Parenting interventions for male young offenders: a review of the evidence on what works.

Approximately one in four incarcerated male young offenders in the UK is an actual or expectant father. This paper reviews evidence on the effectiveness of parenting interventions for male young offenders. We conducted systematic searches across 20 databases and consulted experts. Twelve relevant evaluations were identified: 10 from the UK, of programmes for incarcerated young offenders, and two from the US, of programmes for young parolees. None used experimental methods or included a comparison group. They suggest that participants like the courses, find them useful, and the interventions may improve knowledge about, and attitudes to, parenting. Future interventions should incorporate elements of promising parenting interventions with young fathers in the community, for example, and/or with older incarcerated parents. Young offender fathers have specific developmental, rehabilitative, and contextual needs. Future evaluations should collect longer-term behavioural parent and child outcome data and should use comparison groups and, ideally, randomization.

Feasibility and acceptability of offering rapid HIV tests to patients registering with primary care in London (UK): a pilot study.

OBJECTIVE: To assess the acceptability and feasibility of offering rapid HIV tests to patients registering with primary care in London, UK. METHODS: All Anglophone and Francophone patients aged between 18 and 55 years attending a large inner city general practice in London for a new patient health check were recruited. All eligible patients were offered a rapid HIV test on oral fluid and asked to participate in a qualitative interview. The uptake of rapid HIV testing among participants was measured and semistructured interviews were carried out focusing on the advantages and disadvantages of testing for HIV in primary care. RESULTS: 111 people attended the health check, of whom 85 were eligible, 47 took part in the study and 20 completed qualitative interviews. Nearly half of eligible participants (38/85, 45%) accepted a rapid HIV test. The main reason for accepting a test was because it was offered as "part of a check up". As a combined group, black African and black Caribbean patients were more likely to test in the study compared with patients from other ethnic backgrounds (p = 0.014). Participants in the qualitative interviews felt that having rapid HIV tests available in general practice was acceptable but expressed concerns about support for the newly diagnosed. CONCLUSIONS: Offering patients a rapid HIV test in primary care is feasible and could be an effective means to increase testing rates in this setting. A larger descriptive study or pragmatic trial is needed to determine whether this strategy could increase timely diagnosis and reduce the proportion of undiagnosed HIV infections in the UK.

Sieve cells in Phloem of a middle devonian progymnosperm.

Phloem tissue from a Middle Devonian member of the Aneurophytales (Progymnospermopsida) is described. This may be the oldest firm evidence of conducting elements of the phloem, extending our knowledge of this tissue back some 35 million years. The discovery indicates a close phylogenetic relation between progymnosperms and gymnosperms and provides a basis for investigating patterns of specialization in the phloem of these groups of plants.

Development of a virtual reality haptic Veress needle insertion simulator for surgical skills training.

The Veress needle is the most commonly used technique for creating the pneumoperitoneum at the start of a laparoscopic surgical procedure. Inserting the Veress needle correctly is crucial since errors can cause significant harm to patients. Unfortunately, this technique can be difficult to teach since surgeons rely heavily on tactile feedback while advancing the needle through the various layers of the abdominal wall. This critical step in laparoscopy, therefore, can be challenging for novice trainees to learn without adequate opportunities to practice in a safe environment with no risk of injury to patients. To address this issue, we have successfully developed a prototype of a virtual reality haptic needle insertion simulator using the tactile feedback of 22 surgeons to set realistic haptic parameters. A survey of these surgeons concluded that our device appeared and felt realistic, and could potentially be a useful tool for teaching the proper technique of Veress needle insertion.

Overexpression of Gs alpha protein in the hearts of transgenic mice.

Alterations in beta-adrenergic receptor-Gs-adenylyl cyclase coupling underlie the reduced catecholamine responsiveness that is a hallmark of human and animal models of heart failure. To study the effect of altered expression of Gs alpha, we overexpressed the short isoform of Gs alpha in the hearts of transgenic mice, using a rat alpha-myosin heavy chain promoter. Gs alpha mRNA levels were increased selectively in the hearts of transgenic mice, with a level 38 times the control. Despite this marked increase in mRNA, Western blotting identified only a 2.8-fold increase in the content of the Gs alpha short isoform, whereas Gs activity was increased by 88%. The discrepancy between Gs alpha mRNA and Gs alpha protein levels suggests that the membrane content of Gs alpha is posttranscriptionally regulated. The steady-state adenylyl cyclase catalytic activity was not altered under either basal or stimulated conditions (GTP + isoproterenol, GTP gamma S, NaF, or forskolin). However, progress curve studies did show a significant decrease in the lag period necessary for GppNHp to stimulate adenylyl cyclase activity. Furthermore, the relative number of beta-adrenergic receptors binding agonist with high affinity was significantly increased. Our data demonstrate that a relatively small increase in the amount of the coupling protein Gs alpha can modify the rate of catalyst activation and the formation of agonist high affinity receptors.

