Octreotide in the treatment of thoracic duct injuries

Anecdotal reports support the use of octreotide in the treatment of traumatic thoracic duct injuries and chylothorax, but no prospective studies have proved its efficacy. We evaluated the effects of octreotide in treating thoracic duct transection in a canine model. Eight mongrel dogs (27.8+/-5.1 kg) were fed one pint of 10.5 per cent milkfat 2 hours before operation. Through a left supraclavicular neck incision, the thoracic duct was identified and transected, producing free flow of chyle. A quarter-inch drain was tunneled subcutaneously from the wound and attached to closed suction. After wound closure dogs were randomized to a control group (n = 4) receiving sham injections of saline subcutaneously three times per day, or a treatment group (n = 4) given 3 microg/kg octreotide three times per day. Postoperatively all dogs were fed a standard low-fat (5-7%) crude fat diet. Drain output was measured each day, and on odd-numbered postoperative days the drainage was analyzed for cholesterol, triglycerides, albumin, and total protein. Fistula closure was defined as drainage <10 ml/24-hour period. Treated dogs achieved fistula closure significantly faster than controls: 3.5+/-1.3 days versus 7.8+/-1.0 days (P = 0.0037). Whereas equivalent amounts of drainage occurred on the day of surgery and on postoperative day one in both groups, by postoperative day 2 the treatment group had significantly less drainage over 24 hours: 63+/-69 ml versus 195+/-79 ml (P = 0.046); this significant difference persisted through postoperative day 5 when drainage began to decrease in the control group. No significant differences between groups were seen in levels of cholesterol, triglycerides, albumin, or protein in the drainage at any time point. We conclude that octreotide is effective in treating thoracic duct injury, leading to an early decrease in drainage and early fistula closure. The mechanism for this effect remains to be clarified.     

Bilateral lesions of the habenula induce attentional disturbances in rats.

The habenular nuclear complex is a major influence on brainstem cell groups that influence attention, but its role in attentional performance has not previously been explored. The present study investigated how habenula lesions affect attentional function as assessed by the 5-choice serial reaction time task (5-CSRTT) in male Lister-Hooded rats. Rats were pretrained in the 5-CSRTT before receiving discrete bilateral lesions of the habenula or a sham procedure. In test sessions immediately following recovery from surgery, lesioned rats showed a marked increase in premature responding. Over the course of testing this increase of premature responding declined in magnitude. In contrast, choice accuracy showed no impairment during the earliest postsurgery test sessions but progressively deteriorated over the course of testing. These opposite time courses strongly imply that different mechanisms mediate these two effects of the habenula lesion. Differential effects of drug treatment on these effects further supported this view. Thus, D-amphetamine (0.2 mg/kg s.c.) increased premature responding without affecting choice accuracy. On the other hand, haloperidol (0.01-0.03 mg/kg i.p.) decreased premature responding without significantly affecting choice accuracy. The results are consistent with the view that elevated premature responding in habenula-lesioned animals is mediated by increased dopaminergic activity, whereas impaired choice accuracy is not. Implications of these findings for the hypothesis that habenula dysfunction is involved in cognitive symptoms of schizophrenia are discussed.     

Radioquimioterapia de la enfermedad limitada del carcinoma pulmonar de célula pequeña. ¿Tratamiento concomitante en protocolos asistenciales?

Purpose We retrospectively reviewed our institution’s database to investigate the outcome and impact of combined radiochemotherapy (RT/CT; concomitant or in sequence) in localised small-cell lung cancer (L-SCLC). Material and methods Between January 1995 to November 1999, 79 patients with L-SCLC received combined RT/CT at our Institution. RT was delivered concurrently or sequentially following the CT. Patients with treatment response received additional prophylactic cranial irradiation (PCI). Results Of the patients treated, 54% had received concurrent CT/RT compared to 46% receiving RT following the CT. PCI was administered to 80% of the patients. Complete response was observed in 66% of patients. With a median follow up of 30 months, median overall survival was 15.9 months; 14.3 months for patients who received RT following CT and 21.6 months for those receiving concurrent CT/RT. The type of schedule of combined radiochemotherapy was an independent prognostic factor for survival free of local recurrence, as was additional PCI for distant metastasis-free survival. Conclusions Our results are similar to those reported previously in the literature. The main point of interest is that our patients were non-selected. We strongly support the use of concurrent CT/RT so as to achieve results comparable to the best in the literature.

