Bone Mineral Density Before and After Surgical Cure of Cushing’s Syndrome Due to Adrenocortical Adenoma: Prospective Study

Osteoporosis is a major complication of Cushing’s syndrome. The aim of the present study was to assess the chronologic effect of surgical cure on bone mineral density (BMD) in patients with Cushing’s syndrome due to adrenal adenoma. BMD was examined in 28 patients before laparoscopic adrenalectomy; 17 patients with reduced BMD were then included in the longitudinal evaluation. BMD was determined using dual energy X-ray absorptiometry (DXA) before and at 3, 6, 12, 18, and 24 months after adrenalectomy. The prevalence of osteoporosis was 64% (95% confidence interval 44–81%). Preoperative BMD of the lumbar spine in the lateral projection was significantly lower than that of the femoral neck (mean ± SD score: −3.53 ± 0.75 vs. −1.54 ± 0.22, p = 0.003). A significant increase in BMD was observed at 3 months after surgery in the lumbar spine (p = 0.0004). Improvement at both sites was maintained at 24 months after surgery. The postoperative percentage change in BMD of the lumbar spine was significantly higher than that of the femoral neck (mean ± SD 36.7% ± 26.5% vs. 11.2% ± 12.1%, p = 0.01). The change in the seven premenopausal patients was significantly higher than that in the three postmenopausal patients (p = 0.0006). Surgical cure of hypercortisolism provides significant improvement in BMD in patients with Cushing’s syndrome due to adrenal adenoma. The improvement is particularly apparent in the lumbar spine measured in the lateral projection. Premenopausal women are more likely to benefit from surgery in terms of secondary osteoporosis.     

A mechanism based understanding of cancer pain and development of novel strategies of cancer pain treatment

As advances in cancer detection and treatment have increased the life expectancy of cancer patients, more attention to improving patient quality of life is needed. The World Health Organization (WHO) has proposed a structured approach to drug selection for cancer pain, known as the "WHO analgesic ladder". This approach is capable of providing adequate relief to 70-90% of patients. However, the remaining 10-30% of patients are difficult to treat. The development of optimal analgesics for cancer pain has been hampered by the lack of understanding of basic mechanisms that contribute to cancer pain, which is due in part to the lack of appropriate animal models. Recently, preclinical models of bone cancer pain have been developed. These models have begun to provide insight into the mechanisms by which tumors cause pain and how cancer pain-related sensory information is processed. Once the mechanism by which cancer induces pain is elucidated, this would lead to the identification of molecular targets and the development of mechanism based therapies, which improve the quality of life of all those who suffer from cancer pain.     

Rare mutations of the PIK3CA gene in malignancies of the hematopoietic system as well as endometrium, ovary, prostate and osteosarcomas, and discovery of a PIK3CA pseudogene

Lipid kinase PIK3CA mutations have been described in several cancers. They clustered in two 'hot spots' located in helical (exon 9) and kinase (exon 20) domains associated with increased kinase activity strongly suggesting oncogenic potential. Mutational analysis of previously unexamined tumors showed an amino acid change from threonine to alanine (T1025A) in exon 20 in one of 28 endometrial cancer samples and 6 endometrial cell lines. Additionally, a silent polymorphism (T1025T) was found in two of 20 MDS samples, one of 43 NHL samples, two of 40 osteosarcoma samples and Ishikawa. The polymorphism was established by identifying two of 92 normal samples with the same change. No PIK3CA mutations were found in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and non-Hodgkin lymphomas (NHL) as well as in osteosarcomas, prostate and ovarian cancer samples. Additionally, a previously unidentified PIK3CA pseudogene spanning exons 9-13 on chromosome 22 was discovered.     

Efficacy of calcium channel blocker in the secondary prevention of myocardial infarction--retrospective analysis of the 10-year prognosis or coronary thrombolysis-treated patients.

