60
Another family member had identical symptoms. After her return home and a symptom-free interval of five days she was admitted to hospital with fever, leucocytosis, and peritonitis. Laparotomy revealed a peri-appendicular abscess involving the caecum, and mesenteric lymphadenopathy. Ileocaecal resection was done, and phlegmonous inflammation of the appendix and ulcerative caecal colitis was shown histologically. Pus contained gram-negative rods. The only organism cultured from pus proved to be Salmonella hofit (Swiss National Reference Laboratory for Foodborne Diseases, Bern; and WHO Salmonella Reference Centre, Institut Pasteur Paris). S hofit was isolated preoperatively from faeces. After surgery, ciprofloxacin was started, resulting in defervescence and in restoration of the leucocyte count to normal within 72 hours. Stool cultures for Salmonella spp were negative after six days of treatment.
S hofit was initially isolated from the faeces of a turtle,’ and has occasionally been cultured from sewage.8 Apart from our case, this
serotype has
not
been
isolated
in
Switzerland
(personal
communication, A. Burnens, Swiss National Reference Laboratory for Foodborne Diseases). At the Institut Pasteur about thirty strains, mostly of human origin, have been collected (personal communication, M. Y. Popoff). However, we are aware of only one report of S hofit isolated from the faeces of a patient with diarrhoea:9 this patient had also been to Mauritius.
patients with insulin-dependent diabetes mellitus (IDDM, negative C-peptide test), and 13 patients with NIDDM. After taking a fasting blood sample (into edetic acid and trasylol), 1 mg glucagon was given intravenously and a second blood sample was obtained 6 min later. IAPP was measured by radioimmunoassay with the ’Peninsula DAPsystem’ (Peninsula Laboratories, Belmont, California, USA). Instead of a direct assay with 100 III plasma, IAPP was extracted from 500 III plasma over a ’Seppak C-18’ cartridge and eluted with 86% ethanol in 4% acetic acid. Standards in different concentrations were extracted from charcoaltreated plasma and compared with a non-extracted standard curve. Extraction recovery was 90%. Cross-reaction with CGRP is less than 0-001%. C-peptide concentrations were measured before and
after glucagon-stimulation. We found no difference in fasting IAPP concentrations between the three groups. After stimulation with glucagon IAPP concentration rose significantly (p < 005, paired t test) in controls and patients with NIDDM (p < 0-05), but not in those with IDDM:
Department of Internal Medicine, University Hospital, 4031 Basel, Switzerland
Bacteriology Laboratory, University Hospital, Basel
CLAUDE SCHEIDEGGER RENO FREI
1. Levison ME, Bush LM. Peritonitis and other intra-abdominal infections. In: Mandell
GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases. Edinburgh: Churchill Livingstone, 1990: 636-70. 2. Attwood SEA, Cafferkey MT, West AB, et al. Yersinia infection and acute abdominal pain. Lancet 1987; i: 529-33. 3. Dadswell JV. Acute appendicitis and salmonella infections. Br Med J 1973; i: 740. 4. Thompson RG, Harper IA. Acute appendicitis and salmonella infections. Br Med J 1973; ii: 300.
Lynch JJ, Beneventanto TC. Typhoid fever: an unusual radiographic presentation with appendicitis. Am J Gastroenterol 1980; 73: 168-73. 6. Boyd JF. Pathology of the alimentary tract in Salmonella typhimurium food poisoning. 5.
Gut 1985; 26: 935-44. Sapiro-Hirsch R, Hirsch W. Two new salmonella types: Salmonella uno = 6,8:z29: and Salmonella hofit 39:i:1,5. Acta Med Orient 1958; 17: 80-81. 8. Trichopoulos D, Papadakis JA, Karalis D, Vassiliadis P. Incubation at raised temperature of enrichment media, combined with secondary enrichment in Rappaport’s medium, for the isolation of salmonellas from sewage. J Hyg (Camb) 1975; 74: 205-13. 9. Fourquet R, Mantchala V. Première souche humaine de Salmonella hofit (39:i:1,5). Arch Inst Pasteur Madagascar 1975; 44: 57-60.
7.
