SARS-CoV-2 Infection after Vaccination: A Comparative Profile between Dose 1 and Dose 2.

Since the initial shipment of vaccination campaign against SARS-CoV-2 infection, it was a major concern all over the world regarding appropriate gapping between the first and second dose and also the necessity of booster dose after being vaccinated with the second dose. This cross-sectional type of comparative study was conducted at Kuwait Bangladesh Friendship Government Hospital, from the period of March 01 2021 to August 31 2021, on 148 hospitalized patients who were vaccinated with Astra Zeneca. They were divided into two groups on the background of 1st dose and 2nd dose. Collected data were entered into SPSS-26 version and after data cleaning, descriptive analysis was done with frequency distribution. To find out the significant difference between the two groups considering clinico-demographic information, disease severity, and duration of the last dose of vaccine; the Pearson Chi-square test was done with a significance level ≤0.05. The patients from both groups were mostly male and above 60 years. There were no significant age or sex variations between the two groups. SARS-CoV-2 infection was common after 38 days of dose 1 and after 63 days of dose 2. Fever, cough, running nose, shortness of breath, fatigue, nausea, vomiting, lower oxygen saturation, radiological involvement were comparatively more in patients who got only a single dose. Mild pneumonia (70.7%) was the commonest presentation in both doses of vaccinated patients and single dose vaccinated patients mostly (45.5%) presented with severe pneumonia. Elderly clinically risks group patients were mostly hospitalized with infection after 1 month of the 1st dose and on the other hand after 2 months of completing the 2nd dose. Symptomatic infection and disease severity were more in 1st dose vaccine recipients in comparison to 2nd dose.

Reversal of warfarin anticoagulation using prothrombin complex concentrate at 25 IU kg-1 : results of the RAPID study.

BACKGROUND: Real-world studies of the emergency reversal of warfarin using 4-factor prothrombin complex concentrate (PCC) report unwarranted delays. The delay to receiving PCC was ≥ 8 h in 46·7% of patients with warfarin-associated bleeding (PWAB) treated with a variable PCC dosing protocol in our retrospective audit. OBJECTIVE: To report the impact of a simplified PCC dosing protocol on the interval to reversal of anticoagulation. METHODS: We developed a PCC dosing protocol standardising the initial PCC dose and simplifying dosing calculations. Study end points were the proportion of PWAB achieving international normalised ratio (INR) ≤1·5 and treated within 8 h of presentation, respectively. RESULTS: Of 17, 15 (88·2%) PWABs achieved a post-treatment INR ≤ 1·5; 14 of 17 (82·4%) PWABs were reversed within 8 h. Median intervals between triage and PCC request and PCC request and start of infusion (administration interval) were 126 min (range 39-520) and 30 min (range 5-100), respectively. Compared with the retrospective cohort, RAPID is associated with an improved administration interval (mean 37·7 vs 76 min, P = 0·031) and the proportion of PWABs treated within 30 min (58·8 vs 6·7%, P = 0·009). CONCLUSION: The RAPID protocol reduces unwarranted delays without compromising efficacy.

The involvement of gonadotropin inhibitory hormone and kisspeptin in the metabolic regulation of reproduction.

Recently, kisspeptin (KP) and gonadotropin inhibitory hormone (GnIH), two counteracting neuropeptides, have been acknowledged as significant regulators of reproductive function. KP stimulates reproduction while GnIH inhibits it. These two neuropeptides seem to be pivotal for the modulation of reproductive activity in response to internal and external cues. It is well-documented that the current metabolic status of the body is closely linked to its reproductive output. However, how reproductive function is regulated by the body's energy status is less clear. Recent studies have suggested an active participation of hypothalamic KP and GnIH in the modulation of reproductive function according to available metabolic cues. Expression of KISS1, the KP encoding gene, is decreased while expression of RFRP (NPVF), the gene encoding GnIH, is increased in metabolic deficiency conditions. The lower levels of KP, as suggested by a decrease in KISS1 gene mRNA expression, during metabolic deficiency can be corrected by administration of exogenous KP, which leads to an increase in reproductive hormone levels. Likewise, administration of RF9, a GnIH receptor antagonist, can reverse the inhibitory effect of fasting on testosterone in monkeys. Together, it is likely that the integrated function of both these hypothalamic neuropeptides works as a reproductive output regulator in response to a change in metabolic status. In this review, we have summarized literature from nonprimate and primate studies that demonstrate the involvement of KP and GnIH in the metabolic regulation of reproduction.

