Plasma proteins and a probiotic as ingredients in milk replacer.

Milk replacers containing all milk protein, 25% of protein from porcine plasma protein, 25% of protein from bovine plasma protein, or all milk protein plus probiotic were compared in a 6-wk experiment using 120 Holstein bull calves approximately 7 d of age. All replacers contained an antibiotic except the one that contained probiotic. Calf starter always was available, and calves were weaned when they consumed 680 g/d of starter. Ten calves were selected randomly from each group for sampling of jugular blood at d 1 and 10 of the experiment. A complete blood count was conducted on the samples, and protein fractionation by electrophoresis was performed on sera harvested from the samples. Mean BW gains started to differ at the end of wk 3, and by the end of wk 6 the difference of 2.6 kg was significantly greater for those calves fed porcine or bovine plasma than for calves fed all milk protein (with or without probiotic). The same response was noted for starter consumption; the difference increased to 4.15 kg by the end of wk 6. Most measurements of blood did not differ by treatment; those that were different did not suggest an apparent difference in performance response. Growth performance of calves fed probiotic was not different from that of calves fed antibiotic when both replacers contained all milk protein. Either porcine or bovine plasma protein was an acceptable source of protein.

Fusion of enveloped viruses with sperm cells: interaction of Sendai, influenza, and Semliki Forest viruses with bull spermatozoa.

Incubation of fluorescently labeled Sendai, influenza, as well as Semliki Forest viruses with bull sperm cells resulted in fluorescence dequenching. Fluorescence dequenching was observed with Sendai virus at pH 7.4 while with influenza and Semliki Forest viruses at pH 5.0, a pH value which is required for triggering their fusogenic activity. Control experiments performed with nonfusogenic Sendai and influenza viruses, or with bull sperm cells from which the viral receptors have been removed by treatment with neuraminidase, showed little fluorescence dequenching. These results clearly indicate that animal enveloped viruses are able to interact and to fuse with bull sperm cells. The possibility that following virus-sperm fusion spermatozoa can serve as a carrier of the virus genome and introduce it into recipient eggs during fertilization is discussed.

Heparin-induced thrombocytopenia in the newborn.

This pilot study was initiated to determine whether heparin-induced thrombocytopenia occurs in the newborn and whether thromboembolic complications in the newborn could be related to heparin-induced thrombocytopenia. Thirty-four infants in whom thrombocytopenia (less than 70,000/mm3) (n = 23), precipitous (30% to 50%) fall in platelet count (n = 5), or thromboses (n = 6) developed while they were receiving heparin were studied. Heparin-associated antiplatelet antibodies were demonstrated in 14 infants by platelet aggregation testing. The average gestational age (29 +/- 6 weeks); birth weight (1300 +/- 945 gm); and platelet count at birth (234,000/mm3 +/- 111,000/mm3) of these 14 infants did not differ statistically from the 20 infants without heparin-associated antiplatelet antibodies. An umbilical artery catheter was inserted in all infants except a single patient from each group. Aortic thrombosis was documented by abdominal ultrasonography in 11 of 13 (85%) infants with heparin-associated antiplatelet antibodies. One patient died with a midgut volvulus before the aorta could be examined. Five aortic thromboses were detected in the 20 infants without heparin-associated antiplatelet antibodies. Bleeding was not associated with the heparin-induced thrombocytopenia. One patient with previously demonstrated thrombocytopenia and heparin-associated antiplatelet antibodies had recurrent thrombocytopenia when reexposed to heparin; her platelet count recovered after heparin withdrawal. Thus heparin-induced thrombocytopenia does occur in preterm and term infants receiving heparin and is associated with arterial thromboses. Therefore infants receiving any form or amount of heparin must be carefully monitored for heparin-induced thrombocytopenia.1+

Intense immunosuppression in chronic progressive multiple sclerosis: the Kaiser study.

The value of a short course of intensive immunosuppression with cyclophosphamide in stabilising chronic progressive multiple sclerosis (MS) was examined in a randomised single-blinded, placebo-controlled clinical trial. Forty two patients, from the Kaiser Permanente Medical Care Program, Northern California, were studied. Twenty two patients received a short course of cyclophosphamide in an outpatient neurology clinic until their leucocyte counts fell below 4000/mm3, and 20 patients received folic acid. Level of disability, impairment of functional systems, and performance of social roles were assessed before randomisation and reassessed 12, 18, and 24 months after therapy. In both the cyclophosphamide and folic acid groups, the mean level of disability increased from the baseline examination to the 12 month follow up examination (the primary endpoint) by 0.5 on Kurtzke's Expanded Disability Status Scale, indicating similar disease progression in the two groups. Although immunosuppression therapy can be safely administered to MS patients in an outpatient clinic, evidence of substantial benefits was not found.

Thrombocytopenia associated with heparin-coated catheters in patients with heparin-associated antiplatelet antibodies.

Thrombocytopenia was associated with the presence of heparin-coated pulmonary artery catheters in 12 patients with heparin-associated antiplatelet antibodies. The thrombocytopenia persisted so long as the heparin-coated catheters were in place, even when all other sources of heparin were discontinued. The high morbidity and mortality associated with heparin-induced thrombocytopenia mandates that heparin administration cease and that all heparin-coated catheters be removed from patients with heparin-associated antiplatelet antibodies.

Contractile and metabolic function following an ischemia-reperfusion injury in skeletal muscle: influence of oxygen free radical scavengers.

