Clinical acceptability and immunogenicity of a pentavalent parenteral combination vaccine containing diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis and Haemophilus influenzae type b conjugate antigens in two-, four- and six-month-old Chilean infants

The syndromes of Sotos and Weaver are paradigmatic of the daily nosologic difficulties faced by clinical geneticists attempting to diagnose and counsel, and to give accurate prognoses in cases of extensive phenotypic overlap between molecularly undefined entities. Vertebrate development is constrained into only very few final or common developmental paths; therefore, no developmental anomaly seen in humans is unique to ("pathognomonic" of) one syndrome. Thus, it is not surprising that prenatal overgrowth occurs in several syndromes, including the Sotos and Weaver syndromes. Are they sufficiently different in other respects to allow the postulation of locus (rather than allele) heterogeneity? Phenotypic data in both conditions are biased because of ascertainment of propositi, and the apparent differences between them may be entirely artificial as they were between the G and BBB syndromes. On the other hand, the Sotos syndrome may be a cancer syndrome, the Weaver syndrome not (though a neuroblastoma was reported in the latter); in the former there is also remarkably advanced dental maturation rarely commented on in the latter. In Weaver syndrome there are more conspicuous contractures and a facial appearance that experts find convincingly different from that of Sotos individuals. Nevertheless, the hypothesis of locus heterogeneity is testable; at the moment we are inclined to favor the hypothesis of allele heterogeneity. An international effort is required to map, isolate, and sequence the causal gene or genes.     

Balloon atrial septostomy under two-dimensional echocardiographic control: a new outlook

The comorbidity of eating disorders and reflex sympathetic dystrophy syndrome in the same patients raises the possibility of a common pathway for both conditions. Reflex sympathetic dystrophy syndrome may be manifesting itself in those individuals who have sympathetic overdrive. Microtrauma, often induced by compulsive exercise, and depression may be contributory factors. It is recommended that: patients with eating disorders who develop pain in an extremity should be investigated for possible reflex sympathetic dystrophy syndrome; patients with reflex sympathetic dystrophy syndrome should be discouraged from dieting, and eating disorders should be suspected if they begin to lose weight or are already malnourished.     

Achalasia in Down''s syndrome

Gastrointestinal disorders, including motor disorders of the esophagus, occur more frequently in patients with Down's syndrome than in the general population. We recently diagnosed achalasia in a man with Down's syndrome, an association reported only once before. Of the 643 patients with achalasia treated at our institution over a 30-year period (1962-1992), a total of three had Down's syndrome. We report their clinical, radiological, and manometric findings. Achalasia may be underdiagnosed in patients with Down's syndrome because their intellectual impairment may interfere with their ability to report symptoms adequately. All three patients responded well to conventional treatment.     

Viral hemorrhagic fever]

Rett syndrome and Angelman syndrome are neurodevelopmental disorders characterized by severe intellectual disability, microcephaly, speech disturbance, movement disorders with gait and/or truncal ataxia, and occasionally a similar facial appearance. Both conditions can be difficult to diagnose in girls early in their clinical course and can be difficult to distinguish from each other. Genomic imprinting is a known association in Angelman syndrome and previously has been suggested in Rett syndrome. Our aim was to evaluate the methylation status in a cohort of classical patients with Rett syndrome, using a methylation system for chromosome 15q11-13. Methylation analysis of chromosome 15 has not been previously reported in Rett syndrome. Furthermore, we document the clinical features of 31 girls with classical Rett syndrome and confirm the phenotypic similarities between Rett syndrome and Angelman syndrome. The methylation studies in these girls with Rett syndrome were normal. This excludes an imprinting error of the Angelman syndrome critical region on chromosome 15 (15q11-13) as an association with Rett syndrome, and indicates that methylation studies may be useful in distinguishing Rett syndrome from Angelman syndrome in young patients with an overlapping clinical phenotype. A normal methylation pattern, however, does not exclude the diagnosis of Angelman syndrome and clear distinction between the two syndromes will evolve over time.     

