Consent for regional anaesthesia in the United Kingdom: what is material risk?

Legal principles that apply to the process of informed consent have changed in recent years. Patients should now be given the information that they wish to receive, not the information that health professionals may consider reasonable for them. In obstetric practice informed consent is especially important as young, fit patients may request and receive non-essential but potentially life-threatening interventions. The quantity and detail of information parturients desire do not remain static. They vary over time and from country to country. Our paper examines current opinion amongst parturients in the United Kingdom. We asked 100 obstetric patients to choose the complications of regional anaesthesia that they would like to learn about during informed consent. Nearly all women (82-94%) wished to know about common, less severe side effects. A substantial majority (70-77%) also wished to know about rarer but more severe complications, such as permanent neurological deficit, meningitis and high spinal block. Despite the availability of information for patients from sources such as the Obstetric Anaesthetists' Association and the National Electronic Library for Health, there remains little consensus amongst anaesthetists about what information to provide. Frequently some complications that patients would consider important are not discussed. Changing legal and public expectations demand that we adapt our current practice and improve the accuracy and timing of information provided.

Immunity to influenza A H9N2 viruses induced by infection and vaccination.

Avian influenza A H9N2 viruses are widespread among domestic poultry and were recently isolated from humans with respiratory illness in China. Two antigenically and genetically distinct groups of H9N2 viruses (G1 and G9) are prevalent in China. To evaluate a strategy for vaccination, we compared G1 and G9 viruses for their relative immunogenicity and cross-protective efficacy. Infection of BALB/c mice with representative viruses of either group protected against subsequent challenge with the homologous or heterologous H9N2 virus in the absence of detectable cross-reactive serum hemagglutination inhibition antibody. Mice injected intramuscularly with inactivated G1 whole virus vaccine were completely protected from challenge with either H9N2 virus. In contrast, mice administered inactivated G9 vaccine were only partially protected against heterologous challenge with the G1 virus. These results have implications for the development of human vaccines against H9N2 viruses, a priority for pandemic preparedness.

Lack of responsiveness of a nuclear factor-kappaB-regulated promoter to transactivation by human immunodeficiency virus 1 Tat in HeLa cells.

Transcriptional activation by Tat protein is in large part dependent on interactions with the TAR RNA element located in the 5'-untranslated region of all human immunodeficiency virus type 1 (HIV-1) transcripts. In addition, Tat has been shown to induce nuclear translocation of nuclear factor-kappaB (NF-kappaB), potentially contributing to gene induction. The NF-kappaB responsive reporter construct, (PRDII)(4)-CAT, was used to explore transcription resulting from NF-kappaB activated by Tat. Tat did not activate (PRDII)(4)-CAT, whereas (PRDII)(4)-CAT was highly responsive to either transfected Rel A or to tumor necrosis factor-alpha (TNF-alpha). Despite its inability to directly induce, Tat enhanced the responsiveness of (PRDII)(4)-CAT to either transfected Rel A or to TNF-alpha by approximately 2.5-fold. High levels of CAT activity were seen with HIV-LTR-derived reporters that contained kappaB and TAR elements in response to transfected Tat in the absence of either transfected Rel A or exogenous TNF-alpha, and overexpression of IkappaBalpha with Tat inhibited CAT activity by 60% to 80%, suggesting that some activation of NF-kappaB by Tat was occurring. HIV-LTR reporter activities were enhanced three fold to sixfold compared with Tat alone when additional NF-kappaB was provided by transfection or by activation with TNF-alpha. These data indicate that Tat is unable to activate some NF-kappaB-responsive promoters but is able to synergize with NF-kappaB in the activation of both HIV-derived and non-HIV-derived promoters.

Activation of Bcl-2 promoter-directed gene expression by the human immunodeficiency virus type-1 Tat protein.

