5-HIAA Excretion Research Articles

Cardiac manifestations in mid-gut carcinoid disease.

The extent of heart disease and its relationship to the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), was studied with M-mode, 2D and Doppler echocardiography in 42 consecutive patients, 30 females and 12 males, median age 63 (range 23-75) years with histologically verified mid-gut tumour, liver metastases and 24-h urinary 5-HIAA excretion above 47 mumol.24 h-1. All patients had normal left ventricular ejection fractions, median 65% (interquartile range (IQR) 54-74%). Moderate to severe tricuspid regurgitation (TR) was diagnosed in 22 patients (59%); mitral or aortic regurgitation was found in nine (24%) and six (16%) patients, respectively. The mitral flow peak early (E) on late (A) velocity ratio was significantly decreased compared to age-matched normal subjects. The group of patients with 5-HIAA excretion exceeding 1000 mumol.24h-1 contained significantly more patients with severe TR than those with a lower excretion. The decrease in the E/A ratio may indicate reduced left ventricular compliance, possibly secondary to fibrous changes similar to those seen intra-abdominally and in the right side of the heart. As serotonin is degraded in the lung circulation, other mediators such as tachykinins and cytokines (PDGF) may be involved.

ＣＤＤＰおう吐に対する抗セロトニン薬の効果

The efficacy of ondansetron, an antagonist of serotonin 5HT3-receptor, was compared with that of metoclopramide, an antagonist of dopamin D2-receptors, in the contorol of nausea and vomiting induced by cisplatin treatment in 30 patients with head and neck cancers. Nausea and vomiting were significantly in those treated with ondansetron less than in those receiving metoclopramide. It was concluded that ondansetron is an effective agent for the control of cisplatin-induced nausea and vomiting. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin, was significantly increased in the patients who received cisplatin chemotherapy. There was a significant positive correlation between the degree of nausea induced by cisplatin and the urinary excretion of 5-HIAA, suggesting that the release of serotonin induced by cisplatin causes emesis.

Biogenic amine metabolites in delusional (psychotic) depression and melancholia subtypes of major depression

1. 1. The levels of the urinary main metabolites of norepinephrine 3-methoxy-4-hydroxyphenylglycol (MHPG), of dopamine homovanillic acid (HVA) and of serotonin 5-hydroxyindoleacetic acid (5-HIAA) were measured in 84 patients with major depressive disorder, 34 delusional and 50 nondelusional. Melancholia subtype was also defined (N=62). 2. 2. MHPG was significantly higher in the delusional depressed group (p=0.023). Female patients with delusional major depression also had significantly higher HVA excretion than female patients with non delusional major depression (p=0.036). 5-HIAA excretion was similar in the two patient subgroups. 3. 3. No significant differences in the three monoamine metabolites were found between the melancholic and nonmelancholic depressed patients.

On the mechanism of radiation-induced emesis: The role of serotonin

Purpose : The aim of this study was to determine the mechanism of action of radiation-induced emesis by determining the incidence of radiation-induced emesis following hemibody irradiation; the effects of specific antiemetics especially ondansetron, a 5-hydroxytryptamine receptor antagonist, and to determine the relationship between radiation-induced emesis and serotonin (5-hydroxytryptamine) through its active metabolite, 5-hydroxyindoleacetic acid (5-HIAA). Methods and Materials : Forty-one patients received 53 hemibody treatments of 5–8 Gy following intravenous hydration. The patients were divided into three groups according to prehemibody irrradiation treatment: Group A: no pretreatment antiemetics, 30 patients; Group B: nonondansetron antiemetics (metoclopramide, dexamethasone, prochlorperazine), ten patients; and Group C: ondansetron, 13 patients. The incidence of radiation-induced emesis was determined prehemibody irradiation or baseline and at 1 h posthemibody irradiation in 38 patients and the results expressed as the percent change in 5-HIAA (ng/ug creatinine). Results: The incidence of radiation-induced emesis was 82% ( 14 17 ) following upper/mid hemibody irradiation and 15% ( 2 11 ) following lower hemibody irradiation in Group A; 50% ( 3 6 ) and 25% ( 1 4 ) following upper/mid and lower hemibody irradiation respectively, in Group B; and 0% ( 0 13 ) after upper/mid hemibody irradiation in Group C. The incidence of emesis was significantly different ( p < 0.001) between the patients of Group A and C who received upper/mid hemibody irradiation. The percent change in 5-HIAA excretion following upper/mid hemi-body irradiation were greatest in Group A and smallest in Group C ( p < 0.002). The degree of change following lower hemibody irradiation (15% incidence of emesis) in Group A was lower than upper/mid hemibody irradiation of the same group. Conclusion: The higher incidence of radiation-induced emesis following upper and mid hemibody irradiation in antiemetic naive patients compared to the incidence following lower hemibody irradiation suggests that the critical organ responsible for radiation sickness is in the abdomen. The control of emesis by ondansetron, a 5-HT 3 receptor antagonist, attests to the efficacy of ondansetron in radiation-induced emesis and suggests a role for serotonin in mediating radiation-induced emesis. Finally, the parallel changes in 5-HIAA and the incidence of emesis provides additional evidence for a more direct role for serotonin in radiation-induced emesis.

