Nasogastric tube feeding and percutaneous endoscopic gastrostomy tube feeding in patients with head and neck cancer.

BACKGROUND: For patients with a diagnosis of head and neck cancer, oral nutrition may not provide adequate nutrition during radical radiotherapy or chemoradiation treatment, resulting in enteral feeding initiation. Enteral feeding may be delivered via a nasogastric tube or by a gastrostomy tube. The present study aimed to determine how different treatment modalities impact on requirement for enteral feeding and which method of enteral feeding provided the most benefit to the patient, as demonstrated by weight loss and the number of unscheduled radiotherapy treatment interruptions. METHODS: Patients who were treated with radical radiotherapy or chemoradiation between January 2004 and June 2007 were reviewed retrospectively (n = 196, male = 149, female = 47). Data were collected on demographics, diagnosis, T and N classification, nutritional status, unscheduled radiotherapy treatment interruptions, and type and duration of enteral feeding. Subjects were divided into three subgroups depending on the treatment received. Comparisons were then made between methods of enteral feeding. RESULTS: Combined modality treatment (Induction Chemotherapy and Chemoradiation) results in a higher proportion of patients requiring enteral feeding (66-71% compared to 12% for radiotherapy). Patients fed via a prophylactic percutaneous endoscopic gastrostomy lost the least amount of weight during treatment (-4.6% to +1.4%), although the method of enteral feeding did not statistically influence weight difference at the end of treatment. The enteral feeding method did not influence unscheduled radiotherapy treatment interruptions. CONCLUSIONS: Combined modality treatment results in a greater requirement for enteral feeding, with these patient groups having the greatest weight loss. The findings obtained in the present study indicate that the method of enteral feeding did not statistically influence weight loss at the end of treatment or unscheduled radiotherapy treatment interruptions.

Plasma concentrations of melatonin in panic disorder.

Nocturnal plasma melatonin concentrations were measured in seven patients with panic disorder and eight healthy control subjects. The five patients who had never received psychotropic medication had significantly greater melatonin concentrations from 4:00 a.m. to 7:00 a.m. than the control subjects. In addition it is possible that a phase delay occurred in these unmedicated patients. The findings are discussed in terms of previous studies showing increased melatonin in manic patients and the effect of intense stress on melatonin synthesis. The two patients who had been medication free for only 1 week showed a decreased melatonin rhythm, which is consistent with previous findings in medicated patients.

Clinical pharmacokinetics of dothiepin. Single-dose kinetics in patients and prediction of steady-state concentrations.

The pharmacokinetics of dothiepin were evaluated in 9 depressed patients following a single oral dose of 75 mg. Blood and plasma concentrations of dothiepin and 2 major metabolites, northiaden and dothiepin S-oxide, were measured by gas chromatography/mass fragmentography. The mean (+/-SD) peak plasma concentrations of dothiepin were 49 +/- 27 micrograms/L at 3 +/- 1.2h. Mean (+/-SD) estimates of other parameters were as follows: absorption half-life 1.1 +/- 1.1h; distribution half-life 2.2 +/- 0.8 h; elimination half-life 25 +/- 7h; apparent volume of distribution 70 +/- 62 L/kg; and oral clearance 2.1 +/- 1.6 L/kg/h. The mean (+/-SD) peak plasma concentration of dothiepin S-oxide was 125 +/- 43 micrograms/L at 3.5 +/- 1.3h with an elimination half-life of 22 +/- 12 h. The mean peak plasma concentration of northiaden was 6 +/- 3 micrograms/L at 4.5 +/- 1.1h, with an elimination half-life of 31 +/- 12 h. No significant differences were found in pharmacokinetic parameters compared with a previous study in 7 healthy volunteers. When data for the patients and healthy volunteers were combined (n = 16), pharmacokinetic parameters were not found to be affected by age. However, a significant difference was found between males and females for the elimination half-lives of dothiepin and northiaden, and for the apparent volume of distribution of dothiepin. The 24-hour blood/plasma concentrations of dothiepin and dothiepin S-oxide accurately predicted the steady-state concentrations obtained following 4 weeks' treatment with dothiepin 150 mg nocte.

