Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish.

The widespread availability of programmable site-specific nucleases now enables targeted gene disruption in the zebrafish. In this study, we applied site-specific nucleases to generate zebrafish lines bearing individual mutations in more than 20 genes. We found that mutations in only a small proportion of genes caused defects in embryogenesis. Moreover, mutants for ten different genes failed to recapitulate published Morpholino-induced phenotypes (morphants). The absence of phenotypes in mutant embryos was not likely due to maternal effects or failure to eliminate gene function. Consistently, a comparison of published morphant defects with the Sanger Zebrafish Mutation Project revealed that approximately 80% of morphant phenotypes were not observed in mutant embryos, similar to our mutant collection. Based on these results, we suggest that mutant phenotypes become the standard metric to define gene function in zebrafish, after which Morpholinos that recapitulate respective phenotypes could be reliably applied for ancillary analyses.

Killer immunoglobulin-like receptors and HLA act both independently and synergistically to modify HIV disease progression.

Variation in the host response to infection by pathogens including HIV-1 may be conferred by polymorphic genetic factors such as HLA and killer immunoglobulin-like receptors (KIR) genes. Here, we examined KIR and HLA genotype effects on pretreatment viral load, rate of CD4(+) T-cell decline and progression to AIDS among adult HIV-1-infected patients within the Western Australian HIV Study Cohort. In this study, carriage of KIR genes within the 'B' haplotype (eg KIR2DS2) was specifically associated with a more rapid CD4(+) T-cell decline over time and progression to AIDS. In contrast, KIR gene repertoire had no effect on pretreatment viral load while selected HLA alleles (eg HLA-B*5701, HLA-B*2705) demonstrated significant protective effects on viremia. Furthermore, interactions between specific HLA and KIR genes did appear to influence HIV disease progression. The results suggest that host genetic variation within the HLA and KIR gene complexes have clinically relevant effects on the course of HIV-1/AIDS, acting independently as well as synergistically to modify disease progression at multiple levels.

EEG biofeedback treatment of ADD. A viable alternative to traditional medical intervention?

Literature searches dating back to 1968 were conducted through Psychlit and Medline services to review the scientific literature on EEG biofeedback treatment of ADD. While anecdotal and case reports cite promising evidence, methodological problems coupled with a paucity of research precludes any definitive conclusions as to the efficacy of enhanced alpha and hemisphere-specific EEG biofeedback training. One of the more promising EEG biofeedback treatment paradigms involves theta/beta training. Studies have reported that academic, intellectual, and behavioral gains have been attained with this approach. Significant behavioral and cognitive changes have also been reported following SMR training. However, research into these treatment approaches has also been marred by methodological inadequacies and lack of sufficient follow-up studies. A number of recommendations for future research into this treatment approach are made.

An alternative method for the release criteria and calculation of the total dose equivalent to another individual from a patient treated with a therapeutic dose of 131I.

The Nuclear Regulatory Commission's Regulatory Guide 8.39, "Release of Patients Administered Radioactive Materials," permits licensees to authorize the release of patients treated with 131I [(T 1/2)p = 8.04 d] if the total dose equivalent to another individual from the released individual is not likely to exceed 5 millisieverts (0.5 rem). This paper guides the reader through the derivation of an easy-to-use formula that demonstrates how to calculate the total dose equivalent, using patient-specific parameters that an individual may receive from a patient who has been administered a therapeutic dose of 131I, as compared to the NRC's Reg. Guide 8.39 (see Appendix A). Patient-specific parameters include the individual thyroidal uptake, the patient's physical dimensions, attenuation of radiation by body tissues, buildup of secondary photons, whole body and thyroid retention functions as well as the distance and time the patient is around others. This paper also demonstrates how to calculate an inpatient's discharge time, so that the patient will not expose other individuals above the desired total dose equivalent set by the Radiation Safety Officer (RSO).

A flow sheet for follow-up after chemotherapy extravasation.

