Identification of two novel mutations in non-Jewish factor XI deficiency

Summary. We have studied two heterozygous unrelated CRM non-Jewish FXI-deficient patients. Neither of the patients carries a previously described mutation. Their FXI genes were screened by SSCP analysis following PCR amplification of each exon and the flanking intronic sequences. DNA fragments showing aberrant mobility were cloned and sequenced. The following mutations were identified: in case 1, a T to G transition in exon 12 results in the substitution of Phe-442 by Val (FXI-F442V); in case 2 a C to A transition in exon 5 results in the substitution of Cys-128 by a nonsense codon (FXI-C128X). The missense mutation results in a substitution within the protease domain of FXI. Molecular modelling locates this residue in a structurally conserved region of the protease domain and the amino acid substitution may therefore interfere with either chain folding and subsequent secretion or the stability of the protein in plasma. We conclude that the mutations which we have identified are responsible for the inherited abnormality in these patients.     

EFFECT OF ACUTE AND CHRONIC NEUROLEPTIC THERAPY ON SERUM PROLACTIN LEVELS IN MEN AND WOMEN OF DIFFERENT AGE GROUPS

A single fasting level of serum prolactin was measured in each of sixty control subjects and eighty-three psychiatric patients of both sexes who had been on neuroleptic therapy for 2-4 weeks (acute treatment) or at least 5 years (chronic treatment) and who were aged either 17-45 or 48-85 years. All groups of patients had significantly higher mean prolactin levels than controls. Gender, age group of women, and exposure to acute or chronic treatment were significant variables determining the magnitude of neuroleptic-induced elevation of prolactin. In some of the groups, dose, duration of chronic therapy, and concomitant administration of anticholinergic drugs also influenced prolactin levels. Whereas all acutely treated women had prolactin values above the control range, one out of twelve (8.3%) of the women aged 17-45 years and six out of fourteen (42.9%) of the women aged 48-85 years who were under chronic treatment had normal values. Normal prolactin levels were also found in five out of sixteen (31.2%) of the acutely treated and nine out of twenty-four (37.5%) of the chronically treated men aged 17-85 years.     

Unifocal Langerhans’cell histiocytosis (eosinophilic granuloma) resembling Ewing's sarcoma

In a 9 year old boy, a destructive lesion in the diaphysis of the right femur was wrongly diagnosed as a Ewing's sarcoma on the basis of the radiologic findings and fine needle aspiration cytology report. The clinical and radiologic picture was suggestive of Ewing's sarcoma, but an open biopsy of the lesion revealed a histopathological picture of eosinophilic granuloma. A brief review of the literature is given, together with discussion on the differential diagnosis of a mid shaft femoral lesion in young patients.     

Role of videofluorography in assessing functional abnormalities in patients of head and neck cancer treated with chemoradiotherapy

Aim: The major toxicity following treatment for head neck cancer is swallowing dysfunction which can be easily assessed by videofluorography (VFG), allowing documentation of the site and extent of abnormality thereby facilitating directed management. Methods: Between October 2003 and January 2007, 56 patients with locally advanced head and neck cancer were treated by an accelerated radiotherapy schedule with concurrent weekly cisplatin chemotherapy. Three months following treatment, these patients were locally disease free clinically, but complained of varying degrees of dysphagia and were subjected to a VFG evaluation. Results: This group comprised 52 men and four women with a median age of 56 years. The primary site distribution was: oral cavity (9), oropharynx (22), larynx (19), hypopharynx (5) and unknown primary (1). Swallowing function abnormalities in the form of structural displacement and temporal delays were documented and recorded as weakness of the tongue musculature (n = 6), palatal kink (n = 8), premature leak into the oropharynx (n = 20), impaired hyoid elevation (n = 23), impaired epiglottic tilt (n = 26), unilateral pharyngeal wall impairment (n = 16), residuum in vallecula or pyriform fossa (n = 30), aspiration in trachea (n = 29) and loss of nasopharyngeal seal (n = 7). Multiple abnormalities of different sub‐sites were seen in each patient. Conclusion: VFG can document dysmotility disorders of upper aero‐digestive tract like dysfunction of the base of tongue, larynx and pharyngeal musculature leading to stasis of the bolus and vallecular residuum, epiglottis dysmotility resulting in silent aspirations, and inadequate nasopharyngeal seal leading to nasal regurgitation. A clinical correlation alongwith quantification of VFG findings is required.     

Skeletal maturity in Pakistani children

Skeletal maturity in 750 normal Pakistani children (400 males, 350 females) aged 1–18 y was determined by the Greulich–Pyle atlas system. Male children during first year and female children during first 2 y of life matured in conformity with Greulich–Pyle standards. After that period mean bone ages were lower than the American standards up to 15 y in males and 13 y in females (at or around puberty), which may be due to malnutrition, ill health or other environmental factors. After puberty bone ages were higher than the American standards indicating earlier maturity in Pakistani than Western children. Hence for the proper evaluation of skeletal age in a given region, a longitudinal study on individuals in that region to establish normal standards is necessary.     

Securing cooperation from persons supplying statistical data

Securing the co-operation of persons supplying information required for medical statistics is essentially a problem in human relations, and an understanding of the motivations, attitudes, and behaviour of the respondents is necessary.Before any new statistical survey is undertaken, it is suggested by Aubenque and Harris that a preliminary review be made so that the maximum use is made of existing information. Care should also be taken not to burden respondents with an overloaded questionnaire. Aubenque and Harris recommend simplified reporting. Complete population coverage is not necessary.Neurdenburg suggests that the co-operation and support of such organizations as medical associations and social security boards are important and that propaganda should be directed specifically to the groups whose co-operation is sought. Informal personal contacts are valuable and desirable, according to Blaikley, but may have adverse effects if the right kind of approach is not made.Financial payments as an incentive in securing co-operation are opposed by Neurdenburg, who proposes that only postage-free envelopes or similar small favours be granted. Blaikley and Harris, on the other hand, express the view that financial incentives may do much to gain the support of those required to furnish data; there are, however, other incentives, and full use should be made of the natural inclinations of respondents. Compulsion may be necessary in certain instances, but administrative rather than statutory measures should be adopted. Penalties, according to Aubenque, should be inflicted only when justified by imperative health requirements.The results of surveys should be made available as soon as possible to those who co-operated, and Aubenque and Harris point out that they should also be of practical value to the suppliers of the information.Greater co-operation can be secured from medical persons who have an understanding of the statistical principles involved; Aubenque and Neurdenburg suggest that a course in elementary statistical methodology be introduced in the curriculum of medical schools.Methods for improving co-operation, and thus the compilation of statistics, in particular countries are discussed by Lal and de Shelly Hernández, who deal with India and Venezuela respectively.