6-1 "TELL ME ABOUT YOURSELF": The Patient-Centered Interview.
      Physicians should focus more attention on patient's concerns, feelings, and ideas. Inattention to the person of the patient, to the patient's characteristics and concerns, leads to inadequate clinical data-gathering, non-adherence, and poor outcomes. Each patient's experience of illness is unique. "To know what kind of a person has a disease is as essential as knowing what kind of disease a person has." The art (of listening) is long; time is short.
      Practical point: Primary care physicians must go beyond disease-centeredness in the clinical encounter. They must become expert at listening without interruption and with undivided attention, and then lead patients to disclose more about themselves. RTJ

6-2 OPTIMAL TREATMENT OF ACUTE CORONARY SYNDROMES — An Evolving Strategy
      This article summarizes the latest recommendations. A reference algorithm is presented on p 1941.
      Practical point: Primary care clinicians can serve their patients optimally by immediately beginning non-interventional measures (aspirin, heparin, oral beta-blocker, and medication for pain control). Primary care clinicians remote from emergency centers must keep up with the rapid changes in therapy in order to correlate urgent treatment with their cardiologist colleagues. Each minute of myocardial ischemia adds to risk. The new bolus agents will facilitate early fibrinolysis out of hospital.

6-3 THE EFFECT OF FRUIT AND VEGETABLE INTAKE ON RISK FOR CORONARY DISEASE
      The data support a protective effect of greater consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C rich fruits and vegetables, against CHD.
      Practical point: Primary care clinicians should repeatedly advise patients about the benefits of a healthy diet.

6-4 MIDLIFE VASCULAR RISK FACTORS AND ALZHEIMER'S DISEASE IN LATER LIFE
      Raised systolic BP and high cholesterol concentrations (and particularly the combination) in midlife were associated with increased risk of Alzheimer's disease later in life. This possible added benefit would be most welcome.
      Practical point: Both factors should be controlled in mid-life regardless of any possible benefit on reducing risk of Alzheimer's. Control of both to reduce risk of cardiovascular disease is one of the great challenges and opportunities for primary care clinicians. Any possible reduction in incidence of Alzheimer's would be an additional benefit.

6-5 EFFECT OF RAMIPRIL VS AMLODIPINE IN RENAL OUTCOMES IN HYPERTENSIVE NEPHROSCLEROSIS
      Practical point: African Americans with hypertension are at high risk of renal dysfunction. Obviously, do not wait for renal dysfunction to be established before beginning effective anti-hypertension therapy. We should protect the kidney as well as the heart and brain. Identifying and treating patients at the stage of microalbuminuria (20 to 200 mg/d) would lead to greater benefit than waiting for renal dysfunction to become established. Angiotensin converting enzyme inhibitors are the drugs of choice.

6-6 DRUG TREATMENT FOR OBESITY
      The editorialist comments on a recent study of sibutramine which reported benefit in reducing weight re-gain after a program of weight loss.
      Practical point: Should primary care clinicians prescribe sibutramine, or any other weight-loss drug? I would vote against it. I believe use should be limited to special clinics where suitable candidates can be carefully screened and followed. The adverse effect on BP is a serious downside.

6-7 HELICOBACTER PYLORI AND SYMPTOMATIC RELAPSE OF GASTRO-ESOPHAGEAL REFLUX DISEASE
      Eradication of the infection led to a benefit -- a longer asymptomatic period before relapse of symptoms.
      Practical point: This study contradicts previous studies which suggested a harmful effect of eradication. Eradication therapy should be considered to reduce risk of stomach cancer, recurrence of peptic ulcer, and possibly for a slight reduction in severity of dyspepsia.

6-8 LONG-TERM OUTCOME OF MEDICAL AND SURGICAL THERAPIES FOR GASTROESOPHAGEAL REFLUX DISEASE
      Antireflux surgery should not be advised with the expectation that patients will no longer take antisecretory drugs. It is clearly not a cancer-preventing procedure.
      Practical point: Primary care clinicians should inform their patients with long term troublesome GERD about the long-term results of surgery vs medical treatment and allow them to decide.

