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Biomedical subjects

K Mohnike

Publications and source records attributed to K Mohnike.

At least 19 recordsLinked to original sources
PubMed2006

[CranioNet -- an interdisciplinary strategy for craniopharyngioma].

In patients with craniopharyngioma, pituitary failure and often lifelong hormone replacement therapy, persisting ophthalmological problems with impaired vision, cranial nerve palsies, and psychoneurological deficits will lead to a persisting impairment in quality of life and social competence. Some patients completely depend on assistance. To prevent this, a major goal is an early diagnosis and limitation of operative radicality to minimize postoperative complications. Surgery in centers with special expertise is mandatory. Radiotherapeutical strategies are relatively safe and improve the outcome and recurrence-free survival after incomplete surgical resection or after local recurrence. Multidisciplinary concepts and prospective data acquisition are desirable with regard to therapy and outcome in patients with craniopharyngioma. Problems in the follow-up period are the development of atherosclerotic complications and metabolic syndrome as a consequence of occasionally excessive obesity, which may impair the long-term survival of the patients. Cause and progression of these complications are not fully understood, therapeutical strategies for the morbid obesity are not available. Only interdisciplinary co-operation will help to develop and evaluate therapeutical concepts for the management of this rare disease.

Combined Modality Therapy↗
PubMed2002

Expression of components of the IGF signalling system in childhood acute lymphoblastic leukaemia.

BACKGROUND: Alterations in the insulin-like growth factor (IGF) system have been reported for different tumours. They are of particular interest in the search for new prognostic and therapeutic approaches in cancer. In childhood acute lymphoblastic leukaemia (ALL) the amount of "tumour mass" at diagnosis can exceed 1 kg. To understand the endocrine, paracrine, and autocrine potential of the malignant transformed progenitor cells, the ability of these cells to express components of the IGF system needs to be investigated. AIM: To characterise the expression pattern of genes of the IGF system in malignant lymphoblasts of children suffering from ALL. METHODS: Reverse transcription polymerase chain reaction of Ficoll separated mononuclear cells from 142 children with ALL, 127 cord blood samples, and 55 blood samples of age matched controls were studied. RESULTS: The expression of IGF-I, IGF-II, IGF binding protein 5 (IGFBP-5), and CTGF (IGFBP-rP2) was seen in a higher proportion of mononuclear cells of patients with ALL than in controls. Patients with ALL who were in continuous remission had a lower percentage of IGFBP-2 and IGFBP-3 expressing mononuclear cells at diagnosis than did those who developed a relapse. Only malignant lymphoblasts of B cell origin showed expression of CTGF (IGFBP-rP2). Malignant lymphoblasts of T cell origin more often expressed IGFBP-2 and IGFBP-5, whereas IGF-II and IGFBP-3 expression was seen more often in lymphoblasts of B cell origin. CONCLUSIONS: Malignant lymphoblasts of patients with ALL express components of the IGF system and therefore promote their own growth in an autocrine, paracrine, or endocrine manner. Whether these components will be useful as prognostic factors in the stratification of ALL treatment in children needs to be evaluated.

Biomarkers, Tumor↗
PubMed2001

Short stature homeobox-containing gene deletion screening by fluorescence in situ hybridisation in patients with short stature.

UNLABELLED: The short stature homeobox-containing gene (SHOX) on the short arm of the X and Y chromosomes is an important determining factor of stature phenotype. Absence of the SHOX gene is a main cause for short stature in patients with Turner syndrome. Mutations of the SHOX gene can also be responsible for Léri-Weill syndrome (dyschondrosteosis). The aim of this study was to determine the frequency of SHOX deletions in short stature children and to delineate indications for SHOX deletion screening. Out of 50 probands, 35 had idiopathic short stature, 12 cases showed additional anomalies of the forearms (in particular Madelung deformity) and three patients were affected by a congenital heart defect. Chromosomal investigations with fluoresence in situ hybridisation did not reveal a SHOX deletion in any patient with idiopathic short stature. In five of the 12 patients (41.7%) with anomalies of the forearms, a SHOX deletion on one sex chromosome could be detected. No deletion was observed in the three cases with additional heart defects. CONCLUSION: The frequency of short stature homeobox-containing gene deletions in patients with idiopathic short stature appears to be very low and does not require a fluorescence in situ hybridisation analysis. Short stature in association with anomalies of the forearms such as Madelung deformity makes a deletion more probable and therefore screening for such deletions is recommended in these cases.

