Antikeratin antibodies in rheumatoid arthritis. Methods and clinical significance

A method to determine antikeratin antibodies (AKA) is described. AKA were detected by indirect immunofluorescence technique on rat esophagus as antigen in sera of patients with definite rheumatoid arthritis (RA). The frequency of AKA in rheumatoid factor (SCAT/Waaler-Rose) positive RA was 64% and in SCAT-negative RA, 28%. Of 61 control patients with non-RA rheumatic diseases, none was AKA-positive. Of healthy controls, 2.5% were AKA-positive. In serum from 88 definite RA patients, AKA were compared with precoded clinical features. A highly significant correlation to AKA was found with the presence of rheumatoid hand deformity. Some correlation to positive SCAT titre and s-Haptoglobin was observed. Our study suggests that determination of AKA will be of value in the diagnosis of RA, especially in rheumatoid factor negative cases and that the presence of AKA indicates a more aggressive form--or results of an aggressive course--of the disease.     

Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors.

Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can be a target for MAb-mediated virus neutralization.     

Trigeminal complications arising after surgery of cranial base meningiomas

Chronic severe facial pain is a feared sequel of cranial base surgery. This study explores the symptomatology, incidence and impact on the individual of postoperative de novo trigeminal nerve affection as well as the recovery potential. Out of 231 patients operated for cranial base meningiomas at the Karolinska University Hospital during 7 years, 25 complained of de novo trigeminal symptoms at clinical follow-up 3 months after surgery. Six were later lost to follow-up leaving 19 participants in the study, which was conducted using a questionnaire and a structured telephone interview. All patients complained of facial numbness, affecting the V1 branch in 10/19 patients (53%), the V2 branch in 18/19 (95%) and the V3 branch in 9/19 (47%). Surprisingly, only three (16%) suffered from trigeminal pain, which could be adequately managed by pharmacotherapy. However, five patients (26%) demonstrated ocular dysaesthetic problems. Twelve (63%) described their handicap to be mild, while seven (37%) had daily or severe symptoms. Five patients (26%) reported no improvement over time, while nine (47%) showed improvement and four (21%) stated good recovery. Only one patient (5%) claimed complete symptom remission. In the present study, 11% of the patients presented with a de novo postoperative affection of the trigeminal nerve after removal of a cranial base meningioma; 37% of these reported daily/severe symptoms. Only 26% showed good recovery, observed in patients without tumour infiltration of the nerve or intraoperative nerve damage. In spite of frequent complaints of numbness, pain was uncommon (16%) and often manageable by pharmacotherapy, while ocular symptoms turned out to be more frequent and more disabling than expected.     

Effect of antihypertensive treatment on kidney function in diabetic nephropathy.

The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin dependent diabetics (mean age 30). During the mean pretreatment period of 32 (range 23-66) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 72 (range 32-91) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mm Hg to 129/84 mm Hg and albuminuria decreased from 1038 micrograms/min to 504 micrograms/min. The rate of decline in the glomerular filtration rate decreased from 0.89 (range 0.44-1.46) ml/min/month before treatment to 0.22 (range 0.01-0.40) ml/min/month during treatment. The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment (greater than or equal to 6 years). One patient died from acute myocardial infarction (glomerular filtration rate 46 ml/min/1.74 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.     

Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy

The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria. In an initial one week randomised single blind trial of captopril versus placebo, captopril (for nine patients) reduced arterial blood pressure from 148/94 (SD11/6) to 135/88 (8/7) mm Hg (p less than 0.05) and albuminuria from 1549 (range 352-2238) to 1170 (297-2198) micrograms/min (p less than 0.05), while glomerular filtration rate remained stable. No significant changes occurred in seven patients treated with placebo. During the 12 weeks of captopril treatment arterial blood pressure in all patients fell from 147/94 (11/6) to 135/86 (13/7) mm Hg (p less than 0.01), albuminuria fell from 1589 (range 168-2588) to 1075 (35-2647) micrograms/min (p less than 0.01), and glomerular filtration rate fell from 99 (SD19) to 93 (25) ml/min/1.73 m2 (p less than 0.01). The renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased concentrations of angiotensin I and renin. The study showed that glomerular filtration rate is not dependent on angiotensin II, that captopril reduces albuminuria, probably by lowering glomerular hypertension, and that captopril represents a valuable new drug for treating hypertension in diabetics dependent on insulin with nephropathy.     

Impaired vascular function during short-term poor glycaemic control in Type 1 diabetic patients.

