The Emerging Role of Copeptin.

Direct measurement of the nonapeptide vasopressin has been limited by analyte instability ex vivo and in vivo rapid degradation, low serum concentrations requiring a sensitive assay and inherent secretory pulsatility. Copeptin is a 39 amino acid glycopeptide cleavage product of vasopressin synthesis with high stability, providing a marker of vasopressin secretion. Copeptin measurement has applications in diagnosis of diabetes insipidus and other diseases with altered vasopressin secretion. This review summarises our current understanding of serum copeptin measurement in diabetes insipidus and possible future applications of copeptin assays. As vasopressin is a stress hormone, there is emerging evidence on the use of copeptin for diagnosis and prognostication of disorders such as syndrome of inappropriate anti-diuretic hormone secretion, diabetes mellitus, critical illness, stroke, cardiovascular disease, respiratory disease, renal disease and thermal stress. Copeptin concentration measurement is likely to improve the diagnostic reliability of diabetes insipidus and, as a marker of stress, may have diagnostic or prognostic utility in specific clinical circumstances. Further studies are needed to determine if goal-directed therapy using plasma copeptin concentrations may improve patient outcomes.

Expression of heat shock proteins in chronic pancreatitis: protective or pathogenic roles?

The tissue-distributions of heat shock proteins (HSP) identified by monoclonal antibodies ML-30, TB-78, CA-Str7-1, and MAB 72/73 have been examined in formalin-fixed and paraffin wax-embedded tissues from 10 normal pancreatic specimens and 92 cases of chronic pancreatitis. The chronic pancreatitis cases were divided by probable etiology into alcohol-related, postacute pancreatitis, or idiopathic. The HSP identified by ML-30 and CA-Str7-1 were constitutively expressed, with a regional distribution, by duct and ductular epithelial cells in all normal pancreatic tissues. The HSP detected by ML-30 were expressed uniformly throughout the cytoplasm of the majority of ductular epithelial cells in all cases of chronic pancreatitis, irrespective of suspected etiology, and in the ducts of all but two cases of alcohol-associated chronic pancreatitis. The HSP defined by CA-Str7-1 were identified in the majority of duct or ductular epithelial cells in most of the cases of chronic pancreatitis, although possible differential expression was observed with respect to etiology (ie, there seemed to be less HSP in cases of postalcohol pancreatitis). The HSP identified by TB-78 were not constitutively expressed by normal pancreatic tissues but were found in a few scattered epithelial cells in two of these cases. However, significant expression of these HSP were observed in most epithelial cells in a population of cases regarded as either alcohol-associated (0.05 > p > 0.02) or postacute chronic pancreatitis (0.01 > p > 0.001). The HSP identified by monoclonal antibody MAB 72/73 were either not demonstrable or were expressed at very low levels in both the normal and inflamed pancreatic tissues. Expression of the four groups of HSP molecules appeared to be differentially regulated both in normal pancreatic and in chronic pancreatitis tissues. These differences in expression may indicate different functions in normal tissues, with either a protective or a pathogenic role for these proteins in the diseased state. Our current findings support the hypothesis that expression of certain HSP, particularly those identified by TB-78, may be involved in the pathogenesis of distinct subtypes of chronic pancreatitis. Our data do not suggest that HSP are the primary targets of immune-mediated cytotoxic activity; nevertheless, enhanced expression of these molecules by pancreatic ductular epithelial cells does provide an environment in which increased amounts of endogenous intracellular peptides may be transported to the cell surface, thereby becoming potential targets of immune-surveillance and cell-mediated cytotoxicity. Conversely, HSP may play a protective role in such a manner that selected groups of pancreatic ductular epithelial cells withstand cytotoxic damage of chemical, metabolic, or immune origin, and for significantly increased periods of time than they would otherwise; HSP thereby conserve a population of "reserve" epithelial cells from which pancreatic regeneration might occur. Identification of distinct pathogenic groups, defined according to precise immunohistochemical criteria, might provide the basis of a functional assessment and hence allow development of biologically appropriate strategies for managing individual patients with chronic pancreatitis.

A preliminary study of possible prognostic factors of traumatic liver injury seen at University Hospital, 1984-1991.

A retrospective study was carried out on 42 patients (38 males, 4 females, mean age 25.9) with liver injury at the University Hospital, Kuala Lumpur from 1994 through to 1991. Prognostic factors that might help to identify those patient survival was related to pulse rate on arrival ( < or = 120 beats per minute, p = 0.027), systolic blood pressure at induction of anaesthesia ( > or = to 80 mmHg, p = 0.003) and intraoperative blood transfusion of < or = to 4 units (p = 0.05). This data were supported by the 95% confidence interval suggesting that these factors may be strong prognostic indicators individually. Increased mortality was also associated with increased total blood transfused (p = 0.002) and grade of liver injury (p = 0.02). Although the factors we have identified reflect both the severity of injury and resuscitative and surgical efforts, further studies using a prospective design are required to confirm these findings.

Retroperitoneal malignant fibrous histiocytoma with renal involvement.

