Deflazacort and fluoximesterone in advanced, pretreated breast cancer. A very simple, low dose, orally administered regime (10 to 15 mg of fluoximesterone + 6 mg of deflazacort daily for periods of 1 to several months) resulting in mild-acceptable toxicity (essentially some weight gain) determined subjective improvement in 2/3 of 34 evaluable patients (out of 36 treated) and an objective measurable tumor reduction in 1/3, although most patients had been previously treated with chemotherapy and hormone treatment and proved primarily or secondarily refractory. The receptor status at the beginning of fluoximesterone+deflazacort treatment was not known, except in one negative-receptor patient, who responded to the combination after becoming resistant to tamoxifen (see photo). In some patients the condition of hormone refractoriness would suggest a no-treatment policy, but a trial with this regime is always convenient as it may improve both duration and quality of life.


Endobronchial metastases in colorectal adenocarcinoma. Between 1982 and 1990, 2388 bronchoscopic examinations were carried out in patients with cancer in our hospital. A diagnosis of endobronchial metastasis was established in 30 patients (2.09%), with the following primary tumors in descending order of frequency: breast, large bowel, melanoma, neuroblastoma, leiomyosarcoma and endometrial. Despite the rarity of endobronchial metastases secondary to colon adenocarcinoma, we were able to study 3 cases from our Center. In one case the diagnosis of endobronchial metastasis was simultaneous with that of the primary tumor, and in the other 2 this metastatic complication occurred 16 and 42 months, after the original diagnosis. When this complication occurred, the stage of the disease was advanced in all 3 cases: 2 were Dukes' stage C and one stage D. Although this metastatic location usually implies a very negative prognosis as regards life expectancy, it did not seem to significantly reduce the latter in our patients.


Hyalinizing trabecular adenoma of the thyroid. Report of two cases, with cytologic, immunohistochemical and ultrastructural studies. The cytologic, histologic, immunocytochemical and ultrastructural features of 2 cases of hyalinizing trabecular adenoma (HTA) of the thyroid are described. The difficulty of a cytologic diagnosis and the need for an immunohistochemical profile of the lesions for a final histologic diagnosis are emphasized.


Primary Hodgkin's disease of the stomach. A case report. Primary gastric Hodgkin's disease is rare and has been reported in only 2% of patients with primary gastric lymphomas. Its existence is quite controversial, and new immunohistochemical techniques and flow cytometry have reduced the frequency of diagnosis of this pathology. The authors describe a case of primary gastric Hodgkin's disease in a 61-year-old woman.


Teleangiectatic sarcomatoid carcinoma of the breast. We report a case of breast carcinoma in a lactating woman with an osteosarcomatous and chondrosarcomatous metaplasia and multicystic hemorrhagic appearance. Grossly and on low microscopic power it simulated a teleangiectatic osteosarcoma. Clinical and mammographic presentation and fine needle aspiration biopsy initially suggested a hemangioma which resulted in delayed treatment.


Prophylactic effect of a Lactobacillus casei preparation on the recurrence of superficial bladder cancer. BLP Study Group. A randomized controlled study was conducted in patients with superficial bladder cancer in order to investigate the safety of an orally administered (3 g/day) Lactobacillus preparation, biolactis powder (BLP), and its preventive effect on the recurrence after transurethral resection of the bladder tumor (TUR-Bt). Of 58 cases enrolled in the study 23 cases in the BLP group and 25 cases in the control group completed the study. There were no significant differences in the patient characteristics for the complete cases between the two groups. Comparison of the disease-free duration by the Kaplan-Meier method revealed that the 50% recurrence-free interval after TUR-Bt was prolonged by BLP treatment (350 days) to 1.8 times that in the control group (195 days). A significant difference between the groups was detected by the long-rank test (p = 0.03). No adverse side effect was observed. The results suggest that oral administration of BLP is useful for the prevention of the recurrence of superficial bladder cancer.


Value of serum laminin P1 as a diagnostic and monitoring parameter in transitional cell carcinoma of the bladder. In a combined (cross-sectional and longitudinal) study, the serum concentration of laminin P1 was measured by radioimmunoassay in 16 patients with benign inflammatory bladder disorders and 47 patients with transitional cell carcinoma of the bladder. The results were compared with the serum laminin P1 values in 50 healthy control subjects. In the cross-sectional study, the mean value of serum laminin P1 was significantly higher in bladder cancer patients than either the controls (p < 0.0001) or patients with benign inflammatory bladder disorders (p < 0.001). Similarly, the mean values of all different stages of grades of the tumor were significantly higher than either the controls or patients with benign inflammatory disorders. Progressive increase in the mean values of serum laminin P1 could also be found with deterioration of the stage or grade of the tumor. However, the difference between the mean values of the different cancer stages or grades did not reach statistical significance. In the longitudinal study, no significant difference could be detected between the mean values of patients with superficial tumor recurrence and those with remission of the disease (p > 0.5). Nevertheless, in the invasive cancer group, the levels of serum laminin P1 were directly proportional with progression of the disease (Z = 2.94; p < 0.01).


Endocrine treatment prior to radical retropubic prostatectomy in patients with T3 prostate cancer: a retrospective study of 22 patients. Twenty-two patients with locally advanced prostatic carcinoma stage T3, N0, M0 have been treated with LH-RH agonists during a mean time of 5 months prior to radical retropubic prostatectomy. Although tumors appeared to be confined to the organ in 68% of the patients after endocrine treatment, pathological examination of the surgical specimens showed in 89% evidence of extraprostatic disease, which questions the clinical impression of 'downstaging'. A disparity between the tumor grade of the biopsy and that of the operative specimen as well as an increased size of tumor-involved lymph nodes despite endocrine treatment led us to speculate that a certain proportion of patients will bear the risk of disease progression during preoperative androgen deprivation. Furthermore, there was local recurrence early in the postoperative course and at the high rate of 39%.


Effects of vasoactive intestinal polypeptide on isolated rat urinary bladder smooth muscle. The effect of vasoactive intestinal polypeptide (VIP) on the contractile activity of the urinary bladder was investigated in the rat. VIP caused a weak contraction and a small potentiation of carbachol- and acetylcholine-induced contractions. The present results may provide the evidence that VIP could be a modulator in the urinary bladder.


Testicular dysplasia causing disturbance of spermiogenesis in patients with unilateral torsion of the testis. Fifty-five patients were followed up for their state of fertility at a time varying in length after testicular torsion. In addition to the spermiogram they were screened for sperm antibodies. Biopsy samples were collected from the contralateral (not contorted) testis in 34 patients at the time of torsion or immediately afterwards. Two to 8 years after torsion only 7 out of 55 patients had a normal spermiogram. Nineteen had an OAT syndrome, 10 had asthenospermia and 19 had teratospermia. Sperm antibodies occurred very rarely at the time of torsion (2/36) or at the time of a further checkup (2/36). Immunological damage to the noncontorted testis by the contorted one seems therefore rather unlikely. Histology of the contralateral testis, the samples of which were taken at the time of torsion (30) or up to 4 months later (4), showed pathological conditions in 30/34 cases (desquamation of the germinative epithelium, atrophy of the Leydig cells, malformation of spermatoblasts) and normal spermiogenesis in 4 cases only. Hence, a preexistent congenital testicular dysplasia must be assumed to be the cause of the observed disturbance of spermiogenesis and reduced fertility.


Seminal plasma transferrin concentration: relationship with seminal parameters and plasma hormone levels. Seminal plasma transferrin concentrations were determined in 155 infertile male patients and in 15 pregnancy-proven fertile males (control group); then the relationship between these concentrations and seminal parameters and plasma hormone levels was investigated. The concentrations of seminal plasma transferrin in patients with a sperm concentration below 20 x 10(6)/ml were significantly lower than those in the control group (p < 0.01). There was no significant difference in seminal plasma transferrin concentration between patients with a sperm concentration of 40 x 10(6)/ml or more and the control patients. A positive correlation was observed between sperm concentration and seminal transferrin content (r = 0.56; p < 0.05). However, correlations between seminal transferrin concentration and sperm motility and between seminal plasma transferrin content and sperm morphology did not show any significance, nor did the seminal transferrin content correlate with plasma LH, FSH, prolactin or testosterone levels. It, therefore, seems that while transferrin is indicative of certain physiopathological conditions in the germ cells, this protein is not a distinctive marker of the fertility potential of an individual.


Candida antigen detection by a latex agglutination test in candiduria patients. We evaluated a latex agglutination test commercially available in kit form for the identification of Candida pyelonephritis in candiduria patients. Tests were performed on sera from 11 patients with fever and candiduria plus other positive candidal sites (group A), 12 patients were fever and candiduria alone (group B), 17 afebrile patients with candiduria alone (group C), and 27 afebrile patients without documented candiduria or bacteriuria (group D). Positive antigenemia with a titer of 1:4 or greater was detected in 9 candiduria patients with fever: 7 (63.6%) in group A and 2 (16.7%) in group B. The incidence of group B, in which Candida pyelonephritis was strongly suspected, was significantly less than that of group A and did not significantly differ from that of groups C and D. These results suggest that this test has little value in the diagnosis of Candida pyelonephritis without disseminated candidiasis.


ESWL of stones in the mid-ureter.

ESWL of stones in the mid-ureter. Two hundred and twenty patients with a ureteric calculus were treated by in situ ESWL; in 60 of these the stone was located in the mid-ureter. Treatment was given without anesthesia or with sedoanalgesia only. Complete or partial stone clearance at the time of discharge from hospital was achieved in 95% irrespective of the site of the stone and there were no complications. It is suggested that in situ ESWL is effective in the treatment of stones in mid ureter as well as those in upper and lower ureter.


Pseudo-adrenal incidentaloma: magnetic resonance imaging in a patient with para-adrenal Castleman's disease. We report a case of para-adrenal angiofollicular lymph node hyperplasia (Castleman's disease) of the hyaline-vascular type. The mass could not be differentiated from an adrenal tumor by ultrasonography and computed axial tomography (CT). However, magnetic resonance imaging (MRI) suggested the possibility of an extra-adrenal origin of the mass. The intensity of the mass by MRI was homogeneous and of a higher intensity in the T2-weighted image than in the T1-weighted image, a finding similar to lymphadenopathy, lymphatic tumorous mass or metastatic tumor of the lymph node. Ultrasonography, CT and MRI may not be useful in characterizing Castleman's disease, but MRI was useful to distinguish asymptomatic para-adrenal masses from those of adrenal origin.