Acute fasting-induced repression of the hypothalamic-pituitary-gonadal axis is reversed by RF-9 administration in the adult male macaque.

Recently, hypothalamic RFRP-3 (a mammalian ortholog of avian GnIH) signaling has been proposed as an important negative modulator of the reproductive axis. The current study examined whether repression of reproductive hormonal expression during short-term fasting conditions in higher-order primate is influenced by altered RFRP-3 signaling. Eight intact postpubertal male macaques (Macaca mulatta) were administered a single intravenous bolus of RF-9 (n = 4), a potent and putative RFRP-3 receptor antagonist, or vehicle (n = 4) following a 48-h fasting condition. Intermittent blood samples were collected every 30 min during the 4-h post-bolus period, and blood glucose, plasma cortisol, and testosterone concentrations were measured. Relative to fed conditions, fasting reduced glucose and testosterone levels (p < 0.005) and increased cortisol levels (p < 0.05). Relative to baseline, mean testosterone levels were elevated 150 min after RF-9 (p < 0.05) but not vehicle administration. In addition, elevated mean plasma testosterone levels following RF-9 administration were equivalent to levels observed in normal fed monkeys. These results suggest an important role for RFRP-3 signaling in conveying metabolic state information to the reproductive axis in higher primates.

Primate HPT axis response to the peripheral kisspeptin challenge under different time periods of food restriction in monkeys.

Metabolism and reproduction are closely linked. Both long- and short-term fasting-induced metabolic deficiency suppresses reproductive function in mammals. Recently, we have shown that 48-h fasting-induced metabolic deficiency attenuates the reproductive axis responsiveness to peripheral kisspeptin injection in the sexually mature monkeys. But currently there is no data to show whether shorter time periods of fasting also alter the reproductive axis responsiveness to kisspeptin. Therefore, this study was aimed to examine the reproductive axis responsiveness to kisspeptin administration in the adult male rhesus monkey fasted for 12-, 18-, and 24h. Intravenous boli of vehicle (1 ml) and human kisspeptin-10 (KP10; 50 µg) were given to 5 intact sexually mature male rhesus monkeys in both fasting (12-, 18-, 24-h) and ad libitum feeding conditions. Specific immunoassays were used to determine plasma hormones concentrations. KP10 injection highly stimulated testosterone secretion in all conditions. However, mean testosterone concentrations in 3-h post-KP10 injection period were significantly (p<0.01) decreased in 18- and 24-h fasted monkeys when compared to 12-h fasted and fed monkeys. Moreover, 18- and 24-h fasting conditions also significantly (p<0.05) delayed the duration to the first significant increase in T levels after KP10 injection. Vehicle injection did not alter these parameters in any conditions. Present results indicate that 18- and 24-h fasting conditions suppressed the testosterone response to KP10 administration both in initiation and quantity. These results suggest that 18- and 24-h fasting-induced inhibition of the reproductive functions in the mature male macaque may partly involve attenuation in the reproductive axis responsiveness to endogenous kisspeptin stimulation.

Intratesticular action of kisspeptin in rhesus monkey (Macaca mulatta).

Kisspeptin-Kiss1R signalling in mammals has been implicated as an integral part of the reproductive cascade. Kisspeptinergic neurons upstream of GnRH neurons are involved in the activation of the hypothalamic GnRH pulse generator during pubertal onset. Thus, the major research focus has been on the central effects of kisspeptin. The demonstration of the presence of KissR expression in human testes suggests additional unknown actions of kisspeptin-KISS1R signalling at the distal component of the male reproductive axis. Here we explored the impact of kisspeptin at the testis in the adult male rhesus monkey. We employed the clamped monkey model to assess the intratesticular actions of kisspeptin. Plasma testosterone and LH levels were monitored in four adult male monkeys. The peripheral administration of human kisspeptin-10 (50 µg, iv bolus) caused a single LH pulse, which was followed by a robust increase in plasma testosterone levels sustained for at least 180 min. This response was abolished when kisspeptin was administered to GnRH receptor antagonist (acyline) pre-treated animals. However, kisspeptin administration significantly (P < 0.005) elevated hCG-stimulated testosterone levels in acyline pre-treated monkeys when compared with saline+ hCG treatment. These results revealed a novel peripheral facet of kisspeptin signalling.

