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Biomedical subjects

P Lamesch

Publications and source records attributed to P Lamesch.

At least 19 recordsLinked to original sources
PubMed2003

Liver transplantation for hepatic and neurological Wilson's disease.

Wilson's disease (WD) is an autosomal-recessive inherited disorder of copper metabolism characterized by excessive deposition of copper throughout the body. If medical treatment fails in cases of fulminant hepatic failure and progressive hepatic dysfunction due to advanced cirrhosis, liver transplantation (OLTx) has been demonstrated to be a valuable treatment option. Between December 1993 and December 2002, 225 OLTxs in 198 patients were performed in our institution. In this consecutive series six patients (three females and three males) were liver grafted for WD. The follow-up ranged from 3 to 7 years. All patients are alive with well-functioning grafts at present. The ceruloplasmin levels increased after transplantation and remained normal. The Kayser-Fleischer ring disappeared in all patients, and urinary copper excretion normalized. The neurological manifestations in the two patients with severe neurological symptoms showed after 2 to 5 years a downward tendency; in one the ataxic movements disappeared completely. The psychiatric disorder in one patient disappeared as well the mild neurological symptoms in the patient with CHILD A cirrhosis. These two patients are fully recovered and returned to work. OLTx should be considered as a treatment option in patients with severe progressive neurological deficits even in cases with stable liver function since liver grafting definitely cures the underlying biochemical defect. In such cases an early decision for liver transplantation is justified because neurological deficits may become irreversible.

Copper↗
PubMed2002

Graves' disease is associated with an altered CXCR3 and CCR5 expression in thyroid-derived compared to peripheral blood lymphocytes.

The mechanisms by which T cells accumulate in the thyroid and support the autoimmune process in patients with Graves' disease (GD) are poorly understood. Chemokines and their receptors may be involved in this process. We have analysed the expression of CXCR3 and CCR5 as Th1-specific chemokine receptors, CCR3 as a marker for Th2 cells, CXCR4 (expressed on unprimed, naive T cells) and CCR2 (known to be involved in autoimmunity) on peripheral blood (PBL) and thyroid-derived lymphocytes (TL) using flow cytometry. Chemokine receptor expression on PBL of GD patients (n = 16) did not differ from that of normal controls (n = 10). In GD, CXCR3+ (67.3 +/- 4.0% versus 45.7 +/- 2.1%) and CCR5+ T cells (42.5 +/- 3.4% versus 18.8 +/- 2.1%) showed a significant enrichment in the TL compared to PBL. The positive cells were contributed mainly by the CD4+CD45R0+ subset. TL are mostly primed CD45R0+ T cells, but surprisingly, they had significantly higher levels of CXCR4+ cells among TL (96.2 +/- 1.0%) compared to PBL (66.8 +/- 4.2%). However, CXCR4 has been induced during in vitro isolation of TL. There was no correlation between chemokine receptors and the level of TSH-receptor and thyroid peroxidase autoantibodies. CCR3+ and CCR2+ cells remained unchanged in TL compared to PBL. We could confirm the results using RT PCR and immunohistology. In summary, TL showed a different chemokine receptor pattern compared to PBL from the same patient. This indicates a role for CXCR3 and CCR5 in the recruitment of T cells to the thyroid in GD.

Adult↗
PubMed2001

Familial isolated primary hyperparathyroidism--a multiple endocrine neoplasia type 1 variant?

