Immunological characterization of guanine nucleotide-binding proteins: effects of a monoclonal antibody against the gamma subunit of transducin on guanine nucleotide-binding protein-receptor interactions.

Guanine nucleotide-binding proteins (G proteins) transduce signals from agonist- and light-sensitive receptors. In the visual excitation system, the photon receptor rhodopsin is coupled to the G protein Gt (transducin). Gt is composed of alpha, beta, and gamma subunits; the alpha subunit binds guanine nucleotide, whereas the beta and gamma subunits, which are tightly associated, appear to facilitate interaction of alpha with receptor and pertussis toxin-catalyzed ADP-ribosylation of alpha. To study the function of transducin, monoclonal antibodies were developed against the purified protein. Monoclonal antibody 2H3 reacted with Gt gamma but not G gamma from bovine brain or rabbit liver. In the absence of photolyzed rhodopsin, both intact 2H3 and Fab fragments of 2H3 were able to inhibit completely, in a concentration-dependent manner, ADP-ribosylation of transducin by pertussis toxin 2H3 had no effect on ADP-ribosylation in the presence of photolyzed rhodopsin. The GTPase activity of transducin, which is dependent on rhodopsin, was inhibited only 50% by 2H3. These data are consistent with the hypotheses that an epitope recognized by 2H3 may be important in the formation of the alpha beta gamma complex or that interaction of 2H3 with gamma may alter conformation of the latter and, thereby, inhibit complex formation. Further, reactions of gamma with 2H3 appear to be prevented by interaction with rhodopsin, suggesting that its interaction either shields or alters the epitope recognized by 2H3.     

Antiemetic care for patients with breast cancer: focus on drug interactions and safety concerns.

PURPOSE: The drug interactions and adverse events that should be considered when individualizing antiemetic therapy for patients undergoing treatment for breast cancer are reviewed. SUMMARY: A variety of antiemetic agents are available, including antihistamines, dopamine-receptor antagonists, serotonin-receptor antagonists, and neurokinin-receptor antagonists. To ensure optimal symptom control for each patient without unnecessarily prolonging treatment, patient- and treatment-specific risk factors must be considered. Neurokinin-receptor antagonists, the newest class of antiemetics, are effective in preventing acute and delayed chemotherapy-induced nausea and vomiting but must be used in combination with a serotonin-receptor antagonist and a corticosteroid. The serotonin-receptor antagonists have become the mainstay of antiemetic therapy, but current guidelines do not distinguish among the different agents in this class. However, there are distinct pharmacologic differences that may affect the potential for drug interactions and, ultimately, patient outcomes and the occurrence of adverse events. Therefore, the potential for drug interactions must be considered when selecting an antiemetic, particularly for patients who are taking multiple concomitant medications. Further, because a number of breast cancer therapies and some antiemetic agents carry cardiovascular warnings or precautions and since breast cancer patients may already be suffering from cardiovascular complications, the possible cardiotoxic effects of the antiemetic or chemotherapy agents or the combinations of these agents should be considered. CONCLUSION: Antiemetic treatment is essential for patients with breast cancer who are undergoing moderately to highly emetogenic cytotoxic treatment. When selecting an antiemetic, clinicians must select an agent that provides optimal protection against nausea and vomiting while avoiding drug-drug interactions and additional adverse events.     

Timely initiation of dialysis--single-exchange experience in 39 patients starting peritoneal dialysis.

OBJECTIVE: To establish the effectiveness and patient acceptability of initiating peritoneal dialysis (PD) according to published guidelines. SETTING: A university teaching hospital and a neighboring district general hospital. DESIGN: Nonrandomized prospective pilot study. PATIENTS: 39 patients with a Kt/V > 2.0 attending predialysis clinics at both hospitals agreed to participate in this study. METHODS: Patients were started on a single exchange of dialysate overnight. Dialysis adequacy was monitored at least every 2 months and incremental increases in dialysis were used to maintain combined urinary and dialysis Kt/V above 2.0. Routine laboratory parameters and complications of dialysis were monitored during the follow-up period. RESULTS: The mean weekly Kt/V at initiation of dialysis was 2.09. Median actuarial survival on a single exchange before requiring incremental dialysis was 297 days. At the end of the study period, all patients were still alive: 8 remained on 1 exchange, 18 were on more than 1 exchange, 8 had switched to hemodialysis, and 5 had received renal transplants. During the 12,665 patient-days on single-exchange dialysis, there were 14 hospital admissions of 12 patients. This resulted in a mean of 1.64 hospital days per patient-year for the whole group. During the follow-up period there were 2 episodes of bacterial peritonitis, 3 pleural leaks, 1 patent processus vaginalis, and 1 inguinal hernia that required surgical intervention. The use single daily icodextrin exchanges was associated with a 46% incidence of culture-negative peritonitis. CONCLUSIONS: This pilot study has shown that a timely start of dialysis with a single overnight PD exchange is acceptable to patients. Incremental dialysis as residual renal function falls is easily managed and patients also find this acceptable. Complication and hospitalization rates were low. The presence of residual renal function often allows complications to be managed without the need for hemodialysis. The use of icodextrin as a single-exchange dialysate is associated with sterile peritonitis in a significant proportion of cases.     

