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Biomedical subjects

R Koch

Publications and source records attributed to R Koch.

At least 55 records · Page 3Linked to original sources
PubMed2002

Lipid status and long-chain polyunsaturated fatty acid concentrations in adults and adolescents with phenylketonuria on phenylalanine-restricted diet.

Blood lipid studies are reported in 25 adults and 2 adolescents with PKU who had been on phenylalanine-restricted diets for a mean period of 22.6 years (range 7-39 years). Measurements included plasma concentrations of phenylalanine, cholesterol, lipoproteins, triglycerides and fatty acid profiles, including the analysis of seven fatty acids in plasma and red blood cells. Lipid screening identified 7 subjects with significantly elevated cholesterol/HDL ratios ranging from 5.6 to 10.3. Triglyceridaemia was documented in 5 of these 7, with concentrations ranging between 0.24 and 4.5 mmol/L (219-402 mg/dl) with a mean of 3.5 mmol/L (310 mg/dl). The fatty acid analyses demonstrated slight but statistically significant reductions in the concentrations of long-chain polyunsaturated fatty acids (LCPUFA), including plasma docosahexaenoic (DHA) and arachidonic acid (AA), and red blood cell DHA concentrations. The pattern resembles that reported previously in children, but alterations in the mean levels are less severe. In six of the adult patients plasma DHA or AA concentrations were less than 50% of controls. Since DHA and AA have important physiological roles, including brain and retinal function, it is recommended that blood lipid concentrations be monitored in all patients with PKU, including adults, and that DHA and AA supplementation be provided, particularly in those patients in whom the blood concentrations of these substances are reduced significantly.

Adolescent↗
PubMed2002

Phenylketonuria in adulthood: a collaborative study.

During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural problems.

Adult↗
PubMed2002

Infrequent genetic alterations of the tumor suppressor gene PTEN/MMAC1 in squamous cell carcinoma of the oral cavity.

BACKGROUND: Fifty tumor specimens from primarily untreated patients were analyzed to elucidate the involvement of the tumor suppressor gene PTEN/MMAC1 in the development of oral squamous cell cancer. METHODS: Eight microsatellite markers, spanning 10 cM of genomic DNA located centromeric, telomeric or intragenic of PTEN/MMAC1 were used for loss of heterozygosity (LOH) and breakpoint analysis. The microsatellite panel within or in close proximity (1 cM) to the 10q23.3 locus showed a LOH rate of 12%. Complete sequence analysis of the genes coding region was performed in all 10 cases that exhibited LOH in one of the eight microsatellite markers within or around the PTEN/MMAC1 gene. Comparative multiplex PCR reactions served to screen for homozygous deletions. RESULTS: There was no association between allelic loss of the gene, overall patient survival and recurrence-free survival. Sequencing did not reveal any mutation in the coding region of PTEN/MMAC1. Differential PCR analysis failed to detect any homozygous deletion. CONCLUSIONS: We conclude that PTEN/MMAC1 gene alterations do not play a key role in tumorigenesis of oral squamous cell cancers.

Adult↗
PubMed2001

Minute SiGe quantum dots on Si(001) by a kinetic 3D island mode.

We investigated the initial growth stages of Si(x)Ge(1-x)/Si(001) by real time stress measurements and in situ scanning tunneling microscopy at deposition temperatures, where intermixing effects are still minute (< or =900 K). Whereas Ge/Si(001) is a well known Stranski-Krastanow system, the growth of SiGe alloy films switches to a 3D island mode at Si content above 20%. The obtained islands are small (a few nanometers), are uniform in shape, and exhibit a narrow size distribution, making them promising candidates for future quantum dot devices.

Journal Article↗
PubMed2001

Magnetic anisotropy of a cyclic octanuclear Fe(III) cluster and magneto-structural correlations in molecular ferric wheels.