OBJECTIVE: Familial isolated primary hyperparathyroidism (FIHP) is defined as hereditary primary hyperparathyroidism without the association of other diseases or tumors. Linkage analyses suggest that different genotypes can lead to the same phenotype of primary hyperparathyroidism. Hereditary syndromes associated with primary hyperparathyroidism are multiple endocrine neoplasia type 1 and type 2 (MEN 1 and MEN 2). In MEN 1, multiple parathyroid adenomas occur in more than 90% of the patients. Therefore, it has been suggested that FIHP could represent a variant or partial expression of MEN 1. DESIGN: We report on a large FIHP kindred with a MEN1 gene mutation. Nineteen family members (aged 10 to 87 years) were screened. Furthermore, statistical comparison by Fisher's exact tests of FIHP families with MEN1 gene mutations and MEN 1 families with two or more endocrinopathies was carried out to investigate genotype-phenotype correlations. METHODS: Mutational analysis of leucocyte DNA was carried out by direct sequencing of the complete coding region of the MEN1 gene. Screening of MEN 1 manifestations was carried out by determination of serum calcium, phosphate, parathyroid hormone, prolactin, ACTH, cortisol, IGF-I, gastrin, glucose, insulin, glucagon, serum potassium, aldosterone, plasma renin and urinary hydroxyindoleacetic acid. RESULTS: We detected an in-frame deletion mutation in exon 8 of the MEN1 gene resulting in the deletion of one glutamine acid residue at position 363. It was found in eight individuals. Two of these family members (aged 42 and 60 years) were operated for primary hyperparathyroidism, and three (aged 13 to 40 years) showed mild hypercalcemia and parathyroid hormone levels within the upper normal range or slightly elevated, without any clinical symptoms. Two individuals (aged 12 and 19 years) were normocalcemic. One could not be tested. None of them had clinical evidence of other MEN 1 manifestations. Statistical comparison of the mutation types in families with FIHP and families with two or more MEN 1-associated endocrinopathies reported in other studies reveals a significant difference. In families with FIHP, missense/in-frame mutations have been found in 87.5% of cases whereas in families with tumors in various endocrine glands these mutation types occur much less frequently (21-34%, P<0.05). CONCLUSIONS: These studies indicate that FIHP can represent a partial MEN 1 variant and is often caused by missense/in-frame mutations.

Adolescent↗
PubMed2001

Frequency of the calcium-sensing receptor variant A986S in patients with primary hyperparathyroidism.

OBJECTIVE: Recent studies have shown an influence of the calcium-sensing receptor variant A986S on the serum calcium concentration, suggesting that this genetic variant could be a candidate for various bone and mineral disorders. The intention of this study was therefore to investigate the frequency of the described calcium-sensing receptor variants A986S, R990G and Q1011E in patients with primary hyperparathyroidism to test the hypothesis as to whether these variants represent risk factors for the development of primary hyperparathyroidism. DESIGN: Fifty patients with primary hyperparathyroidism were included in the study. One hundred and two healthy blood donors served as controls. METHODS: Detection of the genetic variants A986S, R990G and Q1011E was done by direct sequencing of exon 7 of the calcium-sensing receptor in leucocyte DNA. RESULTS: The heterozygous variant A986S was found in 34% (17 of 50) of the healthy age- and sex-matched controls and 40% (20 of 50) of the patients with primary hyperparathyroidism. This difference was not statistically significant (P=0.68). However, in male patients the heterozygous variant A986S was found more frequently (67%, 6 of 9) than in male controls (20%, 2 of 10, P=0.07). The variants R990G and Q1011E were found less frequently (8-20%) in patients and controls without significant differences between the groups. Patients with the heterozygous variant Q1011E had significantly higher serum calcium and parathyroid hormone levels than patients with the wild-type variant (P<0.01). There was no correlation of serum calcium (total and corrected for albumin) with the calcium sensing receptor variant A986S in 102 healthy blood donors (P=0.45). CONCLUSIONS: The calcium-sensing receptor variants do not, therefore, seem to be major genetic determinants for the development of primary hyperparathyroidism. The variant A986S may possibly represent a risk factor for the development of parathyroid neoplasia in men. Moreover, the presence of the genotype Q1011E might influence the clinical course of the disease. The previously reported significant correlation of serum calcium levels with the genetic variant A986S in healthy subjects could not be confirmed.

Aged↗
PubMed2000

Neoadjuvant photodynamic therapy before curative resection of proximal bile duct carcinoma.

BACKGROUND: Hilar bile duct carcinoma has an 80% probability of local recurrence after curative resection, which might be reduced if neoadjuvant photodynamic therapy is feasible. CASE AND TREATMENT: After intravenous injection of sodium porfimer we treated an adenocarcinoma of the proximal common bile duct (T2 N0 M0, Bismuth type II) in a 72-year-old man with red laser light (applied from the lumen at a dose 250 Joules/cm2), and the adjacent right and left hepatic and common bile duct at a dose of 125 Joules/cm2. After 23 days the tumor was completely resected (adenocarcinoma pT2 pNO; G2). RESULTS: In the lumenal, 4-mm-thick layer the bile duct specimen exhibited complete tumor necrosis with pigmentation of photodegraded porfimer and no viable tumor cells, while in the outer layer of the wall (at 5-8-mm depth) viable cancer cell nests without degraded porfimer were seen. The bile duct tissue showed little damage. Eighteen months after surgery, neither tumor recurrence nor stricture formation was found at the pretreated bilioenteric anastomoses. CONCLUSIONS: a) Photodynamic therapy with sodium porfimer seems to be confined to the superficial 4-mm layer of bile duct cancer. b) Neoadjuvant photodynamic therapy is feasible for hilar bile duct carcinoma.

