Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families.

Segregation analysis of breast cancer in families can provide the logical basis and the specific genetic models for mapping and identifying genes responsible for human breast cancer. Patterns of breast cancer occurrence in families were investigated by complex segregation analysis. In a sample of 1579 nuclear families ascertained through a population-based series of probands, an autosomal dominant model with a highly penetrant susceptibility allele fully explained disease clustering. From the maximum-likelihood Mendelian model, the frequency of the susceptibility allele was 0.0006 in the general population, and lifetime risk of breast cancer was 0.82 among susceptible women and 0.08 among women without the susceptibility allele. Inherited susceptibility affected only 4% of families in the sample: multiple cases of this relatively common disease occurred in other families by chance. The same genetic models, with higher gene frequency, explained disease clustering in an extended kindred at high risk of breast cancer. Evidence for a highly penetrant, autosomal dominant susceptibility allele for breast cancer in a high-risk family and the general population suggests that high-risk families can serve as models for understanding breast cancer in the population as a whole.     

Chronic recurrent multifocal osteomyelitis and psoriasis—A report of a new association and review of related disorders

In summary, we have described two patients with CRMO and psoriasis, and have reviewed the musculoskeletal manifestations associated with pustular eruptions of the palms and soles. In view of the frequent occurrence of PPP in patients with CRMO, we suggest that the occurrence of psoriasis in our two patients is more than coincidence, and that noninfectious, inflammatory lesions of bone may be another musculoskeletal manifestation of psoriasis. This rare association, as well as the association of PPP with disorders associated with new bone formation, may shed new insights on the relatively common finding of periosteal elevation associated with psoriatic arthritis and the occasional severe juxta-articular osteolytic destructive bone lesions seen in psoriatic arthritis.     

Surgical division of Wolff-Parkinson-White pathways utilizing the closed-heart technique: a 2-year experience in 47 patients

Kent bundle interruption for ventricular preexcitation has been successfully accomplished utilizing several different surgical techniques. The external closed-heart technique of Guiraudon combining surgical dissection and cryoablation has been used to interrupt 52 accessory pathways in 47 consecutive patients since May, 1985. The 35 male and 12 female patients ranged in age from 10 to 67 years (mean, 30 years). There were 25 left free wall, 13 right free wall, 13 posterior septal, and 1 anterior septal accessory pathways. Preoperative and intraoperative electrophysiological studies were performed in all patients to induce the arrhythmia and localize all accessory pathways. The operation consisted of dissection of the atrioventricular fat pad. Following this, the delta wave and retrograde accessory pathway conduction disappeared, thereby indicating successful pathway ablation. In 4 patients with right-sided accessory pathways, interruption of the pathway required cryoablation. Cryolesions (made with cryoprobe at -60 degrees C for two minutes) were created in the region of the accessory pathway insertion. All accessory pathways were successfully ablated without any deaths or heart block. Concomitant surgical procedures were performed in 4 patients. Two patients required a second operation the next day for an accessory pathway not found at the initial operation. Three patients had postpericardiotomy syndrome, and 4 had recurrent atrial fibrillation requiring therapy. The remaining patients have had no arrhythmia recurrence and have remained drug free after a follow-up of 1 month to 22 months (mean, 12.5 months). We conclude that the closed-heart technique of accessory pathway ablation is safe and reproducible, obviates the necessity for aortic cross-clamping and cardioplegic arrest, and allows instantaneous monitoring of conduction over the pathway.     

Primary care referrals for lumbar spine radiography: diagnostic yield and clinical guidelines.

BACKGROUND: Primary care requests for radiographs of the lumbar spine have come under increasing scrutiny. Guidelines aiming to reduce unnecessary radiographs by limiting referrals to patients at high risk of serious disease have been widely distributed. Trial evidence suggests that guidelines can reduce radiography referrals. It is not clear whether this reduction has been achieved in routine practice. AIM: This study, using routine data, was conducted to measure trends in pnmary care referrals for lumbar spine radiography at two hospitals between 1994 and 1999. DESIGN OF STUDY: Analysis of primary care requests for lumbar spine radiography from computerised records. SETTING: Addenbrooke's Hospital, Cambridge (1 July 1994 to 30 June 1999), and Ipswich General Hospital (1 July 1995 to 30 June 1999), United Kingdom. METHOD: All primary care requests for lumbar radiography were identified electronically from computerised information systems. A random sample of 2100 radiography reports were classified according to clinical importance. These classifications were used to examine whether the proportion of radiographs demonstrating potentially more serious findings had increased between 1994 and 1999. RESULTS: There was no evidence that primary care referrals for radiography of the lumbar spine had decreased between 1994 and 1999 at either hospital. General practitioners did not progressively refer more high-risk patients for lumbar radiography. Only a small proportion of patients had important radiographic findings that might warrant specialist referral or specific therapy. CONCLUSION: The implementation of diagnostic guidelines offers much to the NHS. However in these two hospitals, the reduction in radiograph utilisation evident in trials was not achieved. Guideline development is a resource intensive process; distribution must be supported by more effective implementation strategies.     

