Raised Serum Alkaline Phosphatase Levels Research Articles

Understanding an isolated raised serum ALP level

Susan Thomas explains how to proceed when dealing with an asymptomatic patient with a raised serum alkaline phosphatase level

New insights in to systemic amyloidosis: primary amyloidosis associated with tubercular lymphadenitis

Tuberculosis is generally followed by secondary amyloidosis. The association of primary systemic amyloidosis with tuberculosis is very rare. There is only one case thus far reported in literature. We report such a rare case of primary amyloidosis with tuberculous lymphadenopathy. A 45 year old woman presented at the medicine department of all India institute of medical sciences, New Delhi with on & off erythematous rashes over both eyes for 1 year; low grade fever, fatigue and significant weight loss for 4 months, dysphagia for solid food since 1 month. Main finding on examination were pallor, macroglossia, bilateral periorbital erythematous rashes (racoon eyes), hepatomegaly & cardiomegaly. She had raised serum alkaline phosphatase level. Chest x-ray revealed cardiomegaly. USG abdomen revealed multiple retroperitoneal mesenteric lymph nodes and hepatomegaly. USG guided FNAC from mesenteric lymph node showed acid fast bacillus. Histological examination of liver biopsy showed amyloid deposition on congo red stain. Patient was treated with DOTS category I ATT with Bortezomib and Dexamethasone based weekly chemotherapy.

Risk Factors for Development of Biliary Stricture in Patients Presenting with Bile Leak after Cholecystectomy

Background/AimsThis study was aimed at determining the factors associated with the development of benign biliary stricture (BBS) in patients who had sustained a bile duct injury (BDI) at cholecystectomy and developed bile leaks.MethodsA retrospective analysis of 214 patients with BDI who were referred to our center between January 1989 and December 2009 was done.ResultsOne hundred fifty-three (71%) patients developed BBS (group I), and 61 (29%) were normal (group II). By univariate analysis, female gender (p=0.02), open cholecystectomy as the index operation (p=0.0001), delay in the referral from identification of injury (p=0.04), persistence of an external biliary fistula (EBF) beyond 4 weeks (p=0.0001), EBF output >400 mL (p=0.01), presence of jaundice (p=0.0001), raised serum total bilirubin level (p=0.0001), raised serum alkaline phosphatase level (p=0.0001), and complete BDI (p=0.0001) were associated with the development of BBS. Furthermore, open cholecystectomy as the index operation (p=0.04), delayed referral (p=0.02), persistent EBF (p=0.03), and complete BDI (p=0.001) were found to predict patient outcome in the multivariate analysis.ConclusionsFor the majority of patients with BDI, the risk of developing BBS could have been predicted at the initial presentation.

Super, red palm and palm oleins improve the blood pressure, heart size, aortic media thickness and lipid profile in spontaneously hypertensive rats.

BackgroundOleic acid has been shown to lower high blood pressure and provide cardiovascular protection. Curiosity arises as to whether super olein (SO), red palm olein (RPO) and palm olein (PO), which have high oleic acid content, are able to prevent the development of hypertension.Methodology/Principal FindingsFour-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were fed 15% SO, RPO or PO supplemented diet for 15 weeks. After 15 weeks of treatment, the systolic blood pressure (SBP) of SHR treated with SO, RPO and PO were 158.4±5.0 mmHg (p<0.001), 178.9±2.7 mmHg (p<0.001) and 167.7±2.1 mmHg (p<0.001), respectively, compared with SHR controls (220.9±1.5 mmHg). Bradycardia was observed with SO and PO. In contrast, the SBP and heart rate of treated WKY rats were not different from those of WKY controls. The SO and PO significantly reduced the increased heart size and thoracic aortic media thickness observed in untreated SHR but RPO reduced only the latter. No such differences, however, were observed between the treated and untreated WKY rats. Oil Red O enface staining of thoracic-abdominal aorta did not show any lipid deposition in all treated rats. The SO and RPO significantly raised serum alkaline phosphatase levels in the SHR while body weight and renal biochemical indices were unaltered in both strains. Serum lipid profiles of treated SHR and WKY rats were unchanged, with the exception of a significant reduction in LDL-C level and total cholesterol/HDL ratio (atherogenic index) in SO and RPO treated SHR compared with untreated SHR.ConclusionThe SO, RPO and PO attenuate the rise in blood pressure in SHR, accompanied by bradycardia and heart size reduction with SO and PO, and aortic media thickness reduction with SO, RPO and PO. The SO and RPO are antiatherogenic in nature by improving blood lipid profiles in SHR.

