Estimation of prostatic growth using serial prostate-specific antigen measurements in men with and without prostate disease.

Prostate growth curves were estimated from serial prostate-specific antigen (PSA) measurements on frozen sera in three groups of men: (a) 16 men with no prostatic disease by urological history and examination; (b) 20 men with a histological diagnosis of benign prostatic hyperplasia (BPH) who had undergone simple prostatectomy; and (c) 18 men with a histological diagnosis of prostate cancer. The median number of repeated PSA measurements over an 8- to 26-yr period prior to histological diagnosis or exclusion of prostate disease was eight and 11 for noncancer and cancer subjects, respectively. Predicted rates of change in PSA (PSA velocity) were linear and curvilinear for control and BPH subjects, respectively. Subjects with cancer demonstrated both a linear and an exponential phase of PSA velocity. Based on time to double PSA, we estimated the epithelial doubling time for men without prostate disease to range from 54 +/- 13 yr at age 40 to 84 +/- 13 yr at age 70. For men with BPH, doubling times ranged from 2 +/- 13 yr at age 40 to 17 +/- 5 yr at age 85. Subjects with local/regional and advanced/metastatic cancer had similar PSA doubling times of 2.4 +/- 0.6 yr and 1.8 +/- 0.2 yr, respectively. These data are consistent with what is known about prostatic growth with age in men without prostate disease and BPH, and the kinetics of prostate cancer growth. Estimates of prostatic growth rate from changes in PSA may be useful clinically in management of men with prostate disease.

Radial and ulnar cortical thickness of the second metacarpal.

Differential bone mass at various skeletal sites, which may be due to mechanical stress exerted by the muscles attached to the bone, has been demonstrated for athletes who exert one limb more than the other. The question arises as to whether this bilateral asymmetry extends to the two sides of the same bone with different muscular attachments. The objectives of this study were to ascertain whether the radial and ulnar sides of the second metacarpal have similar cortical thickness and determine if bone mass decreases equally with age on the radial and ulnar sides. Hand-wrist radiographs were obtained from 201 male and 191 female Caucasian participants of the Baltimore Longitudinal Study of Aging. Differences between radial and ulnar cortical thickness within age groups were tested with Student's t-test and between age groups using analysis of variance. RAdial cortical thickness of the second metacarpal was found to be 11-12% greater in men and 10-12% greater in women than ulnar cortical thickness in both the left and right hands. Age-related changes in radial cortical thickness were evident in both sexes. In men, radial cortex decreased linearly from age 40 to 89. For women, there was a sharp decline in radial thickness from age 50 to age 60. Ulnar cortical thickness declined from age 50 to 60 for women only. Muscle attachment along the radial length of the second metacarpal may influence the accumulation of bone mass on the radial side at younger ages while muscle disuse may precipitate the loss of bone preferentially from the radial side.

Biochemical parameters associated with low bone density in healthy men and women.

A causal role in age-related bone loss has been attributed to alterations in vitamin D status, the bone mineral regulating hormones, and/or renal function. We assessed biochemical parameters of bone metabolism and renal function in healthy subsets of young and old men (n = 191) and women (n = 120) and evaluated the relationships between these parameters and bone mineral density (BMD) in the radius, spine, and femur. There were no significant associations between BMD at any site and serum 25-OHD, 1,25-(OH)2D, PTH, or creatinine clearance in either young men or in young or old women, after controlling for age. In old men, however, lower radius BMD was significantly related to higher PTH and higher 1,25-(OH)2D and marginally related to lower 25-OHD values. In young men, there were unexpected but significant associations between lower femoral neck BMD and higher serum osteocalcin and urinary calcium/creatinine excretion after age adjustment. In old women, lower spine and radius BMD was also significantly correlated with higher serum osteocalcin. In this healthy, vitamin D-replete population, there were significant cross-sectional declines in BMD in the femur in young and old men and at all sites in old women. Elevated remodeling may be an important feature that contributes to reduced femoral BMD in young men and reduced spine and radius BMD in old women. However, compromised renal function or levels of 1,25-(OH)2D or elevated PTH appear to be neither necessary nor relevant as determinants of osteopenia in the spine or femur in these normal, healthy men and women.

