Effect of antidepressant medication on morning and evening thyroid function tests during a major depressive episode.

BACKGROUND: This study sought to determine whether changes in thyroid function that may occur during antidepressant treatment are related to a direct effect of the drug on the thyroid axis or to a change in clinical state. METHODS: Morning and evening thyroid function was evaluated in 30 euthyroid inpatients who met DSM-IV criteria for major depressive episode, by determination of free triiodothyronine, free thyroxine, and thyrotropin levels before and after 8 AM and 11 PM protirelin challenges (200 micrograms intravenously), on the same day. Results at baseline were compared with those after 1 month of antidepressant treatment with either amitriptyline hydrochloride, fluoxetine hydrochloride, or toloxatone. RESULTS: Clinical efficacy and effects on thyroid function did not differ across the 3 antidepressant drugs. Compared with pretreatment values, significant reductions in basal serum 8 AM free thyroxine, 11 PM free thyroxine, and 8 AM free triiodothyronine levels and increases in 11 PM maximum increment in plasma thyrotropin level and the difference between 11 PM and 8 AM maximum increment in plasma thyrotropin values were observed in responders (n = 11) but not in partial responders (n = 6) or nonresponders (n = 13). Moreover, nonresponders exhibited lower pretreatment 11 PM thyrotropin values (basal and maximal increment above basal) than responders. CONCLUSIONS: The results suggest that (1) changes in thyroid function are related to clinical recovery rather than to a direct effect of the antidepressant drug and (2) patients with the lowest pretreatment evening thyrotropin secretion have the lowest rate of antidepressant response, and this may contribute to treatment resistance.

Multihormonal responses to clonidine in patients with affective and psychotic symptoms.

The neuroendocrine responses to the alpha(2)-adrenoreceptor agonist clonidine (CLO) (0.35 mg if body weight <65 kg or 0.375 mg if body weight> or =65 kg, PO) were studied in a large group of subjects: 134 drug-free inpatients--with either DSM-IV schizophrenia (SCZ, n=31), schizoaffective disorder (SAD, n=16), or major depressive episode (MDE, n=87) - and 22 hospitalized controls (HCs). Comparison with a previous placebo test performed in a subgroup of 92 subjects (46 MDEs, 20 SCZs, 8 SADs, and 18 HCs) showed that CLO induced a significant increase of growth hormone, prolactin (PRL) and thyrotropin (TSH) levels but no significant change in adrenocorticotropin and cortisol release. According to diagnostic categories, we found significantly lower GH stimulation in MDEs and in SADs compared to HCs or to SCZs. In addition, we found significantly lower CLO induced PRL and TSH stimulations in paranoid SCZ patients compared to controls and disorganized SCZ patients. Taken together, these results suggest a hyposensitivity of noradrenergic alpha(2)-receptors in patients with affective symptoms.

Thyroid axis activity and serotonin function in major depressive episode.

Recent studies in depression have reported alterations in both hypothalamic-pituitary-thyroid (HPT) axis activity and serotonin (5-HT) function; however, the functional relationships between the two systems have not been well defined in patients with major depressive episode. Thyrotropin (TSH) response to 0800 and 2300 h protirelin (TRH) challenges, and adrenocorticotropic hormone (ACTH), cortisol, and prolactin (PRL) responses to D-fenfluramine (D-FEN), a specific 5-HT releasing/uptake-inhibiting agent, were examined in 60 drug-free DSM-IV major depressed inpatients and 20 hospitalized controls. Compared with controls, patients showed lower basal serum 2300 h TSH, 2300 h maximum increment in serum TSH above baseline (delta TSH) and difference between 2300 h delta TSH and 0800 h delta TSH (delta delta TSH) levels. The hormonal responses to D-FEN (i.e. delta ACTH, delta cortisol and delta PRL) were interrelated. No significant difference in basal and post-D-FEN ACTH, cortisol or PRL values were found between controls and patients. A negative relationship between hormonal responses to D-FEN and 2300 h delta TSH and delta delta TSH values was observed in the depressed group. When patients were classified on the basis of their delta TSH test status, patients with reduced delta delta TSH values (i.e. with HPT axis abnormality) had hormonal D-FEN responses comparable to those of controls. Patients with normal delta delta TSH values (i.e. without HPT axis abnormality) showed lower ACTH, cortisol and PRL responses to D-FEN than controls and patients with abnormal delta delta TSH values. These results suggest that: (1) pathophysiological mechanisms other than 5-HT dysregulation may be involved in TSH blunting in major depressed patients; (2) 5-HT function is reduced in some depressed patients, especially those without HPT axis abnormality; and (3) HPT dysregulation may be regarded as a compensatory mechanism for diminished central 5-HT activity.