     

Metabolism of 8-prenylnaringenin, a potent phytoestrogen from hops (Humulus lupulus), by human liver microsomes.

The female flowers of hops are used throughout the world as a flavoring agent for beer. Recently, there has been increasing interest in the potential estrogenic properties of hop extracts. Among the possible estrogenic compounds in hops, 8-prenylnaringenin is perhaps most significant due to its high in vitro potency exceeding that of other known phytoestrogens. Since data regarding the pharmacokinetic properties of this compound are lacking, we investigated the in vitro metabolism of 8-prenylnaringenin by human liver microsomes. A total of 12 metabolites were identified, and biotransformation occurred on the prenyl group and the flavanone skeleton. The major site of oxidation was on the terminal methyl groups, and of the two possible isomers, the transisomer was more abundant. The double bond on the prenyl group was also oxidized to an epoxide that was opened by intramolecular reaction with the neighboring hydroxyl group. On the flavanone skeleton, the major site of oxidation was at 3'position on the B ring. Other metabolites included oxidation at carbon-3 as well as desaturation of the C ring to produce 8-prenylapigenin. An unusual hydroxy quinone product formed by ipso hydroxylation of the B ring of 8-prenylnaringenin was also detected. This product was probably an intermediate for the B ring cleavage product, 8-prenylchromone.     

Zoonotic Transmission of Diphtheria from Domestic Animal Reservoir,Spain

Toxigenic Corynebacterium ulcerans is as an emerging zoonotic agent of diphtheria. We describe the zoonotic transmission of diphtheria caused by toxigenic C. ulcerans from domestic animals in Spain, confirmed by core-genome multilocus sequence typing. Alongside an increasing number of recent publications, our findings highlight the public health threat posed by diphtheria reemergence.     

Metabolite profiling of 14C-omacetaxine mepesuccinate in plasma and excreta of cancer patients

1. Omacetaxine mepesuccinate (hereafter referred to as omacetaxine) is a protein translation inhibitor approved by the US Food and Drug Administration for adult patients with chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors.

2. The objective was to investigate the metabolite profile of omacetaxine in plasma, urine and faeces samples collected up to 72?h after a single 1.25-mg/m² subcutaneous dose of ¹⁴C-omacetaxine in cancer patients.

3. High-performance liquid chromatography mass spectrometry (MS) (high resolution) in combination with off-line radioactivity detection was used for metabolite identification.

4. In total, six metabolites of omacetaxine were detected. The reactions represented were mepesuccinate ester hydrolysis, methyl ester hydrolysis, pyrocatechol conversion from the 1,3-dioxole ring. Unchanged omacetaxine was the most prominent omacetaxine-related compound in plasma. In urine, unchanged omacetaxine was also dominant, together with 4′-DMHHT. In feces very little unchanged omacetaxine was found and the pyrocatechol metabolite of omacetaxine, M534 and 4′-desmethyl homoharringtonine (4′-DMHHT) was the most abundant metabolites.

5. Omacetaxine was extensively metabolized, with subsequent renal and hepatic elimination of the metabolites. The low levels of the metabolites found in plasma indicate that the metabolites are unlikely to contribute materially to the efficacy and/or toxicity of omacetaxine.