Small hyperechoic renal tumors displaying no fat content on CT. We report two cases of small renal adenocarcinoma and one case of small angiomyolipoma, which were identified as hyperechoic tumors by ultrasonography. None of the three tumors displayed fat content on plain CT. Since CT cannot reliably identify the intratumoral structure of small hyperechoic renal tumors, we recommend intraoperative pathological examination when CT findings do not correspond with the results of ultrasonography.


Paraurethral actinomycosis.

Paraurethral actinomycosis. Actinomycosis of the genitourinary tract is rare. Herein we report a case of actinomycosis of the urethra following staged hypospadia repair. Pathophysiology and treatment options of this rare lesion are discussed.


Growth factors in urologic tissues: detection, characterization, and clinical applications. During the last two decades, enormous strides have been made in understanding cellular and molecular biology. The direction of treatment of many neoplasms and other diseases are starting at the microscopic level. Growth factors are polypeptides that play a part in the development and maintenance of living tissues. We, as well as others, have investigated the role that growth factors play particularly in urologic tissues, both benign and malignant. We review several well-known growth factors and their function in prostate, kidney, and bladder tissues, as well as their functions in other regulating processes of the human body, and also the use of growth factors as tumor markers, and antibodies to growth factors as possible treatment of disease.


Renal tumors in young adults.

Renal tumors in young adults. Primary renal malignancies are relatively rare in young adults. Eighteen patients between the ages of twenty and forty years underwent nephrectomy for renal tumors at our institution between 1947 and 1989. Data were reviewed in this group regarding method of presentation, duration of symptoms, tumor histology, pathologic stage, and survival. Tumor histology parallels that of older patients, the majority being adenocarcinoma (78%). The duration of symptoms prior to seeking medical attention was long, averaging eighty-four weeks. The overall survival rate, excluding nontumor deaths, was 50 percent. No patient with nodal or distant metastases survived, regardless of histology.


Traumatic dislocation of testes and bladder rupture. Traumatic dislocation of the testes with bladder rupture occurred in 2 multiply injured patients with pelvic fracture. One had a history of retractile testes and the other of previous testicular dislocation. Surgical correction was performed after closed reduction failed. These injuries must be recognized and treated promptly to maximize the likelihood of testicular salvage. If early intervention is not possible, duplex ultrasonography and pulsed Doppler analysis are the optional valuative studies.


Urothelial tumors of upper tract following treatment of primary bladder transitional cell carcinoma. We studied, retrospectively, the incidence of upper tract urothelial tumors following the treatment of primary transitional cell carcinoma of the bladder in 638 patients. Subsequent tumor development was found in 20 patients (3.1%) with a mean latency interval between initial treatment of the bladder cancer and diagnosis of the upper urinary tract tumor of eighty months. We did not find a significant difference among treatment modalities on the incidence of upper tract occurrences. Other than carcinoma in situ, tumor stage was not an independent predictive variable.


Pneumoscrotum: report of two cases and review of mechanisms of its development. Scrotal emphysema and, less frequently, pneumatocele are uncommon signs of pneumoscrotum caused by a variety of pathogenic and iatrogenic disease processes. The finding of air in the scrotal sac may be an early sign of a life-threatening condition or may represent an incidental finding associated with more benign conditions. The three basic mechanisms by which air becomes localized to the scrotum are discussed, the literature is reviewed, and 2 new cases are presented.


Follow-up of clean intermittent catheterization for children with neurogenic bladders. Intermittent catheterization remains the primary method of treatment in the management of patients with neurogenic bladders such as those with meningomyelocele. In a follow-up of a previous study, we re-examined the urologic status of patients with neurogenic bladders continuing on a regimen of clean intermittent catheterization five years after the completion of the first study. Thirty-seven of the original 49 patients were available for follow-up, and no significant differences were found between those lost to follow-up and those included in this study. Among the patients re-evaluated, reflux remained unchanged or improved in most patients, renal function was maintained, and the urinary tract infection rate remained low. Additionally, continuation of an intermittent catheterization program does provide independence and social continence in most young adults with meningomyelocele. We conclude that a long-term intermittent catheterization program is associated with stable reflux status, renal function, and infection rate, and that compliance with a catheterization program can result in improved social continence and independence.


Urachal abscesses: protean manifestations, their recognition, and management. We present the manifestations, their recognition, and treatment of urachal disorders, as well as report on 3 cases of urachal abscess in children. A review of the English literature is included.


Primary congenital bladder diverticula in boys. Three male patients ranging in age at diagnosis from eight to seventeen years were found to have presumed primary congenital bladder diverticula. All 3 patients had a solitary documented urinary tract infection (Staphylococcus 2, Escherichia coli 1), 1 patient presented with gross hematuria, and in 1 patient the diverticulum was an incidental finding. In all cases, there was no radiologic evidence on voiding cystourethrography of physiologic or anatomic ureteral or bladder outlet obstruction. In a nine-year-old boy there was ipsilateral renal agenesis, an intra-abdominal undescended testis, and an atretic ureter arising from the diverticulum. The older boy had Ehlers-Danlos syndrome. If the diverticulum is enlarging, compromises the ureterovesical valve mechanism, or by virtue of incomplete bladder emptying is believed to promote urinary tract infection, it should be removed. A surgically conservative course is followed in the Ehlers-Danlos syndrome because of the bleeding tendency and tissue abnormalities.


Primary melanoma of urinary bladder.

Primary melanoma of urinary bladder. The fourth case of primary melanoma of the bladder is presented together with a review of the previously reported cases and the relevant literature on malignant melanoma in urology. The criteria for classification of the bladder lesion as the primary site are discussed. The eighty-one-year-old female patient was felt not to be suitable for extensive surgery and was successfully treated with a combination of radiation and immunotherapy with recombinant alpha 2 interferon. After previous monthly recurrences of the tumor the patient is in complete remission fifteen months after initiation of therapy. It appears that this form of treatment might be a valuable alternative to radical surgery in elderly patients.


Incidental prostate adenocarcinoma in a thirty-year-old Native American. We report a case of prostatic adenocarcinoma in a thirty-year-old Native American. The tumor was an incidental autopsy finding. We speculate on the biological and clinical significance of prostate tumors in young males.


Effect of early bladder stimulation on spinal shock: experimental approach. The period of spinal shock which frequently follows spinal cord injury is associated with bladder areflexia and urinary retention. We studied the effect of early bladder electric stimulation on detrusor activity during the spinal shock phase in the dog. The animals had a spinal cord section at T10 vertebra, and their bladder management was assigned to one of the three following groups: intermittent catheterization, indwelling catheterization, and electric bladder stimulation. The parameters for evaluating each treatment included: blood chemistry, and radiographic and urodynamic tests. The most important finding was the early return of detrusor activity in the group of animals treated by early electric stimulation of the bladder.


Combined effect of interleukin 2 and cyclophosphamide in therapy of mice with transitional cell carcinoma. We investigated the effect of combination therapy with interleukin 2 (IL-2) and cyclophosphamide (CPM) in C3H/HeN mice implanted with mouse bladder tumor cells (MBT2). MBT2-bearing mice were treated with a single intraperitoneal injection of 120 mg/kg CPM on day 10 and/or subcutaneous administration of 5 x 10(4) units IL-2/day from day 11 to day 20. As a result, the growth of tumor in mice treated with IL-2 alone was slightly suppressed. On the other hand, regression was observed in all mice treated with CPM alone, although regrowth of tumor was seen in all of them. However, when IL-2 was administered with CPM, regrowth of tumor was completely suppressed. An immunologic study was done that showed cytotoxicity against YAC-1 and P815 in the spleen cells was suppressed in mice treated with CPM alone, but that both recovered to control levels when IL-2 was administered with CPM. Cytotoxicity against MBT2 in the spleen cells was most elevated in mice treated with both IL-2 and CPM. These findings suggested that clinical evaluation of combination therapy with IL-2 and CPM may be worthwhile.


Managing superficial bladder cancer: an overview. More than 90 percent of bladder cancers are transitional cell carcinoma (TCC). Superficial TCC is defined as a transitional cell tumor that is confined to the mucosa (Stages Ta or carcinoma in situ) or that has invaded the lamina propria (Stage T1). When treating patients with superficial bladder cancer, urologists are faced with a number of important tasks. First, the initial tumor or tumors must be removed. Second, the other parts of the urothelium must be assessed for the presence of premalignant or malignant abnormalities. Third, the depth and extent of invasion (i.e., tumor stage) must be determined. Fourth, the clinician must decide whether additional treatment (e.g., intravesical chemotherapy or immunotherapy, cystectomy, or radiotherapy) is indicated. Finally, the patient must be monitored for the development of subsequent tumors. This article provides an overview of the management of superficial bladder cancer.


Clinicopathological investigation of primary, uncomplicated maedi-visna virus infection. Maedi-visna virus infection in a flock of sheep in Scotland was associated with respiratory disease, neurological disease, mastitis and lameness. The major clinical signs were dyspnoea (particularly on exercise), progressive fore- and hindlimb ataxia and balance defects, mammary induration and multilimb lameness, occasionally with enlarged carpal joints. Pathological examinations revealed lesions in the lungs, central nervous system, mammary glands and joints which were consistent with those induced by maedi-visna virus. The was no clinical or pathological evidence of concurrent sheep pulmonary adenomatosis, and pulmonary bacterial infections, when they occurred, were superimposed on the lesions due to maedi-visna virus.


Trial of the efficacy and immunological response to an inactivated mycoplasma F38 vaccine. Goats on two zero grazed farms carrying 1621 animals with a history of contagious caprine pleuropneumonia were subjected to a vaccine trial with an inactivated mycoplasma F38 vaccine. The results indicated that the vaccine produced an immune response, that it was very effective in reducing morbidity and mortality rates, and that a booster dose one month after the first dose of vaccine gave extra protection.


Pathogens in dog bite wounds in dogs in Harare, Zimbabwe. Over a year swabs were taken from 87 untreated bite wounds in dogs seen by veterinary practitioners in Harare, Zimbabwe. Swabs were also taken from normal skin adjacent to the wound site, and gingival swabs were collected from normal dogs coming to the same clinics. The swabs were cultured aerobically for pathogens, particularly Staphylococcus intermedius, and the antibiotic sensitivities of the pathogens were determined by disc diffusion assay. The most common pathogens isolated from the wounds were S intermedius (23 per cent), Escherichia coli (18 per cent) and non-lactose-fermenting coliforms (14 per cent). S intermedius was common on the normal skin of the dogs with infected wounds, and was associated with wounds on the abdomen, hindlimbs and tail and wounds that were more than three days old. This organism was, however, isolated only infrequently from the gums and there was little correlation in general between the prevalence of pathogens in the mouth and their prevalence in wounds. Of the S intermedius isolates from wounds, 30 per cent were resistant to penicillin and multiple antibiotic resistance was common among the enterobacterial isolates. The majority of the pathogens were sensitive to cotrimoxazole.


