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Biomedical subjects

S Jacob

Publications and source records attributed to S Jacob.

At least 19 recordsLinked to original sources
PubMed2006

Sphincter incontinence: is regenerative medicine the best alternative to restore urinary or anal sphincter function?

Incontinence is a major public health concern in aging societies. It is caused by age-dependent spontaneous apoptosis of muscle cells in the urinary and fecal sphincters, and is aggravated in women due to birth trauma. Compared to other currently employed invasive surgical management techniques associated with morbidity and recurrence, replacement or regeneration of dysfunctional sphincter through stem cell therapy and tissue engineering techniques hold great promise. This review focuses on the pathophysiological analysis of urinary incontinence and the possible application of muscle-derived-stem cells, satellite cells, chondrocytes and adipose-derived-stem cells in restoring sphincter functions.

Anal Canal↗
PubMed2006

[Pharmacotherapy of diabetes mellitus type 2. From the glucocentric tradition towards cardiovascular risk management].

Patients with diabetes type 2 are not directly endangered by dysglycemia but they suffer vascular complications. The diabetic patient with existing cardiovascular disease has a particularly high risk for further cardiovascular complications and therefore requires specific attention. This is not only due to the hyperglycemia, but due to the coexistence of further cardiovascular risk factors, such as hypertension, dyslidemia, visceral fat accumulation, chronic inflammation and coagulopathy, also clinically described as the metabolic syndrome. These patients need an intense and multi-modal therapeutic approach, not only for improvement of glycemic control. Also other vascular risk factors should be handled aggressively, such as blood pressure, coagulopathy and dyslipidemia. Recent studies--as STENO 2--indicate that a multi-modal and aggressive approach in diabetic patients can markedly improve their prognosis. Therefore, the current practice of a glucocentric approach should be changed towards a more vascular approach.

Cardiovascular Diseases↗
PubMed2006

[The importance of rehabilitation with cardiovascular diabetic patients after surgical interventions].

Patients with diabetes nowadays are not directly endangered by dysglycemia, but they suffer vascular complications. The diabetic patient with existing cardiovascular (CV) disease has a particularly high risk for further CV complications and, therefore, requires specific attention. These patients need an intense and multimodal therapeutic approach which includes a strong interdisciplinary cooperation between the cardiologist and the diabetologist. Cardiac rehabilitation can effectively improve prognosis of CV patients with numbers needed to treat (NNT) comparable to standard pharmacological treatment. In diabetics, after coronary surgery, metabolism frequently and markedly deteriorates, and this requires strict metabolic monitoring and close cooperation between the diabetes team and the other professionals (cardiologist, nurses, physiotherapists, psychologists . . .) to reduce complications arising from hyperglycemia and also hypoglycemia and to improve the CV risk factors by lifestyle changes. Frequently, diabetes is only diagnosed during the hospital stay for CV complication; therefore, in these patients, specific attention is required for teaching and inauguration of therapy. Due to the high risk of these patients and the need of qualified metabolic co-treatment, following CV surgery, diabetic patients should be treated preferentially in rehabilitation centres specialised in both cardiac and metabolic care. Recent studies indicate that a multimodal and aggressive approach in CV diabetic patients can markedly improve their prognosis.

Blood Glucose↗
PubMed2006

[Heart-diabetes-network--a concept for improved care for diabetic cardiovascular patients following cardiac surgical intervention].

Diabetic patients with heart disease are high risk patients for further vascular complications and therefore need an intensive and multimodal, interdisciplinary intervention. Due to the "segmentation" of medical care into primary care physician, specialists, acute and secondary care (rehabilitation) clinics, the patients will be taken care of on each individual segment with regard to the current requirements and specialties of the care provider. Such--each section, the GP, the cardiologist and the diabetologist, the heart centre and the rehabilitation clinic, represent individual and often strictly separate segments, which each will focus only on the acute problem and will collect (only) data required for the care in their particular segment. A multimodal approach can improve the chronic care and prognosis of these patients, as shown in several studies. The proposed network model should increase multi-disciplinary cooperation of the different levels of health care segments and overcome current barriers. It is thus necessary to provide common guidelines for diagnostic and therapeutic procedures and to improve communication between each individual sector. This could help to improve the secondary prevention in these high risk patients.

