Evaluation of a bedside blood ketone sensor: the effects of acidosis, hyperglycaemia and acetoacetate on sensor performance.

AIMS: To assess the performance of a handheld bedside ketone sensor in the face of likely metabolic disturbances in diabetic ketoacidosis, namely: pH, glucose and acetoacetate. METHODS: The effects of pH (7.44-6.83), glucose (5-50 mmol/l) and acetoacetate (0-5 mmol/l) were examined in venous blood to investigate the accuracy of betahydroxybutyrate measurement (0-5 mmol/l) by a handheld ketone sensor. Sensor results were compared with a reference method. Linear regression models were fitted to the difference between the methods with the concentration of metabolite as the explanatory factor. RESULTS: Decreasing pH and increasing glucose had no effect on the accuracy of the handheld ketone sensor; the gradients of the fitted lines were -0.14 and -0.003, respectively. The 95% confidence intervals were -0.7-0.4 and -0.01-0.004, respectively (P = 0.59 and 0.4, respectively). In the acetoacetate study, a positive relationship between the sensor and reference method results was found, the gradient was 0.09. The 95% confidence interval was 0.05-0.14 (P < or = 0.001), indicating that high concentrations of acetoacetate interfere with the sensor performance. CONCLUSIONS: Acidosis and hyperglycaemia have minimal effects on the sensor performance. However, high concentrations of acetoacetate result in some overestimation of betahydroxybutyrate. This bedside ketone sensor provides useful data over a broad range of conditions likely to be encountered during moderate to severe diabetic ketoacidosis.

Analytical and clinical aspects of adrenocorticotrophin determination.

Adrenocorticotrophin (ACTH) is formed from the cleavage of pro-opiomelanocortin. Measurement of plasma ACTH is a key step in the differential diagnosis of hypothalamic-pituitary-adrenal disorders. Prior to the development of radioimmunoassay, the bioassays employed for the determination of ACTH were highly complex, time-consuming and costly in terms of number of animals used. Their sensitivity was such that the normal early morning peak of ACTH could not be determined. The introduction of immunoassay methodology enabled the measurement of low normal ACTH concentrations. Immunological recognition of ACTH by the antibodies employed offered improvements with regard to specificity. The development of two-site immunometric assays further improved specificity and the ability to measure low normal ACTH concentrations without the need to extract large volumes of plasma. The quantification of ACTH is now routinely performed in clinical laboratories, with non-radioisotopic methods becoming increasingly popular. ACTH measurement is of limited value in distinguishing between the causes of Cushing's syndrome, as there is considerable overlap in circulating ACTH concentrations in subjects with either a pituitary or an ectopic tumour. The role of ACTH precursor and related peptides in normal and pathological states and the clinical utility of their measurement remain to be fully elucidated. However, there is evidence that measurement of ACTH precursors can be a useful diagnostic tool in identifying the aetiology of Cushing's syndrome. This review will primarily address methodological aspects of ACTH measurement in the diagnosis of clinical conditions.

Detection of maternal serum hCG glycoform variants in the second trimester of pregnancies affected by Down syndrome using a lectin immunoassay.

AIM: To assess whether glycoform variants of human chorionic gonadotrophin (hCG) are present in altered concentrations in the maternal serum in pregnancies affected by Down syndrome. METHODS: In a series of 50 cases of pregnancies complicated by Down syndrome and 278 unaffected pregnancies, we have examined maternal serum levels of hCG glycoforms (GlyhCG) in samples collected in the second trimester (14 to 21 weeks) using a sialic acid binding lectin immunoassay. We have compared these levels with those of other second trimester serum markers (Free beta-hCG, alpha fetaprotein (AFP) and Total hCG) and modelled detection rates and false positive rates of various biochemical markers in conjunction with maternal age using a maternal age standardized population. RESULTS: Maternal serum GlyhCG in cases of Down syndrome was significantly elevated (Median MoM 1.81) with 15 of 50 (30%) cases above the 95th centile for unaffected pregnancies. Free beta-hCG was also elevated (Median MoM 2.16) with 18 of 50 (36%) cases above the 95th centile. AFP levels were reduced (Median MoM 0.75) with 9 of 50 (18%) cases below the 5th centile. Total hCG levels whilst elevated (Median MoM 1.88) had only 15 of 50 (30%) cases above the 95th centile. Maternal serum GlyhCG levels showed significant correlation with total hCG and free beta-hCG (r = 0.6880 and 0.6922) in the Down group but not with AFP (r = 0.1237). When GlyhCG was combined together with AFP and maternal age, at a 5% false positive rate, the modelled detection rate was 53%, some 13% lower than when free beta-hCG was used and some 7% lower than when total hCG was used. CONCLUSION: Maternal serum GlyhCG, as measured by the sialic acid-binding lectin immunoassay is unlikely to be of additional value when screening for Down syndrome in the second trimester.

