[Increased risk of infection in patients with diabetes mellitus type 1 or 2]. / Toegenomen risico op infecties bij patiënten met diabetes mellitus type 1 of 2.

OBJECTIVE: To determine the risk of common infections in patients with diabetes mellitus type 1 (DM1) or type 2 (DM2). DESIGN: Prospective controlled study. METHODS: In a 12-month prospective cohort study as part of the Second Dutch National Survey of General Practice, 705 adult DM1 and 6,712 DM2 patients were compared with 18,911 control patients who had hypertension without diabetes. Outcome measures were medically-attended episodes of infections of the respiratory tract, urinary tract, skin and mucous membranes. Multivariate and multinomial logistic regression analysis was applied to determine independent risks of infections and their recurrence in patients with diabetes compared to controls. RESULTS: Upper respiratory-tract infections were as common in diabetes patients as in controls. Diabetes patients had a higher risk of lower respiratory-tract infections (DM2: odds ratio (OR): 1.30; 95% CI: 1.11-1.52), urinary-tract infections (DM1: OR: 1.56; 95% CI: 1.13-2.15; DM2: OR: 1.21; 95% CI: 1.07-1.38), bacterial skin or mucous-membrane infections (DM1: OR: 1.48; 95% CI: 1.01-2.15; DM2: OR: 1.32; 95% CI: 1.13-1.55) and mycotic skin or mucous-membrane infections (DM2: OR: 1.41; 95% CI: 1.24-1.61). The risk of recurrence of these common infections was seen to be increased. CONCLUSIONS: Patients with type-1 and type-2 diabetes are at increased risk of lower respiratory-tract infections, urinary-tract infections and skin or mucous-membrane infections.

Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus.

BACKGROUND: Clinical data on the association of diabetes mellitus with common infections are virtually lacking, not conclusive, and often biased. We intended to determine the relative risks of common infections in patients with type 1 and type 2 diabetes mellitus (DM1 and DM2, respectively). METHODS: In a 12-month prospective cohort study conducted as part of the Second Dutch National Survey of General Practice, we compared 705 adult patients who had DM1 and 6712 adult patients who had DM2 with 18,911 control patients who had hypertension without diabetes. Outcome measures were medically attended episodes of infection of the respiratory tract, urinary tract, and skin and mucous membranes. We applied multivariable and polytomous logistic regression analysis to determine independent risks of infections and their recurrences in patients with diabetes, compared with control patients. RESULTS: Upper respiratory infections were equally common among patients with diabetes and control patients. Patients with diabetes had a greater risk of lower respiratory tract infection (for patients with DM1: adjusted odds ratio [AOR], 1.42 [95% confidence interval {CI}, 0.96-2.08]; for patients with DM2: AOR, 1.32 [95% CI, 1.13-1.53]), urinary tract infection (for patients with DM1: AOR, 1.96 [95% CI, 1.49-2.58]; for patients with DM2: AOR, 1.24 [95% CI, 1.10-1.39]), bacterial skin and mucous membrane infection (for patients with DM1: AOR, 1.59 [95% CI, 1.12-2.24]; for patients with DM2: AOR, 1.33 [95% CI, 1.15-1.54]), and mycotic skin and mucous membrane infection (for patients with DM1: AOR, 1.34 [95% CI, 0.97-1.84]; for patients with DM2: AOR, 1.44 [95% CI, 1.27-1.63]). Risks increased with recurrences of common infections. CONCLUSIONS: Patients with DM1 and DM2 are at increased risk for lower respiratory tract infection, urinary tract infection, and skin and mucous membrane infection. Studies are warranted into management of such infections in patients with diabetes.

The influence of the hand circulation on the assessment of venous distensibility of the human forearm with venous occlusion plethysmography.

