In-vitro fertilization and the ovarian hyperstimulation syndrome.

Eight patients who developed severe ovarian hyperstimulation syndrome (OHSS) were identified among 1302 patients undergoing in-vitro fertilization (IVF) over a 1 year period (prevalence of 0.6%); 63% had ultrasonically diagnosed polycystic ovaries (PCO) and 75% were undergoing their first attempt at IVF. Pretreatment with a superactive luteinizing hormone-releasing hormone (LHRH) analogue significantly increased the prevalence of severe OHSS (1.1% versus 0.2%, P less than 0.05) compared with ovarian stimulation with clomiphene citrate and human menopausal gonadotrophin (HMG). The mean serum oestradiol concentration on the day of human chorionic gonadotrophin (HCG) administration was 8200 +/- 2300 pmol/l. A mean of 19.6 +/- 6.8 follicles had been aspirated and 13.1 +/- 7.7 oocytes recovered at transvaginal ultrasound-directed oocyte recovery. All patients had an embryo transfer and luteal support in the form of HCG. The clinical pregnancy rate was 88%, multiple pregnancy rate 71% and implantation rate 63.5 +/- 41.3%. In a group of seven patients who were hospitalized for moderate OHSS during the same period, peak oestradiol levels were significantly lower than in those with severe OHSS (P less than 0.05). Of the group with moderate OHSS, 57% had PCO, the clinical pregnancy rate was 100% and multiple pregnancy rate 43%. Patients with ultrasound-diagnosed PCO have an increased risk of developing OHSS and the dose of HMG administered to them should be minimized. In patients at risk of developing OHSS, progesterone instead of HCG should be used for luteal support. Transfer of a maximum of two embryos or freezing all embryos for transfer in a subsequent cycle may reduce the likelihood of multiple pregnancy.     

Entrapment of platelets in the penis during and after erection

Because of the development of hypercoagulability and the deposition of fibrin in the penis during erection a study of the possible role of platelets in this process was undertaken. Platelet response was studied in 9 adult chacma baboons (Papio ursinus) using autologous in vitro indium-111-labelled platelets and sequential scintigraphy of the penis during erection. The blood pooling pattern was obtained using in vivo technetium-99m-labelled red cells in a similar investigation. A statistically significant retention of platelets occurred during and after erection, which could not be attributed to blood pooling (P less than 0,05). Entrapment of platelets could lead to enhanced activity and activation, and might play a significant role in hypercoagulability and fibrin deposition during erection. Therefore platelets could be an important factor in the pathogenesis of ageing impotence.     

The clinical utility of provocative radionuclide oesophageal transit in the evaluation of non-cardiac chest pain.

We combined edrophonium provocative testing with the technique of radionuclide oesophageal transit (RET) in 30 consecutive patients with non-cardiac chest pain (NCCP) and 12 controls. The oesophageal transit time of aqueous technetium-99m sulfur colloid was determined before and after intravenous infusion of 80 micrograms/kg edrophonium chloride (ED). Patient symptoms during provocative RET (P-RET) were recorded. Thirteen (43%) of the patients had abnormal study results, whereas all control subjects had normal results. Three groups considered abnormal were observed: (a) in two patients (6%), the pain was reproduced and transit pre- and post-ED administration was prolonged (greater than 15 s); (b) in six patients (20%), the pain was reproduced, but transit was normal pre- and post-ED; (c) in five patients (17%), transit pre- and post-ED was prolonged, but no pain was reproduced. In five patients (17%), ED prolonged the transit time greater than 15 s without pain, but the baseline transit was normal. Transit time was measurable in 23 patients. Mean pre-ED transit time was 10.2 +/- 7.4 s (mean +/- SD) and post-ED, 12.4 +/- 8.0 s (P = 0.3). We conclude that ED has no significant effect on transit time, and the pain induced by ED rarely correlates with an abnormal transit; P-RET provides additional information to baseline RET, increasing sensitivity, and may be a useful screening method in the evaluation of patients with NCCP.     

Quantitative effects of cerebral infarction on spatial learning in rats.

Outcome following stroke is difficult to measure because the behavioral response to infarction is variable. We hypothesized that cognitive function, such as spatial learning, may be a reproducible and sensitive outcome variable. We developed an animal model of multifocal cerebral ischemia in order to study the effects of infarction on learning. To cause ischemia, several hundred microspheres were injected into the internal carotid arteries of rats. After ischemia, behavior was measured using a global rating and a Morris water maze. Postmortem serial brain sections were stained and the size of the infarctions was measured. We found that intracerebral microspheres caused cortical infarction and an impairment of spatial learning. This impairment was not due to occlusion of the internal carotid artery and was not found in animals who received a sham injection of saline. The degree of learning impairment was not correlated with the volume density of the infarctions or with the volume density of the remaining cerebral hemisphere. The learning impairment clearly differentiated normal from lesioned animals, and the impairment was probably due to a delay in acquisition of spatial information rather than a defect in retention or retrieval. Measurement of learning deficit after cerebral ischemia is an efficient and sensitive method for evaluating new stroke treatments and possibly for exploring structure function relationships.     

