Sedaghatian congenital lethal metaphyseal chondrodysplasia--observations in a second Iranian family and histopathological studies

In 1980, Sedaghatian described in two brothers and one sister a neonatally lethal disorder associated with slight rhizomelic limb shortness, mild platyspondyly, and severe metaphyseal dysplasia. Here data are presented on another Iranian infant with the Sedaghatian syndrome who died on day 4 and was found to have histologic evidence of severe epimetaphyseal dysplasia. The occurrence in children of both sexes in one instance, born to normal parents who were first cousins, and currently apparent confinement of the disorder to Iranians suggests that the Sedaghatian syndrome is an autosomal recessive trait with high gene frequency in Iranians. This may be a more complexly pleiotropic syndrome than suggested by the roentgenograms, since one of Sedaghatian's patients also had "microphthalmia, asymmetry of ears, depressed nasal bridge, broad nose, short neck, prominent sternum, and short lower extremities."     

Sedaghatian congenital lethal metaphyseal chondrodysplasia—observations in a second Iranian family and histopathological studies

In 1980, Sedaghatian described in two brothers and one sister a neonatally lethal disorder associated with slight rhizomelic limb shortness, mild platyspondyly, and severe metaphyseal dysplasia. Here data are presented on another Iranian infant with the Sedaghatian syndrome who died on day 4 and was found to have histologic evidence of severe epimetaphyseal dysplasia. The occurrence in chil-dren of both sexes in one instance, born to normal parents who were first cousins, and currently apparent confinement of the disorder to Iranians suggests that the Sedaghatian syndrome is an autosomal recessive trait with high gene frequency in Iranians. This may be a more complexly pleiotropic syndrome than suggested by the roentgenograms, since one of Secaghatian's patients also had “microphthal-mia, asymmetry of ears, depressed nasal bridge, broad nose, short neck, promi nent sternum, and short lower extremities”.     

A female case of Sedaghatian type spondylometaphyseal dysplasia

Sedaghatian type spondylometaphyseal dysplasia is a rare osteochondrodysplasia first described in 1980. The original report describes an Iranian infant with mild rhizomelic limb shortening, severe metaphyseal cupping and irregularity and platyspondyly who died shortly after birth. The baby was born to a consanguineous couple who had reportedly had two similarly affected infants, one male and one female. No documented radiology is available on the female infant. Since this publication, 10 further case reports of male infants with this condition have appeared in the literature all of whom have died shortly after birth. We report a fully documented female case of Sedaghatian type spondylometaphyseal dysplasia providing further evidence to support an autosomal recessive mechanism of inheritance.     

A case control study of cardiovascular health in chemical war disabled Iranian victims

Background:

Sulfur mustard (SM) is an alkylating chemical warfare agent that was widely used during Iran–Iraq war between 1983 and 1988. SM exposure leads to various late complications. The aim of this study was to determine the late cardiovascular effects of SM in war-disabled Iranian victims.

Materials and Methods:

This was a retrospective cohort case control study on 50 patients with symptoms of SM exposure and 50 cases who had been in Iran–Iraq war, without chemical injury. We performed exercise stress test and echocardiography for all of patients.

Results:

The study group comprised 100 males of mean age 45.6 ± 6.2 years. In chemical war injury group, two patients (4%) had positive exercise stress test. On coronary angiography, they were found to have coronary artery disease. One patient had severe mitral regurgitation and normal coronary angiography; he was referred for mitral valve replacement. Left ventricular (LV) diastolic abnormality was detected in 23% of these subjects. In another group, 5% had LV diastolic abnormality (P = 0.02) and all of them had normal stress test.

Conclusions:

Cardiovascular abnormalities are another late complication in chemical war disabled Iranian victims. Diastolic dysfunction was the most common abnormality in both groups of patients.     

No increased risk of infant hypospadias after maternal use of loratadine in early pregnancy

The original report published in 2001 on a possible association between maternal use of loratadine and an increased risk of infant hypospadias, based on data in the Swedish Medical Birth Register 1995-2001, has been followed up by continued surveillance in the same register. The original "signal" was based on 15 infants with hypospadias among 2780 loratadine-exposed infants born, representing an adjusted odd ratio of about 2.3, statistically significant. Since then another 10 cases have been identified, and 12.5 expected. For the period 2001-2004, another 1911 loratadine-exposed infants have been identified and only two had hypospadias (4 expected). Our present position is that the primary finding was a "signal" which had occurred by chance and the follow-up agrees with independent studies which indicate an absence of an association. This illustrates the care with which apparent statistically significant increases have to be handled when no prior hypothesis exists.     

