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Biomedical subjects

M Frank

Publications and source records attributed to M Frank.

At least 109 records · Page 6Linked to original sources
PubMed1995

Hormonal oral contraceptives, urinary porphyrin excretion and porphyrias.

The influence of hormonal oral contraceptives on the urinary porphyrin excretion of 40 healthy females has been studied. Two different hormonal oral contraceptives (combinations of gestoden or desogestrel, respectively, and ethinylestradiol) were applied for half a year. In each case twenty women received one of these two combinations. Porphyrin precursors delta-aminolevulinic acid and porphobilinogen were normal in all subjects as well as the mean of uroporphyrin and coproporphyrin. One healthy female developed a mild secondary coproporphyrinuria. In this case coproporphyrin isomer I was slightly enhanced and isomer III slightly lowered. Furthermore it could be shown that three females with repeated premenstrual clinical expression of an acute hepatic porphyria (acute intermittent porphyria and hereditary coproporphyria) could be treated successfully with a hormonal oral contraceptive or other exogenous hormones to stabilize the latent, subclinical phase of the disease.

Adult↗
PubMed1995

Circulating and tissue guanylin immunoreactivity in intestinal secretory diarrhoea.

Guanylin is a recently discovered peptide hormone that activates intestinal guanylate cyclase (GC-C) and thereby stimulates intestinal chloride secretion. Immunohistochemistry showed its presence in enterochromaffin (EC) cells of the gut. In vitro studies suggested that guanylin plays an important role in the endogenous modulation of intestinal salt and water secretion. In the present study the concentration of circulating immunoreactive (IR)-guanylin in plasma of patients with intestinal diarrhoea due to chronic bowel inflammation and patients with carcinoid tumours were measured with a specific radioimmunoassay. In 22 patients with Crohn's disease and eight patients with ulcerative colitis, plasma concentrations of IR-guanylin were 44 +/- 3 and 42 +/- 4 fmol mL-1, respectively. Levels were not different from that in 44 healthy volunteers suggesting that the circulating hormone is not involved in diarrhoea of these patients. In 17 patients with symptomatic carcinoid tumors the median concentration of circulating IR-guanylin was significantly enhanced (94 +/- 16 fmol mL-1, range 37-312 fmol mL-1). Immunohistochemistry revealed the presence of immunoreactive guanylin in carcinoid tissues, suggesting that these tumours co-release guanylin along with their usual resident hormone, serotonin. Enhanced local secretion of guanylin may play a causal role in diarrhoea of these patients and its elevation in plasma may be of diagnostic value in this type of endocrine tumours.

Adult↗
PubMed1995

Treatment of porphyria cutanea tarda by the effect of chloroquine on the liver.

Porphyria cutanea tarda (PCT) is characterized by cutaneous symptoms in association with hepatic accumulation and urinary excretion of mainly uro- and heptacarboxyporphyrins. 24 PCT patients excreting urinary porphyrins between 1.9 and 5.8 mumol/24 h (normal < 0.2) were treated with chloroquine at a dose of 125 mg twice a week. During the first phase of therapy urinary porphyrin excretion transiently increased 1.1- to 2.9-fold indicating a phase of mobilization. A slight initial elevation was also found regarding the activities of serum aminotransferases reflecting the hepatotoxic effect of chloroquine. The clinical symptoms disappeared after a period ranging from 2 to 6 months, and after an average of 12 months the porphyrin excretion in all patients had returned to nearly normal values.

Adult↗
PubMed1995

[Liver cirrhosis in protoporphyria: bile acid therapy and liver transplantation].

Protoporphyria is an important differential diagnosis in patients with jaundice and cutaneous photosensitivity. In 1975 erythropoietic protoporphyria and liver damage of unknown origin were diagnosed in a 24 year old patient with photosensibility since early childhood. Laparoscopic liver biopsy confirmed protoporphyrin-associated liver cirrhosis in 1983. Therapy with ursodeoxycholic acid was initiated and liver function was stable during an 18 month period. In december 1989 the patient developed severe intrahepatic cholestasis with rapid deterioration of liver function. Liver transplantation was performed in 1990. The patient is now five years after transplantation in an excellent clinical condition. This 20 year observation period gives insight in the pathogenesis of protoporphyrin-induced hepatobiliary complications in a latent and overt phase. The relevant diagnostic and prognostic porphyrin parameters and therapy of protoporphyric liver disease are discussed.

Adult↗
PubMed1995

Characterization of a rat gene, rMAL, encoding a protein with four hydrophobic domains in central and peripheral myelin.