Adenocarcinoma↗
PubMed2000

Acute rejection of hepatic allografts from HLA-DR13 (Allele DRB1(*)1301)-positive donors.

Acute rejection of hepatic allografts does not show consistent association with the number of mismatches of HLA classes I and II. Therefore, we investigated the relation between specific donor or recipient HLA antigens and the occurrence of acute rejection. HLA typing of 35 liver transplant recipients and donors was performed by serological standard technique, with confirmation and subtyping by polymerase chain reaction with sequence-specific primers. HLA class I antigens were not associated with the occurrence of acute rejection. The graft was positive for HLA-DR13 in 8 of 13 transplant recipients (62%) with acute rejection, but only 4 of 22 recipients (18%; P =.024; P(Bonferroni-corrected) =.33, not significant) without rejection. The graft was positive for DRB1*1301 in 7 of 13 recipients (54%) with acute rejection, but only 1 of 22 recipients (5%) without rejection (P =.002; P(Bonferroni-corrected )=.028). This patient had experienced long-lasting bacterial sepsis, which markedly reduced the risk for acute rejection. We speculate that the expression of donor DRB1*1301 (if mismatched) may increase the risk for acute hepatic allograft rejection.

Acute Disease↗
PubMed2000

Diabetes mellitus and islet cell specific autoimmunity as adverse effects of immunsuppressive therapy by FK506/tacrolimus.

The induction of diabetes has been recognised as adverse effect of the immunsuppressive drug FK506/Tacrolimus. The aim of this study was to clarify whether insulinopenia or insulin resistance dominates and whether islet cell autoantibodies are present in patients treated by FK506. We investigated 58 patients 1-3 years after liver transplantation while under therapy with FK506 or CsA and prednisolone (0-7.5 mg) for basal blood glucose levels and islet-cell specific autoantibodies. A subgroup of 20 patients on FK506, 10 patients on cyclosporin and 15 healthy volunteers were metabolically tested by oGTT. Five patients had diabetes pre-transplantation. After transplantation, 9/28 FK506-treated patients developed newly diagnosed diabetes compared to 0/25 cyclosporin-treated patients (p<0.01). Both patient groups showed significantly higher fasting blood glucose, insulin or C-peptide levels compared to controls. Through the oGTT, FK506-treated patients without diabetes, but not cyclosporin-treated patients, had higher C-peptide levels compared to controls (p<0.05). Five/32 patients on FK506 compared to 0/26 patients on cyclosporin (p<0.05) had islet cell specific autoantibodies, mainly ICA without GAD- or IA2-Ab, a feature described for latent autoimmune diabetes in adults. ICA positivity was correlated to the diabetes associated HLA haplotype DR4/DQ*0302 (p<0.05). Although the interpretation of our metabolic data in patients with concomitant liver disease and prednisolone therapy has limitations, we suggest insulin resistance caused by treatment with FK506. However, manifestation of diabetes was associated with relative insulinopenia rather than insulin resistance in patients on FK506. Immunsuppressive therapy by FK506 was not able to suppress islet cell autoimmunity, and may even induce it in genetically predisposed patients.

Adult↗
PubMed2000

Frequency of somatic MEN1 gene mutations in monoclonal parathyroid tumours of patients with primary hyperparathyroidism.