Malignant fibrous histiocytoma is a mesenchymal tumour which can involve the genitourinary organs primarily or by secondary extension. Both conditions are rare. We report four cases of retroperitoneal malignant fibrous histiocytoma involving the kidney by local extension. Diagnosis was difficult because of diverse, non-specific clinical features and may only be reached at operation or post mortem. Prognosis is poor. Although en bloc tumour resection with nephrectomy was possible in two patients, they returned with recurrences.

Retroperitoneal malignant fibrous histiocytoma causing profuse bleeding per rectum.

A case is reported of retroperitoneal malignant fibrous histiocytoma (MFH) invading into the colon, causing fresh bleeding per rectum. It illustrates the difficulty encountered in the pre-operative diagnosis of this condition, especially in a patient with an atypical presentation of profuse lower gastrointestinal bleeding.

Beware the anomalous portal vein.

Portal vein thrombosis is an unusual potential complication of liver resection. In our case it was due to ligation of the right branch of the portal vein during right hepatectomy in a patient without portal vein bifurcation. Hepatic angiography can delineate this abnormality and influence the choice of surgical management.

Expression of major histocompatibility antigens in human chronic pancreatitis.

T-lymphocytic infiltration of the exocrine pancreas and liver in patients with chronic pancreatitis has suggested that cell mediated immune mechanisms may play a part in the pathogenesis of this disease. As expression of major histocompatibility (MHC) antigens is a prerequisite for organ specific autoimmunity, the expression of HLA class I (beta 2-microglobulin) and class II (HLA-DR) determinants have been analysed, together with the presence of T-lymphocytes, in 93 patients (64 men and 29 women, mean age 40.6 years) having an operation for chronic pancreatitis. Ethanol (63 patients), recurrent acute pancreatitis (12), congenital lesions (2), and unknown (16) were suggested to be the causes of the disease. Immunohistochemical staining of formalin fixed and paraffin wax embedded tissue sections used conventional immunohistochemical techniques with specific anti-serum samples. No MHC expression was identified in 10 histologically normal pancreatic control specimens or in four cases of chronic pancreatitis secondary to obstruction by neuroendocrine tumours within the head of the pancreas. beta 2-microglobulin expression by pancreatic exocrine epithelial cells was seen in 76 chronic pancreatitis specimens (82%) while HLA-DR was present in 61 (66%). Simultaneous expression of both class I and II determinants was seen in 53 (57%) of cases. MHC determinant expression was not found in 10 cases (11%) of chronic pancreatitis. In the positive specimens, expression was confined to ductal and ductular (interlobular and intralobular) epithelium with no staining of acinar cells. Staining was not related to the suspected cause of the disease or age. T-lymphocytes were more prominent in chronic pancreatitis mean (SEM) (131 (15) cells per high powered field) than controls (5 (1), p < 0.01). Aberrant MHC expression by exocrine pancreatic epithelial cells occurring in the presence of an appreciable T-cell infiltration confirmed that the appropriate cellular conditions were present for cell mediated cytotoxicity to contribute to the pathogenesis of chronic pancreatitis.

A study of primary drug resistance in pulmonary tuberculosis in west Malaysia 1984-1987.

Eight hundred and fifty-six strains of Mycobacterium tuberculosis from previously untreated patients with pulmonary tuberculosis from various states in West Malaysia were studied during the period 1984 to 1987. All the strains were tested for in vitro susceptibility to the anti-tuberculosis drugs isoniazid (INH), streptomycin (SM), rifampicin (RMP) and ethambutol (ETB). One hundred and twenty-one of the isolates (14.18%) were resistant to 1 drug while 17 (1.97%) were resistant to 2 drugs. No strain was found to be resistant to more than 2 drugs. The prevalence of primary resistance to INH was 4.20%, SM was 7.59%, RMP was 0.95% and ETB was 1.44%. In 1.86% of isolates, resistance was noted to both INH and SM, while 0.11% were resistant to both RMP and ETB. There was no significant difference in distribution of resistant bacilli between the sexes (p > 0.01).

Chromosome 17 allele loss in hepatocellular carcinoma but not in synchronous liver adenoma.

A 51-year-old female underwent resection of two synchronous liver tumours, a hepatocellular carcinoma and an adenoma. DNA analysis revealed allele loss on chromosome 17 (17p13, near the locus of p53 tumour suppressor gene) in the hepatocellular carcinoma but not in the adenoma. This finding may support the view that loss of p53 tumour suppressor gene is associated with tumour progression.

Fibreoptic bronchoscopy in the diagnosis of pulmonary tuberculosis--a Malaysian experience.

We report our experience on the use of fibreoptic bronchoscopy in the diagnosis of pulmonary tuberculosis. The case records of 1,274 patients who underwent fibreoptic bronchoscopy at the National Tuberculosis Centre, Kuala Lumpur, Malaysia during a three-year period were reviewed. In 120 of them the final diagnosis was tuberculosis. Bronchoscopy confirmed the diagnosis in 37 patients (30.8%). This was achieved by bronchial aspiration for culture in 26 patients (70.3%) and bronchial biopsy for histopathology in 11 patients (29.7%). It was the exclusive method of confirmation in 16 patients (13.3%). Sputum culture was positive in 62 patients (51.7%) including 41 patients (34.2%) in whom bronchoscopy was unhelpful. Six patients had diagnosis confirmed by other means while in 36 others (30%) it was based on clinical features and supportive basic investigations. There were no complications noted. We conclude that while sputum examination remains the mainstay for diagnosing pulmonary tuberculosis, fibreoptic bronchoscopy serves as a safe and useful adjunct.