Reproductive correlates of bone mass in elderly women. Study of Osteoporotic Fractures Research Group.

Results from previous studies of reproductive factors and bone density have been conflicting; some demonstrate a beneficial effect, but others show a detrimental effect on bone density. The present study investigates the association of parity, lactation, and menstruation with radial bone density in 2230 white women, 65 years of age and older. Bone density was assessed by single-photon absorptiometry. Linear multiple regression was utilized to determine if reproductive factors were associated with radial bone density. The number of births, duration of menstrual bleeding, age at menarche, and years menstruating were significant independent predictors of postmenopausal bone density of the radius. A 1.4% increase in distal radius bone density was observed with each additional birth. Women who began menstruation at age 9 had 6.3% higher bone density than women who began at age 16. Women who menstruated for 3 days during each menstrual cycle had 2.8% less distal radius bone density than women who bled for 7 days. Each decade of menstruation was associated with a 2% greater distal radius bone density. No difference in bone density was demonstrated for women who breast-fed and women who did not. Length of the menstrual cycle, amount of menstrual flow, and irregularity of the menstrual cycle were not significantly associated with radial bone mineral density. In conclusion, pregnancy and menstruation are associated with postmenopausal bone density of the radius.

Upper extremity bone mass and osteoarthritis of the knees: data from the Baltimore Longitudinal Study of Aging.

To examine the association of upper extremity bone mass with osteoarthritis (OA) of the knee, bilateral standing knee radiographs, taken between 1985 and 1991, in 430 Caucasian male and 266 Caucasian female subjects aged 40 years and above in the Baltimore Longitudinal Study of Aging, were read by one investigator for grade of OA using Kellgren-Lawrence scales. Several measures of upper extremity bone mass, size, and density, including combined cortical thickness (CCT), total width and percentage of cortical area of the second metacarpal, and bone mineral content (BMC), width, and density of the distal third of the left radius measured with single photon absorptiometry, were assessed at the same visit. In univariate analyses, men and women with definite knee OA were significantly older, men had significantly greater radial width, and women had significantly lower bone mass as measured by both CCT and BMC. After adjustment for age and body weight, however, men with knee OA had significantly higher BMC and radial width while neither of these measures of upper extremity bone mass and size was significantly associated with the presence of definite knee OA in women. Neither measure of upper extremity bone density was significantly associated with definite knee OA in either sex. These data suggest that, although men (but not women) with definite knee OA have significantly higher levels of adjusted radial bone mass and size, subjects with knee OA do not have significantly higher levels of adjusted bone mineral density at either upper extremity site.

TAU as a susceptibility gene for amyotropic lateral sclerosis-parkinsonism dementia complex of Guam.

BACKGROUND: A Guam variant of amyotrophic lateral sclerosis (ALS-G) and parkinsonism dementia complex (PDC-G) are found in the Chamorro people of Guam. Both disorders have overlapping neuropathologic findings, with neurofibrillary tangles in spinal cord and brain. The cause of ALS-G-PDC-G is unknown, although inheritance and environment appear important. Because neurofibrillary tangles containing tau protein are present in ALS-G-PDC-G, and because mutations in the tau gene (TAU) cause autosomal dominant frontotemporal dementia, TAU was examined as a candidate gene for ALS-G-PDC-G. METHODS: TAU was evaluated by DNA sequence analysis in subjects with ALS-G-PDC-G, by linkage analysis of TAU polymorphisms in an extended pedigree from the village of Umatac, and by evaluation of linkage disequilibrium with polymorphic markers flanking and within TAU. RESULTS: Linkage disequilibrium between ALS-G-PDC-G and the TAU polymorphism CA3662 was observed. For this 2-allele system, PDC and ALS cases were significantly less likely than Guamanian controls to have the 1 allele (4.9% and 2% vs 11.5%, respectively; Fisher exact P =.007). DNA sequence analysis of TAU coding regions did not demonstrate a mutation responsible for ALS-G-PDC-G. Analysis of TAU genotypes in an extended pedigree of subjects from Umatac showed obligate recombinants between TAU and ALS-G-PDC-G. Linkage analysis of the Umatac pedigree indicates that TAU is not the major gene for ALS-G-PDC-G. CONCLUSIONS: The genetic association between ALS-G-PDC-G implicates TAU in the genetic susceptibility to ALS-G-PDC-G. TAU may be a modifying gene increasing risk for ALS-G-PDC-G in the presence of another, as yet, unidentified gene.

