A RARE CASE OF OXYTOCIN-INDUCED MATERNAL CARDIAC BRADYARRHYTHMIA DURING LABOUR.

The report a rare case of oxytocin-induced severe maternal bradyarrhythmia of a young healthy term primigravida with a singleton pregnancy in spontaneous labour. Augmentation of labour was initiated immediately following the diagnosis of poor progression of labour at four centimetres dilatation. An oxytocin infusion was administered as per standard hospital titration protocol. The patient developed ongoing, persistent episodes of severe bradycardia within six hours of commencement of the oxytocin infusion, as detected by routine pulse oximeter for maternal heart rate monitoring and confirmed manually. Oxytocin was ceased as soon this was recognised, and delivery was expedited by emergency caesarean section both for inadequate progress in labour and the inability to continue oxytocin infusion. Despite being theoretically known to cause cardiac arrhythmias, as a side effect, to our knowledge this is the first reported case in published literature of oxytocin-induced maternal bradycardia.

AtSUC2 has a role for sucrose retrieval along the phloem pathway: evidence from carbon-11 tracer studies.

The location of the phloem within a plant, and its vulnerability to disruption, make it a difficult tissue to study and therefore non-invasive studies of phloem functionality are important. Here we compare, phloem transport, measured non-invasively, in wild type Arabidopsis thaliana, and transposon-insertion mutants for AtSUC1 or AtSUC2, giving in vivo information on the importance of these sucrose transporters for phloem transport. The suc2 mutant showed an increase in both phloem leakage and transport time, consistent with reduced sucrose uptake into both transport and collection phloem. The results are consistent with the AtSUC2 transporter being important for retrieval of leaked sucrose in the transport phloem of Arabidopsis. There was no difference in phloem transport properties between the wild type and the suc1 mutants, implying that the AtSUC1 transporter does not play a significant role within the transport phloem of Arabidopsis under the conditions of our study.

The commutability of external quality assurance serum and reference serum materials between the VITROS Albumin Slide and four other routine albumin methods.

BACKGROUND: Between-method differences in external quality assurance schemes (EQAS) are assumed to be indicative of between-method differences in results for fresh diagnostic serum samples. However, this assumption is only valid if the EQAS fluid is shown to be commutable between methods with the fresh human samples. Using fresh human serum samples, we studied the commutability of six UK National EQAS (UKNEQAS) samples and two reference serum preparations using five methods for the measurement of albumin. METHODS: The VITROS Albumin Slide was compared with two liquid reagent bromocresol green-based methods and two immunoturbidimetric methods. Thirty fresh human serum samples, six UKNEQAS samples and two reference materials were analysed over a period of five days by all methods. The reference materials were: a certified protein reference material, CRM470 (protein reference preparation) and the Scandinavian NFKK Reference Serum X. RESULTS: A concentration-dependent tendency towards non-commutability was seen for the six UKNEQAS samples. Two of the methods recovered the CRM470 above the upper limit of the expected range and the remaining three were within the expected range. CONCLUSIONS: Assessment of commutability is important in the investigation of between-method differences in EQAS. External quality assurance and reference materials should have been demonstrated to be commutable and be available at multiple concentrations, before they may be considered appropriate for the assessment of accuracy.

Ovarian cancer metastatic to the brain: what is the optimal management?

PURPOSE: To better define determinants of survival and optimal management strategies for patients with ovarian cancer and brain metastases. METHODS: A review of literature using Medline identified 15 case series of ovarian cancer patients with brain metastases (OBM). Each article was abstracted for survival data, and in all cases, the intervals between ovarian cancer diagnosis and brain metastasis identification, and between brain metastasis identification and last follow-up were recorded. Cases were categorized by patient characteristics and treatment modality for brain metastases. Estimated survival probabilities were plotted using the Kaplan-Meier method with differences between subgroups analyzed by the log-rank test. Cox proportional hazards model was used to identify independent prognostic factors age, number of metastasis, and treatment modality associated with survival. RESULTS: The median interval from ovarian cancer diagnosis to brain metastasis in 104 identified patients was 19.5 months. Brain metastasis was single in 43%, multiple in 41%, and not reported in 16% of cases. About 81.7% of patients were treated for their brain metastases using external radiation therapy (XRT), chemotherapy, and surgery. XRT was utilized in 76% of 104 patients and in 93% of treated patients. The most commonly used modalities were XRT alone (40%) and craniotomy and XRT (17%). The median survival (MS) for all patients regardless of treatment type was 6 months. Patients who received any treatment lived longer than those not receiving surgery/chemotherapy/XRT (MS; 7 months vs. 2 months, P = 0.0001). Patients with single brain metastasis had a longer median survival (21 months vs. 6 months, P = 0.049) when treated with craniotomy plus radiation and/or chemotherapy compared to treatment regimens that excluded craniotomy. In a multivariate analysis, only treatment type was significant in predicting survival. CONCLUSION: OBM portends a poor prognosis, however, long-term survival is possible. Patients appear to benefit from therapy, especially selected groups of OBM patients with single brain metastasis treated with radiation therapy and surgery.