AIMS: To determine the influence of the hand circulation on the determination of venous distensibility with venous occlusion plethysmography. METHODS: In a randomised study, duplicate measurements of forearm venous distensibility, with and without a wrist cuff, were made over occlusion periods of 3 and 12 min in eight volunteers. Treatments were compared with paired Student's t-tests and differences are presented as 95% confidence intervals (CI). Intra-subject variability was assessed with analysis of variance. RESULTS: Non-significant differences in increases in forearm volume between the occlusions with and without wrist cuff were found for the 3 min occlusion (CI: -0.4, + 0.2%) and the 12 min occlusion period (CI: -0.7, + 0.2%). However, the coefficient of variation was lower with the use of a wrist cuff; after 3 min occlusion (12% vs 19%) and after 12 min of occlusion (14% vs 24%). Forearm volume after 12 min of venous occlusion was 0.5% (CI: + 0.4, + 0.7) higher than after 3 min. CONCLUSIONS: Although venous distensibility was equal when assessed with and without wrist cuff, exclusion of the hand circulation reduces intraindividual variability. Equilibrium in forearm volume is not reached after 3 min period of venous occlusion, as often assumed. The magnitude of the additional increase after prolonged occlusion stresses the need for well-controlled studies.

RSH (Smith-Lemli-Opitz) syndrome: "severe" phenotype with ectrodactyly.

We describe the antenatal ultrasound findings of growth retardation, oligohydramnios, mesomelic limb shortness, and cardiac, renal, and hand defects in a fetus who was postnatally diagnosed as having RSH ("Smith-Lemli-Opitz") syndrome. An unusual finding was ectrodactyly of both hands.

Quantification of rat pre-pro-thyrotropin releasing hormone (TRH) mRNA by reverse transcription-polymerase chain reaction using external and internal standardisation.

We have developed a quantitative reverse transcription polymerase chain reaction (RT-PCR) method, using both internal and external standardisation, to quantitate fg amounts of pre-pro-thyrotropin releasing hormone (pre-pro-TRH) mRNA in the paraventricular nucleus (PVN) of individual laboratory rats. A constant amount of internal standard is coamplified with both the cDNA of each unknown specimen and a dilution series of an identical RT-PCR generated external standard, allowing quantitation of the samples by interpolation from the external standard curve. Pre-pro-TRH mRNA levels in the PVN were reduced by thyroxine (T4) treatment to 48% of those in control animals, and were increased by thyroidectomy to 155% of the control levels. By combining external and internal standardisation, our method allows multiple samples and treatment groups to be assayed concurrently, thereby eliminating inter-assay variability, whilst retaining the advantages of internal standardisation. It will facilitate further studies of the control of TRH gene expression in pathophysiological conditions.

Pharmacokinetic and pharmacodynamic profiles of sumatriptan in migraine patients with headache recurrence or no response.

OBJECTIVES: Sumatriptan is effective in the acute treatment of migraine. However, about 15% of patients with migraine do not experience headache relief after sumatriptan, and up to 40% may experience recurrence of headache within 24 hours. We studied whether pharmacokinetic or pharmacodynamic differences may explain these different clinical effects. METHODS: We compared the pharmacokinetic profiles of subcutaneous sumatriptan in 14 patients who consistently had headache relief without headache recurrence, in 12 patients who had headache recurrence in every attack, and in six patients who did not have headache relief after sumatriptan. Because the antimigraine action of sumatriptan may be mediated through vasoconstriction of cranial blood vessels, we also compared in these patients changes in blood vessel diameter and blood velocity in the common, internal, and external carotid arteries. RESULTS: Despite sufficient power of the study, no important differences in pharmacokinetic and pharmacodynamic profiles between the three patient groups were detected. CONCLUSION: Headache recurrence and lack of headache relief after sumatriptan do not appear to be explained by pharmacokinetic or pharmacodynamic differences between patients, which may be an important finding for the development of novel antimigraine drugs.

Perinatal death in two sibs with infantile cortical hyperostosis (Caffey disease).

We describe 2 sibs with lethal, prenatal-onset cortical hyperostosis. Antenatal sonographic diagnosis of the first sib was that of short limb dwarfism and thoracic dysplasia (nonspecific), possibly osteogenesis imperfecta. The second sib had a similar appearance on ultrasonography. The thickened, irregularly echodense diaphyses were an aid to diagnosis. Although sporadic cases and autosomal dominant inheritance have been described, an autosomal recessive cause for the lethal prenatal onset cases cannot be excluded.

