Imported measles. A potential control problem

From Dec 23, 1978, through Jan 31, 1979, an outbreak of five laboratory-confirmed cases and four clinical cases of measles occurred in a Vietnamese refugee population living in a single housing complex in Albuquerque, NM. The index cases were in two refugee siblings in whom measles was incubating on arrival in the United States. Despite spread through three subsequent generations of disease transmission within the Vietnamese population, there was no additional spread into the general Albuquerque population. Responsible factors included the age distribution of susceptible persons, the social isolation of the refugee population, and the physical structure of the housing complex. There is a need to identify the problem of imported measles in "ethnic islands" in need of vaccination.     

Office otology follow-up

The validation of otological care in the previous quarter century has been based, by and large, on short-term follow-up information. The rapid variation in procedures introduced during this period indicates that there may be need for further consideration. Analyses based on relatively short duration have led the "acceptance" of a variety of diagnostic and treatment methods which have proven disappointing in some cases. To help avoid this invalid "acceptance," a review of patients with significant follow-up may result in a more critical evaluation of future procedural changes. This presentation will be in four parts: 1. History of the office structure. 2. Discussion of five long-term patients that illustrates and supports certain otological concepts. 3. A review of surgical care for chronic suppurative otitis media in 1968. 4. A review of patients treated for serous otitis media with myringotomy and tubal insertion in 1968.     

Sodium nitroprusside: pharmacology, toxicology and therapeutics

Sodium nitroprusside is a potent, effective, and readily reversible direct vasodilating agent. It is broken down by hemoglobin into cyanide, which is in part detoxified by liver and kidney to thiocyanate. Some cyanide, especially in nitroprusside- "resistant" individuals who need large amounts of the drug, appears to remain free to cause cyanide poisoning. Patients requiring inordinate amounts probably should not continue to receive the drug, although maximum dosage limits for long-term therapy are not established. Blood thiocyanate levels do not indicate the extent to which free cyanide is limiting oxygen utilization in essential tissue, nor do blood cyanide levels. Metabolic acidosis, elevated lactate levels, elevated lactate/pyruvate ratios, and elevated mixed venous blood oxygen content are at present the best indications of the presence of cyanide poisoning during nitroprusside administration. Nitroprusside appears useful for induction of hypotension during surgery, and for treatment of hypertensive emergencies from all causes, although continuance for more than a few days is probably unwise. The reductions of cardiac afterload and ventricular filling pressure by nitroprusside appear useful in treatment of severe myocardial failure or infarction, but studies of myocardial cyanide toxicity are needed before complete acceptance of this therapy is warranted. Initial dose rates between 0.5 and 1.5 mug/kg/min are recommended only as starting points for very careful titration. Total projected intra-operative dosage should be calculated as quickly as possible and should not exceed 3-3.5 mg/kg. It is hoped that future studies will reveal the maximum dose of nitroprusside that can safely be metabolized in a 24-hour period, and may indicate that cofactors of rhodanase such as thiosulfate, or cobalamins such as hydroxocobalamin, can be administered with nitroprusside to prevent cyanide poisoning.     

Gastric pacing improves emptying and symptoms in patients with gastroparesis

BACKGROUND & AIMS: No effective treatment is available for patients with gastroparesis refractory to standard medical therapy. The aim of this study was to investigate the effects of gastric pacing on gastric electrical activity, gastric emptying, and symptoms in patients with gastroparesis. METHODS: Nine patients with gastroparesis participated in this study. Four pairs of cardiac pacing wires were implanted on the serosa of the stomach. The protocol consisted of two portions: a temporary inpatient study period and an outpatient study for a period of 1 month or more. RESULTS: Gastric pacing entrained the gastric slow wave in all subjects and converted tachygastria in 2 patients into regular 3-cpm slow waves. Gastric emptying was significantly improved after the outpatient treatment with gastric pacing. The gastric retention at 2 hours was reduced from 77.0% +/- 3.3% to 56.6% +/- 8.6% (P < 0.05). Symptoms of gastroparesis were substantially reduced at the end of the outpatient treatment (1.51 +/- 0.46 vs. 2.84 +/- 0.61; P < 0.04). Eight of 9 patients no longer relied on jejunostomy tube feeding, and no adverse events were noted related to the pacing unit. CONCLUSIONS: Gastric pacing seems to be able to improve symptoms of gastroparesis and to accelerate gastric emptying in patients with gastroparesis. More controlled studies are necessary to further investigate the role of gastric pacing in clinical practice.     

Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies

The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (> 10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to > 1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk about 1.10 Gy.     

Fusion-competent vaccines: broad neutralization of primary isolates of HIV

Current recombinant human immunodeficiency virus (HIV) gp120 protein vaccine candidates are unable to elicit antibodies capable of neutralizing infectivity of primary isolates from patients. Here, "fusion-competent" HIV vaccine immunogens were generated that capture the transient envelope-CD4-coreceptor structures that arise during HIV binding and fusion. In a transgenic mouse immunization model, these formaldehyde-fixed whole-cell vaccines elicited antibodies capable of neutralizing infectivity of 23 of 24 primary HIV isolates from diverse geographic locations and genetic clades A to E. Development of these fusion-dependent immunogens may lead to a broadly effective HIV vaccine.     

Cloning, expression, and characterization of a DNA binding domain of gpNu1, a phage lambda DNA packaging protein

Terminase is an enzyme from bacteriophage lambda that is required for insertion of the viral genome into an empty pro-capsid. This enzyme is composed of the viral proteins gpNu1 (20.4 kDa) and gpA (73.3 kDa) in a holoenzyme complex. Current models for terminase assembly onto DNA suggest that gpNu1 binds to three repeating elements within a region of the lambda genome known as cosB which, in turn, stimulates the assembly of a gpA dimer at the cosN subsite. This prenicking complex is the first of several stable nucleoprotein intermediates required for DNA packaging. We have noted a hydrophobic region within the primary amino acid sequence of the terminase gpNu1 subunit and hypothesized that this region constitutes a protein-protein interaction domain required for cooperative assembly at cosB and that is also responsible for the observed aggregation behavior of the isolated protein. We therefore constructed a mutant of gpNu1 in which this hydrophobic "domain" has been deleted in order to test these hypotheses. The deletion mutant protein, gpNu1DeltaK, is fully soluble and, unlike full-length protein, shows no tendency toward aggregation; However, the protein is a dimer under all experimental conditions examined as determined by gel permeation and sedimentation equilibrium analysis. The truncated protein is folded with evidence of secondary and tertiary structural elements by circular dichroism and NMR spectroscopy. While physical and biological assays demonstrate that gpNu1DeltaK does not interact with the terminase gpA subunit, the deletion mutant binds with specificity to cos-containing DNA. We have thus constructed a deletion mutant of the phage lambda terminase gpNu1 subunit which constitutes a highly soluble DNA binding domain of the protein. We further propose that the hydrophobic amino acids found between Lys100 and Pro141 define a self-association domain that is required for the assembly of stable nucleoprotein packaging complexes and that the C-terminal tail of the protein defines a distinct gpA-binding site that is responsible for terminase holoenzyme formation.     

Comment on the letter ''imaging in transient regional osteoporosis''

Canada's hospitals are slowly coming to grips with the millennium bug, but Anita Elash reports that no one really knows what impact the move into the year 2000 will have on computers and medical devices, either in the hospital or doctor's office.     

Silicon and aluminium interactions in haemodialysis patients

BACKGROUND: Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity. METHODS: We measured serum aluminium and silicon levels from haemodialysis patients from four different centres. RESULTS: Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) micromol/l when serum silicon was less than 150 micromol/l, and lower, 1.1 (0.2-2.8) micromol/l when serum silicon levels were greater than 150 micromol/l (P = 0.03). CONCLUSIONS: In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.