Maternal serum hyperglycosylated human chorionic gonadotrophin (HhCG) in the first trimester of pregnancies affected by Down syndrome, using a sialic acid-specific lectin immunoassay.

In a series of 54 cases of pregnancies complicated by Down syndrome and 224 unaffected pregnancies we examined maternal serum levels of hyperglycosylated human chorionic gonadotrophin (HhCG) in samples collected in the first trimester (11-13 weeks) using a sialic acid-specific lectin immunoassay. We compared these levels with those of other potential first trimester serum markers [free beta-hCG, pregnancy-associated plasma protein A (PAPP-A) and total hCG (ThCG)] and modeled detection rates and false-positive rates of various biochemical markers in conjunction with fetal nuchal translucency (NT) and maternal age using an maternal age standardized population. Maternal serum HhCG in cases of Down syndrome were significantly elevated (median MoM 1.97) with 24/54 (44%) of cases above the 95th centile for unaffected pregnancies. Free beta-hCG was also elevated (median MoM 2.09) with 33% of cases above the 95th centile. PAPP-A levels were reduced (median MoM 0.47) with 38% below the 5th centile. ThCG levels, whilst elevated (median MoM 1.34), had only 20% of cases above the 95th centile. Maternal serum HhCG levels were not correlated with fetal NT but showed significant correlation with ThCG and free beta-hCG and with PAPP-A in the Down syndrome group (r=0.536). Maternal serum HhCG levels in cases with Down syndrome had a significant correlation with gestational age, increasing as the gestation increased. When HhCG was combined together with fetal NT, PAPP-A and maternal age, at a 5% false-positive rate the modeled detection rate was 83%, some 6% lower than when free beta-hCG was used and some 4% better than when ThCG was used. Maternal serum HhCG is unlikely to be of additional value when screening for Down syndrome in the first trimester.

Evolution of Streptococcus pneumoniae serotypes and penicillin susceptibility in Latin America, Sireva-Vigía Group, 1993 to 1999. PAHO Sireva-Vigía Study Group. Pan American Health Organization.

BACKGROUND: Since 1993 the Pan American Health Organization has coordinated a surveillance network with the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay aimed at monitoring capsular types and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive disease in children <6 years of age. METHODS: The surveillance system included children 6 years of age and younger with invasive disease caused by S. pneumoniae. The identification, capsular typing and susceptibility to penicillin of the isolates were conducted using a common protocol, based on standard methodologies. RESULTS: By June, 1999, 4,105 invasive pneumococcal isolates had been collected mainly from pneumonia (44.1%) and meningitis (41.1%) cases. Thirteen capsular types accounting for 86.1% of the isolates (14, 6A/6B, 5, 1, 23F, 19F, 18C, 19A, 9V, 7F, 3, 9N and 4) remained the most common types during the surveillance period. Diminished susceptibility to penicillin was detected in 28.6% of the isolates, 17.3% with intermediate and 11.3% with high level resistance. Resistance varied among countries and increased during this period in Argentina, Colombia and Uruguay. Serotypes 14 and 23F accounted for 66.6% of the resistance. CONCLUSION: These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.

The nature of human chorionic gonadotrophin glycoforms in gestational thyrotoxicosis.

