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Biomedical subjects

C Keller

Publications and source records attributed to C Keller.

At least 199 records · Page 11Linked to original sources
PubMed1998

Congenital myotonic dystrophy requiring prolonged endotracheal and noninvasive assisted ventilation: not a uniformly fatal condition.

In this report we present two infants with congenital myotonic dystrophy (CMD) who were successfully weaned from prolonged ventilatory support using nasal continuous positive airway pressure (N-CPAP). The first infant received 127 days of endotracheal mechanical ventilation as part of 141 days of total ventilatory support, including N-CPAP; the second infant received 27 days of endotracheal mechanical ventilation as part of 84 days of total ventilatory support. Noninvasive N-CPAP facilitated weaning these two infants from ventilatory support, thereby minimizing the morbidity associated with prolonged intubation. The developmental outcomes of our two infants were comparable to infants not requiring prolonged endotracheal mechanical ventilation. We suggest that this noninvasive modality of ventilatory support may be advantageous in the management and beneficial to the outcome of infants with CMD who are respirator-dependent >30 days.

Adult↗
PubMed1998

Effects of smoking on renal hemodynamics in healthy volunteers and in patients with glomerular disease.

Patients with renal disease who smoke have a poor renal functional prognosis, but the mechanisms involved have not been explored. In this controlled study, the effects of smoking and sham smoking were compared in 15 healthy normotensive volunteers. All were occasional smokers and abstained from smoking for 48 h as documented by urinary cotinine measurements. These data were compared with those of seven patients with biopsy-confirmed IgA glomerulonephritis, also occasional smokers. Renal clearance examinations were obtained after hydration in the supine position before and while smoking two cigarettes or sham cigarettes in random order on 2 consecutive days. GFR and effective renal plasma flow were determined using In111-diethylenetriamine penta-acetic acid and 131I-hippurate with a dual tracer infusion clearance technique. In an ancillary study with six volunteers, the effect of smoking was compared with the effect of nicotine-containing chewing gum. In healthy volunteers, sham smoking caused a minor but significant increase of mean arterial pressure (MAP) and GFR with no significant change of effective renal plasma flow, filtration fraction (FF), or renovascular resistance. Smoking caused a significant and more marked increase of MAP (from baseline 92.8+/-8.98 to 105+/-7.78 mmHg) and heart rate (from 61.7+/-7.52 to 86.4+/-9.87 min(-1)), accompanied by a significant increase in arginine vasopressin (from 1.27+/-0.72 to 19.9+/-27.2 pg/ml) and epinephrine (from 37+/-13 to 140+/-129 pg/ml). During smoking, GFR decreased in all but one volunteer (from 120+/-17.7 to 102+/-19.3 ml/min per 1.73 m2), and this was accompanied by a significant decrease of FF (from 21.3+/-4.24 to 17.4+/-3.41%) and an increase in renovascular resistance (from 97.6+/-27.2 to 108+/-30.4 mmHg x min/ml per 1.73 m2). These findings were reproduced with nicotine-containing chewing gum. In contrast, when patients with IgA glomerulonephritis smoked, a similar increment in MAP was noted, the changes of FF were not uniform, and a small but consistent increase of urinary albumin/creatinine ratio was observed. An additional 20 volunteers were subjected to the smoking arm of the study for statistical evaluation of the GFR change in patients. The difference between the change of GFR between all volunteers (n = 35) and patients (n = 7) was significant (P < 0.005). It is concluded that the known effects of smoking and nicotine on the sympathetic nervous system and on systemic hemodynamics are accompanied by significant acute changes in renal hemodynamics and albuminuria. These findings are of interest because of the known effects of smoking on progression of renal disease.

Adult↗
PubMed1998

D-thyroxine reduces lipoprotein(a) serum concentration in dialysis patients.