The magnetic anisotropy of the cyclic octanuclear Fe(III) cluster [Cs subsetFe(8)[N(CH(2)CH(2)O)(3)](8)]Cl was investigated. Based on a spin Hamiltonian formalism and the consequent use of all symmetries, the magnetic anisotropy could be calculated exactly to first order, i.e., in the strong exchange limit. Experimentally, the magnetic anisotropy was investigated by magnetic susceptibility and high-field torque magnetometry of single crystals. The field and angle dependence of the torque at 1.7 K could be accurately reproduced by the calculations with one single parameter set, providing accurate results for the coupling constant and single-ion zero-field-splitting. These magnetic parameters are compared to those of several related hexanuclear ferric wheels and are discussed with respect to magneto-structural correlations for both coupling constant and single-ion anisotropy.

Journal Article↗
PubMed2001

Complete defluorination of 1,2,3,4-tetramethyl-5-(trifluoromethyl)cyclopentadiene by titanium tetrakis(dimethylamide)--selective formation of a cyclic hexanuclear titanium fluoroamide and 6,6-dimethylaminotetramethylfulvene.

1,2,3,4-Tetramethyl-5-(trifluoromethyl)cyclopentadiene (Cp*CF3-H, 1) reacts with [Ti(NMe2)4] (2) under mild conditions to give [Ti(mu-NMe2)(NMe2)(mu-F)(F)]6 (3) in nearly quantitative yield. The molecular structure of 3 consists of a ring of six [TiF2(NMe2)2] edge-bridged octahedra. Titanium complexes containing the Cp*CF3 ligand, which was the primary intention of these investigations, were not observed. C5Me4=C(NMe2)2 (4) was isolated as a by-product. The complete defluorination of an aliphatic CF3 group occurs during the reaction. The reaction mechanism involves the primary formation of a difluorofulvene intermediate C5Me4=CF2 (5), which was monitored by NMR studies. Density functional theory calculations predict a highly charged C6 atom (+0.87) in 5, which is discussed as the driving force of the reaction.

Journal Article↗
PubMed2001

Quality of life of patients with laryngeal carcinoma: a post-treatment study.

This study was designed to determine the quality of life of patients successfully treated for laryngeal cancer. A questionnaire was mailed to 233 patients. A total of 124 responses were suitable for analysis. The questionnaire consisted of three components: sociodemographic data, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ - C 30, version 2.0), and EORTC QLQ, Head and Neck Module (H & N 35). The assessment included five treatment groups: chordectomy, partial laryngectomy, irradiation as primary therapy, laryngectomy, laryngectomy and radiotherapy. The evaluation for the functional scales of the EORTC QLQ - C 30 resulted in a higher quality of life of patients with maintained larynx in comparison to laryngectomised patients. In the symptom scales, patients after laryngectomy and/or radiotherapy suffered more from fatigue, pains and appetite loss. Laryngectomees stated more financial difficulties. The evaluation of the ENT-specific EORTC module showed that patients after laryngectomy had more symptoms. Typical symptoms after radiotherapy were a dry mouth, sticky saliva and coughing. Noticeably, no differences existed among the several groups with regard to voice production. The EORTC QLQ- H & N 35 does not appear to be sensitive enough to assess this parameter.

Adult↗
PubMed2001

Sequence of melanocyte migration into human scar tissue.

Scars of human skin can on occasions provide a very useful ancillary method of identification of an unknown deceased. If the age of any visible scars can be estimated objectively, then this might be of some assistance in the identification procedure. Melanocytes migrate into scar tissue as it ages and their number within the epidermal basal layers alters during the maturation of a scar. A total of 64 scar samples, all from previous surgical sites, were taken in the course of autopsies. Each scar was stained by the H & E method and by an immunohistochemical method using polyclonal S100 antibody. The number of melanocytes in the basal layer was counted in the epidermis overlying the scar and in the adjacent epidermis. This ratio was matched with the documented age of the scar and a statistical evaluation was carried out matching the chronological age of the scars to the melanocyte/basal epidermal cells ratio. Scars with a duration between 1 and 3 years showed a mean ratio of 1.85 and a maximum ratio of 1.94, 1.8 years after a surgical operation. The number of basal melanocytes declined thereafter and reached that of the adjacent epidermis after about 10 years. The immunohistochemical detection of melanocytes can be used for the diagnostic ageing of scars which may be a valuable contribution to improve the identification of unknown deceased persons.