Dopaminergic function and the cortisol response to dexamethasone in psychotic depression.

1. It has been hypothesized that psychotic symptoms in depression may be due to increased dopamine activity secondary to hypothalamic-pituitary-adrenal (HPA) axis overactivity. 2. To test this hypothesis, the authors examined the cortisol response to dexamethasone suppression test (DST, 1 mg orally) and multihormonal responses to apomorphine (APO, 0.75 mg s.c.)--a dopamine agonist--in 150 drug-free hospitalized patients with DSM-IV major depressive episode with psychotic features (MDEP, n=35), major depressive episode without psychotic features (MDE, n=74), or schizophrenia paranoid type (SCZ, n=41), and 27 hospitalized healthy controls (HCs). 3. MDEPs showed increased activity of the HPA system (i.e. higher post-DST cortisol levels) than HCs, SCZs and MDEs. However, there were no differences in adrenocorticotropic hormone (ACTH), cortisol, prolactin and growth hormone (GH) responses to APO between MDEPs and MDEs and HCs. On the other hand, SCZs showed lower APO-induced ACTH stimulation and a higher rate of blunted GH than HCs, MDEs and MDEPs, suggesting a functional alteration of the hypothalamic dopamine receptors in SCZs. 4. In the total sample and in each diagnostic group, DST suppressors and non-suppressors showed no differences in hormonal responses to APO. 5. These results suggest a lack of causal link between HPA axis hyperactivity and dopamine dysregulation. In contrast to schizophrenia, psychotic symptoms in depression seem not to be related to dopamine function dysregulation.

Noradrenergic dysfunction and antidepressant treatment response.

The purpose of this study was to investigate differences in outcome following treatment with two different antidepressants in depressed patients according to their pretreatment hormonal response to clonidine. In all, 62 drug-free DSM-IV recurrent major depressed patients and 20 normal controls were studied. Patients were subsequently treated for 4 weeks with fluoxetine (n=28), or amitriptyline (n=34), and were then classified as responders or nonresponders according to their final Hamilton depression scale score. Compared to controls, depressed patients showed lower GH response to CLO (DeltaGH) (P<0.0002). One control (5%) and 35 depressed patients (56%) had blunted DeltaGH values. The efficacy of the two antidepressants was not significantly different: 15 patients responded to AMI (44%), seven patients responded to FLUOX (25%) (P>0.15). However, in the subgroup of patients with blunted DeltaGH levels, the rate of responders was higher for AMI (11/21) compared to FLUOX (1/14) treated patients (P<0.01). These results suggest that in depressed patients a blunted GH response to CLO could predict antidepressant response.

Community-acquired septicaemia in southern Viet Nam: the importance of multidrug-resistant Salmonella typhi.