Heteropolymerization of S, I, and Z alpha1-antitrypsin and liver cirrhosis.

The association between Z alpha1-antitrypsin deficiency and juvenile cirrhosis is well-recognized, and there is now convincing evidence that the hepatic inclusions are the result of entangled polymers of mutant Z alpha1-antitrypsin. Four percent of the northern European Caucasian population are heterozygotes for the Z variant, but even more common is S alpha1-antitrypsin, which is found in up to 28% of southern Europeans. The S variant is known to have an increased susceptibility to polymerization, although this is marginal compared with the more conformationally unstable Z variant. There has been speculation that the two may interact to produce cirrhosis, but this has never been demonstrated experimentally. This hypothesis was raised again by the observation reported here of a mixed heterozygote for Z alpha1-antitrypsin and another conformationally unstable variant (I alpha1-antitrypsin; 39Arg-->Cys) identified in a 34-year-old man with cirrhosis related to alpha1-antitrypsin deficiency. The conformational stability of the I variant has been characterized, and we have used fluorescence resonance energy transfer to demonstrate the formation of heteropolymers between S and Z alpha1-antitrypsin. Taken together, these results indicate that not only may mixed variants form heteropolymers, but that this can causally lead to the development of cirrhosis.

Human blood group isoantigen expression on normal and malignant gastric epithelium studied with anti-A and anti-B monoclonal antibodies.

Variation in human blood group isoantigen expression on normal and malignant gastric epithelium was demonstrated with monoclonal antibodies to blood groups A and B in an indirect immunoperoxidase technique. The expected isoantigen expression was demonstrated on endoscopic biopsy specimens of normal gastric mucosa from 11 patients. Of 17 patients with gastric carcinoma (blood group A, 15; blood group AB, 2), complete loss of isoantigen expression was noted in 6 (35%). In these 6 patients, blood group isoantigen remained both in the adjacent uninvolved mucosa and at the margin of resection. The loss of isoantigen did not appear to be related to the degree of differentiation within the tumor, to the secretor status of the patient, or to the blood subgroup. Lymph node metastases reflected the isoantigen status of the primary tumor, being positive in 5 of 6 expression in all 17 patients or in an additional 15 patients studied with blood group O. These findings were discussed in the light of previously reported work on the localization of blood group isoantigens on malignant and nonmalignant gastric epithelium with the use of conventional antisera and a variety of immunohistologic techniques.

Glycine 119 of bovine growth hormone is critical for growth-promoting activity.

Bovine GH (bGH) analogs with single amino acid substitutions at positions 117 (bGH-E117L), 119 (bGH-G119R), and 122 (bGH-A122D) were generated. These analogs bind to mouse liver membrane preparations with affinities similar to native bGH. However, transgenic mice which express the analogs demonstrate different phenotypes ranging from dwarfism to gigantism. For example, expression of bGH or bGH-E117L result in large transgenic mice. In contrast, transgenic mice with a growth phenotype similar to nontransgenic animals result from expression of bGH-A122D. Surprisingly, transgenic mice with relatively high serum levels of bGH-G119R possessed a dwarf phenotype. Together these results suggest that Gly 119 and Ala 122 are involved in growth-promoting activity of GH.

Amino acid residues in the third alpha-helix of growth hormone involved in growth promoting activity.

