Pulmonary arteriovenous malformations: techniques and long-term outcome of embolotherapy

Over a 10-year period, 276 pulmonary arteriovenous malformations (PAVMs) were occluded with balloon embolotherapy in 76 patients, 67 (88%) of whom had hereditary hemorrhagic telangiectasia. Eleven patients (14%) were discovered by means of family screening with measurement of arterial blood gases and chest radiography. Epistaxis, dyspnea, hemoptysis, and hemothorax occurred in 79%, 71%, 13%, and 9% of patients, respectively. Clinical histories of strokes and transient ischemic attacks were present in 18% and 37% of patients, respectively. Computed tomographic scans of 59 patients showed stroke in 36%. Sixty-five percent of PAVMs were located in the lower lobes, which correlated with the finding of more pronounced hypoxemia in the upright position. After embolotherapy, symptomatic hypoxemia was corrected, and serial values have remained constant for 5 years. Complications were minimal, and no patient required surgery. Balloon embolotherapy is effective long-term therapy for PAVMs, and family screening should be pursued because of the possibility of a higher frequency of paradoxical embolization (stroke) than previously recognized.     

Growth of the uterus

BACKGROUND: The pattern of growth of the uterus was examined by ultrasound examinations of 358 girls who attended a paediatric endocrine outpatient department but were shown not to have any endocrine defect. METHOD: The uterus was measured in length and width at the cervix and at the fundus (cm). Endometrial thickness was measured (mm). Scans were divided by Tanner breast stage and the dimensions compared by one way analysis of variance (ANOVA, with the Student Newman Keuls post hoc test). RESULTS: There was an increase in uterine length, diameter of the fundus, and endometrial thickness at each breast stage from 1 to 5 (ANOVA, p < 0.05), and in the diameter of the cervix with each breast stage from 1 to 4 (ANOVA, p < 0.05). The ratio of the fundus to the cervix increased from 0.95 to 1.29 between breast stages 1 and 4. CONCLUSION: The onset of puberty is marked by an increase in the dimensions of the uterus and in endometrial thickness, but also by a change in the shape of the uterus from a tubular to a pear shaped organ.     

The effect of calcium-regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from neonatal rabbit bones

It has previously only been possible to assess osteoclastic bone resorption in intact bone, where other cell types may modify or mediate osteoclastic responses to environmental agents. We have recently developed techniques which enable us to measure bone resorption by osteoclasts extracted from bone and have used these techniques to assess the effects of prostaglandins (PGs) and calcium-regulating hormones on bone resorption by these cells. Osteoclasts were mechanically disaggregated from neonatal rabbit long bones and cultured on slices of devitalized cortical bone for 8 or 24 h. After this time, osteoclasts were associated with the appearance in the scanning electron microscope of characteristic resorption pits, the volume of which was calculated by computer-assisted morphometric and stereophotogrammetric techniques after removal of cells. Salmon calcitonin inhibited osteoclastic bone resorption at concentrations of 1 pg/ml and above, while PTH and 1,25-dihydroxyvitamin D3 were without significant effect. This suggests that the latter hormones do not increase bone resorption in intact bone through a direct effect on osteoclasts. PGI2, PGE1, and PGE2, all of which are known to stimulate resorption when added to intact bone, paradoxically reduced resorption in our cultures. It appears likely that PGs act as direct inhibitors of osteoclastic bone resorption but have an additional effect on other cells in bone, which are induced by PGs to cause osteoclastic stimulation.     