Human immunodeficiency virus type 1 (HIV-1) Tat transcriptionally activates expression from a number of viral and cellular promoters. Recent studies demonstrate the ability of Tat to differentially modulate cellular responses to apoptotic signaling. The antiapoptotic effects of Tat appear to correlate with increased expression of Bcl-2, a cellular protein that enhances cellular survival. Here, endogenous expression of HIV-1 Tat in HeLa and Jurkat cells elevates levels of Bcl-2. Transient expression assays performed in HeLa cells demonstrate that Tat directly or indirectly enhances Bcl-2 promoter-directed gene expression by more than 10-fold. Analyses of Tat mutants demonstrate that two noncontiguous regions in the N- and C-termini of Tat mediate maximal transactivation of the Bcl-2 promoter. The requirement for C-terminal sequences contrasts with transactivation of the HIV-1 long terminal repeat in which the N-terminal 57 amino acids are required but downstream residues are not. Bcl-2 promoter analyses suggest that sequences required for Tat responsiveness are located upstream of P1 and between the P1 and P2 promoter units. Results from these studies reveal effects of HIV-1 Tat on Bcl-2 expression and provide a putative mechanism by which endogenously expressed Tat affects cellular survival through the up-regulation of Bcl-2.

Completion of tuberculosis therapy for patients reported in the United States in 1993.

SETTING: The highest priority for tuberculosis (TB) control is to ensure patients complete therapy. However, standardized, detailed evaluation of national performance on completion of therapy in the United States has been lacking. Since 1982, the Centers for Disease Control and Prevention (CDC) has had a program objective that at least 90% of TB cases complete therapy. Since 1986, the standard of practice for patients with drug-susceptible TB has been 6 months of therapy. OBJECTIVE: To determine completion of therapy rates and duration of therapy for US TB patients reported in 1993. DESIGN: Expanded TB surveillance data on all US TB patients reported to the CDC in 1993 with initial therapy of two or more drugs were analyzed with respect to completion and duration of therapy. RESULTS: A disposition (reason therapy stopped) was obtained on 98.7% of 23 489 treated patients. Overall, 91.2% of evaluable patients completed therapy. The overall completion rate at 12 months of therapy was 66.8%, and 90% completion was reached at 23 months. For patients with initially drug-susceptible TB, completion was 7.1% at 6 months, 66.5% at 12 months, and reached 90% at 22 months. CONCLUSION: While completion rates ultimately exceeded 90% nationwide, there was considerable delay in reaching this objective, especially in patients with drug-susceptible TB. It is critical that health departments and health care providers identify and remedy any deficiencies responsible for prolonged therapy.

Perioperative care of a Jehovah's Witness with a leaking abdominal aortic aneurysm.

We describe a Jehovah's Witness patient who survived emergency repair of a leaking abdominal aortic aneurysm. In accordance with his beliefs, the patient expressed a wish not to be given blood and this was respected. At completion of surgery, his haemoglobin was 2.8 g dl-1 and his albumin was 8 g l-1. He was kept heavily sedated in the intensive care unit and treated with i.v. iron, folinic acid and s.c. epoetin alfa. He was discharged to the high dependency unit 18 days after surgery with a haemoglobin of 6.4 g dl-1 and an albumin of 27 g l-1. After rehabilitation, he was discharged home approximately 14 weeks after surgery.

Purified Tat induces inflammatory response genes in Kaposi's sarcoma cells.

OBJECTIVE: Kaposi's sarcoma (KS) is a neoplasm strongly associated with HIV-1 infection and marked by leukocytic infiltration. The infiltrating leukocytes are a possible source of inflammatory cytokines, human herpesvirus 8 (HHV8) and the HIV-1 transactivator protein Tat. This study examines whether Tat directly induces expression of cellular adhesion molecules and cytokines in KS cells and whether this induction differs in kinetics and magnitude from induction by tumour necrosis factor (TNF) alpha. DESIGN AND METHOD: Changes in gene expression in response to recombinant Tat compared with those to TNFalpha were evaluated at the messenger (m) RNA and protein level using cells that were cultured from KS lesions. RESULTS: Tat induced the expression of the adhesion molecules vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) and the cytokines monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6). The inductions were observed at both the protein and mRNA levels. The pattern of mRNA induction over time in response to Tat differed from that to TNFalpha, with higher peak levels that occurred earlier in response to Tat. The expression of these genes is, in part, regulated by the transcription factor NF-kappaB. Tat and TNFalpha activated comparable levels of NF-kappaB. CONCLUSIONS: The ability of the HIV-1 Tat to induce the expression of genes with kinetics that are distinct from those seen in TNFalpha induction suggests that mechanisms in addition to activation of NF-kappaB contribute to the observed induction. Tat may contribute to the pathogenesis of AIDS-related KS through induction of cellular genes that are pro-proliferative and proinflammatory and may enhance the recruitment of leukocytes, which are a possible source of further cytokines, Tat and HHV8.

