HIV Protease: Historical Perspective and Current Research

The retroviral protease of human immunodeficiency virus (HIV) is an excellent target for antiviral inhibitors for treating HIV/AIDS. Despite the efficacy of therapy, current efforts to control the disease are undermined by the growing threat posed by drug resistance. This review covers the historical background of studies on the structure and function of HIV protease, the subsequent development of antiviral inhibitors, and recent studies on drug-resistant protease variants. We highlight the important contributions of Dr. Stephen Oroszlan to fundamental knowledge about the function of the HIV protease and other retroviral proteases. These studies, along with those of his colleagues, laid the foundations for the design of clinical inhibitors of HIV protease. The drug-resistant protease variants also provide an excellent model for investigating the molecular mechanisms and evolution of resistance.     

Ileocolic Intussusception Caused by a Giant Ulcerating Lipoma of Bauhin’s Valve: an Unusual Cause of Intestinal Obstruction in the Adult

We report a case of intestinal obstruction in a 73-year-old woman caused by ileocolic intussusception. The underlying cause was a giant submucosal ulcerating lipoma (6?×?3.3?×?3.8 cm) extending from the superior mucosal lip of Bauhin’s valve. Abdominal ultrasonography showed a pathognomonic target-like mass appearing as multiple concentric rings. CT scan confirmed the diagnosis. Because of apparent obstruction, a laparotomy with right hemicolectomy and ileocolic anastomosis was performed. Lipomas most frequently occur in the cecum and ascending colon where they represent the most common submucosal mesenchymal tumor. They typically occur in elderly women with an incidence that varies from 0.15 to 0.56 %. Pain, rectal bleeding, and obstruction are typical symptoms. When faced with an intussusception in children, reduction with air per rectum can be performed. In adults, however, malignant cell spreading and seeding is of big concern. Since approximately 20–50 % of all underlying causes are malignant, explorative surgery is favored in adults.     

Attachment to Caregivers and Type 1 Diabetes in Children

Attachment is a behavioral and physiological system, which enables individual’s dynamic adaptation to its environment. Attachment develops in close interaction between an infant and his/her mother, plays an important role in the development of the infant’s brain, and influences the quality of interpersonal relationships throughout life.Security of attachment is believed to influence individual response to stress, exposing insecurely organized individuals to deregulated autonomic nervous system and exaggerated hypothalamic-pituitary-adrenal activity, which, in turn, produces increased and prolonged exposure to stress-hormones. Such stress responses may have considerable implications for the development of diverse health-risk conditions, such as insulin resistance and hyperlipidemia, shown by numerous studies.Although the mechanisms are not yet fully understood, there is compelling evidence highlighting the role of psychological stress in the development of type 1 diabetes (T1D). One of the possible contributing factors for the development of T1D may be the influence of attachment security on individual stress reactivity. Thus, the suggestion is that insecurely attached individuals are more prone to experience increased and prolonged influence of stress hormones and other mechanisms causing pancreatic beta-cell destruction.The present paper opens with a short overview of the field of attachment in children, the principal attachment classifications and their historic development, describes the influence of attachment security on individual stress-reactivity and the role of the latter in the development of T1D. Following is a review of recent literature on the attachment in patients with T1D with a conclusion of a proposed role of attachment organization in the etiology of T1D.     

Secondary haemophagocytic lymphohistiocytosis: Experience from the Uppsala University Hospital

Background. Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by fever, hepatosplenomegaly, cytopenia, and progressive multiple-organ failure. HLH in adults is often secondary to autoimmune diseases, cancer, or infections in contrast to familial HLH. Treatment of secondary HLH is directed against the triggering disease in addition to immunosuppressive therapy, the latter commonly according to the HLH-2004 protocol.Methods. We conducted a retrospective study to identify triggering diseases, disease-specific and immunosuppressive therapy administered, and prognosis in adult patients with secondary HLH. Patient data were collected from October 2010 to January 2015.Results. Ten adult patients with secondary HLH were identified. Seven were men, and the median age at diagnosis was 62 years. Five cases were triggered by malignant disease and five by infection. The median patient fulfilled five of the eight HLH-2004 diagnostic criteria. All patients fulfilled the criteria fever, cytopenia, and ferritin >500 µg/L. Median time from hospital admission to HLH diagnosis was 20 days. Four patients received immunosuppressive therapy according to the HLH-2004 protocol. The prognosis was dismal, especially for the patients with malignancy-associated HLH, of whom all died.Conclusion. HLH should be suspected in patients who present with fever, cytopenia, and ferritin >500 µg/L. Secondary HLH has a dismal prognosis. None of the patients with HLH triggered by malignancy survived. Achieving remission of the triggering disease seems to be important for a favourable outcome as, in all surviving patients, the haemophagocytic syndrome resolved after remission of the underlying infection.