=
As expected C-peptide concentrations increased in both controls and NIDDM patients. The C-peptide concentrations in IDDM patients were very low, both in fasting and stimulated conditions: no correlation between change in IAPP concentration and change in C-peptide concentration could be found. These results demonstrate the presence of IAPP in human plasma. Furthermore, despite the small number of subjects, the findings seem to indicate a correlation between an active pancreatic beta-cell mass, as present in healthy people and patients with NIDDM, and the capacity to release IAPP after stimulation with a suitable pharmacological agent. This finding accords with Johnson and colleagues’9 observation that IAPP is secreted by pancreatic beta cells. The finding of measurable fasting plasma IAPP in patients with IDDM suggests that IAPP is released from organs other than the pancreas, such as the stomach. We conclude that increased IAPP production might precede the formation of islet amyloid and functional impairment and/or destruction of beta cells
Department of Internal Medicine, University Hospital, 3584 CX Utrecht, Netherlands, Department of Internal Medicine, St Elisabeth Hospital, Amersfoort;
Islet-amyloid polypeptide in human plasma
and Endocrinology Laboratory, Bergweg Hospital, Rotterdam
B. C. VAN JAARSVELD W. H. L. HACKENG M. G. NIEUWENHUIS D. W. ERKELENS R. A. GEERDINK C. J. M. LIPS
Sm,—Pancreatic islet amyloid deposits are characteristic of patients
dependent diabetes mellitus (NIDDM). This amyloid is derived from a 37-aminoacid polypeptide, islet-amyloid polypeptide (IAPP), which has almost 50% structural homology with calcitonin-gene-related-peptide (CGRP).1 IAPP is present in normal pancreatic beta cells, in the same secretory granules as insulin.2 However, in patients with NIDDM the number of beta cells containing IAPP is decreased concomitantly with the appearance of intracellular and extracellular islet amyloid.3 The human IAPP gene has been identified and is
with non-insulin pancreatic islet
located on chromosome 12.’* The role of IAPP in the pathogenesis of NIDDM remains to be established. The clinical manifestation in cats seems to be preceded by increased beta-cell IAPP production and the formation of amyloid in the pancreatic islets.6 IAPP inhibits in-vitro glycogen synthesis in rat muscle; insulin stimulation of glucose uptake is opposed.7 IAPP mRNA has been found not only in the pancreas but also in other organs such as the stomach, suggesting a possible regulatory function of IAPP in carbohydrate metabolism.8 We have studied the presence of IAPP in plasma of 11 healthy controls (fasting blood glucose levels less than 6-0 mmol/1), 8
C, Wilander E, Hayden DW, O’Bnen TD, Johnson KH Amyloid fibrils in human insulinoma and islets of Langerhans ofthe diabetic cat are derived from a neutropeptide-like protein also present in normal islet cells. Proc
1. Westermark P, Wernstedt
Natl Acad Sci USA 1987; 84: 3881-85. Johnson KH, O’Brien TD, Hayden DW, et al. Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques. Am J Pathol 1988; 130: 1-8. 3. Westermark P, Wilander E, Westermark GT, Johnson KH. Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulindependent) diabetic and non-diabetic individuals. Diabetologia 1987; 30: 887-92. 4. Mosselman S, Hoeppener JWM, Zandberg J, et al. Islet amyloid polypeptide
2.
identification and chromosomal localization of the human gene. FEBS Lett 1988, 239: 227—32. 5. Mosselman S, Hoeppener JWM, Lips CJM, Jansz HS. The complete islet amyloid polypeptide precursor is encoded by two exons. FEBS Lett 1989; 247: 154-58. 6. Johnson KH, O’Brien TD, Jordan K, Westermark P. Impaired glucose tolerance is associated with increased islet amyloid polypeptide (IAPP) immunoreactivity in pancreatic beta cells. Am J Pathol 1989; 135: 245-50. 7. Cooper GJS, Leighton B, Dimitriadis GD, et al. Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle. Proc Natl Acad Sci USA 1988; 85: 7763-66. 8. Ferrier GJM, Pierson AM, Jones PM, Bloom SR, Girgis SI, Legon S. Expression of the rat amylin (IAPP/DAP) gene. J Mol Endocrinol 1989; 3: R1-R4. 9. Johnson KH, O’Bnen TD, Betsholtz C, Westermark P. Islet amyloid, islet-amyloid 1989; 321: 513-18. J polypeptide, and diabetes mellitus. N Engl Med
Another family member had identical symptoms. After her return home and a symptom-free interval of five days she was admitted to hospital with fever, leucocytosis, and peritonitis. Laparotomy revealed a peri-appendicular abscess involving the caecum, and mesenteric lymphadenopathy. Ileocaecal resection was done, and phlegmonous inflammation of the appendix and ulcerative caecal colitis was shown histologically. Pus contained gram-negative rods. The only organism cultured from pus proved to be Salmonella hofit (Swiss National Reference Laboratory for Foodborne Diseases, Bern; and WHO Salmonella Reference Centre, Institut Pasteur Paris). S hofit was isolated preoperatively from faeces. After surgery, ciprofloxacin was started, resulting in defervescence and in restoration of the leucocyte count to normal within 72 hours. Stool cultures for Salmonella spp were negative after six days of treatment.