PURPOSE/OBJECTIVES: To introduce and describe the development and implementation of a flow sheet used to document patient follow-up after chemotherapy extravasation. DATA SOURCES: Published articles, institutional standards of nursing practice, and the Oncology Nursing Society Cancer Chemotherapy Guidelines. DATA SYNTHESIS: Extravasation is a potentially serious and severe complication of vesicant chemotherapy administration. A tool was designed to streamline documentation of patient symptoms, nursing interventions, patient education, and follow-up care after a suspected or actual extravasation. CONCLUSIONS: The flow sheet improves nursing documentation after a suspected or actual vesicant chemotherapy extravasation and provides a consistent, concise method for monitoring extravasations over time. IMPLICATIONS FOR NURSING PRACTICE: The flow sheet standardizes nursing assessment, intervention, patient education, and follow-up care after a suspected or actual chemotherapy extravasation. Use of the flow sheet saves time and improves consistency of nursing documentation.

Clinical and morphometric results of penetrating keratoplasty with one-piece anterior-chamber or suture-fixated posterior-chamber lenses in the absence of lens capsule.

The clinical records and serial corneal endothelial images of 25 acapsular, pseudophakic eyes with Kelman-style, one-piece, anterior-chamber intraocular lenses and 24 acapsular, pseudophakic eyes with suture-fixated, posterior-chamber intraocular lenses following penetrating keratoplasty were reviewed to determine clinical success and endothelial survival after 1 year. Twenty-two (88%) of 25 grafts in the anterior-chamber intraocular lens group and 23 (96%) of 24 grafts in the sutured posterior-chamber intraocular lens group were clear after 1 year; best corrected visual acuity of 20/40 or better was noted in 25% of the eyes in the anterior-chamber intraocular lens group and 29% of the eyes in the sutured posterior-chamber intraocular lens group. The mean intraocular pressure for the anterior-chamber intraocular lens group was significantly lower than for the sutured posterior-chamber intraocular lens group at 3 months (17 +/- 4 vs 21 +/- 7 mm Hg) and at 6 months (17 +/- 3 vs 20 +/- 5 mm Hg); but did not differ at 1 year. The mean percent of endothelial cell loss after 1 year did not differ between the anterior-chamber intraocular lens group (32% +/- 26%) and the sutured posterior-chamber intraocular lens group (27% +/- 26%). No clinical or endothelial morphometric advantages were noted after 1 year for the suture-fixated, posterior-chamber intraocular lens over the Kelman-style, one-piece anterior chamber, intraocular lens following pseudophakic penetrating keratoplasty; however, a long-term, prospective, randomized study of these two intraocular lens types is recommended.

Long-term follow-up of Candida endophthalmitis in the premature infant.

In the March 1981 issue of the Journal of Pediatrics, Baley, Annable and Kleigman discussed the natural course of Candida endophthalmitis in the premature infant. We now have long-term follow-up on the three surviving infants along with follow-up on an additional eight patients. Though vitrectomy is routinely performed in adults, we recommended that it not be performed in premature infants with systemic candidiasis and associated vitreo-retinal pathology. These 11 infants with candidal endophthalmitis secondary to systemic candidiasis demonstrated minimal residual ocular pathology after having been treated with systemic antifungals alone. Neither vitreous taps nor intravitreal injections should be performed in infants with ocular candidiasis.

Enzymic activities of carbohydrate, purine, and pyrimidine metabolism in the Anaeroplasmataceae (class Mollicutes).

