Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment

Anabolic effects of PTH have been observed at several skeletal sites in humans by dual x-ray absorptiometry without differentiating between an actual increase in bone volume and an increase in mineral content within already established bone. The present study addressed this issue by evaluating the bone mineralization density distribution of iliac crest bone biopsies before and after PTH treatment for 18-36 months in men and women with osteoporosis using quantitative backscattered electron imaging. In cortical bone, pairwise comparison of the two biopsies before and after treatment revealed a reduction in the typical calcium concentration in men (-3.32%; P = 0.02, by paired t test), but no change in women, and the heterogeneity of mineralization increased in both males and females [+18.80% (P = 0.09) and +18.14% (P = 0.005), respectively]. In cancellous bone, there was no change in the typical calcium concentration, but there was a greater heterogeneity of mineralization in both men and women [+19.65% (P = 0.02) and +21.59% (P = 0.056), respectively] due to newly formed bone matrix. Small angle x-ray scattering performed on a subgroup of subjects revealed normal collagen/mineral structure. The findings confirm the observations that PTH stimulates skeletal remodeling, resulting in an increased percentage of newly formed bone matrix of lower mineral density.     

A microarray minisequencing system for pharmacogenetic profiling of antihypertensive drug response

We aimed to develop a microarray genotyping system for multiplex analysis of a panel of single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in blood pressure regulation, and to apply this system in a pilot study demonstrating its feasibility in the pharmacogenetics of hypertension. A panel of 74 SNPs in 25 genes involved in blood pressure regulation was selected from the SNP databases, and genotyped in DNA samples of 97 hypertensive patients. The patients had been randomized to double-blind treatment with either the angiotensin II type 1 receptor blocker irbesartan or the beta 1-adrenergic receptor blocker atenolol. Genotyping was performed using a microarray based DNA polymerase assisted 'minisequencing' single nucleotide primer extension assay with fluorescence detection. The observed genotypes were related to the blood pressure reduction using stepwise multiple regression analysis. The allele frequencies of the selected SNPs were determined in the Swedish population. The established microarray-based genotyping system was validated and allowed unequivocal multiplex genotyping of the panel of 74 SNPs in every patient. Almost 7200 SNP genotypes were generated in the study. Profiles of four or five SNP-genotypes that may be useful as predictors of blood pressure reduction after antihypertensive treatment were identified. Our results highlight the potential of microarray-based technology for SNP genotyping in pharmacogenetics.     

The patient's perspective of irritable bowel syndrome

OBJECTIVE: The researchers wanted to understand how irritable bowel syndrome (IBS) affects patients' lives and their interactions with physicians and the health care system. STUDY DESIGN: A qualitative study was performed using focus groups of people with physician-diagnosed IBS. Immersion/crystallization was used to identify overriding themes. POPULATION: Adult volunteers with a previous physician diagnosis of IBS were included. OUTCOMES MEASURED: The outcomes were patient-reported symptoms, episode triggers, treatments, lifestyle changes, and interactions with their physicians that were related to IBS, and overriding themes identified from the focus groups. RESULTS: The subjects described IBS as a chronic episodic illness that affects their daily lives. Interaction with the medical community seldom clarified understanding of the condition or improved its management. Three overriding themes emerged from the groups: a sense of frustration, a sense of isolation, and a search for a niche in the health/sick role continuum. Frustration was evident in the perceived inability to control symptoms, prevent episodes, identify episode triggers, and obtain medical validation of the condition. The constant anticipation of the next IBS episode, the need for immediate access to toilet facilities, and the nature of the bowel symptoms often required withdrawal from social activities and resultant isolation. CONCLUSIONS: IBS is perceived as a chronic condition resulting in frustration and social isolation, and physicians are perceived to be providing inadequate medical information or support to patients with IBS.     

Asymmetric involvement of the spinal cord involving both large and small anterior horn cells in a case of familial amyotrophic lateral sclerosis

A case of familial amyotrophic lateral sclerosis revealing neuronal loss in the anterior horns and Clarke's columns, Lewy body-like intracytoplasmic inclusions in some remaining cells, cord-like thickening of cell processes, mild perivascular infiltration of lymphocytes, and degeneration of the middle root zone in the posterior column and of the spinocerebellar tract is described. Two highly unusual features were noted. First, there was a marked asymmetry of the neuronal loss and tract degeneration in the spinal cord. The left side was much more severely affected than the right side. Second, both large and small neurons disappeared almost completely on the left side of the lumbar anterior horn.     

