High sensitivity blood-based M-protein detection in sCR patients with multiple myeloma.

We assessed the ability of a mass spectrometry-based technique, called monoclonal immunoglobulin rapid accurate mass measurement (miRAMM), to extend the analytical range of M-protein detection in serum samples obtained from myeloma patients in stringent complete response (sCR) post-autologous stem cell transplant (ASCT). To aid the M-protein detection post ASCT, the accurate molecular mass of the M-protein light chain at diagnosis was determined in all patients (N=30) and used to positively identify clones in the sCR serum. Day 100 post-ASCT, sCR samples had miRAMM identifiable M-proteins in 81% of patients. Patients who had achieved only a partial remission (PR) pre-ASCT and those with IgG isotypes serum samples had the highest rate of M-protein detection by miRAMM. miRAMM positivity at single time points (day 100, 6 months or 12 months) did not correlate with progression-free survival (PFS). In contrast, sCR patients who did not decrease their miRAMM M-protein intensities in serial measurements had shorter PFS than those whose miRAMM intensities decreased (median 17.9 months vs 51.6 months; P<0.0017). miRAMM M-protein is a more sensitive blood-based test than traditional M-protein tests and could cost effectively aid in serially monitoring complete remission for continue response or biochemical relapse.

The adverse effect of hydrosalpinges on in vitro fertilization pregnancy rates and the benefit of surgical correction.

OBJECTIVE: To test the hypothesis that IVF-ET pregnancy rates (PRs) for patients with tubal factor infertility are decreased in patients with hydrosalpinges and that surgical correction reverses this effect. DESIGN: Retrospective chart review. SETTING: Private practice IVF-ET program. PATIENT(S): Patients (n = 160) undergoing 238 cycles of IVF-ET were stratified into groups based on the presence of hydrosalpinges and whether surgical correction had been performed. Patients >39 years old and patients with male factor infertility were excluded from the study. INTERVENTION(S): Patients with hydrosalpinges were offered surgical correction. MAIN OUTCOME MEASURE(S): Clinical pregnancy defined by an intrauterine gestational sac. RESULT(S): Patients with hydrosalpinges had significantly decreased implantation rates and PRs per transfer (2.8% and 8.5%, respectively) than patients with tubal factor infertility but without hydrosalpinges (15.7% and 38.6%). Surgical correction improved implantation rates and PRs in patients with prior failed cycles (16.1% and 37.5%) and in patients undergoing surgery before IVF-ET (21.8% and 51.7%). The type of surgery performed did not affect success rates in the small number of patients evaluated. CONCLUSION(S): The presence of a hydrosalpinx during an IVF-ET cycle results in significant decreases in implantation rates and PRs. Surgical treatment of hydrosalpinges before IVF-ET cycles improves implantation rates and PRs.

Penicillin-resistant Streptococcus mitis as a cause of septicemia with meningitis in febrile neutropenic children.

PURPOSE: The purpose of this report is to emphasize the importance of occurrence of Streptococcus mitis meningitis in febrile neutropenic children with hematopoietic malignancy. PATIENTS AND METHODS: Symptoms of meningitis and sepsis (fever, headache, changes in mental status) were seen in three patients who were severely neutropenic and undergoing cytotoxic chemotherapy for CNS relapse of their underlying malignancy (acute lymphoblastic leukemia (ALL), n = 2; Burkitt's lymphoma, n = 1). Chemotherapy had included cytosine arabinoside administered 7-14 days prior to presenting with sepsis and meningitis. All three patients had buccal mucositis or sinusitis. Blood cultures and CSF cultures showed S. mitis resistant to penicillin but sensitive to vancomycin. Vancomycin, at a dosage of 60 mg/kg/day to maximize CNS levels of antibiotic, was administered to all three children. RESULTS: Two of the patients recovered from S. mitis meningitis; recovery was associated with an improvement in their peripheral granulocyte counts. One patient, who remained neutropenic, died despite being treated with both intravenous and intraventricular vancomycin. CONCLUSION: Physicians caring for patients who are neutropenic and febrile need to be aware of the risk of meningitis occurring with S. mitis sepsis. Early treatment with high dosages of vancomycin (60 mg/kg/day) and an attempt to limit the duration of neutropenia are important factors in the outcome of such patients.

The predictive value of serum progesterone and 17-OH progesterone levels on in vitro fertilization outcome.