Wrapping and compaction of myelin sheaths around axons require specific membrane and membrane-associated proteins. Transmembrane proteins like proteolipid protein (PLP), the peripheral myelin protein 22 (PMP-22) and P0 as well as myelin basic protein (MBP) are crucial for this process. We have isolated a rat cDNA, initially denominated NS 3, that is mainly expressed in the myelinating cells of the nervous system, the oligodendrocytes and Schwann cells. The cDNA encodes a highly hydrophobic protein of 16.8 kDa with four putative transmembrane domains. The putative NS 3 protein lacks a N-terminal hydrophobic leader sequence and has no consensus sequence for N-linked glycosylation. In contrast to PLP and PMP-22, the first and third putative transmembrane domain of the NS 3 protein contain charged amino acids, a feature which resembles the structure of gap junction proteins. Sequence analysis showed that NS 3 is the rat homolog of a human gene called MAL that was cloned from, and is expressed in various T-cell lines. Therefore, we call this gene rMAL (rat MAL). In the nervous system, the expression of rMAL, mRNA begins after birth and is highest during myelination. In situ hybridization shows that rMAL mRNA is exclusively expressed in white and gray matter oligodendrocytes in the CNS and in myelinating Schwann cells in peripheral nerves. Immunohistochemistry using a peptide-specific antibody localized the rMAL protein in the myelinated areas of the CNS and PNS. Furthermore, we demonstrate by immunoblot analysis that rMAL is a component of myelin. Its structure and distribution suggest that the rMAL protein might play an important role in compact myelin. We propose that the name rMAL protein refers to rat Myelin And Lymphocyte protein.

Animals↗
PubMed1995

[Measuring the concentration of various plasma and placenta extract proteolytic and vascular factors in pregnant patients with HELLP syndrome, pre-/eclampsia and highly pathologic Doppler flow values].

OBJECTIVE: Impaired trophoblast invasion plays a major role in the development of preeclampsia. Therefore various factors that are involved in invasion were investigated in gestational disease. METHODS: In pregnant women with HELLP-syndrome (n = 18), pre-/eclampsia (n = 21) and highly pathological Doppler flow measurements (hpD) (n = 13), plasma and placental tissue extract concentrations of uPA, uPA-receptor, tPA, PAI-1, MMP-8, MMP-9, TIMP-1, thrombomodulin, and angiogenin were measured using ELISA. RESULTS: In all three collectives, PAI-1 plasma concentrations were significantly higher (p < 0,05) than in normal pregnancies, in patients with HELLP-syndrome, tPA and TIMP-1 plasma levels were also elevated. MMP-9 concentrations in placental tissue extracts were lower in pre-/eclampsia than in normal pregnancies. CONCLUSIONS: Impaired placental implantation and remodelling in gestational disease is reflected by changes in plasma and placental tissue extract concentrations of various factors that are involved in these processes.

Adult↗
PubMed1994

Management of gastroenteropancreatic endocrine tumors: the place of somatostatin analogues.

The place of the long-acting somatostatin analogue octreotide in the management of symptoms in patients with functional gastroenteropancreatic (GEP) tumors and of growth in patients with metastatic disease is reviewed in this report. Numerous studies indicate that octreotide is, currently, the therapeutic principle of first choice in the symptomatic treatment of patients with carcinoid syndrome, Verner-Morrison syndrome and glucagonoma syndrome but not of insulinoma and gastrinoma patients. A beneficial effect on tumor growth has been demonstrated in 40% of patients with metastatic GEP tumor with stabilization of the disease as the most favorable response. However, further studies have to identify subgroups of patients in whom octreotide alone or in combination with alpha-interferon inhibits tumor growth.

Carcinoid Tumor↗
PubMed1994

[Combined treatment of metastatic endocrine tumors of the gastrointestinal tract with octreotide and interferon-alpha].

14 patients with metastatic endocrine gastro-entero-pancreatic carcinoma (6 patients with Carcinoid-syndrome, 3 with gastrinoma and 5 with non-functioning tumor) have been treated with Octreotide 3 x 200 micrograms/die plus Interferon-Alpha 3 x 5 Mio U/week after documented tumor progression during preceding Octreotide-monotherapy. 6 out of 14 patients responded favourable to the treatment: one patient with partial regression and 5 patients with stillstand of tumor growth. In only one patient initial tumor stillstand for 6 months was followed by tumor progression whereas in five patients a beneficial effect on tumor growth could be documented up to 34 months. Inhibition of tumor growth and tumor progression was not necessarily paralleled by respective changes in peripheral hormone levels. These results should initiate a controlled prospective study to prove the hypothesis that in patients with metastasized endocrine gastro-entero-pancreatic tumors the combination of Octreotide and Interferon-Alpha is superior to monotherapy with Octreotide or Interferon-Alpha and to identify those patients who respond to this combined therapy.

