Low inhibin B levels alone are not a reliable marker of dysfunctional spermatogenesis in childhood cancer survivors.

Hormone and semen analyses were carried out to examine the diagnostic value of hormones and hormone combinations as markers of spermatogenesis in male patients who had received oncological treatment in childhood. Hormone analyses from 73 participants and spermiograms from 42 participants were evaluated. Spearman's correlation coefficients and measures of diagnostic accuracy were calculated for the hormone and semen analysis values. Inhibin B levels of <80 ml/ml, follicle-stimulating hormone (FSH) levels of >10 IU l(-1) and a combination of the two parameters showed positive predictive values for azoospermia of 0.423, 0.6154 and 0.6667 respectively. While 32% of the 73 participants showed a combination of abnormal inhibin B and FSH values, which strongly indicates impaired spermatogenesis, 31% of the 42 spermiogram results revealed azoospermia. The hormone and semen analyses showed that approximately one-third of the participants had fertility impairment. Inhibin B alone thus does not reflect spermatogenesis as well as inhibin B in combination with FSH in patients who have undergone cancer treatment in childhood. Both parameters should therefore be evaluated in paediatric cancer follow-up programmes to allow better identification of treatment regimens that cause persistent azoospermia in male childhood cancer survivors.

[Hemangiopericytoma of the buccal mucosa. A case report]. / Hämangioperizytom der Wange. Ein Patientenbeispiel.

Hemangiopericytoma describes a rare mesenchymal neoplasm which can occur at any site on the body and represents 1% of vascular tumors. Histologically, it is characterized by a vascular pattern with high cellularity. These tumors occur in particular near the torso and surface variants are rare. Due to the unspecific clinical picture, it is often confused with other benign mesenchymal tumors. The heterogenous course and high risk of recurrence with hemangiopericytomas necessitate long-term clinical follow-up.

Having children after surviving cancer in childhood or adolescence - results of a Berlin survey.

OBJECTIVE: To assess the desire to have children, the actual number of children, and children's health in a survey of 752 adult survivors of paediatric or adolescent cancer in Berlin, Germany. PATIENTS: The German Childhood Cancer Registry ( Deutsches Kinderkrebsregister, DKKR) listed 752 paediatric cancer patients who had been treated in 1 of the 2 paediatric oncology centres in Berlin since 1980 and were 18 years of age or older at the time of the survey. METHODS: A 4-page questionnaire assessing pubertal development, fertility, the desire to have children, the actual number of children, and children's health was sent to 574 former patients located using data from the DKKR and German Residents' Registration Office. RESULTS: In total, 45% (n=260) of patients (140 women, 120 men) returned the questionnaire. The mean age was 10.9 years at the time of diagnosis and 24.3 years at the time of the present survey. Various aspects of puberty were assessed to evaluate pubertal development. Of all study participants, 77% indicated a general desire to have children. Reasons given for not having children included 'Still too early to have children' (67%), 'Fear that my child will develop cancer' (9%), and 'Fear that cancer will recur' (6%). Transient amenorrhoea, lasting from 1 to 30 months, occurred in 25 of 74 patients after chemo- and radiotherapy. Five of 136 participants indicated that they had already reached menopause. Seventeen per cent of all participants or their partners had already been pregnant. The miscarriage rate was 13%. Thirty participants gave birth to or fathered a total of 41 children, of whom 40 were healthy and 1 was born with a foot deformity (Pes equinovarus). Among participants' children, mean weight at birth was 3 458 g, and mean head circumference was 35 cm. DISCUSSION: The desire to have children was lower among our survey participants than in the general population of the same age (77% vs. 90%). Participants' fears that their children might develop cancer or that their own cancer might recur are often unfounded. Paediatric cancer survivors, relatives, and attending physicians should be well informed about this issue by paediatric oncologists. The proportion of miscarriages, mean weight at birth, and mean head circumference at birth in our study were comparable to the German general population. OUTLOOK: We intend to conduct a nationwide survey entitled 'Fertility after Chemo- and Radiotherapy in Paediatric and Adolescent Patients' (FeCt). The aim is to gain valuable data with a larger number of participants and more statistical power to determine whether specific cytotoxic drugs or radiation increase the risk of infertility, and if so, at what doses. For the study, the DKKR has the addresses of more than 5 000 former patients in Germany who are now adults. The results will be used to plan future treatment optimisation studies, and to assess the need for prophylactic measures in cases where fertility-compromising therapies are unavoidable. This nationwide survey 'FeCt' will be supported by the Deutsche Kinderkrebsstiftung.