Adolescent↗
PubMed2001

Preferential inactivation of a dupX(q23 --> q27-28) chromosome in a girl with mental retardation and dysmorphy.

We report on an 18-year-old female with de novo tandem duplication Xq23-->Xq27-28. The breakpoints of the duplication segment have been mapped by FISH using a panel of locus specific YACs. Despite selective inactivation of the aberrant X chromosome, proven by a combination of molecular and cytogenetic studies, the patient exhibits mental retardation, dysmorphic features and short stature. Possible mechanisms explaining this unexpected finding are discussed.

Adolescent↗
PubMed2001

Hyperinsulinism in syndromal disorders.

UNLABELLED: Analysis of a German database comprising a total of 54 patients with neonatal manifestations of persistent hyperinsulinism revealed 5 patients in whom hyperinsulinism was associated with additional clinical symptoms, suggesting an underlying syndromal disorder. Three of the patients presented with a similar yet unknown clinical entity characterized by severe psychomotor retardation, chronic pulmonary disease, hypothyroidism and congenital heart defects. A fourth patient was affected by severe congenital central hypoventilation syndrome. The fifth patient presented with Beckwith-Wiedemann syndrome, with unusually severe and persistent hyperinsulinism requiring subtotal pancreatectomy. CONCLUSION: Our results indicate that, in addition to the well-known biochemical pathways, more complex pathophysiological mechanisms can result in persistent hyperinsulinism that presents clinically with a disease involving multiple organs.

Female↗
PubMed2000

Immunogenicity and reactogenicity of the Biken acellular pertussis vaccine in young adults.

To assess the reactogenicity and immunogenicity of the Biken acellular pertussis vaccine (Pa) following administration of a single vaccine dose to young adults with or without a history of prior pertussis immunization, 104 healthy, male and female adults without primary pertussis immunization were enrolled in Mainz (former West Germany; "not previously pertussis vaccinated", N-PPV-group); in parallel, 103 adults with a history of having received >/=four doses of a combined diphtheria-, tetanus-toxoid, whole-cell pertussis vaccine (DTwP) were enrolled in Magdeburg (former East Germany; "previously pertussis-vaccinated", PPV-group). Large areas of redness (>20 mm) were seen in 2.9%/1.0% of subjects in the N-PPV/PPV group, and a large swelling was seen in 6.8%/1.0%, respectively. As compared to baseline concentrations, antibody titers to PT and FHA were 77-(PT)/64-(FHA) (N-PPV group) and 94-(PT)/126-(FHA) fold (PPV group) higher. The study vaccine was safe and induced infrequent and mostly mild, local and general symptoms that all resolved spontaneously; it was highly immunogenic in adults, whether or not they had been previously vaccinated with DTwP.

Adhesins, Bacterial↗
PubMed1998

Elevated serum levels of IGFBP-2 found in children suffering from acute leukaemia is accompanied by the occurrence of IGFBP-2 mRNA in the tumour clone.

Insulin-like growth factor-binding proteins (IGFBPs) are important modulators of IGF action. In 50 children suffering from acute lymphoblastic leukaemia (ALL), we studied the serum levels of IGFBP-1,-2 and-3. The mean standard deviation score (SDS) values were estimated to be 0.7, 3.1 and -1.7 for the IGFBP-1,-2 and-3, respectively, compared with the normal range defined by a SDS from -2 to +2. IGFBP-1 and-3 were normal, but for IGFBP-2 we found a significantly elevated serum level compared with control groups (P < 0.05). However, during chemotherapy this increased serum IGFBP-2 normalized. In addition, we found a correlation between higher serum levels and the detection rate of the IGFBP-2 transcript in corresponding cells. In patients with ALL, the detection rates of IGFBP-2 mRNA were estimated to be 72% and 35% at the time of diagnosis and at day 33 of chemotherapy respectively; in the control groups (healthy children and children at their initial presentation of diabetes mellitus), the values were 28% and 33% respectively. Based on the correlation between IGFBP-2 serum levels and the corresponding gene expression as well as the normalization of IGFBP-2 levels during chemotherapy, we concluded that the increased serum level mainly originated from the tumour clone itself. Furthermore, possible functional consequences of elevated IGFBP-2 were outlined.

