.

OBJECTIVE: To clarify in vivo, using isolated small intestinal loops perfused with radioactive 14C-oxalate, whether intestinal hyperabsorption or reduced secretion is important in magnesium deficiency (MgD), as this is a potential cause of calcium oxalate urolithiasis. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were either fed a standard diet (control, 12 rats) or a magnesium-deficient diet (MgD, 12 rats) for 19 weeks. One hour before the animals were killed, a defined length of a small intestinal loop was isolated and filled with 5 mL of 0.9% NaCl and a defined amount of intravenous 14C-oxalate applied. Using this method it was possible to determine the secretion of unlabelled oxalate into the intestinal lumen, from the specific activity in plasma. RESULTS: Plasma oxalate levels doubled under MgD; urinary calcium and phosphorus also increased significantly, while urine oxalate tended to decrease. The secretion of oxalate into the intestinal lumen of MgD animals increased significantly, by five times that of the control. The relative supersaturation for calcium oxalate remained constant. Elementary analysis of renal tissue showed an increase in calcium and phosphorus under MgD, in the sense of nephrocalcinosis, but no concretions were detected (no nephrolithiasis). CONCLUSION: In contrast to earlier studies, there is no evidence that hyperoxaluria is responsible for the possible development of urolithiasis in MgD. This was confirmed by calcium phosphate deposits in renal tissue, even though there was no evidence of oxalate urolithiasis. The increase in plasma oxalate seems to be completely compensated by strongly increased oxalate secretion into the intestinal lumen.

Animals↗

Alfuzosin in the treatment of high leak-point pressure in children with neurogenic bladder.

OBJECTIVE: To decrease the detrusor leak-point pressure (LPP) of > 40 cmH2O in children with a neurogenic bladder, using the alpha1-adrenergic blocking agent alfuzosin. PATIENTS AND METHODS: Videocystometry was used to measure the detrusor LPP and several other variables before and 3 weeks after the oral administration of alfuzosin (2.5-7.5 mg/day) in 17 children (mean age 6.3 years) with an upper motor neurone lesion. RESULTS: The mean (sd) detrusor LPP decreased from 68 (37) to 46 (31) cmH2O (P < 0.01), reflex volume (defined as the volume at the first uninhibited bladder contraction of > 15 cmH2O) increased from 78 (69) to 112 (118) mL (+ 44%), bladder compliance increased from 9.3 (6.1) to 19.6 (14.6) mL/cmH2O (+ 111%), maximal vesical pressure decreased from 84 (40) to 70 (47) cmH2O (- 17%), and the mean number of uninhibited bladder contractions decreased from 6.3 to 3.5 (- 44%). The therapy was well tolerated; side-effects were rare and not severe. Intermittent catheterization could be avoided in six children. CONCLUSION: Alfuzosin decreases the detrusor LPP in children with a neurogenic bladder caused by an upper motor neurone lesion, significantly and therapeutically, and should be considered as an alternative or addition to intermittent catheterization and anticholinergic drugs in selected patients.

Adolescent↗

[Development, state of the art and future perspectives of surgery for morbid obesity].

Obesity is the most common form of malnutrition and morbid obesity is increasingly recognized as a major health concern. Drug treatments of the morbid obese have entirely failed in the long run. These circumstances have constituted incentives for surgeons to develop techniques resulting in malabsorptive or restrictive effects on food intake. Several techniques achieve weight loss through both these mechanisms and most likely also by changing the gastrointestinal signalling system. Within the last 50 years surgery for morbid obesity has been developed stepwise, like other surgical methods. More than 50 surgical anti-obesity techniques have been described. Half a dozen techniques have been left over and are performed mainly laparoscopically now a days. The outcome of these techniques over the last 30 years is reported in this article. It is the aim to illustrate that bariatric surgery is safe and so far more long-term efficient than any other technique available for the treatment of morbid obesity.

Cross-Sectional Studies↗

[Bariatric surgery -- stereotypes and paradigms].

Many physicians regard obesity as a sin and treat fat patients with disdain befitting a moral leper. Non-bariatric physicians, being a product of our culture, seem more likely to have an obesity paradigm close to that of the public. Many members of the public regard obesity surgery as dangerous. Many insurers reject morbid obese patients from bariatric surgical treatment with the paradigmal statement that obesity is totally the fault of a fat person. These medical experts do not accept obesity as a disease (which WHO does) and therefore social courts also reject applications of patients who want to undergo bariatric surgery. Morbid obesity is a multifactorial problem with genetic, biochemical, hormonal, environmental, behavioral and cultural elements. It is recognized as an extreme health hazard which is rarely the result of an aberrant moral problem or true addictive behavior. We need to change effectively the negative paradigms towards obesity and its surgery from some of our colleagues, hospital administration, medical insurers and the public. The existing prejudices are not acceptable.

Attitude of Health Personnel↗

[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↗