Effects of inhibition of serotonin synthesis on 5-hydroxyindoleacetic acid excretion, in healthy subjects.

The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin, reflects the content and turnover of gastrointestinal (GI) serotonin. Employing longitudinal measurements of 5-HIAA, the authors investigated in healthy subjects (n = 43) how manipulations of serotonin synthesis affect GI serotonin. Under conditions of serotonin-free diets, the intersubject and intrasubject variability (coefficient of variation) for 5-HIAA excretion averaged 33% and 14%, respectively. Dietary tryptophan restrictions to 50% of minimal daily requirements (which is equivalent to a 10-fold reduction in baseline tryptophan intake) decreased by half the urinary excretion of 5-HIAA, irrespective of the caloric content of diet. Restoration to the regular tryptophan intake produced a rapid normalization of the 5-HIAA excretion. Neutral amino acids are known to compete with the intestinal transport absorption mechanisms of tryptophan. Administration of neutral amino acids (1.8 g, by mouth, three times a day, before each meal) or of carbidopa (50 mg, by mouth, three times a day for 3 days) to a normal tryptophan diet failed to alter significantly the 5-HIAA excretion. Further, neutral amino acids failed to enhance the reduction in 5-HIAA produced by the low-tryptophan diet. The failure of these treatments to reduce 5-HIAA excretion could be due to large capacity transport and decarboxylation systems for tryptophan. Other possibilities are discussed. In summary, dietary tryptophan is essential for the maintenance of GI serotonin. Reductions or increases in dietary tryptophan are the easiest and most effective method to alter GI serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromogranin A and pancreastatin-like immunoreactivity in human carcinoid disease

Objective: To evaluate chromogranin A (CgA) and pancreastatin-like immunoreactivity (PST-LI) as tumor markers in human carcinoid disease, compared with urinary excretion of 5-hydroxyindole acetic acid (5-HIAA), and to evaluate their role as indicators of survival. Patients and methods: Urinary 5-HIAA excretion was determined by a spectrophotometric method, while serum CgA and PST-LI were determined by radioimmunoassay methods in 38 patients with midgut, 10 with foregut and one with hindgut carcinoids. Results: In midgut carcinoid patients levels of 5-HIAA, CgA and PST-LI were raised by 76, 82 and 76%, respectively. The median CgA level in midgut carcinoid patients was significantly higher than in the controls (193 compared with 12ng/ml; P<0.01). In the midgut carcinoid patients, the median CgA value was significantly higher in women who died (1990 ng/ml) than in those who survived (46ng/ml; P<0.01), and significantly higher than in men, either survivors or non-survivors. The median PST-LI value was significantly higher in midgut carcinoid patients than in the control group (2282 compared with 33 pg/ml; P< 0.01). In women, the median PST-LI level was significantly higher in non-survivors than in survivors (9088 compared with 1337 pg/ml; P<0.01), and significantly higher than in male survivors and non-survivors. In foregut carcinoid patients, levels of CgA, PST-LI and 5-HIAA were increased in nine, eight and one patient, respectively. The median CgA and PST-LI levels in the foregut group were similar to the midgut group. Conclusion: CgA and PST-LI are useful markers in the diagnosis of both midgut and foregut carcinoids. They are as good as, or more sensitive than, 5-HIAA.

The urinary excretion of tryptophan and tryptophan metabolites in the chronic ethanol-fed rat.