Parvovirus B19 infection associated with unilateral cervical lymphadenopathy, apoptotic sinus histiocytosis, and prolonged fatigue.

This report describes the case of a 16 year old girl with a history of high fever, prolonged fatigue, and cervical lymphadenopathy of the right side. In addition, the patient showed neutropenia, thrombopenia, and pronounced reticulopenia. Cervical ultrasound showed unilateral hypoechoic lymph nodes up to 23 mm in diameter suspicious for malignant lymphoma. Histology of a cervical lymph node specimen revealed massive nodular histiocytic proliferation and prominent apoptosis without necrosis. Parvovirus B19 was detected by polymerase chain reaction and immunohistochemistry in the lymph node. In summary, this case is an unusual presentation of parvovirus B19 infection. The virus was identified as the potential causative agent of unilateral cervical lymphoma and apoptotic sinus histocytosis, thus broadening the clinicopathological spectrum of parvovirus B19 induced diseases.

Childhood all blasts retain phenotypic and genotypic characteristics upon long-term serial passage in NOD/SCID mice.

For children with an early bone marrow relapse or relapsed T-cell acute lymphoblastic leukemia (ALL), allogeneic bone marrow transplantation (BMT) is currently the only therapeutic option with a curative approach. Here, the graft versus leukemia (GvL) effect seems to play an important role for long-term immunological control of leukemia. If a bone marrow donor is not available, autologous stem cell transplantation after high-dose chemotherapy has been used as an alternative option. The objective of this work was the induction of tumor specific cytotoxic T-lymphocytes (CTL) against autologous leukemic cells in order to generate the missing GvL effect after autoBMT. The first step was the establishment of an optimized and reliable mouse model. The second step was the induction of a GvL effect in an allogeneic approach to serve as a basis for further GvL experiments in an autologous approach in this mouse model. Leukemic cells from 11 out of 16 different pediatric patients were successfully established in mice and in one case passaged over 19 generations without changes of genotype or phenotype. The antileukemic activity of allogeneic human MNC as a GvL reaction and an accompanying GvHD in the mouse model was shown. Xenotransplanted ALL can be considered a clinically relevant model mimicking the human conditions and as a useful preclinical tool for the evaluation of novel immuno- or genetherapeutic approaches.

Effect of oral creatine supplementation on muscle [PCr] and short-term maximum power output.

Our purpose was to determine the effect of creatine supplementation on power output during a 30-s maximal cycling (Wingate) test. Nine males underwent 3 randomly ordered tests following ingestion of a creatine supplementation (CRE), placebo (PLA), and control (CON) CRE was ingested as creatine monohydrate (CrH2O) dissolved in a flavored drink (20g.d-1 for 3 d), while PLA consisted of the drink only. Tests were performed 14 d apart on a Monarch ergometer modified for immediate resistance loading. Needle biopsies were taken from the vastus lateralis at the end of each treatment period and before the exercise test. No difference was found between conditions for peak, mean 10-s, and mean 30-s power output, percent fatigue, or post-exercise blood lactate concentration. Similarly, no difference between conditions was observed for ATP, phosphocreatine (PCr), or total creatine (TCr); however, the TCr/ATP was higher in the CRE condition (P < 0.05) than in the CON and PLA conditions. Findings suggest that 3 d of oral Cr supplementation does not increase resting muscle PCr concentration and has no effect on performance during a single short-term maximal cycling task.

Control of ammonia toxicity to Hyalella azteca by sodium, potassium and pH.

