Surgical management of intrathoracic aortic aneurysm.

The pathology, clinical features, indications for surgery and the results of intrathoracic aneurysm are analysed in thirty-nine consecutive patients who underwent surgery at Singapore General Hospital from January 1986 through December 1990. There were twenty cases of non-dissecting aneurysm and nineteen cases of dissecting aneurysm or aortic dissection. The 30 day survival for the twenty patients with non-dissecting aneurysm was sixteen patients (80%). The best results were obtained in patients with aortic root aneurysms. The overall 30-day survival for the nineteen patients with aortic dissection was twelve patients (64%). The mortality was especially high in patients with acute aortic dissection (46%). Recent advances in the management of these aneurysms make early recognition and diagnosis mandatory to achieve the best results.


The pre-operative treatment of oesophageal carcinoma with synchronously administered chemotherapy and radiotherapy.

Forty-six patients with either squamous cell cancer of the oesophagus or adenocarcinoma involving the lower oesophagus have been treated with synchronously administered radiotherapy and chemotherapy (5FU & Cisplatin) prior to resection of the oesophagus. Endoscopically, complete regression of tumour occurred in 21 patients (46%) and when the oesophagus was resected in these patients, it was found that 11 of the resected specimens contained residual tumour deep to the mucosa. Thus, the actual complete regression rate in the 46 patients was 22%. The postoperative mortality rate was 13% (22% in the first half of the series and 4% in the second half). The median survival rate was 36 months in the 24 patients operated on for squamous cancer of the oesophagus, and 14.5 months in 18 patients operated on for adenocarcinoma of the cardia. Eight patients are alive and disease free at more than three years from surgery, and all of these patients had a squamous cell carcinoma, and all had a complete histological response from their preoperative radiotherapy and chemotherapy.


Erectile dysfunction in Singapore men: presentation, diagnosis, treatment and results.

Three hundred and thirteen new cases were seen in more than two years at the Sexual Dysfunction Clinic at the Division of Urology, Toa Payoh Hospital (TPH). Patients were assessed by history, clinical examination, psychological evaluation, hormonal and biochemical tests; special investigations such as monitoring of nocturnal penile tumescence, cavernosography, selective pudendal arteriography and tests of neurological function were performed where indicated. Two hundred and twenty-seven patients (72.5%) had impotence due to organic causes while 86 patients (27.5%) were found to have psychogenic impotence. Diabetes mellitus and vascular disease account for the large proportion of organic impotence (81%). Patients with psychogenic impotence responded fairly well to psychosexual therapy and drug treatment in certain cases. Forty-four patients underwent medical therapy which consisted mainly of pharmacologically induced penile erections by the use of papaverine, phentolamine or prostaglandin E-1; 21 patients (48%) who were on self-injection therapy became non-compliant subsequently. One hundred and fourteen andropausal patients with low testosterone levels received hormonal replacement. Thirty-one patients underwent surgery--stripping and ligation of the deep dorsal vein of the penis (13 patients), microsurgical arterial revascularisation (two patients) and penile prosthetic implantation (16 patients). Our success rates for the operations were 54%, 100% and 88% respectively.


Preliminary experience in ileal neobladder reconstruction.

In the treatment of transitional cell carcinoma of the bladder, the recent trend is towards radiation or chemotherapy which can be either regional or systemic. There have also been good results with giving Mitomycin or Bacillus Calmette Guerin instillation into the bladder for superficial tumours. There are occasions where patients present with large bulky tumours which cannot be controlled by endoscopic measures, invasion involving multiple sites and carcinoma in-situ which progresses to invasion. In these occasions, we have to resort to surgical clearance of the tumour. If it is possible, all patients would not like to wear a urinary bag for the rest of their lives. A bladder replacement if ever possible is always welcomed because the patient can pass urine from the natural passage. Due to the magnitude of a radical cystectomy and status of the urethra, it is not always technically possible to reconstruct the bladder. With improvement of operative techniques and suture materials, there has been a recent development of a method of bladder reconstruction that uses an ileal pouch. We report our early experience with this operation.


Urological trauma.

Major urological trauma is life threatening and frequently associated with trauma to other organs. A conservative approach to lesser degrees of damage to the kidney is fully justified whilst a shattered kidney or a pedicle injury calls for surgical exploration. Renal injuries between these two extremes require careful assessment and clinical judgement to decide the best management. An intravenous urogram remains the mainstay of investigation but computed tomography, ultrasound and arteriography can be useful in some circumstances. The management of urethral trauma remains controversial and depends largely on the assessment of whether the posterior urethra is partially or completely ruptured. There remain two schools of thought concerning early or late intervention but all are agreed that suprapubic diversion is essential and that a urethral catheter should not be passed blindly in the initial stages. A ruptured bladder should always be repaired and early intervention is recommended for ureteric injuries. Severe trauma to the testis is best managed operatively to reduce the morbidity.


Computerised 3-dimensional vector volume analysis--the role of a new method for assessing anal sphincter competence.

The results of manometric assessment (using conventional parameters) in idiopathic faecal incontinence overlap with normals, especially if the impairment is not severe. Computerised three-dimensional vector volume analysis is a recently introduced method of integrating the pressure profile along the anal canal in multiple radial directions, which may detect minor sphincter weaknesses more accurately. We compared the two methods in 47 subjects (normals = 25, patients with idiopathic faecal incontinence = 22), to analyse the same data derived from a station pull-through manometric technique. The conventional parameters of mean resting and maximum voluntary contraction pressures did not differ significantly between normal and incontinent subjects. The anal canal length in incontinent patients was significantly shorter (mean 2.9 SEM 0.2 cm in normals and 2.0 SEM 0.3 cm in incontinent; p less than 0.5). The computer calculated vector volumes and pressure symmetries (both at rest and during contraction) were not significantly different between the two groups. Although local areas of weaknesses may be identified on computerised vector diagrams, the vector volume calculations gave little additional objective information to the conventional indices to discriminate milder degrees of idiopathic faecal incontinence.


Microsurgery and its clinical impact.

Microsurgery is a technique of magnifying the visual horizon of the surgeon to enable him to see better, dissect better and perform micro-manipulation. This is to help the surgeon to perform very precise surgery that was not possible in the past. The greatest impact has been in our ability to suture small vessels and to allow us to shift tissues readily from one part of the body to another. It can be considered as a form of "spare part surgery" by using biological tissue consisting of toe, digits, bone, cartilage, skin muscle, intestine and other organs for reconstruction. The techniques are now widely accepted as important techniques in reconstructive surgery. The increasing application of these techniques are now being seen more and more in limb preservation surgery for trauma, tumour resection, congenital abnormality and organ transplant. The potential wide application of the technique in hetero transplant, especially in foetal surgery and foetal tissue transplant is now limited only by immunological rejection.


Current concepts in the treatment of soft tissue sarcomas.

Soft tissue sarcomas encompass a wide variety of lesions and continue to pose a different treatment problem. However the outlook is improving. Recent advances in pre-treatment assessment and pathological assessment of soft tissue sarcomas have resulted in more accurate clinical staging. In addition, recent advances in surgical adjuvant treatment programmes hold promise for better results.


Metastatic bone disease: current concepts of clinicopathophysiology and modern surgical treatment.

Metastases to bone are a common problem confronting both the orthopaedic oncologist and cancer specialists. Early diagnosis requires a knowledge of the pathogenesis of bone metastases. A primary route of metastatic cells is via Batson's vertebral vein plexus. An understanding of the pathophysiology enables the surgeon to plan effective treatment. As many patients continue to survive for prolonged periods following the detection of bone metastases, it is important to plan treatment that is durable and functional. Non-operative treatment is utilised for small lesions (less than 25 percent of the cortical diameter). Radiotherapy (generally 3000 cGy in ten fractions), patient education (to avoid excessive torsional loads), and systemic chemotherapy or hormonal therapy are the mainstays of non-operative treatment. The indications for surgical treatment include: (1) lesions greater than 50 percent the diameter of the cortex, (2) permeative lesions in high stress areas (subtrochanteric region of the hip, mid-femoral diaphysis, mid humeral metaphysis), and (3) lesions in which pain persists following external beam irradiation. Early and effective treatment improves the remaining quality of life in patients with metastatic bone disease. A knowledge of the pathogenesis and pathophysiology aids the clinician in making an early diagnosis.


Surgical management of anal incontinence.

The complex nature of the continence mechanism is reflected in the difficulties experienced in the surgical management of patients with faecal incontinence. Apparent anatomical abnormalities may be identified but the functional outcome following surgery may be unsatisfactory. It is therefore important to improve both the selection of patients as well as the surgical procedures themselves. Selection of patients for appropriate treatment should be based on clinical findings as well as anorectal physiology tests. Most patients referred for assessment fall into one of six categories: incontinence with a normal sphincter; minor incontinence due to local anal conditions; direct sphincter injury; neurogenic ("idiopathic") incontinence; rectal prolapse; generalised neurological condition. Minor anal conditions causing incontinence must be carefully identified for appropriate treatment. A large amount of work has been done over the past ten years on the pathophysiology of major incontinence and new surgical procedures have been developed. A common difficulty is deciding whether anterior sphincter attenuation or neurogenic weakness is the dominant lesion causing incontinence; overlapping sphincter repair is indicated for the former and postanal repair for the latter. Anorectal physiology studies can be helpful in differentiating these conditions and are now used routinely in the assessment of patients.


Vascular trauma.

An arterial injury causes either major haemorrhage with hypovolaemia and shock or ischaemia in the distribution of the damaged vessel. Initial management consists of establishment of an airway and haemodynamic stabilisation. If there is persisting hypotension because of continuing bleeding, further resuscitation is carried out in the operating room. A rapid systematic examination is performed with a thorough evaluation of motor and sensory function, as vascular injuries are often accompanied by nerve injuries, which should be well defined prior to any attempts at vascular repair. Arteriography, if available promptly, is useful in stable patients. It allows assessment of the extent of injury and of distal vessels and may prevent unnecessary exploration of neck and extremity injuries. However, it should not delay the vascular repair beyond six hours from the time of injury. It is useful if the site of injury is unclear, the trajectory of a missile is unknown or there are multiple pellet injuries but it is unnecessary if there is an obvious vascular injury. It is helpful to have facilities available for intra-operative arteriography. Repair of arterial injury is performed whenever possible. Prolonged ischaemia, beyond six to eight hours, causes irreversible nerve damage and will lead to an unsatisfactory result, even if re-vascularisation is successful. The principle of proximal and distal control and adequate debridement of damaged artery and surrounding tissue must be adhered to. The type of repair depends on the nature and extent of the arterial injury and includes lateral repair, end-to-end anastomosis and vein graft interposition.(ABSTRACT TRUNCATED AT 250 WORDS)


Holistic comfort: operationalizing the construct as a nurse-sensitive outcome.

