Heat Sink Effect on Tumor Ablation Characteristics as Observed in Monopolar Radiofrequency,Bipolar Radiofrequency,and Microwave,Using Ex Vivo Calf Liver Model

Thermal ablation of liver tumors near large blood vessels is affected by the cooling effect of blood flow, leading to incomplete ablation. Hence, we conducted a comparative investigation of heat sink effect in monopolar (MP) and bipolar (BP) radiofrequency ablation (RFA), and microwave (MW) ablation devices.With a perfused calf liver, the ablative performances (volume, mass, density, dimensions), with and without heat sink, were measured. Heat sink was present when the ablative tip of the probes were 8.0 mm close to a major hepatic vein and absent when >30 mm away. Temperatures (T1 and T2) on either side of the hepatic vein near the tip of the probes, heating probe temperature (T3), outlet perfusate temperature (T4), and ablation time were monitored.With or without heat sink, BP radiofrequency ablated a larger volume and mass, compared with MP RFA or MW ablation, with latter device producing the highest density of tissue ablated. MW ablation produced an ellipsoidal shape while radiofrequency devices produced spheres.Percentage heat sink effect in Bipolar radiofrequency : Mono-polar radiofrequency : Microwave was (Volume) 33:41:22; (mass) 23:56:34; (density) 9.0:26:18; and (relative elipscity) 5.8:12.9:1.3, indicating that BP and MW devices were less affected.Percentage heat sink effect on time (minutes) to reach maximum temperature (W) = 13.28:9.2:29.8; time at maximum temperature (X) is 87:66:16.66; temperature difference (Y) between the thermal probes (T3) and the temperature (T1 + T2)/2 on either side of the hepatic vessel was 100:87:20; and temperature difference between the (T1 + T2)/2 and temperature of outlet circulating solution (T4), Z was 20.33:30.23:37.5.MW and BP radiofrequencies were less affected by heat sink while MP RFA was the most affected. With a single ablation, BP radiofrequency ablated a larger volume and mass regardless of heat sink.     

Increased Morbidity and Mortality of Emergency Laparotomy in Elderly Patients

Background

There is an increasing incidence of elderly patients requiring emergency laparotomy. Our study compares the outcomes of elderly patients undergoing emergency laparotomy against the outcomes of non-elderly patients.

Methodology

Patients who underwent emergency laparotomy between 2015 and 2017 from the National University Hospital, Singapore, were included. Apart from demographic data, indication of surgery and surgical procedure performed were collected. Prospectively collected nutritional scores were evaluated. Outcome measures included duration of surgery, length of ICU and total hospital stay, post-operative complications, and mortality indices. We performed multivariate Cox regression analysis to determine the contribution of various risk factors towards overall survival following emergency laparotomy.

Results

A total of 170 emergency laparotomies were performed. Compared to non-elderly patients, elderly patients had a significantly longer mean stay in hospital (31.5 vs. 18.6 days, p = 0.006) and mean stay in ICU (13.1 vs. 5.3 days, p = 0.003). More elderly patients suffered from post-laparotomy complications compared with non-elderly patients (65.8% vs. 37.4%, p < 0.001). 30-day mortality (31.5% vs. 8.8%, p = 0.019) and 1-year mortality (27.9% vs. 14.3%, p = 0.023) were higher in elderly patients compared with non-elderly patients. Interestingly, there was no statistically significant difference between elderly and non-elderly groups in both the global 3-MinNS as well as the global SGA nutritional scores. ASA status (HR 2.61, 95% CI 1.05–6.45, p = 0.038) was an independent risk factor for decreased survival following emergency laparotomy. Notably, while age ≥ 65 demonstrated a significant correlation with survival on univariate analysis (HR 1.03 (1.01–1.05), p = 0.003), this effect was lost following multivariate regression (HR 1.01 (0.453–2.23), p = 0.989).

Conclusion

Elderly patients suffer worse morbidity and mortality following emergency laparotomy. This is likely contributed by comorbidities resulting in higher ASA status.

     

PINK1 mutations in sporadic early-onset Parkinson's disease.

Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.     

Food deprivation and hypothalamic neuropeptide gene expression: effects of strain background and the diabetes mutation.

We have used a novel method to identify genes expressed in the hypothalamus which may be potentially involved in controlling food intake and energy metabolism. We assumed that food deprivation, a powerful stimulus of food intake, would stimulate the activity of neural pathways involved in feeding behavior which should be reflected in an increase in the synthesis of any relevant neuropeptide and its messenger RNA. A study of 5 neuropeptides in 5 strains of mice has identified neuropeptide Y (NPY) as a gene whose expression in the hypothalamus is controlled by nutritional status, suggesting that hypothalamic NPY neurons are a link in the neural network regulating feeding behavior and energy metabolism. In addition, we have studied the effect of the diabetes mutation on neuropeptide gene expression during fasting and refeeding. Our findings suggest that abnormal NPY and enkephalin gene expression in the hypothalamus may be two important determinants of the expression of the diabetes mutation.     