Effect of combination of antacid and cimetidine on 24-hour intragastric acidity in patients with asymptomatic duodenal ulcer

By means of a Latin square design, the effect of antacid alone and in combination with cimetidine on a 24-hour intragastric hydrogen ion (H+) activity and serum gastrin profiles was studied in eight patients with duodenal ulcer. Antacid given seven times a day (one and three hours after meals and at bedtime) combined with 600 mg BID of cimetidine (C + A7) achieved greater suppression of H+ after breakfast, overnight, and over the 24-hour period than did antacid alone seven times daily (A7). Antacid given four times a day (one and three hours after lunch and after supper) combined with cimetidine BID (C + A4) maintained the neutralizing capacity during this time, but was less effective than the C + A7 regimen. However, C + A4 produced more suppression of nocturnal H+ than did A7. A higher percentage of the readings at or above pH 4.0 were obtained with C + A7 than with A7 or C + A4. A greater postprandial integrated gastrin response was obtained with all active treatments as compared with a placebo regimen. The mean peak cimetidine concentration (Cmax) was higher but the time to peak (Tmax) was shorter after the morning than after the evening dose. The area under the cimetidine concentration-time curve and the Cmax and Tmax values after the morning and evening doses of cimetidine were not affected by the coadministration of antacid. In conclusion: (1) combination therapy of cimetidine plus antacid is more effective than antacid alone in the reduction of intragastric H+; (2) antacid alone fails to suppress the overnight intragastric acidity; and (3) antacid given concurrently with cimetidine does not interfere with pharmacokinetic determinants of plasma cimetidine concentration.     

Immune responses to labial infection of BALB/c mice with herpes simplex virus type 1.

The kinetics of appearance of five humoral antibody responses (micro-neutralization assay [NT], complement fixation [CF], enzyme-linked immunosorbent assay [ELISA], radioimmunoassay [RIA], antibody-dependent cell-mediated cytotoxicity [ADCC]), were compared during labial infection of BALB/c mice with herpes simplex virus type 1 strain Patton. The ELISA/RIA antibody responses were present in most mice by day 5 after infection, at the beginning of the herpetic lip lesions; antibody effective in ADCC showed identical early kinetics. In contrast, NT/CF antibodies were not detected in most mice until day 10, at the time of resolution of the herpetic lip lesions. The humoral immune responses persisted for at least 6 months after infection. The NT and CF responses were closely correlated in time of appearance and titers (r = 0.9), as were the ELISA and RIA responses (r = 0.99). However, there was little correlation between NT/CF and ELISA/RIA responses (r = 0.02). The kinetics of the delayed type hypersensitivity response showed similar kinetics of appearance to the ELISA/RIA/ADCC humoral responses, and peaked similarly, but waned gradually over 2 months. The importance of antibody in protection against labial herpes simplex virus type 1 infection was demonstrated by the ability of passively transferred convalescent serum (that produced a minimum NT titer of 10 in recipient mice) to protect against development of herpetic lesions and death.     

Comparison of three immunosuppressive regimens in cadaver renal transplantation: long-term cyclosporine, short-term cyclosporine followed by azathioprine and prednisolone, and azathioprine and prednisolone without cyclosporine

We conducted a randomized trial in seven Australian hospitals of the efficacy and safety of three immunosuppressive regimens after first transplantation of a cadaver kidney: long-term cyclosporine, short-term (three months) cyclosporine followed by azathioprine and prednisolone, and azathioprine and prednisolone without cyclosporine. Patients assigned to long-term cyclosporine (n = 138) or short-term cyclosporine followed by azathioprine and prednisolone (n = 141) had similar actuarial 12-month survival (98.4 vs. 96.4 percent) and graft survival (83.9 vs. 82.1 percent). Patients assigned to receive only azathioprine and prednisolone (n = 138), with optional use of antithymocyte globulin, had a significantly poorer survival rate (91.3 percent, P = 0.015) because of deaths from cardiac causes and infection, but their graft survival of 76.0 percent (P = 0.31) did not differ significantly from that of either group receiving cyclosporine. After the switch from cyclosporine to azathioprine and prednisolone, 15 percent of patients had reversible rejection episodes, but the frequency of rejection and graft loss did not differ from that in the long-term cyclosporine group. After the change to azathioprine and prednisolone, serum creatinine levels declined in nearly all patients, so that after three months they were comparable to those in the group receiving azathioprine and prednisolone only, and significantly lower than those in the group receiving long-term cyclosporine therapy (P less than 0.003). We conclude that the two cyclosporine regimens result in comparable patient and graft survival, but that changing to azathioprine and prednisolone at three months improves graft function.