Bone “mass” and the “mechanostat”: A proposal

The observed fit of bone mass to a healthy animal's typical mechanical usage indicates some mechanism or mechanisms monitor that usage and control the three longitudinal growth, bone modeling, and BMU-based remodeling activities that directly determine bone mass. That mechanism could be named a mechanostat. Accumulated evidence suggests it includes the bone itself, plus mechanisms that transform its mechanical usage into appropriate signals, plus other mechanisms that detect those signals and then direct the above three biologic activities. In vivo studies have shown that bone strains in or above the 1500–3000 microstrain range cause bone modelling to increase cortical bone mass, while strains below the 100–300 microstrain range release BMU-based remodeling which then removes existing cortical-endosteal and trabecular bone. That arrangement provides a dual system in which bone modeling would adapt bone mass to gross overloading, while BMU-based remodeling would adapt bone mass to gross underloading, and the above strain ranges would be the approximate “setpoints” of those responses. The anatomical distribution of those mechanical usage effects are well known. If circulating agents or disease changed the effective setpoints of those responses their bone mass effects should copy the anatomical distribution of the mechanical usage effects. That seems to be the case for many agents and diseases, and several examples are discussed, including postmenopausal osteoporosis, fluoride effects, bone loss in orbit, and osteogenesis imperfecta. The mechanostat proposal is a seminal idea which fits diverse evidence but it requires critique and experimental study.     

Metabolic responses in feline “red” and “white” skeletal muscle to shock and ischemia

In order to investigate possible differences in the reaction to hypoxic conditions between “red” and “white” skeletal muscle, cats were subjected to a 2 h period of either hemorrhagic shock or hind limb tourniquet ischemia, and the hypoxia induced changes were studied in the soleus and lateral gastrocnemius muscles. Muscle biopsies were analysed for ATP, CP, glucose, G 6–P and lactate. Using microelectrodes, the resting membrane potential was repeatedly measured. Both experimental models resulted in increased tissue lactate levels and a successive decrease in the membrane potential of both muscles studied. No reduction of the high energy phosphagen content (ATP+CP) occurred in any of the muscles during shock. The tourniquet ischemia resulted in a 40% reduction of the ATP+CP content in the soleus muscle, whereas in the gastrocnemius muscle no significant reduction occurred. A significant correlation was found between the tissue lactate content and the membrane potential under both conditions and in both muscles studied. It is concluded that “red” muscles are more susceptible to metabolic derangement than “white” muscles during total ischemia, whereas during hypovolemia “red” muscles appear to be protected from early hypoxic damage, probably due to a redistribution of skeletal muscle blood flow.     

Psychiatric “Co-occurrence”? I'll Stick with “Comorbidlty”

Lilienfeld et al's critique of the use of the term comorbid in psychopathological research is critically examined. They are incorrect in asserting that the original use of the term in medical epidemiology was intended to restrict it to disease entities. Furthermore, the ways in which medical comorbidity can be understood apply equally well to understanding the comorbidity of psychiatric or psychological disorders. Just as it has been useful to use the general term psychiatric disorders to include symptom patterns and syndromes and few If any true diseases, so to it is useful to apply the generic term of comorbidity to the joint occurrence of psychiatric disorders. Because methodological factors can sometimes contribute to artifactual comorbidity which is uninformative about the disorders being studied is no reason to abandon the term comorbidity in psycho-pathological research.     

Smith-Lemli-Opitz syndrome: Thirty-year follow-up of “S” of “RSH” syndrome

We have reassessed patient “S,” one of the first 3 individuals recognized to have Smith-Lemli-Opitz (or RSH) syndrome, at age 34 years, and we describe his physical, developmental, and behavioral manifestations. This reassessment provides formal evidence that this individual has the cholesterol biosynthetic defect which is thought to be the cause of Smith-Lemli-Opitz syndrome. Dietary manipulation appears to have had a beneficial effect on the patient's behavior and suggests that even in adults with this condition, dietary cholesterol supplementation may be indicated. Am. J. Med. Genet. 68:260–262, 1997. © 1997 Wiley-Liss, Inc.     

