Effects of latex avoidance on latex sensitization, atopy and allergic diseases in patients with spina bifida.

BACKGROUND: Ten years ago, avoidance measures such as the performance of latex-free operations were implemented in children with spina bifida. Since then, latex sensitization and latex allergy have decreased in this high-risk group. OBJECTIVE: To study the effect of primary latex-free prophylaxis on the prevalence of allergic diseases and atopy as a marker for sensitization spreading in children with spina bifida. METHODS: One hundred and twenty children with spina bifida born after the introduction of latex-free prophylaxis and operated on under latex-free conditions ('current group') were examined for latex sensitization, latex allergy, sensitization to aero- and food allergens and allergic diseases. Results were compared to a 'historic' (not latex-free operated) group of children with spina bifida and comparable age (n = 87) and to a recent sample of children from the general population (n = 12,403). RESULTS: In comparison with the 'historic group', latex sensitization (55% vs 5%, P < 0.001) and latex allergy (37% vs 0.8%, P < 0.001) were significantly reduced in the 'current group'. Furthermore, a significant reduction could be demonstrated for sensitization to aeroallergens (41.4% vs 20.8%, P = 0.001) and for allergic diseases (35% vs 15%, P = 0.001). The prevalence for atopy, sensitization to aero-/foodallergens and for allergic diseases in children of the 'current group' was similar to those in children of the weighted population sample. CONCLUSIONS: Latex avoidance in children with spina bifida prevents latex sensitization and latex allergy. Additionally, it also seems to prevent sensitization to other allergens and allergic diseases which might be explained by the prevention of sensitization spreading.

The beta2-microglobulin/cystatin C ratio--a potential marker of post-transplant lymphoproliferative disease.

BACKGROUND: As a consequence of more intensified immunosuppression, post-transplant lymphoproliferative disease (PTLD) is increasingly observed in patients after solid-organ transplantation. Beta2-microglobulin, a low-molecular weight protein (MW 11.8 kDa), is produced by all nucleated cells as part of the HLA complex. Its serum concentration is directly correlated with prognosis in patients with lymphatic neoplasms. Like other low-molecular weight proteins, beta2-microglobulin is eliminated by glomerular filtration. This complicates its use as a tumor marker in renal insufficiency. Cystatin C, a low-molecular weight protein of 13.3 kDa, is a new marker of kidney function largely unaffected by extrarenal disease. We, therefore, sought to assess the potential of the beta2-microglobulin/cystatin C ratio (beta2M/Cys) as a marker of lymphoproliferation. PATIENTS AND METHODS: Beta2M/Cys was determined by particle-enhanced immunonephelometry in sera from 132 children with different degrees of renal insufficiency, 5 of whom had lymphoproliferative disease. Renal function was assessed using the Schwartz formula. RESULTS: Beta2M/Cys was constant between 1.2 and 2.4 mg/mg for Schwartz GFR > or = 40 ml/min x 1.73 m2. With lower GFR, beta2M/Cys rose progressively, maximum values being found in the hemodialysis patients (4.85-11.73). Healthy renal transplant recipients had beta2M/Cys comparable to controls. With acute lymphoproliferative disease, all but one patient had significantly elevated beta2M/Cys between 2.68 and 3.68 mg/mg, which returned to normal in remission (1.67-2.35 mg/mg). The sensitivity of a beta2M/Cys ratio > 2.4 mg/mg for the detection of PTLD was 80%, the specificity 100%, positive predictive value 100%, negative predictive value 90%. CONCLUSION: The beta2-microglobulin/cystatin C ratio is a promising parameter of lymphoproliferation in patients with normal or mildly impaired renal function.

Hypokalemic salt-losing tubulopathy with chronic renal failure and sensorineural deafness.