Cardiovascular Surgical Procedures↗
PubMed2006

Clinical heterogeneity in mild chronic inflammatory demyelinating polyneuropathy.

We describe the clinical presentation, progression and electrodiagnostic features of three patients with a mild form of chronic inflammatory demyelinating polyneuropathy (CIDP). The unusually mild but also variable clinical picture was a cause of diagnostic uncertainty in all, but CIDP was eventually confirmed by extensive electrophysiological studies in each case, as well as by histology in one. Cerebrospinal fluid protein was raised in only one patient. Two patients were treated by intravenous immunoglobulins and both improved. Awareness of the existence of this relatively benign form of CIDP in its various presentations is essential as it can be functionally disabling, progress to more severe symptomatology, and as patients may benefit from immunomodulatory therapy.

Adult↗
PubMed2005

[Practice guidelines: conservative treatment of fibroids].

The conservative treatment of uterine fibroids is essentially based on symptomatology and patient's choice of treatment. The gynaecologist must develop a clear therapeutic protocol based on clinical examination, available test results and consideration of patient preference. The therapeutic options include close surveillance, hormonal treatments, conservative operative endoscopy and arterial embolization.

Female↗
PubMed2005

Gluten sensitivity and neuromyelitis optica: two case reports.

Neuromyelitis optica is a clinical syndrome characterised by acute transverse myelitis plus an acute or subacute optic neuritis with or without recovery. Although once believed to be a variant of multiple sclerosis, diagnostic criteria have recently been proposed for neuromyelitis optica, making it a clinically distinct syndrome. The term gluten sensitivity refers to a state of heightened immunological responsiveness to ingested gluten in genetically susceptible individuals, as indicated by circulating antibodies to gliadin. Several neurological complications have been described associated with gluten sensitivity ranging from peripheral neuropathy and cerebellar ataxia to an increased risk of epilepsy. Although myelopathy has been described in some case reports of coeliac disease, neuromyelitis optica has never been described in association with gluten sensitivity. We describe two cases of gluten sensitivity presenting as neuromyelitis optica with no previous history of significant gastrointestinal symptoms. Gluten sensitivity was confirmed by immunological and histological studies.

Adult↗
PubMed2004

Serum adiponectin levels predict the effect of short-term dietary interventions on insulin sensitivity in humans.

AIMS/HYPOTHESIS: Fat-rich diets can acutely induce insulin resistance. Data from adiponectin knock-out mice suggest that this effect might be increased in the absence of adiponectin. In the present study we tested whether plasma adiponectin concentrations influence changes in insulin sensitivity induced by a short-term dietary intervention in humans. METHODS: We analysed data from 27 healthy, non-obese men with normal glucose tolerance. These men ate a diet high in fat and a diet high in carbohydrates for three days each. RESULTS: The high-fat diet induced a significant drop in insulin sensitivity (determined by euglycaemic-hyperinsulinaemic clamp) compared to baseline (0.100+/-0.009 vs 0.083+/-0.007 micro mol.kg(-1).min(-1).(pmol.l(-1)), p=0.01). The drop in insulin sensitivity was more pronounced in subjects with low serum adiponectin (0.094+/-0.011 vs 0.077+/-0.010 micro mol.kg(-1).min(-1).(pmol.l(-1)), p=0.02) than in subjects with high serum adiponectin (0.103+/-0.011 vs 0.090+/-0.040 micro mol.kg(-1).min(-1).(pmol.l(-1)), p=0.16). In the whole group the high-carbohydrate, low-fat diet did not cause an increase in insulin sensitivity (0.095+/-0.007 vs 0.102+/-0.009 micro mol.kg(-1).min(-1).(pmol.l(-1)), p=0.06). However, insulin sensitivity was significantly increased in the subgroup with low serum adiponectin levels (0.084+/-0.013 vs 0.099+/-0.018 micro mol.kg(-1).min(-1).(pmol.l(-1)), p=0.01). In an additional multivariate analysis post-intervention insulin sensitivity was predicted by pre-intervention insulin sensitivity ( p<0.001) and adiponectin concentrations ( p=0.001). CONCLUSIONS/INTERPRETATION: These data indicate that the reduction in insulin sensitivity achieved by a short-term high-fat diet is more pronounced in non-obese subjects with low serum adiponectin. Thus it is possible that the restriction of dietary fat and a diet high in carbohydrates might be particularly effective in subjects with low adiponectin such as obese or Type 2 diabetic individuals.