Low sodium haemodialysis reduces interdialytic fluid consumption but paradoxically increases post-dialysis thirst.

BACKGROUND: Interdialytic weight gain (IDWG) can be reduced by lowering the dialysate sodium concentration ([Na]) in haemodialysis patients. It has been assumed that this is because thirst is reduced, although this has been difficult to prove. We compared thirst patterns in stable haemodialysis patients with high and low IDWG using a novel technique and compared the effect of low sodium dialysis (LSD) with normal sodium dialysis (NSD). METHODS: Eight patients with initial high IDWG and seven with low IDWG completed hourly visual analogue ratings of thirst using a modified palmtop computer during the dialysis day and the interdialytic day. The dialysate [Na] was progressively reduced by up to 5 mmol/l over five treatments. Dialysis continued at the lowest attained [Na] for 2 weeks and the measurements were repeated. The dialysate [Na] then returned to baseline and the process was repeated. RESULTS: Baseline interdialytic day mean thirst was higher than the dialysis day mean for the high IDWG group (49.9+/-14.0 vs 36.2+/-16.6) and higher than the low weight gain group (49.9+/-14.0 vs 34.1+/-14.6). This trend persisted on LSD, but there was a pronounced increase in post-dialysis thirst scores for both groups (high IDWG: 46+/-13 vs 30+/-21; low IDWG: 48+/-24 vs 33+/-18). The high IDWG group demonstrated lower IDWG during LSD than NSD (2.23+/-0.98 vs 2.86+/-0.38 kg; P<0.05). CONCLUSIONS: Our results indicate that patients with high IDWG experience more intense feelings of thirst on the interdialytic day. LSD reduces their IDWG, but paradoxically increases thirst in the immediate post-dialysis period.     

Effects of acute hypovolaemia by furosemide on tracheal transepithelial potential difference and mucus in dogs.

Furosemide is a potent diuretic that affects water transfer across the respiratory epithelium, which is closely related to the transepithelial potential difference (PD). Water is a critical factor that determines mucus transport; an important lung defence mechanism that removes particles and microorganisms from the respiratory system. The aim of the present study was to investigate the acute effects of furosemide and hypovolaemia on tracheal PD and mucus properties. A total of 36 male mixed-breed dogs were submitted to anaesthesia, mechanical ventilation and haemodynamic monitoring. They were randomly assigned to three groups consisting of: a control group, a furosemide (40 mg i.v.) + hypovolaemia group, and a furosemide (40 mg i.v.) + volume replacement group. Tracheal PD and mucus samples were collected at time 0, 1 and 2 h after intervention. Mucus properties were analysed by means of a magnetic microrheometer and in vitro mucociliary transportability on the frog palate. Compared to controls, furosemide decreased PD to intermediate values, and only significantly when associated with hypovolaemia (-13+/-5 and -8+/-2 mV, time 0 and 2 h, respectively). In addition to the direct effect of furosemide, these results indicate that hypovolaemia also affects ion transport in the tracheal membrane. Furosemide and hypovolemia have no acute effects on respiratory mucus properties.     

Cognitive impairment of acute onset in the Consortium to Investigate Vascular Impairment of Cognition (CIVIC) study: occurrence, correlates, and outcomes.

OBJECTIVE: Having demonstrated that dementia of acute onset represents a distinct syndrome with distinct outcomes, the authors investigated whether similar attributes describe cognitive impairment of acute onset (CIAO). METHODS: The authors conducted a secondary analysis of the Consortium to Investigate Vascular Impairment of Cognition study. RESULTS: Ninety patients met our criteria for CIAO. Compared with cognitive impairment of gradual onset, CIAO was associated with vascular features (odds ratio [OR]: 12.3, 95% confidence interval [CI]: 3.2-47.9), dementias other than Alzheimer disease (OR: 6.5, 95% CI: 2.1-20.8), and decreased survival (hazard ratio: 2.8, 95% CI: 1.6-4.6). CONCLUSIONS: Patients with CIAO are clinically identifiable and have distinct outcomes.     

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.