OBJECTIVE: We examined the charge heterogeneity and carbohydrate complexity of hCG in healthy pregnant Asian subjects and Asian women with gestational thyrotoxicosis to assess whether particular glycoforms of hCG are associated with the thyrotoxicosis of pregnancy. DESIGN: Blood was taken at 8-16 weeks of gestation from five pregnant Asian women with clinical symptoms of gestational thyrotoxicosis and biochemical indicators of hyperthyroidism and from six age-matched healthy pregnant women. hCG charge heterogeneity and carbohydrate complexity were assessed by fast protein liquid chromatography chromatofocusing and concanavalin A affinity chromatography, respectively. The degree of terminal sialylation of the different glycoforms was measured by ricin affinity chromatography, which detects exposed galactose residues following desialylation. RESULTS: Free T3, free T4 and hCG levels were elevated and TSH suppressed in the thyrotoxic subjects compared to controls (P < 0.007). Overall, the glycoform distribution of the hCG in the blood from the control and thyrotoxic groups was similar, with a median pI of 4.34 (median and range: 3.78-4.68) and pI 4.23 (3.98-4.38). Free T4 (P < 0.028) and free T3 (P < 0.03) levels were positively correlated to both the absolute hCG concentration and the percentage of hCG forms between pI 3.36-4.0. The distribution of simple (73-88.6%), intermediate (9.7-26.4%) and complex (0.1-7.3%) branching oligosaccharide forms was similar in both groups, as was the percent hCG which bound to ricin (< 3.2%). CONCLUSION: We conclude that excessive thyroid stimulation in the thyrotoxic patients is associated both with the absolute concentration of hCG and the relative proportion of acidic glycoforms between pI 3.36 and 4.0.

Novel fluorescent broth microdilution method for fluconazole susceptibility testing of Candida albicans.

A comparative evaluation of the reference National Committee for Clinical Laboratory Standards (NCCLS) broth microdilution method with a novel fluorescent carboxyfluorescein diacetate (CFDA)-modified microdilution method for the susceptibility testing of fluconazole was conducted with 68 Candida strains, including 53 Candida albicans, 5 Candida tropicalis, 5 Candida glabrata, and 5 Candida parapsilosis strains. We found trailing endpoints and discordant fluconazole MICs of < 8 microg/ml at 24 h and of > or =64 microg/ml at 48 h for 12 of the C. albicans strains. These strains satisfy the definition of the low-high MIC phenotype. All 12 low-high phenotype strains were correctly shown to be susceptible at 48 h with the CFDA-modified microdilution method. For the 41 non-low-high phenotype C. albicans strains, the CFDA-modified microdilution method yielded 97.6% (40 of 41 strains) agreement within +/-1 dilution at 24 h compared with the reference method and 92.7% (38 of 41 strains) agreement within +/-1 dilution at 48 h compared with the reference method. The five strains each from C. tropicalis, C. glabrata, and C. parapsilosis that were tested showed 100% agreement within +/-2 dilutions for the two methods being evaluated.

A biological, immunological and physico-chemical comparison of the current clinical batches of the recombinant FSH preparations Gonal-F and Puregon.

The immunopotency and in-vitro biopotency of clinical batches of Gonal-F((R)) and Puregon((R)) (recombinant human follicle stimulating hormones) were compared and their carbohydrate chains investigated for charge heterogeneity and internal carbohydrate complexity. Immunopotency (IU/pmol) for both Gonal-F and Puregon was 0.35 +/- 0.01 and biopotency (ED(50), pmol/l) was similar, being 7.3 +/- 0.6 and 5.4 +/- 0.2 respectively. Charge distributions were essentially the same with no difference either in median isoelectric point (pI) (between 4.26 and 4.50), or in the bulk of material fractionated between pI 4 and 5 (66.0 +/- 1.8% Gonal-F and 72.0 +/- 1.8% Puregon). However, there were minor differences in charge at extremes of pI, Gonal-F being slightly more acidic: 18.2% Gonal-F versus 9.8% Puregon at pI 3.5-4.0 (P: = 0.03) and 6.7% Gonal-F versus 10.7% Puregon at pI 5.0-5.5 (P: = 0.03). Carbohydrate complexity was the same: 9.3 versus 10.9 (complex), 76.6 versus 78.6 (intermediate) and 14.1 versus 10.5% (simple). In summary, Gonal-F and Puregon have similar immunopotency, in-vitro biopotency and internal carbohydrate complexity, differing slightly in charge heterogeneity, Gonal-F having more acidic glycoforms. We conclude them to be intrinsically very similar, expecting no difference in clinical efficacy on the basis of respective structure.

Invasive disease due to group B streptococcal infection in adults: results from a Canadian, population-based, active laboratory surveillance study--1996. Sentinel Health Unit Surveillance System Site Coordinators.