A case series of Paget's disease of bone in Chinese

OBJECTIVE. To report a series of patients with Paget's disease of bone that is rarely diagnosed in the Chinese, and to describe their presentations and clinical characteristics. DESIGN. A retrospective case series and literature review. SETTING. A regional public hospital in Hong Kong. PATIENTS. Patients with a diagnosis of Paget's disease of bone (or osteitis deformans) documented in the Clinical Management System of the Hospital Authority and being followed up in the medical endocrine clinic of the Pamela Youde Nethersole Eastern Hospital were identified in July 2011. This was performed using the Clinical Data Analysis and Reporting System of the Hospital Authority. Corresponding case notes and radiological imaging data were retrieved and reviewed. Patients with diagnostic X-ray or computed tomography findings of Paget's disease of bone were included in this series. The demographic data, clinical features, and investigation results of the cases were retrieved, recorded, and analysed. RESULTS. Seven Chinese patients (5 men and 2 women; mean age, 66 years) diagnosed to have Paget's disease of bone from 2000 to 2010 were identified. All but one were asymptomatic and presented as an incidental finding (isolated raised serum alkaline phosphatase level or abnormal X-ray). The most commonly involved sites were the skull and pelvis. The majority (71%) of the patients had polyostotic disease. During follow-up, there were no disease-related complications, nor was malignant transformation identified. None reported positive family history. CONCLUSION. In this series of seven Chinese patients with Paget's disease, most were asymptomatic and presented with an isolated raised serum alkaline phosphatase level during routine testing. The disease was predominantly found in males and the elderly, and commonly involved the skull and pelvis.

Correlation between MRI appearances and serum alkaline phosphatase levels in Osteogenic sarcoma.

Magnetic resonance imaging is a pictorial depiction of the patho-anatomy of a bony lesion. As different parts of the tumor in Osteogenic sarcoma concurrently undergo various biological processes i.e. osteoblastic new bone formation, cell death, necrosis, bony destruction and revascularization etc., we hypothesized that the image seen in MRI could be used to assess the tumor behavior at that time. This study was done as a preliminary study with the aim to find whether the MRI pictures can have identifiable patterns and if present whether they can be linked to biological behavior. We could identify 2 distinct patterns in T2 weighted images which correlated well with serum alkaline phosphatase a serum marker and the duration of symptoms and so we are reporting our observations. T2 weighted MRI pictures of 15 cases of Osteogenic sarcoma were studied for identifiable patterns in matrix. These patterns if found were to be linked to biological behavior in the form of serum alkaline phosphatase levels and duration of symptoms. We could identify 2 unique patterns named by us as Group 1 Heterogeneous type (4cases) which had a raised serum alkaline phosphatase level and had a history at presentation of less than 3 months duration. In Group 2 homogenous type (5 cases) the serum alkaline phosphatase levels were low and the cases presented after 6 months. As we could not identify any logical pattern in rest of the cases we labeled them as miscellaneous. MRI patterns can be used as markers of disease activity as there are 2 clear poles correlating well with serum alkaline phosphatase levels (high or low). Intermediate patterns may be the natural biological behavior and waxing and waning of the tumor disease activity.