Autopsy↗
PubMed2001

Genetic implications for newborn screening for phenylketonuria.

The genetic implications for PKU are similar to those for any inherited disorder, but require an intimate knowledge of the dietary care required by these women. Unfortunately, today most women with PKU have discontinued dietary treatment by adulthood and find the restricted phe diet onerous and difficult. Fortunately, this is changing. "Diet for life" is the usual, although not yet universally, adopted practice today, but even so, there are women who conceive "off diet." This inhibits intellectual development of the fetus. If intensive services are provided for such women, fetal outcome can be improved by good blood phe control between 120 and 360 uM/L. Although prenatal diagnosis is available by fetal mutation studies, many women today resist the benefits of genetic counseling. Unfortunately, insurance companies often are unwilling to pay for such procedures as mutation analysis or the provision of low phe diets. Overall, public policy for the care of women with genetic disorders is in a state of flux and strong leadership is required to improve services.

Female↗
PubMed2001

Plaque, gingival health and post-operative sensitivity in titanium inlays and onlays: a randomized controlled clinical trial.

OBJECTIVES: Few clinical data on the use of titanium for restorative appliances are available. The aim of this study was to clinically evaluate titanium restorations compared to gold alloy restorations with regard to plaque, gingival health and post-operative sensitivity. METHODS: In 54 patients, 99 titanium restorations were placed. The control group comprised 56 patients with 96 high gold alloy restorations. The material was chosen by random. Each patient received one or two Class II restorations. Plaque Index (Silness and Löe, 0-3), Gingival Index (Löe and Silness, 0-3), and post-operative sensitivity (1-4, 1=none) were rated at 2 weeks, 3 months, 6 months, 12 months, and 18 months, post-operatively. RESULTS: The mean plaque scores ranged from 0.89 to 0.99 in the titanium group, and from 0.88 to 1.04 in the gold group. The mean gingival scores ranged from 0.91 to 1.07 in the titanium group, and from 0.82 to 0.99 in the gold group. The mean plaque and gingival scores of the titanium and gold group did not differ significantly at any visit (P>0.05). To evaluate post-operative sensitivity, patients with one MOD restoration each were included, resulting in 46 titanium and 44 high gold restored teeth. Mean values of the post-operative sensitivity scores in the titanium group were significantly higher than in the gold group (P<0.05). The restoration material was found to be the dominating variable with regard to post-operative sensitivity, which was not influenced by age, sex and the application of calcium hydroxide liner. CONCLUSIONS: It is concluded that neither higher plaque scores nor adverse effects on gingival health are to be expected in titanium restorations.

Adolescent↗
PubMed2001

Phenylketonuria: tyrosine beyond the phenylalanine-restricted diet.

Controversies exist on the role of tyrosine in the pathogenesis of phenylketonuria (PKU) and, consequently, on the therapeutic role of tyrosine. This review examines data and theoretical considerations on the role of tyrosine in the pathogenesis and treatment of PKU. It is concluded that treatment with tyrosine alone to replace the phenylalanine-restricted diet cannot be justified. A treatment with large neutral amino acids (LNAA) including tyrosine to restore the balance in the transport of phenylalanine and other LNAA across the blood-brain barrier deserves further investigation. Such studies should prove the safety and the efficacy of such a treatment, finding the optimal dose of all LNAA, disclosing the correct age to start and the way to monitor treatment biochemically.

Amino Acids, Neutral↗
PubMed2001

Patients with persistent APC-resistance without factor V Leiden mutation.