In a prospective study conducted between mid 1993 and 1994, 437 adults and children were admitted with community-acquired septicaemia to an infectious diseases hospital in southern Viet Nam. Gram-negative aerobes accounted for 90% of isolates and were predominantly Salmonella typhi (67%), Sal. para-typhi A (3%), Escherichia coli (10%), and Klebsiella spp. (5%). Other Salmonella spp. (1%), Pseudomonas aeruginosa (1%), Neisseria meningitidis (0.5%) and Haemophilus influenzae (0.2%) were uncommon. Staphylococcus aureus (5.5%) and Streptococcus pneumoniae (2%) were the most common Gram-positive isolates. Patients with enteric fever were younger (median age 16 years, range 1-63) than the other patients (median age 43 years, range 1-88) (P < 0.001) and had a lower mortality rate (0.3% vs. 23%; relative risk 69.5, 95% confidence interval 9.5-507.8; P < 0.0001). Over 70% of the Sal. typhi isolated were multi-drug-resistant, and 4% were resistant to nalidixic acid. Multidrug-resistant Sal. typhi is a major cause of community-acquired septicaemia in Viet Nam.

Treatment of bacillary dysentery in Vietnamese children: two doses of ofloxacin versus 5-days nalidixic acid.

Nalidixic acid (NA: 55 mg/kg daily for 5 days) is the recommended treatment for uncomplicated bacillary dysentery in areas where multidrug-resistant Shigella are prevalent. An open randomized comparison of this NA regimen with 2 doses of ofloxacin (total 15 mg/kg) was conducted in 1995/96 in 135 Vietnamese children with fever and bloody diarrhoea. Sixty-six children with a bacterial pathogen isolated were eligible for analysis. Of the 63 Shigella isolates, 39 (62%) were resistant to multiple antibiotics. Resolution times for fever and diarrhoea were similar in the 2 groups, but excretion time of stool pathogen was significantly longer in the NA recipients [median (range) days 1 (1-9) vs 1 (1-2), P = 0.001]. There were 9 (25%) treatment failures in the NA regimen and 3 (10%) in the ofloxacin group; P = 0.1. Two patients had NA-resistant Shigella flexneri. One of these isolates was selected during NA treatment. From a clinical and public health standpoint a 2-dose regimen of ofloxacin is preferable to nalidixic acid in the treatment of bacillary dysentery.

Prolactin response to D-fenfluramine and suicidal behavior in depressed patients.

Previous studies of the prolactin response to D-fenfluramine in depressed patients have yielded inconsistent results. This may be because they did not address the question of suicidality. We carried out this study to test the hypothesis that lower prolactin response to D-fenfluramine is more closely associated with suicidal behavior than with depression itself. A D-fenfluramine test was performed in a sample of 18 healthy control subjects and in 85 drug-free inpatients with a DSM-III-R diagnosis of major depressive episode (49 with a history of suicide attempt, 36 without). Depressed inpatients with a history of suicide attempt showed a significantly lower prolactin response to D-fenfluramine compared to depressed inpatients without such a history and compared to control subjects. Healthy control subjects and depressed inpatients without a history of suicide attempt showed comparable levels of prolactin after D-fenfluramine. Time elapsed since suicide attempt did not influence prolactin level (baseline or post-stimulation). Results show that in our depressed drug-free inpatient sample, prolactin response to D-fenfluramine seems to be a marker of suicidality, but not of depression itself. We suggest that it is a trait marker of suicidality.

The role of the polymerase chain reaction in the diagnosis of bacterial meningitis in Vietnam.

Bacterial meningitis remains an important cause of morbidity and mortality in Vietnam. Diagnosis is hampered by the ready availability of antibiotics in the community, leading to late presentation, masked clinical signs, and poor organism detection during the microscopical examination and culture of cerebrospinal fluid (CSF). In order to improve organism detection at the Hospital for Tropical Diseases in Ho Chi Minh City, a diagnostic PCR-based protocol was developed. This protocol was followed in the investigation of CSF samples from 36 patients with clinical signs of bacterial meningitis. Each sample was first tested in a semi-nested PCR using primers for the 16sRNA gene common to all bacteria. The products of this reaction were then amplified using a 16sru8 primer and primers specific for Neisseria meningitidis, Haemophilus influenzae or Streptococcus spp. The samples found positive for Streptococcus were further investigated in a nested PCR using primers specific for the pneumolysin gene of S. pneumoniae. The sensitivity of detection was increased from 36% with culture to 44% with PCR. Although the sample size was small, the results indicate that PCR would be a feasible and useful adjunct in the diagnosis of bacterial meningitis, particularly in areas where community antibiotic use is common.