Predictors of complications after inguinal lymphadenectomy.

OBJECTIVE: The aim of this study was to identify predictors of complications in patients undergoing inguinal lymphadenectomy (LND) in the treatment of vulvar carcinoma. METHODS: Clinical information was abstracted from records of patients with invasive vulvar cancer. All patients underwent LND. Closed suction drains were placed in groin incisions and removed when output was less than 30 ml/24 h. Associations between variables were studied by chi(2) and t tests. RESULTS: Sixty-seven patients undergoing 112 LND were evaluated. Eighty-eight percent of patients underwent radical vulvar surgery and LND while 12% underwent LND alone. Patients were treated with either unilateral (22) or bilateral (45) LND. Seventy-three percent received extended postoperative prophylactic antibiotics. The median duration of suction drainage was 15 days for one drain and 14 days for two drains. Early postoperative cellulitis (<30 days after surgery) developed in 35.4%, early wound breakdown in 19.4%, early lymphedema in 4.8%, and early lymphocyst formation in 13.1%. Late cellulitis (>30 days after surgery) developed in 22.2%, late wound breakdown in 3.2%, late lymphedema in 29.5%, and late lymphocysts in 5%. Patients developing early cellulitis were more likely to have early wound breakdown (P = <0.001, RR 14.2) or early lymphocyst formation (P = 0.016, RR 7.6). Type of procedure, antibiotic use, need for adjuvant therapy, and duration of suction drainage did not influence early complications. Early complications and management strategies did not predict late complications. CONCLUSIONS: Chronic lymphedema occurs in nearly 30% of patients after LND. Late complications after LND were not predicted by early complications. New strategies for prevention of chronic lymphedema are needed.

A retrospective analysis of radical hysterectomies done for cervical cancer: is there a role for the Pfannenstiel incision?

OBJECTIVE: The goal of this work was to review patients with early-stage cervical cancer undergoing radical hysterectomy, comparing Pfannenstiel and vertical midline incisions for surgical feasibility, complications, and length of stay. METHODS: Patients were identified by searching our institutional database. Data were collected from review of each patient's medical record, including demographics, cancer stage, histology, procedural information, length of stay, and complications. Associations between variables were studied using chi(2) and two-tailed t tests. Multivariate analysis was performed using logistic regression. RESULTS: Between March 1996 and June 2000, 113 patients from the University and Presbyterian Hospitals, Oklahoma City, Oklahoma, underwent radical hysterectomy and pelvic and paraortic lymph node dissection with records available for review. Group 1 consisted of 40 patients who had vertical incisions and group 2 consisted of 73 patients who had Pfannenstiel incisions. There was no difference in race, number of previous abdominal surgeries, distribution of stage, histology, percentage of type III hysterectomies, estimated blood loss, nodal counts, pathologic margin positivity, and postoperative complications among the two groups. Group 2 were younger (41.6 vs 46.5, P = 0.02) and had a lower average QI than group 1 (24.9 vs 28.9, P = 0.001). Group 2 also had a shorter average hospital stay (4.6 days vs 5.8 days, P = 0.04) and shorter operative time (215 min vs 273 min, P = 0.09). Multivariate analysis resulted in Pfannenstiel incisions (P = 0.002), younger age (P = 0.004), and smaller body mass index (P = 0.01) being significant predictors of length of stay. CONCLUSIONS: Pfannenstiel incisions are feasible without increased morbidity and equal nodal retrieval as compared with vertical midline incisions in patients with early-stage cervical cancer. Pfannenstiel incisions may offer an advantage besides cosmesis in the form of shorter operating room time and earlier discharge from the hospital.

Non-immune hydrops after 20 weeks' gestation: review of 10 years' experience with suggestions for management.

