Interfering vaccine (defective interfering influenza A virus) protects ferrets from influenza, and allows them to develop solid immunity to reinfection.

Defective interfering (DI) virus RNAs result from major deletions in full-length viral RNAs that occur spontaneously during de novo RNA synthesis. These RNAs are packaged into virions that are by definition non-infectious, and are delivered to cells normally targeted by the virion. DI RNAs can only replicate with the aid of a coinfecting infectious helper virus, but the small size of DI RNA allows more copies of it to be made than of its full-length counterpart, so the cell produces defective virions in place of infectious progeny. In line with this scenario, the expected lethal disease in an influenza A virus-mouse model is made subclinical by administration of DI virus, but animals develop solid immunity to the infecting virus. Hence DI virus has been called an 'interfering vaccine'. Because interfering vaccine acts intracellularly and at a molecular level, it should be effective against all influenza A viruses regardless of subtype. Here we have used the ferret, widely acknowledged as the best model for human influenza. We show that an interfering vaccine with defective RNAs from an H3N8 virus almost completely abolished clinical disease caused by A/Sydney/5/97 (H3N2), with abrogation of fever and significant reductions in clinical signs of illness. Animals recovered fully and were solidly immune to reinfection, in line with the view that treatment converts the otherwise virulent disease into a subclinical and immunizing infection.

Treatment of epidemic and pandemic influenza with neuraminidase and M2 proton channel inhibitors.

A small armentarium of anti-influenza drugs now exists, and includes the M2 blockers (amantadine and rimantadine) and the neuraminidase inhibitors (Relenza and Tamiflu). The neuraminidase inhibitors have certain advantages, including a broader spectrum of antiviral activity, including influenza A and B viruses. On the other hand, there is now much clinical experience with the M2 blockers, and these drugs are inexpensive. It is clear that influenza in different community groups needs to be managed in specific and targeted ways. For example, in the over-65-years and at-risk groups, vaccination will remain a mainstay of disease prevention. However, up to 40% of those in these groups may fail to receive vaccine, and therefore the antivirals can be used therapeutically, or, in defined circumstances, as prophylactics. At present, influenza is hardly managed in the community. The infrequent global outbreaks, pandemics, present further problems. The more extensive use of the two classes of antivirals, and also vaccines, in the important interpandemic years will provide a very significant investment in health benefits in the face of a new pandemic virus in an otherwise completely vulnerable population.

Advance directives: barriers to completion.

The concept of advance directives, although sound in theory, appears to be failing to meet the needs of many patients. Advance directives have been endorsed by both the healthcare profession and the general public, yet few individuals have documented their wishes for treatment preferences in end-of-life decisions. A review of 15 research articles revealed three main barriers to the completion and effective use of advance directives. These barriers are: (a) lack of education or knowledge regarding advance directives, (b) difficulties with paperwork completion, and (c) discordance between patient, family members or proxy, and provider. Future research is suggested to generate information that will facilitate meeting the needs of patients and their families in this most difficult aspect of healthcare delivery.

Accuracy and usefulness of atrial pacing in conjunction with transthoracic echocardiography in the detection of cardiac ischemia.

Transthoracic echocardiography combined with transesophageal atrial pacing was performed in a community outpatient setting and compared with single-photon emission computed tomography (SPECT) and with coronary arteriography to determine the accuracy and usefulness of the technique. Two groups were defined: group A consisted of 65 of 189 patients who underwent all 3 procedures within a 90-day period; group B consisted of 53 patients who had atrial pacing with transthoracic echocardiography. Seventy-one patients had previously undergone atrial pacing with simultaneous transesophageal echocardiography. Atrial pacing to induce abnormal wall motion as an indicator of ischemia was performed by increasing the double product to > 20,000. We obtained a sensitivity and specificity of 87% and 88% for group A and 72% and 80% for group B, respectively. We believe that transthoracic echocardiography with atrial pacing is indicated as a means of stress echocardiography in its own right, especially in nonambulatory and chronotropically incompetent patients, as well as in the presence of an ambiguous result on SPECT testing. It is highly accurate compared with our previous study with atrial pacing and simultaneous transesophageal echocardiography, better tolerated, more easily accepted, less invasive, and less costly. Thus, it is a useful stress modality in the detection of myocardial ischemia.

Accuracy and usefulness of atrial pacing in conjunction with transesophageal echocardiography in the detection of cardiac ischemia (a comparative study with scintigraphic tomography and coronary arteriography).

A comparative study of transesophageal echocardiography with single-photon emission computed tomography (SPECT) and coronary arteriography was performed in a community outpatient setting to determine accuracy and feasibility of the technique. Forty-one of 55 patients underwent all 3 procedures within a 90-day period. Fourteen patients underwent only SPECT and were compared with transesophageal echocardiography with pacing (TEEP). Atrial esophageal pacing was performed with transesophageal echocardiography to increase double product and induce ischemia, which would manifest as abnormal wall motion. The results in these patients indicated a sensitivity and specificity of 92% and 87% for TEEP and 96% and 82% for SPECT, respectively, using angiography as the gold standard. In 14 patients, the sensitivity of TEEP using SPECT as standard was 80% and the specificity was 87%. The 1 view that appeared to pick up the highest yield of abnormalities was the transgastric short-axis view. Thus, TEEP is indicated in the detection of chronotropically incompetent patients and those unable to exercise whose transthoracic images are not optimal. It is highly accurate compared with angiography or SPECT.

Cardiac beri beri--an old disease in modern Singapore--2 case reports.

This case report presents two Malay brothers who developed acute high output congestive cardiac failure within two weeks of each other. They gave a history of excessive alcohol consumption for six months, and glue sniffing for one year. The serum pyruvate levels were elevated in both prior to treatment. Haemodynamic studies were done in the second brother, and measurements obtained before, during and after treatment. A dramatic clinical response to parenteral thiamine was observed in both patients in the acute stage. The haemodynamic study was repeated after three months and showed a normal pattern.