Uremia raises lipoprotein(a) (Lp(a)) serum concentration and the risk of arteriosclerosis in dialysis patients. The treatment of high Lp(a) levels is not satisfactory today. The decrease of Lp(a) in hypothyroid patients on L-T4 therapy raised the question of whether dextro-thyroxine (D-thyroxine) reduces not only serum cholesterol, but also Lp(a) serum concentration. In a single-blind placebo-controlled study, the influence of D-thyroxine therapy on Lp(a) serum concentration was evaluated in 30 hemodialysis patients with elevated Lp(a) serum levels. Lp(a) was quantified in parallel by two methods, i.e., rocket immunoelectrophoresis and nephelometry, and apo(a) isoforms were determined by a sensitive immunoblotting technique. Regardless of the apo(a) isoforms, 6 mg/d D-thyroxine reduced elevated Lp(a) levels significantly by 27 +/- 13% in 20 dialysis patients (P < 0.001) compared with 10 control subjects (-9.9 +/- 8.4%). In parallel, D-thyroxine therapy significantly lowered total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and LDL cholesterol/HDL cholesterol ratio (P < 0.01); raised T4 and T3 serum levels; and suppressed thyroid-stimulating hormone secretion without causing clinical symptoms of hyperthyroidism in any of the patients. D-Thyroxine reduces elevated serum Lp(a) concentration in dialysis patients. The effect in nondialysis patients can be expected but remains to be proven.

Aged↗
PubMed1997

Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots.

Epidemiological evidence has suggested that some pediatric leukemias may be initiated in utero and, for some pairs of identical twins with concordant leukemia, this possibility has been strongly endorsed by molecular studies of clonality. Direct evidence for a prenatal origin can only be derived by prospective or retrospective detection of leukemia-specific molecular abnormalities in fetal or newborn samples. We report a PCR-based method that has been developed to scrutinize neonatal blood spots (Guthrie cards) for the presence of numerically infrequent leukemic cells at birth in individuals who subsequently developed leukemia. We demonstrate that unique or clonotypic MLL-AF4 genomic fusion sequences are present and detectable in neonatal blood spots from individuals who were diagnosed with acute lymphoblastic leukemia at ages 5 months to 2 years and, therefore, have arisen during fetal hematopoiesis in utero. This result provides unequivocal evidence for a prenatal initiation of acute leukemia in young patients. The method should be applicable to other fusion genes in children with common subtypes of leukemia and will be of value in attempts to unravel the natural history and etiology of this major subtype of pediatric cancer.

Artificial Gene Fusion↗
PubMed1997

Pemberton's maneuver - a clinical test for latent superior vena cava syndrome caused by a substernal mass.

A 62-year-old white male presented with facial erythema and jugular vein distension in upright position which progressed to cyanosis and facial edema while keeping both arms elevated (Pemberton sign). A CT scan revealed a large substernal goiter as the cause of superior vena cava syndrome. Symptoms and signs disappeared after thyroid surgery. First reported in 1946 Pemberton's maneuver is a useful but unrecognized clinical sign for oligosymptomatic superior vena cava syndrome caused by a substernal mass.

Erythema↗
PubMed1997

[Nephropathy and hypertension in type II diabetes].

BACKGROUND: In Germany nephropathy in patients with type II diabetes has become the most frequent single cause of uremia requiring renal replacement therapy. This calls for effective measures of prevention. DIABETIC NEPHROPATHY AND HYPERTENSION: In patients with established diabetic nephropathy, hypertension is the most important pathogenetic factor which is susceptible to therapeutic intervention. Some pathogenetic mechanisms are discussed which impact on antihypertensive therapy. Interaction between hypertension and diabetic nephropathy is analyzed. CONCLUSION: Diabetic nephropathy in patients with type II diabetes has become the most frequent cause of endstage renal failure in Germany. Preventive measures, i. e. near normal glycemia and particularly antihypertensive treatment, have been proven to interfere with progression of renal failure in diabetic nephropathy. Early recognition is possible by testing for urinary albumin (microalbuminuria). In patients with diabetic nephropathy, blood pressure should be lowered to values well within the range of normotension by dietary salt restriction and antihypertensive drug therapy.

Combined Modality Therapy↗
PubMed1997

Peritumoural brain oedema in intracranial meningiomas: influence of tumour size, location and histology.