ALS and PDC of Guam: forty-year follow-up.

BACKGROUND: It was noticed in the mid-1950s that the incidence of ALS and parkinsonism--dementia complex (PDC) were much higher on Guam than anywhere else in the world. In 1958, a registry of patients and controls was established to ascertain the familial and genetic aspects of these diseases. Patients and individually matched controls and their relatives were registered from 1958 to 1963. The registry was updated and analyzed in 1998 through 1999. OBJECTIVE: To ascertain whether first-degree relatives of patients had a higher risk for developing ALS or PDC than relatives of controls. METHODS: During the period of 1958 to 1963, 126 new patients and 126 individually matched controls and their respective first-degree relatives and spouses were evaluated neurologically and registered. Forty years later, the number of new cases among the patient and control relatives were compared to an expected number of new cases based on the age- and sex-specific incidence of ALS and PDC in the population at large. RESULTS: From 1958 to 1999, there were 102 new ALS or PDC cases among relatives of patients and 33 among relatives of controls. These values were compared with the derived expected values. There were more observed than expected new cases among patients' relatives, and less observed cases than expected among the controls' relatives. CONCLUSIONS: Relatives of patients with ALS or PDC have significantly higher risks for developing the disease than the Guamanian population, whereas relatives of controls have significantly lower risks.

Dermatoglyphics in the identification of women either with or at risk for breast cancer.

Fingerprints and palm prints were studied in 78 breast cancer patients, 391 patients at increased risk for developing breast cancer, and 64 control patients for the purpose of finding a pattern that would identify those women with breast cancer or those who are predisposed to its development. A pattern of 6 or more digital whorls was identified more frequently in women with breast cancer than in those without the disease (P less than 0.01). This finding was independent of known risk factors for breast cancer and was present in 28% of the cancer patients. No correlation was noticed between palm prints and breast cancer. The positive predictive value of 6 or more digital whorls was comparable to that of mammography and that of breast biopsy. With increasing age there was an increase in the positive predictive value associated with 6 or more digital whorls. It is concluded that digital dermatoglyphics may have a future role in identifying women either with or at increased risk for breast cancer such that either risk reduction measures or earlier therapy may be instituted.

Digital and palmar dermatoglyphics in dementia of the Alzheimer type.

Digital and palmar dermatoglyphics were examined in 29 men and 27 women with dementia of the Alzheimer type (DAT) and 112 age-, sex-, and racial group-matched controls. Female patients had significantly (p less than 0.05) more accessory triradii and complete Sydney creases than controls; no dermatoglyphic differences were detected in the males. Separating the patients by age of onset prior to or after age 65 years did not help differentiate patients from controls by dermatoglyphic profile. This study failed to confirm either the previously reported dermatoglyphic differences between DAT patients and controls or the reported similarity of the dermatoglyphic pattern of DAT to that of Down syndrome patients.

Potential role of an additive genetic component in the cause of amyotrophic lateral sclerosis and parkinsonism-dementia in the western Pacific.

Amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) are neurological degenerative disorders that occur in three high incidence foci in the western Pacific: among the Chamorros of Guam and the Commonwealth of the Northern Marianas Islands, among Japanese on the Kii peninsula of Honshu Island, and among the Auyu and Jakai peoples of southern West New Guinea. Previous studies have implicated both genetic susceptibility and environmental risk factors in the causation and familial clustering of these disorders. The data analyzed consist of 2,026 individuals in nuclear families ascertained on Guam through two mechanisms: (1) nuclear families were included in the study if one or both parents in the family were affected with ALS or PD or both; and (2) a group of "controls" was selected by obtaining nuclear families where neither parent was affected and both had lived through the age of risk. Clinically, ALS and PD are two distinct disorders. However, preliminary analyses indicated that combining all three diagnoses into one affected diagnosis for genetic analyses (thereby assuming any genetic effect on susceptibility to the two disorders was due to the same genetic mechanism) was reasonable. An age, sex and birth cohort-specific liability was defined and segregation analysis was performed under both logistic and normal models for this liability at the time of disease onset. Under either model, purely environmental, Mendelian dominant and Mendelian recessive hypotheses could be rejected, but a two-allele additive major locus hypothesis could not be rejected.