An investigation was made into the hypothesis that chronic ethanol ingestion disturbs the metabolism of tryptophan which is reflected by alterations in the urinary excretion of the metabolites 5-hydroxyindoleacetic acid (5-HIAA), anthranilic acid (AA) and indoleacetic acid (IAA). In particular, we investigated whether experimental chronic alcoholism is associated with a decrease in the tryptophan metabolite ratios as suggested in the literature. Male Wistar rats were chronically fed a nutritionally-complete liquid diet in which ethanol comprised 35% of total calories: controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. At 6 weeks, 24 h urine samples were collected for the analysis of tryptophan, 5-HIAA, AA and IAA by HPLC. During ethanol-feeding there were reductions in the daily urinary excretion (i.e. mumol/24 h) of tryptophan (-57%, P = 0.026) and concomitant increases in 5-HIAA excretion (62%, P = 0.057). Expression of data in terms of lean tissue mass (i.e. urinary creatinine) revealed identical conclusions. An analysis was performed on the molar ratios of these urinary analytes. The tryptophan: total metabolite ratio was significantly decreased (by -53%), but the AA: total metabolite ratio was not significantly altered (P = 0.102). The ratios 5-HIAA/AA and 5-HIAA/IAA were slightly increased, but they did not attain statistical significance (P > 0.351). It was concluded that chronic ethanol feeding is associated with significant changes in the urinary excretion of tryptophan and its related metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of Carcinoid Syndrome with Recombinant Interferon Alpha-2a

The prognosis and the quality of life of patients with carcinoid tumors is related either to symptoms from the substances secreted or to progressive tumor growth. Medical treatment with cytotoxic agents is of marginal value for increasing life expectancy and reducing clinical symptoms. Recent studies with interferon have shown interesting results. In the present investigation, 22 patients with carcinoid tumors and syndrome were treated with recombinant interferon alpha-2a (r-IFN alpha-2a) at the dose of 6 x 10(6) IU intramuscularly daily for 8 weeks and three times weekly thereafter. The primary tumor was localized in the foregut (n = 11), midgut (n = 7), hindgut (n = 1), and unknown site (n = 3). Most cases had liver metastasis. Seventeen patients had elevated 5-hydroxyindoloacetic acid (5-HIAA) excretion and 5 had flushing and/or diarrhea as the only clinical manifestation. Six cases presented a complete syndrome (flushing, diarrhea and 5-HIAA excretion). Control of symptoms was obtained in 80% and a 5-HIAA level reduction in 58% of the patients. The interferon treatment was more effective for control of the carcinoid syndrome than for control of tumor growth. The treatment was well tolerated and fever, myalgia, anorexia and fatigue were the most frequent side-effects.

Time course of ethanol-induced changes in serotonin metabolism

The effect of acute ethanol consumption on serotonin metabolism was examined in healthy volunteers in the fasted and fed state by determination of plasma and urinary levels of the serotonin metabolites 5-hydroxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTOL). The plasma and urinary levels of 5-HIAA were reduced by about 40% and 25%, while the 5-HTOL levels were increased on an average 7-fold and 50-fold, respectively, after oral intake of ethanol (0.8 g/kg) over 30 min in a fasted state. The maximal effect on both 5-HIAA and 5-HTOL levels was found 4–6 h after starting drinking. Urinary 5-HTOL and the 5-HTOL/5-HIAA ratio did not return to baseline until 19 h after the start of the administration ( i.e., about 10 h after ethanol reached zero level). The mean 24-h excretion of 5-HTOL was increased 15-fold by the ethanol intake, while the 5-HIAA excretion was not significantly different. A clear dose dependent effect was observed in one individual who also ingested a lower amount of ethanol (0.5 g/kg). When ethanol (0.8 g/kg) was ingested over 3 h together with food, the urinary level of 5-HTOL and the 5-HTOL/5-HIAA ratio did not return to baseline until after 20–22 h. In other subjects who had unlimited access to ethanol and ingested between 1.3–2.3 g/kg together with food, the time to reach baseline 5-HTOL/5-HIAA ratio in urine ranged from 20 h to over 26 h.