OBJECTIVES: Investigation of small numbers of parathyroid tumours by X-chromosome inactivation analysis suggests that the majority of them are monoclonal lesions most likely caused by a somatic mutation. Somatic mutations in the MEN1 gene located on chromosome 11q13 have recently been identified in 12-17% of solitary parathyroid tumours in patients with sporadic primary hyperparathyroidism, and they may be the precipitating genetic defect leading to monoclonal cell proliferation in these tumours. DESIGN: To determine the prevalence of MEN1 gene mutations in monoclonal parathyroid neoplasias we investigated 33 parathyroid tumours of patients with primary hyperparathyroidism for clonality and mutations in the MEN1 gene. METHODS: X-chromosome inactivation analysis was used to assess the clonal status of the tumours, direct sequencing of the complete coding region was applied to identify mutations in the MEN1 gene. RESULTS: Twenty-eight female patients (26 patients with solitary adenoma, 2 patients with hyperplasia) were informative for the polymorphism of the androgen receptor on the X-chromosome and could be tested for inactivation pattern. Nineteen of twenty-six (73%) solitary adenomas were monoclonal. Somatic mutations in the MEN1 gene were identified in nine cases. Six of them were found in the relatively large second exon of the MEN1 gene (A49D, 193del36, 402delC, 482del22, 547delT, W126X). One was found in exon 5 (904del9), one in exon 7 (Y327X) and one in exon 9 (R415X). Of the monoclonal tumours, 5 out of 19 (26%) harboured a somatic MEN1 gene mutation. CONCLUSIONS: In summary, 73% of the solitary parathyroid adenomas were monoclonal. In 26% of the monoclonal tumours a somatic MEN1 gene mutation has been identified. However, for 74% of monoclonal tumours of the parathyroids the underlying genetic defects are still not known.

Adenoma↗
PubMed1999

Coincidence of hot thyroid nodules and primary hyperparathyroidism.

Hyperthyroidism is frequently associated with hypercalcemia, which usually subsides after successful treatment of hyperthyroidism. Moreover, thyroid nodules are frequently detected by preoperative thyroid ultrasound in patients with primary hyperparathyroidism. Sensitised by the observation of a patient with coexisting hyperthyroidism and hyperparathyroidism we prospectively evaluated thyroid nodules in euthyroid patients with hyperparathyroidism by thyroid scintigraphy. Whereas the first patient with hyperparathyroidism was hyperthyroid the subsequent four patients with hyperparathyroidism and thyroid nodules had normal fT3 and fT4. Two patients had hypercalcemia and nephroureterolithiasis. Three patients suffered from hypercalcemia and bone pain due to osteoporosis. In the hyperthyroid patient hypercalcemia persisted after euthyroidism was achieved intact parathyroid hormone was found to be elevated. Subsequently, thyroid nodules, detected by preoperative ultrasound in four euthyroid patients with primary hyperparathyroidism, were identified as compensated hot nodules by thyroid scintigraphy. All patients underwent combined subtotal thyroidectomy and parathyroid resection. Histology showed hyperplastic parathyroid glands in one patient and a single parathyroid adenoma in four cases. Postoperatively calcium and PTH levels returned to normal and TSH levels increased in all patients. Persistence of hypercalcemia after successful treatment of hyperthyroidism should be reason for the determination of parathyroid hormone. Thyroid nodules detected by preoperative ultrasound in patients with hyperparathyroidism living in areas of iodine deficiency should be further evaluated by scintigraphy even if TSH is normal. In the case of hot thyroid nodules both parathyroid and partial thyroid resection should be performed.

Aged↗
PubMed1999

Thyroidectomy in iodine induced thyrotoxic storm.

Between January 1996 and September 1997 we treated 4 patients with iodine-induced thyrotoxic storm (2 females, 2 men; age 54-77 years). Iodine contamination was due to iodine-containing contrast media in 3 patients and iodine-containing disinfectant in 1 patient. Thyroid storm with tachycardia, hypertension, sweating, tremor, weight loss and coma occured 3-10 weeks after iodine contamination. These symptoms were accompanied by raised fT4- and fT3-values. All 4 patients were initially treated with antithyroid drugs for 7 days, whereas 2 patients with coronary artery disease, demonstrated by coronary angio-graphy, were treated with antithyroid drugs for 2 weeks. Because of unsuccessful antithyroid drug treatment, all 4 patients underwent subtotal thyroidectomy. There were no perioperative complications. We conclude that early thyroidectomy is the appropriate treatment for iodine-induced thyrotoxicosis even in patients with severe accompanying diseases.

Aged↗
PubMed1998

The extracellular thyrotropin receptor domain is not a major candidate for mutations in toxic thyroid nodules.