OBJECTIVE: To characterize a rare inherited hypokalemic salt-losing tubulopathy with linkage to chromosome 1p31. METHODS: We conducted a retrospective analysis of the clinical data for 7 patients in whom cosegregation of the disease with chromosome 1p31 had been demonstrated. In addition, in 1 kindred, prenatal diagnosis in the second child was established, allowing a prospective clinical evaluation. RESULTS: Clinical presentation of the patients was homogeneous and included premature birth attributable to polyhydramnios, severe renal salt loss, normotensive hyperreninemia, hypokalemic alkalosis, and excessive hyperprostaglandin E-uria, which suggested the diagnosis of hyperprostaglandin E syndrome/antenatal Bartter syndrome. However, the response to indomethacin was only poor, accounting for a more severe variant of the disease. The patients invariably developed chronic renal failure. The majority had extreme growth retardation, and motor development was markedly delayed. In addition, all patients turned out to be deaf. CONCLUSION: The hypokalemic salt-losing tubulopathy with chronic renal failure and sensorineural deafness represents not only genetically but also clinically a disease entity distinct from hyperprostaglandin E syndrome/antenatal Bartter syndrome. A pleiotropic effect of a single gene defect is most likely causative for syndromic hearing loss.

Perioperative management of central diabetes insipidus in kidney transplantation.

Central diabetes insipidus is clinically masked in dialysis patients. We report a 12-year-old girl receiving a living-related donor graft for renal failure from Alport syndrome, in whom a craniopharyngioma had been resected 6 months before transplantation. Pretransplant evaluation had documented central hypothyroidism, growth hormone deficiency, and presumptive hypogonadotropic hypogonadism. The corticotropin-releasing factor test had been normal. Four hours after transplantation, urine output exceeded 1,000 ml/h without diuretic therapy. Serum sodium concentration was 155 mmol/l, serum osmolality 333 mmol/kg, and plasma antidiuretic hormone 4.9 ng/l, while urine osmolality was 233 mmol/kg. Desmopressin acetate was started by continuous intravenous infusion at 1 microgram/day. Serum electrolytes rapidly normalized, urine output stabilized at 2 l/day. The patient was discharged 4 weeks after transplantation with good allograft function, receiving intranasal desmopressin acetate 10 micrograms twice daily. Pre-existing central diabetes insipidus is unmasked after successful kidney transplantation, leading to rapid dehydration and hypernatremia, which can be prevented by prompt institution of desmopressin therapy.

Physeal fractures of the ankle.

Because the distal tibia is the third most common physeal injury, being able to assess and treat such a fracture accurately is a skill worth enhancing. Many factors contribute to the outcome of physeal injuries, but the physician's general knowledge of the physis, ability to order the right diagnostic tests, and classify the fracture can be the determining factors of quality care.

Small-bowel obstruction and perforation. A rare complication of an esophageal stent.

To bridge a malignant stenosis after esophageal cancer recurrence two silicon-coated wall stents were inplanted in a 52-year-old patient within 6 months. Two weeks after the second stent was implanted, clinical examination showed dislocation of the prosthesis. Intraoperatively the two stents were found sticking in the side-to-side jejunostomy of a former Billroth II operation, leading to perforation there.

[Rehn-Delorme operation in pelvic floor insufficiency]. / Operation nach Rehn-Delorme bei der Beckenbodeninsuffizienz.

Rehn-Delorme's procedure was introduced as one of a couple of methods to remove rectal prolapse with insufficiency of the pelvic floor. Rehn-Delorme's procedure wasn't well accepted until the last twenty years, when some authors reported good results with low recurrence rate of the prolapse, especially for old people with high risk or otherwise unfit for abdominal surgical procedures. On the German Clinic for Diagnostic during the years 1991-1994 in a therapeutical concept of the conjoint problems "chronic constipation--rectal prolapse-faecal incontinence" 205 patients, aged 20 to 86 years, were operated on with that procedure. In a retrospective study, evaluating 78 patients who underwent only that operation, we studied the change of faecal incontinence after removing the outlet obstructing mucosal prolapse. The mortality was zero, the total complication-rate was 15.1%, bleeding (2.9%), suture line disruption (7.3%), abscesses (1.5%) and stenosis (1%) acceptable. The Kirwan continence-score increased significantly. Three cases with normal continence before operation get worse because of removing the obstructing mucosal wall.

[HIV positive patients in routine surgical practice]. / HIV-positive Patienten im chirurgischen Alltag.

In our daily surgical practice we encounter increasingly HIV-infected and AIDS patients. From January 1 1987 until December 31 1988 119 outpatients and 35 hospitalized patients were treated in the surgical department. They belonged mainly to the known risk groups. Abscesses and diagnostic excisions were predominant in the outpatients while hospitalized patients presented the full scale of surgical diseases. The clinical course was not different from that of other patients. 181 members of the medical staff of our hospital were registered after contact with blood or body fluids of HIV-infected patients and followed. A seroconversion was not observed so far.

