A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice

Huntington's disease (HD) is a dominant disorder characterized by premature and progressive neurodegeneration. In order to generate an accurate model of the disease, we introduced an HD-like mutation (an extended stretch of 72-80 CAG repeats) into the endogenous mouse Hdh gene. Analysis of the mutation in vivo reveals significant levels of germline instability, with expansions, contractions and sex-of-origin effects in evidence. Mice expressing full-length mutant protein display abnormal social behaviour in the absence of acute neurodegeneration. Given that psychiatric changes, including irritability and aggression, are common findings in HD patients, our data are consistent with the hypothesis that some clinical features of HD may be caused by pathological processes that precede gross neuronal cell death. This implies that effective treatment of HD may require an understanding and amelioration of these dysfunctional processes, rather than simply preventing the premature death of neurons in the brain. These mice should facilitate the investigation of the molecular mechanisms that underpin the pathway from genotype to phenotype in HD.     

Alopecia-anosmia-deafness-hypogonadism syndrome revisited: report of a new case

Johnson et al [1983] reported on a large family with alopecia-anosmia-deafness-hypogonadism syndrome. We report the detailed findings of an unrelated, affected individual and emphasize the presence of hypohidrosis in our case. Our case indicates that this syndrome is not a private syndrome.     

Normal and abnormal development of the lip and palate

Largely because fusion of the lip and the palate are developmental weak points, common facial clefts may arise in a great many ways, both experimentally and in man. However, we believe that the vast majority of human clefts have similar origins with minor variations. One must always question the appropriateness of animal models. Apparently appropriate animal models are giving us considerable insight into the manner in which genetic and environmental factors alter development and how they interact with one another in the developing embryo. These studies help us understand the nature of the multifactorial threshold concept as it applies to cleft lip and cleft palate, and they emphasize the potential importance of even "minor" environmental factors in determining on which side of the threshold for clefting an individual embryo may fall.     

Role of the lymphatic circulatory system in shock

That the lymphatic vessel participates in the regulation of interstitial dynamics through its ability to contract and propel fluid and protein from the extravascular tissues back to the bloodstream has not been fully appreciated. The "lymph pump" appears to be regulated by local physiologic forces as well as neurogenic and humoral factors. We have assessed the effects of hemorrhage and endotoxin on the ability of the lymph vessel to propel fluid in sheep using a model system that permits the quantitation of lymphatic pumping in vivo without the complication of variable lymph inputs. A major blood loss was found to enhance lymphatic contractile activity and fluid pumping. Considering the large reservoir of fluid and protein in the interstitium and lymph, we speculate that stimulation of the "lymph pump" after hemorrhage might help to re-expand the vascular space. On the other hand, the intravenous administration of endotoxin inhibited lymphatic pumping, suggesting that impaired lymph propulsion in sepsis may contribute to edema by reducing the ability of the lymphatic vessel to remove extravasated protein from the tissues.     

Immune changes associated with insulin dependent diabetes may remit without causing the disease: a study in identical twins

Activation of T lymphocytes and islet cell antibodies were studied in two groups of insulin dependent diabetics and their non-diabetic identical cotwins. Group 1 comprised 12 "short term" twin pairs (diabetic twin diagnosed less than five years previously) in whom only a third of the cotwins were likely to develop diabetes; 10 of the 12 non-diabetic cotwins showed increased values of activated T lymphocytes, islet cell antibodies, or both. Group 2 comprised 10 "long term" twin pairs (diabetic twin diagnosed more than 11 years previously) in whom none of the non-diabetic cotwins was likely to develop diabetes; these pairs were selected because all the non-diabetic cotwins had shown islet cell antibodies at some time in the past, but only two still did so (one with an increased value of activated T cells). There was relative glucose intolerance in the cotwins of the short term group but not in those of the long term group. Non-diabetic cotwins of diabetics may show the immune changes associated with insulin dependent diabetes and relative glucose intolerance, but these changes may remit without leading to diabetes.     

Infiltrating angiolipoma or intramuscular hemangioma? A report of five cases

We report five cases of tumors composed primarily of angiomatous and adipose tissue occurring within skeletal muscle in relatively young individuals. Pain is frequently the presenting symptom. The tumors have been described in the literature as angiolipomas, infiltrating angiolipomas, and intramuscular hemangiomas. A discussion of the use of these terms is included. It is our conclusion the term "intramuscular hemangioma" is most appropriate for these lesions.     

Use of VA ECMO and percutaneous palliation of ductal dependent coarctation in a neonate with trisomy 21 and COVID-19 pneumonia

We present a case of a neonate with trisomy 21, ductal-dependent aortic coarctation, and severe respiratory failure secondary to coronavirus disease 2019 (COVID-19) pneumonia. The neonate was managed with venoarterial extracorporeal membrane oxygenation (VA ECMO), palliative stenting of the coarctation, and a vascular plug occlusion of a large patent ductus arteriosus. The patient was successfully weaned off extracorporeal membrane oxygenation (ECMO). The patient is currently awaiting a definitive surgical repair in the near future.