The third amphiphilic alpha-helix of GH has been found to be an important motif in the biological activities of the molecule. To further characterize this growth-promoting domain, three bovine (b) GH analogs were designed: one contained a scrambled third amphiphilic alpha-helix (SAH); a second contained a scrambled hydrophilic region of the helix (SAP); and a third contained a scrambled hydrophobic region of the helix (SAB). Transgenic mice that expressed these mutated bGH genes were produced. SAH transgenic mice displayed a phenotype identical to nontransgenic littermates. SAB transgenic mice grew slightly larger than nontransgenic littermates but remained smaller than bGH transgenic mice. On the other hand, SAP transgenic mice exhibited a dwarf phenotype. We subsequently generated individual amino acid substitutions in the hydrophilic region of the helix. The results from the growth rates of corresponding transgenic mice demonstrated that most bGH analogs with individual amino acid substitution within the third alpha-helix retained wild type-like growth-promoting activity except those with alterations at positions 115, 119, 122, and 123. Together these residues are predicted to form a cleft in the helix. To further substantiate the importance of the cleft, we deleted Gly 119 (delta 119). This resulting bGH analog was inactive in vivo as well as in in vitro assays. These results indicated that the primary structure of the third alpha-helix is critical for GH's growth-promoting activity and Gly 119 is a crucial amino acid in this region. Three adjacent amino acids, Asp 115, Ala 122, and Leu 123, also contribute to the growth-enhancing ability of the molecule.

Antigen-specific immunosuppression induced by liver transplantation in the rat.

We have demonstrated that DA hearts grafted into PVG rats were completely protected from rejection by simultaneous liver transplantation from the same donor. In subsequent experiments PVG animals were given DA hearts followed 5 or 6 days later by livers from the same donor strain. Instead of the expected rapid rejection, all the grafts survived for at least 18 days, despite showing definite graft-swelling, a reliable clinical sign of early rejection, immediately prior to liver transplantation. In all 13 rats the heart size returned to normal and a strong beat returned within a few days. 6 animals survived indefinitely with healthy, beating heart grafts and the remaining 7 animals died of liver transplant rejection, but in these animals also the hearts were beating normally immediately prior to death. Histological examination of the hearts revealed no active rejection, but there was extensive myocardial scarring, compatible with resolution of a rejection reaction. It seems, therefore, that the liver grafts had entirely absorbed the vigorous immune response, terminating that which had already begun in the heart. This immunosuppressive effect was donor-specific and far more powerful than that of the immunosuppressive agent cyclosporine.

Orthotopic rat liver transplantation after long-term preservation by continuous perfusion with fluorocarbon emulsion.

Isolated rat livers have been stored for up to 25 hr using a continuous pulsatile perfusion technique with and without fluorocarbon emulsion oxygen carrier in the perfusate. After preservation, orthotopically isografted livers can maintain recipient animals in good health. The longest surviving animal is alive at 12 months. A prosthetic cuff technique for the portal vein anastomosis was specially developed for this experimental series. It has simplified vascular anastomosis after the portal vein cannulation that is required for machine preservation of the donor liver. We believe that the described method in the rat liver isograft model might be useful for studies of liver preservation.

Hypothermic preservation of the rat liver assessed by orthotopic transplantation. II. Evaluation of citrate solutions.

Rat livers were flushed with isotonic citrate solution (IC), hypertonic citrate solution (HC), or Collins' solution (C2), and were stored at 0 degree C for 8-16 hr. Following 8-hr preservation, the number of animals surviving for one month was greatest with IC grafts (6/8) and least with C2 grafts (2/7). There was no significant difference between the two citrate groups. Following 12-hr preservation, the IC group was superior to the HC group (3/6 vs. 1/6). Following 16-hr preservation, all four animals in each citrate group died within 24 hr. The ability of livers to produce bile was greater in the citrate groups, compared with the C2 group. A bile flow rate less than 0.3 microliter/min/g liver, 15 min after implantation, appeared to predict subsequent poor survival. There were no significant histological differences between biopsies taken from each group at the end of the transplant operation. Biochemical measures of liver function were best in animals that had received IC grafts, and functional damage after preservation was consistently greater in the C2 group than the citrate groups. The best results were obtained with grafts preserved with IC solution.

Successful 48-hour preservation of the rat liver by continuous hypothermic perfusion with haemaccel-isotonic citrate solution.