The toxicity of ammonia to Hyalella azteca at constant pH in artificial media was controlled by sodium and potassium, and not by calcium, magnesium, or anions. Small increases in the LC50 for total ammonia (from 0.15 to 0.5 mM) occurred as sodium was increased from 0.1 to 1 mM and above, but major increases in the LC50 (to over 10 mM total ammonia) required the addition of potassium. Potassium was, however, more effective at reducing ammonia toxicity at high (1 mM) sodium than at low (0.1 mM) sodium. Ammonia toxicity was independent of pH at low sodium and potassium concentrations, when ammonia toxicity appeared to be associated primarily with aqueous ammonium ion concentrations. At high sodium and potassium concentrations, the toxicity of ammonia was reduced to the point where un-ionized ammonia concentrations also affected toxicity, and the LC50 became pH dependent. A mathematical model was produced for predicting ammonia toxicity from sodium and potassium concentrations and pH.

Allogeneic bone marrow transplantation for a subset of children with acute lymphoblastic leukemia in third remission: a conceivable alternative?

In the BFM Relapse Study registry we retrospectively identified 136 patients with a first marrow relapse who had undergone BMT in second complete remission (CR2) (group A) and 33 patients who received transplants only after a 2nd bone marrow (BM) relapse had occurred (group B). Event-free survival (EFS) rates at 6 years after BMT were 0.49 +/- 0.05 and 0.48 +/- 0.09 for patients transplanted in CR2 and CR3, respectively. In context with the BFM chemotherapy trials for relapsed childhood ALL there is a clear benefit from BMT in 2nd CR for children with unfavorable prognostic features (isolated early BM relapse, very early BM relapse or BM relapse of T cell ALL). Similar control of leukemia can be achieved with either chemotherapy or BMT in late BM relapse of ALL. Assuming a 60% failure rate with chemotherapy for patients in second relapse, a third remission can be achieved in about 60% of patients who have received chemotherapy, rendering them eligible for BMT in 3rd CR. With this strategy 58% of these patients would survive and late sequelae of BMT be restricted to a minority. To withhold BMT in CR2 and not perform BMT before a 2nd BM relapse has occurred, may be a conceivable alternative for children with late ALL BM relapse, at least if no related donor is available.

Allogeneic BMT vs. chemotherapy in late bone marrow relapsed childhood non-T/non-B ALL: results of BFM ALL relapse studies. BFM Relapse Study Group.

In first BM relapsed non-T/non-B ALL, the outcome is not significantly different after radio-chemotherapy compared with allogeneic BMT. Therefore, radio-chemotherapy is convenient af first late BM relapse and BMT may be performed not before a second BM relapse had occurred. Only a small subgroup of children with isolated BM relapse and peripheral blast cells > or = 10,000/microliter at diagnosis of first relapse has a dismal prognosis after radio-chemotherapy and might benefit from BMT.

Autologous bone-marrow transplants compared with chemotherapy for children with acute lymphoblastic leukaemia in a second remission: a matched-pair analysis. The Berlin-Frankfurt-Münster Study Group.

It is unclear how best to treat children with acute lymphoblastic leukaemia (ALL) who are in a second remission. Treatment with bone-marrow transplants from HLA-identical siblings results in a statistically greater likelihood of leukaemia-free survival than does chemotherapy. Less than 25% of relapsed patients are able to benefit from this therapy due to a lack of matching donors; chemoradiotherapy or autologous BMT are considered for the rest. We compared treatment results for children who underwent autologous BMT with those who had chemotherapy. All patients were registered between 1983-94 in the multicentre trials. We selected groups of patients by matching variables associated with treatment outcome and duration of second remission. 52 matched-pairs were studied. The probability of event-free survival at 9 years was 0.32 (SD 0.07) for patients receiving chemotherapy versus 0.26 (SD 0.07) for patients who underwent autologous BMT. For two groups--children with prognostic factors indicating high risk of relapse and those with factors indicating lower risk--the outcome from transplantation did not differ significantly from that of chemotherapy: no advantage of autologous BMT over chemotherapy as post-induction treatment for children with ALL in a second remission could be detected with regard to event-free survival. Because autologous BMT has been used as the final step of treatment it is possible that its relative ineffectiveness has been due to the lack of continuation therapy after transplant. Attempts should be made to complement autologous BMT by subsequent immunotherapy, molecular biotherapy, chemotherapy, or a combination of these.

