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.     

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.     

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.     

The “Ins” and “Outs” of the Depressive Disorders Section of DSM‐5

In this article, we review and evaluate changes in the depressive disorders section from DSM‐IV to DSM‐5. We describe characteristics of three new depressive disorders: disruptive mood dysregulation disorder, premenstrual dysphoric disorder, and persistent depressive disorder. We also discuss the controversial decision in DSM‐5 to remove the bereavement exclusion from the criteria for major depressive disorder. Next, we review the decision to replace the diagnosis of depressive disorder not otherwise specified with two new diagnoses: other specified depressive disorder and unspecified depressive disorder. Finally, we discuss the inclusion of two novel specifiers in the DSM‐5 depressive disorders section: “with anxious distress” and “with mixed features.” For each of these changes, we examine the relevant research and discuss implications of the changes for research and clinical practice.     

The “long-thumb” brachydactyly syndrome

A unique variety of brachydactyly associated with skeletal and joint anomalies and possible cardiac conduction defects has been observed in three generations of one family in a pattern consistent with autosomal-dominant transmission. This combination of anomalies has not previously been seen together as a single syndrome. We report clinical and radiographic studies in three of the four affected family members.     

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.     

Regulation of Respiration: “The Black Box”

A close relation between the state of wakefulness, the electroencephalogram, and the respiration has been demonstrated (Bülow 1963). In the present paper it was assumed that as opening and closing of the eyes influence the EEG and thus probably the state of wakefulness, the responsiveness of the respiratory center may likewise be influenced by the single act of closing the eyes. Seven subjects were studied in the steady state of rest breathing ambient air, 4–5 % CO₂ in air, or 11 % O₂ in nitrogen. In experimental periods of 4–5 minutes their pulmonary ventilation and alveolar Pco₂ were measured while they randomly were either reading a book, or were blindfolded. It was found that in all three conditions closing of the eyes resulted in a mean decrease of V_E of 8 to 14 % with a concomitant increase of PACO₂ of about 1 mmHg. It is tentatively suggested that other and stronger central or peripheral stimuli impinging on the reticular formation of the brain may explain the changed sensitivity of the respiratory center towards the chemical stimuli in conditions like exercise, chronic hypoxia etc.