[Endoscopic palliative tube and laser therapy in advanced cancer of the esophagus and cardia]. / Endoskopisch-palliative Tubus- und Laser-Therapie bei fortgeschrittenem Carcinom von Oesophagus und Kardia.

The treatment of patients with advanced carcinomas of esophagus and gastric cardia endoscopic palliation should restore the passage for normal oral uptake. We compared the results of two methods: endoscopic neodym-YAG-laser-therapy (group I: 24 patients) and endoscopic perturbation (group II: 56 patients). An initial recanalisation was achieved after 1-4 sessions in group I and after 1-2 sessions in group II. Recurrence of dysphagia caused in median 5 endoscopic interventions in group I and 2 in group II. We observed no complications in group I and 5 complications in group II. The median survival times were not significantly different. The results and the follow-up show no definite superiority of one of the two methods, the selection of treatment modality depends on the technical possibilities and the personal experience of the physicians.

Temporary chemoembolization of colorectal liver metastases with degradable starch microspheres.

Increasing drug delivery to the tumor should induce improved tumor response. To study this the effect of degradable starch microspheres (DSM) and mitomycin was evaluated in 11 patients with chemoembolization of colorectal liver metastases (CRLM) and previous floxuridine (FUDR) treatment. In 10 patients access to the hepatic artery was obtained either by infusaid pump or infusion chambers. Indications for chemoembolization were: Failure of continuous FUDR treatment (n = 7), biliary sclerosis (n = 2), incomplete liver perfusion (n = 2), extensive disease (n = 2). Preliminary observations showed a wide range of required DSM dose. Therefore each individual dose was determined by the use of digital subtraction angiography (DSA). Seventy-five percent of the DSM dosage, which induced reversed flow in the common hepatic artery, was selected for treatment. DSM was then administered four times every 2 hours/day/monthly. The last DSM doses were mixed with 10 mg mitomycin C. Observed response rates, controlled by chemotherapy (CT) and tumor markers, were: complete response 1/11; partial response 3/11; stable disease 2/11; progression 5/11. The median duration of response was 6.5 (range 3-21) months. DSM application induced redistribution of arterial flow towards previously unperfused portions of the liver. The required DSM doses decreased about 20-30% from the first to the last chemoembolization cycle. Although there was no systemic toxicity, embolization was associated with several local side effects. Moderate to heavy pain in spite of morphia and neuroleptics was experienced in 55% of all treatments. Some patients demonstrated an elevation in body temperature of up to 39 degrees C. Postembolization liver biopsies revealed more intense tumor necrosis associated with more severe hepato-toxicity than was seen with continuous FUDR treatment. It is concluded that the optimal sequence and dosage of mitomycin and DSM has to be further evaluated in prospective trials before clinical application.

More than additive toxicity of the combination of 1-methyl-1-nitrosourea plus 1,3-bis(2-chloroethyl)-1-nitrosourea in the rat.

The combination toxicity index of 1-methyl-1-nitrosourea plus 1,3-bis (2-chloroethyl)-1-nitrosourea determined in the rat was 0.32. This overadditive combination toxicity appears mainly to be due to severe damage of the intestinal mucosa as diagnosed by histological examination and to damage of pluripotent stem cells in the bone marrow as could be assessed by the spleen colony technique. The molar ratio of 1-methyl-1-nitrosourea to 1,3-bis(2-chloroethyl)-1-nitrosourea resulting in maximum mortality was about 6. Concomitantly measured DNA interstrand cross-linking in bone marrow cells revealed a slight increase in DNA interstrand cross-linking following both drugs compared to 1, 3-bis(2-chloroethyl)-1-nitrosourea alone.

Experiments on the efficacy and toxicity of locoregional chemotherapy of liver tumors with 5-fluoro-2'-deoxyuridine (FUDR) and 5-fluorouracil (5-FU) in an animal model.

For the investigation of locoregional chemotherapy of liver neoplasms we developed a standardized animal model in the rat. Continuous infusion therapy or repeated bolus injections of FUDR or 5-FU were given via the hepatic artery, the portal vein or the vena cava in tumor-bearing animals. The efficacy of the treatment was determined by measuring the tumor volume 3 weeks after tumor cell implantation. For the evaluation of the local and systemic toxicity serum GOT, GPT, and total bilirubin were determined. DNA single strand breaks were assessed in isolated liver and bone marrow cells. Inhibition of colony formation of bone marrow stem cells was determined by CFU-C and CFU-S bioassay. A significant reduction of tumor growth was observed only after continuous infusion of FUDR via the hepatic artery. Systemic toxicity was lowest in this group for both compounds while the local liver toxicity was only slightly elevated.