Nationwide survey of drug-resistant tuberculosis in the United States.

OBJECTIVE: To determine antituberculosis drug resistance patterns, geographic distribution, demographic characteristics, and risk factors of reported tuberculosis (TB) patients in the United States. DESIGN: Survey of reported TB cases in the United States. For culture-positive cases reported to the Centers for Disease Control and Prevention, we asked health departments to provide drug susceptibility test results from initial Mycobacterium tuberculosis isolates. STUDY POPULATION: Culture-positive TB cases in the United States reported during the first quarter of 1991. MAIN OUTCOME MEASURES: Individual TB case reports submitted to the Centers for Disease Control and Prevention and drug susceptibility test results. RESULTS: Resistance to one or more antituberculosis drugs was found in 14.2% of cases. Resistance to isoniazid and/or rifampin was found in 9.5% of cases whose isolates were tested against one or both drugs; such cases were found in 107 counties in 33 states. Resistance to both isoniazid and rifampin (multidrug-resistant [MDR] TB) was found in 3.5% of cases whose isolates were tested against both drugs; such cases were found in 35 counties in 13 states. New York City accounted for 61.4% of the nation's MDR TB cases. The 3-month population-based incidence rate of MDR TB in New York City was 52.4 times (95% confidence interval [CI], 35.5 to 78.3) that of the rest of the nation (9.559 vs 0.182 cases per million population). Compared with the rate in non-Hispanic whites in the rest of the nation (0.032 cases per million), the relative risk of MDR TB in New York City non-Hispanic whites was 39.0 (95% CI, 8.1 to 164.5), 299.3 (95% CI, 112.5 to 927.1) in Hispanics, 420.9 (95% CI, 121.0 to 1515.8) in Asian/Pacific Islanders, and 701.0 (95% CI, 296.4 to 2018.1) in non-Hispanic blacks. CONCLUSIONS: With nearly 10% of TB patients resistant to isoniazid and/or rifampin, greater use of four-drug regimens and directly observed therapy is indicated. Aggressive intervention to prevent the further spread of MDR TB is needed to find every TB patient and to provide optimal patient management to ensure completion of chemotherapy.

Tuberculosis morbidity in the United States: final data, 1990.

The number of tuberculosis cases reported to CDC has been increasing since 1988, after a long historic decline. In 1990, 25,701 cases were reported, an increase of 9.4% over the 1989 figure and the largest annual increase since 1953. From 1985 to 1990, reported cases increased by 15.8%. Disproportionately greater increases in reported cases occurred among Hispanics, non-Hispanic blacks, and Asians/Pacific Islanders. In contrast, decreases were observed among non-Hispanic whites and American Indians/Alaskan Natives. By age, the largest increase in reported cases occurred in the 25- to 44-year age group; this increase may be largely attributable to rising numbers of tuberculosis cases among persons with human immunodeficiency virus infection or acquired immunodeficiency syndrome. Notable increases also occurred among children. The proportion of cases among foreign-born persons has risen steadily, from 21.6% in 1986 to 24.4% in 1990.

Tuberculosis diagnosed at death in the United States.

From 1985 through 1988, 5.1 percent of TB cases reported in the United States were diagnosed at death. Differences in the proportions diagnosed at death by race/ethnicity, sex, and place of birth (United States vs foreign-born) were relatively small. The proportion of cases diagnosed at death increased with age, from 0.7 percent in patients less than 5 years old to 18.6 percent among patients 85 years and older. Only 26.0 percent of cases diagnosed alive were among those 65 years and older, but 60.3 percent of those diagnosed at death were in this age group. Eighteen percent of cases with miliary, meningeal and peritoneal TB were diagnosed at death, compared with 4.8 percent among those with pulmonary TB. These data indicate that TB too often remains unrecognized and that, to prevent continuing deaths from this curable disease, a high index of suspicion of TB remains important, particularly among the elderly and among persons with extrapulmonary sites of disease.