Skeletal muscle contraction and metabolism was evaluated using an in vivo, intact autoperfused canine hindlimb model during 7 hours of reperfusion following 4 hours of complete ischemia, with and without bolus administration of superoxide dismutase (SOD) and catalase (CAT) at the start of reperfusion. Contractile tension of paw dorsiflexion during reperfusion demonstrated small but statistically non-significant increases of recovery towards pre-ischemic baseline with SOD/CAT (i.e. 43% +/- 10 vs 32% +/- 9 with muscle-stimulated tetanic tension). Oxygen utilization by the hindlimb rose during reperfusion from a baseline in the control group of 2.4 +/- 0.3 ml 02/min to 5.4 +/- 1.1 during the first 10 minutes and plateaued at 3.5 +/- 1.3 by the first hour with no differences in the SOD/CAT group. Lactate clearance was prompt (increase from a pre-ischemia value of zero to 0.93 +/- .14 mM/min by 5 minutes and return to near-zero by 1 hour in controls) exhibiting no sustained anaerobic metabolism and was not affected by SOD/CAT. These finding demonstrate irreversible loss of 60-70% of skeletal muscle contraction with preservation of aerobic metabolic capacity at 225% of basal activity. Bolus administration of SOD/CAT at the start of reperfusion offered no significant improvement in metabolic or contractile function. These observations, in a model simulating the in vivo setting, necessitate evaluating alternate ischemia reperfusion conditions and modified free-radical inhibitor protocols before any clinical benefit can be assumed.

Reexposure to heparin of patients with heparin-associated antibodies.

Four patients with heparin-associated antiplatelet antibodies who were not receiving platelet function-inhibiting agents received heparin during surgery, angiography, or hemodialysis. Three of the four patients had complications that were attributed to heparin-induced platelet aggregation. The complications included a superficial femoral artery thrombosis, a thrombotic stroke after a carotid endarterectomy, and recurring thrombosis of a graft inserted for dialysis. Nine patients received aspirin (325 mg b.i.d.) or dipyridamole (Persantine) (200 to 300 mg daily) before reexposure to 5000 to 12,000 units of heparin during 11 vascular procedures. The procedures included two carotid endarterectomies, three aortofemoral bypasses, one femoropopliteal bypass, two femorotibial in situ saphenous vein bypasses, one iliofemoral thrombectomy, one bilateral iliac artery angioplasty, and one axillobifemoral bypass. Platelet counts averaged 173,000/mm3 before heparin reexposure, fell to an average of 86,000/mm3 within 24 hours of heparin reexposure, and returned to normal within 48 hours after the reexposure. None of these patients had a thromboembolic or hemorrhagic complication. Patients with heparin-associated antiplatelet antibodies are at risk for developing thrombocytopenia and thromboembolic complications on reexposure to heparin. The platelet function-inhibiting agents, aspirin and Persantine, protect the patients from the thromboembolic complications but not the thrombocytopenia associated with limited heparin reexposure.

Heparin-coated catheters and heparin-induced thrombocytopenia.

Ten patients with heparin-coated pulmonary artery catheters had heparin-induced thrombocytopenia, which persisted after all other sources of heparin were discontinued. The thrombocytopenia occurred in approximately 0.4% of the patients receiving heparin-coated catheters and remitted when the catheters were removed. The platelet counts averaged 59,000/mm3 at the time of the diagnosis and recovered to an average of 143,000/mm3 by 3 days (range 2 to 4 days) after removal of the heparin-coated catheters. One patient required a second catheter 31 days after the first catheter had been removed. When the second heparin-coated catheter was inserted, the platelet count decreased from 307,000/mm3 to 102,000/mm3 in 4 days. Segments of heparin-coated pulmonary artery catheters were placed in platelet-rich plasma and incubated with serum from patients with known heparin-associated antiplatelet antibodies or with serum from volunteers with no exposure to heparin. The heparin-coated catheters induced platelet aggregation in all samples containing serum from patients with heparin-induced thrombocytopenia. However, platelet aggregation did not occur when the catheters were incubated with the serum of the volunteers. Non-heparin-coated catheters failed to produce platelet aggregation when incubated with either sera. The high mortality and morbidity rates associated with heparin-induced thrombocytopenia mandate that afflicted patients receive no more heparin, at least until the heparin-associated antiplatelet antibodies are no longer detectable. Patients with heparin-coated catheters who have thrombocytopenia should be tested for the presence of heparin-associated antiplatelet antibodies. If heparin-induced thrombocytopenia is confirmed, the catheters must be removed if the thrombocytopenia is to be reversed and complication avoided.

The heparin-induced thrombocytopenia syndrome: an update.

One hundred sixty-nine patients with heparin-induced thrombocytopenia are reported and compared with the 62 patients reported in 1983. Prompt recognition of heparin-induced thrombocytopenia and immediate cessation of heparin administration lowered the complication and death rates from 61% (38/62) to 22.5% (38/169) and from 23% (14/62) to 12% (21/169), respectively. Platlet count and duration of heparin administration were not useful in predicting the outcome of the heparin-induced thrombocytopenia syndrome. Patients who received heparin in therapeutic doses were at higher risk for developing complications than were patients receiving lower doses of heparin. Platelet aggregation tests became negative as early as 7 days after discontinuation of heparin but persisted as long as 28 months. Heparin reexposure (2 days to 34 months after positive aggregation studies) was uneventful in 13 of 15 patients, whereas two patients suffered devastating thrombotic complications. Five patients continued to receive heparin despite positive platelet aggregation tests. The serious complications suffered by two of these five patients illustrate the necessity to discontinue heparin as soon as the diagnosis of heparin-induced thrombocytopenia is established.