Constitutive activation of the cyclic adenosine monophosphate (cAMP) cascade by either thyrotropin receptor (TSHR) or gsp mutations is considered to be the major molecular cause of toxic thyroid nodules (TTNs). In a recent study we investigated a consecutive series of 31 TTNs and identified 15 somatic TSHR mutations (n = 14 in exon 10; n = 1 in exon 9) but no mutations in gsp exons 7-10. The purpose of the present study was to determine whether the extracellular TSHR domain would be a candidate for mutations causing TTNs. Therefore, we screened TSHR exons 1-8 in the remaining 16 TTNs without mutations in TSHR exons 9 and 10 and gsp exons 7-10 of our previous study. Except for a known functional polymorphism in exon 1 (Pro 52 Thr) in 2 TTNs and a silent base exchange in exon 7 (187 Asn) in 7 other TTNs no TSHR mutations were identified. To clarify the molecular etiology of TTNs without TSHR or gsp mutations, candidate genes in other steps of the cAMP cascade have to be considered.

Amino Acid Sequence↗
PubMed1997

[Perforation of the cervical esophagus after ventral fusion of the cervical spine. Defect coverage by muscle-plasty with the sternocleidomastoid muscle: case report and review of the literature].

The therapy for spontaneous or artificial perforation of the esophagus remains a controversial matter. The following case report deals with the medical history of an artificial esophageal perforation after operative treatment of cervical disc disease. A 68-year-old male patient underwent a C4/C5 and C5/C6 discectomy with interbody fusion of C7-T1 vertebral body, according to Smith-Robinson. During this operation, a 3-cm-long lesion was made in the posterior wall of the esophagus, which was treated 24 h later with a primary suture. The clinical follow-up was complicated by mediastinitis with subsequent multiorgan failure. After recovery from this critical condition the patient dysphagia, which was related to a persistent lesion in the posterior esophageal wall with endoscopically demonstrated dislocation of a screw. After removal of the screw, the lesion was covered by means of sternocleidomastoid myoplasty. Moderate postoperative dysphagia was successfully treated by bougienage.

Aged↗
PubMed1997

[Surgical treatment of intrahepatic cholangiocarcinoma].

Cholangiocarcinoma is the second most frequent malignant tumor, after hepatocarcinoma, of the liver; it is diagnosed in approximately 10% of the cases. This retrospective study reviewed follow-up in 50 patients with intrahepatic cholangiocarcinoma treated from June 1979 through February 1993. Among these 50 patients, 32 underwent liver resection and 18 had a liver transplantation. After resection, the median survival was 13.9 months. Tumor stage was seen to have an effect on the Kaplan-Meier plots although the differences were not significant. Four patients died from tumor recurrence more than five years after curative resection, 4 patients are living today. After transplantation, the median survival was 5 months. Among the 18 patients, 1 recipient who had a stage II tumor is currently living 42 months after transplantation with no evidence of recurrence. Despite the high degree of malignancy of intrahepatic cholangiocarcinoma, a certain number of patients do benefit from liver resection, justifying this aggressive surgical approach. Inversely, transplantation does not appear to be an exceptional therapeutic alternative. In the future, cholangiocarcinomas will require multimodal therapeutics.

Bile Duct Neoplasms↗
PubMed1995

[Ergotamine-induced anorectal lesions].

During the past 10 years several reports on perianal ulcerations secondary to chronic use of ergotamine suppositories were published. The present case reports deal with 2 female patients who used ergotamine suppositories for treatment of sick head aches for several years. In both cases the suppositories were used chronically. The first patient, a 60 year old woman has been treated repeatedly because of recurrent perianal ulcerations. An infection and a carcinoma could be excluded. The diagnosis of ergotamine induced ulcerations could be suspected only after a detailed work up of the patients past medical history and interview of family members. The ulcerations healed within a few months after broad excision and withdrawal of the medication. The second patient, a 51 year old woman complained of severe obstipation which occurred within a few months. The investigations showed a circular stenosis in the lower third of the rectum. The patient was treated successfully by bougienage under general anaesthesia. These case reports demonstrate the difficulties in diagnosis such lesions and emphasize the importance of a close medical follow-up when ergotamine suppositories are used for treatment of migraine. Whenever possible, a continuous treatment should be avoided.

Anal Canal↗