Atypical case of Smith-Lemli-Opitz syndrome: implications for diagnosis

Anti-GQ1b antibodies were assayed by an enzyme-linked immunosorbent assay in sera from patients with non-neurological disorders (N = 20), and with various neurological disorders (N = 59), including nine cases of Miller Fisher syndrome, 16 cases of Guillain-Barré syndrome and one case of acute post-infectious ophthalmoparesis. Such antibodies were found in most cases (8 out of 9) of Miller Fisher syndrome, and at very high titres, in one case of Guillain-Barré syndrome characterised by an initial ophthalmoparesis, and in the case of isolated post-infectious ophthalmoparesis. The latter was characterised by a long-lasting occurrence of these antibodies. Anti-GQ1b antibodies are specific for an immune-mediated neuropathy of the cranial, especially oculomotor, nerves.     

Munchausen's syndrome and substance abuse

The syndrome of factitious disorders with physical symptoms was named "Munchausen's syndrome" by Richard Asher (1951). The present article contains an interesting case report of a patient who has a history of Munchausen's syndrome, substance abuse, and genuine physical illness. A review of the literature supports a strong association of substance abuse in patients with Munchausen's syndrome. Also important for clinicians to remember is that patients with Munchausen's syndrome often have true physical illnesses which need appropriate treatment. The patient described here has successfully begun treatment with methadone maintenance, but further study will be needed regarding methadone maintenance's role in the management of Munchausen's syndrome.     

In vivo efficacy of SM-20302, a GP IIb/IIIa receptor antagonist, correlates with ex vivo platelet inhibition in heparinized blood but not in citrated blood

This study analyzed temporal changes of striatal dopamine-D2 receptor binding during the course of different extrapyramidal movement disorders using 123I-iodobenzamide (IBZM) SPECT. METHODS: Eighteen patients (9 with Parkinson's disease, 9 with parkinsonian plus syndrome) were followed for 11-53 mo. Dopamine-D2 receptor binding was assessed using 123I-IBZM SPECT at the beginning and at the end of the follow-up period. SPECT data were acquired 120 min postinjection of 3-5 mCi 123I-IBZM. A semiautomated algorithm was applied to the raw data for semiquantitative evaluation of regional cerebral receptor binding. RESULTS: Intraobserver (r = 0.992) and interobserver (r = 0.930) variance was low for the semiautomated interpretation of the SPECT examination of the dopaminergic D2 receptor binding, reflecting a highly reproducible SPECT algorithm. Mean specific dopamine-D2 receptor binding was lower in patients with parkinsonian plus syndrome compared to patients with Parkinson's disease on the initial (p < 0.001) as well as the follow-up study (p < 0.001). In patients with Parkinson's disease, we observed an unaffected receptor binding compared to a reduced binding of radiotracer in patients with parkinsonian plus syndrome during the course of the disease (p < 0.001). CONCLUSION: During the follow-up, patients with Parkinson's disease showed a constant dopamine-D2 receptor binding. In contrast, patients with parkinsonian plus syndrome revealed a decline of the binding of dopamine-D2 receptor. These findings are in agreement with histopathological data that demonstrated a preserved dopamine-D2 receptor status in patients with Parkinson's disease and a decline of the dopamine-D2 receptors in patients with parkinsonian plus syndrome. SPECT examinations using 123I-IBZM are useful for assessing dynamic changes of dopamine-D2 receptors in extrapyramidal movement disorders. Semiquantitative SPECT evaluations may provide valuable information for clinical management and prognosis of the patient with extrapyramidal movement disorders.     