Decreased nocturnal plasma melatonin levels in patients with recurrent acute intermittent porphyria attacks

Acute intermittent porphyria (AIP) is a hereditary disease characterized biochemically by a defect in the heme pathway enzyme porphobilinogen deaminase. There is wide variability in the neurologic clinical expression of AIP, and the disorder remains latent in most gene carriers. The natural history of the disease and results in a porphyric rat model sugget a significant relationship between tryptophan metabolites and clinical expression of the disease. In the present study, we examined urine and blood tryptophan metabolite levels in AIP women before, during and after acute attacks and treatment by heme arginate. Heme arginate treatment promptly decreased total tryptophan levels (from 69 ± 9, to 44 ± 5, mean ± SEM, μmole/l, p < 0.001), serotonin blood levels (from 629 ± 103, to 356 ± 80, nmole/l, p < 0.01) and the urinary excretion of 5-HIAA (from 3.9 ± 0.6, to 2.2 ± 0.4, μmole/mmole creatinine, p < 0.01). The plasma level of melatonin was found much lower than the normal control level at night (86.2 ± 70.3, vs the normal range, 409 ± 78.9, pmole/l ± SEM) and day time (38.8 ± 22.0, vs 75 ± 13.7). Heme arginate treatment did not influence melatonin levels. Our results support the involvement of abnormal tryptophan metabolism in the pathophysiology of AIP acute attacks. Low melatonin plasma levels in porphyric women suggest that the defect of the pineal hormone may be responsible for the recurrent aspect of porphyric attacks. A desynchronization of biological rhythms in AIP patients may increase the inducibility of hepatic ALA synthase to environmental risk factors and, specially, to sex steroid hormones.

Changes in serotonin metabolism in cancer patients: its relationship to nausea and vomiting induced by chemotherapeutic drugs.

The metabolism of serotonin was studied in cancer patients of their first day of their first course of chemotherapeutic drugs either with strongly or moderately emetogenic regimens. It was observed that strongly emetogenic treatments induce greater increases in serotonin release than moderately emetogenic regimens. High-dose cisplatinum (75 +/- 5 or 83.8 +/- 5 mg m-2) produced a marked increase in the plasma levels and in the urinary excretion of 5-hydroxyindole acetic acid (5-HIAA). Neither platelet nor plasma (platelet-free plasma) serotonin were significantly modified by high-dose cisplatinum. Dacarbazine (283 +/- 22 mg m-2), another strongly emetogenic agent, induced acute nausea and emesis paralleled by marked increases in the urinary excretion of 5-HIAA. Both for high-dose cisplatinum and dacarbazine, the increases in serotonin metabolism occurred with a similar time-course than those of vomiting, and lasted for a period of 4 to 8 h. Low-dose cisplatinum (30.8 +/- 3 mg m-2) as well as cyclophosphamide-based chemotherapies (520 +/- 30 mg m-2) produced very small increases in the urinary excretion of 5-HIAA. Platelet and plasma serotonin levels failed to increase in cyclophosphamide-treated patients. Octreotide, a long-acting somatostatin analog, did not inhibit the increase in urinary 5-HIAA and the nausea and vomiting produced by high-dose cisplatinum. These results suggest that for treatments that induce marked increases in serotonin release such as high-dose cisplatinum or dacarbazine: (a) the amount and time course of serotonin release induced by chemotherapeutic drugs determines the severity, time of onset and pattern of emesis observed; (b) platelet serotonin play no role in chemotherapy-induced emesis; (c) strongly emetogenic regimens release serotonin from enterochromaffin cells; and (d) intestinal release of serotonin is the consequence of the damage induced by the chemotherapeutic drugs on the gut mucosa.

Relationship of Urinary Serotonin Excretion to Cigarette Smoking and Respiratory Symptoms: The Normative Aging Study

The relationship of 2-h urinary excretion of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) to cigarette smoking and respiratory symptoms was examined among 631 male participants in the Normative Aging Study (age range, 44 to 85 years). The amount of serotonin excreted in urine was inversely related to age (p less than 0.001). Mean 2-h excretion of serotonin varied from 8.01 micrograms for men 40 to 49 years of age to 5.84 micrograms for those 70 years of age or over. No clear relationship was evident between the amount of 5-HIAA excreted in urine and age. After adjustment for age, current smokers were found to excrete more serotonin (p less than 0.001) and 5-HIAA (p = 0.001) than never smokers. Former smokers did not differ significantly from never smokers in these respects. After adjustment for age and smoking status in a multivariate model, chronic cough was a significant predictor of serotonin excretion (p = 0.005); chronic cough was less predictive of 5-HIAA excretion (p = 0.07). Other respiratory symptoms were unrelated to urinary excretion of serotonin and 5-HIAA. The mechanisms underlying the observed relationships of urinary serotonin and 5-HIAA excretion to smoking and to chronic cough and their potential relevance to chronic bronchitis remain to be determined.

