Use of site-specific antibodies to characterize the circulating form of big insulin-like growth factor II in patients with hepatitis C-associated osteosclerosis

Hepatitis C-associated osteosclerosis (HCAO) is a rare syndrome of adult-onset osteosclerosis. An understanding of the factor(s) leading to the stimulation of bone formation in these patients may provide novel anabolic approaches for the treatment of osteoporosis. We have demonstrated that HCAO patients have a specific increase in circulating big IGF-II (IGF-IIE) and IGF-binding protein-2 (IGFBP-2) levels, and that IGF-IIE and IGFBP-2 circulate together in a bioavailable, 50-kDa complex. Patients with nonislet cell tumor hypoglycemia (NICTH) also have increased circulating IGF-IIE and IGFBP-2 levels. However, HCAO patients do not exhibit hypoglycemia, nor do NICTH patients exhibit obvious osteosclerosis. Thus, to better understand the reason(s) for the differing clinical manifestations of the IGF-IIE excess in the two syndromes, we characterized IGF-IIE in HCAO and NICTH sera using recently developed antibodies (Ab) recognizing either the full-length IGF-IIE 89-amino acid C-terminal extension peptide (IIE(138-156) Ab) or specific cleavage forms of IGF-IIE (IIE(78-88) Ab and IIE(89-101) Ab). The predominant IGF-IIE form in HCAO serum migrated on SDS-PAGE as a single band at approximately 18 kDa that reacted with the IIE(89-101) Ab. On the other hand, the predominant form in NICTH serum migrated as a doublet of 14 and 16 kDa that reacted with the IIE(78-88) Ab. There results are consistent with differential processing of the IGF-IIE precursor at predicted cleavage sites producing IGF-IIE(1-104) and IGF-IIE(1-88) in HCAO and NICTH, respectively. As these two forms may have differing biological activities and/or targeting properties, our findings may explain at least in part the different manifestations of IGF-IIE overproduction in the two syndromes.     

Vertebral cryptococcosis simulating tuberculosis

Infection with the fungus Cryptococcus neoformans is seen predominantly in two forms: (a) pulmonary and (b) cerebromeningeal. Skeletal cryptococcosis is uncommon. There have been only occasional case reports of thoracic vertebral cryptococcosis presenting as cord compression. A young female had cervical lymphadenopathy diagnosed as tuberculosis by fine needle aspiration cytology (FNAC) and was on antitubercular therapy (ATT) for 5 months. She developed rapidly progressive paraparesis and imaging demonstrated a destructive vertebral body lesion involving T2-3 with a paraspinal abscess producing cord compression. A costotransversectomy with excision of the diseased bone and bone grafting was done. Histopathological examination revealed cryptococcosis. The patient was put on antifungal medication, but expired 2 weeks after surgery. Radiological, magnetic resonance imaging and surgical finding of vertebral cryptococcosis can mimic tuberculosis. The definite diagnosis of cryptococcosis depends upon microscopic identification of the organism. A high index of suspicion leading to early surgical confirmation and institution of anti fungal therapy is necessary to reduce the mortality and morbidity.     

Incidence of childhood distal forearm fractures over 30 years: a population-based study

Context  The incidence of distal forearm fractures in children peaks around the time of the pubertal growth spurt, possibly because physical activity increases at the time of a transient deficit in cortical bone mass due to the increased calcium demand during maximal skeletal growth. Changes in physical activity or diet may therefore influence risk of forearm fracture. Objective  To determine whether there has been a change in the incidence of distal forearm fractures in children in recent years. Design, Setting and Patients  Population-based study among Rochester, Minn, residents younger than 35 years with distal forearm fractures in 1969-1971, 1979-1981, 1989-1991, and 1999-2001. Main Outcome Measure  Estimated incidence of distal forearm fractures in 4 time periods. Results  Comparably age- and sex-adjusted annual incidence rates per 100 000 increased from 263.3 (95% confidence interval [CI], 231.1-295.4) in 1969-1971 to 322.3 (95% CI, 285.3-359.4) in 1979-1981 and to 399.8 (95% CI, 361.0-438.6) in 1989-1991 before leveling off at 372.9 (95% CI, 339.1-406.7) in 1999-2001. Age-adjusted incidence rates per 100 000 were 32% greater among male residents in 1999-2001 compared with 1969-1971 (409.4 [95% CI, 359.9-459.0] vs 309.4 [95% CI, 259.3-359.5]; P = .01) and 56% greater among female residents in the same time periods (334.3 [95% CI, 288.6-380.1] vs 214.6 [95% CI, 174.9-254.4]; P<.001). The peak incidence and greatest increase occurred between ages 11 and 14 years in boys and 8 and 11 years in girls. Conclusions  There has been a statistically significant increase in the incidence of distal forearm fractures in children and adolescents, but whether this is due to changing patterns of physical activity, decreased bone acquisition due to poor calcium intake, or both is unclear at present. Given the large number of childhood fractures, however, studies are needed to define the cause(s) of this increase.      

