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The current debate on issuing identity cards to the British population was foreshadowed during the First World War, when the National Registration Act of 1915 provided for a register of all men and women between 15 and 65, later used to aid conscription. The National Register was produced by Bernard Mallet, the Registrar General of England and Wales. The information demands of the war also provided an opportunity for Mallet to press forward his pre-war agenda of reforming the system of routine registration of births, marriages and deaths. His desire for reform was shaped by the pressing eugenic questions of the day - infant mortality and national efficiency - and as the war progressed, he developed his ideas to include a permanent universal register of all individuals. This article examines the fate of Mallet's proposals, and shows how lack of political consensus and lack of support, even from colleagues in the General Register Office for Scotland, prevented his proposals coming to fruition.

Primary effusion lymphoma (PEL) is an unusual class of non-Hodgkin's lymphoma, which is characterised by lymphomatous effusions in body cavities, but no associated mass lesions. It is usually associated with an immunodeficient state most often with the human immunodeficiency virus (HIV). We describe a case of a man with HIV-negative, human-herpes-virus-8 (HHV8)-negative PEL, with a history of heavy alcohol intake. The abdominal cavity was the only area involved; no solid tumour masses were observed on scanning, and the bone-marrow investigations were normal. The ascites contained numerous pleomorphic lymphoid, lymphoplasmacytoid cells of B-cell origin. The immunophenotyping was moderately positive for CD 38 and 138, and strongly positive for Ki 67. It is postulated that the immunosuppressed state in this patient may have been caused by the long history of heavy alcohol intake.

A Mexican group reported transplantation of cocultured neonatal porcine islets and Sertoli cells resulting in insulin independence in nonimmunosuppressed type 1 diabetes patients. We have transplanted similar islets alone (naked islets) or cocultured islets with sertoli cells (islet/sertoli cells) into an omental site and other locations of seven nondiabetic, nonimmunosuppressed, nonhuman primates. Porcine endogenous retrovirus was not detected in recipient blood 8 weeks after porcine islet grafts, and porcine C-peptide was detected at a very low level in all animals. Histology examination failed to demonstrate obviously recognizable islets, but in the animals transplanted with islet/Sertoli cells at the omentum site, there were some surviving glucagons, pan-cytokeratin, and inhibin stained cells at 8 weeks.

The testis has been shown to be a privileged site for transplantation of allogenic islets in rodents, and the testicular cell aggregates are thought to confer this immunologic privilege. Recently, a group in Mexico reported transplantation of cocultured neonatal porcine islets and Sertoli cells resulting in insulin independence in nonimmunosuppressed type 1 diabetes patients. We have transplanted similar islets alone (naked islets) or cocultured islets with Sertoli cells (islet/Sertoli cells) into an omental site and other locations of nonimmunosuppressed, streptozotocin-induced diabetic male Sprague Dawley (SD) rats. Histologic examination showed viable neonatal porcine islets survived in xenografted rodents for at least 2 days, and some glucagon and inhibin stained cells appear to have survived for 4 days posttransplantation. However, histological examination did not demonstrate any difference in xenograft survival in the islets/Sertoli cells mixture compared to naked islets when transplanted into these nonimmunosuppressed diabetic rats.

The membrane fusion protein (MFP) component, MexA, of the MexAB-OprM multidrug efflux system of P. aeruginosa is proposed to link the inner (MexB) and outer (OprM) membrane components of this pump as a probable oligomer. A cross-linking approach confirmed the in vivo interaction of MexA and MexB, while a LexA-based assay for assessing protein-protein interaction similarly confirmed MexA multimerization. Mutations compromising the MexA contribution to antibiotic resistance but yielding wild-type levels of MexA were recovered and shown to map to two distinct regions within the N- and C-terminal halves of the protein. Most of the N-terminal mutations occurred at residues that are highly conserved in the MFP family (P68, G72, L91, A108, L110, and V129), consistent with these playing roles in a common feature of these proteins (e.g., oligomerization). In contrast, the majority of the C-terminal mutations occurred at residues poorly conserved in the MFP family (V264, N270, H279, V286, and G297), with many mapping to a region of MexA that corresponds to a region in the related MFP of Escherichia coli, AcrA, that is implicated in binding to its RND component, AcrB (C. A. Elkins and H. Nikaido, J. Bacteriol. 185:5349-5356, 2003). Given the noted specificity of MFP-RND interaction in this family of pumps, residues unique to MexA may well be important for and define the MexA interaction with its RND component, MexB. Still, all but one of the MexA mutations studied compromised MexA-MexB association, suggesting that native structure and/or proper assembly of the protein may be necessary for this.