Cervical internal carotid artery dissecting hemorrhage: diagnosis using MR

Two men underwent high-resolution magnetic resonance (MR) imaging of the internal carotid artery (ICA) 12 and 16 days after spontaneous dissection of this vessel. One underwent follow-up MR imaging 7 weeks later. T1-weighted images were obtained in both cases, and T2-weighted images were obtained in one patient. In both cases, the MR findings corresponded to the angiographic abnormalities. On both the T1- and T2-weighted images, there was a hyperintense lesion expanding the wall and narrowing the lumen of the ICAs. Follow-up MR imaging showed complete resolution of the mural lesion. Axial images best demonstrated the anatomic and MR signal alterations. The hyperintensity of the lesion on both T1- and T2-weighted images indicated a short T1 and a long T2 as expected in a subacute hematoma. High-resolution MR imaging, therefore, can specifically demonstrate a thrombosed carotid dissection noninvasively at least as early as 12 days. The potential to diagnose carotid dissection in the acute phase using high-field-strength MR imaging and its importance for the prevention of embolic strokes are also discussed.     

The epidemiology of sarcoidosis in Rochester, Minnesota: a population-based study of incidence and survival

Using the unique data resources of the Rochester Epidemiology Project, a community-based study of clinically diagnosed sarcoidosis was conducted. In this population-based study, the 75 Rochester, Minnesota, residents with sarcoidosis initially diagnosed between 1946 and 1975 (incidence cohort) were followed through their comprehensive medical records in the community to January 1, 1982. The age- and sex-adjusted incidence of sarcoidosis was 6.1 per 100,000 person-years. The age-adjusted incidence of sarcoidosis was similar in males (5.9) and females (6.3), with a peak incidence in males 30 to 39 years old (18.7) and in females 40 to 49 years old (15.6). A secular increase in sarcoidosis incidence was noted in the period 1946-1975 for females, with a marked increase in the number and percentage of biopsy-documented cases. Seasonal variation in sarcoidosis incidence was minimal, with a seasonal peak of 31% of the Rochester cases being diagnosed during the spring (March-May). Survival, compared with that of the North Central United States, was unimpaired in this sarcoidosis incidence cohort.     

Occult cerebral vascular malformations: high-field MR imaging

Occult cerebral vascular malformations (OCVMs) have characteristic appearances on high-field magnetic resonance (MR) images. These consist of circumscribed regions of low intensity, most prominent on T2-weighted images and representing hemosiderin deposits. Interspersed within most of these lesions are multiple areas of various signal intensity patterns, which correspond to hematomas in different stages of evolution and to fibrous regions containing calcium as well as hemosiderin. Forty-six lesions were found in 19 patients (34 supratentorial and 12 infratentorial). The supratentorial lesions tended to be subcortical or periventricular. Computed tomography depicted 24 of the 46 lesions demonstrated by high-field MR. Comparison of images obtained with both low-field MR (0.12 T and 0.35 T) and high-field MR (1.5 T) revealed that high-field MR imaging was superior in depicting OCVMs. High-field MR appears to be both sensitive and specific for OCVMs and may obviate the need for possible biopsy of these lesions.     

Conditions associated with carpal tunnel syndrome.

With use of a comprehensive medical records-linkage system, we identified the comorbid conditions and risk factors in the residents of Rochester, Minnesota, who had a diagnosis of carpal tunnel syndrome during 1961 through 1980. In 43.2% of the 1,016 patients, no associated conditions were found on review of the medical records, whereas associated conditions were documented in 56.8%. The most frequent of these conditions were Colles' fracture, rheumatoid arthritis, hormonal agents or oophorectomy (or both), diabetes mellitus, and, among men, occupations that involved excessive use of the hands. Rheumatoid arthritis, diabetes mellitus, and pregnancy were significantly more frequent among the study patients with carpal tunnel syndrome than in the general population of Rochester, Minnesota. The standardized morbidity ratio was 3.6 for rheumatoid arthritis, 2.3 for diabetes mellitus, and 2.5 for pregnancy. The population attributable risk for pregnancy among women 15 to 44 years old was 7.0%. The standardized morbidity ratio for polymyalgia rheumatica was not significantly increased.