Acquired homozygosity of the rearranged bcr allele during the acute leukemic phase of a patient with Ph-negative chronic myeloid leukemia

A 45-year-old male patient with Ph-negative chronic myeloid leukemia (CML) had rearranged bcr-3' and bcr-5' gene regions in Southern blot studies when leukemia was diagnosed. During development of terminal blast crisis, successive blood samples showed a progressive decrease in the amount of germline bcr DNA and its complete loss by full blast crisis. There were also increased amounts of rearranged bcr DNA consistent with acquired homozygosity. A similar result was obtained with an IgV lambda probe and indicated homozygosity of a significant part of chromosome 22. The bcr-abl gene complex behaves as a somatic dominant in CML, and we suggest that its acquired homozygosity is a mechanism of bcr-abl amplification similar to duplication of the Ph chromosome commonly found in the blast crisis of CML.     

Informant ratings of cognitive decline of elderly people: relationship to longitudinal change on cognitive tests

Formal assessment of cognitive decline with cognitive tests can be difficult, requiring either two measurement points or a comparison of 'hold' with 'don't hold' tests. Informant-based assessment provides an alternative approach because informants can adopt a longitudinal perspective and directly rate cognitive change. A study was carried out to assess the validity of informant ratings collected by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A community sample of 500 subjects aged 74 or over underwent four cognitive tests on two occasions 3½ years apart. On the second occasion, informants filled out the IQCODE. Subjects rated as having moderate or severe decline were found to have greater change on the cognitive tests. These findings support the validity of informant ratings of cognitive decline.     

The effect of azathioprine (Imuran) on the kinetics of monocytes and macrophages during the normal steady state and an acute inflammatory reaction

The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24-48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.     

Crohn's disease and myasthenia gravis: a possible role for thymectomy.

A female patient with a three year history of Crohn's disease of the colon developed myasthenia gravis. Despite diversion of the faecal stream by an ileostomy, and total colectomy, the patient had continuing problems with perineal and perianal abscesses and fistulas. Her myasthenia gravis became unresponsive to anti-cholinergics so a thymectomy was performed. The perineal and perianal disease improved subsequently. This case supports the theory that functional disturbances of the thymus may have a role in the pathogenesis of inflammatory bowel disease.     

Retinoblastoma: Achieving new standards with methods of chemotherapy

The management of retinoblastoma (RB) has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC) is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC) is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms “RB,” and “treatment,” “chemotherapy,” “systemic chemotherapy,” “IVC,” “IAC,” “periocular chemotherapy,” or “intravitreal chemotherapy.” Relevant English language articles were extracted, reviewed, and referenced appropriately.     

Review of spectral domain enhanced depth imaging optical coherence tomography of tumors of the choroid

Background:Spectral domain enhanced depth imaging optical coherence tomography (EDI-OCT) can provide anatomic localization of intraocular tumors.Aims:The aim was to identify topographical and intrinsic patterns of choroidal tumors on EDI-OCT.Results:Using EDI-OCT, choroidal nevus displayed a smooth, dome-shaped topography with overlying retinal pigment epithelium alterations, drusen, and occasional subretinal cleft demonstrating photoreceptor loss. Small choroidal melanoma showed smooth, moderately dome-shaped topography, commonly with overlying shallow subretinal fluid that often depicted “shaggy” photoreceptors. Choroidal metastasis showed a minimally “lumpy, bumpy” surface topography and with overlying subretinal fluid and shaggy photoreceptors. Choroidal hemangioma showed a smooth, dome-shaped topography, with expansion of the affected small, medium, and large choroidal vessels. Choroidal lymphoma showed varying topography with increasing tumor thickness as “flat, rippled, or undulating (seasick)” surface. Choroidal osteoma displayed a smooth undulating surface with visible intralesional horizontal lines suggestive of bone lamellae and occasional horizontal and vertical tubules with intralesional “spongy” flecks. Choroidal melanocytosis appeared as uniformly thickened choroid with increased stromal density surrounding the normal choroidal vascular structures.Conclusions:Enhanced depth imaging-OCT can depict characteristic patterns that are suggestive of various choroidal tumors.     

Mental health of youth orphaned due to AIDS in South Africa: biological and supportive links to caregivers

This research explored the biological and social support relationship between youth orphaned due to AIDS and his/her caregiver to identify protective factors that are related to positive mental health outcomes. These youth have significantly higher levels of depression, anxiety, and post-traumatic stress (PTS) symptoms compared to those orphaned due to other causes and non-orphans. Using a 2009 cross-sectional data-set from South Africa, 254 youth orphaned due to AIDS were purposively selected from the overall sample of 732 to further examine this caregiver relationship. Caregiver relation was analyzed in several combinations to determine if it was significantly related to mental health outcomes, with only anxiety showing significance. Those living with a biological parent had significantly higher anxiety symptoms than those living with a grandparent, other kin, or non-kin. Anxiety was also significantly related to an increased age, lower levels of emotional support, and lower levels of instrumental/financial support (R² = .153). Age was the only significant variable from the model that was related to depression symptoms (R² = .111). PTS symptoms were related to increases in age, lower levels of emotional support, instrumental/financial support, and satisfaction with the caregiver (R² = .194). Gender and age were related to suicidal tendencies, specifically boys were 2.26 times more likely to exhibit suicidal tendencies compared to girls, and every yearly increase in age results in the youth being 1.22 times more likely to exhibit suicidal tendencies. Strengthening the caregiver’s ability to provide social support for the child is critical, irrespective of any biological kin relationship.