6-9 NATURAL HISTORY OF CERVICAL HUMAN PAPILLOMAVIRUS INFECTION IN YOUNG WOMEN: A Longitudinal Cohort Study
      In this cohort of young women, only limited inferences could be drawn from the characteristics of HPV status at a single point in time. Longer observation in older women is needed.
      Attempts to exploit the association between HPV and cervical intraepithelial neoplasia (CIN) to improve effectiveness of screening is limited. Any lead time (time from detection of HPV to development of CIN) gained by detecting HPV is likely to be short.

6-10 NATURAL HISTORY OF HUMAN PAPILLOMA VIRUS INFECTIONS
      "A positive HPV test, especially in young women, rarely represents disease that could, if unrecognized, progress to cervical cancer."
      "Knowing more about the natural history of HPV infection, especially in young women, reinforces the view that testing should not be carried out among women under age 35."

6-11 WHY SHOULD WOMEN HAVE LOWER REFERENCE LIMITS FOR HAEMOGLOBIN AND FERRITIN CONCENTRATIONS THAN MEN?
      "The data from humans point to the possibility that the current lower reference levels for red blood cell counts and hemoglobin and serum ferritin concentrations in women have been derived from sampling populations that are deficient in iron."
      Reclassification of these parameters in women to the same values as for men would be expected to have fundamental and positive implications for women's health and welfare.
      Practical point: Primary care clinicians should be aware of the near universal likelihood of iron deficiency in young women. Supplementation is reasonable.

6-12 DIAGNOSIS AND CARE OF PATIENTS WITH ANOREXIA NERVOSA IN PRIMARY CARE SETTINGS
      Clinical diagnosis of AN is often obscure. Patients with mild cases usually seek help for non-specific symptoms such as asthenia, dizziness, and lack of energy. Presentation may be remarkable for its lack of complaints. Family members may bring patients to the physician because of concerns about amenorrhea or weight loss.
      The primary care physician is often the first to consult and suspect AN. Early clinical suspicion and diagnosis is likely to lead to more effective treatment.
      The primary care clinician is involved with arranging and coordinating a comprehensive and multidisciplinary treatment program.
      Practical point: Suspect anorexia nervosa and bulimia in a thin young woman who exercises excessively and has amenorrhea.

6-13 RANDOMIZED TRIAL OF CRANBERRY-LIGONBERRY JUICE AND LACTOBACILLUS GG DRINK FOR THE PREVENTION OF URINARY TRACT INFECTION IN WOMEN.
      Daily consumption of cranberry juice reduced the recurrence of urinary tract infections in young women. Lactobacillus did not.
      Practical point: Primary care clinicians may suggest cranberry juice as a prophylactic measure in women with frequent recurrences.

6-14 SMOKING CESSATION AND THE COURSE OF MAJOR DEPRESSION
      Smokers with a history of depression who abstained from smoking were at high risk of developing a new episode of major depression.
      Practical point: How should primary care clinicians respond to this information? Which is worse -- continuing smoking or developing another episode of major depression? Is cigarette smoking always bad? Obviously, millions of persons choose to smoke fully knowing the risks. There must be some benefit. Relentlessly pushing some patients to stop smoking could drive them away. A frank discussion about pros and cons might lead to a trial of nicotine replacement.

6-15 TIME TO TAKE SOUNDINGS IN ACUTE RHEUMATIC FEVER.
      Doppler echocardiographic demonstration of subclinical carditis represents definite heart disease. The criteria for confirmation require that the regurgitant jet must extend 1 cm back of the valve and be holosystolic (mitral) and holodiastolic (aortic).
      Practical point: Although rheumatic fever is rare in the US, it still occurs. Primary care clinicians should be aware that echocardiography may be a valuable aid in early diagnosis and lead to more effective prophylaxis.

6-16 DO DOCTORS POSITION DEFIBRILLATION PADDLES CORRECTLY?
      The International Liaison Committee of Resuscitation guidelines specify placement of the centers of the two paddles:
      Sternal paddle — below the right clavicle in the mid-clavicular line
      Apical paddle — to the left of the nipple with the center of the electrode in the mid-axillary line.