Purpose: To describe corneal intrastromal epithelial cysts and present a minimally invasive surgical technique successfully used to treat such a lesion., Methods: A 5-year-old girl with a progressive, vision-threatening, intrastromal corneal opacity in the left eye is described. The patient had a history of accommodative esotropia and bilateral medial rectus recession two years before presentation. A presumptive diagnosis of an epithelial cyst secondary to iatrogenic seeding of the limbal corneal stroma was made. Because of documented growth toward the visual axis and a decrease in best-corrected visual acuity, surgical treatment was initiated. The cyst was incised and debrided through a 2.0-mm, partial-thickness, limbus-parallel, clear corneal incision., Results: Cytologic analysis of the cyst contents showed intact and degenerated epithelial cells, thereby confirming the diagnosis. The cyst walls were scraped through the nonenlarged incision, and irrigation resulted in nearly complete clearing of the opacity. Stable vision and no recurrences were documented with 21 months of follow-up., Conclusion: This minimally invasive surgical approach may be a good alternative to previously described treatments for intrastromal corneal cysts.

A method for simultaneous measurement of tyrosine hydroxylase (TH) activation and phosphorylation in permeabilised and intact bovine adrenal chromaffin cells (BACCs) was established. Permeabilised cells were stimulated with cyclic AMP (1--10 microM) in the presence of [32P]ATP and L-[carboxyl-(14)C]tyrosine. Intact BACCs were preincubated with 32P(i) for 3 h and stimulated with forskolin (1--5 microM) in the presence of L-[carboxyl-(14)C]tyrosine. On stimulation each well was covered with a sealed 'chimney' fitted with a small plastic cup containing 300 microl of 1.0 M NaOH that trapped the 14CO(2) released. TH activity was determined by measuring 14C radioactivity. TH phosphorylation was measured in the same cells by separating the solubilized proteins on SDS PAGE followed by autoradiography and/or HPLC analysis. It was found that H89, a protein kinase A inhibitor, significantly blocked both TH phosphorylation and activation in response to cyclic AMP in permeabilised cells. However, in intact cells, H89 was effective only in respect to forskolin-stimulated TH activity and did not block the forskolin-stimulated TH phosphorylation of Ser-40. The reason(s) for this lack of correlation between TH activation and phosphorylation is presently not understood.

Because of their unique radicular anatomy, mandibular molars require careful treatment planning for post-and-core fabrication. Indications for post-and-core fabrication for endodontically treated mandibular molars are discussed, and immediate and cast post-and-core techniques are reviewed. An alternative design for a cast post and core is also presented.

It has been argued, for example by Ingmar Persson, that genetic therapy performed on a conceptus does not alter the identity of the person that develops from it, even if we are essentially persons. If this claim is true then there can be person-regarding reasons for performing genetic therapy on a conceptus. Here it is argued that such person-regarding reasons obtain only if we are not essentially persons but essentially animals. This conclusion requires the defeat of the origination theory, which says that personal identity is determined by the identity of the foetus from which one originates. It is argued that the origination theory is false in the special case relevant to performing genetic therapy on a conceptus for person-regarding reasons.

A 537 base pair cDNA clone for murine GIP has been isolated. The elucidated sequence encodes an open reading frame of 432 base pairs which codes for a 144 amino acid precursor. Murine GIP is predicted to differ from the human hormone by three amino acid substitutions: arginine for histidine at position 18, arginine for lysine at position 30 and serine for lysine at position 34. GIP mRNA levels in STC6-14 cells incubated in the presence of varying glucose concentrations was investigated using a competitive-PCR method. In the presence of a 5-mM glucose stimulus, 1 x 10(5) GIP cells were found to contain 3.9 +/- 0.59 amol of GIP mRNA while the same number of cells contained 11.6 +/- 1.4 amol when subjected to a high (25 mM) glucose stimulus.

Background: Propranolol has been shown to be effective in both primary and secondary treatment of variceal haemorrhage; most primary prevention trials have only included patients with large oesophageal varices., Aim of the Study: The aim of this study was to look at the effect of propranolol in the primary prevention of variceal bleeding and its long-term effects on mortality in unselected patients with chronic liver disease., Methodology: Three hundred and nineteen patients were included in a double-blind parallel group study in three centres to receive propranolol 160 mg long-acting (LA) or placebo. Patients were followed up for a minimum of one year., Results: There were eleven episodes of variceal bleeding and 38 deaths with no statistically significant difference in bleeding rates between the two treatment groups. Child's group and history of ascites were the most important prognostic factors determining the likelihood of early death and variceal bleeding respectively., Conclusions: In this study we failed to demonstrate a significant effect of propranolol on first variceal bleeding or in prolonging survival in unselected patients with chronic liver disease. Our results, however, might have been influenced by the low event rate observed in these unselected group of patients and suggest that careful selection of patients who are most likely to benefit from propranolol is important.

