The confirmatory test for a positive protein result by the reagent strip method uses:

DIAGNOSIS

The history and examination usually make the diagnosis obvious. A finger stick positive for high blood glucose or a strongly positive urine dipstick for glucose, together with a positive keto-diastix, strongly suggests the diagnosis of DKA. Confirmation is usually made with arterial blood gases and a low arterial pH.

The extent of laboratory abnormalities is estimated by measuring blood glucose, serum osmolality, plasma electrolytes, arterial blood gases, and blood and urine ketones, and by determination of the anion gap: (Na+ + K+) − (Cl− + HCO3) (see Chapter 41). Some of the possible problems with interpreting laboratory tests are outlined in Box 46.3. Serum lactate should be measured if there is renal insufficiency or hypovolemia in order to differentiate lactic acidosis from ketoacidosis. Many patients with diabetes have underlying disease, such as diabetic nephropathy, that makes them more vulnerable to insults such as hypotension. Measurement of blood urea and creatinine will give some indication of renal function. A 12-lead electrocardiogram (ECG), cardiac enzymes, and a chest radiograph may indicate myocardial ischemia. A cerebral computed tomography (CT) scan may be indicated if there are focal neurological signs or a persistent decrease in the level of consciousness.

Investigations for precipitating factors obviously overlap with possible complications of acute diabetic emergencies. Possible MI or cerebral events can be the cause or result of the disease, especially in elderly patients with HONC.

Infection is a very common major precipitating factor, especially in DKA. Blood, urine, and sputum cultures and a white cell count and differential need to be performed. A chest radiograph can indicate pneumonia. A CT scan and possibly a lumbar puncture may be indicated if meningitis is suspected. Cultures from wounds and facial radiographs to exclude sinusitis may have to be performed. A CT and/or ultrasound of the abdomen may be indicated, as well as serum amylase.

Possible alternative diagnoses of DKA are listed in Box 46.4. A rare manifestation of diabetic deterioration, euglycemic ketoacidosis, can occur, especially in young patients and often during a concurrent infection. Plasma glucose is relatively normal (<15 mmol/liter) and the patient may still be administering insulin. Symptoms such as nausea, vomiting, and clouding of the level of consciousness may occur, and ketoacidosis rapidly supervenes. This rare presentation highlights the importance of measuring urinary ketones as well as glucose in diabetic patients. A further diagnostic trap can occur, although rarely, when there is little acetate or acetone. In these cases, plasma levels of the other ketone, β-hydroxybutyrate, need to be specifically requested.

Treatment

Complete abstinence from alcohol intake is the most effective treatment of alcoholic myopathy because it avoids the persistence in the toxic effects on the muscle fibers (Fernández-Solà et al., 2000). Due to the cumulated and dose-dependent effect of ethanol intake in this disease, abstention form alcohol not only avoids the acute harmful effects, but also discontinues the progressive appearance of chronic effects in the skeletal muscle.

In acute alcoholic myopathy, transitory functional rest is recommended, because it avoids muscle stretching and improves local muscle tenderness and pain. If malnutrition, vitamin deficiencies or ionic disturbance coexist, adequate supplementation of these deficiencies may contribute to a prompt recovery from the myopathy. In the occasional cases in which acute rhabdomyolysis develops, it is important to establish large parenteral fluid supplementation, including sodium bicarbonate supplementation in order to improve the renal blood flow and avoid tubular acute necrosis and development of acute renal failure In this sense, it is useful to monitor the urine pH with reactive strips (Labstix® or similar) in order to maintain an urinary pH higher than 6. In the cases that evolve to acute renal failure, renal function failure should be supported by transitory hemodialysis. In the context of these patients, it is also important to consider the frequent possibility of the appearance of abstinence syndrome with delirium tremens, and establish adequate sedative support with clometiazole of benzodiazepines. Similarly, convulsions are frequent in this context, with the additional risk of broncho-pulmonary aspiration, which may contribute to worsen the clinical status of the patient.