In 1996, a population-based surveillance program for invasive adult group B streptococcal (GBS) diseases in Canada was undertaken, to define the epidemiologic and microbiologic characteristics of the disease. Nine public health units across Canada, representing 9.6% of the population, participated in the program. In total, 106 culture-positive cases of invasive adult GBS disease were reported, which represented an incidence rate 4.6 per 100,000 adults (41/100, 000 for pregnant and 4.1/100,000 for nonpregnant adults). Sixty-two (58.5%) of the 106 cases occurred in females, and, of these, 15 (14. 2%) were associated with pregnancy. Serotype V was the most common, accounting for 31% of the 90 GBS isolates typed (26.7% of nonpregnant and 4.4% of pregnant cases). This was followed by serotypes III (19%), Ia (17%), Ib (10%), II (9%), and VII (1%). Thirteen percent were nontypeable. All isolates were susceptible to penicillin, ampicillin, and vancomycin. Resistance to erythromycin and clindamycin was 6.7% and 4.4%, respectively.

The development of a sialic acid specific lectin-immunoassay for the measurement of human chorionic gonadotrophin glycoforms in serum and its application in normal and Down's syndrome pregnancies.

OBJECTIVE: We have developed and validated a lectin-immunoassay for the recognition of sialic acid residues on hCG glycoforms in serum. DESIGN: This assay employs a hCG specific capture antibody and a sialic acid specific lectin (Wheat Germ Agglutinin) labelled with horse radish peroxidase. RESULTS: The standard curve covered hCG concentrations of 0-4000 IU/l (3rd IS for hCG, 75/537) with an analytical sensitivity of 1.0 IU/l. The within and between batch coefficient of variation was < 7% for all doses. Cross-reactivity of < 1% with TSH, LH, FSH, hCGalpha, hCGbeta and desialylated hCG confirmed assay specificity. Dilutions of serum of < 10% final concentration were parallel to the standard curve (within and between batch CV, < 6%). The assay working range was 100 - > 500 000 IU/l and the recovery of hCG from serum was in the range of 94.5% to 115.4%, with a mean value of 102.1%. The assay detected a time dependent change in hCG sialylation during normal pregnancy with the relative abundance of sialylated hCG declining after week 9 and increasing after week 15 of gestation. In addition preliminary studies showed that maternal serum hCG concentrations measured with the lectin-immunoassay were elevated in high risk Down's pregnancies (as defined by conventional screening tests between weeks 16-18 gestation, median multiple of median, 3.14; range 1.81-19.12, P < 0. 001) and low risk (1.57, 0.49-6.14, P = 0.034) compared to normal (1. 00, 0.32-3.20) pregnancies. Furthermore, the lectin immunoassay had greater discriminatory power compared to conventional immunoassay of hCG and hCGbeta between normal and both low and high risk Down's pregnancies. CONCLUSION: This assay will allow analysis of serum samples for the investigation of sialylated variants of hCG glycoforms in various pathological and physiological situations.

The hemodynamic effects of inhaled nitric oxide and endogenous nitric oxide synthesis blockade in newborn piglets during infusion of heat-killed group B streptococci.