Nosocomial infection surveillance in an Egyptian neonatal intensive care unit.

BACKGROUND: Nosocomial infections (NIs) have become a matter of major concern and an important cause of morbidity and mortality in neonatal intensive care units (NICUs). AIM: The objective of this study was to determine the incidence, anatomical sites and causative organisms of NI in an Egyptian NICU, and to assess the impact of NI on length of stay and mortality. METHODS: This was a descriptive hospital-based study carried out for 12 months in the NICU of the Mansoura University Children's Hospital. NI rates were calculated using different denominators (overall nosocomial infection rate, nosocomial infection incidence density, device-specific infection rates and device-days infection rates). FINDINGS: Of the 238 neonates evaluated, 49 developed 51 nosocomial infective episodes, equating to an incidence rate of 21.4% or 13.8 infections per 1000 bed-days. Pneumonia was the most frequently occurring infection (11.3%) followed by bloodstream infection (8.8%). The most frequently isolated organisms were Klebsiella spp. (33.3%) followed by Escherichia coli (21.6%). NIs were associated with prolonged hospital stay. CONCLUSION: NI is a significant problem in the Mansoura University Children's Hospital NICU. Gram-negative bacteria, especially Klebsiella spp., were the predominant causes of neonatal NI, as has been described in other studies from developing countries.

Differential response of the primate HPG axis to N-methyl-D, L-aspartate, but not to Kisspeptin challenge under euglycemic and hypoglycemic conditions.

Hypoglycemia inhibits the hypothalamic-pituitary-gonadal (HPG) axis by still incompletely deciphered mechanisms. Many evidences suggest that the hypoglycemia-induced inhibition of the HPG axis involves alteration of the hypothalamic gonadotropin-releasing hormone (GnRH) release, but neuroendocrine factors responsible for this alteration are yet to be completely elucidated. The current study was carried out to ascertain whether insulin-induced hypoglycemic suppression of the HPG axis involves modulation of responsiveness of the GnRH neuron to kisspeptin and excitatory amino acids (EAA) drives. Five intact chair-restraint habituated adult male rhesus monkeys (Macaca mulatta) were given intravenous boli of GnRH, hCG, human kisspeptin-10 (KP10), NMDA (N-methyl-D, L-aspartate, an EAA analogue), and vehicle in both insulin (1 IU/kg)-induced hypoglycemic (IIH) and normal euglycemic conditions. Specific RIAs were used for measuring plasma cortisol and T concentrations. KP10 and NMDA administration stimulated significantly (p<0.005) T secretion in both euglycemic and hypoglycemic monkeys. Mean post-KP10 T concentrations and AUC were comparable between euglycemic and hypoglycemic monkeys. However, mean post-NMDA T levels and AUC in hypoglycemic animals were significantly lower (p<0.01-0.005) as compared to the corresponding values in euglycemic animals. T response to GnRH and hCG was similar between hypoglycemic and euglycemic monkeys. Vehicle did not affect plasma T concentrations in all conditions. Our results demonstrate that while the primate HPG axis response to kisspeptin stimulation remains intact that to EAA excitation is attenuated in hypoglycemic conditions, suggesting that hypogonadism in IIH is contributed, in part, by reduced sensitivity of the GnRH neurons to EAA signaling in the primate hypothalamus.

Decrease in hypothalamic Kiss1 and Kiss1r expression: a potential mechanism for fasting-induced suppression of the HPG axis in the adult male rhesus monkey (Macaca mulatta).