Patients with chronic alcoholic myopathy should also avoid intense muscle exercise, which may increase the toxic effects of ethanol even more by muscle stretching. In addition, it is recommended that the use of other toxic substances such as cocaine or heroine that may potentiate the toxic effect of ethanol be avoided. This also includes the need to avoid toxic pharmacological agents such as statins, antiretrovirals (zidovudine) or colchicine. Adequate correction of chronic ionic, vitamin, calorie and protein deficiencies also contribute to a greater improvement of skeletal myopathy. Progressive active physiotherapy is recommended in these patients to avoid muscle atrophy. Moreover, it is important to consider and treat the frequent systemic organ involvement due to the toxic effects of ethanol other than in the skeletal muscle. In this regard, liver cirrhosis and dilated cardiomyopathy should also be considered and adequately compensated in the setting of alcoholic myopathy. In some cases recovery from chronic skeletal myopathy is only partial and some functional limitations may persist over time.

Evidence to Confirm the Presence of Cerebrospinal Fluid

Diagnosis

A diagnosis of diabetes mellitus requires documentation of appropriate clinical signs (i.e. polyuria, polydipsia, polyphagia, weight loss) in addition to persistent fasting hyperglycemia and glucosuria. The blood glucose concentration can be measured in the veterinary hospital using a cage-side portable blood glucose monitoring device (PBGM) on venous or capillary blood. A urine sample (free catch voided sample or via cystocentesis) should be obtained to check for the presence of glucosuria. Urine reagent test strips (e.g., KetoDiastix; Ames Division, Miles Laboratories, Inc, Elkhart, Ind.) can also be used cage-side in the veterinary hospital allowing for rapid confirmation of diabetes mellitus in addition to evaluating for the presence or absence of ketonuria.

Normal blood glucose concentrations vary from 53 to 117 mg/dl (2.9–6.5 mmol/l) in the resting state in dogs and from 57 to 131 mg/dl (3.1–7.2 mmol/l) in cats.34 Hyperglycemia is considered to be present when the blood glucose concentration exceeds 117 mg/dl in dogs. In cats, hyperglycemia is less well defined but is usually considered to be present when the blood glucose concentration exceeds 130 mg/dl. There is no set cut-off value established for blood glucose concentration above which the animal is considered to be diabetic. However, mild to moderate hyperglycemia is unlikely to cause recognizable clinical signs and therefore veterinary care will not be sought by the owner until the blood glucose concentration exceeds the renal capacity for glucose reabsorption (approximately 300 mg/dl in cats, 180 mg/dl in dogs). In addition, persistent hyperglycemia as well as glucosuria must be documented before a diagnosis of diabetes mellitus can be established as other factors may be contributing. Documented causes of hyperglycemia and/or glucosuria in small animal patients in addition to diabetes mellitus include stress, critical illness (such as heart failure and sepsis), administration of drugs, and renal defects. In cats, stress hyperglycemia is a well-documented and frequent cause of mild to severe elevations in blood glucose. In one study of healthy cats, blood glucose measurements as high as 613 mg/dl, with and without glucosuria, were associated with struggling during venipuncture.35 Typically, stress hyperglycemia should resolve within 90–120 min although in some hospitalized sick cats moderate hyperglycemia may be persistent. It is this author's recommendation to repeat a blood glucose measurement in 3 h to monitor for resolution or persistence of hyperglycemia when stress hyperglycemia is suspected.

Fructosamine, a product of an irreversible reaction between glucose and the amino groups of plasma proteins, reflects the mean blood glucose concentration over the preceding 1–2 weeks (vs 2–3 weeks in people). In a cat experimental study, fructosamine levels have been demonstrated to increase above the reference range within 3–7 days and to reach a steady state within 8–20 days depending on the degree of hyperglycemia.36 When the serum fructosamine levels are well above the normal range (> 400 mmol/l) in a dog or cat, this test provides additional supportive evidence for the diagnosis of diabetes. Additionally, since serum fructosamine levels are not affected by sudden changes in blood glucose concentration, it can be a used to differentiate between transient stress-induced hyperglycemia and diabetes in cats.36–39 However, it should be noted that a normal fructosamine level does not rule out a diagnosis of diabetes in an animal since normal values may be obtained when the onset of diabetes is recent or when only mild to moderate increases in blood glucose are occurring. In addition, fructosamine may also be influenced by hypoalbuminemia (< 2.5 g/dl), hyperlipidemia (triglycerides > 150 mg/dl), and concurrent hyperthyroidism (likely due to increased plasma protein turnover).40–42 Therefore, fructosamine levels should be interpreted cautiously in animals with these concurrent conditions. Despite these limitations, fructosamine can still provide additional supporting evidence for a diagnosis of diabetes mellitus and is frequently used for evaluation of glycemic control in the longer-term management of this disease.

