TcRho1, a farnesylated Rho family homologue from Trypanosoma cruzi: cloning, trans-splicing, and prenylation studies.

Rho GTPases are members of the Ras superfamily and are involved in signal transduction pathways, including maintenance of cell morphology and motility, cell cycle progression, and transcription activation. We report the molecular identification in trypanosomatids (Trypanosoma cruzi) of the first member of the Rho family. The cloned Rho protein, TcRho1, shares approximately 40% homology with other members of the Rho family. Southern blot analysis revealed that TcRHO1 is a single copy gene per haploid genome, and Northern blot assays showed a transcript of 1200 nucleotides in length. Mapping the 5'-untranslated region of TcRHO1 transcripts revealed at least five different transcripts derived from differential trans-splicing. Three of the five transcripts contain the trans-splicing site within the coding region of the TcRHO1 gene. TcRho1 also contains the C-terminal sequence CQLF (CAAX motif), which is predicted to direct post-translation prenylation of the cysteine residue. A synthetic peptide containing this C-terminal motif, when tested against Q-Sepharose chromatography fractions from T. cruzi cytosol, was shown to be efficiently farnesylated, but not geranylgeranylated, despite the fact that the CAAX motif with X = Phe specifies geranylgeranylation by mammalian protein geranylgeranyltransferase I. Furthermore, immunoblot analyses of epimastigote protein with anti-S-farnesylcysteine methyl ester and anti-TcRho1 antisera strongly suggested that TcRho1 is farnesylated in vivo. The farnesylation of proteins such as Rho GTPases could be the basis for the selective cytotoxic action of protein farnesyltransferase inhibitors on trypanosomatids versus mammalian cells.

Eficacia terapéutica del Nimesulide en el tratamiento de la dorso lumbalgia de origen traumático / Therapeutic effectiveness of the nimesulide in the treatment of the low back pain of traumatic origin

Se realizó un estudio abierto, no controlado, multicéntrico, realizado con intención de tratar, en 60 pacientes con dorsolumbalgia mecánica, en el cual evaluó la efectividad y seguridad de nimesulide 100 mg dos veces al día, administrado durante 15 días. El tratamiento produjo un alivio significativo en los escores de dolor entre el día de inicio del tratamiento y los 5 días, con un alivio adicional importante entre los días 5 y 10, sin alivios adicionales para el día 15. El tiempo medio para la desaparición total del dolor fue de 8,5 días. La limitación funcional fue evaluada el día 0 y el día 15, obteniéndose una mejoría significativa desde el punto de vista estadístico. Se reportaron efectos adversos en 4 de los pacientes, de los cuales sólo uno ameritó la suspensión del tratamiento

Antibody immunoglobulin G (IgG) response to Alouattamyia baeri (Diptera:Cuterebridae) parasitism of howler monkeys, Alouatta palliata, in Panama.

Larval bot fly burdens and the presence of immunoglobulin G (IgG) antibodies to larval antigens of Alouattamyia baeri (Shannon & Greene) were determined in howler monkeys, Alouatta palliata authority, from Barro Colorado Island, Panama, during July and August of 1991 and 1992. Monkeys produced antibodies (IgG) to both 1st- and 3rd-instar proteins of the monkey bot as measured by an enzyme immunoassay. The response to 1st-instar antigen was correlated with number of bots for the 1991 data and for pooled data from 1991 and 1992. No correlation was observed for the response to 3rd instar antigen. First-instar extracts were composed of 9 major proteins as visualized by SDS-PAGE. Bands at 17, 25, and 32 kDa were positive in Western blots. Third-instar extracts contained at least 13 major bands, with those at 120 and 130 kDa reactive in immunoblots. The immune response to A. baeri may be involved in limiting larval bot numbers.

An outbreak of cholera from food served on an international aircraft.