Eleven rat livers were stored at 7 degrees C for 24 or 48 hr using a continuous nonpulsatile perfusion method. The perfusate was based on the isotonic citrate preservation solution but contained, in addition, gelatin polypeptides (Haemaccel, Hoechst) and fluorocarbon emulsion (FC-43, Green Cross Corp.). Isologous livers were orthotopically transplanted after preservation, and long-term survival was 3/6 following 24 hr preservation and 4/5 following 48 hr preservation. All the biopsies taken immediately after revascularization were histologically normal. The seven surviving animals were killed at two months and histology showed biliary obstruction, but in all cases the hepatocytes appeared to be well preserved. These late histological findings are common in any use of this transplantation model and are believed to be associated with the difficulty of obtaining a satisfactory anastomosis of the bile duct. The perfusate described here is capable of providing reliable 48 hr preservation of the rat liver.

Liver transplantation in the rat. Biochemical and histological evidence of complete tolerance induction in non-rejector strains.

Orthotopic liver allografts in the rat survive indefinitely without immunosuppressive agents, despite incompatibility between donor and recipient for antigens of the major histocompatibility complex. This is strain-dependent. In the DA to PVG strain combination, liver grafts are never rejected. This is not due to failure of the recipient to mount an immune response against the donor tissue, because there is unequivocal histological evidence of a rejection response during the first few weeks after grafting. This response is moderate and disappears to leave a histologically normal liver, apart from mild bile duct proliferation. Liver function tests show evidence of damage during the phase of cellular infiltration, but these test results also return to normal levels within a few weeks. In the DA to BN strain combination liver grafts are rapidly rejected, and this process is accompanied by histological signs of a violent and progressive destructive cellular response with gross alterations in liver function test results that are progressive until the death of the recipients. F1 hybrid recipients between these two strains (BN X PVG)F1 show intermediate levels of both histological damage and elevated liver function values, but they do not reject their grafts. Recovery from the rejection episode appears to be complete, as judged histologically. However, biochemical values remain slightly elevated, indicating either that the original damage was so severe that it was inconsistent with complete functional recovery or that there is continuous damage that is not visible histologically.

Damage to the biliary tract during preservation.

Biliary complications following liver transplantation continue to present major difficulties. Damage to the biliary tract has been reported after preservation of the liver before transplantation. Studies in the rabbit are reported that confirm the extensive biliary autolysis during preservation. This damage is directly related to the presence of bile in the biliary tract and can be reduced by the washout of bile and biliary perfusion.

The possibility of resuscitating livers after warm ischemic injury.

The number of clinical liver transplants that can be performed is limited by the availability of suitable donor organs. If it were possible to harvest and use livers after cardiac arrest, the supply could be improved. The mechanisms of damage in warm ischemia are not yet well understood and the consequences of transplanting a liver that is unable to provide immediate life-support are unacceptable. This study aims to identify areas for more detailed study in an attempt to improve the quality of livers harvested after significant warm ischemia, and to select acceptable organs for transplantation. Porcine livers were subjected to 75 min of warm ischemia and then perfused at 37 degrees C for 3 hr, during which period biochemical monitoring was carried out. At the end of the perfusion, histological and transmission electron microscopical studies were made. Large amounts of the intracellular enzymes ALT, AST, and LDH were released into the perfusate during the first 30 min of perfusion, but this--and the further amounts released during the subsequent 2.5 hr--was influenced by the composition of the perfusate. The inclusion of the substrates fructose and oleate, plus amino acids, substantially reduced this release and also improved the ability of the livers to metabolize ammonia. Oxygen free-radical scavengers had a significant, but smaller, beneficial effect. Electron microscopy confirmed the value of perfusion in improving cell morphology, and the additional value of including metabolic substrates. This study shows that hepatocellular structure and function can be improved by appropriate perfusion methods that also provide a simple means of monitoring some important functions. Both metabolic support and neutralization of oxygen free-radical action have a role to play in this approach to rendering ischemically injured livers acceptable for clinical use.

Serum alpha-glutathione S-transferase--a sensitive marker of hepatocellular damage associated with acute liver allograft rejection.