Value of a single-tube widal test in diagnosis of typhoid fever in Vietnam.

The diagnostic value of an acute-phase single-tube Widal test for suspected typhoid fever was evaluated with 2,000 Vietnamese patients admitted to an infectious disease referral hospital between 1993 and 1998. Test patients had suspected typhoid fever and a blood culture positive for Salmonella typhi (n= 1,400) or Salmonella paratyphi A (n = 45). Control patients had a febrile illness for which another cause was confirmed (malaria [n = 103], dengue [n = 76], or bacteremia due to another microorganism [n = 156] or tetanus (n = 265). An O-agglutinin titer of >/=100 was found in 18% of the febrile controls and 7% of the tetanus patients. Corresponding values for H agglutinins were 8 and 1%, respectively. The O-agglutinin titer was >/=100 in 83% of the blood culture-positive typhoid fever cases, and the H-agglutinin titer was >/=100 in 67%. The disease prevalence in investigated patients in this hospital was 30.8% (95% confidence interval, 26.8 to 35.1%); at this prevalence, an elevated level of H agglutinins gave better positive predictive values for typhoid fever than did O agglutinins. With a cutoff titer of >/=200 for O agglutinin or >/=100 for H agglutinin, the Widal test would diagnose correctly 74% of the blood culture-positive cases of typhoid fever. However, 14% of the positive results would be false-positive, and 10% of the negative results would be false-negative. The Widal test can be helpful in the laboratory diagnosis of typhoid fever in Vietnam if interpreted with care.

Quantitation of bacteria in blood of typhoid fever patients and relationship between counts and clinical features, transmissibility, and antibiotic resistance.

Salmonella typhi was isolated from 369 and Salmonella paratyphi A was isolated from 6 of 515 Vietnamese patients with suspected enteric fever. Compared with conventional broth culture of blood, direct plating of the buffy coat had a diagnostic sensitivity of 99.5% (95% confidence interval [CI], 97.1 to 100%). Blood bacterial counts were estimated by the pour plate method. The median S. typhi count in blood was 1 CFU/ml (range, <0.3 to 387 CFU/ml), of which a mean of 63% (95% CI, 58 to 67%) were intracellular. The mean number of bacteria per infected leukocyte was 1.3 (interquartile range [IQR], 0.7 to 2.4) CFU/cell (n = 81). Children (< 15 years old; n = 115) had higher median blood bacterial counts than adults (n = 262): 1.5 (range, <0.3 to 387) versus 0.6 (range, <0.3 to 17.7) CFU/ml (P = 0.008), and patients who excreted S. typhi in feces had higher bacteremias than those who did not: a median of 3 (range, <0.3 to 32) versus 1 (range, <0.3 to 68) CFU/ml (P = 0.02). Blood bacterial counts declined with increasing duration of illness (P = 0.002) and were higher in infections caused by multidrug-resistant S. typhi (1.3 [range, <0.3 to 387] CFU/ml; n = 313) than in infections caused by antibiotic-sensitive S. typhi (0.5 [range, <0.3 to 32] CFU/ml; n = 62) (P = 0.006). In a multivariate analysis this proved to be an independent association, suggesting a relationship between antibiotic resistance and virulence in S. typhi.

Comparison of ofloxacin and ceftriaxone for short-course treatment of enteric fever.