Peritumoural brain oedema was examined retrospectively in 175 patients with 179 intracranial meningiomas. The influence of tumour size, location and histology were investigated. Tumour volume and localization, and the presence of peritumoural brain oedema (PTBOe) were determined by computed tomography (CT). The oedema-tumour volume ratio was defined as Oedema Index (Oel). All patients underwent microsurgical removal of the tumour. Surgically resected meningiomas were classified histopathologically based on criteria of the new World Health Organization (WHO) classification. A close relationship was found between the tumour size and the incidence of peritumoural oedema: with increasing size of the tumour the incidence of oedema also rises, the oedema index, however decreases. Frontobasal and temporobasal meningiomas showed a significant increase in the oedema incidence and the mean oedema index. If major parts of the surface of meningiomas were adjacent to subarachnoid cisterns only a slight tendency for the development of oedema was observed. WHO-III-meningiomas showed a significantly higher oedema incidence (61.1% vs. 94.4%; p < 0.004) and mean oedema index (Oel = 2.7 vs. 3.7; p < 0.0009) than WHO-I-meningiomas. Brain tissue was affected in 59 cases. 19 meningiomas with infiltration into adjacent brain parenchyma revealed a statistically significant increase in oedema incidence (94.7% vs. 51.7%; p < 0.0003) and mean oedema index (Oel = 3.9 vs. Oel = 2.2; p < 0.0001) when compared to tumours without any brain tissue involvement in the histopathological specimens. Tumours with large volume, fronto-temporo-basal location and anaplastic histology were not only associated with the highest incidence of oedema formation but also presented with an overproportionate infiltrative growth. Thus, a disruption of the arachnoid or a true brain infiltration may be an essential factor for the development of a PTBOe.

Adult↗
PubMed1997

Pathogenesis and course of renal disease in IDDM/NIDDM: differences and similarities.

In the past the opinion prevailed that renal prognosis was less adverse in non-insulin-dependent diabetes mellitus (NIDDM) as compared with insulin-dependent diabetes mellitus (IDDM). This notion has to be revised in the light of recent evidence, based on epidemiologic data of NIDDM patients reaching endstage renal failure and a comparison of the cumulative prevalence of proteinuria and renal failure, respectively, in NIDDM as compared with IDDM. It has also been established that initial renal hemodynamic changes are quite comparable in NIDDM and in IDDM. It follows that past complacency about the renal sequelae of NIDDM is no longer justified and that preventive measures to interfere with the development of diabetic nephropathy are similarly important in NIDDM and IDDM.

Diabetes Mellitus, Type 1↗
PubMed1997

Nephropathy of type II diabetes: evidence for hereditary factors?

Family studies point to an important genetic element in the genesis of diabetic nephropathy, but it is not known whether renal abnormalities are present prior to the onset of diabetes. To address this issue we examined all consecutive patients suffering from type II diabetes with a duration of more than 10 years who attended a diabetes outpatient clinic. Ninety-four patients had nephropathy, 307 did not. All offspring who were phenotypically normal (no hypertension, normal oral glucose tolerance, non-smoking) and agreed to participate were examined, 26 from nephropathic and 30 from non-nephropathic diabetic parents. They were compared with 30 offspring matched for age, gender and BMI from non-diabetic parents as controls. We measured urinary albumin excretion under baseline conditions and at several time points after ingestion of 300 g cooked beef and submaximal treadmill exercise, respectively. In addition, casual blood pressure, ambulatory blood pressure, urinary albumin and urinary alpha-1-microglobulin were measured. Primary renal disease was excluded by clinical examination. Under baseline conditions, median urinary albumin excretion rate (AER; microgram/min) was significantly (P < 0.005) higher in offspring of nephropathic type II diabetic patients (7.8; range 1.04 to 19.5) than in the offspring of non-nephropathic type II diabetic patients (4.8; 0.36 to 17.5) and controls (4.4; 0.16 to 18.4). Submaximal treadmill exercise caused a greater proportional increase of AER in offspring of nephropathic type II diabetics (median 16-fold) than in offspring of non-nephropathic diabetic patients (6.3-fold) or controls (4.8-fold). In offspring of nephropathic diabetic patients casual and particularly ambulatory systolic blood pressures were significantly higher, but AER was not correlated with blood pressure. In summary, higher values, albeit within the normal range, for baseline and postexercise albuminuria were noted in phenotypically normal offspring of parents with type II diabetes and nephropathy. The observation suggests that changes in transglomerular albumin traffic are demonstrable prior to the onset of diabetes and diabetic nephropathy in subjects with a potential genetic predisposition to these conditions.

Adult↗
PubMed1997

Pharmacodynamics and pharmacokinetics of rocuronium in intensive care patients.