Isolated extramedullary relapse in children with acute lymphoblastic leukemia: a comparison between treatment results of chemotherapy and bone marrow transplantation. BFM Relapse Study Group.

The purpose of this study was to determine the therapeutic efficacy of different treatment strategies, namely chemotherapy, allogeneic and autologous bone marrow transplantation (BMT), for extramedullary relapse of acute lymphoblastic leukemia (ALL) in children in second or subsequent remission. Between 1983 and 1993, 165 patients up to 19 years of age with extramedullary relapse of ALL were registered in the multicenter ALL-REZ BFM trials. One hundred and thirty four children received chemotherapy only; 17 children were grafted from HLA-identical sibling donors 152 days (46-392 days) after diagnosis of relapse, and 14 children underwent autologous BMT after a median time of 137 (range 23-300) days. Event-free survival (EFS) at 5 years was 0.47 +/- 0.05 for patients receiving chemotherapy: 0.76 +/- 0.07 for late, 0.33 +/- 0.08 for early and 0.33 +/- 0.07 for very early relapsed patients. Sixty five patients are in complete remission (CR), 61 patients relapsed, 5 died from therapy related complications, 2 patients in CR were lost to follow-up and one patient developed a second malignancy. For patients who had undergone BMT, EFS at 5 years was 0.36 +/- 0.10 without significant difference between autologous BMT (8 of 14 in CR, 6 relapsed) and allogeneic BMT (6 of 17 in CR, 4 died of acute toxicity, and 7 relapsed).(ABSTRACT TRUNCATED AT 250 WORDS)

The Massachusetts General Hospital (MGH) Hairpulling Scale: 1. development and factor analyses.

We developed the MGH Hairpulling Scale to provide a brief, self-report instrument for assessing repetitive hairpulling. Seven individual items, rated for severity from 0 to 4, assess urges to pull, actual pulling, perceived control, and associated distress. We administered the scale to 119 consecutive patients with chronic hairpulling. Statistical analyses indicate that the seven items form a homogenous scale for the measurement of severity in this disorder.

Influence of fractionated total body irradiation on mucosal toxicity in intensified conditioning regimens for autologous bone marrow transplantation in pediatric cancer patients.

From April 1988 to March 1991 28 children with generalized solid tumors (N = 15) or hematologic malignancies (N = 13) received intensified myelotoxic regimens followed by autologous stem cell rescue (ABMT). These intensified regimens consisted of 12 Gy fractionated total body irradiation (FTBI) and 2 (or 3) cytotoxic drugs (group A, n = 19) or a combination of 3 cytotoxic drugs (group B, n = 9). FTBI-containing regimens produced more severe mucositis > = WHO grade 3 (p = 0.01) and a longer duration of severe mucositis. The mucositis had a median duration of 8 days (range 0-28) in group A compared with median 0 days (range 0-7) in group B (p < 0.01). Acute renal and liver toxicity were not different. The probability of overall survival at day +100 was 89% in all patients. In terms of long-term survival FTBI containing regimen did not prove superior: 5 out of 19 patients in group A and 6 out of 9 patients in group B have been survivors for a minimum of 3 years. In conclusion, severe gastrointestinal toxicity of such intensive regimens is avoidable if FTBI is omitted.

[Sympatho-adrenergic reactions during drug-induced hypotension. A comparative study on probands]. / Sympatho-adrenerge Reaktionen bei medikamentös induzierter Hypotension. Eine vergleichende Studie an Probanden.

