Vascular endothelial growth factor response with propranolol therapy in patients with infantile hemangioma.

Vascular endothelial growth factor-A (VEGF-A) is a master regulator of angiogenesis, with higher levels in infantile hemangioma (IH). The effects of propranolol on IH are not fully understood and may involve vasoconstriction, angiogenesis inhibition, and apoptosis induction. Therefore, we examined the effects of propranolol therapy on levels of VEGF-A in patients with IH in the proliferative phase and compared the VEGF-A levels to those in untreated patients in the involuting or involuted phases, as well as studied the consistency between the clinical and VEGF responses in patients receiving treatment. In a prospective study, we compared 24 patients with IH in the proliferative phase to 9 patients with IH in the involuting or involuted phase, assessing clinical responses to therapy and changes in VEGF-A levels after 3 months. The median VEGF level before treatment was 275 pg/ml; however, after 3 months, the level significantly decreased to 100 pg/ml (P = 0.007). Median VEGF was significantly higher in patients in the proliferative phase after 3 months of treatment (100 pg/ml) as compared to those in the involuting phase (50 pg/ml). We found no significant correlation between VEGF level and IH size reduction. Propranolol therapy induced a significant decline in VEGF levels at the 3-month evaluation in patients in the proliferative phase; however, this did not reach the levels of IH in the involuting phase. VEGF response was not translated to a clinical response in some patients with IH. These results put in uncertainty the clinical benefit of targeting VEGF pathway in IH.

Altered regulation of hepatic efflux transporters disrupts acetaminophen disposition in pediatric nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, representing a spectrum of liver pathologies that include simple hepatic steatosis and the more advanced nonalcoholic steatohepatitis (NASH). The current study was conducted to determine whether pediatric NASH also results in altered disposition of acetaminophen (APAP) and its two primary metabolites, APAP-sulfate and APAP-glucuronide. Pediatric patients with hepatic steatosis (n = 9) or NASH (n = 3) and healthy patients (n = 12) were recruited in a small pilot study design. All patients received a single 1000-mg dose of APAP. Blood and urine samples were collected at 1, 2, and 4 hours postdose, and APAP and APAP metabolites were determined by high-performance liquid chromatography. Moreover, human liver tissues from patients diagnosed with various stages of NAFLD were acquired from the Liver Tissue Cell Distribution System to investigate the regulation of the membrane transporters, multidrug resistance-associated protein 2 and 3 (MRP2 and MRP3, respectively). Patients with the more severe disease (i.e., NASH) had increased serum and urinary levels of APAP-glucuronide along with decreased serum levels of APAP-sulfate. Moreover, an induction of hepatic MRP3 and altered canalicular localization of the biliary efflux transporter, MRP2, describes the likely mechanism for the observed increase in plasma retention of APAP-glucuronide, whereas altered regulation of sulfur activation genes may explain decreased sulfonation activity in NASH. APAP-glucuronide and APAP-sulfate disposition is altered in NASH and is likely due to hepatic membrane transporter dysregulation as well as altered intracellular sulfur activation.

The interplay between vitamin D and COVID-19: protective or bystander?

The world is currently facing the COVID-19 pandemic, caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Due to a lack of specific treatment and prophylaxis, protective health measures that can reduce infection severity and COVID-19 mortality are urgently required. Clinical and epidemiological studies have shown that vitamin D deficiency can be linked to an increased risk of viral infection, including COVID-19. Therefore, in this review, we looked at various possible roles of vitamin D in reducing the risk of COVID-19 infection and severity. We describe in this article that individuals at high risk of vitamin D deficiency should consider taking vitamin D supplements to keep optimal concentrations. Moreover, we discuss different possible mechanisms by which vitamin D can efficiently reduce the risk of infections through modulation of innate and adaptive immunity against various types of infections. It is advisable to perform further studies addressing the observed influence of vitamin D levels to reduce the risk of COVID-19 infection and mortality.

Postmastectomy radiotherapy reduces locoregional recurrence in elderly women with high-risk breast cancer.

