Probable autosomal recessive inheritance of polysplenia, situs inversus and cardiac defects in an Amish family

We report on an Amish family with five individuals in two generations with complex congenital heart disease. Autopsy findings in one and clinical examination in the others support the diagnosis of polysplenia "syndrome." In a mouse model, this spectrum of situs abnormalities and cardiovascular defects shows recessive inheritance with homozygotes having either situs solitus or situs inversus or ambiguous situs. The parents of the four affected sibs are fourth cousins. We think that the father of these four children is an affected but clinically normal homozygote, that his deceased sister was an affected homozygote, and it seems likely that they too had consanguinous parents.     

Further observations on familial hypobetaliproteinaemia

A family with hypobetalipoproteinaemia with 10 affected members is described. In six patients low density lipoprotein cholesterol (LDL-c) concentrations were about 10 % of normal. In four LDL-c was reduced to about 50 % of normal; these four patients probably represent the "intermediate" form of hypobetalipoproteinaemia. This variation in total cholesterol concentration and LDL-c among the affected individuals of the same family could reflect differences of expression in a single aberrant gene or additive expression of a gene at a second locus.     

Effects of size-equivalence and symmetry in enumeration tasks

Previous research has shown that in enumeration tasks, "subitizing" is a rapid and an accurate process used with 1-4 items, and that "counting" is a slow and an inaccurate process used with over four items. It has been suggested that the former task is preattentive, whereas the latter task is attentive. We investigated whether item-size invariance and pattern symmetry affected subitizing and counting speeds. Participants enumerated dots, which were continuously presented, as quickly and as accurately as possible. Results of Experiment 1 indicated that the variance of dot-size was independent of enumeration time, suggesting that the variance in attentional allocation to each dot affected neither subitizing nor counting processes. Results of Experiment 2 indicated that pattern symmetry did not increase the capacity for subitizing, but increased the speed of counting. These results suggest that the capacity of subitizing is four items regardless of item-size invariance and pattern regularity. Moreover, the pattern configuration affected the speed of counting, whereas item features did not.     

Tapeto-retinal degeneration in four Norwegian counties II

In four Norwegian counties (fylker) 89 probands with tapeto-retinal degeneration have been traced and examined by the author. 407 of their nearest relatives (mostly first degree relatives) were also examined. A total of 63 of the relatives were found to be affected, of whom 42 had not been registered previously. After completion of the examinations the mode of inheritance differed from that previously estimated in 50% of the families. Of the 48 families with "classical" retinitis pigmentosa, 8% showed autosomal dominant, 50% autosomal recessive and 2% X-linked recessive inheritance. The remaining 40% were families with solitary cases without consanguinity between the parents of the affected person. Of five families with retinitis pigmentosa of pericentral type, four demonstrated an autosomal dominant pattern of inheritance.     

Familial Mediterranean fever in Armenians: autosomal recessive inheritance with high gene frequency

Familial Mediterranean fever (FMF) is a recurrent episodic inflammatory disorder of unknown pathogenesis that occurs with high frequency in non-Ashkenazi Jews and Armenians. However, there are some differences in the clinical manifestations of FMF in these ethnic groups. FMF has been reported to be an autosomal recessive disease in non-Ashkenazi Jews, with a male/female ratio of 1.7, indicating reduced penetrance in females. However, the inheritance is less clear for Armenians. To resolve this problem, we studied prospectively families of 64 Armenian index cases randomly ascertained at the UCLA FMF clinic. Fifty-three families containing 176 sibs in addition to the probands were analyzed by genetic segregation analysis (exclusions included: six single-child families, four families in which one of the parents was also affected, and a family with incomplete information). Upper and lower bounds of the segregation ratio were estimated, and ranged from .10 +/- .03 to .18 +/- .05 when only definitely affected sibs were classified as affected; .17 +/- .04 to .27 +/- .05 when considering "possibly affected" sibs as affected; and .19 +/- .04 to .30 +/- .05 when incomplete penetrance in females was corrected. A value of .25 is the expected segregation ratio for autosomal recessive inheritance, and our data are consistent with this mode of inheritance. We can reject autosomal dominant inheritance, where the expected segregation ratio is .5. Using extended pedigree data, we calculated an FMF gene frequency of 0.073 and a carrier rate of 1/7, which is about four times the frequency in non-Ashkenazi Jews.(ABSTRACT TRUNCATED AT 250 WORDS)     

A postaxial Polydactyly and progressive myopia syndrome of autosomal dominant origin

A new "postaxial polydactyly-progressive myopia" syndrome of autosomal dominant inheritance is delineated on the basis of nine affected persons in four generations of one family.     

