Outcome of low-dose ganciclovir for cytomegalovirus disease prophylaxis in renal-transplant recipients

To assess the outcome of low-dose-ganciclovir prophylaxis (500 mg twice a day for 3 months) in renal-transplant recipients, a retrospective analysis of 185 patients transplanted between 1998 and 2001 was performed. There were 29 (15.6%) patients who belonged to the highest risk group, donor cytomegalovirus (CMV) positive, recipient negative (D + R-), and 37 (20%) patients in the lowest risk group, D-R-. Induction immunosuppression consisted of polyclonal antibody or OKT3 (n = 62, 33.5%), interleukin-2 receptor antibody (n = 61, 33%), and no induction (n = 62, 33.5%). CMV disease occurred in 13 (7%) patients. Highest incidence was in D + R- group (17.2%), with no cases in D-R- group (P = 0.03). Tissue-invasive CMV occurred in 4 of these 13 patients. In patients developing CMV disease, there was no evidence of ganciclovir resistance and no mortality over a mean follow-up of 42 months. Low-dose ganciclovir was found to be as effective in decreasing the incidence of clinical CMV disease as high-dose ganciclovir (1 gm three times a day for 3-6 months) in previous studies.     

Metabolism of dietary ODAP in humans may be responsible for the low incidence of neurolathyrism

OBJECTIVES: The reasons for the very low incidence of the disease neurolathyrism in humans even after excessive consumption of the pulse, Lathyrus sativus, under severe drought and famine conditions, and its continued consumption by large populations during normal periods without any deleterious effects have been examined in the context of a possible metabolism or detoxification of beta-N-oxalyl-L-alpha, beta-diaminopropionic acid (ODAP), the major neurotoxic amino acid of L. sativus. DESIGN AND METHODS: ODAP in urine samples from 54 subjects habitually consuming the pulse and in three volunteers on an L. sativus diet was determined by the OPT method following clean up of the samples on an alumina column. Urinary oxalate was also determined in these individuals. RESULTS: Twenty-five subjects showed no excretion of ODAP and it was only less than 0.7% of the dietary intake in the remaining 29 subjects. Urinary excretion of ODAP in three volunteers was also less than 1% with a peak excretion in the 4-h sample. The 4-h blood sample from one volunteer had a maximum ODAP concentration of 177 microM. The urinary oxalate content in the volunteers was nearly 3-fold higher compared to controls. CONCLUSIONS: The low excretion of dietary ingested ODAP in humans is in sharp contrast to that seen in animals and indicates a metabolism or detoxification of ODAP which may be unique to humans and may explain the low incidence of neurolathyrism.     

Increased brain lysosomal pepstatin-insensitive proteinase activity in patients with neurodegenerative diseases.

A recent study has shown mutations in CLN2 gene, that encodes a novel lysosomal pepstatin-insensitive proteinase (LPIP), in the pathophysiology of late-infantile neuronal ceroid lipofuscinosis (LINCL). We have measured the LPIP activities in brains from various forms of human neuronal ceroid lipofuscinoses (NCL), canine ceroid lipofuscinosis and other neurodegenerative disorders with a highly sensitive assay using a tetrapeptide Gly-Phe-Phe-Leu-amino-trifluoromethyl coumarin (AFC) as substrate. Brain LPIP has a pH optimum of 3.5 and an apparent km of 100 microM for the crude enzyme. The enzyme activity is totally absent in LINCL patients. Pronounced increase in the LPIP activity was seen in patients suffering from infantile (INCL), juvenile (JNCL) and adult (ANCL) forms of neuronal ceroid lipofuscinoses. LPIP activity was also found to be increased about two-fold in Alzheimer's disease when compared with normal or age-matched controls, while in globoidal-cell leukodystrophy (Krabbe's disease) it was similar to the normal controls. Although mannose-6-phosphorylated LPIP is increased 13-fold in brains of patients with JNCL, this form of LPIP did not have any enzyme activity. The mechanism by which LPIP activities are increased in a wide range of neurodegenerative diseases is unknown, although neuronal loss, followed by gliosis are common characteristics of these diseases.     

The use of RhBMP-2 in single-level transforaminal lumbar interbody fusion: a clinical and radiographic analysis

The “off label” use of rhBMP-2 in the transforaminal lumbar interbody fusion (TLIF) procedure has become increasingly popular. Although several studies have demonstrated the successful use of rhBMP-2 for this indication, uncertainties remain regarding its safety and efficacy. The purpose of this study is to evaluate the clinical and radiographic outcomes of the single-level TLIF procedure using rhBMP-2. Patients who underwent a single-level TLIF between January 2004 and May 2006 with rhBMP-2 were identified. A retrospective evaluation of these patients included operative report(s), pre- and postoperative medical records, and dynamic and static lumbar radiographs. Patient-reported clinical outcome measures were obtained from a telephone questionnaire and included a modification of the Odom’s criteria, a patient satisfaction score, and back and leg pain numeric rating scale scores. Forty-eight patients met the study criteria and were available for follow-up (avg. radiographic and clinical follow-up of 19.4 and 27.4 months, respectively). Radiographic fusion was achieved in 95.8% of patients. Good to excellent results were achieved in 71% of patients. On most recent clinical follow-up, 83% of patients reported improvement in their symptoms and 84% reported satisfaction with their surgery. Twenty-nine patients (60.4%) reported that they still had some back pain, with an average back pain numeric rating score of 2.8. Twenty patients (41.7%) reported that they still had some leg pain, with an average leg pain numeric rating score was 2.4. Thirteen patients (27.1%) had one or more complications, including transient postoperative radiculitis (8/48), vertebral osteolysis (3/48), nonunion (2/48), and symptomatic ectopic bone formation (1/48). The use of rhBMP-2 in the TLIF procedure produces a high rate of fusion, symptomatic improvement and patient satisfaction. Although its use eliminates the risk of harvesting autograft, rhBMP-2 is associated with other complications that raise concern, including a high rate of postoperative radiculitis.     

Non-secretory myeloma: a rare variant of multiple myeloma

The spectrum of plasma cell neoplasm represents indolent conditions like Monoclonal Gammopathy of Undetermined Significance (MGUS) to more aggressive multiple myeloma and plasma cell leukemia. Non-secretory myeloma comprises less than 01% of this spectrum where serum protein electrophoresis and quantitative immunoglobulins remain essentially normal. We are presenting a case report of this rare variant involving the sternum of an adult male.