Changes in the plasma concentrations of lipids and lipoprotein fractions in dogs infected with Leishmania infantum. A study was made of serum concentrations of cholesterol, phospholipids, triglycerides, cholesterol bound to high-density lipoproteins (HDL), HDL1-cholesterol, HDL2-cholesterol and cholesterol bound to low-density lipoproteins (LDL) in 16 dogs naturally infected with Leishmania infantum (ZMON-1) taken from an endemic focus. Results were compared with those of a control group of ten healthy dogs. Statistically significant increases in cholesterol, triglyceride and LDL-cholesterol levels were observed. There was, however, a statistically significant decrease in HDL-cholesterol level, mainly at the expense of the HDL2-cholesterol subfraction. Cholesterol transport is therefore shown to undergo changes which may be attributed to the consumptive evolution of the disease, immunocomplex deposits in cells, hepatic disorders and interactions between the parasite and the normal cholesterol metabolism of the host.


Interaction of parasitism and nutrition in goats: effects on haematological parameters, correlations, and other statistical associations. Weaned wether goats (n = 144) approximately 6 months of age were placed in a 2 x 3 factorial experiment to test the effects and interaction of two levels of nutrition (growth+maintenance, NUT1; and twice growth+maintenance, NUT2) and three levels of Haemonchus contortus burden (0, 500, and 2000 larvae administered every 2 weeks; W0, W500, and W2000, respectively) on packed cell volume, red blood cell count, total serum protein and leukocytes. The statistical analysis revealed clear and proportionate differences among levels of infection for all variables. A significant (P < 0.05) nutritional effect was also found associated with all the variables except leukocytes. Nutrition by worm load interactions were found for packed cell volume and leukocytes. The neutrophil/lymphocyte ratio was higher in the NUT1-infected animals, leading to the nutrition by worm load interaction for leukocytes. An analysis for the different leukocyte types revealed significant (P < 0.05) differences among infection levels for lymphocytes, while nutrition level was found to be a significant effect for basophil count and immature white cells. Several significant correlations were observed between pairs of variables. Faecal egg output could be predicted from actual worm count in three of the four necropsy periods. The clear differences observed for blood parameters were not present in production traits, suggesting that physiological thresholds may play an important role in framing the metabolic activity of biological organisms. Total serum protein was the best indicator of these effects on production parameters.


Seasonal patterns of total and Ostertagia-specific IgE in grazing cattle. Serum samples, collected monthly from January through December 1988 from 10 cows, their calves, and 10 yearling heifers, were used to determine total and Ostertagia-specific IgE levels. In addition, serum pepsinogen concentration, fecal egg counts, and body weights were measured. The following observations were made. (1) Total and Ostertagia-specific IgE levels followed similar seasonal patterns, being generally highest in the spring. (2) Breed and/or sire effects on total IgE levels were observed, with cattle from Angus-cross lines having higher levels than cattle of the other breeds tested. (3) Based on fecal egg counts, adult populations of Ostertagia ostertagi paralleled circulating IgE levels in the calves.


Immunoglobulin E recognition of Dirofilaria immitis antigens is more specific than immunoglobulin G. The chronological development of the serum IgE and IgG response to microfilaria, third and fourth stage larvae, and male and female adult Dirofilaria immitis was examined by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunoelectrotransfer blot (EITB). Dirofilaria immitis-specific IgE and IgG levels peaked 16-18 weeks post-infection after increasing in response to the fourth larval molt. Specific IgG levels plateaued after patency, while IgE continued to decline. The use of ammonium sulfate cut sera showed there was no quenching or blocking of IgE binding by IgG in the ELISA and EITB methods used in this study. IgE-specific EITB showed 30-49 bands for the five respective extracts that were identified by M(r) or relative mobility. Eighty-five to 100 bands were visualized by IgG-specific EITB for the same five extracts. The isotype-specific ELISA and EITB were shown to be closely related by significant correlations (P < 0.0001) between S/N ratios and the number of bands found on blots. The isotype-specific EITB bands non-specifically recognized were greater in size than 21 kDa for IgG and 45 kDa for IgE. Recognition of bands changed over time with some bands being recognized only by prepatent sera. Ten antigen bands of seven M(r) were consistently and specifically recognized by IgE in the five-stage extracts by sera from prepatent and patent infections; only one such M(r) at 13.9 kDa, was described for IgG. A potentially diagnostic 31.9 kDa antigen band was identified on the IgE-specific EITB of D. immitis female extract and was shown to be recognized by IgE in sera from all infected dogs at all time points examined from 2 weeks until 1 year post-inoculation. Overall, IgE reactivity was more specific for D. immitis infections than IgG reactivity.


Attempts to immunize cattle against Ostertagia ostertagi infections employing 'normal' and 'chilled' (hypobiosis-prone) third stage larvae. Immunity to Ostertagia ostertagi infections in calves develops slowly and only becomes manifest towards the end of a grazing season in which they have been exposed to the parasite. In an attempt to hasten the onset of immune reactions, three immunization protocols were set up. Twenty four heifers were allocated into four groups. Beginning in January, animals in two of the groups were inoculated with four 1-monthly increasing dosages of either 'normal' or 'chilled' (hypobiosis-prone) larvae, those in the third group received a single large infection with 'chilled' larvae and those in the fourth group served as non-infected controls. All animals were turned out on a common pasture in late April. Development of immunity was evaluated through determinations of faecal egg counts, live weight gains, serum pepsinogen levels and specific serum antibody responses of three isotypes (IgG1, IgG2 and IgA). Significantly reduced egg excretions in the immunized groups were apparent early in the season, indicating that the immunizations had, in this respect, been efficacious. The 'chilled' and 'normal' larvae seemed equally efficient given as multiple and single infections. A single large dosage of 'chilled' larvae seemed to have adverse effects. Only moderate antibody responses were elicited probably because of low challenge infection level on pasture. Considerable variation in responses existed between and within the four groups, for which reason conclusions regarding correlations between antibody isotype responses and immune effects on parasites could not be made.


Immunosuppression of in vivo and in vitro lymphocyte responses in swine induced by Trichinella spiralis or excretory-secretory antigens of the parasite. The in vivo and in vitro effects of Trichinella spiralis excretory-secretory (ES) antigens on porcine peripheral blood lymphocyte (PBL) responses induced with mitogens (phytohemagglutinin, PHA; concanavalin A, Con A; pokeweed mitogen, PWM) or unrelated antigen (Protein A) were studied to determine whether ES antigens depress lymphocyte responses in experimental swine trichinosis, and/or if this response was manifested after lymphocytes from infected pigs had been pretreated with ES antigens. Additionally, the range of inhibition of lymphocyte responses was tested in parasite-free pigs using different doses of ES antigens and compared with the responsiveness of control cultures from the same animals. The responses of lymphocytes from pigs inoculated with 4 x 10(3) muscle larvae (ML) were strongly depressed (P < 0.05) at post-inoculation days (PID) 7 (after stimulation with PHA), 14, 35 (Con A or PWM), and 49 (PWM). At PID 56 and 63 the lymphocytes from T. spiralis-infected pigs responded better (P < 0.05) to all three mitogens than those from non-infected controls. After 7 weeks post-inoculation, PBL which were pretreated with 10 or 250 micrograms ml-1 of ES antigens showed significantly weaker (P < 0.05, P < 0.001) responses to PWM or PHA, respectively, than those from non-infected animals. The responsiveness of lymphocytes from both groups of pigs to Protein A was not affected by the pretreatment with ES antigens in vitro. The responses of lymphocytes from the parasite-free pigs induced by PHA, PWM or Protein A were strongly depressed (P < 0.01) after in vitro pretreatment regardless of the dose of ES antigens (5, 10, 15, or 20 micrograms ml-1) applied.


Studies on the development and survival periods of the non-parasitic stages of Boophilus microplus (Canestrini), in the climatic conditions of Ranchi (India). Engorged female ticks of Boophilus microplus were exposed in wire-gauze cylinders and glass tubes in an experimental grass plot at monthly intervals during 1989, and egg laying, egg development and larval survival periods observed and recorded. Rainfall and atmospheric relative humidity had an important influence on tick activity. Egg production was maximum, hatching percentage was high, incubation and prehatch periods were short, and larval survival and total longevity periods were long for ticks exposed during the warm and humid rainy season from June to September. Dry atmospheric conditions severely affected egg development, egg hatch and larval survival. Eggs failed to hatch in the dry months from December to April and only 29-38% hatched after a long incubation period of 41 days in November and May. On grass, the larvae of ticks exposed in November survived for the shortest period of 28 days and the larvae of ticks exposed in June survived for the longest period of 133 days. Low winter temperatures reduced egg production and prolonged the pre-oviposition, oviposition and incubation periods. It is suggested that the results of this study might be helpful in the development of measures to control tick infestation by planned dipping and restricted grazing during the period from late June to January when the pasture has a substantial load of larval ticks.


Studies on Rhinoestrus purpureus (Diptera: Oestridae) larvae infesting donkeys (Equus asinus) in Egypt. III. Pupal duration under controlled conditions. The pupal duration of Rhinoestrus purpureus was studied under variable degrees of temperature and relative humidity (RH). It was found that pupal duration was affected by temperature but not by RH. An increase in the temperature above 22 degrees C decreased the pupal duration: 26-27 days at 22 degrees C, 16-24 days at 27 degrees C, 13-15 days at 32 degrees C. At 37 degrees C, the pupated larvae failed to pupate and died. The deformity ratio of emerged flies was 25-30% at 22-32 degrees C, but it was directly proportional to RH at a constant temperature of 32 degrees C: 26.1% at 75% RH, 16.7% at 50% RH, 6.7% at 30% RH. It was concluded that the optimum temperature and RH for obtaining normal active flies were 32 degrees C and 30%, respectively.


Canine neosporosis in South Africa.

Canine neosporosis in South Africa. Neospora caninum was identified in tissues of one neonatal and two adolescent dogs by a specific immunohistochemical technique during a retrospective study. The histological lesions included multifocal polymyositis, multifocal parasitic myocarditis, interstitial pneumonia, severe multifocal encephalitis and myelitis with perivascular cuffing. This report extends the known range of the parasite to the African continent.