An open, randomized comparison of ofloxacin (200 mg, every 12 h) given orally for 5 days and ceftriaxone (3 g, once daily) given intravenously for 3 days in the treatment of uncomplicated enteric fever was conducted in Ho Chi Minh City, Vietnam. Salmonella paratyphi type A was isolated from six patients. Salmonella typhi was isolated from 41 patients; 63% of these isolates were resistant to multiple antibiotics: ampicillin, chloramphenicol, sulfamethoxazole, trimethoprim, and tetracycline. Of the culture-confirmed cases, treatment with ofloxacin resulted in complete cure of all 22 patients, whereas 18 of 25 patients treated with ceftriaxone were completely cured (P < 0.01). In the ceftriaxone group, there were six acute treatment failures and one relapse. Mean +/- standard deviation fever clearance times were 81 +/- 25 h for ofloxacin and 196 +/- 87 h for ceftriaxone (P < 0.0001). Short-course treatment with oral ofloxacin (5 days) is significantly better than that with ceftriaxone (3 days) and will be of particular benefit in areas where multiresistant strains of S. typhi are encountered.

A randomized controlled comparison of azithromycin and ofloxacin for treatment of multidrug-resistant or nalidixic acid-resistant enteric fever.

To examine the efficacy and safety of short courses of azithromycin and ofloxacin for treating multidrug-resistant (MDR, i.e., resistant to chloramphenicol, ampicillin, and cotrimoxazole) and nalidixic acid-resistant enteric fever, azithromycin (1 g once daily for 5 days at 20 mg/kg/day) and ofloxacin (200 mg orally twice a day for 5 days at 8 mg/kg/day) were compared in an open randomized study in adults admitted to a hospital with uncomplicated enteric fever. A total of 88 blood culture-confirmed patients were enrolled in the study (86 with Salmonella enterica serovar Typhi and 2 with S. enterica serovar Paratyphi A). Of these, 44 received azithromycin and 44 ofloxacin. A total of 68 of 87 (78%) isolates were MDR serovar Typhi, and 46 of 87 (53%) were nalidixic acid resistant. The MIC(90) (range) of azithromycin was 8 (4 to 16) microgram/ml for the isolates. The MIC(90) (range) of ofloxacin for the nalidixic acid-sensitive isolates was 0.03 (0.015 to 0.06) microgram/ml and for the nalidixic acid-resistant isolates it was 0.5 (0.25 to 1.0) microgram/ml. There was no significant difference in the overall clinical cure rate with ofloxacin and azithromycin (38 of 44 [86.4%] versus 42 of 44 [95.5%]; P = 0.27) or in the patients infected with nalidixic acid-resistant typhoid (17 of 21 [81.0%] versus 24 of 25 [96.0%]; P = 0.16). However, patients with nalidixic acid-resistant typhoid treated with ofloxacin had a longer fever clearance time compared with those treated with azithromycin (174 [60 to 264] versus 135 [72 to 186] h; P = 0.004) and had positive fecal cultures after the end of treatment (7 of 17 [41%] versus 0 of 19 [0%]; P = 0.002). Both antibiotics were well tolerated. A 5-day course of azithromycin was effective for the treatment of enteric fever due to MDR and nalidixic-acid-resistant serovar Typhi, whereas the ofloxacin regimen chosen was less satisfactory for these strains.

Nasal carriage in Vietnamese children of Streptococcus pneumoniae resistant to multiple antimicrobial agents.