6-17 EFFICACY AND SAFETY OF INFLIXIMAB MONOTHERAPY FOR PLAQUE-TYPE PSORIASIS
      Patients with moderate to severe psoriasis receiving infliximab (an antibody to tumor necrosis factor) experienced a high degree of clinical benefit and rapid time to response. Tumor necrosis factor has a pivotal role in the pathogenesis of psoriasis.
      Practical point: Primary care clinicians should establish a referral relationship with dermatologists who will be able to offer new treatments which will more safely and effectively reduce the severe physical and psychological effects psoriasis brings to many individuals.

6-18 HIGH-DENSITY LIPOPROTEIN CHOLESTEROL AND ISCHEMIC STROKE IN THE ELDERLY: The Northern Manhattan Stroke Study
      Increased HDL-c levels were associated with reduced risk of ischemic stroke in the elderly. This is possibly another benefit of statin drugs which raise HDL-c.
      Practical point: Primary care clinicians should consider the entire lipid profile, not just the total cholesterol or the LDL-cholesterol, when advising patients about risks.

6-19 GLUCOSAMINE FOR OSTEOARTHRITIS: Magic, Hype, or Confusion?
      "We conclude that there is more confusion and hype than magic about glucosamine. The rationale for its use in unclear; the best dose and route of administration are unknown, and the published trials do not allow any conclusion about its efficacy or cost effectiveness. However, it seems to be safe.
      Practical point: When patients confront primary care clinicians about use of glucosamine, how should they respond? I would neither prescribe it nor dissuade patients who are convinced of its benefit from taking it since it appears to be safe.

6-20 GENE THERAPY FOR HEMOPHILIA
      An article in this issue of NEJM reports results of introduction of a factor VIII gene into skin fibroblasts ex vivo and then implanting the cells into the peritoneal cavity of patients with hemophilia. Detectable levels of factor VIII appeared in the serum of patients who received such cells. Therapeutic levels persisted for several months.
      Practical Point: None at present. I abstracted the article because of the promise of a great leap forward in therapy of a historically devastating disease.

6-21 FATTY FISH CONSUMPTION AND RISK OF PROSTATE CANCER.
      Consumption of large amounts of fatty fish over years was associated with a decreased incidence of PC.
      Practical point: Another possible benefit of fish. Primary care clinicians should recommend fish consumption in the healthy diet for protection against cardiovascular disease -- and now, possibly to protect against PC.

6-22 THUNDERSTORMS AND ASTHMA
During a thunderstorm, a downdraft of air sweeps up pollen and other particles and concentrates them in a shallow band of air at ground level. Patients with asthma should note any association with weather patterns, and take air-conditioned shelter if possible.
      Practical point: In individual patients, primary care clinicians might determine the incidence of exacerbations of asthma related to weather. Recommendations to avoid outdoor air during storm times might be appropriate.

1. The Nurses' Health Study and the Health Professionals' Follow-up Study entered over 126 000 persons age 34 to 59. At baseline all were free of cardiovascular disease, cancer and diabetes.
2. Assessed diet by a food-frequency questionnaire on several occasions over the follow-up period.
3. Followed during 8 to 14 years.

1. After adjustment for standard cardiovascular risk factors, those in the highest quintile of fruit and vegetable intake had a relative risk of CHD of 0.8 vs those in the lowest quintile.
2. Each serving per day of a fruit or vegetable was associated with a 4% lower risk.
3. Green leafy vegetables and vitamin C rich fruits and vegetables contributed most to the apparent protective effect.

1. Intake of green leafy vegetables and vitamin C-rich fruits and vegetables was inversely related to risk of CHD.
2. The decrease in risk began at the level of 4 servings a day. Further reductions seemed to occur at up to 8 servings daily.
3. Previous studies reported a reduction in risk from nuts and whole grains.
4. The inverse association was slightly stronger in those taking supplements.

1. Prospective, population-based study in two areas of Finland followed a total of over 1400 participants studied in 1972, 1977, 1982, and 1987. After an average of 21 years, participants (then age 65-79) took part in a final examination in 1998.
2. Main outcome measures — midlife BP and cholesterol concentrations and development of Alzheimer's disease in late life.