Fasting suppresses functioning of the hypothalamic-pituitary-gonadal (HPG) axis by mechanisms that are incompletely understood. In 2003, hypothalamic kisspeptin-Kiss1r signaling was discovered to play a significant role in regulating the HPG axis. We have recently shown that in adult male macaques, short-term fasting attenuates the response of the HPG axis to an exogenous kisspeptin challenge. In the present study, we explored the mechanism underlying this attenuated response by examining the modulation of the hypothalamic expression of KISS1 and KISS1R under short-term fasting and normal feeding conditions in the adult male macaques. Hypothalamic mRNA was extracted from normal fed (n=3) and 48-h fasted (n=3) monkeys. KISS1, KISS1R, and GNRH1 mRNA were quantified by reverse transcription followed by real-time polymerase chain reaction. In addition, blood samples were collected for measurement of plasma concentrations of glucose, cortisol, leptin, and testosterone. In contrast to fed animals, plasma glucose, leptin, and testosterone levels decreased and cortisol levels increased in fasted animals. The hypothalamic expression of KISS1 and KISS1R mRNA was significantly lower (p<0.05) in fasted monkeys compared to fed monkeys while hypothalamic GNRH1 mRNA expression was comparable between the 2 groups. Thus, our results demonstrate that expression of hypothalamic KISS1 and KISS1R decrease after a short-term fasting in monkeys. This decrease may contribute to the suppression of the HPG axis during fasting conditions in primates. In addition, our finding of lower expression of KISS1R in fasted monkeys provides an explanation for the attenuation in the HPG axis response to peripheral kisspeptin challenge during short-term fasting.

Study on the effect of peripheral kisspeptin administration on basal and glucose-induced insulin secretion under fed and fasting conditions in the adult male rhesus monkey (Macaca mulatta).

Kisspeptin (KP)-Kiss1r, a ligand-receptor pair, has recently been implicated as a pivotal regulator of the neuroendocrine reproductive axis. KISS1 (encoding KP) as well as KISS1R (encoding receptor for KP) are expressed in several peripheral tissues including the pancreas. But the specific role of KP in the physiology of pancreas is still incompletely deciphered. This study was designed to examine the effect of peripheral KP administration on basal and glucose-induced plasma insulin (an important pancreatic hormone) secretion under fed and fasting conditions in the adult male rhesus monkey. A set of 4 chair-restraint habituated intact adult male rhesus monkeys were assigned to receive intravenous bolus administration of human kisspeptin-10 (KP10, 50 µg), and vehicle (1 ml) in normal fed and fasting conditions without or with glucose infusions. Plasma concentrations of insulin were measured by using a specific IRMA. Glucose infusion significantly stimulated plasma insulin levels (p<0.005). Vehicle administration did not affect both basal and glucose stimulated insulin in fed as well as in fasting condition. KP10 administration had no effect on the basal insulin levels in both fed and fasting as compared to pretreatment or vehicle treatment levels, while it significantly heightened glucose stimulated insulin levels (p<0.05) in both fed and fasted monkeys. The present results show that KP administration does not affect the basal secretion of insulin under both fed and fasting condition while potentiated the glucose-induced insulin levels in the adult male rhesus monkey. Therefore, these findings suggest a potential role of KP in the physiology of pancreas.

Effect of peripheral kisspeptin administration on adiponectin, leptin, and resistin secretion under fed and fasting conditions in the adult male rhesus monkey (Macaca mulatta).

In the last few years, kisspeptin-KISS1R signaling has appeared as a major regulator of the reproductive function in several vertebrate species. However, KISS1(encoding kisspeptin) and its putative receptor, KISS1R, are expressed in several other tissues. Adipose tissue, which secretes many peptides with diverse functions in normal physiology, expresses KISS1, which is modulated by gonadal steroids as well as by body nutritional status. Similarly, KISS1Rexpression is also found in adipose tissue, but the local role of kisspeptin in adipocyte function is currently unknown. Therefore, in the present study the effects of exogenous human kisspeptin-10 (KP10) were studied on three important adipokines, namely, adiponectin, leptin, and resistin in a set of four chair-restraint habituated intact adult male rhesus monkeys under; 1) normal fed conditions, 2) 24-h fasting conditions, and 3) 48-h fasting conditions. Plasma resistin and leptin levels decreased (p<0.01), whereas adiponectin levels increased (p<0.05) in fasted monkeys. Kisspeptin administration significantly increased (p<0.05) mean plasma adiponectin levels under fed and 24-h fasting conditions as compared to pretreatment or vehicle-treatment levels. A stimulatory effect was also observed on the 48-h fasting stimulated plasma adiponectin levels, but it lacked statistical significance. In contrast, no effect of kisspeptin was observed on mean plasma leptin and resistin levels. Thus, the present study demonstrated a stimulatory effect of peripheral kisspeptin administration on the plasma adiponectin levels under fed and 24-h fasting conditions in the adult male rhesus monkey. These findings, therefore, assign a novel role to kisspeptin, a regulator of adipocyte function in higher primate.