A portable light source for bright light treatment.

A novel, portable, inexpensive bright light source is described. This unit, which has been demonstrated to exhibit physiological effects similar to those of the more conventional light boxes, offers a less restrictive home treatment for patients with seasonal affective disorder and sleep disorders.

Urinary 6-sulphatoxy melatonin levels within the menstrual cycle and in patients with premenstrual syndrome.

The present investigation examined the production of urinary 6-sulphatoxy melatonin (aMT.6S) during the early follicular and late luteal (premenstrual) phases in healthy, normal women and in patients with premenstrual syndrome (PMS). There was no significant difference in levels of aMT.6S on either day 6 or 26 of the menstrual cycle between control subjects and those with PMS. There also was no significant change in urinary aMT.6S levels within the menstrual cycle. These findings do not support an involvement of melatonin in the development of PMS symptomatology and are not supportive of the proposed role of melatonin in regulating ovulation in humans. However, our analysis of 12-hr urine samples may have been insensitive to small, yet possibly biologically significant, changes in the amplitude and period of melatonin excretion during the early hours of the morning.

Melatonin, cortisol and prolactin response to acute nocturnal light exposure in healthy volunteers.

An investigation of the cortisol and prolactin responses accompanying acute melatonin suppression by light (600 lux) in humans is described. Light given from midnight to 0300h suppressed nocturnal plasma melatonin concentrations by 65%. Despite this significant suppression of melatonin, no significant effect on plasma cortisol or prolactin concentrations was observed. These data support recent studies which argue that, if there is a relationship between melatonin, the hypothalamo-pituitary, and the hypothalamo-pituitary-adrenal axis in humans, it is neither direct nor simple.

Human melatonin response to light at different times of the night.

Normal control subjects were examined on three separate occasions with light of sufficient intensity to suppress nocturnal plasma melatonin concentrations. One hour of light was given at each of the following times: (a) 2100-2200h; (b) midnight to 0100h; (c) 0400-0500h. Melatonin synthesis was just becoming apparent at 2100h. There was significant suppression of melatonin by light when given at midnight-0100h and 0400-0500h, but not when light was given at 2100-2200h. In each case following light, melatonin synthesis was shown to resume, even after light applied in the second half of the dark period (0400-0500h). A second experiment was undertaken to examine a possible "rebound" in melatonin levels following light given at 2100-2200h. Six further control subjects were exposed to light at this time, and plasma melatonin levels were measured until 0400h. No rebound in melatonin concentrations was observed. These results are compared with other studies of melatonin response to evening light exposure.

Interpatient variations in antipsychotic therapy.

There is wide interpatient variability not only in therapeutic response to a given dose of antipsychotic drug but also in steady-state plasma levels and the presence and degree of unwanted pharmacologic effects. Such variations have been attributed to individual metabolism, pharmacologic differences, and age--all of which may need careful consideration in prescribing an appropriate dosage regimen for a given patient.

Clinical effects of serotonin reuptake inhibitors in the treatment of depressive illness.

The serotonergic hypothesis of depression has stimulated the development of a range of chemically diverse compounds that have an exclusive effect on this neurotransmitter for potential use as antidepressant drugs. The group of serotonin reuptake inhibitors are at various stages of clinical development. The authors review the efficacy, side effect profiles, and toxicity of zimelidine, fluvoxamine, and citalopram in detail and ifoxetine, fluoxetine, indalpine, paroxetine, and sertraline in brief. Evidence suggests that, compared with tricyclic antidepressants, these drugs may cause fewer anticholinergic effects and lower cardiotoxicity in the treatment of major depressive disorders. These advantages need to be weighed against an emerging pattern of gastrointestinal complaints, insomnia, and akathisia. The place of serotonin reuptake inhibitors in therapy can be fully evaluated only after further studies, particularly those involving long-term use. The adverse experience associated with zimelidine suggests that caution and vigilance should be exercised in future studies of agents in this class. These drugs will undoubtedly provide important insights into depressive illness and some anxiety disorders and may fulfill their initial promise.

