Studies on the mechanism of bacterial resistance to complement-mediated killing. II. C8 and C9 release C5b67 from the surface of salmonella minnesota S218 because the terminal complex does not insert into the bacterial outer membrane

The mechanism for consumption of terminal complement components and release of bound components from the surface of serum-resistant salmonella minnesota S218 was studied. Consumption of C8 and C9 by S218 occurred through interaction with C5b67 on the bacterial surface because C8 and C9 were consumed when added to S218 organisms previously incubated in C8-deficient serum and washed to remove all C5b67 on the bacterial surface because C8 and C9 were consumed when added to S218 organisms previously incubated in C8- deficient serum and washed to remove al but cell bound C5b67. Rapid release of (125)I C5 and (125)I C7 from the membrane of S218 was dependent on binding of C8 because (125)I C5 and (125)I C7 deposition in C8D serum was stable and was twofold higher in C8D than in PNHA, and addition of purified C8 or C8 and C9 to S218 previously incubated in C8D serum caused rapid release of (125)I C5 and (125)I C7 from the organism. Analysis by sucrose density gradient ultracentrifugation of the fluid phase from the reaction of S218 and 10 percent PNHS revealed a peak consistent with SC5b-9, in which the C9:C7 ratio was 3.3:1, but the NaDOC extracted bound C5b-9 complex sedimented as a broad peak with C9:C7 of less than 1.2:1. Progressive elution of C5b67 and C5b-9 from S218 but not serum-sensitive S. minnesota Re595 was observed with incubation in buffers of increasing ionic strength. Greater than 90 percent of the bound counts of (125)I C5 or (125)I C9 were released from S218 by incubation in 0.1 percent trypsin, but only 57 percent of (125)I C9 were released by treatment of Re595 with trypsin. These results are consistent with the concept that C5b-9 forms on the surface of the serum-sensitive S. minnesota S218 in normal human serum, but the formed complex is released and is not bactericidal for S218 because it fails to insert into hydrophobic outer membrane domains.     

Cervicogenic headache

Eleven female patients with cervicogenic headache (mean age, 43 years; range, 25-59 years) have been examined with the pupillometer. The pupillary diameter was examined in the basal state (that is, the status before pharmacologic stimulation) and after topically administered tyramine (2%), phenylephrine (1%), and hydroxyamphetamine (1%). A total of 51 tests were performed, 35 in the asymptomatic period and 16 during pain attacks. In a control group consisting of 26 age-matched women a total of 39 tests were carried out. Before pharmacologic stimulation (that is, in the "basal state") the pupils were smaller in the asymptomatic (pain-free) period than during pain attacks in the patients and also as compared with that of control individuals. The anisocoria (the difference in pupillary size in the same individual) observed was not significantly different between the patient group and control individuals either in the basal state (before pharmacologic stimulation) or after pharmacologic stimulation. The mydriasis resulting from the instillation of the three sympathicomimetic drugs was symmetrical in both controls and patients both during and between the pain attacks. This finding is in clear contrast to what is found in cluster headache, in which there is a "Horner-like" syndrome on the symptomatic side. These two headaches thus seem to differ essentially with regard to this variable.     

QUADAS的制定:用于系统评价中评价诊断性研究质量的工具

背景在以系统评价为基石的循证医学时代,需要有恰当的质量评价工具。对诊断性研究的评价目前尚缺乏系统开发且经过验证的评价工具。本研究的目的是采用共识决策法整合经验证据和专家意见,制定在系统评价时用于评价原始诊断性研究质量的工具。方法按照循证原则,我们在之前发表的3篇诊断性研究文献的综述的基础上,初选出一些条目形成列表,然后通过Delphi流程逐步调整列表,形成质量评价工具。参与Delphi流程的都是诊断性研究领域的专家。结果共有9位诊断学领域的专家参与Delphi流程。经过4轮Delphi流程后,专家们对哪些条目应纳入评价工具达成共识,我们把这个评价工具命名为QUADAS。纳入条目从最初的28个减少到14个,涵盖了疾病谱、金标准、疾病进展偏倚(disease progression bias)、证实偏倚(verification bias)、评价偏倚、临床评价偏倚、合并偏倚、试验的实施、病例退出以及不确定结果。QUADAS工具中的每个条目都配有评分细则。结论本研究项目开发出了用于诊断性试验系统评价的循证质量评价工具。下一步工作是确定其适用性和有效性。     