Cell-free extracts of two strictly anaerobic mollicutes, Anaeroplasma intermedium 5LA and Asteroleplasma anaerobium 161T, were tested for enzymic activities of intracellular carbohydrate metabolism. Asteroleplasma anaerobium was also tested for enzymes of purine and pyrimidine metabolism. Both organisms had enzymic activities associated with the nonoxidative portion of the pentose phosphate pathway, and with the Embden-Meyerhoff-Parnas pathway. The 6-phosphofructokinase (PFK) of Asteroleplasma anaerobium was ATP-dependent, whereas the PFK of Anaeroplasma intermedium was PPi-dependent. The two anaerobic mollicutes also differed with respect to the enzymes that converted phosphoenolpyruvate (PEP) to pyruvate; Anaeroplasma intermedium had pyruvate kinase activity, but Asteroleplasma anaerobium had pyruvate, orthophosphate dikinase activity (PPi-dependent). Both organisms had lactate dehydrogenase activity which was activated by fructose 1,6-bisphosphate (Fru-1,6-P2). Anaeroplasma intermedium had activity for PEP carboxykinase (activated by Fru-1,6-P2), but Asteroleplasma anaerobium did not. PEP carboxytransphosphorylase activity was not detected in either organism. Anaeroplasma intermedium had malate dehydrogenase and isocitrate dehydrogenase activities, but it had no activities for the three other tricarboxylic acid cycle enzymes examined; Asteroleplasma anaerobium had malate dehydrogenase activity only. Asteroleplasma anaerobium had enzymic activities for the interconversion of purine nucleobases, (deoxy)ribonucleosides, and (deoxy)ribomononucleotides, including PPi-dependent nucleoside kinase, reported heretofore only in some other mollicutes. Asteroleplasma anaerobium could synthesize dTDP by the thymine salvage pathway if deoxyribose 1-phosphate was provided, and it had dUTPase, ATPase, and dCMP kinase activities. It lacked (deoxy)cytidine deaminase, dCMP deaminase, and deoxycytidine kinase activities.

Survey of the professional interrelations between dermatologist and pharmacist.

A national survey of dermatologists and pharmacists was conducted to characterize the involvement of the community pharmacist in the area of skin diseases and to elicit suggestions to improve professional interrelations. The results show the dermatologists' major complaint is pharmacists' inability or unwillingness to compound prescriptions. The study clearly indicates the need for increased communication between the two professions in matters such as inventory control, prescription refill procedures, and substitution guidelines. The pharmacists, in general, admitted a deficiency in their educational preparedness to recognize common skin disorders, thus limiting their ability to assess the severity of patients' complaints.

The mother-litter relationship in developmental rat studies: cannibalism vs caring.

This incidence of cannibalism was studied in a series of developmental studies (on neonatal lesions, prenatal stress, prenatal surgery, unoperated controls) in which rats were manipulated during either the prenatal or early postnatal periods. Cannibalism during the preweaning period occurred in from 0 to 33% of the litters, depending on the treatment group. It was found in most cases, however, that mothers who cannibalized were also good caretakers of their remaining pups. The same litters were also involved in preweaning tests of mother-young interactions to determine if experimental treatments altered the maternal-filial relationship. It was found that as early as postnatal Day 4, nursing episodes were predominantly pup-initiated in the lesioned litters but mother-initiated in control litters.

Multidisciplinary audit of digoxin.

Use review of digoxin as part of a medical care evaluation study in a hospital is described. This drug audit within the hospital's quality assurance program used a multidisciplinary approach. The study was designed to measure the incidence of digoxin toxicity, evaluate monitoring practices for digoxin use and evaluate the adequacy of digoxin dosing patterns. Forty-eight patients were involved. Results indicated that some patients were not adequately assessed in regard to renal function and digoxin serum level. Further, there was a 17% incidence of digoxin toxicity. Studies such as this give pharmacists an opportunity to use their knowledge of proper drug use through a structured hospital program.

Watery diarrhea syndrome. Two unusual cases and further evidence that VIP is a humoral mediator.

Two unusual cases of the watery diarrhea syndrome are presented. In one patient an adrenal medullary tumor, a pheochromocytoma that produced vasoactive intestinal polypeptide (VIP) was excised with total relief of symptoms. The second patient a 65-year-old man with abrupt onset of massive watery diarrhea that led to acidosis and coma was symptomatically controlled for one year on 10 mg/day of prednisone. Elevated levels of VIP returned to normal after prednisone therapy was started. A benign islet cell tumor not localized by angiography was removed by distal pancreatic resection. Tissue levels of VIP were markedly elevated. VIP is a humoral mediator of the water diarrhea syndrome. Both benign and malignant pancreatic and extrapancreatic tumors may cause the watery diarrhea syndrome. Steroids may cause symptomatic relief of the diarrhea by lowering peptide levels to normal. The term watery diarrhea syndrome may be more accurate than the pancreatic cholera syndrome.