The structural and semantic complexities of the construct of comfort are explicated and a rationale is presented for operationalizing the construct for holistic nursing practice and research. A review of the literature about comfort provides theoretical support for the concept's taxonomic structure, which was presented in an earlier publication and is modified in the present article. In addition to being useful for generating assessment tools for practice, the taxonomic structure of comfort can be utilized to develop instruments for outcome research.


The influence of sociopolitical, scientific, and technologic forces on the study and treatment of neonatal pain.

This article describes how sociopolitical, scientific, and technologic forces have influenced neonatal pain research and clinical practice. Changing beliefs about pain from the perspective of patients, physicians, nurses, and scientists investigating the neurobiology of pain are discussed. The impact of the development of the specialty of neonatology and its associated technologic advances on neonatal pain is explored. In addition, the influence of increased scientific knowledge about the neurodevelopment of the neonate and neurobiology of the sensory system on neonatal pain is presented. Finally, changes in society's views of children and the role of parents are addressed. The article concludes with a discussion of the relative importance of each of the factors in stimulating recent interest in neonatal pain. The opportunities for nurses to contribute to scientific research to improve the care of neonates in pain are highlighted.


Culture and pain: a Mesoamerican perspective.

Culture has been identified as a factor that influences a person's reaction to and expression of pain. Research in the area of pain and culture has not established a clear link between cultural meanings and attitudes associated with pain and pain behaviors. The purpose of this ethnohistoric study was to explore the beliefs related to the experience of pain within ancient Mesoamerica. The six themes that emerged from this study represent efforts related to the discovery of the epistemics of cultural meanings of pain in contemporary Mesoamerican cultures, specifically Mexican-Americans. These findings serve as a benchmark from which to understand Mexican-American meanings, expressions, and care associated with pain.


Relieving pain through ordinariness in nursing: a phenomenologic account of a comforting nurse--patient encounter.

This article describes a nursing encounter between Sue, a nurse, and Becky, a patient. Sue and Becky related to one another through a sense of shared humanity that not only relieved some of Becky's pain, but also created some possibilities for changing patterns in her life that had been built up over a long period. The article suggests that nurses and patients relate to one another through their affinity as humans. Within the context of caring, nurses such as Sue are ordinary people perceived as being extraordinarily effective by the very ways in which their humanness shines through their knowledge and skills to make their whole being with patients something more than just professional helping. An implication for nursing knowledge arising from Sue's and Becky's interaction, and from the study generally, is the need to reconceptualize the nurse as person, so that nurses are described not only in terms of their professional roles and functions but also as people who share the everyday human qualities of their patients.


Undermedication for pain: an ethical model.

Ethical decision making for, and with, clients experiencing pain and needing narcotic analgesia is especially problematic as evidenced by research findings. This article demonstrates the application of Greipp's model to ethical decision making for clients experiencing pain. Particular attention within this model is given to learned potential inhibitors of the nurse as they influence the outcome (decision). The application of this model to decision making and pain management will generate further scientific inquiry by identifying the areas of breakdown in ethical decision making for and by clients experiencing pain so that remediation strategies may be planned.


A descriptive study of nursing judgment in the assessment and management of cardiac pain.

Unrelieved cardiac pain in patients admitted to a coronary care unit (CCU) with a diagnosis of coronary artery disease was examined from the perspective of nursing judgment. The purpose of this study was to reveal expert clinical knowledge and judgment in this specific area of critical care practice. Using a naturalistic approach, nurses were observed and interviewed as they made judgments about cardiac pain. Qualitative data analysis identified patterns of nursing actions and thought processes. Findings indicated that clinical knowledge of the titration of drugs was used in the treatment of cardiac pain, and qualitative distinctions and sense of saliency were also important in pain assessment. Intuitive thought processes were identified in the clinical judgment of expert nurses.


The dyspnea experience: nociceptive properties and a model for research and practice.

Dyspnea has been defined as the unpleasant sensation of difficult breathing and the reaction to that sensation. Dyspnea research, however, has largely used a unidimensional, sensory model of dyspnea devoid of the affective and motivational dimensions that uniquely characterize this sensation in clinical populations. Dyspnea might be more comprehensively viewed as a nociceptive phenomenon which, like pain, has affective dimensions expressed as distress in response to aversiveness. A multidimensional, ecologic model of the dyspnea experience is presented that incorporates nociceptive sensation properties and is suggestive of new directions for dyspnea research uniquely relevant to nursing science.


The meaning of pain management: a concept analysis.

As it relates to the person experiencing chronic nonmalignant pain, the conceptual meaning of pain management has not been clarified previously. This article describes a concept analysis of pain management that resulted in a definition of the term and three defining attributes: pain relief, pain modulation, and self-efficacy. A model case is provided with examples of borderline and related cases. The findings of this analysis will contribute to instrument development, theory testing, and an understanding that should positively impact the self-management of persons experiencing chronic nonmalignant pain.


Effect of fermented oatmeal soup on the cholesterol level and the Lactobacillus colonization of rat intestinal mucosa.

Rats were fed with freeze-dried oatmeal soup fermented by six different Lactobacillus strains from rat and man; the formula is intended for enteral feeding. The serum cholesterol levels after 10 d were lower for rats eating oatmeal as compared to a commercial product, Biosorb Sond. Colonizing ability of the administered strains were evaluated in vivo. Only Lactobacillus reuteri R21c were able to, effectively, colonizing the mucosa; it represented about 30% of the Lactobacillus population 24 d after termination of the administration. L. reuteri R21c was easily recognized by the ability to produce a yellow pigment on agar plates. The identity was confirmed by carbohydrate fermentations (API 50CH), plasmid pattern and endonuclease restriction analysis of the chromosomal DNA.


Genetic analysis of methylotrophic yeast Candida boidinii PLD1.

This paper reports the initial experiments for genetic analysis of the haploid methylotrophic yeast Candida boidinii PLD1. The collection of multiply marked auxotrophic mutants was obtained after treatment with UV-light or X-rays. Protoplasts from several mutants were fused by the PEG-CA2+ technique and five prototrophic hybrids were isolated. The genetic structure of the hybrids was studied by means of spontaneous and induced mitotic segregation. Our data suggest that hybrids are diploids, heterozygous by parental auxotrophic markers. We obtained genetic linkage between mutations lys2-8-met-3 from one hand and ade-17-arg-24 from the other. The genetic maps constructed showed similar characteristics concerning both the order of the markers and their map distances.


Physical and genetic characterization of linear DNA plasmids from the heterothallic yeast Saccharomycopsis crataegensis.

Five strains of the heterothallic yeast Saccharomycopsis crataegensis have been previously shown to contain DNA and/or RNA plasmidlike molecules (Shepherd et al. 1987). Three DNA plasmids, designated pScrl-1, -2 and -3, were found in strain NRRL Y-5902, while two were identified in each of NRRL strains Y-5903 and Y-5904. DNA plasmids were not identified in S. crataegensis strains Y-5910 or YB-192. Four S. crataegensis strains (Y-5903, Y-5904, Y-5910 and YB-192) were also shown to possess double-stranded RNA (dsRNA) molecules not found in strain Y-5902 (Shepherd et al. 1987). Hybridization studies now demonstrate the DNA plasmids in Y-5903 and Y-5904 to be highly homologous to their respective size counterparts (pScrl-1 and pScrl-2) in Y-5902 and to show some homology to pScrl-3. Restriction endonuclease mapping studies confirm the linear nature of each plasmid and establish identical restriction maps for a 1.4 kilobase (kb) region in pScrl-2 and -3. This 1.4 kb region accounts for the hybridization homology of pScrl-2 and pScrl-3 noted by Shepherd et al. (1987) and for homology of the plasmids of Y-5903 and Y-5904 to pScrl-3 of Y-5902. The pScrl plasmids show no homology to the dsRNA molecules of S. crataegensis, the 2 microM circular DNA of Staccharomyces cerevisiae, the 'killer' plasmids of Kluyveromyces lactis, or the linear DNA plasmids of Pichia inositovora. In crosses between linear DNA plasmid-containing and dsRNA-containing strains, only progeny containing the pScrl plasmids were recovered. Poor spore viability and a lack of complete tetrad recovery limited the extent of the analysis, but the findings suggest a cytoplasmic mode of inheritance for these linear DNAs.


Adhesive knob formation by conidia of the nematophagous fungus Drechmeria coniospora.

We studied conidiogenesis and adhesive knob formation (maturation) by newly developed conidia of the nematophagous fungus Drechmeria coniospora. Upon conidiogenesis on infected nematodes or during saprophytic growth of the fungus in axenic cultures compact clusters of conidia developed. Less than 10% of such clustered conidia matured; mature conidia were invariably located on the periphery of the clusters. The kinetics and rate of maturation of conidia were studied in in vitro systems and in soil. In both cases adhesive knobs were formed; the rate at which knobs were formed appeared to be determined by the age of the conidia, the temperature and the soil moisture. In addition, knob formation was suppressed at increasing conidial densities. Under favorable conditions, however, over 90% of the conidia matured within a period of 3 days. The rate of knob formation was neither influenced by the presence of nematodes nor by that of exogenous nutrients, which suggests that maturation is an autonomous process. Electron-microscopical analysis indicated that budding of the conidia at the initial stage of maturation occurred simultaneously with the deposition of the sticky, adhesive layer around the wall of the developing knob. The ecological significance of the time- and spatially separated maturation of conidia after conidiogenesis is discussed with respect to survival of the conidia.


Isoprenoid quinones and fatty acids of Zoogloea.