The wide hepatic distribution, high cytosolic concentration, and short in vivo plasma half-life of serum alpha-glutathione s-transferase are properties which may make monitoring this enzyme more clinically useful than conventional biochemical liver function tests as a marker of hepatocellular damage associated with acute liver allograft rejection. In a prospective longitudinal study of 58 liver transplants in 45 patients, serum alpha-glutathione S-transferase concentrations rose significantly more consistently and more rapidly than conventional liver function tests in association with acute rejection. However, a rise in alpha-glutathione S-transferase was less specific for rejection than conventional liver function tests although none of the tests had a positive predictive value for rejection of greater than 32%. Compatible with the particularly short in vivo plasma half-life of this enzyme, alpha-glutathione S-transferase concentrations fell to or toward normal more rapidly than conventional liver function test measurements following uncomplicated transplantation as well as during high-dose steroid treatment of rejection. This may be valuable, both in improving the resolution of biochemical changes associated with early rejection episodes and in determining when treatment of rejection has been successful. Further studies are warranted, however, to assess whether the fall in GST during rejection treatment does genuinely reflect the histological resolution of rejection.

Preservation of the canine liver for 24-48 hours using simple cold storage with UW solution.

The results of a series of 29 orthotopic liver transplants in the dog are described. The livers were preserved in a new cold storage fluid, UW solution, and were successfully transplanted after periods of storage of 24, 30, 36, and 48 hr. All six animals transplanted after 24 hr survived beyond 5 days after transplantation and had excellent graft function. Four of six survived for at least 5 days after 30 hr of cold storage, and five of five after 36 hr. Five of six consecutive dogs that received transplants that had been cold-stored for 48 hr survived for 5 or more days. This solution represents a substantial advance over all existing cold storage solutions for liver preservation.

An association between cytomegalovirus infection and chronic rejection after liver transplantation.

BACKGROUND: Previous studies suggest a link between cytomegalovirus (CMV) infection and chronic rejection. Since these studies, more sophisticated diagnostic methods with high sensitivity and specificity for CMV have been developed and effective therapy/prophylaxis for CMV is now available. We sought CMV prospectively by polymerase chain reaction of serum and urine and by conventional methods in a group of 33 patients undergoing 57 transplants during 1993 or 1994, selected from a larger series. There were 13 grafts lost to chronic rejection. The remaining 44 grafts that did not develop chronic rejection served as controls and comprised 15 successful primary grafts, 15 second transplants, 8 third transplants, and 6 primary grafts that were lost for reasons other than chronic rejection. RESULTS: The combination donor CMV antibody negative with recipient antibody positive and the duration of CMV infection >30 days were associated with an increased relative risk of chronic rejection. In contrast, the presence of CMV infection alone, symptomatic CMV infection, the detection of CMV by PCR of serum or urine, and the peak/cumulative viral load were not predictive. CMV infection occurred earlier in those undergoing a second transplant for chronic rejection than for those undergoing a second transplant for other reasons. In addition, a human leukocyte antigen B mismatch was associated with prolonged CMV infection. CONCLUSION: These data are consistent with the hypothesis that prolonged subclinical cytomegalovirus infection is associated with an increased risk of chronic rejection.

CsA levels in the early posttransplant period--predictive of chronic rejection in liver transplantation?

The increasing success of clinical liver transplantation has brought rejection to the forefront as a cause of morbidity and graft loss. The relationship of immunosuppressive drug doses and levels to acute and chronic rejection remains a matter of debate. The effect of blood CsA levels and drug doses on the incidence of acute and chronic rejection and the impact of acute rejection episodes on the occurrence of chronic rejection were studied in 146 grafts in 132 patients. These patients were transplanted in the 4-year period from June 1989 using CsA-based immunosuppression (CsA, azathioprine, prednisolone). Liver grafts in patients maintained on median CsA levels (whole blood, trough level) of > or = 175 micrograms/L in the first 28 days posttransplant had a significantly lower incidence of chronic rejection (2 out of 49 vs. 22 out of 97; P = 0.002). There was no significant difference in incidence of graft loss due to fatal sepsis (6% vs. 5%) or nephrotoxicity between the high and low CsA level groups. The overall graft loss rate was lower in the higher CsA level group (22% vs. 37%). The total doses of the individual drugs did not correlate with the incidence of acute or chronic rejection. Although the occurrence of acute rejection itself did not determine later chronic rejection, late occurrence (P < 0.00001) and multiple episodes (two or more; P = 0.0002) of acute rejection were significant risk factors for the occurrence of chronic rejection. We conclude that to minimize graft loss to rejection, CsA levels should be maintained at greater than 175 micrograms/L in the early posttransplant period, and late and recurrent episodes of acute rejection should be prevented.