OBJECTIVE: To determine the effects of therapy with inhaled nitric oxide (NO) gas and partial or complete blockade of endogenous NO synthesis with N(omega)nitro-L-arginine (L-NA) on the hemodynamic responses to group B streptococci infusion in newborn piglets. DESIGN: Randomized, acute intervention study. SETTING: Animal research laboratory. SUBJECTS: Twenty-five anesthetized piglets younger than 3 days of age divided into five groups. INTERVENTIONS: Heat-killed group B streptococci (GBS) were infused systemically until a 50% increase in pulmonary artery pressure (PAP) was obtained, and the infusion was continued for another 2 hrs. The five groups were designed as follows: group 1, sepsis control: continuous GBS infusion, with two brief trials (10 mins) of inhaled NO given after the initial development of pulmonary hypertension and again 2 hrs later; group 2, continuous inhaled NO: NO was given at 40 ppm for 2 hrs during GBS infusion; group 3, high-dose L-NA pretreatment: 10 mg/kg L-NA bolus followed by 1 mg/kg/min before, and continuing throughout, GBS infusion; group 4, high-dose L-NA: same dose as in group 3, but given after the start of the GBS infusion with continuous inhaled NO at 40 ppm; and group 5, low-dose L-NA: 3 mg/kg bolus given after start of GBS infusion with continuous inhaled NO at 40 ppm. MEASUREMENTS AND MAIN RESULTS: The sepsis controls, group 1, had an increase in PAP, which took 15-45 mins to develop, from a mean of 3.4 (SD 0.7) to 5.9 (1.9) kPa (p < .05), at which time the cardiac index had decreased from 169 (28) to 146 (46) mL/kg/min (p < .05). Brief inhaled NO during the early phase decreased PAP to normal. Two hours later, PAP had increased to 6.1 (0.2) kPa and cardiac index had decreased to 88 (31) mL/kg/min. Inhaled NO after 2 hrs decreased PAP to 3.2 (0.5) kPa and increased cardiac index to 106 (44) ml/kg/min (p < .05). Continuous inhaled NO (group 2) ameliorated the deterioration in cardiac index, which at 2 hrs was 140 (30) mL/kg/min (significantly greater than in the sepsis controls) (p < .05). The L-NA-pretreated animals (group 3) had a greater increase in PAP and pulmonary vascular resistance index when GBS infusion was started. PAP increased from 3.0 (0.7) to 7.3 (1.5) kPa within 15 mins, and cardiac index simultaneously decreased to 68 (20) mL/kg/min. Cardiac index subsequently rapidly deteriorated to 48 (21) mL/kg/min, and only one of five animals survived for 2 hrs. Group 4 animals also developed a rapid deterioration in cardiac output, and only two of five survived for 2 hrs. Group 5 animals had results indistinguishable from group 2 animals. CONCLUSION: Pulmonary hypertension and shock resulting from GBS infusion in newborn piglets are much worse if endogenous NO production is completely inhibited. Continuous inhaled NO with or without low-dose L-NA inhibits the decrease in cardiac output.

Pneumococcal immunization and public health: the Canadian experience.

Pneumococcal vaccine has been poorly used in Canada, despite strong recommendations for its use by the Canadian National Advisory Committee on Immunization. In a recent survey of health officials, however, seven of the 12 Canadian provinces and territories were found to either have a programme for all persons > 65 years of age or were planning to implement one within the next year. Factors that have contributed to this increased interest include: better data on disease incidence and preventable illness from population-based surveillance; data on emerging resistance of Streptococcus pneumoniae in Canada to penicillin and other antimicrobials; implementation of vaccine programmes for the elderly by public health officials in Ontario, Nova Scotia and British Columbia; completion of a cost-benefit study of pneumococcal vaccine for Canada; and increased attention to pneumococcal vaccination at national immunization meetings and in the medical literature. Increased availability of vaccine and competitive pricing are also making programmes for the elderly more feasible and affordable. A national meeting entitled 'Preventing Pneumococcal Disease: A Canadian Consensus Conference' was held in February 1998 to further build on this growing interest.

Fatal group A Streptococcal toxic shock-like syndrome in a child with varicella: report of the first well documented case with detection of the genetic sequences that code for exotoxins spe A and B, in São Paulo, Brazil.

A previously healthy seven-year-old boy was admitted to the intensive care unit because of toxaemia associated with varicella. He rapidly developed shock and multisystem organ failure associated with the appearance of a deep-seated soft tissue infection and, despite aggressive treatment, died on hospital day 4. An M-non-typable, spe A and spe B positive Group A Streptococcus was cultured from a deep soft tissue aspirate. The criteria for defining Streptococcal toxic shock-like syndrome were fulfilled. The authors discuss the clinical and pathophysiological aspects of this disease as well as some unusual clinical findings related to this case.

Molecular epidemiological survey of penicillin-resistant Streptococcus pneumoniae from Asia, Europe, and North America.

One hundred penicillin-resistant Streptococcus pneumoniae (PRSP) strains from Asia, Europe, and North America were analyzed using pulsed-field gel electrophoresis; fingerprinting of penicillin binding protein (pbp) genes; and BOX PCR. Results show that six PFGE patterns (three patterns comprising > or = 2 serotypes) were found widespread and accounted for 64 of the 100 PRSP strains.

Assessment of the effect of amphotericin B on the vitality of Candida albicans.

