Irradiation of murine lip mucosa in combination with 5-fluorouracil, administered by single dose injection or continuous infusion

The possible interaction of 5-fluorouracil (5-FU) and irradiation on mouse lip mucosa was studied, with special interest for the influence of the route of administration of the drug, either by single intraperitoneal (i.p.) injection or by 7 days continuous subcutaneous infusion. Apart from the possible modification by the drug of radiation-induced damage to the lip mucosa assessment was made of the systemic toxicity. No modification of the radiosensitivity of mouse lip mucosa nor of its repair capacity was observed with the use of 5-FU given either by i.p. injection or by continuous infusion. However, the combination of 5-FU and irradiation resulted in an increased systemic toxicity which was only seen when 5-FU was administered by an i.p. injection in close timing with irradiation. It is suggested that this increased systemic toxicity is caused by the combined effects of irradiation and 5-FU on the alimentary tract, although we could not demonstrate the mechanism of it.     

Effect of decreasing the dose rate of irradiation on the mouse lip mucosa. Comparison with fractionated irradiations

The effect of continuous irradiation, delivered at five different dose rates (642, 76.8, 14.1, 2.9 and 1.5 Gy.h-1), has been investigated using the mouse lip mucosa. There was a striking dose rate effect (DRE) below 14.1 Gy.h-1 while above this dose rate the DRE was relatively small. No DRE was observed between irradiations delivered at 642 and 76.8 Gy.h-1. A comparison was made with the previously published results of high dose rate (84 Gy.h-1) fractionated irradiation (2, 4, 10 and 20 fractions). For both types of irradiation treatment an alpha/beta value of 7.4 Gy and a half-time for repair of 47 min was derived.     

Drop‐offs in the isoniazid preventive therapy cascade among children living with HIV in western Kenya, 2015–2019

IntroductionIsoniazid preventive therapy (IPT) can reduce the risk of tuberculosis (TB) in children living with HIV (CLHIV), but data on the outcomes of the IPT cascade in CLHIV are limited.MethodsWe evaluated the IPT cascade among CLHIV aged <15 years and newly enrolled in HIV care in eight HIV clinics in western Kenya. Medical record data were abstracted from September 2015 through July 2019. We assessed the proportion of CLHIV completing TB symptom screening, IPT eligibility assessment, IPT initiation and completion. TB incidence rate was calculated stratified by IPT initiation and completion status. Risk factors for IPT non‐initiation and non‐completion were assessed using Poisson regression with generalized linear models.ResultsOverall, 856 CLHIV were newly enrolled in HIV care, of whom 98% ([95% CI 97–99]; n = 841) underwent screening for TB symptoms and IPT eligibility. Of these, 13 (2%; 95% CI 1–3) were ineligible due to active TB and 828 (98%; 95% CI 97–99) were eligible. Five hundred and fifty‐nine (68%; 95% CI 64–71) of eligible CLHIV initiated IPT; median time to IPT initiation was 3.6 months (interquartile range [IQR] 0.5–10.2). Overall, 434 (78%; 95% CI 74–81) IPT initiators completed. Attending high‐volume HIV clinics (aRR = 2.82; 95% CI 1.20–6.62) was independently associated with IPT non‐initiation. IPT non‐initiation had a trend of being higher among those enrolled in the period 2017–2019 versus 2015–2016 (aRR = 1.91; 0.98–3.73) and those who were HIV virally non‐suppressed (aRR = 1.90; 95% CI 0.98–3.71). Being enrolled in 2017–2019 versus 2015–2016 (aRR = 1.40; 1.01–1.96) was independently associated with IPT non‐completion. By 24 months after IPT screening, TB incidence was four‐fold higher among eligible CLHIV who never initiated (8.1 per 1000 person years [PY]) compared to CLHIV who completed IPT (2.1 per 1000 PY; rate ratio [RR] = 3.85; 95% CI 1.08–17.15), with a similar trend among CLHIV who initiated but did not complete IPT (8.2/1000 PY; RR = 4.39; 95% CI 0.82–23.56).ConclusionsDespite high screening for eligibility, timely IPT initiation and completion were suboptimal among eligible CLHIV in this programmatic cohort. Targeted programmatic interventions are needed to address these drop‐offs from the IPT cascade by ensuring timely IPT initiation after ruling out active TB and enhancing completion of the 6‐month course to reduce TB in CLHIV.     