Nine Zoogloea strains including the type strain of Z. ramigera (IAM 12136 = ATCC 19544 = N.C. Dondero 106) and newly isolated strains were investigated for isoprenoid quinone composition and whole-cell fatty acid profiles. Seven of the tested strains, having phenotypic properties typical of Zoogloea, were characterized by their production of both ubiquinone-8 and rhodoquinone-8 as major quinones, whereas the remaining two strains, Z. ramigera IAM 12669 (= K. Crabtree I-16-M) and IAM 12670 (= P.R. Dugan 115), formed ubiquinone-10 and ubiquinone-8, respectively, as the sole quinone. All rhodoquinone-producing strains contained palmitoleic acid and 3-hydroxy-decanoic acid as the major components of nonpolar and hydroxylated fatty acids, respectively. Marked differences were noted in the fatty acid composition between the strains with and without rhodoquinones. The chemotaxonomic data suggested that the rhodoquinone-lacking strains should be excluded from the genus Zoogloea. Since there have been no reliable taxonomic tools for Zoogloea, rhodoquinone analysis may provide a new criterion of great promise for identifying Zoogloea strains.


Genetic identification of natural Saccharomyces sensu stricto yeasts from Finland, Holland and Slovakia.

Genetic and karyotypic studies of natural Saccharomyces sensu stricto yeasts from Finland, Holland and Slovakia revealed three wild sibling-species: Saccharomyces cerevisiae, Saccharomyces bayanus and Saccharomyces paradoxus.


Sporobolomyces lactosus, a new species of ballistosporous yeast equipped with ubiquinone-10.

A new species of ballistospore-forming yeasts was recovered and its description given. Sporobolomyces lactosus, isolated from activated sludge treating petrochemical wastes, produces pinkish-coral to pink colored colonies, assimilates lactose and has Q-10 as the major ubiquinone.


[Surgical treatment of gastric cancer in the aged].

The present status of surgical treatment for gastric cancer in the aged was reviewed. The incidence among the aged in the overall operated patients with gastric cancer has increased yearly and recently has reached approximately 35%. The incidence of early gastric cancer in the aged has increased 40% in recent times. Pulmonary failure and anastomotic leak of the alimentary tract are the most common post-operative complications in the aged; these easily lead to the development of multiple organ failure with high mortality. Precise pre-operative evaluation of functional disorder in each organ and pre-, post-operative nutritional and transfusional support is indispensable to overcome these complications. Surgeons are required to perform appropriate surgical maneuvers with minimum operation time and minimum blood loss with full consideration for the adequate surgical indication in accordance with both the spread of the cancer and the general condition of the aged patient. Mental care to avoid post-operative mental disorders is also crucial.


[Indication and problems of radiation therapy of elderly patients with cancer].

The incidence of cancer and the patients treated with radiation therapy increased with age. Of 5778 patients treated with radiation therapy at the Center for Adult Diseases, Osaka, 37.5% are over 65, and 10.8% are over 75 years old. Older patients with cancer have a lower survival rate. Patients over the age of 75 with carcinoma of the pharynx, esophagus, lung, and uterine cervix have decreased survival compared with younger patients. However, for the patients with carcinoma of the larynx, age is not a determinant of prognosis. With respect to radiation therapy, it is not clear whether elderly patients differ from younger ones in responsiveness. However, a decreased tolerance for radiation therapy might be expected and under-dosing with radiation therapy may be more prevalent. More study of the optimal management of elderly patients with cancer is needed.


[Chemotherapy in the elderly].

Because of the increase in the incidence of malignancies with advancing age, we have need to make decision on the chemotherapy of elderly patients with cancer. However, until recently, studies about response to treatment and toxicities in the elderly patients have been quite limited. Many of clinical trials have excluded elderly patients with advanced cancer. In leukemia and Hodgkin's lymphoma, definite trends of decreased levels of response and survival in relationship to increased age have been reported. This reduced rates of response in elderly leukemia patients do not appear to be due to chemotherapy resistance but rather to high rates of death among elderly patients during remission induction therapy or to inadequate salvage therapy. On the other hand, older patients with solid cancers can be treated with chemotherapy as successfully as younger patients. General expectations of response, remission, and survival are similar for the older and younger patients. With the exception of small increase in the incidence of hematologic toxicity in the older group, both younger and older patients experience the same frequency of toxic reactions. Aging is a highly individualized process that cannot be defined by chronological landmarks. Therefore, it can be said that there is no reason to exclude from adequate chemotherapy, simply on the basis of age alone. But, observations on the proper role of chemotherapy in older patients are very limited, and further studies are needed in this area.


[Electron microscopic study on the method of evaluation of SRC assay].

The subrenal capsule assay (SRC) is a rapid and precise method for evaluation of chemotherapeutic agents. However, it seems to present some difficulties with regard to sensitivity, since evaluation is done by measurement of graft size. In this study, SRC was performed on six clinical cases of colorectal cancer using nude mice, which were given UFT 15 or 20 mg/kg orally or 2.5 mg/kg CDDP subcutaneously for 2-6 days. Histological changes in the grafted tumors were then observed by electron microscopy. Mucous granules and other features were assessed for evaluation of assay sensitivity. The number of mucous granules seemed to be the most reliable parameter that paralleled the sensitivity evaluated by tumor diameter. Other features such as nuclear mitosis, lysosomal increment and abnormal accumulation of ribosomes, had little correlation with sensitivity. However, further exploration is warranted with regard to local defects of the cytoplasm. This ultrastructural examination suggested that grafted tumor cells were damaged slightly by implantation under the renal capsule, and that the SRC using tumor size as a parameter is clinically useful under conditions where the tumor xenografts show good viability and proliferation in the control group.


[Serum concentration of HCFU and 5-FU after oral administration of HCFU in postoperative digestive cancer patients].

In an attempt to establish the optimum dose of HCFU, the effect of the presence of stomach on the absorption of HCFU and both the rise and maintenance of blood HCFU levels was evaluated in patients with gastric cancer (total gastrectomy group) and with colorectal cancer (non-gastrectomy group). The blood concentrations of HCFU fractions and 5-FU were determined in terms of pharmacokinetic parameters in these groups. The Tmax was significantly different between the two groups, with HCFU fraction and 5-FU levels that were significantly higher in the total gastrectomy group 30 minutes after administration. No differences were found in Cmax or AUC. There were no significant differences in Cmax or AUC among the various subgroups given different doses of HCFU (100, 150 and 200 mg) in either group, although dose-dependency was observed. Similar results were obtained in crossover tests. The 5-FU remained at an effective concentration of 0.05 microgram/ml, 4 hours after a single dose of 100 mg HCFU.


[Neo-adjuvant chemotherapy with tegafur suppository for rectal cancer--evaluation of the antitumor effects, tissue levels of 5-FU and inhibition of thymidylate synthase. Tochigi Colorectal Cancer Study Group].

We evaluated antitumor effect histologically and assayed the tissue levels of 5-fluorouracil (5-FU) and thymidylate synthase (TS) activity using surgical specimens obtained from the patients with rectal cancer, who were given tegafur suppositories prior to surgery. The antitumor effect was evaluated histologically according to classification of the general rules for the gastric cancer study (Japanese Research Society for Gastric Cancer). In 39 patients, 16 tumor specimens revealed no effect (grade-0), 22 tumors grade-1 effect, and one was not evaluable because of the severe inflammatory changes. In 23 of these patients, resected specimens were available for the assay. 5-FU levels in cancer tissues were significantly higher than those in normal tissues, and TS inhibition rates (TSIR) were almost identical, averaging around 20%, in both cancer and normal tissues. Comparing the 5-FU levels and TS activity according to the histological effects (i.e.: 'grade-0' vs 'grade-1'), the 5-FU levels in the tumors achieved grade-1 were significantly higher than in the tumors showed 'grade 0' (p less than 0.01), and TSIR in the former were relatively greater than in the latter (p = 0.053). It is suggested that both tissue levels of 5-FU and TSIR may be useful parameters to predict the anti-tumor effect against rectal cancer after administration of 5-FU and its derivatives.


[Pharmacokinetics and toxicological study on the intraperitoneal administration of cisplatin and etoposide in gynecological malignancies].

We administered cisplatin and etoposide into the peritoneal cavity of 13 postoperative patients with gynecological malignancies, and studied the pharmacokinetics and toxicity in the combination of both drugs. Cisplatin 100 mg/body and etoposide 200 mg-400 mg/body were mixed together in 500 ml or 1,500 ml of normal saline and administered intraperitoneally on the day of operation and two or three weeks later. The peritoneal peak level of free cisplatin, diluted with 500 ml, was about two times higher than that, diluted with 1,500 ml. However, there was no difference in the peritoneal and plasma AUC. The peritoneal level and AUC of etoposide, diluted with 500 ml, was about two times higher than that, diluted with 1,500 ml. Among the groups of 1,500 ml, peritoneal and plasma levels and AUC were almost proportional to the doses. Nausea and vomiting were experienced in all patients. With the increase of etoposide, more marrow suppression was observed. However, we encountered no other significant side effects. In conclusion, intraperitoneal administration of cisplatin and etoposide in this setting can be used safely with minimum side effects, and the dilution of 1,500 ml seems to be better.


[Transient subacute encephalopathy induced by high-dose methotrexate treatment in children with acute lymphoblastic leukemia and malignant lymphoma].

Transient subacute encephalopathy was detected in 4 of 83 patients undergoing treatment with high-dose methotrexate (HD-MTX) and citrovorum factor rescue for childhood acute lymphoblastic leukemia and malignant lymphoma from 1984 to 1991. Subacute encephalopathy occurred in relatively older patients and early in the course of treatment with HD-MTX. The average interval between the HD-MTX course and the onset of the neurologic disturbance was 6.5 days. All 4 patients treated had no neurological sequelae. Laboratory evaluations disclosed nontoxic plasma MTX levels at onset of symptom and not detected in liquor. CT in 4 patients disclosed no abnormality, but MR images revealed abnormal signal intensity patterns of cerebral white matter in 2 cases. In one case the abnormal MR finding resolved after 3 months. The pathogenesis of this neurologic symptom remains unknown, but further HD-MTX treatment may be acceptable in follow-up of MR image, because the prognosis of subacute encephalopathy seems favorable.