Marginal adaptation and micro-porosity of class II restorations of a high copper amalgam and a palladium-free gallium-based alloy.

The aim of the current investigation was to compare the marginal adaptation and internal porosity of a gallium (Ga)-based alloy (Galloy) with a high copper amalgam (Permite C DP) when used in moderately sized conventional class II cavities. Ten dentists placed two restorations of each material in standardized class II cavities in typodont teeth set in a phantom head. The proximal surfaces of the restored teeth were subsequently examined using an optical microscope and colour photographs were taken. The teeth were then serially sectioned before being re-examined microscopically and re-photographed. Three dentists rated the photographs of the restorations on two occasions, 2 weeks apart, for marginal adaptation and internal porosity using a six and five point scoring criteria, respectively. Inter- and intra-examiner agreements were assessed with weighted kappa statistics. The Ga-based alloy exhibited inferior marginal adaptation and a significantly higher level of porosity and internal defects compared with the dental amalgam. Marginal defects were mainly concentrated at the gingival third of the proximal boxes for both alloys. The poor marginal adaptation and extensive internal porosity detected for the Ga-based alloy was attributed to the difficulty in the alloy condensation related mainly to the 'stickiness' of the alloy to the condensers and to the rapid change in the plasticity of the alloy during condensation. This could possibly be a factor in the post-operative complications reported with the clinical use of this alloy.

Multi-laboratory evaluation of procedures for reducing the volume of cord blood: influence on cell recoveries.

BACKGROUND: Various procedures can be used to isolate stem and progenitor cells from cord blood. This study evaluated the hydroxyethyl starch sedimentation (HES) with two centrifugation steps, and the top and bottom (T&B) isolation of buffy coat following a single centrifugation, and two filter systems for processing cord blood, one developed by Asahi Kasei Medical (filter A) and the second by Terumo (filter B). METHODS: Each of seven laboratories was randomly assigned the evaluation of either the HES or T&B method and one of the filter methods (n=8 cord blood units, per laboratory, for each method). The leukocyte-containing fraction with the stem/progenitor cells was recovered from the filters by reverse flushing. Utilizing the routine traditional processing and testing procedures of each laboratory, in vitro parameters were determined, with samples obtained after collection, after processing and after freezing/thawing. The results were expressed as the percentage recovery of viable cells in processed vs. collected samples (performance 1; PF1) and in thawed vs. processed samples (performance 2; PF2). The composite results obtained by the seven laboratories were summarized. RESULTS: The median PF1 percentage recovery of total nucleated cells (TNC) was comparable with both traditional methods (HES 79%, T&B 86%) and statistically reduced with both filtration procedures (filter A 58%, filter B 61%). Mononuclear cell (MNC) PF1 recovery was highest statistically with the T&B method (91%) and reduced on using filter A (77%) and filter B (70%) and the HES method (72%). CD34+ cell recovery was judged to be essentially comparable with the four methods, although the range of unit recoveries differed. The percentage recovery of TNC and MNC in PF1 was influenced by the volume of the collected cord blood, especially with use of the filtration procedures. This correlated with TNC content. A greater percentage of red cells and platelets was removed during processing with both filter methods. The time to process cord blood preparations with filter A was significantly shorter than the other methods. Processing with the HES method took the longest time. The recoveries for TNC, MNC and CD34+ cells in PF2 did not appear to be influenced by the specific processing procedure. DISCUSSION: These data indicate that filters that capture stem and progenitor cells may be an appropriate methodology for processing cord blood collected for banking.

Feeding strategies during dry summer for lactating desert goats in a rainfed area under tropical conditions.