Some conditions detrimental to human well-being, such as sickle-cell anaemia, cystic fibrosis, muscular dystrophy, Lesch-Nyhan disease and various immunodeficiencies, are genetically determined. One potential means of preventing the development of such conditions is the manipulation of genetic material in the conceptus of an organism which would otherwise develop such conditions. Genetic manipulations could take the form either of excising and substituting genetic material, excising but not substituting genetic material, adding but not excising genetic material or reorganizing existing genetic material. To succeed, manipulation would have to change genetic structure so as to change its informational content. It might be thought, however, that all or some such manipulations would involve causing particular individuals to cease to exist and involve bringing into existence new, distinct individuals. Gene therapy could not, therefore, be a procedure which improved the circumstances of the particular individual to whom it is applied. It might be suggested that once the metaphysics of identity and the facts of gene therapy are understood, certain interesting conclusions concerning the ethics of gene therapy emerge. Some such conclusions have been discussed in this journal by Noam J. Zohar and Jeffrey P. Kahn. More, however, needs to be said about them since neither Zohar nor Kahn draws the correct conclusions. While both have pertinent things to say, neither has given a completely clear account of the metaphysics of gene therapy and so neither has completely traced out the implication of the metaphysics for the ethics of gene therapy. This paper attempts to remedy these defects.

Myocardial creatine phosphokinase (CPK) activity and myocardial blood flow (MFB, 15 +/- mu microspheres) were measured at 24 hours after ligation of the left anterior descending coronary artery in nine untreated anesthetized dogs, in eight dogs pretreated with intravenous propranolol 5 mg/kg and in eight which had both pretreatment as well as infusion of propranolol (1.25 mg/kg/hour) after occlusion. Loss of CPK activity from the border and center zones of the myocardial infarct was similar in extent in dogs which had pretreatment but no infusion of propranolol as it was in the control group. Loss of CPK from the center zone was greater (P less than 0.005) in dogs receiving pretreatment followed by constant infusion of the drug. Propranolol had no significant effect on collateral blood flow to the border or center zone of the infarct. In separate experiments, there was no important difference in hemodynamic measurements, except a slower heart rate (P less than 0.01), when pretreated dogs were compared with control dogs up to 2 hours after coronary ligation. We conclude that propranolol given in this dose does not influence nyocardial damage, on the basis of regional myocardial blood flow or tissue CPK depletion values at 24 hr after coronary occlusion.

The relationship between early and late epicardial electrocardiographic changes as well as those in regional myocardial blood flow (MBF) and the severity of myocardial damage was determined in 12 anesthetized dogs with left anterior descending coronary artery ligation. Radioactive microspheres (15 mum) were used to measure regional MBF at 15 min (early) and 24 h (late) after coronary occlusion. Severity of myocardial damage was assessed by the extent of myocardial creatine phosphokinase depletion 24 h after coronary ligation. There was a close linear correlation between myocardial creatine phosphokinase activity and regional MBF both early (r=0.93, 2P less than 0.001) and late (r=0.88, 2P less than 0.001). An inverse but less precise relationship existed between acute epicardial ST-segment elevation and early (r=-0.41, 2P less than 0.001), or late (r=0.35, 2P less than 0.05) regional MBF. Similarly, a weak correlation was found between myocardial creatine phosphokinase (IU/mg protein) at 24 h and early epicardial ST (millivolt) elevation (r=-0.36, 2P less than 0.02). In the center zones of the infarct with MBF 1/10 of normal, about 35% of the areas with normal QRS width had no epicardial ST-segment elevation 15 min after coronary occlusion. About 44% of the areas which developed pathological Q-waves in the electrocardiogram at 24 h had no ST elevation 15 min after coronary ligation. Late evolution of abnormal Q-waves occurred almost invariably in areas in which the early MBF was reduced to less than 50% of normal and in areas which subsequently had myocardial creatine phosphokinase levels reduced to less than 60% of normal. After coronary occlusion, the severity of the ultimate myocardial damage, which was directly proportional to the degree of reduction in MBF, was therefore not reliably predicted by the early epicardial ST-segment elevation. The data obtained in these studies suggest the need for caution in the use of acute ST-segment elevation as a predictive index of the extent or severity of myocardial ischemic damage.

A double framework system is indicated when implant location could result in an overcontoured or compromised metal ceramic prosthesis. Precise design of the auxiliary substructure should provide for all necessary reorientations and corrections before constructing the metal ceramic framework. The additional cost and complexity of this technique must be weighed against the esthetic and morphologic requirements of the patient.