Endocardial cushion defect: Further studies of “isolated” versus “syndromic” occurrence

The isolated occurrence of endocardial cushion defect (ECD) has been suggested to differ from its occurrence within the context of a syndrome, with regard to the nature (complete or partial) of the defect and the associated cardiovascular malformations. Analysis of data derived from the Baltimore-Washington Infant Study of congenital cardiovascular malformations supports the observation that “syndromic” ECD tends to be of the complete atrioventricular canal type and is less frequently associated with left cardiac anomalies than the isolated form. However, each syndrome has a unique impact on the overall cardiovascular “phenotype,” including the ECD. This is especially true for Down and Ivemark syndromes, which are most frequently associated with ECD, but also for other syndromes as well. It is also suggested that isolated ECD is specifically associated with gastrointestinal and urinary tract anomalies. However, in Down syndrome ECD appears to be a specific cardiovascular expression of the trisomic state that is unrelated to other noncardiac malformations. Additional information on the association of ECD with other less common genetic syndromes is needed in order to further investigate the possible genetic basis of this cardiac defect. © 1992 Wiley-Liss, Inc.     

Exploring “personal” and “shared” sense of community identity in Durham City,England

“Personal” and “shared” aspects of sense of community identity are explored in a an established community in Durham City, England. Durham City has a history of over 1,000 years of continuous settlement, and is generally viewed as a stable and relatively harmonious setting. In the study 102 residents responded to a Community Response Questionnaire based on Puddifoot's taxonomy of elements of sense of community. The findings suggest the existence of three underlying “personal” dimensions of Sense of Community Identity (SOCI), namely, “Sense of Personal Support,” “Sense of Personal Contentedness,” and “Personal Involvement,” and three “shared” dimensions of SOCI, namely, “Perceived Community Engagement,” “Perceived Neighborliness,” and “Perceived Settledness.” This article discusses these findings and the prospect of creating a measure for comparative analysis around these dimensions. © 2003 Wiley Periodicals, Inc.     

“Primary” leptomeningeal medulloblastoma

We report the case of an 8-year-old boy who presented with a 2-month history of headaches and mild visual impairment and was found to have a medulloblastoma with primary leptomeningeal involvement. No mass lesion was found on imaging studies, during subsequent intraoperative surgical inspection or at autopsy. The pathologic findings were first documented on cerebrospinal fluid cytologic examination and biopsy of the cerebellum and were later confirmed at necropsy. To our knowledge, this is the third reported case of medulloblastoma identified with primary leptomeningeal involvement without a cerebellar mass and the first such case with documented autopsy findings.     

“Hypotyrosinemia” in Phenylketonuria

It has been postulated that the significant incidence of learning disabilities in well-treated patients with phenylketonuria (PKU) may be due, in part, to reduced production of neurotransmitters as a result of deficient tyrosine transport across the neuronal cell membrane. Hypotyrosinemia has been reported in treated and untreated PKU but virtually no data are available. We decided to examine this in our patient population and to compare it with the published norms, patient data from our hospital clinical biochemical laboratory database, and a group of normal children and adolescents in a private pediatric practice. We found that the mean nonfasting plasma tyrosine in 99 classical PKU patients was 41.1 μmol/L, in 26 mild (atypical) PKU patients 53.3 μmol/L, and in 35 non-PKU mild hyperphenylalaninemia patients 66.6 μmol/L. This compared to nonfasting plasma tyrosine levels in 102 non-PKU subjects of 64.0 μmol/L in our hospital biochemistry database, 69.1 μmol/L in 58 volunteers in the private office practice, and 64–78.8 μmol/L in infants, children, and adolescents in the literature review. Our data support the previously undocumented statements in the literature that plasma tyrosine levels are low in PKU.