Evaluation of maternal plasma creatine kinase activity as a marker of abnormal early pregnancy

We have tested the value of maternal plasma creatine kinase activity for diagnosing ectopic pregnancies obtained after in-vitro fertilization and embryo transfer. Plasma creatine kinase was assayed in 57 patients: 20 normal, 23 miscarriages and 14 ectopic pregnancies, for a total of 240 samples. All values were in the lower part of the normal range except only one in a miscarrying patient. A statistically significant difference was observed for a cut-off value of 45 IU/l between normal and ectopic pregnancies. However, for this cut-off point, the measurement of plasma creatine kinase activity had a sensitivity of 0.50 and a specificity of 0.76 for the diagnosis of ectopic pregnancy. The positive predictive value was 0.69. Creatine kinase activity measurements are thus of no practical value in this particular population, in which an early and specific marker of ectopic implantation would be of paramount interest. The association of human chorionic gonadotrophin (HCG) determinations and ultrasound scanning of the pelvis still remain the best paraclinical support for an early diagnosis of ectopic implantation.      

Isolation and characterization of human and rabbit sperm tail fibrous sheath

Using mechanical and chemical dissection methods, fibrous sheath was isolated both from normal ejaculated human spermatozoa and from rabbit cauda epididymal spermatozoa. The same techniques did not produce a pure preparation of fibrous sheath from ejaculated rabbit spermatozoa, suggesting that further cross-linking and stabilization of sperm structures occurs in response to components of the seminal plasma. The isolation procedures were monitored by phase contrast microscopy and the purity of the fibrous sheath was verified by electron microscopy. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of isolated human fibrous sheath revealed at least 14 protein bands of which the most intensely stained were of molecular weight 84, 72, 66.2, 57, 32 and 28.5 kDa. The rabbit fibrous sheath revealed at least 10 protein bands, of which the most intensely stained were 35.2, 32.7 and 28.5 kDa. The amino acid composition of the purified fibrous sheath from human and rabbit spermatozoa was similar, being high in aspartic acid and/or asparagine and glutamic acid and/or glutamine, serine, alanine, leucine, lysine and glycine, but low in histidine, tyrosine and isoleucine. This composition is similar to that reported for the rat and suggests that mammalian sperm tail fibrous sheaths are composed of similar types of proteins, although there are apparent differences in protein components between species.      

Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome

Champion KJ, Bunag C, Estep AL, Jones JR, Bolt CH, Rogers RC, Rauen KA, Everman DB. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio‐facio‐cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild‐type BRAF but is less strongly activating than the cancer‐associated p.V600E mutation.     

Exploring the utility of whole‐exome sequencing as a diagnostic tool in a child with atypical episodic muscle weakness

The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future.     

Dietary factors in oral leukoplakia and submucous fibrosis in a population-based case control study in Gujarat, India

OBJECTIVES: To investigate the relationship of specific nutrients and food items with oral precancerous lesions among tobacco users.
DESIGN: A population-based case-control study. SETTING: Villages in Palitana taluk of Bhavnagar district, Gujarat, India.
SUBJECTS AND METHODS: An interviewer-administered food frequency questionnaire, developed and validated for this population, was used to estimate nutrient intake in blinded, house-to-house interviews. Among 5018 male tobacco users, 318 were diagnosed as cases. An equal number of controls matched on age (±5 years), sex, village, and use of tobacco were selected.
MAIN OUTCOME MEASURES: Odds ratios (OR) from multiple logistic regression analysis controlling for relevant variables (type of tobacco use and economic status).
RESULTS: A protective effect of fibre was observed for both oral submucous fibrosis (OSF) and leukoplakia, with 10% reduction in risk per g day^-1 ( P < 0.05). Ascorbic acid appeared to be protective against leukoplakia with the halving of risk in the two highest quartiles of intake (versus the lowest quartile: OR = 0.46 and 0.44, respectively; P < 0.10). A protective effect of tomato consumption was observed in leukoplakia and a suggestion of a protective effect of wheat in OSF.
CONCLUSION: In addition to tobacco use, intake of specific nutrients may have a role in the development of oral precancerous lesions.     