von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome

BACKGROUND: Thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome are severe microvascular disorders of platelet clumping with similar signs and symptoms. Unusually large multimers of von Willebrand factor, capable of agglutinating circulating platelets under high shear stress, occur in the two conditions. We investigated the prevalence of von Willebrand factor-cleaving protease deficiency in patients with familial and nonfamilial forms of these disorders. METHODS: Plasma samples were obtained from 53 patients with thrombotic thrombocytopenic purpura or hemolytic-uremic syndrome. Von Willebrand factor-cleaving protease was assayed in diluted plasma samples with purified normal von Willebrand factor as the substrate. The extent of the degradation of von Willebrand factor was assessed by electrophoresis in sodium dodecyl sulfate-agarose gels and immunoblotting. To determine whether an inhibitor of von Willebrand factor-cleaving protease was present, we measured the protease activity in normal plasma after incubation with plasma from the patients. RESULTS: We examined 30 patients with thrombotic thrombocytopenic purpura and 23 patients with the hemolytic-uremic syndrome. Of 24 patients with nonfamilial thrombotic thrombocytopenic purpura, 20 had severe and 4 had moderate protease deficiency during an acute event. An inhibitor found in 20 of these patients was shown to be IgG in five of five tested plasma samples. Of 13 patients with nonfamilial hemolytic-uremic syndrome, 11 had normal levels of activity of von Willebrand factor-cleaving protease during the acute episode, whereas in 2 patients, the activity was slightly decreased. All 6 patients with familial thrombotic thrombocytopenic purpura lacked von Willebrand factor-cleaving protease activity but had no inhibitor, whereas all 10 patients with familial hemolytic-uremic syndrome had normal protease activity. In vitro proteolytic degradation of von Willebrand factor by the protease was studied in 5 patients with familial and 7 patients with nonfamilial hemolytic-uremic syndrome and was normal in all 12 patients. CONCLUSIONS: Nonfamilial thrombotic thrombocytopenic purpura is due to an inhibitor of von Willebrand factor-cleaving protease, whereas the familial form seems to be caused by a constitutional deficiency of the protease. Patients with the hemolyticuremic syndrome do not have a deficiency of von Willebrand factor-cleaving protease or a defect in von Willebrand factor that leads to its resistance to protease.     

Clinical study of the relation of borderline personality disorder to Briquet's syndrome (hysteria), somatization disorder, antisocial personality disorder, and substance abuse disorders

OBJECTIVE: The criteria for borderline personality disorder seem to select patients with very high rates of Briquet's syndrome (hysteria), somatization disorder, antisocial personality disorder, and substance abuse disorders. This study was undertaken to determine whether systematic assessment of patients with borderline personality disorder would reveal characteristic features of that condition which would distinguish it from these other disorders. METHOD: Eighty-seven white female patients (75 in St. Louis and 12 in Milan, Italy) who had borderline personality disorder according to both the DSM-III-R criteria and the Revised Diagnostic Interview for Borderlines were further examined with the DSM-III-R Checklist and the Perley-Guze Hysteria Checklist to determine their patterns of psychiatric comorbidity. RESULTS: Every patient had at least one additional DSM diagnosis. Patients in St. Louis and Milan averaged five and four additional diagnoses, respectively. Eighty-four percent of the patients in St. Louis met criteria for either somatization disorder, Briquet's syndrome, antisocial personality disorder, or substance abuse disorders. Patterns of comorbidity for panic (51%), generalized anxiety disorder (55%), and major depression (87%) in St. Louis were consistent with those in other studies. CONCLUSIONS: The data indicate that the boundaries for the borderline condition are not specific and identify a high percentage of patients with these other disorders. Furthermore, the comorbidity profiles closely resemble the psychiatric profiles of patients with these disorders. If the borderline syndrome is meant to include all of these disorders, its usefulness as a diagnosis is limited. Until the fundamental features of borderline personality disorder that distinguish it from the others are identified, it is recommended that clinicians carefully assess patients for these other diagnoses. Efforts should be made to change the borderline personality disorder criteria by shifting away from overlap with the criteria for the other disorders.     

Is functional dyspepsia just a subset of the irritable bowel syndrome?

To determine whether functional dyspepsia and irritable bowel syndrome are different entities, epidemiological data, factor analysis studies, physiological data and associated psychological symptoms were reviewed. Between 30% and 60% of patients with either diagnosis also meet the criteria for the other diagnosis, a level greater than expected to occur by chance but not sufficient to infer an identity. Most factor analysis studies identify independent clusters of symptoms corresponding to functional dyspepsia and irritable bowel syndrome. Visceral hypersensitivity is seen throughout the gastrointestinal tract in both disorders, but the motility patterns seen in association with functional dyspepsia (principally antral hypomotility and delayed gastric emptying) differ from the motility patterns seen in irritable bowel syndrome. Psychological symptoms are similar in these two disorders but are not believed to be aetiological for either of them. Thus, based on a factor analysis of gastrointestinal symptoms and differences in intestinal motility, functional dyspepsia and irritable bowel syndrome appear to be different entities.     