German syndrome in sibs

We present a male-female sib pair born to Ashkenazi Jewish parents with "arthrogryposis," hypotonia-hypokinesia sequence and lymphedema. Of all the "arthrogryposis" hypotonia syndromes, the condition in these sibs appears to be most like that of the patients of German et al [1975] and the patient of Salmon [1978]. They appear to be the first sib pair with German syndrome, which suggests autosomal recessive inheritance. Three of the four known families with affected children have been Ashkenazi Jews.     

Curve of perceptive intellectual deterioration in hemodialysis patients

In order to optimize the results of kidney transplant, i.e. patient's acceptance and speedy recovery, the available organ resources must be combined with appropriate "preparation" of the patient's mental state. In order to plot the "mental deterioration curve" of patients on a hemodialysis program, the present study was made on 62 patients in a general hospital in Spain. The possible repercussions of treatment of kidney disease on intellectual (Weschler's Adult Intelligence Scale-WAIS test) and perceptive (Benton test) capacity were investigated. Samples were grouped according to whether they had been on dialysis for up to four years (less than 4) or more than four years (greater than 4). The WAIS test for the greater than 4 group indicated a lower I.Q. These results indicated that it was after four years on dialysis that greater negative effects began to be seen in perceptive-intellectual capacity. The Benton test indicated that time on hemodialysis adversely affected the patient's capacities. A sharp decline was seen particularly between two and four years in the less than 4 group, suggesting that patients' mental conditions vary with time on dialysis but that their resources and capacities are still fairly untroubled by the treatment in the first two years. In the light of these findings, the deterioration curve should be taken into account when planning kidney transplant, in order to take advantage of the initial period if possible.     

The grandchildren of patients with pyloric stenosis

Of 138 grandchildren of patients, four had pyloric stenosis confirmed at Ramstedt's operation. For the four categories of grandchildren of male index patients the proportion affected was 0/27, 1/17, 1/41, and 0/35 for sons' sons, sons' daughters, daughters' sons, and daughters' daughters, respectively. For the four categories of grandchildren of female index patients the proportion affected was 0/5, 1/3, 0/5, and 1/5, respectively. Though numbers are small certain findings are noteworthy. The relatively high risk to the relatives of female index patients appears even more marked in the grandchildren than the children. The grandchildren of male index patients show the sharp decrease in proportion affected that one would expect with a multifactorial threshold model, but of the few grandchildren born so far to female index patients, as many are affected as the children. In only one of the four instances was the affected grandchild born to an affected child. There is no support for the hypothesis that the higher risk to the children of female index patients is the result of a direct maternal effect on the developing fetus.     

Effects of therapist title on competence as perceived by a psychiatric sample

A study was conducted on how perceptions of a therapist's competence are affected by the therapist's title. Psychiatric inpatients (58 males and 24 females) viewed one of four copies of a videotaped session of the interaction between a male therapist and a male client. One tape described the therapist as "Doctor," one tape described him as "Mister," one by his first name, and one with no name or title. The therapist was rated by the patients on 11 qualities related to competence. Of 11 analyses, 1 title effect was found, and females rated the therapist higher on two qualities. Overall, 9 of the qualities showed no effect for title or for ratings by gender.     

The natural history of Huntington disease: possible role of "aging genes"

In this paper we consider a model in which genetic factors that control aging also modify expression of the Huntington disease (HD) gene. Significant correlation coefficients were obtained for age-at-onset (AO) and age-at-death (AD) between affected parents and their affected offspring. However, more relevant to our hypothesis, the correlations between mean AD in normal sibs and AD in the affected parent (r = .57) and mean AD in their affected sibs (r = .54) are also significant. When onset is used instead of death for affected individuals the coefficients are .46 and .52, respectively. Also, AD in the normal parent is significantly correlated with AD in his affected (r = .39) and normal (r = .36) offspring. Current genetic theories on aging and related trends in HD are discussed. Our results and evidence from gerontological studies support the hypothesis that HD gene carriers with "superior" aging genes manifest symptoms later in life and have increased longevity over those with "inferior" aging genes.     

Patient safety incident reports related to traditional Japanese Kampo medicines: medication errors and adverse drug events in a university hospital for a ten-year period

Background

Kampo medicine is traditional Japanese medicine, which originated in ancient traditional Chinese medicine, but was introduced and developed uniquely in Japan. Today, Kampo medicines are integrated into the Japanese national health care system. Incident reporting systems are currently being widely used to collect information about patient safety incidents that occur in hospitals. However, no investigations have been conducted regarding patient safety incident reports related to Kampo medicines. The aim of this study was to survey and analyse incident reports related to Kampo medicines in a Japanese university hospital to improve future patient safety.

Methods

We selected incident reports related to Kampo medicines filed in Toyama University Hospital from May 2007 to April 2017, and investigated them in terms of medication errors and adverse drug events.