We have studied dose requirements, recovery times and pharmacokinetics of rocuronium in 32 intensive care patients. After an initial dose of 50 mg, rocuronium was administered as maintenance doses of 25 mg whenever two responses to train-of-four (TOF) stimulation reappeared (bolus group; n = 27) or by continuous infusion to maintain one response in the TOF (infusion group; n = 5). Median requirements for rocuronium were 27.4 (range 14.5-68.3) mg h-1 and 43.7 (30.9-50.3) mg h-1 in patients in the bolus and infusion groups, respectively. Median total duration of rocuronium administration was 29.0 (12.4-95.5) h and 63.4 (24.0-140.3) h, respectively. Median time from administration of the last bolus dose and end of infusion to recovery of the fourth twitch in the TOF was 100 (45-300) min and 60 (15-155) min, respectively. Arterial blood samples were obtained for up to 10 h after cessation of rocuronium administration, and concentrations of the parent compound and its putative metabolites were measured using high pressure liquid chromatography (HPLC). The plasma concentration profile (n = 12) was described adequately by a two-compartment model. Mean plasma clearance (Cl), steady-state distribution volume (Vss), mean residence time (MRT) and elimination half-life (T1/2 beta) were 3.16 (SD 1.15) ml kg-1 min-1, 769 (334) ml kg-1, 262 (120) min and 337 (163) min, respectively. Recovery times, Vss, MRT, and T1/2 beta differed from previously published data obtained after rocuronium infusion of moderate duration in surgical patients.

Adolescent↗
PubMed1997

Altered action of angiotensin II in patients with type 2 diabetes mellitus of recent onset.

OBJECTIVE: Angiotensin II (Ang II) increases insulin sensitivity in healthy volunteers. This effect is thought to be mediated, at least in part, by an increase in skeletal muscle blood flow. In the past it had been documented that some biological actions of Ang II are altered in diabetes. We addressed the issue of whether this is also true for its action on insulin sensitivity. DESIGN AND METHODS: Twelve healthy volunteers (aged 43+/-9 years) and 15 patients with type 2 diabetes mellitus (NIDDM) of recent onset (aged 45+/-9 years) were allocated in random order in a double-blind placebo-controlled design to be administered a sham infusion or an infusion of 2 ng Ang II/kg per min. Insulin-stimulated glucose uptake (the M value) was measured with the euglycaemic clamp technique, leg muscle blood flow (MBF) with plethysmography, blood pressure with a Dinamap device, and glomerular filtration rate and effective renal plasma flow with the steady-state inulin (Cin) and p-aminohippurate (CPAH) clearance methods, respectively. RESULTS: In volunteers the mean M-value after Ang II infusion (10.1+/-1.5 mg/kg per min) was significantly higher (P < 0.01) than that after sham infusion (8.2+/-0.9 mg/kg per min). In contrast, in diabetic patients it was not significantly different with Ang II (6.1+/-1.3 mg/kg per min) and sham infusion (5.5+/-1.2 mg/kg per min). The difference in the mean absolute increase in the M value (deltaM) between groups was significant (P< 0.02). The Ang II-induced increase in MBF under euglycaemic conditions was attenuated in diabetic patients (from 15.0+/-3.5 to 15.5+/-3.9 ml/100 ml per min, NS) compared with volunteers (from 16.8+/-3.3 to 19.1+/-3.7 ml/100 ml per min, P< 0.01). Again, the difference between the mean absolute increases in MBF (deltaMBF) in the groups was significant (P < 0.01). A significant correlation was found between deltaMBF and deltaM (r= 0.62, P<0.01). The absolute acute increase in mean arterial blood pressure with Ang II was similar in diabetic patients and volunteers. Mean Cin, CPAH and fractional sodium excretion values were significantly lower and renal vascular resistances and filtration fractions higher during the Ang II than they were during the placebo clamp period. This was observed in patients as well as in healthy subjects, but the effects of Ang II on renal haemodynamics and sodium handling were more pronounced in diabetic patients. CONCLUSIONS: In patients with NIDDM of recent onset the stimulatory effect of Ang II on insulin sensitivity and on skeletal muscle blood flow is attenuated. In contrast, the effects of Ang II on renal perfusion and sodium handling are more pronounced in patients with NIDDM than they are in healthy subjects.

Adult↗
PubMed1997

Laryngeal mask lubrication. A comparative study of saline versus 2% lignocaine gel with cuff pressure control.