Craniofacial-deafness-hand syndrome revisited

In 1983 Sommer described a new syndrome in a mother and her infant daughter which was subsequently called the syndrome of craniofacial, hand anomalies and sensorineural deafness. The syndrome consisted of a normal calvarium with a flat facial profile, hypertelorism and small palpebral fissures with an antimongoloid slant, a depressed nasal bridge with a button tip and slitlike nares and a small "pursed" mouth. Profound sensorineural hearing loss and ulnar deviation of the hands with flexion contractures of digits three, four and five was evident. The family had another child, a son, two years after the birth of the index case that had the exact manifestations as his mother and sister. Because of three affected family members in two generations and a phenotype of midfacial anomalies and dystopia canthorum resembling Waardenburg syndrome, a search for mutations in the PAX3 gene was undertaken. A missense mutation in the paired domain of PAX3 (Asn47Lys) was detected. We have provided a 20-year follow-up of a syndrome characterized by craniofacial anomalies, hearing loss and hand deformities and which is caused by a PAX3 missense mutation.     

Autosomal dominant osteopetrosis type II with “malignant” presentation: further support for heterogeneity?

The osteopetroses are a heterogeneous group of disorders characterised by generalised bony sclerosis. The autosomal dominant form usually has a "benign" prognosis, in contrast to the "malignant" course of the autosomal recessive variety. In this paper we describe a kindred in which the phenotypic spectrum varied from an asymptomatic condition in adults to a severely affected infant, presenting with anaemia, hepatosplenomegaly, hydrocephalus and blindness. The findings in this family are reported and discussed to elucidate further the possible genetic heterogeneity in autosomal dominant osteopetrosis.     

Genotype characterization and phylogenetic analysis of hepatitis B virus isolates from Iranian patients

Hepatitis B virus (HBV) is one of the major causative agents of acute and chronic liver disease worldwide and is believed to be responsible for a million deaths annually. Eight genotypes of HBV, A to H, have been described on the basis of similarity of the complete genomes sequence. Although, it is reported that the predominant HBV genotype in the Mediterranean area and the middle east is genotype D, there are no reports on HBV genotypes prevalent in Iran. In this study, the C and S regions of HBV from 26 chronic hepatitis B Iranian patients were amplified and sequenced. Phylogenetic analysis revealed that all Iranian HBV isolates sequences were classified into genotype D with bootstrap values of 100%, 73%, and 100% (1,000 replicates each) for S, C, and preS2 regions, respectively. The mean percent intra-distance of S and C regions were 0.8% and 2.3%, respectively. The mean percent inter-distance of S and C regions between Iranians and genotype D isolates were 1.7% and 3.0%, respectively, and the range of mean percent nucleotide distance of S and C regions between Iranians and the other reference isolates were 7.9%-17.5% and 4.8%-14.7%, respectively. Thirteen out of 23 HBV C region sequences showed nucleotide "A" at position 1896 (precore mutant) in C region. Nucleotide 1858 showed presence of "T" in all isolates. No insertion or deletion was found in both regions. SimPlot and BootScanning analyses did not show any recombination between Iranian isolates and other genotypes in both regions.     

Dyssegmental dysplasia Silverman-Handmaker type in a consanguineous Druze Lebanese family: Long term survival and documentation of the natural history

We report on a male infant born with clinical and radiographic evidence of a lethal form of dyssegmental dysplasia not comparable to Silverman-Handmaker type, who had a prolonged survival of more than eight months. He had ocular and central nervous system abnormalities which have not been previously described. His course included significant feeding and respiratory difficulties, severe physical and psychomotor retardation, and recurrent fever of unknown etiology believed to be of central origin. The relatively long survival of this infant enabled us to focus on the natural history of this rare syndrome. The infant was born to first cousin parents of Druze Lebanese origin supporting an autosomal recessive mode of inheritance for the condition. This is the first documentation of dyssegmental dysplasia Silverman-Handmaker type in a family of Druze Lebanese ethnicity. Am. J. Med. Genet. 75:164–170, 1998. © 1998 Wiley-Liss, Inc.     