This study was undertaken to compare the influence of different regimens for induced hypotension down to Power a limit of 80 mmHg (systolic) on sympatho-adrenergic responses in 10 volunteers. Volunteers were investigated in five batteries of tests using glyceryl trinitrate (10 micrograms/kg BW/min), sodium nitroprusside (10 micrograms/kg BW/min maximal dosage), nifedipine (0.35 micrograms/kg BW/min) and urapidil (bolus injections of 25, 25 and 50 mg, followed by an infusion of 180 ml/h) and placebo. Catecholamines in plasma were detected by HPLC/ECD within a period of 1 h of hypotension and 1 h of recovery at 11 measuring points. Using sodium nitroprusside and glyceryl trinitrate, a significant hypotension was achieved. Urapidil was less potent. No hypotension was observed during or after treatment with nifedipine. Heart rate increased during treatment with sodium nitroprusside and glyceryl trinitrate. Sodium nitroprusside, glyceryl trinitrate and urapidil caused significant rises in noradrenaline levels. With nifedipine, noradrenaline increased within the normal range. Adrenaline left the normal range only during urapidil treatment. MAP, HR, and levels of noradrenaline and adrenaline returned to the initial values 5 min after discontinuation of the sodium nitroprusside infusion. After treatment with glyceryl trinitrate and urapidil, MAP was still low even 60 min after discontinuation of treatment. Urapidil caused marked increases in noradrenaline and adrenaline, which persisted even into the recovery phase. With regard to clinical management and sympatho-adrenergic responses, sodium nitroprusside is the most useful of these compounds for the reduction of hypotension. Having similar potency and active metabolites, glyceryl trinitrate has a longer duration of action.(ABSTRACT TRUNCATED AT 250 WORDS)

[Mother and child stress parameters during cesarean section with general and peridural anesthesia]. / Mütterliche und kindliche Stress-Parameter bei Schnittentbindungen in Allgemein- und Periduralanaesthesie.

This study compared maternal and fetal stress responses during cesarean section in either general anesthesia (GA) or epidural anesthesia (EA). Ten patients received GA with thiopental induction, intubation, and controlled ventilation with nitrous oxide and oxygen. After delivery, anesthesia was supplemented with fentanyl 0.2-0.3 mg. Ten patients received EA via catheter, using bupivacaine 0.5%, and prilocaine or lidocaine 1%. Maternal mean arterial pressure (MAP), HR, and plasma concentrations of epinephrine and norepinephrine (by HPLC/ECD), ADH, ACTH and cortisol (by RIA) were determined before and after induction, after delivery, at the end of the operation and 30 minutes postoperatively. Fetal catecholamine levels in umbilical artery blood were measured immediately after delivery. In addition, fetal blood gas analyses and Apgar scores were compared. Fetal epinephrine was slightly increased in the EA group (EA 132 pg/ml, GA 52 pg/ml). Norepinephrine was similar in both groups (EA 1.218 pg/ml, GA 1.124 pg/ml). Blood gas analyses and Apgar scores were also comparable. A negative correlation was found between norepinephrine and pH values in fetal umbilical artery blood (P = 0.01). Maternal epinephrine levels were lower under EA and below the normal range (EA 23 pg/ml, GA 77 pg/ml, P = 0.002); levels increased during GA and decreased during EA (P = 0.01). No statistical differences were seen in maternal norepinephrine (EA 206 pg/ml, GA 354 pg/ml). MAP was lower during EA (group levels EA 81 mmHg, GA 95 mmHg, P = 0.0002) and HR was higher during GA (group levels EA 89/min, GA 104/min, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Sympatho-adrenergic reactions following theophylline administration with the use of various anesthesia technics]. / Sympatho-adrenerge Reaktionen nach Theophyllin-Applikation bei Anwendung verschiedener Anaesthesieverfahren.

The mechanism of action of theophylline is still the subject of controversy. Possible mechanisms that have been suggested are inhibition of phosphodiesterase, release of catecholamines, effects on intracellular calcium, and adenosine antagonism. With regard to these aspects, it was the aim of this study to compare sympatho-adrenal responses after theophylline application during different anesthetic techniques. A total of 60 patients scheduled for orthopedic surgery were investigated: they were divided into three groups of 20 patients who received either halothane anesthesia with thiopentone induction, modified neurolept anesthesia with fentanyl and midazolam, or spinal anesthesia with bupivacaine and mepivacaine. Within these three groups, the patients were randomly allocated to a theophylline collective receiving an injection of theophylline, 4 mg/kg body weight and to the control group. Plasma levels of epinephrine and norepinephrine (by HPLC/ECD), glucose, lactate and free glycerol and MAP and HR were determined over a period of 120 min. In all groups, epinephrine levels increased immediately after injection of theophylline; group levels of epinephrine were higher in the theophylline-groups than in controls (P less than 0.0001). A remarkable increase was observed within 60 min. Peak epinephrine concentrations were comparable after single injections of 100 micrograms or infusions of 5 micrograms/min. The norepinephrine increase after theophylline injection was brief and less pronounced. MAP, HR, glucose, lactate and free glycerol were not influenced by theophylline. A comparison of the theophylline patients showed no statistical differences attributable to the different anesthetic techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

