Intraoperative ultrasound guidance in breast-conserving surgery shows superiority in oncological outcome, long-term cosmetic and patient-reported outcomes: Final outcomes of a randomized controlled trial (COBALT).

BACKGROUND: The multicenter randomized controlled COBALT trial demonstrated that ultrasound-guided breast-conserving surgery (USS) results in a significant reduction of margin involvement (3.1% vs. 13%) and excision volumes compared to palpation-guided surgery (PGS). The aim of the present study was to determine long term oncological and patient-reported outcomes including quality of life (QoL), together with their progress over time. METHODS: 134 patients with T1-T2 breast cancer were randomized to USS (N = 65) or PGS (N = 69). Cosmetic outcomes were assessed with the Breast Cancer Conservative Treatment cosmetic results (BCCT.core) software, panel-evaluation and patient self-evaluation on a 4-point Likert-scale. QoL was measured using the EORTC QLQ-C30/-BR23 questionnaire. RESULTS: No locoregional recurrences were reported after mean follow-up of 41 months. Seven patients (5%) developed distant metastatic disease (USS 6.3%, PGS 4.4%, p = 0.466), of whom six died of disease (95.5% overall survival). USS achieved better cosmetic outcomes compared to PGS, with poor outcomes of 11% and 21% respectively, a result mainly attributable to mastectomies due to involved margins following PGS. There was no difference after 1 and 3 years in cosmetic outcome. Dissatisfied patients included those with larger excision volumes, additional local therapies and worse QoL. Patients with poor/fair cosmetic outcomes scored significantly lower on aspects of QoL, including breast-symptoms, body image and sexual enjoyment. CONCLUSION: By significantly reducing positive margin status and lowering resection volumes, USS improves the rate of good cosmetic outcomes and increases patient-satisfaction. Considering the large impact of cosmetic outcome on QoL, USS has great potential to improve QoL following breast-conserving therapy.

[A study of the connection between coercive measures used in a closed acute psychiatric ward and the socio-demographic and clinical characteristics of the patients involved]. / Dwang- en drangmaatregelen binnen een gesloten acute psychiatrische opnameafdeling; relatie met socio-demografische en klinische kenmerken.

BACKGROUND: Admission at a closed acute psychiatric ward is a severe and possibly life changing experience for a patient. Sometimes admission is accompanied by coercive measures. Despite the impact that these measures may have on the patient, very little research has been published concerning this patient population. AIM: To obtain insight into the connection between the socio-demographic characteristics of patients admitted to a closed acute psychiatric ward and the coercive measures to which they were subjected. METHOD: For a year a database was compiled to give us information about the socio-demographic and clinical characteristics of patients admitted to a closed acute psychiatric ward in The Hague in the Netherlands. This record enables us to analyse the relation between these characteristics and coercive measures. RESULTS: The majority of patients admitted were male, single, childless and were unemployed or not in education but were receiving some form of welfare payment. 33% of admissions were in fact re-admissions. 20% of the admissions/re-admissions were secluded during the admission procedure - for the following reasons: symptoms of a psychotic disorder, a manic episode and/or aggression. Secluded patients were younger and had more serious psychiatric problems; they functioned less well and had been in hospital longer than patients who had not been secluded upon admission. During the admission procedure 14% of patients received emergency medication. CONCLUSION: These results have given us more insight into the connection between the use of coercive measures in psychiatry and the socio-demographic characteristics and clinical characteristics of the patients involved. This information could serve as reference material for future research.

Detection of single-nucleotide polymorphisms in Plasmodium falciparum by PCR primer extension and lateral flow immunoassay.