In February 1992, an outbreak of cholera occurred among persons who had flown on a commercial airline flight from South America to Los Angeles. This study was conducted to determine the magnitude and the cause of the outbreak. Passengers were interviewed and laboratory specimens were collected to determine the magnitude of the outbreak. A case-control study was performed to determine the vehicle of infection. Seventy-five of the 336 passengers in the United States had cholera; 10 were hospitalized and one died. Cold seafood salad, served between Lima, Peru and Los Angeles, California was the vehicle of infection (odds ratio, 11.6; 95% confidence interval, 3.3-44.5). This was the largest airline-associated outbreak of cholera ever reported and demonstrates the potential for airline-associated spread of cholera from epidemic areas to other parts of the world. Physicians should obtain a travel history and consider cholera in patients with diarrhoea who have travelled from cholera-affected countries. This outbreak also highlights the risks associated with eating cold foods prepared in cholera-affected countries.

Firearms in New Mexico.

To determine the prevalence of firearm ownership and storage practices in New Mexico, we did a random-digit-dialing survey of New Mexico residents in October 1991. Of 200 households surveyed, 79 (40%) had 1 or more firearms in the home. Rural households were more likely than urban households to have firearms (44% versus 30%), and households with annual incomes of greater than $25,000 were more likely to have a firearm than households with incomes of $25,000 or less (41% versus 33%). Household firearm ownership did not vary with the presence of young (< 15 years old) children (38% with children versus 41% without). Handguns were generally owned for self-protection, and rifles were owned for hunting. Of households with firearms, 24% stored them unsafely (unlocked and loaded or unloaded but with ammunition nearby), including 21% of households with young children. Of the households with handguns only, 40% stored these firearms unsafely compared with 13% of those with rifles only. The prevalence of gun ownership in New Mexico is similar to that reported in national surveys; handguns are stored less safely than rifles; and the presence of young children in the home does not appear to improve firearm storage safety.

Hepatic CT enhancement: a method to demonstrate reproducibility.

Optimal techniques for intravenous administration of contrast material in computed tomographic (CT) examination of the liver remain controversial mainly because of inaccurate methods of data evaluation. This study tested the reproducibility of hepatic contrast material enhancement within the same patient and the accuracy of two methods of data analysis. Fourteen patients received identical CT examinations. Attenuation of liver and vessels was measured before and after administration of contrast material, and enhancement was calculated for each image. Data were analyzed by averaging enhancement values obtained over 5- and 10-second intervals and by using a new computer program that creates an enhancement-time curve and measures area under the curve (AUC) for any specific time interval. Data were compared between patients' first and second examinations. Mean liver enhancement was nearly identical at all time intervals with the AUC technique. Analysis of interpatient data showed marked variability of all parameters at all measured time intervals, suggesting that results from comparative studies within the same patient may be more accurate than those for studies of two different treatment groups. The AUC technique is preferable to other methods of data analysis for contrast enhancement evaluation.

Operational evaluation of treatment for tuberculosis. Results of 8- and 12-month regimens in Peru.

To measure the effectiveness of treatment for pulmonary tuberculosis in Peru we evaluated the fate of 2,669 patients who had tuberculosis diagnosed in 1981. Two regimens were used: (1) isoniazid, rifampin, pyrazinamide, and streptomycin daily for 2 months, then either isoniazid and streptomycin twice a week or isoniazid and thiacetazone daily for 6 months; and (2) isoniazid, streptomycin, and thiacetazone daily for 2 months, then either isoniazid and streptomycin twice weekly or isoniazid and thiacetazone daily for 10 months. Patients were not assigned at random to the 2 treatment regimens; thus, the results cannot be directly compared. In the 8-month group, 70% had a favorable outcome, 14% abandoned, 9% failed, 3% died, and 3% relapsed. In the 12-month group, 53% had a favorable outcome, 34% abandoned, 6% failed, 4% died, and 2% relapsed. In patients who did not abandon treatment, the results of both regimens were nearly identical. Patients in both groups who had been treated previously had significantly lower rates of cure than those not treated previously.