BACKGROUND: Calcium channel blockers (CCBs) may have a positive influence on the long-term prognosis of Japanese patients with ischemic heart disease. METHODS AND RESULTS: The effect of nifedipine-retard (NR) (n=202) compared with that of non-CCB treatment (n=92) on the secondary prevention of myocardial infarction (MI) was retrospectively investigated in patients who had survived acute MI between 1987 and 1996. The primary endpoint was the occurrence of cardiac death or non-fatal MI. The median follow-up was 6.3+/-2.4 years. The incidence of cardiac events was 8.9% in the NR group and 14.1% in the non-CCBs group (p=0.14, odds ratio (OR): 0.584, 95% confidence interval (CI): 0.286-1,193). However, subanalysis revealed that NR significantly reduced the incidence of cardiac events in patients aged less than 55 years (4.2 vs 18.2%, p=0.016, OR: 0.180, 95%CI: 0.045-0.721) and those who did not smoke (8.6 vs 16.4%, p=0.048, OR: 0.462, 95%CI: 0.203-0.999). CONCLUSION: Although this was a retrospective analysis, it showed that NR did not cause an increase in the incidence of cardiac events in post-MI patients; it even prevented cardiac events, especially in those who were less than 55 years of age and in non-smokers, suggesting the potential usefulness of CCBs in the secondary prevention of MI in Japan.     

Analysis of T cell receptor V(beta) gene expression and clonality in bronchoalveolar fluid lymphocytes from a patient with chronic eosinophilic pneumonitis

Chronic eosinophilic pneumonitis (CEP) is characterized by longstanding respiratory symptoms accompanied by a massive pulmonary eosinophil infiltration. T lymphocytes in bronchoalveolar lavage (BAL) from patients with chronic eosinophilic pneumonitis are considered to recognize unknown antigens. To analyze the pathogenesis of CEP, we examined the T cell receptor (TCR) repertoire and T cell clonotype of BAL lymphocytes and peripheral blood lymphocytes (PBLs) in a 66-year-old woman patient with CEP. The expression of TCR BV gene was analyzed by the family PCR method using specific primers for 20 TCR BV genes and BC gene. The clonotype of BAL and peripheral T cells was examined by the PCR-single-strand conformation polymorphism (SSCP) method. Functional sequences of some T cell clones were also carried out. A TCR repertoire of BAL T cells was heterogeneous as well as PBLs. However, SSCP analysis showed that distinct T cell clonotypes were detected in BAL T cells, TCR BV3, BV4, BV6, BV8, BV9, BV14, and BV18-positive T cell clones especially, expanded clonally in BAL from the patient. Sequencing analysis showed that GVD, LGG, RDXS, and SSG amino acid sequence motif were found in the CDR3 in lung-specific T cells. BAL-specific T cell clones accumulated in the patient with CEP. Thus, we can conclude that BAL T cells are induced by the antigen-driven stimulation and these cells might play a crucial role in the generation of CEP. Accepted for publication: 27 February 2001     

Megacystis-microcolon-intestinal hypoperistalsis syndrome: in utero sonographic appearance and the contribution of vesicocentesis in antenatal diagnosis.

OBJECTIVE: The purpose of this report is to describe the in utero sonographic appearance of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) and examine the role of vesicocentesis. METHODS: Two cases of the sonographic appearance of MMIHS were reviewed. We performed vesicocentesis in 2 fetuses with MMIHS and performed vesicoamniotic shunting in 1 of them. The sonographic findings after these procedures were compared with those before puncture. RESULTS: In both cases, ultrasound examination showed a massively enlarged fetal bladder and bilateral hydroureteronephrosis with a normal amount of amniotic fluid. Fetal urinary sodium and chloride concentrations were within normal limits in both cases; this suggested normal fetal renal function. Generally, it is difficult to detect the dilated fetal bowel in MMIHS, probably because of the disturbance caused by a large bladder. In our cases, however, the ultrasound examination clearly showed fetal bowel dilatation after these procedures; this made the antenatal diagnosis of MMIHS more definite. CONCLUSIONS: The sonographic features after vesicocentesis may be helpful in confirming the antenatal diagnosis of MMIHS.     