The resistance of Plasmodium falciparum to some antimalarial drugs is linked to single-nucleotide polymorphisms (SNPs). Currently, there are no methods for the identification of resistant parasites that are sufficiently simple, cheap, and fast enough to be performed at point-of-care, i.e., in local hospitals where drugs are prescribed. Primer extension methods (PEXT) were developed to identify 4 SNPs in P. falciparum positioned at amino acids 86, 184, and 1246 of the P. falciparum multidrug resistance 1 gene (pfmdr1) and amino acid 76 of the chloroquine resistance transporter gene (pfcrt). The PEXT products were visualized by a nucleic acid lateral flow immunoassay (NALFIA) with carbon nanoparticles as the detection labels. PCR-PEXT-NALFIAs showed good correlation to the reference methods, quantitative PCR (qPCR) or direct amplicon sequence analysis, in an initial open-label evaluation with 17 field samples. The tests were further evaluated in a blind study design in a set of 150 patient isolates. High specificities of 98 to 100% were found for all 4 PCR-PEXT genotyping assays. The sensitivities ranged from 75% to 100% when all PEXT-positive tests were considered. A number of samples with a low parasite density were successfully characterized by the reference methods but failed to generate a result in the PCR-PEXT-NALFIA, particularly those samples with microscopy-negative subpatent infections. This proof-of principle study validates the use of PCR-PEXT-NALFIA for the detection of resistance-associated mutations in P. falciparum, particularly for microscopy-positive infections. Although it requires a standard thermal cycler, the procedure is cheap and rapid and thus a potentially valuable tool for point-of-care detection in developing countries.

[Manic-psychotic symptoms as clinical manifestation of hyperparathyroidism]. / Manisch-psychotische verschijnselen in het kader van hyperparathyreoïdie met aspecifiek beloop.

We discuss the case history of a woman aged 49 years who displayed manic-psychotic symptoms as a clinical manifestation of hyperparathyroidism. Following resection of the parathyroid she developed severe depression. Primary hyperparathyroidism (PHPT) is characterised by an increase of the parathyroid hormone (PTH), which in turn leads to an increase in the plasma calcium. PHPT can be accompanied by various psychiatric symptoms ranging from personality changes and severe depression to obsessive-compulsive and paranoid symptoms.

[Folie à famille: a Surinamese-Hindustani family with a shared paranoid delusion and severe undernourishment]. / Folie à famille: een Surinaams-Hindoestaans gezin met een gedeelde paranoïde waan en ernstige ondervoeding.

Folie à famille is a rare psychiatric condition in which several family members develop similar psychotic symptoms. We describe the case of a family of four with a shared paranoid delusion, who all obtained complete remission after being treated with antipsychotics on different psychiatric wards.

Direct blood PCR in combination with nucleic acid lateral flow immunoassay for detection of Plasmodium species in settings where malaria is endemic.

Declining malaria transmission and known difficulties with current diagnostic tools for malaria, such as microscopy and rapid diagnostic tests (RDTs) in particular at low parasite densities, still warrant the search for sensitive diagnostic tests. Molecular tests need substantial simplification before implementation in clinical settings in countries where malaria is endemic. Direct blood PCR (db-PCR), circumventing DNA extraction, to detect Plasmodium was developed and adapted to be visualized by nucleic acid lateral flow immunoassay (NALFIA). The assay was evaluated in the laboratory against samples from confirmed Sudanese patients (n = 51), returning travelers (n = 214), samples from the Dutch Blood Bank (n = 100), and in the field in Burkina Faso (n = 283) and Thailand (n = 381) on suspected malaria cases and compared to RDT and microscopy. The sensitivity and specificity of db-PCR-NALFIA compared to the initial diagnosis in the laboratory were 94.4% (95% confidence interval [CI] = 0.909 to 0.969) and 97.4% (95% CI = 0.909 to 0.969), respectively. In Burkina Faso, the sensitivity was 94.8% (95% CI = 0.88.7 to 97.9%), and the specificity was 82.4% (95% CI = 75.4 to 87.7%) compared to microscopy and 93.3% (95% CI = 87.4 to 96.7%) and 91.4% (95% CI = 85.2 to 95.3%) compared to RDT. In Thailand, the sensitivity and specificity were 93.4% (CI = 86.4 to 97.1%) and 90.9 (95% CI = 86.7 to 93.9%), respectively, compared to microscopy and 95.6% (95% CI = 88.5 to 98.6%) and 87.1% (95% CI = 82.5 to 90.6) compared to RDT. db-PCR-NALFIA is highly sensitive and specific for easy and rapid detection of Plasmodium parasites and can be easily used in countries where malaria is endemic. The inability of the device to discriminate Plasmodium species requires further investigation.

Carbon nanoparticles in lateral flow methods to detect genes encoding virulence factors of Shiga toxin-producing Escherichia coli.