Management of refractory peritonitis to maintain the peritoneum for subsequent dialysis.

Peritonitis and its sequelae remain major clinical problems in treating peritoneal dialysis (PD) patients. One of these sequelae is the formation of intra-abdominal adhesions, preventing a patient from returning to peritoneal dialysis after a Tenckhoff catheter is removed for refractory peritonitis. We have recently applied a technique that appears to reduce the incidence of this severe complication. When it is determined that a catheter will be removed for refractory peritonitis, hourly peritoneal dialysis exchanges are performed for 12 hr prior to surgery. Postoperatively, the abdomen is rested for 48 hr, after which a temporary peritoneal dialysis catheter is placed at the bedside and hourly exchanges (with antibiotics) are performed for 2-3 days or until the dialysis fluid white blood cell count improves. Then the temporary catheter is removed and the abdomen is rested until the Tenckhoff catheter is replaced in 10-14 days. We treated 5 consecutive patients with refractory peritonitis (2 Pseudomonas, 1 Proteus, 1 Candida, 1 S. aureus) with this technique. All 5 patients were able to return successfully to peritoneal dialysis. At our institution over the past five years, 9 patients with refractory peritonitis due to the same organisms have had their catheters removed. Only 5 (56%) were able to return to PD. Although preliminary, our technique holds promise for those patients wishing to return to peritoneal dialysis after having a catheter removed for refractory peritonitis.     

The clearance of a single i.v. bolus of recombinant human erythropoietin from the serum of patients with myelodysplastic syndromes and its effects on erythropoiesis.

The serum erythropoietin (EPO) concentration in patients with myelodysplasia (MDS) varies widely at similar hemoglobin concentrations, although the reasons for this variation are unclear. We have studied the pharmacokinetics of an i.v. bolus of recombinant human EPO in ten subjects with myelodysplasia. Basal serum EPO concentration varied from 210 to 5984 mU/ml. Plasma half-time clearance (t1/2) varied from 3.9 to 20.0 h. A significant positive correlation was found between t1/2 and basal EPO concentration. An increase in immature peripheral blood reticulocytes was found on days 1 and 2 after EPO treatment; this may represent either an effect on hemopoiesis or on reticulocyte release from the bone marrow.     

Orthotopic liver transplantation at Groote Schuur Hospital.

We present data on 10 patients (5 men and 5 women, aged 21-56 yrs) with end-stage liver disease or tumour who underwent orthotopic liver transplantation at Groote Schuur Hospital between October 1988 and June 1991. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the implantation of the liver. The venovenous bypass method was used in all but 2 patients. Postoperative immunosuppression was usually achieved with cyclosporin, azathioprine and low-dose steroids. Six patients were treated with prophylactic OKT3. Rejection episodes were treated with bolus doses of intravenous steroids. The indications for liver transplantation included chronic active hepatitis progressing to cirrhosis (5), biliary cirrhosis in association with inflammatory bowel disease (1), sclerosing cholangitis (2), alpha 1-antitrypsin deficiency (1), and tumour (1). All patients with chronic liver disease had experienced at least one complication, examples of which included encephalopathy, bacterial peritonitis, ascites, variceal bleeding and septicaemia. Serious postoperative complications included acute rejection of the transplanted liver, renal and liver failure that responded to intensive care support and medical management. One patient died on the 11th postoperative day with complications of bleeding oesophageal ulcer, shock and fungaemia. The remaining patients are alive and well 1-31 months after transplantation.     

Insulinlike growth factor 1 production is inhibited in human sepsis

We studied the response of 14 normal volunteers and five septic patients to a 48-hour course of exogenous biosynthetic human growth hormone (hGH) or placebo. Six normal controls (group 1) received saline, eight normal controls received hGH (group 2), and five septic patients also received biosynthetic hGH (group 3). Urinary urea excretion declined, and splanchnic amino acid uptake was maintained only in group 2 subjects. Septic patients exhibited changes in amino acid and urea dynamics comparable to those of subjects receiving placebo. Insulinlike growth factor 1 (IGF-1) production and plasma concentrations increased in group 2 in a fashion corresponding to the changes in nitrogen exchange, whereas septic patients exhibited no change in IGF-1 level. Therefore, in this septic patient group, exogenous hGH was ineffective in attenuating nitrogen losses and stimulating IGF-1 production. This supports the hypothesis that IGF-1 is a mediator of the anabolic effect of hGH.     

Massive macroglossia, amyloidosis and myeloma

A 74 year old man with light-chain myeloma developed amyloidosis with macroglossia after 10 years of therapy with alkylating agents. Over a 2-year period his tongue enlarged to persistently protrude from his mouth, inhibit his speech, interfere with normal swallowing and eventually threaten his airway. As a life-saving procedure the tumorous anterior two-thirds of the tongue was resected, with excellent primary healing. Within two weeks the patient's speech became comprehensible and his ability to eat returned to normal. Although rare in amyloidosis, massive macroglossia may occur and surgical correction is easily achieved.