Thymus-dependent monoclonal antibody-induced protection from transferred diabetes

It is well established that long-term protection from insulin-dependent diabetes mellitus (IDDM) can be afforded to non-obese diabetic (NOD) mice by a short course of non-depleting (nd) anti-CD4 monoclonal antibodies (mAb). Since it is increasingly apparent that the CD8⁺ T cell plays a prominent role in the development of IDDM, we have investigated the effect of an anti-CD8 mAb (YTS 105) of the same isotype in both spontaneous and induced IDDM in NOD mice. Treatment with YTS 105 for 3 weeks was able to prevent the transfer of IDDM for a long period, and also substantially reduced spontaneous IDDM in female NOD mice. The role of the thymus in tolerance induction by these antibodies was studied. In the adult transfer model, thymectomized NOD mice, unlike their euthymic counterparts, were not protected long-term by treatment with YTS 105, and began to become overtly diabetic shortly after treatment. This was also true when the nd anti-CD4 mAb was used. Protection from spontaneous disease was not affected in the same way by thymectomy. The reasons for the observed effect of the thymus in the transfer model, and the differences between the two models that may explain the contrasting results are discussed.     

Low postoperative hematocrit increases cerebrovascular damage after hypothermic circulatory arrest.

OBJECTIVE: The objective of this study was to evaluate the systemic and cerebral effects of different postoperative hematocrit management following cardiopulmonary bypass and deep hypothermic circulatory arrest. DESIGN: Animal case study. SETTING: Laboratory. SUBJECTS: Four-week-old Yorkshire piglets. INTERVENTIONS: Twelve piglets were subjected to cardiopulmonary bypass (hematocrit = 25%) and 100 mins of deep hypothermic circulatory arrest (15 degrees C). After weaning cardiopulmonary bypass, they were randomized to either group L or H, in which the postoperative hematocrit was maintained approximately 20% vs. approximately 30%, respectively, and survived for 6 hrs. MEASUREMENTS AND MAIN RESULTS: Changes in body weight, bioimpedance, and colloid oncotic pressure were assessed. Near-infrared spectroscopy and immunohistochemical assays for cerebral transforming growth factor-beta(1) and caspase-3 were performed. Postoperative weight gain (kg) and decreases in bioimpedance (ohms) were significantly less in group H (1.5 +/- 0.2 [H] vs. 2.4 +/- 0.6 [L], p = .01; 39.3 +/- 15.5 [H] vs. 89.1 +/- 29.6 [L], p = .01). Mean colloid oncotic pressure (mm Hg) was significantly higher in group H (10.8 +/- 1.6 [H] vs. 8.2 +/- 0.8 [L], p = .01) at 6 hrs postoperatively. Oxyhemoglobin, oxidized cytochrome aa(3) (muM x differential path-length factor), and tissue oxygenation index (%) were significantly better in group H (65.7 +/- 31.8 [H] vs. -104.7 +/- 55.2 [L], p = .0001; 0.52 +/- 4.1 [H] vs. -12.8 +/- 6.1 [L], p = .0001, and 55.7 +/- 4.6% [H] vs. 45.3 +/- 6.4% [L], p = .004, respectively). Cerebral transforming growth factor-beta(1) and caspase-3 scores were significantly better in group H (3.0 +/- 0.6 [H] vs. 1.9 +/- 0.9 [L], p = .04 and 1.8 +/- 0.5 [H] vs. 3.2 +/- 0.8 [L], p = .02, respectively). Mean arterial pressure (mm Hg) was consistently higher with group H (94.7 +/- 13.0 [H] vs. 78.3 +/- 11.5 [L], p = .003) despite comparable central venous pressure ( approximately 11 mm Hg). CONCLUSIONS: Lower postoperative hematocrit was associated with increased fluid retention, lower perfusion pressure, and worse cerebrovascular injury following deep hypothermic circulatory arrest. Postoperative hematocrit management may have profound systemic and cerebral effects after deep hypothermic circulatory arrest and merits further investigation.     

Proactive telephone support provided to breastfeeding mothers of preterm infants after discharge: a randomised controlled trial

Aim

The aim was to evaluate the effectiveness of proactive telephone support provided to breastfeeding mothers of preterm infants after discharge from neonatal intensive care units (NICU).

Methods

Between March 2013 and December 2015, a randomised controlled trial was conducted at six NICUs across Sweden. At each NICU, a breastfeeding support team recruited, randomised and delivered the support to participating mothers. The intervention group received a daily proactive telephone call up to 14 days after discharge from the support team. The control group could initiate telephone contact themselves. Primary outcome was exclusive breastfeeding eight weeks after discharge. Secondary outcomes were maternal satisfaction with breastfeeding, attachment, quality of life and parental stress.

Results

In total, 493 mothers were randomised, 231 to intervention group and 262 to control group. There were no differences between the groups for exclusive breastfeeding, odds ratio 0.96, 95% CI 0.66–1.38, nor for maternal satisfaction with breastfeeding, attachment or quality of life. The intervention group reported significantly less parental stress than the controls, t = 2.44, 95% CI 0.03–0.23, effect size d = 0.26.

Conclusion

In this trial, proactive telephone support was not associated with increased exclusive breastfeeding prevalence eight weeks following discharge. However, intervention group mothers showed significantly lower parental stress.     