PURPOSE: In order to identify parameters which predict prognosis for success with in vitro fertilization, 17-hydroxyprogesterone and progesterone levels were evaluated in 254 patients undergoing 296 in vitro fertilization cycles. Selected response and outcome data were recorded. RESULTS: Patients with intermediate values of serum progesterone (0.7-0.8 ng/ml) at the time of human chorionic gonadotropin administration achieved significantly higher pregnancy rates than patients with lower (< 0.7 ng/ml) or higher (> 0.8 ng/ml) levels. The clinical pregnancy rates were 46%, 31%, and 27% respectively (P = 0.02). There was no change in 17-hydroxyprogesterone concentration which predicted a higher pregnancy rate. CONCLUSION: Excellent clinical pregnancy rates were noted in cycles with a progesterone level of 0.7-0.8 ng/ml, as well as good results in cycles above 0.8 ng/ml. There is therefore no reason to administer human chorionic gonadotropin at a smaller follicle size to prevent a rise in serum progesterone.

Tumor necrosis factor alpha inhibits signaling from the insulin receptor.

Insulin resistance is a common problem associated with infections and cancer and, most importantly, is the central component of non-insulin-dependent diabetes mellitus. We have recently shown that tumor necrosis factor (TNF) alpha is a key mediator of insulin resistance in animal models of non-insulin-dependent diabetes mellitus. Here, we investigate how TNF-alpha interferes with insulin action. Chronic exposure of adipocytes to low concentrations of TNF-alpha strongly inhibits insulin-stimulated glucose uptake. Concurrently, TNF-alpha treatment causes a moderate decrease in the insulin-stimulated autophosphorylation of the insulin receptor (IR) and a dramatic decrease in the phosphorylation of IR substrate 1, the major substrate of the IR in vivo. The IR isolated from TNF-alpha-treated cells is also defective in the ability to autophosphorylate and phosphorylate IR substrate 1 in vitro. These results show that TNF-alpha directly interferes with the signaling of insulin through its receptor and consequently blocks biological actions of insulin.

Age-related cysteine uptake as rate-limiting in glutathione synthesis and glutathione half-life in the cultured human lens.

The study included human lenses of ages ranging from newborn to 92 years. Protein-free reduced glutathione decreased 14-fold, whereas protein-free oxidized glutathione increased 2.6-fold with increasing age. L-Cyst(e)ine uptake g-1 lens of very old cultured lenses decreased 70% from that exhibited in newborn lenses, demonstrating a marked decline of L-cyst(e)ine uptake as a function of age. In these same lenses the synthesis of reduced glutathione (mumol g-1 lens) decreased 73% with age. It was concluded that the glutathione decrease observed in the aging human lens was associated with decreased uptake of L-cyst(e)ine, decreased glutathione synthesis and possibly an increase in protein-free oxidized glutathione. The high correlation of L-cyst(e)ine uptake and glutathione synthesis supports the hypothesis that L-cyst(e)ine uptake is a rate-limiting factor of glutathione synthesis in the intact human lens. By the use of buthionine sulfoximine, the half-life of glutathione was estimated to be 90 hr in the cultured human lens.

Cysteine and glutathione metabolism in organ-cultured rat corneas.

The capability of organ-cultured rat corneas to metabolize cysteine and synthesize glutathione was assessed by use of radioactive L-cyst(e)ine. Metabolites from protein-free tissue extracts were separated and quantified by HPLC, using radioisotope and ultraviolet detectors. Most of the radioactivity detected in the rat cornea was found in three areas of the HPLC elution profile: 1) reduced glutathione, 2) cystine and 3) in a rapidly eluting area (the 'five-minute' area) consisting of several unidentified peaks. The proportion of radioactivity found within the five-minute area increased with time of incubation and became the dominant radioactive peak area by 48 hours of incubation. In contrast to rat lens extracts, the synthesis of glutathione in rat cornea formed a minor portion of the L-cysteine metabolic products. The unlabeled reduced glutathione concentration was relatively stable over a 48-hour incubation period. Synthesis of glutathione was prevented by 0.3 mM buthionine sulfoximine, resulting in more than 90% of the radioactivity being contained in the five-minute peak area. Inhibition of glutathione synthesis allowed the estimation of glutathione's half-life to approximate 10.5 hours in the organ-cultured rat cornea.

Conditions for maximizing and inhibiting synthesis of glutathione in cultured rat lenses: an application of HPLC with radioisotope detection.