Measurements of plasma insulin concentrations are not routinely done to diagnose diabetes mellitus in dogs and cats. Generally, insulin concentrations are low at the time of diagnosis and are not predictive of whether diabetic remission (in cats) will be possible.

Once a diagnosis of diabetes mellitus has been established, a thorough clinicopathologic evaluation is recommended to evaluate for other concurrent conditions. Concurrent diseases, such as pancreatitis, may be present which may worsen insulin resistance and hinder successful disease treatment. The minimum laboratory evaluation that is recommended for the newly diagnosed diabetic animal includes a complete blood count, serum biochemical panel, and urinalysis with bacterial culture. A bacterial culture of the urine is recommended even in animals with an unremarkable urine sediment. Additionally, a blood measurement of pancreatic lipase immunoreactivity (PLI) in both dogs and cats should be considered as pancreatitis is a common concurrent disease in diabetic animals.14 If available, abdominal ultrasonography can be used to further evaluate the abdominal organs for presence of disease.

Clinical Applications

Monitoring of urine or blood ketones levels

Home measurement of ketones may greatly assist in the prevention of DKA. A combination of high blood glucose concentration (above 250 mg/dL) and elevated urine or blood ketones indicates high likelihood that DKA is present.

Ketones can be measured in urine or blood.

Urine ketone measurements use a “dip stick” method based on a chemical reaction with acetoacetate (eg, Chemstrip from Roche; Clinistix, Ketostix, Keto-Diastix from Bayer).

Blood β-OHB tests are available for use in the laboratory (eg, Sigma or Cobos, Roche) and home monitoring (Precision Xtra meter, Abbott MediSense). Recently Abbott/MediSense unveiled a hand-held device, the Precision Xceed Pro System, for measurement of blood glucose and β-OHB in hospitals. β-OHB monitoring using hand-held devices is as accurate as reference laboratory method, at least up to 3 mmol/L [5,28,29].

Blood ketone testing has several advantages over urine ketone testing:

β-OHB is a better marker of ketosis than acetoacetate

β-OHB is “real-time” whereas ketonuria is usually “old news”

Ketonuria does not accurately reflect severity of ketonemia

A dehydrated person may not be able to void and some people are too ill or exhausted to do the urine test

Urine ketone strips have a short shelf life after opening.

Bedside measurement of β-OHB in blood is more sensitive (80%) in detecting ketosis than urine analysis (63%). A negative blood β-OHB test has a better negative predictive value than negative urine test in ruling out ketosis [30].

++ Change in Leukocyte Esterase Strip Test

Both papers cited for the use of leukocyte esterase had concern for bias and applicability, specifically in the reference standard domain. Wetters et al [11] included a prospective consecutive cohort of total knee arthroplasty and total hip arthroplasty patients with suspicion for infection. However, their study used 2 different urine reagent strips, considered the test positive when graded + or ++ using Chemstrip 7 (Roche Diagnostics, Indianapolis, IN) or moderate and large when using Multistix 7 (Siemens Healthineers, Erlangen, Germany). There was no comparison between both reagents since each patient was tested using one of these 2 reagent strips and not both. Their reference standard test for PJI was different between patients aspirated in the office and patients undergoing revision surgery. For example, Wetters et al [11] included a synovial fluid WBC count of 3000/μL and a mean of greater than 10 polymorphonuclear cells in the 5 most cellular fields examined when delineating criteria for PJI diagnosis. Parvizi et al [12], on the other hand, used a WBC count of 1700/μL and a PMN% in the synovial fluid of ≥64%.