Resistance to antimicrobial agents in Streptococcus pneumoniae is increasing rapidly in many Asian countries. There is little recent information concerning resistance levels in Vietnam. A prospective study of pneumococcal carriage in 911 urban and rural Vietnamese children, of whom 44% were nasal carriers, was performed. Carriage was more common in children <5 years old than in those >/=5 years old (192 of 389 [49.4%] versus 212 of 522 [40.6%]; P, 0.01). A total of 136 of 399 isolates (34%) had intermediate susceptibility to penicillin (MIC, 0.1 to 1 mg/liter), and 76 of 399 isolates (19%) showed resistance (MIC, >1.0 mg/liter). A total of 54 of 399 isolates (13%) had intermediate susceptibility to ceftriaxone, and 3 of 399 isolates (1%) were resistant. Penicillin resistance was 21.7 (95% confidence interval, 7.0 to 67.6) times more common in urban than in rural children (35 versus 2%; P, <0.001). More than 40% of isolates from urban children were also resistant to erythromycin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline. Penicillin resistance was independently associated with an urban location when the age of the child was controlled for. Multidrug resistance (resistance to three or more antimicrobial agent groups) was present in 32% of isolates overall but in 39% of isolates with intermediate susceptibility to penicillin and 86% of isolates with penicillin resistance. The predominant serotypes of the S. pneumoniae isolates were 19, 23, 14, 6, and 18. Almost half of the penicillin-resistant isolates serotyped were serotype 23, and these isolates were often multidrug resistant. This study suggests that resistance to penicillin and other antimicrobial agents is common in carriage isolates of S. pneumoniae from children in Vietnam.

Epidemic typhoid in vietnam: molecular typing of multiple-antibiotic-resistant Salmonella enterica serotype typhi from four outbreaks.

Multidrug-resistant Salmonella enterica serotype Typhi isolates from four outbreaks of typhoid fever in southern Vietnam between 1993 and 1997 were compared. Pulsed-field gel electrophoresis, bacteriophage and plasmid typing, and antibiotic susceptibilities showed that independent outbreaks of multidrug-resistant typhoid fever in southern Vietnam are caused by single bacterial strains. However, different outbreaks do not derive from the clonal expansion of a single multidrug-resistant serotype Typhi strain.

Melioidosis in Southern Vietnam: clinical surveillance and environmental sampling.

From 1992-1998, Burkholderia pseudomallei was isolated from only 9 (0.25%) of 3653 cultures of blood from febrile patients admitted to the Centre for Tropical Diseases in Ho Chi Minh City, an infectious disease referral center for southern Vietnam. Soil was sampled from 407 sites in 147 rice fields along the 5 major roads radiating from Ho Chi Minh City. B. pseudomallei was isolated from 73 sites (18%) in 39 rice fields (27%), but only 15 (21%) of the 71 isolates from 9 (6%) of 147 fields were the virulent l-arabinose (ara)-negative biotype. All except 1 of the fields with the ara-negative biotype were close to the homes of the patients with melioidosis. The low incidence of melioidosis in the provinces around Ho Chi Minh City may be explained by the restricted distribution of ara-negative B. pseudomallei in the soil in this area.

Molecular typing of multiple-antibiotic-resistant Salmonella enterica serovar Typhi from Vietnam: application to acute and relapse cases of typhoid fever.

The rate of multiple-antibiotic resistance is increasing among Salmonella enterica serovar Typhi strains in Southeast Asia. Pulsed-field gel electrophoresis (PFGE) and other typing methods were used to analyze drug-resistant and -susceptible organisms isolated from patients with typhoid fever in several districts in southern Vietnam. Multiple PFGE and phage typing patterns were detected, although individual patients were infected with strains of a single type. The PFGE patterns were stable when the S. enterica serovar Typhi strains were passaged many times in vitro on laboratory medium. Paired S. enterica serovar Typhi isolates recovered from the blood and bone marrow of individual patients exhibited similar PFGE patterns. Typing of S. enterica serovar Typhi isolates from patients with relapses of typhoid indicated that the majority of relapses were caused by the same S. enterica serovar Typhi strain that was isolated during the initial infection. However, some individuals were infected with distinct and presumably newly acquired S. enterica serovar Typhi isolates.

Serology of typhoid fever in an area of endemicity and its relevance to diagnosis.

