Nonsteroidal anti-inflammatory drugs (NSAIDs) and the kidney

In patients with PG-dependent renal function, NSAID administration constantly reduces GFR and RBF in a dose-dependent fashion. In this situation, the risk of overt acute renal failure is high and should be taken into proper account. In contrast, the incidence of NSAID-related renal structural alterations appears to be very low, yet the absolute number of patients may be significant considering the wide use of such drugs. Concerning the antiproteinuric effect of NSAIDs, the unfavourable ratio risk/benefit does not seem to support their indication in proteinuric nephropathies. The development of PGHS-2 selective inhibitors is promising, and may open new therapeutical strategies in the treatment of the progression of renal disease.      

Outcome of gestational diabetes in Bengali Asians living in an east London health district.

The characteristics and outcome of pregnancy complicated by gestational glucose intolerance are described in a consecutive series of 69 Bengali Asian patients and a parallel group of 22 Caucasian patients. The Bengali patients were older and of higher parity than the Caucasians and more frequently required insulin therapy. However, the outcome of pregnancy was similar in terms of antenatal clinic attendance, the number of antenatal hospital admissions, glycaemic control, birthweight and mode of delivery. Of those patients who attended for postnatal glucose tolerance test, 20% of the Bengali population demonstrated persisting abnormality of glucose tolerance, whereas no abnormalities were evident in the Caucasian group. These findings are consistent with the high prevalence and early age of onset of non-insulin-dependent diabetes in Asian populations. The World Health Organisation (WHO) criteria for the diagnosis of impaired glucose tolerance proved insufficiently sensitive for the diagnosis of gestational diabetes. This was particularly demonstrated by four patients with apparently normal glucose tolerance by WHO criteria who subsequently required insulin therapy.     

Aminophylline in the emergency department. Maximizing safety and efficacy

An experimental technique designed to predict theophylline doses needed to attain therapeutic theophylline concentrations in 43 emergency department (ED) patients was compared with a standard conventional regimen in 46 ED patients. The experimental protocol utilized a computer-assisted dosage prediction program that incorporated baseline theophylline concentration rapidly obtained using a bedside assay. The standard protocol used conventional loading and infusion rates, as well as an estimate of time of last theophylline dose based on patient history. Plasma theophylline concentrations, estimated 1 and 6 hours after commencement of aminophylline therapy in each regimen, were compared. The experimental protocol was equally rapid but much more accurate in achieving targeted theophylline concentrations. Experimental dosage prediction was associated with a higher proportion of theophylline concentrations in the therapeutic range at 1 (81 percent vs 26 percent; p less than 0.001) and 6 hours (91 percent vs 37 percent; p less than 0.001). There was a trend toward fewer toxic concentrations recorded at 1 (0 percent vs 7 percent; p = 0.27) and 6 hours (0 percent vs 10 percent; p = 0.08). This protocol, which was performed quickly and without difficulty by residents in a busy hospital ED, offers an opportunity to improve the efficacy and decrease the toxicity of theophylline use in asthma emergencies.     

Second primary tumors in patients with oral cancer.

BACKGROUND. Patients with cancer of the oral cavity and pharynx have been described to be particularly susceptible to the development of new cancers. METHODS. Using data collected during 1973-1987 by nine population-based cancer registries in the United States, the authors evaluated risks of second primary cancers among 21,371 patients in whom oral and pharyngeal cancers were diagnosed. RESULTS. The rate of development of second tumors was 3.7% per year. The risk of a second primary cancer was 2.8 times greater than expected, with 20-fold excesses of second oral or esophageal cancers and 4-fold to 7-fold increases of respiratory cancers. Increased risks persisted unabated for cancers diagnosed 5 or more years after oral cancer, suggesting that the second cancers were new primary tumors and not misdiagnosed metastases. The increased risks of second primary tumors were found among both men and women and black and white patients; they were most prominent among patients who were 60 years or younger. CONCLUSIONS. The exceptionally high rate of cancer recurrence among patients with oral cancer (exceeding that for all other cancers) points to the need for close medical surveillance. Special emphasis should be placed on advising patients to avoid or limit consumption of tobacco and alcohol, the main risk factors for oral and most second cancers.     

Incidence of AIDS dementia in a two-year follow-up of AIDS and ARC patients on an initial phase II AZT placebo-controlled study: San Diego cohort.

In a prospective study to determine the incidence of clinical dementia in patients with AIDS and ARC, 29 men and 3 women, 19 with ARC and 13 with AIDS, were examined neurologically and neuropsychologically every 6 months for 2 years during a placebo-controlled zidovudine (AZT) licensing trial. Most received two MRI brain scans. Although no patient was clinically demented at baseline, 9 (28%) developed dementia during the 2 years. Progression to dementia was associated with neuropsychological deterioration and with worsening on MRI during a preceding 6-month period, but not with baseline treatment group assignment. The results suggest that patients at CDC Stage IV who do not receive antiretroviral treatment earlier in their illness may develop clinical dementia at an annual rate of about 14%.     

ADAMTS-4 activity on a proteoglycan vs. a polypeptide is controlled by the ancillary domains

Introduction In combination with the catalytic domain, the ancillary domains of the ADAMTS' are proposed to regulate activity via interactions with sulfated GAGs, the extracellular matrix (ECM) and cell surface. Interactions with both GAGs and the ECM have been attributed to the thrombospondin (TSP) type 1 motifs and spacer region ( Kuno and Matsushima 1998 ; Flannery et al. 2002 ). ADAMTS‐1, ‐4 and ‐5, all undergo cleavage within their respective spacer regions ( Flannery et al. 2002 ; Rodriguez‐Manzaneque et al. 2000 ; Georgiadis et al. 2002 ), an event which has been reported to increase activity towards the interglobular domain of aggrecan and decrease the heparin affinity of ADAMTS‐4 ( Flannery et al. 2002 ; Gao et al. 2002 ). Materials and methods V5‐ and His‐tagged recombinant human ADAMTS‐4 constructs terminating after the catalytic (?DTS), disintegrin‐like (?TS), TSP (?S) or spacer region (Full) were expressed in High‐Five cells. Proteoglycanase activities of the resultant proteins were assayed with solution digests of aggrecan and a polyacrylamide‐entrapped aggrecan particle assay. Proteolytic activity was measured using a novel, nonglycosylated, reporter substrate assay. Results All forms of ADAMTS‐4 were active to varying degrees in the reporter substrate assay. Digestion of aggrecan in solution digests was apparent in all proteins with the exception of the catalytic domain in isolation (?DTS). Activity towards aggrecan decreased with increasing truncation of the protein. Discussion Removal of the cysteine‐rich‐spacer domain and further C‐terminal truncations decrease the activity of ADAMTS‐4 towards aggrecan, whilst the proteolytic activity remains intact. Cleavages releasing the ancillary domains of ADAMTS' may therefore alter the catalytic activity of these enzymes against proteoglycans and also nonglycosylated polypeptides. More information is required about potential substrates for the processed forms of ADAMTS‐4.