Blood groups, immunoglobulin allotypes and dermatoglyphic features of patients with amyotrophic lateral sclerosis and parkinsonism-dementia of Guam.

Blood group frequencies, immunoglobulin allotypes, and dermatoglyphic patterns were determined on patients with amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD), two chronic, degenerative, neurologic disorders of unknown cause found commonly among the Chamorros of the Mariana Islands, in an attempt to identify a specific genetic or phenetic marker associated with either disorder. With the exception of the Kidd system, no significant differences were found in blood group frequencies nor in immunoglobulin allotypes between ALS patients, PD patients, and unaffected controls. The dermatoglyphic analysis demonstrated that ALS patients had higher frequencies of palmar patterns and accessory triradii in the IV interdigital area, and PD patients had significantly higher frequencies of complete simian creases and of palmar patterns in the thenar/I interdigital area than unaffected controls. The frequencies of the remaining dermatoglyphic traits showed no significant differences. We conclude that none of the marker systems tested show a particular pattern of association in patients and controls or a genetic predisposition to either disorder, and that early identification of at-risk individuals remains elusive.

Serum levels of insulin-like growth factor-I are related to age and not to body composition in healthy women and men.

BACKGROUND: Aging is accompanied by decreased bone and lean body mass, increased fat mass, and reduced growth hormone (GH) axis function, reflected in diminished levels of insulin-like growth factor-I (IGF-I). Similar changes in body composition occur in nonelderly, GH-deficient adults and are reversible with GH administration, suggesting that diminished GH/IGF-I axis activity may contribute to such age-related changes. To determine the precise pattern of IGF-I decline with age, and to test the hypothesis that this decline is related to concomitant changes in body composition and bone metabolism independent of age, we conducted a cross-sectional survey in 351 healthy participants in the Baltimore Longitudinal Study of Aging. METHODS: We evaluated relationships among IGF-I, age, and total and regional adiposity, as assessed by body mass index (BMI) and waist-to-hip ratio (WHR); lean body mass, as estimated from urinary creatinine excretion (Crex/ht); bone mineral density (BMD), as assessed by single and dual photon absorptiometry scanning; and circulating levels of parathyroid hormone (PTH), 1,25-(OH)2 D3, 25-OHD, and osteocalcin. RESULTS: Serum IGF-I levels declined with age (p < .0001) in both men (r = -.51) and women (r = -.67). In men, the decline was linear, whereas IGF-I levels decreased faster in women < 45 years of age than in older women (p < .01) or in men (p < .001). IGF-I was inversely related to BMI (p < .005), WHR (p < .001), and PTH (p < .01) in women. IGF-I was positively related to BMD of the hip and radius in both genders (p < .0003) and to Crex/ht (p < .0005) and osteocalcin (p < .0001) in men. With increasing age, Crex/ht and BMD decreased (p < .0001) and WHR, PTH, and osteocalcin increased (p < .005) in both genders, whereas BMI increased only in women (p < .005). After adjustment for age, IGF-I was not significantly related to BMI, WHR, Crex/ht, or BMD in either gender. IGF-I was positively related to 1,25-(OH)2 D3 (p < .01) independently of age in women. CONCLUSIONS: Advancing age, rather than declining serum levels of IGF-I, appears to be a major determinant of life-time changes in body composition and BMD in women and men.

Association of radiographic features of osteoarthritis of the knee with knee pain: data from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To examine the association between self-reported knee pain and radiographic features of osteoarthritis (OA) of the knee. METHODS: A sample of participants in the Baltimore Longitudinal Study of Aging (452 Caucasian males and 223 Caucasian females) completed questionnaires and underwent a standing radiograph of both knees at the same biennial visit between 1984 and 1989. Radiographs were interpreted using both the Kellgren-Lawrence and individual features scales. Odds ratios were calculated for the association of radiographic features with knee pain after adjustment for age, sex, and body mass index. RESULTS: Overall, 156 (23%) persons reported ever having knee pain, and 104 (15%) reported current knee pain (within the previous year). Both ever knee pain and current knee pain were significantly associated with the presence of definite knee OA (Kellgren-Lawrence grade > or = 2) and with the presence of all individual features. There was a direct relationship between all measures of severity of radiographic OA and knee pain. CONCLUSION: These data demonstrate that radiographic features of knee OA are significantly associated with knee pain. The data also support the continued use of the Kellgren-Lawrence grading scale for defining knee OA in population studies.