Prediction of serum cortisol response to dexamethasone in normal volunteers: a multivariate approach.

Dexamethasone (DEX, 0.5 mg orally at 11 PM) challenge was used for the assessment of hypothalamic-pituitary-adrenal (HPA) activity in 20 normal volunteers. Age and pre-DEX serum cortisol levels were theè evaluated as predictors of postDEX serum cortisol levels using step-wise multiple regression analysis. Both age and preDEX serum cortisol levels were significant predictors of postDEX serum cortisol levels. It is suggested that the adjustment for age and preDEX serum cortisol level could be useful for the interpretation of abnormal postDEX levels.

Modulating role of lithium on dopamine turnover, prolactin release, and behavioral supersensitivity following haloperidol and reserpine.

The effects of haloperidol, reserpine, and concomitant lithium were evaluated in biochemical, endocrine, and behavioral studies in the rat. Concomitant administration of a chronic regimen of haloperidol and lithium did not prevent the development of tolerance as noted by dopamine metabolites in the striatum or olfactory tuberculum. Nor did chronic lithium alter behavioral response in rats treated with reserpine and challenged with the dopamine agonist apomorphine. Additionally, prolactin release was increased by haloperidol, but was not altered by acute or chronic lithium treatment. These findings are discussed in the light of present knowledge of pre- and postsynaptic receptor changes and the effects of lithium.

The effect of 5,7-dihydroxytryptamine on the serum corticosterone resistance to suppression by dexamethasone.

The effect of serotonin (5-HT) deficiency on hypothalamic-pituitary-adrenal (HPA) activity was investigated by using 5,7-dihydroxytryptamine (5,7-DHT) for the selective destruction of central 5-HT neurons, and corticosterone response to suppression by dexamethasone as the index of HPA activity. Dexamethasone was shown to significantly suppress serum corticosterone levels in sham-treated rats, but did not suppress corticosterone in the 5,7-DHT-lesioned animals. This finding supports the conclusion that 5-HT is involved in the negative feedback mechanism of HPA regulation.

Stress causes an increase in endogenous monoamine oxidase inhibitor (tribulin) in rat brain.

Two hours of cold restraint stress in rats resulted in significantly increased brain concentrations of endogenous monoamine oxidase inhibitor (tribulin). Young and old rats showed the same order of response. Tribulin levels were also increased by immobilisation stress alone but to a lesser extent.

Effect of ageing on melatonin synthesis induced by 5-hydroxytryptophan and constant light in rats.

1. This paper describes the effect of the serotonin precursor 5-hydroxytryptophan (5-HTP) on pineal melatonin synthesis young and old rats. 2. 5-HTP itself increased pineal melatonin levels in old rats but did not change melatonin concentrations in young rats kept under 12 hr/12 hr light/dark conditions. 3. After continuous exposure to light for 72 hrs, 5-HTP induced a significant increase in melatonin levels in young rats but did not change the 5-HTP effect on melatonin in old animals. 4. These results are discussed in consideration of previous reports of altered beta-receptor up-regulation by light in old animals, and suggest that the age-related decrease in melatonin synthesis is not entirely related to changes of the enzymatic machine for melatonin synthesis.

The response of the pineal melatonin biosynthesis to the selective MAO-A inhibitor, clorgyline, in young and middle-aged rats.

