Fitzsimons Army Medical Center

Patients with psychiatric disorders (as well as general medical conditions) often describe their lives in terms of suffering. Although suffering is honored as a central focus of physicians' concerns, it is not even indexed in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Generally connoting severe, prolonged distress, suffering can be distinguished from pain, depression, and anxiety. The aims of this article are to consider whether attending to suffering per se in psychiatric patients merits attention independent of other commonly assessed psychiatric symptoms such as anxiety, depression, and conventional distress, and how targeting suffering per se might add value to psychiatric patient care. Sources for this article were obtained via a selective literature search in PubMed using the terms "suffering" in the title and the terms "psychiatric disorder," "mental illness," "assessment," "measurement," "scale," "existential suffering," and "unbearable suffering." Articles of interest were followed up using a snowball technique to examine "similar articles" and "cited by" titles to find additional pertinent articles. Definitions of suffering in the medical literature stress its subjectivity, particularity, complexity, and connection to a wide variety of noxious sensations, as well as real and anticipated deficits, losses, and thwarted motivations. These can affect the entire spectrum of universal human needs, from basic biological issues through intrapsychic, interpersonal, and social issues, encompassing existential concerns of meaning, purpose, and transcendence. Based on these factors, a definition of suffering in patients with psychiatric disorders is proposed. Although efforts to measure suffering have been limited and numerous gaps in the literature are evident, several scales may offer suitable bases for the study of suffering in patients with psychiatric disorders. Ascertaining sources of suffering may require new types of inquiry and additional time. Well-described, evidence-informed strategies and time-honored psychotherapy techniques are available for addressing the numerous concerns that contribute to suffering. Patients with psychiatric disorders whose distinct, multidimensional sources of suffering are identified, acknowledged, and addressed may experience better treatment quality, greater treatment satisfaction, and possibly better outcomes than those whose clinicians' attention is limited to conventional psychiatric signs and symptoms.

The clinical and histopathological findings in 26 children with non-Hodgkin's lymphoma without initial marrow involvement are reviewed. A marked male predominance similar to that observed in previous series was noted. Biopsy material was classified according to the recommendations of Rappaport in 22 cases. All have diffuse lymphomas, and 16 of 22 patients had diffuse, poorly-differentiated, lymphocytic lymphoma. Twelve of 26 patients had involvement of the mediastinum as part of their initial presentation. Of these 12, 5 developed lymphomatous involvement of the central nervous system prior to the development of leukemic transformation of the bone marrow. This observation suggests that prophylactic therapy against CNS relapse be considered for children with mediastinal non-Hodgkin's lymphoma, even in the absence of initial marrow involvement.

Polyomavirus and papillomavirus (papovavirus) capsids are composed of 72 capsomeres of their major capsid proteins, VP1 and L1, respectively. After translation in the cytoplasm, L1 and VP1 pentamerize into capsomeres and are then imported into the nucleus using the cellular alpha and beta karyopherins. Virion assembly only occurs in the nucleus, and cellular mechanisms exist to prevent premature capsid assembly in the cytosol. We have identified the karyopherin family of nuclear import factors as possible "chaperones" in preventing the cytoplasmic assembly of papovavirus capsomeres. Recombinant murine polyomavirus (mPy) VP1 and human papillomavirus type 11 (HPV11) L1 capsomeres bound the karyopherin heterodimer alpha2beta1 in vitro in a nuclear localization signal (NLS)-dependent manner. Because the amino acid sequence comprising the NLS of VP1 and L1 overlaps the previously identified DNA binding domain, we examined the relationship between karyopherin and DNA binding of both mPy VP1 and HPV11 L1. Capsomeres of L1, but not VP1, bound by karyopherin alpha2beta1 or beta1 alone were unable to bind DNA. VP1 and L1 capsomeres could bind both karyopherin alpha2 and DNA simultaneously. Both VP1 and L1 capsomeres bound by karyopherin alpha2beta1 were unable to assemble into capsids, as shown by in vitro assembly reactions. These results support a role for karyopherins as chaperones in the in vivo regulation of viral capsid assembly.