The epidemiology of aggression. Health consequences of war in Nicaragua.

KIE: The authors were among a group of 200 health workers from the United States and Canada who visited Nicaragua in October 1984 to observe the health consequences of the "limited covert war" there. The task force reported that biological effects of the war include the killing of 7,000 persons, an increased prevalence of infectious diseases, and a severe disruption of the improvement in health services achieved by the Nicaraguan government since 1979. Because of the diversion of resources to military purposes, the building of new health service posts, development of teaching programs, and upkeep of equipment have been severely curtailed. Depression and other psychological problems have increased. Maintaining that sufficient information has been obtained to document a pattern of activity by the contras that violates principles of medical neutrality under the Geneva Convention, the authors urge physicians and other health workers to speak out against the war.^ieng

Operational evaluation of treatment for tuberculosis. Results of a "standard" 12-month regimen in Peru.

To measure the operational effectiveness of treatment for tuberculosis in Peru was evaluated the outcome of a 12-month treatment regimen in 2,510 patients who had tuberculosis diagnosed in 1980. All patients had acid-fast bacilli detected by sputum microscopy and were to be treated with isoniazid, streptomycin, and thiacetazone daily for 2 months followed by either isoniazid and streptomycin twice a week or isoniazid and thiacetazone daily. Only 47% had a favorable outcome, 41% abandoned treatment, 6% failed treatment, 4% died, and 2% relapsed. Of 1,483 patients who completed treatment, 79% had a favorable outcome, whereas 21% had an unfavorable result (treatment failure, relapse, or death). These data indicate that failure to complete treatment is the major reason for the low rate of success but that, in addition, the effectiveness of the regimen in patients who complete treatment is not optimal.

25-hydroxyvitamin D3 (calcifediol) therapy of juvenile renal osteodystrophy: beneficial effect on linear growth velocity.

A prospective study of renal osteodystrophy in moderate renal insufficiency was undertaken to assess the effects of 25(OH)D3 (Calcifediol) on healing of bone lesions and improvement of linear growth. One year after entering the study, the mean group growth velocity increased into the normal range and remained there in the next two therapy years. A significant correlation existed between pretherapy and one-year therapy values of growth velocity and serum 25(OH)D3 concentration. Qualitative bone histology obtained by transilial bone biopsy was also evaluated during the course of study. Catch-up growth was not seen, but potential for such growth may exist in later years in our patients.

Early diagnosis of juvenile renal osteodystrophy.

Renal osteodystrophy has assumed growing importance as a major and frequently disabling complication of chronic renal failure in children since the advent of successful hemodialysis and renal transplantation programs. The frequency and severity of renal osteodystrophy appears greatest in younger children with congenital diseases of the kidney and urinary tract, who experience long intervals of chronic renal failure prior to reaching end-stage. Twenty-nine children with varying degrees of chronic renal failure were studied to learn: (1) how early renal osteodystrophy can be diagnosed; and (2) how the various clinical, biochemical, and hormonal abnormalities correlate with abnormal bone histomorphometry as determined from percutaneous transilial bone biopsies. Results showed: (1) marked-to-moderate reductions in GFR (mean = 35 ml/minute/1.73 m2; range 11 to 65 ml/minute/1.73 m2); (2) elevations of serum PTH concentrations in all patients with a GFR < 45 ml/minute/1.73 m2; (3) abnormal bone histomorphometry in all patients with elevated PTH concentrations; (4) "early" renal osteodystrophy (elevated PTH concentrations and abnormal bone histomorphometry but normal serum chemistry values and radiographs) in one quarter of the patients; (5) poor correlations of serum chemistry values and radiographs with bone histomorphometry; and (6) a wide range of histologic abnormalities including predominant osteomalacia (n = 7), predominant hyperparathyroidism (n = 6), or a mixed picture (n = 11).