1. Clorgyline increased pineal melatonin and N-acetylserotonin (NAS) and decreased 5-hydroxyindoleacetic acid (5-HIAA) content in 3 and 12 months of age male Sprague-Dawley rats kept under 12:12 h light: dark schedule. Exposure to light for 24 h before clorgyline administration resulted in additional elevation of NAS and melatonin. NAS and melatonin levels after clorgyline injections were significantly higher while 5-HIAA levels were significantly lower in young than in middle-aged rats. 2. The 5-HIAA/5-HT ratio (index of monoamine oxidase activity) was higher in middle-aged than in young rats suggesting the lesser degree of clorgyline-induced inhibition of MAO-A in old than in young rats. 3. It is suggested that melatonin response to a single dose of the selective MAO-A inhibitor might be used for the assessment of the aging changes of the rat (and human) pineals.

Entonox analgesia for prostatic biopsy.

We performed a prospective randomised double-blind study to evaluate the efficacy of Entonox (nitrous oxide) as an analgesic for trans-rectal ultrasound (TRUS) and prostate biopsy. A total of 50 patients breathed either Entonox or air during sextant prostatic biopsies all of which were performed by the same surgeon. The degree of pain experienced was recorded on a 100 mm visual analogue pain scale. A total of 17 further patients were excluded from the study because they wished to drive home after TRUS. Most patients breathing air experienced moderate pain (median pain score 34), whereas those breathing Entonox experienced minimal pain (median pain score 11). Two patients who used Entonox and one breathing air experienced severe pain. We conclude that patients undergoing prostate biopsy without analgesia experience moderate pain and this can be reduced significantly by using Entonox.

Chronic effect of the irreversible and reversible selective MAO-A inhibitors on rat pineal melatonin biosynthesis.

Acute administration of the irreversible MAO-A inhibitor, clorgyline (2.0 mg/kg, s.c.) and the reversible MAO-A inhibitor, moclobemide (10 mg/kg, s.c.), increased rat pineal melatonin and related indoles content (HPLC-fluorimetric method). Chronic (21 days) administration of clorgyline attenuated the acute effect of clorgyline on pineal melatonin biosynthesis. The acute effect of moclobemide on melatonin biosynthesis was not affected by chronic moclobemide administration. The observed difference in the chronic effects of irreversible and reversible selective MAO-A inhibitors on melatonin biosynthesis could have clinical implications.

A kinetic analysis of platelet monoamine oxidase activity in patients with panic attacks.

A kinetic analysis of platelet monoamine oxidase (MAO) was performed in 22 patients with panic disorder and 14 normal controls, using tyramine as a substrate. Patients and controls did not differ significantly for either Km or Vmax, when same sex contrasts were carried out. The results do not support some studies that have shown elevated MAO activity in patients with panic attacks. The reasons for the discrepancies between previous studies and the present one are explored.

High-affinity platelet [3H]LSD binding is decreased in panic disorder.

Platelet [3H]LSD binding was measured in 15 patients with panic attacks and 15 controls. The mean (+/- SD) Bmax values of the patients (14.1 +/- 6.3 fmol/mg protein) and of the controls (18.5 +/- 4.7 fmol/mg protein) were significantly different (P less than 0.05, Mann-Whitney U-test). Mean (+/- SD) values of Kd for the patients (0.55 +/- 0.34 nM) and for the controls (0.51 +/- 0.12 nM) were not significantly different (P greater than 0.1, Mann-Whitney U-test). The results are discussed in terms of a serotonergic hypothesis of the aetiology of panic disorders.

Blood and plasma concentrations of dothiepin and its major metabolites and clinical response.

Ten patients suffering from primary depressive illness were treated with 150 mg/d of dothiepin for 4 weeks. Blood and plasma concentrations of dothiepin and two metabolites, dothiepin S-oxide and northiaden were measured by gas chromatography-mass spectrometry. Severity of depression was assessed using the Hamilton Depression Rating Scale. No significant correlation was found between amelioration score or percentage change and either blood or plasma concentrations of dothiepin, its metabolites or total drug and metabolite concentrations at week 4.