Food deprivation and age modulate neuropeptide gene expression in the murine hypothalamus and adrenal gland.

We have developed a rapid and simple method for quantitative Northern blot analysis of rare messenger RNA species from single mouse hypothalami and adrenals. This technique has allowed us to study the effects of food deprivation on neuropeptide gene expression in the mouse hypothalamus and adrenal gland. The potential modulatory effects of sex and age were also investigated. Food deprivation induced a two-fold increase in the amount of hypothalamic neuropeptide Y (NPY) mRNA, but did not increase NPY mRNA in the brainstem. Age had a significant effect on levels of NPY messenger RNA levels in the hypothalamus. However, there were no gender-associated effects. Sexually immature females (6 weeks old) had higher levels of NPY expression than mature females (9 weeks old). In contrast, in the adrenal gland, increasing maturity was associated with higher levels of NPY mRNA. As in the hypothalamus, fasting caused approximately two-fold increases in NPY mRNA over levels in the ad libitum fed state for both mature and immature mice. Thus, hypothalamic NPY neurons are responsive to nutritional deprivation and developmental status, suggesting that NPY neurons may be important in energy homeostasis.     

Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

The aim of the study was to determine whether a prior diagnostic testicle biopsy can predict success or failure of testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI) in patients with non-obstructive azoospermia caused by testicular failure, and what is the minimum threshold of sperm production in the testis which must be surpassed for spermatozoa to reach the ejaculate. Forty- five patients with non-obstructive azoospermia caused by testicular failure underwent diagnostic testicle biopsy prior to a planned future TESE-ICSI procedure. The diagnostic testicle biopsy was analysed quantitatively, and correlated with the quantitative findings of spermatogenesis in patients with normal spermatogenesis, as well as with the results of subsequent attempts at TESE-ICSI. Men with non- obstructive azoospermia caused by germinal failure had a mean of 0-6 mature spermatids/seminiferous tubule seen on a diagnostic testicle biopsy, compared to 17-35 mature spermatids/tubule in men with normal spermatogenesis and obstructive azoospermia. These findings were the same for all types of testicular failure whether Sertoli cell only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia. Twenty-two of 26 men with mature spermatids found in the prior testis biopsy had successful retrieval of spermatozoa for ICSI, 12 of their partners became pregnant, and are either ongoing or delivered. The study suggests that 4-6 mature spermatids/tubule must be present in the testis biopsy for any spermatozoa to reach the ejaculate. More than half of azoospermic patients with germinal failure have minute foci of spermatogenesis which are insufficient to produce spermatozoa in the ejaculate. Prior diagnostic testicle biopsy analysed quantitatively (for the presence of mature spermatids) can predict subsequent success or failure with TESE-ICSI. Incomplete testicular failure may involve a sparse multi-focal distribution of spermatogenesis throughout the entire testicle, rather than a regional distribution. Therefore, it is possible that massive testicular sampling from many different regions of the testes may not be necessary for successful TESE-ICSI.      

Adhesion inhibitory activity of β-lactoglobulin isolated from infant formulae

β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis.     

Distinctive immunoglobulin E anti-house dust allergen-binding specificities in a tropical Australian Aboriginal community

BACKGROUND: There is evidence that the specificity of the IgE binding in allergy tests can vary for different populations. OBJECTIVE: We aimed to examine the allergenic specificity of IgE binding in sera from house dust mite (HDM)-atopic subjects in a tropical Australian Aboriginal community. METHODS: Sera shown to contain IgE antibodies to an HDM extract of Dermatophagoides pteronyssinus were examined for IgE binding to a panel of nine purified HDM allergens from this mite species by quantitative microtitre assays. IgG antibody binding (IgG1 and IgG4) was also measured. RESULTS: The IgE-binding activity in the sera from the Aboriginal community was not directed to the expected major groups 1 and 2 HDM allergens but instead to the group 4 amylase allergen. There was also little IgE binding to the potentially cross-reactive tropomyosin (Der p 10) or arginine kinase (Der p 20) allergens. The IgG4 antibody was rarely detected and limited to the Der p 4 allergen. IgG1 antibody binding was frequently measured to all the allergens regardless of an individual's atopic status, whereas in urban communities it is restricted to the major allergens and to atopic subjects. CONCLUSION: The high IgE anti-HDM response of Australian Aboriginals predominantly bound Der p 4 and not the Der p 1 and 2 allergens, showing a distinctive allergy that could affect the disease outcome and diagnosis.