The use of carbon nanoparticles is shown for the detection and identification of different Shiga toxin-producing Escherichia coli virulence factors (vt1, vt2, eae and ehxA) and a 16S control (specific for E. coli) based on the use of lateral flow strips (nucleic acid lateral flow immunoassay, NALFIA). Prior to the detection with NALFIA, a rapid amplification method with tagged primers was applied. In the evaluation of the optimised NALFIA strips, no cross-reactivity was found for any of the antibodies used. The limit of detection was higher than for quantitative PCR (q-PCR), in most cases between 10(4) and 10(5) colony forming units/mL or 0.1-0.9 ng/µL DNA. NALFIA strips were applied to 48 isolates from cattle faeces, and results were compared to those achieved by q-PCR. E. coli virulence factors identified by NALFIA were in very good agreement with those observed in q-PCR, showing in most cases sensitivity and specificity values of 1.0 and an almost perfect agreement between both methods (kappa coefficient larger than 0.9). The results demonstrate that the screening method developed is reliable, cost-effective and user-friendly, and that the procedure is fast as the total time required is <1 h, which includes amplification.

Rapid DNA multi-analyte immunoassay on a magneto-resistance biosensor.

We present the rapid and sensitive detection of amplified DNA on a giant magneto-resistance sensor using superparamagnetic particles as a detection label. The one-step assay is performed on an integrated and miniaturized detection platform suitable for application into point-of-care devices. A double-tagged PCR amplification product of the LamB gene of the Escherichia coli bacterium was used to investigate binding kinetics of the assay. We applied magnetic actuation to concentrate the target-particle complexes at the sensor surface and to remove unbound particles from the sensor surface. We achieved biological dose-response curves detecting 4-250pM amplicon concentrations in a one-step format in total assay times of less than 3min. Using various tag-antibody combinations specific for one of the individual genes, multi-analyte detection is shown of several antibiotic resistance genes of the food pathogen Salmonella.

Yang-Yang thermodynamics on an atom chip.

We investigate the behavior of a weakly interacting nearly one-dimensional trapped Bose gas at finite temperature. We perform in situ measurements of spatial density profiles and show that they are very well described by a model based on exact solutions obtained using the Yang-Yang thermodynamic formalism, in a regime where other, approximate theoretical approaches fail. We use Bose-gas focusing [I. Shvarchuck, Phys. Rev. Lett. 89, 270404 (2002)] to probe the axial momentum distribution of the gas and find good agreement with the in situ results.

[Candy sprays and -gels: effect on salivary flow and pH]. / Snoepsprays en -gels: invloed op speekselsecretie en zuurgraad.

After seeing a child with dental erosion in a pediatric dental clinic the fondness and use of sweets were asked. With a questionnaire it became clear that recently various candy sprays and -gels are available to keep a sweet and fresh taste in the mouth at school. The buffer capacity of a number of sprays and gels were determined and they were tested in the mouth. The taste determines the increase in salivary flow rate. The effects of a taste stimulus on increasing the flow rate and decreasing the pH disappear within 2 until 3 minutes. Concluding: the Candy sprays and particularly the Juicy Drop Pop belong, from the dental point of view, to children sweets with high risk for dental caries and erosion. The use of these fluid sweets has to be reduced as much as possible.

Diagnosis of schistosomiasis by reagent strip test for detection of circulating cathodic antigen.

A newly developed reagent strip assay for the diagnosis of schistosomiasis based on parasite antigen detection in urine of infected individuals was evaluated. The test uses the principle of lateral flow through a nitrocellulose strip of the sample mixed with a colloidal carbon conjugate of a monoclonal antibody specific for Schistosoma circulating cathodic antigen (CCA). The strip assay to diagnose a group of highly infected schoolchildren in Mwanza, Tanzania, demonstrated a high sensitivity and association with the intensity of infection as measured both by egg counts, and by circulating anodic antigen and CCA levels determined by enzyme-linked immunosorbent assay. A specificity of ca. 90% was shown in a group of schistosome-negative schoolchildren from Tarime, Tanzania, an area where schistosomiasis is not endemic. The test is easy to perform and requires no technical equipment or special training. The stability of the strips and the conjugate in the dry format lasts for at least 3 months at ambient temperature in sealed packages, making it suitable for transport and use in areas where schistosomiasis is endemic. This assay can easily be developed to an end-user format.

Principles of some novel rapid dipstick methods for detection and characterization of verotoxigenic Escherichia coli.