OBJECTIVE: To analyze the etiologies and outcomes for a southeastern section of the United States, and to organize an efficient approach to evaluation. METHODS: We reviewed 82 cases of non-immune hydrops presenting after 20 weeks' gestation over a 10-year period. RESULTS: Overall perinatal mortality was 86.6%. Fetuses diagnosed with hydrops before 24 weeks' gestation had a perinatal mortality of 95%, with nearly one-third having abnormal karyotypes. The etiology of hydrops diagnosed after 24 weeks' gestation was more likely to remain idiopathic or to be related to cardiothoracic abnormalities. CONCLUSION: Before 24 weeks' gestation, the high risk of mortality and abnormal karyotype justifies offering families funipuncture in the hope of finding a treatable cause of non-immune hydrops. After 24 weeks' gestation, when fewer abnormal karyotypes are found, funipuncture may also be pivotal in diagnosing the cause of non-immune hydrops.

Rapid computer-assisted infrared analysis of urinary calculi using photoacoustic detection.

The application of commercial spectrum-analysing software to quantitative analysis of urinary stones by Fourier transform infrared spectrophotometry is described. The infrared technique is straightforward in comparison with other stone analysis procedures of similar scope and affords significant time savings. The use of partial least squares regression in the analysis program enables better quantitation of stone components than has been hitherto possible using infrared methods. All the principal and many less common stone constituents can be detected and measured. Photoacoustic detection was employed, thus enabling non-destructive analysis with minimal sample preparation. A comparison is made between the infrared procedure and the hybrid thermogravimetric plus "wet" chemistry technique, which it has superseded for routine urinary stone analysis in the author's department.

Effectiveness of combined limonene and 4-hydroxyandrostenedione in the treatment of NMU-induced rat mammary tumours.

Limonene, a monocyclic monoterpene, occurs naturally in orange peel oil. It has been shown to exhibit both chemopreventive and chemotherapeutic activity without toxicity in rodent models. In this study we examined the effect of limonene both at maximally optimal and suboptimal doses and in combination with suboptimal doses of 4-hydroxyandrostrenedione on nitrosmethylurea-induced rat mammary tumours. A 10% limonene dose mixed in the diet caused tumour regression in all animals. A 5% limonene dose was only able to cause regression in 50% of the rats (P < 0.05). A suboptimal dose of 4-hydroxyandrostrenedione (12.5 mg kg-1) resulted in tumour regression in 75% of rats. A combination of 5% limonene with 4-hydroxyandrostrenedione (12.5 mg kg-1) resulted in a greater tumour regression (83.3%) than either agent given individually (P < 0.001 and 0.006 for limonene/4-hydroxyandrostrenedione vs limonene alone and 4-hydroxyandrostrenedione alone respectively.

Leiomyoma of the tongue presenting as congenital airway obstruction.

Leiomyoma is a benign tumor of smooth muscle origin that is most commonly found in the uterus, gastrointestinal tract, and skin. Intraoral leiomyomas are rare, usually asymptomatic, and, most often present in the fifth decade of life. A review of the literature since 1884 yielded only 125 cases, including 23 of the tongue. We report the first case of a congenital leiomyoma of the tongue presenting with airway obstruction. A 6-day-old female infant, intubated since birth for respiratory distress, was evaluated for an obstructing oropharyngeal mass. The tumor was pedunculated, mucosa-covered, and localized to the posterior tongue. The mass was completely excised using a CO2 laser. There has been no recurrence in 1 year of follow-up.

Development of a novel class of cyclic hexapeptide oxytocin antagonists based on a natural product.