Pancreatic exocrine and endocrine function after operations for chronic pancreatitis.

Exocrine and endocrine function of the pancreas was assessed in the early postoperative period (< or = 2 months) and subsequently (mean, 25 months; range, 3 to 120) in 103 patients (69 men, 34 women; mean age, 42.4 +/- 11.6 years) undergoing operation for chronic pancreatitis. Alcohol was the main causative agent (69%) and pain the most frequent indication (87%) for operation. Drainage procedures (n = 23) did not alter pancreatic function either initially or on long-term follow-up. In the early postoperative period, distal pancreatectomy (n = 42) often impaired endocrine function without affecting exocrine function; seven patients (17%) became diabetic, and results of oral glucose tolerance test showed deterioration in 23 of 28 patients (82%, p < 0.05). On subsequent follow-up, 11 patients developed exocrine failure (p < 0.01) and 10 patients endocrine (p < 0.01) failure. Proximal pancreatectomy (n = 38) precipitated clinical exocrine failure in 14 patients (37%, p < 0.01), yet pancreolauryl tests in 18 patients showed little objective change in exocrine status (0.50 > p > 0.10). Endocrine function was initially spared after proximal pancreatectomy, but six additional patients (16%, p < 0.05) required treatment for diabetes at a mean of 19 months (range, 3 to 34). Deterioration in pancreatic function is thus not an invariable immediate consequence of pancreatic drainage procedures or partial pancreatectomy for chronic pancreatitis. Progression of disease must account, in part, for failure of both exocrine and endocrine function on long-term follow-up. Drainage operations appear to delay this progressive decline in pancreatic function.

Different DNA changes in primary and recurrent hepatocellular carcinoma.

DNA restriction fragment length polymorphism analysis was carried out on a primary and recurrent hepatocellular carcinoma in a hepatitis B virus negative patient. For the primary tumour, allele losses were found on the short arm of chromosome 17 (probe: p144-D6, 17p13) and the long arm of chromosome 5 with the probe Lambda MS8 (5q35-qter); other probes showed either no allele loss or a non-informative pattern. The recurrent cancer also showed allele loss with p144-D6, but not with Lambda MS8. In addition, the recurrent tumour had allele losses with Lambda MS43 (12q24.3-qter), pYNZ22 (17p13), and DNA rearrangement revealed by the probe Lambda MS32 (1q42-43), a pattern not seen in the primary lesion. These results indicate that the second hepatocellular carcinoma was of independent clonality and probably represents a de novo neoplasm rather than a recurrence.

Do patients with the sleep apnea/hypopnea syndrome drink more alcohol?

As alcohol ingestion may worsen the sleep apnea/hypopnea syndrome, we have investigated the alcohol consumption of patients with the sleep apnea/hypopnea syndrome in comparison to control subjects to determine whether patients with the sleep apnea/hypopnea syndrome drink excessively. A lifetime alcohol history was taken from each. There was no significant difference between the 50 patients with the sleep apnea/hypopnea syndrome and 95 age-matched controls in either the lifetime (patients 27, SEM 5 x 10(3); controls 26, SEM 4 x 10(3) units) or current (12, SEM 2; 12, SEM 2 units per week) alcohol consumption. There was no evidence that alcohol consumption was related to the development of arterial carbon dioxide retention or peripheral edema in such individuals.

Nasofacial zygomycosis.

Zygomycosis is an uncommon polymorphic fungal disease. One clinical subtype, nasofacial zygomycosis, is caused by infectious exposure to the organism Conidiobolus coronatus. A case affecting the nose and lips of a 42-year-old Malay man is reported here. The clinicopathologic features and management of this disease are described, and its differential diagnosis is discussed.

Morphological and immunohistochemical analysis of the human liver in chronic pancreatitis.

Morphological and immunohistological appearances of liver biopsy specimens are described in a personal series of 52 patients undergoing operation for chronic pancreatitis. The findings are compared with those in a series of 10 histologically normal liver biopsy specimens from patients without pancreatitis. Alcohol was the prime aetiological agent in 40 of the 52 patients (77%). No obvious damage to hepatic parenchymal cells or biliary structures was observed but minor morphological changes of alcohol associated liver disease were seen in 42% of specimens. The most consistent finding, present in 48 specimens (92%), was a chronic inflammatory cell infiltration of portal tracts. In all but one case, T lymphocytes predominated, but a few B cells were present. In four biopsy specimens, T cells spilled over into adjacent hepatic parenchyma, but there was no evidence of T cell mediated cytotoxic damage to the parenchymal cells or biliary epithelium. It is suggested that these inflammatory cells are in transit from the pancreas through the liver via the portal circulation and may reflect the underlying pathogenesis of chronic pancreatitis rather than alcoholic liver disease.