AIMS: The verotoxigenic Escherichia coli (VTEC) serotype most commonly associated with verotoxin (VT) production is O157:H7, but other serotypes have also been implicated in food-borne illness. These serotypes exhibit much greater genetic and biochemical diversity than E. coli O157:H7, making screening for all VTEC difficult. Here we describe development and testing of novel multi-analyte antibody-based dipstick methods for presumptive detection of VTEC cells and VTs, including non-O157 serotypes. METHODS AND RESULTS: The dipsticks are formatted as paddle-style and lateral flow devices. Test materials included raw milk, minced beef, apple juice and salami, spiked with VTEC. Prototype paddle dipsticks gave 47 of 48 E. coli O157-positive samples correct, and, simultaneously, 27 of 31 O26-positive samples correct, across the four food types. Prototype lateral flow dipsticks gave 12 of 12 E. coli O157-positive milk samples correct and, simultaneously, 28 of 28 positive VT samples correct. CONCLUSIONS: This work demonstrates that simple and rapid detection of more than one VTEC characteristic (toxin production and type, serogroup) is possible in a single dipstick test device, directly from a food enrichment culture. SIGNIFICANCE AND IMPACT OF THE STUDY: The development of simple easy-to-use rapid methods for simultaneous detection and preliminary characterization of VTEC will enable the risk presented by all VTEC to be more thoroughly assessed (e.g. in surveillance studies, outbreak investigations).

Ultrasound-guided lumpectomy of nonpalpable breast cancer versus wire-guided resection: a randomized clinical trial.

BACKGROUND: The wire-guided excision of nonpalpable breast cancer often results in tumor resections with inadequate margins. This prospective, randomized trial was undertaken to investigate whether intraoperative ultrasound (US) guidance enables a better margin clearance than the wire-guided technique in the breast-conserving treatment of nonpalpable breast cancers. METHODS: Patients with a preoperative histological diagnosis of nonpalpable breast cancer that could be visualized both with US and mammography were included. Patients were randomized to undergo either a wire-guided or a US-guided excision. Adequate margins were defined as >or=1 mm. RESULTS: Of 49 included patients, 23 were assigned to undergo wire-guided excision and 26 to undergo US-guided excision. One patient crossed over to US-guided excision after inadvertent wire displacement. Mean tumor diameter, specimen weight, and operating time were similar in both groups. The excision was adequate in 24 (89%) of 27 US-guided excisions and 12 (55%) of 22 wire-guide excisions (P =.007). CONCLUSIONS: US-guided excision seems to be superior to wire-guided excision with respect to margin clearance of mammographically detected and US-visible nonpalpable breast cancers. Patients do not have to undergo the unpleasant wire placement before surgery.

A randomised, double-blind comparison of milnacipran and imipramine in the treatment of depression.

This multicentre, double-blind, randomised trial in 109 patients compared the efficacy and tolerance of the novel selective serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressant milnacipran (50 mg twice daily, n=53) with the established tricyclic agent imipramine (75 mg twice daily, n=56) over a period of 6 weeks, in patients with major depression (Montgomery-Asberg depression rating score (MADRS) > or =25). Initiation of antidepressant medication was conducted during a 2-week period of hospitalisation, after a 3- to 7-day washout period. Concomitant psychiatric medication was limited to lorazepam, cyamemazine, chloral hydrate and long-term uncomplicated lithium therapy. Assessment for efficacy using the MADRS and Hamilton rating scales of depression, a visual analogue scale and global evaluation revealed both agents to be highly effective (P=0.0001) in this group of patients. Milnacipran was found to be of similar efficacy to imipramine. Tolerance, assessed by physiological and biochemical examinations with routine inventory and spontaneous report of adverse events, revealed a clear advantage for milnacipran. The incidence of anticholinergic events with milnacipran was about half that with imipramine and the overall incidence of adverse events by either reporting method was markedly lower with milnacipran than with imipramine. Furthermore, the patient drop-out rate with imipramine was double that experienced with milnacipran. Milnacipran appears to possess equal antidepressant efficacy to imipramine but with markedly superior tolerance. Therefore, milnacipran constitutes an important new treatment option in major depression.

Synthetic peptides derived from the beta2-beta3 loop of Raphanus sativus antifungal protein 2 that mimic the active site.