[Short-duration bladder instillation therapy with pirarubicin for superficial bladder tumor based on pharmacodynamic study].

From our experimental study, an instillation of THP for 5 minutes was attempted in 23 patients with superficial bladder tumors. THP (30 mg dissolved in 50 ml of distilled water) was instilled into the bladder 6 times every 48 hours. Of 23 patients, 9 (39%) showed complete disappearance of the bladder tumors, while partial disappearance (more than 50% tumor reduction) was observed in 3 cases (13%). Therefore the overall response rate was 52%. Neither urinary frequency nor hematuria was observed in all the cases, while painful urination was observed in 3 cases (13%). This newly designed bladder instillation therapy was effective against superficial bladder tumors with low incidence of local side effects.


[Chemotherapy-associated hemolytic uremic syndrome--a case report].

A 63-year-old male had undergone combination chemotherapy including adriamycin, cisplatin, mitomycin C, 5-fluorouracil and vindesine for six months for double cancer of esophagus and stomach. He complained of lassitude during therapy, and laboratory examinations revealed microangiopathic hemolytic anemia, thrombocytopenia and hyperbilirubinemia. Despite administration of prednisolone, dipyridamole and fresh frozen plasma, the patient died six days later. Postmortem examination disclosed multiple microthrombi in the liver, kidney and pancreas. It was presumed that MMC had caused the illness.


[A case report of metastatic colonic carcinoma in the liver effectively treated by long-term, ambulatory and continuous, intra-hepatic-arterial infusion of 5-fluorouracil using disposable multi-day-type infusor].

A 42-year-old female was diagnosed as having sigmoid colonic carcinoma with multiple metastases in the liver. Following sigmoid colectomy and descending colostomy, a catheter was inserted from the right gastroepiploic artery to the proper hepatic artery. From the day of surgery 5-Fluorouracil was administered in doses of 250 mg/day continuously through a catheter over the 2-month period of hospitalization. After the patient was discharged, 250 mg/day of 5-Fluorouracil was administered at home using Vaxter Infusor according to a regimen of 10-day continuous infusion and subsequent 4-day rest. Five months after the initial operation, the serum CEA level decreased dramatically, and CT scan of the liver revealed the complete disappearance of the metastases. The patient underwent a second operation in which the colostomy was closed, and she is doing well at this writing. This case suggests that long-term, ambulatory, continuous and intra-hepatic-arterial infusion of 5-Fluorouracil can be a very effective treatment not only in reducing the hepatic metastases but also in improving the quality of life of patients with colonic carcinoma.


[Cell culture and its application current methods for a synchronous culture of mammalian cells].

Synchronization of cells to various phases of the cell cycle in mammalian cells is crucial to analyze cell cycle progression and many other cellular functions. To date, various methods have been developed, such as mitotic selection, use of cell-cycle mutants, use of drugs which inhibit DNA replication (nucleoside analogue, excess thymidine, hydroxyurea, and aphidicolin), elutriation, deprivation of nutrients (amino acid, and serum), and new promising drugs of protein kinase inhibitors. Although above methods have both advantage and disadvantage, a practical and satisfactory method can be chosen from these method if taking into account goals of experiments and cell types to use. In near future, more powerful and reliable ones will be discovered since our understanding of the cell cycle has been increasing quite abruptly.


Benign pigmented nevi in children. Prevalence and associated factors: the West Midlands, United Kingdom Mole Study.

Prevalence of benign melanocytic nevi (moles) has been shown to be a major predictor of malignant melanoma. In this study the prevalence of moles in a group of 2140 children, aged 4 to 11 years, was determined. A standard questionnaire was completed by the parents of each child and included information on environmental and life-style factors. Examination data for each child were linked to the data obtained from the questionnaire. Prevalence increases rapidly throughout childhood and studies of children may indicate which factors contribute to mole development. Boys had more moles than girls, as did white children when compared with other ethnic groups. Prevalence of moles increased with age in children of both sexes. Among whites, skin color had little influence on mole prevalence. The following characteristics, however, were associated with an increased prevalence of moles: a propensity to burn rather than tan, a history of sunburn, a tendency to freckle, and a life-style involving increased sun exposure. A striking positive association between prevalence of moles and number of foreign holidays in a hot climate was observed. This association was independent of a history of sunburn. The study supports the hypothesis that environmental factors influence the prevalence of moles in childhood.


Histologic and immunohistochemical study comparing xanthoma disseminatum and histiocytosis X.

As xanthoma disseminatum and histiocytosis X share clinicopathologic features, difficulties in diagnosis can arise. The use of immunocytochemical markers for S100 protein, factor XIIIa, lysozyme, alpha 1-antitrypsin, for adherence of peanut agglutinin and of antibodies LN3 (HLA-DR), Leu-M1 (CD15), QBEnd/10 (CD34), MAC 387, and KP1 (CD68) as an aid to conventional histology has been studied in routinely fixed skin biopsy specimens from seven patients with xanthoma disseminatum and 12 patients with histiocytosis X. Typically xanthoma disseminatum occurs in discrete foci below an intact epidermis with individual cells set within a delicate fibrillary connective tissue stroma. In contrast, histiocytosis X usually occurs as a diffuse lichenoid infiltrate that can extend to deeper tissues. Epidermal invasion is common and the cells tend to lie free separated by edema fluid. Characteristic histiocytosis X cells are ovoid with an indented or kidney-shaped nucleus that occupies half or more of the cell. Xanthoma disseminatum cells differ in showing irregular scalloped borders, a more extensive cytoplasm, and an ovoid vesicular nucleus. Most xanthoma disseminatum cells labeled strongly for factor XIIIa and with KP1; a few cells labeled only weakly with peanut agglutinin. In contrast, most histiocytosis X cells labeled for S100 protein and with LN3 and peanut agglutinin. All the other markers remained negative in both conditions and were thus noncontributory for differentiating xanthoma disseminatum from histiocytosis X. We conclude that the differences in labeling patterns are a useful aid to histologic diagnosis of histiocytosis X and xanthoma disseminatum and they also reflect their separate histiogenesis.


Peroxisomal abnormality in fibroblasts from involved skin of CHILD syndrome. Case study and review of peroxisomal disorders in relation to skin disease.

Peroxisomal deficiency has been described in a number of syndromes characterized by chondrodysplasia punctata, including the Conradi-Hünermann (C-H) syndrome. Because of overlapping clinical features of X-chromosome inheritance, ichthyosis, and limb-reduction defects in C-H and CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndromes, we examined peroxisomal content using diaminobenzidine cytochemistry and peroxisomal functions in fibroblasts from involved vs uninvolved skin of CHILD syndrome. Fibroblasts from involved skin of a patient with CHILD syndrome accumulated cytoplasmic lipid, visualized with the fluorescent probe, nile-red. Ultrastructurally, fibroblasts of involved skin of CHILD syndrome accumulated lamellated membrane and vacuolar structures. By diaminobenzidine ultracytochemistry, fewer peroxisomes were present. Moreover, the activities of two peroxisomal enzymes, catalase and dihydroxyacetone phosphate acyltransferase, were decreased (approximately 30% of normal). However, peroxisomal oxidation of very-long-chain and branched-chain fatty acids was preserved. Moreover, plasma very-long-chain fatty acids, plasma phytanic acid, and erythrocyte plasmalogen content were normal. The CHILD, C-H, and rhizomelic chondrodysplasia punctata syndromes are all characterized by ichthyosis, chondrodysplasia punctata, and limb defects, as well as peroxisomal deficiency. Thus, these syndromes may be related pathogenically. Because peroxisomes are involved in prostaglandin metabolism, peroxisomal deficiency may directly contribute to the previously reported alterations in prostaglandin metabolism in fibroblasts of involved skin of fibroblasts.


Primary cutaneous aspergillosis near central venous catheters in patients with the acquired immunodeficiency syndrome.

Aspergillosis in patients with the acquired immunodeficiency syndrome is unusual, and the clinicopathologic features of primary cutaneous aspergillosis in this setting are undefined. Our findings show that the manifestations can differ from those of primary cutaneous aspergillosis in other immunocompromised patients. Two men with the acquired immunodeficiency syndrome developed foci of primary cutaneous aspergillosis beneath adhesive tape near central venous catheter sites. Typical lesions were flesh-colored to pink, umbilicated papules that clinically resembled molluscum contagiosum. Biopsy specimens showed variably ruptured follicles that contained collections of fungal hyphae typical of Aspergillus species. Cultures in one case identified Aspergillus fumigatus. The use of nonocclusive dressings and local wound care resulted in involution of several lesions. Primary cutaneous aspergillosis begins as saprophytic involvement of hair follicles secondary to the altered microenvironment beneath adhesive tape. Systemic antifungal therapy is prudent, but in the absence of neutropenia or other traditional risk factors for dissemination, it appears that Aspergillus in patients with the acquired immunodeficiency syndrome can produce relatively indolent cutaneous lesions with a tendency to resolve once precipitating factors are removed.


Xeroderma pigmentosum variant with multisystem involvement.

Xeroderma pigmentosum (XP) is a hereditary disorder characterized by recessive inheritance and elevated rates of skin carcinogenesis. There are seven complementation groups (A through G) for which the genetic defect results in a failure to repair DNA damage from UV light and sunlight; one group, the variant, fails to replicate UV-damaged DNA correctly. Patients in XP groups A, B, D, and G have associated neurologic problems, the most severe being known as the DeSanctis-Cacchione syndrome. We describe a patient with XP from consanguineous parents who has severe multisystem involvement similar to that of the DeSanctis-Cacchione syndrome. Extensive laboratory investigation showed that cells from this patient exhibit DNA replication after irradiation with UV light that is characteristic of the XP variant. The cells also show normal sensitivity to UV light and normal excision repair, consistent with XP variant classification. The presence of the neurologic symptoms is quite unusual in an XP variant. Our patient clearly fits into the XP variant category based on normal survival, caffeine toxic reaction, photoproduct excision and repair, and the deficient replication of UV-damaged DNA. This patient seems to be rare, however, among XP variants in displaying severe neurologic symptoms. Because of the consanguineous parents, the possibility that some of this patient's findings are from non-XP-related abnormalities must also be entertained. However, other consanguineous patients with XP variant, eg, XPIOCA, have been described who do not show neurologic abnormalities. In view of the difficulty of defining an XP group from clinical symptoms alone, we urge the term xeroderma pigmentosum variant be used only in the context of the laboratory studies of patients with XP that contain normal repair but deficient semiconservative replication of UV-damaged DNA.