Palmar and plantar pads and flexion creases of the rat (Rattus norvegicus).

The recent detection of dermal ridge configurations on the volar pads of the rat (Rattus norvegicus) has created opportunities for experimental studies of dermatoglyphics. In the present work, the palmar and plantar surfaces of the rat were studied to establish the feasibility of comparative rat and human dermatoglyphic investigations. The studied features included the volar pads and flexion creases. The number and location of the palmar and plantar pads in the rat were found to be similar to those of humans. The exception was a previously unrecognized small pad on the palms and soles of the rat, located on the radial and tibial side, respectively, of the proximal component of the first interdigital pad. This pad has no parallel in human embryos. Rats were found to have flexion creases in the non-pad areas between the neighboring pads, similar in location and appearance to those of humans. Unlike humans, however, rats also have boundary creases, separating the pad and non-pad areas. The marked similarities in the morphology of the volar areas between rats and humans make the rat ideally suitable for experimental studies of dermatoglyphics and flexion creases. Results of such studies should be applicable to human developmental dermatoglyphics, including those pertaining to medical disorders.

Palmar and plantar pads and flexion creases of genetic polydactyly mice (Pdn).

Attempts to gain a better understanding of the relationship between the epidermal ridge patterns (dermatoglyphics) and flexion creases on the volar aspects of human hands and feet and specific medical disorders led to a search for a suitable animal model, allowing studies of the fetal development of the pertinent structures. A common experimental animal, the rat (Rattus norvegicus), was found to be an excellent candidate, owing to the strong resemblance of the volar pads and flexion creases on its palmar and plantar surfaces to those of human subjects. A hereditary preaxial polydactyly mouse (Pdn) provides an opportunity to study the effects of this malformation on the surrounding morphological structures and, specifically, on the volar pads, i.e., the sites over which the dermatoglyphic patterns develop. The hands and feet of the wild-type (+/+) mice show no anomalies, and their major pad and flexion crease configurations correspond to those of normal rats. The heterozygous (Pdn/+) mice, in spite of having a thumb/big toe with a duplicated distal phalanx on their hands/feet, did not display any alterations in palmar/plantar pads. The homozygous (Pdn/Pdn) mice have a protrusion in the thenar area and one to three supernumerary digits on the preaxial portion of both the hands and feet. The effect of these anomalies was found to be limited to the pad and flexion crease configurations in the preaxial areas; the postaxial sites were not affected. The original number of pads on the thenar/first interdigital areas of Pdn/Pdn mice was apparently identical to that of the +/+ and Pdn/+mice. The preaxial protrusion, however, affected the number, size, and location of the pads observed in the newborn mice, resulting in varying pad configurations, such as fused and scattered pads or a pad cluster formed by gathering the neighboring pads. These pad modifications were induced by the preaxial plantar/palmar protrusion only and were not affected by the presence of supernumerary preaxial digits. In view of the similarities in the morphology and fetal development of human and mouse distal limbs, the present study is relevant to human subjects, particularly to the understanding of the significance of dermatoglyphic variations in individuals with specific medical disorders. Future studies of naturally occurring or experimentally induced limb malformations in mice or rats should provide valuable insights into the development of human hands and feet and into factors contributing to their congenital anomalies.

Dermatoglyphics and aging.

The objectives of the present study were to compare the frequencies of various dermatoglyphic features among male adults of four different age groups (30-44 years of age, 45-59, 60-74, and 75 years of age and older) and to compare the dermatoglyphic frequencies of a sample of normal 7-year-old males with those of each of the four adult groups. The results indicated that, for the most part, the four adult groups had very similar dermatoglyphic frequencies. The dermatoglyphics of the 7-year-olds were also found to be very similar to those of the 30- to 44-year-old adults; however, they showed, progressively, more significant dermatoglyphic differences as they were compared with succeedingly older age groups.