Tuberculosis: an increasing problem among minorities in the United States.

Although the number of tuberculosis cases reported annually in the United States has decreased markedly during the past three and a half decades, the decrease among whites has been considerably greater than among nonwhites. As a result of this widening gap, nearly two-thirds of the cases reported in 1987 occurred in minority populations and, for the first time in history, the number of cases among blacks exceeded the number of cases among non-Hispanic whites. From 1985 to 1987, tuberculosis among blacks increased 6.3 percent and among Hispanics, by 12.7 percent, but it decreased 4.8 percent among non-Hispanic whites. Much of the increase appears attributable to tuberculosis occurring among persons infected with the human immunodeficiency virus (HIV). Although there are many obstacles to the elimination of the disease in minority populations, numerous strategies have been developed and are being implemented to address this situation.

The epidemiology of tuberculosis in the United States.

Tuberculosis (TB) in the United States is primarily and increasingly a disease of minorities and the foreign-born. TB among non-Hispanic whites is predominantly a disease of the elderly, while among minorities and the foreign-born, it is primarily concentrated in young adults. In the past few years, TB has increased among young adults, especially those who are black or Hispanic. Available data support the hypothesis that the spread of human immunodeficiency virus (HIV) infection has increased the risk of TB. A substantial proportion of TB in the United States is potentially preventable through the administration of preventive therapy to high-risk populations.

The epidemiology of tuberculosis in the United States. Implications for diagnosis and treatment.

Tuberculosis in the United States is primarily and increasingly a disease of minorities and the foreign-born. Tuberculosis among non-Hispanic whites is predominantly a disease of the elderly, whereas among minorities and the foreign-born, it is primarily concentrated in young adults. In the past few years, tuberculosis has increased among young adults, especially those who are black or Hispanic. Available data support the hypothesis that the spread of human immunodeficiency virus infection has increased the risk of tuberculosis. A substantial proportion of tuberculosis in the United States is potentially preventable through the administration of preventive therapy to high-risk populations.

Effect of ganglion blockade on cerebrospinal fluid norepinephrine.

The source of norepinephrine (NE) in CSF has been unclear. It has been suggested that CSF NE indicates central neural noradrenergic tone and is determined differently from plasma NE. If CSF NE depended specifically on NE release in the CNS, then interference with ganglionic neurotransmission would be expected to decrease plasma NE but not CSF NE. Hypotension caused by ganglionic blockade might be expected to increase CSF NE reflexively. We infused the ganglion blocker, trimethaphan, intravenously into anesthetized dogs and measured the effects on mean arterial blood pressure (MAP) and on cisterna magna CSF levels of NE. The results were compared with those obtained on administration of saline, clonidine (2 micrograms/kg), yohimbine (0.25 mg/kg), or nitroprusside and with those obtained when hypotension during ganglion blockade was prevented by concurrent treatment with phenylephrine. Trimethaphan decreased MAP by 40%, arterial NE by 64%, and CSF NE by 61%. Nitroprusside administered intravenously to produce the same 40% depressor response increased arterial NE by 612% and CSF NE by 155%. Prevention of ganglion blockade-induced hypotension using phenylephrine did not prevent the decrease in CSF NE caused by trimethaphan, and when phenylephrine was discontinued, the resulting hypotension was not associated with increases in CSF NE. The similar decreases in plasma NE and CSF NE during ganglionic blockade, and the abolition of reflexive increases in CSF NE during hypotension in ganglion-blocked subjects, cast doubt on the hypothesis that CSF NE indicates central noradrenergic tone and are consistent instead with at least partial derivation of CSF NE from postganglionic sympathetic nerve endings.

Intrinsic gamma aminobutyric acid receptors modulate the release of catecholamine from canine adrenal gland in situ.