Biomarkers, Tumor↗
PubMed1993

Gastric argyrophil (enterochromaffin-like), gastrin, and somatostatin cells after proximal selective vagotomy in man.

The number, size, and volume density of endocrine cells was determined in biopsies obtained endoscopically in patients after proximal selective vagotomy (PSV; N = 31), antrectomy (N = 9), untreated duodenal ulcer (DU) disease (N = 11), and in controls (N = 15). Serum gastrin was significantly elevated after PSV (mean 60 pg/ml) compared to DU patients (29 pg/ml), controls (26 pg/ml), and after antrectomy (11 pg/ml). Volume density of fundic argyrophil (largely enterochromaffin-like) cells after PSV (0.74%) and in DU disease (0.63%) were significantly (P < 0.001) higher when compared with controls (0.37%) but lower after antrectomy (0.24%; P < 0.02). The density of argyrophil cells was not influenced by the interval following PSV or the magnitude of hypergastrinemia. Antral gastrin cells were increased after vagotomy, whereas the antral and fundic somatostatin cell numbers were reduced after PSV. It is concluded that: (1) a major role of the vagal nerve as a trophic factor for enterochromaffin-like cells could not be demonstrated after PSV, and (2) moderate hypergastrinemia after PSV did not induce proliferation of ECL cells.

Adult↗
PubMed1993

Home blood glucose monitoring: effectiveness in a general population of patients who have non-insulin-dependent diabetes mellitus.

OBJECTIVE: To determine whether home blood glucose monitoring as used by non-insulin-dependent diabetes mellitus patients followed in primary care nonresearch clinics improves glycemic control or reduces utilization of the outpatient laboratory. DESIGN: A retrospective chart review for 229 patients receiving outpatient supplies for home testing of either blood or urine. SETTING: A variety of nonresearch clinics at a Veterans Affairs Medical Center, a teaching hospital affiliated with an academic university medical center. PATIENTS: Outpatient veterans followed in diabetes, primary care, internal medicine, or endocrine clinics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean glycosylated hemoglobin for an unselected group monitoring glycemic control by urine testing only was 11.32% and for those using blood monitoring was 11.37%. Frequency and duration of monitoring had no apparent impact on glucose control. There was no decrease in the utilization of the laboratory among those patients practicing home blood glucose monitoring. CONCLUSIONS: For non-insulin-dependent diabetic patients followed in a nonresearch clinic setting, the benefits of home blood glucose monitoring remain to be proven.

Adult↗
PubMed1993

Surgery for membranous subaortic stenosis. Long-term follow-up.

From 1958 to 1992, 105 patients were operated for discrete (or membranous) subaortic stenosis (DSAS). Our surgical techniques changed during this period. Before 1980 DSAS was removed by a sharp excision leaving the part on the mitral valve untouched (n = 58). After 1980 blunt dissection was used to enucleate DSAS completely (n = 47). The operation for DSAS was combined with aortic valve replacement (AVR) in 7 instances. Follow-up with recent echo-Doppler studies was complete in 100 patients. Recurring or persisting DSAS led to reoperation in 17 patients. Sixteen of them had had sharp, incomplete resections. One patient from the group of complete blunt enucleations was reoperated on twice. The interval between the first operation and the first reoperation averaged 9.7 years (range: 1-33 years). Nine reoperated patients had AVR. The risk factors for AVR were older age at first operation or late reoperation. In our early experience five patients died after operation. Another three patients died following one or more reoperations. Blunt dissection never led to complete AV block. It follows the anatomical cleavage planes and always allowed for complete and safe removal of DSAS. Although the follow-up is shorter, blunt enucleation thus far has had a lower incidence of reoperation.

Adolescent↗
PubMed1993

[Anesthesia with propofol during an exacerbated course of acute intermittent porphyria].

In the eighth week of pregnancy the medical indication for induced abortion was established due to an exacerbating acute intermittent porphyria with life-threatening neurological symptoms. delta-aminolaevulinic acid and porphobilinogen were excessively increased in urine prior to the operation. Anaesthesia was induced with a bolus of propofol, alfentanil and droperidol, maintained by 67% of nitrous oxide and small bolus injections of the three drugs. The patient regained consciousness immediately after the operation, and reached full orientation and cooperativeness within five minutes. The postoperative period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. Chorion gonadotropins and porphyria markers decreased within the next four weeks accompanied by a simultaneously progressing clinical improvement. The use of propofol and the other drugs appears justified even in exacerbated porphyria.

Abortion, Therapeutic↗
PubMed1993

Nucleolar organizer regions and glycoprotein-hormone alpha-chain reaction as markers of malignancy in endocrine tumours of the pancreas.