Early Adolescent Nutritional Rickets

To evaluate early adolescents with nutritional rickets and their responses to treatment. 203 adolescents (aged 10 to 13 years) presenting with clinical features of lower-limb deformity, carpopedal spasm, joint swelling, a significant limp, or non-traumatic joint pain were screened for nutritional rickets. Multi-specialty examinations were performed. Family size, number of earning members, number and gender of children, preference for vegetarian food, composition of the meals, and the amount of milk consumed in a day were recorded. Radiographs of wrists, knees, ankles, and pelvis, as well as serum calcium, phosphate, and alkaline phosphatase levels were evaluated. The diagnosis of nutritional rickets was made based on a combination of clinical, radiological, and biochemical criteria, and confirmed by the responses to treatment. Children with nutritional rickets were treated by a single large intramuscular dose of vitamin D (600,000 IU) along with oral calcium and supplementary vitamin D as well as advice on diet and sunlight exposure. 40 females and 11 males were diagnosed as having nutritional rickets. 65% presented with bilateral knee pain with aggravation at night, 37% presented with lower-limb deformity, 24% had joint swelling especially at the wrist and ankle, 6% had a significant limp and walked with an antalgic gait secondary to pathological fractures. No patient reported carpopedal spasm. All patients had rachitic changes on radiographs in some but not all bones (100% in the ulna, 45% in the radius, 37% in the upper tibia, 37% in the lower fibula and 22% in the lower tibia). Three patients had pathological fractures. 55% had hypocalcaemia, 41% had hypophosphataemia and 100% had raised serum alkaline phosphatase levels. The mean time for biochemical resolution was 12 (range, 3-24) weeks. For radiological resolution it was 5 (range, 2-6) months, with the lower end of ulna being last to resolve. Radiographs of the lower end of ulna and serum alkaline phosphatase levels can be used as a screening and monitoring tool for nutritional rickets in early adolescents. There may be a high prevalence of subclinical vitamin-D deficiency in our adolescent population.

Preclinical Toxicokinetic Evaluation of Phortress [2-(4-Amino-3-Methylphenyl)-5-Fluorobenzothiazole Lysylamide Dihydrochloride] in Two Rodent Species

Background and Aims: The 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole prodrug Phortress exerts potent and selective antitumour activity in vitro and in vivo. Preclinical toxicokinetic studies in 2 rodent species were undertaken to determine Phortress’ maximum tolerated dose and advise a safe starting dose for clinical evaluation. Methods: Plasma pharmacokinetic parameters were determined by high-performance liquid chromatography and fluorescence detection following Phortress administration to mice (10 mg/kg, intravenously on days 1 and 8). Phortress (20 mg/kg, on days 1 and 8) was administered to CYP1A1/βGAL reporter mice; tissues were examined macro- and microscopically. Toxicological and pharmacodynamic endpoints were examined in organs of rodents receiving Phortress (10 mg/kg or 20 mg/kg, on days 1 and 8). CYP1A1 expression and Phortress-derived DNA adducts were determined in lungs and livers (on days 11 and 36). Results: No accumulation of Phortress was detected in murine plasma. β-Galactosidase activity inferred Phortress-derived induction of cyp1a1 transcription in the livers of transgenic mice; no total body weight loss was encountered in these animals. However, a fall in lung:body weight and kidney:body weight ratios, raised serum alkaline phosphatase levels and hepatic histopathological disturbances in animals receiving 20 mg/kg Phortress indicate organ sites of potential toxicity. CYP1A1 protein was induced transiently in the lungs of both species and in the livers of rats. Elimination of hepatic DNA adducts and rat pulmonary adducts was evident; however, murine pulmonary adducts persisted. Conclusion: Rodent preclinical toxicology established that mice represent the more sensitive rodent species, resolving a maximum tolerated dose of 10 mg/kg Phortress.

Steroid sensitive systemic disease with anaemia in the elderly: a manifestation of giant cell arteritis?

