Hodgkin's disease in primary care

Hodgkin's disease is a common hematologic malignancy in young adults. The typical patient is a young adult male presenting with painless cervical adenopathy or a mediastinal mass on chest X-ray. If diagnosed early and aggressively treated, long-term survival rates are excellent. The subtypes of Hodgkin's disease are differentiated by pathologic examination of an affected lymph node. Chemotherapy, with or without adjuvant radiation, is the favored therapeutic regimen for most patients. A comprehensive approach to care, which incorporates psychosocial implications, can improve quality of life for Hodgkin's disease patients.     

Modulation of cloned skeletal muscle sodium channels by the scorpion toxins Lqh II, Lqh III, and LqhαIT

The scorpion alpha-toxins Lqh II, Lqh III, and Lqh alphaIT from Leiurus quinquestriatus hebraeus are representatives of typical alpha-toxins, specific for either mammals (Lqh II) or insects (Lqh alphaIT), and alpha-like toxins (Lqh III) which act on both mammals and insects. For a comparative study of the effects of these toxins on mammalian sodium channels we stably expressed rat skeletal muscle sodium channel alpha subunits (microI) in HEK 293 cells and measured Na+ currents in the whole-cell patch-clamp mode. The alpha- and alpha-like toxins strongly slowed down channel inactivation with a half-maximal effect at 1.4 nM (Lqh II), 5.4 nM (Lqh III), and 0.5 nM (Lqh alphaIT). The recovery from fast inactivation was accelerated by all toxins with the potency sequence: Lqh II>Lqh alphaIT>Lqh III. The voltage dependence of inactivation and recovery from inactivation were reduced while the threshold for activation was only slightly shifted by approximately equal to 10 mV without altering the slope factors, suggesting uncoupling of the impaired inactivation from the activation. The toxins induced an increase in peak inward current, which was accounted for by an increased maximal open-channel probability. Although all three toxins induced similar modifications of the channel properties, their kinetics of association and dissociation were very different. Between -140 and -80 mV toxin association was not voltage dependent. In 100 nM toxin the association time constants were: 1.3 s (Lqh II), 20 s (Lqh III), and 3.8 s (Lqh alphaIT). At positive voltages the toxin dissociated from the channel; at +100 mV the dissociation time constants were 30, 321, and 135 ms, respectively. In contrast to the association, dissociation was voltage dependent with a similar slope of about 12 mV per e-fold change for all three toxins. The strong differences in the association and dissociation kinetics of these toxins may identify them as members of different scorpion alpha-toxin subgroups.     

Successful treatment of severe aplastic anemia by bone marrow transplantation from HLA nonidentical family members: preliminary results utilizing cyclophosphamide and 600 cGY fractionated total body irradiation

We have performed bone marrow transplants on four children with severe aplastic anemia who lacked an human leukocyte antigen (HLA)-identical sibling donor. Patients were prepared with cyclophosphamide and 600 cGy fractionated total body irradiation, and then received marrow from a parent donor mismatched for one (two patients), two (one patient), or three (one patient) HLA antigens. All four patients engrafted. One died early of acute graft-versus-host disease. The three others showed sustained complete hematopoietic reconstitution. Two are alive and hematologically normal 43-87 months after transplant. Both have had acute and chronic graft-versus-host disease (CGVHD), and one of the two remains on immunosuppressive drugs. The fourth died at 48 months after transplant of CGVHD. The previous experience with HLA-incompatible marrow transplants is reviewed, and the rationale for this preparative regimen is discussed. Cyclophosphamide and 600 cGy fractionated total body irradiation is an effective preparative regimen for children with severe aplastic anemia receiving transplants from HLA-nonidentical parental donors, allowing engraftment and full hematologic reconstitution.     

Asymptomatic bacteriuria in normal and high-risk pregnancy

A routine urine culture was performed in 1130 normal pregnant women and in 211 high-risk pregnancies (136 diabetics and 75 women with a previous urinary tract infection). Asymptomatic bacteriuria was found in 5.9% of the normal pregnancies, 12.5% among the diabetics and in 18.5% of the previous urinary tract infection patients. The higher incidence of a clinical urinary tract infection among patients with asymptomatic bacteriuria was found statistically significant (p less than 0.001) in all three groups. A high correlation was found between a negative urine culture in early pregnancy and the absence of development of cystitis and pyelonephritis in later pregnancy. The incidence of asymptomatic bacteriuria in normal pregnant women who developed cystitis later in pregnancy was 33.3% and in those developing pyelonephritis, 66%. In the two high-risk pregnancy groups, the incidence of asymptomatic bacteriuria among those developing clinical infection was even higher, 58.3 and 85.7%, respectively, among the diabetics, and 60 and 66.6% respectively, among the previous urinary tract infection patients.     