1. A total of 57 participants were diagnosed as having dementia; 48 fulfilled the diagnostic criteria (DSM - IV) for probable or possible Alzheimer's.
2. All 48 showed generalized or temporal brain atrophy. None had appreciable vascular pathology on magnetic resonance scans.
3. After adjustment for possible confounders, those with raised systolic BP (> 160) or high cholesterol (> 250) had a significantly greater risk of Alzheimer's in later life. Odds ratio for raised systolic BP = 2.3; for raised cholesterol = 2.1; for the combination of both = 3.5.

1. Both raised systolic BP (but not diastolic) and high cholesterol in midlife were associated with later development of Alzheimer's disease. The combination of both increased risk to a greater degree.
2. Participants who developed Alzheimer's were more likely to have received antihypertensive drug treatment.
3. "Our findings are partly corroborated by the only drug trial to date showing that blood pressure control may prevent dementia, which was carried out in patients with isolated systolic blood pressure."
   ("Prevention of Dementia in Randomized, Double-blind, Placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial" Lancet 1998; 352: 1347-51)
4. "Hypertension and hypercholesterolemia may increase the risk of dementia by inducing atherosclerosis and impairing blood flow, but they may also directly induce the neurodegeneration of Alzheimer's disease."

1. Entered over 650 self-identified African Americans with hypertension. All had a reduced glomerular filtration rate. None had identified diabetes or causes of renal failure other than hypertension. Mean duration of hypertension = 14 years. Patients were taking a variety of drugs for hypertension.
2. Mean baseline characteristics: BP 151/86; age range 18-70; urine protein -- men 610 mg/d, women 400 mg/d; serum creatinine -- men 2.2 mg/dL, women 1.8 mg/dL; glomerular filtration rate (GFR) 20 to 65 mg/min per 1.73 m2 of body surface. (Ie, at entry, all had long-standing hypertension, and significant renal dysfunction.)
3. Randomized to: 1) amlodipine, 5 to 10 mg daily; or 2) ramipril, 2.5 to 10 mg daily. Dosage was adjusted to achieve the BP goal of at least a mean arterial BP below 107 mm Hg. A variety of other drugs were added if the target BP was not achieved.
4. Primary outcome measure = rate of change in glomerular filtration rate.
5. Clinical endpoints included degree of proteinuria, and development of end stage renal disease and death. Follow-up = 3 years.

1. Among those with 24 h protein excretion over 300 mg, the ramipril group had a 36% slower decline in GFR over 3 years compared with the amlodipine group.
2. Over 3 years, compared with the amlodipine group, the ramipril group had a 36% slower decline in GFR, and a 48% reduced risk of end-stage renal disease and death.
3. The ramipril group also had a decline of 20% in protein excretion vs a 58% increase in the amlodipine group during the first 6 months of the study. Thereafter, moderate increases occurred. (Note -- ramipril slowed, but did not stop, the decline in renal function.)

1. Compared with amlodipine, treatment with ramipril offered greater benefits in patients with mild to moderate hypertensive, nephrosclerotic renal disease.
2. Ramipril was associated with a slowing in decline in GFR and slowed progression of proteinuria. Also lowered incidence of end-stage renal disease and death.
3. Patients with proteinuria of 300 mg/d or above at baseline received the greatest benefit.
4. CCBs may have a disadvantage because they dilate the glomerular afferent arteriole, leading to increased glomerular pressure and loss of renal autoregulation. Intraglomerular pressure rises even as systemic pressure falls. ACEI generally reduce intraglomerular pressure and do not interfere with autoregulation.
5. The authors suggest that the benefits of ramipril might extend to individuals without proteinuria.
6. These results are consistent with prior observations that ACEI have a renal protective effect in patients with non-diabetic as well as diabetic renal disease.
7. Measurement of urinary protein is recommended to guide initial therapy selection.