Improved Diagnosis of Carcinoid Tumors by Measurement of Platelet Serotonin

Carcinoid patients are diagnosed biochemically on the basis of increased urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA); urinary and platelet serotonin concentrations are considered to provide complementary information. Using established HPLC methods with fluorometric detection, we evaluated the clinical usefulness of measurements of urinary 5-HIAA and urinary, plasma, and platelet serotonin in 30 consecutive patients with histologically proven carcinoid tumors of fore-, mid-, and hindgut origin before treatment. Ten patients showed no signs of serotonin overproduction; 14 had increased concentrations of urinary 5-HIAA and platelet serotonin; and platelet serotonin, but not urinary 5-HIAA, was increased in 6. None had increased urinary 5-HIAA excretion without an increase in platelet serotonin content. In cases with high rates of tumor serotonin secretion, platelet serotonin reached a maximum and did not correlate with serotonin secretion rate, whereas urinary 5-HIAA was correlated. Increased platelet serotonin was correlated with increased plasma serotonin and with occurrence of carcinoid syndrome. Increased urinary serotonin, allegedly caused by increases in circulating 5-hydroxytryptophan, almost invariably coincided with increased platelet serotonin, but not necessarily with above-normal urinary 5-HIAA excretion. From these results and long-term monitoring of three patients during treatment, we conclude that platelet serotonin is more sensitive than urinary 5-HIAA for detecting carcinoids that secrete only small amounts of serotonin.

A dose-escalation study of recombinant interferon-alpha in patients with a metastatic carcinoid tumour

The efficacy of interferon alpha-2b in doses up to 12 × 10 6 IU three times weekly was studied in 21 patients with a metastatic carcinoid tumour. Of these 21 patients, 19 were evaluable for response. Patients were treated with escalating dosages of interferon alpha-2b: 3 × 10 6 IU, 6 × 10 6 IU and 12 × 10 6 IU. The escalation was performed every 8 weeks when no objective tumour regression was observed. Patients were also evaluated for biochemical response and symptomatic improvement. One objective tumour regression was observed. Of the 15 patients with elevated 5-hydroxyindole acetic acid (5-HIAA) excretion, 5 (33%) had a more than 50% decrease in 5-HIAA excretion. Relief of symptoms occurred in 11 patients (58%). This improvement was already apparent during the initial 8 weeks of treatment. Increasing the dose to 6 or 12 × 10 6 IU interferon alpha-2b did not result in further symptomatic improvement. In contrast toxicity was considerable with the higher dosages of interferon alpha-2b. It is concluded that low dose interferon alpha-2b (3 × 10 6 IU) three times weekly is as effective as higher dosages of interferon alpha-2b at ameliorating symptoms of the carcinoid syndrome.

Urinary excretion of 5-hydroxyindole-3-acetic acid and 5-hydroxytryptophol after oral loading with serotonin

The urinary excretion patterns of the serotonin (5-hydroxytryptamine; 5-HT) metabolites 5-hydroxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTOL) were examined after ingestion of bananas, a food rich in 5-HT. The bananas contained on an average 25 μg 5-HT/g pulp. Both urinary 5-HIAA and 5-HTOL increased markedly (15- to 30-fold) shortly after eating 3–4 bananas, with the highest concentrations found in urine specimens collected after 2–4 h, and did not return to normal until after 8–10 h. The excretion of 5-HIAA increased from a control mean value of 3.9 mg/24 h to 12.7 mg/24 h, when conventional diets were supplemented with 3–4 bananas. The corresponding results for 5-HTOL were 16.8 μg/24 h and 60.7 μg/24 h, respectively. Of the banana-derived 5-HT ingested, 60–80% was recovered in the urine as 5-HIAA and only 0.3–0.5% as 5-HTOL. However, since both the time-course and relative increase in 5-HTOL was similar to that of 5-HIAA, there was no effect on the urinary 5-HTOL to 5-HIAA ratio. By contrast, acute alcohol consumption produced a considerable elevation of this ratio.

Correlatos bioquímicos da depressão em crianças

The degree of depression in 88 abandoned children was analysed through a depression rating scale adapted to prepubertal children. The items were grouped into three dimensions: sociological-relational, psychological and biological. In 46 children from this sample it was dosed plasmatic cortisol and the urinary excretion of catecholamine, VMA, HVA and 5-HIAA. When analysing the principal components, the sociological and psychological dimensions were the most important ones in the sample, followed by age and catecholamine variables. The group of male depressed children presented a higher level of catecholamine urinary excretion and a lower peak of plasmatic cortisol than the non-depressed group. The variable age, in both sexes, was correlated with the biochemical variable catecholamine. Biochemical alterations are present in depressed children but it is difficult to show a correlation of dependence between them and the phenomenological aspects of depression.