Furthermore, both studies were assigned a high risk of bias for the flow and timing domain. This was due to the fact that approximately one-third of their cohort was excluded due to blood or debris in the aspiration, or because a result could not be differentiated between positive and negative. Parvizi et al [12] included a nonconsecutive cohort, and also had a large number of bloody samples and missing data leading to the inclusion of only 108 patients out of 177. Although they had an appropriate interpretation of the Chemstrip 7 reagent test, they suffered from the lack of a single gold standard for the diagnosis of a PJI.

5 Treatment of patients with PA/male LUTS

Case selection is always key in clinical practice and in the setting of the family physician. The best patient to manage is one above 40 years of age, symptomatic with nocturia, slower stream and sensation of incomplete voiding, has a normal PSA level, no palpable bladder and no haematuria or pyuria on the labstix.

Phytotherapy: Hexanic extract of Serenoa (HESr), can be used as initial treatment for patients with mild LUTS. Double blind studies have shown that it has anti-inflammatory activity in men with BPH-related LUTS. Plus, it is well known as a safe product indicated in the management of symptomatic BPH patients [6].

α Blockers: Those patients who are bothered and without a palpable bladder and not better with phytotherapy can be started on a trial of α blockers after counselling on the side effects especially postural hypotension. The usual advice is not to change the position of the head too quickly when getting up from bed and to be careful on bending down to fetch items in the lower shelves in the super market. Patients also need to be careful when bending to play tennis or golf. It is encouraged to use selective α blockers to eliminate the need for titration. Most studies show that the effect of α blockers are seen after 2 weeks and it is important not to give up too early and wait for results of this trial of medication. In general a trial of 4–6 weeks is reasonable as some patients may develop spells of urinary urgency in the first 3–4 weeks; irritable bladder symptoms are largely resolved by 4–6 weeks while the obstructive symptoms are resolved much earlier at 2–4 weeks. If the family physician does not see any improvement after 4–6 weeks of medication, the consideration is to refer to the urologist to investigate. If the medication is effective after 4–6 weeks, patients can be given further courses of the α blocker and monitored at intervals of 3–4 months, with PSA tested on a yearly basis if there are no concerns. Patients should be advised that α blockers relieve symptoms only but do not prevent progression of the disease. This is because α blockers do not reduce the size of the prostate [7]. Patients' symptoms may wax and wane and therefore it may be reasonable for patients to trial off the α blockers, or take them only on an as-needed basis.

Antibiotics: Prostatitis may be present at the time of presentation. This may present more like irritable bladder symptoms with intermittent dysuria and elevated PSA. It is reasonable to give a course of prostate-targeted antibiotics at the start of α blockers to improve the response to prostate medication. If the PSA remains elevated at 2–3 months follow-up after a course of antibiotics, then referral to the urologist should be made.

5-α Reductase inhibitors (5-ARIs): 5-ARIs may be added to those with larger prostate volumes on DRE (more than 30–40 g or when DRE shows a globular shape) and PSA above 1.5 μg/L. The 5-ARIs would not be effective if PSA is below 1.5 μg/L as it indicates a small prostate [8]. The PSA levels would decrease to half of the initial PSA levels after 3–6 months. A rise beyond half the initial PSA level may indicate a prostate infection or malignancy. The 5-ARIs can reduce the prostate size but cannot correct the shape of the prostate, which contributes more significantly to obstruction. Therefore, patients with a large prostate adenoma and high grade intravesical prostatic protrusion may be better treated with surgery. Only surgery can restore the prostate to its normal shape and configuration. Counselling is fundamental in the prescription of 5-ARIs. The advantages of a reduction in prostate size with a reduction in need for surgery and hair preservation over several years need to be discussed along with a drop in ejaculatory volume and in some cases erectile dysfunction.

Combination therapy: A combination of α blockers and 5-ARIs can be considered for the subset of patients with bothersome symptoms and a large prostate size of more than 30 g. However, in elderly patients, combination therapy can be prescribed only after weighing the significant risks of postural hypotension and falls.

Red flags for referral: Red flags for referral to urologists are persistent bothersome symptoms, gross haematuria, urinary incontinence, hard prostate, palpable bladder, PSA above 4 μg/L and proven urinary tract infection [9].