Adolescent↗
PubMed1998

Catch-up growth after childhood-onset substitution in primary hypothyroidism: is it a guide towards optimal growth hormone treatment in idiopathic growth hormone deficiency?

Catch-up growth was analyzed in 20 prepubertal children with primary hypothyroidism (PH) starting treatment at an age of 4.4 (1.2-10.1) years and a height (HT) SD score (HT SDS) of -3.1 (+/-0.8). All patients were followed for at least 3 prepubertal years. HT velocity was 12.3 +/- 2.3, 9.0 +/- 1.8 and 7.5 +/- 2.2 cm/year, and change in HT SDS was 1.60 +/- 0.56, 0.57 +/- 0.33 and 0.28 +/- 0.38 during the 1st, 2nd and 3rd year, respectively. The 11 children followed to adult height reached a HT SDS of -0.11 +/- 1.1, all within their target HT range. HT gain (DeltaHT SDS) during the 1st year was correlated with the degree of catch-up growth (r2 = 0.78, p < 0.001). While catch-up growth in childhood-onset PH is complete, this is not the case in GH deficiency (GHD). Based on the auxological characteristics of the patients with PH, HT velocities during the first 2 years were predicted applying prediction models devised for prepubertal children with idiopathic GHD. The modalities of GH treatment observed in the models were used to calculate predicted HT velocities of the PH patients. Observed HT velocities in PH were higher than predicted HT velocities during the 1st (10.67 +/- 1.37 cm/year, p < 0.01) and 2nd (8.35 +/- 0.86 cm/year, p = 0.128) year. The data show that catch-up potential in idiopathic GHD of childhood onset is reduced compared to PH. Since early catch-up as well as total HT recovery in children with GHD are often not reached by present treatment modalities, catch-up growth in PH may serve as a model towards optimizing GH treatment. The data suggest that initial GH doses of 1.0 IU/kg/week, rather than the presently recommended 0. 6 IU/kg/week, need to be given in GHD in order to achieve the degree of early catch-up observed in PH and to consequently improve the final outcome.

Body Height↗
PubMed1997

Final height and puberty in 40 patients after antileukaemic treatment during childhood.

UNLABELLED: Endocrine dysfunction and damage of the epiphysial growth plates have been reported as late effects of antileukaemic treatment during childhood. It is a common opinion that cranial irradiation (CI) is the most important factor for blunted growth. Accordingly, recent therapeutic strategies in acute lymphoblastic leukaemia (ALL) avoid cranial irradiation. Here we analysed longitudinal data on growth and puberty of 54 children in first complete remission, who were treated with 18 Gy CI or not submitted to radiotherapy. Two chemotherapeutic protocols were compared which were similar during the induction period but differed in the intensity of maintenance therapy. In cranial irradiated patients both in males and females the pubertal growth spurt started at a mean age of 1.2 years (SD: 0.93 years) earlier than controls. Age at diagnosis and age at pubertal growth spurt were significantly correlated (r = 0.35, P = 0.017). Similarly, menarche occurred at a mean age (n = 22) of 12.1 years and was correlated with the age at start of therapy in girls who were treated with 18 Gy CI (r = 0.61, P = 0.01). Adult height was reached spontaneously in 30 patients treated during prepubertal age and in 10 treated shortly before or during puberty. In all prepubertal patients treated for 2-3 years with intensive maintenance therapy blunted growth resulted in a significant loss of -1.85 H-SDS (median, P = 0.0051) compared to height at diagnosis. However, if continuation treatment used only methotrexate and 6-mercaptopurine (i.e. BFM protocol) final height equalled projected adult height, despite 18 Gy CI. CONCLUSIONS: (1) multiagent chemotherapy is of major impact for growth and puberty; (2) 18 Gy cranial irradiation is below the critical dosage responsible for blunted growth; (3) loss in potential growth might be prevented by current CT strategies; (4) onset of puberty depends on age when antileukaemic therapy is applied.