This investigation was concerned with factors which would maximize and inhibit L-cyst(e)ine uptake and glutathione synthesis of rat lenses cultured for 24 hours in a medium containing [35S]-L-cystine. The lenticular protein-free extract was separated and quantified by use of HPLC equipment which included an in-line radioisotope detector coupled with extensive post-run computer analysis. Six thiols were assessed for their ability to increase the uptake of L-cyst(e)ine and its utilization for glutathione synthesis. The most successful was 2-mercaptoethanol, which increased the L-cyst(e)ine uptake 3.6-fold and glutathione synthesis 2.9-fold. This work demonstrated that the rate of glutathione synthesis was directly proportional to the rate of uptake of L-cyst(e)ine. An inhibitor of glutathione synthesis, buthionine sulfoximine, in a concentration range of 0.11-3 mM, decreased uptake of the [35S]-label by one-third. The 3.0 mM concentration inhibited glutathione synthesis 98.7% and decreased glutathione 51% in 24 hours. The data indicate that half the glutathione disappeared in 23 hours in these cultured rat lenses. Because determination of this value did not depend upon the variable rate of cysteine transport, the value may approximate the in vivo value.

Glutathione synthesis and glutathione redox pathways in naphthalene cataract of the rat.

This investigation examined many parameters during the course of early development of naphthalene-induced cataract in a time span of 0 to 79 days of treatment. Feeding naphthalene daily to Black-Hooded rats resulted in gradual progressive development of cataract. The first faint opacities were detectable after 7 days. Free soluble total glutathione (oxidized and reduced) of these lenses was shown to gradually decrease to a maximum loss of about 20%, a value reached by day 30 of treatment. No activity loss of either enzyme required for glutathione synthesis (gamma-glutamylcysteine synthetase or glutathione synthetase) was observed in homogenates of naphthalene versus control lenses. There was also neither impairment of [35S]-L-cystine uptake nor of [35S]-glutathione synthetic capacity in lenses cultured from rats after 12, 24 or 36 days of naphthalene feeding when compared to control lenses. Hence, glutathione loss cannot be explained by a damaged glutathione synthesis system. Progressive activity loss of glutathione peroxidase and glutathione reductase was observed. The loss of glutathione peroxidase activity was especially remarkable. Thus, the defense system against oxidative damage is impaired and may be a significant factor in naphthalene-induced cataract of the rat.

Oral clomiphene citrate and vaginal progesterone suppositories in the treatment of luteal phase dysfunction: a comparative study.

Oral clomiphene citrate (CC) and vaginal progesterone suppositories (PS) are common treatment modalities in luteal phase dysfunction (LPD). Little is known regarding the relative efficacy of these agents. To study the use of CC and PS in the management of LPD, a retrospective cohort study of patients presenting with infertility was undertaken. Sixty-five patients in whom LPD was diagnosed and corrected, as judged by endometrial biopsies, were studied; 35 were treated with PS and 30 with CC. Using Student's t-tests and chi-square analyses, the two treatment groups were demographically comparable. Using life-table analysis, no one therapeutic approach proved superior. Clomiphene citrate and PS are comparable treatment modalities in the setting of LPD given correction of endometrial lag.

Central venous catheter infections in pediatric patients--in a community hospital.

We reviewed the records of 23 pediatric patients who had received at least one central venous catheter during a two-year period. Nine patients had acute lymphoblastic leukemia (ALL), nine had other hematologic/oncologic diagnoses, and five had cystic fibrosis. Twenty-nine of 65 febrile episodes in 16 patients were associated with a catheter-related infection. Twenty of 40 catheters were associated with an infection over a period of 7,229 catheter days. For every 1,000 catheter days, four episodes of infections were observed. The number of infections/1,000 catheter days, the average life of a catheter (approximately equal to 180 days), and mean number of days elapsing before the first infection were not significantly different in the three diagnostic groups. Broviac catheters were used most often (24/40), followed by Quinton (9/40) and Port-a-Cath (7/40). Broviac catheters lasted twice as long (224 days, p less than 0.01) as Quinton and Port-a-Cath. Gram-positive cocci were isolated most frequently and Staphylococcus epidermidis was the most common pathogen. No consistent relationship between an absolute neutrophil count of less than 1,000/mm3 and infection with gram-positive cocci was seen. However, seven of eight episodes of gram-negative bacillary infections occurred in patients with an absolute neutrophil count of less than 1,000/m3 (p less than 0.005). Those patients who were not considered terminally ill responded well to antimicrobials. Catheter removal was necessary in only two instances.