Osteoarthritis of the hand: age-specific joint-digit prevalence rates.

The left hand of each of 903 white males, most of them well-educated professionals, was evaluated for osteoarthritis, in the ongoing Baltimore Longitudinal Study of the Gerontology Research Center. The results of the joint-digit prevalence study indicated that: 1) the prevalence of osteoarthritis varies from one digit to the other; 2) osteoarthritis is considerably more prevalent in the distal than the proximal interphalangeal joints, regardless of digit or age group; 3) this disease is not only more prevalent in the distal interphalangeal joints, but it usually appears in a more severe form in the distal than in the proximal interphalangeal or the metacarpophalangeal joints. 4) Assuming that the presence of osteoarthritis in one joint is independent of the presence of the disease in the other joint of the same digit, there is an excess of digits with osteoarthritis in both the distal and proximal interphalangeal joints. This is suggestive of either a common etiology or that the presence of the disease in one joint enhances the development of osteoarthritis in the other joint of the same digit.

Osteoarthritis of the hand: longitudinal studies.

Evaluation of the osteoarthritic grades of the hands of 478 participants of the ongoing Baltimore Longitudinal Study suggests that: 1) Joint degeneration due to osteoarthritis is a relatively slow process. The maximum rate of degeneration is seen in the distal interphalangeal joints where the average increase is about 1 grade per individual in an interval of 12 to 16 years between visits in each age group. The rate of degeneration in the proximal interphalangeal joints is much lower than that of the distal interphalangeal joints. 2) The progress of the degeneration in the distal interphalangeal joints of an individual (longitudinally evaluated) follows closely that which is observed at the population level (cross-sectional joint-digit study). That is, it is directly related to the age and the interval between visits. This is not always seen in the proximal interphalangeal joint data. 3) The rate of change in the osteoarthritic grade of individual hands agrees closely with that of their distal interphalangeal joints. This further supports the conclusions reached in a first report that what has been referred to as osteoarthritic grade of the hand of an individual may actually be the higher grade among the distal interphalangeal joints.

Toe and plantar dermatoglyphics in adult American Caucasians.

The scarcity of information on control data of toe and plantar dermatoglyphics led us to undertake this study of adult American Caucasians. Toe and sole prints of 168 male and 83 female participants of the Baltimore Longitudinal Study of Aging were analyzed. Toe pattern frequencies demonstrate that fibular loops are the most prevalent pattern on the toes in both males and females. Pattern distribution by digit shows that arches are most often located on the fifth toe while whorls are found with greatest frequency on the third toe. Plantar pattern frequencies indicate that the most common pattern found in the hallucal area is the distal loop. Open fields are frequently found in the II and IV interdigital areas while distal loops are prevalent in the III area. These results are compared to the finger and palmar patterns of the same individuals. The distribution of patterns on the toes and fingers of the same individuals appear to be quite different. Population comparisons did not demonstrate a clear racial difference in the toe pattern frequencies or in the plantar areas.

Age, sex and bilateral variability in cortical bone loss and measurements of the second metacarpal.

Bilateral hand-wrist radiographs were obtained from 176 female and 448 male adult participants of the Baltimore Longitudinal Study of Aging (BLSA). Between-age group analysis revealed no change with age in total width (TW) of the second metacarpal but a significant increase in medullary width (MW) along with decreases in per cent cortical area (PCA) and combined cortical thickness (CCT) in both sexes. The magnitude of change was greater in females compared to males after the fifth decade, suggesting an interaction of the female climacteric with those processes causing bone resorption at the endosteal surface. Those women currently on estrogen exhibited significantly higher PCA and CCT and lower MW for their respective ages compared to non-users. In females, body mass index (weight/height2) was also associated with increased PCA and CCT and decreased MW. In general, the second metacarpal was longer and larger for right hands compared to left, and for males compared to females. Right hand dominance further enhances growth of the right second metacarpal so that bilateral differences for TW, MW, CCT and LEN become statistically significant. Conversely, left hand dominance promotes growth of the left metacarpal so that none of the variables studied showed significant bilateral differences.