Milk is a complex fluid composed of proteins, sugars, lipids and minerals, in addition to a wide variety of bioactive molecules including vitamins, trace elements and growth factors. The composition of these components reflects the integrated activities of distinct synthetic, secretion and transport processes found in mammary epithelial cells, and mirrors the differing nutritional and developmental requirements of mammalian neonates. Five general pathways have been described for secretion of milk components. With the exception of lipids, which are secreted a unique pathway, milk components are thought to be secreted by adaptations of pathways found in other secretory organs. However little is known about the molecular and cellular mechanisms that constitute these pathways or the physiological mechanisms by which they are regulated. Comparisons of current secretion and transport models in the mammary gland, exocrine pancreas and salivary gland indicate that significant differences exist between the mammary gland and other exocrine organs in how proteins and lipids are packaged and secreted, and how fluid is transported.

BackgroundAnalyzing apoptosis has been an integral component of many biological studies. However, currently available methods for quantifying apoptosis have various limitations including multiple, sometimes cell-damaging steps, the inability to quantify live, necrotic and apoptotic cells at the same time, and non-specific detection (i.e. "false positive"). To overcome the shortcomings of current methods that quantify apoptosis in vitro and to take advantage of the 96-well plate format, we present here a modified ethidium bromide and acridine orange (EB/AO) staining assay, which may be performed entirely in a 96-well plate. Our method combines the advantages of the 96-well format and the conventional EB/AO method for apoptotic quantification.ResultsWe compared our method and the conventional EB/AO method for quantifying apoptosis of suspension cells (Jurkat) and adherent cells (A375) under normal growth and apoptosis-inducing conditions. We found that our new EB/AO method achieved quantification results comparable to those produced using the conventional EB/AO method for both suspension and adherent cells.ConclusionBy eliminating the detaching and washing steps, our method drastically reduces the time needed to perform the test, minimizes damage to adherent cells, and decreases the possibility of losing floating cells. Overall, our method is an improvement over the currently available techniques especially for adherent cells.

Objectives: To evaluate the long term effect of ongoing intervention to improve treatment of depression in primary care.Design: Randomised controlled trial.Setting: Twelve primary care practices across the United States.Participants: 211 adults beginning a new treatment episode for major depression; 94% of patients assigned to ongoing intervention participated.Intervention: Practices assigned to ongoing intervention encouraged participating patients to engage in active treatment, using practice nurses to provide care management over 24 months.Main outcome measures: Patients' report of remission and functioning.Results: Ongoing intervention significantly improved both symptoms and functioning at 24 months, increasing remission by 33 percentage points (95% confidence interval 7% to 46%), improving emotional functioning by 24 points (11 to 38) and physical functioning by 17 points (6 to 28). By 24 months, 74% of patients in enhanced care reported remission, with emotional functioning exceeding 90% of population norms and physical functioning approaching 75% of population norms.Conclusions: Ongoing intervention increased remission rates and improved indicators of emotional and physical functioning. Studies are needed to compare the cost effectiveness of ongoing depression management with other chronic disease treatment routinely undertaken by primary care.

A 23-year-old male was referred to our hospital for evaluation of new-onset seizures. Signs and symptoms of neuroglycopenia, including weakness, dizziness, and confusion, appeared during fasting and resolved promptly with intravenous dextrose administration. Insulin, proinsulin, and C-peptide levels were consistent with a diagnosis of insulinoma. Screening tests for multiple endocrine neoplasia type 1 and surreptitious sulfonylurea uses were negative. Preoperative localization of the insulinoma by transabdominal ultrasonography, computed tomography, and indium-111 octreoscanning were unsuccessful. Endoscopic ultrasonography (EUS) identified a 6- to 7-mm tumor at the juncture of the head and body of the pancreas. Surgical exploration confirmed the preoperative localization, and an 8-mm tumor was simply enucleated. The patient has been free of symptoms for 18 months since surgery. This report describes the utility of EUS to localize a solitary pancreatic insulinoma and provides a comparison of EUS and other preoperative localization techniques.