Nine elderly patients presented with features of a multisystem disorder thought to be either a connective tissue disease of undefined type or disseminated malignancy. Associated features were a normochromic anaemia, raised erythrocyte sedimentation rate (ESR) (or plasma viscosity) and raised serum alkaline phosphatase levels. None had symptoms to suggest either giant cell arteritis or polymyalgia rheumatica. Temporal artery biopsy was performed before trial of corticosteroid therapy in four, and two showed giant cell arteritis. All nine responded dramatically to corticosteroids and the anaemias resolved. One died after 6 y, and the rest are well after 1 to 7 y.

Vitamin D deficiency and otosclerosis.

A prospective study of 47 patients with otosclerosis was undertaken to investigate the possible etiologic role of vitamin D undernutrition. The population comprised 27 women and 20 men, with a mean age of 46.4 years (range 21 to 79). The disease was bilateral in 43 patients, and cochlear involvement was present in 84.4%. The mean duration of symptoms was 17.1 years. Vitamin D status was evaluated by measuring the plasma 25-hydroxy vitamin D3 (25-OHD), which is the main storage metabolite. Abnormally low 25-OHD levels were found in 10 patients (21.7%) and borderline low levels in another two. Raised serum alkaline phosphatase levels were present in 32.6%, calcium in 6.5%, and inorganic phosphate in 4.3%. Calcium and vitamin D replacement therapy resulted in significant hearing improvement in 3 of 16 patients; these data support a causal correlation. Vitamin D deficiency is probably a factor in the etiology of some cases of otosclerosis and is important, since the deafness resulting from cochlear involvement may be reversible.

Epidemiology of Postmenopausal Spinal and Long Bone Fractures

The incidence of spontaneous postmenopausal fractures and their relationship to menopausal age and bone mass were determined in a representative sample of 70-year-old Danish women. Two hundred and eighty-five women (1.2% of all women in that age group) were examined by case history, by 125I photon absorptiometry in both forearms (BMC), by metacarpal index (CA/TA), and by lateral radiographs of the spine. Twenty-four per cent of the participants had sustained single fractures, and 20% multiple fractures. Nineteen per cent had fractures of the lower forearm, 5% of the proximal humerus, 4% of the hip, and 5% crush fractures of the spine. These comprise Group I fractures, the most definite expressions of osteoporosis. The remaining other long bone fractures (7%) and spinal wedge fractures (18%) comprise Group II fractures. Group I cases were characterized by an earlier onset of the menopause and a definite decrease in bone mass, as judged from BMC and CA/TA, as compared with the nonfracture group. Group II cases did not display this distinction. Of Group I cases, those with multifractures differed from those with single fractures by having a five-year earlier occurrence of first fracture, a further decrease in bone mass, and a slightly raised serum alkaline phosphatase level. Serum calcium and phosphate levels were the same in all groups.

Serum alkaline phosphatase elevation in female rats treated with ethinyl estradiol

Ethinyl estradiol treatment to female rats resulted in increased levels of serum alkaline phosphatase, but was not associated with any other manifestation of toxicity such as increased serum transaminases or toxic lesions. Elevated serum alkaline phosphatase seen in rats treated with chloroform was associated with frank hepatotoxicity. Induction of hepatic drug metabolising enzymes in rats by phenobarbitone treatment did not result in raised serum alkaline phosphatase levels. Estradiol benzoate treatment to rats also did not increase serum alkaline phosphatase levels. Ethinyl estradiol also resulted in increased alkaline phosphatase content in the liver, intestine and bone. The raised intestinal alkaline phosphatase content of rats treated with phenobarbitone or estradiol benzoate was not associated with an increase in the serum levels. There was histochemical evidence of induction of canalicular alkaline phosphatase in the liver in Ethinyl Estradiol treatment. The study of the electrophoretic separation of serum alkaline phosphatase of ethinyl estradiol treated rats revealed the presence of a new fast moving fraction, similar to those seen in bile duct ligated rats. It is concluded that the serum alkaline phosphatase increase during ethinyl estradiol treatment at least in part is from the liver, due to new synthesis.