Currently, the laboratory diagnosis of typhoid fever is dependent upon either the isolation of Salmonella enterica subsp. enterica serotype Typhi from a clinical sample or the detection of raised titers of agglutinating serum antibodies against the lipopolysaccharide (LPS) (O) or flagellum (H) antigens of serotype Typhi (the Widal test). In this study, the serum antibody responses to the LPS and flagellum antigens of serotype Typhi were investigated with individuals from a region of Vietnam in which typhoid is endemic, and their usefulness for the diagnosis of typhoid fever was evaluated. The antibody responses to both antigens were highly variable among individuals infected with serotype Typhi, and elevated antibody titers were also detected in a high proportion of serum samples from healthy subjects from the community. In-house enzyme-linked immunosorbent assays (ELISAs) for the detection of specific classes of anti-LPS and antiflagellum antibodies were compared with other serologically based tests for the diagnosis of typhoid fever (Widal TO and TH, anti-serotype Typhi immunoglobulin M [IgM] dipstick, and IDeaL TUBEX). At a specificity of > or =0.93, the sensitivities of the different tests were 0.75, 0.55, and 0.52 for the anti-LPS IgM, IgG, and IgA ELISAs, respectively; 0.28 for the antiflagellum IgG ELISA; 0.47 and 0.32 for the Widal TO and TH tests, respectively; and 0.77 for the anti-serotype Typhi IgM dipstick assay. The specificity of the IDeaL TUBEX was below 0.90 (sensitivity, 0.87; specificity, 0.76). The serological assays based on the detection of IgM antibodies against either serotype Typhi LPS (ELISA) or whole bacteria (dipstick) had a significantly higher sensitivity than the Widal TO test when used with a single acute-phase serum sample (P < or = 0.007). These tests could be of use for the diagnosis of typhoid fever in patients who have clinical typhoid fever but are culture negative or in regions where bacterial culturing facilities are not available.

Quinolone-resistant Salmonella typhi in Viet Nam: molecular basis of resistance and clinical response to treatment.

Nalidixic acid-resistant Salmonella typhi (NARST) was first isolated in Viet Nam in 1993. Analysis of the quinolone resistance-determining region of gyrA in 20 NARST isolates by polymerase chain reaction and single-stranded conformational polymorphism yielded two novel patterns: pattern II corresponding to a point mutation at nucleotide 87 Asp-->Gly (n = 17), and pattern III corresponding to a point mutation at nucleotide 83 Ser-->Phe (n = 3). In trials of short-course ofloxacin therapy for uncomplicated typhoid, 117 (78%) of 150 patients were infected with multidrug-resistant S. typhi, 18 (15%) of which were NARST. The median time to fever clearance was 156 hours (range, 30-366 hours) for patients infected with NARST and 84 hours (range, 12-378 hours) for those infected with nalidixic acid-susceptible strains (P < .001). Six (33.3%) of 18 NARST infections required retreatment, whereas 1 (0.8%) of 132 infections due to susceptible strains required retreatment (relative risk = 44; 95% confidence interval = 5.6-345; P < .0001). We recommend that short courses of quinolones not be used in patients infected with NARST.

Respuestas multihormonales a una serie de pruebas neuroendocrinas en psiquiatría: una aproximación multivariada / Multihormonal responses to a series of neuroendocrine challenges in psychiatry: a multivariate approach

Mediante una batería neuroendocrina que incluye la prueba de supresión por dexamotasona, la prueba de estimulación con TRH y respuestas hormonales a apomorfina (PRL, GU, ACTH y cortisol) se estudian 86 pacientes hospitalizados, sin medicación, con los diagnósticos según DSM-IV con Depresión Mayor, esquizofrenia y trastorno esquizoafectivo y 18 controles. Se establecen las diferencias hormonales de los diversos grupos clínicos mediante el análisis factorial de correspondencia, lo que permite formular las posibles procesos fisiopatológicos subyacentes y la identificación de terapias farmacológicas apropiadas. Los resultados sugieren una disregulación cronobiológica del eje hipotálamo-hipófisis-tiroides en la depresión y una disregulación dopaminérgica en presencia de síntomas psicóticos productivos