Adiponectin↗
PubMed2004

[Reduced insulin effect in subclinical fatty liver].

BACKGROUND AND OBJECTIVE: Steatosis of the liver is known to be associated with impaired insulin action and is considered to be a feature of the metabolic syndrome. In the present study we addressed the question whether liver fat content, as measured by proton MR spectroscopy ( (1)H MRS), in healthy subjects without clinical signs (hepatomegaly, elevation of transaminases) of relevant liver disease correlates with whole-body insulin sensitivity. METHODS: 21 (18 males and 3 females, age 35 +/- 11 years) non-diabetic subjects underwent the euglycemic-hyperinsulinemic clamp test for determination of whole body insulin action. Liver fat content was measured by means of proton MR spectroscopy ( (1)H MRS). Lipid content was calculated as percentage share of the lipid signal in relation to the entire signal of the spectrum (water and lipid signals). Clinically relevant steatosis of the liver was ruled out by standard magnetic resonance imaging (MRI). Subjects with a history of alcohol intake of more than 40 g/d were excluded from analysis. RESULTS: In a single correlation analysis percentage liver fat strongly correlated with insulin sensitivity index (ISI) (r = 0.7, p = 0.001). After adjusting for the effects of percentage body fat (PFAT) percentage liver fat remained an independent determinant of ISI (p = 0.01). CONCLUSION: Our results suggest that liver fat content is an important predictor of whole-body insulin sensitivity in healthy subjects. The correlation of liver fat content with insulin sensitivity was found in the absence of clinical steatosis and was independent of body fat content.

Adult↗
PubMed2004

Trans-nasal endo-assisted pharyngoplasty: a cadaver study.

A possible new technique of endoscopic pharyngoplasty is described and has been developed in cadavers. The trans-nasal route is used for endoscopic visualisation of the velopharyngeal sphincter. Hynes pharyngoplasty is performed using both trans-oral and trans-nasal routes. This approach allows better visualisation and performance of the Hynes pharyngoplasty at the desired level, "high" in the nasopharynx, without splitting the soft palate.

Cadaver↗
PubMed2004

Erythropoietin: a candidate compound for neuroprotection in schizophrenia.

Erythropoietin (EPO) is a candidate compound for neuroprotection in human brain disease capable of combating a spectrum of pathophysiological processes operational during the progression of schizophrenic psychosis. The purpose of the present study was to prepare the ground for its application in a first neuroprotective add-on strategy in schizophrenia, aiming at improvement of cognitive brain function as well as prevention/slowing of degenerative processes. Using rodent studies, primary hippocampal neurons in culture, immunohistochemical analysis of human post-mortem brain tissue and nuclear imaging technology in man, we demonstrate that: (1) peripherally applied recombinant human (rh) EPO penetrates into the brain efficiently both in rat and humans, (2) rhEPO is enriched intracranially in healthy men and more distinctly in schizophrenic patients, (3) EPO receptors are densely expressed in hippocampus and cortex of schizophrenic subjects but distinctly less in controls, (4) rhEPO attenuates the haloperidol-induced neuronal death in vitro, and (4) peripherally administered rhEPO enhances cognitive functioning in mice in the context of an aversion task involving cortical and subcortical pathways presumably affected in schizophrenia. These observations, together with the known safety of rhEPO, render it an interesting compound for neuroprotective add-on strategies in schizophrenia and other human diseases characterized by a progressive decline in cognitive performance.

Adult↗
PubMed2004

The Gly482Ser variant in the peroxisome proliferator-activated receptor gamma coactivator-1 is not associated with diabetes-related traits in non-diabetic German and Dutch populations.