Recombinant alpha‐2b interferon in patients with malignant carcinoid tumour

Seventeen patients with malignant carcinoid tumour, ten of whom had the malignant carcinoid syndrome, were treated with recombinant alpha-2b interferon by subcutaneous injection (3 MU per dose) three times per week for a median of 12 weeks (range 4-48). No objective tumour responses were observed; however, there was a greater than 50% reduction in 24-hour urinary 5-hydroxyindolacetic acid (5-HIAA) excretion in four of ten patients (40%) with elevated pretreatment levels. Five of ten patients (50%) with flushing, five of seven patients (71%) with diarrhoea and both patients with wheezing experienced relief of symptoms. Three of four patients (75%) with weight loss as their only problem experienced weight gain. Responses occurred within the first eight weeks of treatment, but were generally of short duration. Toxicity occurred in all patients, and consisted mainly of fever, chills, anorexia, fatigue and weight loss. Four patients ceased therapy due to toxic reactions. Although interferon has activity against carcinoid tumours, its benefits are short-lived and toxicity limits its use with increasing dose. Patients with carcinoid syndrome appear to achieve the best therapeutic response, and it is likely that low doses (9-20 million IU weekly) are as effective as higher doses (36-72 million IU weekly).

A study of cyproheptadine in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome

Sixteen patients with metastatic neuroendocrine tumors and the malignant carcinoid syndrome were treated with cyproheptadine (Periactin, Merck, Sharp & Dohme, West Point, PA) at maximum tolerable doses that ranged from 12 to 48 mg daily. Usual side effects were mild sedation and dry mouth, but three patients found it impossible to sustain treatment due to nausea and vomiting. Most patients had significant relief of diarrhea, frequently associated with weight gain. Relief of flushing was uncommon. The therapeutic benefit produced by cyproheptadine would appear to be a peripheral effect because 5-hydroxyindoleacetic acid (5-HIAA) excretion in these patients was not reduced. Although there have been case reports of objective tumor regression with cyproheptadine therapy, this was not observed in any of these 16 patients. Cyproheptadine would appear to be a useful therapeutic tool for the management of diarrhea associated with the malignant carcinoid syndrome. An appropriate initial total daily dose is 0.4 mg/kg divided in three fractions with prompt modification to produce minimal and tolerable side effects.

Low power laser biostimulation of chronic oro-facial pain. A double-blind placebo controlled cross-over study in 40 patients

The efficacy of low power laser stimulation in the treatment of chronic oro-facial pain conditions was investigated in a double-blind placebo controlled modified cross-over study in 40 patients. The laser was an invisible infrared (IR) diode laser with an emission at 904 nanometer (nm). Treatment effect was evaluated by means of VAS-scales and global assessment of pain. Outcome of treatment was correlated to changes in urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). The clinical impression was that placebo was superior to laser stimulation. No statistically significant difference between the analgesic effect of the laser and placebo irradiation was found on VAS-scales. A significant ( P = 0.05) increase in 5-HIAA excretion was found in the placebo group. It is concluded that the possibility of a substantial placebo response should be taken into consideration using 904 nm (IR) lasers for pain treatment in patients with this type of chronic oro-facial pain.

Carboplatin in the treatment of metastatic carcinoid tumours and paraganglioma: a phase II study

A total of 13 patients with metastatic carcinoid tumour, paraganglioma, or unclassified "apudoma" were treated with single-agent carboplatin at a dose of 400 mg/m2 given by intravenous infusion every 4 weeks, on the basis that this new agent shows high activity against small-cell lung cancer that also has "apudoma" characteristics. No objective tumour responses were seen. Overall, 2 patients achieved minor regression, 4/9 (44%) showed a reduction of greater than 50% in urinary 5-HIAA excretion and 8/13 (62%) reported symptomatic improvement. Treatment was well tolerated, with neutropenia and thrombocytopenia being the main toxicities. Carboplatin, like other cytotoxic agents, does not appear to have major activity against these tumours, although further studies in patients with metastatic paraganglioma are warranted.