Psychopathology and autobiographical memory in stroke and non-stroke hospitalized patients

BACKGROUND: Psychopathology and autobiographical memory were investigated in a cohort of stroke and non-stroke hospitalized patients. Both these cohorts have been identified as having high levels of psychopathology (Katon and Sullivan 1990; Burvill et al., 1995). Difficulties recalling specific autobiographical memories (overgeneral memory) have been identified as important psychological variables in depression and predictors of outcome (Williams and Scott 1988; Brittlebank et al., 1993). Intrusive autobiographical memories have also been found to be associated with depression and overgeneral memory in depressed women (Kuyken and Brewin, 1995) and depressed cancer patients (Brewin et al., 1998a). This study looked at levels of psychopathology and autobiographical memories in stroke and non-stroke hospital patients. METHOD: 417 patients were screened, of the 176 eligible 103 agreed to participate (54 stroke and 49 non-stroke). Participants were assessed for overgenerality using the Autobiographical Memory Test and intrusiveness of memories using the Impact of Events Scale. Also assessed were PTSD-like symptoms (PCL-S), mood (HADS, GHQ-28) and cognitive ability (MMSE, verbal fluency, digit span and estimated pre-morbid IQ). RESULTS: No significant differences were found between stroke and non-stroke patients on severity of depression, anxiety, severity of PTSD-like symptoms or autobiographical memories. Backward multivariate regression analyses for combined data (stroke and non-stroke) indicated that overgeneral memory recall, intrusive memories of past events and intrusive memories of illness were significant independent predictors of depression (HADS). Avoidance of intrusive memories and reported childhood distress were not predictors of overgeneral memory recall. Significant predictors of overgeneral memory recall were; Gender, antidepressant medication, and estimated IQ. CONCLUSION: Significant levels of psychopathology were identified in this cohort. However, there were no significant differences in the levels of depression, anxiety, PTSD symptoms and autobiographical memory between stroke and non-stroke hospitalized patients. Of particular interest was the finding that PTSD-like symptoms did not appear to be influenced by the nature of the person's illness. In combined data (stroke and non-stroke) autobiographical memories (intrusive images of their illness, intrusive memories of other events and overgeneral memory recall variables) were significant predictors of depression in this cohort. This suggests that psychological intervention of memory processes may be a worthwhile target in psychological intervention for depression in these cohorts. Gender, cognitive impairment, antidepressant medication, and estimated IQ were significant predictors of overgeneral memory recall and further investigation into the validity of these findings are warranted. Suggestions for further research and limitations of the study are also discussed.     

Palmitic and stearic acids similarly affect plasma lipoprotein metabolism in cynomolgus monkeys fed diets with adequate levels of linoleic acid

This study was designed to evaluate whether the exchange of specific saturated fatty acids [SFA; palmitic acid (16:0) for stearic acid (18:0)] would differentially affect plasma lipids and lipoproteins, when diets contained the currently recommended levels of total SFA, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA). Ten male cynomolgus monkeys were fed one of two purified diets (using a cross-over design) enriched either in 16:0 (palmitic acid diet) or 18:0 (stearic acid diet). Both diets provided 30% of energy as fat (SFA/monounsaturated fatty acid/PUFA: 1/1/1). The palmitic acid and stearic acid diets were based on palm oil or cocoa butter (59% and 50% of the total fat, respectively). By adding different amounts of sunflower, safflower and olive oils, an effective exchange of 16:0 for 18:0 of approximately 5% of energy was achieved with all other fatty acids being held constant. Monkeys were rotated through two 10-wk feeding periods, during which time plasma lipids and in vivo lipoprotein metabolism (following the simultaneous injection of (131)I-LDL and (125)I- HDL were evaluated). Plasma triacyglycerol (0.40 +/- 0.03 vs. 0.37 +/- 0.03 mmol/L), plasma total cholesterol (3.59 +/- 0.18 vs. 3.39 +/- 0.23 mmol/L), HDL cholesterol (1.60 +/- 0.16 vs 1.53 +/- 0.16 mmol/L) and non-HDL cholesterol (2.02 +/- 0.26 vs. 1.86 +/- 0.23 mmol/L) concentrations did not differ when monkeys consumed the palmitic acid and stearic acid diets, respectively. Plasma lipoprotein compositional analyses revealed a higher cholesteryl ester content in the VLDL fraction isolated after consumption of the stearic acid diet (P < 0.10), as well as a larger VLDL particle diameter (16.3 +/- 1.7 nm vs. 13.8 +/- 3.6 nm; P < 0.05). Kinetic analyses revealed no significant differences in LDL or HDL transport parameters. These data suggest that when incorporated into diets following current guidelines, containing adequate PUFA, an exchange of 16:0 for 18:0, representing approximately 11 g/(d.10.46 mJ) [ approximately 11 g/(d.2500 kcal)] does not affect the plasma lipid profile and has minor effects on lipoprotein composition. Whether a similar effect would occur in humans under comparable dietary conditions remains to be established.     

Non-randomized comparison of surgical modalities for paranasal sinus mycoses with intracranial extension.

Mycotic infections of paranasal sinuses are frequently reported in southern Asia. Aspergillus and Mucor species are the predominant ones. Intracranial extension of paranasal sinus mycoses is a difficult problem to manage. We report 18 cases of paranasal sinus mycoses with intracranial extensions. The commonest manifestations were nasal discharge (67%), nasal obstruction (50%), ocular symptoms such as proptosis (44%), telecanthus (39%) and ophthalmoplegia. Computerized tomography scans were found to be quite informative regarding the nature and extent of the disease (100% sensitivity and 78% specificity). A combined intracranial-extracranial approach (six cases) gave a distinct advantage over only adopting an extracranial approach (12 cases). A 17% incidence of CSF leak was noted by adopting only an extracranial approach as well as a recurrence in four cases out of the 12 that were treated using this method (P < 0.05). A slight increase in morbidity was associated with the combined intracranial-extracranial treatment, but no recurrence or significant complications were noted in this approach.