Receptors for 5-hydroxytryptamine in rabbit blood vessels: activation of alpha adrenoceptors in rabbit thoracic aorta.

Experiments were carried out to identify the receptors mediating the contraction of the rabbit thoracic aorta to 5-hydroxytryptamine (5-HT). Isolated aortic rings were mounted in tissue baths for the measurement of isometric contraction and 5-HT dose-response curves were obtained in the presence and absence of receptor antagonists. Prazosin, 1 X 10(-7) M, or 30-min pretreatment with 1 X 10(-5) M benextramine had no effect on the contractile response of aorta to 5-HT up to 1 X 10(-5) M, whereas 2 brom-D-lysergic acid diethylamide, 1 X 10(-7) M, shifted the 5-HT dose-response curve far to the right. Alpha receptor blockade with either prazosin or benextramine in the presence of 2 brom-D-lysergic acid diethylamide produced a greater blockade than that caused by 2 brom-D-lysergic acid diethylamide alone. When 5-HT dose-response curves were extended to 1 X 10(-3) M, three phases were identified. The first, a dose-related contraction, was mediated exclusively by serotonergic receptors. The second, a relaxation to approximately 40% of maximum, occurred at 1 X 10(-5) M and appeared to result from the rapid development of tachyphylaxis. The third phase was a dose-related contraction to concentrations of 5-HT above 1 X 10(-5) M and was inhibited by either prazosin or pretreatment with benextramine. Similar results were obtained in aortic rings from reserpine-pretreated rabbits. It is concluded that the contractile response to concentrations of 5-HT below 1 X 10(-5) M is mediated exclusively by serotonergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Postoperative neurosurgical infections due to bacillus species.

The cases of 2 patients with postoperative ventriculitis due to Bacillus species bacteria are presented. Bacillus licheniformis was isolated from one patient following removal of an intraventricular meningioma, and Bacillus cereus from another patient following placement of a ventriculoperitoneal shunt. Both isolates were resistant to a variety of antibiotics, but both were sensitive to gentamicin and chloramphenicol. These cases emphasize several points; (a) Bacillus species, usually thought to be nonpathogenic, may produce intracranial infections; (2) species identification is important for epidemiological purposes and for the selection of appropriate chemotherapeutic agents; and (3) in cases of suspected ventriculitis, chloramphenicol or gentamicin should be considered for Gram's staining revealing gram-positive bacilli. In addition, we recommend that when planning antibiotic prophylactic regimens, consideration should be given to including one of these agents to assure coverage of Bacillus species.

Multiple splenic aspergillomas in a patient with acute lymphoblastic leukemia.

A case of multiple splenic aspergillomas (mycetomas) without systemic involvement is a patient with acute lymphoblastic leukemia is described. The patient underwent splenectomy without concomitant antifungal therapy. There has been no recurrence of the disease for over two years. Granulocytopenia and airborn contamination may have played a role in the acquisition of this disease. The value of serology, radionuclide scans and cultures in the diagnosis of Aspergillus infections is explored. The role of granulocyte transfusions, antifungal chemotherapy and the achievement of bone marrow remission in localization of the fungal disease is discussed.

Pyogenic osteomyelitis versus pseudo-osteomyelitis in Gaucher's disease. Report of a case and review of the literature.

Presented is a young girl with Gaucher's disease who developed acute bone pain accompanied by signs of inflammation and who was felt to have possible pyogenic osteomyelitis. The lack of significant pathogenic bacterial growth on culture and the findings at orthopedic surgery led the authors to conclude that this child probably represented a case of pseudo-osteomyelitis, but the isolation of an anaerobe from the operative culture of the involved bone leaves the exact diagnosis unclear. Since this child underwent an open surgical procedure, she was treated with antibiotics to prevent the possible development of chronic osteomyelitis. This anaerobic growth on culture, although strongly felt to be a contaminant, also played a role in this decision. She had an uneventful hospital course and subsequently has done well. It is suggested that great caution be taken before subjecting a patient with Gaucher's disease to orthopedic surgical procedures. If pyogenic osteomyelitis is strongly suspected, obtaining multiple blood cultures and culture by needle aspirate may be preferred over an open surgical procedure. The use of empiric antibiotic therapy without an attempt at further diagnosis is not recommended. If an orthopedic surgical procedure is necessary in a patient with Gaucher's disease, antibiotic coverage is indicated and long-term observation of the operative sight for drainage and/or other signs of chronic inflammatory changes in mandatory.