Glomerular filtration rate

A.	Inulin clearance -- Men 100-150 mL/min; women 105-130 mL/min
B.	Creatinine clearance -- 91 to 130 mL/min

Serum creatinine -- < 1.5 mg/dL
Urine protein excretion -- men 0 to 60 mg/d; women 0 to 90 mg/d RTJ

1. Double-blind, randomized trial entered 70 patients; 58 completed the trial All had symptoms of GERD. All had either endoscopically proven reflux esophagitis or a pathological reflux on 24-hour pH monitoring.
2. 29 patients had proven H pylori infections; 33 patients without infection served as H pylori controls.
3. All patients received lansoprazole (a proton pump inhibitor) therapy to reduce acid production for 8 weeks.
4. Randomized to one of 3 groups:

   1)	H pylori positive:      A. Received antibiotic therapy      B. Served as H pylori positive controls
   2)	H pylori negative controls

5. Follow-up = 6 months.

1. In 13 patients eradication was successful In 16 H pylori remained positive (3 treatment failures and 13 who were not treated) In 29 controls, H pylori was never present
2. In all patients in whom H pylori was successfully eradicated, the active component of gastritis (neutrophil granulocytes) disappeared
3. Among those who remained positive (untreated, failures, and controls) the GERD symptoms relapsed earlier (Mean of 54 days). Among those in whom eradication was successful, relapse occurred at a mean of 100 days. Patients who remained positive and those who did not have the infection (controls) relapsed at the same time.
4. Time to relapse was also affected by severity of the esophagitis. When results were corrected for the effects of esophagitis grade, patients who remained positive still relapsed earlier.
5. No beneficial effect on patients with severe esophagitis (grade II and IV). These patients relapsed almost immediately.

1. Results of studies with duodenal ulcer patients have indicated that eradication of H pylori substantially raises the risk of GERD. (H pylori-positive ulcer patients may have a different pattern of acid secretion than those without ulcer disease.
2. But, other studies do not support the view that eradication in ulcer patients aggravates or precipitates GERD symptoms.
3. The presence of H pylori led to a shorter symptom free interval. Therefore . . . "eradication therapy should be considered in patients with GERD."

1. At baseline (10 years previously), all had severe GERD, with a high proportion of esophageal ulcers, strictures, and BE. 52% of the original cohort participated in the follow-up.
2. Main outcome measures: use of antireflux medication, symptom scores, grade of esophagitis, frequency of treatment of esophageal structure, frequency of subsequent antireflux operations, general health scores, satisfaction with antireflux therapy, incidence of esophageal adenocarcinoma. ]
3. Median follow-up = 10 years.

1. At follow-up: Medical (n=91) Surgical (n=38) A. Regular use of antireflux medication 92% 62% B. There were no significant differences in grade of esophagitis, frequency of treatment for esophageal stricture, subsequent antireflux operations, physical and mental scale scores, and overall satisfaction with therapy.
2. Patients with BE at baseline developed adenocarcinoma at a rate of 4/1000 per year. Adenocarcinomas developed in patients without Barrett esophagus at a rate of 0.7/1000 per year. Not a statistically significant difference.
3. Survival during the mean of 10 years of follow-up was less in the original surgical group due to a higher death rate from heart disease. The authors offer no explanation.

1. In this study of patients with severe GERD, Barrett esophagus developed into adenocarcinoma at a rate of 0.4% per year. This, and other studies have suggested that the cancer risk associated with BE has been overestimated. Acceptance of this low rate could have a profound influence on recommendations regarding endoscopic surveillance in patients with BE. The cancer incidence among patients with severe GERD who did not have BE was 0.07% per year).
2. GERD was an uncommon cause of mortality, even in elderly patients with severe GERD.
3. Almost all patients in the medical group continued to take antireflux medication (including proton pump inhibitors), but 62% of surgical patients also continued to take antireflux medication on a regular basis. This suggests that antireflux surgery should not be advised with the expectation that medication will no longer be needed.
4. During follow up, a substantial number of patients in both groups had one or more antireflux operations (10% medical vs 16% surgical) and had treatment for esophageal stricture (8% vs 14%).
5. Most patients in both groups were satisfied with their therapy.