BACKGROUND: Activated protein C (APC) resistance and factor V Leiden mutation are major risk factors for deep venous thrombosis. Previous work has led to the view that the coagulation phenotype and the genetic defect are associated in almost all patients. It has been reported about single APC-resistant patients without associated factor V Leiden, but significance and thrombotic risk of this constellation have not yet been established. PATIENTS AND METHODS: We tested 486 consecutive patients with deep venous thrombosis, arterial disease or other than vascular disease for APC-resistance with a factor VIII based assay. RESULTS: 149 patients (31%) showed a pathological APC-ratio. Sensitivity and specificity for detection of factor V Leiden were 100% and 40%, respectively. At 6 months follow-up APC-ratio returned to normal in 55% of the patients with initial pathological APC-resistance. At 12 months follow-up 91% of the patients with persistent APC-resistance showed a pathological ratio as well. CONCLUSIONS: Patients with APC-resistance not due to factor V Leiden can be attributed to one subset with reversible APC-resistance--possibly due to a hypercoagulable state in an acute thrombotic situation, and to another with persistent APC-resistance.

Activated Protein C Resistance↗
PubMed2001

Spleen enlargement in healthy donors during G-CSF mobilization of PBPCs.

BACKGROUND: Recombinant human G-CSF is widely used to mobilize PBPCs in healthy donors for allogeneic transplantation. There have been concerns about donor safety because of splenic ruptures during G-CSF application. To address this problem, changes in splenic size in 91 healthy donors during G-CSF mobilization of allogeneic PBPCs were investigated. STUDY DESIGN AND METHODS: For mobilization, G-CSF in a dosage of 7.5 microg per kg per day was administered for 5 days and PBPC collection started Day 5. Splenic size was determined by ultrasound before G-CSF application was started and on the day of the first apheresis. RESULTS: The mean increase in splenic length was 11 mm (range, 0-28 mm; p<0.0001), whereas a mean increase of 5 mm in width (range, 0-14 mm; p<0.0001) was measured. No major side effects could be observed. There was no significant correlation between the increase in splenic size and the hematologic values, or the age and body-mass index. In a multivariant analysis, no independent risk factor for the development of a spleen enlargement over 19 mm in length and 9 mm in thickness was found in 20 percent of investigated donors. CONCLUSION: In this prospective trial, a significant spleen enlargement was observed in healthy donors during G-CSF mobilization of allogeneic PBPCs. Further investigations are needed to define the degree of spleen enlargement with higher G-CSF dosages to improve donor safety.

Blood Donors↗
PubMed2001

Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets.

Treatment of phenylketonuria (PKU) consists of restriction of natural protein and provision of a protein substitute that lacks phenylalanine but is enriched in tyrosine. Large and unexplained differences exist, however, in the tyrosine enrichment of the protein substitutes. Furthermore, some investigators advise providing extra free tyrosine in addition to the tyrosine-enriched protein substitute, especially in the treatment of maternal PKU. In this article, we discuss tyrosine concentrations in blood during low-phenylalanine, tyrosine-enriched diets and the implications of these blood tyrosine concentrations for supplementation with tyrosine. We conclude that the present method of tyrosine supplementation during the day is far from optimal because it does not prevent low blood tyrosine concentrations, especially after an overnight fast, and may result in largely increased blood tyrosine concentrations during the rest of the day. Both high tyrosine enrichment of protein substitutes and extra free tyrosine supplementation may not be as safe as considered at present, especially to the fetus of a woman with PKU. The development of dietary compounds that release tyrosine more slowly could be beneficial. We advocate decreasing the tyrosine content of protein substitutes to approximately 6% by wt (6 g/100 g protein equivalent) at most and not giving extra free tyrosine without knowing the diurnal variations in the blood tyrosine concentration and having biochemical evidence of a tyrosine deficiency. We further advocate that a better daily distribution of the protein substitute be achieved by improving the palatability of these products.

