Pseudo-endophthalmitis caused by intravitreal lipid transudation in association with proliferative diabetic retinopathy and hyperlipidemia

A 20-year-old woman with a 13-year history of insulin-dependent diabetes mellitus presented with a history of malaise, fever, a non-healing ulcer of the great toe, and an insect bite incurred during recent travel to a foreign country. Milky white infiltrates accompanied by inflammatory cells located within close proximity to neovascular fronds in both vitreous cavities led to the suspicion of bilateral metastatic endophthalmitis. Studies conducted during hospitalization failed to show evidence of systemic blood born infection. A diagnostic vitrectomy in one eye failed to grow organisms, though lipid laden macrophages were identified by electron microscopy. The clinical appearance improved in both eyes during her hospitalization coincident with improved diabetic control. It was later concluded that the milky white infiltrates were associated with hyperlipidemia as a consequence of poorly controlled diabetes and a familial tendency toward hyperlipidemia.     

Long-term treatment of ventricular tachycardia with amiodarone in presence of severe left ventricular dysfunction.

A group of 34 consecutive patients with coronary artery disease (n = 29) or dilated cardiomyopathy (n = 5) (3 women, 31 men, age 38-80 yr) who had severely impaired left ventricular function (left ventricular ejection fraction less than or equal to 40%) and high-grade ventricular ectopic activity (sustained or nonsustained ventricular tachycardia or ventricular fibrillation) were treated with amiodarone (mean dose: 206 mg/d) and followed for 1-117 (mean: 49) months. In the total group, there were seven sudden deaths, five deaths due to pump failure, one non-cardiac death, and two successful heart transplantations during follow-up. Thus the annual cardiac mortality in these carefully selected and followed patients was 8, 6%, the annual cardiac event rate was 10, 1%. The cumulative cardiac survival-rate was 62% after 5 years and 41% after 10 years. In five patients, treatment was interrupted after 10 to 43 months, three of the patients were alive at follow-up and two suffered cardiac death, resulting in an annual cardiac death rate of 12% in this subgroup of treatment. Based on the results of this retrospective analysis we conclude that in patients with low left ventricular ejection fraction and nonsustained or sustained ventricular tachycardia treated with low dose amiodarone, mortality was unexpectedly low. Thus, it may be the antiarrhythmic treatment to be considered in patients with ventricular tachycardia and severe left ventricular dysfunction.     

Coupling of lactose molecules to the carrier protein hinders the spleen and bone marrow uptake of doxorubicin conjugated with human albumin.

Several attempts have been made to enhance doxorubicin (DOXO) concentrations in tumour cells by drug conjugation with human albumin (HSA). HSA-DOXO has the drawback of causing DOXO accumulation in spleen and bone marrow, with a consequent leucopoenia not produced when lactose molecules are coupled to the carrier protein. In the present experiments we demonstrated that the effect of HSA lactosamination is not a consequence of a more rapid disappearance from the bloodstream of the lactosaminated conjugate (L-HSA-DOXO), which is rapidly internalized by the liver through the asialoglycoprotein receptor, but is due to a hindered uptake by spleen and bone marrow cells caused by the coupled lactose molecules. Experiments in vitro showed that HSA-DOXO produced an inhibition of murine macrophage proliferation not caused by L-HSA-DOXO. This result can be explained by higher amounts of the former conjugate entering in these cells and suggests macrophages as the cell type responsible for the spleen and bone marrow internalization of HSA-DOXO hindered by lactose coupling. Importantly, lactosamination of HSA did not reduce the marked uptake of HSA-DOXO by chemically induced rat hepatocellular carcinoma. L-HSA-DOXO, by avoiding DOXO accumulation in bone marrow is an attractive candidate for clinical trials against tumors which were found to actively internalize this conjugate in laboratory animals, such as hepatocellular carcinoma.     

Postoperative radiotherapy of the prostate for patients undergoing radical prostatectomy with positive margins, seminal vesicle involvement and/or penetration through the capsule

A group of 159 patients previously reported as having margins positive for disease after radical prostatectomy with or without adjunctive postoperative radiation was reanalyzed to determine whether the reported benefit did indeed exist. Upon re-examination of the 159 patients 15 were identified who did not receive radical prostatectomy but who were analyzed as if they had received this therapy. An updated review of the total pool of 159 patients with analysis as to failure, death of any cause or death of prostatic cancer demonstrated no benefit of postoperative radiation therapy for margin positive disease. Exclusion of patients who did not receive radical prostatectomy and analysis as described also failed to identify any benefit of postoperative adjunctive radiation therapy.     

Immunoglobulin heavy chain Diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement.
DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences.
Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen.
The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.     

Relocation mortality in dementia: The effects of a new hospital

Relocation mortality has been cited as an important factor when considering the placement of elderly patients. This study describes the fate of dementia patients relocated to facilitate the move to a new hospital. Some wards were moved as intact units—that is, the patients were kept together and there was little change in the nursing or medical staff. Two other wards were closed, and these patients were dispersed to several existing and new wards and experienced changes of nursing and medical staff. All patients underwent prerelocation and postrelocation orientation programmes. The mortality figures for the total patient group before and after the relocation do not show any statistically significant increase in mortality postrelocation. However, for wards that were closed and where the patients suffered maximum disruption to patient group and nursing staff, there was a significant increase in mortality rates.     

Open extremity fracture penetrating the skull

We present a case in which an open fracture of the ulna penetrated the skull and caused a comminuted, depressed skull fracture with a large intraparenchymal hematoma containing bone fragments.     

Multi-joint limbs permit a flexible response to unpredictable events

The human arm is kinematically redundant, which may allow flexibility in the execution of reaching movements. We have compared reaching movements with and without kinematic redundancy to unpredictable double-step targets. Subjects sat in front of a digitising tablet and were able to view an arc of four targets reflected in the mirror as virtual images in the plane of the tablet. They were instructed to move, from a central starting point, in as straight a line as possible to a target. In one-third of trials, the target light switched to one of its neighbours during the movement. Subjects made 60 movements using shoulder, elbow and wrist and then another 60 movements in which only shoulder and elbow movement were allowed. By restraining the wrist, the limb was made non-redundant. The path length was calculated for each movement. In single-step trials, there was no significant difference between path lengths performed with and without wrist restraint. As expected there was a significant increase in path length during double-step trials. Moreover this increase was significantly greater when the wrist was restrained. The variability across both single- and double-step movements was significantly less while the wrist was restrained. Importantly the performance time of the movements did not alter significantly for single-step, double-step or restrained movements. These results suggest that the nervous system exploits the intrinsic redundancy of the limb when controlling voluntary movements and is therefore more effective at reprogramming movements to double-step targets. Received: 24 March 1997 / Accepted: 7 July 1997     

Disposition of Tablet and Capsule Formulations of Digoxin in the Elderly

Study Objective . To compare digoxin tablets and liquid-filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state. Design . A randomized, crossover trial, each period lasting 3 weeks, with no washout period. Setting . A university hospital. Patients . Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease. Interventions . The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites. Measurements and Main Results . No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p=0.05). One subject had a 4-fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability. Conclusions . Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products.