Twin pregnancy complicated by single intrauterine death. Problems and outcome with conservative management

During an 11-year period we encountered 16 pregnancies in which one twin died in utero and the pregnancy continued. Eight of these twin pregnancies were monochorionic. None of the women developed severe disseminated intravascular coagulation. The fetal outcome indicates that the prognosis for a surviving dichorionic twin is relatively good, with immaturity the main hazard. By contrast the surviving monochorionic twin has a poor prognosis with a high frequency of neurological damage. This damage is not related to intrapartum or neonatal problems and at present cannot be diagnosed before birth. There is no evidence that birth of the surviving twin by caesarean section will improve the prognosis. Early diagnosis of monochorionic twins and subsequent ultrasound follow up should identify fetal growth discrepancy and possible twin to twin transfusion requiring early delivery.     

Racial Variation in Serum Uric Acid Concentration in Pregnancy: a Comparison between European, New Zealand Maori and Polynesian Women

A prospective study was undertaken to measure serum uric acid levels in normal pregnant women of different races, to ascertain if there was any significant interracial variation. A total of 48 women were studied of which 13 were European, 11 New Zealand Maori, 22 Pacific Islanders and 2 Indian. In the second trimester, European, Maori and Cook Island women had similar uric acid levels and other Polynesian groups showed significantly higher levels. In the third trimester, both Maori and Cook Island women showed a marked rise so that their levels came to equal those of other Polynesian groups, all 3 having significantly higher levels than European women. The importance of these observations relates to the use of uric acid levels in the management of patients with gestational proteinuric hypertension. It is possible that in these cases unusually high results may alarm the clinician into hasty intervention.     

Enhancing in vitro fertilization of mouse oocytes by partial zona pellucida digestion

This work was undertaken in order to evaluate the effect of partial zona digestion on fertilization in vitro of mouse oocytes and assess zona surface changes induced by the procedure. Three hundred forty-six oocytes allocated for treatment were exposed to Ham's F-10 medium supplemented with 0.5% Pronase for either 3 min (188 oocytes) or 5 min (158 oocytes); 324 oocytes served as controls. Oocyte losses incurred as a result of the procedure were small (15 oocytes; 4.3%). Control and Pronase-treated oocytes were each divided into four subgroups and inseminated with 5 ×10 ⁵,5 ×10 ⁴,5 ×10 ³,or 5 ×10 ² sperm cells/ml. Fertilization was assessed 8 hr following insemination by the appearance of two pronuclei and development to the two- to four-cell stage the following day. The morphology of the zona pellucida following Pronase treatment was assessed by phase-contrast and scanning electron (SEM) microscopies performed immediately after treatment. Fertilization rate of control oocytes was 80% at a sperm concentration of 500,000/ml and gradually declined to ~30% at 500 cells/ml. In contrast, treated oocytes inseminated with 500 sperm cells/ml demonstrated a normal rate of fertilization. At this low sperm concentration the longer Pronase treatment was significantly (P < 0.05) more efficient in enhancing fertilization (69 and 88% for 3 and 5 min of Pronase treatment, respectively). Polyspermic fertilization was not observed in any of the subgroups. Phase-contrast microscopic examination of oocytes at the time of Pronase treatment showed an initial swelling of the zona pellucida for 30–60 sec with a time-dependent increase in its transparency. SEM demonstrated that the fine meshlike structure of the outer surface of zona pellucida digested away, leaving a smoother surface. These morphologic changes were not associated with a diminution in sperm binding or penetration. This work demonstrates that partial zona digestion, which causes uniform dissolution of the zona pellucida and reduction of its thickness, is simple and safe. The procedure significantly increased fertilization efficiency at very low sperm concentrations and could, by itself or in conjunction with other methodologies, improve the reproductive capacity of men producing sperm with a reduced penetrating ability.