Seroprevalence of Toxoplasma gondii in llamas (Lama glama) in the northwest USA. Serum samples from 283 llamas (Lama glama) from Oregon, Washington State and Idaho were tested for antibodies to Toxoplasma gondii using the modified agglutination test. Antibodies were found in 95 (33.5%) llamas. Percent seropositivity in serum dilutions of 1:25, 1:50, 1:500, and 1:5000 was 9.5%, 18.3%, 4.9%, and 0.7%, respectively.


Effect of feeding lasalocid to pregnant ewes experimentally infected with Toxoplasma gondii. Sixteen 50 day gestational ewes were fed lasalocid at the rate of 30 g t-1 and were orally inoculated with 100 infective Toxoplasma gondii oocysts 5 days after beginning feeding of lasalocid. Seventeen control ewes were similarly inoculated with T. gondii and were not fed lasalocid. The rate of abortion and neonatal mortality in both treated and untreated ewes was similar, indicating that feeding lasalocid was not effective in preventing T. gondii abortion in sheep.


Fatal toxoplasmosis in domestic rabbits in the USA. Three rabbits from two sources died after an acute illness characterized by fever, lethargy and diarrhea in one rabbit and no clinical signs in two rabbits. The most striking lesion in all three rabbits was foci of necrosis of the spleen and liver associated with massive presence of multiplying Toxoplasma gondii tachyzoites. The diagnosis was confirmed by specific staining with anti-T. gondii serum in an avidin-biotin complex immunohistochemical stain.


Sarcocystis neurona-associated ataxia in horses in Brazil. Sarcocystis neurona-like schizonts were found in sections of brain and spinal cord of two ataxic horses from Brazil. The diagnosis was supported by staining with anti-Sarcocystis serum in an immunohistochemical test. One of the affected horses was born in Argentina and raised in Brazil, and the other horse was born and raised in Brazil.


Specificity of the carbon immunoassay (CIA) test for the diagnosis of Toxoplasma infections. A rapid and low cost procedure, the carbon immunoassay (CIA) test, was evaluated for the diagnosis of Toxoplasma gondii infections. Using a closely related parasite (Besnoitia jellisoni) as antigen, and homologous or heterologous immune sera, it was demonstrated by light and electron microscopy that CIA is a very reliable and specific test. As it is neither expensive nor time-consuming, it can be recommended for general and routine laboratory use.


Effect of fenbendazole molasses supplement block treatment on nematode infection and subsequent weight gain of weanling beef calves. Two trials were conducted to evaluate the effect of fenbendazole molasses supplement block treatment on weight gain of weanling beef calves. An initial (November) oral fenbendazole (5 mg kg-1) treatment was administered to all animals in both trials. In Trials 1 and 2, respectively, two fenbendazole molasses supplement block treatments were administered 6 (6.4 mg kg-1) and 16 (7.0 mg kg-1) weeks later and 7 (3.4 mg kg-1) and 14 (3.8 mg kg-1) weeks later. During the treatment periods, calves were maintained on dormant bermuda grass pasture, supplemented with hay and protein/mineral blocks. The first block treatment was administered approximately midway through the supplement period to suppress the infection level when nutrition was marginal. The second treatment was administered just prior to ryegrass grazing. Trial 1 and 2 treatments resulted in reducing the infection level, as indicated by reduced mean fecal egg counts. Treatment group mean fecal egg counts remained lower than control group mean counts throughout each trial. In Trial 1, the treatment group gained 29.5 kg more than the control group. In Trial 2, the control group gained 15.5 kg more than the treatment group. Fecal egg count data indicated that the infection level during Trial 1 was higher than during Trial 2. This difference could influence weight gain.


Preliminary observations on helminth parasite populations of the dromedary in northern Mali. An abattoir survey on gastrointestinal parasites of the dromedary (Camelus dromedarius) was carried out in March/April 1987 in northern Mali. Parasitological examination of the digestive tract contents of 11 dromedaries revealed that Haemonchus longistipes was the predominant parasite with a prevalence as high as 85.7%. The genera Impalaia, Trichostrongylus, Cooperia, and Oesophagostomum were also recovered, but with a lower level of infection and frequency. The larval stage of the canine cestode Echinococcus granulosus was recorded in a single instance.


Preparation of latex sensitized with rabbit IgG antibody for slide reversed passive agglutination. A method is described for preparing latex particles sensitized with IgG antibody (IgG-sensitized latex) applicable to the slide reversed passive agglutination (RPLA) test. Soap-free latex (latex) was sensitized with IgG which had been isolated from rabbit anti-bovine lactoferrin serum using protein A Sepharose CL 4B. Unadsorbed protein-binding sites on the surface of latex were blocked with bovine serum albumin (BSA). IgG-sensitized latex that gave better agglutination in RPLA could be selectively obtained by centrifugation at 19 900g for 15 min in 0.01 mol/L glycine buffer (pH 7.3; specific gravity 1.042) containing 3% NaCl, 5% saccharose and 2% choline chloride. By dispersing this IgG-sensitized latex in 0.01 mol/L glycine buffer (pH 7.3) containing 1-2% BSA, a uniformly suspended, highly reactive, readily agglutinable preparation was obtained.


Epidemiological observations on stomach worms of donkeys in Morocco. Over two consecutive years, weekly examinations for the presence of nematodes were conducted on 185 stomachs from donkeys originating mainly from the Rabat, Casablanca and Settat regions of Morocco. All the animals, except one, were infected by at least one of four helminth species. Trichostrongylus axei was found in 93.5%, Habronema muscae in 89.7%, H. majus in 85.4% and Draschia megastoma in 1.1% of donkeys. Most animals were infected by two (23.8%) or three (71.9%) species. High burdens of T. axei were observed in the winter of both years and in the mid-summer of the second year. Peak burdens of Habronema were found at various times throughout both years. There were more adult H. majus than H. muscae. The periods of peak levels of infection by these parasites were related to environmental conditions suitable for the development and survival of infective larvae of T. axei and for the build-up of muscid fly vectors of Habronema and Draschia spp.


Interspecies differences in the pharmacokinetics of kanamycin and apramycin. Comparative studies on some selected pharmacokinetic parameters for kanamycin in sheep, goats, rabbits, chickens and pigeons, and for apramycin in sheep, rabbits, chickens and pigeons were carried out after intravenous administration of the two drugs at a dose of 10 mg/kg. The results revealed that a two-compartment open model was most suitable for kanamycin, while for apramycin a one-compartment open model was usually optimal. The log distribution rate constant (alpha) of kanamycin was significantly correlated to the log of the body mass (r = 0.919, n = 5, p < 0.05). Interspecies differences in the apparent volume of distribution (Vda) of kanamycin were small. These differences were larger for apramycin, as were the variations in the area under the serum concentration-time curve (AUC) and in the total body clearance (ClB) of both kanamycin and apramycin, both having almost a threefold difference depending on the species but without any correlation to body mass. The values of the log half-life of kanamycin in the mammals in this study and also those from data in the literature revealed a significant correlation with log body mass between animal species according to the equation: t1/2 beta = 38.47W0.21 (r = 0.7648, n = 10, p < 0.05).


Muscarinic receptor subtypes in equine tracheal smooth muscle. Selective muscarinic receptor antagonists were used to identify muscarinic receptor subtypes in equine trachealis strips. The M1 receptor antagonist pirenzepine (10(-7) mol/L to 3 x 10(-5) mol/L) and the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, 10(-9) mol/L to 3 x 10(-7) mol/L3) dose dependently inhibited the contractile responses to electrical field stimulation (EFS) and exogenous acetylcholine (ACh). Schild plots yielded a pA2 value for pirenzepine vs ACh of 6.75 +/- 0.09, which is consistent with the affinity for M2 or M3 receptors, and a pA2 value for 4-DAMP vs ACh of 8.47 +/- 0.09, which is in agreement with the affinity for M3 receptors. The M2 receptor antagonist gallamine (10(-5) mol/L and 10(-4) mol/L) did not affect the response of trachealis to exogenous ACh and low-frequency EFS (0.1-2 Hz) but decreased the responses to high-frequency EFS (4-16 Hz). These results suggest that the muscarinic receptors mediating contractions induced by ACh in equine tracheal smooth muscle are of the M3 subtype. The lack of an increase in the response to EFS following gallamine suggests that functional prejunctional inhibitory M2 receptors are not present on the cholinergic nerves innervating equine tracheal smooth muscle.


The effect of long-term exposure to phosphamidon on the ruminal microorganisms and circulating carboxylesterase of Bubalus bubalis. The effect of long-term exposure to the organophosphate insecticide phosphamidon on the ruminal microorganisms and serum carboxylesterase of buffalo calves was investigated. Oral administration of phosphamidon in doses of 0.25 and 0.5 mg/kg per day for 120 days caused significant inactivation of carboxylesterase activity (16-32%) without eliciting any intoxicating signs apart from mild intermittent diarrhoea in the animals receiving the higher dose. The higher dose also produced a significant reduction in the total number of rumen protozoa (16-24%). However, the insecticide had no discernible effect on the total bacterial count or pH of the rumen liquor.


Studies on co-localization of 7B2 and pancreatic hormones in normal and tumoural islet cells. The distribution of protein 7B2, a protein with structural characteristics of GTP-binding proteins, has been studied in normal pancreatic islets and in a series of 70 pancreatic endocrine tumours with emphasis on the co-localization of 7B2 and the different pancreatic hormones. Although all cell types of normal islets were found to store 7B2, variations from intense expression to absence of reaction were seen within each cell type. In particular, B cells showed intense immunostaining for 7B2 in small compact islets and weak or no staining in larger islets with lobular arrangement. Pancreatic polypeptide (PP) cells expressed 7B2 intensely in the PP-rich area of ventral embryological origin, but were mostly non-reactive in the PP-poor area. The A cells, located along intralobular blood vessels, were more frequently immunoreactive for 7B2 than those at the periphery of the islets. Immuno-electron microscopy revealed a preferential localization of 7B2 in secretory granules of islet cells, with more intense localization in the peripheral halo of alpha granules. Benign islet cell tumours more frequently expressed 7B2 than their malignant counterparts. Although often expressed in a lower number of tumour cells than the tumour-specific hormone, 7B2 was usually co-localized with the latter. In contrast, no relationship was found with the localization of proinsulin. It is concluded that 7B2 is a non-permanent component of the cell granule compartment, probably involved in events related to exocytosis and without relationship to intracellular prohormone processing.