S hofit was initially isolated from the faeces of a turtle,’ and has occasionally been cultured from sewage.8 Apart from our case, this
serotype has
not
been
isolated
in
Switzerland
(personal
communication, A. Burnens, Swiss National Reference Laboratory for Foodborne Diseases). At the Institut Pasteur about thirty strains, mostly of human origin, have been collected (personal communication, M. Y. Popoff). However, we are aware of only one report of S hofit isolated from the faeces of a patient with diarrhoea:9 this patient had also been to Mauritius.
patients with insulin-dependent diabetes mellitus (IDDM, negative C-peptide test), and 13 patients with NIDDM. After taking a fasting blood sample (into edetic acid and trasylol), 1 mg glucagon was given intravenously and a second blood sample was obtained 6 min later. IAPP was measured by radioimmunoassay with the ’Peninsula DAPsystem’ (Peninsula Laboratories, Belmont, California, USA). Instead of a direct assay with 100 III plasma, IAPP was extracted from 500 III plasma over a ’Seppak C-18’ cartridge and eluted with 86% ethanol in 4% acetic acid. Standards in different concentrations were extracted from charcoaltreated plasma and compared with a non-extracted standard curve. Extraction recovery was 90%. Cross-reaction with CGRP is less than 0-001%. C-peptide concentrations were measured before and
after glucagon-stimulation. We found no difference in fasting IAPP concentrations between the three groups. After stimulation with glucagon IAPP concentration rose significantly (p < 005, paired t test) in controls and patients with NIDDM (p < 0-05), but not in those with IDDM:
Department of Internal Medicine, University Hospital, 4031 Basel, Switzerland
Bacteriology Laboratory, University Hospital, Basel
CLAUDE SCHEIDEGGER RENO FREI
1. Levison ME, Bush LM. Peritonitis and other intra-abdominal infections. In: Mandell
GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases. Edinburgh: Churchill Livingstone, 1990: 636-70. 2. Attwood SEA, Cafferkey MT, West AB, et al. Yersinia infection and acute abdominal pain. Lancet 1987; i: 529-33. 3. Dadswell JV. Acute appendicitis and salmonella infections. Br Med J 1973; i: 740. 4. Thompson RG, Harper IA. Acute appendicitis and salmonella infections. Br Med J 1973; ii: 300.
Lynch JJ, Beneventanto TC. Typhoid fever: an unusual radiographic presentation with appendicitis. Am J Gastroenterol 1980; 73: 168-73. 6. Boyd JF. Pathology of the alimentary tract in Salmonella typhimurium food poisoning. 5.
Gut 1985; 26: 935-44. Sapiro-Hirsch R, Hirsch W. Two new salmonella types: Salmonella uno = 6,8:z29: and Salmonella hofit 39:i:1,5. Acta Med Orient 1958; 17: 80-81. 8. Trichopoulos D, Papadakis JA, Karalis D, Vassiliadis P. Incubation at raised temperature of enrichment media, combined with secondary enrichment in Rappaport’s medium, for the isolation of salmonellas from sewage. J Hyg (Camb) 1975; 74: 205-13. 9. Fourquet R, Mantchala V. Première souche humaine de Salmonella hofit (39:i:1,5). Arch Inst Pasteur Madagascar 1975; 44: 57-60.
7.