Recurrent "Flexispira rappini" bacteremia in an adult patient undergoing hemodialysis: case report

A blood culture from a 65-year-old febrile man undergoing hemodialysis revealed, 5 days after inoculation, an unusual gram-negative fusiform rod with darting motility. During another episode of fever 21 days later, this Campylobacter-like organism was again recovered from three blood cultures and subcultured under an H2-enriched microaerobic atmosphere. The organism was catalase negative and oxidase positive and hydrolyzed urea rapidly. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of whole-cell proteins was indistinguishable from that of "Flexispira rappini" LMG 8738 described by Archer et al. in 1988 (J. R. Archer, S. Romero, A. E. Ritchier, M. E. Hamacher, B. M. Steiner, J. H. Bryner, and R. F. Schell, J. Clin. Microbiol. 26:101-105, 1988). The analysis of the 16S ribosomal DNA sequence revealed a similarity of 99.3% between the two strains. The patient recovered completely after a 4-week course of meropenem therapy. This is the first reported case of a recurrent "F. rappini" bacteremia in an adult patient, which confirms that this organism may be an invasive pathogen in immunocompromised patients, like other newly described Helicobacter species.     

Supplemental Stimulation of Premature Infats: A Treatment Model

Examined the human infant literature on supplemental stimulationto delineate a course of intervention based no the ontogenyof the nervous system and the impact that systematic stimulationmay have on behavioral organization in the premature infant.Effects of vestibular, tactilel/kinesthetic, auditory, and oralstimulation are discussed with respect to their similarity tothe intra- or extrauterine environment. Long-standing theoreticaland methodological problems are discussed, and a "sequentialmultimodal treatment model" is introduced.     

An explosive familial epidemic of viral hepatitis B with a horizontal transmission]

The authors describe the course of an explosive epidemic of viral hepatitis B (VHB) where all members of a seven-member family contracted the disease. The probable source of infection was an infant with a history of anicteric VHB with transition into chronicity and with HBs and HBe antigenaemia. Four members of the family contracted the disease between the 126th and 172nd day after his return from hospital to the family and another two members of the family contracted the disease three months later. Generally accepted risk factors for transmission of VHB could be ruled out. Saliva is suspected as a transfer factor of the disease. Five children had the anicteric form of VHB with an atypical but protracted course, in two with probable development of a chronic character of the disease. Adult patients had the icteric form of the disease. All cases were diagnosed by biochemical examination and confirmed by a positive finding of HBsAg and/or a positive finding of anti HBs antibodies.     

Impaired IL-12- and IL-23-Mediated Immunity Due to IL-12Rβ1 Deficiency in Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease

Purpose

Inborn errors of IFN-γ-mediated immunity underlie Mendelian Susceptibility to Mycobacterial Disease (MSMD), which is characterized by an increased susceptibility to severe and recurrent infections caused by weakly virulent mycobacteria, such as Bacillus Calmette–Guérin (BCG) vaccines and environmental, nontuberculous mycobacteria (NTM).

Methods

In this study, we investigated four patients from four unrelated consanguineous families from Isfahan, Iran, with disseminated BCG disease. We evaluated the patients’ whole blood cell response to IL-12 and IFN-γ, IL-12Rβ1 expression on T cell blasts, and sequenced candidate genes.

Results

We report four patients from Isfahan, Iran, ranging from 3 months to 26 years old, with impaired IL-12 signaling. All patients suffered from BCG disease. One of them presented mycobacterial osteomyelitis. By Sanger sequencing, we identified three different types of homozygous mutations in IL12RB1. Expression of IL-12Rβ1 was completely abolished in the four patients with IL12RB1 mutations.

Conclusions

IL-12Rβ1 deficiency was found in the four MSMD Iranian families tested. It is the first report of an Iranian case with S321* mutant IL-12Rβ1 protein. Mycobacterial osteomyelitis is another type of location of BCG infection in an IL-12Rβ1-deficient patient, notified for the first time in this study.

     

Malignant tumor of humerus with features of "adamantinoma" and Ewing's sarcoma

This female patient was born in 1935 and died in 1976 with a malignant bone tumor involving the proximal humerus following multiple local recurrences, axillary lymph node metastases, and pulmonary metastases. Histologically, over the course of time, there was an increase in features of an atypical Ewing's sarcoma, at the expense of findings of a typical, extra-cranial so-called adamantinoma. In contrast to another report, our case showed neither epithelial nor endothelial features on fine structural examination, but rather primitive mesenchymal cells, as is described for Ewing's sarcomas.     

A neonatal echovirus 11 outbreak in an obstetric clinic.