1. Recruited 1075 women age 15-19 who were sexually active. All had normal cervical smears and were HPV negative at baseline.
2. Rechecked every 6 months for HPV and CIN. Mean follow-up = 3 years.
3. Determined HPV DNA by polymerase chain reaction.
4. When an abnormal smear was reported, patients were referred to a research clinic where a sample of colposcopically abnormal epithelium was removed for histological examination. Treatment was postponed until there was histological evidence of high-grade CIN (CIN 2 or 3). Once CIN 2 or CIN 3 developed, these individuals were excluded from the study. (Ie, the study supplied no information on development of carcinoma of the cervix.)

1. HPV infections:
   

   What percentage of women became HPV positive?

   Cumulative risk at 3 years was 44%; 60% at 5 years.

   What types of HPV are most common?

   HPV -16 was the most common. Seven other types were detected. Many women had unidentified types. Some women were positive for 2 to 4 different types during the follow-up period.

   Once infection developed, how long did it remain present?

   A median of 14 months. Infections were self-limited.

   (Comment: An extraordinary prevalence of infection. Infections waxed and waned.)
   
2. Abnormal smears:

   How many women developed abnormal smears?

   Cumulative risk at 3 years of any abnormal smear was 28%. (Again, a high prevalence of cytologic abnormalities.

   What stage CIN developed?

   Borderline nuclear abnormality -- 43%.
   Mild dyskaryosis -- 42%
   Moderate or high grade dyskaryosis -- 15%. The majority -- CIN 2 or CIN 3
   

   How long did the episodes of abnormality last?

   Median duration = 9 months. (The dyskaryosis cleared itself. Some women had more than one episode of dyskaryosis. Duration in those with more severe dyskaryosis was longer than those with milder dyskaryosis.

   (Comment: As with the infection, the abnormal cytology waxed and waned. The acquisition rate of CIN abnormalities was high.)
   
3. Relation between HPV and abnormal smears:

   How many women did not have HPV at time of appearance of abnormal smear?

   40% tested negative for HPV up to and including the visit when the first abnormal smear was reported.
   Although most episodes of cytological abnormality were associated with HPV, some women who developed abnormalities remained negative. Five women who remained negative developed high grade CIN. These five women tested negative on 16 occasions.

   What was the risk of developing high grade CIN?

   Overall, 2% of those who became positive for HPV progressed to high grade CIN. Risk was greatest in those testing positive for HIV 16

   How long did the high grade CIN last?

   Risk of developing high grade CIN was maximum between 6 to 12 months after first detection of HPV and declined rapidly thereafter. Relative risk of high-grade CIN at 18 months was 3 vs 19 at 6 to 12 months.

   What was the temporal relationship between abnormal smears and identification of HPV?

   HPV appeared before the abnormal smear -- 27%
   Detected at the same time -- 33%
   Compared with women who remained negative for HPV, those who became positive developed a higher grade of abnormality Risk was maximum at an average of 6 months, and declined rapidly thereafter.
   Recurrent episodes of HPV-associated cytological abnormalities were usually associated with detection of a new HPV type.
   

   What were the implications of viral load (high vs low)?

   More women with a high viral load at their first HPV-positive sample had an abnormal smear than those with a low viral load. Some women developed a high viral load following a first determination of a low viral load. Cumulative risk = 45% at 3 years.

1. The risk of acquisition of HPV infection was very high in these young women. A similar risk has been reported in North American college students. Acquisition of HPV is apparently inevitable in this age group.
2. HPV infections, or at least the period during which the virus can be continuously detected, are usually of short duration. But infections may disappear and reappear. This could be due to:

   Reactivation of endogenous infection
   Low levels of HPV fluctuating around threshold of detectability
   Inadequate sampling
   New exposure.
   