Serum antibodies to heparan sulfate glycosaminoglycans in Guillain-Barré syndrome and other demyelinating polyneuropathies

We tested for serum antibodies to glycosaminoglycans (GAGs), including heparan sulfate, in patients with Guillain-Barré syndrome (GBS) and other disorders. We used ELISA methods that optimize immunoglobulin binding to carbohydrate antigens to measure serum antibodies to heparan sulfate GAGs in GBS, and control neuromuscular and immune disorders. We found serum IgM or IgG antibodies to heparan sulfate GAGs in 34% of patients with GBS. Serum IgM binding to heparan sulfate GAGs was also found in some chronic demyelinating polyneuropathies, with the highest frequency (33%) in patients with IgM anti-MAG M-proteins. Antibodies to heparan sulfate GAGs were rare (1%) in control serums from patients with other disorders. This result is the first demonstration of high titer serum antibodies to a specific antigen in a substantial group of, and with some specificity for, patients with the classically described GBS syndrome of acute-onset, motor-sensory polyneuropathy with demyelinating features.     

Minimizing alcohol exposure of the breastfeeding infant

A 50-year-old woman developed an acute febrile dermatosis on two occasions concurrently with recurrent Crohn's disease of the colon. Based on the presence of painful erythematous plaques on both hands and forearms, on the leukocytosis with excess bands in peripheral blood, on the histology showing dermal infiltration by mature granulocytes, and on the prompt response to steroids, the diagnosis was made of Sweet's syndrome associated with Crohn's disease. Sweet's syndrome is thought to be a hypersensitivity reaction that leads to parainflammatory (e.g., infections, autoimmune disorders, vaccinations) and paraneoplastic (myeloproliferative disorders, solid malignancy) associations, with a frequency of 10-30%. The association of Sweet's syndrome with Crohn's disease is very rare, but the gastroenterologist should readily differentiate it; it is important to be aware that such patients may have a nonspecific elevated activity index owing to the underlying dermatosis.     

Melatonin treatment for circadian rhythm sleep disorders

We administered 1-3 mg melatonin to 11 patients (eight men, three women, aged 16-46 years) with circadian rhythm sleep disorders; nine with delayed sleep phase syndrome and two with non-24-hour sleep-wake syndrome. Sleep logs were recorded throughout the study periods and actigraph and rectal temperature were monitored during treatment periods. Melatonin was administered 1-2 h before the desirable bedtime for expected phase-shifting, or 0.5-1 h before habitual bedtime for gradual advance expecting an hypnotic effect of the melatonin. Melatonin treatments were successful in 6/11 patients. Timing and dose of melatonin administration, together with its pharmacological properties for circadian rhythm sleep disorders, should be further studied.     

The hemostatic system function of patients with severe forms of diphtheria

Hemostasis of 100 patients with severe diphtheria infection was studied throughout the disease. The patients were found to have marked procoagulant, anticoagulant and fibrinolytic disorders. Antithrombogenic activity of the vascular wall was also abnormal. The above impairments correlated with the symptoms severity and are interpreted as DIC syndrome which ran subclinically or as hemorrhagic syndrome. The majority of the patients underwent a hyperhypocoagulant phase of DIC syndrome.     

Entrapment neuropathies

Relative frequency of entrapment neuropathies was studied from amongst the patients referred to an electrodiagnostic medicine laboratory for electrophysiological studies. During the study period electrophysiological procedures were done on 650 patients with various peripheral nerve disorders. The entrapment neuropathies constituted 8.5%. Carpal tunnel syndrome (CTS) was the commonest entrapment neuropathy (83.6%). Diagnosis of CTS was established in 84 Patients referred with the diagnosis of CTS. Electrophysiological tests confirmed the diagnosis of thoracic outlet syndrome in 4 (15.4%) of the 26 patients referred with this diagnosis and in 5 (19.3%) of them the diagnosis turned out to be CTS. Diagnosis of cubital tunnel syndrome was not suspected clinically in all the 3 patients, they were referred with the diagnosis of ulnar neuropathy. In both the patients with tarsal tunnel syndrome the initial diagnosis was peripheral neuropathy.     

