744
months. Her protein C activity and antigen concentrations were both repeatedly 20 units/dL Again, after complete sequencing of the coding regions of the protein C genes, one homozygous aminoacid replacement (Ala-.Thr) was predicted at position 267.2 Her parents are cousins and her daughter, aged 31 years, is heterozygous protein C deficient and remains symptom-free despite two pregnancies and 6 years of oestrogen-progestagen treatment. Patient 3-A 42-year-old woman remained symptom-free until the 5th month of her first pregnancy, at age 24, when DVT developed. During her second pregnancy she received prophylactic heparin at the end of pregnancy and post partum; severe skin necrosis occurred when oral anticoagulant treatment was started. She later had another episode of DVT and a few episodes of superficial vein thromboses. Because on a second occasion skin necrosis occurred in association with oral anticoagulation, she now receives episodic heparin treatments. Protein C activity and antigen were 23 and 22 units/dl, respectively. The patient was homozygous for a Gly z Ser transition in the triplet coding for glycine at position 301. Her parents are first cousins. Her mother possibly had DVT during pregnancy and post partum, and died at age 51 from stroke associated with hypertension. Two of her children are heterozygous for protein deficiency and are symptom-free. These 3 cases have some features in common: no purpura fulminans or massive thrombosis at birth, late onset of thrombotic symptoms (between 17 and 45 years), repeated episodes of skin necrosis related to oral anticoagulation, consanguinity, and, finally, detectable protein activity and antigen in plasma. DNA analysis of the protein genes demonstrated that all 3 patients were homozygous for a single nucleotide replacement in the protein C gene. The three mutations all seem to result in much reduced but detectable protein activity and antigen in plasma, indicating that the variant protein C molecules are either produced at a reduced rate or removed from the circulation at an increased rate. The delayed onset of thrombosis and its mild clinical expression in these homozygotes suggest that at birth the reduced protein C levels are sufficiently high to protect the patient against development of the massive thrombosis and purpura fulminans seen in the severely deficient homozygous or double
heterozygous patients.3 In these 3 homozygous patients, skin necrosis, often associated with biological signs of DIC, was a common complication of oral anticoagulation. This raises questions about the clinical management of such patients. Administration of protein C concentrates might be helpful to prevent skin necrosis at the start of oral anticoagulants. J.CONARD Central
Laboratory of Haematology.
Hôtel-Dieu, 75181 Paris, France Haemostasis and Thrombosis Research Unit.
University Hospital, Leiden, Netherlands
M. H. HORELLOU P. VAN DREDEN M. SAMAMA P. H. REITSMA S. POORT R. M. BERTINA
1 Samama M, Horellou MH, Soria J, Conrad J, Nicolas G. Successful progressive anticoagulation in a severe protein C deficiency and previous skin necrosis at the initiation of oral anticoagulant treatment. Throw Haemost 1984; 51: 132-33. 2. Reitsma PH, Poort SR, Allaart CF, Briet E, Bertina RM The spectrum of genetic defects in a panel of 40 Dutch families with symptomatic protein C deficiency type I. heterogeneity and founder effects. Blood 1991; 78: 890-94 3. Marlar RA, Montgomery RR, Broekmans AW. Diagnosis and treatment of homozygous protein C deficiency. J Pediatr 1989; 114: 528-34.
Prevention of shoulder pain after
laparoscopy SIR,-Dr Narchi and colleagues (Dec 21/28, p 1569) describe a way to prevent shoulder pain after day-care laparoscopy. They state that 35-60% of patients complain of postoperative shoulder pain and that this can delay discharge. Although intraperitoneal instillation of a local anaesthetic may be suitable for diagnostic laparoscopy, it would not be so during laparoscopy done for fertility treatment. Over 4500 laparoscopies have been done at our two centres during GIFT treatment over the past 5 years. We routinely used the double-puncture method for both diagnostic laparoscopy and GIFT. At the end of the procedure, valves of both the cannulae
(subumbilical and suprapubic) are opened and we allow gas to escape. The patient continues to lie in the Trendelenburg position, which allows most of the residual gas to collect in the pelvis and lower abdominal region. An assistant then applies gentle, steady pressure to the flanks and at the same time the subumbilical cannula is gradually withdrawn, after which the operator applies additional gentle pressure to the epigastric and umbilical area. Thus most of the residual gas escapes via the suprapubic cannula. While this is being done the suprapubic cannula is gradually withdrawn. The operating table is then straightened and incisions are sutured. Since we have adopted this procedure the frequency of shoulder pain after laparoscopy has decreased strikingly and we cannot recollect any patient who had to stay overnight solely because of such pain. Although we think that Narchi and colleagues’ suggestion of intraperitoneal instillation of a local anaesthetic is interesting, it may not be strictly necessary since the same results can be achieved by providing the patient with an abdominal squeeze at the end of a laparoscopic procedure. Dubal Fertility and Women’s Health Centre
PANKAJ SHRIVASTAV PRASHANT NADKARNI
London
Fertility Gynaecological Centre, 112A Harley St, London W1 N 1AF, UK
IAN CRAFT
Breastfeeding and intelligence SIR,-Dr Lucas and colleagues (Feb 1, p 261) suggest that breast milk is associated with higher IQ at 71-8 years of age in children born prematurely, even after adjustment for confounding variables such as maternal education and social class. Our follow-up studies of very-low-birthweight children does not accord with their findings. We have followed to 8 years of age two cohorts of children-85 consecutive survivors of birthweight 500-999 g bom in the 63 months from Jan 1, 1977, and 124 consecutive survivors of birthweight 1000-1500 g born in the 18 months from Oct 1,1980. We attempted to see the children at ages of 2, 5, and 8 years, corrected for premature birth. At these ages, psychologists administered Bayley scales of infant development, Wechsler preschool and primary scale of intelligence (WPPSI), and Wechsler intelligence scale for children (revised) (WISC-R), respectively. Data on breastfeeding over the first 2 years of life were collected at the 2-year assessment. There were three groups of children with respect to breastfeeding; group 1 had received no breast milk at all, group 2 had received expressed milk but had never been directly breast fed, and group 3 were eventually directly breast fed. Of the 209 survivors to 8 years of age, 201 (96-2%) were assessed at 8 years. 5 children with cerebral palsy could not complete the WISC-R. Of the 196 children with a WISC-R, 181 (92-3%) had data relating to breastfeeding in the first 2 years. The children who had received expressed breast milk had psychological test scores similar to those of children who had received no breast milk, whereas those directly breast fed had significantly higher scores (tables i and n). We then used multiple linear regression analysis to adjust for the potential confounding variables used by Lucas et al-namely, social class (professional and skilled workers’ families vs remainder), maternal education (mother’s schooling < 10 years vs remainder), birthweight, gestational age, age of mother, gender, and duration of assisted ventilation. The adjusted data showed that children who had received expressed breast milk had lower psychological test scores than those who had received no breast milk, but no difference was significant. On the other hand, children who had received direct breastfeeding had psychological test scores TABLE ]-PSYCHOLOGICAL TEST SCORES RELATED TO BREAST FEEDING