Production of anti-NC1 antibody by affected male dogs with X-linked hereditary nephritis: a probe for assessing the NC1 domain of collagen type IV in dogs and humans with hereditary nephritis. Some patients with hereditary nephritis (HN) who have received a renal transplant have been shown to form antibody with specificity for the NC1 domain of collagen type IV, a major constituent of glomerular basement membranes (GBM). We attempted to duplicate this phenomenon in a family of dogs with X-linked HN, a model for human X-linked HN, by immunizing affected male dogs with normal dog NC1 domain. A collagenase digest was prepared from normal dog GBM, the NC1 domain was separated into dimer (approximately 50 kDa) and monomer (24 kDa and 26 kDa) components by SDS-PAGE, and injected into two affected male dogs. Antisera obtained from both dogs contained antibody which reacted with the NC1 domain of dog and human GBM by a plate-binding radioimmunoassay, bound to the dimer and 26 kDa monomer bands by Western blotting, and staining dog and human GBM by immunofluorescence (IF). The affected male dog antiserum reacted equally by radioimmunoassay with the NC1 domain isolated from GBM of unaffected, affected male, and carrier female dogs in the family with X-linked HN, and bound by Western blotting to dimers and the 26 kDa monomer band of the NC1 domain of GBM in each group of dogs. However, the affected male dog antiserum differentiated these dogs by IF; it produced global staining of GBM of unaffected dogs, failed to stain GBM of affected male dogs, and produced segmental staining of GBM of carrier female dogs. Absorption of the affected male dog antiserum with normal dog NC1 domain eliminated the staining of dog GBM by IF, whereas staining persisted after absorption with affected male dog NC1 domain. The abnormal staining patterns of GBM seen by IF in the affected male and carrier female dogs and the results of the absorption studies imply an abnormality of one or more determinants in the 26 kDa monomer band of the NC1 domain of their GBM. Amino acid sequencing of this band identified the alpha 1(IV) chain of collagen type IV, a finding that has implications for the pathogenesis of canine X-linked HN. Absent and segmental staining respectively were also seen by IF in GBM of a male and female patient with HN, using the affected male dog antiserum. Thus, the results obtained in affected male and carrier female dogs with X-linked HN may also be relevant to patients with this disease.


Cystatin C in the human pancreas and gut: an immunohistochemical study of normal and neoplastic tissues. The occurrence of immunoreactive cystatin C (CC) in normal and neoplastic cells of the human pancreas and gut was investigated using an indirect streptavidin-biotin method on formaldehyde-fixed and paraffin-embedded tissues. Virtually all pancreatic islet cells and many neuroendocrine cells throughout the gastrointestinal tract showed strong CC immunoreactivity and a granular cytoplasmic staining pattern. All 14 endocrine pancreatic tumours (insulinomas, glucagonomas, gastrinomas and non-producing tumours), as well as 16 of 17 gut carcinoid tumours, were also strongly CC immunoreactive. In addition, non-endocrine epithelial cells of pancreatic ducts and the gastrointestinal mucosa and 20 of the 24 adenocarcinomas from these sites showed weak CC immunoreactivity. Thus, CC cannot be used as a reliable immunohistochemical marker for endocrine gastro-entero-pancreatic tumours despite the fact that the protein is strongly expressed in a majority of such tumours.


DNA-cytophotometry and immunocytochemistry in ovarian tumours of borderline malignancy and related peritoneal lesions. A total of 34 surgical specimens, obtained from 13 patients with ovarian tumours of borderline malignancy (OTBM), were investigated by conventional histology, immunocytochemistry and DNA cytophotometry. The lesions were obtained by primary ovarian surgery or second-look procedures and altogether comprised 19 (single and bilateral) OTBM, 8 cases of endosalpingiosis, 4 in situ and 2 invasive peritoneal implants and 1 overt adenocarcinoma. The morphological findings were related to follow-up data, which showed neoplasms with clinically malignant behaviour in 2 patients. The histology of the extra-ovarian manifestations was not associated with their immunocytochemical properties or with their DNA content. There were no correlations between the evolution of disease and microscopical features but the clinical course appeared to be linked to the DNA content of the extra-ovarian lesions, which was of greater prognostic importance than DNA ploidy of the ovarian tumours. Recurrence-free survival was noted in all 5 patients with diploid or euploid extra-ovarian proliferations, while the 2 clinically malignant cases fell into the group of 3 patients with noneuploid or aneuploid specimens. DNA estimations may be a methodology which increases the prognostic value of second-look procedures in OTBM patients.


Oestrogen retards the development of spontaneous thymomas in BUF/Mna rats. BUF/Mna rats develop spontaneous thymomas with nearly 100% incidence in both sexes. While the thymomas in males develop from around 9 months of age, those in females start from 13-15 months of age. To clarify the mechanism of the delay of thymomagenesis in females, the effect of sex hormones on the development of thymomas was examined after either gonadectomy or oestrogen treatment. Prepubertal ovariectomy accelerated the thymoma development in females, whereas orchiectomy did not affect it. An intraperitoneal injection of oestriol (20 mg) into males at 2 months of age remarkably diminished the thymic weight to about one-tenth of age-matched controls at 16 months of age. These results suggest that oestrogen can actually retard the onset of thymoma in spite of genetic control of its incidence. However, oestrogen did not cause thymic involution when it was injected into rats over 9 months of age. Immunohistochemically, there seemed to be no distinct difference in distribution of oestrogen-receptor-bearing epithelial cells between thymomas and 2- to 3-month-old thymuses. The oestrogen sensitivity of the thymus might be destined to be lost, as the thymic epithelial cells start neoplastic changes with the impairment of oestrogen-receptor function.


Expression of transforming growth factor alpha in human tissues: immunohistochemical study and northern blot analysis. The expression of transforming growth factor alpha (TGF-alpha) was examined in various human tissues and the fetus, using immunohistochemistry and Northern blot analysis. TGF-alpha immunoreactivity was detected mainly in the epithelial cells of the digestive tract, liver, pancreas, kidney, thyroid, adrenal, skin, mammary gland and genital organs. In the digestive tract, epithelial cells with regenerative change or hyperplastic change showed strong immunoreactivity to TGF-alpha. Peripheral nerve, vessels, megakaryocytes and macrophages in the lung and spleen were also positive for TGF-alpha. By Northern blot analysis the expression of TGF-alpha mRNA was confirmed in the digestive tract, salivary gland, thyroid, kidney and mammary gland. In the human fetus, the nerve tissues, liver, adrenal and kidney were positive for TGF-alpha. Strong immunoreactivity to TGF-alpha was observed in the hepatocytes of the fetus. These findings indicate that TGF-alpha is produced by a variety of non-neoplastic cells in both adult and fetal tissues.


Histology and immunocytochemistry of differentiated thyroid carcinomas do not predict radioiodine uptake: a clinicomorphological study of 62 recurrent or metastatic tumours. Sixty-two metastases or recurrences of differentiated thyroid carcinomas were investigated using conventional histology and immunocytochemistry for thyroglobulin (TG), thyroxine (T4) and triiodothyronine (T3). In each patient, 131I total body scans had been performed 4-10 weeks before surgery. Twenty-seven of the 62 tumours exhibited a predominance of follicles (A1), while 35 either exclusively or predominantly consisted of papillae or, in the case of follicular carcinomas, were predominantly trabecular or solid in structure (A2). TG and T4 immunoreactivity was observed in 60 cases, only 4 of these also expressing T3. Positive radioiodine uptake (RIU) was noted in 27 of 62 (44%) cases (A1:18/27 = 67%; A2:9/35 = 26%), 25 of which showed intraluminal TG and T4 positivity. Two follicular carcinomas showing RIU lacked follicular lumina, but exhibited strong diffuse cytoplasmic positivity for both TG and T4. In another 95 differentiated thyroid carcinomas, the structure of primary and secondary lesions was assessed. Of these, 27 (28%) showed a discordant pattern (A1/A2 or A2/A1) when comparing the structure of primary and secondary lesions. Our data suggest that differentiated thyroid carcinomas show a dissociation of TG/T4 expression and RIU, defects of iodine uptake and storage being found more frequently than a depression of TG and T4 synthesis. Intact synthesis of TG and T4, but not of T3 may be regarded as a prerequisite for RIU. Positive RIU is based on the presence of mature neoplastic follicles containing TG and T4 immunoreactive colloid and among follicular carcinomas, positive RIU may be encountered in neoplasms lacking follicular lumina but exhibiting strong cytoplasmic TG and T4 staining. Finally, the RIU of recurrent and metastatic PC and FC is not predictable from histological features of the primaries.


Immunohistochemical study on the distribution of sarcoplasmic reticulum calcium ATPase in various human tissues using novel monoclonal antibodies. Novel monoclonal antibodies were raised against sarcoplasmic reticulum calcium (Ca2+)-ATPase of human skeletal muscle. Immunohistochemical analysis demonstrated that these antibodies, designated 6F5 and 7F10, bind Ca(2+)-ATPase of non-muscle tissue of the adult including parathyroid, islets of Langerhans, anterior lobe of the pituitary gland and photoreceptor cells of the retina as well as skeletal muscle. A positive reaction was also found for fetal tissues including skeletal muscle, heart, chondrocytes and peripheral nerves. Our results for distribution suggest that Ca(2+)-ATPase is strongly expressed in the tissues and cells in which signal transduction is actively carried out by Ca2+ release from the cytoplasmic Ca2+ pool.


Androgens and the testis.

Androgens and the testis. The present survey focuses on some unique features of the testis as an androgen target tissue. Within the testis androgens act in a paracrine rather than in an endocrine fashion. All the available evidence suggests that the concentration of androgens that surrounds testicular target cells is much higher than that observed in peripheral target tissues, but the exact concentration remains unknown. The concentration of androgens required to maintain spermatogenesis considerably exceeds that observed in the peripheral circulation although it is probably lower than that which exists within the testis. The effects of androgens on spermatogenesis are indirect and are mediated by somatic cells. Sertoli cells are the most likely mediators of the effects of androgens on germ cell development. These cells contain androgen receptors which are upregulated by FSH and by androgens and they respond to androgens in vitro. They are not the only androgen-responsive cells in the testis, however, and some effects of androgens on Sertoli cells (epithelial cells) are indirect and are actually mediated by paracrine factors produced by underlying peritubular cells (mesenchymal cells). Androgen-regulated mesenchymal-epithelial interactions may not be limited to the testis but may be a more general feature of androgen action in several target tissues and our data suggest that the mediators involved may be very similar or identical. A final interesting aspect of androgen action in the testis is that the compartment which responds to androgens (the tubular compartment) may locally modulate the activity of the compartment which is responsible for androgen production (the interstitial compartment). A complex network of paracrine mediators is responsible for these interactions.


