Intravenous cyclophosphamide is the drug of choice for steroid dependent nephrotic syndrome

BACKGROUND: Steroid dependency is a major problem seen after therapy for idiopathic nephrotic syndrome in childhood. Although there is consensus about the usage of cyclophosphamide (CYC) in frequent relapsers, there is still a controversy concerning its usage in steroid-dependent nephrotic syndrome (SDNS). METHODS: In the present study, nineteen children with SDNS were treated with CYC: ten via the intravenous (i.v.) route, and nine via the oral route. Remission was then maintained with prednisolone. Oral CYC therapy consisted of CYC at a dose of 2 mg/kg per day for 12 weeks. Intravenous (i.v.) CYC therapy consisted of CYC 500 mg/m2 per month (with intravenous 3500 cc/m2 per 24 h one-third saline hydration) for 6 months. RESULTS: The cumulative dose of CYC was 168 mg/kg in the oral group and 132 mg/kg in the IV group. Daily oral CYC dose was 1.96~0.31 mg/kg, whereas i.v. CYC dose was 0.73~0.03 mg/kg. Long-term complications and side-effects such as alopecia, infection and hemorrhagic cystitis were not observed in the i.v. CYC treated group. In the long term, the dosage of prednisolone that held remission after CYC, the annualized relapse rates and the subsequent relapse time were significantly better in the i.v. CYC group, and the number of patients in remission for 2 years was significantly higher in the i.v. treated group (P<0.05). CONCLUSIONS: In SDNS, i.v. CYC has a long lasting effect with lower annualized relapse rates and longer subsequent relapse time with a lower steroid dosage required to maintain remission than oral CYC. The results of the present study showed the safety of the i.v. route, and it is the preferable treatment in noncompliant patients for its long lasting remission and simple and inexpensive follow up.     

Analysis of the Intracellular Transport Properties of Recombinant La Crosse Virus Glycoproteins

The G1 and G2 glycoproteins of La Crosse virus, a member of theBunyavirusgenus of the Bunyaviridae, are encoded as a single open reading frame (ORF) in the viral middle-sized RNA segment. The primary product from this ORF is processed, either cotranslationally or shortly after translation, into the two glycoproteins and a nonstructural protein, NSm, of unknown function. We have expressed La Crosse glycoproteins using vaccinia vectors and studied their processing and localization. When expressed in the native G2-NSm-G1 configuration, both G1 and G2 targeted to the Golgi apparatus as shown by their colocalization with wheat germ agglutinin and acquired resistance to endoglycosidase H. When expressed independently, G2 was targeted to the Golgi apparatus but G1 was retained in the endoplasmic reticulum, indicating that a G1–G2 association is required for Golgi targeting of G1. In contrast to results with other members of the Bunyaviridae, we found that expression of G1 and G2 from separate vectors did not lead to the transport of the G1–G2 complex to the Golgi. However, disruption of the NSm region with a foreign sequence did not interfere with transport of the complex. When a portion of the β-galactosidase gene was inserted in frame into NSm, the glycoproteins derived from this construct were processed and targeted properly and were capable of mediating cell-to-cell fusion.     

MATERNAL DIET AND FATTY ACID PATTERN OF BREAST MILK

ABSTRACT. The effect of habitual maternal diet on the fatty acid composition of breast milk was evaluated by conducting a dietary survey of lactating mothers and by analyzing their breast milk samples. The mean energy intake of the mothers was 9.8 MJ during the first survey week (20 mothers, 6-8 weeks post partum) and 8.6 MJ during the second survey week (13 mothers, 17-22 weeks post partum). Protein, fat and carbohydrate intake comprised 16%, 39% and 45% of the total energy intake, respectively. The breast milk samples contained 3.8% fat. Half of the fatty acids of the diets and breast milk were saturated (S), and one third were monoenoic. Polyunsaturated (P) fatty acids comprised 15% in the diets and 13% in the breast milk. The average P/S ratio was 0.3 both in the diets and breast milk samples. Carbohydrate intake correlated negatively ( p <0.05) with arachidic acid of breast milk, and both protein and fat intakes correlated positively ( p <0.05) with palmitic acid of breast milk. The maternal diet had no effect on the total fat content of breast milk. A positive correlation was found between the saturated ( p <0.05) and polyunsaturated ( p <0.01) fatty adds of maternal diet and breast milk. As to the single fatty acids, the only significant correlation was found with linoleic acid ( p <0.01). However, the variation of linoleic acid intake explained only about 27% of the variation occurring in the breast milk.     