Subclinical hepatic encephalopathy: relationship between neuropsychological deficits and standard laboratory tests assessing hepatic status.

A multivariate analysis of the relationship between biochemical measures of hepatic function and neuropsychological assessments of specific cognitive domains was performed on data obtained from 74 patients with chronic liver disease and subclinical hepatic encephalopathy. Biochemical tests of hepatic protein synthesis correlated significantly with measures of impaired language efficiency, perceptual speed, and psychomotor efficiency. Biochemical indices of impaired processing of nitrogenous compounds correlated with visuopractic deficits. Hepatic blood flow indices correlated with language inefficiency. Interestingly, biochemical measures of hepatic injury did not demonstrate a significant association with any neuropsychological parameter assessed. These results suggest that subclinical hepatic encephalopathy is the consequence of a multifactorial hepatic dysfunction, and that acute hepatic injury, as assessed by elevation of aminotransferases, does not appear to be involved in the pathogenesis of subclinical hepatic encephalopathy.     

Change in glycemia in a four-year interval in younger-onset insulin-dependent diabetes.

Hyperglycemia is an important risk factor for the development of retinopathy and nephropathy in people with diabetes mellitus. There are few population-based data on changes in glycemia over time. The purpose of this study was to examine changes in glycemia, as measured by glycosylated hemoglobin in 1980 to 1982 and in 1984 to 1986, in a large population-based study of people who were diagnosed to have diabetes before the age of 30 years and who used insulin (n = 697). Glycosylated hemoglobin was measured by a microcolumn technique at both examinations. There was a significant (P < .001) fall in the mean glycosylated hemoglobin from 10.8 to 10.1% over the 4-year interval of the study. In contrast, there was no change in the glycosylated hemoglobin (6.2%) in a similarly aged nondiabetic comparison group over the same period. The decrease in mean glycosylated hemoglobin over the 4-year period in the diabetic group was associated with several characteristics of diabetes management. These include changes in the insulin regimen (going from intermediate- or long-acting insulin only to combinations with short-acting insulin), an increase in the number of doses of insulin per day, and a higher frequency of self-monitoring of blood glucose level. It was also associated with an increased number of reported insulin reactions. These data suggest that recent changes in treatment and management of diabetes may be related to a significant decrease in glycemia.     

Artifacts due to stimulus correlated motion in functional imaging of the brain

To assess the effect of stimulus correlated motion on the appearance of functional magnetic resonance images, conventional visual and motor protocols were each performed by four normal volunteers and an image co-registration technique was used to retrospectively monitor subject motion. In three studies synthetic data sets were constructed from single baseline images using the positional information obtained from the co-registration procedure. Cumulative difference images were then created from both the synthetic and functional image sets. Stimulus correlated motion was detected in all eight studies and the synthetic cumulative difference images showed striking similarities to the equivalent functional images in each case.     

Aspergillus osteomyelitis of the thumb in a 5-year-old child

Aspergillus osteomyelitis is a rare condition and is a recognized infection of the immunosuppressed. The pediatric cases that were documented suggest that in children, chronic granulomatous disease is the major underlying disease [Tack et al.1982 73(2):295–300, Baez-Escudero et al. 2000 Case report—primary sternal Aspergillus osteomyelitis. Infect Med 17(7):505–516]. We report an interesting case of Aspergillus osteomyelitis of the thumb in a 5-year-old boy with aplastic anemia. The infection progressed despite a combination of antifungal therapy with Voriconazole and surgical debridement. The thumb was amputated and the child recovered. This case highlights the difficulty in diagnosing Aspergillus osteomyelitis and also the failure of conventional management in this child, which resulted in the amputation of the thumb as a life-saving measure. We believe this to be the first case report of Aspergillus osteomyelitis in the thumb.     

Relationship between Mandarin speech reception thresholds and pure-tone thresholds in the geriatric population.

BACKGROUND/PURPOSE: In the geriatric population, the reliability of pure-tone threshold (PTT) is sometimes poorer than that in young adults because of various reasons. This study assessed the relationship between Mandarin speech reception thresholds (SRTs) and PTTs in the aged and developed SRT as a measure for corroborating PTT. METHODS: This prospective study enrolled 46 consecutive subjects over 60 years of age. The results of SRT and PTT were collected from one ear randomly selected from each subject. Simple linear and multiple regressions were used to determine the correlation and linear regression coefficients between SRTs and PTTs at various frequencies. RESULTS: In the simple regression analysis, the correlation coefficient was highest at 1000 Hz (r = 0.949) and 500 Hz (r = 0.922), followed by 250 Hz (r = 0.850) and 2000 Hz (r = 0.792). In the multiple regression model with SRT as the dependent variable and PTTs as predictor variables, the resultant multiple correlation coefficient R was 0.967, while R2 was 0.936. In this model, PTTs at the frequencies of 500 Hz and 1000 Hz contributed significantly to the variance in SRTs with p values of 0.029 and < 0.001, respectively. These results demonstrated that the Mandarin SRT is strongly associated with PTTs at the frequencies of 500 Hz and 1000 Hz. CONCLUSION: This study established the agreement between Mandarin SRTs and PTTs in the low tone area of speech frequencies in the geriatric population. In clinical settings, SRT test can be rapidly and easily performed and is relatively inexpensive. It is a vital indicator of the accuracy of PTT measurement.