Possible Werner syndrome. A unique association with spontaneous digital gangrene in infancy and decreased life span of cultured skin fibroblasts.

Werner syndrome is a hereditary disease characterized by several features generally associated with aging. However, the differences between Werner syndrome and the normal aging process are clear. Werner syndrome is usually diagnosed through the clinical signs and symptoms it presents. In recent years, however, the cultured skin fibroblasts of patients have grown slowly and patients have a short life span; these characteristics provide a useful diagnostic aid. We recently examined a 42-year-old single man who had short fingers, marked facial scars resulting from chilblain-like eruption in infancy, glaucoma caused by uveitis developed in his middle age, callosities on the soles, and immaturation of sexual glands. Repeated peripheral blood examinations showed a positive result for antinuclear factor, slight elevation of immunoglobulin levels, and a low leukocyte count. His family had repeated consanguineous marriages and his parents were cousins. We cultured skin fibroblasts from the patient's forearm and compared them with those of four normal control male subjects. The patient's skin fibroblasts showed a remarkably low population growth rate and a total replicative life span. The patients presented unique clinical features for Werner syndrome such as chilblain-like eruption in infancy and glaucoma caused by uveitis. Cell culture studies revealed cellular abnormalities compatible with Werner syndrome. We thus diagnosed the patients as possibly having Werner syndrome.


Congenital erythropoietic porphyria. A mild variant with low uroporphyrin I levels due to a missense mutation (A66V) encoding residual uroporphyrinogen III synthase activity.

Congenital erythropoietic porphyria, an inborn error of heme biosynthesis, results from the deficient activity of the enzyme uroporphyrinogen III synthase. The clinical manifestations in unrelated patients with this autosomal recessive disorder are remarkedly variable, ranging from mild cutaneous involvement to severe transfusion-dependent hemolytic anemia. Biochemical and molecular studies were undertaken to investigate the nature of the unusually mild phenotype in a 15-year-old boy with only cutaneous manifestations. The proband's levels of total porphyrins, urinary uroporphyrin I, and erythrocyte coproporphyrin I were elevated, but not as dramatically as in other patients with this porphyria. Interestingly, the erythrocyte uroporphyrinogen III synthase activity in the proband was about 21% of the normal mean, indicating the presence of significant residual activity. In cultured lymphoblasts from the proband, his father, and mother, the enzymatic activities were 10%, 70%, and 50% of the normal mean, respectively. Molecular analyses revealed that the proband was heteroallelic for two uroporphyrinogen III synthase missense mutations: the C73R allele inherited from his mother and the A66V allele transmitted by his father. The A66V allele encoded residual enzymatic activity in vitro while the C73R allele did not. The A66V allele accounted for the proband's low levels of porphyrin accumulation and mild clinical manifestations. Such genotype-phenotype correlations should provide understanding of the remarkable clinical variability in other patients with this inherited porphyria.


Information excess in medicine. Overview, relevance to dermatology, and strategies for coping.

The amount of biomedical information contained in scientific journals has grown to the point that complete coverage of this material is impossible. The number of articles and journals being published has been growing at an exponential rate since 1750. Thirty-four thousand references from 4000 journals are added each month to the National Library of Medicine MEDLINE database from among the more than 100,000 scientific journals now published. This increase in scientific literature reflects not greater productivity but simply a larger number of scientists at work. Most articles written are eventually published in the medical literature, but a large number of scientific articles are of less than optimal quality, and most scientific articles that are published are never cited. Articles of higher quality and usefulness cluster in a few journals that enjoy great use in medical libraries and high scores on bibliometric scores such as the Science Citation Index. To assess the reading habits of dermatologic trainees and evaluate how they cope with this information excess, a survey was distributed to 36 residents in three training programs. The average number of medical journal reading hours per month was 17; the number of hours devoted to reading issues of the Archives of Dermatology, the Journal of the American Academy of Dermatology, and the Journal of Investigative Dermatology were 3.2, 5.0, and 1.4, respectively; and the average resident read seven peer-reviewed journals, two to four dermatologic tabloids, and four peer-reviewed medical journals. Critically and consistently reading a limited number of high-quality peer-reviewed journals as well as taking advantage of information available through computer networks and bibliographic and full-text databases is the best approach to coping with the volume of medical literature. Translating this information into a change in attitude and modification of physician behavior is best accomplished when local role models incorporate new ideas into their practice and teaching. Modifications that would, in fact, bring about truly useful changes, such as decreasing the number of new publications, melding journals already present into smaller numbers of publications rather than instituting new journals, altering the "publish-or-perish" rules, and writing more comprehensive articles rather than multiple small contributions, all await fundamental alterations in long-accepted policies in medicine.


Scabies in chronic health care institutions.

The diagnosis and management of outbreaks of scabies in health care facilities may be difficult. As there is little information available regarding the extent of this problem we conducted a questionnaire study to provide an indication of the occurrence of scabies in chronic health care facilities in the province of Ontario, Canada. It also documented the facilities' approach to the management of the disease. Two outbreaks of scabies in chronic health care facilities are described. The questionnaire study revealed that 25% of the institutions reported that they had problems with scabies over a 1-year period. A minority had a written policy with respect to dealing with the management of scabies, particularly in the setting of a mass outbreak. Scabies is a common problem in chronic health care facilities; however, diagnosis and management may be difficult. The development of a specific protocol for the management of such outbreaks by the appropriate public health agencies would be useful.


Birth weight and hospital admission before the age of 2 years.

Admission rates to hospital of children born weighing 1500 g or less were compared with those born with birth weights over 1500 g in a retrospective analysis of routinely collected data from the Oxford Record Linkage Study. The children were born in the three five year periods 1968-72, 1974-8, and 1979-83 to women resident in Oxfordshire and West Berkshire. The main measures of the study were survival rates to 28 days after birth and hospital admissions of survivors up to the age of two years. Among babies weighing 1500 g or less, neonatal survival rates rose from 350.2 per 1000 total births in 1968-72 to 577.4 per 1000 among births in 1979-83. Over the same period, the proportion of children admitted to hospital at least once before the age of 2 years rose from 218.6 per 1000 survivors to 444.4 per 1000. In the children with birth weights over 1500 g, survival rates rose from 985.5 to 995.9 per 1000 births and hospital admission rates rose from 98.2 to 144.4 per 1000 survivors over the same time period. Although very low birthweight children did not contribute significantly to total hospital bed occupancy, because their numbers were small in relation to the total number of children in the population, their contribution increased between the five year periods 1968-72 and 1979-83. It should therefore be continuously monitored using routine systems.


Suspected child abuse: cost in medical time and finance.

In a prospective study the number of children attending the Royal Liverpool Children's Hospital (RLCH) for examination after allegations of child abuse, and the type of abuse involved, was recorded from July to December 1990. The cost to the hospital of these examinations and initial investigations was assessed. The study was carried out in the major and minor accident and emergency departments and the Rainbow Centre of the RLCH. In six months 181 children were examined. Cases of sexual abuse and non-accidental injury were seen in equal numbers. Girls outnumbered boys and 60% were referred by social services. The costs over the six month period were 31,739 pounds. The minimum projected annual cost is 63,500 pounds. We conclude that the cost of running an effective service for the initial assessment of children who are possible victims of child abuse is considerable in practical terms and in medical time.


Screening of hearing impairment in the newborn using the auditory response cradle.

The Auditory Response Cradle (ARC) is a fully automated microprocessor controlled machine that was designed for the hearing screening of full term neonates. In order to evaluate the ARC, 6000 babies were screened at a district maternity hospital over a period of three years. Every infant subsequently entered a three year follow up programme. One hundred and two babies (1.7%) failed the ARC screen (that is, they failed two ARC tests) and 20 of these were found to have some hearing impairment: in 10 it was severe (80-90 dBHL), in seven moderate (45-60 dBHL), and in three it was mild to moderate (less than 45 dBHL). In addition, of the 20 babies who failed a first test and were discharged before a second could be performed, two were confirmed to have a severe hearing loss; 79 infants failing the screen were cleared on further testing, giving the ARC a false positive rate of 1.3%. On following up all 6000 infants for three years, seven children who passed the neonatal screen were subsequently found to have a hearing loss. For two babies the aetiology was unknown but for five the hearing impairment was either due to a hereditary progressive loss or definite postnatal factors. Progressive and acquired hearing losses cannot be detected at a neonatal screen and this emphasises the need for follow up screens at other stages in the child's life. In this long term study the ARC has been found to have a high detection rate for severe hearing loss and confirms the practical possibility of using a behavioural technique for the universal screening of hearing in neonates.


Growth of infants with neonatal growth hormone deficiency.

In view of contradictory reports on the growth hormone dependency of early postnatal growth we studied the growth curves of 15 infants with neonatal growth hormone deficiency. In seven infants the growth curve was parallel to the standards of the infancy-childhood-puberty (ICP) model (group 1), but in the remaining infants there was an immediate deviation of the growth curve (group 2). In this group the mean (SD) at 4 and 9 months of age was -3.3 (1.1) and -4.9 (1.4), respectively, when compared with the ICP model. The mean birth length in both groups was decreased and five out of 15 had a birth length of less than -2 SD. Serial measurements of the growth hormone response to provocation tests in two patients in group 2 showed decreasing concentrations, while four patients with documented complete growth hormone deficiency belonged to group 2. We conclude that growth hormone is needed for early infant growth and that the normal growth pattern in some infants with neonatal pituitary dysfunction is due to incomplete insufficiency.


Sequelae of haemolytic uraemic syndrome.