Feeding strategies aimed at improving the nutritive value of crop residues through chemical treatment or utilizing other available feed resources as small ruminant feeds were carried out during the hot dry summer season when rangeland pasture deteriorates drastically. The study utilized small-scale farmer animals and crop residues chemically treated as animal feeds. Other feeds were groundnut haulms (GNH) and tree pods (TP) of Faidherbia albida. A total of 30 adult lactating goats with their kids (30) were allocated in completely randomized design to the following treatments: untreated sorghum straw (USS, control), sorghum straw treated with 4.7% urea solution (TSS), TSS+treepods (TSS+TP), USS+groundnuthaulms (USS+GNH) and TSS+GNH. Parameters investigated were: changes in body weight (BW) of the does and their kids as well as milk composition of the does. The results showed that dry matter intake (DMI) was reduced (P<0.05) by urea treatment, but it was increased (P<0.05) by supplementation. In vitro organic matter digestibility (IVOMD) was improved (P<0.05) by urea treatment and supplementation with either GNH or TP. BW of does decreased (P<0.05) in the TSS group, while a significant increase was obtained in the TSS+GNH group. BW of the kids belonging to the does given USS+GNH or TSS+TP was higher (P<0.05) than BW of the kids that belonged to the does fed other rations. However, no losses in BW were detected. It could be concluded that the combination of urea treatment and supplementation with either GNH or TP improved DMI, BW, digestibility and milk yield.

The epidemiology of schistosomiasis in Egypt: summary findings in nine governorates.

Health questionnaires and parasitologic examinations of urine and stool were evaluated from a stratified random sample of 89,180 individuals from 17,172 households in 251 rural communities in 9 governorates of Egypt to investigate the prevalence of, risk factors for, and changing pattern of infection with Schistosoma sp. in Egypt. A subset, every fifth household, or 18,600 subjects, had physical and ultrasound examinations to investigate the prevalence of and risk factors for morbidity. Prevalence of S. haematobium in 4 governorates in Upper Egypt in which it is endemic ranged from 4.8% to 13.7% and averaged 7.8%. The geometric mean egg count (GMEC) ranged from 7.0 to 10.0 ova/10 ml of urine and averaged 8.1. Age stratified prevalence of infection peaked at 15.7% in the 10-14-year-old age group and decreased to 3.5-5.5% in all groups more than 25 years of age. Age-stratified intensity of infection peaked at approximately 10.0 ova/10 ml of urine in the 5-14-year-old age groups and was about half that in all groups more than 25 years of age. Males had higher infection rates and ova counts than females in all age groups. Schistosoma mansoni was rare in Upper Egypt, being consequential in only Fayoum, which had a prevalence of 4.3% and an average intensity of infection of 44.0 ova/g of stool. Risk factors for S. haematobium infection were male gender, an age <21 years old, living in smaller communities, exposures to canal water; a history of, or treatment for, schistosomiasis, a history of burning micturition or blood in the urine, and reagent strip-detected hematuria or proteinuria. The more severe grades (II and III) of ultrasonography-detected periportal fibrosis (PPF) were rare (15 of 906) in these schistosomiasis haematobia-endemic governorates. Risk factors for morbidity (ultrasonography-detected urinary bladder wall lesions and/or obstructive uropathy) were similar to those for infection, with the exception that risk progressively increased with age. Subjects with active S. haematobium infections were 3 times as likely as those without active S. haematobium infections to have urinary tract morbidity. The prevalence of S. mansoni in 5 governorates in Lower Egypt, where it is endemic, ranged from 17.5% to 42.9% and averaged 36.4%. The GMEC ranged from 62.6 to 93.3 eggs/g of stool and averaged 81.3. Age-stratified prevalence of infection peaked at 48.3% in the 15-19-year-old age group, but averaged 35-45% in all groups more than 10 years of age. The intensity of infection was highest in the 10-14-year-old age group, and showed a range of 70-85 eggs/g of stool in those > or =5 years of age. Males had higher infection rates and ova counts than females in all age groups. Schistosoma haematobium was rare in these governorates; Ismailia (1.8%) had the highest infection rate. Risk factors for S. mansoni were male gender, an age >10 years old, living in smaller communities, exposures to canal water, a history of, or treatment for, schistosomiasis or blood in the stool, detection of splenomegaly by either physical examination or ultrasonography, and ultrasonography-detected PPF. The more severe grades (II and III) accounted for 463 (13.3%) of the 3,494 having ultrasonography-detected PPF. Risk factors for morbidity (ultrasonography-detected PPF) were similar to those for infection except that inhabitants of smaller communities were not at increased risk. Active S. mansoni infection increased the odds ratio (OR) of having PPF by 1.37. In comparison with others with normal-size livers, subjects having hepatic enlargement in either the midclavicular line or the midsternal line detected by physical examination or ultrasonography had a reduced risk (ORs = 0.64-0.72) of PPF. The prevalences of lesions detected by ultrasonography were 23.7% for enlargement of right lobe of the liver, 11.3% for enlargement of left hepatic lobe, 20.6% for splenomegaly, and 50.3% for PPF. Schistosoma mansoni has almost totally replaced S. haematobium in Lower E