AIMS: Clinical trials of adjuvant radiotherapy after mastectomy have largely excluded women aged 70 years or over, even though they comprise 30% of the breast cancer population. This study examined outcomes in elderly women with high-risk breast cancer treated with or without postmastectomy radiotherapy (PMRT). MATERIALS AND METHODS: Data were analysed for 233 women aged 70 years or over with high-risk breast cancer (tumours > 5 cm or > or = 4 positive axillary nodes) treated with mastectomy and referred to the British Columbia Cancer Agency from 1989 to 1997. Tumour and treatment characteristics were compared between two cohorts: women treated with PMRT (n = 147) vs women treated without PMRT (n = 86). Univariate and multivariate analyses of 10-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence, breast cancer-specific survival and overall survival were carried out. RESULTS: Median follow-up time was 5.5 years. The distribution of tumour sizes was similar in the two groups. Compared with women treated without PMRT, higher proportions of women who underwent PMRT had four or more positive nodes (83% vs 67%, P = 0.01) and positive surgical margins (14% vs 4%, P = 0.02). Systemic therapy, used in 94% of women, was comparable in the two cohorts (P = 0.63). Elderly women treated with PMRT had significantly lower LRR compared with women treated without PMRT (16% vs 28%, P = 0.03). No differences in distant recurrence, breast cancer-specific survival or overall survival were observed in the two treatment groups (all P > 0.05). On multivariate analysis, the omission of PMRT and the presence of high-grade histology were significant predictors of LRR, whereas an increasing number of positive nodes was significantly associated with distant recurrence and overall survival. CONCLUSIONS: In women aged 70 years or over with tumours greater than 5 cm or four or more positive nodes, significantly lower LRR was observed in women treated with radiotherapy compared with women treated without radiotherapy. PMRT should be considered in the management of elderly women with these high-risk characteristics.

Changes in human milk vitamin E and total lipids during the first twelve days of lactation.

Our previous study showed vitamin E deficiency in newborns (69.7%) and mothers at term (85.9%) when the ratio between serum vitamin E in mg/dl and total lipids in g/dl was used as an indicator of vitamin E status. This study was conducted to determine the human milk content of vitamin E. During the first 12 days of lactation milk vitamin E levels remained almost constant (day 1, 0.68 mg/dl; day 12, 0.65 mg/dl), milk total lipid levels increased daily (day 1, 1.11 g/dl; day 12, 3.60 g/dl), and the ratio between milk vitamin E and total lipids dropped steadily (day 1, 1.3; day 12, 0.2). In spite of this drop in vitamin E status, it is unlikely that vitamin E availability will be affected in neonates, because normal neonates absorb milk fats well and this ability increases with age.

Follicle stimulating hormone levels as a predictor of recovery of spermatogenesis following cancer therapy.

Infertility, both temporary and permanent, is a well-recognized complication of certain cancer treatments. The main objective of this study was to determine whether recovery of fertility in male patients, could be predicted by monitoring changes in serum follicle stimulating hormone (FSH) levels. Twenty male patients participated in the study. Sperm counts and serum FSH levels were measured before, during and after treatment. Azoospermia was universal in all 20 patients during the first year, with significantly raised FSH in almost all the patients. Reduction of FSH levels during the second year was frequently followed by recovery of spermatogenesis. Patients in whom the FSH did not fall during the second year were highly unlikely to regain fertility.

Pulmonary complications of bone marrow transplantation: the impact of variations in total body irradiation parameters.

In this article we report and discuss the pulmonary complications in patients who received a single exposure total body irradiation (TBI) to a total dose of 7.5 Gy at a dose rate of 0.15 Gy/min, a TBI regimen which has the advantage of being given in a single, relatively short exposure, with an active treatment time of less than 1 hour. This forms a part of the bone marrow transplantation programme for the management of certain haematological malignancies at the Leicester Regional Centre. Between July 1986 and October 1990, we treated 31 patients with such a regimen. Full respiratory function tests (RFT) were carried out, prior to TBI, in the majority of patients. After a mean follow-up period of 34 months, 13 patients were alive; full RFT were repeated in all of them. Of the total of 31 patients, only one patient died, from late non-specific pneumonitis; in this case, high dose busulphan was added to conventional cyclophosphamide and TBI. Another patient died as a direct result of cytomegalovirus pneumonia. Comparison of pre- and post-TBI RFT showed no resultant obstructive, restrictive or transfer factor defects. In the three patients who did not have pre-TBI RFT, post-TBI RFT did not reveal any significant change from expected values for age, sex and height. Several major centres have reported their experience using various combinations of different total doses, dose rates and fractionations. Having compared our results with theirs, we conclude that, following this relatively short and convenient single exposure TBI, there is no evidence of increased acute or chronic pulmonary toxicity.

New methods for assessing liver function in infants and children.