Twenty two patients with previous episodes of haemolytic uraemic syndrome (HUS) were investigated for evidence of deficits in cognitive, behavioural, and academic function. Patients were pair matched with 22 controls for age (+/- 1 year), gender, and socioeconomic status. HUS patients had numerically lower cognitive and achievement scores and higher behavioural problem ratings than their controls on every measure. None of the group differences was significant at the 0.01 level. Significance values between 0.10 and 0.01 were obtained for the Wechsler full scale and verbal intelligence quotient scores and for several of the achievement measures and behaviour ratings. These results were conservatively interpreted as trends and are considered to provide preliminary indications of a post-HUS deficit in behaviour, verbal intelligence, and the verbally based skills of reading comprehension and vocabulary. The findings provide interim guidelines for follow up care but require confirmation and elaboration in a larger study.


Randomised trial of a ready-to-feed compared with powdered formula.

Forty three infants were assigned randomly to a ready-to-feed infant formula or a standard formula that required reconstitution from powder. Despite similar nutrient composition of the two formulas those fed the powdered formula had significantly increased body weight and skinfold thickness gains, and became significantly heavier than a further group of 20 breast fed infants by 3 and 6 months. Of those fed the powdered formula 6/19 had become overweight (above the 90th or 97th centile) by 6 months, whereas 1/19 fed the ready-to-feed product was overweight at this age. While differences in fat absorption might have been contributory, our data suggest that errors in reconstitution of formula from powder might be the main cause for the growth differences observed. If it is appropriate to take the breast fed infant as a model, infants fed ready-to-feed formula in this study showed a more physiological pattern of growth than those fed a standard formula reconstituted from powder. These results require replication using other formulas as the findings have potentially important implications for infant feeding.


Management and response to treatment of Helicobacter pylori gastritis.

Gastritis associated with Helicobacter pylori was present in gastric biopsies from 24/95 (25%) children and adolescents undergoing endoscopy for recurrent abdominal pain and upper gastrointestinal symptoms. H pylori associated gastritis occurred mainly in older children (8-16 years) and was significantly associated with low socioeconomic class and a family history of peptic ulcer disease. Antral nodularity was a common endoscopic finding in H pylori positive children. Eighteen children, all over 5 years of age, were treated with tripotassium dicitratobismuthate (De-Nol) for two months and ampicillin for two weeks. In 12 children follow up gastric biopsies were obtained six weeks after completion of treatment. In 9/12 (75%) children H pylori was eradicated, and gastritis improved.


Positive rolandic sharp waves in the EEG of the premature newborn: a five year prospective study.

In a prospective study of 301 premature newborn infants, neonatal tracings were done to evaluate the use of the electroencephalogram (EEG) and positive rolandic sharp waves (PRSW) in the diagnosis and prognosis of periventricular leucomalacia. Each infant had ultrasonographic studies and standardised neurological examinations at 1 year of age or later. Two hundred and eighty infants were followed up at 1 year. This study demonstrated that the absence of PRSW was correlated with a favourable motor development (98.2%) and confirmed the great value of PRSW in the diagnosis and the prognosis of periventricular leucomalacia. PRSW were sensitive (98%) and specific (84%) markers of developmental motor disability and were a sensitive (96%) marker of severe spastic diplegia. A frequency above 2/minute was a specific (92%) sign of severe spastic diplegia. Social and language developmental abnormalities were not correlated with the neonatal EEG.


Occurrence of suppurative lymphadenitis after a change of BCG vaccine.

BCG vaccines are the oldest vaccines in use today, but the protective effect of the vaccination is still controversial. The risk of contracting tuberculosis is low compared with the possible complications after this vaccination. In Austria the formerly used BCG vaccine was not available in the required amount and another vaccine was released by the drug authorities. This product, with a more virulent strain, was used between August and December 1990, and this increased the incidence of complications. Eighty four of 1950 vaccinated newborn babies developed severe suppurative lymphadenitis three to 28 weeks after the vaccination, and surgical treatment was found to be necessary. Isoniazid treatment did not prove to be successful when the lymph node exceeded a certain size. Culture was successful in 46% up to week 20; after 20 weeks no culture became positive. All cultured bacteria were isoniazid sensitive. The question of general vaccination is raised and several points were considered before we came to the conclusion that except for high risk groups a general vaccination programme for neonates is not justified in Western countries.


Necrobacillosis with pancytopenia.

Two young children whose presentation with necrobacillosis caused considerable diagnostic difficulty resulting in referral to an oncology unit are described. In both cases their severe suppurative multisystem illness was complicated by pancytopenia. One had bone marrow infarcts and severe endocarditis in addition to pulmonary involvement and the other had osteitis which resulted in a deformed humerus.


Protein S deficiency: early presentation and pulmonary hypertension.

Protein S deficiency usually presents in adults with recurrent or unexplained thrombosis and is thought to have autosomal dominant inheritance. We describe the case of a 5 year old girl with pulmonary hypertension but no evidence of venous thrombosis until postmortem examination. Her parents were first cousins. This potentially treatable condition should be sought in children and their relatives screened.


Fetal abnormality: an audit of its recognition and management. Northern Regional Survey Steering Group.

A voluntary survey set up by local clinicians has documented all lethal abnormality in a geographically defined area of northern England where there were 361,037 registered births between 1982 and 1990, and monitored the incidence of all significant physical abnormality since January 1984. The survey aims to maintain a register of all pregnancies where an abnormality is suspected before birth, and those where an abnormality is only identified after birth, together with a record of how the diagnosis was established. Information on management and outcome a year after birth is also collected. Nearly half the total decline in perinatal mortality in the region between 1982 and 1990 is accounted for by an increase in the antenatal recognition of lethal abnormality, isolated hydrocephalus, or a neural tube defect and subsequent termination of pregnancy. Although the reporting of many non-lethal conditions was incomplete during the pilot study in 1984, it has become progressively more complete since then. The number of cases confirmed postnatally varied little between units between 1985-9, but audit showed that the proportion recognised antenatally varied fivefold for reasons unconnected with unit size or the amount of antenatal ultrasound work done. For a number of serious conditions more than 10% of all antenatal diagnoses were completely wrong. Survey data are, for the first time, making it possible to monitor the accuracy of the ultrasound-based screening and diagnostic services for identifying specific fetal abnormalities. They are also providing clinicians with an invaluable confidential database of a whole region's collective experience of dealing with complex fetal abnormality.


Potential impact of population screening for prenatal diagnosis of congenital heart disease.

The potential impact of prenatal screening for the detection of congenital heart disease (CHD) was assessed by prospective analysis of 428 consecutive infant admissions to a supraregional centre; 28 (6.5%) did not have CHD and were excluded from analysis. Of the 400 cases with CDH, 396 (99%) underwent fetal ultrasonography but scanning was performed only before 18 weeks' gestation in 200 (50%). One hundred and forty nine (37%) of all cardiac abnormalities and 149/283 (53%) of severe abnormalities were considered to be detectable prenatally in a screening echocardiographic four chamber view had this technique been used. Prenatal diagnosis of severe CHD actually occurred in only eight (2%) cases and was after 30 weeks' gestation in all. There were 181/347 (52%) of all mothers and 177/253 (70%) of the subgroup with severe abnormalities who expressed an opinion volunteered their preference for termination of pregnancy if mid-trimester diagnosis had been available. Mid-trimester detection of congenital heart disease rarely occurs at present despite fetal ultrasound scanning in almost all pregnancies. More than half of all severe congenital heart defects seen in infancy are potentially detectable by screening. Major training at primary scan level and modification of the timing of existing fetal anomaly scanning would be required for a screening programme to be effective.


Skin temperature and heart rate rhythms in infants of extreme prematurity.

Nine preterm infants of 26 to 29 weeks' gestational age and 792 to 1200 g birth weight spent six to 17 weeks in our neonatal medical unit. Hourly recordings of skin temperature and heart rate were carried out. The first five to 15 weeks were spent in the intensive care ward, in continuous light, due to various medical conditions. After recovery they were moved to a nursery for one to nine weeks, with 12 hourly periods of light and darkness. Four infants developed circadian rhythms in temperature and three in heart rate in light-dark periods, the remainder failing to do so. Some infants take longer than others to develop circadian rhythms but the reasons for this are not clear. It is suggested that earlier exposure to a light-dark environment may synchronize the 'body clock' to a 24 hour period in more preterm infants.


Prediction of impaired metabolic adaptation by antenatal Doppler studies in small for gestational age fetuses.

The increased risk of hypoglycaemia for infants who are small for gestational age (SGA) is well known, and further information regarding metabolic adaptation can be gained by examining the profiles of glucose and other metabolic fuels in such infants. Not all SGA infants experience hypoglycaemia, however, and the ability to identify, antenatally, those at most risk would be helpful for obstetric and neonatal management. This study investigated metabolic differences between two groups of SGA infants who had antenatal umbilical artery Doppler studies. Fourteen had end diastolic velocities (EDV) present and 11 had absent EDV. The absent EDV group had significantly lower non-esterified fatty acid (NEFA) concentrations at birth, and lower blood glucose and NEFA concentrations in the first six hours after birth. After the first day, few metabolic differences were found between the two groups. Antenatal Doppler studies may identify those SGA infants who fail to achieve neonatal metabolic adaptation and are most at risk of early neonatal hypoglycaemia.


Superior mesenteric artery blood flow velocity in necrotising enterocolitis.

Doppler measurements of blood flow velocity were obtained from the superior mesenteric artery (SMA), coeliac axis, and anterior cerebral artery (ACA) of 19 infants with suspected necrotising enterocolitis, which was classified as confirmed (n = 9) or unconfirmed (n = 8). Infants with confirmed disease were compared with controls who were either enterally fed or who were receiving intravenous fluids. SMA velocity was significantly higher in the infants with confirmed necrotising enterocolitis (36.5 cm/s) than in unfed controls (20.4 cm/s) or infants with unconfirmed enterocolitis (19.6 cm/s). Three infants with confirmed disease had data from before the onset of symptoms. One had low SMA velocity on the first day of life, and one showed no increase in SMA velocity after enteral feeds were started. SMA velocity is increased when infants develop symptoms of necrotising enterocolitis, suggesting that total gut ischaemia is not present at the time that the disease is clinically apparent, although it may precede the onset of symptoms and play a part in the pathogenesis of the disorder.


Development of cutaneous microflora in premature neonates.