We compared 2% lignocaine gel with saline as a lubricant for the laryngeal mask airway in 126 patients receiving positive pressure ventilation in whom cuff pressures were limited to 60 cmH2O and peak airway pressures to less than 17 cmH2O. The incidence of sore throat was similar for both groups and there were no emergence problems. There were significantly more intra- and postoperative complications in the lignocaine group (p < 0.05) but the frequency of sore throat was similar when the device was inserted at the first attempt. Positive pressure ventilation to normal end-tidal CO2 values was possible in all patients. Lignocaine gel is an unsuitable lubricant for the laryngeal mask airway. Cuff pressure limitation to 60 cmH2O does not necessarily impede ventilation and may be an important factor in reducing emergence and postoperative complications.

Anesthetics, Local↗
PubMed1997

Laryngeal mask bite blocks--rolled gauze versus Guedel airway.

BACKGROUND: Biting on the silicone tube and pilot balloon of the laryngeal mask airway (LMA) may obstruct or damage them with the teeth and a bite block is recommended. The recommended bite block is a wad of gauze swabs rolled into a cylindrical shape and placed alongside the LMA. It is considered that this avoids irritating the posterior pharyngeal wall and damage to teeth whilst supporting the LMA tube when taped to it. The Guedel airway is commonly used as a bite block with the tracheal tube and many anaesthetists also use it with the LMA. The aim of the following study was to compare rolled gauze swabs with a Guedel airway as a bite block for the LMA. METHODS: We compared the Guedel airway with rolled gauze swabs as a bite block for the laryngeal mask airway (LMA) in 120 ventilated patients in whom cuff pressures were limited to 5.87 kPa (60 cm H2O) and anaesthesia management was standardised. RESULTS: In the Guedel airway group, there was a higher incidence of ventilatory problems (0 vs 4, P < 0.05), bleeding (0 vs 8, P < 0.01), hoarseness (0 vs 4, P < 0.05) and sore throat (2 vs 12, P < 0.01). CONCLUSION: 1. The Guedel airway is an unsuitable bite block for the LMA. 2. Cuff pressure limitation is compatible with adequate ventilation. 3. The combination of LMA and Guedel airway probably prevents either from sitting in the correct anatomical position.

Adult↗
PubMed1997

Reconstitution of a MEC1-independent checkpoint in yeast by expression of a novel human fork head cDNA.

A novel human cDNA, CHES1 (checkpoint suppressor 1), has been isolated by suppression of the mec1-1 checkpoint mutation in Saccharomyces cerevisiae. CHES1 suppresses a number of DNA damage-activated checkpoint mutations in S. cerevisiae, including mec1, rad9, rad24, dun1, and rad53. CHES1 suppression of sensitivity to DNA damage is specific for checkpoint-defective strains, in contrast to DNA repair-defective strains. Presence of CHES1 but not a control vector resulted in G2 delay after UV irradiation in checkpoint-defective strains, with kinetics, nuclear morphology, and cycloheximide resistance similar to those of a wild-type strain. CHES1 can also suppress the lethality, UV sensitivity, and G2 checkpoint defect of a mec1 null mutation. In contrast to this activity, CHES1 had no measurable effect on the replication checkpoint as assayed by hydroxyurea sensitivity of a mec1 strain. Sequence analysis demonstrates that CHES1 is a novel member of the fork head/Winged Helix family of transcription factors. Suppression of the checkpoint-defective phenotype requires a 200-amino-acid domain in the carboxy terminus of the protein which is distinct from the DNA binding site. Analysis of CHES1 activity is most consistent with activation of an alternative MEC1-independent checkpoint pathway in budding yeast.

Amino Acid Sequence↗
PubMed1997

Strategies for weight control success in adults.

Recent evidence demonstrates that only about 5% of individuals embarking on a weight loss program show lasting weight reduction. While many weight loss strategies have demonstrated poor results, some combinations of approaches have been successful. Empirical evidence demonstrates that certain conceptual approaches can contribute to the development of strategies to facilitate weight loss. This manuscript addresses three conceptual approaches that direct intervention strategies. Cognitive-behavioral strategies are directed toward modification of eating behaviors, and the social-contextual approach is directed toward the social and partnership approach to intervention. Biophysical strategies that have demonstrated success in weight loss include the effect of dietary restriction and exercise on weight loss. Using this synthesis of empirical evidence for success in weight loss, practitioners can develop individually tailored intervention strategies for their clients.

Adult↗