A Giant Ovarian Cyst in a Neonate

BackgroundAntenatally diagnosed abdominal cysts are common, and frequently are ovarian in origin, which usually regress spontaneously. Surgery is indicated in the infantile period in case of very large, persisting or symptomatic cysts. Many surgeons feel that watchful waiting can be justified in newborns with simple and complex cysts.CaseWe present a neonate with an ovarian cyst diagnosed antenatally by ultrasound (US) and showing persistent enlargement within 3 months after birth when reached a diameter of 13 cm. Assessment and treatment is described.ConclusionThe extremely large, non-resolving ovarian cysts in neonates present a major challenge for clinicians and should be treated by surgery to avoid complications. We advocate laparotomy and cystectomy when possible to avoid unnecessary loss of functional ovarian tissue.     

Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms

BACKGROUND: Most disability produced by psychotic illnesses, especially schizophrenia, develops during the prepsychotic period, creating a case for intervention during this period. However, only recently has it been possible to engage people in treatment during this phase. METHODS: A randomized controlled trial compared 2 interventions in 59 patients at incipient risk of progression to first-episode psychosis. We termed this group ultra-high risk to emphasize the enhanced risk vs conventional genetic high-risk studies. Needs-based intervention was compared with specific preventive intervention comprising low-dose risperidone therapy (mean dosage, 1.3 mg/d) and cognitive behavior therapy. Treatment was provided for 6 months, after which all patients were offered ongoing needs-based intervention. Assessments were performed at baseline, 6 months, and 12 months. RESULTS: By the end of treatment, 10 of 28 people who received needs-based intervention progressed to first-episode psychosis vs 3 of 31 from the specific preventive intervention group (P=.03). After 6-month follow-up, another 3 people in the specific preventive intervention group became psychotic, and with intention-to-treat analysis, the difference was no longer significant (P=.24). However, for risperidone therapy-adherent patients in the specific preventive intervention group, protection against progression extended for 6 months after cessation of risperidone use. CONCLUSIONS: More specific pharmacotherapy and psychotherapy reduces the risk of early transition to psychosis in young people at ultra-high risk, although their relative contributions could not be determined. This represents at least delay in onset (prevalence reduction), and possibly some reduction in incidence.     

Energy balance during an ironman triathlon in male and female triathletes

Energy balance of 10 male and 8 female triathletes participating in an Ironman event (3.8-km swim, 180-km cycle, 42.2-km run) was investigated. Energy intake (EI) was monitored at 7 designated points by dietary recall of food and fluid consumption. Energy expenditure (EE) during cycling and running was calculated using heart rate-VO, regression equations and during swimming by the multiple regression equation: Y = 3.65v+ 0.02W- 2.545 where Yis VO,in L x min(-1), v is the velocity in m s(-1), Wis the body weight in kilograms. Total EE (10,036 +/- 931 and 8,570 +/- 1,014 kcal) was significantly greater than total EI (3,940 +/- 868 and 3,115 +/- 914 kcal, p <.001) for males and females, respectively, although energy balance was not different between genders. Finishing time was inversely related to carbohydrate (CHO) intake (g x kg(-1) x h(-1)) during the marathon run for males (r = -.75,p <.05), and not females, suggesting that increasing CHO ingestion during the run may have been a useful strategy for improving Ironman performance in male triathletes.     

Deaths from drugs of abuse in Sheffield 1997-1999: what are the implications for GPs prescribing to heroin addicts?

OBJECTIVE: Our aim was to examine the characteristics of drug abuse deaths in Sheffield between 1997 and 1999 with particular attention on the role of prescribed medication and the impact of increased methadone prescribing. METHODS: Information was made available on all deaths reported to the City of Sheffield Coroner between 1 January 1997 and 31 December 31 1999. These records were searched to identify individuals who died from a 'drug of abuse'-related poisoning. RESULTS: A total of 82 drug of abuse-related deaths occurred in Sheffield during the 3-year period. The number of deaths rose from 16 in 1997 to 34 in 1999 (112%), with the largest increase occurring between 1997 and 1998. The mean age over the period of study was 29.4 years (SD 7.5 years), the overwhelming majority of which were male (92%), single (89%) and unemployed (84%). Heroin on its own or in combination with other drugs was considered to be responsible for death in 70% of all cases. Deaths attributable either wholly or partially to methadone poisoning fell from 37% in 1997 to 18% in 1999. CONCLUSIONS: Given that the proportion of deaths involving methadone over this period fell against a background of increased prescribing, then it would appear that the availability of methadone is not a factor involved in the increase in the number of drug of abuse-related deaths in this study.     

What is this thing called hormone replacement therapy? Discursive construction of medication in situated practice

The use of hormone replacement therapy (HRT) involves complex decisions for mid-aged women owing to controversy about the meaning of menopause and uncertainty regarding risks and benefits. Qualitative studies show that women can hold apparently contradictory beliefs, for example, both resisting and relying on medicalization. Focus group data (48 participants) and discourse analysis theorizing were used to investigate the complex discursive field available to women to construct HRTand to explain apparent contradictions. Interpretative repertoires identified in this study (threatening change, natural, biomedical, and drug) support previous findings. It is not contradictory to use different repertoires to achieve different discursive acts. The application of these findings to the development of decision tools that help women to arrive at individually appropriate decisions is discussed.     

Integrating HIV prevention and care services: the Seattle "Collaboration Project".

The "Collaboration Project" explored whether human immunodeficiency virus (HIV) prevention providers in Seattle-King County refer their HIV+ clients into care services and whether HIV care service providers discuss sex and drug use risk reduction or make referrals for clients with ongoing risk reduction needs. Data uncovered demographic disparities between provider populations that may impact cross-system collaboration, particularly regarding provider demographic reflectiveness of the consumers being served. Ninety percent of prevention providers referred clients to care services; only one quarter discussed sexual risk reduction, while half discussed drug use risk reduction. Knowledge of cross-system resources was generally high, although gaps emerged between providers in several resource areas. Based on these findings, several key changes have been implemented.