High Dosage Haloperidol in Chronic Schizophrenia

In a double blind chlorpromazine-controlled trial, high dosage haloperidol (100 mg daily) given for three months, appreciably improved the mental state of male chronic 'drug resistant' schizophrenic inpatients in the rehabilitation/long-stay unit of one psychiatric hospital. The results of a three-month follow-up suggested that the improvement could be maintained in some patients on lower doses of the drug. Serious extrapyramidal side effects were not seen at high doses. However, the majority of patients on haloperidol showed a deterioration in ward behaviour, possibly related to drowsiness, and developed raised serum alkaline phosphatase levels. These side effects disappeared in the follow-up period when either the drug was discontinued or the dose of haloperidol reduced.

Effect of long-term tetracycline therapy, steroid therapy and colectomy in pericholangitis associated with ulcerative colitis.

SUMMARYThe effect of long‐term tetracycline and steroid therapy, colectomy and biliary drainage on the clinical course, the results of liver‐function tests and hepatic histological changes in seven cases of pericholangitis and ulcerative colitis have been assessed. Tetracycline was given to six patients for periods varying from one and a half to six years in a maintenance dose of 500 mg. per day, and prednisone was given to three patients for periods of five, five and ten years respectively. None of the forms of treatment used had an effect on the clinical course, the pathological changes or the results of liver‐function tests in this disease. Attacks of cholestasis and cholangitis occurred with equal frequency and severity both before and after therapy. The hypercholesterolæmia and raised serum alkaline phosphatase level persisted, and the expected progression from acute to subacute to chronic pericholangitis, and in some cases to post‐necrotic cirrhosis, occurred in spite of therapy.

CALCIUM METABOLISM AND THE BONES AFTER PARTIAL GASTRECTOMY. II. THE NATURE AND CAUSE OF THE BONE DISORDER.

SUMMARYSome aspects of calcium metabolism were investigated in 100 patients after partial gastrectomy in an endeavour to define the nature of the skeletal abnormality and to detect factors responsible for its development. Fifty subjects not operated upon were used as the control group. The following abnormal biochemical values were found in the patients after partial gastrectomy : low serum calcium levels in six patients ; low serum phosphate levels in six patients ; raised serum alkaline phosphatase levels in 15 patients ; low serum total protein level in one patient ; and low serum albumin level in one patient. In addition, the excretion of calcium in the urine was lower in the patients after gastrectomy than in the control subjects, and the “clearance” of phosphate was higher in the patients after gastrectomy. Patients with changes in the bones after gastrectomy differed from the patients with normal bones after operation in having a higher mean serum level of alkaline phosphatase and a lower mean urinary excretion of calcium.Twenty‐two patients after partial gastrectomy were further investigated by bone biopsy, the calcium infusion test and fæcal fat determination. Eight control subjects also underwent the calcium infusion test. On the basis of these investigations, 13 patients were considered to have an “osteomalacic” syndrome. The main features of the syndrome were generalized skeletal pain, bone tenderness, skeletal rarefaction and histological changes of osteoporosis and early osteomalacia. We have used the term “osteomalacic” syndrome to describe this condition, because the classical biochemical features of osteomalacia were only infrequently present, and because osteomalacia and osteoporosis were present together. The biochemical changes that were present in the 13 patients with the syndrome were elevation of the serum alkaline phosphatase levels in five patients, increased retention of infused calcium in the calcium infusion test in seven patients, hypocalcæmia in one patient and hypophosphatæmia in another patient. Anæmia, steatorrhœa and an inadequate diet were frequently present in these cases.Factors that appeared to be of importance in the pathogenesis of the bone disorder following gastrectomy were inadequate intake of calcium and protein in the diet, and steatorrhœa. A deficiency of vitamin D also was inferred to account for the changes that were detected.The observations made in the present investigation suggest that bone disease is relatively common after gastric surgery, but that in most cases the disorder is only of moderate severity and does not constitute a serious disability to the patient. However, an awareness of the association of bone disease and gastric surgery is important, as some patients after gastrectomy may require treatment with calcium, vitamin D and an anabolic steroid.