Results

Out of 21,324 total incident reports filed in the 10-year survey period, we discovered 108 Kampo medicine-related incident reports. However, five cases were redundantly reported; thus, the number of actual incidents was 103. Of those, 99 incidents were classified as medication errors (77 administration errors, 15 dispensing errors, and 7 prescribing errors), and four were adverse drug events, namely Kampo medicine-induced interstitial pneumonia. The Kampo medicine (crude drug) that was thought to induce interstitial pneumonia in all four cases was Scutellariae Radix, which is consistent with past reports. According to the incident severity classification system recommended by the National University Hospital Council of Japan, of the 99 medication errors, 10 incidents were classified as level 0 (an error occurred, but the patient was not affected) and 89 incidents were level 1 (an error occurred that affected the patient, but did not cause harm). Of the four adverse drug events, two incidents were classified as level 2 (patient was transiently harmed, but required no treatment), and two incidents were level 3b (patient was transiently harmed and required substantial treatment).

Conclusions

There are many patient safety issues related to Kampo medicines. Patient safety awareness should be raised to prevent medication errors, especially administration errors, and adverse drug events in Kampo medicine.

     

Epithelioid germinal centers in overwhelming childhood infections. The aftermath of nonspecific destruction of follicular B cells by natural killer cells

The destruction of proliferating lymphoid cells within germinal centers with subsequent replacement by histiocytoid cells has been described in infants and children dying of viral and bacterial infections. The etiology and significance of "epithelioid germinal centers" (EGCs) are unknown. The cells implicated in forming EGCs have included histiocytes and dendritic reticulum cells. We have studied four children at autopsy who died at ages ranging from 10 months to 7 years. Three contracted fatal infections, one with fulminant meningococcemia, one with bacterial sepsis, and one with viral hepatitis. The fourth child contracted viral pneumonitis and died of acetaminophen toxicity. Epithelioid germinal centers were found in numerous lymphoid organs (spleen, lymph nodes, and Peyer's patches) in all four cases. Avidin-biotin complex immunohistochemical analysis performed on formalin-fixed splenic tissue from the first three cases and snap-frozen splenic tissue from the second case revealed an absence of B cells in the follicular centers. The mantle zones surrounding follicles were thin but intact. The histiocytoid cells expanding the germinal centers were positive for S100 and R4/23 (dendritic reticulum cells) and negative for numerous histiocyte markers (alpha 1-antitrypsin, alpha 1-antichymotrypsin, and lysozyme). Increased numbers of killer cells (Leu-7) were present within the affected germinal centers in the three cases in which material was available for immunohistochemical studies. Overwhelming infections in these patients seem to result in anomalous natural killer cell activation resulting in localized nonselective destruction of follicular centers similar to anomalous natural killer cell activity reported to occur in fatal infectious mononucleosis. This may lead to an acquired immunodeficiency that precludes long-term survival in affected patients.     

A family with spinal anaplastic ependymoma: evidence of loss of chromosome 22q in tumor

Familial ependymal tumors are a very rare disease, the pathogenesis of which is unknown. Previous studies indicate an involvement of tumor suppressor genes localized within chromosomal region 22q, whereas details are still unclear. Here we report a non-neurofibromatosis type-2 (non-NF2) Japanese family in which two of the four members are affected with cervical spinal cord ependymoma, and one of the four is affected with schwannoma. Loss of heterozygosity (LOH) studies were carried out searching for common allelic loss at chromosomal region 22q11.2-qtel in two of the affected patients. Our findings support a prediction for existence of a tumor suppressor gene on chromosome 22 especially related to the tumorigenesis of familial ependymal tumors.     

Catel-Manzke syndrome: two new patients and a critical review of the literature

We report two new female patients with typical features of Catel-Manzke syndrome (MIM 302380) and the follow-up of the first patient affected by this syndrome. In addition to the Pierre Robin anomaly, the hallmark of this palatodigital syndrome is a bilateral hyperphalangy and clinodactyly of the index finger. Classified into four groups there are now (1) 23 reported cases of the typical, (2) six cases of the extended Catel-Manzke syndrome showing more than two accessory bones in the hand, (3) two patients showing unilateral hyperphalangy and clinodactyly of the index finger (4) two patients described with isolated features of the "Manzke dysostosis" without Pierre Robin anomaly. The karyotype of our three patients was normal. A search for submicroscopic chromosomal abnormalities by array CGH was performed. In addition, we sequenced candidate genes which are known to be involved in phalangeal development. However, no pathogenic aberrations or mutations were found.     