Formation of brushite, monetite and whitlockite during equilibration of human enamel with acid solutions at 37 degrees C.

The residues of 5 samples of powdered human enamel, each subjected to 5 sequential equilibrations at 37 degrees C with either 17 or 4 mmol/l phosphoric acid, were examined microscopically. With 17 mmol/l acid, both brushite and monetite were found after 1 equilibration but, after further equilibrations, brushite was no longer present and the abundance of monetite crystals increased. Formation of monetite probably contributed to the lower metastability of this system compared to similar low-pH systems at 25 degrees C, where monetite does not form. Neither brushite nor monetite were present after equilibration with 4 mmol/l acid. Whitlockite was identified by transmission electron microscopy and electron diffraction in all residues. In the 4 mmol/l systems, the ionic activity product (IMWH) for magnesium whitlockite, Ca9Mg(HPO4)(PO4)6, became constant after 1-3 equilibrations, at a mean value of 3.6 (+/-0.51 SE).10(-105), which may reflect saturation with respect to this solid. For the 17 mmol/l systems, higher values of IMWH, and supersaturation with respect to monetite, were interpreted as evidence for persistent metastability due to slow crystal growth of whitlockite and monetite. It is concluded that neither brushite nor monetite are likely to form within carious lesions, but the results are consistent with the known association of whitlockite with caries.

Effect of tamoxifen on the pharmacokinetics of doxorubicin in patients with non-Hodgkin's lymphoma.

The authors examined the effect of tamoxifen (TAM), a multiple-drug resistance modulator, on the pharmacokinetics of doxorubicin (DOX) in patients with non-Hodgkin's lymphoma treated according to the CHOP-protocol which included DOX, cyclophosphamide, vincristine, and prednisone. The dose of DOX was 50 mg/m2, but was reduced 25% if the patient was older than 60 years. Of these, 10 randomly-selected patients received a daily dose of 480 mg of TAM (Group-1) and 10 others did not (Group-2). Blood samples were collected at different time intervals, and DOX was measured in plasma by liquid chromatography. The concentration-time data of DOX exhibited the characteristics of the two-compartment open model well. The mean (SEM) values of alpha, beta, k12, k21, k10, Vc, Vss, AUC, total clearance, and mean residence time observed in Group-1 were 4.06 (0.96) hr(-1), 0.0395 (0.0068) hr(-1), 3.13 (0.79) hr(-1), 0.264 (0.052) hr(-1), 0.708 (0.19) hr(-1), 525 (156) l/m2, 1060 (163) l/m2, 1145 (234) microg x hr/l, 49.3 (8.5) l/hr x m2, and 26.8 (6.6) hours, respectively. Those in Group-2 were 4.99 (1.13) hr(-1), 0.0432 (0.0073) hr(-1), 2.46 (0.63) hr(-1), 0.111 (0.026) hr(-1), 2.46 (0.86) hr(-1), 231 (53) l/m2, 812 (149) l/m2, 1690 (276) microg x hr/l, 30.3 (4.1) l/hr x m2, and 29.7 (5.1) hours, respectively. Of these parameters, the difference between the two groups was significant (p < or = 0.0169) only in k21. Thus, the coadministration of TAM at the earlier-mentioned dose appears generally to have no significant influence on the pharmacokinetics of doxorubicin when used in the CHOP-protocol.