A new structural class of cyclic hexapeptide oxytocin antagonists derived from Streptomyces silvensis and typified by L-365,209 (cyclo-[L-prolyl1-D-phenylalanyl2-L- isoleucyl3-D-dehydropiperazyl4-L-dehydroperazyl5-D-(N- methyl)phenylalanyl6]) was recently reported. In this paper we further delineate the structure-activity profile for this new class by systematic study of L-365,209 analogs obtained by total synthesis. The optimal combination of cyclic amino acid ring sizes at positions 1, 4, and 5 and the role of the N-alkyl substituent at position 6 was elucidated. The lipophilic amino acids at positions 2 and 3 and the unusual amino acid D-dehydropiperazic acid at position 4 were found to be the most critical residues for obtaining good oxytocin receptor affinity. Analogs containing a basic side chain at the less critical 5- and 6-positions maintained good receptor affinity and also had useful levels of water solubility for intravenous formulation. By combining potency- and solubility-enhancing substitutions, several analogs were identified that have the desired combination of properties in vitro (22, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-pipecolyl-L-pipeco lyl-D- histidyl]; 25, cyclo-[L-prolyl-D-2-naphthylalanyl-L-isoleucyl-D-pipecolyl-L -pipecolyl-D- histidyl]; 26, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-dehydropiperazyl-L-++ pipecolyl-D-histidyl]; 33, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-pipecolyl-L- piperazinylcarboxy-D-(N-methyl)phenylalanyl]; 34, cyclo-[L-prolyl-D-phenylalanyl-L-isoleucyl-D-dehydropiperazyl-L-or nithyl- D-(N-methyl)phenylalanyl]). In general, this class exhibited good selectivity for binding to the oxytocin receptor versus the arginine vasopressin V1a and V2 receptor subtypes, although increased V2 receptor affinity was observed in one case (32, cyclo[L-prolyl-D-2-naphthylalanyl-L-isoleucyl-D-pipecolyl-L- lysyl-D-(N- methyl)phenylalanyl]). Unexpectedly, compound 33 was found to stimulate contractions of the isolated rat uterus via activation of the uterine bradykinin receptor. Compounds 22, 25, 26, 33, and 34 were found to be potent antagonists of oxytocin-stimulated contraction of the rat uterus in vitro and in vivo. Compounds 22 and 25 were additionally characterized as potent antagonists of oxytocin-stimulated uterine contractions in the near-term pregnant rhesus monkey. These studies thus demonstrate the selectivity and efficacy of certain members of this novel class of antagonists and suggest their use as pharmacological tools in further defining the role of oxytocin in both term and preterm labor.

Orally active, nonpeptide oxytocin antagonists.

The first nonpeptide antagonists of the neurohypophyseal hormone, oxytocin (OT) are described. Derivatives of the spiroindenepiperidine ring system, these compounds include L-366,509, an orally bioavailable OT antagonist with good in vivo duration. The potential use of these agents for treatment of preterm labor and their significance as new nonpeptide ligands for peptide receptors are discussed.

Differential distribution of tenascin in the normal, hyperplastic, and neoplastic breast.

We studied by immunohistochemistry the distribution of tenascin with the monoclonal antibody 100EB2, and compared it with that of laminin in breast tissue samples from fetal, adult resting, lactating, and aging parenchyma, variants of fibrocystic disease, fibroadenomas, cystosarcoma phylloides, and ductal and lobular carcinomas. Monoclonal antibodies were applied to cryosections by the avidin-biotin-complex method; selected samples were studied by double immunofluorescence, and by Western blot analysis. In adult resting and aging breasts, tenascin immunoreactivity was noted in the periductal and periacinar stromal regions as thin irregular bands; in the lactating breast, broader periductal bands were observed. In these samples, laminin immunoreactivity was a single continuous line around ducts, acini, and vessels. In fetal breasts, tenascin appeared as thick periductal bands, whereas laminin remained as a delicate single line. In FCD, tenascin increased around ducts showing hyperplasia, papillomas and apocrine metaplasia, whereas laminin retained its delicate linear pattern. Similar patterns were seen in fibroadenomas and cystosarcoma phylloides with variable tenascin reactivity in the stroma beyond the ducts. Tenascin immunoreactivity was markedly increased around ducts containing in situ carcinoma appearing as broad bands, whereas that of laminin showed a linear, frequently discontinuous appearance. Prominent stromal tenascin immunoreactivity was seen in infiltrating ductal and lobular carcinomas, whereas laminin was virtually absent save for scattered lines. The abundance of tenascin in the carcinomatous stroma contrasted with its scarcity in the non-neoplastic stromal regions. By Western blotting, both chains of tenascin with molecular weights 250,000 and 180,000 were shown in ductal and lobular carcinomas as well as in normal breast. Tenascin immunoreactivity was noted in the periepithelial stromal regions of adult resting and aging breast ducts and acini. The amount of tenascin was moderately enhanced in certain physiologic conditions (fetal growth, gestation), as well as hyperplasias, dysplasias (fibrocystic disease) and benign tumors, whereas it was markedly enhanced in intraductal and infiltrating carcinomas. During fetal mammary development, adult physiologic and pathologic hyperplasias, and in carcinomas, the increasing tenascin reactivity contrasted with the stable or decreasing laminin reactivity.

Left ventricular free wall rupture following acute myocardial infarction and cardiac amyloid.

A 74-year-old man died of left ventricular free wall rupture 6 days following an acute inferoposterior wall myocardial infarction. His hospital course was complicated by pump failure which proved resistant to inotropic support, diuresis, and percutaneous transluminal coronary angioplasty. At necropsy, extensive amyloid deposition was noted. This case constitutes an unusual clinical setting for myocardial rupture because of the severity of systolic left ventricular dysfunction as well as cardiac amyloidosis.