An echovirus 11 outbreak occurred among neonates in an obstetric clinic in November 2003. Thirteen neonates were transferred to our medical center, and all were found to have echovirus 11 infection. Viral studies were performed for 32 other infants born in the clinic during the same period, including 30 asymptomatic neonates and 2 febrile infants transferred to another hospital. Two of the asymptomatic infants had echovirus 11 isolated from rectal swabs. The first patient transferred to our medical center developed extensive hemorrhage and died 6 days later. Three family members of this infant were also proved to have echovirus 11 infections. One other infant had a fulminant course and had residual hepatic impairment. The other infants had no complications. Viral studies in the 24 nursery staff were all negative. This outbreak shows how a neonatal enterovirus outbreak can occur in a nursery, starting from an infected infant in the incubation period. Early recognition and prompt management of an outbreak is important to prevent further spread of the infection.     

Examination of feces and serum for diagnosis of infant botulism in 336 patients.

In the 12-year period 1975 to 1987, feces from 336 infants were examined for botulinal neurotoxin and Clostridium botulinum. All the infants had illnesses which prompted their physicians to consider infant botulism in the diagnosis. Stool specimens from 113 of the infants yielded organisms that produced botulinal neurotoxins assumed to be responsible for the illness. The types of botulinal toxin in the confirmed cases were distributed as follows: 38 A, 69 B, 2 atypical B, 1 E, 1 F, 1 A + B, and 1 B + F. The type A and B toxins in a single infant were produced by two different strains of organism, and the type B and F toxins in another infant were produced by a single strain. The physiological characteristics of all the isolated toxigenic organisms except two were consistent with those of group I (proteolytic) C. botulinum. The toxigenic isolate from the infant with type E botulism was identified as C. butyricum, and that from the infant with type F botulism was identified as C. barati. Toxin of the same type as produced by the isolated organisms was identified in feces of 98 of 111 culture-positive infants. Botulinal toxin was identified in the serum of 9 of 67 culture-positive infants (8 of 22 infants with type A organisms; 1 of 43 infants with type B organisms; neither of 2 infants with A + B or atypical type B organisms). Botulinal toxin was not detected in feces (206 infants) or in serum (114 infants) of the culture-negative infants. The culture-positive infants had clinical features and a course of illness consistent with those of infant botulism. Most of the culture-negative infants probably had illnesses other than botulism, but specimens might have been obtained late in some infants' illnesses, when the organism had disappeared.     

Neonatal Proteus meningoencephalitis. Case report.

Proteus is an uncommon pathogen in neonatal meningitis and has, to our knowledge, not previously been described from Scandinavia. Our case illustrates the typical course of the disease when onset is within the first two weeks of life. The typical patient is a previously healthy, sometimes slightly preterm infant, who develops multiple brain abscesses and has a very poor prognosis. In cases with a later onset, factors predisposing for infection are common and the outcome is less severe. Our patient was a girl born at a gestational age of 36 full weeks, who was a little less alert than normal during the first three days and then became dramatically sick with convulsions and apnoeas. She died at the age of six days with severe brain damage.     

A procedure for the measurement of infant skin conductance and its initial validation using clap induced startle

Studies examining psychophysiologic markers of infant emotional development abound. However, few studies have used skin conductance (SC), though it measure's sympathetic activity, and none have measured SC on infants sitting up and actively engaged with another person, a significant challenge given the measures sensitivity to movement artifact. In this pilot/feasibility study, we present a procedure for measuring infant SC during active engagement with another person who executes a series of startling claps to elicit an SC response. We measured SC on the plantar surface of the foot of seventeen 5-month-old infants. We found unconditioned SC responses that were related to the intensity of physical startle reactions for each clap trial. We also found anticipatory, conditioned SC responses that occurred within 5 s before each clap that occurred when the researcher raised his clasped hands. These conditioned SC responses grew linearly in intensity over trials. We conclude that SC may be a useful addition to the infant researcher's armamentarium and may indeed be used to measure physiologic reactivity in infants even when actively engaged with another person. Addition of SC measurement to research on infant emotion and emotional communication is likely to advance our understanding of the psychophysiologic foundations of infant emotional development.     

Hyperpipecolic acidemia associated with hepatomegaly, mental retardation, optic nerve dysplasia and progressive neurological disease

A male infant with hyperpipecolic acidemia is described. To our knowledge this is only the second report of this disorder. As with the previous case, our patient's course was characterized by persistent hepatomegaly, severe mental retardation, progressive loss of developmental milestones and diminished visual acuity associated with nystagmus, abnormal discs and retinal changes. Death occurred at 2 years of age, following a progressive loss of neurological function. Pipecolic acid was repeatedly present in the serum at a concentrattion of 4-5 mg %. Trace amounts of this compound were also detected in the urine. In addition, an adaption of the method of Piez et al. (1956) for the direct quantitation of pipecolic acid in serum was evaluated and found to be very useful for the biochemical diagnosis of this disorder.