Amino Acids↗
PubMed2001

Dehydroepiandrosterone decreases mortality rate and improves cellular immune function during polymicrobial sepsis.

OBJECTIVE: Sepsis is associated with a marked depression of cellular immune function. The steroid hormone dehydroepiandrosterone (DHEA) is proposed to have immunoenhancing activities. We, therefore, investigated the effect of DHEA on the mortality rate and cellular immune functions in an experimental model of sepsis. DESIGN: Randomized animal study. SETTING: Level I trauma center, university research laboratory. SUBJECTS: Male NMRI mice. INTERVENTIONS: Mice were subjected to laparotomy (sham) or cecal ligation and puncture (CLP). Mice were treated with (sham/DHEA; CLP/DHEA) or without (sham; CLP) the steroid hormone DHEA (30 mg/kg sc). Animals were killed 48 hrs after the onset of sepsis. MEASUREMENTS AND MAIN RESULTS: The survival rate of septic mice was determined 24 and 48 hrs after onset of sepsis. Forty-eight hours after the septic challenge, a white blood cell count was performed and serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta concentrations were monitored using ELISA. Furthermore, the delayed type of hypersensitivity (DTH) reaction was evaluated on the basis of ear pinna swelling after dinitrofluorobenzene (DNFB) administration, and clinical variables (body weight, temperature, heart rate, fluid input/output, food intake) were monitored using metabolic cages. DHEA administration improved the survival rate (87% vs. 53% after 48 hrs; p <.001). This was accompanied by a restoration of the depressed DTH reaction and a reduction in TNF-alpha serum concentrations (20.7 +/- 1.4 pg/mL vs. 32.4 +/- 6.6 pg/mL). CONCLUSIONS: These results demonstrate that DHEA administration leads to an increased survival following a septic challenge. The immunoenhancing effect of DHEA is accompanied by a reduction of TNF-alpha release and an improved activity of T-cellular immunity. DHEA administration may, therefore, be beneficial in systemic inflammation.

Adjuvants, Immunologic↗
PubMed2001

Intake and blood levels of fatty acids in treated patients with phenylketonuria.

BACKGROUND: Investigators in Italy and Spain have suggested that therapy for patients with phenylketonuria (PKU) may result in essential fatty acid (EFA) deficiency. Objectives of this study were to determine if the diets of patients with PKU in the United States provided adequate EFA intakes and whether patients could form long-chain polyunsaturated fatty acids. METHODS: Patients (1-13 years of age) with classic PKU undergoing therapy and their non-PKU sibling closest in age were compared. Nutrient intakes were calculated from 3-day diet diaries. Fatty acids in plasma and erythrocytes were identified and quantified. Paired t tests compared results for the patients and their non-PKU siblings. RESULTS: Twenty-eight patients and 26 siblings were studied. Mean fat intake was greatest by siblings (34.8 +/- 1.3% of energy) and lowest by Phenyl-Free-fed patients (19.5 +/- 1.2% of energy; P < 0.05). Fat intake (30.4 +/- 1.8% of energy) by Phenex-fed patients did not differ from that of siblings. Percentage of energy ingested as C18:2n-6 and C18:3n-3 did not differ significantly between patients and siblings. No clinically significant, consistent differences were found in fatty acid levels (wt%) in plasma or erythrocytes between patients with PKU and siblings. CONCLUSIONS: No patient in this study exhibited a Holman index of EFA deficiency. Siblings ingested animal protein containing C20:5n-3 and C22:6n-3 fatty acids, and this may account for their greater wt% of these plasma and erythrocyte fatty acids. Because patients with PKU do not ingest fatty acids >C18 but C20:4n-6, C20:5n-3, and C22:6n-3 were found in their plasma and erythrocytes, in vivo synthesis from C18:2n-6 and C18:3n-3 appears to occur. Lack of EFA deficiency in patients in this study may be the result of the use of canola and soy oils containing C18:2n-6 and C18:3n-3 rather than olive oil in the diets.

Adolescent↗