Assessment of liver function in infants and children has traditionally relied on static indices of hepatic structure, cellular integrity, or function and are often based on the release of substances from damaged tissues. There has been a rapid development of dynamic tests based on the measurement of substances metabolized or cleared from blood by the liver. These tests, which have been touted to offer a more precise quantitative estimation of hepatic functional capacity, include the measurement of serum bile acids and the hepatic metabolism of xenobiotic compounds such as caffeine and lidocaine. Serum bile acid measurements appear to be reliable indicators of enterohepatic circulation and may be useful in screening for liver disease. It has been observed that caffeine metabolism is decreased in patients with various forms of liver disease in correlating with disease status. Caffeine has the advantage of being well tolerated when administered orally; the saliva level parallels the serum concentration, making a non-invasive test feasible. Lidocaine is metabolized by oxidative de-ethylation to monoethylglycinexylide (MEGX); analysis of MEGX by common laboratory instrumentation makes rapid evaluation of liver function possible. The MEGX values correlated were with pretransplant liver disease assessment. These tests are currently being evaluated at other centers and, if the initial studies are repeated, they offer the hope for reliable dynamic tests of hepatic function.

Study of referral process between general practitioners and specialists in health insurance clinics in Alexandria.

The present study was designed to investigate the reasons for which patients are referred by G.Ps to G.M. specialists, and to assess the extent to which referred cases need specialist care. The study sample included specialists of general medicine working at 4 of the H.I.O. polyclinics and all G.Ps who referred cases that were considered as inappropriate referrals by the study specialists, as well as 20% of Patients referred to G.M. specialists by G.Ps. were systematically randomly selected during a period of 10 consecutive days. The results indicated that the rate of inappropriate referral to G.M. specialists was high, the rate of discrepancy between G.P. and specialist diagnoses was generally high, there was a high discrepancy between G.Ps and specialists regarding the reason for inappropriate referral, and there was poor communication from the lower (G.P.) to the higher (specialists) levels in the referral process. Reasons for referral to specialists were not recorded by G.Ps in 100% of cases. To overcome these problems H.I.O. should place special emphasis on the professional training and continuing education of G.Ps, with special attention to the few common conditions that were responsible for the greater proportion of referral problems. At the same time, H.I.O. should strengthen the technical and administrative control over G.P. referral behavior.

Study of workload of general medicine specialists working in the health insurance clinics.

This study was conducted at 4 of the H.I.O. polyclinics in Alex. with the objective of examining the change in visit rate per 1000 beneficiaries for general medicine specialty at H.I.O. clinics during a 4-year period (1985-1988) and to detect any trends that may have a bearing on the H.I.O. standards for supply of specialists. Data were collected from H.I.O. statistics department, H.I.O. regulations, and also through researcher's observation and specialists' interview. The collected data was used to describe the workload in terms of annual visit rate, actual number of working hours, the specialists' average production hours per day, the specialists' average idle time per day, the estimated number of required specialist working hours per day, and the specialists' recommended working hours per day. The results revealed a rising trend in the rate of use of general medicine specialist services and a definite shortage of supply of general medicine specialists was found in all clinics compared to H.I.O. standards. On the other hand, recommended supply based on specialist opinion was less than the H.I.O. standards but more than the current supply. Accordingly H.I.O. should re-estimate the specialist population standard and should seek the commitment of specialists to the revised standards.

Utilization of maternal health services offered by the Health Insurance Organization in Alexandria.

This study examines the extent of utilization of maternal health services (MHS) currently offered by Health Insurance Organization (HIO) in Alexandria. A total of 1040 insured married females working in primary, preparatory and secondary schools in three educational regions in Alexandria were interviewed. Data was collected about socio-economic status of females, their knowledge about MHS offered by HIO, as well as sources of receiving MHS other than HIO. Barriers preventing utilization of such services and recommendations for improvement were explored from beneficiaries. The results revealed that for the last pregnancy, about half the sample utilized antenatal services and about one fourth utilized natal services, while a very small percentage (8%) utilized family planning services. The private sector was the main source for receiving MHS for non-utilizer. Lack of confidence and low quality of services were the main barriers preventing utilization. Complete physical examination, examination of fetal heart sound and improvement of physical environment of obstetrics and gynecology department were the main recommendations for improvement of MHS offered by HIO.

Nonalcoholic fatty liver disease: a comprehensive review of a growing epidemic.

Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD.

Foreign body ingestion: children like to put objects in their mouth.

BACKGROUND: Foreign body ingestion is a common problem in the pediatric age group. Infants and young children explore objects by putting them in the mouth. DATA SOURCES: We reviewed the most recent literatures regarding the incidence, clinical presentation, as well as the most recent advances in the diagnostic and therapeutic modalities of foreign body ingestion in children. RESULTS: In 2007 more than 125 000 foreign body ingestions in patients of 19 years old and younger were reported to American Poison Control Centers in the USA. The majority of ingested foreign bodies pass spontaneously. CONCLUSIONS: Some foreign bodies can be harmful and require evaluation and intervention. The challenge in management is to distinguish the patients who require intervention from those who can be safely observed. In this review we suggest an algorithm for evaluation and management of children suspected to ingest a radiopaque foreign body.