Coagulase-negative staphylococci (C-NS) are a frequent cause of bacteraemia in premature neonates. It is likely that the strains of C-NS causing bacterial sepsis in premature neonates have their origin on the patient's skin surface. We have studied the quantitative development of the skin microflora at eight sites on premature neonates. A swab wash method was used to sample and enumerate the cutaneous microflora of premature neonates admitted to an intensive care unit with respiratory distress syndrome. The numbers of bacteria present on the skin increased rapidly by 100-fold in the first week of life. The species of C-NS found on neonatal skin were similar to those found on adult skin. However, the bacterial population was 10(3) lower by comparison. There was considerable variation in numbers of bacteria and in the proportion resistant to antibiotics from day to day. There appeared to be no association between antibiotic usage and the proportion of isolates resistant to antibiotics, although the resident bacteria were in many cases resistant to a variety of antibiotics. C-NS were isolated from 92% of samples from which bacteria were isolated. Staphylococcus epidermidis was found at all sites and accounted for 82% of each colonial type of staphylococcus isolated. Other organisms isolated included Propionibacterium sp, alpha-haemolytic streptococci, aerobic spore-bearing bacilli, aerobic coryneforms, Candida albicans, Klebsiella oxytoca, Pityrosporum sp, Klebsiella pneumoniae, and Escherichia coli. The results of this study suggest that the skin of premature neonates is colonised with antibiotic resistant C-NS during the first week of life and that the chance of contamination of an intravascular catheter at insertion increases during this period.


Complement activation in neonatal infection.

To investigate the usefulness of indices of complement activation in the diagnosis of infections in the neonatal period, activation products C4d, Ba, and C3d were measured in 42 babies with a putative diagnosis of infection based on clinical/laboratory criteria, and compared with conventional clinical and haematological criteria of infection and with C reactive protein. The diagnosis of sepsis was confirmed by culture and identification of organisms in 17. Fourteen babies in whom infection was not suspected formed the control group. In babies with proved infection, concentrations of the fragments C4d, Ba, and C3d were higher than in babies with suspected infection in whom microbiological tests were negative, and concentrations of Ba and C3d were higher than in controls. C reactive protein and the platelet count were not significantly different in babies with proved infection and those with negative microbiological tests, but in the latter, C reactive protein concentrations were higher than in controls. Of the indices studied, high concentrations of Ba predicted microbiologically proved infection with the highest sensitivity (47.1%) and specificity (92.0%). Ba thus seems to be useful as an early indicator of infection in the neonatal period.


Receiver operating characteristic curves for comparison of serial neutrophil band forms and C reactive protein in neonates at risk of infection.

The performance of indirect indices of infection in the newborn vary because of differences in techniques, including diagnostic cut off levels. We have compared serial neutrophil band cell counts with C reactive protein measured by rate nephelometry. The 'gold standard' was a positive culture and the performance of the tests was compared by the technique of receiver operating characteristics (ROC) as well as sensitivity and specificity. A total of 172 septic screens were performed in 56 patients. The operational diagnostic cut off values were: C reactive protein greater than 8 mg/l, immature:total neutrophil ratio (I:T ratio) greater than 0.2, and band count greater than 5%. Compared with the sensitivity of C reactive protein (71%), I:T ratio (34%) was significantly different but band count (69%) was not. The specificity of C reactive protein (72%) was better than band count (39%) but no better than I:T ratio (73%). ROC curves were constructed for all possible diagnostic cut off values of the tests and superior performance was demonstrated for C reactive protein compared with band count and I:T ratio. We conclude that C reactive protein is a useful early indicator of infection in neonates and that ROC curves permit comprehensive and graphic comparison between tests and the calculation of optimal diagnostic cut off values.


Neutrophil chemotaxis and adhesion in preterm babies.

To investigate the increased susceptibility to infection of very immature preterm neonates, neutrophil chemotaxis, Mac-1 adhesion receptor expression, and adherence to human umbilical vein endothelial cell monolayers (HUVE) were examined in neonates born at less than or equal to 32 weeks' gestation. Chemotaxis of neutrophils from well preterm neonates towards casein or zymosan activated serum (ZAS) was reduced (mean SE) being for casein 88.6 (3.8) microns; ZAS 76.2 (4.3) microns compared with adults (casein 117.8 (1.4) microns; ZAS 112.1 (1.4) microns), but similar to term neonate neutrophils (casein 92.7 (4.5) microns; ZAS 75.9 (3.1) microns). Stimulated Mac-1 expression showed a similar pattern: reduced on preterm neutrophils compared with adults, but similar to term neonates. Preterm and term neonate neutrophils were both hyperadherent to HUVE when unstimulated, but showed an equally impaired ability to increase adhesion following stimulation. Casein stimulated chemotaxis and stimulated Mac-1 expression 'matured' towards adult levels of performance four weeks after preterm birth. The increased incidence of sepsis in immature preterm infants is not due to greater defects of neutrophil migration.


Serum erythropoietin concentrations in symptomatic infants during the anaemia of prematurity.

A comparison was carried out between a series of neonates who weighed less than 1500 g at birth and received red cell transfusions for symptomatic anaemia of prematurity (group 1, n = 14) and controls of similar gestational age and weight, who remained well and were not transfused during their nursery stay (group 2, n = 10). Mean (SD) haemoglobin concentrations at birth were 163 (12) g/l and 183 (17) g/l (p = 0.004), respectively. Transfusion resulted in significantly better weight gain in six infants who had been growing poorly:mean (SE) 8.8 (2.8) g/day improved to 23.3 (2.1) g/day (p less than 0.002). Geometric mean (SD) serum immunoreactive erythropoietin (SiEp) concentrations (17.7 (1.3) U/l) for the whole group of infants were similar to those of normal adults (17.4 (4.7) U/l) despite considerably reduced haemoglobin values. There was a significant inverse correlation between haemoglobin and log SiEp concentrations in the infants requiring transfusion (r = -0.43; p less than 0.01), but this was not apparent in the untransfused babies. Moreover, at haemoglobin concentrations below 120 g/l the mean (SE) SiEp concentration of 20 (1.08) U/l in group 1 was significantly higher than in group 2 (14 (1.06) U/l; p = 0.002). These data suggest that an increased concentration of SiEp early in the course of the anaemia of prematurity helps to identify those infants who would benefit from red cell transfusions, but that clinical criteria, although ill defined, do so equally well.


UK experience in neonatal extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a life support technique capable of supporting pulmonary, cardiac, or cardiopulmonary function. It has proved most successful in neonatal respiratory failure. We report the initial UK experience with a survival rate of 80% in 15 neonates (gestations 36-41 weeks, birth weights 2690-3990 g) whose condition exceeded American criteria for ECMO treatment for a prolonged period before referral. Ages at referral varied from 11 to 240 hours and the duration of bypass required varied from 30 to 240 hours respectively.


Episodic bradycardia in preterm infants.

To analyse factors likely to precipitate bradycardia, 27 preterm infants born at 32 weeks' gestation or less were studied on 89 occasions. Polygraphic recordings of electrocardiography, oxygen saturation, and respiratory effort were made. Subsequently, upper airway flow was measured by a mask and pressure transducer. In 605 episodes detected during initial recordings, time of onset of bradycardia correlated positively with apnoea duration, with bradycardia often occurring as respiratory effort resumed. Airway closure occurred in 88% of apnoeas associated with bradycardia during flow measurements, and was significantly more common than in apnoea without bradycardia (64%). We suggest that bradycardia is most commonly a reflex response to the resumption of respiratory effort against a closed upper airway as apnoea is terminated, and that this reflex is potentiated by hypoxaemia.


Cerebrovascular carbon dioxide reactivity and failure of autoregulation in preterm infants.

Changes in cerebral blood flow velocity (CBFV) in response to a rise in arterial carbon dioxide tension (PaCO2) in 94 ventilated preterm infants were determined using Doppler ultrasound to assess whether the nature of this change might predict subsequent neurological injury. Concomitant changes in mean arterial pressure (MAP) were recorded. Both CBFV and MAP rose significantly in response to the rise in PaCO2, the response being significantly less in the first 24 hours. Analysis indicated that the change in CBFV in the first day of life in infants less than or equal to 30 weeks' gestation was dependent to a great extent on the concomitant change in MAP. Similar dependence also occurred after administration of pancuronium to infants whose CBFV response was previously independent of changes in MAP. This dependency lasted for the duration of paralysis. Changes in CBFV after a rise in PaCO2 did not predict subsequent neurological injury. The influence of pancuronium on cerebrovascular regulation warrants further study.


Traumatic neonatal intracranial bleeding and stroke.

Ischaemia within the regions supplied by vertebral and posterior cerebral arteries has been described as a complication of birth injury, either by direct trauma or by compression from a herniated temporal uncus. Ischaemia within the territory of the middle cerebral artery has been documented after a stretch injury of the vessel's elastica interna. From a series of seven personal observations on birth trauma and related cerebral stroke, we describe three neonates with the uncal herniation type of occipital stroke and four infants with hypoperfusion of the middle cerebral artery or one of its major branches. In three of the latter a basal convexity subdural haemorrhage probably induced the ischaemia, whereas in the other it was associated with haemorrhagic contusion of the parietal lobe. Experimental work and reports on older children support the idea that vasospasm due to surrounding extravasated blood can be one of the responsible mechanisms. Both forceps delivery and difficult vacuum extraction can be implicated in this supratentorial injury, leading to permanent neurological damage in at least half of the survivors in this series.


Athetoid cerebral palsy with cysts in the putamen after hypoxic-ischaemic encephalopathy.

Three cases of athetoid cerebral palsy after hypoxic-ischaemic encephalopathy (HIE) are reported. All three neonates had haemorrhagic lesions in the basal ganglia and thalami on magnetic resonance imaging (MRI). Prior cranial ultrasound had detected the lesions in only two cases. In all three children athetoid movements began within the first year of life. Follow up MRI scans showed bilateral symmetrical cystic lesions in the posterior putamen. Although haemorrhagic lesions within the basal ganglia are a common MRI finding in neonates with HIE, few of these babies develop athetoid cerebral palsy. We believe this to be the first report of discrete cystic lesions found in the basal ganglia of children with athetoid cerebral palsy.


Regional cerebral blood flow velocity changes after indomethacin infusion in preterm infants.