The value of silver staining of nucleolar organizer regions (AgNORs) and human chorionic gonadotropin alpha-chain reaction (HCG-alpha) as markers of malignancy was investigated in 60 primary pancreatic endocrine tumours, 37 of which had metastasized at the time of surgery, and in one of which metastases developed 4 years after surgery. Assessment of AgNORs by digital image analysis revealed few but large AgNORs (mean number 2.5 +/- 1.1; mean area 0.32 +/- 0.1 microns 2) in the 22 benign tumours and many but small AgNORs (mean number 5.1 +/- 1.9, P < 0.05; mean area 0.18 +/- 0.09 microns 2, P < 0.01) in the malignant tumours. Quantification of the number of AgNORs per tumour cell nucleolus (AgNOR distribution score) showed that 96% (26/27) of tumours exhibiting at least 5% of cells with more than six AgNORs per nucleolus showed metastases either at the time of diagnosis or up to 4 years after surgery. HCG-alpha immunoreactive cells were present in 25/38 (66%) malignant tumours and in 4/22 (18%) benign tumours. Combined evaluation of AgNOR distribution and HCG-alpha scores showed a high positive predictive value of 96% in cases with a raised AgNOR distribution score irrespective of the HCG-alpha status. A good negative predictive value (81%) was, however, only obtained if both parameters, AgNOR distribution and HCG-alpha scores, were negative. Thus, investigation of AgNORs and HCG-alpha is helpful in predicting malignancy in a high percentage of pancreatic endocrine tumours.

Adolescent↗
PubMed1993

Ambulatory pH monitoring in the management of reflux.

Ambulatory pH monitoring is a useful tool in the diagnosis and treatment of different esophageal and pharyngeal complaints. We have studied its use in an office setting in 15 patients with suspected gastroesophageal reflux disease (GERD). The patients were monitored for at least 18 hours while wearing a two-channel probe at home. Data obtained confirmed severe GERD in 6 patients and chest pain without GERD in 2 patients. Two patients continued to have symptoms in spite of appropriate therapy, while 2 untreated patients had symptoms of GERD with normal pH studies. We feel this technique is relatively safe and cost-effective and causes minimal disruption of the patient's life-style, while enabling the physician to monitor therapy and help achieve a good therapeutic outcome.

Adult↗
PubMed1993

[Diagnostic porphyrinopathies in hereditary hyperbilirubinemia].

Secondary porphyrinopathias were investigated in hereditary hyperbilirubinemias of the types Dubin-Johnson syndrome (DJS), Rotor's syndrome (RS), Gilbert's syndrome (GS) and compared with the findings in alcohol-induced cholestasis. The determination of urinary coproporphyrin excretion including its isomer I and III relation allows to diagnose and differentiate DJS from the other two forms of hereditary hyperbilirubinemias. An isomer I proportion of > 80% (normal < 32%) in association with a normal coproporphyrin excretion is pathognomonic for DJS. An increased coproporphyrinuria with about 70% isomer I is found in RS; a normal urinary coproporphyrin excretion combined with an isomer I increase of about 50-70% indicates the frequent GS. Alcohol-related cholestasis reveals a distinct pathologic coproporphyrinuria and elevated isomer I proportions between 37-67%. Due to the overlapping of isomer alterations in DJS-gene carriers, patients with GS and patients with exogenous toxically-induced cholestasis, additional diagnostic criteria are required to clarify the porphyrinopathia in its clinical context.

Adolescent↗
PubMed1993

[Porphyrin-induced biliary cirrhosis in protoporphyria: indications for liver transplantation].

A 51-year-old patient, who had experienced photosensitivity from childhood on, fell ill with an icterus accompanied by abdominal complaints. At the age of 46 years an erythropoietic protoprophyria had been diagnosed by an excessive protoporphyrinemia. Meanwhile, in consequence of the protoporphyria's erythrohepatic progression, a biliary liver cirrhosis developed, associated with portal hypertension and marked splenomegalie. As a remission of the protoporphyria-induced hepatobiliary complication could not be achieved by conservative medical treatment, the indication for orthotopic liver transplantation was established. The operation proceeded without complications, and the postoperative course, too, revealed no problems. With primarily good bile production, bilirubin and aminotransferases soon declined to normal values. Urinary coproporphyrin excretion was found to be normal after transplantation, only a domination of isomer I still peristed. Furthermore, a distinct elevation of protoprophyrin continued to exist both in erythrocytes and plasma as expression of the immanent enzyme deficiency typical for the genodermatosis protoporphyria. In the liver explant a micronodular transformation of parenchyma was found besides a deposition of reddish-brown protoporphyrin pigment in hepatocellular cytoplasma and Kupffer's cells, in addition to pigment casts in the canaliculi and within single portal bile ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