Immunohistochemical analysis documented the presence of gamma-aminobutyric acid (GABA)-containing fibers and GABA-containing chromaffin cells in canine adrenal glands. A dense network of fibers was visualized at the boundary between medullary and cortical cells, and, in the medullary tissue, GABA-containing fibers surrounded chromaffin cells. Some of these fibers enter the adrenal medulla together with splanchnic cholinergic nerves. The functional role of the GABAergic system in the regulation of catecholamine release from adrenal chromaffin cells was studied in canine adrenal glands in situ, using an autoperfusion system for the adrenal gland that was designed to eliminate indirect central effects of drugs or their metabolites on catecholamine release. The present study documents that GABA modulates the spontaneous release of catecholamines and the release elicited by electrical stimulation of the splanchnic nerve. GABAA receptor agonists such as THIP or muscimol increased the catecholamine content in adrenal effluent blood, whereas bicuculline (0.05 mmol/2 ml min-1), a GABAA receptor antagonist, reduced it. Baclofen (0.094 mmol/2 ml min-1), a GABAB receptor agonist, failed to alter the catecholamine content in adrenal effluent blood. The increased release of catecholamines elicited by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3[2H]-one (THIP; 0.143 mmol/2 ml min-1) was prevented by bicuculline (0.05 mmol/2 ml min-1) but not by hexamethonium (2.48 mmol/2 ml min-1) or naloxone (0.122 mmol/2 ml min-1). Furthermore, denervation of the adrenal glands failed to prevent the THIP-elicited release of catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Infection and disease among contacts of tuberculosis cases with drug-resistant and drug-susceptible bacilli.

Three hundred ninety-eight tuberculosis patients with tubercle bacilli resistant to isoniazid and/or streptomycin were matched by age, race, sex, and geographic area to an equal number of patients with tubercle bacilli susceptible to 9 drugs, including isoniazid and streptomycin, in an effort to determine whether the risk of infection and disease among contacts of patients with resistant bacilli is different from the risk among contacts to patients with susceptible bacilli. The risk of infection among contacts of previously untreated patients was not significantly different, regardless of whether the bacilli were drug-resistant or susceptible. However, the risk of infection increased if the index patient with resistant bacilli had been previously treated. We found no evidence of a lower risk of infection among contacts exposed to bacilli resistant to the highest concentration of isoniazid tested or among contacts exposed to bacilli resistant to both isoniazid and streptomycin. There was a strong association between infection risk among contacts and the age of the index case; younger patients were more infectious. Index cases tended to infect most (or all) or few (or none) of their contacts. The investigation of contacts of patients excreting drug-resistant bacilli should be given high priority.

On the mechanism of renal vasoconstriction induced by acetylcholine in indomethacin-treated dogs.

Renal arterial infusion of acetylcholine (ACh) in control dogs produced a natriuresis and diuresis and an increase in renal plasma flow (RPF) without a change in glomerular filtration rate (GFR) or in renin secretory rate (RSR). In dogs pretreated with indomethacin (Indo), an inhibitor of prostaglandin synthetase, renal arterial infusion of ACh first produced a rise, then a decline in urine flow, sodium excretion (UNaV) and GFR that was accompanied by a progressive fall in RPF and a progressive rise in RSR. The rise in RSR was potentiated by renal arterial infusion of an alpha-adrenergic receptor blocker, phenoxybenzamine (Phenoxy), and attenuated, but not completely abolished, by beta-adrenergic receptor blockade with propranolol (Prop). Chemical denervation with reserpine alone, or in combination with chronic surgical renal denervation, failed to prevent the fall in RPF, GFR and UNaV and the rise in RSR produced by ACh in Indo-treated dogs. Renal arterial infusion of Phenoxy and intravenous infusion of Prop, alone or in combination with renal arterial infusion of an angiotensin II antagonist, saralasin, failed to maintain the vasodilatory, diuretic and natriuretic effects of ACh in Indo-treated dogs. Elimination of endogenous vasopressin by hypophysectomy also failed to prevent the vasoconstriction induced by ACh in Indo-treated dogs. The results suggest that ACh produced renal vasoconstriction in Indo-treated dogs by mechanism(s) other than an increase in renal adrenergetic activity or an increase in the activity of the renin-angiotensin system. The results also suggest that the vasoconstriction was independent of vasopresin.