AIM: To study the effects of short-term poor glycaemic control on vascular function in Type 1 diabetic patients. METHODS: Ten Type 1 diabetic patients, with diabetes duration of less than 10 years and normal urinary albumin excretion and ophthalmoscopy, were studied. All patients were examined after 48 h of good vs. poor glycaemic control within a 3-week period. Blood glucose was measured seven times daily for 2 days before each examination. External ultrasound was used to measure the dilatory response of the brachial artery to post-ischaemic increased blood flow (endothelium-dependent dilation) and to nitroglycerin (endothelium-independent dilation). Plasma concentration of von Willebrand factor antigen, adhesion molecules, vascular endothelial growth factor, homocystein and cholesterol were also measured. RESULTS: The median blood glucose levels in the 48 h before the examinations were [median (range), good vs. poor control]: 6.3 (5.0-7.6) vs. 15.9 (11.3-17.8) (mmol/l). The flow-associated vasodilation (% of baseline) was reduced during poor control: 102.7 (94.7-110.8) vs. 104.0 (99.6-118.5) (P < 0.05) as were the nitroglycerin-induced dilation (% of baseline): 114.5 (103.3-127.9) vs. 120.2 (106.8-148.0) (P < 0.05). P-von Willebrand factor antigen was high during poor control (kIU/l): 1.14 (0.73-1.84) vs. 0.86 (0.72-1.39) (P < 0.05) and so was P-vascular endothelial growth factor (ng/l): 288 (133-773) vs. 254 (90-383) (P < 0.05). CONCLUSIONS: Short-term (48 h) hyperglycaemia in Type 1 diabetic patients may disturb vascular function, possibly mediated through smooth muscle cell dysfunction as well as endothelial dysfunction. We suggest that prolonged and repeated episodes of hyperglycaemia could possibly lead to permanent vascular dysfunction and thereby development and progression of vascular complications in diabetes.     

Location and concentration of estrogen,progesterone, and androgen receptors in the bladder and urethra of the rabbit

The objective of this study was to determine location and concentration of estrogen, androgen and progesterone receptors in the bladder and urethra of the rabbit. Two urethral and two bladder specimens were obtained from four 12-week-old female New Zealand white rabbits. Rat monoclonal antibody (AN 1–15) to human androgcn receptor and (H222) to human estrogen receptor and mouse monoclonal antibody (PR6) to chicken progesterone receptor were used. Immunocytochemical staining was performed and specimens were evaluated lor presence and location of steroid receptors. Androgen receptors were found in the highest concentrations in urethral and bladder epithelium. Low to low/moderate concentration were found in smooth muscle. Estrogen receptors were found in moderate to moderate/high concentrations in urethral epithelium and bladder and urethral smooth muscle. Progesterone receptors were not found in appreciable concentrations from any location, though the animals were not pretreated with estrogen. The rabbit model suggests a mechanism by which estrogen therapy can be effective in treating postmenopausal lower urinary tract symptoms. Progesterone receptors were not found in appreciable concentrations, suggesting progesterone therapy may not diminish the effectiveness of estrogen therapy by acting on urethral progesterone receptors. The effect of androgcns on the lower urinary tract needs further investigation to determine if androgen therapy can alleviate lower urinary tract symptoms. © 1995 Wiley-Liss, Inc.     

Intracranial traumatic and non-traumatic haemorrhagic complications of warfarin treatment

An increased referral of patients with anticoagulation related haemorrhages necessitated an analysis of causes and outcome of these complications in a patient group that reflected Swedish therapeutic traditions of anticoagulation treatment. Prospectively, all patients from Stockholm evaluated for warfarin related intracranial haemorrhage occuring during 1987 were analysed and their 6 month outcome recorded. Sixty-eight patients were included. The results of intracranial haemorrhagic complications were catastrophic with a 77% mortality rate. Their incidence was much higher than expected. Forty-one patients had non-traumatic intracerebral haematomas, 1 had a non-traumatic subarachnoid haemorrhage and 26 had traumatic injuries. In the 42 patients with non-traumatic haemorrhages, the indications for anticoagulation were cerebral ischaemic events in a majority (27/42). The remaining 15 patients had different indications for anticoagulation. They also had an increased frequency of hypertension (p<0.05). In the 26 patients with traumatic haematomas, only 6/26 patients had previous cerebral ischaemic injuries (p<0.01). Valvular heart prothesis was their most common indication (11/26) for anticoagulation. Caution in instituting anticoagulation therapy in patients with hypertension or cerebrovascular disease, which is an important indication for anticoagulation in Sweden, is mandatory. Adherence to strict treatment regimens and their continous reevaluation may help to avoid complications. The finding of more patients than expected with haemorrhagic complications is not compatible with the risk evaluations used to justify anticoagulation therapy in the patient groups studied. Clinical practice must have changed with time, showing that risk evaluations from controlled trials or retrospectively collected clinical data from selected patients are not necessarily applicable for long-term clinical practice.