Rs-AFPs are antifungal proteins, isolated from radish (Raphanus sativus) seed or leaves, which consist of 50 or 51 amino acids and belong to the plant defensin family of proteins. Four highly homologous Rs-AFPs have been isolated (Rs-AFP1-4). The structure of Rs-AFP1 consists of three beta-strands and an alpha-helix, and is stabilized by four cystine bridges. Small peptides deduced from the native sequence, still having biological activity, are not only important tools to study structure-function relationships, but may also constitute a commercially interesting target. In an earlier study, we showed that the antifungal activity of Rs-AFP2 is concentrated mainly in the beta2-beta3 loop. In this study, we synthesized linear 19-mer peptides, spanning the entire beta2-beta3 loop, that were found to be almost as potent as Rs-AFP2. Cysteines, highly conserved in the native protein, are essential for maintaining the secondary structure of the protein. Surprisingly, in the 19-mer loop peptides, cysteines can be replaced by alpha-aminobutyric acid, which even improves the antifungal potency of the peptides. Analogous cyclic 19-mer peptides, forced to adopt a hairpin structure by the introduction of one or two non-native disulfide bridges, were also found to possess high antifungal activity. The synthetic 19-mer peptides, like Rs-AFP2 itself, cause increased Ca2+ influx in pregerminated fungal hyphae.

[Psychiatric manifestations of lupus erythematosus systemic and Sjogren's syndrome]. / Troubles psychiatriques du lupus érythémateux disséminé et du syndrome de Gougerot-Sjögren. A propos d'une observation d'un syndrome de Gougerot-Sjögren secondaire associé à un lupus érythémateux disséminé.