Structural aspects of bile acids involved in the regulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase.

We have recently reported that coordinate down-regulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase by bile acids results in suppression of bile acid synthesis in cultured rat hepatocytes [Twisk, J., De Wit, E. & Princen, H. M. G. (1995) Biochem. J. 305, 505-511]. In the current study, we have assessed the effects of a large group of different bile acids, both naturally occurring and synthetic, on these two key enzymes, to elucidate structural features which render bile acids potent as regulators of bile acid synthesis. Addition of 50 microM deoxycholate or cholate, two relatively hydrophobic bile acids, to the culture medium of hepatocytes resulted in strong suppression of cholesterol 7 alpha-hydroxylase (suppression of 75%) and 88%, respectively) and sterol 27-hydroxylase activity (suppression of 76% and 72%, respectively). These effects were also reflected in the mRNA levels and the transcriptional activities of the two enzymes, showing a parallel suppression of both parameters in response to cholate (suppression of 78% and 43% for cholesterol 7 alpha-hydroxylase mRNA and transcription, respectively, and suppression of 76% and 42% for sterol 27-hydroxylase mRNA and transcription, respectively). In contrast, no effects were observed with the two hydrophilic bile acids, beta-muricholate and ursocholate. Transient expression analysis in cultured rat hepatocytes, using a promoter-reporter construct containing the proximal part of the cholesterol 7 alpha-hydroxylase promoter, demonstrated a reduction of transcriptional activity by cholate (reduction of 72%), but not by ursocholate. Assessment of the effects of 27 different bile acids, varying in the number, position and orientation (alpha/beta) of hydroxyl groups on the steroid nucleus of the molecule, on cholesterol 7 alpha-hydroxylase mRNA showed only a moderate correlation with the hydrophobicity index of the bile acid involved (r = 0.61; P < 0.0001). Analysis of the three-dimensional structure of a number of these bile acids suggests that hydroxyl groups situated in close proximity to each other within the molecule, creating a hydrophilic environment, as in the case of cholate, may be a prerequisite for a strong inhibitory potency. Deviation from this situation leads to a markedly lesser effect on suppression of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase.

A subset of V delta 1+ T cells proliferates in response to Epstein-Barr virus-transformed B cell lines in vitro.

It has previously been shown that murine tissue derived T-cells expressing the gamma delta T-cell receptor can respond to autologous (stressed) cells implying the recognition of an autoantigen. Here we report that a large proportion of human synovial tissue and peripheral blood derived V delta 1+ gamma delta T-cell clones proliferate in response to stimulation with autologous and allogeneic EBV-transformed B-lymphoblastoid cell lines (LCL). In contrast, V delta 1- gamma/delta and alpha/beta TCR+ T-cell clones isolated from the same tissue samples did not display proliferation towards the LCL. The proliferative response of these V delta 1+ clones was dependent on contact between responder and stimulator cells and could be blocked by a MoAb to LFA-1 and by antibodies to the gamma delta TCR/CD3 complex. Because the responses of these clones to LCL cells appear to be independent of the gamma-chain co-expressed with the V delta 1-chain these resemble a superantigen response. The capacity of this subset of V delta 1+ T-cell clones to proliferate after stimulation with LCL may imply the recognition of an endogenous epitope. Moreover, since so far we have been able to isolate only LCL reactive gamma delta T-cell clones from synovial tissue and peripheral blood of reactive arthritis patients and not from peripheral blood of healthy individuals, the frequency of such 'autoreactive' gamma delta cells may be higher in these patients.

Increased placental resistance and late decelerations associated with severe proteinuric hypertension predicts poor fetal outcome.