The processes involved in cell death are complex, and individual techniques measure specific fractions of the total population. The interaction of Candida albicans with amphotericin B was measured with fluorescent probes with different cellular affinities. These were used to provide qualitative and quantitative information of physiological parameters which contribute to fungal cell viability. SYBR Green I and 5,(6)-carboxyfluorescein were used to assess membrane integrity, and bis-(1,3-dibutylbarbituric acid)trimethine oxonol and 3,3-dihexyloxacarbocyanine iodide were used to evaluate alterations in membrane potential. The fluorescent indicators were compared with replication competency, the conventional indicator of viability. By using these tools, the evaluation of the response of C. albicans to amphotericin B time-kill curves delineated four categories which may represent a continuum between alive and dead. The data showed that replication competency (CFU per milliliter) as determined by conventional antifungal susceptibility techniques provided only an estimate of inhibition. Interpretation of fluorescent staining characteristics indicated that C. albicans cells which were replication incompetent after exposure to greater than 0.5 microgram of amphotericin B per ml still maintained degrees of physiological function.

Mycobacteriocidal action of exogenous nitric oxide.

We tested the hypothesis that exposure of extracellular Mycobacterium tuberculosis to low concentrations (< 100 ppm) of nitric oxide (NO) for short periods (24 h or less) will result in microbial killing. We observed that NO had both dose- and time-dependent cidal effects that were very significant by two-way analysis of variance (F ratios of 13.4 [P < 0.001] and 98.1 [P < 0.0001], respectively). Conceivably, extracellular bacilli in patients with pulmonary tuberculosis might be vulnerable to exogenous NO.

Determination of trimethoprim-sulfamethoxazole resistance in Streptococcus pneumoniae by using the E test with Mueller-Hinton agar supplemented with sheep or horse blood may be unreliable. The Pneumococcal Study Group.

An international, multicenter study compared trimethoprim-sulfamethoxazole MICs for 743 Streptococcus pneumoniae isolates (107 to 244 isolates per country) by E test, using Mueller-Hinton agar supplemented with 5% defibrinated horse blood or 5% defibrinated sheep blood, with MICs determined by the National Committee for Clinical Laboratory Standards broth microdilution reference method. Agreement within 1 log2 dilution and minor error rates were 69.3 and 15.5%, respectively, on sheep blood-supplemented agar and 76.9 and 13.6%, respectively, with horse blood as the supplement. Significant interlaboratory variability was observed. E test may not be a reliable method for determining the resistance of pneumococci to trimethoprim-sulfamethoxazole.

Does in vitro susceptibility to rifabutin and ethambutol predict the response to treatment of Mycobacterium avium complex bacteremia with rifabutin, ethambutol, and clarithromycin? Canadian HIV Trials Network Protocol 010 Study Group.

The in vitro susceptibilities of baseline Mycobacterium avium complex (MAC) blood isolates from 86 patients with AIDS who were treated with clarithromycin, ethambutol, and rifabutin were determined to examine whether these results predict bacteriologic response to treatment. No patient received prior prophylaxis with clarithromycin or azithromycin. Minimum inhibitory concentrations (MICs) of clarithromycin for all isolates were < or = 2 micrograms/mL. The median MIC of rifabutin was between 0.25 and 0.5 microgram/mL, and all isolates were susceptible to < or = 2 micrograms of rifabutin/mL. The median MIC of ethambutol was 4 micrograms/mL, and the MIC90 was 8 micrograms/mL. There was no correlation between ethambutol susceptibility and subsequent bacteriologic clearance. At all time points through week 12, bacteriologic clearance occurred more frequently in patients with isolates for which MICs of rifabutin were lower, but this difference was statistically significant only at week 2. Susceptibility testing for baseline MAC isolates from AIDS patients not previously treated with clarithromycin or azithromycin does not appear to be useful in guiding therapy.

Gonadotrophin heterogeneity and biopotency: implications for assisted reproduction.

The extensive heterogeneity of the gonadotrophin hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH), is due primarily to the heterogeneous nature of their carbohydrate side-chains, in particular sialic acid residues. In this review, we discuss the role of carbohydrate chains in receptor binding and activation, biological activity, and metabolic half-life. The synthesis and secretion of the various glycoforms of both FSH and LH appear to be under endocrine control with gonadotrophin-releasing hormone (GnRH), oestradiol and testosterone playing important roles. Evidence for different glycoforms having variable biopotency or different encoded functions is increasing, and the production and secretion of more or less acidic gonadotrophin species in different physiological states may represent an important mechanism whereby the pituitary regulates gonadal cell and organ function. This has potential importance for the development of new pharmaceutical reagents and new therapeutic regimens in assisted reproduction. It is envisaged that the use of existing and new forms of FSH/LH will allow patients to be treated in a more controlled and physiological manner, with treatment regimens individualized to the needs of the patient.