[The quantitative analysis of amide local anesthetics using high pressure liquid chromatography and ultraviolet detection (HPLC/UV)]. / Die quantitative Analyse von Amid-Lokalanaesthetika mittels Hochdruck-Flüssigkeits-Chromatographie und UV-Detektion (HPLC/UV).

This study was undertaken to develop a time- and cost-effective method for the detection of lidocaine, mepivacaine, prilocaine, bupivacaine, and etidocaine by HPLC/UV. The chromatographic system consisted of a C18-column (300 x 3.9 mm) for reversed-phase chromatography and a mobile phase of 30% acetonitrile and 70% 0.05 M sodium phosphate buffer. For the analysis of lidocaine, mepivacaine, and prilocaine, the buffer was adjusted to pH 5.8. The buffer for the analysis of bupivacaine and etidocaine was adjusted to pH 3.5. The flow rate was 1 ml/min. UV detection took place at a wavelength of 210 nm. All blood samples were taken from a central venous line. After plasma separation, 1 microgram (100 microliters) of internal standard was added to 1 ml plasma. The samples were alkalized and extracted with ether, followed by the extraction of the organic phase in 250 microliters 0.05 N sulphuric acid; 50 microliters of this solution was injected into the system. The chromatographic system allowed the separation of bupivacaine and etidocaine (pH 3.5) as well as lidocaine and mepivacaine or prilocaine (pH 5.8). Separation of prilocaine and mepivacaine in one run was not satisfactory. Recovery rates for all local anesthetic substances were about 90%, standard variations below 3%, and coefficients of variation below 2%. The detection limit was about 30 ng/ml. The method is suitable for clinical practice. Only minor methodological modifications are necessary for the detection of the amide local anesthetics in current clinical use.

Changes in 3 beta-hydroxysteroid dehydrogenase activity in the developing rabbit ovary.

The presence of 3 beta-hydroxysteroid dehydrogenase in the maturing rabbit ovary was demonstrated biochemically and histochemically. Enzyme activity was negligible to absent in ovaries from rabbits less than 44 days old. The greatest activity was located in the microsomal fraction of ovaries from mature rabbits. The enzyme characteristics were: Vmax = 33.1 +/- 9.6 nmol/min/mg protein and Km = 2.16 +/- 0.28 microM. Ovaries from pregnant hyperglycemic rabbits had enzyme which showed a Vmax of 51.4 +/- 8.2 nmol/min/mg protein and Km = 2.41 +/- 0.31 microM. These results indicate that rabbit ovarian tissue becomes steroidogenically active at a time when gonadotropin levels are elevated.

Comparative toxicity of two-dexamethasone derivatives following topical ocular instillation to rabbits. II. Systemic histopathological changes.

Dexamethasone-21-tertiary butyl acetate (dexamethasone TBA) and dexamethasone alcohol at concentrations of 0.2, 0.1, 0.01, and 0.001% were topically instilled into the right eyes of groups of 10 rabbits for 21 consecutive days. Vehicle control and untreated control groups were used for comparative evaluation. The dose-dependent changes for each compound were (1) lipid and glyocogen infiltration of liver, (2) hydropic changes of liver, (3) vacuolation and multifocal hepatic necrosis of liver, (4) atrophy of Peyer's patches of intestines, (5) white pulp atrophy of the spleen and (6) atrophy of the adrenal cortex. No pathological changes were noted for other tissues including the eye. In conclusion, the results indicate that systemic histopathologic changes for both steroids were comparable and typical for steroids.