Cyclosporine in glomerular disease

Cyclosporine was introduced in 1981 as an immunosuppressive agent in renal transplantation. Its use was soon extended to the treatment of various glomerular disorders. In light of its known immunomodulating effects, the use of cyclosporine has been most prominent in those glomerular diseases thought to have an immune basis. The most careful studies of cyclosporine in glomerular diseases have been performed in the pediatric population with idiopathic nephrotic syndrome (i.e., minimal change disease and focal segmental glomerulosclerosis), although data are accumulating regarding efficacy and safety in adults with idiopathic nephrotic syndrome. In patients who are steroid-dependent, cyclosporine therapy can induce complete or partial remission in a significant proportion of cases; success rates in patients with steroid-resistant nephrotic syndrome are less encouraging. Treatment with cyclosporine allows for dose reduction or elimination of corticosteroids, and the consequent salutary effect on growth in the child and glucose and bone metabolism in all patients. Studies that suggest a potential benefit of cyclosporine in recurrent nephrotic syndrome in renal allografts and in other glomerular diseases are also discussed.     

Heart and autonomic nervous system in connective tissue disorders

Heart rate variability (HRV) is a suitable diagnostic tool in identifying patients with autonomic nervous system (ANS) disorders even in pre-clinical stage. We have enrolled in this study all patients with large variety of connective tissue disorders, given the possibility of an involvement of ANS in these diseases. The study population consisted in eighty-five patients (68 females and 17 males), 35 of whom affected by systemic lupus erythematosus, 16 by rheumatoid arthritis, 14 by Sj?gren syndrome, 12 by progressive systemic sclerosis, 3 by Beh?et syndrome and 5 by antiphospholipid antibodies syndrome. The mean age ranged between 33.7 of patients with lupus erythematosus and 51.8 of those with Sj?gren syndrome. As control, we enrolled healthy subjects of different age, divided into two groups, to rule out the aging as potential source of considered parameters alteration. The autonomic function has been evaluated by 24 hours ambulatory monitoring, using a Zymed 1210 Scanner with Zymed 3.74-PC 1990 software. We have considered: in the time domain, the standard deviation of the RR intervals average (SDNN) and the percentage of RR adjacent intervals differing each other more than 50 msec (pNN50); in the frequency domain, the low (LF) and high (HF) frequencies, the LF/HF ratio, and the total power (RT). The HRV parameters resulted abnormal in every type of the connective tissue diseases considered: particularly SDNN, pNN50, LF, HF and RT (p < or = 0.01). In conclusion: the results of our study suggest that autonomic neuropathy may be present in any kind of connective tissue disorders even in preclinical stage.     

The course of geriatric depression with "reversible dementia": a controlled study

OBJECTIVE: The goals of this longitudinal investigation were 1) to study the rate of development of irreversible dementia in elderly depressed patients with a dementia syndrome that subsided after improvement of depression and 2) to compare it with that of depressed, never-demented patients. METHOD: The subjects were 57 elderly patients consecutively hospitalized for major depression. At entry into the study, 23 subjects also met criteria for "reversible dementia," while 34 were without dementia. After a systematic clinical evaluation, the subjects were followed up at approximately yearly intervals for an average of 33.8 months. RESULTS: Irreversible dementia developed significantly more frequently in the depressed group with reversible dementia (43%) than in the group with depression alone (12%). Survival analysis showed that the group with reversible dementia had a 4.69-times higher chance of having developed dementia at follow-up than the patients with depression alone. No clinical characteristics at entry into the study were found to discriminate the subjects who developed irreversible dementia during the follow-up period from those who remained nondemented. CONCLUSIONS: These findings suggest that geriatric depression with reversible dementia is a clinical entity that includes a group of patients with early-stage dementing disorders. Therefore, identification of a reversible dementia syndrome is an indication for a thorough diagnostic workup and frequent follow-ups in order to identify treatable neurological disorders.