UNLABELLED: We present one case of Sjögren's syndrome (SS) secondary to systemic lupus erythematosus (SLE) with predominant psychiatric manifestations, treated with success by cyclophosphamide. From this case, we review the psychiatric aspects of these two autoimmune diseases as described in the literature and we present the etiopathogenic hypothesis and treatment of the psychiatric disorders. Case report--In August 1996, a 38 year old man was admitted in our psychiatric department for agitation. Primary SS had been diagnosed in July 1996. He had previously attempted to suicide but was never hospitalized in a psychiatric department. During the hospitalization in our department, the patient had auditive hallucinations and felt persecuted. He received loxapine 400 mg/day and was remitted in a few days. He was discharged to a convalescent home with the diagnosis of brief psychotic disorder. In October 1996, he was readmitted to our department for agitation. He had shown agitated behavior and aggression in the convalescent home. There were no hallucinations and no affective disorders. He became calm rapidly and was discharged home a few days later. In November 1996, he was found in a coma by a neighbor. He was admitted to an intensive care unit. The lumbar punction revealed blood cells. Cerebral computer tomography showed subarachnoid hemorrhage. The diagnosis was meningeal hemorrhage due to vasculitis. After regaining consciousness, the patient complained of reduced visual acuity. This was believed to be due to retrobulbar neuritis and the patient's vision improved slightly with corticosteroids. The third hospitalization in our department occurred in February 1997 for depression. The patient had shut himself away for days in his apartment. He had suicidal ideas. His mood improved progressively under fluoxetine 40 mg/day. He was discharged to a convalescent home with the diagnosis of major depressive disorder. The fourth and last admission in our department occurred in June 1997. There were disturbances of memory and orientation. He felt sad and guilty about accusation of sexual abuse on his daughter. He presented typical histrionic symptoms: he had catatonic attitudes only in public areas such as the corridors. Cerebral computer tomography and electroencephalogram were normal. There was no biological abnormality. Signs of confusion rapidly disappeared. He felt better after reintroduction of fluoxetine 40 mg/day. Diagnosis was non-specified depressive disorder, but this episode could be retrospectively seen as delirium. After being hospitalized on these four occasions in one year in our psychiatric department, the diagnosis of his systemic disease was revised by rheumatologists. The patient was diagnosed as suffering from systemic lupus erythematosus associated with secondary Sjögren's syndrome. From September 1997, he received cyclophosphamide 2 g intraveinously per month during 6 months. His vision improved dramatically. His ocular dryness became milder. His mood is now stable. He has not suffered from hallucinations or delusion since. Psychiatric disorders in SLE--During the course of SLE, the occurrence of psychiatric manifestations varies widely from 5 to 83%. They include psychotic disorders, major depressive disorders, subtle cognitive disorders and personality disorders of histrionic type. Etiopathogenic hypothesis are: direct activity of the disease on the central nervous system by autoantibodies (antiphospholipide and antiribosome P autoantibodies) (18, 19) or cytokines (interleukin 2, interleukin 6, alpha interferon) (38, 59), side-effects of glucocorticosteroids and hydroxychloroquine (16) or anxious reaction to a chronic and potentially lethal illness (43, 54). Nevertheless, immunologic and cerebral imagery research suggests that psychiatric disorders are related to vasculitis and non-inflammatory vasculopathy of the small cerebral blood vessels. The management of the patients should include treatment of the disease itself and specific psychotropic treatment. Glucocorticosteroids and especially intravenous infusions of immunosuppressive agents, such as cyclophosphamide, are effective. Psychotropic drugs must be used, making sure to avoid SLE-inducing drugs, like chlorpromazine, carbamazepine and lithium carbonate (19, 20, 45). In addition, psychologic care is essential. Psychiatric disorders in SS--During the course of the primary SS, the occurrence of psychiatric disorders is large as well: from 20 to 70% (47, 61, 62). They are mainly major depressive disorders, anxiety disorders, cognitive disorders and dementia. Brief psychotic disorders and delirium are rare. Etiopathogenic hypotheses are similar as those in SLE, with some differences: antiphospholipide and antiribosome P autoantibodies are not usually found in SS and anti-Ro (SSA) autoantibodies in serum are associated with psychiatric disorders (3-11, 61). According to Drosos et al. (29, 30), psychiatric disorders are explained by psychological distress. This slowly progressive fluctuating disease creates constant discomfort from dysphagia, dyspareunia and functional disability. Some of these manifestations can be treated by corticosteroids and psychotropic drugs. Drugs with anticholinergic side-effects, like phenothiazines, tricyclic antidepressants and hydroxyzine which can enhance the oral dryness have to be avoided. Social and psychological support is important too. DISCUSSION: The diversity of psychiatric morbidity in SLE and SS may be due to differences in patient selection and a lack of uniform clinical criteria. Studies which use standardized diagnostic criteria and control groups don't allow one to come to a conclusion about the relative prevalence of the psychiatric disorders in these autoimmune diseases. This will probably be resolved thanks to the recently published "American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes" (1). Finally, we can ask ourselves if there is a significant number of undiagnosed SLE and SS in psychiatric departments. Two studies report systematic search for SLE in psychiatric patients. In 1992, Hopkinson et al. (39) searched for several autoantibodies in serum samples of nearly 300 hospitalized psychiatric patients. In 1993, Van Dam et al. (65) did the same with more than 2,000 patients admitted to a psychiatric hospital. Hopkinson et al. found 1% undiagnosed SLE, which is much higher than in general population, and recommended to search SLE in every patient with a high erythrocyte sedimentation rate in psychiatric services. Results of the Van Dam et al. study suggest on the contrary, that SLE is not a common cause of admission to psychiatric hospitals. There is no study which report systematic search of Sjögren's syndrome in a psychiatric department. This is probably because most of patients receive or have recently received psychotropics with anticholinergic side-effects which is an exclusion criteria of SS. CONCLUSION: Psychiatrists should keep in mind that SLE and primary SS are potential causes of psychiatric manifestations when examining patients with multiple unexplained somatic complaints and psychiatric symptoms. They should then search for autoantibodies in the serum after careful physical examination. Diagnosis of SLE or SS could lead to a better adapted prescription of corticosteroids and/or immunosuppressive drugs and specific psychotropic drugs, making sure to avoid lupus-inducing drugs in SLE and drugs with anticholinergic effects in SS. The existence of psychiatric manifestations in SLE and SS constitutes an indisputable clinical reality that each practitioner must be able to recognize and treat.

The unfolding/denaturation of immunogammaglobulin of isotype 2b and its F(ab) and F(c) fragments.

The unfolding and further denaturation of IgG and its F(ab) and F(c) fragments were studied both on a macroscopic and molecular level, using differential scanning calorimetry and circular dichroism spectroscopy, respectively. It was shown that the structural integrity of the F(ab) and F(c) units was retained after fragmentation of the IgG. The F(ab) fragment denatured at approximately 61 degrees C and the F(c) fragment at 71 degrees C. The structural transitions observed in the whole IgG is the sum effect of those determined for the isolated F(ab) and F(c) fragments.