Cytomegalovirus infections in seropositive patients after transfusion. The effect of red cell storage and volume

Antibody responses to cytomegalovirus (CMV) after red cell (RBC) transfusion were studied in 84 seropositive surgery patients and 82 seropositive oncology patients. The surgery patients were randomized to receive RBCs stored either 3 to 8 or 20 to 42 days after donation. Of 38 patients receiving RBCs stored 8 days or less, 3 developed a rise in titer (4-fold increase) of IgG antibody to CMV 8 to 12 weeks after transfusion. This rate of response (8%) did not differ significantly (p = 0.23) from that (16%) in the 46 patients receiving RBCs stored 20 to 42 days. Seropositive oncology patients were randomized to receive RBCs from seronegative or random donors. Five (19%) of 27 oncology patients receiving seronegative RBCs and 13 (23%) of 55 patients receiving random RBCs (mean, 2 seropositive RBC units/patient) developed a rise in titer of antibody to CMV. No CMV morbidity occurred in either patient group. For both patient groups, a rise in titer of antibody to CMV was associated with the number of transfused RBC units. These results confirm that CMV-seronegative RBCs are unnecessary for infrequently transfused seropositive patients. They also suggest that multiple transfusions of stored RBCs are as immunosuppressive as multiple transfusions of RBCs used within a few days after donation.     

Purinergic receptors on insulin-secreting cells

Summary— The insulin secreting B cell is fitted with the two types of purinergic receptors: P₂ (for ATP and/or ADP) and P₁ (for adenosine). The activation of P₂ purinoceptors by ATP or ADP evokes a biphasic stimulation of insulin secretion from isolated perfused rat pancreas; this stimulation is dose-dependent between 10^?6 and 10^?4 M. Non hydrolysable structural analogues are also effective, and the relative potency of various agonists (2-methylthio ATP ? ATP = ADP = α, β-methylene ATP ? AMP) gave evidence for a P_2y purinoceptor subtype. Proposed mechanisms include both an increased Ca²⁺ uptake and an increased intracellular Ca²⁺ mobilization via the hydrolysis of polyphosphoinositides. ATP (or ADP) potentiates physiological insulin-secreting agents (glucose and acetylcholine) and P₂ purinoceptors could play a physiological role in the stimulation of insulin secretion. The activation of P₁ purinoceptors (adenosine receptors) decreases insulin secretion. Using structural analogues of adenosine, the receptor was characterized as an A₁ subtype; it is coupled to a pertussis toxin sensitive G protein and it inhibits adenylate cyclase. It is of physiological relevance that the B cell has the two types of purinoceptors with opposite effects. Recently, a metabolically stable structural analogue of ADP, adenosine-5′-0-(2-thiodiphosphate) or ADPßS, has been described as a potent secretory agent, effective at nanomolar concentrations on isolated perfused rat pancreas. In vivo, this substance is able to increase insulin secretion and to improve glucose tolerance after IV administration in rats and oral administration in dogs. Furthermore in streptozotocin-induced diabetes, ADPßS retains its insulin secreting effects. These results suggest that P_2y purinoceptors could be a new target for antidiabetic drugs.     

INTRACEREBRAL HAEMORRHAGE IN A YOUNG ADULT: CONSIDER AMPHETAMINE ABUSE

SUMMARY We present the case of a young female who suffered a massive intracerebral bleed following the ingestion of a small quantity of amphetamine (speed). Physicians should be aware that amphetamine abuse can lead to cerebrovascular events in young adults.