[Immunodiagnosis of Taenia saginata cysticercosis]. Many different serological tests have been investigated in order to replace the current "knife and eye" method at the slaughterhouse, which detects only a small fraction of the cattle infected with cysticercosis. Among the assays for the detection of antibodies against the cysticerci of Taenia saginata, the ELISA is certainly the most sensitive, although it is unable to detect lightly infected animals. Consequently it only allows a group diagnosis in naturally infected cattle. The use of purified antigens of T. saginata, T. crassiceps and T. hydatigena did not improve significantly the reliability of these antibody detection tests. Recently monoclonal antibodies have been developed against surface or excretory- and secretory antigens of T. saginata metacestodes, allowing the detection of circulating antigens in the serum of infected cattle. Furthermore these monoclonal antibodies can distinguish animals carrying living, infectious cysticerci from those harbouring only dead cysticerci. Research is currently going on in order to improve the sensitivity of this antigen detection test, so that it can replace the current unreliable meat inspection methods in the slaughterhouse.


Diabetic bone disease. Low turnover osteoporosis related to decreased IGF-I production. The influence of insulin on plasma and bone mineral homeostasis was studied in the BB rat model, which develops an autoimmune form of diabetes at the age of about 100 days. Untreated diabetes of short duration resulted in hypercalciuria and intestinal calcium malabsorption despite increased free concentrations of serum 1,25-dihydroxyvitamin D. The concentrations of two vitamin D-dependent calcium-binding proteins were also decreased: a low duodenal calbindin-D 9K concentration corresponding to the low intestinal active calcium absorption and a low serum osteocalcin concentration, corresponding to a low bone formation and highly correlated with serum IGF-I concentration. Indeed, on bone histology a very low number of osteoblasts and low osteoblast activity (osteoid formation and mineral apposition rate) were observed. Similar abnormalities persisted in rats with long-standing diabetes resulting in markedly decreased bone mass and increased brittleness of bone. Diabetes therefore resulted in low-turnover osteoporosis. Several hormones (testosterone, growth hormone and 1,25-dihydroxyvitamin D) and growth factors (IGF-I and its binding proteins) with known effects on bone were markedly decreased in diabetic rats. A continuous infusion of testosterone, GH or 1,25-(OH)2D3 for 14 d by miniosmotic pumps could not improve the biochemical or histomorphometric abnormalities. Insulin infusion for 2 weeks, however, rapidly increased and overcorrected the number of osteoblasts, normalized serum osteocalcin and IGF-I concentrations but could not yet normalize bone mineralization. Continuous infusion of IGF-I alone did not improve the osteoblast number of osteocalcin but markedly stimulated bone mineralization. From these data we can conclude that both insulin and IGF-I are potent bone growth factors but with different mode of action. In human type 1 diabetes, a similar decrease in serum osteocalcin and IGF-I was observed. A reduction of regional bone mass, both in long and trabecular bones, is frequently observed in human diabetes. Cumulative data from case control studies indicate that the life-time fracture risk is increased in diabetes.


[The etiological structure of acute bacterial meningitis in different regions]. In 1985-1989 the etiological structure of acute bacterial meningitides (ABM) in children was studied in 4 largest industrial cities in different regions of the European part of the former USSR, as well as in 2 industrial cities of western Siberia. Due to the common methodological approach used in all investigations, comparable data were obtained in all cities. These investigations revealed that meningococci caused 53.0-86.7% of all cases of ABM in children, which corresponded to moderately increased morbidity rate in meningococcal infection (3.9-11.0 cases per 100,000 of the population, mostly 5.0-7.0 cases) in these cities with its progressive decrease during 3-4 years of observation. The gradual change of meningococci from group A, prevailing in the '70s and early '80s, to group B and in some cases the appearance of group C meningococci, accompanied by a decrease in morbidity rate, were noted. In St. Petersburg the indices of ABM morbidity in children aged up to 5 years for 1987 and 1988, caused by Haemophilus influenzae (0.74 and 4.13) and pneumococci (3.23 and 4.86), could be calculated. A great number of ABM cases of unclear etiology (15.9-33.3%) suggests that the number of ABM cases caused by these two infective agents was underestimated.


[The HIV infection processes in a hospital: the prognostic possibilities]. The method of mathematical simulation of the processes of HIV infection in hospitals and clinics is proposed with the aim of predicting the spread of HIV infection throughout the territory of this country. An original mathematical model reproducing, on the whole, the essential properties of HIV infection processes in the course of medical interventions requiring skin punctures has been worked out. An adequate mathematical and computer model imitating the process of HIV infection in a hospital is a convenient instrument for making up prognostic evaluation and for the epidemiological analysis of cases of HIV infection occurring at medical institutions throughout this country.


[The ultrastructure of a new species of Chlamydia--Chlamydia pneumoniae]. The dynamic study of a new Chlamydia species, C. pneumoniae (strain TWAR, isolate TW-480), inoculated into the monolayer culture of cells L-929 was made 24, 48, 72 and 96 hours after inoculation. When compared with C. trachomatis and C. psittaci, C. pneumoniae were found to stand between these two species with respect to the morphology of their intracytoplasmic microcolonies (inclusions): they were round, almost bubble-like, but more densely packed with chlamydiae, surrounded by an undulate membrane, preserving its integrity until the late stages of their development cycle. In cells L-929 C. pneumoniae had a typical development cycle accompanied by the formation of vegetative and spore-like cells, reticular and elementary bodies, as well as intermediate cells, though this process was slower than in C. trachomatis and C. psittaci. Besides normal elementary bodies, many altered ones were formed in the process of the development of C. pneumoniae in cells L-929. Most of these alterations were similar to the process of bacterial L-transformation and could be regarded as the manifestation of chlamydial pathology related to the adaptation to new host cells.


[HIV infection in the Warsaw Clinic of Infectious Hepatology]. An epidemiological survey of patients in the Warsaw Clinic of Infectious Hepatology, the Polish National Center of AIDS Control, has been made. The epidemiological evaluation of risk groups and the age of HIV-infected persons has revealed that in Poland they are similar to those in Europe and in the USA (homosexuals and addicts aged 26-30 years). In 12% of the hospitalized patients the full clinical picture of AIDS, in 11.3% pre-AIDS (ARC) and in 58.1% lymphadenopathy (LAS) have been registered. In 18.4% of the patients only antibodies to HIV have been detected. The necessity of timely laboratory examinations for the determination of antibodies to HIV, whose presence may be signalled by any clinical symptom of the disease, has been shown.


[A comparative evaluation of the effectiveness of methods for serological sampling examinations]. Blood serum samples of 3,448 schoolchildren of grades 1-10 in 35 schools of Dushanbe were examined in the passive hemagglutination test in 1988 and 1989. The proportion of persons unprotected against diphtheria and tetanus was estimated by common methods in different kinds of selective serologic survey: mass screening (43.4-83.0%), testing in selected groups reduced 2, 3 and 5 times, cluster sampling. The reduction of the groups to be examined (from 3,033 to 250 persons) was not accompanied by essential changes (t < 2) in the characteristics of mass immunity against diphtheria and tetanus. The cluster method was shown to be highly reliable also in the study of population immunity.


[The characteristics of the epidemic process of hospital infections in maternity hospitals influenced by an operational management system]. As shown in this investigation, the introduction of the algorithmic system of the control of the epidemiological process of hospital infections (HI) in maternity hospitals makes it possible to reduce HI-induced morbidity and mortality rates more than by half, as well as to alter their nosological and age structures, without additional economic expenditures and under the existing material conditions of maternity hospitals. Such success is achieved by the observation of infection precursors indicating the activation of the mechanisms of the transmission of Staphylococcus, Escherichia and Klebsiella infections and the risk factors (preconditions) facilitating this activation with the immediate involvement of all relevant specialists into action at the stage when an increase in the contamination of newborns and puerperal women is noted and not as late as at the stage of morbidity and mortality.


[The antibody response of animals to a corpuscular meningococcal group-B preparation with different methods of immunization]. As revealed in animal experiments, the formation of antibodies to group-B N. meningitidis antigens (group-specific polysaccharide, lipopolysaccharide and outer membrane proteins) in response to administration of meningococcal corpuscular preparations depends on the method of administration, the dose, and the number of administrations. In the sera of rabbits, immunized orally, antibodies to all three antigens in sufficiently high titers have been detected.


[The effect of a ribosomal Shigella sonnei vaccine on cellular immune reactions]. The influence of S. sonnei ribosomal vaccine on hematopoiesis, T- and B-cell-mediated immune reactions has been studied in the course of the development of experimental vaccinal process. The vaccine stimulated hematopoiesis, that was characterized by a dose-dependent increase in colony-forming units in the spleen (CFUs), a rise in CFUs in the blood and bone marrow and an increase in the pool of proliferating stem cells in bone marrow, shortly after injection. A pronounced immunostimulating effect of the vaccine on the formation of antibody-producing cells (APC) to heterologous antigen (sheep red blood cells) in the spleen has been established, and the vaccine has also been found to stimulate, though to a lesser extent, APC synthetizing specific antibodies to S. sonnei LPS. The injection of S. sonnei ribosomal vaccine influences the functional activity of effector T-cells; in its turn this phenomenon produces phasic changes in the migration activity of spleen cells in the presence of specific LPS and surface polysaccharide antigen of S. sonnei in phase I.


[The use of monolaurates for removing endotoxins from preparations of cell-free pertussis vaccine]. The possibility of using monolaurates for removing endotoxin from acellular pertussis vaccines developed at the Laboratory of Immunomodulators, Mechnikov Research Institute for Vaccines and Sera (Moscow), has been studied. Monolaurates PEG-400 and PEG-600 obtained, respectively, from Fluka Chemie AG and Ferak GmbH (Germany) have been used. The use of monolaurate PEG-600 ensures the decrease of the toxicity of acellular pertussis vaccines by 2.34-6.3 times.


[The protein admixture content in a tick-borne encephalitis vaccine and its purification by means of microfiltration]. The method of rocket immunoelectrophoresis permits the detection of all antigenic admixtures in tick-borne encephalitis (TBE) vaccine. Human serum albumin constitutes the main part of protein admixtures in the preparation. Purification by microfiltration is an effective stage of the technological process of obtaining purified TBE vaccine.


[The evaluation of the mutagenic activity of pertussis vaccinal preparations]. Two vaccine preparations obtained from Bordetella pertussis, whole-cell vaccine constituting one of the components of adsorbed DPT vaccine and acellular vaccine, were tested for mutagenicity. The doses of the preparations covered the range 1-100 ED50. Ames' test and the metaphase analysis of marrow cells of C57BL/6J mice were used. The acellular preparation was also tested on thymectomized mice, taking into consideration chromosomal aberrations in marrow metaphases. Whole-cell and acellular pertussis vaccines did not induce mutations in Salmonella typhimurium and chromosomal aberrations in mouse marrow cells.