=
As expected C-peptide concentrations increased in both controls and NIDDM patients. The C-peptide concentrations in IDDM patients were very low, both in fasting and stimulated conditions: no correlation between change in IAPP concentration and change in C-peptide concentration could be found. These results demonstrate the presence of IAPP in human plasma. Furthermore, despite the small number of subjects, the findings seem to indicate a correlation between an active pancreatic beta-cell mass, as present in healthy people and patients with NIDDM, and the capacity to release IAPP after stimulation with a suitable pharmacological agent. This finding accords with Johnson and colleagues’9 observation that IAPP is secreted by pancreatic beta cells. The finding of measurable fasting plasma IAPP in patients with IDDM suggests that IAPP is released from organs other than the pancreas, such as the stomach. We conclude that increased IAPP production might precede the formation of islet amyloid and functional impairment and/or destruction of beta cells
Department of Internal Medicine, University Hospital, 3584 CX Utrecht, Netherlands, Department of Internal Medicine, St Elisabeth Hospital, Amersfoort;
Islet-amyloid polypeptide in human plasma
and Endocrinology Laboratory, Bergweg Hospital, Rotterdam
B. C. VAN JAARSVELD W. H. L. HACKENG M. G. NIEUWENHUIS D. W. ERKELENS R. A. GEERDINK C. J. M. LIPS
Sm,—Pancreatic islet amyloid deposits are characteristic of patients
dependent diabetes mellitus (NIDDM). This amyloid is derived from a 37-aminoacid polypeptide, islet-amyloid polypeptide (IAPP), which has almost 50% structural homology with calcitonin-gene-related-peptide (CGRP).1 IAPP is present in normal pancreatic beta cells, in the same secretory granules as insulin.2 However, in patients with NIDDM the number of beta cells containing IAPP is decreased concomitantly with the appearance of intracellular and extracellular islet amyloid.3 The human IAPP gene has been identified and is
with non-insulin pancreatic islet
located on chromosome 12.’* The role of IAPP in the pathogenesis of NIDDM remains to be established. The clinical manifestation in cats seems to be preceded by increased beta-cell IAPP production and the formation of amyloid in the pancreatic islets.6 IAPP inhibits in-vitro glycogen synthesis in rat muscle; insulin stimulation of glucose uptake is opposed.7 IAPP mRNA has been found not only in the pancreas but also in other organs such as the stomach, suggesting a possible regulatory function of IAPP in carbohydrate metabolism.8 We have studied the presence of IAPP in plasma of 11 healthy controls (fasting blood glucose levels less than 6-0 mmol/1), 8
C, Wilander E, Hayden DW, O’Bnen TD, Johnson KH Amyloid fibrils in human insulinoma and islets of Langerhans ofthe diabetic cat are derived from a neutropeptide-like protein also present in normal islet cells. Proc
1. Westermark P, Wernstedt
Natl Acad Sci USA 1987; 84: 3881-85. Johnson KH, O’Brien TD, Hayden DW, et al. Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques. Am J Pathol 1988; 130: 1-8. 3. Westermark P, Wilander E, Westermark GT, Johnson KH. Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulindependent) diabetic and non-diabetic individuals. Diabetologia 1987; 30: 887-92. 4. Mosselman S, Hoeppener JWM, Zandberg J, et al. Islet amyloid polypeptide
2.
identification and chromosomal localization of the human gene. FEBS Lett 1988, 239: 227—32. 5. Mosselman S, Hoeppener JWM, Lips CJM, Jansz HS. The complete islet amyloid polypeptide precursor is encoded by two exons. FEBS Lett 1989; 247: 154-58. 6. Johnson KH, O’Brien TD, Jordan K, Westermark P. Impaired glucose tolerance is associated with increased islet amyloid polypeptide (IAPP) immunoreactivity in pancreatic beta cells. Am J Pathol 1989; 135: 245-50. 7. Cooper GJS, Leighton B, Dimitriadis GD, et al. Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle. Proc Natl Acad Sci USA 1988; 85: 7763-66. 8. Ferrier GJM, Pierson AM, Jones PM, Bloom SR, Girgis SI, Legon S. Expression of the rat amylin (IAPP/DAP) gene. J Mol Endocrinol 1989; 3: R1-R4. 9. Johnson KH, O’Bnen TD, Betsholtz C, Westermark P. Islet amyloid, islet-amyloid 1989; 321: 513-18. J polypeptide, and diabetes mellitus. N Engl Med