Low-density lipoprotein cholesterol/apolipoprotein B ratio may be a useful index that differs in statin-treated patients with and without coronary artery disease: a case control study

Low density lipoproteins (LDLs) are heterogeneous aggregations of molecules of different particle sizes, and small-size LDLs are more potent risk factors for atherosclerosis. We examined the qualitative characteristics of LDLs in patients with stable coronary artery disease (CAD) receiving statin therapy. LDL-particle size was estimated based on the LDL-cholesterol/apolipoprotein B ratio (LDL-C/apoB) in 214 age-adjusted men receiving statin therapy. The LDL-C/apoB ratio was significantly lower in the CAD (+) group (n = 107) than in the CAD (-) group (n = 107) (median, 1.17 versus 1.19, P = 0.0095). LDL-C/apoB was significantly lower in patients with serum TG ≥ 150 mg/dL than in those with serum TG < 150 mg/dL, and in patients with serum HDL-C < 40 mg/dL than in those with serum HDL-C ≥ 40 mg/dL (1.06 versus 1.18, P = 0.012; 1.08 versus 1.22, P = 0.0023). Stepwise logistic regression analysis revealed that elevated serum TG was an independent predictor for smaller sizes of LDLs, both in the overall subjects (β : -0.165, P = 0.02) as well as in the subset with serum LDL-C < 100 mg/dL (β : -0.252, P = 0.011). This study demonstrated that not only the absolute serum LDL-C level, but also the qualitative characteristics of LDL may be monitored for secondary prevention of CAD. Such monitoring is particularly important in patients with elevated serum TG levels, which is associated with smaller sizes of LDL-particles.     

Relationship between bone mineral density and bone stiffness in bone fracture

Objectives Using cancellous bone blocks of racehorses, the relationship between bone mineral density (BMD), which indicates bone strength, and stiffness in bone fracture occurrences was studied.Methods Two groups of cancellous bone blocks were prepared: a fractured group, using the first phalangeal bones of seven racehorses with sagittal fractures; and a nonfractured group, using the first phalangeal bones of nine autopsied racehorses without any fractures. By a peripheral quantitative computed tomography scan, the BMD values were shown as color images and evaluated. In addition, the BMD values obtained from the fractured and nonfractured groups were compared with the stiffness values obtained from a compression test.Results The difference between the average BMD values of the fractured and nonfractured groups was easily observed on the BMD color-conversion display image. The average BMD of the fractured group (472.1 mg/cm³) was significantly higher than that of the nonfractured group (284.5 mg/cm³, P = 0.005). Moreover, the average stiffness of the fractured group (5564.5 N/cm) was significantly higher than that of the nonfractured group (3808.6 N/cm, P = 0.008).Conclusion These results suggest that the occurrence of a fracture does not depend on the BMD or the bone stiffness value.     

Apolipoprotein E polymorphism in Japanese patients with Alzheimer''s disease or vascular dementia.

Apolipoprotein E (ApoE) plays a key part in lipid metabolism both in the liver, and in the CNS. To clarify the association of ApoE polymorphism with Alzheimer's disease and vascular dementia in Japan, 13 patients with early onset (age > or = 65) sporadic Alzheimer's disease, 40 patients with late onset (age < or = 65) sporadic Alzheimer's disease, 19 patients with vascular dementia, and 49 non-demented control subjects were analysed. The results showed a significantly increased frequency of the epsilon 4 allele in the patients with late onset sporadic Alzheimer's disease (0.25), but not in the patients with early onset sporadic Alzheimer's disease (0.04) or in the patients with vascular dementia (0.13) compared with controls (0.09). The raised frequency of the epsilon 4 allele in the patients with late onset sporadic Alzheimer's disease was of a lower magnitude than that in United States and Canadian studies. This may in part be due to a lower epsilon 4 frequency in the normal Japanese population and reflect the lower morbidity from Alzheimer's disease in Japan.