Relationship between antipyrine metabolism and acetylation phenotype in health and chronic liver diseases.

The authors examined the activity of N-acetyltransferase and that of microsomal P-450 isoenzymes in health and hepatic disease state by determining the acetylation phenotype and the total (CLAP) and metabolic clearances of antipyrine to form norantipyrine or N-demethylantipyrine (MCLnora), 3-hydroxymethylantipyrine (MCLhma), and 4-hydroxyantipyrine (MCLha) in 21 healthy subjects and in 33 patients with chronic liver diseases (CLD) and investigated the relationship between the activities of these two enzyme systems. The acetylation phenotype was determined according to the urinary caffeine metabolites test. The mean and (SEM) of CLAP, MCLhma, MCLha, and MCLnora in healthy subjects were 2.42 (0.264), 0.193 (0.031), 0.322 (0.045), and 0.288 (0.04) L/h, and those observed in patients with CLD were 0.98 (0.1), 0.076 (0.015), 0.131 (0.026), 0.103 (0.022) L/h, respectively. The prevalence of fast acetylation among the healthy subjects and patients with CLD was 38% and 39%, respectively. Although all metabolic clearances appear to be reduced in healthy slow acetylators, the reduction was only significant in MCLnora, indicating a direct association between the activity of N-acetyltransferase and that of P-450 IIIA3 responsible for the N-demethylation of antipyrine. Conversely, slow acetylators with CLD exhibited significantly higher CLAP and near-significantly larger metabolic clearances including MCLnora, which suggests that P-450 activity in fast acetylators is more sensitive to chronic liver diseases than in slow acetylators.

Effects of low fluoride concentrations on formation of caries-like lesions in human enamel in a sequential-transfer bacterial system.

Human enamel surfaces were exposed to sequential batch cultures of Streptococcus mutans NCTC 10832 in a sucrose-rich medium containing 0-5 mg/l added fluoride (F). In 10-day experiments, subsurface lesion formation was partly inhibited by 1 mg/l F and completely by 2 and 5 mg/l F, but small lesions formed in 2 mg/l F in 21-day experiments. Analysis of the spent media, together with analogous, bacteria-free experiments, suggested that lesion inhibition involved two main effects. First, inhibition of bacterial acid production reduced the pH fall, resulting in reduced undersaturation with respect to hydroxyapatite and consequently reduced rate of demineralization. Secondly, interaction of F with enamel mineral resulted in a small increase in reprecipitation during periods of supersaturation and a much larger reduction in demineralization during periods of undersaturation. It is concluded that, at low F concentrations, inhibition of bacterial acid production is a major factor in lesion inhibition, which may contribute significantly to caries prevention in vivo where plaque fluid F levels are raised by frequent topical applications.

Pharmacokinetics of azathioprine after repeated oral and single intravenous administration.

The pharmacokinetics of azathioprine (AZN) were examined in 28 renal transplant patients treated orally with 25 to 150 mg AZN once daily in combination with cyclosporin A and prednisone, and after single intravenous (IV) injection of 5 mg/kg AZN using the rabbit as an in vivo model. The steady-state concentrations of AZN observed in these patients ranged from 6 to 583 micrograms/L, and the interday coefficients of variation of the concentration in three randomly selected patients were 38%, 12%, and 4.6%. The frequency distribution pattern of the apparent oral clearance (TCLor) of AZN separates the patients almost equally into poor (TCLor = 0.126 to 4 L/hour.kg) and extensive metabolizers (TCLor = 5 to 12 L/hour.kg). The data obtained from the IV administration displayed the two-compartment model characteristics with mean (standard error of the mean) of alpha, beta, Vc, and total body clearance of 15.3 (2)/hour, 2.38 (.64)/hour, 1.05 (.3) L/kg, and 8.12 (1.26) L/hour.kg, respectively. The large variability in the pharmacokinetic parameters of AZN in patients and even in rabbits under carefully controlled conditions that may be ascribed to the complexity of its metabolism necessitates a careful approach to its dose selection.