Comparison of DNA damage in various tissues, myelosuppression and serum levels of transaminases and bilirubin in tumor-bearing female Sprague-Dawley rats treated with 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (HECNU).

Female Sprague-Dawley rats bearing methylnitrosourea-induced mammary carcinomas were treated with 100 mumol 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (HECNU)/kg to investigate the time course of DNA-DNA interstrand cross-linking (DNA-XL) as measured by alkaline elution in tumor, bone marrow and liver cells. The inhibition of bone marrow stem cell colony formation in culture (CFU-C) and in spleens of lethally irradiated mice (CFU-S), serum transaminase levels and total bilirubin were concomitantly determined. All parameters were evaluated at different times from 4 to 72 h after treatment. The highest amounts of DNA-XL were found in tumor cells, peaking at 24 h after treatment. A parallel increase was observed in bone marrow cells up to 16 h with a subsequent rapid decrease to about one-third of DNA-XL in tumor cells after 72 h. Concomitantly, CFU-C and CFU-S were suppressed, the nadir being at 24 h after treatment. In liver cells, however, constant low levels of DNA-XL were found, which had disappeared after 48 h. In accordance with this observation, serum transaminase levels were only slightly elevated.

Synthesis, toxicity, and therapeutic efficacy of 4-amino-N-(2'-aminophenyl)-benzamide: a new compound preferentially active in slowly growing tumors.

The present paper describes 4-amino-N-(2'-aminophenyl)benzamide (GOE1734) with regard to synthesis; toxicity in mice, rats, and dogs; and differential therapeutic efficacy in slowly and rapidly proliferating rat tumors. GOE1734, an analog of a group of compounds known for other than antitumor effects with relatively simple N-acyl-O-phenylenediamine structure, is characterized by a low bacterial mutagenic potential after in vitro metabolic activation and DNA-DNA crosslinking activity after in vivo treatment. Maximum tolerated doses in rats and dogs amount to 4 and 1 mg/kg, respectively. High growth-inhibiting efficacy was obtained in intratibially implanted osteosarcoma, in methylnitrosourea-induced primary mammary carcinoma, and in acetoxymethyl-methylnitrosamine-induced colorectal adenocarcinoma. GOE1734 proved to be ineffective in transplanted Yoshida sarcoma and Walker 256 carcinosarcoma when single or multiple doses were administered at dose levels that were moderately toxic or not toxic. Some antitumor effects were observed in L5222 leukemia after ip transplantation, but no effect could be observed after ic implantation or in vitro incubation and subsequent retransplantation of these cells. Since the latter three rat tumors are characterized by relatively short tumor volume doubling times (0.5-2 days), whereas the first three grow slower (tumor volume doubling time, 11-19 days), the remarkable differential antitumor activity of GOE1734 in fast and slowly growing malignancies is striking.

Relationship between DNA damage and the inhibition of stem cells in murine bone marrow after single and repeated administration of BCNU and HECNU.

The effects of dose and schedule of administration of either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (HECNU) were compared in terms of induction of DNA damage in the bone marrow of male C6B3F1 mice or in the inhibition of two stem cell lines contained therein. At equimolar doses HECNU induced a 3- to 40-fold deeper nadir of proliferation of both stem cell lines compared to BCNU, but subsequently a 2- to 30-fold quicker recovery of these lines was observed. An enhancement of myelotoxicity was only found following injections with intervals of 1 week. Myelosuppression was almost twice as great, when six instead of three weekly injections of 50 mumol/kg were given. When, however, sufficient time was allowed for recovery, doubling the number of significantly larger doses of drug was tolerated at the level of the bone marrow stem cell. The maximum inhibition of pluripotent- and granulocyte-committed stem cells following HECNU was paralleled by higher amounts of DNA-DNA interstrand crosslinks in the entire bone marrow compared to BCNU. During the initial stages, the degree of myelosuppression did, to some extent, parallel the number of DNA-DNA interstrand crosslinks induced in the bone marrow as a whole, but this relation was lost after the initial period.