   The investigators could not distinguish between these possibilities. Th duration of infection cannot be measured with certainty.
3. High viral loads were associated with cytological abnormalities. But viral load seemed to wax and wane over time.
4. Cross sectional surveys reveal a high prevalence of cytological abnormalities in sexually active teenagers. Many of these abnormalities are transient, spontaneously regressing. Many women have more than one episode of CIN.
5. Most women who progressed to high grade CIN did so rapidly.
6. HPV infections often precede onset of CIN. The period between infection and CIN is frequently short.
7. There is a widely held view that persistent HPV infection is a prerequisite for the development of high grade CIN, a prolonged period of HPV exposure is not necessary for progression to take place. Ie, high grade CIN may be a surprisingly early manifestation of infection. Little lead time might be gained by detection of HPV.
8. Not all women who developed CIN were positive for HPV. A substantial number remained negative.
9. The International Biological Study on Cervical Cancers reported detection of HPV in 99.7% of cervical cancers. Thus, HPV negative high grade CIN, if it exists, has little malignant potential. However, the possible importance of HPV negative high grade CIN should not be discounted.
10. There is now understandable enthusiasm for exploiting the association between HPV and CIN to improve the efficiency of cervical screening programs. This would bring a risk of causing unnecessary anxiety and increasing management dilemmas.

The criteria for AN:

Intense fear of weight gain
Undue emphasis on body shape
Body weight < 85% of predicted
Amenorrhea for 3 consecutive periods.

Criteria for bulimia nervosa (BN):

Recurrent episodes of eating a larger amount than most persons, or a sense of not having control over eating.
Recurrent, inappropriate, compulsive behavior to prevent weight gain — self-induced vomiting, abuse of laxative, diuretics, or other medications. Excessive exercise.
Bingeing and purging at least twice a week for 3 months.
Self-evaluation unduly influenced by body weight and shape.

1. Open, randomized trial entered 150 women (mean age 30) with UTI caused by E coli — a typical group at risk.
2. All had a recent UTI. None were taking antimicrobial prophylaxis.
3. Randomized to: 1) 50 mL of a cranberry-ligonberry juice (80% cranberry) concentrate daily for 6 months; 2) 100 mg of a lactobacillus drink 5 days a week for 1 year; or 3) no intervention control group.
4. Followed for UTI recurrence over 1 year.

1. At 6 months, 8 (16%) of women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had at least one recurrence.
2. Number needed to treat with cranberry for 6 months to prevent one UTI = 5.
3. Lactobacillus was not effective.

1. "Our study confirms the common belief that symptomatic recurrences of urinary tract infection can be prevented with cranberry juice."
2. Cranberry juice could reduce use of prophylactic antimicrobials.

1. Enrolled 100 smokers in a cessation program. Followed 76 to completion of the study. All were smoking over 1 pack per day. All had a history of major depression, but were currently free of depression, and had not been on antidepression medication for at least 6 months.
2. Participants were self-selected. All wanted to stop smoking. All were at the mild-to-moderate end of the spectrum of depressive illness. They were more representative of patients seen in primary care than in a psychiatrist's office.
3. Assessed recurrence of depression at 3 and 6 months after cessation.

1. 76 of 100 (76%) were followed for 6 months. Many subjects failed to return for follow-up.

   A.	42 (55%) successfully maintained cessation. Of these abstainers, 14 (18%) had a recurrence of depression.
   B.	34 (45%) relapsed into smoking. Of these, 2 (6%) had a recurrence of depression.

1. Smokers with a history of major depression who stopped smoking were 7 times more likely to have a recurrence of depression than individuals who continued to smoke.
2. Unlike withdrawal symptoms, depression did not generally arise immediately after cessation, but was distributed across the entire study period.
3. "Some smokers with a history of depression undoubtedly sense that cessation provokes depression, and they fear trying to stop." It is not known if antidepression medication would be a better alternative than continued smoking.
4. Data suggest that nicotine decreases vulnerability to depression. "Nicotine or nicotine-like drugs could be useful antidepressant treatments."

The International Liaison Committee on Resuscitation guidelines specify placement of the centers of the two paddles:

Sternal paddle — below the right clavicle in the mid-clavicular line
Apical paddle — to the left of the nipple with the center of the electrode in the mid-axillary line.

1. Randomized 33 patients with moderate to severe psoriasis to: 1) intravenous infliximab 5 or 10 mg at weeks 0, 2, and 6; or 2) placebo.
2. Follow-up at 10 weeks for physician's global assessment of response.