The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) is involved in regulation of fatty acid oxidation, skeletal muscle fiber type specificity, and gluconeogenesis. The prevalent Gly482Ser variant in PGC-1 was shown to be associated with type 2 diabetes in some but not all studies. Moreover, it is unclear whether it influences prediabetic subphenotypes in non-diabetic populations. We studied the association of this variant with glucose tolerance (oral glucose tolerance test), insulin sensitivity (euglycemic hyperinsulinemic clamp) of glucose disposal and antilipolysis, insulin secretion (hyperglycemic clamp, 10 mM), maximal oxygen consumption (VO(2)max, bicycle ergometry), and intramyocellular lipids (magnetic resonance spectroscopy, tibialis and soleus muscle) in a normal glucose tolerant German cohort (n = 423) and a normal (n = 65) and impaired glucose tolerant (n = 94) cohort from the Netherlands. No statistically significant association with an examined phenotype was detected in any of the study cohorts. Specifically, VO(2)max and the soleus-to-tibialis ratio of intramyocellular lipid contents as a surrogate parameter of fiber type specificity was not different between the genotype groups. We conclude, that the Gly482Ser variant in PGC-1 is not associated with diabetes-related traits or skeletal muscle fiber type composition in a non-diabetic German and Dutch population.

Adult↗
PubMed2004

Effects of moxonidine vs. metoprolol on blood pressure and metabolic control in hypertensive subjects with type 2 diabetes.

Subjects with type 2 diabetes experience an increased cardiovascular morbidity and mortality, related to a high prevalence of hypertension, dyslipidemia, and obesity. Antihypertensive treatment with beta-adrenergic receptor blockers may have deleterious metabolic consequences, including worsening of lipid profiles and insulin sensitivity. The centrally-acting sympatholytic agent moxonidine may improve these variables. In this randomised, double-blind multicenter study, the effects of two widely used antihypertensive agents--moxonidine (MOX) and the beta (1)-selective adrenergic receptor blocker metoprolol (MET)--on blood pressure and metabolic control were directly compared in hypertensive subjects with type 2 diabetes. Patients received either MOX (0.2 - 0.6 mg/d) or MET (50 - 150 mg/d) for 12 weeks, intending comparable blood pressure control. In total 200 patients were randomized. Here we report results from the per protocol population consisting of 127 patients (MOX 66, MET 61) but similar results were found in the ITT population. Reductions in systolic (SBP) and diastolic (DBP) blood pressures after 12 weeks were similar in both groups: In the MOX group, mean SBP (+/- SD) decreased from 154 +/- 12 to 142 +/- 17 mmHg and mean DBP from 91 +/- 9 to 83 +/- 9 mmHg. In the MET group, mean SBP decreased from 152 +/- 13 to 140 +/- 15 mmHg, and mean DBP from 90 +/- 8 to 84 +/- 10 mmHg. Mean HbA (1C) values did not differ between groups after 12 weeks (MOX 8.1 +/- 1.4 Hb%, MET 8.1 +/- 1.5 Hb%, intention-to-treat population). However, fasting plasma glucose decreased in the MOX group (median change - 5 mg/dl), but increased in the MET group (+ 16 mg/dl; p < 0.05). Median changes in the insulin resistance index (HOMA (IR)) were + 0.56 micro IU x mol/L (2) in the MET group, and - 0.27 micro IU x mol/L (2) in the MOX group. Correspondingly, fasting triglycerides increased with a median change of + 29.5 mg/dL in the MET group, but decreased in the MOX group (- 27.5 mg/dl; p < 0.05). These results indicate that MOX, unlike MET, may elicit beneficial adaptations in glucose and lipid metabolism in hypertensive subjects with type 2 diabetes, although mean HbA (1c) values did not differ. In long-term treatment in this high-risk population, MOX thus may decrease global vascular disease risk to a greater extent than MET.

Adult↗
PubMed2004

A novel nonsense mutation in GCK exon 9 co-segregates with diabetes phenotype.

Maturity-onset diabetes of the young is an autosomal dominant form of non-insulin dependent diabetes mellitus and is caused by mutations in at least six different genes. In the most common forms, i.e. MODY2 and MODY3, the glucokinase (GCK) and the hepatocyte nuclear factor (HNF)-1alpha gene is affected, respectively. We have screened the GCK gene and HNF-1alpha gene by direct sequencing in three German families with early onset type-2-diabetes, possibly MODY. Next to known polymorphisms we have identified two novel intronic insertions in GCK and a novel non-sense mutation in exon 9 (C364 X). The latter mutation has an autosomal dominant inheritance pattern. Accordingly, this novel mutation segregates with diabetes phenotype in this family.

Animals↗