[Experimental influenzal and tuberculous infections under conditions of specific and nonspecific immunosuppression]. The course of influenza and tuberculosis infections under the conditions of disturbances in the immune response of experimental animals has been studied. As revealed in the survival test, the induction of secondary T- and B-cell-mediated immunodeficiency in mice leads to an increase in the sensitivity of the body to influenza virus, especially in cases of T-cell-mediated immunodeficiency. The injection of BCG in combination with cyclophosphamide into mice induces tolerance to this antigen in the animals; this tolerance has a "split" character, i.e. it affects only T-cell-mediated, but not humoral immunity. The induction of T-cell-mediated immunodeficiency or tolerance to BCG in mice has been shown (in the survival test) to lead to the development of the sensitivity of the animals to experimental tuberculosis infection. B-cell-mediated immunodeficiency did not influence the animal survival rate.


[A comparative immunochemical analysis of allergoids and allergens]. In comparison with allergens having protein fragments with a molecular weight not exceeding 110 kD, allergoids have been found to consist of larger fragments with a molecular weight of 10-150 kD. Allergoids have less charged components than initial allergens and less antigenic components. Allergoids retain their capacity for stimulating the production of antibodies, specific to all antigenic components.


[The characteristics of the colonization resistance of the intestines in conventional animals with a history of clinical death]. After modeling the terminal state caused by the acute loss of blood in rats their intestinal microflora was studied, as was their resistance to colonization. Decreased resistance to colonization was registered early after resuscitation (up to 3 days), which was confirmed by the translocation of bacteria into internal organs, decreased number of lactobacilli in the contents of the small intestine and elevated level of enterobacteria in the intestine. Disturbances in resistance to colonization was also manifested by prolonged colonization of the digestive tract of the resuscitated animals by Escherichia coli indicator strain K12pSS-120 carrying Shigella sonnei (phase I) invasiveness plasmid.


Characterization of contact dermatitis and atopy using bioengineering techniques. A survey. Bioengineering techniques useful in the characterization of contact dermatitis and atopy are surveyed, including non-invasive techniques for the measurement of skin colour, blood flow, skin surface temperature, skin surface contour, water barrier, and skin surface hydration. Ultrasound measurement of skin thickness and edema formation, and ultrasound cross-sectional imaging are also included. Structural and pathophysiological findings in the different types of dermatitis are outlined. Weal or hive formation is covered additionally.


Scaling, dry skin and gender. A bioengineering study of dry skin. Dry skin and scaling was studied in a group of 72 healthy volunteers by using subjective self-assessment and by clinical assessment by a dermatologist, as well as application of noninvasive bioengineering techniques to measure scaling and epidermal hydration. The study revealed that 67% of the volunteers had subjective complaints, while only 5.6% had definite clinical signs of dry skin at the time of examination. Subjective complaints were more common in women than in men (p < 0.001), though neither clinical nor objective measurements showed any sex difference, which suggests that other factors may play a role in the way men and women perceive dry skin. Subjective and clinical scores were correlated (p < 0.02), though neither was significantly correlated to objective measurements. Grading of skin scaling on D-squame tapes correlated with densitometry of the tapes (p < 0.001), as did the electrical capacitance (p < 0.001). Both clinical and objective methods can identify dry skin. However, the study showed that in healthy persons a number of irrational factors play a role in the use of moisturizers, and while these factors cannot be measured, they must be taken into account. Healthy, but dry skin is a vaguely defined clinical entity, which may explain the generally poor correlation between the two methods. This underlines the need for several methods to be used simultaneously in order to elicit complementary information.


A three-hour test for rapid comparison of effects of moisturizers and active constituents (urea). Measurement of hydration, scaling and skin surface lipidization by noninvasive techniques. An in vivo skin test for rapid comparison of the efficacy of moisturizers is introduced. Test substances were applied to flexor side forearm skin, and measurements by non-invasive techniques were performed after 3 h. As indicators of epidermal hydration, the electrical conductance and capacitance were measured. To quantify the effects on scale pattern, D-Squame tapes were scored and the optical transmission measured. Moreover, skin surface lipids resulting from lotion lipids were measured. Lotions and different concentrations of urea could be ranked in a consistent way, viz. untreated skin < vehicle < 3% urea lotion < 10% urea lotion. Urea was concluded to be very potent as a skin humidifier and as a descaling agent, particularly in 10% concentration. Humidity characteristics correlated much better with the concentration of urea than with lipidization of the skin surface due to lotion lipids. A 3-hour test period was sufficient for the evaluation of the effects of moisturizers on both epidermal hydration and scale pattern. With a rapid test method, sources of variation such as diurnal and day-to-day variations, dosage and non-compliance are easily controlled. Further, by using non-invasive methods, the assessment has been rendered objective.


A double-blind comparison of two creams containing urea as the active ingredient. Assessment of efficacy and side-effects by non-invasive techniques and a clinical scoring scheme. From a group of 72 healthy individuals, 47 with evidence of dry skin according to measurements by non-invasive techniques were enrolled for a 3-week study with double-blind and randomized treatment of one forearm, using either 3% urea cream (HTH lotion 'light') or 10% urea cream (HTH lotion 'Original'). The contralateral forearm served as an untreated control. Two volunteers had to be excluded because measurements of skin surface lipids gave evidence of vehicle components on the skin surface at the time of final evaluations. Evaluations took place not less than 12 h after the last application. According to questionnaire replies, the two creams were equally effective. This was confirmed by "blind" evaluation of the skin hydration state by a dermatologist, measurements of electrical capacitance and conductance indicating epidermal and skin surface hydration, and by D-Squame tape assessments including optical transmission of tapes with stratum corneum and scales from adhering skin, as well as visual scoring of the tapes. The methods showed a high degree of correlation, i.a. a definite relation between increase in electrical hydration parameters, reduced scaling according to the D-Squame tape evaluations, and clinical improvement of dryness. In skin treated with 10% urea cream the transepidermal water loss (TEWL) decreased, indicating an improved water barrier function. Skin colour measurement according to the CIE colour system showed that skin treated with the 3% urea cream turned in the direction of yellow, and there was generally a tendency for the brightness to decrease. Thus, the 3% urea cream gave the skin a more golden colour. There was no change in redness with any of the creams. Neither data from the questionnaire, the clinical examination, nor results of TEWL and colour measurements indicated any local irritant effect of urea causing water barrier damage or inflammation. In conclusion, the 3% and 10% urea creams were both found efficient, resulting in improvement of hydration and reduction of scaling. Both were non-toxic. However, specific differences did appear, viz. the 3% urea cream turned the skin colour golden, while the 10% urea cream improved the skin's water barrier function.


An experimental study of irritant effects of urea in different vehicles. The properties of urea as an irritant were investigated. Seventeen healthy volunteers were patch tested with 20% urea using petrolatum and water, respectively, as vehicles. Irritant effects of urea were assessed by clinical evaluation of patch test reactions as well as by various non-invasive methods. The inflammatory response was quantified by laser Doppler flowmetry measuring the superficial blood flow, and by ultrasound A-scan reflecting the edema formation. Impairment of the barrier function was indicated by measurement of transepidermal water loss (TEWL). It is concluded that 20% urea in petrolatum applied under occlusion for 24 h elicits significant inflammation (i.e. increase in blood flow and skin thickness) and causes impairment of the skin barrier (i.e. increased TEWL). The irritant impact of urea on the skin depends upon the vehicle used, the irritant effect being intensified when urea is dispensed in petrolatum compared with water.


Market research surveys in the marketing of consumer products. To achieve commercial success, any skin care product having given functional properties will on the consumer market also depend on a high degree of attraction, comfort and effective marketing. To accomplish this, consumer surveys are necessary in the various stages of product development and the marketing process. A brief description of the latter is given and of the various types of related surveys. To illustrate certain product tests, examples are given of the relaunch of HTH in the nordic markets.


Urea in the treatment of dry skin.

Urea in the treatment of dry skin. Urea is a unique physiological substance. It has frequently been used in dermatological therapy for more than 20 years. The relevant properties of urea with regard to its use in dermatological preparations are discussed in this brief review. Urea's natural presence in the horny layer, its water solubility, dipolar character and relation to concentrated solutions of electrolytes, are highlighted. The clinical use of urea creams is discussed with respect to indications, side-effects and combinations with other substances.


Dry skin in atopic dermatitis.

Dry skin in atopic dermatitis. Atopic dermatitis (AD) is a common, chronically recurring skin disorder. Dry skin is a common finding in patients with AD, apart from the dermatitis. Although there are obvious clinical signs of an impaired barrier function of the skin, few investigators have studied this aspect of AD. The stratum corneum, where the barrier is located, has been studied with different techniques in patients with AD, and the results are now presented. The water-binding capacity of dry atopic skin was found to be reduced when measured with an in vitro microbalance technique. TEWL (transepidermal water loss) measured with and Evaporimeter Ep1, was increased in dry skin and in clinically normal skin of atopics on predilection areas. Water content was decreased in dry atopic skin, when measured with the Corneometer CM 420. In a quantitative electron microscopic study, the lamellar bodies were found to have an increased relative volume in dry atopic skin. When using chromatographic analysis, preliminary data suggested reduced amounts of extractable stratum corneum lipids in patients with AD. In a clinical study, 80% of the patients with AD regarded their skin as being dry. Fifty percent were found to have areas of dry skin, on clinical examination. By scanning electron microscopy (SEM), the surface pattern of dry atopic skin was found to be coarse and irregular. When using profilometry, quantitative differences in roughness parameters were found in dry atopic vis-à-vis to normal skin.(ABSTRACT TRUNCATED AT 250 WORDS)


Hypoparathyroidism in beta-thalassemia major. Clinical and laboratory observations in 24 patients. In the last 18 years, we have observed 24 cases of hypoparathyroidism (HPT) in beta-thalassemia major. At present, 4.5% of patients followed regularly in our department have this complication. HPT is thought to be mainly the consequence of iron deposition in the parathyroid glands. The age of our patients when HPT was diagnosed ranged from 11 to 24 years (mean 16.5 years). Their serum ferritin levels ranged from 810 to 15,200 ng/ml (mean 3,772 ng/ml). The severity of HPT varied widely. In only 3 patients was hypocalcemia severe with signs of tetany, seizures or cardiac failure. The onset of HPT was preceded or followed in most patients by other endocrine and/or cardiac complications. We found no clear relationship between HPT and serum ferritin levels in our patients, suggesting either an individual sensitivity to iron toxicity or early damage of the parathyroid gland before chelation had reduced the iron overload. However, the diagnosis of no new cases of HPT in the last 3 years coinciding with the much improved regime of chelation therapy suggests that chelation may have helped to prevent the development of HPT.