     

Influence of genetic polymorphisms of CYP1A1 and GSTM1 on the urinary levels of 1-hydroxypyrene

The aim of the present study is to evaluate the influence of the genetic polymorphism of two enzymes involved in the biotransformation of xenobiotics, cytochrome P450 1A1 (CYP1A1) and glutathione-S-transferase M1 (GSTM1), on the urinary levels of 1-hydroxypyrene (1-OH-P) in workers exposed to polycyclic aromatic hydrocarbons (PAHs) and in unexposed workers (controls). The study group consisted of 30 controls recruited among employees of a service company and 171 PAHs-exposed workers from two electric steel plants and an iron foundry (all males, ranging between 18 and 60 years of age). Determination of airborne PAHs and urinary 1-OH-P was performed by high-performance liquid chromatography (HPLC) with fluorimetric detection. Polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) was used to determine the genetic polymorphisms of CYP1A1 (CYP1A1*2A and CYP1A1*2B) and GSTM1. No influence of the genetic polymorphism of CYP1A1 and GSTM1 on the urinary levels of 1-OH-P was observed in this study.     

Membrane permeability characteristics of perfused human senile cataractous lenses

Human cataractous lenses were removed by the cryoprobe technique and were maintained for up to 24 hr in a solution of similar ionic composition to human aqueous humour. The bimodal distribution of internal sodium concentrations was similar to that previously reported for unincubated human lenses. Lenses with lower total and free sodium contents had relatively higher membrane potentials and they lost 86Rb at a slower rate than lenses with high internal sodium. The 86Rb efflux in these lenses was stimulated four-fold by removing external calcium. The efflux was reduced by increasing external calcium, but was increased during a small (60 mosmol) hyperosmotic shock. A similar hyperosmotic shock also surprisingly increased 86Rb efflux. Lenses with increasing internal sodium (and calcium) levels showed an increasing rate of loss of 86Rb and the stimulation by calcium removal was progressively diminished. The efflux from lenses with disturbed ion levels was also relatively insensitive to changes in external osmolarity and to increasing external potassium. Lenses with raised sodium concentrations also had an increased inulin space. Frog, rat and rabbit lenses were also exposed to the same range of stimuli and only frog lenses responded to the low calcium solution with more than a four-fold increase in efflux rate. Although only a two- to four-fold increase in efflux rate was obtained from rabbit lenses exposed to Ca-free conditions, this was the only type of animal lens so far tested that, like the human lens, responded to both hyperosmotic and isosmotic shocks with an increase in efflux rate. All three species of mammalian lenses responded with an increase in efflux rate when exposed to a hyperosmotic test solution while in the frog, the efflux rate from the lens decreased. The glucose efflux from human cataractous lenses was inhibited by cytochalasin B in a similar manner to the efflux from rat and frog lenses. It was concluded, therefore, that the cryoprobed human lens can be kept for a limited period in a relative simple artificial aqueous humour solution. The potassium permeability characteristics of low sodium cataracts remained relatively intact and showed a unique response (relative to lenses from other animals) when exposed to various stimuli that are known to be potentially cataractogenic.     

Hormonal contraception and HIV-positive women: metabolic concerns and management strategies

As HIV-positive women live longer lives, and as testing for HIV becomes more routine, clinicians can expect to see more HIV-positive women in their practices. The need to be aware of management issues particular to this population becomes increasingly important. Metabolic dysregulation is a common, long-term complication associated with HIV and is one of the most difficult to manage. Hormonal contraception also is associated with metabolic dysregulation. As more HIV-positive women choose long-term, reversible contraception, the potential for concomitant and additive side effects, and the need for careful, proactive management strategies to avoid these complications, will become more important. This article reviews research detailing the metabolic dysfunction associated with hormonal contraception and with HIV-seropositivity. It highlights reasons for concern regarding the potential, although as yet theoretical, increased risk for metabolic dysfunction when hormonal contraception is used in the presence of HIV. Suggestions for management strategies for women living with HIV who choose to use hormonal contraception are presented. These strategies should be viewed as suggestions for management until substantitive research becomes available.