Nasal peak inspiratory flow through Turbuhaler® in children with symptomatic rhinitis and in healthy children

Topical treatment of allergic or vasomotor rhinitis is possible by means of pressurized metered dose inhalers, aqueous spray, or dry powder inhalers. In children, little is known about nasal drug delivery by dry powder inhalation. The airflow through the device is critical for the drug release and a sufficient nasal inspiratory flow is needed for intranasal drug delivery from a dry powder inhaler. In order to investigate from what age children with allergic or vasomotor rhinitis can reliably use such a device, device-dependent nasal peak inspiratory flow (DnPIF) was measured. The maximal DnPIF was measured in children aged 4–13 years making use of a dry powder inhaler (Turbuhaler^®) connected to a spirometer (Vitalograph^®). In the clinically relevant context, instructions from the doctor and one week's use of a Turbuhaler at home were found to be sufficient to obtain a good inhalation technique and were shown to improve DnPIF at least as effectively as visual feedback training at the clinic. Children with rhinitis, as well as healthy children from the age of 6 years, were able to generate a DnPIF sufficient to obtain a reliable nasal delivery of a dry powder drug dose. DnPIF values correlated with age. Consequently, a recommendation to use a nasal Turbuhaler from the age of 6 for topical drug delivery in the treatment of allergic or vasomotor rhinitis seems reasonable.     

Antimicrobial Activity of Synthetic Salivary Peptides Against Voice Prosthetic Microorganisms

Objectives: To investigate whether synthetic salivary antimicrobial peptides have an inhibitory effect on the growth of bacteria and yeasts isolated from used silicone rubber voice prostheses. Methods: The antimicrobial activities of six synthetic salivary peptides (histatin 5, dhvar1, dhvar4, dhvar5, lactoferrin b 17–30 [LFb 17–30], and cystatin S1–15) at concentrations of 2 and 4 mg/mL were determined against different oropharyngeal yeast (four) and bacterial (eight) strains and against a “total microflora” isolated from explanted voice prostheses using agar diffusion tests. The spectrum of susceptible microorganisms was determined qualitatively. Results: Histatin 5 and cystatin S1–15 did not show any antimicrobial activity against the microorganisms involved in this study. Dhvar1 was active against some of the oropharyngeal microorganisms tested, including the yeast strains, but not against Rothia dentocariosa, Staphylococcus aureus, Escherichia coli, and the total microflora. Dhvar4 was active against all microorganisms tested, including the total microflora. Dhvar5 lacked activity against E coli and the total microflora. LFb 17–30 did not inhibit the growth of any of the yeast strains involved and showed only minor activity against some of the bacterial strains. LFb 17–30 slightly inhibited the growth of the total microflora from an explanted prosthesis. Conclusions: The synthetic salivary peptide dhvar4 has a broad antimicrobial activity against all microorganisms that are commonly isolated from explanted voice prostheses, including yeasts. Therewith, it may represent a useful drug, as an alternative for antibiotics and antimycotics employed in various ways to prolong the lifetime of voice prostheses in laryngectomees.     

Prognostic significance of argyrophilic nucleolar organizer regions in nasopharyngeal carcinoma

Increased expression of argyrophilic nucleolar organizer regions (AgNORs) has been identified in certain malignant tumors including nasopharyngeal carcinoma (NPC). However, its prognostic significance in NPC is uncertain and remains to be evaluated. To address this we silver-stained 63 paraffin sections of NPC cases, and examined the correlation between AgNOR count and area, calculated by the CAS 200 image analysis system, and tumor behavior, locoregional control, and survival of patients. The mean AgNOR count and area were 1.62 ± 0.31 and 3.98 ± 11.4 μm², respectively. The AgNOR area was positively associated with T stage (r = 0.26, P = 0.04). The Mann-Whitney test confirmed no significant difference in AgNOR area and count between patients with different outcomes. Multivariate analysis using the Cox proportional hazard model showed neither AgNOR count nor area to be significant predictors of actuarial survival or disease-free survival. It is concluded that AgNOR does not have an independent and significant prognostic value in NPC. AgNOR expression may be merely a reflection of malignant phenotype as well as cellular activity but not necessarily the ultimate behavior of the tumor. Received: 14 March 2000 / Accepted: 30 May 2000     

A solitary manifestation of mastocytosis in the head and neck

Solitary mastocytosis in adulthood is a rare finding. Only two such lesions have been reported in the head and neck. We describe a 27-year-old woman who had a 10-year history of a forehead swelling that had fluctuated in size. Light trauma or pressure on the lesion resulted in an increase in its size. A mass was found to be situated just below the galea and was successfully removed surgically using a high forehead lift. Histologically, the specimen contained predominantly mast cells. A systemic mastocytosis was excluded by a multidisciplinary diagnostic approach and measurement of the 24-h urinary excretion of histamine metabolites. After 36 months of follow-up there has been no recurrence. Received: 20 May 1999 / Accepted: 15 July 1999