Cerebral blood flow velocity was assessed during infusion of indomethacin over 30 minutes. Eleven preterm infants with symptomatic patent ductus arteriosus were studied on 12 occasions. Indomethacin infusion was associated with a significant reduction in time averaged mean velocity (TAMV), peak systolic velocity (PSV), and end diastolic velocity in both the anterior cerebral artery and middle cerebral artery. The fall in the TAMV and PSV was gradual with maximal change 30-40 minutes after the start of the infusion. It was concluded that administration of indomethacin by slow infusion produces haemodynamic alterations to the cerebral circulation comparable in magnitude with changes described with bolus administration. Indomethacin remains a useful and effective treatment for patent ductus arteriosus in preterm infants, but should continue to be used with caution.


Randomised trial of umbilical arterial catheter position: Doppler ultrasound findings.

Umbilical arterial catheters (UAC) were randomly assigned in 69 infants to a high (n = 36) or to a low (n = 33) position. Serial Doppler ultrasound measurements of blood flow velocity in their superior mesenteric arteries, coeliac axis, renal arteries, and anterior cerebral arteries were then obtained. There were no differences in blood flow velocity between high and low UAC groups on days 1, 3, and 7. At 2 weeks, those infants with a high UAC still in place had significantly higher velocities in the mesenteric artery than those infants who had no catheter in place. Infants with high UACs remaining in place for more than 7 days were found to have an increase in abdominal distension and tenderness, whereas this was not the case for those with low UACs. Catheter position has no effect on visceral blood flow if the UAC stays in place for one week or less, whereas prolonged use of a high UAC may alter intestinal blood flow and increase the incidence of abdominal symptoms.


Cord blood lymphocyte responses to food antigens for the prediction of allergic disorders.

Proliferative responses of cord blood lymphocytes (CBLs) to food antigens and cord blood IgE concentrations were measured in 37 full term newborn infants for the prediction of allergic disorders. In these 37 infants who were followed up for two years, allergic history of the family was found in four (sensitivity 57.1%) and cord blood IgE concentrations were greater than 0.5 IU/ml in three (sensitivity 42.9%) of seven infants who developed allergic disorders. When CBLs were stimulated twice by ovalbumin or bovine serum albumin, the value of the stimulation index in proliferative responses of CBLs to ovalbumin or bovine serum albumin was greater than 1.5 in six (sensitivity 85.7%) of seven infants who developed allergic disorders. The specificity of the responses of CBLs in the prediction of the development of allergic disorders was 93.3%. The proliferative responses of CBLs to food antigens were useful in the prediction of not only development of allergic disorders but also offending allergens. These observations provide further evidence that sensitisation is occurring in utero. This would appear to be increasingly important in the genesis of early atopic problems. As our follow up is only two years, in utero sensitisation is a prediction for the early development of atopic disease but only longer follow up will show whether this holds good for allergic disorders at any age.


Risk of developing atopic disease after early feeding with cows' milk based formula.

A follow up of a cohort of 736 healthy full term children with exposure to cows' milk based formula and breast milk from donors on the maternity ward was performed. The children were divided into three exposure groups according to the feeding patterns on the maternity ward. Group 1 received only mother's milk, group 2 mother's milk and human donors' milk, and group 3 received mother's milk, donors' milk and cows' milk based formula. The children were investigated at 7 years of age, by examining their medical files, and at 11 and 14 years, by questionnaires regarding symptoms of atopic disease. No significant differences between the three groups at follow up were found in the cumulative incidences of atopic diseases. The amount of formula given did not affect the risk of developing atopic disease. Children with a family history of such diseases ran the same risk of subsequent atopic disease whether they were fed formula or breast milk alone. Cows' milk based formula given on the maternity ward does not seem to increase the risk of developing atopic disease.


Newly diagnosed diabetes: a study of parental satisfaction.

A national survey of 509 parents of children with newly diagnosed diabetes elicited a 92% response rate, showing that 96% of children were admitted to hospital, 42% staying in hospital longer than one week and 41% received an intravenous infusion. More than 90% of parents expressed satisfaction with the information given at diagnosis, the preparation they received before discharge home, and the outpatient follow up services. Home visits from a diabetes nurse specialist (DNS) were received by 73% of families and 44% reported that the DNS was the most supportive person in the first year after diagnosis. Readmission during the first 12 months after diagnosis was required by 23% of children, more often in the youngest age group. Poor liaison with schools and the lack of diabetes knowledge in teachers were the sources of greatest dissatisfaction. Children under the care of paediatricians with no specialist interest in diabetes were significantly more likely to be kept in hospital longer at diagnosis and parents were less satisfied with outpatient care and school liaison. The study supports previous recommendations that diabetes nurse specialists are a priority resource in providing support services and that every district should have a paediatrician with a special interest in diabetes and a designated children's diabetic clinic.


Genetic risk for asthma, allergic rhinitis, and atopic dermatitis.

In order to explore the genetic risk of a child with a family history of allergies developing asthma, allergic rhinitis, or atopic dermatitis, questionnaires filled in by 6665 families were analysed. The data were collected in a population based cross sectional survey of 9-11 year old schoolchildren living in Munich and southern Bavaria. The relation between asthma, allergic rhinitis, and atopic dermatitis and the number of allergic first degree relatives, and the type of allergic disease was examined. Analyses were done separately for families with single or multiple allergic diseases. In families with one allergic parent the risk of the child developing asthma was increased by asthma in a parent, with an odds ratio (OR) of 2.6 (95% confidence interval 1.7 to 4.0) but not by parental allergic rhinitis with OR 1.0 (0.7 to 1.5) or atopic dermatitis, OR 1.0 (0.6 to 1.6). For allergic rhinitis the highest risk with OR 3.6 (2.9 to 4.6) was observed with allergic rhinitis of one parent, apparently lower for asthma of one parent, OR 2.5 (1.6 to 4.0) or atopic dermatitis, OR 1.7 (1.1 to 2.5). Children with parental atopic dermatitis had a high risk for atopic dermatitis, OR 3.4 (2.6 to 4.4), compared with children with parental asthma, OR 1.5 (1.0 to 2.2), or parental allergic rhinitis, OR 1.4 (1.1 to 1.8). Risk factors in families with combined allergies of two relatives (parents and siblings) were analysed separately for the different combinations. These results support the hypothesis that asthma, allergic rhinitis, and atopic dermatitis are multifactorial diseases brought about by various familial and environmental influences.


Early immune responses to Dermatophagoides pteronyssinus and atopic predisposition.

Responses to the house dust mite during infancy may be important determinants of asthma in susceptible individuals. This study assessed early IgG subclass antibody responses to Dermatophagoides pteronyssinus in children of atopic parents. Sixteen atopic and 15 non-atopic children were selected from a birth cohort, and atopic status was established according to follow up over the first two years. IgG1 and IgG4 antibodies to D pteronyssinus were measured by enzyme linked immunosorbent assay at 7 days and 3, 6, 12, and 24 months. In all children D pteronyssinus IgG1 fell at 3 months (indicating maternal antibody loss), rose progressively to 12 months, and waned at 24 months. D pteronyssinus IgG4 was only detectable at 7 days. Children who were atopic by 2 years and therefore at greater risk of asthma, tended to have higher D pteronyssinus IgG1 at 6 and 12 months. These data suggest greater exposure or responsiveness to dust mite during infancy than in the second year.


Breast feeding and oral rehydration at home during diarrhoea to prevent dehydration.

In a case-control study we evaluated the role of maternal behaviour, as reflected in maintenance of breast feeding and the use of oral rehydration therapy (ORT) at home during acute diarrhoea, in preventing dehydration in infants and young children. A systematic 5% sample was taken of all children aged 1-35 months attending the treatment centre of the International Centre for Diarrhoeal Disease Research, Bangladesh, with acute watery diarrhoea of six days or less between August 1988 and September 1989. There were 285 children with moderate or severe dehydration as cases and 728 with no dehydration as controls in the study. In a multivariate analysis using a logistic regression model we showed that withdrawal of breast feeding during diarrhoea was associated with a five times higher risk of dehydration compared with continuation of breast feeding during diarrhoea at home. Lack of ORT with either complete formula or a salt and sugar solution at home was associated with 57% higher risk of dehydration compared with receipt of a reasonable amount of ORT after controlling for several confounders. The confounding variables--that is, lack of maternal education, history of vomiting, high stool frequency, young age and infection with Vibrio cholerae 01--were also shown to be risk factors of dehydration. Health education programmes should promote continued breast feeding and adequate oral rehydration therapy for infants with acute diarrhoea at home.


Reversible cerebral shrinkage in kwashiorkor: an MRI study.

Protein energy malnutrition is associated with cerebral atrophy which may be detrimental to intellectual development. The aim of this study was to document the anatomical abnormalities which lead to the appearance of cerebral atrophy using magnetic resonance imaging (MRI) in the acute stage of kwashiorkor and to monitor changes during nutritional rehabilitation. Twelve children aged 6 to 37 months requiring admission to hospital for the treatment of kwashiorkor were studied. The children were evaluated clinically, biochemically, and by MRI of their brains on admission and 30 and 90 days later. Brain shrinkage was present in every child on admission. White and grey matter appeared equally affected and the myelination was normal for age. At 90 days, the cerebral changes had resolved in nine and improved substantially in the remainder, by which time serum proteins and weight for age were within the normal range. The findings of this study suggest that brain shrinkage associated with kwashiorkor reverses rapidly with nutritional rehabilitation.


Solitary mastocytoma causing recurrent blistering in infancy.

Two children with solitary mastocytoma in infancy, both of whom had recurrently blistering scalp lesions, are reported in order to emphasise the diagnostic importance of this distinctive history.


Pituitary gigantism.

A case of pituitary gigantism resulting from a pituitary adenoma which secreted growth hormone is described. The patient was successfully treated by surgery, which led to the normalisation of endogenous growth hormone secretion. An acceptable final height was achieved with high dose intramuscular testosterone treatment.


Paediatric care in Hungary.

In this overview, I have attempted to highlight the problems of medical care, particularly paediatric care, in Hungary and to describe the changing nature of its organisation and financing. We hope that through our efforts we can surmount these difficulties, improve the quality of medical care in our country, and create a more rational economic and scientific basis for future medical development and advances.