Pitfalls in the prenatal diagnosis of propionic acidemia

Prenatal diagnosis of propionic acidemia can be performed by two independent methods: measuring an elevated quantity of the metabolite methylcitrate in amniotic fluid; and demonstrating deficient activity of propionyl-CoA carboxylase in amniocytes cultured from the fluid. Discordant results in a pregnancy at risk for propionic acidemia were obtained. Elevated concentration of methylcitrate indicated an affected fetus, but the activity of propionyl-CoA carboxylase was normal. An affected female infant was born. Chromosome variant analysis demonstrated that between passage two and four overgrowth of the female fetal cells by contaminating maternal cells led to the "false negative" results obtained by enzyme assay. This experience demonstrates the value of analysis of abnormal metabolites in amniotic fluid and highlights a problem that could confound the prenatal diagnosis of any condition assessed by enzyme activity.     

Infantile refsum disease in four Amish sibs

Infantile Refsum disease (IRD) appears with varying degrees of impaired vision, hearing loss, developmental delays, and neuromotor deficiencies. We report on four Amish sibs with IRD from a consanguineous marriage; biochemical testing supported the diagnosis of IRD. Of particular interest in this sibship are characteristic poorly formed yellow-orange teeth in at least three of the four affected sibs and behavior problems in the affected females.     

How do lay people assess the quality of physicians’ communicative responses to patients’ emotional cues and concerns? An international multicentre study based on videotaped medical consultations

Objective

to establish which kind of physician communicative responses to patient cues and concerns are appreciated by lay people.

Methods

A balanced sample (259 people) was recruited in public places to participate in a full day observation of four videotaped standardized medical consultations. In a two-step procedure participants gave their individual quality ratings of the whole consultations and then of a set of four fragments from each consultation. They contained a patient negative emotional expression and the subsequent physician response, according to the VR-CoDES.

Results

Higher quality ratings were given to physician responses which provided space to the patient to talk and to the explicit expressions of empathy. The explicit responses were favored above non-explicit responses. Participants’ global evaluation of the whole consultation affected their quality assessments of the fragments (halo-effect). In a multivariate model, lay people's background characteristics appeared to be relevant: to be female, of lower educational level and living in Belgium or Italy predicted higher ratings.

Conclusions

Providing space to patients is appreciated by all participants, combined with the need for tailor made communication.

Practice implications

To teach physicians listening skills and how to show empathy with distressed patients should be a core element in medical education.     

The accuracy of self monitoring blood glucose meter systems in Kampala Uganda

Background

Many blood glucose self-monitoring systems are privately and publicly used by people in Uganda and technical and human errors may occur during their operation. Many patients were referred to Kololo polyclinic laboratory to have their blood glucose checked because the values obtained on the patients'' glucose meter systems did not tally with familiar clinical signs and symptoms. This prompted an experimental set up to check glucose meter systems using a larger number of patients.

Objective

The objective was to collate the technical conditions and standing operational procedures of four common glucose meter systems; observe the time, ambient temperature and humidity at which the meter systems operate locally; and compare the performance of three meter systems A, B, and C with the Sensorex glucose meter system on a number of capillary blood samples.

Setting

Kololo polyclinic laboratory-a privately run facility in Kampala, Uganda.

Design

An experimental set up to compare four glucose meter systems.

Methods

Instruction manuals of the four glucose monitoring systems were studied and used to familiarize with the meter operations. One hundred and fourteen capillary blood specimens were assayed for blood glucose. Blood glucose values were instantly read off the four randomly set meter systems A, B, C, and Sensorex, noting the time, ambient temperature and humidity. Results from meter systems A, B, and C were regressed against those of Sensorex using Epi-Info computer program.

Results

Blood glucose concentration levels on meter system A tallied with those on Sensorex meter system. However, those on meter system B and C were significantly lower and different. Temperature and humidity adversely affected the analytical performance of meter systems B and C in the Kampala environ.

Conclusion

Some of the blood glucose monitoring systems in Kampala, Uganda are poor performers and may lead to the mismanagement of patients. There is need for a system to ensure national quality control of blood glucose monitoring systems.     

Espin gene (ESPN) mutations associated with autosomal dominant hearing loss cause defects in microvillar elongation or organisation

Background

Espins are actin bundling proteins present in hair cell stereocilia. A recessive mutation in the espin gene (Espn) has been detected in the jerker mouse and causes deafness, vestibular dysfunction, and hair cell degeneration. More recently mutations in the human espin gene (ESPN) have been described in two families affected by autosomal recessive hearing loss and vestibular areflexia.

Objective

To report the identification of four additional ESPN mutations (S719R, D744N, R774Q, and delK848) in patients affected by autosomal dominant hearing loss without vestibular involvement.

Results

To determine whether the mutated ESPN alleles affected the biological activity of the corresponding espin proteins in vivo, their ability to target and elongate the parallel actin bundles of brush border microvilli was investigated in transfected LLC‐PK1‐CL4 epithelial cells. For three mutated alleles clear abnormalities in microvillar length or distribution were obtained.

Conclusions

The results further strengthen the causative role of the espin gene in non‐syndromic hearing loss and add new insights into espin structure and function.