1. Responders (good, excellent, or clear):

   Infliximab 5 mg	82%
   Infliximab 10 mg	91%
   Placebo	18%

2. Median time to response was 4 weeks.
3. No serious adverse effects. Headache occurred more commonly in the active treatment groups.

1. There are 2 major pathological lesions seen in psoriasis: 1) epidermal hyperproliferation with abnormal differentiation, 2) and inflammatory infiltration of the epidermis and dermis.
2. These processes are driven mainly by activated T cells which release chemokines and cytokines that signal hyperproliferation and abnormal differentiation. TNF is one of the signal molecules involved. Increased concentrations have been found in psoriatic lesions.
3. Blockade of TNF should reduce inflammation, keratinocyte proliferation, and the differentiation abnormalities of psoriasis.
4. The response was similar to that of cyclosporine, and greater than that reported for the soluble TNF inhibitor etanercept.
5. The findings support the pivotal role of TNF in the pathogenesis of psoriasis.
6. Infliximab has been reported to benefit rheumatoid arthritis and Crohn's disease. It is FDA approved for these indications.

1. Population-based case-control study 1993 through 1997. About 2/3 were over age 65.

   Cases (n > 500) had a first ischemic stroke
   Controls ( n > 900) without stroke, matched by age, sex, and ethnicity.

2. Determined lipid profiles in all.

1.  

   	Cases (stroke)	Controls (no stroke)
   HDL-c mg/dL (mean)	40	47
   < 34	34%	20%
   35-48	47%	42%
   > 50	19%	37%

2. A protective effect was observed for HDL-c levels of at least 35 mg/dL. More controls than cases had HDL-c concentrations over 35.
3. A dose response relationship was present: adjusted odds ratio cases/controls = 0.31 for those with HDL-c > 50
4. The protective effect of HDL-c was significant in those age 65-70 and those over age 75; less so in those under age 65.
5. Protective effect occurred in all racial groups.

1. Compelling data from statin trials show impressive stroke reductions among persons with established coronary disease (secondary prevention). [Statins raise HDL-c] Efficacy of statins has been reported significantly greater among those with initially lower HDL-c levels.
2. This case-control study demonstrated a protective efffect for ischemic stroke of higher HDL-c levels in men, women, the elderly, blacks, and Hispanics.
3. The protective effect persisted after adjustment for total cholesterol, LDL-c, and triglyceride levels.
4. Ultrasound studies have reported higher HDL-c is related to lower degrees of carotid atherosclerosis.
5. The National Cholesterol Education Program recommends the addition of HDL-c to cholesterol testing, and changed the recommended lower level to 40 mg/dL

The review comments:

Of all the genetic disorders, the hemophilias represent a combination of features that makes a favorable response to gene-replacement treatment likely. The clinical manifestations are entirely attributable to the lack of a single gene product which circulates in minute amounts in plasma. Tightly controlled gene expression is not essential. A small increase in the plasma level of factor VIII markedly ameliorates the symptoms. Many different types of cells are capable of making coagulation factors. The site of synthesis is not critical to function.

"Hemophilia is likely to be the first common severe genetic condition to be cured by gene therapy." "We can confidently predict that the new millennium will see an end to this ancient scourge."

1. Population-based study of twins followed over 6000 male twin pairs in Sweden for over 30 years. Sweden is a country with a traditionally high consumption of fatty fish from Northern waters (salmon, herring, mackerel) which contain large amounts of omega-3 acids.
2. In 1967, questionnaires were sent to twin pairs born between 1886 and 1925. (Sweden maintains a twin registry.)
3. The questionnaire investigated life-style factors, including fish consumption.
4. Followed the cohort to 1997, determining incidence of PC from a National Cancer Registry.

1. During the follow-up of up to 30 years (average = 21 years), there were 455 cases of PC diagnosed at a mean age of 77.
2. An increasing consumption of fish was associated with a decreasing frequency of PC. Men who ate no fish had a 2- to 3-fold higher frequency of PC than those who ate moderate to high amounts of fish.

1. The authors speculate on a possible mechanism for the protective effect of omega-3 acids. Consumption of fish high in omega-3 results in lower blood levels of tumor growth-enhancing prostaglandins.