Effect of cimetidine on peripheral blood lymphocytes from chronic uremic patients: improvement of burst-promoting activity. We have studied the in vitro effect of cimetidine, an inhibitor of suppressor T lymphocytes, on T lymphocytes of 6 uremic subjects and on normal T lymphocytes preincubated with the serum from the same patients. Cimetidine has been shown to increase the burst-promoting activity (BPA) of uremic T lymphocytes and to partially improve the BPA of normal T lymphocytes preincubated with uremic serum. The present study shows that suppressor T lymphocytes are not affected by uremic inhibitors and that chronic uremia, besides inducing a decrease in the number of helper T lymphocytes, impairs their ability to stimulate the BFU-E in vitro growth.


Effects of physical stress on complete blood count and venous blood gas profile of individuals with sickle cell trait. The association between sickle cell trait (SCT) and adverse effects of exercise has been controversial. While individuals with SCT are at higher risk of sudden death, the mechanism for this outcome remains to be elucidated. In order to shed light on this controversy, we have monitored venous blood count and blood gas parameter values in normal and SCT subjects during treadmill exercise. White and red blood cell counts and hemoglobin changed significantly over time in both the SCT and normal groups, with peak exercise values different from pre-exercise or post-exercise values. Red blood cell counts showed significant group-time interaction; increase in count during exercise was accentuated in SCT subjects. All blood gas parameters showed significant changes over time in both groups. O2 content was significantly higher in SCT than AA at all time intervals. O2 saturation, pO2 and CO binding to hemoglobin showed significant group-time interaction. Furthermore, O2 saturation for the combined groups was significantly greater at peak exercise and at rest than before exercise. It is possible that treadmill exercise causes microvascular shunting in SCT subjects, leading to a decrease in the peripheral utilization of oxygen.


IgM autoagglutinins in warm autoimmune hemolytic anemia: a poor prognostic feature. The presence of both complete IgM autoagglutinins and IgG autoantibodies in warm autoimmune hemolytic anemia (AIHA) is an uncommon finding. Over a 6-year period, only 5 of 115 (4.1%) patients with AIHA had IgM and IgG autoantibodies. In 3 of the 5 cases, the complete IgM autoagglutinins reacted up to 30 degrees C and these patients responded well to corticosteroid or other therapies for warm AIHA. The 2 patients who had warm (37 degrees C) reactive IgM autoagglutinins, were refractory to corticosteroids, splenectomy and cytotoxic drugs, and died due to the complications of hemolytic anemia. The data in these 5 cases suggest that the thermal amplitude of the IgM antibody in these unusual AIHA cases may be predictive of refractoriness to therapy and poor clinical outcome.


Paroxysmal nocturnal haemoglobinuria in Indians. Paroxysmal nocturnal haemoglobinuria (PNH) was diagnosed in 11 patients attending the haematology clinic of a private community hospital in Hyderabad, India over a 3-year period. Compared to PNH occurring in Caucasians, the patients were younger, and showed a marked male preponderance; severe thrombocytopenia, haemorrhagic complications from thrombocytopenia and infectious complications were not seen. Thrombotic complications were common. Fever during periods of haemoglobinuria was a notable feature in 4 patients. None of the patients had the aplastic anaemia PNH syndrome.


Spontaneous remission with cyclic leukocytosis in chronic myelogenous leukemia. A 41-year-old female with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia was observed for 7 years. Cytotoxic therapy was not instituted until blastic crisis developed in the last 4 months. Successive hematologic measurements revealed cyclic fluctuations in blood leukocyte and platelet counts. These cycles had an average duration of 71 days during the 43 months observed. The oscillation amplitude decreased gradually over time, followed by hematologic remission until the last 4 months. The possible relationship between long-term survival and cyclic leukocytosis is discussed.


Ketoconazole and high-dose methylprednisolone predisposing to cyclosporine-induced seizures: report of 3 cases. Three consecutive cases of severe aplastic anemia undergoing immunosuppressive therapy with cyclosporin A (CyA) and high-dose methylprednisolone (HDMP) developed grand mal seizures after receiving ketoconazole treatment. All the seizures were reversed after transient discontinuation of those drugs. To our knowledge, it has not been reported as yet that the combination of ketoconazole and HDMP may considerably increase the risk of CyA-induced seizure. We would advise that ketoconazole and HDMP not be taken concomitantly with CyA treatment, and whenever ketoconazole therapy is needed, CyA be started with as small a dose as possible.


Successful plasmapheresis in corticosteroid-resistant hemolysis in infectious mononucleosis: role of autoantibodies against triosephosphate isomerase. A 19-year-old girl fell ill with a high temperature and cervical lymphadenopathy. The detection of heterophile antibodies as well as Epstein-Barr-virus-specific antibodies confirmed the diagnosis of infectious mononucleosis. In the course of the infection, the patient developed severe hemolytic anemia with her hemoglobin falling from 14 to 8 g/dl. High-dose corticosteroid therapy did not stop hemolysis; this could only be achieved by seven plasmapheresis sessions. Antibodies against triosephosphate isomerase (TPI) and the blood group marker 'i' were found in the patient's serum. Anti-i cold agglutinins were not active at 37 degrees C, whereas antibodies against TPI caused increased 51Cr release from marked patient's erythrocytes in vitro. Plasmapheresis removed the autoantibodies effectively and stopped the hemolysis. After 8 weeks, the patient gradually recovered.


Neutrophilic pustulosis associated with chronic myeloid leukemia: a special form of Sweet's syndrome. Report of two cases. Two subjects with Ph-positive chronic myeloid leukemia (CML) in whom pustular Sweet's syndrome was diagnosed are reported. The first patient was a 47-year-old woman who developed fever, painful ulcers of the oral mucosa and vagina and generalized pustulous skin lesions 2 years after the diagnosis of CML. Histologically, the skin lesions consisted of dense neutrophilic infiltrates with perifollicular disposition. The microbiologic studies were negative. The lesions showed a favorable response to corticosteroids, but fever recurred with every attempt of tapering prednisone; it finally disappeared with the addition of oral cyclophosphamide. The second patient was a 45-year-old man who developed fever and disseminated pustules with histologic features consistent with Sweet's syndrome and negative microbiologic studies at 2.5 years after diagnosis of CML. The picture showed a dramatic response to prednisone and did not recur after the drug was discontinued. In both patients, CML remained stable after resolution of Sweet's syndrome.


A novel chromosomal translocation t(3;17)(q29;q11) in a case with polycythemia vera. We report a novel chromosomal translocation t(3;17)(q29;q11) in a case with polycythemia vera (PV). The present case (38-year-old male) developed the spent phase of PV after a 10 years' clinical course and showed excessive proliferation of myeloid cells in the bone marrow. The karyotype analysis of the bone marrow cells showed chromosomal translocation t(3;17)(q29;q11), and the same aberration was detected in the granulocyte-colony-stimulating-factor-stimulated peripheral blood cells, suggesting the cells with the t(3;17)(q29;q11) showed myeloid differentiation. It is known as well that the retinoic acid receptor gene, which is related with a myeloid disorder, is located in 17q11. Thus, the novel chromosomal translocation could be associated with the pathogenesis of the disorder in this patient.


Distribution of IgG subtypes in maternal anti-D sera and their prognostic value in Rh haemolytic disease of the new-born. In 107 Rh(D)-immunized women having Rh(D)-positive pregnancy screening for IgG subtypes was carried out between the 34th and 36th week of gestation. Using polyclonal IgG subtype-specific reagents, all four IgG subclasses were detected in anti-D sera though IgG1 and IgG3 were the most predominant classes. IgG3 anti-D was usually low titre. At the same level of Rh(D) antibody titre, haemolytic disease of the new-born was more severe when anti-D was IgG1 type than IgG3 type. When the IgG1 and IgG3 anti-D subtypes existed together, the risk of having a stillborn child was very high compared to other subtypes (IgG1 + IgG3 34.8%, IgG1 19.2% and IgG3 15.4%).


Novel type of clonally involved cytoplasmic immunoglobulin-negative cells in multiple myeloma: flow cytometric study. In order to identify myeloma cells and their precursor cells, we studied bone marrow samples from 39 patients with multiple myeloma, including 2 with plasma cell leukemia, using dual parameter cytometry of both DNA and cytoplasmic immunoglobulin (Cyt-Ig). Myeloma cells from 25 patients (64.1%) were aneuploid and those from the remaining 14 patients were diploid. In 25 patients with aneuploid myeloma, we found a small component of cells which had aneuploid DNA content without Cyt-Ig in addition to myeloma cells showing aneuploidy with Cyt-Ig. These aneuploid Cyt-Ig-negative cells were considered to be clonally involved because they were aneuploid, and detected predominantly in patients with stage III myeloma. This suggests that these cells may contribute to disease progression. The characteristics of these cells are described and the relationship between these cells and myeloma precursor cells is discussed.


Diagnosis of glucose-6-phosphate dehydrogenase (G6PD) mutations by DNA amplification and allele-specific oligonucleotide probes. We have recently identified that at least four types of mutation are responsible for the glucose-6-phosphate dehydrogenase (G6PD) polymorphism in the Chinese of Taiwan. Two mutations (487 G-->A and 493 A-->G) occurring at nucleotide position 487 and 493, respectively, create Alu I and Ava II recognition sites which enabled us to directly examine these two mutations by PCR/restriction enzyme (RE) digestion. However, the other two mutations (1376 G-->T and 1388 G-->A), which do not generate any recognizable restriction sites, were detected by DNA sequencing method which is not suitable for rapid diagnosis. Using the PCR technique, we have successfully developed a simple and rapid method for the detection of 1376 and 1388 mutations. This method involves the selective amplification of a DNA fragment from human G6PD gene with specific oligonucleotide primers, followed by hybridization with allele-specific oligonucleotide (ASO) probes. Using the PCR/ASO and PCR/RE methods, we have successfully examined two families and 20 unrelated subjects with G6PD deficiency. Our results indicate that the PCR/ASO method is suitable for the rapid determination of 1376 and 1388 mutations. The combined use of PCR/ASO and PCR/RE methods will be suitable for rapid diagnosis of four known G6PD mutations in Chinese.