The flow velocity wave forms generated by Doppler ultrasound examination of the umbilical artery were correlated with fetoplacental blood flow and numerically expressed as a ratio between the systolic (A) and the end-diastolic point (B). The technique is non-invasive and simple to perform. A cohort analytical study was done to see whether useful information could be obtained from the A/B ratio that could help in the management of patients with severe proteinuric hypertension. Fifty patients with severe proteinuric hypertension at less than 34 weeks' gestation were studied and serial Doppler ultrasound examinations of the umbilical artery were performed. No ultrasound results were made available to the clinician. An A/B ratio of 6 or greater was regarded as increased. Twenty-eight of the patients had an increased A/B ratio; in this group these 14 infants were small for gestational age, 14 developed late decelerations and there were 12 perinatal deaths. The remaining 22 patients had an A/B ratio of less than 6 and only 3 produced infants which were small for gestational age; 2 fetuses developed late decelerations and there was 1 perinatal death. A significant difference was found between the two groups in respect of these results. The group with an abnormal A/B ratio also experienced more neonatal morbidity. The A/B ratio of the umbilical artery wave form may assist in planning delivery of patients with severe proteinuric hypertension more accurately.

Urinary 5 alpha-androstane-3 alpha,17 beta-diol levels in normal and hirsute women: discriminating power and relation to other urinary steroids.

The urinary levels of seven steroids, 5 alpha-androstane-3 alpha,17 beta-diol, 5 beta-androstane-3 alpha,17 beta-diol, androsterone, etiocholanolone, tetrahydrocortisone, tetrahydrocortisol and allotetrahydrocortisol were measured in both normal (n = 18) and hirsute (n = 24) women. The results confirmed 5 alpha-androstane-3 alpha,17 beta-diol as the most significant steroid with respect to discrimination between hirsute and normal subjects. Investigation of the inter-steroid relationships, using multivariate techniques established that the mode of steroid metabolism was different between the two groups. Whereas in normal women the strong correlation amongst all the androgen metabolites inferred a predominant hepatic route to 5 alpha-androstane-3 alpha,17 beta-diol formation, the same analogy was not applicable to the hirsute subjects. Excellent agreement was found for the predicted vs actual excretion of 5 alpha-androstane-3 alpha,17 beta-diol in normal women, based on a regression model involving the six other steroids as independent variables. When the same model was used for estimation of 5 alpha-androstane-3 alpha,17 beta-diol levels in thirteen hirsute subjects, misclassified as "normal", 50% gave values which were considerably less than actually measured. It is suggested that this discrepancy, with respect to these hirsute subjects is a reflection of extrahepatic production of 5 alpha-androstane-3 alpha,17 beta-diol due to increased 5 alpha-reductase activity.

Ultrasonographic criteria for the conservative management of antenatally diagnosed fetal ovarian cysts.

Routine antenatal ultrasonography at regular intervals will detect fetal ovarian cysts. Before the era of ultrasound, the attending physician was unaware of the presence of these cysts. It is therefore imperative that a protocol for the management of asymptomatic, antenatally diagnosed ovarian cysts be developed. The vast majority of these cysts are benign and functional; laparotomy during the neonatal period is not only unnecessary but may be harmful. In a prospective study undertaken at Tygerberg Hospital, Parowvallei, South Africa, six ultrasound criteria were drawn up for the safe, conservative management of these neonates. Adherence to these criteria enabled us to manage five of seven neonates conservatively. Laparotomy in one neonate showed a benign functional ovarian cyst. Retrospectively, this case should have been managed conservatively. In the remaining neonate a laparotomy for an acute abdomen demonstrated torsion of an ovarian cyst, emphasizing the necessity for adequate follow-up.

Adenocarcinoma of the stomach in pregnancy--ultrasonographic diagnosis. A case report.

The ultrasonographic findings in a rare case of adenocarcinoma of the stomach in pregnancy are described. The patient presented with hyperemesis gravidarum in the second trimester.

[Ovulation induction for in vitro fertilisation at the Tygerberg Hospital]. / Ovulasie-induksie vir in vitro-bevrugting in Tygerberg-hospitaal.