Adolescent↗
PubMed1993

Clinical studies of IGFBP-2 by radioimmunoassay.

A specific radioimmunoassay for human IGFBP-2 was developed using a polyclonal antiserum directed against a partial sequence (hIGFBP-2(176-190)). The tracer was prepared by radioiodination of a [Tyr]o-hIGFBP-2(176-190) derivative. The assay was used to study IGFBP-2 levels in numerous clinical and experimental situations. There was little circadian fluctuations of serum level which showed a marked age-dependence with high levels at birth and senescence and low levels during puberty. Decreased IGFBP-2 levels were present in untreated insulin-dependent diabetes mellitus (IDDM), in acromegaly and during dexamethasone suppression test. GH deficiency, fasting, IGF-I administration to patients with GH receptor deficiency, hepatic failure and insulinomas caused a moderate increase of serum IGFBP-2. Markedly elevated levels were found in chronic renal failure, non-islet cell tumour induced hypoglycemia and leukaemias. The fact that all possible relationships between insulin secretion and IGFBP-2 levels could be identified suggests that insulin is not a major regulator. In general, there was an inverse relationship with serum IGFBP-3 (except IDDM) and IGFBP-2 levels were high in situations where free IGF-II should be expected to be high. The tentative conclusion would therefore be that free IGF-II is a major regulator of circulating IGFBP-2.

Animals↗
PubMed1993

[Hypoglycemia in childhood].

The article reviews the history of hypoglycaemia in children, documenting its importance in the genesis of neurological damage while attacking conventional dogmas on postnatal changes and the definitions of hypoglycaemia. A great deal of further research needs to be performed on the levels of blood glucose leading to "functional" neurological changes, as well as further research on the effects of hypoglycaemia on NMDA receptors. Of greatest practical importance would be new and better monitoring techniques to obtain more precise biochemical data that are instantly available to the clinical staff at the bedside. Finally, modern technology can be applied in defining one particular cause of what may be regarded as "idiopathic hypoglycaemia". A knowledge of basic biochemical processes can be used to predict patterns of metabolite profiles which are pathognomonic of the underlying disease.

Animals↗
PubMed1993

[Differential diagnosis and therapy of hypoglycemia in childhood].

Occurrence of hypoglycaemia is directly connected to fuel balance. Compared to free fatty acids, glucose is rapidly exhausted. Therefore, besides disturbances in available glucose (i.e. defects in gluconeogenesis or glycogenolysis) as well as their hormonal control, defects of beta-oxidation might be possible causes. According to recent investigations they occurred with similar frequency. A blood glucose level of 2.6 mmol/l (= 47 mg%) already represents a critical concentration of brain function. Based on pathophysiological concepts concentrations of glucose, free fatty acids, ketone bodies and insulin must be determined from a single plasma sample. Together with case history and clinical symptom findings, these parameters are useful to get a reliable tentative diagnosis. Therefore, descriptions like "ketotic" or "idiopathic" hypoglycaemia can be avoided and suitable treatment can be started. Suspected diagnosis must be confirmed by means of chromatographic, enzymatic, and if necessary histological investigations. Successful treatment depends mainly on early diagnosis. This is of importance in case of surgery in organic hyperinsulinism, but likewise for advisory help to families with infants suffering from beta-oxidation defects, to avoid prolonged fasting.

Child↗
PubMed1991

[Parameters of mineral metabolism in children and adolescents in athletic training].

Changes in bone structure like chondronecrosis and osteonecrosis occurred in a group of adolescent athletes especially gymnasts. To determine the etiology calcium, inorganic phosphorus, alkaline phosphatase activity and levels of 25-OH-Vit D were investigated. Single low calcium values were present in nearly the half of the athletes. In 37% the vitamin-D-levels were depressed. Such results were found in athletes with and without changes in bone structure. A vitamin D supplementation is recommended if low vitamin D levels are found. Vitamin D deficiency is not the only reason for the disturbances of the bone. Other factors are to take in consideration like nutrition, delayed bone maturation and its consequences, and the mechanical load.

Adolescent↗