Strangulation in child abuse: CT diagnosis

The central nervous system is commonly affected in child abuse. Between April 1985 and July 1986 three infants were identified in whom the primary mode of injury had been strangulation. In each case computed tomography (CT) demonstrated a large cerebral infarction confined to vascular territories associated with small subdural hematomas. There was no history or visible evidence of significant head trauma. Autopsy of one infant confirmed the presence of a hemispheric infarct, thin subdural hematoma, and an area of subintimal hemorrhage in the carotid artery ipsilateral to the infarct. The remaining two patients survived with residual hemiparesis. CT findings of a large cerebral infarction with an associated subdural hematoma in an infant without a history of a significant trauma should suggest the possibility of child abuse and may be the primary manifestation of abuse in some patients.     

Effect of Propranolol on Ventricular Rate During Atrial Fibrillation in the Wolff-Parkinson-White Syndrome

Atrial fibrillation was induced during an electrophysiology study in 10 patients with the Wolff-Parkinson-White (WPW) syndrome, after determination of baseline properties of the accessory atrioventricular (AV) connection; intravenous propranolol (0.2 mg/kg) was then administered. Atrial fibrillation terminated during the drug infusion in three patients, allowing determination of propranolol's effects on conduction and refractoriness during sinus rhythm, before atrial fibrillation was reinduced. In these three patients propranolol had no effect on refractoriness or conduction properties of the accessory AV connection during sinus rhythm. The mean ventricular rate during atrial fibrillation was slowed by 15–56 beats/min in six patients, had no effect on the mean rate in three patients, and markedly increased the ventricular rate (203 to 267 beats/min) in one patient. In this patient, 54% of QRS complexes during atrial fibrillation were narrow, compared to 0–25% in the other patients. Propranolol reduced the percentage of QRS complexes that were narrow from 13 ± 16% to 1 ± 2% (mean ± standard deviation, p < 0.05). We conclude that propranolol may slow the ventricular rate during atrial fibrillation in some patients with the WPW syndrome, probably by blockcing the effects of adrenergic activation. However, propranolol should not be used in patients with the WPW syndrome who have atrial fibrillation, if most QRS complexes during atrial fibrillation are preexcited. When a large percentage of QHS complexes are narrow, propranolol may increase the ventricular rate, probably by eliminating concealed retrograde conduction in the accessory AV connection.     

Recombination aneusomy of chromosome 5 associated with multiple severe congenital malformations

A male infant is described in whom congenital anomalies were recognized prenatally by ultrasound examination. The infant was delivered following spontaneous labor and died approximately 15 min after birth. An autopsy revealed major anomalies in the central nervous system (holoprosencephaly with premaxillary agenesis), the gastrointestinal system (esophageal atresia) and the heart (tetralogy of Fallot). Chromosomal studies revealed recombinant chromosome 5 [46,XY, rec(5), dup q, inv(5)(p15q32)], resulting in partial trisomy 5q and partial monosomy 5p. Cytogenetic investigation of the family revealed a pericentric inversion of chromosome 5 in the father and paternal grandmother, 46,XY (and XX, respectively,) inv(5)(p15q32). The congenital anomalies in this infant are more extensive and severe than previously reported in cases of recombination aneusomy involving chromosome 5.     

Massive Cerebral Edema Associated with Fulminant Hepatic Failure in Acetaminophen Overdose

Cerebral edema may complicate the course of fulminant hepatic failure. Response to conventional therapy has been disappointing. We present a patient with fatal acetaminophen-induced fulminant hepatic failure, with signs and symptoms of cerebral edema, unresponsive to conventional medical therapy. Cranial decompression was carried out. A justification of the need for further evaluation of cranial decompression in such patients is presented.