Characterization of Sinoatrial Parasympathetic Innervation in Humans

INTRODUCTION: The response to sinoatrial parasympathetic nerve stimulation (shortened atrial refractoriness) was used to determine the atrial distribution of these nerve fibers in humans. We hypothesized that, in humans, parasympathetic nerves that innervate the sinoatrial node also innervate the right atrium and that the greatest density of innervation is near the sinoatrial nodal fat pad. METHODS AND RESULTS: Temporary epicardial wire electrodes were sutured in pairs in the sinoatrial nodal fat pad, high right atrium, and right ventricle by direct visualization during coronary artery bypass surgery in nine patients. Appropriate electrode placement was confirmed by electrically stimulating the fat pad in the operating room to prolong sinus cycle length by 50%. Experiments were performed in the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial stimulation was performed via an endocardial electrode catheter advanced to the right atrium. The catheter tip electrode was moved in 1-cm concentric zones around the epicardial wires by fluoroscopic guidance. Atrial refractoriness was determined in the presence and absence of sinoatrial parasympathetic nerve stimulation at each catheter site. In 8 of 9 patients, parasympathetic nerve stimulation reproducibly prolonged sinus cycle length by 50%. There was no effect on AV nodal conduction (no prolongation of PR interval) and no change in AV nodal refractoriness. Atrial effective refractory periods reproducibly shortened in response to parasympathetic nerve stimulation in 1-cm zones up to 3 cm surrounding the fat pad, by a mean (+/- SEM) of 26.6+/-4.3 msec (zone 1), 11.4+/-1.8 msec (zone 2), and 10.0+/-2.5 msec (zone 3), respectively (P = 0.0001). At distances > 3 cm from the fat pad, the effective refractory period did not shorten. CONCLUSION: Stimulation of parasympathetic nerves that innervate the sinoatrial node shortened atrial refractoriness in humans.     

Long-term proton pump inhibitor use is a risk factor for mortality in patients hospitalized for COVID-19

Background and aimThe aim of this study is to evaluate whether the long-term (≥4 weeks) use of proton pump inhibitors (PPIs) is a risk factor for intubation requirement and mortality in patients hospitalized for COVID-19.Materials and methods In this multicentric retrospective study, a total of 382 adult patients (≥18 years of age) with confirmed COVID-19 who were hospitalized for treatment were enrolled. The patients were divided into two groups according to the periods during which they used PPIs: the first group included patients who were not on PPI treatment, and the second group included those who have used PPIs for more than 4 weeksResultsThe study participants were grouped according to their PPI usage history over the last 6 months. In total, 291 patients did not use any type of PPI over the last 6 months, and 91 patients used PPIs for more than 4 weeks. Older age (HR: 1.047, 95% CI: 1.026–1.068), current smoking (HR: 2.590, 95% CI: 1.334–5.025), and PPI therapy for more than 4 weeks (HR: 1.83, 95% CI: 1.06–2.41) were found to be independent risk factors for mortalityConclusionThe results obtained in this study show that using PPIs for more than 4 weeks is associated with negative outcomes for patients with COVID-19. Patients receiving PPI therapy should be evaluated more carefully if they are hospitalized for COVID-19 treatment.     

Nonsurgical Treatment Modalities for Primary Cutaneous Malignancies

BACKGROUND Various modalities have been available to treat primary cutaneous malignancies. Although not indicated for certain aggressive tumors, many of the newest regimens involve noninvasive techniques. It behooves both the nonsurgeon and the surgeon alike to be apprised of all treatment options, their indications, and their efficacy.
OBJECTIVE The objective was to review the indications and published data on various nonsurgical treatment options for primary cutaneous malignancy.
METHODS AND MATERIALS This study is a literature review.
CONCLUSIONS Many nonsurgical treatment options exist for primary cutaneous malignancies. In determining which modalities to implement, consideration must be given to careful patient selection, tumor type, and appropriate expectations. Additionally, adjunctive/combination therapy may be used before or after surgery.