The protocol for in vitro fertilisation (IVF) at Tygerberg Hospital is presented and the results are analysed. Indications for ovulation induction for IVF included the following: (a) irreversible tubal damage; (b) infertility due to immunological factors; (c) male factor-infertility; and (d) endometriosis. A combination of human menopausal gonadotrophin (HMG) and clomiphene citrate (Clomid; Mer-National) and human chorionic gonadotrophin was used. Clomid is given in dosages of 100 mg for 5 days depending on the cycle length. Three doses of HMG (150 IU) are given on alternate days, starting on the second day of clomiphene treatment. If the leading follicle has not reached a mean diameter of 14 mm the day after the last HMG dose, another dose is given. This dosage is continued until the leading follicle reaches a diameter of 14 mm. A total of 109 cycles in 100 patients was analysed. Ova were considered to be mature as soon as the dominant follicle had reached a sonographic average diameter of 18 mm, another two follicles of 16 mm average diameter being present. Serum luteinising hormone levels were determined 4-hourly from the stage when the leading follicles exceeded an average diameter of 14 mm. In this study the pregnancy rate was 21,3% per laparoscopy and 24,4% per embryo transfer. The oestradiol levels on the 5th day of treatment have a predictive value of the length of stimulation.

A case of the Neu-Laxova syndrome: prenatal ultrasonographic monitoring in the third trimester and the histopathological findings.

A diagnosis of the Neu-Laxova syndrome was made by ultrasonography in the third trimester of pregnancy. Initial ultrasonographic examination, at approximately 28 wk gestation, showed intrauterine growth retardation (IUGR), hypoechoic skeletal structures, kyphosis, feeble fetal activity, and restricted limb movement. Subsequent sonograms showed microcephaly with a receding forehead and prominent eyes, generalised edema and flexion deformities of limbs. Late third trimester findings included polyhydramnios, swelling and webbing of the knee and elbow joints, and severe edema of the hands and feet, giving the impression of absent digits. The clinical features of this case are consistent with group II of Curry's classification of the Neu-Laxova syndrome [Curry, 1982]. The histopathological findings, a triad of dermatological features, poor cortex formation of the long bones, and central nervous system (CNS) dysgenesis, are discussed. In view of the 25% recurrence rate, at risk pregnancies should be carefully monitored by ultrasonography: at 6-8 wk for accurate dating, at 12-16 weeks for active fetal limb movement, and at 16-24 wk for facial and skeletal anomalies, the detection of IUGR, and polyhydramnios.

Prenatal ultrasonographic features of the Pena-Shokeir I syndrome and the trisomy 18 syndrome.

The prenatal ultrasonographic features found in two cases each of the Pena-Shokeir I and the trisomy 18 syndromes are described. All four cases were referred for ultrasonographic evaluation of polyhydramnios, clinically detected in the third trimester. A detailed ultrasonographic study of the craniofacial structures, intrathoracic organs, and limbs showed scalp edema, multiple ankyloses, camptodactyly, rocker-bottom feet, cardiac arrhythmias, and lung hypoplasia. Chromosome analysis showed trisomy 18 in two cases; in the other two cases the diagnosis of the Pena-Shokeir I was confirmed after delivery. The similarity of the two syndromes with respect to ultrasound findings is discussed.

The antenatal ultrasonographic detection of the Holt-Oram syndrome.

The Holt-Oram syndrome is an autosomal dominant disease with 100% penetrance. No correlation exists between the maternal clinical expression and that of the affected offspring. The syndrome includes a wide range of cardiac and skeletal malformations. Real-time ultrasound, with a detailed study of the fetal heart and skeletal system, can play a crucial role in the counselling of affected pregnant women. This study describes the ultrasonographic findings of 2 affected fetuses at risk (at 34 and 14 weeks' gestational age). Ultrasonography detected and correctly estimated the severity of the cardiac and skeletal expressions.

Ultrasonic demonstration of fetal skeletal dysplasia. Case reports.

Reports on prenatal diagnosis in cases of skeletal dysplasia have mostly been in high-risk mothers with a suspect genetic background where the fetal lesion could probably be predetermined. We deal with routine ultrasonographic appraisal of the fetal skeleton when dysplasia is not initially suspected, and relate our experience of the lethal forms of this condition. During the 4-year period 1981-1984, 6 cases of skeletal dysplasia, including thanatophoric dysplasia, achondrogenesis, the Ellis-van Creveld syndrome (chondro-ectodermal dysplasia) and osteogenesis imperfecta, were detected; the ultrasonographic findings are discussed.